bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrin Mac1 mediates paraquat and maneb-induced learning and memory impairments in mice through NADPH oxidase–NLRP3 inflammasome axis-dependent microglial activation
Authors: Hou Liyan , Liu Jianing , Sun Fuqiang , Huang Ruixue , Chang Rui , Ruan Zhengzheng , Wang Ying , Zhao Jie , Wang Qingshan 
Published: February 2023

Abstract
Introduction
The mechanisms of cognitive impairments in Parkinson’s disease (PD) remain unknown. Accumulating evidence revealed that brain neuroinflammatory response mediated by microglial cells contributes to cognitive deficits in neuropathological conditions and macrophage antigen complex-1 (Mac1) is a key factor in controlling microglial activation.

Objectives
To explore whether Mac1-mediated microglial activation participates in cognitive dysfunction in PD using paraquat and maneb-generated mouse PD model.

Methods
Cognitive performance was measured in wild type and Mac1−/− mice using Morris water maze test. The role and mechanisms of NADPH oxidase (NOX)–NLRP3 inflammasome axis in Mac1-mediated microglial dysfunction, neuronal damage, synaptic degeneration and phosphorylation (Ser129) of α-synuclein were explored by immunohistochemistry, Western blot and RT-PCR.

Results
Genetic deletion of Mac1 significantly ameliorated learning and memory impairments, neuronal damage, synaptic loss and α-synuclein phosphorylation (Ser129) caused by paraquat and maneb in mice. Subsequently, blocking Mac1 activation was found to mitigate paraquat and maneb-elicited microglial NLRP3 inflammasome activation in both in vivo and in vitro. Interestingly, stimulating activation of NOX by phorbol myristate acetate abolished the inhibitory effects of Mac1 blocking peptide RGD on paraquat and maneb-provoked NLRP3 inflammasome activation, indicating a key role of NOX in Mac1-mediated NLRP3 inflammasome activation. Furthermore, NOX1 and NOX2, two members of NOX family, and downstream PAK1 and MAPK pathways were recognized to be essential for NOX to regulate NLRP3 inflammasome activation. Finally, a NLRP3 inflammasome inhibitor glybenclamide abrogated microglial M1 activation, neurodegeneration and phosphorylation (Ser129) of α-synuclein elicited by paraquat and maneb, which were accompanied by improved cognitive capacity in mice.

Conclusions
Mac1 was involved in cognitive dysfunction in a mouse PD model through NOX–NLRP3 inflammasome axis-dependent microglial activation, providing a novel mechanistic basis of cognitive decline in PD.
Women and working in healthcare during the Covid-19 pandemic in Brazil: bullying of colleagues
Authors: da Silva Paulo Roberto , Porto Paloma , Rocha Mariela Campos , Tamaki Eduardo Ryô , Corrêa Marcela Garcia , Fernandez Michelle , Lotta Gabriela , Pimenta Denise Nacif 
Published: February 2023

Abstract
Background
Based on a feminist approach, we analyzed the experiences of workplace bullying suffered by women front-line healthcare professionals dealing with the Covid-19 pandemic. We start from studies that show that women make up 70% of the global health workforce, 85% in the area of nursing, and 90% in the case of social care workers. An unequivocal need thus exists to address gender issues regarding the composition of the labor force in the health area. The pandemic has aggravated recurring problems involving healthcare professionals at the various caregiving levels, such as mental harassment (bullying) and its effects on mental health.

Methods
Data were gathered from an online survey of a convenience (non-probability) sample composed of 1,430 volunteer respondents, all women that work in the public health system in Brazil. The analyses and discussions involved the responses to a questionnaire containing 12 closed-ended questions and one open-ended question.

Results
The results revealed a context of workplace bullying aggravated by precarious material, institutional and organizational conditions in the area of health services against the backdrop of the Covid-19 pandemic in Brazil. This context has variously led to aggression, isolation, heavy workloads, and invasion of privacy, humiliation, persecution and fear as it was possible to see, mainly, in the answers to the study’s open-ended question. This situation degrades both work relations and the integrity of the healthcare professionals who work on the front line to treat Covid-19 cases.

