bluuebunny/crossref_metadata_2025_split huggingface dataset:
Empowering the biomedical research community: Innovative SAS deployment on the All of Us Researcher Workbench
Authors: Humes Izabelle , Shyr Cathy , Dillon Moira , Liu Zhongjie , Peterson Jennifer , Jeor Chris St , Malkes Jacqueline , Master Hiral , Mapes Brandy , Azuine Romuladus , Mack Nakia , Abdelbary Bassent , Gamble-George Joyonna , Goldmann Emily , Cook Stephanie , Choupani Fatemeh , Baskir Rubin , McMaster Sydney , Lunt Chris , Watson Karriem , Lee Minnkyong , Schwartz Sophie , Munshi Ruchi , Glazer David , Banks Eric , Philippakis Anthony , Basford Melissa , Roden Dan , Harris Paul A 
Published: August 2024

Abstract

Objectives
The All of Us Research Program is a precision medicine initiative aimed at establishing a vast, diverse biomedical database accessible through a cloud-based data analysis platform, the Researcher Workbench (RW). Our goal was to empower the research community by co-designing the implementation of SAS in the RW alongside researchers to enable broader use of All of Us data.

Materials and Methods
Researchers from various fields and with different SAS experience levels participated in co-designing the SAS implementation through user experience interviews.

Results
Feedback and lessons learned from user testing informed the final design of the SAS application.

Discussion
The co-design approach is critical for reducing technical barriers, broadening All of Us data use, and enhancing the user experience for data analysis on the RW.

Conclusion
Our co-design approach successfully tailored the implementation of the SAS application to researchers' needs. This approach may inform future software implementations on the RW.
Safety, pharmacokinetics, and pharmacodynamics of efzimfotase alfa, a second-generation enzyme replacement therapy: phase 1, dose-escalation study in adults with hypophosphatasia
Authors: Dahir Kathryn M , Shannon Amy , Dunn Derek , Voegtli Walter , Dong Qunming , Hasan Jawad , Pradhan Rajendra , Pelto Ryan , Pan Wei-Jian 
Published: August 2024

Abstract
Hypophosphatasia (HPP) is a rare, inherited metabolic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (TNSALP). Efzimfotase alfa (ALXN1850) is a second-generation TNSALP enzyme replacement therapy in development for HPP. This first-in-human open-label, dose-escalating phase 1 trial evaluated efzimfotase alfa safety, tolerability, pharmacokinetics, pharmacodynamics, and immunogenicity. Fifteen adults (5/cohort) with HPP received efzimfotase alfa in doses of 15 mg (cohort 1), 45 mg (cohort 2), or 90 mg (cohort 3) as one intravenous (i.v.) dose followed by 3 weekly subcutaneous (s.c.) doses. The primary objective was to assess safety and tolerability. Secondary objectives included pharmacokinetics, pharmacodynamics of ALP substrates known to be biomarkers of disease (inorganic pyrophosphate [PPi] and pyridoxal 5′-phosphate [PLP]) and immunogenicity. Treatment-emergent adverse events (TEAEs) occurred in 12 (80%) participants. Eight (53%) participants had injection site reactions (ISRs), observed after 10 of 41 (24%) s.c. injections. Most ISR TEAEs were mild and resolved within 1–2 d. Peak and total exposures of efzimfotase alfa increased in a greater-than-dose proportional manner over the range of 15–90 mg after i.v. and s.c. dosing. The arithmetic mean elimination half-life was approximately 6 d; absolute bioavailability was 28.6%–36.8% over the s.c. dose range of 15–90 mg. Dose-dependent reductions in plasma concentrations of PPi and PLP relative to baseline reached nadir in the first week after i.v. dosing and were sustained for 3–4 wk after the last s.c. dose. Four (27%) participants tested positive for antidrug antibodies (ADAs), 3 of whom were ADA positive before the first dose of efzimfotase alfa. ADAs had no apparent effect on efzimfotase alfa pharmacokinetics/pharmacodynamics. No participants had neutralizing antibodies. Efzimfotase alfa demonstrated acceptable safety, tolerability, and pharmacokinetic profiles and was associated with sustained reductions in biomarkers of disease in adults with HPP, supporting further evaluation in adult and pediatric patients.
Registration: ClinicalTrials.gov NCT04980248 (https://clinicaltrials.gov/study/NCT04980248).
Sex-based difference in immune responses and efficacy of the pneumococcal conjugate vaccine
Authors: Tchalla Essi Y I , Betadpur Anagha , Khalil Andrew Y , Bhalla Manmeet , Bou Ghanem Elsa N 
Published: August 2024

