Zeitschriftenartikel zum Thema „Keifu“

Magnesium transporter A (MgtA) is an active transporter responsible for importing magnesium ions into the cytoplasm of prokaryotic cells. This study focuses on the peptide corresponding to the intrinsically disordered N-terminal region of MgtA, referred to as KEIF. Primary-structure and bioinformatic analyses were performed, followed by studies of the undisturbed single chain using a combination of techniques including small-angle X-ray scattering, circular dichroism spectroscopy, and atomistic molecular-dynamics simulations. Moreover, interactions with large unilamellar vesicles were investigated by using dynamic light scattering, laser Doppler velocimetry, cryogenic transmission electron microscopy, and circular dichroism spectroscopy. KEIF was confirmed to be intrinsically disordered in aqueous solution, although extended and containing little β-structure and possibly PPII structure. An increase of helical content was observed in organic solvent, and a similar effect was also seen in aqueous solution containing anionic vesicles. Interactions of cationic KEIF with anionic vesicles led to the hypothesis that KEIF adsorbs to the vesicle surface through electrostatic and entropic driving forces. Considering this, there is a possibility that the biological role of KEIF is to anchor MgtA in the cell membrane, although further investigation is needed to confirm this hypothesis.

In September 1984, the UN Secretary-General (Respondent) offered five-year fixed-term contracts as interpreters to Rong Qiu, Kefu Zhou, and Jiping Yao (Applicants), who had just completed the UN training course for interpreters at the Beijing Institute of Foreign Languages. The letters of appointment accepted by the Applicants stated that they were “on secondment from the Government of China.” They received very good performance ratings, and in the spring of 1989 their department recommended that they be offered probationary, career-track appointments when their contracts expired.

In this paper we introduce the PDCA theory into the computer communication, realize the computer cyclic block control, and get the overall arrangement network of computer sensor. In the first part we introduce the application of PDCA in computer, the second part we establish of the mathematical model of computer block cyclic control theory. In order to verify the availability of mathematical model, we designed the computer control experiment of digital sensor. After the temperature calibration of DHT11 sensor in temperature check box, the calibration data is stored in the OTP memory in the form of a program. And we use Keilu Vision2 compiler to realize the LED display of detected temperature. It provides the technical reference for the application of computer control technology.

Latar belakang peneliti membuat skripsi ini adalah ketika penulis melakukan observasi terlihat minat masyarakat yang tidak andil ke masjid untuk melaksanakan shalat dan imamnya orang-orang keitu saja dalam melaksanakan shalat sehingga imam di masjid tersebut tidak baik dalam dari segi bacaannya. Dan imam tersebut selalu ingin menjadi imam di masjid tersebut tanpa menghiraukan bacaannya. Sedangkan jama’ah nya sudah belajar tentang bagaimana menjadi imam yang baik dalam melaksanakan shalat. Sering terjadi dalam melaksanakan ibadah shalat shaf shalat perempuan dan laki-laki kurang terisi, Majelis taklim yang tidak berjalan rutin. Penelitian ini bertujuan untuk mengetahui bagaimana Bentuk Proses Pelaksanaan Kegiatan Keagamaan Di Masjid Miftahul Jannah Di Kenagarian Koto Padang Kecamatan Koto Baru Kabupaten Dharmasraya.
 Pendekatan yang digunakan dalam penelitian ini adalah pendekatan kualitatif, artinya peneliti akan melihat langsung fenomena yang terjadi di masyarakat. Daalam penelitian ini, peneliti menggunakan bentuk penelitian deskriptif kualitatif. Informan kunci dalam penelitian ini adalah pengurus masjid miftahul jannah, sedangkan informan pendukung adalah masyarakat. Peneliti menggunakan teknik wawancara dan didukung dengan dokumentasi, Data yang terkumpul kemudian dianalisis dengan menggunakan teknik analisis dekskriptif.
 Dari penelitian yang penulis lakukan dapat ditarik kesimpulan bahwa bentuk proses pelaksanaan kegiatan keagamaan di masjid miftahul jannah yaitu: Pelaksanaan shalat berjamaah, Majelis taklim,Taman pendidikan Al-Qur’an (TPA), Bimbingan Zikir, Pelaksanaan Ceramah dan Pelaksanaan Shalat Jumat.

Latar belakang peneliti membuat skripsi ini adalah ketika penulis melakukan observasi terlihat minat masyarakat yang tidak andil ke masjid untuk melaksanakan shalat dan imamnya orang-orang keitu saja dalam melaksanakan shalat sehingga imam di masjid tersebut tidak baik dalam dari segi bacaannya. Dan imam tersebut selalu ingin menjadi imam di masjid tersebut tanpa menghiraukan bacaannya. Sedangkan jama’ah nya sudah belajar tentang bagaimana menjadi imam yang baik dalam melaksanakan shalat. Sering terjadi dalam melaksanakan ibadah shalat shaf shalat perempuan dan laki-laki kurang terisi, Majelis taklim yang tidak berjalan rutin. Penelitian ini bertujuan untuk mengetahui bagaimana Bentuk Proses Pelaksanaan Kegiatan Keagamaan Di Masjid Miftahul Jannah Di Kenagarian Koto Padang Kecamatan Koto Baru Kabupaten Dharmasraya.
 Pendekatan yang digunakan dalam penelitian ini adalah pendekatan kualitatif, artinya peneliti akan melihat langsung fenomena yang terjadi di masyarakat. Daalam penelitian ini, peneliti menggunakan bentuk penelitian deskriptif kualitatif. Informan kunci dalam penelitian ini adalah pengurus masjid miftahul jannah, sedangkan informan pendukung adalah masyarakat. Peneliti menggunakan teknik wawancara dan didukung dengan dokumentasi, Data yang terkumpul kemudian dianalisis dengan menggunakan teknik analisis dekskriptif.
 Dari penelitian yang penulis lakukan dapat ditarik kesimpulan bahwa bentuk proses pelaksanaan kegiatan keagamaan di masjid miftahul jannah yaitu: Pelaksanaan shalat berjamaah, Majelis taklim,Taman pendidikan Al-Qur’an (TPA), Bimbingan Zikir, Pelaksanaan Ceramah dan Pelaksanaan Shalat Jumat.

In April of 1868, the Restoration government issued an anti-Christian proscription—‘a fixed law for all ages’ it was styled. Christianity was declared a pernicious sect; rewards were offered for information leading to the discovery of Christians. In the name of the proscription, the government carried out a persecution which, in the first four years of the new era, resulted in the deaths of as many as 500 native Christians. These men, women and children died from torture, starvation or from sickness induced by the conditions in which they were kept. The native Christians were, of course, from the recently discovered hidden Christian communities around Nagasaki. The Nagasaki Christian affair is a fascinating one to which I shall return, but I mention it at the outset since it serves usefully to stress the climate of the times as far as Christianity was concerned. Given this climate, it is remarkable that there emerged by 1871, or thereabouts, a small number of enlightened intellectuals who criticized government policy on Christianity and went so far as to advocate religious freedom. The most famous of the few were Mori Arinori, Nakamura Keiu, Fukuzawa Yukichi and Nishi Amane—names known to anyone familiar with early Meiji intellectual history. There is, however, one other name that needs to be added to this short list. That is Fukuba Bisei. The little known Fukuba Bisei was, perhaps, the most remarkable of these men since he was an early Meiji Shintoist.

