bluuebunny/crossref_metadata_2025_split huggingface dataset:
The generation of HepG2 transmitochondrial cybrids to reveal the role of mitochondrial genotype in idiosyncratic drug-induced liver injury
Authors: Ball Amy Louise , Jolly Carol E , Lennon Mark G , Lyon Jonathan J , Alfirevic Ana , Chadwick Amy E 
Published: June 2023

Background:Evidence supports an important link between mitochondrial DNA (mtDNA) variation and adverse drug reactions such as idiosyncratic drug-induced liver injury (iDILI). Here, we describe the generation of HepG2-derived transmitochondrial cybrids, to investigate the impact of mtDNA variation on mitochondrial (dys)function and susceptibility to iDILI. This study created 10 cybrid cell lines, each containing distinct mitochondrial genotypes of haplogroup H or haplogroup J backgrounds.Methods:HepG2 cells were depleted of mtDNA to make rho zero cells, before the introduction of known mitochondrial genotypes using platelets from healthy volunteers (n=10), thus generating 10 transmitochondrial cybrid cell lines. The mitochondrial function of each was assessed at basal state and following treatment with compounds associated with iDILI; flutamide, 2-hydroxyflutamide, and tolcapone, and their less toxic counterparts bicalutamide and entacapone utilizing ATP assays and extracellular flux analysis.Results:Whilst only slight variations in basal mitochondrial function were observed between haplogroups H and J, haplogroup-specific responses were observed to the mitotoxic drugs. Haplogroup J showed increased susceptibility to inhibition by flutamide, 2-hydroxyflutamide, and tolcapone, via effects on selected mitochondrial complexes (I and II), and an uncoupling of the respiratory chain.Conclusions:This study demonstrates that HepG2 transmitochondrial cybrids can be created to contain the mitochondrial genotype of any individual of interest. This provides a practical and reproducible system to investigate the cellular consequences of variation in the mitochondrial genome, against a constant nuclear background. Additionally, the results show that inter-individual variation in mitochondrial haplogroup may be a factor in determining sensitivity to mitochondrial toxicants.Funding:This work was supported by the Centre for Drug Safety Science supported by the Medical Research Council, United Kingdom (Grant Number G0700654); and GlaxoSmithKline as part of an MRC-CASE studentship (grant number MR/L006758/1).
A novel framework based on deep learning for COVID-19 diagnosis from X-ray images
Authors: JavadiMoghaddam SeyyedMohammad 
Published: June 2023

Background
The coronavirus infection has endangered human health because of the high speed of the outbreak. A rapid and accurate diagnosis of the infection is essential to avoid further spread. Due to the cost of diagnostic kits and the availability of radiology equipment in most parts of the world, the COVID-19 detection method using X-ray images is still used in underprivileged countries. However, they are challenging due to being prone to human error, time-consuming, and demanding. The success of deep learning (DL) in automatic COVID-19 diagnosis systems has necessitated a detection system using these techniques. The most critical challenge in using deep learning techniques in diagnosing COVID-19 is accuracy because it plays an essential role in controlling the spread of the disease.

Methods
This article presents a new framework for detecting COVID-19 using X-ray images. The model uses a modified version of DenseNet-121 for the network layer, an image data loader to separate images in batches, a loss function to reduce the prediction error, and a weighted random sampler to balance the training phase. Finally, an optimizer changes the attributes of the neural networks.

Results
Extensive experiments using different types of pneumonia expresses satisfactory diagnosis performance with an accuracy of 99.81%.

Conclusion
This work aims to design a new deep neural network for highly accurate online recognition of medical images. The evaluation results show that the proposed framework can be considered an auxiliary device to help radiologists accurately confirm initial screening.
Soil organic carbon pools and carbon management index under different land use systems in North western Himalayas
Authors: Mir Yasir Hanif , Ganie Mumtaz Ahmad , Shah Tajamul Islam , Aezum Aziz Mujtaba , Bangroo Shabir Ahmed , Mir Shakeel Ahmad , Dar Shahnawaz Rasool , Mahdi Syed Sheeraz , Baba Zahoor Ahmad , Shah Aanisa Manzoor , Majeed Uzma , Minkina Tatiana , Rajput Vishnu D. , Dar Aijaz Ahmad 
Published: June 2023

