bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mpox Evolution: Has the Current Outbreak Revealed a Pox on “U”?
Authors: Kohli Rahul M , Isaacs Stuart N 
Published: December 2022

AbstractThe recent mpox (monkeypox) outbreak has prompted genomic studies to track global spread of the disease. These studies have also revealed unexpected patterns of mutations that implicate the action of the immune defense APOBEC3 family of enzymes, which catalyze conversion of cytosine (C) to uracil (U) in DNA, in viral evolution. As poxviruses have conventionally been regarded as slow-evolving viruses, the rapid emergence of APOBEC3 mutational signatures begs a series of important and open questions regarding how host-pathogen interactions may have changed and whether these mutations are bystanders or have roles in pathogenesis.
Persistence of Immunogenicity of a Purified Inactivated Zika Virus Vaccine Candidate in Healthy Adults: 2 Years of Follow-up Compared With Natural Infection
Authors: Acosta Camilo J , Diaz Clemente , Nordio Francesco , Han Htay-Htay , Moss Kelley J , Bohning Kelly , Kumar Pradeep , Liu Mengya , Patel Hetal , Pacciarini Filippo , Mwangi Vincent , Walter Elke , Powell Tim D , El Sahly Hana M , Baldwin Whitney R , Santangelo Joseph , Anderson Evan J , Dubin Gary 
Published: December 2022

Abstract

Background
We report 2-year persistence of immune response to Takeda's prophylactic purified formalin-inactivated whole Zika virus vaccine candidate (TAK-426) compared with that observed after natural infection.

Methods
A randomized, observer-blind, placebo-controlled, dose-selection, phase 1 trial was conducted in 18–49-year-old adults at 9 centers (7 in the United States, 2 in Puerto Rico) from 13 November 2017 to 24 November 2020. Primary objectives were safety, tolerability, and immunogenicity of 3 increasing doses of TAK-426 administered as 2 doses 28 days apart to flavivirus (FV)–naive and FV-primed adults. Here, we report on safety and persistence of immunity up to 2 years after primary vaccination with 10-μg TAK-426, the highest dose, and compare neutralizing antibody responses with those observed after natural infection.

Results
TAK-426 at 10-μg had an acceptable safety profile in FV-naive and FV-primed adults up to 24 months after dose 2. Seropositivity for neutralizing antibodies was 100% at 1 year, and 93.8% and 76.2% at 2 years in FV-naive and FV-primed groups, respectively. TAK-426 responses were comparable in magnitude and kinetics with those elicited by natural Zika virus infection.

Conclusions
These results support the further clinical development of TAK-426 for both FV-naive and FV-primed populations.

Clinical Trials Registration
NCT03343626
We Can Manage: Experimental Evidence From Savings Groups in Uganda
Authors: Bjorvatn Kjetil , Tungodden Bertil 
Published: December 2022

Abstract
Village savings and loans associations (VSLAs) are promoted as an important tool for economic and social empowerment, primarily targeting women. However, there is relatively limited evidence on the impact of VSLAs, and no evidence on whether such programs work better for some groups than for others. Using a large-scale field experiment on a VSLA targeting people with disabilities in Uganda, we document positive effects of the program on economic empowerment, social empowerment and general well-being. The effects are overall somewhat stronger for the male participants, and in particular we find no evidence of social empowerment for women. Our findings suggest that VSLAs can be an important tool for improving the situation also for economically active persons with disabilities, but that additional measures need to be implemented to achieve a more comprehensive empowerment of women.
Stable Isotopes Indicate Seasonal Changes in Natal Geographic Origins and Host Plants of Ostrinia furnacalis (Guenée) Migrants Across the Bohai Strait in China
Authors: Shen Xiujing , Guo Jianglong , Yang Xianming , Wei Shujun , Wu Kongming 
Published: December 2022