Zeynuddin el-Keşşî (ö.607/1210-625/1228), klasik sonrası İslam düşüncesinin önemli isimlerinden biridir. Fahreddîn er-Râzî’nin (ö.607/1210) öğrencisidir ve ondan ders almıştır.Zeynüddin el-Keşşî'nin hayatı hakkında kaynaklarda az bilgi bulunmaktadır. Ancak eserlerinin kendi döneminde yaşayanlar ve kendisinden sonra gelenler tarafından bilindiği ve bir şöhrete sahip olduğu söylenebilir. Ölüm tarihi hakkında kesin bir bilgi bulunmamaktadır. Eserleri üzerinde yaptığımız incelemeye göre Keşşî 1210-1228 tarihleri arasında vefat etmiştir. Halid er-Ruayheb'in verdiği bilgiye göre el-Keşşî'nin 1221-1222 yıllarında Nişabur ve Herat halkının Moğollar tarafından uğradığı baskın ve katliamlar sırasında ölmüş olması muhtemeldir. Mevcut eserlerine baktığımızda el-Keşşî'nin çağdaşı müellifler gibi çok yönlü bir ilmî kişiliğe sahip olduğunu söyleyebiliriz. Çünkü o, felsefe, kelam ve mantık alanlarında eserler vermiştir. Ancak Keşşî’yi İslam düşüncesinde bilinir kılan eseri Hadâiku’l-Hakâik’tir. Mukaddime de Keşşî’nin bilinen diğer bir eseridir. Keşşî’nin Hadâiku’l-Hakâik isimli eseri; mantık, tabiat ve ilahiyat üçlemesinden oluşmaktadır. Onun bu üçlemesi İbn Sînâ’nın İşaretler ve Tembihler isimli eserinin tasnifini benimsediğini gösterir. Biz daha önce Keşşî’nin mantık, tabiat ve ilahiyat bölümlerinden oluşan Hadâiku’l-Hakâik’inin mantık bölümünü tahkik ve tercüme ederek dilimize kazandırmıştık. Daha sonraki çalışmalarımız sırasında onun el-Mûcez fi’l-Mantık isimli eseriyle karşılaştık. Onun bu eseri suret ve içerik bakımından Hadâiku’l-Hakâik ve elimizde şerhi olan Mukaddime ile uyum içindedir. Keşşî, Hadâiku'l-Hakâik'te mantık konularını tasavvur ve tasdik ikilisi üzerine inşa ederken el-Mûcez fi'l-Mantık'ta böyle bir tasnif yapmamış konuları doğrudan tasavvur ve tasdik kapsamına girecek şekilde ele almıştır. Ancak biz ilgilisine yol göstereceği ümidiyle tahkik metnine ve tercümeye ilgili başlıkları ekledik. Keşşî el-Mûcez fi’l-Mantık’ta konuları özlü olarak ele almış ve ayrıntılara girmemiştir. Bu yüzden eserin pratik bir ihtiyaca binaen yazıldığı söylenebilir. Çalışmamız iki katmanlıdır: Birincisi, ilgililerine yeni anlamların doğacağı ümidiyle eserin edisyon kritiği yapılmış ve eser dilimize tercüme edilmiştir. İkincisi, eser, tasnifi ve içeriği bakımından değerlendirilmiştir. Tespitlerimize göre eserin tek bir nüshası bulunmaktadır ve daha önce üzerine herhangi akademik bir çalışma yapılmamıştır. Keşşî, el-Mûcez fi’l-Mantık'ta modal önermelerin düz ve ters döndürülmeleri ile modal kıyasların sonuç vermeleri noktasında diğer mantıkçılardan farklı düşünmektedir. Onun bu farklı görüşleri kendisinden sonraki önde gelen müelliflerin çoğu tarafından eleştirilmiştir. Mesela Hunecî (ö.646/1248) Keşfu’l-Esrâr’da, Ebherî (ö.663/1265) Keşfu’l-Hakâik fi Tahrîri’d-Dekâik’te, Urmevî (ö.682/1283) Metâliu’l-Envar’da, Kutbuddîn er-Râzî (ö.767/1365) Levâmiu’l- Esrar fi Şerhi Metâliu’l- Envar’da, Kâtibî (ö.675/1277) Şerhu Keşfi’l-Esrâr’da, Semerkandî (ö.722/1322) Kıstasu’l-Efkâr ve Şerhu Kıstasu’l-Efkâr’da isim vererek Keşşî’ye atıfta bulunmuştur.

Background:Although, most lupus nephritis patients present with chronic glomerulonephritis or nephrotic syndrome, some patients develop rapidly progressive glomerulonephritis (RPGN), which is a clinical syndrome characterized by rapid loss of renal function over a short period of time (days to months). Multitarget therapy using tacrolimus and mycophenolate mofetil (MMF) has been reported to be effective as induction therapy of Class III to Class V lupus nephritis1. However, its efficacy on lupus nephritis presented with RPGN has not been well reported.Objectives:We aimed to examine the efficacy of multitarget therapy on lupus nephritis presented with RPGN.Methods:We retrospectively analyzed patients with biopsy-proven lupus nephritis, who clinically showed RPGN, and were treated by multitarget therapy with tacrolimus and MMF in our department. Data were expressed as mean±SD.Results:Five lupus nephritis patients (3 female) with RPGN were treated by multitarget therapy as induction therapy. Mean age was 36.6±13.5 years old. Renal biopsy at treatment revealed Class IV(A) in 2, Class IV(A+C) in 1 and Class IV(A)+V in 2. The percentage of glomerular crescents was 23.1±25.4%. eGFR and proteinuria at the initiation of treatment were 46.8±11.5 mL/min/1.73m2and 7.7±3.4 g/gCr, respectively. Patients were initially treated with methylprednisolone pulse therapy followed by 0.8-1.0 mg/kg of prednisolone (PSL), 2-3 mg/day of tacrolimus and 1000 mg/day of MMF. At 6 months, eGFR and proteinuria improved to 72.9±11.3 mL/min/1.73m2and 0.19±0.13 g/gCr, respectively. At 12 months, eGFR and proteinuria further improved to 76.8±7.8 mL/min/1.73m2and 0.10±0.07 g/gCr, respectively and the dose of PSL was reduced to 6.6±1.5 mg/day. Three patients became positive for cytomegalovirus antigenemia and were successfully treated with antiviral therapy.Conclusion:Multitarget therapy is effective in lupus nephritis even in patients presented with RPGN.References:[1]Liu Z, Zhang H, Liu Z,et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial.Ann Int Med2015; 162: 18-26.Disclosure of Interests:Yoichi Imai: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Junya Suwa: None declared, Yuko Ohishi: None declared, Mitsuharu Watanabe: None declared, Masao Nakasatomi: None declared, Hiroko Hamatani: None declared, Toru Sakairi: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc. b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.

Regarding the character of the Korean Civil Code, the author argued in 1985 that in some aspects, it was “a legislative embodiment created to overcome the dual structure caused by the “theory receptions(=gakusetsu keiju) from Germany,” that is, the systematic contradiction between the Civil Code and the academia(theory as well as praxis) of Civil Law.” This argument was met with prolonged and severe criticism from Professor Yang Chang-soo during an academic conference in 1990. I have been silent for a long time after answering his criticisms on the spot, item by item. This is because I believed that “truth proves itself.” However, Yang Chang-soo repeated the same criticisms without having responded to my counter arguments to his criticisms, he repeated the same criticism three decades later. He pointed out the following: 1. “I(=Yang) feel saddened that such a series of research on the codification process and background of the Korean Civil Code was first published in Japanese, not Korean.” I am moved by the critic’s patriotism. However, must such research necessarily be published in Korean first? 2. “Your thesis shows a weak sense of the awareness regarding the liquidation of colonialism.” I cannot help but accept his harsh criticism. 3. Yang presents the following specific arguments to support his criticism: ① Parts that cannot be explained by the solution of the dual structure, ② Change in real right ③ Co-ownership, ④ Right to a lease on a deposit basis, ⑤ Effects of the completion of extinctive prescription, ⑥ Three mandatory provisions in consumer loan contracts, ⑦ Prior Refusal of performance and rescission, ⑧ Culpa in contrahendo, ⑨ Swiss legal elements in the Korean Civil Code, etc. 4. I believe I have refuted the above arguments quite sufficiently. Ultimately, might it not be that Yang’s various criticisms are actually weakly based? There has always been a certain resentment toward Japanese culture in Korean culture. Nevertheless, the exchange of academia as well as praxis on (civil) law between Korea and Japan is not only necessary, but its expansion will bring about more valuable synergy effects than the exchange between any other areas. This does not stop at simply exploring the establishment and historical development of current Korean law and comparing its contents. The value of the exchange of (civil) law academia between Korea and Japan lies rather in its’ near future.