Current study was conducted to evaluate the effect of important land uses and soil depth on soil organic carbon pools viz. total organic carbon, Walkley and black carbon, labile organic carbon, particulate organic carbon, microbial biomass carbon and carbon management index (CMI) in the north Western Himalayas, India. Soil samples from five different land uses viz. forest, pasture, apple, saffron and paddy-oilseed were collected up to a depth of 1 m (0–30, 30–60, 60–90 cm). The results revealed that regardless of soil depth, all the carbon pools differed significantly (p < 0.05) among studied land use systems with maximum values observed under forest soils and lowest under paddy-oilseed soils. Further, upon evaluating the impact of soil depth, a significant (p < 0.05) decline and variation in all the carbon pools was observed with maximum values recorded in surface (0–30 cm) soils and least in sub-surface (60–90 cm) layers. CMI was higher in forest soils and lowest in paddy-oilseed. From regression analysis, a positive significant association (high R-squared values) between CMI and soil organic carbon pools was also observed at all three depths. Therefore, land use changes and soil depth had a significant impact on soil organic carbon pools and eventually on CMI, which is used as deterioration indicator or soil carbon rehabilitation that influences the universal goal of sustainability in the long run.
A new species of Pristimantis (Anura: Strabomantidae) from white-sand forests of central Amazonia, Brazil
Authors: Mônico Alexander Tamanini , Ferrão Miquéias , Moravec Jiří , Fouquet Antoine , Lima Albertina P. 
Published: June 2023

The white-sand ecosystems in the Solimões-Negro Interfluve are among the less studied in Amazonia. Recent herpetological surveys conducted west of Manaus, Brazil (central Amazonia) indicate that white-sand forests host a unique anuran fauna comprising habitat specialized and endemic species. In the present study we describe a new species of rain frog belonging to the Pristimantis unistrigatus species group from the white-sand forest locally called “campinarana” (thin-trunked forests with canopy height below 20 m). The new species is phylogenetically close to rain frogs from western Amazonian lowlands (P. delius, P. librarius, P. matidiktyo and P. ockendeni). It differs from its closest relatives mainly by its size (male SVL of 17.3–20.1 mm, n = 16; female SVL of 23.2–26.5 mm, n = 6), presence of tympanum, tarsal tubercles and dentigerous processes of vomers, its translucent groin without bright colored blotches or marks, and by its advertisement call (composed of 5–10 notes, call duration of 550–1,061 ms, dominant frequency of 3,295–3,919 Hz). Like other anuran species recently discovered in the white-sand forests west of Manaus, the new species seems to be restricted to this peculiar ecosystem.
Changes in Patient Care Experience After Private Equity Acquisition of US Hospitals
Authors: Bhatla Anjali , Bartlett Victoria L. , Liu Michael , Zheng ZhaoNian , Wadhera Rishi K. 
Published: January 2025

ImportancePrivate equity acquisitions of health care facilities have rapidly increased over the past decade. However, little is known about the effects of private equity acquisitions of US hospitals on patient care experience.ObjectiveTo evaluate whether the acquisition of hospitals by private equity firms was associated with changes in measures of patient-reported experience compared with matched control hospitals from 2008 through 2019.Design, Settings, and ParticipantsThis cohort study identified 73 US hospitals newly acquired by private equity firms and 293 matched control (nonacquired) US hospitals from 2008 through 2019. An event study, difference-in-differences design was used to evaluate changes in patient experiences measures from 3 years before to 3 years after private equity acquisition.Main Outcomes and MeasuresThe primary outcomes were 2 global measures of patient-reported care experience from the Hospital Consumer Assessment of Healthcare Providers and Systems (HCAHPS) survey, which included patients’ overall hospital rating and willingness to recommend the hospital. Secondary outcomes included the 7 other HCAHPS measures encompassing clinical process, communication, and environmental measures.ResultsThere were 73 private equity–acquired hospitals and 293 matched control hospitals. The percentage of patients rating hospitals as a 9 or 10, on a scale of 0 to 10, decreased at private equity–acquired hospitals (65.0% before acquisition and 65.2% after acquisition) when compared with control hospitals (66.2% to 69.2%) during the postacquisition period relative to the preacquisition period with a difference-in-differences estimate of −2.4 percentage points (95% CI, −3.9 to −0.9). In addition, the percentage of patients who would definitely recommend the hospital also decreased at private equity–acquired hospitals (66.9% before acquisition and 65.5% after acquisition) compared with control hospitals (68.2% to 69.3%) with a difference-in-difference estimate of −2.1 percentage points (95% CI, −3.6 to −0.7). For both of these global measures of patient experience, the difference between private equity–acquired and control hospitals increased over time and was largest in year 3 after acquisition (−5.2 percentage points [95% CI, −8.8 to −1.5] and −4.4 percentage points [95% CI, −8.0 to −0.70] for each measure, respectively). For secondary measures of patient care experience, there was a decrease in patient-reported responsiveness of hospital staff at private equity–acquired hospitals compared with control hospitals (−1.3 percentage points [95% CI, −2.4 to −0.2]), but no differential change across other measures of clinical process, communication, and environment.Conclusions and RelevancePatient care experience worsened after private equity acquisition of hospitals. These findings raise concern about the implications of private equity acquisitions on patient care experience at US hospitals.
Safety and Vision Outcomes Following Gene Therapy for Bietti Crystalline Dystrophy
Authors: Chen Xiuju , Liu Xiao , Cui Shihe , Wang Gang , Liu Yiting , Qu Guang , Jiang Lixin , Liu Yong , Li Xiaoxin 
Published: January 2025

