bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of ambient air pollution with hemoglobin levels and anemia in the general population of Korean adults
Authors: Hwang Juyeon , Kim Hyun-Jin 
Published: April 2024

AbstractBackgroundEmerging evidence has suggested significant associations between ambient air pollution and changes in hemoglobin levels or anemia in specific vulnerable groups, but few studies have assessed this relationship in the general population. This study aimed to evaluate the association between long-term exposure to air pollution and hemoglobin concentrations or anemia in general adults in South Korea.MethodsA total of 69,830 Korean adults from a large-scale nationwide survey were selected for our final analysis. Air pollutants included particulate matter with an aerodynamic diameter less than or equal to 10 micrometers (PM10), particulate matter with an aerodynamic diameter less than or equal to 2.5 micrometers, nitrogen dioxide, sulfur dioxide (SO2), and carbon monoxide (CO). We measured the serum hemoglobin concentration to assess anemia for each participant.ResultsIn the fully adjusted model, exposure levels to PM10, SO2, and CO for one and two years were significantly associated with decreased hemoglobin concentrations (allp < 0.05), with effects ranging from 0.15 to 0.62% per increase in interquartile range (IQR) for each air pollutant. We also showed a significant association of annual exposure to PM10with anemia (p = 0.0426); the odds ratio (OR) [95% confidence interval (CI)] for anemia per each increase in IQR in PM10was estimated to be 1.039 (1.001–1.079). This association was also found in the 2-year duration of exposure (OR = 1.046; 95% CI = 1.009–1.083; adjusted Model 2). In addition, CO exposure during two years was closely related to anemia (OR = 1.046; 95% CI = 1.004–1.091; adjusted Model 2).ConclusionsThis study provides the first evidence that long-term exposure to air pollution, especially PM10, is significantly associated with reduced hemoglobin levels and anemia in the general adult population.
Droplet-based microfluidic platform for detecting agonistic peptides that are self-secreted by yeast expressing a G-protein-coupled receptor
Authors: Asama Ririka , Liu Cher J. S. , Tominaga Masahiro , Cheng Yu-Ru , Nakamura Yasuyuki , Kondo Akihiko , Wang Hsiang-Yu , Ishii Jun 
Published: April 2024

Abstract
Background
Single-cell droplet microfluidics is an important platform for high-throughput analyses and screening because it provides an independent and compartmentalized microenvironment for reaction or cultivation by coencapsulating individual cells with various molecules in monodisperse microdroplets. In combination with microbial biosensors, this technology becomes a potent tool for the screening of mutant strains. In this study, we demonstrated that a genetically engineered yeast strain that can fluorescently sense agonist ligands via the heterologous expression of a human G-protein-coupled receptor (GPCR) and concurrently secrete candidate peptides is highly compatible with single-cell droplet microfluidic technology for the high-throughput screening of new agonistically active peptides.

Results
The water-in-oil microdroplets were generated using a flow-focusing microfluidic chip to encapsulate engineered yeast cells coexpressing a human GPCR [i.e., angiotensin II receptor type 1 (AGTR1)] and a secretory agonistic peptide [i.e., angiotensin II (Ang II)]. The single yeast cells cultured in the droplets were then observed under a microscope and analyzed using image processing incorporating machine learning techniques. The AGTR1-mediated signal transduction elicited by the self-secreted Ang II peptide was successfully detected via the expression of a fluorescent reporter in single-cell yeast droplet cultures. The system could also distinguish Ang II analog peptides with different agonistic activities. Notably, we further demonstrated that the microenvironment of the single-cell droplet culture enabled the detection of rarely existing positive (Ang II-secreting) yeast cells in the model mixed cell library, whereas the conventional batch-culture environment using a shake flask failed to do so. Thus, our approach provided compartmentalized microculture environments, which can prevent the diffusion, dilution, and cross-contamination of peptides secreted from individual single yeast cells for the easy identification of GPCR agonists.

