bluuebunny/crossref_metadata_2025_split huggingface dataset:
Missing History: Anarcha, Betsey, and Lucy’s Legacy in Gynecologic Textbooks
Authors: Lee Jennifer H. , Sanchez Ciara , Johnson Bria , Woodburn Katherine L. , Iglesia Cheryl B. 
Published: October 2024

Abstract
The legacy of J. Marion Sims as the “father of gynecology” has become widely controversial among medical professionals and lay public because of ethical concerns surrounding the development of his surgical techniques and his exploitation of enslaved women for his experiments. Notably, in April 2018, the City of New York relocated a commemorative statue of Sims from Central Park following an art commission’s investigation of his controversial practices. The relocation was viewed by many as a public acknowledgement of the contributions of Anarcha, Betsey, Lucy, and the other enslaved women to the advancement of gynecologic surgery. However, despite the increased public awareness of the women’s sacrifices in recent years medical literature has not kept pace. We compared the portrayal of Sims and these enslaved women within current gynecology textbooks, prior editions, and historical medical literature. We found that gynecologic textbooks more often mention J. Marion Sims by name (74%) compared to the enslaved women he experimented on (24%). Neither current gynecologic surgery textbooks nor primary historical sources contain significant references to these women, meaning much of their story has been lost to history. While there has been increased public knowledge of the sacrifices of Anarcha, Betsey, and Lucy and other enslaved women, lay recognition is not enough. Full acknowledgment of their contributions necessitates crediting their roles in Sims’ experiments and stating their names in medical literature.
Protein profile of the Escherichia coli strain, BW25113, exposed to two novel iron-halide compounds: Fe(Hampy)2Cl4 and Fe(Hampy)2Br4.
Authors: Abedin Nusrat , Wagner Sarah , Khalkar Yukta Sanjay , Johnson Zulekha , Egbowon Biola F. , Hargreaves Alan J. , Fitzpatrick Anthony J. , Miles Amanda K. , Dafhnis-Calas Felix 
Published: October 2024

The mortality rate and economic burden of infections caused by antimicrobial resistant pathogens are increasingly higher. This frustrating scenario emphasizes the urgent need for developing new antimicrobial drugs. We have previously addressed this problem by studying the antimicrobial activity of two novel iron-halide complexes, Fe(Hampy)2Cl4 (iron-tetrachloride) and Fe(Hampy)2Br4 (iron-tetrabromide). Both compounds showed bactericidal and antibiofilm activities against bacteria with an antimicrobial resistance phenotype. Herein, we used a proteomics approach to investigate the protein-expression profile of bacterial cells previously exposed to both iron-halide complexes. For this study, the Escherichia coli strain, BW25113, was used as a model to facilitate the rapid identification of deregulated proteins. Heat map analysis of the common deregulated proteins highlighted that both complexes caused downregulation of proteins associated with key metabolic pathways, biofilm formation, cell-envelope biogenesis, and iron ion binding. In addition, network study suggested that the most influential proteins of the tetrachloride activity were those involved in TCA cycle, oxidative phosphorylation, iron ion homeostasis and carbon/secondary metabolism. This protein-protein interaction analysis also hinted that the main drivers of the tetrabromide activity were proteins involved in translation, ribosomal biogenesis, and cell motility. The above results strongly suggested how the presence of different halide ligands could be used to generate compounds with potentially different molecular mechanisms. Importantly, the findings of this study can also be used as a reference to compare with the protein profile of a bacteria exposed to future variants of the iron-halide complexes.
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Authors: Lavoie Noemie C , Poulain Alexandre J 
Published: October 2024

