bluuebunny/crossref_metadata_2025_split huggingface dataset:
LSD1: an emerging face in altering the tumor microenvironment and enhancing immune checkpoint therapy
Authors: Mamun M A A , Zhang Yu , Zhao Jin-Yuan , Shen Dan-Dan , Guo Ting , Zheng Yi-Chao , Zhao Li-Juan , Liu Hong-Min 
Published: July 2023

AbstractDysregulation of various cells in the tumor microenvironment (TME) causes immunosuppressive functions and aggressive tumor growth. In combination with immune checkpoint blockade (ICB), epigenetic modification-targeted drugs are emerging as attractive cancer treatments. Lysine-specific demethylase 1 (LSD1) is a protein that modifies histone and non-histone proteins and is known to influence a wide variety of physiological processes. The dysfunction of LSD1 contributes to poor prognosis, poor patient survival, drug resistance, immunosuppression, etc., making it a potential epigenetic target for cancer therapy. This review examines how LSD1 modulates different cell behavior in TME and emphasizes the potential use of LSD1 inhibitors in combination with ICB therapy for future cancer research studies.
Intranasal administration of Lactobacillus johnsonii attenuates hyperoxia-induced lung injury by modulating gut microbiota in neonatal mice
Authors: Chen Chung-Ming , Yang Yu-Chen S. H. , Chou Hsiu-Chu , Lin Shan 
Published: July 2023

Abstract
Background
Supplemental oxygen impairs lung development in newborn infants with respiratory distress. Lactobacillus johnsonii supplementation attenuates respiratory viral infection in mice and exhibits anti-inflammatory effects. This study investigated the protective effects of intranasal administration of L. johnsonii on lung development in hyperoxia-exposed neonatal mice.

Methods
Neonatal C57BL/6N mice were reared in either room air (RA) or hyperoxia condition (85% O2). From postnatal days 0 to 6, they were administered intranasal 10 μL L. johnsonii at a dose of 1 × 105 colony-forming units. Control mice received an equal volume of normal saline (NS). We evaluated the following four study groups: RA + NS, RA + probiotic, O2 + NS, and O2 + probiotic. On postnatal day 7, lung and intestinal microbiota were sampled from the left lung and lower gastrointestinal tract, respectively. The right lung of each mouse was harvested for Western blot, cytokine, and histology analyses.

Results
The O2 + NS group exhibited significantly lower body weight and vascular density and significantly higher mean linear intercept (MLI) and lung cytokine levels compared with the RA + NS and RA + probiotic groups. At the genus level of the gut microbiota, the O2 + NS group exhibited significantly higher Staphylococcus and Enterobacter abundance and significantly lower Lactobacillus abundance compared with the RA + NS and RA + probiotic groups. Intranasal L. johnsonii treatment increased the vascular density, decreased the MLI and cytokine levels, and restored the gut microbiota in hyperoxia-exposed neonatal mice.

Conclusions
Intranasal administration of L. johnsonii protects against hyperoxia-induced lung injury and modulates the gut microbiota.
Phenotypic heterogeneity in human genetic diseases: ultrasensitivity-mediated threshold effects as a unifying molecular mechanism
Authors: Sun Y. Henry , Wu Yueh-Lin , Liao Ben-Yang 
Published: July 2023

AbstractPhenotypic heterogeneity is very common in genetic systems and in human diseases and has important consequences for disease diagnosis and treatment. In addition to the many genetic and non-genetic (e.g., epigenetic, environmental) factors reported to account for part of the heterogeneity, we stress the importance of stochastic fluctuation and regulatory network topology in contributing to phenotypic heterogeneity. We argue that a threshold effect is a unifying principle to explain the phenomenon; that ultrasensitivity is the molecular mechanism for this threshold effect; and discuss the three conditions for phenotypic heterogeneity to occur. We suggest that threshold effects occur not only at the cellular level, but also at the organ level. We stress the importance of context-dependence and its relationship to pleiotropy and edgetic mutations. Based on this model, we provide practical strategies to study human genetic diseases. By understanding the network mechanism for ultrasensitivity and identifying the critical factor, we may manipulate the weak spot to gently nudge the system from an ultrasensitive state to a stable non-disease state. Our analysis provides a new insight into the prevention and treatment of genetic diseases.
Sustainable biorefining and bioprocessing of green seaweed (Ulva spp.) for the production of edible (ulvan) and non-edible (polyhydroxyalkanoate) biopolymeric films
Authors: Manikandan N. Arul , Lens Piet N. L. 
Published: July 2023

