bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of four neutralizing antigenic sites on the enterovirus D68 capsid
Authors: Dai Wenlong , Li Xue , Liu Zeyu , Zhang Chao 
Published: December 2023

ABSTRACT
Enterovirus D68 (EV-D68) is an emerging human pathogen associated with respiratory diseases and/or acute flaccid myelitis. Neutralizing antigenic sites of EV-D68 have not yet been comprehensively studied. In this study, we generated multiple neutralizing monoclonal antibodies (MAbs) directed against EV-D68 prototype or clinical strains. All these antibodies can inhibit EV-D68 attachment. The antibody epitopes were identified by selection and sequence analysis of prototype or clinical strain-derived neutralization-resistant mutants. The epitopes were then grouped into four distinct neutralizing antigenic sites (I to IV) by cross-neutralization analysis of the mutants with the MAbs and by spatial considerations. Site I, including residues 81, 85, and 87 of VP1 protein, is located in the VP1 BC loop, near the fivefold axis, and at the north rim of the canyon (the receptor binding site). Site II, involving residues 137, 139, and 142 of VP2, is situated in the VP2 EF loop and at the south rim of the canyon. Site III is composed of VP1 C-terminal residues 285 and 293 and resides on the south side of the canyon of neighboring asymmetric unit. Site IV contains residue 70 (βB strand) of VP2 from an asymmetric unit and residues 74 and 79 (BC loop) of VP3 from an adjacent unit and is located around the threefold axis. The four antigenic sites show various degrees of sequence variation. The identification of the four neutralizing antigenic sites on EV-D68 capsid provides a better understanding of the recognition of EV-D68 by neutralizing antibodies and viral evolution and immune escape.

IMPORTANCE
Enterovirus D68 (EV-D68) is an emerging respiratory pathogen associated with acute flaccid myelitis. Currently, no approved vaccines or antiviral drugs are available. Here, we report four functionally independent neutralizing antigenic sites (I to IV) by analyses of neutralizing monoclonal antibody (MAb)-resistant mutants. Site I is located in the VP1 BC loop near the fivefold axis. Site II resides in the VP2 EF loop, and site III is situated in VP1 C-terminus; both sites are located at the south rim of the canyon. Site IV is composed of residue in VP2 βB strand and residues in the VP3 BC loop and resides around the threefold axis. The developed MAbs targeting the antigenic sites can inhibit viral binding to cells. These findings advance the understanding of the recognition of EV-D68 by neutralizing antibodies and viral evolution and immune escape and also have important implications for the development of novel EV-D68 vaccines.
Aminoglycoside uptake, stress, and potentiation in Gram-negative bacteria: new therapies with old molecules
Authors: Lang Manon , Carvalho André , Baharoglu Zeynep , Mazel Didier 
Published: December 2023

SUMMARY
Aminoglycosides (AGs) are long-known molecules successfully used against Gram-negative pathogens. While their use declined with the discovery of new antibiotics, they are now classified as critically important molecules because of their effectiveness against multidrug-resistant bacteria. While they can efficiently cross the Gram-negative envelope, the mechanism of AG entry is still incompletely understood, although this comprehension is essential for the development of new therapies in the face of the alarming increase in antibiotic resistance. Increasing antibiotic uptake in bacteria is one strategy to enhance effective treatments. This review aims, first, to consolidate old and recent knowledge about AG uptake; second, to explore the connection between AG-dependent bacterial stress and drug uptake; and finally, to present new strategies of potentiation of AG uptake for more efficient antibiotic therapies. In particular, we emphasize on the connection between sugar transport and AG potentiation.
Complete genome sequence of Japanese encephalitis virus strain SDWF-2021 isolated from a
Culex
mosquito pool from a duck farm
Authors: Li Chenxi , Zhao Wen 
Published: December 2023

ABSTRACT

We report here the complete genome sequence of Japanese encephalitis virus (JEV) strain SDWF-2021, isolated from a
Culex
mosquito pool in a duck farm located in Shandong, China. The isolated JEV genetically belong to genotype I, which is the dominant genotype circulation in China.
Complete genome sequence of
Limnobacter thiooxidans
CS-K2
T
, isolated from freshwater lake sediments in Bavaria, Germany
Authors: Naruki Miu , Watanabe Aoi , Warashina Tomoro , Morita Teppei , Arakawa Kazuharu 
Published: December 2023

