bluuebunny/crossref_metadata_2025 huggingface dataset:
Hydroxyapatite microbeads containing BMP-2 and quercetin fabricated via electrostatic spraying to encourage bone regeneration
Authors: Lee Seoyun , Park Honghyun , Oh Jeong-Seop , Byun Kyubin , Kim Dae-Yong , Yun Hui-suk , Kang Byung-Jae
Published: February 2023

Background

Hydroxyapatite (HAp) possesses osteoconductive properties, and its granular form can serve as an effective drug delivery vehicle for bone regeneration. Quercetin (Qct), a plant-derived bioflavonoid, is known to promote bone regeneration; however, its comparative and synergistic effects with the commonly used bone morphogenetic protein-2 (BMP-2) have not been investigated.

Methods

We examined the characteristics of newly formed HAp microbeads using an electrostatic spraying method and analyzed the in vitro release pattern and osteogenic potential of ceramic granules containing Qct, BMP-2, and both. In addition, HAp microbeads were transplanted into a rat critical-sized calvarial defect and the osteogenic capacity was assessed in vivo.

Results

The manufactured beads had a microscale size of less than 200 μm, a narrow size distribution, and a rough surface. The alkaline phosphatase (ALP) activity of osteoblast-like cells cultured with the BMP-2-and-Qct-loaded HAp was significantly higher than that of either Qct- or BMP-2-loaded HAp groups. The mRNA levels of osteogenic marker genes such as ALP and runt-related transcription factor 2 were found to be upregulated in the HAp/BMP-2/Qct group compared to the other groups. In micro-computed tomographic analysis, the amount of newly formed bone and bone surface area within the defect was significantly higher in the HAp/BMP-2/Qct group, followed by the HAp/BMP-2 and HAp/Qct groups, which is consistent with the histomorphometrical results.

Conclusions

These results imply that electrostatic spraying can be an efficient strategy to produce homogenous ceramic granules and that the BMP-2-and-Qct-loaded HAp microbeads can serve as effective implants for bone defect healing.
Enhanced mucosal immune responses and reduced viral load in the respiratory tract of ferrets to intranasal lipid nanoparticle-based SARS-CoV-2 proteins and mRNA vaccines
Authors: Boley Patricia A. , Lee Carolyn M. , Schrock Jennifer , Yadav Kush Kumar , Patil Veerupaxagouda , Suresh Raksha , Lu Songqing , Feng Maoqi Mark , Hanson Juliette , Channappanavar Rudra , Kenney Scott P. , Renukaradhya Gourapura J.
Published: February 2023

Background

Unlike the injectable vaccines, intranasal lipid nanoparticle (NP)-based adjuvanted vaccine is promising to protect against local infection and viral transmission. Infection of ferrets with SARS-CoV-2 results in typical respiratory disease and pathology akin to in humans, suggesting that the ferret model may be ideal for intranasal vaccine studies.

Results

We developed SARS-CoV-2 subunit vaccine containing both Spike receptor binding domain (S-RBD) and Nucleocapsid (N) proteins (NP-COVID-Proteins) or their mRNA (NP-COVID-mRNA) and NP-monosodium urate adjuvant. Both the candidate vaccines in intranasal vaccinated aged ferrets substantially reduced the replicating virus in the entire respiratory tract. Specifically, the NP-COVID-Proteins vaccine did relatively better in clearing the virus from the nasal passage early post challenge infection. The immune gene expression in NP-COVID-Proteins vaccinates indicated increased levels of mRNA of IFNα, MCP1 and IL-4 in lungs and nasal turbinates, and IFNγ and IL-2 in lungs; while proinflammatory mediators IL-1β and IL-8 mRNA levels in lungs were downregulated. In NP-COVID-Proteins vaccinated ferrets S-RBD and N protein specific IgG antibodies in the serum were substantially increased at both day post challenge (DPC) 7 and DPC 14, while the virus neutralizing antibody titers were relatively better induced by mRNA versus the proteins-based vaccine. In conclusion, intranasal NP-COVID-Proteins vaccine induced balanced Th1 and Th2 immune responses in the respiratory tract, while NP-COVID-mRNA vaccine primarily elicited antibody responses.