Abstract
Vaccine-mediated protection and susceptibility to Streptococcus pneumoniae (pneumococcus) infections are influenced by biological sex. The incidence of invasive pneumococcal disease remains higher in males compared to females even after the introduction of the pneumococcal conjugate vaccine. However, sex-based differences in the immune response to this conjugate vaccine remain unexplored. To investigate those differences, we vaccinated adult male and female mice with pneumococcal conjugate vaccine and assessed cellular and humoral immune responses. Compared to females, male mice displayed lower levels of T follicular helper cells, germinal center B cells, and plasmablasts, which are all required for antibody production following vaccination. This was linked to lower IgG and IgM levels against pneumococci and lower isotype switching to IgG3 in vaccinated males. Due to lower antibody levels, sera of vaccinated male mice had lower efficacy in several anti-pneumococcal functions, including neutralization of bacterial binding to pulmonary epithelial cells as well as direct cytotoxicity against S. pneumoniae. Importantly, while the vaccine was highly protective in females, vaccinated males succumbed to infection more readily and were more susceptible to both lung-localized infection and systemic spread following S. pneumoniae challenge. These findings identify sex-based differences in immune responses to pneumococcal conjugate vaccine that can inform future vaccine strategies.
Mesenchymal stem cell-derived exosomal microRNA-367-3p mitigates lower limb ischemia/reperfusion injury in mouse skeletal muscle via EZH2 targeting
Authors: Sun Huanhuan , Wang Jueqiong , Bi Wei , Zhang Feng , Zhang Kai , Tian Xitao , Gao Xiang , Zhang Yanrong 
Published: August 2024

Abstract

Objective
This study aimed to investigate the protective effect of bone marrow mesenchymal stem cell-derived exosomes (BMSCs-exo) against lower limb ischemia/reperfusion (I/R) injury-induced pyroptosis in skeletal muscle.

Methods
A mouse model of lower limb I/R injury was utilized to assess the impact of BMSCs-exo, particularly when loaded with microRNA-367-3p (miR-367-3p), on pyroptosis. Histological examination, wet weight/dry weight ratio measurements, and luciferase assays were employed to elucidate the mechanisms involved.

Key findings
BMSCs-exo effectively suppressed pyroptosis in injured skeletal muscle tissue. Loading BMSCs-exo with miR-367-3p enhanced this protective effect by downregulating key pyroptosis-related proteins. Luciferase assays identified enhancer of zeste homolog 2 (EZH2) as a direct target of miR-367-3p in BMSCs-exo.

Conclusions
BMSCs-exo loaded with miR-367-3p safeguarded mouse skeletal muscle against pyroptosis-induced I/R injury by targeting EZH2. These findings offer valuable insights into potential therapeutic strategies for lower limb I/R injuries, emphasizing the therapeutic potential of BMSCs-exo in mitigating tissue damage caused by pyroptosis.
Protein kinase MeSnRK2.3 positively regulates starch biosynthesis by interacting with the transcription factor MebHLH68 in cassava
Authors: Li Ke , Li Yajun , Liu Chen , Li Mengtao , Bao Ruxue , Wang Haiyan , Zeng Changying , Zhou Xincheng , Chen Yinhua , Wang Wenquan , Chen Xin 
Published: August 2024

