bluuebunny/crossref_metadata_2025_split huggingface dataset:
Factors influencing senior care and living preferences among older adults in Jiangsu, China: a cross-sectional survey study
Authors: Wang Yanan , Wang Yaning , Liu Yitong , Xu Wenkun , Yang Zhuoya , Xu Zhongying , Zhong Yaqin 
Published: June 2024

Abstract
Background
As the population ages, senior care for older adults in China has become increasingly important and has attracted the attention of both government and society. This study aimed to explore preferences and influencing factors related to senior care among older Chinese adults and thus propose effective and targeted strategies for the development of a comprehensive care system for older adults in the aging Chinese population.

Methods
Data were obtained from a cross-sectional survey conducted in sixteen communities or villages in Jiangsu Province, China, from July to September 2021. Guided by the Andersen Behavioral Model, multivariate logistic regression was conducted to identify factors associated with preferences for senior care arrangements.

Results
A total of 870 respondents were included in the study, 60.11% of whom preferred receiving care in their own homes, while only 13.68% chose residential care facilities (RCFs). For predisposing factors, rural respondents preferred receiving care in their own homes compared to urban respondents (children’s home: OR = 0.55, P < 0.01; RCF: OR = 0.58, P < 0.01). Concerning enabling factors, respondents who were not employed (OR = 2.30, P < 0.01) and those without financial support (OR = 2.73, P < 0.05) preferred RCFs to their own homes. Respondents receiving life assistance (sometimes: OR = 2.76, P < 0.001; regularly: OR = 2.57, P < 0.01; every day: OR = 3.57, P < 0.001) preferred their children’s homes to their own homes. In terms of need factors, respondents with noncommunicable diseases (NCDs, OR > 1, P < 0.05), those who knew about RCFs (some: OR = 0.53, P < 0.005; no: OR = 0.10, P < 0.001) and those with a good impression of RCFs (fair: OR = 3.72, P < 0.05; good: OR = 11.91, P < 0.001) preferred receiving care in RCFs compared to their counterparts.

Conclusions
Older Chinese adults’ senior care preferences were affected by predisposing factors, enabling factors, and need factors. Policy-makers should consider targeted measures to identify more precise senior care services and thus address aging challenges in China.
Combined associations of visceral adipose tissue and adherence to a Mediterranean lifestyle with T2D and diabetic microvascular complications among individuals with prediabetes
Authors: Chen Hao-Wen , Liu Kuan , Cao Bi-Fei , Zhong Qi , Zhou Rui , Li Liang-Hua , Wang Shi-Ao , Wei Yan-Fei , Liu Hua-Min , Wu Xian-Bo 
Published: June 2024

Abstract
Background
It’s unclear if excess visceral adipose tissue (VAT) mass in individuals with prediabetes can be countered by adherence to a Mediterranean lifestyle (MEDLIFE). We aimed to examine VAT mass, MEDLIFE adherence, and their impact on type 2 diabetes (T2D) and diabetic microvascular complications (DMC) in individuals with prediabetes.

Methods
11,267 individuals with prediabetes from the UK Biobank cohort were included. VAT mass was predicted using a non-linear model, and adherence to the MEDLIFE was evaluated using the 25-item MEDLIFE index, encompassing categories such as “Mediterranean food consumption,” “Mediterranean dietary habits,” and “Physical activity, rest, social habits, and conviviality.” Both VAT and MEDLIFE were categorized into quartiles, resulting in 16 combinations. Incident cases of T2D and related DMC were identified through clinical records. Cox proportional-hazards regression models were employed to examine associations, adjusting for potential confounding factors.