BackgroundRecent studies showed the efficacy of multitarget therapy with mycophenolate mofetil (MMF) and calcineurin inhibitor for induction therapy for lupus nephritis (LN)1. However, long-term outcomes have not been well elucidated.ObjectivesWe retrospectively analyzed the long-term outcomes of multitarget therapy of MMF and tacrolimus.MethodsWe examined 27 LN patients (4 male, 23 female) treated with multitarget therapy for induction therapy between Oct. 2009 and Nov. 2018 in our department. Complete remission (CR) was defined as 1) UPCR<0.5 g/gCr, and 2) serum creatinine (S-Cr) normal or if abnormal, within 15% of baseline; 1) and 2) were observed in 2 consecutive visits. Relapse was defined as UPCR>1.0 g/gCr or intensification of immunosuppressive treatment after achievement of CR.ResultsThe mean age was 38.6±11．6 years old. 17 patients were new-onset LN, and 10 patients were relapse LN. UPCR and eGFR before treatment were 4.42±2.98 g/gCr and 71.5±32.9 mL/min/1.73m2, respectively. Renal histology was Class III in 1, III+V in ４, IV in 12. IV+V in 9 and V in 1 by ISN/RPS 2003 classification. CR at 6 and 12 months were 59% and 74%, respectively. Patients were treated by multitarget therapy for median of 25 months (IQR, 5.5-37). Finally, 26 (96%) patients achieved CR. During multitarget therapy, there were 15 serious adverse events: deep vein thrombosis in 2, myocardial infarctions in 2, cervical intraepithelial neoplasia in 2, heart failure in 1, herpes zoster in 1, viral myocarditis in 1, cytomegalovirus gastroenteritis in 1, cholecystitis in 1, pyelonephritis in 1, bacterial enteritis in 1, sepsis in 1, and breast cancer in 1. During the median observation period of 94 months (IQR, 63-111.5) after the initiation of multitarget therapy, 1 patient died due to sudden death. No patient reached end-stage kidney disease or doubling S-Cr. 16 patients relapsed at median of 32 months (IQR,13.8-64.5) after CR; 8 patients relapsed on multitarget therapy, and 8 patients relapsed after cessation of multitarget therapy. Relapse was associated with chronic lesions in renal biopsy and normal or higher C4 levels at treatment initiation by Kaplan Meier analysis (Log-rank, P=0.006, P<0.001, respectively).ConclusionMultitarget therapy effectively induced CR and maintained renal function in long-term period. However, relapse was often observed during or after withdrawal of multitarget therapy.References[1]Liu Z, Zhang H, Liu Z, et al. Multitarget therapy for induction treatment of lupus nephritis: a randomized trial. Ann Int Med 2015; 162: 18-26.Disclosure of InterestsYoichi Imai: None declared, Hidekazu Ikeuchi: None declared, Junya Suwa: None declared, Yuko Ohishi: None declared, Mitsuharu Watanabe: None declared, Masao Nakasatomi: None declared, Hiroko Hamatani: None declared, Toru Sakairi: None declared, Yoriaki Kaneko: None declared, Keiju Hiromura Speakers bureau: Chugai, Astellas., Grant/research support from: Chugai, Astellas.

Abstract Background: Neoadjuvant treatments with novel combination immunotherapies for resectable non-small cell lung cancer (NSCLC) are being developed. Combination therapy with antiangiogenic agents and anti-PD-1/PD-L1 antibody has shown enhanced antitumor effects. EAST ENERGY is a single-arm multicenter phase 2 trial of neoadjuvant pembrolizumab and ramucirumab in patients with PD-L1-positive stage IB-IIIA NSCLC (NCT04040361). In this study, we aimed to identify biomarkers that predicts the efficacy of the neoadjuvant therapy. Furthermore, we aimed to elucidate the effect of the neoadjuvant therapy on the tumor microenvironment (TME). Methods: Patients enrolled in the EAST ENERGY trial (n=24) for whom pre- and post-treatment specimens were available (n=20) were included in this study. RNA-sequencing and multiplex immunohistochemistry (mIHC) were used to examine the association between the immunological phenotype of the TME and major pathological response (MPR), and changes in the TME before and after treatment. Results: MPR was achieved in 50.0% (12/24) of patients. Biomarker analyses with RNA-sequencing revealed that high expression of cancer-associated genes, and upregulation of interferon-gamma and interferon-alpha response in pre-treatment tumor were associated with MPR (q value<0.001). mIHC in pre-treatment samples revealed that abundance of CD8+ T cells in the pre-treatment TME was associated with MPR (p=0.039). On the other hand, infiltration of immunosuppressive cells such as Treg or M2-macrophages were not associated with resistance for the treatment (p=0.836, 0.639, respectively). Next, to clarify the effect of the neoadjuvant therapy on the TME, comparative analyses of pre- and post-treatment samples was performed. In gene set enrichment analysis, the neoadjuvant therapy enhanced gene set associated with interferon-gamma response (q value=0.051). Furthermore, angiogenesis-related gene set were downregulated after the treatment (q value=0.090). mIHC analyses revealed that the number of CD8+ T cells in the TME was significantly increased after the neoadjuvant therapy (p<0.001). Notably, Tregs/CD8+ T cells ratio and the number of M2-macrophage in the TME were significantly decreased after the neoadjuvant therapy (p=0.032, 0.003, respectively). Conclusion: In the neoadjuvant therapy with pembrolizumab and ramucirumab, immune-activated status before treatment serves as a potential biomarker for predicting treatment response. Moreover, combining ramucirumab with pembrolizumab reduced immunosuppressive cells in the TME and inhibited tumor angiogenesis. These results suggest that this combination therapy modifies the TME and augments antitumor immunity. Larger clinical trial is warranted to assess the efficacy of neoadjuvant therapy with ramucirumab and pembrolizumab in patients with PD-L1-positive NSCLC. Citation Format: Kotaro Nomura, Shogo Kumagai, Shohei Koyama, Keiju Aokage, Yoshihisa Shimada, Kiyotaka Yoh, Masashi Wakabayashi, Miki Fukutani, Hideki Furuya, Tomohiro Miyoshi, Kenta Tane, Joji Samejima, Tetsuro Taki, Takuo Hayashi, Jun Matsubayashi, Genichiro Ishii, Norihiko Ikeda, Hiroyoshi Nishikawa, Masahiro Tsuboi. Biomarker analysis of pembrolizumab and ramucirumab neoadjuvant therapy for PD-L1-positive stage IB-IIIA lung cancer: EAST ENERGY trial [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 1211.

Background:Dendritic cells (DCs) play important roles in inducing immune response as well as maintaining immune tolerance. Src homology 2 domain-containing protein tyrosine phosphatase-1 (Shp1) is a negative regulator of signaling in hematopoietic cells and is expressed in a variety of immune cells including DCs. Shp1 homozygous mutant mice (motheaten mice) develop multiple immunological abnormalities and they die around four weeks after birth because of severe pneumonitis. Motheaten mice produce large amounts of autoantibodies, and besides, B-1a cells, a distinct B cell subset, which are an important source of autoantibodies increase in these mice. The functional abnormality of DCs in motheaten mice has not been characterized, but DCs and macrophages increase in various organs of motheaten mice.To analyze the function of Shp1 in DCs, we generated Shp1 conditional knockout mice (Shp1 CKO) in whichShp1gene is specifically depleted in CD11c+cells. We found that aged shp1 CKO developed autoimmune glomerulonephritis. We also found that they developed severe tubulointerstitial nephritis (TIN) at the age of 40 weeks, which is characterized by the infiltration of CD11c+and F4/80+cells. CD4+T cells from Shp1 CKO produce much more amount of IFNγ. Collectively, Shp1 in DCs acts as a key regulatory molecule to protect against autoimmunity.Objectives:We analyzed salivary glands of CKO to confirm whether they have autoimmune sialadenitis because TIN is known to be the most common renal manifestations of Sjögren’s syndrome in human.Methods:Shp1 CKO are generated by crossing a mouse line carrying floxedShp1allele to mice expressing Cre recombinase under the control of the CD11c promoter. Sex- and age-matchedPtpn6fl/fllittermates withoutCregene were studied as controls. We analyzed secretory function of the salivary glands in response to pilocarpine stimulation in Shp1 CKO at the age of 40 weeks or older. We then performed histological examination of salivary glands (submandibular glands and sublingual glands) with light-microscopy and immunohistochemical staining. The mononuclear cells prepared from the salivary glands were analyzed by flow cytometry (FCM). We also quantified anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies by ELISA.Results:Shp1 CKO secreted less saliva flow compared to control mice by pilocarpine stimulation. Histological study showed Shp1 CKO exhibited massive infiltration of inflammatory cells in salivary glands associated with periductal foci and periductal fibrosis. Most of infiltrated cells were stained by anti- CD4 or B220 mAbs. FCM revealed that B cells increased in the salivary glands of Shp1 CKO. In addition, B-1a cells also increased in the salivary glands of the mice. The levels of anti-SSA/Ro60 antibodies and anti-SSB/LA antibodies were increased in Shp1 CKO.Conclusion:CD11c-specific ablation of Shp1 induces the ectopic generation of lymphoid structure in salivary glands and impairment of salivary secretion. Autoantibody profile in Shp1 CKO resembled that in human Sjögren’s syndrome. Our findings suggest that aged Shp1 CKO have the potential to become a new mouse model for the analysis of Sjögren’s syndrome.References:[1]Green C. M. et al. J Heredity. 1975; 250-258.[2]Kaneko T. et al. J Immunology. 2012; 5397-540.[3]Watanabe M. et al. Biochem Biophys Rep. in press.Disclosure of Interests:Masato Kinoshita: None declared, Yoriaki Kaneko Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.b, Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Mitsuharu Watanabe: None declared, Yoichi Imai: None declared, Shreya Shrestha: None declared, Junya Suwa: None declared, Yuko Ohishi: None declared, Hiroko Hamatani: None declared, Masao Nakasatomi: None declared, Toru Sakairi: None declared, Hidekazu Ikeuchi Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Yoshihisa Nojima: None declared, Keiju Hiromura Grant/research support from: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc., Speakers bureau: CHUGAI PHARMACEUTICAL CO., LTD.Astellas Pharma Inc.

