bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vaccine hesitancy and other challenges to sexually transmitted infection vaccine acceptance
Authors: Footman Alison , Griner Stacey B. 
Published: November 2024

Purpose of review
Development of vaccines that protect against sexually transmitted infections (STIs), including for chlamydia, gonorrhea, and syphilis, has progressed greatly over the past decade. However, little research has been conducted to examine STI vaccine acceptance and hesitancy and how these factors may impact future uptake. This review examines literature that could provide additional insights into factors that would impact STI vaccine acceptance and hesitancy.

Recent findings
Vaccine hesitancy remains a threat to the uptake of future STI vaccines despite recent findings that highlight high levels of acceptability. Vaccine characteristics including side effects postvaccination and cost could impact future uptake of these vaccines. Accurate information about the benefits of vaccination and the vaccine development process could help to improve vaccine acceptance.

Summary
STI vaccine development is progressing, leading to great promise that a chlamydia, gonorrhea, or syphilis vaccine will one day be available. However, data is limited on factors that could impact vaccine acceptance, hesitancy, and uptake. This research is instrumental in creating policies, programming and vaccination campaigns that could impact acceptance and uptake along with affordability and accessibility. Additional research is needed to better promote STI vaccines.
Abdominal Fascial Plication and the Risk of Venous Thromboembolism in Abdominoplasty Patients
Authors: Swanson Eric 
Published: November 2024

Background
Repair of the abdominal fascia at the time of abdominoplasty is a valuable method to improve the contour of the abdomen. However, this maneuver has been linked to an increased risk of venous thromboembolism (VTE). This review was undertaken to evaluate the evidence.

Methods
An electronic literature review was conducted to identify publications on the subject of abdominal fascial repair during abdominoplasty and VTE risk. Key words included abdominoplasty, fascial plication, intra-abdominal pressure, and venous thrombosis.

Results
Three large clinical studies were identified. One retrospective study using matched comparisons reported nearly identical VTE rates for patients treated with and without abdominal fascial plication (1.5% vs 1.7%). Another retrospective study reported significantly more VTEs (2.3%) in abdominoplasty patients undergoing fascial repair compared with panniculectomy patients who did not undergo fascial plication (0.36%). The author also recommended a modified Caprini score, adding fascial repair as a risk factor. Only 1 prospective study reported a large number of consecutive plastic surgery outpatients evaluated with Doppler ultrasound. This group included 188 abdominoplasty patients, all treated with fascial plication and without muscle paralysis. Only 1 VTE was diagnosed on the day after abdominoplasty (0.5%).

Discussion
Retrospective studies are susceptible to confounders and confirmation bias. Caprini scores do not have a scientific foundation. Chemoprophylaxis increases the risk of bleeding without reducing the risk of VTE.

Conclusions
The best available evidence supports performing a fascial repair. An effective and safe alternative to Caprini scores and chemoprophylaxis is avoidance of muscle paralysis and early detection of VTEs using ultrasound screening.
Predicting whole-brain neural dynamics from prefrontal cortex fNIRS signal during movie-watching
Authors: Gao Shan , Nash Ryleigh , Burns Shannon , Leong Yuan Chang 
Published: November 2024

AbstractFunctional near-infrared spectroscopy (fNIRS) offers a portable, cost-effective alternative to functional magnetic resonance imaging (fMRI) for non-invasively measuring neural activity. However, fNIRS measurements are limited to cortical regions near the scalp, missing important medial and deeper brain areas. We introduce a predictive model that maps prefrontal fNIRS signals to whole-brain fMRI activity during movie-watching. By aligning neural responses to a common audiovisual stimulus, our approach leverages shared dynamics across imaging modalities to map fNIRS signals to broader neural activity patterns. We scanned participants with fNIRS and utilized a publicly available fMRI dataset of participants watching the same TV episode. The model was trained on the first half of the episode and tested on a held-out participant watching the second half to assess cross-individual and cross-stimulus generalizability. The model significantly predicted fMRI time courses in 66 out of 122 brain regions, including in areas otherwise inaccessible to fNIRS. The predicted fMRI time course also replicated intersubject functional connectivity patterns and retained semantic information about the movie content. Our publicly available model enables researchers to infer broader neural dynamics from localized fNIRS data, offering new opportunities for studying the neural basis of complex cognitive processes during naturalistic tasks.
A simple new alternative to the linear-quadratic model (and where the LQ model comes from)
Authors: Bilinsky L. M. 
Published: November 2024