ABSTRACT

Limnobacter thiooxidans
CS-K2
T
is a Gram-negative bacterium first isolated from the sediment of the littoral zone of a freshwater lake in Germany. We here present the complete annotated genome sequence of this thiosulfate-oxidizing bacterium, spanning 3.54 Mb and encoding 3,192 protein-coding sequences.
Tillage effects on growing season nitrous oxide emissions in Canadian cropland soils
Authors: Pelster David E. , Matteau Jean-Pascal , Farrell Richard , Hernandez Ramirez Guillermo 
Published: December 2023

Minimizing tillage has been promoted as an agricultural practice that may mitigate greenhouse gas emissions through carbon sequestration. However, there is some ambiguity regarding the effect of minimum tillage (MT) on emissions of other greenhouse gases, in particular soil nitrous oxide (N2O) emissions. To determine how effective MT could be in helping Canada mitigate greenhouse gas emissions, we used a meta-analysis to compare growing season N2O emissions from MT versus conventional tillage (CT). Overall, MT had 12% lower N2O emissions compared to CT ( P = 0.03). However, there was high variability due to soil texture and growing season precipitation (GSP), with MT tending to emit more N2O than CT in climates where GSP exceeded 600 mm, particularly for soils with sand content less than 60%. Therefore, unless long-term tillage trials, which are urgently needed in eastern Canada, show a reduction in N2O emissions over time, MT should be used as a greenhouse gas mitigation measure only in dry climates or on sandy soils.
Enhancement of electronic and magnetic properties in Cr2O3 monolayer honeycomb-kagome by hydrogenation and oxygenation
Authors: Mohamed Nehal , Moaied Mohammed 
Published: December 2023

AbstractThis study investigates the structural, electronic, and magnetic properties of pristine, hydrogenated, and oxygenated Cr2O3 monolayer honeycomb-kagome (HK) surface using first-principles calculations based on density functional theory (DFT). Molecular dynamics and phonon dispersion calculations demonstrate the thermal and dynamic stability of these systems, implying their feasibility for laboratory synthesis. The results revealed that the adsorption of hydrogen and oxygen atoms on the Cr2O3 monolayer surface exhibited negative adsorption energies, indicating that these structures are energetically favorable. Specifically, the adsorption of oxygen atoms transforms the initial half-metallic nature of the monolayer into semiconducting behavior. Moreover, the introduction of hydrogen and oxygen atoms considerably enhances the Curie temperature of the surface. These findings offer a practical approach for enhancing the electronic and magnetic properties of Cr2O3 monolayer HK surface, thereby facilitating their prospective application in spintronics.
“Sometimes It’s Like Putting the Track in Front of the Rushing Train”: Having to Be ‘On Call’ for Work Limits the Temporal Flexibility of Crowdworkers
Authors: Lascău Laura , Brumby Duncan P. , Gould Sandy J. J. , Cox Anna L. 
Published: December 2023

Research suggests that the temporal flexibility advertised to crowdworkers by crowdsourcing platforms is limited by both client-imposed constraints (e.g., strict completion times) and crowdworkers’ tooling practices (e.g., multitasking). In this article, we explore an additional contributor to workers’ limited temporal flexibility: the design of crowdsourcing platforms, namely requiring crowdworkers to be ‘on call’ for work. We conducted two studies to investigate the impact of having to be ‘on call’ on workers’ schedule control and job control. We find that being ‘on call’ impacted (1) participants’ ability to schedule their time and stick to planned work hours, and (2) the pace at which participants worked and took breaks. The results of the two studies suggest that the ‘on-demand’ nature of crowdsourcing platforms can limit workers’ temporal flexibility by reducing schedule control and job control. We conclude the article by discussing the implications of the results for (a) crowdworkers, (b) crowdsourcing platforms, and (c) the wider platform economy.
Pilot Study of High-Dose Pemetrexed in Patients with Progressive Chordoma
Authors: Kesari Santosh , Wagle Naveed , Carrillo Jose A. , Sharma Akanksha , Nguyen Minhdan , Truong Judy , Gill Jaya M. , Nersesian Raffi , Nomura Natsuko , Rahbarlayegh Elnaz , Barkhoudarian Garni , Sivakumar Walavan , Kelly Daniel F. , Krauss Howard , Bustos Matias A. , Hoon Dave S.B. , Anker Lars , Singh Arun S. , Sankhala Kamalesh K. , Juarez Tiffany M. 
Published: December 2023

Abstract

Purpose:
Chordomas are ultrarare tumors of the axial spine and skull-base without approved systemic therapy. Most chordomas have negative expression of thymidylate synthase (TS), suggesting a potential for responding to the antifolate agent pemetrexed, which inhibits TS and other enzymes involved in nucleotide biosynthesis. We evaluated the therapeutic activity and safety of high-dose pemetrexed in progressive chordoma.

