bluuebunny/crossref_metadata_2025 huggingface dataset:
Human rights organizations and transitional justice agenda-setting: Evidence from peace agreement provisions
Authors: Bell Sam R. , Kitagawa Risa
Published: June 2022

How do human rights organizations (HROs) shape transitional justice policy in countries emerging from conflict? We investigate this question in the context of peace processes, a vital stage when many key post-conflict policies are determined. Using granular data on the content of peace agreements, we show that the robust presence of HROs significantly increases the likelihood of provisions promising criminal accountability for wartime abuses. Yet this association is conditional on prior ratification of international human rights instruments and the existence of impartial third parties in the peace process—background factors that lower barriers to effective HRO advocacy. These findings reveal a novel pathway through which HROs secure transitional justice on the national agenda after conflict.
Patient Experience and Satisfaction with Opioid-Related Screening and Intervention in North Dakota Community Pharmacies
Authors: Lothspeich Emily , Werremeyer Amy , Chase Sarah , Huseth-Zosel Andrea
Published: June 2022

Background: Screening for patient-level opioid-related risk in the community pharmacy setting has increased patient education about opioids and naloxone distribution, helping to mitigate the impact of the opioid epidemic. However, patient experience and satisfaction with opioid screening and education is unknown. Fear of patient dissatisfaction may limit pharmacists' willingness to implement screening activities. Objective: To report patient experience and satisfaction of a convenience sample of patients undergoing screening and intervention for opioid-related risk as a part of the ONE Program (formerly ONE Rx). Methods: Patients who received ONE Program screening and intervention from their community pharmacist were recruited to participate in a 9 item survey regarding their experience and satisfaction. Results were analyzed by urban and rural location of participants. Results: Urban (n = 42) and rural (n = 32) patients who completed the survey reported positive experiences namely feeling comfortable with the ONE process (86.5%), the process taking an appropriate amount of time (93.2%) and feeling safer as a result of their pharmacist’s attention to their opioid-related medication risk (86.3%). Urban patients were significantly more likely than rural patients to report positive attitude and behavior changes as a result of the ONE process. Conclusion: High levels of patient satisfaction and positive experience with the ONE Program screening and intervention process for patient-level opioid-related risks may encourage community pharmacists to more broadly implement such activities.
Secondary recycled polyvinylidene–limestone composite in 4D printing applications for heritage structures: Rheological, thermal, mechanical, spectroscopic, and morphological analysis
Authors: Kumar Vinay , Singh Rupinder , Ahuja Inderpreet Singh
Published: June 2022

Polymer 3D printing has motivated researchers toward the use of this technology for the maintenance and repair of heritage structures. This results in the exploration of different thermoplastic composites as smart materials having properties like programmable features (one-way, two-way), sensing, etc. Also, the excessive use of thermoplastics in various fields has resulted in plastic solid waste management issues. Several studies have been reported on plastic solid waste management with 3D printing. But hitherto little has been reported on the use of heritage site debris as reinforcement in the thermoplastic matrix for addressing issues of plastic solid waste management as well as for inducing controlled 4D capabilities; for better maintenance and repair of the heritage site with shorter maintenance and repair time. The present study is focused on secondary (2˚) recycling of polyvinylidene fluoride thermoplastic material by reinforcing limestone (CaCO3 of 220 mesh size as per American Foundry Society (AFS)) collected as debris from heritage site for 3D printing applications followed by an analysis of its possible 4D capabilities. Different compositions/proportions of polyvinylidene fluoride–limestone were explored for acceptable rheological (melt flow index and viscosity), thermal (based on differential scanning calorimetry), mechanical (based on universal testing machine), and spectroscopic properties (based on attenuated total reflection-Fourier transformed infrared and photoluminescence). Piezoelectric property analysis of 3D printable composition/proportion and shape-memory effect of each composition/proportion was performed to investigate the 4D characteristics of the proposed composite. The results of the study suggest that polyvinylidene fluoride–6% limestone is a better composition/ proportion with acceptable rheological, thermal, and mechanical properties (melt flow index 2.429 g/10 min, viscosity 12742.9 Pa-s, thermal heat capacity 31.66 Jg−1, and Young's modulus 286.56 MPa) for selected heritage structures. For 4D capabilities, piezoelectric coefficient (D33 21.79 pC/N) and shape recovery (44.31%) have been ascertained for the best composition/ proportion selected. Further morphological analysis has been reported to support the test results.
Financial Distress Assessment Using Related Party Transactions
Authors: Mahtani Umesh S.
Published: June 2022