Abstract
The Asian corn borer, Ostrinia furnacalis (Guenée), is a notorious pest of maize that migrates seasonally in Asia. Two migration peaks were found on Beihuang island in the Bohai Strait of China by observing the number of migrants. However, the origins and host plants of the migrants in the two migration periods remain unclear. Here, stable hydrogen (δ2H) and carbon (δ13C) isotope levels were measured to infer the origin and host plants of the O. furnacalis captured on Beihuang island in 2017–2019. δ2H in wings of spring-summer O. furnacalis captured from May to June ranged from −99 to −56‰, while that of autumn migrants from August to September ranged from −127 to −81‰. Based on the linear relationship between δ2H in the wing of migrants (δ2Hw) and δ2H in precipitation (δ2Hp), the spring-summer O. furnacalis likely originated from the summer maize area in the Huang-Huai-Hai Plain in China. In contrast, the autumn migrants came from the northern spring maize area in Liaoning, Jilin and Inner Mongolia. Based on δ13C, the spring-summer migrants fed on both C3 plants such as wheat (47.76%) and C4 weeds or belonged to the over winter individuals in maize field (52.24%), while the autumn migrants mainly fed on maize (C4, 91.21%). The results point to a northward migration in spring-summer and southward migration in autumn of O. furnacalis. Our study gives an important knowledge for improving the forecasting and management level of this pest.
Retrospective study on the effectiveness of medroxyprogesterone acetate in the treatment of ER-positive/HER2-negative post-menopausal advanced breast cancer: an additional analysis of the JBCRG-C06 Safari study
Authors: Kawaguchi Hidetoshi , Yamamoto Yutaka , Saji Shigehira , Masuda Norikazu , Nakayama Takahiro , Aogi Kenjiro , Anan Keisei , Ohtani Shoichiro , Sato Nobuaki , Takano Toshimi , Tokunaga Eriko , Nakamura Seigo , Hasegawa Yoshie , Hattori Masaya , Fujisawa Tomomi , Morita Satoshi , Yamaguchi Miki , Yamashita Toshinari , Yotsumoto Daisuke , Toi Masakazu , Ohno Shinji 
Published: December 2022

AbstractBackgroundOnly old evidence exists to back up the use of medroxyprogesterone acetate. Therefore, this study aimed to explore the factors that influence the time to treatment failure of medroxyprogesterone acetate in real-world settings as late-line treatment.MethodsThis was a cohort study that used the database of the Safari study on oestrogen receptor-positive post-menopausal advanced breast cancer (UMIN000015168). We created Kaplan–Meier curves for time to treatment failure with medroxyprogesterone acetate. Further, univariate and multivariate analyses were performed using a Cox hazard model of the clinicopathological factors involved in the time to treatment failure of medroxyprogesterone acetate.ResultsFrom the 1031 patients in the Safari study, 279 patients were selected as the population for the analysis of effectiveness of medroxyprogesterone acetate monotherapy. In the analysis of medroxyprogesterone acetate by treatment line, the median time to treatment failure was 3.0 months for third-line treatment and 4.1 months for fourth and subsequent treatment lines. In cases where medroxyprogesterone acetate was used as a third-line or later endocrine treatment, multivariate analysis showed that the length of the disease-free interval was correlated with the length of time to treatment failure of medroxyprogesterone acetate (P = 0.004). With medroxyprogesterone acetate monotherapy as the fourth-line or later treatment, 20% of the patients achieved a time to treatment failure of 12 months or longer.ConclusionIn actual clinical practice, patients treated with medroxyprogesterone acetate alone as the fourth or subsequent treatment lines showed a time to treatment failure of 4 months, suggesting that there is merit in using medroxyprogesterone acetate even in late treatment lines, especially in patients with long disease-free interval and those who are difficult to treat using other antineoplastic agents.
Switch-maintenance avelumab immunotherapy following first-line chemotherapy for patients with advanced, unresectable or metastatic urothelial carcinoma: the first Japanese real-world evidence from a multicenter study
Authors: Miyake Makito , Shimizu Takuto , Oda Yuki , Tachibana Akira , Ohmori Chihiro , Itami Yoshitaka , Kiba Keisuke , Tomioka Atsushi , Yamamoto Hiroaki , Ohnishi Kenta , Nishimura Nobutaka , Hori Shunta , Morizawa Yosuke , Gotoh Daisuke , Nakai Yasushi , Torimoto Kazumasa , Fujii Tomomi , Tanaka Nobumichi , Fujimoto Kiyohide 
Published: December 2022