Patients and Methods:
Adult patients with previously treated, progressive chordoma participated in an open-label, single-institution, single-arm, pilot clinical trial of intravenous pemetrexed 900 mg/m2 every 3 weeks and supportive medications of folic acid, vitamin B12, and dexamethasone. The primary endpoint was objective response rate according to RECIST v1.1. Secondary endpoints included adverse events, progression-free survival (PFS), tumor molecular profiles, and alterations in tissue and blood-based biomarkers.

Results:
Fifteen patients were enrolled and the median number of doses administered was 15 (range, 4–31). One patient discontinued treatment due to psychosocial issues after four cycles and one contracted COVID-19 after 13 cycles. Of the 14 response-evaluable patients, 2 (14%) achieved a partial response and 10 (71%) demonstrated stable disease. Median PFS was 10.5 months (95% confidence interval: 9 months–undetermined) and 6-month PFS was 67%. Adverse events were expected and relatively mild, with one grade 3 creatinine increased, and one each of grade 3 and 4 lymphopenia. No grade 5 adverse events, unexpected toxicities, or dose-limiting toxicities were observed. Several patients reported clinical improvement in disease-related symptoms.

Conclusions:
High-dose pemetrexed appears tolerable and shows objective antitumor activity in patients with chordoma. Phase II studies of high-dose pemetrexed are warranted.
INX-315, a Selective CDK2 Inhibitor, Induces Cell Cycle Arrest and Senescence in Solid Tumors
Authors: Dietrich Catherine , Trub Alec , Ahn Antonio , Taylor Michael , Ambani Krutika , Chan Keefe T. , Lu Kun-Hui , Mahendra Christabella A. , Blyth Catherine , Coulson Rhiannon , Ramm Susanne , Watt April C. , Matsa Sunil Kumar , Bisi John , Strum Jay , Roberts Patrick , Goel Shom 
Published: December 2023

Abstract

Cyclin-dependent kinase 2 (CDK2) is thought to play an important role in driving proliferation of certain cancers, including those harboring CCNE1 amplification and breast cancers that have acquired resistance to CDK4/6 inhibitors (CDK4/6i). The precise impact of pharmacologic inhibition of CDK2 is not known due to the lack of selective CDK2 inhibitors. Here we describe INX-315, a novel and potent CDK2 inhibitor with high selectivity over other CDK family members. Using cell-based assays, patient-derived xenografts (PDX), and transgenic mouse models, we show that INX-315 (i) promotes retinoblastoma protein hypophosphorylation and therapy-induced senescence (TIS) in CCNE1-amplified tumors, leading to durable control of tumor growth; (ii) overcomes breast cancer resistance to CDK4/6i, restoring cell cycle control while reinstating the chromatin architecture of CDK4/6i-induced TIS; and (iii) delays the onset of CDK4/6i resistance in breast cancer by driving deeper suppression of E2F targets. Our results support the clinical development of selective CDK2 inhibitors.

Significance:
INX-315 is a novel, selective inhibitor of CDK2. Our preclinical studies demonstrate activity for INX-315 in both CCNE1-amplified cancers and CDK4/6i–resistant breast cancer. In each case, CDK2 inhibition induces cell cycle arrest and a phenotype resembling cellular senescence. Our data support the development of selective CDK2 inhibitors in clinical trials.
See related commentary by Watts and Spencer, p. 386.
This article is featured in Selected Articles from This Issue, p. 384
Inhibition of PRL2 Upregulates PTEN and Attenuates Tumor Growth in Tp53-deficient Sarcoma and Lymphoma Mouse Models
Authors: Nguele Meke Frederick , Bai Yunpeng , Ruiz-Avila Diego , Carlock Colin , Ayub Jinan , Miao Jinmin , Hu Yanyang , Li Qinglin , Zhang Zhong-Yin 
Published: December 2023