Conclusions
We established a droplet-based microfluidic platform that integrated an engineered yeast biosensor strain that concurrently expressed GPCR and self-secreted the agonistic peptides. This offers individually isolated microenvironments that allow the culture of single yeast cells secreting these peptides and gaging their signaling activities, for the high-throughput screening of agonistic peptides. Our platform base on yeast GPCR biosensors and droplet microfluidics will be widely applicable to metabolic engineering, environmental engineering, and drug discovery.
Impaired proprioception and magnified scaling of proprioceptive error responses in chronic stroke
Authors: Tulimieri Duncan Thibodeau , Semrau Jennifer A. 
Published: April 2024

Abstract
Background
Previous work has shown that ~ 50–60% of individuals have impaired proprioception after stroke. Typically, these studies have identified proprioceptive impairments using a narrow range of reference movements. While this has been important for identifying the prevalence of proprioceptive impairments, it is unknown whether these error responses are consistent for a broad range of reference movements. The objective of this study was to characterize proprioceptive accuracy as function of movement speed and distance in stroke.

Methods
Stroke (N = 25) and controls (N = 21) completed a robotic proprioception test that varied movement speed and distance. Participants mirror-matched various reference movement speeds (0.1–0.4 m/s) and distances (7.5–17.5 cm). Spatial and temporal parameters known to quantify proprioception were used to determine group differences in proprioceptive accuracy, and whether patterns of proprioceptive error were consistent across testing conditions within and across groups.

Results
Overall, we found that stroke participants had impaired proprioception compared to controls. Proprioceptive errors related to tested reference movement scaled similarly to controls, but some errors showed amplified scaling (e.g., significantly overshooting or undershooting reference speed). Further, interaction effects were present for speed and distance reference combinations at the extremes of the testing distribution.

Conclusions
We found that stroke participants have impaired proprioception and that some proprioceptive errors were dependent on characteristics of the movement (e.g., speed) and that reference movements at the extremes of the testing distribution resulted in significantly larger proprioceptive errors for the stroke group. Understanding how sensory information is utilized across a broad spectrum of movements after stroke may aid design of rehabilitation programs.
Effects of bone marrow sparing radiotherapy on acute hematologic toxicity for patients with locoregionally advanced cervical cancer: a prospective phase II randomized controlled study
Authors: Li Wen , Ma Lan , Li Fang , Li Kemin , Zhang Yang , Ren Hongtao , Bao Xing , Guo Yuyan , Guo Ya , Wang Mincong , Li Dan , Duan Yuanqiong , Ma Xiulong , Wang Zhongwei , Wang Yali , Yin Rutie 
Published: April 2024

Abstract
Objective
To evaluate effects of bone marrow sparing (BMS) radiotherapy on decreasing the incidence of acute hematologic toxicity (HT) for locoregionally advanced cervical cancer (LACC) patients treated by pelvic irradiation.

Materials and methods
LACC patients were recruited prospectively from May 2021 to May 2022 at a single center and were evenly randomized into the BMS group and the control group. All patients received pelvic irradiation with concurrent cisplatin (40 mg/m2 weekly), followed by brachytherapy and BM V40 < 25% in the BMS group was additionally prescribed. Acute HT was assessed weekly. Binary logistic regression model and receiver operating characteristic (ROC) curve were used for predictive value analysis. The trial was registered with Chinese clinical trial registry (ChiCTR2200066485).

Results
A total of 242 patients were included in the analysis. Baseline demographic, disease and treatment characteristics were balanced between the two groups. In the intention-to-treat population, BMS was associated with a lower incidence of grade ≥ 2 and grade ≥ 3 acute HT, leukopenia and neutropenia s(72.70% v 90.90%, P < 0.001*; 16.50% vs. 65.30%, P < 0.001*; 66.10% vs. 85.10%, P = 0.001*; 13.20% vs. 54.50%, P < 0.001*; 37.20% vs. 66.10%, P < 0.001*; 10.70% vs. 43.80%, P < 0.001*). BMS also resulted in decreased dose delivered to the organs at risk (OARs) including rectum, bladder and left and right femoral head. Univariate and multivariate analyses showed that BM V40 was an independent risk factor for grade ≥ 3 acute HT (odds ratio [OR] = 2.734, 95% confidence interval [CI] = 1.959–3.815, P < 0.001*). Cutoff value was 25.036% and area under the curve (AUC) was 0.786. The nomogram was constructed, which was rigorously evaluated and internally cross-validated, showing good predictive performance.