ImportanceBietti crystalline dystrophy (BCD) is a severe genetic retinopathy caused by variants in the CYP4V2 gene. Currently, there is no approved treatment for BCD.ObjectiveTo evaluate safety and vision outcomes following gene therapy with adeno-associated virus (AAV) encoding CYP4V2 (rAAV-hCYP4V2, NGGT001 [Next Generation Gene Therapeutics]).Design, Setting, and ParticipantsThis open-label, dose-escalation nonrandomized clinical trial was conducted from February 2023 to May 2024 at 2 study sites in China. Patients with genetically confirmed biallelic disease-linked CYP4V2 variants received subretinal injections of rAAV2-hCYP4V2 at 1 of 2 dosage levels and were followed up for 12 months.InterventionA single unilateral injection of 1.5 × 1011 or 3.0 × 1011 total vector genomes of recombinant AAV-hCYP4V2 in the worse eye, based on visual acuity letter score.Main Outcomes and MeasuresThe primary outcome was safety, assessed by clinical examination of ocular inflammation and evaluated by routine clinical chemistry and immunogenicity testing. Secondary outcomes were changes in visual function from baseline in best-corrected visual acuity (BCVA), microperimetry, and contrast sensitivity 12 months after treatment.ResultsAmong 12 patients with BCD (6 patients per dose group), mean (SD) patient age was 40.5 (7.1) years, and 5 patients (42%) were female. No severe adverse events related to the treatment were observed. However, mild intraocular inflammation was noted in 1 participant. The median (IQR) baseline BCVA letter score for the study eye was 34 (10-53), equivalent to 20/200 Snellen, while the nonstudy eye had a median (IQR) BCVA of 60 (40-67), equivalent to approximately 20/63 Snellen. At 12 months, the study eye improved by a mean (SD) letter score of 13.9 (13.1) compared with 6.3 (7.4) in the nonstudy eye. The 12-month median (IQR) BCVA for the study eye was 53 (37-64) (equivalent to approximately 20/80 Snellen) and 62 (42-70) (approximately 20/50 Snellen) for the nonstudy eye.Conclusions and RelevanceThis open-label, exploratory nonrandomized clinical trial identified no serious safety concerns related to gene therapy over 12 months’ follow-up among patients with BCD. While improvement in BCVA was noted, the magnitude was within test-retest values typically noted in eyes with very low levels of visual acuity, and BCVA improvement in both the study and nonstudy eyes could be related to a learning effect, with greater improvement in the study eye possibly related to study eyes’ being the worse-seeing eye.Trial RegistrationClinicalTrials.gov Identifier: NCT06302608
Noise Exposure History and Age-Related Changes to Hearing
Authors: Dillard Lauren K. , Humes Larry E. , Matthews Lois J. , Dubno Judy R. 
Published: January 2025