AbstractObjectiveTo develop the first Japanese real-world evidence of switch-maintenance avelumab in advanced, unresectable or metastatic urothelial carcinoma (aUC).MethodsA multicenter-derived database registered 505 patients diagnosed with aUC between 2008 and 2021. Of these, 204 patients (40%) were selected and stratified according to the type of therapy used: maintenance avelumab group (27 [5.3%]), second-line (2 L) pembrolizumab group (103 [20%]) and 2 L cytotoxic chemotherapy group (74 [15%]). The progression-free survival and overall survival from the initiation of following therapy were compared. Tumor response was evaluated based on the Response Evaluation Criteria in Solid Tumors guideline v1.1 during the treatment period. A detailed analysis was performed in the maintenance avelumab group to investigate possible factors associated with response to avelumab therapy.ResultsThe maintenance avelumab group had a longer overall survival, not progression-free survival, compared with the other two treatment groups. The median treatment-free interval between the last dose of first-line (1 L) chemotherapy and the initiation of avelumab therapy was 6 weeks (range, 3–22). Disease control rate of maintenance avelumab therapy in patients with a treatment-free interval of ≤6 weeks was higher than that in patients with a treatment-free interval of &gt;6 weeks (77 vs 40%, P = 0.029). The patients showing objective response to 1 L chemotherapy were less likely to experience tumor relapse (4 of 19) after the initiation of avelumab therapy compared with those showing stable disease (7 of 8).ConclusionsObjective response to 1 L chemotherapy and early induction of maintenance avelumab therapy may be associated with increased benefit from maintenance avelumab therapy.
Rich Hairdressers and Fancy Car Repairmen: The Rise of a Service Worker Elite in the USSR and the Evolution of Soviet Society in the 1970s
Authors: Ivanova Anna 
Published: December 2022

Abstract
In the Soviet Union during the 1970s, many service workers, such as salespeople, hairdressers, and car mechanics who worked in the state-owned retail sector, rose to prominent financial positions. They achieved this mobility because they had access to coveted goods and services that were in short supply. Soviet citizens’ disposable incomes were growing, producing a desire to consume in a more sophisticated way. However, shortages of the planned economy meant that people often could not satisfy their growing demands for consumption. Service providers illegally sold goods and services on the side for higher prices and became wealthy by collecting a huge portion of the money that the populace could not spend in the state retail system. The Soviet state was reluctant to prosecute these dealers because it needed their services to provide for consumers and to avoid pursuing large-scale economic reform. However, the enrichment of service workers caused resentment among the broader population. The newly rich, as opposed to members of an older Soviet upper class including party and state officials and the cultural and academic elite, flaunted their wealth and created a new mass culture of luxurious lifestyle. They not only became role models for some Soviet youth, but also created a sense among many Soviet citizens that socialism was in crisis. The prominent status of this new elite and its conspicuous consumption contradicted traditional socialist values of modesty, collectivism, and the priority of spiritual over material concerns.
The legal determinants of health (in)justice
Authors: Coggon John , Kamunge-Kpodo Beth 
Published: December 2022

ABSTRACT
The mutual influences of social epidemiology and ideas of justice, each on the other, have been seminal in the development of public health ethics and law over the past two decades, and to the prominence that these fields give to health inequalities and the social—including commercial, political, and legal—determinants of health. General and political recognition of injustices in systematised health inequalities have further increased given the crushingly unequal impacts of the COVID-19 pandemic; including impacts of the legal and policy responses to it. However, despite apparent attention from successive UK governments to injustices concerning avoidable inequalities in health opportunities and outcomes, significant challenges impede the creation of health laws and policy that are both effective and ethically rigorous. This article critically explores these points. It addresses deficiencies in a UK health law landscape where health care contexts and medico-ethical assumptions predominate, to the great exclusion of broader social and governmental influences on health. The article explains how a public health framing better serves analysis, and engages with a framework of justice-oriented questions that must be asked if we are to understand the proper place and roles of law and regulation for the public’s health.
Distraction arthroplasty combined with autologous bone grafting for diffuse-type tenosynovial giant cell tumour with articular cartilage defect and subchondral bone cysts: A case report
Authors: Ikuta Yasunari , Nakasa Tomoyuki , Sumii Junichi , Nekomoto Akinori , Kawabata Shingo , Adachi Nobuo 
Published: December 2022

