bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential effects of PGAM5 knockout on high fat high fructose diet and methionine choline-deficient diet induced non-alcoholic steatohepatitis (NASH) in mice
Authors: Li Li , Guo Chengcheng , Yu Yue , Tie Lu , Lu Guotao , Liu Feng , Han Xueyao , Ji Linong , Zou Xiantong 
Published: August 2023

Abstract
Background
Phosphoglycerate mutase 5 (PGAM5), a phosphatase involved in mitochondrial homeostasis, is reported to be closely related to the metabolic stress induced by high-fat diet (HFD) or cold. In this study, we aimed to investigate the effects of PGAM5 on hepatic steatosis, inflammation and fibrosis in nonalcoholic steatohepatitis (NASH).

Methods and results
We generated PGAM5 global knockout (GKO) mice and their wildtype (WT) littermates using CRISPR/CAS9. The mice were fed with a high fat high fructose (HFHF) diet for 12 weeks or a methionine choline-deficient (MCD) diet (methionine choline supplemented (MCS) as control) for 6 weeks. Hepatic PGAM5 expression was up-regulated in humans with NASH and WT mice fed with HFHF and MCS, and reduced in WT mice fed with MCD diet. In HFHF-fed mice, GKO had reduced body weight, hepatic triglyceride (TG) content and serum transaminase along with decreased hepatic pro-inflammatory and pro-fibrotic responses compared with their WT control. GKO had increased expression of antioxidative gene glutathione peroxidase-6 (GPX6) and activation of mammalian target of rapamycin (mTOR). In mice fed with MCS diet, GKO significantly increased serum TNF-α and IL-6 and decreased hepatic GPX6 mRNA expression. There was no difference in hepatic steatosis, inflammation or fibrosis between GKO and WT mice fed with MCD diet. We investigated the role of PGAM5 deficiency in a variety of cell types. In differentiated THP-1 cells, PGAM5 silencing significantly increased pro-inflammatory cytokine secretion and decreased antioxidative proteins, including nuclear factor erythroid 2- related factors (NRF2), heme oxygenase-1 (HO-1) and GPX6 without affecting mTOR activity. In HepG2 cells with steatosis, PGAM5 knockdown reduced insulin sensitivity, increased mTOR phosphorylation and reduced the expression of NRF2, catalase (CAT), HO-1 and GPX6. Conversely, PGAM5 knockdown reduced TG accumulation, increased insulin sensitivity, and increased antioxidative genes in 3T3-L1 cells, despite the up-regulation in mTOR phosphorylation.

Conclusions
PGAM5-KO relieved hepatic steatosis and inflammation in HFHF model, promoted inflammation in MCS-fed mice and had no effects on the MCD-fed model. The distinct effects may be owing to the different effects of PGAM5-KO on anti-oxidative pathways in energy-dependent, possible involves mTOR, and/or cell type-dependent manner. Our findings suggest that PGAM5 can be a potential therapeutic target for NASH.
Effects of gut microbial therapy on lipid profile in individuals with non-alcoholic fatty liver disease: an umbrella meta-analysis study
Authors: Naghipour Amirhossein , Amini-Salehi Ehsan , Orang Gorabzarmakhi Mahdi , Shahdkar Milad , Fouladi Bahman , Alipourfard Iraj , Sanat Zahra Momayez 
Published: August 2023

Abstract
Background
Non-alcoholic fatty liver disease (NAFLD), the most common liver disease, is closely associated with metabolic conditions such as obesity and diabetes mellitus, which significantly impact human health outcomes. The impaired lipid profiles observed in NAFLD individuals can further contribute to cardiovascular events. Despite the high prevalence of NAFLD, there is currently no confirmed intervention approved for its treatment. This study aimed to summarize the results of meta-analysis studies of randomized control trials assessing the impact of gut microbial therapy (probiotics, synbiotics, and prebiotics) on the lipid profile of individuals with NAFLD.

Methods
A systematic search was conducted on PubMed, Scopus, Web of Science, and Cochrane Library up to November 1, 2022. Meta-analyses surveying the impact of microbial therapy on lipid profile parameters (triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and total cholesterol (TC)) in the NAFLD population were included in our umbrella review. The final effect size (ES) was estimated, and sensitivity and subgroup analyses were performed to explore heterogeneity.

