bluuebunny/crossref_metadata_2025_split huggingface dataset:
Kidney Transplantation Outcomes From Uncontrolled Donation After Circulatory Death: A Systematic Review and Meta-analysis
Authors: Vijayan Keshini , Schroder Hugh J. , Hameed Ahmer , Hitos Kerry , Lo Warren , Laurence Jerome M. , Yoon Peter D. , Nahm Christopher , Lim Wai H. , Lee Taina , Yuen Lawrence , Wong Germaine , Pleass Henry 
Published: February 2024

Background.
Uncontrolled donation after circulatory death (uDCD) is a potential additional source of donor kidneys. This study reviewed uDCD kidney transplant outcomes to determine if these are comparable to controlled donation after circulatory death (cDCD).

Methods.
MEDLINE, Cochrane, and Embase databases were searched. Data on demographic information and transplant outcomes were extracted from included studies. Meta-analyses were performed, and risk ratios (RR) were estimated to compare transplant outcomes from uDCD to cDCD.

Results.
Nine cohort studies were included, from 2178 uDCD kidney transplants. There was a moderate degree of bias, as 4 studies did not account for potential confounding factors. The median incidence of primary nonfunction in uDCD was 12.3% versus 5.7% for cDCD (RR, 1.85; 95% confidence intervals, 1.06-3.23; P = 0.03, I2 = 75). The median rate of delayed graft function was 65.1% for uDCD and 52.0% for cDCD. The median 1-y graft survival for uDCD was 82.7% compared with 87.5% for cDCD (RR, 1.43; 95% confidence intervals, 1.02-2.01; P = 0.04; I2 = 71%). The median 5-y graft survival for uDCD and cDCD was 70% each. Notably, the use of normothermic regional perfusion improved primary nonfunction rates in uDCD grafts.

Conclusions.
Although uDCD outcomes may be inferior in the short-term, the long-term outcomes are comparable to cDCD.
Assessment of IgM DSAs in Transplant Recipients: Relationship to De Novo IgG DSAs and Risk for Antibody Rejection
Authors: Zhang Xiaohai , Jordan Stanley C. 
Published: February 2024

Background.
The presence of anti-HLA donor-specific antibodies (DSAs) is associated with antibody-mediated rejection (AMR) and inferior graft survival. However, recent data suggest that ~50% of AMR episodes are IgG DSA negative and possibly related to non-HLA DSAs. After the initial activation of B cells to alloantigen, IgM is the first immunoglobulin produced. In addition, both IgM and IgG isotopes can activate the classic complement pathway and induce complement-dependent cytotoxicity to allograft targets. Current practices focus on the assessment of IgG DSAs with little concern for the assessment of IgM DSAs.

Methods.
Here, we examined anti-HLA IgM in a cohort of 22 patients who developed de novo IgG DSAs by a modified single-antigen bead-based test.

Results.
We found IgM HLA DSAs developed before IgG DSAs. The median time from the detection of IgM DSAs to the appearance of de novo IgG DSAs was 461 d. Most patients had IgM DSAs against the same HLA-DQ antigens, for which IgG de novo DSAs were also later detected. IgM DSAs were detected in patients with biopsies suspected of AMR.

Conclusions.
The detection of IgM DSAs could be an early indicator of alloimmune responses to allografts before IgG de novo DSAs appear.
Abdominal Wall Tension and Early Outcomes after Posterior Component Separation with Transversus Abdominis Release: Does a “Tension-Free” Closure Really Matter?
Authors: Miller Benjamin T , Ellis Ryan C , Maskal Sara M , Petro Clayton C , Krpata David M , Prabhu Ajita S , Beffa Lucas RA , Tu Chao , Rosen Michael J 
Published: February 2024

BACKGROUND:
Ventral hernias result in fibrosis of the lateral abdominal wall muscles, increasing tension on fascial closure. Little is known about the effect of abdominal wall tension on outcomes after abdominal wall reconstruction. We aimed to identify an association between abdominal wall tension and early postoperative outcomes in patients who underwent posterior component separation (PCS) with transversus abdominis release (TAR).

STUDY DESIGN:
Using a proprietary, sterilizable tensiometer, the tension needed to bring the anterior fascial elements to the midline of the abdominal wall during PCS with TAR was recorded. Tensiometer measurements, in pounds (lb), were calibrated by accounting for the acceleration of Earth’s gravity. Baseline fascial tension, change in fascial tension, and fascial tension at closure were evaluated with respect to 30-day outcomes, including wound morbidity, hospital readmission, reoperation, ileus, bleeding, and pulmonary complications.