Conclusion
We conclude that bullying is a psychosocial phenomenon that heightens the oppression and subordination still experienced by women in the contemporary context, but with new hues in a scenario of frontline response to Covid-19.
Design and performance analysis of 3D-printed stiffness gradient femoral scaffold
Authors: Liu Linlin , Liu Chang , Deng Congying , Wang Xin , Liu Xiangde , Luo Maolin , Wang Shuxian , Liu Juncai 
Published: February 2023

AbstractStudies on 3D-printed porous bone scaffolds mostly focus on materials or structural parameters, while the repair of large femoral defects needs to select appropriate structural parameters according to the needs of different parts. In this paper, a kind of stiffness gradient scaffold design idea is proposed. Different structures are selected according to the different functions of different parts of the scaffold. At the same time, an integrated fixation device is designed to fix the scaffold. Finite element method was used to analyze the stress and strain of homogeneous scaffolds and the stiffness gradient scaffolds, and the relative displacement and stress between stiffness gradient scaffolds and bone in the case of integrated fixation and steel plate fixation. The results showed that the stress distribution of the stiffness gradient scaffolds was more uniform, and the strain of host bone tissue was changed greatly, which was beneficial to the growth of bone tissue. The integrated fixation method is more stable, less stress and evenly distributed. Therefore, the integrated fixation device combined with the design of stiffness gradient can repair the large femoral bone defect well.
Study protocol: short against long antibiotic therapy for infected orthopedic sites — the randomized-controlled SALATIO trials
Authors: Uçkay Ilker , Wirth Stephan , Zörner Björn , Fucentese Sandro , Wieser Karl , Schweizer Andreas , Müller Daniel , Zingg Patrick , Farshad Mazda 
Published: February 2023

Abstract
Background
Few studies address the appropriate duration of post-surgical antibiotic therapy for orthopedic infections; with or without infected residual implants. We perform two similar randomized-clinical trials (RCT) to reduce the antibiotic use and associated adverse events.

Methods
Two unblinded RCTs in adult patients (non-inferiority with a margin of 10%, a power of 80%) with the primary outcomes “remission” and “microbiologically-identical recurrences” after a combined surgical and antibiotic therapy. The main secondary outcome is antibiotic-related adverse events. The RCTs allocate the participants between 3 vs. 6 weeks of post-surgical systemic antibiotic therapy for implant-free infections and between 6 vs. 12 weeks for residual implant-related infections. We need a total of 280 episodes (randomization schemes 1:1) with a minimal follow-up of 12 months. We perform two interim analyses starting approximately after 1 and 2 years. The study approximatively lasts 3 years.

Discussion
Both parallel RCTs will enable to prescribe less antibiotics for future orthopedic infections in adult patients.

Trial registration
ClinicalTrial.gov NCT05499481. Registered on 12 August 2022.
Protocol version: 2 (19 May 2022)
Osteoarthritis: a narrative review of molecular approaches to disease management
Authors: Salman Loay A. , Ahmed Ghalib , Dakin Stephanie G. , Kendrick Benjamin , Price Andrew 
Published: February 2023

AbstractOsteoarthritis (OA) is a chronic, progressive degenerative whole joint disease that affects the articular cartilage, subchondral bone, ligaments, capsule, and synovium. While it is still believed to be a mechanically driven disease, the role of underlying co-existing inflammatory processes and mediators in the onset of OA and its progression is now more appreciated. Post-traumatic osteoarthritis (PTOA) is a subtype of OA that occurs secondary to traumatic joint insults and is widely used in pre-clinical models to help understand OA in general. There is an urgent need to develop new treatments as the global burden is considerable and expanding. In this review, we focus on the recent pharmacological advances in the treatment of OA and summarize the most significant promising agents based on their molecular effects. Those are classified here into broad categories: anti-inflammatory, modulation of the activity of matrix metalloproteases, anabolic, and unconventional pleiotropic agents. We provide a comprehensive analysis of the pharmacological advances in each of these areas and highlight future insights and directions in the OA field.
Sex differences in the associations of body size and body shape with platelets in the UK Biobank cohort
Authors: Christakoudi Sofia , Tsilidis Konstantinos K. , Evangelou Evangelos , Riboli Elio 
Published: February 2023

Abstract
Background
Obesity is accompanied by low-grade inflammation and leucocytosis and increases the risk of venous thromboembolism. Associations with platelet count, however, are unclear, because several studies have reported positive associations only in women. Associations with body shape are also unclear, because waist and hip circumferences reflect overall body size, as well as body shape, and are correlated strongly positively with body mass index (BMI).