AbstractA sustainable biorefining and bioprocessing strategy was developed to produce edible-ulvan films and non-edible polyhydroxybutyrate films. The preparation of edible-ulvan films by crosslinking and plasticisation of ulvan with citric acid and xylitol was investigated using Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) analysis. The edible ulvan film was tested for its gut-friendliness using Lactobacillus and Bifidobacterium spp. (yoghurt) and was shown to improve these gut-friendly microbiome's growth and simultaneously retarding the activity of pathogens like Escherchia coli and Staphylococcus aureus. Green macroalgal biomass refused after the extraction of ulvan was biologically processed by dark fermentation to produce a maximum of 3.48 (± 0.14) g/L of volatile fatty acids (VFAs). Aerobic processing of these VFAs using Cupriavidus necator cells produced 1.59 (± 0.12) g/L of biomass with 18.2 wt% polyhydroxybutyrate. The present study demonstrated the possibility of producing edible and non-edible packaging films using green macroalgal biomass as the sustainable feedstock.
Graphical Abstract
Inflammatory cytokines as potential biomarkers for early diagnosis of severe malaria in children in Ghana
Authors: Obeng-Aboagye Elizabeth , Frimpong Augustina , Amponsah Jones Amo , Danso Samuel E. , Owusu Ewurama D. A. , Ofori Michael Fokuo 
Published: July 2023

Abstract
Background
Severe malaria (SM) is a fatal multi-system disease which accounted for an estimated 619,000 deaths in 2021. Less than 30% of children presenting with SM are diagnosed and treated promptly, resulting in increased mortality and neurologic impairments in survivors. Studies have identified cytokine profiles that differentiate the various clinical manifestations of malaria (severe and uncomplicated). However, the diagnostic capability of these cytokines in differentiating between the disease states in terms of cut-off values has not yet been determined.

Methods
The plasma levels of 22 pro-inflammatory cytokines (Eotaxin/CCL 11, interferon-gamma (IFN-γ), interleukin (IL)- 2, IL-6, IL-1β, IL-12p40/p70, IL-17A, RANTES, MCP-1, IL-15, IL-5, IL-1RA, IL-2R, IFN-α, IP-10, TNF, MIG, MIP-1α, MIP-1β, IL-7, IL-8 and Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF), and 3 anti-inflammatory cytokines-(IL-4, IL-13 and IL-10) in patients with SM, uncomplicated malaria (UM) and other febrile conditions, were measured and compared using the Human Cytokine Magnetic 25-Plex Panel. The receiver operating characteristic (ROC) curve analysis was used to determine the diagnostic value of these cytokines.

Results
The level of the pro-inflammatory cytokine, IL-17A, was significantly higher in the SM group as compared to the UM group. Levels of the anti-inflammatory cytokines however did not differ significantly among the SM and UM groups. Only IL-1β and IL-17A showed good diagnostic potential after ROC curve analysis.

Conclusion
The data show that levels of pro-inflammatory cytokines correlate with malaria disease severity. IL-1β and IL-17A showed good diagnostic potentials and can be considered for use in clinical practice to target treatment.
Risk factors of early bacterial infection and analysis of bacterial composition, distribution and drug susceptibility after cadaveric liver transplantation
Authors: Liu Min , Li Cuiying , Liu Jing , Wan Qiquan 
Published: July 2023

Abstract
Background
This study provided a theoretical basis for the clinical diagnosis and treatment of bacterial infection after liver transplantation through analyzing the pathogenic distribution, drug sensitivity and risk factors of bacterial infection after liver transplantation.

Methods
We collected clinical data from 207 recipients undergoing liver transplantation of graft from donation after citizens’ death donors in the Third Xiangya Hospital of Central South University from January 2019 to December 2021 and analyzed the composition and distribution of bacterial pathogens, drug resistance and risk factors of infection.