AbstractI present a new dose-survival equation for fitting clonogenic assay data collected for irradiated cells, one motivated by the hypothesis that all cellular activities can be partitioned into two states (“state R” and “state Q”) which differ in their sensitivity to low-LET radiation. The LQ model can be derived from it by taking a Taylor expansion. The empirical observation that rapidly proliferating cancer cells have a straighter dose-survival relationship, while slowly proliferating cancer cells and normal cells have a curvier one featuring a shoulder region, is explained in terms of state R and state Q. The new equation (1) provides a convention for classifying cells as radioresistant, (2) provides a means of reducing, or possibly eliminating, cell cycle phase as a variable in treatment outcome, and (3) may enable standardization of the results reported for clonogenic assays. Finally, a novel hypothesis is offered for the “oxygen enhancement ratio” phenomenon.
Association of APOE gene polymorphisms and multiple risk factors with hypertension in middle-aged and elderly Tibetan population in Tibet on Bayesian network model
Authors: Zhang Yufei , Zhang Jing , Yao Yuan , Yan Jiaojiao , Chun Hua , Xiong Hai 
Published: November 2024

BACKGROUNDThe distribution of Apolipoprotein E (APOE) gene and its relationship with hypertension at high altitude in Tibet have not been elucidated. The purpose of this study was to understand the distribution of APOE genotypes and APOE rs7412, rs429358 genotypes in the middle-aged and elderly Tibetan population in Tibet, and to explore the related influencing factors by constructing a Bayesian network model of hypertension in middle-aged and elderly Tibetans.METHODSFrom November 2021 to November 2022, a multi-stage cluster random sampling method was employed to collect data from 511 middle-aged and elderly Tibetans residing in the Ali region, Nagqu City, and Shannan City of Tibet. The APOE gene, rs429358 and rs7412 single nucleotide polymorphisms (SNPs) were analyzed by fluorescence polymerase chain reaction (PCR). Multivariate logistic regression analysis and Bayesian Network (BN) were applied to examine the relationship between Covariates and hypertension.RESULTSAmong all subjects, the frequencies of genotypes ε2/ε3, ε2/ε4, ε3/ε3 and ε3/ε4 were 14.8%,1.8%,75.0%, and 8.4%, respectively. APOE gene rs7412 locus CC, CT and TT genotype frequencies were 83.4%, 0 and 16.6%, respectively, and rs429358 locus TT, TC and CC genotypes, genotype frequencies were 89.8%, 10.2% and 0. The results of this study indicated no correlation between APOE genotypes, APOE rs7412, rs429358 genotypes, and the prevalence of hypertension in middle-aged and elderly Tibetan population in Tibet. Sex, age, overweight obesity, hyperhomocysteinemia (HHcy) and High Altitude Pulmonary Edema (HAPC) represent direct risk factors for hypertension based on a Bayesian network.CONCLUSIONSAPOE genotype and APOE rs7412, rs429358 genotypes were not genetically correlated with hypertension in middle-aged and elderly Tibetan populations in Tibet. The Bayesian network model revealed the direct and indirect factors and the strength of the association of the hypertension. Additionally, it elucidated the complex network relationships among these factors, which provided a scientific basis for the early prevention of hypertension among middle-aged and elderly Tibetan populations in Tibet.
Optimizing Neoadjuvant Treatment Response Prediction for Triple-Negative Breast Cancer Using Clinical Trial Data and Deep Auxiliary Learning
Authors: Moon Chang In , Zhang Bing 
Published: November 2024

AbstractMotivationTriple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and poor prognosis. Developing predictive models for TNBC treatment responses is crucial but challenging due to data scarcity and the reliance on cell line data, which limits clinical translational value. Leveraging omics data from clinical trials, particularly through auxiliary learning, offers a potential solution to enhance predictive accuracy and reduce data requirements.ResultsIn this study, we propose a new approach utilizing deep auxiliary task reweighting learning methods to automatically reweight auxiliary tasks, thereby optimizing the performance of the primary task of predicting TNBC treatment responses. We benchmark various auxiliary learning methods, including ARML, AdaLoss, GradNorm, and OL AUX, against traditional supervised machine learning algorithms and single-task learning baselines. Our results characterize the performance of auxiliary learning across various contexts, including utilizing parallel treatment arms within a multi-arm clinical trial, leveraging treatment arms from different clinical trials, and integrating multiple arms with the same treatment regimens across separate clinical trials. The last scenario also provides an opportunity for validating prediction models on an independent dataset, demonstrating the superior performance of the auxiliary learning models in predicting pathological complete response (pCR) in TNBC patients treated with standardized combinational chemotherapy with Taxane, Anthracycline, and Cyclophosphamide (TAC).Availability and ImplementationSource code and additional resources can be accessed athttps://github.com/moonchangin/DeepAuxTxPred TNBC.
Unique pharmacology of mGlu homo- and heterodimers
Authors: McCullock Tyler W. , Couch Tyler , Kammermeier Paul J. 
Published: November 2024