Abstract

The phosphatases of regenerating liver (PRL) are oncogenic when overexpressed. We previously found that PRL2 deletion increases PTEN, decreases Akt activity, and suppresses tumor development in a partial Pten-deficient mouse model. The current study aims to further establish the mechanism of PTEN regulation by PRL2 and expand the therapeutic potential for PTEN augmentation mediated by PRL2 inhibition in cancers initiated without PTEN alteration. The TP53 gene is the most mutated tumor suppressor in human cancers, and heterozygous or complete deletion of Tp53 in mice leads to the development of sarcomas and thymic lymphomas, respectively. There remains a lack of adequate therapies for the treatment of cancers driven by Tp53 deficiency or mutations. We show that Prl2 deletion leads to PTEN elevation and attenuation of Akt signaling in sarcomas and lymphomas developed in Tp53 deficiency mouse models. This results in increased survival and reduced tumor incidence because of impaired tumor cell proliferation. In addition, inhibition of PRL2 with a small-molecule inhibitor phenocopies the effect of genetic deletion of Prl2 and reduces Tp53 deficiency–induced tumor growth. Taken together, the results further establish PRL2 as a negative regulator of PTEN and highlight the potential of PRL2 inhibition for PTEN augmentation therapy in cancers with wild-type PTEN expression.

Significance:
Prl2 deletion attenuates Tp53 deficiency–induced tumor growth by increasing PTEN and reducing Akt activity. Targeting Tp53-null lymphoma with PRL inhibitors lead to reduced tumor burden, providing a therapeutic approach via PTEN augmentation.
Generation and Evolution of Internal Solitary Waves in a Coastal Plain Estuary
Authors: Li Renjian , Li Ming 
Published: December 2023

Abstract
Large-amplitude internal solitary waves were recently observed in a coastal plain estuary and were hypothesized to evolve from an internal lee wave generated at the channel–shoal interface. To test this mechanism, a 3D nonhydrostatic model with nested domains and adaptive grids was used to investigate the generation of the internal solitary waves and their subsequent nonlinear evolution. A complex sequence of wave propagation and transformation was documented and interpreted using the nonlinear wave theory based on the Korteweg–de Vries equation. During the ebb tide a mode-2 internal lee wave is generated by the interaction between lateral flows and channel–shoal topography. This mode-2 lee wave subsequently propagates onto the shallow shoal and transforms into a mode-1 wave of elevation as strong mixing on the flood tide erases stratification in the bottom boundary layer and the lower branch of the mode-2 wave. The mode-1 wave of elevation evolves into an internal solitary wave due to nonlinear steepening and spatial changes in the wave phase speed. As the solitary wave of elevation continues to propagate over the shoaling bottom, the leading edge moves ahead as a rarefaction wave while the trailing edge steepens and disintegrates into a train of rank-ordered internal solitary waves, due to the combined effects of shoaling and dispersion. Strong turbulence in the bottom boundary layer dissipates wave energy and causes the eventual destruction of the solitary waves. In the meantime, the internal solitary waves can generate elevated shear and dissipation rate in local regions.

Significance Statement
In the coastal ocean nonlinear internal solitary waves are widely recognized to play an important role in generating turbulent mixing, modulating short-term variability of nearshore ecosystem, and transporting sediment and biochemical materials. However, their effects on shallow and stratified estuaries are poorly known and have been rarely studied. The nonhydrostatic model simulations presented in this paper shed new light into the generation, propagation, and transformation of the internal solitary waves in a coastal plain estuary.
The National Resident Matching Program: An Outdated Business Model Due for Reform
Authors: Nasef Hazem , Awan Muhammad Usman , Hernandez Nickolas , Cruz Francis , Havron Will , Elkbuli Adel 
Published: December 2023