Results
A total of 90 bacterial infections occurred in 55 recipients within two months after liver transplantation, and the incidence of bacterial infection was 26.6% (55/207). The gram-negative bacteria (46/90, 51.1%) were more prevalent than gram-positive bacteria (44/90, 48.9%). Common sites of infection were the abdominal/biliary tract (26/90, 28.9%), lung (22/90, 22.4%) and urinary tract (22/90, 22.4%). Fourteen cases (6.8%) died after liver transplantation. Klebsiella pneumoniae (17/90, 18.9%) was the most frequent gram-negative bacteria causing infection in liver transplant recipients and 58.7%, 50%, 80.4% and 89.1% of gram-negative bacteria were sensitive to amikacin, minocycline, tigecycline and polymyxin B, respectively. The most common gram-positive bacteria was Enterococcus faecium (30/90, 33.3%) and 97.7%, 100%, 86.4%, 100% and 100% of gram-positive bacteria were sensitive to vancomycin, teicoplanin, daptomycin, tigecycline and linezolid, respectively. Univariate analysis revealed that bacterial infection was associated with female, age (≥ 50 years old), preoperative albumin (≤ 30 g/L), operation duration (≥ 400 min), intraoperative blood loss (≥ 3000 ml) and postoperative ventilator support. Binary Logistic regression analysis showed that female (OR = 3.149, 95% CI: 1.418–6.993, P = 0.005), operation duration (≥ 400 min) (OR = 2.393, 95% CI: 1.202–4.765, P = 0.013) and intraoperative blood loss (≥ 3000 ml) (OR = 2.052, 95% CI: 1.007–4.183, P = 0.048) were independent risk factors for bacterial infection after liver transplantation.

Conclusion
The incidence of early bacterial infection after liver transplantation was high, and the infection sites were mainly abdominal/biliary tract, respiratory tract and urinary tract. The most common pathogenic bacterium was gram-negative bacterium. Our study also identified several independent risk factors for bacterial infection after liver transplantation, including female gender, operation duration of 400 min or more, and intraoperative blood loss of 3000 ml or more. By addressing these risk factors, such as implementing strategies to optimize surgical procedures and minimize blood loss, healthcare professionals can work towards reducing the incidence of bacterial infections following liver transplantation.
Impacts of seasonal flooding on geographical access to maternal healthcare in the Barotse Floodplain, Zambia
Authors: Mroz Elizabeth Jade , Willis Thomas , Thomas Chris , Janes Craig , Singini Douglas , Njungu Mwimanenwa , Smith Mark 
Published: July 2023

AbstractBackgroundSeasonal floods pose a commonly-recognised barrier to women’s access to maternal services, resulting in increased morbidity and mortality. Despite their importance, previous GIS models of healthcare access have not adequately accounted for floods. This study developed new methodologies for incorporating flood depths, velocities, and extents produced with a flood model into network- and raster-based health access models. The methodologies were applied to the Barotse Floodplain to assess flood impact on women’s walking access to maternal services and vehicular emergency referrals for a monthly basis between October 2017 and October 2018.MethodsInformation on health facilities were acquired from the Ministry of Health. Population density data on women of reproductive age were obtained from the High Resolution Settlement Layer. Roads were a fusion of OpenStreetMap and data manually delineated from satellite imagery. Monthly information on floodwater depth and velocity were obtained from a flood model for 13-months. Referral driving times between delivery sites and EmOC were calculated with network analysis. Walking times to the nearest maternal services were calculated using a cost-distance algorithm.ResultsThe changing distribution of floodwaters impacted the ability of women to reach maternal services. At the peak of the dry season (October 2017), 55%, 19%, and 24% of women had walking access within 2-hrs to their nearest delivery site, EmOC location, and maternity waiting shelter (MWS) respectively. By the flood peak, this dropped to 29%, 14%, and 16%. Complete inaccessibility became stark with 65%, 76%, and 74% unable to access any delivery site, EmOC, and MWS respectively. The percentage of women that could be referred by vehicle to EmOC from a delivery site within an hour also declined from 65% in October 2017 to 23% in March 2018.ConclusionsFlooding greatly impacted health access, with impacts varying monthly as the floodwave progressed. Additional validation and application to other regions is still needed, however our first results suggest the use of a hydrodynamic model permits a more detailed representation of floodwater impact and there is great potential for generating predictive models which will be necessary to consider climate change impacts on future health access.
A potential correlation between adipokines, skeletal muscle function and bone mineral density in middle-aged and elderly individuals
Authors: Wang Wenhao , Gu Xuchao , Cao Ziyi , Wang Xiaojun , Lei Yiming , Xu Xiaoli , Wang Shiwen , Wu Tao , Bao Zhijun 
Published: July 2023