AbstractBackground and PurposeMetabotropic glutamate receptors (mGlus) are obligate dimer G protein coupled receptors that can all homodimerize and heterodimerize in select combinations. Responses of mGlu heterodimers to selective ligands, including orthosteric agonists and allosteric modulators, are largely unknown.Experimental ApproachThe pharmacological properties of each group II and III mGlu homodimer (except mGlu6) and several heterodimers were examined when stochastically assembled in HEK293T cells, or specifically measured using an improved G protein mediated BRET assay employing complimented fragments of NanoLuciferase.ResultsStochastically assembled receptors adopted unique signaling characteristics. Some favored the potency, efficacy or signaling kinetics of a dominant subunit, while others exhibited blended profiles reflective of a combination of homo- and heterodimers at various ratios of expressed receptor. Finally, group II and III mGlu dimers were examined for responses to selective agonists and allosteric modulators. Effects of glutamate and selective group II and III orthosteric agonists were found to result in unique concentration response profiles when examining each combination of group II and II mGlu. Effects of select allosteric modulators were examined for each mGlu2 containing dimer as well as several group III dimer pairs. Likewise, allosteric modulator effects were often unique across dimers containing the targeted subunit of the ligand being tested.ConclusionsResults demonstrate that mGlu dimers respond uniquely to selective ligands, and show that the mGlu family is not governed by generalizable rules dictating consequences of dimeric subunit interactions leading to signaling consequences.
The evolutionary path of the epithelial sodium channel δ-subunit in Cetartiodactyla points to a role in sodium sensing
Authors: Zahnow Fynn , Jäger Chiara , Mohamed Yassmin , Vogelhuber Gianluca , May Fabian , Ciocan Alexandra Maria , Manieri Arianna , Maxeiner Stephan , Krasteva-Christ Gabriela , Cobain Matthew R. D. , Podsiadlowski Lars , Crespo-Picazo José Luis , García-Párraga Daniel , Althaus Mike 
Published: November 2024

AbstractThe epithelial sodium channel (ENaC) plays a key role in osmoregulation in tetrapod vertebrates and is a candidate receptor for salt taste sensation. There are four ENaC subunits (α, β, γ, δ) which form αβγ- or δβγ ENaCs. While αβγ-ENaC is a ‘maintenance protein’ controlling sodium and potassium homeostasis, δβγ-ENaC might represent a ‘stress protein’ monitoring high sodium concentrations. The δ-subunit emerged with water-to-land transition of tetrapod vertebrate ancestors. We investigated the evolutionary path of ENaC-coding genes in Cetartiodactyla, a group comprising even-toed ungulates and the cetaceans (whales/dolphins) which transitioned from terrestrial to marine environments in the Eocene. The genesSCNN1A(α-ENaC),SCNN1B(β-ENaC) andSCNN1G(γ-ENaC) are intact in all 22 investigated cetartiodactylan families. WhileSCNN1D(δ-ENaC) is intact in terrestrial Artiodactyla, it is a pseudogene in 12 cetacean families. A fusion ofSCNN1Dexons 11 and 12 under preservation of the open reading frame was observed in the Antilopinae, representing a new feature of this clade. Transcripts ofSCNN1A,SCNN1BandSCNN1Gwere present in kidney and lung tissues of Bottlenose dolphins, highlighting αβγ-ENaC’s role as a maintenance protein. Consistent withSCNN1Dloss, Bottlenose dolphins and Beluga whales did not show behavioural differences to stimuli with or without sodium in seawater-equivalent concentrations. These data suggest a function of δ-ENaC as a sodium sensing protein which might have become obsolete in cetaceans after the migration to high-salinity marine environments. Consistently, there is reduced selection pressure or pseudogenisation ofSCNN1Din other marine mammals, including sirenians, pinnipeds and sea otter.
Spatio-temporal T cell tracking for personalized TCR-T designs in childhood cancer
Authors: Sentís Inés , Melero Juan L. , Cebria-Xart Alex , Grzelak Marta , Soto Marta , Michel Alexandra , Rovira Quirze , Rodriguez-Hernandez Carlos J. , Caratù Ginevra , Urpi-Badell Andrea , Sauvage Christophe , Mendizabal-Sasieta Ana , Maspero Davide , Pascual-Reguant Anna , Muñoz Perez Juan Pablo , Mora Jaume , Harari Alexandre , Nieto Juan C. , Avgustinova Alexandra , Heyn Holger 
Published: November 2024