Abstract
Starch biosynthesis involves numerous enzymes and is a crucial metabolic activity in plant storage organs. Sucrose non-fermenting related protein kinase 2 (SnRK2) is an abscisic acid (ABA)-dependent kinase and a significant regulatory enzyme in the ABA signaling pathway. However, whether SnRK2 kinases regulate starch biosynthesis is unclear. In this study, we identified that MeSnRK2.3, encoding an ABA-dependent kinase, was highly expressed in the storage roots of cassava (Manihot esculenta) and was induced by ABA. Overexpression of MeSnRK2.3 in cassava significantly increased the starch content in the storage roots and promoted plant growth. MeSnRK2.3 was further found to interact with the cassava basic helix–loop–helix 68 (MebHLH68) transcription factor in vivo and in vitro. MebHLH68 directly bound to the promoters of sucrose synthase 1 (MeSUS1), granule-bound starch synthase I a (MeGBSSIa), and starch-branching enzyme 2.4 (MeSBE2.4), thereby up-regulating their transcriptional activities. Additionally, MebHLH68 negatively regulated the transcriptional activity of sucrose phosphate synthase B (MeSPSB). Moreover, MebHLH68 phosphorylated by MeSnRK2.3 up-regulated the transcription activity of MeSBE2.4. These findings demonstrated that the MeSnRK2.3–MebHLH68 module connects the ABA signaling pathway and starch biosynthesis in cassava, thereby providing direct evidence of ABA-mediated participation in the sucrose metabolism and starch biosynthesis pathways.
LEP rs7799039 and LEPR rs1137101 gene variants are not associated with clinical features in patients with metabolic syndrome in the Turkish population
Authors: Jabbarli Marjan , Senkal Naci , Tuncel Fatima Ceren , Oyaci Yasemin , Guzel Dirim Merve , Kose Murat , Pehlivan Sacide , Medetalibeyoglu Alpay 
Published: August 2024

Abstract

Objectives
Genetic predisposition plays a role in the etiology of metabolic syndrome (MetS), an important health problem worldwide. Leptin (LEP), produced by adipose tissue, plays a crucial role in the development of MetS. In this study, we evaluated the effects of LEP and LEP receptor (LEPR) variants on clinical findings and risk of developing MetS in the Turkish population.

Methods
A total of 320 patients were included in the study, of whom 150 were patients with MetS and 170 were healthy controls. DNA was extracted from blood samples. LEP rs7799039 and LEPR rs1137101 variants were genotyped using the polymerase chain reaction–based restriction fragment length polymorphism method. The genotype distributions of these variants and clinical and laboratory findings were compared.

Results
The LEP rs7799039 GA and AA genotypes and A allele frequencies were higher in participants with MetS than in the control group. For LEP rs7799039, the genotype AA-GA was higher in males, and the GG genotype was higher in females. On analyzing the clinical outcomes associated with these variants, it was observed that individuals possessing LEP rs7799039 GA and AA genotypes displayed elevated levels of triglycerides. In addition, those with the AG-GG genotype of LEPR rs1137101 had lower mean hemoglobin levels.

Conclusion
Our results showed that the LEP rs7799039 and LEPR rs1137101 variants may be associated with both the risk of MetS development and clinical findings. Among the various contributors to MetS, a genetic predisposition is commonly recognized as the primary cause.
Combatant Command Medical Entry Standards
Authors: Hall Andrew , Chenault Janet , Olsen Cara , Medina Sheila , Patel Neha , Hanson Matthew , Matthews Joseph 
Published: August 2024

ABSTRACT

Introduction
The medical entry standards for the United States Central Command (USCENTCOM) restrict individuals with various medical conditions from entering the deployed environment. The impact of this program is unknown.

Materials and Methods
The total number of army personnel deployed to USCENTCOM, the number of individuals with a medical entry waiver adjudicated by United States Army Central (USARCENT), and the evacuation number for each population were compared for calendar year 2023 (CY2023).

Results
A total estimated population of 20,519 U.S. Army personnel were deployed to USCENTCOM. A population of 1,918 received a medical entry waiver due to a disqualifying medical condition. The evacuation rate for the general population was 2.4% compared to the 1.4% evacuation rate of the population with a medical entry waiver (P = .0027).

Conclusion
The medical entry standards, as written and adjudicated in 2023, resulted in a relatively reduced evacuation rate for individuals with otherwise prohibited medical conditions compared to the general deployed population.
Population genomics of the endangered freshwater mussel, Arcidens wheeleri (Unionoidea: Unionidae: Anodontini), in the Little River, Arkansas, USA
Authors: Adcock Mia C , Moles Kendall R , Garrison Nicole L , Donohoo Samantha A , Whelan Nathan V 
Published: August 2024