ABSTRACT
Tenosynovial giant cell tumour (TGCT) encompasses a group of lesions that present with synovial differentiation and most commonly occur in the joint synovium, bursae, and tendon sheaths. Diffuse-type TGCT (Dt-TGCT), previously known as pigmented villonodular synovitis, is one of the most common benign soft-tissue tumours of the foot and ankle and usually affects young adults. The differential diagnosis of Dt-TGCTs remains a clinical problem because their clinical symptoms are similar to those of inflammatory arthritis, including rheumatoid arthritis. Moreover, persistent Dt-TGCTs can lead to articular deterioration, including osseous erosions and subchondral bone cysts. Joint-preserving procedures are considered optimal for treating younger patients with ankle osteoarthritis because the indication of ankle arthrodesis and total ankle arthroplasty is limited. Thus, ankle distraction arthroplasty could be an alternative for treating Dt-TGCT with articular deterioration in young patients. Here, we report about a woman in her early 30s who presented with ankle pain owing to a Dt-TGCT with an articular cartilage defect and subchondral bone cysts. We performed ankle distraction arthroplasty combined with an autologous bone graft. A follow-up examination at 2 years revealed preservation of physical function and pain alleviation. These findings suggest that distraction arthroplasty is a viable treatment option for remedying the destruction of the articular cartilage and subchondral bone owing to Dt-TGCTs in young adults.
Computationally-guided design and selection of high performing ribosomal active site mutants
Authors: Kofman Camila , Watkins Andrew M , Kim Do Soon , Willi Jessica A , Wooldredge Alexandra C , Karim Ashty S , Das Rhiju , Jewett Michael C 
Published: December 2022

AbstractUnderstanding how modifications to the ribosome affect function has implications for studying ribosome biogenesis, building minimal cells, and repurposing ribosomes for synthetic biology. However, efforts to design sequence-modified ribosomes have been limited because point mutations in the ribosomal RNA (rRNA), especially in the catalytic active site (peptidyl transferase center; PTC), are often functionally detrimental. Moreover, methods for directed evolution of rRNA are constrained by practical considerations (e.g. library size). Here, to address these limitations, we developed a computational rRNA design approach for screening guided libraries of mutant ribosomes. Our method includes in silico library design and selection using a Rosetta stepwise Monte Carlo method (SWM), library construction and in vitro testing of combined ribosomal assembly and translation activity, and functional characterization in vivo. As a model, we apply our method to making modified ribosomes with mutant PTCs. We engineer ribosomes with as many as 30 mutations in their PTCs, highlighting previously unidentified epistatic interactions, and show that SWM helps identify sequences with beneficial phenotypes as compared to random library sequences. We further demonstrate that some variants improve cell growth in vivo, relative to wild type ribosomes. We anticipate that SWM design and selection may serve as a powerful tool for rRNA engineering.
DrugCentral 2023 extends human clinical data and integrates veterinary drugs
Authors: Avram Sorin , Wilson Thomas B , Curpan Ramona , Halip Liliana , Borota Ana , Bora Alina , Bologa Cristian G , Holmes Jayme , Knockel Jeffrey , Yang Jeremy J , Oprea Tudor I 
Published: December 2022

Abstract
DrugCentral monitors new drug approvals and standardizes drug information. The current update contains 285 drugs (131 for human use). New additions include: (i) the integration of veterinary drugs (154 for animal use only), (ii) the addition of 66 documented off-label uses and iii) the identification of adverse drug events from pharmacovigilance data for pediatric and geriatric patients. Additional enhancements include chemical substructure searching using SMILES and ‘Target Cards’ based on UniProt accession codes. Statistics of interests include the following: (i) 60% of the covered drugs are on-market drugs with expired patent and exclusivity coverage, 17% are off-market, and 23% are on-market drugs with active patents and exclusivity coverage; (ii) 59% of the drugs are oral, 33% are parenteral and 18% topical, at the level of the active ingredients; (iii) only 3% of all drugs are for animal use only; however, 61% of the veterinary drugs are also approved for human use; (iv) dogs, cats and horses are by far the most represented target species for veterinary drugs; (v) the physicochemical property profile of animal drugs is very similar to that of human drugs. Use cases include azaperone, the only sedative approved for swine, and ruxolitinib, a Janus kinase inhibitor.
The Caulobacter crescentus DciA promotes chromosome replication through topological loading of the DnaB replicative helicase at replication forks
Authors: Ozaki Shogo , Wang Dengyu , Wakasugi Yasutaka , Itani Naoto , Katayama Tsutomu 
Published: December 2022

