bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomimetic composite hydrogel promotes new bone formation in rat bone defects through regulation of miR-19b-3p/WWP1 axis by loaded extracellular vesicles
Authors: Guo Rongkang , Wu Chaohan , Liu Fan , Dong Tianhua , Zhang Tao 
Published: November 2023

Abstract
Objective
This study aims to investigate the mechanism by which biomimetic composite hydrogels loaded with bone marrow mesenchymal stem cells (BMSCs) derived microRNA-19b-3p/WWP1 axis through extracellular vesicles (EVs) affect the new bone formation in rat bone defects.

Methods
First, synthesize the bionic composite hydrogel Gel-OCS/MBGN. Characterize it through field-emission scanning electron microscopy (FE-SEM), X-ray diffraction (XRD), and FTIR. Then, conduct performance tests such as rheology, dynamic mechanical analysis, in vitro mineralization, and degradation. Rat BMSCs were selected for in vitro cell experiments, and EVs derived from BMSCs were obtained by differential centrifugation. The EVs were loaded onto Gel-OCS/MBGN to obtain Gel-OCS/MBGN@EVs hydrogel. Cell viability and proliferation were detected by live/dead cell staining and CCK-8 assay, respectively. ALP and ARS staining was used to evaluate the osteogenic differentiation of BMSCs. Differential gene expression analysis of osteogenic differentiation was performed using high-throughput sequencing. TargetScan database predicted the binding site between miR-19b-3p and WWP1, and a dual-luciferase reporter assay was performed to confirm the targeting binding site. A rat bone defect model was established, and new bone formation was evaluated by Micro-CT, H&E staining, and Masson's trichrome staining. Immunofluorescence staining and immunohistochemistry were used to detect the expression levels of osteogenic-related factors in rat BMSCs. RT-qPCR and Western blot were used to detect the expression levels of genes and proteins in tissues and cells.

Result
Gel-OCS/MBGN was successfully constructed and loaded with EVs, resulting in Gel-OCS/MBGN@EVs. The in vitro drug release experiment results show that Gel-OCS/MBGN could sustainably release EVs. Further experiments have shown that Gel-OCS/MBGN@EVs could significantly promote the differentiation of BMSCs into osteoblasts. Experiments have shown that WWP1 is a key factor in osteogenic differentiation and is regulated by miR-19b-3p. EVs promote osteogenic differentiation by suppressing WWP1 expression through the transmission of miR-19b-3p. In vivo animal experiments have demonstrated that Gel-OCS/MBGN@EVs significantly promote bone repair in rats with bone defects by regulating the miR-19b-3p/WWP1 signaling axis.

Conclusion
Functional Gel-OCS/MBGN@EVs were obtained by constructing Gel-OCS/MBGN and loading EVs onto it. EVs could deliver miR-19b-3p to BMSCs, inhibit the expression of WWP1, and promote the osteogenic differentiation of BMSCs, ultimately promoting bone regeneration in rats with bone defects.

Graphical Abstract
Inhibitory receptor CD47 binding to plasma TSP1 suppresses NK-cell IFN-γ production via activating the JAK/STAT3 pathway during HIV infection
Authors: Lang Bin , Wang Meiting , Zhang Zining , Fu Yajing , Han Xiaoxu , Hu Qinghai , Ding Haibo , Shang Hong , Jiang Yongjun 
Published: November 2023

Abstract
Background
Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear.

Methods
Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling.

Results
CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1–CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK–STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production.

Conclusions
The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.
Association of vitamin B2 intake with cognitive performance in older adults: a cross-sectional study
Authors: Zhou Lingyan 
Published: November 2023

Abstract
Background
To scrutinize the relationship between vitamin B2 consumption and cognitive function based on the NHANES database.

Methods
This cross-sectional study included eligible older adults from the NHANES 2011–2014. Vitamin B2 intake was determined from dietary interview data for two 24-h periods. Cognitive function was evaluated through the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), Animal Fluency Test (AFT), and Digit Symbol Substitution Test (DSST). The regression analyses were used to evaluate the association of vitamin B2 intake with cognitive performance. Stratified analyses based on gender, race, and body mass index (BMI) were conducted.

Results
Higher vitamin B2 intake was correlated with higher scores on each test. As compared to the lowest quartile, the highest quartile of vitamin B2 intake was related to a 45.1-fold increase (P = 0.004) on the DSST test sores. Moreover, those who were males, non-Hispanic whites, or had a BMI of 18.5 to 30 kg/m2 had a stronger relationship between total vitamin B2 consumption and cognitive function.