Conclusions
Receiving BMS pelvic irradiation could reduce the incidence of acute HT in LACC patients, and BM V40 < 25% may be a significant factor in reducing the risks of acute HT.
Bazi Bushen ameliorates age-related energy metabolism dysregulation by targeting the IL-17/TNF inflammatory pathway associated with SASP
Authors: Shen Xiaogang , Li Mengnan , Li Yawen , Jiang Yuning , Niu Kunxu , Zhang Shixiong , Lu Xuan , Zhang Runtao , Zhao Zhiqin , Zhou Liangxing , Guo Zhifang , Wang Siwei , Wei Cong , Chang Liping , Hou Yunlong , Wu Yiling 
Published: April 2024

Abstract
Background
Chronic inflammation and metabolic dysfunction are key features of systemic aging, closely associated with the development and progression of age-related metabolic diseases. Bazi Bushen (BZBS), a traditional Chinese medicine used to alleviate frailty, delays biological aging by modulating DNA methylation levels. However, the precise mechanism of its anti-aging effect remains unclear. In this study, we developed the Energy Expenditure Aging Index (EEAI) to estimate biological age. By integrating the EEAI with transcriptome analysis, we aimed to explore the impact of BZBS on age-related metabolic dysregulation and inflammation in naturally aging mice.

Methods
We conducted indirect calorimetry analysis on five groups of mice with different ages and utilized the data to construct EEAI. 12 -month-old C57BL/6 J mice were treated with BZBS or β-Nicotinamide Mononucleotide (NMN) for 8 months. Micro-CT, Oil Red O staining, indirect calorimetry, RNA sequencing, bioinformatics analysis, and qRT-PCR were performed to investigate the regulatory effects of BZBS on energy metabolism, glycolipid metabolism, and inflammaging.

Results
The results revealed that BZBS treatment effectively reversed the age-related decline in energy expenditure and enhanced overall metabolism, as indicated by the aging index of energy expenditure derived from energy metabolism parameters across various ages. Subsequent investigations showed that BZBS reduced age-induced visceral fat accumulation and hepatic lipid droplet aggregation. Transcriptomic analysis of perirenal fat and liver indicated that BZBS effectively enhanced lipid metabolism pathways, such as the PPAR signaling pathway, fatty acid oxidation, and cholesterol metabolism, and improved glycolysis and mitochondrial respiration. Additionally, there was a significant improvement in inhibiting the inflammation-related arachidonic acid-linoleic acid metabolism pathway and restraining the IL-17 and TNF inflammatory pathways activated via senescence associated secretory phenotype (SASP).

Conclusions
BZBS has the potential to alleviate inflammation in metabolic organs of naturally aged mice and maintain metabolic homeostasis. This study presents novel clinical therapeutic approaches for the prevention and treatment of age-related metabolic diseases.
Anti-inflammatory therapies are associated with delayed onset of anemia and reduction in transfusion requirements in critically ill patients: results from two studies
Authors: Bolscher Madelief , Koster Stephanie C. E. , Koopmans Matty , Haitsma Mulier Jelle L. G. , Derde Lennie P. G. , Juffermans Nicole P. 
Published: April 2024

Abstract
Background
Anemia is a hallmark of critical illness, which is largely inflammatory driven. We hypothesized that the use of anti-inflammatory agents limits the development of anemia and reduces the need for red blood cell (RBC) transfusions in patients with a hyper-inflammatory condition due to COVID-19.

Methods
An observational cohort (n = 772) and a validation cohort (a subset of REMAP-CAP, n = 119) of critically ill patients with hypoxemic respiratory failure due to COVID-19 were analyzed, who either received no treatment, received steroids or received steroids plus IL-6 blocking agents. The trajectory of hemoglobin (Hb) decline and the need for RBC transfusions were compared using descriptive statistics as well as multivariate modeling.

Results
In both cohorts, Hb level was higher in the treated groups compared to the untreated group at all time points. In the observational cohort, incidence and number of transfused patients were lower in the group receiving the combination treatment compared to the untreated groups. In a multivariate analysis controlling for baseline Hb imbalance and mechanical ventilation, receipt of steroids remained associated with a slower decline in Hb level and the combination treatment remained associated with a slower decline of Hb and with less transfusions. Results remained the same in the validation cohort.