ABSTRACT
North America is a hotspot of freshwater mussel diversity. However, over the last century, many anthropogenic stressors have led to substantial declines in freshwater mussels of the families Unionidae and Margaritiferidae in North America. Conserving the remaining mussel fauna is a priority, as they play an integral role in freshwater ecosystems. The Little River in Arkansas is home to one of the last remaining populations of the federally endangered freshwater mussel, Arcidens wheeleri (Unionidae: Anodontini). Population dynamics information is lacking for A. wheeleri, and no population genetics study has been conducted on this species. A greater understanding of the genetic diversity within a population can serve as a benchmark for developing an effective management plan. We sampled A. wheeleri from three locations in the Little River. Genomic data were generated with a single-enzyme restriction-site-associated DNA sequencing approach to assess genetic diversity and structure of A. wheeleri in the Little River. Genetic structure analyses indicated one genetic population among the three locations, with limited, fine-scale subpopulation structure. Observed heterozygosity values were considerably lower than expected heterozygosity values, with Ho = 0.14 and He = 0.22, likely indicating a genetic bottleneck. Demographic analysis of the Little River population of A. wheeleri also suggests a historical bottleneck. Furthermore, a high inbreeding coefficient (FIS = 0.33) indicates A. wheeleri in the Little River is losing genetic diversity. Data generated indicate considerable risk of extirpation for A. wheeleri from the Little River and should serve as a baseline for future monitoring. Given its high risk of extinction, we recommend increased study of A. wheeleri across its range and on-the-ground conservation actions that include habitat protection and restoration, which are the only options until a successful host fish and protocols are identified for propagation.
Flexible contracts and ethnic economic inequalities across gender during the UK’s COVID-19 recession
Authors: Ochmann Nico , Clark Ken , Nazroo James , Aparicio-Casto Andrea , Šťastná Michaela 
Published: August 2024

Abstract
Was it their disproportionate presence in flexible employment or in shut-down occupations that made some ethnic minority groups vulnerable to adverse labour market outcomes during the coronavirus disease 2019 (COVID-19) recession? Using the COVID-19 recession in the UK as a case study, we employ weighted linear probability models with 2021 data from the Evidence for Equality National Survey to look at changes in economic indicators across ethnic groups and gender. We report heterogeneity in flexible employment rates within the non-White group and between the non-White and the White British group. By using a conditional decomposition method, we conclude that those ethnic minority groups who were disproportionately on flexible contracts experienced worse economic effects than the White British group.
Assessment of psycho-oncology in the Middle East and North Africa region: a systematic review and meta-analysis
Authors: Al-Hussaini Maysa , Abdel-Razeq Hikmat , Shamieh Omar , Al-Ani Abdallah , Hammouri Muhammad , Mansour Asem 
Published: August 2024

Abstract

Background
The Middle East and North Africa (MENA) region is expected to witness a significant increase in the burden of cancer. Contrary to Western literature, the burden of psycho-oncology is yet to be established within the MENA region. This study reviews all available evidence characterizing the psychological burden among patients with cancer across the MENA region.

Methods
We systematically explored the PubMed/MEDLINE, Cochrane/CENTRAL, and Web of Science (WoS) databases for reports on the psychiatric burden among patients with cancer residing within the MENA region from January 2000 until January 2023. Raw proportion were extracted and analyzed using a random-effects model.

Findings
Eighty-three studies comprised of 16 810 participants, representing 14 countries, met our inclusion criteria. Across the MENA region, the prevalence of depression, anxiety, and distress were 44% (95% CI, 39%-50%), 47% (95% CI, 40%-54%), and 43% (95% CI, 30%-56%), respectively. Prevalence of depression was significantly different across countries, with Palestine (73%; 95% CI, 42%-91%) reporting the highest rate while Morocco (23%; 95% CI, 7%-56%) reported the lowest. Similarly, anxiety significantly differed across MENA nations ranging from 64% (95% CI, 3%-99%) in Morocco to 28% (95% CI, 18%-42%) in Tunisia. Rates of depression and anxiety were significantly different across measurement tools but not between Arabic-speaking versus Persian/Farsi-speaking countries. Meta-regression models showed that neither publication year nor age affected the prevalence of both anxiety and depression (P = .374 and .091 for depression and P = .627, and .546 for anxiety, respectively).