Results
Over a median follow-up of 13.77 years, we observed 1408 incident cases of T2D and 714 cases of any DMC. High adherence to the MEDLIFE, compared to the lowest quartile, reduced a 16% risk of incident T2D (HR: 0.84, 95% CI: 0.71–0.98) and 31% for incident DMC (0.69, 0.56–0.86). Conversely, compared to the lowest quartile of VAT, the highest quartile increased the risk of T2D (5.95, 4.72–7.49) and incident any DMC (1.79, 1.36–2.35). We observed an inverse dose-response relationship between MEDLIFE and T2D/DMC, and a dose-response relationship between VAT and all outcomes (P for trend < 0.05). Restricted cubic spline analysis confirmed a nearly linear dose-response pattern across all associations. Compared to individuals with the lowest MEDLIFE quartile and highest VAT quartile, those with the lowest T2D risk had the lowest VAT and highest MEDLIFE (0.12, 0.08–0.19). High MEDLIFE was linked to reduced T2D risk across all VAT categories, except in those with the highest VAT quartile. Similar trends were seen for DMC.

Conclusion
High adherence to MEDLIFE reduced T2D and MDC risk in individuals with prediabetes, while high VAT mass increases it, but MEDLIFE adherence may offset VAT’s risk partly. The Mediterranean lifestyle’s adaptability to diverse populations suggests promise for preventing T2D.
Bidirectional modulation of TCA cycle metabolites and anaplerosis by metformin and its combination with SGLT2i
Authors: Harada Makoto , Adam Jonathan , Covic Marcela , Ge Jianhong , Brandmaier Stefan , Muschet Caroline , Huang Jialing , Han Siyu , Rommel Martina , Rotter Markus , Heier Margit , Mohney Robert P. , Krumsiek Jan , Kastenmüller Gabi , Rathmann Wolfgang , Zou Zhongmei , Zukunft Sven , Scheerer Markus F. , Neschen Susanne , Adamski Jerzy , Gieger Christian , Peters Annette , Ankerst Donna P. , Meitinger Thomas , Alderete Tanya L. , de Angelis Martin Hrabe , Suhre Karsten , Wang-Sattler Rui 
Published: June 2024

Abstract
Background
Metformin and sodium-glucose-cotransporter-2 inhibitors (SGLT2i) are cornerstone therapies for managing hyperglycemia in diabetes. However, their detailed impacts on metabolic processes, particularly within the citric acid (TCA) cycle and its anaplerotic pathways, remain unclear. This study investigates the tissue-specific metabolic effects of metformin, both as a monotherapy and in combination with SGLT2i, on the TCA cycle and associated anaplerotic reactions in both mice and humans.

Methods
Metformin-specific metabolic changes were initially identified by comparing metformin-treated diabetic mice (MET) with vehicle-treated db/db mice (VG). These findings were then assessed in two human cohorts (KORA and QBB) and a longitudinal KORA study of metformin-naïve patients with Type 2 Diabetes (T2D). We also compared MET with db/db mice on combination therapy (SGLT2i + MET). Metabolic profiling analyzed 716 metabolites from plasma, liver, and kidney tissues post-treatment, using linear regression and Bonferroni correction for statistical analysis, complemented by pathway analyses to explore the pathophysiological implications.

Results
Metformin monotherapy significantly upregulated TCA cycle intermediates such as malate, fumarate, and α-ketoglutarate (α-KG) in plasma, and anaplerotic substrates including hepatic glutamate and renal 2-hydroxyglutarate (2-HG) in diabetic mice. Downregulated hepatic taurine was also observed. The addition of SGLT2i, however, reversed these effects, such as downregulating circulating malate and α-KG, and hepatic glutamate and renal 2-HG, but upregulated hepatic taurine. In human T2D patients on metformin therapy, significant systemic alterations in metabolites were observed, including increased malate but decreased citrulline. The bidirectional modulation of TCA cycle intermediates in mice influenced key anaplerotic pathways linked to glutaminolysis, tumorigenesis, immune regulation, and antioxidative responses.

Conclusion
This study elucidates the specific metabolic consequences of metformin and SGLT2i on the TCA cycle, reflecting potential impacts on the immune system. Metformin shows promise for its anti-inflammatory properties, while the addition of SGLT2i may provide liver protection in conditions like metabolic dysfunction-associated steatotic liver disease (MASLD). These observations underscore the importance of personalized treatment strategies.
Citrate synthase variants improve yield of acetyl-CoA derived 3-hydroxybutyrate in Escherichia coli
Authors: Rajpurohit Hemshikha , Eiteman Mark A. 
Published: June 2024