Abstract
The replicative DNA helicase translocates on single-stranded DNA to drive replication forks during chromosome replication. In most bacteria the ubiquitous replicative helicase, DnaB, co-evolved with the accessory subunit DciA, but how they function remains incompletely understood. Here, using the model bacterium Caulobacter crescentus, we demonstrate that DciA plays a prominent role in DNA replication fork maintenance. Cell cycle analyses using a synchronized Caulobacter cell population showed that cells devoid of DciA exhibit a severe delay in fork progression. Biochemical characterization revealed that the DnaB helicase in its default state forms a hexamer that inhibits self-loading onto single-stranded DNA. We found that upon binding to DciA, the DnaB hexamer undergoes conformational changes required for encircling single-stranded DNA, thereby establishing the replication fork. Further investigation of the functional structure of DciA revealed that the C-terminus of DciA includes conserved leucine residues responsible for DnaB binding and is essential for DciA in vivo functions. We propose that DciA stimulates loading of DnaB onto single strands through topological isomerization of the DnaB structure, thereby ensuring fork progression. Given that the DnaB-DciA modules are widespread among eubacterial species, our findings suggest that a common mechanism underlies chromosome replication.
Heterogeneous nuclear ribonucleoprotein K is overexpressed in acute myeloid leukemia and causes myeloproliferation in mice via altered Runx1 splicing
Authors: Aitken Marisa J L , Malaney Prerna , Zhang Xiaorui , Herbrich Shelley M , Chan Lauren , Benitez Oscar , Rodriguez Ashley G , Ma Huaxian , Jacamo Rodrigo , Duan Ruizhi , Link Todd M , Kornblau Steven M , Kanagal-Shamanna Rashmi , Bueso-Ramos Carlos E , Post Sean M 
Published: December 2022

Abstract
Acute myeloid leukemia (AML) is driven by numerous molecular events that contribute to disease progression. Herein, we identify hnRNP K overexpression as a recurrent abnormality in AML that negatively correlates with patient survival. Overexpression of hnRNP K in murine fetal liver cells results in altered self-renewal and differentiation potential. Further, murine transplantation models reveal that hnRNP K overexpression results in myeloproliferation in vivo. Mechanistic studies expose a direct functional relationship between hnRNP K and RUNX1—a master transcriptional regulator of hematopoiesis often dysregulated in leukemia. Molecular analyses show that overexpression of hnRNP K results in an enrichment of an alternatively spliced isoform of RUNX1 lacking exon 4. Our work establishes hnRNP K’s oncogenic potential in influencing myelogenesis through its regulation of RUNX1 splicing and subsequent transcriptional activity.
Prediction of all-cause mortality for chronic kidney disease patients using four models of machine learning
Authors: Tran Nu Thuy Dung , Balezeaux Margaux , Granal Maelys , Fouque Denis , Ducher Michel , Fauvel Jean-Pierre 
Published: December 2022

ABSTRACT

Background
The prediction tools developed from general population data to predict all-cause mortality are not adapted to chronic kidney disease (CKD) patients, because this population displays a higher mortality risk. This study aimed to create a clinical prediction tool with good predictive performance to predict the 2-year all-cause mortality of stage 4 or stage 5 CKD patients.

Methods
The performance of four different models (deep learning, random forest, Bayesian network, logistic regression) to create four prediction tools was compared using a 10-fold cross validation. The model that offered the best performance for predicting mortality in the Photo-Graphe 3 cohort was selected and then optimized using synthetic data and a selected number of explanatory variables. The performance of the optimized prediction tool to correctly predict the 2-year mortality of the patients included in the Photo-Graphe 3 database were then assessed.

Results
Prediction tools developed using the Bayesian network and logistic regression tended to have the best performances. Although not significantly different from logistic regression, the prediction tool developed using the Bayesian network was chosen because of its advantages and then optimized. The optimized prediction tool that was developed using synthetic data and the seven variables with the best predictive value (age, erythropoietin-stimulating agent, cardiovascular history, smoking status, 25-hydroxy vitamin D, parathyroid hormone and ferritin levels) had satisfactory internal performance.

Conclusions
A Bayesian network was used to create a seven-variable prediction tool to predict the 2-year all-cause mortality in patients with stage 4–5 CKD. Prior to external validation, the proposed prediction tool can be used at: https://dev.hed.cc/?a=jpfauvel&n=2022-05%20Modele%20Bayesien%2020000%20Mortalite%207%20variables%20Naif%20Zou%20online(1).neta for research purposes.