Interpretation
We report an abnormally high rate of psychiatric burden among patients with cancer in the MENA region. Thus, establishing appropriate psycho-oncologic interventions within the MENA region is of utmost importance.
Progenitor and explosion properties of SN 2023ixf estimated based on a light-curve model grid of Type II supernovae
Authors: Moriya Takashi J , Singh Avinash 
Published: August 2024

Abstract
We estimate the progenitor and explosion properties of the nearby Type II SN 2023ixf using a synthetic model grid of Type II supernova light curves. By comparing the light curves of SN 2023ixf with the pre-existing grid of Type II supernovae containing about 228000 models with different combinations of the progenitor and explosion properties, we obtain the $\chi ^2$ value for every model and evaluate the properties of the models providing small values of $\chi ^2$. We found that the light-curve models with a progenitor zero-age main-sequence mass of $10\, {M}_\odot$, explosion energy of $(2\\!-\\!3) \times 10^{51}\:\mbox{erg}$, $^{56}\mbox{Ni}$ mass of 0.04–$0.06\, {M}_\odot$, mass-loss rate of $10^{-3}$–$10^{-2}\, {M}_\odot \:\mbox{yr}^{-1}$ with wind velocity of $10\:\mbox{km}\:\mbox{s}^{-1}$, and dense, confined circumstellar matter radius of $(6\\!-\\!10) \times 10^{14}\:\mbox{cm}$ match well to the observed light curves of SN 2023ixf. The photospheric velocity evolution of these models is also consistent with the observed velocity evolution. We note that the progenitor mass estimate could be affected by the adopted progenitor models. Although our parameter estimation is based on a pre-existing model grid and we do not perform any additional computations, the estimated parameters are consistent with those obtained by the detailed modeling of SN 2023ixf previously reported. This result shows that comparing the pre-existing model grid is a reasonable way to obtain a rough estimate for the properties of Type II supernovae. This simple way to estimate the properties of Type II supernovae will be essential in the Vera C. Rubin Observatory’s Legacy Survey of Space and Time (LSST) era when thousands of Type II supernovae are expected to be discovered yearly.
Feminism, reproductive labour, and the gendered welfare state in Britain’s National Insurance Act of 1911
Authors: Schwartz Laura 
Published: August 2024

Abstract
In 1911, numerous women’s organizations, of varying political interests, mounted a campaign against the National Insurance Bill. Such opposition emerged despite feminist support for increased welfare provision in general and especially for the maternity benefit that the Bill proposed to introduce. Feminists criticized National Insurance for discriminating against women, especially its failure to recognize the economic contribution of women’s unwaged reproductive labour. They lobbied and campaigned for a series of amendments, some of which were successful. Feminist opposition to National Insurance sheds new light on an ongoing historiographical debate over the degree to which women were able to influence early welfare states prior to enfranchisement. Their activities cannot be easily contained within a framework of ‘maternalist feminism’, and call into question distinctions between ‘maternalist’/‘social’ feminism and ‘equality’ feminism, and middle-class and working-class women’s agendas. Instead, feminist campaigns around National Insurance reveal an early analysis of ‘social reproduction’ (the origins of which are usually traced back only to ‘second wave’ feminism) whereby British feminists participated in international conversations contesting the gendered definitions of work that went on to inform insurance-based welfare states across Europe.
High titer expression of antibodies using linear expression cassettes for early-stage functional screening
Authors: Wu Shuang , Tsukuda Joni , Chiang Nancy , Hao To , Chen Yongmei , Hötzel Isidro , Balasubramanian Sowmya , Nakamura Gerald , Kelly Ryan L 
Published: August 2024

Abstract
Antibody discovery processes are continually advancing, with an ever-increasing number of potential binding sequences being identified out of in vivo, in vitro, and in silico sources. In this work we describe a rapid system for high yield recombinant antibody (IgG and Fab) expression using Gibson assembled linear DNA fragments (GLFs). The purified recombinant antibody yields from 1 ml expression for this process are approximately five to ten-fold higher than previous methods, largely due to novel usage of protecting flanking sequences on the 5′ and 3′ ends of the GLF. This method is adaptable for small scale (1 ml) expression and purification for rapid evaluation of binding and activity, in addition to larger scales (30 ml) for more sensitive assays requiring milligram quantities of antibody purified over two columns (Protein A and size exclusion chromatography). When compared to plasmid-based expression, these methods provide nearly equivalent yield of high-quality material across multiple applications, allowing for reduced costs and turnaround times to enhance the antibody discovery process.