Abstract
Background
The microbial chiral product (R)-3-hydroxybutyrate (3-HB) is a gateway to several industrial and medical compounds. Acetyl-CoA is the key precursor for 3-HB, and several native pathways compete with 3-HB production. The principal competing pathway in wild-type Escherichia coli for acetyl-CoA is mediated by citrate synthase (coded by gltA), which directs over 60% of the acetyl-CoA into the tricarboxylic acid cycle. Eliminating citrate synthase activity (deletion of gltA) prevents growth on glucose as the sole carbon source. In this study, an alternative approach is used to generate an increased yield of 3-HB: citrate synthase activity is reduced but not eliminated by targeted substitutions in the chromosomally expressed enzyme.

Results
Five E. coli GltA variants were examined for 3-HB production via heterologous overexpression of a thiolase (phaA) and NADPH-dependent acetoacetyl-CoA reductase (phaB) from Cupriavidus necator. In shake flask studies, four variants showed nearly 5-fold greater 3-HB yield compared to the wild-type, although pyruvate accumulated. Overexpression of either native thioesterases TesB or YciA eliminated pyruvate formation, but diverted acetyl-CoA towards acetate formation. Overexpression of pantothenate kinase similarly decreased pyruvate formation but did not improve 3-HB yield. Controlled batch studies at the 1.25 L scale demonstrated that the GltA[A267T] variant produced the greatest 3-HB titer of 4.9 g/L with a yield of 0.17 g/g. In a phosphate-starved repeated batch process, E. coli ldhA poxB pta-ackA gltA::gltA[A267T] generated 15.9 g/L 3-HB (effective concentration of 21.3 g/L with dilution) with yield of 0.16 g/g from glucose as the sole carbon source.

Conclusions
This study demonstrates that GltA variants offer a means to affect the generation of acetyl-CoA derived products. This approach should benefit a wide range of acetyl-CoA derived biochemical products in E. coli and other microbes. Enhancing substrate affinity of the introduced pathway genes like thiolase towards acetyl-CoA will likely further increase the flux towards 3-HB while reducing pyruvate and acetate accumulation.
Racial inequalities in the development of multimorbidity of chronic conditions: results from a Brazilian prospective cohort
Authors: Oliveira Fernanda Esthefane Garrides , Griep Rosane Härter , Chor Dora , Barreto Sandhi Maria , Molina Maria del Carmen Bisi , Machado Luciana A. C. , Fonseca Maria de Jesus Mendes da , Bastos Leonardo Soares 
Published: June 2024

Abstract
Background
The occurrence of multimorbidity and its impacts have differentially affected population subgroups. Evidence on its incidence has mainly come from high-income regions, with limited exploration of racial disparities. This study investigated the association between racial groups and the development of multimorbidity and chronic conditions in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

Methods
Data from self-reported white, brown (pardos or mixed-race), and black participants at baseline of ELSA-Brasil (2008–2010) who were at risk for multimorbidity were analysed. The development of chronic conditions was assessed through in-person visits and self-reported diagnosis via telephone until the third follow-up visit (2017–2019). Multimorbidity was defined when, at the follow-up visit, the participant had two or more morbidities. Cumulative incidences, incidence rates, and adjusted incidence rate ratios (IRRs) were estimated using Poisson models.

Results
Over an 8.3-year follow-up, compared to white participants: browns had a 27% greater incidence of hypertension and obesity; and blacks had a 62% and 45% greater incidence, respectively. Blacks also had 58% more diabetes. The cancer incidence was greater among whites. Multimorbidity affected 41% of the participants, with a crude incidence rate of 57.5 cases per 1000 person-years (ranging from 56.3 for whites to 63.9 for blacks). Adjusted estimates showed a 20% higher incidence of multimorbidity in black participants compared to white participants (IRR: 1.20; 95% CI: 1.05–1.38).