Conclusions

Intranasal NP-COVID-Proteins vaccine may be an ideal candidate to elicit increased breadth of immunity against SARS-CoV-2 variants.
Association of milk consumption with all-cause mortality and cardiovascular outcomes: a UK Biobank based large population cohort study
Authors: Zhou Jian , Wu Ziyi , Lin Zhengjun , Wang Wanchun , Wan Rongjun , Liu Tang
Published: February 2023

Background

The association of milk consumption with mortality and cardiovascular disease (CVD) outcomes was unclear.

Objective

The present study was performed to reveal the association of full cream, semi-skimmed, skimmed, soy, and other milk with all-cause mortality and CVD outcomes.

Methods

A prospective cohort study was performed using data from the UK Biobank. This study recruited 450,507 participants without CVD at baseline between 2006 and 2010 from UK Biobank and followed them up through 2021. Cox proportional hazard models were adopted to calculate the hazard ratios (HRs) and 95% confidence interval (CI) to understand the correlation between milk consumption and clinical outcomes. Subgroup and sensitivity analyses were further conducted.

Results

Among the participants, 435,486 (96.7%) were milk consumers. Multivariable model indicated that the adjusted HR of association between milk consumption and all-cause mortality was 0.84 (95% CI 0.79 to 0.91; P = 0.000) for semi-skimmed milk; 0.82 (0.76 to 0.88; P = 0.000) for skimmed milk and 0.83 (0.75 to 0.93; P = 0.001) for soy milk. Semi-skimmed, skimmed, and soy milk use were significantly related to lower risks of CVD mortality, CVD event, and stroke.

Conclusion

Compared with non-milk users, semi-skimmed milk, skimmed milk, and soy milk consumption were related to a lower risk of all-cause mortality and CVD outcomes. Among them, skim milk consumption was more beneficial for all-cause mortality, while soy milk consumption was more beneficial for CVD outcomes.
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

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

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

Studies 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

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

Osteoarthritis (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

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

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

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

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

The 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

Prolonged 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

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).
Non-communicable disease burden among inpatients at a rural district hospital in Malawi
Authors: Olds Peter , Kachimanga Chiyembekezo , Talama George , Mailosi Bright , Ndarama Enoch , Totten Jodie , Musinguzi Nicholas , Hangiwa Dickson , Bukhman Gene , Wroe Emily B.
Published: February 2023

Background

The burden of non-communicable diseases (NCDs) is high in Malawi. However, resources and training for NCD care remain scarce, especially in rural hospitals. Current care for NCDs in the developing world focuses on the WHO’s traditional 4 × 4 set. However, we do not know the full burden of NCDs outside of that scope, like neurological disease, psychiatric illness, sickle cell disease, and trauma. The goal of this study was to understand the burden of NCDs among inpatients in a rural district hospital in Malawi. We broadened our definition of NCDs beyond the traditional 4 × 4 set of NCDs, and included neurological disease, psychiatric illness, sickle cell disease, and trauma.

Methods

We conducted a retrospective chart review of all inpatients who were admitted to the Neno District Hospital between January 2017 and October 2018. We broke patients down by age, date of admission, type, and number of NCD diagnoses, and HIV status, and constructed multivariate regression models for length of stay and in-hospital mortality.

Results

Of 2239 total visits, 27.5% were patients with NCDs. Patients with NCDs were older (37.6 vs 19.7 years, p < 0.001) and made up 40.2% of total hospital time. We also found two distinct populations of NCD patients. The first were patients 40 years and older with primary diagnoses of hypertension, heart failure, cancer, and stroke. The second were patients under 40 years old with primary diagnoses of mental health conditions, burns, epilepsy, and asthma. We also found significant trauma burden, accounting for 40% of all NCD visits. In multivariate analysis, carrying a medical NCD diagnosis was associated with longer length of stay (coefficient 5.2, p < 0.001) and a higher risk of in-hospital mortality (OR 1.9, p = 0.03). Burn patients also had significantly longer length of stay (coefficient 11.6, p < 0.001).

Conclusions

There is a significant burden of NCDs in a rural hospital in Malawi, including those outside of the traditional 4 × 4 set. We also found high rates of NCDs in the younger population (under 40 years of age). Hospitals must be equipped with adequate resources and training to meet this burden of disease.
Combined ambient ionization mass spectrometric and chemometric approach for the differentiation of hemp and marijuana varieties of Cannabis sativa
Authors: Chambers Megan I. , Beyramysoltan Samira , Garosi Benedetta , Musah Rabi A.
Published: February 2023

Background

Hemp and marijuana are the two major varieties of Cannabis sativa. While both contain Δ9-tetrahydrocannabinol (THC), the primary psychoactive component of C. sativa, they differ in the amount of THC that they contain. Presently, U.S. federal laws stipulate that C. sativa containing greater than 0.3% THC is classified as marijuana, while plant material that contains less than or equal to 0.3% THC is hemp. Current methods to determine THC content are chromatography-based, which requires extensive sample preparation to render the materials into extracts suitable for sample injection, for complete separation and differentiation of THC from all other analytes present. This can create problems for forensic laboratories due to the increased workload associated with the need to analyze and quantify THC in all C. sativa materials.