In the past few years, several companies in India have filed for bankruptcy, after facing financial distress. Investigations showed that many of these companies, which were from the infrastructure sector, had high values of related party transactions (RPTs) before and during the financial crisis. In this study, RPTs towards sales, loans or payments are analysed for these companies to assess if they have a pattern that can be an indicator of ensuing financial distress. The article develops a model for assessing financial distress with a combination of RPTs and accounting variables. The sample uses financial data from 2010 to 2016 of 18 companies facing financial distress and combines with 15 financially stable companies from the same sector. The study shows that combining RPTs and accounting variables in a model provides higher accuracy in assessing financial distress when compared to a model with accounting variables only. The study recommends that such transactions by financially unstable companies should be monitored closely by lenders and investors, to ensure there is no diversion of funds during the distress period. There are few studies in India or globally on the pattern of RPTs made by financially distressed companies.
The Geomediatized Geographies of Marginalized Older Digital Citizens
Authors: Klausen Maja
Published: June 2022

In this article, I approach the Danish digitalization strategy as a Lefebvrian conceived space, focusing on how its ideology and spatial codes denote a normative vision for how citizens should and ought to be. Drawing on the non-media-centric concept of geomediatization and a feminist new materialist approach to gentrification as assemblage, the article explores the lived spaces of older (64+) marginalized citizens living in Sydhavnen, Copenhagen, an area currently undergoing gentrification. By focusing on the interplay between digitalization of the public sector and urban gentrification, the article sheds light on an emergent power geometry in which the potential for belonging is carved out differently for different citizens. In doing so, the article critically explores the more-than-representational geography of the digitalization strategy and contributes to the budding field of geomediatization studies.
Uniaxial mechanical behaviors of recycled coarse aggregate concretes cast with conventional and equivalent mortar volume methods
Authors: Yu Yong , Yang Bi-xuan , Liao Zheng , Xu Jin-jun , Hu Shou-wang , Zheng Yu
Published: June 2022

Among the various kinds of adjustment methods to improve the material properties of recycled aggregate concrete (RAC), equivalent mortar volume (EMV) method is widely considered as economic and effective. This is mainly because that only an extra content of natural aggregates (NAs) is needed to be added in the mixture during fabricating RAC. To objectively evaluate the method, this study conducted a series of discrete element mesoscale simulations to illustrate and compare the mechanical behaviors and failure mechanisms for conventional and EMV methods designed RAC samples under uniaxial loadings. Particularly, the influences of the replacement ratio of RAs, the mixture’s water-to-cement ratio and the spatial location of coarse aggregates on the two RACs’ strength and deformation characteristics were analyzed. Additionally, generic expressions used for estimating the mechanical properties of conventional and EMV methods cast RAC samples were also tried to be established in the article. It was found by this study that: (a) As the replacement ratio grows, both the conventional RAC’s compressive strength and elastic modulus reduce monotonously, however, the tensile strength’s variation trend is highly dependent on the relative strength of new-to-old mortar; (b) Regardless of the RAC’s water-to-cement ratio, an EMV design method can always improve the elastic modulus of RAC effectively; (c) When the new mortar strength is lower than that of old mortar, adopting an EMV mix-design method notably improves the RAC’s tensile and compressive strengths, however, if the old mortar strength is obviously smaller, the EMV method’s enhancement to the concrete’s strength is limited; (d) Variabilities for compressive and tensile strengths of EMV method designed RAC samples are commonly higher than those of conventional RAC samples; and (e) Uniaxial mechanical property of RAC sample cast either using a conventional or EMV method can both be predicted with a same formulas.
Design of an Automatic Jackson-Pratt Drain Auxiliary System for Postoperative Management Applications
Authors: Seol Jaehwang , Yoon Ki-Cheol , Park Jeongyun , Kim Kwang Gi
Published: June 2022

