bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of obesity and subsequent weight reduction on cardiac morphology and function in cats
Authors: Partington Catheryn , Hodgkiss-Geere Hannah , Woods Georgia R. T. , Dukes-McEwan Joanna , Flanagan John , Biourge Vincent , German Alexander J. 
Published: April 2024

Abstract
Background
In people, obesity is a risk factor for cardiovascular disease, associated with systemic hypertension, cardiac remodelling and systolic and diastolic dysfunction. Weight reduction can reverse myocardial remodelling and reduce risk of subsequent cardiovascular disease. In cats, far less is known regarding the effects of obesity and subsequent weight reduction on cardiovascular morphology and function. This prospective study aimed to assess cardiac morphology and function, heart rate variability, cardiac biomarkers and body composition before and after controlled weight reduction in cats with obesity. Body composition analysis (by dual energy x-ray absorptiometry, DEXA) and cardiovascular assessment (echocardiography, systemic arterial systolic blood pressure, electrocardiography, plasma cardiac biomarkers) were performed prior to weight management in twenty cats with obesity. These investigations were repeated in eleven cats that reached target weight.

Results
At baseline, systemic hypertension was not documented, but the majority of cats with obesity (15 out of 19) showed echocardiographic evidence of diastolic dysfunction. Eleven of 20 cats had increased maximal end-diastolic septal or left ventricular free wall thickness (≥ 6.0 mm) at baseline. Median (interquartile range) percentage of weight lost in the cats reaching target weight was 26% (17–29%), with a median reduction in body fat mass of 45% (26–64%). Both the end-diastolic left ventricular free wall (median magnitude of change -0.85 mm, IQR -0.05 mm to -1.55 mm, P = 0.019; median percentage reduction 14.0%) and end-diastolic interventricular septum (median magnitude of change -0.5 mm, IQR -0.2 mm to -1.225 mm, P = 0.047; median percentage reduction 7.9%) thickness decreased after weight reduction. Following weight reduction, pulsed wave tissue Doppler imaging of the left ventricular free wall was consistent with improved diastolic function in 4 out of 8 cats, however there was no significant difference in overall diastolic function class. Further, there was no change in heart rate variability or cardiac biomarkers with weight reduction.

Conclusion
An increase in left ventricular wall thickness and diastolic dysfunction were common echocardiographic features in cats with obesity within our study and may be reversible with successful weight and fat mass loss. Further studies are required to clarify the clinical consequences of these findings.
Evolving insights into the improvement of adoptive T-cell immunotherapy through PD-1/PD-L1 blockade in the clinical spectrum of lung cancer
Authors: Li Yutao , Sharma Amit , Schmidt-Wolf Ingo G.H. 
Published: April 2024

AbstractUndeniably, cancer immunotherapies have expanded the spectrum of cancer treatment, however, some patients do not respond to immunotherapies. This scenario is no different for lung cancer, whose two main types, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), still pose a serious clinical challenge. Adoptive T-cell therapies (ATC), which primarily include cytokine-induced killer (CIK) cell therapy, chimeric antigen receptor T-cell (CAR T-cell) therapy and γδ-T-cell therapy, strengthen the patient’s immune system in combating cancer. Combining ATC with immune checkpoint inhibitors (ICI) further enhances the effectiveness of this approach to eradicate cancer. With a particular emphasis on CIK cell therapy, which recently completed 30 years, we highlight the role of the PD-1/PD-L1 axis in NSCLC and SCLC. Besides, we provide insights into the potential synergies of PD-1/PD-L1 inhibitors with adoptive T-cell immunotherapy in reshaping the treatment paradigm for lung cancer.
The association of the platelet/high-density lipoprotein cholesterol ratio with self-reported stroke and cardiovascular mortality: a population-based observational study
Authors: Zhang Huifeng , Xu Ying , Xu Yaying 
Published: April 2024

Abstract
Background
Previous studies have shown that the relationship between high-density lipoprotein cholesterol (HDL-C) and stroke is controversial, and the association between the platelet/high-density lipoprotein cholesterol ratio (PHR), a novel marker for inflammation and hypercoagulability states, and stroke has not been established.

Methods
This study presents an analysis of cross-sectional data from the 2005–2018 National Health and Nutrition Examination Survey (NHANES). Stroke history, HDL-C levels, and platelet counts were obtained during cross-sectional surveys. The PHR was calculated as the ratio of the number of platelets to HDL-C concentration. Weighted logistic regression was used to assess the associations of HDL-C and the PHR with stroke. Nonlinearity of this relationship was determined through restricted cubic splines (RCSs) and two-piecewise linear regression for identifying inflection points. Furthermore, Cox regression was utilized to prospectively analyze the associations of the PHR and HDL-C concentration with cardiovascular disease (CVD) mortality in stroke survivors.