ImportanceNoise exposure is a major modifiable risk factor for hearing loss, yet it is not known whether it affects the rate of hearing decline in aging.ObjectiveTo determine the association of noise exposure history with the rate of pure-tone threshold change per year.Design, Setting, and ParticipantsThis longitudinal cohort study was conducted in the ongoing community-based Medical University of South Carolina Longitudinal Cohort Study of Age-Related Hearing Loss (1988 to present with the sample based in Charleston, South Carolina, and surrounding area). Following a comprehensive baseline examination, participants attended annual examinations, during which audiometric data were collected. Participants with audiometric data from at least 2 examinations and noise exposure history data were included in the study. Data were analyzed between September 2023 and July 2024.ExposureNoise exposure history, determined by a self-reported questionnaire and history of military service, was categorized as no/little, some, or high exposure.Main Outcomes and MeasuresOutcome measures were individual audiometric thresholds (0.25 kHz to 8.0 kHz) and pure-tone average (PTA) of thresholds at frequencies 0.5 kHz, 1.0 kHz, 2.0 kHz, and 4.0 kHz, averaged bilaterally. Linear mixed regression models were used to estimate the association of age (per every 1 additional year) with the rate of threshold change at each frequency and PTA, for each noise exposure category. The association of noise exposure with the rate of annual threshold change was determined by an interaction term of age (longitudinal time variable) and noise exposure in regression models.ResultsOf 1347 participants, the mean (SD) baseline age was 63 (14) years, and 772 (57%) were female. The mean (SD) follow-up time was 5.1 (5.7) years. Compared to the no/little noise exposure group, groups with some and high noise exposure had significantly higher baseline thresholds from 2.0 kHz to 8.0 kHz and PTA, and 1.0 kHz to 8.0 kHz and PTA, respectively. Those with high noise exposure (vs no/little) showed higher rates of threshold change per year at 1.0 kHz and 2.0 kHz. Participants with some and high noise exposure showed lower rates of change per year at 3.0 kHz to 8.0 kHz and 4.0 kHz to 8.0 kHz, respectively, where hearing loss had already occurred. The rate of PTA change per year did not differ across noise exposure groups.Conclusions and RelevanceIn this cohort study, noise exposure was associated with poorer baseline hearing and higher rates of annual decline at some midfrequencies. Noise exposure can have immediate and potentially long-term negative impacts on hearing.
A New Strategy for Sulfone‐Containing Electrolytes Design Enabling Long Cycling High‐Voltage Lithium‐Ion Batteries
Authors: Li Yinghui , Amzil Said , Xu Tonghui , Xiao Yiyao , Liu Xingchen , Ru Zhengzheng , Wu Mengqi , Luo Shengyao , Peng Meilan , Tian Shuang , Gao Jie , Shi Siqi , Wang Donghai , Cheng Ya‐Jun , Xia Yonggao 
Published: January 2025

AbstractHigh‐energy‐density lithium‐ion batteries (LIBs) face critical challenges due to the lack of electrolyte solvents that can achieve dual‐interfaces stability. Although ethyl mesylate (EM)‐based sulfone electrolytes are compatible with high‐voltage cathodes, their high viscosity and the tendency of EM's reactive sulfonate ester group to decompose at graphite (Gr) anodes limit their broad applications. Here, a novel electrolyte approach is introduced that uses single co‐solvent ethyl acetate (EA), methyl propionate (MP), or methyl butyrate (MB) in an EM‐based electrolyte to modulate solvation and interfacial chemistry bypassing the high‐concentration lithium salt. These co‐solvents disrupt the EM‐dominated solvation structure, diminishing the EM‐Li+ interaction, allowing more lithium oxalyldifluoroborate (LiODFB) to integrate into the primary Li+ solvation shell and facilitate the formation of stable electrode interphases. The designed electrolytes ensure high‐voltage stability while solving the incompatibility of sulfone solvent EM at the graphite anode. Consequently, a 4.5 V Gr||LiNi0.8Co0.1Mn0.1O2 (NCM811) full cell demonstrates outstanding cycling stability, retaining 89.1% capacity after 500 cycles at 1 C rate, with an average coulombic efficiency of 99.92%. This innovative strategy offers a practical approach for utilizing sulfone solvents in next‐generation high‐voltage lithium‐ion batteries.
Effective Gene Expression Prediction and Optimization from Protein Sequences
Authors: Liu Tuoyu , Zhang Yiyang , Li Yanjun , Xu Guoshun , Gao Han , Wang Pengtao , Tu Tao , Luo Huiying , Wu Ningfeng , Yao Bin , Liu Bo , Guan Feifei , Huang Huoqing , Tian Jian 
Published: January 2025