Background: After surgery, the exudation at a surgical site can cause complications and infections. The exudation is periodically removed through a Jackson-Pratt (JP) drain while maintaining a negative pressure in the JP bulb. However, the JP drainage tube may be clogged due to blood clotting. Thus, the periodic management of the JP drain is essential. In particular, the postoperative management of the JP drain includes squeezing and stripping it. In this study, we proposed a JP drain auxiliary system that can perform automatic stripping to assist specialists and nurses. Methodology: The proposed system was designed based on pre-experimental measurements and operated as a gripping and rolling device. Experimental Results: Twenty experiments were performed, and an average stripping efficiency of 93.8% was obtained. Conclusions: Consequently, we think that the proposed auxiliary system can automatically contribute to increase working efficiency for specialists and nurses.
Healthcare encounters between asylum seekers and health professionals in Maltese primary care
Authors: Depares Joanna , Culley Lorraine
Published: June 2022

Background

There is a substantial body of literature that discusses the problematic nature of asylum seeker healthcare in several European countries. However, little is known about how asylum seekers experience primary healthcare in Malta.

Aim

This paper draws on a qualitative study that aimed to explore the nature of healthcare encounters between asylum seekers and healthcare professionals in Maltese primary healthcare and the contextual processes which influence these interactions.

Methodology

The study utilised critical ethnography, informed by postcolonial theory. Data were collected through observation of encounters between healthcare professionals and asylum seekers (130 hours) and in-depth interviews with asylum seekers ( n11), cultural mediators ( n4) and Maltese healthcare professionals ( n7).

Results

Thematic analysis of the combined data resulted in three themes: ‘the impact of seeking refuge’, ‘seeking mutual understanding’ and ‘seeking resolution’. Healthcare encounters between asylum seekers and professionals are characterised by ‘othering’ practices, pre-conceived expectations and mutual mistrust. These are shaped by a complex interplay of factors, including damaging experiences of migration, derogatory political and public discourses and inadequate resources.

Conclusion

In Maltese primary care, healthcare encounters are highly problematic for both patients and professionals. Nurses could take the lead in developing services to assess complex needs and aid asylum seekers in navigating the healthcare system.
Engagement in athletic career: A study of female Brazilian handball world champions
Authors: Lima Leilane Alves de , Reverdito Riller Silva , Scaglia Alcides José , Galatti Larissa Rafaela
Published: June 2022

The aim of this study was to identify and describe elements that influenced the engagement of the 2013 Brazilian handball female world champions from grassroots to elite sports levels. Seven members of the team participated in a retrospective examination of their athletic development, with a mean of 20 years of sports experience. A semi-structured interview and questionnaire were used for data collection, and the script was based on the development stages of the Developmental Model of Sport Participation1 and the dynamic elements of the Personal Assets Framework2. The thematic analysis showed that the athletes’ personal characteristics, their disparate environments, and the quality of their relationships were significant in their pathway to elite performance. The results show that well-structured settings are not important in the early years, but rather the coaches’ interest in keeping young athletes engaged in sport is one of the key elements. Moreover, the advance in the maintenance years, training in a more structured setting and the coaches’ caring attitude and attention to their athletes’ feelings and emotions can lead to pathways toward excellence.
Direct cost analysis of rapid MRI in the emergency department evaluation of patients suspected of having acute ischemic stroke**
Authors: de Havenon Adam , Orlando Chris , Delic Alen , McNally Joseph Scott , Majersik Jennifer J , Harman Tyler , Alexander Matthew , Reddy Vivek , Lyden Stephanie , Anzai Yoshimi
Published: June 2022

Background

Abbreviated “rapid MRI” protocols have become more common for the evaluation of acute ischemic stroke (AIS). Prior research has not evaluated the effect of rapid MRIs on cost or hospital length of stay in AIS patients.

Methods

We retrospectively identified AIS patients who presented within 6 h of acute neurologic symptom onset to an emergency department (ED) and activated a “brain attack” code. We included sequential patients from January 2012 to September 2015, before rapid MRI was available, who had CT perfusion (CTP) and compared them to patients from October 2015 to May 2018 who had a rapid MRI. We used inverse-probability-weighting (IPW) to balance the cohorts. The primary outcomes were direct cost to our healthcare system and total hospital length of stay (LOS).