Abstract TXB-001 is a well-optimized N-(2-hydroxypropyl)methacrylamide copolymer-based conjugated pirarubicin (THP) and a novel candidate for developing anticancer drugs. It exhibits tumor-specific accumulation due to the enhanced permeability and retention effects and prolonged circulation time compared with free THP. Its hydrazone bond is dissociated under lower pH conditions, providing selective and rapid release of THP in acidic tumor environments. Therefore, TXB-001 is expected to have high efficacy and low toxicity. Anthracycline anticancer drugs have been widely used for the treatment of several cancers, but their use is limited by several adverse effects (AEs), including cardiotoxicity, which is a life-threatening AE. Furthermore, the maximum lifetime cumulative dose is decided for each anthracycline in clinical use, which leads to discontinuation of the medication. Hand-foot syndrome (HFS) is a dose-limiting AE of DOXIL®, a liposomal formulation of doxorubicin (DOX), and although it is not a life-threatening condition, it significantly deteriorates quality of life (QOL). Alopecia is another common AE, which is relatively noninvasive but adversely affects mental health and reduces QOL. In this study, we confirmed the efficacy of TXB-001 in a mice triple-negative breast cancer (TNBC) model and evaluated the cardiotoxicity-, HFS- and alopecia-inducing effects of TXB-001 in mice and rats to compare the severity with existing anthracycline anticancer drugs, including DOXIL®. The pharmacokinetic (PK) analysis in several tissues, including plasma, tumor, heart, skin of the chest, and palmar and plantar areas, was also performed after a single intravenous administration in rodents. As a result, TXB-001 showed an equivalent or greater antitumor effects than other anthracyclines in the TNBC model, and the AEs were scarcely observed. TXB-001 did not decrease left ventricular ejection fraction, with no or little HFS-like changes compared with DOXIL®, which showed significant histopathological changes. TXB-001 also showed weaker alopecia-inducing effects than DOX, DOXIL®, and THP. In the PK analysis, TXB-001 was distributed in the tumor at a higher concentration than in other tissues, except for plasma. Hence, most of the THP, the active ingredient, was released in the tumor. The exposure of the heart in the TXB-001-treated group was one-tenth of that in the DOXIL®-treated group. Moreover, accumulation in the skin, especially in palmar and plantar areas, was observed for DOXIL®, but no accumulation in the skin was observed for TXB-001. This PK profile consistently demonstrated the antitumor activity of TXB-001, without AEs. TXB-001 reduces the chance of dose-limiting and QOL-threatening AEs, and thus, cancer patients can continue treatment, making it a more convenient anticancer drug in clinical use with a wide safety margin. Citation Format: Keiyu Oshida, Mikito Hirakata, Emi Tomikawa, Chizuka Sakai, Masashi Uchida, Rieko Shimozono, Akiko Izawa, Yoko Koga, Tsubasa Okano, Hideki Narumi, Lisa Munakata, Ryo Suzuki, Miki Nonaka, Yasuhito Uezono. TXB-001 is an upgraded conjugated anthracycline that targets tumors with reduced risk of cardiotoxicity, hand-foot syndrome and alopecia [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 679.

Abstract Background:In 2015, the International Myeloma Working Group (IMWG) developed the Revised International Staging System (R-ISS), which combined the ISS with the status of high-risk cytogenetic abnormalities (CAs) and serum levels of lactate dehydrogenase to identify three multiple myeloma (MM) entities with clearly different outcomes. However, although MM tends to affect older adults, the original and validation studies of the R-ISS included relatively younger patients. Furthermore, although studies report that bortezomib-containing therapies can reverse the unfavorable prognostic impact of the t(4;14) CA,most original and validation studies of the R-ISS included few patients who had been treated with bortezomib. Therefore, the results of these studies are less applicable to patients in the era of novel targeted agents. Methods: This study retrospectively analyzed the data of 400 consecutive patients who were newly diagnosed with MM and treated with chemotherapy between January 2006 and December 2017 at Kameda Medical Center, Kamogowa-shi, Japan; Keiju Kanazawa Hospital, Ishikawa, Japan and National Hospital Organization Okayama Medical Center, Okayama, Japan. We included only patients who had been treated with novel agents (e.g., immunomodulatory agents or proteasome inhibitors) to reduce the prognostic impact of heterogeneity in chemotherapy. Results: The 400 included patients had a median age of 72 years (interquartile range [IQR]: 64-79 years). The median observation period was 37.9 months (IQR: 16.4-67.9 months). Ninety-eight (24.5%), 121 (30.2%) and 181 (45.2%) patients were classified as ISS stages I, II, and III, respectively, while 66 (16.5%), 243 (60.8%), and 91 (22.8%) patients were classified as R-ISS stages I, II, and III, respectively. Additionally, 384 (96.0%) patients were treated with bortezomib. R-ISS stages II and III differed significantly in terms of age, with the former including significantly older patients than the latter (median age: 74 and 70 years, respectively; P=0.001). The Kaplan-Meier overall survival (OS) curves according to the ISS and R-ISS stages are shown in Figure 1A and 1B, respectively. The three groups of patients categorized by ISS stage differed significantly in terms of survival duration. By contrast, no significant differences in OS were observed between R-ISS stages II and III (median OS: 63.4 and 54.7 months, respectively; P=0.32).Furthermore, receiver operating characteristic (ROC) curves were developed tocompare the prognostic performances of the ISS and R-ISS. Notably, the area under curve (AUC) was significantly greater for the ISS than for the R-ISS (0.659 vs. 0.608, respectively; P=0.029, Figure 2A). ISS stage III patients recategorized to R-ISS stage III were significantly younger than those recategorized to R-ISS stage II (median age, 70 vs. 77 years; P<0.001) and had a relatively more favorable OS (Figure 3). Patients with high-risk cytogenetic abnormality t(4;14) were significantly younger than the others and also had an improved OS (Figure 4), which was attributed to young age and bortezomib therapy.We again divided the patients into three groups using a modified R-ISS (mR-ISS) categorization in which only t(14;16) and del(17p) were included as high-risk CAs.The three groups categorized by mR-ISS stage exhibited significant differences in survival (Figure 1C).We additionally developed a ROC curve for the mR-ISS, and the resulting AUC value was significantly greater than that obtained for the R-ISS (0.657 vs. 0.608, respectively; P=0.001, Figure 2B). Conclusions: Our study is the first to suggest that the performance of the R-ISS may be somewhat limited when applied to patients with MM who are treated with novel agents in ageing societies. Furthermore, we suggest that this limitation may be attributed to the inclusion of t(4;14) as a high-risk CA in the R-ISS categorization strategy. This potential limitation suggests that the R-ISS should be carefully interpreted on an individual basis when applied to patients in a real-world setting. Our findings are of particular interest because many developed countries, including Western countries, are approaching a period of super-ageing such as that observed currently in Japan. Disclosures Sunami: Celgene: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Merck Sharp and Dohme: Research Funding; Takeda: Research Funding; AbbVie: Research Funding; Sanofi: Research Funding. Takamatsu:Janssen: Honoraria; Bristol-Myers Squibb: Research Funding; Ono: Research Funding; Celgene: Honoraria, Research Funding.