AbstractHigh soluble protein expression in heterologous hosts is crucial for various research and applications. Despite considerable research on the impact of codon usage on expression levels, the relationship between protein sequence and expression is often overlooked. In this study, a novel connection between protein expression and sequence is uncovered, leading to the development of SRAB (Strength of Relative Amino Acid Bias) based on AEI (Amino Acid Expression Index). The AEI served as an objective measure of this correlation, with higher AEI values enhancing soluble expression. Subsequently, the pre‐trained protein model MP‐TRANS (MindSpore Protein Transformer) is developed and fine‐tuned using transfer learning techniques to create 88 prediction models (MPB‐EXP) for predicting heterologous expression levels across 88 species. This approach achieved an average accuracy of 0.78, surpassing conventional machine learning methods. Additionally, a mutant generation model, MPB‐MUT, is devised and utilized to enhance expression levels in specific hosts. Experimental validation demonstrated that the top 3 mutants of xylanase (previously not expressed in Escherichia coli) successfully achieved high‐level soluble expression in E. coli. These findings highlight the efficacy of the developed model in predicting and optimizing gene expression based on protein sequences.
Single‐Cell Multi‐omics Assessment of Spinal Cord Injury Blocking via Cerium‐doped Upconversion Antioxidant Nanoenzymes
Authors: Wang Ke , Zheng Judun , Li Ronghai , Chen Tianjun , Ma Yanming , Wu Ping , Luo Jianxian , Zhu Jingyi , Lin Weiqiang , Zhao Minghai , Yuan Yue , Ma Wen , Lin Xiumei , Wang Yang , Liu Longqi , Gao Peng , Lin Hongsheng , Liu Chuanyu , Liao Yuhui , Ji Zhisheng 
Published: January 2025

AbstractSpinal cord injury (SCI) impairs the central nervous system and induces the myelin‐sheath‐deterioration because of reactive oxygen species (ROS), further hindering the recovery of function. Herein, the simultaneously emergency treatment and dynamic luminescence severity assessment (SETLSA) strategy is designed for SCI based on cerium (Ce)‐doped upconversion antioxidant nanoenzymes (Ce@UCNP‐BCH). Ce@UCNP‐BCH can not only efficiently eliminate the SCI localized ROS, but dynamically monitor the oxidative state in the SCI repair process using a ratiometric luminescence signal. Moreover, the classic basso mouse scale score and immunofluorescence analysis together exhibit that Ce@UCNP‐BCH effectively facilitates the regeneration of spinal cord including myelin sheath, and promotes the functional recovery of SCI mice. Particularly, the study combines snATAC‐eq and snRNA‐seq to reveal the heterogeneity of spinal cord tissue following Ce@UCNP‐BCH treatment. The findings reveal a significant increase in myelinating oligodendrocytes, as well as higher expression of myelination‐related genes, and the study also reveals the gene regulatory dynamics of remyelination after treatment. Besides, the ETLSA strategy synergistically boosts ROS consumption through the superoxide dismutase (SOD)‐related pathways after SOD‐siRNA treatment. In conclusion, this SETLSA strategy with simultaneously blocking and dynamic monitoring oxidative stress has enriched the toolkit for promoting SCI repair.
Bioactive Glycyrrhizic Acid Ionic Liquid Self‐Assembled Nanomicelles for Enhanced Transdermal Delivery of Anti‐Photoaging Signal Peptides
Authors: Wang Zhuxian , Liu Jun , Chen QiuYu , Wu Yufan , Li Yamei , Ou Mingjie , Tang Shuwei , Deng Ziqing , Liu Li , Jiang Cuiping , Zhu Hongxia , Liu Qiang , Yang Bin 
Published: January 2025

AbstractSigal peptides have garnered remarkable efficacy in rejuvenating photoaged skin and delaying senescence. Nevertheless, their low solubility and poor permeability bring about a formidable challenge in their transdermal delivery. To address this challenge, bioactive ionic liquids (ILs) synthesized from natural glycyrrhizic acid (GA) and oxymatrine (OMT) with eminent biocompatibility is first prepared. The components ratios and inherent forming mechanisms of GA‐OMT (GAO) are optimized by molecular dynamics simulations and density functional theory calculations. Remarkably, GAO can significantly improve the sparingly soluble properties of palmitoyl pentapeptide‐4 (PAL‐4), a model peptide drug. Subsequently, GAO self‐assembled micelles loading PAL‐4 (GAO/PAL‐4‐SM) are fabricated without additional auxiliary materials. The permeation and subcutaneous retention of PAL‐4 are significantly promoted with 10wt.% GAO‐SM. Moreover, GAO ILs facilitated PAL‐4 permeation by enhancing its miscibility and interaction with stratum corneum (SC), offering a pulling effect and micellar structures for PAL‐4, as elucidated by computational simulations. In cellular and animal photoaging experiments, GAO/PAL‐4‐SM possessed remarkable capabilities in boosting collagen and hyaluronic acid regeneration, mitigating inflammation and apoptosis, accelerating macrophage M2 polarization, thereby lessening skin wrinkles and leveraging elasticity. Collectively, the research innovatively designed an ILs self‐assembled nano‐micellar transdermal delivery system to enhance the permeability and anti‐photoaging effect of signal peptides.