Results

We included 408 brain attack activations (mean ± SD age 62.1 ± 17.6 years, 47.8% male): 257 in the CTP cohort and 151 in the MRI cohort. Discharge diagnosis was ischemic stroke in 193/408 (47.3%). After patient matching, we found significant reductions for the MRI cohort in total cost (−18.7%, 95% CI −35.0, −2.4, p = 0.02) and hospital LOS (−17.0%, 95% CI −31.2, −2.8, p = 0.02), with no difference in ED LOS ( p = 0.74) as compared to the CTP cohort.

Conclusion

Although these results are preliminary and hypothesis-generating, we found that the use of a rapid MRI protocol in emergency department brain attacks was associated with a 18.7% reduction in total direct cost and 17% reduction in hospital length of stay.
The effects of the use of mobile devices on the E-learning process and perceived learning outcomes in university online education
Authors: Eom Sean
Published: June 2022

This paper examines the impact of using mobile devices, the pivotal element of a student-centered ecosystem, on the learning process and learning outcomes from a system’s view in which mobile technologies are considered a critical success factor to facilitate the dialogue and self-regulatory learning processes, thereby enhancing e-learning outcomes. We synthesize the disparate literature to develop an elevated model. A total of 323 valid and unduplicated responses from students who have completed at least one online course at a Midwestern university in the U.S. were used to examine the structural model, using SmartPLS v. 3.3.2. The results of this study show that the use of mobile devices positively affects student-instructor and student-student dialogues. It also facilitates the self-regulation process, which in turn positively affects the learning outcomes. Integrating mobile technology enables educational institutions to design and build distance learning systems that allow students to be highly flexible with their locations and schedules in the learning process. We discuss several implications of this research for educational institutions and distance learners in a student-centered higher education ecosystem.
Mothering and Stress during COVID-19: Exploring the Moderating Effects of Employment
Authors: Yan Hope Xu , Sayer Liana C. , Negraia Daniela Veronica , Rinderknecht R. Gordon , Doan Long , Drotning Kelsey J. , Fish Jessica N. , Buck Clayton
Published: June 2022

Using primary data from the Assessing the Social Consequences of COVID-19 study, the authors examined how the pandemic affected the stress levels of women with and without coresiding minor children (mothers vs. nonmothers), paying special attention to the moderating role of employment status. The ordinary least squares regression results show that following the pandemic outbreak, among full-time working women, mothers reported smaller stress increases than nonmothers. In contrast, among part-time and nonemployed women, mothers and nonmothers experienced similar stress increases. Also, full-time working mothers reported smaller stress increases than women with most other mothering and employment statuses. Changes in women’s employment status, following pandemic onset, had limited impacts on the patterns of stress change. This study contributes to research on parenting and health by showing that during times of crisis, full-time employment may be protective of mothers’ mental health but may not buffer the mental health deterioration of women not raising children.
Exploring the Transition to Working Life of Entrepreneurship Education Graduates: A Longitudinal Study
Authors: Killingberg Nils Magne , Kubberød Elin , Pettersen Inger Beate
Published: June 2022

In this research, we explore the transition of entrepreneurship education (EE) graduates to working life. Even though many EE graduates find employment in established organisations rather than starting a new venture, few studies have empirically investigated the relevance of EE in this context. This paper addresses this gap by providing an in-depth longitudinal analysis of graduates’ transition from EE to working life, from entering the labour market to becoming an effective operator. In the study we interview 10 graduates from three master’s programmes directly after their graduation and then follow up with an interview 2 years into their careers. It explores how these graduates learn to become legitimate members of their workplace and how they apply their entrepreneurial competencies in this process. This study contributes to the broader debate on the relevance of EE for employability by demonstrating how entrepreneurial competencies foster the transition from EE to working life.
Practical recommendations to combine small-molecule inhibitors and direct oral anticoagulants in patients with nonsmall cell lung cancer
Authors: Otten Leila S. , Piet Berber , van den Heuvel Michel M. , Marzolini Catia , van Geel Robin M.J.M. , Gulikers Judith L. , Burger David M. , Leentjens Jenneke , ter Heine Rob
Published: June 2022

Background

The risk for thromboembolisms in nonsmall cell lung cancer (NSCLC) patients is increased and often requires treatment or prophylaxis with direct oral anticoagulants (DOACs). Small-molecule inhibitors (SMIs) to treat NSCLC may cause relevant drug–drug interactions (DDIs) with DOACs. Guidance on how to combine these drugs is lacking, leaving patients at risk of clotting or bleeding. Here, we give practical recommendations to manage these DDIs.