Method

The work presented herein combines direct analysis in real time—high-resolution mass spectrometry (DART-HRMS) and advanced chemometrics to differentiate hemp and marijuana plant materials. Samples were obtained from several sources (e.g., commercial vendors, DEA-registered suppliers, and the recreational Cannabis market). DART-HRMS enabled the interrogation of plant materials with no sample pretreatment. Advanced multivariate data analysis approaches, including random forest and principal component analysis (PCA), were used to optimally differentiate these two varieties with a high level of accuracy.

Results

When PCA was applied to the hemp and marijuana data, distinct clustering that enabled their differentiation was observed. Furthermore, within the marijuana class, subclusters between recreational and DEA-supplied marijuana samples were observed. A separate investigation using the silhouette width index to determine the optimal number of clusters for the marijuana and hemp data revealed this number to be two. Internal validation of the model using random forest demonstrated an accuracy of 98%, while external validation samples were classified with 100% accuracy.

Discussion

The results show that the developed approach would significantly aid in the analysis and differentiation of C. sativa plant materials prior to launching painstaking confirmatory testing using chromatography. However, to maintain and/or enhance the accuracy of the prediction model and keep it from becoming outdated, it will be necessary to continue to expand it to include mass spectral data representative of emerging hemp and marijuana strains/cultivars.
Interventional therapy of acute coronary syndromes in very old patient population and results of 2 years follow-up
Authors: Boyraz Bedrettin , Peker Tezcan , Akgümüş Alkame , Balun Ahmet
Published: February 2023

Background

Research on cardiovascular treatment options and prognosis in very old age groups of patients is warranted. In our study, we evaluated and followed up on clinical conditions on admission and comorbidities of patients older than 80 years who were admitted to our hospital with acute myocardial infarction and shared our findings.

Results

A total of 144 patients were included in the study, with a mean age of 84.56 ± 5.01 years. No complications resulting in death or requiring surgery were observed in the patients. All-cause mortality was found to be related to heart failure, chronic pulmonary disease shock, and C-reactive protein levels. Cardiovascular mortality was correlated to heart failure, shock on admission, and C-reactive protein levels. No significant difference in mortality was observed between Non-ST elevated myocardial infarction and ST-elevation myocardial infarction.

Conclusions

Percutaneous coronary intervention is a safe treatment option with low complication and mortality rates in very old patients with acute coronary syndromes.
Generation of a mountain-valley wind in an atmospheric boundary wind tunnel: a gust-wind generator study
Authors: Zou Simin , He Xuhui
Published: February 2023

Appropriate modeling of an experimental technology is necessary in order to estimate the aerodynamic characteristic of railway trains and infrastructure (e.g., bridges). Simulation of the earth’s wind characteristics of nature is a well-established practice by using an atmospheric boundary wind tunnel. However, in the mountainous area, the wind characteristics are strikingly different from those of the plain area, the amplitude variation of wind is related to complex terrain. Compared with atmospheric boundary layer winds, which are customarily treated as stationary, winds associated with gust winds originating from mountain areas exhibit rapid changes during a short period. A lack of available field test data and testing techniques has hindered such knowledge of the effect of mountain wind on railway-related applications. To simulate the characteristics of gust winds and prepare for follow-up studies of the impact on the railway-related structures, a gust wind generator was developed in an atmospheric boundary wind tunnel — the CSU wind tunnel. Further, the performance of the gust-wind generator was studied and analyzed under the condition of the combined operation between a gust-wind generator and a wind tunnel.
Diagnostic accuracy for a plasma SARS-CoV-2 Nucleocapsid Protein method
Authors: Kristiansen Søren , Schmidt Laura Emilie , Hillig Ann-Britt Nygaard , Nielsen Thyge Lynghøj , Pedersen Thomas Ingemann , Kirkby Nikolai Søren , Schiøler Thomas , Hillig Thore
Published: February 2023

Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) releases nucleocapsid proteins (NP) into the blood circulation in infected patients. We investigated whether plasma NP analysis could be used for diagnosing an infection and used for nosocomial screening.

