bluuebunny/crossref_metadata_2025_split huggingface dataset:
Last in first out: SIV proviruses seeded later in infection are harbored in short-lived CD4+T cells
Authors: Sambaturu Narmada , Fray Emily J. , Wu Fengting , Zitzmann Carolin , Simonetti Francesco R. , Barouch Dan H. , Siliciano Janet D. , Siliciano Robert F. , Ribeiro Ruy M. , Perelson Alan S. , Molina-París Carmen , Leitner Thomas 
Published: November 2023

HIV can persist in a latent form as integrated DNA (provirus) in resting CD4+T cells of infected individuals and as such is unaffected by antiretroviral therapy (ART). Despite being a major obstacle for eradication efforts, the genetic variation and timing of formation of this latent reservoir remains poorly understood. Previous studies on when virus is deposited in the latent reservoir have come to contradictory conclusions. To reexamine the genetic variation of HIV in CD4+T cells during ART, we determined the divergence in envelope sequences collected from 10 SIV infected rhesus macaques. We found that the macaques displayed a biphasic decline of the viral divergence over time, where the first phase lasted for an average of 11.6 weeks (range 4-28 weeks). Motivated by recent observations that the HIV-infected CD4+T cell population is composed of short- and long-lived subsets, we developed a model to study the divergence dynamics. We found that SIV in short-lived cells was on average more diverged, while long-lived cells harbored less diverged virus. This suggests that the long-lived cells harbor virus deposited starting earlier in infection and continuing throughout infection, while short-lived cells predominantly harbor more recent virus. As these cell populations decayed, the overall proviral divergence decline matched that observed in the empirical data. This model explains previous seemingly contradictory results on the timing of virus deposition into the latent reservoir, and should provide guidance for future eradication efforts.Significance statementHIV can persist in a latent reservoir unaffected by antiretroviral drugs. The genetic variation of this latent virus population is a major obstacle for eradication efforts, but also a clue to when HIV variants are deposited in the reservoirs. Unfortunately, previous studies assessing when the virus was deposited in latent reservoirs have come to contradictory conclusions. Here, we propose SIV proviral DNA exists in both short- and long-lived CD4+T cells, and that these two cell subsets harbor different genetically diverged virus populations. Our model explains the contradictory findings and shows that when CD4+T cells decay under effective drug treatment, which prevents virus replication, the resulting virus divergence decreases and recapitulates observed data. This knowledge should help in improving future eradication efforts.
Characterization of gene regulatory elements and dynamic antimicrobial immune responses in mosquito cells using PRO-seq
Authors: van Hout Femke A.H. , Himanen Samu V. , Vihervaara Anniina , Miesen Pascal 
Published: November 2023

AbstractTheAedes aegyptimosquito transmits arboviruses such as dengue, Zika, and chikungunya virus, posing a substantial threat to global health. The mosquito immune response determines virus transmission, yet, insight into the transcriptional regulation of mosquito immunity remains limited. In this study, we optimized the nascent RNA-sequencing method Precision Run-On sequencing (PRO-seq) forAedes aegyptiAag2 cells. PRO-seq enabled profiling the distribution of active RNA polymerases across the mosquito genome at nucleotide precision and identified the exact transcription start nucleotides (TSN) of expressed genes. Based on exact positioning of the TSN, we uncovered core promoter elements, including the Initiator and Downstream Promoter Elements. Notably, RNA polymerase accumulates at the promoter-proximal region of genes, but transcribes into the divergent region to a lesser extent than in vertebrates. To investigate rapid and dynamic immune responses, Aag2 cells were immune-stimulated with heat-inactivatedE. colifor 1 and 4 hours. Differential gene expression analysis revealed different groups of genes to be induced over time. While Clip domain serine proteases and antimicrobial peptides were induced promptly and sustained, a delayed stress response consisting of heat shock-related genes was only seen at 4 hours after stimulation. Strikingly, gene sets with different temporal expression profiles were associated with distinct transcription factor binding motifs. Altogether, our study provides valuable insights into the functional genomics ofAedes aegyptiand indicates that even within a rapid response, different dynamics emerge, potentially regulated by distinct transcription factors. These insights are crucial to gain a better understanding of the mosquito immune response and its regulation.
From Genomics Data to Causality: An Integrated Pipeline for Mendelian Randomization
Authors: Sharma Jyoti , Jangale Vaishnavi , Swain Asish Kumar , Yadav Pankaj 
Published: November 2023