Methods

For all DOACs and SMIs approved in Europe and the USA up to December 2021, a literature review was executed and reviews by the US Food and Drug Administration and European Medicines Agency were analysed for information on DDIs. A DDI potency classification for DOACs was composed and brought together with DDI characteristics of each SMI, resulting in recommendations for each combination.

Results

Half of the combinations result in relevant DDIs, requiring an intervention to prevent ineffective or toxic treatment with DOACs. These actions include dose adjustments, separation of administration or switching between anticoagulant therapies. Combinations of SMIs with edoxaban never cause relevant DDIs, compared to more than half of combinations with other DOACs and even increasing to almost all combinations with rivaroxaban.

Conclusions

Combinations of SMIs and DOACs often result in relevant DDIs that can be prevented by adjusting the DOAC dosage, separation of administration or switching between anticoagulants.
The impact of androgen deprivation therapy on the lipid profile in patients with prostate carcinoma
Authors: Kumar Niraj , Vasudeva Vibha , Yadav Siddharth , Prasad Vishnu , Patel Samarth
Published: June 2022

Background

Dyslipidemia is directly related to morbidity and mortality in elderly prostate carcinoma patients. The purpose of this study was to evaluate the effects of androgen deprivation therapy (ADT) on the lipid profile among Indian patients with locally advanced and metastatic prostate carcinoma.

Methods

The prospective database of prostate carcinoma patients, who received ADT and whose lipid profile data for the first two years of treatment with ADT was available, were divided into two groups for retrospective analysis: Group A patients are those who had undergone bilateral orchidectomy, while group B patients received luteinizing hormone-releasing hormone agonist (LHRHa). The data analyzed include baseline characteristics, prostate-specific antigen (PSA), and lipid profile.

Results

A total of 69 eligible patients were divided into two groups: group A—29 patients and group B—40 patients. Patients of both the groups reported a significant decrease in the mean serum PSA level from the commencement of ADT and remained close to nadir level till 24 months. In the group A patients, lipid profile parameters except high-density lipoprotein cholesterol showed statistically insignificant deterioration with maximum impact at 6 months. Among the group B patients, the total cholesterol (11.9%), triglycerides (22.2%), and low-density lipoprotein cholesterol (21.1%) increased significantly at 6 months and returned to the near baseline at 12 months and thereafter persisted at the similar level. The mean very low-density lipoprotein level (15.5%) also increased significantly at 6 months and then showed a gradual decline till 24 months of follow-up.

Conclusions

LHRH agonist used as ADT for prostate carcinoma leads to a statistically significant but clinically insignificant temporary worsening in the lipid profile.
Assessment of iron overload in a cohort of Sri Lankan patients with transfusion dependent beta thalassaemia and its correlation with pathogenic variants in HBB, HFE, SLC40A1, and TFR2 genes
Authors: Dissanayake Ruwangi , Samarasinghe Nayana , Waidyanatha Samantha , Pathirana Sajeewani , Neththikumara Nilaksha , Dissanayake Vajira H. W. , Wetthasinghe Kalum , Gooneratne Lallindra , Wickramasinghe Pujitha
Published: June 2022

Background

Iron overload (IO) is a complication in transfusion dependent beta thalassaemia (TDT). Pathogenic variants in genes involving iron metabolism may confer increased risk of IO. The objective of this study was to determine the magnitude of the cardiac and hepatic IO and determine whether pathogenic variants in HFE, SLC40A1 and TFR2 genes increase the risk of IO in a cohort of TDT patients in Sri Lanka.