Methods
We evaluated body shape with the allometric body shape index (ABSI) and hip index (HI), which reflect waist and hip size among individuals with the same weight and height and are uncorrelated with BMI. We examined the associations of BMI, ABSI, and HI with platelet count, mean platelet volume (MPV), and platelet distribution width (PDW) in multivariable linear regression models for 125,435 UK Biobank women and 114,760 men. We compared men with women, post-menopausal with pre-menopausal women, and older (≥ 52 years) with younger (< 52 years) men.

Results
BMI was associated positively with platelet count in women, more strongly in pre-menopausal than in post-menopausal, and weakly positively in younger men but strongly inversely in older men. Associations of BMI with platelet count were shifted towards the inverse direction for daily alcohol consumption and current smoking, resulting in weaker positive associations in women and stronger inverse associations in men, compared to alcohol ≤ 3 times/month and never smoking. BMI was associated inversely with MPV and PDW in pre-menopausal women but positively in post-menopausal women and in men. ABSI was associated positively with platelet count, similarly in women and men, while HI was associated weakly inversely only in women. ABSI was associated inversely and HI positively with MPV but not with PDW and only in women. Platelet count was correlated inversely with platelet size and positively with leucocyte counts, most strongly with neutrophils.

Conclusions
Competing factors determine the associations of BMI with platelet count. Factors with sexually dimorphic action (likely thrombopoietin, inflammatory cytokines, or cortisol), contribute to a positive association, more prominently in women than in men, while age-dependent factors (likely related to liver damage and fibrosis), contribute to an inverse association, more prominently in men than in women.
Sex differences in the percentage of IRF5 positive B cells are associated with higher production of TNF-α in women in response to TLR9 in humans
Authors: Beisel Claudia , Jordan-Paiz Ana , Köllmann Sandra , Ahrenstorf Annika Elise , Padoan Benedetta , Barkhausen Tanja , Addo Marylyn M. , Altfeld Marcus 
Published: February 2023

Abstract
Background
The clinical course and outcome of many diseases differ between women and men, with women experiencing a higher prevalence and more severe pathogenesis of autoimmune diseases. The precise mechanisms underlying these sex differences still remain to be fully understood. IRF5 is a master transcription factor that regulates TLR/MyD88-mediated responses to pathogen-associated molecular patterns (PAMPS) in DCs and B cells. B cells are central effector cells involved in autoimmune diseases via the production of antibodies and pro-inflammatory cytokines as well as mediating T cell help. Dysregulation of IRF5 expression has been reported in autoimmune diseases, including systemic lupus erythematosus, primary Sjögren syndrome, and rheumatoid arthritis.

Methods
In the current study, we analyzed whether the percentage of IRF5 positive B cells differs between women and men and assessed the resulting consequences for the production of inflammatory cytokines after TLR7- or TLR9 stimulation.

Results
The percentage of IRF5 positive B cells was significantly higher in B cells of women compared to men in both unstimulated and TLR7- or TLR9-stimulated B cells. B cells of women produced higher levels of TNF-α in response to TLR9 stimulation.

Conclusions
Taken together, our data contribute to the understanding of sex differences in immune responses and may identify IRF5 as a potential therapeutic target to reduce harmful B cell-mediated immune responses in women.
Health resource allocation in Western China from 2014 to 2018
Authors: Wang Zheng , He Haoyu , Liu Xi , Wei Hongkuang , Feng Qiming , Wei Bo 
Published: February 2023

Abstract
Background
Health equity has persistently been a global concern. How to fairly and appropriately allocate health resources is a research hotspot. While Western China is relatively backward economically and presents difficulties for the allocation of health resources, little attention has been given to the equity of resource allocation there. This study analysed the equity of allocation of beds, physicians and nurses in Western China from 2014-2018 to provide targeted guidance for improving the equity of health resource allocation.

