bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hepatotoxicity of immune checkpoint inhibitors: What is Currently Known
Authors: Zheng Caiyun , Huang Shunmin , Lin Meimei , Hong Baohui , Ni Ruping , Dai Hengfen , Lin Xiuqin , Yang Jing 
Published: February 2023

Background:
This systematic review and network meta-analysis aimed to provide a complete hepatotoxicity profile, hepatotoxicity spectrum, and safety ranking of immune checkpoint inhibitor drugs for cancer treatment.

Methods:
PubMed, Embase, Scopus, CINAHL, Web of Science, psycINFO, Cochrane Library, and ClinicalTrials.gov. websites were searched, and a manual search of relevant reviews and trials up to January 1, 2022, was undertaken. Head-to-head III randomized controlled trials comparing any 2 or 3 of the following treatments or different doses of the same immune checkpoint inhibitor drug were included: programmed death 1 (PD-1), programmed death ligand 1, and cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitors and conventional therapy. We included 106 randomized trials (n=164,782) containing 17 treatment arms.

Results:
The overall incidence of hepatotoxicity was 4.06%. The rate of fatal liver adverse events was 0.07%. The programmed death ligand 1 inhibitor+targeted therapy drug+chemotherapy group had the highest risk of treatment-related increases in all-grade alanine aminotransferase and aspartate aminotransferase levels, and the differences were significant. For immune-related hepatotoxicity, no significant difference was found between PD-1 and CTLA-4 inhibitors for all-grade hepatotoxicity; however, CTLA-4 inhibitors were associated with a higher risk of grade 3–5 hepatotoxicity than PD-1 inhibitors.

Conclusions:
The highest incidence of hepatotoxicity and fatality was observed with triple therapy. The overall incidence of hepatotoxicity was similar between different dual regimens. For immune checkpoint inhibitor monotherapy, the overall risk of immune-mediated hepatotoxicity related to CTLA-4 inhibitors did not differ significantly from that of PD-1 inhibitors. There was no direct relationship between the risk of liver injury and drug dose, whether monotherapy or combination therapy was used.
ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN MILD FAMILIAL EXUDATIVE VITREORETINOPATHY
Authors: Wang You , Lai Yanting , Zhou Xiaodi , Zhang Ting , Sun Limei , Zhang Zhaotian , Huang Li , Li Songshan , Ding Xiaoyan 
Published: February 2023

Purpose:
To investigate ultra-widefield optical coherence tomography angiography (UWF-OCTA) to detect and evaluate mild familial exudative vitreoretinopathy and compare the detective ratio of UWF-OCTA with ultra-widefield scanning laser ophthalmoscopy and ultra-widefield fluorescein angiography.

Methods:
The patients with familial exudative vitreoretinopathy were included in this study. UWF-OCTA, using a 24- × 20-mm montage, was performed for all patients. All images were independently tested for the presence of familial exudative vitreoretinopathy-associated lesions. Statistical analysis was performed with SPSS V.24.0.

Results:
Forty-six eyes of 26 participants were included in the study. Ultra-widefield optical coherence tomography angiography was found to be greatly superior to ultra-widefield scanning laser ophthalmoscopy in detecting peripheral retinal vascular abnormality (P < 0.001) and peripheral retinal avascular zone (P < 0.001). The detection rates of peripheral retinal vascular abnormality, peripheral retinal avascular zone, retinal neovascularization, macular ectopia, and temporal midperipheral vitreoretinal interface abnormality were comparable with ultra-widefield fluorescein angiography images (P > 0.05). Furthermore, vitreoretinal traction (17/46, 37%) and small foveal avascular zone (17/46, 37%) were detected effectively on UWF-OCTA.

Conclusion:
Ultra-widefield optical coherence tomography angiography is a reliable noninvasive tool to detect familial exudative vitreoretinopathy lesions, especially in mild patients or asymptomatic family members. The unique manifestation of UWF-OCTA offers an alternative to ultra-widefield fluorescein angiography for the screening and diagnosis of FEVR.
Sickness Presenteeism and Psychosocial Risk Factors According to Inequality Axes
Authors: Gómez-Domínguez Angela , Ferrer-Rosende Pedro , Esteve-Matalí Laura , Salas-Nicás Sergio , Navarro-Giné Albert 
Published: February 2023