RESULTS:
A total of 100 patients underwent bilateral abdominal wall tensiometry, for a total of 200 measurements (left and right side for each patient). Mean baseline anterior fascial tension was 6.78 lb (SD 4.55) on each side. At abdominal closure, the mean anterior fascial tension was 3.12 (SD 3.21) lb on each side. Baseline fascial tension and fascial tension after PCS with TAR at abdominal closure were not associated with surgical site infection, surgical site occurrence, readmission, ileus, and bleeding requiring transfusion. The event rates for all other complications were too infrequent for statistical analysis.

CONCLUSIONS:
Baseline and residual fascial tension of the anterior abdominal wall do not correlate with early postoperative morbidity in patients undergoing PCS with TAR. Further work is needed to determine if abdominal wall tension in this context is associated with long-term outcomes, such as hernia recurrence.
CRM1 regulates androgen receptor stability and impacts DNA repair pathways in prostate cancer, independent of the androgen receptor
Authors: Kumar Rajendra , Mendonca Janet , Shetty Abhishek , Yang Yuhan , Owoyemi Olutosin , Wilson Lillian , Boyapati Kavya , Topiwala Deven , Thomas Naiju , Nguyen Huong , Luo Jun , Paller Channing J. , Denmeade Samuel , Carducci Michael A. , Kachhap Sushant K. 
Published: February 2024

AbstractAmong the known nuclear exportins, CRM1 is the most studied prototype. Dysregulation of CRM1 occurs in many cancers, hence, understanding the role of CRM1 in cancer can help in developing synergistic therapeutics. The study investigates how CRM1 affects prostate cancer growth and survival. It examines the role of CRM1 in regulating androgen receptor (AR) and DNA repair in prostate cancer. Our findings reveal that CRM1 influences AR mRNA and protein stability, leading to a loss of AR protein upon CRM1 inhibition. Furthermore, it highlights the involvement of HSP90 alpha, a known AR chaperone, in the CRM1-dependent regulation of AR protein stability. The combination of CRM1 inhibition with an HSP90 inhibitor demonstrates potent effects on decreasing prostate cancer cell growth and survival. The study further explores the influence of CRM1 on DNA repair proteins and proposes a strategy of combining CRM1 inhibitors with DNA repair pathway inhibitors to decrease prostate cancer growth. Overall, the findings suggest that CRM1 plays a crucial role in prostate cancer growth, and a combination of inhibitors targeting CRM1 and DNA repair pathways could be a promising therapeutic strategy.
Enhanced Fc Receptor expression and distinct immunomodulatory properties of neutrophils during HIV-1 infection and therapy
Authors: Marsile-Medun Soledad , Souchard Manon , Abba Moussa Daouda , Lorin Valérie , Mouquet Hugo , Reynaud Elisa , Dibsy Rayane , Tuaillon Edouard , Muriaux Delphine , Ngo Giang , Pugnière Martine , Naranjo-Gomez Mar , Pelegrin Mireia 
Published: February 2024

AbstractNeutrophils are innate immune cells that display multiple immunomodulatory properties. Using a mouse model of retroviral infection, we previously uncovered their key immunomodulatory function in promoting protective immunity during antiviral antibody therapy, which occurs through Fc-FcγR interactions. Here, we investigated the immunomodulatory properties of neutrophils in the context of HIV-1 infection and therapy. We conducted a thorough examination of the functional activation and modulation of Fcγ receptors (FcγRs) expression on neutrophils isolated from healthy donors (HD) and people living with HIV-1 (PLWH). Upon stimulation with virions, either free or in the form of immune complexes (ICs) formed with broadly neutralizing antibodies (bNAbs), neutrophils from HD secreted cytokines and chemokines in modest quantities. Interestingly, priming HD neutrophils with pro-inflammatory cytokines augmented their chemokine production upon exposure to HIV-1 and ICs, underscoring the pivotal role of the inflammatory milieu in eliciting a functional response from neutrophils to these stimuli. Noteworthy, under inflammatory conditions, IC-activated neutrophils showed higher secretion of CXCL1 and CCL4 than HIV-1-stimulated neutrophils. Highlighting the critical influence of the inflammatory environment on their functional properties, neutrophils from PLWH displayed increased release of cytokines (IFNγ) and chemokines (CXCL1, CCL2, CCL3 and CCL4) when stimulated with danger signals associated with HIV-1 infection. In addition, PLWH’s neutrophils exhibited higher expression of two activating FcgRs (FcgRI and FcgRIII) than neutrophils from HD. Our study provides new insights into the immunomodulatory properties of neutrophils during HIV-1 infection and therapy. These findings hold potential for optimizing antiviral antibody therapies by harnessing the immunomodulatory properties of neutrophils.
SIMHYB 2: a software tool to explore and illustrate evolutionary forces in Population Genetics teaching and research. Application to Conservation Genetics
Authors: Soto Álvaro , Rodríguez-Martínez David , López de Heredia Unai 
Published: February 2024