Results
Fifteen studies were included in this umbrella review. Microbial therapy significantly reduced TG (ES − 0.31, 95% CI − 0.51, − 0.11, P < 0.01), TC (ES − 1.04, 95% CI − 1.46, − 0.61, P < 0.01), and LDL (ES − 0.77, 95% CI − 1.15, − 0.39, P < 0.01) in individuals with NAFLD. However, the effect on HDL was not statistically significant (ES − 0.06; 95% CI − 0.19, 0.07, P = 0.39).

Conclusion
Considering the absence of approved treatments for NAFLD and the promising role of microbial therapies in improving the three lipid profiles components in individuals with NAFLD, the use of these agents as alternative treatment options could be recommended. The findings underscore the potential of gut microbial therapy, including probiotics, synbiotics, and prebiotics, in managing NAFLD and its associated metabolic complications.

Trial registration
PROSPERO (CRD42022346998).

Graphical Abstract
Gender differences in leukemia outcomes based on health care expenditures using estimates from the GLOBOCAN 2020
Authors: Amini Maedeh , Sharma Rajesh , Jani Chinmay 
Published: August 2023

Abstract
Background
Leukemia contributes significantly to the global cancer burden. Due to the importance of evaluating improvements in leukemia outcomes, the current study aimed to examine the variations in mortality-to-incidence ratio (MIR) between genders and association of MIR with the health expenditures in selected countries.

Methods
The leukemia incidence and mortality rates were extracted from the GLOBOCAN 2020 database. In total, 56 countries were included based on the data quality reports and the exclusion of missing data. The associations of MIR and changes in MIR over time ($$\updelta$$
δ
MIR) with the human development index (HDI), current health expenditure (CHE) per capita, and current health expenditure as a percentage of gross domestic product (CHE/GDP) were investigated using Spearman’s rank correlation coefficient.

Results
In 2020, an estimated 474,519 new cases of leukemia were diagnosed globally, and 311,594 deaths occurred due to the disease. Male patients exhibited a higher incidence and mortality of leukemia compared to females on a global scale. Our analysis revealed that the MIRs were the highest and lowest in Egypt (0.79) and the United States (0.29), respectively. Remarkably, countries with greater HDI, higher CHE per capita, and a higher CHE/GDP tended to have lower MIR in both genders and within gender-specific subgroups. The δMIR demonstrated a significant negative correlation with HDI and CHE per capita, whereas no significant associations were observed among female patients for CHE/GDP. Besides, all three indicators showed trends towards negative correlations with δMIR among males, though these trends were not statistically significant (p>0.05).

Conclusions
Generally, leukemia MIRs tended to be most favorable (i.e., lower) in countries with high HDI and high health expenditure. The gender differences observed in leukemia outcomes may reflect the potential influence of social, material, behavioral, and biological factors.
Association of the androgens with COVID-19 prognostic outcomes: a systematic review
Authors: Zhang Linyu , Sun Xinrui , Feng Ying , Ma Fang 
Published: August 2023

Abstract
Objective
The coronavirus disease 2019 was a global public health emergency in later years (from 2020 to early 2022), and androgens have been associated with infection and prognostic outcomes. However, the relationship between low serum testosterone levels and prognostic outcomes remains inconclusive. This systematic review aimed to investigate the relationship between serum testosterone levels and prognostic outcomes in patients with COVID-19.

Methods
We searched PubMed, MEDLINE, EMBASE and Web of Science electronic databases for all literature from January 1, 2020, to September 1, 2022. In addition, we also searched literature manually. The search terms were COVID-19, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), androgens, and testosterone. There were no language restrictions for retrieval.

Results
Our search identified 2285 articles, resulting in a full-text analysis of 16 studies, including 12 cohort studies and four case-control studies. Low serum testosterone levels were observed to be statistically associated with a higher probability of intensive care unit (ICU) admission in seven studies. In eight studies, higher hospital mortality was associated with lower serum testosterone levels. Six studies found that low serum testosterone levels were associated with a statistically significant difference in lung function impairment. Only four studies found that among living patients, those with lower serum testosterone levels had longer hospital stays. All but one of the included studies had a low risk of bias.