AbstractImmune checkpoint inhibition (ICI) has revolutionized oncology, offering extended survival and long-term remission in previously incurable cancers. While highly effective in tumors with high mutational burden, lowly mutated cancers, including pediatric malignancies, present low response rate and limited predictive biomarkers. Here, we present a framework for the identification and validation of tumor-reactive T cells as a biomarker to quantify ICI efficacy and as candidates for a personalized TCR-T cell therapy. Therefore, we profiled a pediatric malignant rhabdoid tumor patient with complete remission after ICI therapy using deep single-cell T cell receptor (TCR) repertoire sequencing of the tumor microenvironment (TME) and the peripheral blood. Specifically, we tracked T cell dynamics longitudinally from the tumor to cells in circulating over a time course of 12 months, revealing a systemic response and durable clonal expansion of tumor-resident and ICI-induced TCR clonotypes. We functionally validated tumor reactivity of TCRs identified from the TME and the blood by co-culturing patient-derived tumor cells with TCR-engineered autologous T cells. Here, we observed unexpectedly high frequencies of tumor-reactive TCR clonotypes in the TME and confirmed T cell dynamics in the blood post-ICI to predict tumor-reactivity. These findings strongly support spatio-temporal tracking of T cell activity in response to ICI to inform therapy efficacy and to serve as a source of tumor-reactive TCRs for personalized TCR-T designs.
Preclinical Evaluation of PTK7-Targeted Radionuclide Therapy
Authors: Lindland Kim , Westrøm Sara , Dragovic Srdan M. , Li Ruth Gong , Malenge Marion Masitsa , Ho Betty , Juzeniene Asta , Bønsdorff Tina Bjørnlund 
Published: November 2024

AbstractProtein tyrosine kinase 7 (PTK7), a receptor found in tumor-initiating cells, is expressed in various malignancies, including ovarian cancer. While PTK7 has been explored as a target for antibody-drug conjugates, this study is the first to investigate its potential for targeted radionuclide therapy. We developed a murine monoclonal IgG1 antibody (mOI-1) using hybridoma technology and generated a chimeric version (chOI-1) with human IgG1 constant regions. A cell-based screening approach using a library of 6100 cell surface proteins identified PTK7 as the target, confirmed by flow cytometry and surface plasmon resonance analyses. Immunohistochemistry showed strong PTK7 expression in ovarian cancer tissues, andin vitrostudies demonstrated specific binding and internalization of OI-1 in the ovarian cancer cell line SKOV-3-luc. Biodistribution studies using177Lu-DOTA-mOI-1 injected intravenously in xenograft mice with subcutaneous SKOV-3-luc revealed high tumor uptake and retention. Therapeutic efficacy was assessed by intraperitoneal treatment with212Pb-TCMC-chOI-1 in an intraperitoneal xenograft model, showing significant tumor growth inhibition compared to non-radioactive controls. This study provides the first proof-of-principle for using the PTK7-targeting OI-1 antibody as an antibody-radionuclide conjugate (212Pb-labeled), demonstrating its therapeutic potential in a preclinical model of intraperitoneal ovarian cancer. These results support further investigation of OI-1 as a candidate for targeted radionuclide therapy in PTK7-expressing cancers.
Innovative mutant screening identifiesTRANSPARENT TESTA7as a player in seed oil/protein partitioning
Authors: Lécureuil Alain , Corso Massimiliano , Boutet Stéphanie , Gall Sophie Le , Niñoles Regina , Gadea Jose , Guerche Philippe , Jasinski Sophie 
Published: November 2024