Redox reactions determine the availability of mercury species, HgII and Hg0, to anaerobic microbes responsible for the methylation of inorganic Hg into toxic methylmercury. Certain anaerobes also play an important role in Hg cycling in methylation hot spots by reducing HgII to its gaseous elemental form Hg0, yet their contributions remain unquantified due to a paucity of mechanistic information or genetic targets. In this work, we sought to uncover further mechanistic details on anaerobic HgII reduction by the versatile anoxygenic photoheterotroph and fermenter Heliomicrobium modesticaldumIce1. Due to HgII’s electrophilic attraction to thiols, we hypothesized that cellular thiol groups are likely interaction sites involved in HgII reduction. We exposed H. modesticaldum to the thiol-alkylating agent N-ethylmaleimide to irreversibly bind to thiols and found a concentration-dependent inhibition of Hg0 production during anoxygenic photoheterotrophy and fermentation. We propose updated insights into Heliobacterial HgII reduction where HgII-thiol interactions are a key step of the mechanism and discuss potential enzymatic coupling sites that merit further investigation.
Tracking gonadotropin-releasing hormone-mediated movement in-vivo using quantum dot nanoparticles: insights into pathways leading to sperm release
Authors: Julien A.R. , Kouba A.J. , Kabelik D. , Feugang J.M. , Willard S.T. , Kouba C.K. 
Published: October 2024

AbstractAs the number of conservation breeding programs for at-risk amphibians increase, application of assisted reproductive technologies (ARTs) has likewise grown, with hormone therapy being the most widely utilized technique. Significant interest has been raised for viable alternatives to traditional intracelomic injection for hormone treatment that may be simpler, require less hormone, induce a faster response and be more suitable for animals of different sizes or for minimal contact. We utilized quantum dot (QD) nanoparticles conjugated to GnRHa (GnRHa-QDs) as a means of monitoring exogenous GnRHa dispersal through living Fowler’s toads to investigate how delivery route may affect hormone pathway and efficacy after intracelomic, nasal, and oral administration. Real-time GnRHa-QD movement was tracked using in vivo imaging while hormone binding and QD aggregation were validated using fluorescence microscopy and measurements of spermiation responses following the administration of unconjugated GnRHa, unconjugated QDs, and GnRHa-QDs GnRHa alone was found to induce spermiation in 58.3%, 76.9% and 92.3% of males when administered by intracelomic, oral and nasal routes, respectively. When given through intracelomic injection GnRHa-QD caused spermiation and dispersed throughout the abdominal cavity to then aggregate within the brain, heart, liver, gastrointestinal (GI) tract, kidneys, and testes while unconjugated QDs did not. By contrast, GnRHa-QDs administered by oral or nasal routes were observed moving to the tympanic membrane and down the throat to the GI tract of the toads, but only nasal-administered GnRHa-QDs showed organ aggregation and were only found in the kidneys. Unconjugated QDs exhibited similar in vivo signal dispersal as their conjugated counterparts initially but did not aggregate in any organs over time nor induce spermiation. Through the use of novel QD hormone conjugates, in vivo imaging, and histology we were able to gain insight into how hormone pathways and efficacy might be impacted by delivery route which result in variations in physiological response to hormone treatment.
Well-resolved phylogeny supports repeated evolution of keel flowers as a synergistic contributor to papilionoid legume diversification
Authors: Cai Liming , Cardoso Domingos , Tressel Lydia G. , Lee Chaehee , Shrestha Bikash , Choi In-Su , de Lima Haroldo C. , de Queiroz Luciano P. , Ruhlman Tracey A. , Jansen Robert K. , Wojciechowski Martin F. 
Published: October 2024

SummaryThe butterfly-shaped keel flower is a highly successful floral form in angiosperms. These flowers steer the mechanical interaction with bees and thus are hypothesized to accelerate pollinator-driven diversification. The exceptionally labile evolution of keel flowers in Papilionoideae (Fabaceae) provides a suitable system to test this hypothesis.Using 1,456 low-copy nuclear loci, we confidently resolve the early divergence history of Papilionoideae. Constrained by this backbone phylogeny, we generated a time tree for 3,326 Fabales to evaluate the tempo and mode of diversification within a state-dependent evolutionary framework.The first keel flowers emerged around 59.0 Ma in Papilionoideae, predating the earliest fossil by 3–4 million years. The Miocene diversification of Papilionoideae coincided with rapid evolution of keel flowers. At least six independent origins and thirty-two losses of keel flowers were identified in Papilionoideae, Cercidoideae, and Polygalaceae. However, the state-dependent diversification model was not favored.Lack of radiation associated with keel flowers suggests that diversification within Papilionoideae was not solely driven by pollinator-mediated selection, but instead an outcome of the synergistic effects of multiple innovations including nitrogen fixation and chemical defense as well as dispersal into subtropical and temperate regions.
Repertoire, function, and structure of serological antibodies induced by the R21/Matrix-M malaria vaccine
Authors: McDaniel Jonathan R. , Voss William N. , Bowyer Georgina , Rush Scott A. , Spencer Alexandra J. , Bellamy Duncan , Ulaszewska Marta , Goike Jule , Gregory Scott , King C. Richter , McLellan Jason S. , Hill Adrian V.S. , Georgiou George , Ewer Katie J. , Ippolito Gregory C. 
Published: October 2024