ABSTRACTPractical approaches have become a standard in many scientific disciplines, including population genetics. By analyzing properly selected datasets, the students can calculate parameters and draw conclusions about genetic diversity, differentiation and evolution of populations with higher efficiency than if based exclusively on theoretical lessons. However, preparing the appropriate datasets is a hard task and a wrong selection can spoil a well-aimed practice. Here we present SimHyb2, a software tool specifically intended to ease the full understanding of evolutionary forces by the students and to help the teacher to prepare adequate datasets and examples for the practices. It simulates the course of a mixed population under user-defined reproductive and evolutionary conditions. Outputs can be easily adapted for downstream analysis with other popular tools as GenAlExor Structure. Thus, SimHyb2 is very suitable for project-based-learning approaches: students can produce their own datasets in different scenarios of genetic drift, migration, selective advantage, reproductive success… Additionally, SimHyb2 is the only simulation software available to date providing traceable pedigrees of individuals, being therefore very convenient for preparing datasets for parentage analysis, spatial genetic structure or conservation genetics study cases. Satisfactory results from its ongoing utilization in higher education and research are reported.
Structural enrichment attenuates colitis-associated colon cancer
Authors: Sykes Delawrence J. , Solanki Sumeet , Chukkapalli Sahiti , Williams Keyonna , Newman Erika A. , Resnicow Kenneth , Shah Yatrik M 
Published: February 2024

AbstractColorectal cancer (CRC) is a major public health concern and disproportionately impacts racial/ethnic minority populations in the US. Animal models are helpful in examining human health disparities because many stress-induced human health conditions can be recapitulated using mouse models. Azoxymethane (AOM)/ dextran sodium sulfate (DSS) treatment can be used to model colitis-associated cancers. While colitis-associated cancers account for only 2% of colon cancers, the AOM/DSS model is useful for examining links between inflammation, immunity, and colon cancer. Mice were housed in enriched and impoverished environments for 1-month prior to behavioral testing. Following behavioral testing the mice were subjected to the AOM/DSS model. While our analysis revealed no significant behavioral variances between the impoverished and enriched housing conditions, we found significant effects in tumorigenesis. Enriched mice had fewer tumors and smaller tumor volumes compared to impoverished mice. African Americans are at higher risk for early onset colorectal cancers in part due to social economic status. Furthermore, housing conditions and environment may reflect social economic status. Research aimed at understanding links between social economic status and colorectal cancer progression is important for eliminating disparities in health outcomes.
INTREPPPID - An Orthologue-Informed Quintuplet Network for Cross-Species Prediction of Protein-Protein Interaction
Authors: Szymborski Joseph , Emad Amin 
Published: February 2024

AbstractAn overwhelming majority of protein-protein interaction (PPI) studies are conducted in a select few model organisms largely due to constraints in time and cost of the associated “wet lab” experiments.In silicoPPI inference methods are ideal tools to overcome these limitations, but often struggle with cross-species predictions. We present INTREPPPID, a method which incorporates orthology data using a new “quintuplet” neural network, which is constructed with five parallel encoders with shared parameters. INTREPPPID incorporates both a PPI classification task and an orthologous locality task. The latter learns embeddings of orthologues that have small Euclidean distances between them and large distances between embeddings of all other proteins. INTREPPPID outperforms all other leading PPI inference methods tested on both the intra-species and cross-species tasks using strict evaluation datasets. We show that INTREPPPID’s orthologous locality loss increases performance because of the biological relevance of the orthologue data, and not due to some other specious aspect of the architecture. Finally, we introduce PPI.bio and PPI Origami, a web server interface for INTREPPPID and a software tool for creating strict evaluation datasets, respectively. Together, these two initiatives aim to make both the use and development of PPI inference tools more accessible to the community.GRAPHICAL ABSTRACT
Cell Size Controls Photosynthetic Capacity in a Mesoamerican and an Andean Genotype ofPhaseolus vulgarisL
Authors: Egesa Andrew Ogolla , Eduardo Vallejos C. , Begcy Kevin 
Published: February 2024