Objective
To assess the association between psychosocial risk factors (PSRs) and sickness presenteeism (SP) and examine possible differences according to the major axes of inequality in the labor market. Methods: Cross-sectional study based on a representative sample of the Spanish salaried population. Results: Although nearly all PSR show crude associations with SP, when adjusted for every other PSR, only the workers exposed to lack of role clarity (adjusted prevalence ratio [aPR], 1.30; 95% confidence interval [CI], 1.01 to 1.68), having role conflicts (aPR, 1.45; 95% CI, 1.19 to 1.77) and lack of sense of community at work (aPR, 1.30; 95% CI, 1.06 to 1.59) show a significant association. Conclusions: After adjusting for all PSR, those significantly associated to SP belong to the interpersonal relationships domain. Some of the PSR effects change according to the segmentation axes analyzed.
Non-neonatal Men with Rare Testicular Torsion: A Case Series
Authors: O'Driscoll Kieran M. , Narula Samir , Chu Julianne L. , Best Natalie M. , Vemulapalli Pratibha , Gilchrist Brian F. 
Published: February 2023

Abstract
Testicular torsion involves the testicle twisting which results in an infarcted testis. Emergency surgery is required to salvage the affected testis. There are 2 anatomic pathologies associated with testicular torsion: intravaginal testicular torsion and extravaginal testicular torsion (ETT). Extravaginal testicular torsion is seen perinatally and in neonates; beyond this period, ETT is regarded as exceptionally rare. This case series presents 7 cases of ETT seen in men aged 14 to 20 years. This is the largest and oldest group of patients seen with this pathology. These cases were defined by a pediatric surgeon in an inner city hospital in New York. Two patients' testes were not viable at the time of presentation, and the time of onset to presentation ranged from 30 minutes to 11 hours. Each of these cases had an orchiopexy concomitantly of the contralateral testis. This case series poses key questions regarding the etiology of ETT and the surgical management of such cases.
Circular RNA circ_0099188 contributes to lipopolysaccharide (LPS)-induced HPAEpiC cell injury by targeting the miR-1236-3p/HMGB3 axis
Authors: Lin Yuhang , Zeng Zhitao , Pan Kechuan 
Published: February 2023

Abstract

Purpose
This study is designed to explore the role and mechanism of circ_0099188 in LPS-engendered HPAEpiC cells.

Methods
Circ_0099188, microRNA-1236-3p (miR-1236-3p), and High mobility group box 3 (HMGB3) levels were measured using real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were assessed using Cell Counting Kit-8 (CCK-8) and flow cytometry assays. Protein levels of B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), cleaved-caspase 3, cleaved-caspase 9, and HMGB3 were determined using western blot assay. Interleukin-6 (IL-6), IL-8, IL-1β, and tumor necrosis factor α (TNF-α) levels were analyzed using Enzyme-linked immunosorbent assays (ELISA). After predicting using Circinteractome and Targetscan, the binding between miR-1236-3p and circ_0099188 or HMGB3 was verified using a dual-luciferase reporter, RNA Immunoprecipitation (RIP), and RNA pull-down assays.

Results
Circ_0099188 and HMGB3 were highly expressed, and miR-1236-3p was decreased in LPS-stimulated HPAEpiC cells. Also, the downregulation of circ_0099188 might overturn LPS-triggered HPAEpiC cell proliferation, apoptosis, and inflammatory response. Mechanically, circ_0099188 is able to affect HMGB3 expression by sponging miR-1236-3p.

Conclusion
Circ_0099188 knockdown might mitigate LPS-induced HPAEpiC cell injury by targeting the miR-1236-3p/HMGB3 axis, providing an underlying therapeutic strategy for pneumonia treatment.
Incidence of multiple organ failure in adult polytrauma patients: A systematic review and meta-analysis
Authors: Ting Ryan S. , Lewis Daniel P. , Yang Kevin X. , Nguyen Tam Anh , Sarrami Pooria , Daniel Lovana , Hourigan Samuel , King Kate , Lassen Christine , Sarrami Mahsa , Ridley William , Alkhouri Hatem , Dinh Michael , Balogh Zsolt J. 
Published: February 2023

BACKGROUND
Postinjury multiple organ failure (MOF) is the leading cause of late death in trauma patients. Although MOF was first described 50 years ago, its definition, epidemiology, and change in incidence over time are poorly understood. We aimed to describe the incidence of MOF in the context of different MOF definitions, study inclusion criteria, and its change over time.