ABSTRACTThe World Health Organization recently recommended the programmatic use of R21/Matrix-M vaccine forPlasmodium falciparummalaria prevention in children living in malaria-endemic areas. To determine its effects on humoral immunity, we conducted a proteomic analysis of polyclonal IgG antibodies directed against the NANP tetrapeptide of the circumsporozoite protein (CSP) which comprises the vaccine’s core immunogen. In ten malaria-naïve adult volunteers, R21/Matrix-M induced polarized IgG anti-NANP repertoires, heavily skewed forIGHV3-30/3-33genes bearing minimal somatic mutation, which remained static in composition following a controlled human malaria infection challenge. Notably, these vaccine-generated antibodies cross-reacted with another protective CSP epitope, the N-terminal junction region, despite its absence from the R21 construct. NANP-specificIGHV3-30/3-33monoclonal antibodies mined from polyclonal IgG repertoires blocked sporozoite invasionin vitroand prevented parasitemiain vivo. Overall, R21/Matrix-M elicits polarized, minimally mutated, polyclonal IgG responses that can target multiple protective CSP epitopes, offering molecular insight into the serological basis for its demonstrated efficacy againstP. falciparummalaria.
Vispro improves imaging analysis for Visium spatial transcriptomics
Authors: Ma Huifang , Qu Yilong , Zhang Anru R. , Ji Zhicheng 
Published: October 2024

ABSTRACTSpatial transcriptomics (ST) enables the comprehensive analysis of gene expression while preserving the spatial context of tissues. The histological images accompanying ST data provide spatially cohesive information that is often challenging to capture through gene expression alone. However, analyzing such images is challenging due to the presence of fiducial markers and background regions, which can obscure important features and complicate downstream analysis. To address these challenges, we developed Vispro, an end-to-end, fully automated image processing tool tailored for 10x Visium data. Vispro integrates four key modules of fiducial marker detection, fiducial marker removal and image restoration, tissue region detection, and segmentation of disconnected tissue areas. We demonstrated that Vispro enhances the quality of ST images and improves the performance of downstream analyses, including tissue segmentation, cell segmentation, image registration, and histology-based gene imputation.
Inhibition of Androgen Receptor Exposes Replication Stress Vulnerability in Prostate Cancer
Authors: Williams Carly S. , Li Xin , Jang Hongjun , Anand Jay Ramanlal , Lim Won Young , Lee Hyejin , Parks Julie , Zhang Xingyuan , Xie Jialiu , Zhao Jinshi , Wu Di , Armstrong Andrew J. , Bowser Jessica L. , Zou Lee , Hong Jiyong , Somarelli Jason A. , Vaziri Cyrus , Zhou Pei 
Published: October 2024

AbstractStandard initial systemic treatment for patients with metastatic prostate cancer includes agents that target androgen receptor (AR) signaling. Despite an initial positive response to these AR pathway inhibitors (ARPIs), acquired resistance remains a significant challenge. We show that treatment of AR-positive prostate cancer cells with the frontline ARPI enzalutamide induces DNA replication stress. Such stress is exacerbated by suppression of translesion DNA synthesis (TLS), leading to aberrant accumulation of single-stranded DNA (ssDNA) gaps and persistent DNA damage biomarkers. We further demonstrate that the TLS inhibitor, JH-RE-06, markedly sensitizes AR-positive prostate cancer cells, but not AR-negative benign cells, to enzalutamidein vitro.Combination therapy with enzalutamide and JH-RE-06 significantly suppresses cancer growth in a syngeneic murine tumor model over vehicle control or individual treatment groups. These findings suggest that AR inhibition broadly triggers DNA replication stress in hormone-sensitive prostate cancer, thereby exposing a unique vulnerability that can be exploited by a TLS-disrupting adjuvant for targeted therapy.
Differences in Mean Diffusivity values in the Corona Radiata between patients with Alzheimer’s Disease and Healthy Controls
Authors: Asay Daniel J. , Hunsaker Naomi J. 
Published: October 2024