Original Research Paper FUNCTIONAL OUTCOME OF BIPOLAR HEMIARTHROPLASTY IN DISPLACED INTRACAPSULAR FEMORAL NECK FRACTURE IN ELDERLY IN RURAL TERTIARY HOSPITAL <strong>Authors:</strong> <strong>¹</strong><strong>Dr. Saikrishna Rengerla</strong><strong>, </strong><strong>²</strong><strong>Dr. Akhil Lohkare, ³Dr. CM Badole</strong> <em>^1,2</em><em>Senior Resident, Dept of Orthopaedics, MGIMS Sevagram</em> <em>³</em><em>Director-Professor &amp; HOD, Dept of Orthopaedics, MGIMS Sevagram</em> Corresponding Author: Dr. Saikrishna Rengerla, Dept of Orthopaedics, MGIMS Sevagram <strong>Article Received:</strong>&nbsp; 10-08-2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <strong>Revised:</strong>&nbsp; 31-08-2022&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; <strong>Accepted:</strong> 21-09-2022 <strong>ABSTRACT: </strong> Femoral neck fractures, one of the most common injuries in the elderly have always presented great challenges to orthopaedic surgeons. The present study was conducted in 42 elderly patients with closed displaced intracapsular fracture of femoral neck following all inclusion and exclusion criteria who were present to the Orthopaedics department from October 2019-May 2021 to evaluate functional outcome of bipolar hemiarthroplasty in displaced intracapsular femoral neck fracture in elderly who were followed for duration of 6 months at an interval of 6 weeks, 3 months and 6 months. Most of the patients were belonging to 65-69 years of age group accounting to 33.33%. Females outnumbered males accounting to 59.52% with female to male ratio of 1.47:1. Transcervical fractures outnumbered and accounted for 90.48%. There were more left sided fractures accounting for 71.43%. Most of the patients were operated within 7 days of fracture accounting for 45.24% with average hospital stay of 14.71&plusmn;4.79 days. Most common mode of injury was trivial trauma i.e.92.86%. 41mm Bipolar prosthesis size accounted for maximum of 28.6%. Harris Hip Score was used to evaluate the functional outcome of Bipolar Hemiarthroplasty was noted at regular follow ups. &nbsp;Mean Harris Hip score at 6 weeks was 74.21&plusmn;10.07, at 3 months was 77.66&plusmn;10.59, at 6 months was 80.40&plusmn;10.60 with upward trend in the mean score over follow up period. There was 2.38% cases of posterior dislocation noted at 1 month in Uncemented Bipolar Hemiathroplasty postoperatively, 4.76% cases of infection and 7.14% cases of lengthening, 7.14% cases of Bedsores. The final functional outcome at 6 months of follow up revealed excellent results in 13 patients(30.95%), Good in 11 patients(26.19), Fair in 12 patients(28.57%) and Poor results in 6 patients(14.29%). Our study concludes that Bipolar Hemiarthroplasty offers excellent, painless mobility and ease in rehabilitation and return to function. <strong><em>Key words: Bipolar hemiarthroplasty, Elderly patients, Harris hip score, Intracapsular femoral neck fracture, Complications, Functional Outcome.</em></strong> &nbsp; &nbsp; <strong>INTRODUCTION:</strong> Femoral neck fractures, one of the most common injuries in the elderly have always presented great challenges to orthopaedic surgeons. The prevalence of these fractures has increased with improvement in life expectancy, increased incidence of osteoporosis, poor vision, neuro-muscular incoordination and changes in lifestyle leading to sedentary habits⁽¹⁾. In the elderly with osteoporotic bones, a trivial fall is the cause of hip fractures in about 90% of cases⁽²⁾. The prevalence of the fracture also doubles for each decade of life after fifth decade⁽³⁾. Treatment of displaced femoral neck fractures in elderly has been controversial. Open reduction and internal fixation of these fractures in the elderly have poor outcome including high rate of nonunion and avascular necrosis⁽¹⁾. Various prosthesis have been designed which can be broadly divided into two types- unipolar and bipolar. Of unipolar prosthesis, the most commonly used are the THOMPSONS and AUSTIN MOORES prosthesis. Main problems with these prosthesis were stem loosening and migration⁽⁴⁾. In modern days the bipolar prosthesis with cement is the best option wherein they can be more active⁽⁵⁾. PMMA cement offers advantages as its use as a grouting agent to replace thinning trabecular bone thus greatly simplifying rehabilitation. The Bipolar prosthesis was introduced to prevent and retard acetabular wear. These prosthesis have a 22 to 32mm head that articulates with ultra-high-density polyethylene inner liner which is covered with a polished metal outer head that articulates with acetabular cartilage. It causes less articular wear⁽⁴⁾. Advantages of uncemented femoral components is including faster implantation and potential lower risk of fat and marrow embolism compared to cemented implants. Disadvantages of uncemented implants in elderly are potential for retarded osteointegration, osteopenia and concern for fracture and in patients with wide femoral canal has mismatch of proximal/distal diameters^(6,7,8). There was no significant difference in using cemented and uncemented bipolar prosthesis⁽⁹⁾. The aim of the study is to evaluate the functional outcome of Bipolar hemiarthroplasty in closed displaced intracapsular femoral neck fracture in elderly. <strong>METHODOLOGY: </strong> This was a follow up study and conducted in 42 elderly patients with closed displaced intracapsular fracture of femoral neck reported to the Orthopaedics Department of MGIMS and Kasturba hospital following all inclusion and exclusion criteria from October 2019-May 2021. Inclusion criteria was patients of age 60 years and above, nonunited/old fracture neck of femur. Exclusion criteria was pathological fractures of neck of femur, medically unfit for surgery, Bilateral fracture neck femur, Previously operated fracture neck femur of same and opposite side, Non ambulators, those who would not complete 6 months of final follow up. Informed consent was taken at the initiation of study, in English and in regional language, after explaining the procedure in detail. Preoperative Protocol consisted of thorough history taking and clinical examination and evaluation was done and then Anteroposterior radiographs of pelvis with both hip. All study Patients were put on skin traction, given oral or parenteral analgesics to relieve pain. Adequate medical management of associated comorbid conditions like diabetes mellitus, systemic hypertension, COPD and heart diseases was initialized to optimize patient&rsquo;s fitness for anaesthesia. All measures were taken so that the patient could be taken up for surgery at the earliest. Operative Approach was Moore&rsquo;s posterior approach for all patients in Lateral decubitus position on the operating table with the affected side facing up. A curved incision taken from a point 10cm distal to posterior superior iliac spine and extended distally and laterally parallel to the fibres of gluteus maximus to the posterior margin of greater trochanter. Deep fascia was exposed over gluteus maximus, was then split in the direction of its fibres by blunt dissection. By retracting the proximal fibres of the muscle proximally, the greater trochanter was exposed after trochanteric bursa excised. Distal fibres were retracted distally and divided at their insertion over linea aspera. The sciatic nerve was not usually exposed . It was protected with the finger in the lateral part of the incision and gently retracted out of the way. The gemelli and obturator internus and piriformis tendon were divided at their insertions after tagging them for easier identification and reattachment. The posterior part of the capsule thus exposed was incised from distal to proximal along the line of neck of femur and at right angle to it, thus making a L shaped opening in the capsule. The fractured head and neck of the femur were levered out of the acetabulum and size measured using femoral head gauge. The size was confirmed using trial prosthesis by its suction fit in the acetabulum. The acetabulum was prepared by excising remnants of ligamentum teres and soft tissue. The femoral shaft was rasped using a broach(rasp) and prepared for the insertion of the prosthesis. Femoral neck if long was nibbled keeping 2 to 2.5cm of calcar above the lesser trochanter. The appropriate sized prosthesis was then inserted into the femoral shaft(reamed canal) in taking care to place in 10⁰ to 15⁰ of anteversion and impacted into the femur. The reduction of prosthesis done using gentle traction of the thigh. If Prosthesis became loose intraoperatively, cemented procedure were performed. In these cases, the stem was cemented in place using standard cementing technique- lavage, cleaning, drying and plugging of the canal. Absolute haemostasis obtained. After suturing the capsule, the external rotators sutured. The wound closed in layers over a suction drain, were removed at the first changing of dressing after 48hours. Post operatively, patients were kept in the ward with limbs in wide abduction with the help of abduction pillow. Adduction, internal rotation and flexion were avoided. Static exercise in bed for quadriceps and breathing exercises along with active limb movement to decrease limb edema. Ambulation started within a week with walker and progressive weight bearing. Postoperatively DVT prophylaxis was added to high risk patients according to the advice given by Physician/Anaesthetist. Patients were advised not to sit cross legged or squat. All patients were followed up monthly for first 3 months and then at 6 months. Minimum follow up of 6 months and HARRIS HIP SCORE⁽¹⁰⁾was noted and radiographs of the affected hip were taken. Final evaluation of the study was done after completion of study according to criteria. <strong>RESULTS:</strong> 42 study participants fulfilling inclusion and exclusion criteria were selected and evaluated for associated comorbidities and operated by Bipolar Hemiarthroplasty and&nbsp; followed for duration of 6 months at an interval of 6 weeks, 3 months and 6 months during the study period. <strong>Age distribution:</strong> majority of the patients were belonging to 65-69 years of age group accounting to 33.33%, followed by 60-64 years of age group accounting 26.19%, followed by 70-74 years of age group accounting 21.43%, followed by 75-79 years of age group and 80-84 years of age group accounting 7.14% each and followed by &gt;84 years of age group accounting 4.76%. Mean age in general was 68.66 &plusmn; 7.03 with range of 60-85 years. <strong>Gender:</strong> In the present study, females outnumbered males accounting to 25(59.52%) and males proportion was 17(40.48%). Female to male ratio in our study was 1.47:1 <strong>Fracture side distribution:</strong> There were more left sided fractures accounting for 30 cases (71.43%) Garden classification: Patients with Type 4 of Garden classification accounted for maximum of 83.33%, followed by Type 3 for 9.52% and Type 2 for 7.14%. <strong>Anatomical Classification:</strong> Patients with Transcervical fractures outnumbered and accounted for 90.48%, followed by Subcapital fracture for 7.14% and followed by Basicervical for 2.38% <strong>Distribution of patients according to duration between fracture and surgery:</strong> Duration(days) No of patients Percentage &lt;7 days 19 45.24 7-30 days 18 42.86 &gt;30 days 5 11.90 Total 42 100 Mean&plusmn;SD 13.11 &plusmn; 16.20(2-95 days) <strong>Table 1</strong> <strong>Duration between admission and surgery: </strong>In our study, majority of the patients operated within 3-7 days of admission i.e. 26(61.90%) followed by more than 7days i.e. 9(21.43%) and within 3 days in only 7 patients i.e.16.67% <strong>Mode of injury: </strong>In our study most of the patients had trivial trauma which accounted for 39 cases (92.86%) followed by road traffic accident of 3 cases(7.14%) <strong>Distribution of patients according to comorbidities</strong> Comorbidities No of patients Percentage Asthma 4 9.52 Diabetes Mellitus 8 19.05 Chronic Kidney Disease 3 7.14 Hypertension 16 38.10 &nbsp;Rheumatoid Arthritis 1 2.38 Thyroid Disease 1 2.38 Ischemic heart disease 1 2.38 