ABSTRACTBackgroundMendelian randomization (MR) has emerged as a valuable tool for causal inference in genetic epidemiology. Existing MR methods have issues related to pleiotropy and offer limited comprehensiveness. Here, we introduce an integrated MR analysis pipeline designed for GWAS summary statistics data. Our pipeline integrates feature selection, harmonization, and checkpoint mechanisms to improve the accuracy and reliability of MR analysis.MethodsIn classical GWAS, the p-value threshold usually does not guarantee to identify causal single-nucleotide polymorphisms (SNPs). In such cases, t-statistics can be considered as imperative and robust criteria for identifying causal SNPs. Therefore, in this study, we computed the t-statistic for all independent SNPs remained after linkage disequilibrium pruning. Next, prior to harmonization, we removed SNPs having a t-statistic below the average t-statistic value. Furthermore, our pipeline incorporates sensitivity analysis tests at each step to reduce the chances of directional pleiotropy.Result and ConclusionWe applied our pipeline to single-sample and two-sample MR study designs, encompassing diverse populations and a wide range of diseases. Our results demonstrate superior performance compared to existing MR methods. In conclusion, our research presents an integrated MR analysis pipeline that significantly enhances the accuracy and reliability of MR studies. By outperforming existing methods and providing comprehensive validation, this pipeline represents a valuable tool for researchers in genetics and epidemiology.
Applications of Large Language Models (LLMs) in Breast Cancer Care
Authors: Sorin Vera , Glicksberg Benjamin S. , Barash Yiftach , Konen Eli , Nadkarni Girish , Klang Eyal 
Published: November 2023

AbstractPurposeRecently introduced Large Language Models (LLMs) such as ChatGPT have already shown promising results in natural language processing in healthcare. The aim of this study is to systematically review the literature on the applications of LLMs in breast cancer diagnosis and care.MethodsA literature search was conducted using MEDLINE, focusing on studies published up to October 22nd, 2023, using the following terms: “large language models”, “LLM”, “GPT”, “ChatGPT”, “OpenAI”, and “breast”.ResultsFive studies met our inclusion criteria. All studies were published in 2023, focusing on ChatGPT-3.5 or GPT-4 by OpenAI. Applications included information extraction from clinical notes, question-answering based on guidelines, and patients’ management recommendations. The rate of correct answers varied from 64-98%, with the highest accuracy (88-98%) observed in information extraction and question-answering tasks. Notably, most studies utilized real patient data rather than data sourced from the internet. Limitations included inconsistent accuracy, prompt sensitivity, and overlooked clinical details, highlighting areas for cautious LLM integration into clinical practice.ConclusionLLMs demonstrate promise in text analysis tasks related to breast cancer care, including information extraction and guideline-based question-answering. However, variations in accuracy and the occurrence of erroneous outputs necessitate validation and oversight. Future works should focus on improving reliability of LLMs within clinical workflow.
The change in the biomass allocation to stems and leaves in young plants of Dimorphandra wilsonii under eCO2 may harm this endangered species in native areas
Authors: Gonçalves Marina Efigenia , Viegas Geane Cristina Eugenio , Melo Nayara Magry Jesus , Souza João Paulo 
Published: November 2023