Conclusions
Based on available data, low serum testosterone levels are associated with higher rates of ICU admission, hospital mortality, risk of lung failure, inflammatory markers, and longer hospital stays in patients with COVID-19 compared with those having normal serum testosterone levels.
Prevalence of vancomycin-resistant Enterococci in India between 2000 and 2022: a systematic review and meta-analysis
Authors: Smout Emily , Palanisamy Navaneethan , Valappil Sabeel P 
Published: August 2023

AbstractBackgroundVancomycin-resistantEnterococci(VRE) infections are recurrently reported in different parts of India in the last two decades. However, an up-to-date, countrywide information concerning the prevalence and the rate of VRE in India is limited and hence this study aimed to estimate the pooled prevalence of VRE in India.MethodsA literature search was performed using various databases. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed throughout. Cross-sectional studies reporting the prevalence of VRE in India from human samples whereby at least twoEnterococciwere isolated between 1 January 2000 and 31 December 2022 were sought for inclusion. Data were extracted and analysed using Microsoft Excel and Comprehensive Meta-analysis version 4, respectively.ResultsNineteen studies were included in the analyses. A collective total of 3683Enterococciisolates were examined, of which 368 were VRE strains. The pooled prevalence of VRE in India was calculated at 12.4% (95% CI: 8.6–17.5;Q = 189.69;I2 = 90.51%;p = < 0.001).E. faecaliswas the most frequently isolated species (1450 [39.37%]) followed byE. faecium(724 [19.66%]). Amongst the VRE strains,E. faeciumwas the most prevalent (214 [58.15%]) followed byE. faecalis(134 [36.41%]). An upsurge in the rate of VRE infections was observed in India over time: VRE prevalence was estimated at 4.8% between 2000 and 2010 and 14.1% between 2011 and 2020.ConclusionThis study presents the most up-to-date information on the rate of VRE infections in India. Though lower than the findings for some less developed countries, VRE prevalence in India is notable and on the rise.
Investigation of brain iron in anorexia nervosa, a quantitative susceptibility mapping study
Authors: Ravanfar Parsa , Rushmore R. Jarrett , Lyall Amanda E. , Cropley Vanessa , Makris Nikos , Desmond Patricia , Velakoulis Dennis , Shenton Martha E. , Bush Ashley I. , Rossell Susan L. , Pantelis Christos , Syeda Warda T. , Phillipou Andrea 
Published: August 2023

Abstract
Background
Anorexia nervosa (AN) is a potentially fatal psychiatric condition, associated with structural brain changes such as gray matter volume loss. The pathophysiological mechanisms for these changes are not yet fully understood. Iron is a crucial element in the development and function of the brain. Considering the systemic alterations in iron homeostasis in AN, we hypothesized that brain iron would be altered as a possible factor associated with structural brain changes in AN.

Methods
In this study, we used quantitative susceptibility mapping (QSM) magnetic resonance imaging to investigate brain iron in current AN (c-AN) and weight-restored AN compared with healthy individuals. Whole-brain voxel wise comparison was used to probe areas with possible group differences. Further, the thalamus, caudate nucleus, putamen, nucleus accumbens, hippocampus, and amygdala were selected as the regions of interest (ROIs) for ROI-based comparison of mean QSM values.

Results
Whole-brain voxel-wise and ROI-based comparison of QSM did not reveal any differences between groups. Exploratory analyses revealed a correlation between higher regional QSM (higher iron) and lower body mass index, higher illness severity, longer illness duration, and younger age at onset in the c-AN group.

Conclusions
This study did not find evidence of altered brain iron in AN compared to healthy individuals. However, the correlations between clinical variables and QSM suggest a link between brain iron and weight status or biological processes in AN, which warrants further investigation.
Minoxidil weakens newly synthesized collagen in fibrotic synoviocytes from osteoarthritis patients
Authors: Sarkovich Stefan , Issa Peter P. , Longanecker Andrew , Martin Davis , Redondo Kaitlyn , McTernan Patrick , Simkin Jennifer , Marrero Luis 
Published: August 2023