Lung consolidation 1 2.38 <strong>Table 2</strong> <strong>Average hospital stay:</strong> was 14.71&plusmn;4.79 days with maximum of 28 days and minimum of 4 days. <strong>Prosthesis Size:</strong> 41mm Bipolar prosthesis accounted for maximum of 28.6% in 12 cases and least used was 53mm Bipolar prosthesis in 1 case (2.4%) &nbsp; Frequency Percent P R O S T H E S I S 37 mm 2 4.8 39 mm 3 7.1 41 mm 12 28.6 43 mm 7 16.7 45 mm 5 11.9 47 mm 4 9.5 49 mm 6 14.3 51 mm 2 4.8 53 mm 1 2.4 Total 42 100.0 <strong>Table 3</strong> &nbsp; &nbsp; &nbsp; <strong>Position of stem:</strong> Position of stem No of patients Percentage Valgus 5 11.90 Varus 6 14.29 Neutral 31 73.81 Total 42 100 <strong>Table 4</strong> <strong>Intraoperative time and blood loss: </strong>average blood loss was 326.66 &plusmn; 109.18ml with range of 150-750ml and average intraoperative time was 63.45 &plusmn; 11.64 min with range of 45-90 min. <strong>Harris Hip Score: </strong>used to evaluate the functional outcome of Bipolar Hemiarthroplasty which was noted at regular follow ups at 6 weeks, 3 months and 6 months. The Mean Harris Hip score at 6 weeks was 74.21&plusmn;10.07 with range of 47-87. The Mean Harris Hip score at 3 months was 77.66&plusmn;10.59 with range of 50-90. The Mean Harris Hip score at 6 months was 80.40&plusmn;10.60 with range of 52-90. There was an upward trend in the mean score over follow up period. &nbsp; N Minimum Maximum Mean Std. Deviation 6 weeks 42 47.00 87.00 74.21 10.07 3 months 42 50.00 90.00 77.66 10.59 6 months 42 52.00 92.00 80.40 10.60 <strong>Table 5</strong> Graph 1: Distribution of patients according to Harris Hip Score &nbsp; &nbsp; <strong>Distribution of patients according to complications:</strong> Complications No of patients Percentage Dislocation 1 2.38 Infection 2 4.76 Lengthening 3 7.14 Other(Bed Sore) 3 7.14 <strong>Table 6</strong> &nbsp; <strong>Functional outcome: </strong>In our study, the final functional outcome at 6 months of follow up using Harris Hip Score. We observed excellent results in 13 patients(30.95%), Good in 11 patients(26.19), Fair in 12 patients(28.57%) and Poor results in 6 cases(14.29%). &nbsp; &nbsp; <strong>Distribution of patients according to functional outcome at final follow up(6 months)</strong> Functional Outcome No of patients Percentage Poor 6 14.29 Fair 12 28.57 Good 11 26.19 Excellent 13 30.95 Total 42 100 <strong>Table: 7</strong> <strong>DISCUSSION:</strong> Elderly patients with fracture neck of femur who were mobile before injury should be able to restore to their preoperative functional and ambulatory status. In active older patients especially needing early mobilization, conservative method of treatment is not acceptable because it results in non union with unstable hip and limitation of hip movement as well as complications of prolonged immobilization like bedsores, deep vein thrombosis and respiratory infections. Result for femoral neck fracture treatment illustrated by Leighton et al⁽¹¹⁾recommended prosthetic replacement for patients more than 60 years old having femur neck fracture. Bateman and Giliberty in 1974 introduced Bipolar hemiarthroplasty, which is a self articulating prosthesis. Advantage of Bipolar prosthesis is that erosion and protrusion of acetabulum would be less because, there is dual articulation between inner head and shell and acetabulum⁽¹²⁾. The Aim of present study was to evaluate the functional outcome of Bipolar Hemiarthroplasty in displaced intracapsular femoral neck fracture in elderly. 42 patients of fracture neck femur were treated using Bipolar Hemiarthroplasty, both cemented and uncemented. A concept that has been generally held by Orthopaedic surgeons is that Cemented femoral fixation is required in elderly patients because of poor bone stock⁽¹³⁾. However, cemented technique has also been associated with greater risk of fat embolization and hypotension⁽¹³⁾. Many Orthopaedic surgeons feel that stable femoral fixation can be achieved in elderly patients with cementless femoral stem⁽¹⁴⁾. The complications following the Bipolar Hemiarthroplasty is reported in varying incidences. Early surgical complications after Bipolar Hemiarthroplasty may be the origin of cascades leading to general complications and increased mortality. That is why their prevention is very important⁽¹⁵⁾. In present study, there was 1(2.38%) case of posterior dislocation noted in <em>(CASE 1)</em> 76 years old female with multiple co morbidities like right lower lung consolidation, Diabetes Mellitus, Hypertension, Chronic Kidney Disease, Asthma admitted on the same day of trauma with transcervical neck femur fracture of left side due to trivial trauma operated with Uncemented Bipolar Hemiathroplasty and postoperatively at 1 month there was posterior dislocation occurred due to sudden adduction of hip, which was managed by revision Cemented Bipolar Hemiarthroplasty immediately and later after 12 weeks she developed deep infection in wound which was managed by debridement which eventually healed with final Harris Hip Score of 72 at 6 months of follow up. In our study all cases were operated by posterior approaches. Dislocation of the Hip Hemiarthroplasty have been a concern for Orthopaedic surgeons since the advent of the procedure. Furthermore, early dislocation is associated with increased mortality rate⁽¹⁶⁾. Dislocation of the Bipolar prosthesis is a rare phenomenon. It has been reported in literature ranging from 1.1% at one year follow up to 5% at 20 years⁽¹⁷⁾. Saberi S et al⁽¹⁸⁾, in his study related to the complications following Bipolar Hemiarthroplasty amongst the 150 patients at 1 year follow up reported 6.5% dislocation rate. Rajak MK et al⁽¹⁹⁾, reported 3% prosthesis dislocation following Bipolar Hemiarthroplasty. Unwin et al⁽²⁰⁾, reported 6.5% of dislocation rate among all their patients with those having posterior approach being three times more likely to dislocate. &nbsp; <strong><em>CASE 1</em></strong> &nbsp; <strong>&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Pre-operative X-RAY&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp;&nbsp; Post-operative X-RAY</strong> &nbsp; <strong>Dislocation At 1 Month</strong> &nbsp; <strong>Open Reduction of Dislocation with Revision Cemented Prosthesis and Drain Placement</strong> <strong>X-RAY At 3 Months&nbsp; of Revision Procedure</strong> &nbsp; <strong>X-RAY At 6 Months</strong> &nbsp; In our study there were 2(4.76%) cases of infection out of which 1 was superficial wound infection and 1 deep wound infection. 73 year old male patient with no comorbidities observed superficial infection after 4 months of Uncemented Bipolar Hemiarthroplasty who was managed by antibiotic and dressing. Another patient, 76 year old female with multiple comorbidities including Diabetes had developed deep wound infection after cemented Bipolar Hemiarthroplasty as a revision procedure following posterior dislocation after 6 weeks which was managed by debridement and appropriate antibiotic after culture and sensitivity and diabetic control. Naidu KA et al⁽²¹⁾, observed superficial wound infection in 2 patients in the 1^st week of operation, of which 1 patient was diabetic. Treated with proper antibiotic and dressing which resulted in prolongation of their hospital stay. The organism isolated in the above cases were Staphylococcus Aureus. Maruthi CV and Shivanna⁽⁵⁾, observed 1 patient(2%) had a superficial wound infection in the 1^st week of operation which led to the prolongation of the hospital stay treated with proper antibiotics and dressing. The organism isolated was Staphylococcus Aureus. In present study, we observed lengthening of the operated limb in 3 patients upto 1 cm(7.14%). Ponraj RK et al⁽⁹⁾, observed in two cases had limb lengthening(1 cm). Naidu KA et al⁽²¹⁾, reported limb length discrepancy seen in 2 patients(9.09%) of which lengthening was noted in both patients. Rajak MK et al⁽¹⁹⁾, observed limb lengthening in 1(3%) patient about 1.5cm which was managed by compensatory footwear in the opposite limb. While Marya SKS et al⁽²²⁾, observed limb lengthening in 7% of the cases. Limb lengthening of less than 3.5cm was not significant and did not affect outcome. Patel KC et al⁽²³⁾, in 84% of the patient there was no limb length discrepancy. No case showed limb shortening while 16% showed limb lengthening. All the cases in our series were assessed according to Harris Hip Score and graded accordingly as Excellent , Good, Fair and Poor. In present study, we evaluated mean Harris Hip score at the end of 6 months follow up which was 80.4 points. Our findings are consistent with the study of Rajak MR et al⁽¹⁹⁾,Bezwada HP et al⁽²⁴⁾, Ponraj RK et al⁽⁹⁾, Maruthi CV and Shivanna⁽⁵⁾<strong>. </strong> &nbsp; <strong>&nbsp;Studies with Harris Hip Score</strong> STUDIES MEAN HARRIS HIP SCORE Bezwada HP et al⁽²⁴⁾ At 3.5 years 82 points with range of 54-92 Shukla R et al⁽²⁾ At 6 months 74.68 points At 1 year 78.24 points At 2 years 81.40 Saberi S et al⁽¹⁸⁾ At 6 months 74.5 points At 1 year 80.7 points Maruthi CV and Shivanna⁽⁵⁾ At 6 months range of 35 to 94.6 Reddy YH et al⁽²⁵⁾ At 1 year 90.36points Rajak MK et al⁽¹⁹⁾ At 6 months 82.1 points At 1 year 83.1 points Ebrahimpour A et al⁽²⁶⁾ At 1 year 83.5 points Ponraj RK et al⁽⁹⁾ At 6 months 84.2 points Our study At 6 weeks 74.21 points At 3 months 77.66 points At 6 months 80.4 points <strong>Table 8</strong> <strong>Studies with Functional Outcome</strong> Study Duration Excellent Good Fair Poor Naidu KA et al⁽²¹⁾ 22 cases for 6 months 31.82% 54.55% 9.09% 4.54% Kalantri A et al⁽²⁷⁾ 30 cases for 6 months 53.33% 33.3% 16.67% 6.67% Ponraj RK et al⁽⁹⁾ 30 cases for minimum 6 months 23.33% 56.66% 13.33% 6.66% Jindal RC et al⁽²⁸⁾ 30 cases for 6 months 40% 40% 6.7% 13.3% Patel KC et al⁽²³⁾ 50 cases for 12 months 64% 28% 8% 0% Bezwada HP et al⁽²⁰⁾ 248 cases for 3.5 years 10% 55% 30% 5% Rajak MK et al⁽¹⁹⁾ 30 cases for 12 months 33.33% 43.33% 16.66% 6.66% Malhotra R et al⁽²⁹⁾ 32 cases 75% 15.6% 6.3% 3.1% Our study 42 cases for 6 months 30.95% 26.19% 28.57% 14.29% <strong>Table 9</strong> &nbsp; <strong>CONCLUSION:</strong> Our study concludes that Bipolar Hemiarthroplasty is a good method to manage intracapsular fracture neck femur in elderly patients . It offers excellent, painless mobility and ease in rehabilitation and return to function. The surgery is relatively easy to perform, takes less operating time and less blood loss with low complication rate. <strong>REFERENCES:</strong> Adapureddi HT, Kamareddy SB, Kumar A, Paturi SK, Anne S, Reddy JP. Prospective study of management of fracture neck of femur by Hemiarthroplasty with cemented Bipolar. Journal of Evolution of Medical and Dental Sciences. 2015; 4(98): 16309-16314. Shukla R, Singh M, Jain RK, Mahajan P, Kumar R. Functional Outcome of Bipolar Prosthesis versus Total Hip Replacement in the Treatment of Femoral Neck Fracture in Elderly Patients. Malaysian Orthopaedic Journal<em>.</em> 2017; 11(1): 1 -5. Leighton RK: Fractures of the Neck Femur. In: Bucholz RW, Heckman JD,Court-Brown CM. (eds.) Rockwood and Green&rsquo;s fracture in adults. 6^th edition. Philadelphia, Lippincott Williams &amp; Wilkins 2006; 1753-1791. Sharoff L, Nazeer M, Unnikrishnan R. 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AbstractAs the Tokyo Shimbun reported in its recent article, the expression “Japan Is Great!” and a distinctive nationalistic sentiment associated with it flood the mass media in Japan today. Journalists and television personalities praise Japan ad nauseam. Hayakawa Tadanori is an editor and writer who has extensively covered this “Japan-Is-Great” phenomenon. Analyzing issues surrounding nationalism and propaganda both in pre-war and contemporary Japan, he examines topics ranging from patriotic mobilization in pre-war and war-time Japan to post-war propaganda promoting nuclear energy. His most recent book, The Dystopia of “Japan Is Great”: The Genealogy of Singing One's Own Praises in Wartime (“Nihon sugoi” no disutopia: senjika jiga jisan no keifu, Seikyūsha, 2016) analyzes “precursors to the current ‘Japan Is Great!‘ discourse” in publications between 1925 and 1945.