Conclusions
Significant racial disparities in the risk of chronic conditions and multimorbidity were observed. Many associations revealed a gradient increase in illness risk according to darker skin tones. Addressing fundamental causes such as racism and racial discrimination, alongside considering social determinants of health, is vital for comprehensive multimorbidity care. Intersectoral, equitable policies are essential for ensuring health rights for historically marginalized groups.
LDLR c.89_92dup: a novel frameshift variation in familial hypercholesterolemia
Authors: Deng Jialing , Zhang Ju , Meng Shirui , Ding Nan , Hao Yu , Zeng Hui , Lin Jie 
Published: June 2024

Abstract
Background
Familial hypercholesterolemia (FH) is a common inherited metabolic disease that causes premature atherosclerosis, cardiovascular disease, and even death at a young age. Approximately 95% of FH-causing genetic variants that have been identified are in the LDLR gene. However, only 10% of the FH population worldwide has been diagnosed and adequately treated, due to the existence of numerous unidentified variants, uncertainties in the pathogenicity scoring of many variants, and a substantial number of individuals lacking access to genetic testing.

Objective
The aim of this study was to identify a novel variant in the LDLR gene that causes FH in a Chinese family, thereby expanding the spectrum of FH-causing variants.

Methods
Patients were recruited from Beijing Anzhen Hospital, Capital Medical University. FH diagnosis was made according to the Dutch Lipid Clinical Network (DLCN) criteria. Whole-exome sequencing (WES) was conducted to identify the FH-causing variant in the proband, and amplicon sequencing was used to verify the variant in his family members.

Results
A three-generation Chinese family was recruited, and two FH patients were clinically diagnosed, both without known FH-causing variants. These two FH patients and another possible patient carried a novel variant, NC_000019.9(NM_000527.5):c.89_92dup (NP_000518.1:p.Phe32Argfs*21), in the ligand-binding domain of the low-density lipoprotein (LDL) receptor that led to a frameshift. The FH adults in the family showed severe clinical symptoms and statin therapy resistance.

Conclusion
This study identified a novel pathogenic LDLR variant, c.89_92dup, associated with severe FH clinical manifestations and statin therapy resistance.
Podoplanin depletion in tonsil-derived mesenchymal stem cells induces cellular senescence via regulation of the p16Ink4a/Rb pathway
Authors: Kim Ha Yeong , Kim Han Su 
Published: June 2024

Abstract
Background
Mesenchymal stem cells (MSCs) are widely used in the development of therapeutic tools in regenerative medicine. However, their quality decreases during in vitro expansion because of heterogeneity and acquired cellular senescence. We investigated the potential role of podoplanin (PDPN) in minimizing cellular senescence and maintaining the stemness of tonsil-derived MSCs (TMSCs).

Methods
TMSCs were isolated from human tonsil tissues using an enzymatic method, expanded, and divided into two groups: early-passaged TMSCs, which were cultured for 3–7 passages, and late-passaged TMSCs, which were passaged more than 15 times. The TMSCs were evaluated for cellular senescence and MSC characteristics, and PDPN-positive and -negative cells were identified by fluorescence-activated cell sorting. In addition, MSC features were assessed in siRNA-mediated PDPN-depleted TMSCs.

Results
TMSCs, when passaged more than 15 times and becoming senescent, exhibited reduced proliferative rates, telomere length, pluripotency marker (NANOG, OCT4, and SOX2) expression, and tri-lineage differentiation potential (adipogenesis, chondrogenesis, or osteogenesis) compared to cells passaged less than five times. Furthermore, PDPN protein levels significantly decreased in a passage-dependent manner. PDPN-positive cells maintained their stemness characteristics, such as MSC-specific surface antigen (CD14, CD34, CD45, CD73, CD90, and CD105) and pluripotency marker expression, and exhibited higher tri-lineage differentiation potential than PDPN-negative cells. SiRNA-mediated silencing of PDPN led to decreased cell-cycle progression, proliferation, and migration, indicating the significance of PDPN as a preliminary senescence-related factor. These reductions directly contributed to the induction of cellular senescence via p16Ink4a/Rb pathway activation.

Conclusion
PDPN may serve as a novel biomarker to mitigate cellular senescence in the clinical application of MSCs.