Conclusion
Immunomodulatory treatment was associated with a slower decline in Hb level in critically ill patients with COVID-19 and with less transfusion. Findings point toward inflammation as an important cause for the occurrence of anemia in the critically ill.
Nutrition and movement to improve quality of life in patients with knee osteoarthritis: the NUMOQUA study protocol for a randomised controlled trial
Authors: Höld Elisabeth , Chmelar Sabine , Aubram Tatjana , Leitner Gabriele , Nehrer Stefan , Neubauer Oliver , Wagner Karl-Heinz , Wondrasch Barbara 
Published: April 2024

Abstract
Background
Osteoarthritis (OA) has long been considered as a degenerative disease of cartilage tissue resulting from bodily wear and tear. However, there is accumulating evidence that inflammation plays a key role in the pathogenesis of OA. In knee OA, the most common form of OA, exercise therapy as an effective component of early treatment addresses functional deficits, pain and inflammation. Since inflammation is critical for the development and progress of OA, anti-inflammatory therapies must be combined strategically.
In the course of the NUMOQUA project, an anti-inflammatory therapeutic diet named ‘Austrian Osteoarthritis Cuisine’ was developed. It is based on the framework of the New Nordic Diet combined with the food-based dietary guidelines of Austria, the guidelines for OA, the Austrian food culture and the principles of a sustainable diet. The present study examines the implementation of the ‘Austrian OA Cuisine’ combined with the evidence-based training programme GLA:D® (Good Life with osteoArthritis in Denmark) in Austrian patients with knee OA and the effects on quality of life, nutritional and inflammatory status, as well as oxidative stress parameters.

Methods
A total of 60 participants aged 50 to 75 with knee OA will be included and randomly assigned either to the intervention group or the control group. All participants will undergo the GLA:D® programme in the first 6 weeks. Additionally, the intervention group will receive nutritional group training and individual nutritional counselling on the ‘Austrian OA Cuisine’ over 9 months. The control group will receive general information about a healthy lifestyle. Measurements at baseline and at 4 follow-up dates include nutritional, inflammatory and oxidative stress markers. Furthermore, anthropometric, behavioural and clinical data will be obtained. The recruitment process lasted from autumn 2022 to January 2024, followed by the intervention until October 2024.

Discussion
The prevalence of OA is expected to increase in the future due to ongoing demographic changes and rising obesity rates. The expected results will provide important evidence on whether this interdisciplinary therapeutic approach could be a new, cost-effective and sustainable strategy to address the disease process of OA without negative side effects.

Trial registration
ClinicalTrials.gov NCT05955300. Date of registration: 23rd of October 2023.
Effects of combination of strength and balance training on postural control and functionality in people with chronic ankle instability: a systematic review and meta analysis
Authors: Su Yuying , Li Wei , Pan Changbo , Shi Yu 
Published: April 2024

Abstract
Aim
To identify the effects of strength and balance training on dynamic balance and patient reported outcomes in people with chronic ankle instability(CAI).

Method
Five databases(CNKI, WanFang, Web of Science, EBSCO-SPORTD and PubMed were searched in September 2022. The search was conducted on randomized controlled trials(RCTs) that the effects of strength training, balance training and combination of strength and balance training in people with chronic ankle instability compared to a control group. Using Review Manager 5.3 and Stata-SE 15 to conduct Meta-analysis on the included literature. methodological quality and risk of bias were assessed by using the PEDro scale.

Results
A total of 33 Chinese and English RCTs document were screened and 1154 patients with CAI were included in the study. Compared with control group, strength training, balance training and combination of strength and balance training demonstrated to be more effective in terms of improving patient reported outcomes(strength training: SMD = 0.80, 95%CI = 0.39–1.22; balance training: SMD = 0.79, 95%CI = 0.41–1.17; combination of strength and balance training: SMD = 1.28, 95%CI = 0.57, 1.99). Subgroup analysis: Intervention for 6 weeks, more than 3 times a week and more than 30 min each time were the best rehabilitation programs to improve CAI patientreported outcomes. Compared with control group, balance training demonstrated to be more effective in terms of improving Star Excursion Balance Test (SEBT)((anterior: SMD = 0.71, 95%CI = 0.03–1.40; posterolateral: SMD = 0.84, 95%CI = 0.22–1.46; posteromedial: SMD = 0.88, 95%CI = 0.45–1.32). However, strength training and combination of strength and balance training had no improvement effects on SEBT.

Conclusions
Available evidence showed that, results of the comparison between balance training versus strength training suggest that the combination of strength and balance training achieves greater benefits for patient reported outcomes and balance training could bring greater benefits to dynamic balance. Strength training should be used cautiously in clinic to improve the dynamic balance in individuals with CAI.