Conclusion
It's possible that older persons who consume more vitamin B2 have enhanced performance in some areas of cognitive function. To determine the causal link between vitamin B2 consumption and cognitive performance, further long-term research is required.
The local medicinal plant knowledge in Kashmir Western Himalaya: a way to foster ecological transition via community-centred health seeking strategies
Authors: Manzoor Muhammad , Ahmad Mushtaq , Zafar Muhammad , Gillani Syed Waseem , Shaheen Hamayun , Pieroni Andrea , Al-Ghamdi Abdullah Ahmed , Elshikh Mohamed Soliman , Saqib Saddam , Makhkamov Trobjon , Khaydarov Khislat 
Published: November 2023

Abstract
Background
The mountainous region of Kashmir is a biodiversity hotspot, with diverse local communities and a rich cultural history linked to nature. Mountain ecosystems are highly vulnerable to climate change. This study emphasises the need to record the indigenous ethnoecological knowledge of wild plants used for the treatment of various ailments at higher elevations in remote areas where globalisation poses a threat to this traditional knowledge.

Methods
The field survey was carried out in 2020–2022, to collect data on wild medicinal plants. Informants were selected randomly to collect indigenous medicinal knowledge using semi-structured interviews and group discussions. Various quantitative indices were employed to evaluate ethnomedicinal data.

Results
A total of 110 medicinal plants belonging to 49 families were recorded in the study area. These medicinal plants are extensively used by local communities for the treatment of 20 major disease categories. Asteraceae was the dominant family contributing (9.09%) to medicinal plants, followed by Polygonaceae (8.18%), Apiaceae (7.27%), Lamiaceae (5.45%), and Ranunculaceae (5.45%). We observed 166 remedies were used for the treatment of various diseases in humans, and 9 remedies were used for animals. The most frequently used medicinal remedy was tea or decoction (30.91%). Among the medicinal plants, herbs (85.5%) were most frequently used by the local populations of Kashmir, whereas leaves (10.26%) were used for the treatment of various ailments. Out of 110 species, 31 were endemic, 15 of which are endemic to the Kashmir region and 16 to the Western Himalaya. The highest RFC value was reported for Allium humile (0.77), the highest UV value for Fritillaria cirrhosa (1.33), and the highest ICF value for gastro-intestinal/digestive disorders (0.85).

Conclusions
Local communities still rely on wild medicinal plants for primary healthcare. These communities retained valuable indigenous knowledge, which needs to be preserved for the conservation and sustainable utilisation of natural resources. Further field exploration is required to fully explore indigenous knowledge in the mountainous regions of Kashmir, and this knowledge has the potential to support the ongoing ecological transition.
The relation between synovitis of individual finger joints and grip force over the first 5 years in early rheumatoid arthritis — a cohort study
Authors: Rydholm Maria , Sharma Ankita , Jacobsson Lennart , Turesson Carl 
Published: November 2023

Abstract
Objective
The objective of this study was to investigate the relation between swelling and tenderness of individual finger joints and grip force in patients with early rheumatoid arthritis (RA).

Methods
In an inception cohort of patients with early RA (symptom duration < 12 months), all patients were examined by the same rheumatologist, and grip force was measured using the Grippit instrument at inclusion, 1 and 5 years. The average grip force values of each hand were evaluated and expressed as % of expected values, based on age- and sex-specific reference values. Linear regression analyses were used to assess the cross-sectional relation between the involvement of individual finger joints and grip force. In generalized estimating equations, the impact of time-varying synovitis/tenderness on grip force over time was estimated. Analyses were adjusted for wrist involvement, erythrocyte sedimentation rate, and patient-reported pain.

Results
In 215 patients with early RA, grip force was 39% of expected at diagnosis, and increased to 56% after 5 years. Synovitis of the first metacarpophalangeal (MCP) joint (60% and 69% at baseline in the right and left hand) was associated with reduced grip force at inclusion (adjusted ß − 9.2 percentage unit of expected grip force; 95% CI − 13.6 to − 4.8 for both hands combined) and at all follow-up evaluations. Synovitis of MCP I and MCP IV (12% at baseline) was significantly associated with reduced grip force over time in both hands. Proximal interphalangeal (PIP) joint swelling, and tenderness of MCP or PIP joints, had less impact on grip force.