METHODS
Cochrane Library, EMBASE, MEDLINE, PubMed, and Web of Science databases were searched for articles published between 1977 and 2022 in English and German. Random-effects meta-analysis was performed when applicable.

RESULTS
The search returned 11,440 results, of which 842 full-text articles were screened. Multiple organ failure incidence was reported in 284 studies that used 11 unique inclusion criteria and 40 MOF definitions. One hundred six studies published from 1992 to 2022 were included. Weighted MOF incidence by publication year fluctuated from 11% to 56% without significant decrease over time. Multiple organ failure was defined using four scoring systems (Denver, Goris, Marshall, Sequential Organ Failure Assessment [SOFA]) and 10 different cutoff values. Overall, 351,942 trauma patients were included, of whom 82,971 (24%) developed MOF. The weighted incidences of MOF from meta-analysis of 30 eligible studies were as follows: 14.7% (95% confidence interval [CI], 12.1–17.2%) in Denver score >3, 12.7% (95% CI, 9.3–16.1%) in Denver score >3 with blunt injuries only, 28.6% (95% CI, 12–45.1%) in Denver score >8, 25.6% (95% CI, 10.4–40.7%) in Goris score >4, 29.9% (95% CI, 14.9–45%) in Marshall score >5, 20.3% (95% CI, 9.4–31.2%) in Marshall score >5 with blunt injuries only, 38.6% (95% CI, 33–44.3%) in SOFA score >3, 55.1% (95% CI, 49.7–60.5%) in SOFA score >3 with blunt injuries only, and 34.8% (95% CI, 28.7–40.8%) in SOFA score >5.

CONCLUSION
The incidence of postinjury MOF varies largely because of lack of a consensus definition and study population. Until an international consensus is reached, further research will be hindered.

LEVEL OF EVIDENCE
Systematic Review and Meta-analysis; Level III.
Poor sleep quality, insomnia, and short sleep duration before infection predict long-term symptoms after COVID-19
Authors: Salfi Federico , Amicucci Giulia , Corigliano Domenico , Viselli Lorenzo , D’Atri Aurora , Tempesta Daniela , Ferrara Michele 
Published: February 2023

AbstractStudy objectivesMillions of COVID-19 survivors experience a wide range of long-term symptoms after acute infection, giving rise to serious public health concerns. To date, few risk factors for post-COVID-19 conditions have been determined. This study evaluated the role of pre-infection sleep quality/duration and insomnia severity in the incidence of long-term symptoms after COVID-19.MethodsThis prospective study involved two assessments (April 2020 and 2022). At baseline, sleep quality/duration and insomnia symptoms in participants without current/prior SARS-CoV-2 infection were measured using the Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI). At follow-up, we evaluated the presence of twenty-one symptoms (psychiatric, neurological, cognitive, bodily, and respiratory) one month (n=713, infection in April 2020–February 2022) and three months after COVID-19 (n=333, infection in April 2020–December 2021). Zero-inflated negative binomial models were used to estimate the effect of previous sleep on the number of long-term symptoms. Binomial logistic regressions were performed to evaluate the association between sleep outcomes and the incidence of each post-COVID-19 symptom.ResultsAnalyses highlighted a significant effect of pre-infection sleep on the number of symptoms one/three months after COVID-19. Previous higher PSQI and ISI scores, and shorter sleep duration significantly increased the risk of almost every long-term symptom at one/three months from COVID-19.ConclusionThis study suggested a prospective dose-dependent association between pre-infection sleep quality/quantity and insomnia severity with the manifestation of post-COVID-19 symptoms. Promoting sleep health may represent an effective preventive approach to mitigate the COVID-19 sequelae, with substantial public health and societal implications.Statement of significanceDetermining potential risk factors of long COVID is crucial to driving preventive interventions amongst vulnerable populations. The present study is the first to provide insights into the role of pre-infection sleep disturbances in the occurrence of post-COVID-19 conditions. We demonstrated a strong association between previous sleep quality/duration and insomnia severity with the incidence of a broad spectrum of long-term symptoms one and three months after COVID-19. These results may have large-scale implications, considering the alarming rates of both sleep disturbances and post-COVID-19 manifestations worldwide. Further research is warranted to determine the biobehavioral mechanisms involved. Future studies should also evaluate whether treating sleep problems may improve the subsequent long-term consequences of COVID-19.
Stochastic dynamics of ecological populations subjected to environmental perturbations
Authors: Rezaee Sayeh , Nieto Cesar , Vahdat Zahra , Singh Abhyudai 
Published: February 2023