Introduction This study aims to examine the trends across the entire NRMP application cycles from 2007-2008 to 2022-2023, specifically exploring trends across competitive surgical specialties to assess the efficacy of the existing NRMP business model and provide evidence-based recommendations to better address the current needs of both applicants and programs. Methods A cross-sectional study exploring the trends in the mean number of applicants and mean number of total ranked positions per applicant across surgical, the top 5 most competitive surgical specialties, and non-surgical specialties from 2007-2008 to the 2022-2023 match cycles utilizing data from the NRMP database. Results Over the studied 16 match cycles, the mean number of applicants to surgical specialties has increased by 47.99% and the mean number of total ranked positions per applicant has increased by 88.07%. For the top 5 most competitive specialties, the mean number of applicants has increased by 57.66% and the mean number of total ranked positions per applicant has increased by 83.33%. Conclusion Trends across the 16 most recent NRMP cycles show evidence of increased congestion in the match system, the burden of which is primarily placed on applicants. Our findings support the need for drastic reform in the NRMP to relieve this burden, and we discuss practical solutions to allow the NRMP to better meet the needs of applicants and residency programs alike.
Cochlear Implantation in Children With a Long Average Duration of Single Sided Deafness
Authors: Colasacco Christine J. , Morgan Samantha , Bornstein Rivka , Drugge Elizabeth , Stidham Katrina R. 
Published: December 2023

Objectives: Previous research has shown the positive effects of cochlear implantation in children with a short duration of single sided deafness (SSD). This case series assessed the impact of cochlear implantation in a cohort of children with a longer average duration of SSD. Methods: A retrospective chart review of 6 children who received a cochlear implant for SSD. The mean age at time of cochlear implantation was 14.7 years old (median = 15.5, interquartile range (IQR) = 2.5) and mean duration of hearing loss before cochlear implantation was 10.8 years (median = 11.5, IQR = 5.3). Pre- and post-operative audiometric data for aided speech perception testing, sentence recognition in quiet, sentence recognition in noise, and word recognition scores were analyzed. Results: When compared to preoperative hearing aid scores a 24% significant increase in median word score and a 64% significant increase in median sentence recognition score in quiet was observed at 12 months post-op. Conclusion: Cochlear implantation in children with a longer duration of SSD can provide benefit to speech recognition. Lay Summary: This retrospective case series of children with prolonged single sided deafness demonstrated an improvement in word and sentence recognition within 12 months of receiving a cochlear implant.
Decision-making in Choosing an Effective Celebrity Endorsement Strategy Using Fuzzy Forgotten Effects: A Cross-cultural Study
Authors: Patel Karan , Arroyo-Cañada Francicso-Javier , Gil-Lafuente Jaime 
Published: December 2023

The main purpose of this study is to develop models that illustrate the impact of celebrity endorsement on consumer purchase intention, taking into consideration the important dimension of culture: individualism (Spain) versus collectivism (India). The study utilises the analytical model of the fuzzy forgotten effects theory to build a model for decision-making in choosing an effective parameter that affects consumer purchase intentions with respect to celebrity endorsement across two distinct cultures. These models provide insights into the impact of celebrity endorsement over time and across different stages of the consumer decision-making process. The contributions of this research will help marketers to select appropriate celebrity parameters for celebrity endorsements across varied cultures, which would be fruitful for the brand in the long term. This research will also draft a framework for branding managers that can be adopted by companies to increase profitability. This paper applies the theory of forgotten effects with the analysis of cause and effect in the field of marketing. The main contribution of this article is that it allows the second-generation effects to be considered during the decision-making process, which could go unnoticed by decision-makers at first, thereby reducing the risks associated with decision-making. JEL Codes: M31, C02
Demand for Maternal Health Inputs in Eastern States of India
Authors: Roy Ramananda , Bhattacharyya Bhaskar , Mandal Biswajit 
Published: December 2023

Using NFHS-4 data, this study explores the determinants of maternal health care programmes for eastern states of India, which include prenatal care and hospital delivery. To reduce unobserved heterogeneity in the analysis, we employed the Full Information Likelihood Method, also known as the Joint Estimation Technique, in conjunction with individual probit models. Like other studies, we found place of residence, wealth, caste, religion and level of education as significant contributor for demand for both services. But, unlike earlier studies, we found that women’s age increases the use of prenatal care and hospital delivery, and the child’s birth order influences getting prenatal care. To increase the utilisation of maternal health care services, we recommend investing in health infrastructure, increasing the Janani Suraksha Yojana (JSY) subsidy amount and coverage of the Janani Shishu Suraksha Karyakram (JSSK) scheme, and promoting awareness about various government programmes among women through the Accredited Social Health Activists (ASHAs). JEL Codes: I140, I150, I180, O150