Graphical Abstract
Scaling up a brief alcohol intervention to prevent HIV infection in Vietnam: a cluster randomized, implementation trial
Authors: Bartels Sophia M. , Phan Huong T. T. , Hutton Heidi E. , Nhan Do T. , Sripaipan Teerada , Chen Jane S. , Rossi Sarah L. , Ferguson Olivia , Nong Ha T. T. , Nguyen Ngan T. K. , Giang Le Minh , Bui Hao T. M. , Chander Geetanjali , Sohn Hojoon , Kim Sol , Tran Ha V. , Nguyen Minh X. , Powell Byron J. , Pence Brian W. , Miller William C. , Go Vivian F. 
Published: June 2024

Abstract
Background
Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians’ attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians’ knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use.

Methods
Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians’ alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI.
Participants: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months.
Outcomes: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff’s alcohol use and clinic-level alcohol expectations in the EBAI arm.

Discussion
This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases.

Trial Registration
NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885.
Gene count normalization in single-cell imaging-based spatially resolved transcriptomics
Authors: Atta Lyla , Clifton Kalen , Anant Manjari , Aihara Gohta , Fan Jean 
Published: June 2024

Abstract
Background
Recent advances in imaging-based spatially resolved transcriptomics (im-SRT) technologies now enable high-throughput profiling of targeted genes and their locations in fixed tissues. Normalization of gene expression data is often needed to account for technical factors that may confound underlying biological signals.

Results
Here, we investigate the potential impact of different gene count normalization methods with different targeted gene panels in the analysis and interpretation of im-SRT data. Using different simulated gene panels that overrepresent genes expressed in specific tissue regions or cell types, we demonstrate how normalization methods based on detected gene counts per cell differentially impact normalized gene expression magnitudes in a region- or cell type-specific manner. We show that these normalization-induced effects may reduce the reliability of downstream analyses including differential gene expression, gene fold change, and spatially variable gene analysis, introducing false positive and false negative results when compared to results obtained from gene panels that are more representative of the gene expression of the tissue’s component cell types. These effects are not observed with normalization approaches that do not use detected gene counts for gene expression magnitude adjustment, such as with cell volume or cell area normalization.

Conclusions
We recommend using non-gene count-based normalization approaches when feasible and evaluating gene panel representativeness before using gene count-based normalization methods if necessary. Overall, we caution that the choice of normalization method and gene panel may impact the biological interpretation of the im-SRT data.
The effect of different flushing and locking techniques on catheter occlusion rates in central venous catheters: protocol for a multicentre, randomized controlled, parallel-group, open-label, superiority clinical trial
Authors: Li Rongmei , Zhou Mian , Sun Lulu , Sha Lili , Xu Biyun , Li Taishun , Tao Tingting , Yuan Ling 
Published: June 2024

Abstract
Background
Maintaining venous access is of great clinical importance. Running a slow continuous infusion to keep the vein open (KVO) is often used in peripheral intravenous catheters (PIVCs). Previous studies have compared the effects of intermittent flushing and continuous infusion via peripherally inserted central catheters (PICCs). In this study, we applied KVO to central venous catheters (CVCs) and compared the occlusion rate of this technique with that of the intermittent flushing technique.

Method
This is a randomized controlled trial of 14 hospitals in China. A total of 250 patients will be recruited in this study, and they will be randomized at a 1:1 ratio. After study inclusion, patients who will undergo CVC insertion will receive intermittent flushing with prefilled saline syringes (control group) or KVO infusion with elastic pumps (test group). All the catheters will be checked for patency by scoping Catheter Injection and Aspiration (CINAS) Classification on Days 3 and 7. The primary outcome is the rate of catheter occlusion in 7 days. Patients will be followed up until 9 days after CVC insertion, catheter occlusion, or catheter removal. The secondary outcomes are the rate of catheter occlusion in 3 days, nurse satisfaction, cost-effectiveness, adverse event rate, catheter-related bloodstream infection rate, catheter-related thrombosis rate, extravasation rate, phlebitis rate, and catheter migration.

Discussion
We expect that the trial will generate findings that can provide an evidence-based basis for the improvement and optimization of clinical catheter flushing techniques.

Trial registration
Chinese Clinical Trial Registry, ChiCTR2200064007. Registered on 23 September 2022. https://www.chictr.org.cn/showproj.html?proj=177311.