AbstractThe stochastic logistic model is widely used to capture random fluctuations arising from birth-death processes in ecological populations. We use this model to study the impact of environmental perturbations that may occur naturally or as a consequence of population harvesting. In our model formulation, environmental perturbations occur randomly as per a Poisson process, and the perturbations result in each individual dying with a certain probability of death. Moment closure schemes are employed to derive expressions for the mean and variability in population numbers. Moreover, to quantify the impact of population extinction in our model we compute the probability of extinction using the Finite State Projection (FSP) numerical method. Our analysis shows that rare environmental perturbations with a high probability of death lead to overall larger random fluctuations and extinction risk as compared to frequent perturbations with a low probability of death. Finally, we formulate the problem in the context of population harvesting to find the optimal harvesting rate that maximizes the cumulative yield.
Predicting vertical and shear ground reaction forces during walking and jogging using wearable plantar pressure insoles
Authors: Hajizadeh Maryam , Clouthier Allison L. , Kendall Marshall , Graham Ryan B. 
Published: February 2023

ABSTRACTBackgroundThe development of plantar pressure insoles has made them a potential replacement for force plates. These wearable devices can measure multiple steps and might be used outside of the lab environment for rehabilitation and evaluation of sport performance. However, they can only measure the normal force which does not completely represent the vertical ground reaction force (GRF). In addition, they are not able to measure shear forces which play an import role in the dynamic performance of individuals. Indirect approaches might be implemented to improve the accuracy of the force estimated by plantar pressure systems.Research questionThe aim of this study was to predict the vertical and shear components of ground reaction force from plantar pressure data using recurrent neural networks.MethodsGRF and plantar pressure data were collected from sixteen healthy individuals during 10 trials of walking and five trials of jogging using Bertec force plates and FScan plantar pressure insoles. A long short-term memory (LSTM) neural network was built to consider the time dependency of pressure and force data in predictions. The data were split into three subsets of train, to train the LSTM model, evaluate, to optimize the model hyperparameters, and test sets, to assess the accuracy of the model predictions.ResultsThe results of this study showed that our LSTM model could accurately predict the shear and vertical GRF components during walking and jogging. The predictions were more accurate during walking compared to jogging. In addition, the predictions of mediolateral force had higher error and lower correlation compared to vertical and anteroposterior components.SignificanceThe LSTM model developed in this study may be an acceptable option for accurate estimation of GRF during outdoor activities which can have significant impacts in rehabilitation, sport performance, and gaming.
Hidden changes to prespecified primary outcomes of clinical trials completed between 2009 and 2017 in German University Medical Centres: A meta-research study
Authors: Holst Martin R. , Haslberger Martin , Yerunkar Samruddhi , Strech Daniel , Hemkens Lars G. , Carlisle Benjamin G. 
Published: February 2023