Materials and Methods

Fifty-seven (57) patients with TDT were recruited for this study. Serum ferritin was done once in 3 months for a period of one year in all. Those who were ≥ 8 years of age (40 patients) underwent T2* MRI of the liver and heart. Fifty-two (52) patients underwent next generation sequencing (NGS) to identify pathogenic variants in HBB, HFE, SLC40A1 and TFR2 genes.

Results

The median age of the patients of this cohort was 10 years. It comprised of 30 (52.6%) boys and 27 (47.4%) girls. The median level of serum ferritin was 2452 ng/dl. Hepatic IO was seen in 37 (92.5%) patients and cardiac IO was seen in 17 (42.5%) patients. There was no statistically significant correlation between serum ferritin and hepatic or cardiac IO.

Thirty-two (61.5%), 18 (34.6%), 2 (3.8%) of patients were homozygotes, compound heterozygotes and heterozygotes for pathogenic variants in the HBB gene. Eight (15.4%) and 1 (1.9%) patients were heterozygotes for pathogenic and likely pathogenic variants of HFE genes respectively. There were no pathogenic variants for the TfR2 and SLC40A1 genes. The heterozygotes of the pathogenic variants of the HFE were not at increased risk of IO.

Conclusions

Cardiac T2* MRI helps to detect cardiac IO in asymptomatic patients. It is important to perform hepatic and cardiac T2* MRI to detect IO in patients with TDT. There was no statistically significant correlation between pathogenic variants of HBB and HFE genes with hepatic and cardiac IO in this cohort of patients.
The causal relationship between sleep traits and the risk of schizophrenia: a two-sample bidirectional Mendelian randomization study
Authors: Wang Zhen , Chen Miao , Wei Yin-ze , Zhuo Chen-gui , Xu Hong-fei , Li Wei-dong , Ma Liang
Published: June 2022

Background

Observational studies suggest that sleep disturbances are commonly associated with schizophrenia. However, it is uncertain whether this relationship is causal. To investigate the bidirectional causal relation between sleep traits and schizophrenia, we performed a two-sample bidirectional Mendelian randomization (MR) study with the fixed effects inverse-variance weighted (IVW) method.

Methods

As genetic variants for sleep traits, we selected variants from each meta-analysis of genome-wide association studies (GWASs) conducted using data from the UK Biobank (UKB).

Results

We found that morning diurnal preference was associated with a lower risk of schizophrenia, while long sleep duration and daytime napping were associated with a higher risk of schizophrenia. Multivariable MR analysis also showed that sleep duration was associated with a higher risk of schizophrenia after adjusting for other sleep traits. Furthermore, genetically predicted schizophrenia was negatively associated with morning diurnal preference and short sleep duration and was positively associated with daytime napping and long sleep duration.

Conclusions

Therefore, sleep traits were identified as a potential treatment target for patients with schizophrenia.
Sagittal femoral bowing contributes to distal femoral valgus angle deviation in malrotated preoperative radiographs
Authors: Kokubu Yasuhiko , Kawahara Shinya , Hamai Satoshi , Akasaki Yukio , Tsushima Hidetoshi , Momii Kenta , Nakashima Yasuharu
Published: June 2022

Background

The coronal whole-leg radiograph is generally used for preoperative planning in total knee arthroplasty. The distal femoral valgus angle (DFVA) is measured for distal femoral bone resection using an intramedullary guide rod. The effect of coronal and sagittal femoral shaft bowing on DFVA measurement in the presence of malrotation or knee flexion contracture has not been well reported. The objectives of this study were: (1) to investigate the effects of whole-leg malrotation and knee flexion contracture on the DFVA in detail, (2) to determine the additional effect of coronal or sagittal femoral shaft bowing.

Methods

We studied 100 consecutive varus and 100 valgus knees that underwent total or unicompartmental knee arthroplasty. Preoperative CT scans were used to create digitally reconstructed radiography (DRR) images in neutral rotation (NR, parallel to the surgical epicondylar axis), and at 5° and 10° external rotation (ER) and internal rotation (IR). The images were also reconstructed at 10° femoral flexion. The DFVA was evaluated in each DRR image, and the angular variation due to lower limb malposition was investigated.