AbstractPurposeSynovial fibrosis (SFb) formation and turnover attributable to knee osteoarthritis (KOA) can impart painful stiffness and persist following arthroplasty. To supplement joint conditioning aimed at maximizing peri‐operative function, we evaluated the antifibrotic effect of Minoxidil (MXD) on formation of pyridinoline (Pyd) cross‐links catalyzed by Plod2‐encoded lysyl hydroxylase (LH)2b that strengthen newly synthesized type‐I collagen (COL1) in fibroblastic synovial cells (FSCs) from KOA patients. MXD was predicted to decrease Pyd without significant alterations to Col1a1 transcription by FSCs stimulated with transforming growth factor (TGF)β1.MethodsSynovium from 10 KOA patients grouped by SFb severity was preserved for picrosirius and LH2b histology or culture. Protein and RNA were purified from fibrotic FSCs after 8 days with or without 0.5 µM MXD and/or 4 ng/mL of TGFβ1. COL1 and Pyd protein concentrations from ELISA and expression of Col1a1, Acta2, and Plod2 genes by qPCR were compared by parametric tests with α = 0.05.ResultsHistological LH2b expression corresponded to SFb severity. MXD attenuated COL1 output in KOA FSCs but only in the absence of TGFβ1 and consistently decreased Pyd under all conditions with significant downregulation of Plod2 but minimal alterations to Col1a1 and Acta2 transcripts.ConclusionsMXD is an attractive candidate for local antifibrotic pharmacotherapy for SFb by compromising the integrity of newly formed fibrous deposits by FSCs during KOA and following arthroplasty. Targeted antifibrotic supplementation could improve physical therapy and arthroscopic lysis strategies aimed at breaking down joint scarring. However, the effect of MXD on other joint‐specific TGFβ1‐mediated processes or non‐fibrotic components requires further investigation.
Marine inundation history during the last 3000 years at Lake Kogare-ike, a coastal lake on the Pacific coast of central Japan
Authors: Shimada Yumi , Sawai Yuki , Matsumoto Dan , Tanigawa Koichiro , Ito Kazumi , Tamura Toru , Namegaya Yuichi , Shishikura Masanobu , Fujino Shigehiro 
Published: August 2023

AbstractSediment cores collected at Lake Kogare-ike, a coastal lake on the Pacific coast of central Japan, record the marine inundation history during the last 3000 years. The sediments consist mainly of organic mud, sand, gravel, inorganic mud, and volcanic ash, and inundation events were recognized as 19 event deposits (E1–E19, from top to bottom) interbedded with the organic mud. Visual observation by naked eyes and X-ray computed tomography (CT) images identified 16 event deposits based on quantitative and qualitative changes in sand contents and changes in the textures and colors of the sediment samples (E1–E3, E5, E6, E8, E9, and E11–E19). The other three event deposits (E4, E7, and E10) were identified only on the CT images as layers with higher radiodensity than the underlying and overlying organic mud layers. The sedimentary features, the spatial bias of the event deposits toward seaward areas, the diatom assemblages, and the frequency of inundation events suggest that 13 (E1–E10 and E12–E14) of the 19 event deposits were formed by tsunamis or extraordinary storms. To constrain the depositional ages of the event deposits, Bayesian age–depth models were constructed based on radiocarbon dating of plant macrofossils and concentrated fossil pollen and the 137Cs profile. The depositional ages of the event deposits indicate that five or possibly six event deposits can be correlated with historical tsunamis along the Nankai Trough: E2, either of E3 or E4, E5, E7, and E9 correspond to the 1707 CE Hoei, the 1605 CE Keicho, the 1498 CE Meio, the 1096 CE Eicho, and the 684 CE Hakuho tsunamis, respectively. E1 was possibly formed by the 1944 CE Showa-Tonankai tsunami, the 1854 Ansei–Tokai tsunami, the 1959 Isewan typhoon, or a combination of two or all three events.
Imaging of 212Pb in mice with a clinical SPECT/CT
Authors: Kvassheim Monika , Tornes Anna Julie Kjøl , Juzeniene Asta , Stokke Caroline , Revheim Mona-Elisabeth R. 
Published: August 2023

1 Abstract
Introduction
212Pb is a promising radionuclide for targeted alpha therapy. Here, the feasibility of visualising the tumour uptake and biodistribution of 212Pb-NG001 in mice with a clinical SPECT/CT scanner was investigated.

Methods
A mouse phantom with 212Pb was imaged with a clinical- and a preclinical SPECT/CT scanner. Different acquisition and reconstruction settings were investigated on the clinical system (Siemens Symbia Intevo Bold). Two athymic nude mice carrying PC-3 PIP prostate cancer tumours of 235–830 μl received 1.44 MBq of 212Pb-NG001 and were imaged 2, 6, and 24 h post-injection on the clinical SPECT/CT with a Medium Energy collimator and a 40% energy window centred on 79 keV. All acquisition times were 30 min, except the mouse imaging 24 h post-injection which was 60 min. After the final imaging, the organs were harvested and measured on a gamma counter to give an indication of how much activity was present in organs of interest at the last imaging time point.

Results
Four volumes in the mouse phantom of ~ 300 μl with 246–303 kBq/ml of 212Pb were distinguishable on images acquired with the clinical SPECT/CT with a high number of reconstruction updates. With the preclinical SPECT, the same volumes were easily distinguished with 49 kBq/ml of 212Pb. Clinical SPECT/CT images of the mice revealed uptake in tumours and bladders 2 h after injection and in tumours containing down to approximately 15 kBq/ml at 6 and 24 h after injection.