Methods: We collected blood samples from patients admitted to the hospital during a period with reverse transcription polymerase chain reaction (RT-PCR) based-screening of patients for SARS-CoV-2. Retrospectively the SARS-CoV-2 NP plasma concentrations were measured with an enzyme-linked immunosorbent assay (ELISA) method and used for an initial time course study to find the optimal time-point for sampling blood. Next, we estimated the diagnostic accuracy i.e. the clinical sensitivity and specificity at different plasma NP cut-off concentrations.

Results: The time course study revealed profiles with rapid or more slow declines in NP titers after the RT-PCR result. Nevertheless, in the time interval 0 – 7 days after the RT-PCR result, the NP concentration was always above the level of detection at 1.66 pg/ml suggesting that the diagnosis could be established in the time interval of 0 - 7 days. The median time gap between the plasma NP and RT-PCR results was 0.0 days (n = 1957, interval: -26 to + 21 days). Reducing the time gap to seven days, the clinical sensitivity was 90.0% (n= 60, 95% CI, 82.4% to 97.6%) at a specificity of 95.9% (n=1876, 95% CI, 95.0% to 96.8%). Curve analysis by receiver operation characteristics identified a cut-off concentration of 1.87 pg/mL NP as optimal resulting in a positive predictive value of 41.2%, a negative predictive value of 99.7% and a prevalence of 3.1%.

Conclusions: In conclusion, the NP method is acceptable for making the laboratory diagnosis of SARS-CoV-2, and an intended use of plasma NP as a prospective nosocomial screening method is considered feasible.
Uptake of same-day initiation of HIV treatment among adult men and women in Malawi, South Africa, and Zambia: the SPRINT retrospective cohort study
Authors: Huber Amy , Hirasen Kamban , Brennan Alana T. , Phiri Bevis , Tcherini Timothy , Mulenga Lloyd , Haimbe Prudence , Shakwelele Hilda , Nyirenda Rose , Wilson Matola Bilaal , Gunda Andrews , Rosen Sydney
Published: February 2023

Background: Since 2017 global guidelines have recommended “same-day initiation” (SDI) of antiretroviral treatment (ART) for patients considered ready for treatment on the day of HIV diagnosis. Many countries have incorporated a SDI option into national guidelines, but SDI uptake is not well documented. We estimated average time to ART initiation at 12 public healthcare facilities in Malawi, five in South Africa, and 12 in Zambia.

Methods: We sequentially enrolled patients eligible to start ART between January 2018 and June 2019 and reviewed their medical records from the point of HIV diagnosis or first HIV-related interaction with the clinic to the earlier date of treatment initiation or 6 months. We estimated the proportion of patients initiating ART on the same day or within 7, 14, 30, or 180 days of baseline.

Results: We enrolled 826 patients in Malawi, 534 in South Africa, and 1,984 in Zambia. Overall, 88% of patients in Malawi, 57% in South Africa, and 91% in Zambia were offered and accepted SDI. In Malawi, most who did not receive SDI had not initiated ART ≤6 months. In South Africa, an additional 13% initiated ≤1 week, but 21% had no record of initiation ≤6 months. Among those who did initiate within 6 months in Zambia, most started ≤1 week. There were no major differences by sex. WHO Stage III/IV and tuberculosis symptoms were associated with delays in ART initiation.

Conclusions: As of 2020, SDI of ART was widespread, if not nearly universal, in Malawi and Zambia but considerably less common in South Africa. Limitations of the study include pre-COVID-19 data that do not reflect pandemic adaptations and potentially missing data for Zambia. South Africa may be able to increase overall ART coverage by reducing numbers of patients who do not initiate ≤6 months.