AbstractClimate change is among the main threats to ecosystems, affecting biodiversity and ecosystem services. These changes are associated with increased atmospheric carbon dioxide concentration ([CO2]). This study aimed to investigate how [CO2] influences chlorophyll a fluorescence, vegetative growth, biomass production, and the number of root nodules (NRN) of Dimorphandra wilsonii, a critically endangered species. The study was conducted in six open‐top chambers with two CO2 levels, at elevated [CO2] (eCO2, 717 ± 77 ppm) and at ambient [CO2] (aCO2, 539 ± 42 ppm). We monitored vegetative growth weekly, and at the end of the experiment, we measured chlorophyll a fluorescence and biomass production. Dimorphandra wilsonii plants under eCO2 showed higher (p < 0.05) average leaf dry mass, average leaf area, and lower (p < 0.05) root/shoot ratio than plants under aCO2. The greater aerial biomass allocation contributes to maximizing the photosynthesis performance but could also result in the self‐shading of old basal leaves by new distal leaves on branches. This adjustment could be advantageous in the competition for light; however, it would be a disadvantage for below‐ground resource competition (such as water and nutrients), which could result in decreased drought resistance. Also, this adjustment would be unfavorable to D. wilsonii, which occurs in a seasonal climate environment competing with invasive grasses. Thus, it is possible that climate change scenarios with increases in [CO2] and drought periods could negatively influence the establishment of young plants of D. wilsonii in their natural occurrence area, which could worsen the conservation status of the species.
Matter and Method: The Quest for a New‐Materialist Methodology in Management Studies
Authors: Benozzo Angelo , Distinto Marco , Priola Vincenza 
Published: November 2023

AbstractThis paper offers methodological and theoretical contributions to the field of management at the so‐called ‘turn to matter’ postulated within new materialist perspectives. It discusses more‐than‐human perspectives in management research and provides some methodological directions to support new materialist empirical investigations. Theoretically grounded on new materialism and posthumanism, the paper applies the assemblage approach that focuses on understanding the redistribution of agency to the network of people, things and discourses. In developing three exemplars of assemblages, it shows how it is possible to methodologically encompass the entanglement of the material, the organic, the human and the more‐than‐human to explore a phenomenon such as working from home. The paper concludes by reflecting on what new materialist qualitative research in management could become in order to generate new ways of imagining management, organizations and working lives, as more‐than‐human entanglements.
Radiographic age estimation based on degenerative changes of vertebrae
Authors: Adams Bradley J. , Butler Erin , Fuehr Stephanie M. , Olivares‐Pérez Fransheska , Tamayo Alexandra Semma 
Published: November 2023

AbstractAge estimation is an important component of decedent identification. When assessing adult remains, anthropologists frequently use gross examination of skeletal elements, such as clavicles, ribs, and pubic symphyses. For fleshed bodies, this requires the removal of these elements and maceration prior to analysis. A new method was developed using radiographic imaging to estimate age from degenerative changes of the lower thoracic and upper lumbar vertebrae. This technique will complement anthropological age estimation methods in young and middle‐aged adults and may serve as a stand‐alone method for older individuals. Digital radiographs from 240 medical examiner cases were evaluated. The sample included 120 females and 120 males between the ages of 18 and 101 years. A 3‐phased scoring system was used for the target vertebrae. Transition analysis was conducted on binned average scores and a Bayesian approach was used to assign age intervals. At the 90% credible interval, individuals in Bin 1 were under 36 years of age while those in Bin 3 were over 47 years of age. Individuals in Bin 2 showed too much age variation to be informative. No significant differences were found between males and females. These findings will be especially useful in the age estimation of older adults and may eliminate the need for skeletal sampling in medicolegal cases where advanced degenerative changes are radiographically observed in the lower thoracic and/or upper lumbar vertebrae. This method was developed for use on fleshed individuals but may also be applicable to skeletonized remains.
Protective effects of baicalin on diethyl nitrosamine‐induced liver cirrhosis by suppressing oxidative stress and inflammation
Authors: Wang Hui , Chang Yufei , Liu Xiao , Liu Linan , Hua Mingxi , Li Ang 
Published: November 2023