We derive explicit formulas for integrals of certain symmetric polynomials used in Keiju Sono’s multidimensional sieve of E 2 E_2 -numbers, i.e., integers which are products of two distinct primes. We use these computations to produce the currently best-known bounds for gaps between multiple E 2 E_2 -numbers. For example, we show there are infinitely many occurrences of four E 2 E_2 -numbers within a gap size of 94 94 unconditionally and within a gap size of 32 32 assuming the Elliott-Halberstam conjecture for primes and E 2 E_2 -numbers.

Artikulu honetan, 1653. urteko Modo Breve izeneko dokumentua nork eskuizkribatu zuen argitu nahi da. Orain arte Rafael Mikoletaren eskuz eginikoa dela pentsatu izan da. Berriki, ordea, Samuel Sainthill Ingalaterrako jaunaren eskuizkribu bat eskuratu ahal izan dugu, eta zalantza areagotu Modo Breve bera noren eskutik egina den. Auzia argitzeko, azterketa konparatu bat egiten da, grafoskopian erabiltzen den metodo grafonomikoaren bidez; hau da, letren forma, idatziaren ezaugarri orokorrak eta keinu-tipoak aztertu dira. Ondorio nagusi bezala, baiezta daiteke 1653. urteko eskuizkribuaren ezaugarriak Sainthillen idatziaren antzekoak direla, eta ez Mikoletarenaren antzekoak. Azkenik, baieztapen hau ikertzen jarraitzeko bideak proposatzen dira.