SummaryBrassicaceae species mainly accumulate oil and protein in their seeds, which are essential to human life as a source of food, but also as animal feed and resources for green chemistry. To date, Brassicaceae crops such as rapeseed have been selected mainly for their oil content. However, there is a growing interest in their seed protein content. A strong negative correlation between oil and protein content makes it difficult to increase both compounds simultaneously. In this study, anArabidopsis thalianahomozygous EMS mutant library was screened by near-infrared spectroscopy for seed oil and protein content, with the aim of identifying mutants with impaired oil-protein correlation. The mutant most affected in this correlation was found to be in theTRANSPARENT TESTA7gene, which is involved in the flavonoid biosynthetic pathway. Analysis of different mutants in the flavonoid pathway revealed that thett7mutants were the only ones to show such a significant reduction in seed oil content, highlighting a phenotype never described before for thett7mutants and suggesting a specific role for TT7 in the interplay between the oil and flavonoid biosynthetic pathways. Untargeted metabolomic analysis allowed the identification of metabolic features that are highly accumulated and specific tott7seeds compared to the other genotypes and genetic analysis established that the accumulation of kaempferol-3-O-rhamnoside seems to be responsible for the seed oil reduction oftt7mutants.Significance StatementBrassicaceae species accumulate oil and protein in their seeds and understanding how the partitioning of these compounds is regulated is necessary to engineer seeds for specific purposes. By screening an Arabidopsis EMS mutant library, we identified mutants affected in seed oil/protein partitioning, includingtt7, highlighting a link between oil and flavonoid biosynthetic pathways, that we explore further in this paper.
Spatially Resolvedin vivoCRISPR Screen Sequencing via Perturb-DBiT
Authors: Baysoy Alev , Tian Xiaolong , Zhang Feifei , Renauer Paul , Bai Zhiliang , Shi Hao , Li Haikuo , Tao Bo , Yang Mingyu , Enninful Archibald , Gao Fu , Wang Guangchuan , Zhang Wanqiu , Tran Thao , Patterson Nathan Heath , Bao Shuozhen , Dong Chuanpeng , Xin Shan , Zhong Mei , Rankin Sherri , Guy Cliff , Wang Yan , Connelly Jon P. , Pruett-Miller Shondra M. , Chi Hongbo , Chen Sidi , Fan Rong 
Published: November 2024

SUMMARYPerturb-seq enabled the profiling of transcriptional effects of genetic perturbations in single cells but lacks the ability to examine the impact on tissue environments. We present Perturb-DBiT for simultaneous co- sequencing of spatial transcriptome and guide RNAs (gRNAs) on the same tissue section for in vivo CRISPR screen with genome-scale gRNA libraries, offering a comprehensive understanding of how genetic modifications affect cellular behavior and tissue architecture. This platform supports a variety of delivery vectors, gRNA library sizes, and tissue preparations, along with two distinct gRNA capture methods, making it adaptable to a wide range of experimental setups. In applying Perturb-DBiT, we conducted un-biased knockouts of tens of genes or at genome-wide scale across three cancer models. We mapped all gRNAs in individual colonies and corresponding transcriptomes in a human cancer metastatic colonization model, revealing clonal dynamics and cooperation. We also examined the effect of genetic perturbation on the tumor immune microenvironment in an immune-competent syngeneic model, uncovering differential and synergistic perturbations in promoting immune infiltration or suppression in tumors. Perturb-DBiT allows for simultaneously evaluating the impact of each knockout on tumor initiation, development, metastasis, histopathology, and immune landscape. Ultimately, it not only broadens the scope of genetic inquiry, but also lays the groundwork for developing targeted therapeutic strategies.
Single cell analysis of Barrett’s esophagus and carcinoma reveals cell types conferring risk via genetic predisposition
Authors: Wenzel Marten C. , Giel Ann-Sophie , Plum Patrick S. , Hoppe Sascha , Franitza Marek , Jonas Christoph , Dasmeh Pouria , Thieme René , Zhao Yue , Heider Dominik , Palles Claire , Fitzgerald Rebecca Claire , Bruns Christiane J. , Buettner Reinhard , Quaas Alexander , Gockel Ines , Maj Carlo , Chon Seung-Hun , Schumacher Johannes , Hillmer Axel M. 
Published: November 2024

AbstractInherited genetic variants contribute to Barrett’s esophagus (BE) and esophageal adenocarcinoma (EAC) but it is unknown which cell types are involved in this process. We performed single cell RNA-sequencing of BE, EAC and paired normal tissues and integrated data of a genome-wide association study to determine cell type-specific genetic risk and cellular processes that contribute to BE and EAC. The analysis revealed that EAC development is driven to a greater extent by local cellular processes than BE development. One cell type of BE origin (BE-EAC) and cellular processes that control the differentiation of columnar cells are of particular relevance for EAC development. Further, specific subtypes of fibroblasts and endothelial cells contribute to BE and EAC development, while dendritic cells and CD4+ memory T cells contribute exclusively to BE development. The diagnostic use of markers characterizing the identified cell types and cellular processes should be explored in future for EAC prediction.