AbstractBackgroundEvidence exists of a strong association between inflammation and a decrease in skeletal muscle function and bone mineral density (BMD); however, the specific mechanisms of these associations remain unclear. Adipokines, as key regulators of the inflammatory response, may be implicated in these processes. The objective of this study was to explore the potential correlation between adipokines, skeletal muscle function and BMD in middle-aged and elderly individuals.MethodsA comparative cross-sectional study was carried out at the Huadong Hospital Affiliated with Fudan University (Shanghai, China). A total of 460 middle-aged and elderly individuals were recruited, and 125 were enrolled in the analysis. Their biochemical indices, body composition, skeletal muscle function and BMD were measured. Bioinformatic analysis was also employed to identify potential adipokine targets linked to skeletal muscle function and BMD. To validate these targets, plasma and peripheral blood mononuclear cells (PBMCs) were harvested from these individuals and subjected to western blotting (WB) and enzyme-linked immunosorbent assay (ELISA).ResultsIndividuals in this cross-sectional study were categorized into 2 groups according to their median skeletal muscle mass (SMM) (28.8 kg for males and 20.6 kg for females). Individuals with lower SMM exhibited poorer grip strength (P = 0.017), longer 5-Times-Sit-to-Stand Test (FTSST) duration (P = 0.029), lower total hip BMD (P = 0.043), lower femoral neck BMD (P = 0.011) and higher levels of inflammatory markers in comparison with individuals with higher SMM. Bioinformatics analysis identified LEP, ADIPOQ, RBP4, and DPP4 as potential adipokine targets associated with skeletal muscle function and BMD. In vitro experiments demonstrated that individuals with decreased skeletal muscle function and BMD expressed higher levels of these adipokines.ConclusionsSkeletal muscle function is positively correlated with BMD and negatively correlated with levels of inflammatory markers among middle-aged and elderly individuals. Those with lower skeletal muscle function and BMD tend to have a higher expression of LEP, ADIPOQ, RBP4 and DPP4.
Differentiating the role of alcohol in young men’s use of substances with sex: A qualitative study
Authors: Goodyear Trevor , Oliffe John L. , Parent Natasha , Mniszak Caroline , Jenkins Emily , Knight Rod 
Published: July 2023

Abstract
Background
Alcohol consumption is common among young men and occurs in many contexts. The sexualized substance use literature has generated some insight into the role of alcohol alongside other substances in the context of sex, though there remain opportunities for targeted and context-sensitive studies to examine the sexual practices and outcomes associated with alcohol, specifically.

Methods
This interpretive description study explores how experiences and contexts of alcohol use feature in the sexual lives of young men who use substances with sex. Data collection involved in-depth interviews conducted between 2018 and 2021 in Vancouver, Canada, with N = 76 young men (ages 18–30; mean = 23.9 years) who use substances with sex, including men with diverse sexual identities. Data were analyzed in an iterative manner through a social constructivist lens and an interpretive description framework, leveraging constant comparison techniques.

Findings
This analysis yielded three interconnected themes: (1) using alcohol for sexual(ity) freedoms; (2) backgrounding alcohol within a sexualized polysubstance milieu; and (3) navigating the risks and consequences of using alcohol with sex. Alcohol use was found to reduce inhibitions and support experimentation, including by facilitating the transgression of conservative or restrictive social and sexual norms. Alcohol was seldom explicitly classified as a sexualized substance, though it was evidently a widespread and normative social practice. This practice was associated with important risk and consequences, including with respect to consent, pregnancy and sexually transmitted and bloodborne infection risk, and sexual dysfunction.

Conclusions
Findings from this study position alcohol as a backgrounded yet significantly influential substance that young men use with sex. The sexualized use of substances must be understood, and responded to, in a manner that is grounded in harm reduction and that considers the full spectrum of substances—inclusive of but not limited to alcohol—and associated benefits and risks that feature in young men’s sexual lives. Specifically, sexual health and primary care providers working with young men should invite and open up meaningful conversation about how they may be using substances (including alcohol) with sex, while offering de-stigmatizing, sex-positive, and affirming education and supports to promote safer sex and substance use.
Association between Chinese visceral adiposity index and risk of stroke incidence in middle-aged and elderly Chinese population: evidence from a large national cohort study
Authors: Zhang Zenglei , Zhao Lin , Lu Yiting , Meng Xu , Zhou Xianliang 
Published: July 2023

Abstract
Background
Abdominal obesity has long been considered as a crucial risk factor of stroke. Chinese visceral adiposity index (CVAI), a novel surrogate indicator of abdominal obesity, has been confirmed as a better predictor for coronary heart disease than other indicators in Asian population. However, the data on the relationship of CVAI with stroke is limited. The objective of our study is evaluating the relationship between CVAI and stroke incidence.