This paper offers an analysis of the process by which new borders appeared in Inner Asia during the late imperial period. The research focuses on the borders of Russia, Qing, and Mongolia at the time of the collapse of the Qing Empire and political crisis in Russia, which led to its demise in 1917. The author aims to reveal the influence of these processes on the region referring to transborder smuggling via the transformation of the control and power of central governments. In the author’s opinion, two key factors defined the increase in opium smuggling at the Russo-Mongolian border in 1900–1917. First, political destabilization on the outskirts of the Qing Empire. Second, Cossack regiments were sent from the border to Europe to take part in World War I, thus border control was greatly reduced. The research for this study is based upon the materials of the Russian Imperial customs in the town of Kyakhta, the long-time center of Russo-Chinese trade. Based on archival data, one can trace the volumes and routes of opium smuggling from Iran to Mongolia. The area under consideration is well researched as a cross-border smuggling point; however, the problem of the illicit opium trade is still insufficiently analyzed. This is due to both political obstacles and access to sources. This article is the first attempt at a systematic study of opium trafficking through Kyakhta. The destination of the routes was the town of Maimaicheng, located near Kyakhta and inhabited by Chinese merchants. Opium was also bought by the honghuzi – armed robbers operating near the border. However, when the Civil War broke out in Russia (1917–1922), and the Far Eastern Republic was established, opium supply via the Trans-Siberian Railway declined as this route was no longer safe. Therefore, the notion of regional order and disorder is an important category for this research. This framework offers a way of better understanding Trans-Eurasian relations in the twentieth century.

This study investigates possible structural changes of an intrinsically disordered protein (IDP) when it adsorbs to a solid surface. Experiments on IDPs primarily result in ensemble averages due to their high dynamics. Therefore, molecular dynamics (MD) simulations are crucial for obtaining more detailed information on the atomistic and molecular levels. An evaluation of seven different force field and water model combinations have been applied: (A) CHARMM36IDPSFF + CHARMM-modified TIP3P, (B) CHARMM36IDPSFF + TIP4P-D, (C) CHARMM36m + CHARMM-modified TIP3P, (D) AMBER99SB-ILDN + TIP3P, (E) AMBER99SB-ILDN + TIP4P-D, (F) AMBERff03ws + TIP4P/2005, and (G) AMBER99SB-disp + disp-water. The results have been qualitatively compared with those of small-angle X-ray scattering, synchrotron radiation circular dichroism spectroscopy, and attenuated total reflectance Fourier transform infrared spectroscopy. The model IDP corresponds to the first 33 amino acids of the N-terminal of the magnesium transporter A (MgtA) and is denoted as KEIF. With a net charge of +3, KEIF is found to adsorb to the anionic synthetic clay mineral Laponite® due to the increase in entropy from the concomitant release of counterions from the surface. The experimental results show that the peptide is largely disordered with a random coil conformation, whereas the helical content (α- and/or 310-helices) increased upon adsorption. MD simulations corroborate these findings and further reveal an increase in polyproline II helices and an extension of the peptide conformation in the adsorbed state. In addition, the simulations provided atomistic resolution of the adsorbed ensemble of structures, where the arginine residues had a high propensity to form hydrogen bonds with the surface. Simulations B, E, and G showed significantly better agreement with experiments than the other simulations. Particularly noteworthy is the discovery that B and E with TIP4P-D water had superior performance to their corresponding simulations A and D with TIP3P-type water. Thus, this study shows the importance of the water model when simulating IDPs and has also provided an insight into the structural changes of surface-active IDPs induced by adsorption, which may play an important role in their function.

Purpose: Immune checkpoint inhibitors (ICIs) cause ICI-related adverse events (irAEs) such as dry eye and uveitis, which can be severe, sometimes necessitating the suspension of ICI treatment. Retrospective studies have targeted ocular irAEs which can detect only moderate to severe symptomatic uveitis. To the best of our knowledge, this is the first prospective study on ocular irAEs. We aimed to investigate symptomatic and subclinical ocular changes in ICI-treated eyes, to identify early changes in ocular irAE and control conditions without suspending ICI treatment. Methods: 22 participants who began ICI treatment between July 2020 and July 2021 in Keiyu Hospital, Japan (3 women and 19 men; age, 69.1 ± 7.9 years, range, 53–83 years) were prospectively evaluated. The patients underwent ocular examinations before and 1, 3, and every 2 months after the initial dose of ICI. Examinations included measurement of best-corrected visual acuity, fundus biomicroscopy, spectral domain optical coherence tomography (OCT) and aqueous flare. Central choroidal thickness (CCT) was measured using OCT. Results: Among the 22 participants, 6 developed systemic irAEs. Of these 6 patients, one experienced ocular pain after ICI treatment, likely due to dry eye disease. We did not observe any change in CCT or aqueous flare, even in patients with systemic AEs. We were unable to ascertain whether CCT or aqueous flare are valuable clues for the early identification of ocular irAEs. We continue this prospective study with a larger sample size. Conclusions: Systemic irAEs are not necessarily accompanied by ophthalmological changes.

Objective: This study is aimed at evaluating maternal birth weight, recorded in Japan’s Maternal and Child Health Handbooks, as a predictor for large for gestational age (LGA) neonates compared to traditional pregnancy factors.Methods: In this retrospective study, we analyzed maternal and neonatal data from 374 singleton, full‐term pregnancies at Keiju General Hospital (2017–2020). Maternal birth weight was obtained from Japan’s Maternal Child Health Handbooks, and fasting plasma glucose was measured during the 75‐g oral glucose tolerance test (OGTT). Logistic regression models assessed the predictive contributions of maternal birth weight and fasting plasma glucose, adjusted for maternal and pregnancy factors.Results: Among 374 patients, 9.8% of neonates were classified as LGA. This group had a higher proportion of a family history of diabetes (p = 0.04) and greater maternal height (p = 0.01), pre‐pregnancy weight (p = 0.004), weight before delivery (p = 0.03), and maternal birth weight (p = 0.001) than the non‐LGA group. Multivariate analysis showed that maternal birth weight remained a significant predictor of neonatal birth weight after adjusting for other risk factors (odds ratios: 2.92 for maternal birth weight between 3500 and 3999 g and 4.77 for birth weight ≥ 4000 g).Conclusion: This study suggests the potential of incorporating maternal birth weight to improve LGA risk prediction. These findings provide foundational data for further research into the integration of maternal birth weight in risk assessment models and its potential clinical applications.