Conclusion
MCP I synovitis is the major contributor to reduced grip force in patients with early RA. This underlines the importance of the involvement of the thumb for impaired hand function in RA. MCP IV synovitis, but not PIP involvement or finger joint tenderness, also has a substantial impact on grip force.
Single time point quantitation of cerebral glucose metabolism by FDG-PET without arterial sampling
Authors: Cumming Paul , Dias André H. , Gormsen Lars C. , Hansen Allan K. , Alberts Ian , Rominger Axel , Munk Ole L. , Sari Hasan 
Published: November 2023

Abstract
Background
Until recently, quantitation of the net influx of 2-[18F]fluorodeoxyglucose (FDG) to brain (Ki) and the cerebrometabolic rate for glucose (CMRglc) required serial arterial blood sampling in conjunction with dynamic positron emission tomography (PET) recordings. Recent technical innovations enable the identification of an image-derived input function (IDIF) from vascular structures, but are frequently still encumbered by the need for interrupted sequences or prolonged recordings that are seldom available outside of a research setting. In this study, we tested simplified methods for quantitation of FDG-Ki by linear graphic analysis relative to the descending aorta IDIF in oncology patients examined using a Biograph Vision 600 PET/CT with continuous bed motion (Aarhus) or using a recently installed Biograph Vision Quadra long-axial field-of-view (FOV) scanner (Bern).

Results
Correlation analysis of the coefficients of a tri-exponential decomposition of the IDIFs measured during 67 min revealed strong relationships among the total area under the curve (AUC), the terminal normalized arterial integral (theta(52–67 min)), and the terminal image-derived arterial FDG concentration (Ca(52–67 min)). These relationships enabled estimation of the missing AUC from late recordings of the IDIF, from which we then calculated FDG-Ki in brain by two-point linear graphic analysis using a population mean ordinate intercept and the single late frame. Furthermore, certain aspects of the IDIF data from Aarhus showed a marked age-dependence, which was not hitherto reported for the case of FDG pharmacokinetics.

Conclusions
The observed interrelationships between pharmacokinetic parameters in the IDIF measured during the PET recording support quantitation of FDG-Ki in brain using a single averaged frame from the interval 52–67 min post-injection, with minimal error relative to calculation from the complete dynamic sequences.
Preparedness, impacts, and responses of public health emergencies towards health security: qualitative synthesis of evidence
Authors: Khatri Resham B , Endalamaw Aklilu , Erku Daniel , Wolka Eskinder , Nigatu Frehiwot , Zewdie Anteneh , Assefa Yibeltal 
Published: November 2023

Abstract
Background
Natural and human-made public health emergencies (PHEs), such as armed conflicts, floods, and disease outbreaks, influence health systems including interruption of delivery and utilization of health services, and increased health service needs. However, the intensity and types of impacts of these PHEs vary across countries due to several associated factors. This scoping review aimed to synthesise available evidence on PHEs, their preparedness, impacts, and responses.

Methods
We conducted a scoping review of published evidence. Studies were identified using search terms related to two concepts: health security and primary health care. We used Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA-ScR) guidelines to select studies. We adapted the review framework of Arksey and O’Malley. Data were analyzed using a thematic analysis approach and explained under three stages of PHEs: preparedness, impacts, and responses.

Results
A total of 64 studies were included in this review. Health systems of many low- and middle-income countries had inadequate preparedness to absorb the shocks of PHEs, limited surveillance, and monitoring of risks. Health systems have been overburdened with interrupted health services, increased need for health services, poor health resilience, and health inequities. Strategies of response to the impact of PHEs included integrated services such as public health and primary care, communication and partnership across sectors, use of digital tools, multisectoral coordination and actions, system approach to responses, multidisciplinary providers, and planning for resilient health systems.

Conclusions
Public health emergencies have high impacts in countries with weak health systems, inadequate preparedness, and inadequate surveillance mechanisms. Better health system preparedness is required to absorb the impact, respond to the consequences, and adapt for future PHEs. Some potential response strategies could be ensuring need-based health services, monitoring and surveillance of post-emergency outbreaks, and multisectoral actions to engage sectors to address the collateral impacts of PHEs. Mitigation strategies for future PHEs could include risk assessment, disaster preparedness, and setting digital alarm systems for monitoring and surveillance.
Evaluation of the preference for and viability of clean cookstove adoption in rural Tanzania
Authors: Gill-Wiehl Annelise , Sievers Sara , Katikiro Robert , Kammen Daniel M. 
Published: November 2023

Abstract
Background
Sustainable Development Goal (SDG) 7 calls for “universal access to affordable, reliable, modern energy services” for the 2.6 billion individuals lacking access to clean cooking fuels and stoves. Low- and middle-income countries are designing policies towards clean fuels, but often prioritize World Health Organization defined ‘clean’ fuels and stoves to urban areas. As clean solutions are explored, it remains unclear what rural households prefer as their clean alternative.