AbstractOur understanding of Alzheimer’s disease (AD) is at an all time high. Despite the progress being made, AD is currently irreversible and the number of confirmed cases continues to grow world wide. There is a need for deeper understanding of the course of Alzheimer’s and the development of more sensitive diagnostic tools. In the present study, we performedDTI and TBSS analyses of the Corona Radiata (CR) and Uncinate Fasciculus (UF) in the brain. We extracted MD and FA values of 10 AD patients and compared them to 16 healthy controls using ENIGMA DTI protocol. We also analyzed the Mini-mental state examination (MMSE) scores of each subject. We predict that patients with AD will have lower FA scores and higher MD values compared to healthy controls. We also predict that higher MD scores will be predictive of lower MMSE scores. The results indicate a significant difference in MD values in the CR between groups, which indicates greater axonal necrosis in the CR in patients with AD. However, FA values were not different between groups and patients with higher MD values did not have lower MMSE scores.These results indicate that axonal necrosis in the CR does not have a significant effect on executive functioning as measured by the MMSE. However, these results provide support to the notion of using DTI methodologies as a means of diagnosing AD.
Outbreak of Chikungunya Fever in the Central Valley of Chiapas, Mexico
Authors: Gonzalez-Perez Ana Luz , Vazquez Ana , de Ory Fernando , Negredo Anabel , Plante Kenneth S. , Plante Jessica A. , Palermo Pedro M. , Watts Douglas , Sanchez-Seco Maria Paz , Weaver Scott C. , Estrada-Franco Jose Guillermo 
Published: October 2024

AbstractChikungunya virus (CHIKV) was isolated from humans in an outbreak of a febrile illness during July and August 2015 in the central valleys of Chiapas, Mexico. Sera obtained from 80 patients were tested for CHIKV RNA by reverse transcriptase polymerase chain reaction (RT-PCR) and for IgM and IgG antibodies by an enzyme linked immunoassay and a commercial indirect immunofluorescence test for CHIKV and dengue virus (DENV). Of the 80 patients, 67 were positive, including 50 for RNA and 17 for IgM. In addition, one patient was coinfected with CHIKV-DENV and 40 patients were positive for IgG antibody to DENV. The clinical manifestations included a high fever, polyarthralgia, headache, myalgia, rash, digestive disorders, conjunctivitis, and adenopathy associated with cervical and axillary inguinal regions. Complete nucleotide sequences of two of the CHIKV isolates showed that they belonged to the Asian lineage but did not group with other Mexican CHIKV isolates from the Chiapas coast. Our findings documented that different Asian lineage strains of CHIKV were circulating simultaneously during the 2015 outbreak in the Central Valley of Chiapas, Mexico. The 2024 cases suggest an explosive scenario of re-emergence of thousands of new Chikungunya and dengue fever (DENF) cases associated with deaths, and a dangerous increase of the four DENV serotypes throughout the Americas, especially in South American countries that have shown a high influx of human migration to southern Mexico. In Mexico, the state of Chiapas and other southern regions are the most vulnerable.Author SummaryThe first ever recorded outbreak of Chikungunya virus (CHIKV) in the highlands (central valley of Chiapas) Mexico took place in 2015. Clinical data from 80 infected patients together with information provided from virus isolates offered a vision of the diseased and their response linked to different variables such as age, gender, association with pre-existing diseases of some patients, including CHIKF-DENF co-infection. The origins of the Tuxtla Gutierrez CHIKV viruses isolated in the study, including other Mexican isolates, were traced to viruses circulating in regions of Asia in Micronesia and Philippines. Also, we call the attention of the influx of migrants coming from countries having current explosive outbreaks of CHIKV and DENV in the Americas and into southern Mexico. Further we discuss vulnerabilities and point out specially to the geographic location of Chiapas State and its strategic position for attracting the human migrant population.
Effectiveness and Safety of Propofol at Low Doses for Emergency Department Treatment of Migraine
Authors: Côté Stéphane , Simonyan David , Mallet Myriam , Baril Simon , Ouellet Laurie , Berthelot Simon 
Published: October 2024