Registration: Clinicaltrials.gov (NCT04468399; NCT04170374; NCT04470011).
The genome sequence of the black needle fly, Leuctra nigra (Olivier, 1811)
Authors: Clifford Caleala ,   Natural History Museum Genome Acquisition Lab,   Darwin Tree of Life Barcoding collective,   Wellcome Sanger Institute Tree of Life programme,   Wellcome Sanger Institute Scientific Operations: DNA Pipelines collective,   Tree of Life Core Informatics collective, Macadam Craig R. , Price Benjamin W. ,   Darwin Tree of Life Consortium
Published: February 2023

We present a genome assembly from an individual male Leuctra nigra (black needle fly; Arthropoda; Insecta; Plecoptera; Leuctridae). The genome sequence is 536.3 megabases in span. Most of the assembly is scaffolded into 13 chromosomal pseudomolecules, including the X sex chromosome. The mitochondrial genome has also been assembled and is 17.6 kilobases in length.
Pol. "czas" vs "pogoda" ~ Mac. "време". Różnice w konceptualizacji świata
Authors: Topolińska Zuzanna
Published: February 2023

Autorka prezentuje polskie i macedońskie przykłady ilustrujące, jak języki różnią się w konceptualizacji świata i stwierdza, że analiza takich różnic stanowi interesujące źródło informacji o mentalności poszczególnych narodów.
Gliflozins and their beneficial hypoglycaemic effect profile and prevention of cardiovascular complications in patients treated for type II diabetes mellitus
Authors: Sobańska Natalia , Teichman Rafał , Banasiak Aleksandra Paulina , Kasprowicz Jakub , Pierzchała Jakub Rafał , Hyjek Michał , Abram Kamila , Banaś Patryk , Bednarz Katarzyna , Adamus Justyna
Published: February 2023

Introduction: Diabetes mellitus type 2 (DM2) is a population disease, it is predicted that by 2030 the DM2 will affect 7% of the population. Patients due to progress of the disease in case of micro and macro angiovascular changes develop organ complications mainly in terms of cardiovascular disease (CV). Sodium-glucose cotransporter 2 (SGLT2) inhibitors are relatively new group of drugs that apart from the hypoglycemic effect, also have other beneficial effects. Due to the scale and importance of the problem of diabetes complications researchers from around the world are working on its solution.
 
Aim of the study: The aim of this study was to present the effects of SGLT2 inhibitors on cardiovascular complications in DM2 patients.
 
Methods and materials
We reviewed the literature contained in the PubMed database, using keywords: „Diabetes type 2”; „SGLT2 inhibitors”; „Cardiovascular disease”; „Heart failure”
 
Results: In addition to their hypoglycaemic effects, SGLT2 inhibitors have also been shown to have beneficial effects on the CV system. Studies have shown that in DM2 patients treated with gliflozins, the risk of hospitalisation for heart failure decreased by 35% and the risk of death from cardiovascular causes by 38%. Retrospective studies have been carried out in which the efficacy of all drugs in the group in question, and not just individual substances, has been proven. In clinical experiments, phlazines were confirmed to reduce the risk of CV complications, including heart failure, myocardial infarction, angina, stroke or atrial fibrillation.
 
Conclusions: SGLT2 drugs reduce the risk of cardiovascular complications and reduce hospitalisations for heart failure in patients with DM2. Future studies should seek to determine at what stage treatment should be implemented to maximise the resulting benefits to the patient.
The Individual and the Community in Stoic Pragmatism
Authors: Skowroński Krzysztof Piotr
Published: February 2023

The present paper outlines John Lachs’s idea of stoic pragmatism and develops its important part that is the relation between the individual and the community. In his project, Lachs reduces the whole tradition of Stoic philosophy to its later, Roman version and tries to link it with the philosophical tradition of American pragmatism (especially William James, John Dewey, and George Santayana, who is close to pragmatism at some points) hoping that it is possible for these two to "enrich and complete each other" so that to provide "a better attitude to life than either of the two views alone." Stoic pragmatism pursues factual improvement in the quality of life for individuals living in given social circumstances, rather than a new theory about such improvement. Interestingly, stoic pragmatism overlaps at many points with the so-called modern stoicism, a movement that uses Stoic ethics in contemporary contexts.
Ustanawianie obecności jako mechanizm przywództwa politycznego. Przykład Szymona Hołowni
Authors: Marciniak Ewa Maria
Published: February 2023

ESTABLISHING PRESENCE AS A MECHANISM OF POLITICAL LEADERSHIP: THE EXAMPLE OF SZYMON HOŁOWNIA
The article touches upon building the political leadership of Szymon Hołownia, which is analysed in the light of the interactive theory of the emergence of leaders. The issues of complementarity of the needs of the leader and his voters and their mental matching are indicated, including research within the framework of the A Congruency Model of Political Preference (Caprara, Zimbardo). Establishing a presence by Szymon Hołownia via social media is a process in which he exposes content referring to the psychological and cultural sphere to a greater extent and to the sphere of politics to a lesser extent.