Conclusion
Although the preclinical scanner should be used preferentially in biodistribution studies in mice, the clinical SPECT/CT confirmed uptake in small volumes (e.g. ~ 300 μl volume with ~ 250 kBq/ml). Regardless of system, the resolution and sensitivity limits should be carefully determined, otherwise false negative or too low uptakes can be wrongly interpreted.
A life course health development model of HIV vulnerabilities and resiliencies in young transgender women in Peru
Authors: Reisner Sari L. , Aguayo-Romero Rodrigo A. , Perez-Brumer Amaya , Salazar Ximena , Nunez-Curto Aron , Orozco-Poore Casey , Silva-Santisteban Alfonso 
Published: August 2023

Abstract
Background
Globally transgender women (TW) are at heightened vulnerability for HIV infection. In Lima Peru, sharp increases in HIV prevalence are seen among TW ages 25 years and older highlighting the need for early HIV prevention efforts for young TW. This study conducted in-depth qualitative interviews to elucidate the social and developmental contexts of HIV vulnerability for young TW in Lima Peru.

Methods
Between November 2019 and February 2020, young TW ages 16–24 years (n = 21) in Lima Peru were purposively sampled using in-person (e.g., face-to-face outreach) and online (e.g., social media, networking websites) social network-based methods. Interviews were conducted in Spanish and a rapid qualitative analysis was conducted using a modified immersion crystallization methodology to identify themes.

Results
Five themes emerged, informing the conceptualization of a Life Course Health Development Model of HIV Vulnerabilities and Resiliencies: (1) interpersonal contexts (family, school, partners, sexual debut, trans mothers); (2) structural vulnerabilities (poverty, educational constraints, migration, hostile environments, sex work, police violence); (3) concomitant mental health and psychosocial factors (discrimination, violence, depression, suicidality, substance use, life hopes/dreams/future expectations); (4) gender affirmation processes (gender identity development, hormones, surgery, legal name/gender marker change); (5) HIV prevention and treatment barriers (PrEP uptake, HIV care, condom use, risk reduction).

Conclusions
Young TW experience formidable developmental challenges associated with transphobia, violence, and pre-maturely facing accelerated milestones. Developmentally and culturally appropriate interventions to mitigate HIV vulnerability in Peru are needed, including those that consider co-occurring stigma-related conditions in adolescence and young adulthood.
InflANNet: a neural network predictor for Influenza A CTL and HTL epitopes to aid robust vaccine design
Authors: Karthika R. , Muthusamy Sathya , Prabhu Prince R. 
Published: August 2023

Abstract
Background
An efficient and reliable data-driven method is essential to aid robust vaccine design, particularly in the case of an epidemic like Influenza A. Although various prediction tools are existing, most of them focus on the MHC-peptide binding affinity predictions. A tool which can incorporate more features other than binding affinity which characterizes the T-cell epitopes as vaccine candidates would be of much value in this scenario. The objective of this study is to develop two separate neural network models for the predictions of CTLs (cytotoxic T lymphocyte) and HTLs (helper T lymphocyte) with the manually curated datasets as a part of this study from the raw viral sequences of Influenza A.

Results
The epitope datasets curated from the raw sequences of the broadly protective Neuraminidase protein were utilized for building and training the models for CTLs and HTLs. Each set consisted of nearly a balanced mix of vaccine candidates and non-vaccine candidates for both CTLs and HTLs. These were fed to neural networks as they are proven to be powerful for the predictions when compared with the other machine/deep learning algorithms. A set of epitopes experimentally proved were chosen to validate the model which was also tested through mutational analysis and cross-reactivity. The prepared dataset gave some valuable insights into the epitope distribution statistics and their conservancy in various outbreaks. An idea about the most probable range of peptide-MHC binding affinities was also obtained. Both the models performed well giving high accuracies when validated. These epitopes were checked for cross-reactivity with other antigens upon which it proved to be highly conservative and ideal for vaccine formulation.

Conclusions
The combination of various features and the resulting model efficiencies in turn proved that the collected features are valuable in the easy identification of the vaccine candidates. This suggests that our proposed models have more potential for conserved epitope prediction compared to other existing models trained on similar data and features. The possibility of refining the model with more set threshold values based on more parameters is an added feature that makes it more user driven. Furthermore, the uniqueness of the model due to exclusive set of Neuraminidase epitopes paves a robust way for rapid vaccine design.

Graphical abstract