Results

The DFVA increased as the DRR image shifted from IR to ER, and all angles increased further from extension to 10° flexion. The DFVA variation in each position was 1.3° on average. A larger variation than 2° was seen in 12% of all. Multivariate regression analysis showed that sagittal femoral shaft bowing was independently associated with a large variation of DFVA. Receiver operating characteristic analysis showed that more than 12° of sagittal bowing caused the variation.

Conclusion

If femoral sagittal bowing is more than 12°, close attention should be paid to the lower limb position when taking whole-leg radiographs. Preoperative planning with whole-leg CT data should be considered.
FTO rs62033406 A>G associated with the risk of osteonecrosis of the femoral head among the Chinese Han population
Authors: Wang Yuan , Zhong Wei , Wang Shaofeng , Yang Yang , Zhu Bing
Published: June 2022

Background

Fat mass and obesity-related (FTO)mRNA was downregulated in osteonecrosis patients. The study aimed to evaluate the correlation betweenFTOpolymorphisms and the susceptibility of osteonecrosis of the femoral head (ONFH).

Methods

Six polymorphisms inFTOwere genotyped via the Agena MassARRAY in 498 ONFH patients and 498 healthy controls. Multiple genetic models were used to assess the correlation betweenFTOpolymorphisms and ONFH risk by SNPStats. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using a logistic regression model adjusted by age, gender, smoking and drinking.

Results

The risk-increasing association of rs62033406 A>G with ONFH was found (OR = 1.25, 95% CI 1.05–1.50,p = 0.014). Specially,FTOrs62033406 A>G was related to the risk of ONFH in the subgroup at age > 51 years (OR = 1.25,p = 4.00 × 10–4), females (OR = 1.74,p = 1.00 × 10–4), smokers (OR = 1.82,p = 0.005) and drinkers (OR = 1.89,p = 0.002), respectively. The best multi–loci model was the five–loci model, a combination of rs9930333 T>G, rs1558902 T>A, rs56094641 A>G, rs3751812 G>T, and rs62033406 A>G (testing accuracy, 0.5351;p = 0.0004; cross–validation consistency, 10/10).

Conclusion

Our study first revealed thatFTOrs62033406 A>G was a risk factor for ONFH among the Chinese Han population, which might provide the new candidate gene for elucidating the pathogenesis of ONFH.
The function of gut microbiota in immune-related neurological disorders: a review
Authors: Sittipo Panida , Choi Jaeyoon , Lee Soojin , Lee Yun Kyung
Published: June 2022

This review provides an overview of the importance of microbiota in the regulation of gut–brain communication in immune-related neurological disorders. The gastrointestinal (GI) tract hosts a diverse abundance of microbiota, referred to as gut microbiota. The gut microbiota plays a role in the maintenance of GI tract homeostasis and is likely to have multiple effects on brain development and function. The bidirectional communication between the gut microbiota and the brain is termed the microbiota–gut–brain axis. This communication between the intestine and the brain appears to affect human health and behavior, as certain animal studies have demonstrated the association between alterations in the gut microbiota and neurological disorders. Most insights about the microbiota–gut–brain axis come from germ-free animal models, which reveal the importance of gut microbiota in neural function. To date, many studies have observed the impact of the gut microbiota in patients with neurological disorders. Although many studies have investigated the microbiota–gut–brain axis, there are still limitations in translating this research to humans given the complexities of the relationship between the gut microbiota and the brain. In this review, we discuss emerging evidence of how the microbiota–gut–brain axis regulates brain development and function through biological networks, as well as the possible contribution of the microbiota–gut–brain axis in immune-related neurological disorders.
SARS-CoV-2 productively infects human brain microvascular endothelial cells
Authors: Yang Rui-Cheng , Huang Kun , Zhang Hui-Peng , Li Liang , Zhang Yu-Fei , Tan Chen , Chen Huan-Chun , Jin Mei-Lin , Wang Xiang-Ru
Published: June 2022

Background

The emergence of the novel, pathogenic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global health emergency. SARS-CoV-2 is highly contagious and has a high mortality rate in severe patients. However, there is very limited information on the effect of SARS-CoV-2 infection on the integrity of the blood–brain barrier (BBB).

Methods

RNA-sequencing profiling was performed to analyze the transcriptomic changes in human brain microvascular endothelial cells (hBMECs) after SARS-CoV-2 infection. Bioinformatic tools were used for differential analysis. Immunofluorescence, real-time quantitative PCR, and Western blotting analysis were used to explore biological phenotypes.