Methods
This study conducted household energy surveys with main cooks across four villages in Shirati, Tanzania to understand rural household preferences within the viable clean fuels. Data analysis includes descriptive statistics and a generalized linear model with the Poisson family and log link to estimate prevalence ratios, all of which were conducted in Microsoft Excel and STATA 16.1.

Results
The results revealed that while 83% of households (n = 187) stacked a combination of firewood, charcoal, liquified petroleum gas (LPG), and/or kerosene, 82% [95% Confidence Interval: 74%, 89%] of households stated a preference to use LPG. We found that aggregate expenditure on LPG was less than daily purchases of charcoal and firewood. Our analysis found that all villages had a higher prevalence of stacking firewood, charcoal, and LPG, than areas further from the main trading center. Both areas with trading posts had a lower prevalence of using only firewood.

Conclusions
Household preference should be systematically incorporated into clean cooking policy decisions. Our results imply that LPG should not be pursued only in urban contexts. We discuss how preference affect adoption and the need to include user preferences to meet universal clean cooking access (SDG 7).
Public service innovation to fight corruption: metrics and policy in Mexico 2019–2022
Authors: Corona-Treviño Leonel 
Published: November 2023

AbstractThe purpose is to identify and analyze some innovations in public services, PSI, between 2019 and 2022 to evaluate their attempts to deter corruption in a context where the current government’s Mexican public sector has been improving its capacity to fight corruption as the most critical problem. The research is designed to describe 12 PSI selected from the national level. Their innovativeness is measured through an INDICO index adapted from technology firms, which mainly has added a perception of its public value besides their use value. Corruption is measured based on the neo-institutional approach on three axes: public–private relations, its organization, and the agents’ behavior. The question is to measure the impact of the innovations in deterring corruption, which is estimated by the difference in magnitude between the current and the previous one.The findings are:

The neo-institutional theory highlights corruption-related aspects rooted in public–private relations, however, complemented with social and management approaches.

The INDICO index measures, based on a pre-established 10-point quantitative maximum scale distributed between components on capacity -knowledge of the service, training, design, peer evaluation through external links- and on innovation results in public services—its legitimization through public value, and its possible replication (diffusion), which an expert in the field of innovation qualitatively evaluates.

The impact of the selected Public Service Innovations shows that there is a positive effect in reducing the level of corruption. The more systemic or institutionalized corruption is, the more difficult it is to develop effective strategies proving their long-term value.

The PSIs have been managed by the government’s leadership founded on legitimate authority, secured from the victory in the 2018 elections in Mexico, enabling it to put forward its top-to-bottom anti-corruption program. A more extended period, a group of experts, and more cases are desirable to assess PSI sustainability. However, the methodology could be extended to other contexts for policymakers or practitioners in public services and corruption.
Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease
Authors: Xu Wenying , Wang Jie , Li Xin-Ni , Liang Jingxue , Song Lu , Wu Yi , Liu Zhenguo , Sun Bomin , Li Wei-Guang 
Published: November 2023

AbstractDeep brain stimulation (DBS) is a well-established and effective treatment for patients with advanced Parkinson's disease (PD), yet its underlying mechanisms remain enigmatic. Optogenetics, primarily conducted in animal models, provides a unique approach that allows cell type- and projection-specific modulation that mirrors the frequency-dependent stimulus effects of DBS. Opto-DBS research in animal models plays a pivotal role in unraveling the neuronal and synaptic adaptations that contribute to the efficacy of DBS in PD treatment. DBS-induced neuronal responses rely on a complex interplay between the distributions of presynaptic inputs, frequency-dependent synaptic depression, and the intrinsic excitability of postsynaptic neurons. This orchestration leads to conversion of firing patterns, enabling both antidromic and orthodromic modulation of neural circuits. Understanding these mechanisms is vital for decoding position- and programming-dependent effects of DBS. Furthermore, patterned stimulation is emerging as a promising strategy yielding long-lasting therapeutic benefits. Research on the neuronal and synaptic adaptations to DBS may pave the way for the development of more enduring and precise modulation patterns. Advanced technologies, such as adaptive DBS or directional electrodes, can also be integrated for circuit-specific neuromodulation. These insights hold the potential to greatly improve the effectiveness of DBS and advance PD treatment to new levels.