Methods
Data for 2014-2018 obtained from the Statistical Yearbook (2015-2019) of provinces (autonomous regions and municipalities) were used to analyse health resource allocation in terms of beds, physicians and nurses in Western China. The Lorenz curve and Gini coefficient were calculated to evaluate equity in the population dimension and geographic dimension. The Theil index was used to measure the inequity of the three indicators between minority and nonminority areas.

Results
The number of beds, physicians and nurses in Western China showed an increasing trend from 2014-2018. The Lorenz curve had a smaller curvature in the population dimension than in the geographic dimension. The Gini coefficients for health resources in the population dimension ranged from 0.044 to 0.079, and in the geographic dimension, the Gini coefficients ranged between 0.614 and 0.647. The above results showed that the equity of health resource allocation was better in the population dimension than in the geographic dimension. The Theil index ranged from 0.000 to 0.004 in the population dimension and from 0.095 to 0.326 in the geographic dimension, indicating that the inequity in health resource allocation was higher in the geographic dimension. The intergroup contribution ratios of the Theil index in both the population and geographic dimensions were greater than 60%, indicating that the inequity in resource allocation was mainly caused by intergroup differences, namely, the allocation of health resources within the province. Among them, the inequity of physicians and nurses allocation was the most obvious.

Conclusions
From 2014 to 2018, the total amount of health resources have improved in Western China. However, health resource allocation in Western China was still inequitable in the population and geographic dimensions, and the inequity of health resource allocation in the geographic dimension showed a tendency to worsen. Meanwhile, although the inequity of human recourse allocation was alleviated in 2018 compare with 2014, the inequity of human resource distribution within provinces was still obvious. The government can increase the number of health resources and improve the accessibility of health resources by increasing financial investment, strengthening humanistic care for health workers, and establishing internet hospitals.
A review of policies on the involuntary use of psychotropic medications among persons experiencing incarceration in the United States
Authors: Orta Joana , Barton Catherine , Ilao Patricia , Apollonio Dorie E. 
Published: February 2023

Abstract
Background
In Harper v. Washington (1990), the United States Supreme Court established the right of states to involuntary medicate incarcerated individuals in emergency situations without a court order. The extent to which states have implemented this in correctional facilities has not been well characterized. This exploratory qualitative study sought to identify state and federal corrections policies relating to involuntary psychotropic medication for individuals who are incarcerated and classify them by scope.

Methods
State Department of Corrections (DOC) and Federal Bureau of Prisons (BOP) policies relating to mental health, health services, and security were collected between March and June 2021 and coded using Atlas.ti software. The primary outcome was whether states allowed emergency involuntary use of psychotropic medications; secondary outcomes pertained to use of restraint and “use of force” policies.

Results
Of the 35 states plus the Federal BOP that made policies publicly available, 35 out of 36 (97%) allowed the involuntary use of psychotropic medications in emergency situations. The extent of detail contained in these policies varied, with 11 states providing minimal information to guide use. One state (3%) did not allow public review of “use of restraint” policies, and 7 states (19%) did not allow public review of “use of force” policies.

Conclusions
More explicit criteria for emergency involuntary use of psychotropic medications are needed to better protect individuals who are incarcerated, and states should provide more transparency regarding use of restraint and use of force in corrections.
Accelerating STEM education reform: linked communities of practice promote creation of open educational resources and sustainable professional development
Authors: Kleinschmit Adam J. , Rosenwald Anne , Ryder Elizabeth F. , Donovan Sam , Murdoch Barbara , Grandgenett Nealy F. , Pauley Mark , Triplett Eric , Tapprich William , Morgan William 
Published: February 2023