AbstractThe efficiency of CO2flux in the leaf is hindered by a several structural and biochemical barriers which affect the overall net photosynthesis. However, the dearth of information about the genetic control of these features is limiting our ability for genetic manipulation. We performed a comparative analysis between a Mesoamerican and an Andean cultivar ofPhaseolus vulgarisat variable light and CO2levels. The Mesoamerican bean had higher photosynthetic rate, maximum rate of rubisco carboxylase activity and maximum rate of photosynthetic electron transport at light saturation conditions than its Andean counterpart. Leaf anatomy comparison between genotypes showed that the Mesoamerican bean had smaller cell sizes than the Andean bean. Smaller epidermal cells in the Mesoamerican bean resulted in higher stomata density and consequently higher stomatal conductance for water vapor and CO2than in the Andean bean. Likewise, smaller palisade and spongy mesophyll cells in the Mesoamerican than in the Andean bean increased the cell surface area per unit of volume and consequently increased mesophyll conductance. Finally, smaller cells in the Mesoamerican also increased chlorophyll and protein concentration per unit of leaf area. In summary, we show that differential cell size controls the overall net photosynthesis and could be used as a target for genetic manipulation to improve photosynthesis.HighlightPhotosyntheUc performance comparison between a Mesoamerican and an Andean bean genotype showed higher rate at increased light and CO2levels. Differences could be explained by variaUon in cell size.
Neuroestrogens facilitate male-typical behaviors by potentiating androgen receptor signaling in medaka
Authors: Nishiike Yuji , Maki Shizuku , Miyazoe Daichi , Nakasone Kiyoshi , Kamei Yasuhiro , Todo Takeshi , Ishikawa-Fujiwara Tomoko , Ohno Kaoru , Usami Takeshi , Nagahama Yoshitaka , Okubo Kataaki 
Published: February 2024

AbstractIn rodents, estrogens aromatized from androgens in the brain, also known as neuroestrogens, are essential for the development of male-typical behaviors. In many other vertebrates including humans and teleost fish, however, androgens facilitate these behaviors directly via the androgen receptor without aromatization into estrogens. Here we report that male medaka fish lacking Cyp19a1b (a subtype of aromatase predominantly expressed in the brain) exhibit severely impaired male-typical mating and aggression, despite elevated brain androgen levels. These phenotypes can be rescued by estrogen administration, indicating that neuroestrogens are pivotal for male-typical behaviors even in non-rodents. Our results further suggest that neuroestrogens facilitate male-typical behaviors by potentiating androgen action in the brain via the direct stimulation of androgen receptor transcription, thereby revealing a previously unappreciated mechanism of action of neuroestrogens. We additionally show that female fish lacking Cyp19a1b are less receptive to male courtship and conversely court other females, highlighting the significance of neuroestrogens in establishing sex-typical behaviors in both sexes.
The Interaction of NF-κB Transcription Factor with Centromeric Chromatin
Authors: Filliaux Shaun , Bertelsen Chloe , Baughman Hannah , Komives Elizabeth , Lyubchenko Yuri L. 
Published: February 2024

ABSTRACTCentromeric chromatin is a subset of chromatin structure and governs chromosome segregation. The centromere is composed of both CENP-A nucleosomes (CENP-Anuc) and H3 nucleosomes (H3nuc) and is enriched with alpha-satellite (α-sat) DNA repeats. These CENP-Anuchave a different structure than H3nuc, decreasing the base pairs (bp) of wrapped DNA from 147 bp for H3nucto 121 bp for CENP-Anuc. All these factors can contribute to centromere function. We investigated the interaction of H3nucand CENP-Anucwith NF-κB, a crucial transcription factor in regulating immune response and inflammation. We utilized Atomic Force Microscopy (AFM) to characterize complexes of both types of nucleosomes with NF-κB. We found that NF-κB unravels H3nuc, removing more than 20 bp of DNA, and that NF-κB binds to the nucleosomal core. Similar results were obtained for the truncated variant of NF-κB comprised only of the Rel Homology domain and missing the transcription activation domain (TAD), suggesting the RelA TAD is not critical in unraveling H3nuc. By contrast, NF-κB did not bind to or unravel CENP- Anuc. These findings with different affinities for two types of nucleosomes to NF-κB may have implications for understanding the mechanisms of gene expression in bulk and centromere chromatin.
The p300 KAT inhibitor, A-485, inhibits melanogenesis and melanin content in human melanocytes
Authors: Grbic Nicole , Waddell Aaron Richard , Leibowitz Kassidy , Wyant W. Austin , Collard Marianne , Alani Rhoda M. 
Published: February 2024