ABSTRACTIntroductionA migraine treatment protocol implemented in the emergency department of an urban hospital allowed us to evaluate the effectiveness of propofol compared to metoclopramide as well as the safety of the protocol.MethodsWe reviewed the health records of all patients aged 16 years and older treated with propofol for migraine between May 2014 and August 2017 at a teaching hospital in Québec City (CHUL). The care protocol consisted of administering propofol (20 mg) every 5–10 minutes as needed (up to 6 doses), monitoring vital signs before and after each dose and continuous cardiac monitoring. The primary outcome measure was the mean reduction of pain following first-line therapy (propofol or metoclopramide). The secondary outcome measures were 1) adjusted relative risks of requiring rescue medication after first-line therapy; 2) incidence of the following side effects of propofol received as first or second-line therapy: low arterial pressure (< 90 systolic or < 65 mean), desaturation, excessive sedation, arrhythmia. The cohorts were paired for gender, age, triage priority, and month/year of ED visit.ResultsFiles of 34 patients given propofol and 58 given metoclopramide as first-line treatment were analyzed. Five metoclopramide-treated patients received propofol as rescue medication. Among propofol-treated patients, 29.4% experienced pain relief compared to 66% in the metoclopramide group (p < 0.001). Rescue medication was more frequent in first-line propofol patients (82.4% versus 37.9%, p < 0.001). In this group, four participants (10.3%) received intravenous fluid bolus for mean blood pressure below 60, but no persistent desaturation, bradycardia, excessive sedation, or arrhythmia was recorded.ConclusionThough less effective than metoclopramide, propofol at low doses may be an alternative to treat migraine in the ED. Monitoring of vital signs (especially blood pressure) would be prudent but continuous nursing is likely unnecessary.
HospitalEnterococcus faeciumdemonstrates distinct environmental and patient reservoirs: a genomic point prevalence survey
Authors: Macesic Nenad , Cottingham Hugh , Wisniewski Jessica A. , Blakeway Luke V. , Theegala Ravali , Pragastis Katherine , Stewardson Andrew , Bass Pauline , Gritt Megan , Spilsbury Stephanie , Del Rosario-Kelly Denise , Dennison Amanda , Spelman Denis W. , Jenney Adam W.J. , Peleg Anton Y. 
Published: October 2024

AbstractObjectivesEnterococcus faeciumis a common cause of hospital-acquired infections and is associated with vancomycin resistance. The hospital environment is often a reservoir forE. faeciumdue to its ability to survive on surfaces. In 2019 we noted increasing prevalence ofvanA E. faeciumcausing bloodstream infections. We aimed to assess the hospital environment as a reservoir ofvanA E. faecium.MethodsWe conducted a point prevalence survey of the environment at the Alfred Hospital, Melbourne, Australia. We sampled all wards (n=12), 10 surface types and 357 surfaces. ResultingE. faeciumisolates underwent short-read whole genome sequencing and were compared to invasive infection (bloodstream) isolates. Thevanoperon, multi-locus sequence type (MLST) and core genome MLST (cgMLST) were determined.ResultsTwenty percent (73/357) of surfaces isolatedE. faeciumwith a median of 20% positivity per ward (IQR 11.6-30.6%).vanAandvanBwere detected in 12/73 (16%) and 58/73 (79%) environmental genomes, respectively. In contrast, a higher proportion of bloodstream isolates carriedvanA(32/72 [44%],P<0.001). Environmental genomes belonged to 10 MLSTs and 10 cgMLSTs, with ST796/ST78 accounting for 54/73 (74%) genomes. Clinical STs and cgMLSTs overlapped with environmental but were more diverse. We noted 13 putative genomic transmission clusters. One cluster contained 25/44 (57%)vanAgenomes, with the majority being clinical (22/26 genomes, 85%). Environmental-clinical links were observed in 292/895 (33%) putative genomic transmission links. In completed assemblies, thevanAandvanBoperons were located on pRE25-like plasmids and the chromosome, respectively.ConclusionWe noted a 20% prevalence ofE. faeciumenvironmental colonisation but thevanAoperon was detected in only 12/73 genomes. We identified distinct environmental and patient reservoirs, with most environmental genomes carrying thevanBoperon and having distinct STs/cgMLST clusters. Environment-clinical reservoir spillover was detected but accounted for a minority of putative transmission links.