AbstractThe preparation of future scientists, the technical workforce, and informed citizens will require continued transformation to the ways we approach STEM teaching and learning. Undergraduate STEM education is rapidly emerging as a focus of faculty scholarship, but new models for reform need to be developed and tested to accelerate changes in teaching practices. This paper describes a flexible, participant-driven, multi-phase, collaborative approach to developing open educational resources (OERs) that leverages linked communities of practice (CoPs). Equally valuable, our framework for development, adaptation, dissemination, and validation of OERs provides a platform for faculty professional development and sustained support through cooperative mentoring. The three linked CoPs in the framework include incubators for the creation of initial OERs, Faculty Mentoring Networks (FMNs) for the implementation and adaptation of OERs for classroom use, and Education Research Communities to assess the effectiveness of the OERs. The CoPs create numerous benefits for participating faculty, including the ability to collaborate in the Scholarship of Teaching and Learning (SoTL) through scholarly publication of OERs and their assessment; ongoing mentorship in implementation of OERs in the classroom; and development of educational leadership skills and experience. Thus, the three CoPs synergize with one another to build and sustain capacity through providing vetted, up-to-date educational resources, as well as ongoing training and support for faculty. While we developed this approach for the rapidly changing field of bioinformatics, the linked CoP framework will have utility for STEM education reform more broadly and disciplines beyond STEM.
Measurement of Energy Intake Using the Principle of Energy Balance Overcomes a Critical Limitation in the Assessment of Energy Availability
Authors: Tarnowski Caroline A. , Wardle Sophie L. , O’Leary Thomas J. , Gifford Robert M. , Greeves Julie P. , Wallis Gareth A. 
Published: February 2023

AbstractProlonged low energy availability, which is the underpinning aetiology of the Relative Energy Deficiency in Sport and the Female and Male Athlete Triad frameworks, can have unfavourable impacts on both health and performance in athletes. Energy availability is calculated as energy intake minus exercise energy expenditure, expressed relative to fat free mass. The current measurement of energy intake is recognized as a major limitation for assessing energy availability due to its reliance on self-report methods, in addition to its short-term nature. This article introduces the application of the energy balance method for the measurement of energy intake, within the context of energy availability. The energy balance method requires quantification of the change in body energy stores over time, with concurrent measurement of total energy expenditure. This provides an objective calculation of energy intake, which can then be used for the assessment of energy availability. This approach, the Energy Availability - Energy Balance (EAEB) method, increases the reliance on objective measurements, provides an indication of energy availability status over longer periods and removes athlete burden to self-report energy intake. Implementation of the EAEB method could be used to objectively identify and detect low energy availability, with implications for the diagnosis and management of Relative Energy Deficiency in Sport and the Female and Male Athlete Triad.
Gamification of the National Institutes of Health Stroke Scale (NIHSS) for simulation training—a feasibility study
Authors: Harring Astrid Karina V. , Røislien Jo , Larsen Karianne , Guterud Mona , Bugge Helge Fagerheim , Sandset Else Charlotte , Kristensen Dorte V. , Hov Maren Ranhoff 
Published: February 2023

Abstract
Background
Training prehospital personnel in identifying patients with acute stroke is key to providing rapid treatment. This study aimed to investigate whether game-based digital simulation training is a feasible alternative to standard in-person simulation training.

Methods
Second-year paramedic bachelor students at Oslo Metropolitan University in Norway were invited to participate in a study to compare game-based digital simulation (intervention) to standard in-person training (control). For 2 months, students were encouraged to practice the NIHSS, and both groups logged their simulations. Then, they performed a clinical proficiency test, and their results were assessed using a Bland-Altman plot with corresponding 95% limits of agreement (LoA).

Results
Fifty students participated in the study. Individuals in the game group (n = 23) spent an average (SD) of 42:36 min (36) on gaming and performed 14.4 (13) simulations on average, whereas the control group (n = 27) spent 9:28 min (8) simulating and performed 2.5 (1) simulations. Comparing time variables collected during the intervention period, the mean time for each simulated assessment was significantly shorter in the game group (2:57 min vs. 3:50 min, p = 0.004). In the final clinical proficiency test, the mean difference from the true NIHSS score was 0.64 (LoA: − 1.38 to 2.67) in the game group and 0.69 (LoA: − 1.65 to 3.02) in the control group.

Conclusion
Game-based digital simulation training is a feasible alternative to standard in-person simulation training to acquire competence in NIHSS assessment. Gamification seemed to give an incentive to simulate considerably more and to perform the assessment faster, with equal accuracy.

Trial registration
The study was approved by the Norwegian Centre for Research Data (reference no. 543238).