Results
A total of 27,301 eligible participants were included in the study; mean age, 47.28 years and 50.57% were female, among whom 1,040 had a history of stroke. After full adjustment, the odds ratio (OR) of stroke associated with a per standard deviation (SD) increase in the PHR was estimated at 1.13 (95% confidence interval (CI): 1.03 − 1.24, P = 0.01), and the OR of stroke associated with a per SD increase in HDL-C was 0.95 (95% CI: 0.86–1.05, P = 0.30). The RCS indicated a nonlinear relationship for both variables (PPHR = 0.018 and PHDL-C = 0.003), and further piecewise linear regression identified inflection points at PHR = 223.684 and HDL-C = 1.4 mmol/L. Segmental regression indicated that in the PHR ≥ 223.684 segment, the estimated OR of stroke associated with a per-SD increase in the PHR was 1.20 (95% CI: 1.09 − 1.31, P < 0.001), while the association of stroke with HDL-C was not significant before or after the inflection point (P > 0.05). Furthermore, Cox regression and RCS showed that a per-SD increase in the PHR was linearly associated with a greater risk of CVD mortality among stroke survivors (HR: 1.14, 95% CI: 1.06 − 1.22, P < 0.001; nonlinear, P = 0.956), while HDL-C was not significantly associated with CVD mortality.

Conclusion
The association between the PHR and stroke incidence exhibited a significant threshold effect, with an inflection point at 223.684. A PHR exceeding 223.684 was positively associated with stroke, while the association between HDL-C and stroke was not significant. Additionally, the PHR was positively and linearly associated with CVD mortality among stroke survivors.
Immunosuppressive microvesicles-mimetic derived from tolerant dendritic cells to target T-lymphocytes for inflammation diseases therapy
Authors: Lin Minghao , Lei Siyun , Chai Yingqian , Xu Jianghua , Wang Youchao , Wu Chenghu , Jiang Hongyi , Yuan Shanshan , Wang Jilong , Lyu Jie , Lu Mingqin , Deng Junjie 
Published: April 2024

AbstractThe utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.
A reduced exposure heated tobacco product was introduced then abruptly taken off United States shelves: results from a tobacco harm reduction natural experiment
Authors: Noggle Brendan , Ball Kevin M. , Vansickel Andrea Rae 
Published: April 2024

Abstract
Background
A heated tobacco product (HTP) authorized for purchase in the United States by the Food and Drug Administration as a reduced harm product was removed from the market after about 2 years of sales. Adults who used the HTP were surveyed to determine the impact of the introduction and removal of the HTP on past and current tobacco behaviors.

Methods
Adults who were using the HTP before its United States market removal (n = 502) completed a cross-sectional online survey to determine their tobacco use behaviors at three timepoints: prior to HTP initiation, just before HTP market removal, and at the time of the survey which was administered approximately 10 months post-removal. Descriptive statistics summarized outcome variables and paired bivariate testing was used to compare percent change between timepoints. Multivariable logistic regression and general linear models estimated associations of tobacco use behaviors and cigarette consumption.

Results
Overall, significantly fewer adults consumed cigarettes while using HTP than before they tried the product (63.0% vs. 89.9%, p value < 0.0001) and the number of cigarettes consumed per week (CPW) decreased (106.3–39.0, p value < 0.0001). After HTP removal, the percent of adults who consumed cigarettes increased non-significantly (63.0–67.5%, p value = 0.0544) while CPW increased significantly (39.0–76.6 CPW, p value < 0.0001). At the time of the survey, over 25% of the sample continued to use the HTP and 7.2% reported use of no tobacco products. Electronic nicotine delivery system use had increased significantly from the prior period (27.4% increase, p value < 0.0001).

Conclusion
This study demonstrates reduction or elimination of combustible cigarette smoking while adults were using HTPs and some increased smoking after market removal, albeit at lower levels. If unable to find satisfying alternatives, adults who smoke and transition to reduced harm products may return to smoking or purchase products illicitly if their preferred products are removed from the regulated market.
Community-level group sports participation and all-cause, cardiovascular disease, and cancer mortality: a 7-year longitudinal study
Authors: Tsuji Taishi , Okada Eisaku , Saito Masashige , Kanamori Satoru , Miyaguni Yasuhiro , Hanazato Masamichi , Kondo Katsunori , Ojima Toshiyuki 
Published: April 2024

Abstract
Background
Community-level group sports participation is a structural aspect of social capital that can potentially impact individual health in a contextual manner. This study aimed to investigate contextual relationship between the community-level prevalence of group sports participation and the risk of all-cause, cardiovascular disease (CVD), and cancer mortality in older adults.