AbstractBaicalin (BA) is a natural product extract with anti‐inflammatory, antioxidant, and hepatoprotective properties. Given that the exact underlying mechanisms responsible for the impact of BA on liver cirrhosis remain ambiguous, a detailed investigation is sorely needed. Accordingly, a rat liver cirrhosis model was established via the intraperitoneal injection of diethyl nitrosamine (DEN, 100 mg/kg). Following the modeling, these rats were given BA (100 mg/kg) or N‐acetylcysteine (NAC, 150 mg/kg) alone or in combination. The pathological morphology of rat liver tissues in each group was observed by hematoxylin and eosin staining and Masson's trichrome staining. The expression of fibrosis‐related proteins was evaluated by Western blot, and the levels of liver function‐related biochemical indexes, oxidative stress‐related indexes, and inflammatory factors in the serum by enzyme‐linked immunosorbent assays (ELISA). The level of mitochondrial reactive oxygen species was measured by flow cytometry. The results depicted that in the rat model of DEN‐induced liver cirrhosis, BA reduced the expression of fibrosis‐related proteins (collagen type I alpha 1, α‐smooth muscle actin, and transforming growth factor‐β1), thereby alleviating the structural fibrosis of liver tissue. Furthermore, BA could diminish the level of mitochondrial reactive oxygen species, and the serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), interleukin (IL)‐1β, IL‐6, tumor necrosis factor‐α (TNF‐α), and monocyte chemotactic protein‐1 (MCP‐1), while promoting albumin, superoxide dismutase (SOD), and glutathione peroxidase (GSH‐Px) levels. Notably, all these effects of BA above were strengthened following the combined treatment of BA and NAC. On the whole, BA suppresses liver fibrosis by inhibiting oxidative stress and inflammation, thereby exerting a hepatoprotective effect.
An 8‐year observational study of the death places of patients with COPD in Turkey
Authors: İdikut Aytekin , İnam Maide Gözde , Karadeniz Güven Damla , Ceylan Serdar , Karcioğlu Oğuz 
Published: November 2023

AimThe place of death is one of the indicators of the quality of end‐of‐life care, which has become an essential public health issue with the aging of the population and the increase in life expectancy. There is a lack of data regarding the location of deaths caused by chronic obstructive pulmonary disease (COPD), the third‐leading cause of mortality worldwide. This retrospective, cross‐sectional study aimed to investigate the places of death of patients with COPD in Turkey and their trends over the years.MethodsThe study included patients who had a COPD International Classification of Diseases code in the hospital information system and were provided a medication report for this disease in a university hospital's chest diseases outpatient clinic between January 1, 2014, and December 31, 2021. The place and date of death were obtained from the death notification system and recorded as an in‐hospital or out‐of‐hospital death.ResultsA total of 1402 (77.3%) patients died in the hospital and 412 (22.7%) died outside the hospital, and when comparing the pandemic period and before, no significant difference was observed between the places of death. Sixty‐three (49.6%) of 127 patients over the age of 90 years died outside the hospital, and a significant relationship was observed between advanced age and out‐of‐hospital mortality (P < 0.005).ConclusionAccording to our findings, a substantial number of patients with COPD in Turkey die in hospitals. The insufficiency of nursing homes and lack of hospice care cause more hospital deaths. Our data are expected to guide the development of end‐of‐life care policies for patients with COPD in our country. Geriatr Gerontol Int 2023; 23: 938–944.
Liver abscess after drug‐eluting bead transarterial chemoembolization for hepatic malignant tumors: Clinical features, pathogenesis, and management
Authors: Wang Li‐Jun , Yin Liang , Liu Kai‐Cai , Lv Wei‐Fu , Lu Dong 
Published: November 2023

AbstractAimThe study aimed to investigate the clinical features, incidence, pathogenesis, and management of liver abscess after drug‐eluting bead transarterial chemoembolization (DEB‐TACE) for primary and metastatic hepatic malignant tumors.MethodsFrom June 2019 to June 2021, patients with liver abscess after DEB‐TACE for primary and metastatic hepatic malignant tumors were reviewed and evaluated at our hospital. Demographic and clinical data, radiological findings, management approaches, and prognosis were retrospectively analyzed.ResultsIn total, 419 DEB‐TACE procedures were carried out in 314 patients with primary and metastatic liver tumors at our medical center. Twelve patients were confirmed to have liver abscesses after DEB‐TACE through clinical manifestations, laboratory investigations, and imaging. In this study, the incidence of liver abscess was 3.82% per patient and 2.86% per DEB‐TACE procedure. After percutaneous drainage and anti‐inflammatory treatments, 10 patients recovered, and the remaining 2 patients died due to direct complications of liver abscess, such as sepsis and multiple organ failure. The mortality rate of liver abscesses after DEB‐TACE was 16.7% (2/12).ConclusionThe incidence of liver abscess after DEB‐TACE is relatively high and can have serious consequences, including death. Potential risk factors could include large tumor size, history of bile duct or tumor resection, history of diabetes, small DEB size (100–300 μm). Sensitive antibiotics therapy and percutaneous abscess aspiration/drainage are effective treatments for liver abscess after DEB‐TACE.
Drug displacement from protein binding: isolation of a redistributional drug interaction in vivo
Authors: McQUEEN E. G. , WARDELL W. M. 
Published: November 2023