AbstractHyperpigmentation disorders are commonly diagnosed dermatologic conditions that can be cosmetically distressing for patients and cause negative psychosocial impacts. There is a need to better understand the underlying pathophysiology of pigmentary disorders as well as develop improvements in the management of these disorders. Here, we evaluated a p300 (CBP/p300) histone acetyltransferase (HAT) inhibitor, A-485, to determine if epigenetically targeting melanogenesis could be of therapeutic value. We find that A-485 treatment of primary human melanocytes and SK-MEL-30 melanoma cells drastically reduces the mRNA and protein expression of MITF and DCT, genes involved in melanin synthesis, and that this is accompanied by a reduction in melanin content. These results suggest that epigenetically targeting melanin synthesis with the A-485 p300 HAT inhibitor may be beneficial for the treatment of hyperpigmentation disorders.
Prosaposin is cleaved into saposins by multiple cathepsins in a progranulin-regulated fashion
Authors: Hodul Molly , Lane-Donovan Courtney , Mambou Edwina , Yang Zoe , Kao Aimee W. 
Published: February 2024

AbstractProsaposin (PSAP) is a lysosomal protein that plays a key role in sphingolipid metabolism. PSAP is cleaved into four bioactive disulfide-rich peptides, saposins A, B, C, and D, that catalyze sphin-golipidases to promote sphingolipid breakdown. Considering the key role of PSAP and saposins in sphingolipid metabolism and the existence of genetic mutations in PSAP associated with juve-nile-onset lysosomal storage and adult-onset neurodegenerative diseases, maintaining optimal levels of PSAP and saposins is crucial for proper lysosomal function and sphingolipid homeosta-sis. Despite this, the mechanism by which saposins are released from PSAP, and thus available to modulate sphingolipidases, sphingolipid homeostasis, and downstream lysosomal function, is not well understood. Here, we performed a comprehensive study to identify lysosomal enzymes which regulate prosaposin cleavage into saposins.In vitrocleavage assays identified multiple enzymes that can process human prosaposin into multi- and single-saposin fragments in a pH-dependent manner. We confirmed the role of cathepsins D and B in PSAP processing and showed that these and several previously unidentified lysosomal proteases (cathepsins E, K, L, S, V, G and AEP/LGMN) are able to process PSAP in distinctive, pH-dependent manners. In addition, we have demonstrated a novel role for progranulin (PGRN) in the regulation of PSAP cleavage. We found that PGRN and multi-granulin fragments (MGFs) directly regulate the cleavage of PSAP by cathepsin D. With this study, we have identified that multiple cathepsins, PGRN and MGFs work in concert to produce saposins under different conditions, which could present novel opportunities to modulate saposin levels in disease.
The flow of reward information through neuronal ensembles in the accumbens
Authors: Arroyo Benjamin , Hernandez-Lemus Enrique , Gutierrez Ranier 
Published: February 2024

SummaryReward information flows through neuronal ensembles in the nucleus accumbens shell (NAcSh), influencing decision-making. We investigated this phenomenon by training rats in a self-guided probabilistic choice task while recording single-unit activity in the NAcSh. We found that rats dynamically adapted their choices based on an internal representation of reward likelihood. Neuronal ensembles in the NAcSh act as dynamic modules to process different aspects of reward-guided behavior. Ensembles dynamically change composition and functional connections throughout reinforcement learning. The NAcSh forms a highly connected network with a heavy-tailed distribution and neuronal hubs, facilitating efficient reward information flow. Reward delivery evokes higher mutual information between ensembles and unifies network activity, while omission leads to less synchronization. Our recordings shed light on how reward information propagates through dynamically changing ensembles of neurons in the NAcSh. These functional ensembles exhibit flexible membership, dropping in and out and even shrinking in number as the rat learns to obtain (energy) rewards in an ever-changing environment.Graphical Abstract