Methods
In the present study, we enrolled 7242 middle-aged and elderly residents from the China Health and Retirement Longitudinal Study (CHARLS) and placed them into groups according to quartile of CVAI. The outcome of interest was stroke. Kaplan–Meier curves were used to estimate the cumulative incidences of stroke. Cox regression analyses and multivariable-adjusted restricted cubic spline (RCS) curves were performed to evaluate the relationship between CVAI and incident stroke. Multiple sensitivity analyses and subgroups analyses were performed to test the robustness of the findings.

Results
During a median 84 months of follow-up, 612 (8.45%) participants experienced incident stroke, and the incidences of stroke for participants in quartiles (Q) 1–4 of CVAI were 4.42%, 7.29%, 9.06% and 13.04%, respectively. In the fully adjusted model, per 1.0-SD increment in CVAI has a significant increased risk of incident stroke: hazard ratio (HR) [95% confidence interval (CI)] was 1.17 (1.07–1.28); compared with participants in Q1 of CVAI, the HRs (95% CI) of incident stroke among those in Q2–4 were 1.47 (1.10–1.95), 1.62 (1.22–2.15), and 1.70 (1.28–2.27), respectively. Subgroups analyses suggested the positive association was significant in male participants, without diabetes, hypertension and heart disease. The findings were robust in all the sensitivity analyses. Additional, RCS curves showed a significant dose-response relationship of CVAI with risk of incident stroke (P for non-linear trend = 0.319).

Conclusion
Increased CVAI is significantly associated with higher risk of stroke incidence, especially in male individuals, without hypertension, diabetes and heart disease. The findings suggest that baseline CVAI is a reliable and effective biomarker for risk stratification of stroke, which has far-reaching significance for primary prevention of stroke and public health.
Clinical outcomes and safety of anakinra in the treatment of multisystem inflammatory syndrome in children: a single center observational study
Authors: Dizon Brian L.P. , Redmond Christopher , Gotschlich Emily C. , Sule Sangeeta , Ronis Tova , Vazzana Kathleen M. , Sherman Matthew A. , Connor Rachael , Bosk Abigail , Dham Niti , Harahsheh Ashraf S. , Wells Elizabeth , DeBiasi Roberta , Srinivasalu Hemalatha 
Published: July 2023

AbstractBackground and objectiveEvidence for the treatment of multisystem inflammatory syndrome in children (MIS-C) is lacking. Anakinra, which targets IL-1-mediated inflammation, is reserved for refractory cases of MIS-C; however, its use in the treatment of MIS-C is not clearly established.Patients and methodsTo examine a role for anakinra in MIS-C, we performed a single center observational cohort study of all MIS-C patients diagnosed at our children’s hospital from May 15 to November 15, 2020. Demographics, clinical features, diagnostic testing, and cardiac function parameters were compared between MIS-C patients treated with intravenous immunoglobulin (IVIG) monotherapy and IVIG with anakinra (IVIG + anakinra).ResultsAmong 46 patients with confirmed MIS-C, 32 (70%) were in the IVIG + anakinra group, of which 9 (28%) were also given corticosteroids (CS). No patients were treated with anakinra alone. MIS-C patients in the IVIG + anakinra group were enriched in a CV shock phenotype (p = 0.02), and those with CV shock were treated with higher doses of anakinra for a longer duration. Furthermore, MIS-C patients in the IVIG + anakinra group exhibited improvements in fever and cardiac function with or without CS. No significant adverse events were observed, and no differences in IL-1β levels were found among MIS-C patients in the IVIG + anakinra group.ConclusionsAnakinra treatment, which was co-administered with IVIG primarily in patients with severe MIS-C, was associated with improvements in fever and cardiac function, and demonstrated a favorable side-effect profile. These findings suggest a role for adjunctive anakinra in the treatment of severe MIS-C.