Trial registration
(http://www.crd.york.ac.uk/PROSPERO, Registration No. CRD42022371396).
Serotype diversity and antimicrobial susceptibility profiles of Actinobacillus pleuropneumoniae isolated in Italian pig farms from 2015 to 2022
Authors: Guarneri Flavia , Romeo Claudia , Scali Federico , Zoppi Simona , Formenti Nicoletta , Maisano Antonio Marco , Catania Salvatore , Gottschalk Marcelo , Alborali G. Loris 
Published: April 2024

AbstractActinobacillus pleuropneumoniae (APP) is a bacterium frequently associated with porcine pleuropneumonia. The acute form of the disease is highly contagious and often fatal, resulting in significant economic losses for pig farmers. Serotype diversity and antimicrobial resistance (AMR) of APP strains circulating in north Italian farms from 2015 to 2022 were evaluated retrospectively to investigate APP epidemiology in the area. A total of 572 strains isolated from outbreaks occurring in 337 different swine farms were analysed. The majority of isolates belonged to serotypes 9/11 (39.2%) and 2 (28.1%) and serotype diversity increased during the study period, up to nine different serotypes isolated in 2022. The most common resistances were against tetracycline (53% of isolates) and ampicillin (33%), followed by enrofloxacin, florfenicol and trimethoprim/sulfamethoxazole (23% each). Multidrug resistance (MDR) was common, with a third of isolates showing resistance to more than three antimicrobial classes. Resistance to the different classes and MDR varied significantly depending on the serotype. In particular, the widespread serotype 9/11 was strongly associated with florfenicol and enrofloxacin resistance and showed the highest proportion of MDR isolates. Serotype 5, although less common, showed instead a concerning proportion of trimethoprim/sulfamethoxazole resistance. Our results highlight how the typing of circulating serotypes and the analysis of their antimicrobial susceptibility profile are crucial to effectively manage APP infection and improve antimicrobial stewardship.
Purine salvage promotes treatment resistance in H3K27M-mutant diffuse midline glioma
Authors: Peterson Erik R. , Sajjakulnukit Peter , Scott Andrew J. , Heaslip Caleb , Andren Anthony , Wilder-Romans Kari , Zhou Weihua , Palavalasa Sravya , Korimerla Navyateja , Lin Angelica , O’Brien Alexandra , Kothari Ayesha , Zhao Zitong , Zhang Li , Morgan Meredith A. , Venneti Sriram , Koschmann Carl , Jabado Nada , Lyssiotis Costas A. , Castro Maria G. , Wahl Daniel R. 
Published: April 2024

Abstract
Background
Diffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are a fatal form of brain cancer. These tumors often carry a driver mutation on histone H3 converting lysine 27 to methionine (H3K27M). DMG-H3K27M are characterized by altered metabolism and resistance to standard of care radiation (RT) but how the H3K27M mediates the metabolic response to radiation and consequent treatment resistance is uncertain.

Methods
We performed metabolomics on irradiated and untreated H3K27M isogenic DMG cell lines and observed an H3K27M-specific enrichment for purine synthesis pathways. We profiled the expression of purine synthesis enzymes in publicly available patient data and our models, quantified purine synthesis using stable isotope tracing, and characterized the in vitro and in vivo response to de novo and salvage purine synthesis inhibition in combination with RT.

Results
DMG-H3K27M cells activate purine metabolism in an H3K27M-specific fashion. In the absence of genotoxic treatment, H3K27M-expressing cells have higher relative activity of de novo synthesis and apparent lower activity of purine salvage demonstrated via stable isotope tracing of key metabolites in purine synthesis and by lower expression of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the rate-limiting enzyme of purine salvage into IMP and GMP. Inhibition of de novo guanylate synthesis radiosensitized DMG-H3K27M cells in vitro and in vivo. Irradiated H3K27M cells upregulated HGPRT expression and hypoxanthine-derived guanylate salvage but maintained high levels of guanine-derived salvage. Exogenous guanine supplementation decreased radiosensitization in cells treated with combination RT and de novo purine synthesis inhibition. Silencing HGPRT combined with RT markedly suppressed DMG-H3K27M tumor growth in vivo.

Conclusions
Our results indicate that DMG-H3K27M cells rely on highly active purine synthesis, both from the de novo and salvage synthesis pathways. However, highly active salvage of free purine bases into mature guanylates can bypass inhibition of the de novo synthetic pathway. We conclude that inhibiting purine salvage may be a promising strategy to overcome treatment resistance in DMG-H3K27M tumors.