Summary
The pharmacokinetic interaction between phenylbutazone and sulphadoxine has been studied in live sheep.
Intravenous injection of phenylbutazone causes a rapid fall in the concentration of total sulphadoxine together with a simultaneous rise in the concentration of free sulphadoxine in plasma. Both processes are complete within 3 min of the injection of phenylbutazone.
These reciprocal changes in the concentrations of total and free sulphadoxine in plasma do not depend on changes in the absorption, hepatic metabolism or renal excretion of sulphadoxine. By exclusion therefore, it is concluded that the effect of phenylbutazone in this interaction is solely to cause redistribution of the sulphadoxine.
Inhibition of contact sensitivity in the mouse by topical application of corticosteroids
Authors: EVANS D. P. , HOSSACK MARGARET , THOMSON D. S. 
Published: November 2023

Summary
Topical application of oxazolone to the ears of mice previously sensitized to this hapten resulted in a marked increase in ear weight 24 h later.
Topical application of hydrocortisone, betamethasone 17‐valerate, fluocinolone acetonide or triamcinolone acetonide inhibited this response in a dose dependent manner.
The free alcohols of the three fluorinated compounds were only weakly active.
Activity in this model was truly local. Oral administration of hydrocortisone or fluocinolone acetonide at doses comparable to those used topically failed to inhibit the ear swelling.
Some steroids with poor anti‐inflammatory properties had no significant effect.
The application of a multi‐component reaction peptide as a model regenerative active to enhance skin wound‐healing postlaser procedure in a double‐blinded placebo‐controlled clinical trial
Authors: Liao I‐Chien , He Chunyan , Liu Xue Lucia , Barresi‐Thornton Rebecca , Wangari‐Olivero Janet , Qian Mark Kun , Neo Boonhoe , Betts Richard , Ding Chunmei , Juchaux Franck , Chen Ying , Marat Xavier , Zheng Qian , Bouez Charbel 
Published: November 2023

AbstractIntroductionEsthetic procedures are currently among the most effective options for consumers seeking to correct aging signs such as fine lines, wrinkles, and skin tone unevenness. Currently, there is a scientific need for an adjunct active to be paired with esthetic procedures to encourage wound recovery and address postprocedure pigmentation concerns.ObjectiveToward that goal, this study assessed the efficacy of a peptide created from a multi‐component reaction (multi‐component peptide, MCP) as a model active for postprocedure care and evaluated its ability to promote skin healing in an ablative laser‐induced wound model on the forearm.MethodsThe mechanism of action of MCP was investigated using tubo assays, 2D melanocyte, and fibroblast cultures, reconstructed skin equivalents, and ex vivo skin explants. The MCP formula and the clinical benchmark formula of Aquaphor were assessed head‐to‐head by applying the products topically in an ablative laser‐induced wound model (n = 20 subjects). The promotion of wound healing was evaluated by the investigator assessment of epithelial confluence, crusting or scabbing, general wound appearance, erythema, and edema.ResultsMCP was determined to be beneficial to postprocedure skin recovery and healing by four main mechanisms of action: barrier repair as determined in an ex vivo tape‐stripping model, reduction of inflammation and postinflammatory hyperpigmentation, reduction of elastase activity, and stimulation of fibroblast through the mTOR pathway. The formula containing 10% MCP enhanced the kinetics of epithelial confluence and improvement of the crusting or scabbing appearance of the laser‐generated wounds in a laser‐induced mini‐zone wound healing study on the forearm.ConclusionThis study demonstrates the use of MCP as a proof of concept regenerative active that when incorporated into an optimized postprocedure skincare formula can improve skin healing and enhance the appearance of skin after injury with relevance to ablative aesthetic procedures.