AbstractObjectivesTo assess how often clinical trials exhibit primary outcome discrepancies within registry records that would not be caught by comparing results publications to the latest registry entry, but would require analysing the registration history.DesignMeta-research study.SettingAll 1746 randomised clinical trials with published results, registered inClinicalTrials.govor Deutsches Register Klinischer Studien (DRKS), completed at German University Medical Centres between 2009 and 2017. We analysed registry entries for all trials and publications for a random sample of 292 trials.ParticipantsNot applicable.InterventionsNot applicable.Main outcome measures[1] Primary outcome discrepancies between registry entries at key study milestones and [2] the first results publication. [3] ‘Hidden’ discrepancies, i.e., only reported in the registry before the last entry, meaning they would only be detected by assessing the full registry change history. We considered discrepancies major if primary outcomes were newly added, dropped, or changed to or from secondary outcomes. [4] Proportion of publications transparently reporting discrepancies. [5] Characteristics associated with ‘open’ and ‘hidden’ discrepancies.ResultsOf all 1746 trials, 23% (n=393) had primary outcome discrepancies between trial start and latest registry entry, with 8% (n=142) being major. Primary outcomes in publications were different from the latest registry entry in 41% of trials (120 of the 292 sampled trials; 95% CI [35%, 47%]), with major discrepancies in 18% (54 of 292; 95% CI [14%, 23%]). ‘Hidden’ discrepancies were observed in 14% of trials (41/292; 95% CI [10%, 19%]). Only 1% of discrepancies were reported in the publications (2/161, 95% CI [0%, 4%]). Trials were more likely to have a within-registry discrepancy if they had an earlier registration year (OR 0.74; 95% CI [0.69, 0.80]), were registered onClinicalTrials.gov(OR 0.41; 95% CI [0.23, 0.70]), or had been industry-sponsored (OR 0.29; 95% CI [0.21, 0.41]).ConclusionsChanges to primary trial outcomes are common, often have major relevance, are rarely transparently reported and typically not detectable with an inspection of the latest registry entry. Authors need to be more transparent and registry entries of published trials need to require more in-depth analysis to reveal potentially misleading reporting practices.Protocol registrationOpen Science Framework (https://osf.io/t3qva; amendment inhttps://osf.io/qtd2b).
DeepHeme: A generalizable, bone marrow classifier with hematopathologist-level performance
Authors: Goldgof Gregory M. , Sun Shenghuan , Van Cleave Jacob , Wang Linlin , Lucas Fabienne , Brown Laura , Spector Jacob D. , Boiocchi Leonardo , Baik Jeeyeon , Zhu Menglei , Ardon Orly , Lu Chuanyi M. , Dogan Ahmet , Goldgof Dmitry B. , Carmichael Iain , Prakash Sonam , Butte Atul J. 
Published: February 2023

ABSTRACTMorphology-based classification of cells in the bone marrow aspirate (BMA) is a key step in the diagnosis and management of hematologic malignancies. However, it is time-intensive and must be performed by expert hematopathologists and laboratory professionals. We curated a large, high-quality dataset of 41,595 hematopathologist consensus-annotated single-cell images extracted from BMA whole slide images (WSIs) containing 23 morphologic classes from the clinical archives of the University of California, San Francisco. We trained a convolutional neural network, DeepHeme, to classify images in this dataset, achieving a mean area under the curve (AUC) of 0.99. DeepHeme was then externally validated on WSIs from Memorial Sloan Kettering Cancer Center, with a similar AUC of 0.98, demonstrating robust generalization. When compared to individual hematopathologists from three different top academic medical centers, the algorithm outperformed all three. Finally, DeepHeme reliably identified cell states such as mitosis, paving the way for image-based quantification of mitotic index in a cell-specific manner, which may have important clinical applications.
Functional antagonistic interactions and genomic insights into the biosynthetic potential of human gut-derived microbiota
Authors: Hussain Aehtesham , Patwekar Umera , Mongad Dattatray S , Nimonkar Yogesh , Mundhe Swapnil , Paul Dhiraj , Prakash Om , Shouche Yogesh S 
Published: February 2023

ABSTRACTConcerning the biological interactions within the gut microbiome, the specialized small molecules encoded by commensal microbes mediate distinct functional aspects. However, the landscape of antagonistic interactions mediated by specialized strains and their small molecules broadly remains. Here, we sought to evaluate antimicrobial interactions as a defensive contributor to gain new insights into structure-related functions or to bring the therapeutic potential of derived molecules. We elucidated the antagonistic landscape within a collection of 330 human-gut-derived commensal microbial strains cultivated from healthy human subjects. We characterized potential antagonistic strains and found a strain-specific selective inhibition contrary to common antimicrobial drugs that wipe out a broad range of species usually found in environmental microbes. Using functional and genomic approaches for accessing biologically active natural product molecules, we identified significant biosynthetic gene clusters (BGCs) encoding the important compound families in representative gut strains which contribute to antagonistic activities and are important in host defense or maintaining homeostasis in the gut. The subsets of the BGCs were represented in metagenomics sequencing data from healthy individuals. The cell culture secretome of strains revealed potential biomarkers linked to hallmark pathways. Together, these microorganisms encode biosynthetic novelty and represent a source of biologically significant natural products important in developing new treatments for infectious diseases to cut the usage of broad-spectrum antibiotics and represent a way to combat antimicrobial resistance. Consortia of such strains can be utilized as an option for precise editing of the microbiomes or fine-tuning the microbiota-modulating therapies.