Methods
In this 7-year longitudinal cohort study, data from the Japan Gerontological Evaluation Study, a nationwide survey encompassing 43,088 functionally independent older adults residing in 311 communities, were used. Cause of death data were derived from the Japanese governmental agency, The Ministry of Health, Labour and Welfare, for secondary use. “Participation” was defined as engaging in group sports for one or more days per month. To analyze the data, a two-level survival analysis was employed, and hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated.

Results
Among the participants, 5,711 (13.3%) deaths were identified, with 1,311 related to CVD and 2,349 to cancer. The average group sports participation rate was 28.3% (range, 10.0–52.7%). After adjusting for individual-level group sports participation and potential confounders, a higher community-level group sports participation rate was found to be significantly associated with a lower risk of both all-cause mortality (HR: 0.89, 95% CI: 0.83–0.95) and cancer mortality (HR: 0.89, 95% CI: 0.81–0.98) for every 10% point increase in the participation rate. For CVD mortality, the association became less significant in the model adjusted for all covariates (HR: 0.94, 95% CI: 0.82–1.09).

Conclusions
Our findings support the existence of a preventive relationship between community-level group sports participation and the occurrence of all-cause and cancer mortality among older individuals. Promoting group sports within communities holds promise as an effective population-based strategy for extending life expectancy, regardless of individual participation in these groups.
Plant cultural indicators of forest resources from the Himalayan high mountains: implications for improving agricultural resilience, subsistence, and forest restoration
Authors: Haq Shiekh Marifatul , Khoja Aadil Abdullah , Waheed Muhammad , Pieroni Andrea , Siddiqui Manzer H. , Bussmann Rainer W. 
Published: April 2024

Abstract
Aim
Biocultural legacy practices are intricately tied to forestry resources, ethnic identity, and social cohesiveness. This study aims to determine the plant cultural values of forest resources and identify plant cultural indicators in each ethnic group, which can aid in long-term natural resource management plans in the current debate on socio-environmental and ecological transitions.

Methods
Semi-structured interviews, focus group discussions, and field observations were employed to collect data for a comprehensive and systematic ethnobotanical survey from February 2018 to October 2022.

Results
A total of 330 informants reported 154 plant species from 65 families. Asteraceae was the most prominent botanical family, with herbaceous plant groups outnumbering trees and shrubs. The Gujjar and Pahari groups exhibited the highest level of overlap, followed by significant overlaps between the Gujjar and Kashmiri communities. The close affinity observed between the Gujjar and Pahari groups suggests the horizontal pattern of local plant knowledge between these communities, influenced by their sociocultural interactions and intermarriages. Notably, the Pahari community displayed a rich understanding of medicinal plants and shared unique uses for the reported taxa. This study affirms that both ecological factors and sociocultural influences have played significant roles in shaping local plant knowledge. A total of 31 plant species have been identified as plant cultural markers among all four ethnic groups. We observed a positive correlation between plant cultural values and plant use with the Gujjar and Kashmiri ethnic groups. Artemisia absinthium reported the highest use value of (0.57) with use reports of (189). Adonis aestivalis, Cynoglossum nervosum, Geum elatum, Geranium himalayense, Juncus inflexus, Oxalis acetosella, Polygonatum biflorum, and Salvia hians from the Himalayan region are among the plant taxa whose ethnomedicinal applications are described here for the first time.

Conclusion
Our data show that local and indigenous forest knowledge and practices could significantly contribute to forest conservation and ecological transition. This may happen if stakeholders generate clear frameworks and biocultural conservation strategies aimed at both dynamically preserve natural habitats and ways of traditional management of local natural resources.
Guidelines for conscientious objection in Spain: a proposal involving prerequisites and protocolized procedure
Authors: Herreros Benjamín , Ramnath Venktesh R. , Santiago-Saez Andrés , Velasco Sanz Tamara Raquel , Pinto Pastor Pilar 
Published: April 2024

AbstractHealthcare professionals often face ethical conflicts and challenges related to decision-making that have necessitated consideration of the use of conscientious objection (CO). No current guidelines exist within Spain’s healthcare system regarding acceptable rationales for CO, the appropriate application of CO, or practical means to support healthcare professionals who wish to become conscientious objectors. As such, a procedural framework is needed that not only assures the appropriate use of CO by healthcare professionals but also demonstrates its ethical validity, legislative compliance through protection of moral freedoms and patients’ rights to receive health care. Our proposal consists of prerequisites of eligibility for CO (individual reference, specific clinical context, ethical justification, assurance of non-discrimination, professional consistency, attitude of mutual respect, assurance of patient rights and safety) and a procedural process (notification and preparation, documentation and confidentiality, evaluation of prerequisites, non-abandonment, transparency, allowance for unforeseen objection, compensatory responsibilities, access to guidance and/or consultative advice, and organizational guarantee of professional substitution). We illustrate the real-world utility of the proposed framework through a case discussion in which our guidelines are applied.
Positive buttress reduction in femoral neck fractures: a literature review
Authors: Han Shun , Zhang Ze-Yang , Zhou Ke , Yin Gui-Kun , Liu Yu-Chen , Wang Ben-jie , Wen Zhun 
Published: April 2024

Abstract
Background
Femoral neck fractures (FNFs) in young adults are usually caused by high-energy trauma, and their treatment remains a challenging issue for orthopedic surgeons. The quality of reduction is considered an important factor in improving the poor prognosis of patients with FNFs. In recent years, positive buttress closed reduction technique has received widespread attention in the treatment of FNFs. This comprehensive literature review is designed to encapsulate the impacts of both non-anatomic and anatomic reduction on the biomechanical stability, clinical outcomes, and postoperative complications in the management of FNFs, conjecture the efficacy of positively braced reduction techniques and provide a thorough summarization of the clinical outcomes.

Methods
In this literature review, we have examined all clinical and biomechanical studies related to the treatment of FNFs using non-anatomical reduction or positive and negative buttress reduction. PubMed, Web of Science, Google Scholar and Embase Library databases were searched systematically for studies published before September 1, 2023. Published literature on fracture reduction techniques for treating FNFs was reviewed. In addition, we evaluated the included literature using the MINORs tool.

Results
Although the “arch bridge” structure formed by the positive buttress reduction technique improved the support to the cortical bone and provided a more stable biomechanical structure, no significant differences were noted in the clinical efficacy and incidence of postoperative complications between the positive buttress reduction and anatomical reduction.

Conclusion
Positive buttress reduction is an effective treatment method for young patients with FNFs. When facing difficult-to-reduce FNF, positive buttress reduction should be considered first, followed by anatomical reduction. However, negative buttress reduction should be avoided.
Regulation of human microglial gene expression and function via RNAase-H active antisense oligonucleotides in vivo in Alzheimer’s disease
Authors: Vandermeulen Lina , Geric Ivana , Fumagalli Laura , Kreir Mohamed , Lu Ashley , Nonneman Annelies , Premereur Jessie , Wolfs Leen , Policarpo Rafaela , Fattorelli Nicola , De Bondt An , Van Den Wyngaert Ilse , Asselbergh Bob , Fiers Mark , De Strooper Bart , d’Ydewalle Constantin , Mancuso Renzo 
Published: April 2024

Abstract
Background
Microglia play important roles in maintaining brain homeostasis and neurodegeneration. The discovery of genetic variants in genes predominately or exclusively expressed in myeloid cells, such as Apolipoprotein E (APOE) and triggering receptor expressed on myeloid cells 2 (TREM2), as the strongest risk factors for Alzheimer’s disease (AD) highlights the importance of microglial biology in the brain. The sequence, structure and function of several microglial proteins are poorly conserved across species, which has hampered the development of strategies aiming to modulate the expression of specific microglial genes. One way to target APOE and TREM2 is to modulate their expression using antisense oligonucleotides (ASOs).

Methods
In this study, we identified, produced, and tested novel, selective and potent ASOs for human APOE and TREM2. We used a combination of in vitro iPSC-microglia models, as well as microglial xenotransplanted mice to provide proof of activity in human microglial in vivo.

Results
We proved their efficacy in human iPSC microglia in vitro, as well as their pharmacological activity in vivo in a xenografted microglia model. We demonstrate ASOs targeting human microglia can modify their transcriptional profile and their response to amyloid-β plaques in vivo in a model of AD.

Conclusions
This study is the first proof-of-concept that human microglial can be modulated using ASOs in a dose-dependent manner to manipulate microglia phenotypes and response to neurodegeneration in vivo.