Results

A total of 927 differentially expressed genes were identified, 610 of which were significantly upregulated while the remaining 317 were downregulated. We verified the significant induction of cytokines, chemokines, and adhesion molecules in hBMECs by SARS-CoV-2, suggesting an activation of the vascular endothelium in brain. Moreover, we demonstrated that SARS-CoV-2 infection could increase the BBB permeability, by downregulating as well as remodeling the intercellular tight junction proteins.

Conclusions

Our findings demonstrated that SARS-CoV-2 infection can cause BBB dysfunction, providing novel insights into the understanding of SARS-CoV-2 neuropathogenesis. Moreover, this finding shall constitute a new approach for future prevention and treatment of SARS-CoV-2-induced CNS infection.
Primary Healthcare Quality in Conflict and Fragility: a subnational analysis of disparities using Population Health surveys
Authors: Ramadan Marwa , Tappis Hannah , Brieger William
Published: June 2022

Background

Recent global reports highlighted the importance of addressing the quality of care in all settings including fragile and conflict-affected situations (FCS), as a central strategy for the attainment of sustainable development goals and universal health coverage. Increased mortality burden in FCS reflects the inability to provide routine services of good quality. There is also paucity of research documenting the impact of conflict on the quality of care within fragile states including disparities in service delivery. This study addresses this measurement gap by examining disparities in the quality of primary healthcare services in four conflict-affected fragile states using proxy indicators.

Methods

A secondary analysis of publicly available data sources was performed in four conflict-affected fragile states: Cameroon, the Democratic Republic of Congo, Mali, and Nigeria. Two main databases were utilized: the Demographic Health Survey and the Uppsala Conflict Data Program for information on components of care and conflict events, respectively. Three equity measures were computed for each country: absolute difference, concentration index, and coefficients of mixed-effects logistic regression. Each computed measure was then compared according to the intensity of organized violence events at the neighborhood level.

Results

Overall, the four studied countries had poor quality of PHC services, with considerable subnational variation in the quality index. Poor quality of PHC services was not only limited to neighborhoods where medium or high intensity conflict was recorded but was also likely to be observed in neighborhoods with no or low intensity conflict. Both economic and educational disparities were observed in individual quality components in both categories of conflict intensity.

Conclusion

Each of the four conflict-affected countries had an overall poor quality of PHC services with both economic and educational disparities in the individual components of the quality index, regardless of conflict intensity. Multi-sectoral efforts are needed to improve the quality of care and disparities in these settings, without a limited focus on sub-national areas where medium or high intensity conflict is recorded.
‘Such a massive part of rehab is between the ears’; barriers to and facilitators of anterior cruciate ligament reconstruction rehabilitation: a qualitative focus group analysis
Authors: Walker Adam , Hing Wayne , Gough Suzanne , Lorimer Anna
Published: June 2022

Background

Current evidence demonstrates that few patients complete anterior cruciate ligament reconstruction rehabilitation according to evidence-based guidelines. It is important to investigate the viewpoints of our patients to identify patient-reported barriers and facilitators of anterior cruciate ligament reconstruction rehabilitation. Qualitative analysis can provide insight into potential methods for improving the delivery of rehabilitation services.

Methods

In this qualitative study, utilising a social constructionism orientation, viewed through the social phenomenological lens, three focus groups were conducted with individuals 1–20 years post anterior cruciate ligament reconstruction (n = 20, 9 males, 11 females, mean 6.5 years post-surgery, 19–51 years old). Utilising a semi-structured interview guide, participants were asked about their experiences during anterior cruciate ligament reconstruction rehabilitation. Focus groups were recorded, transcribed, and coded using an inductive semantic thematic analysis methodology.

Results

Five organising themes were identified (consisting of 19 sub-themes) to provide a framework to present the data: psychological, physiological, rehabilitation service, rehabilitation characteristics, and interaction with others. Each theme details aspects of rehabilitation, such as exercise delivery, informational support, frequency, and duration of care, kinesiophobia, weight management and interactions with teams and coaches, which present barriers or facilitators for patients to adhere to and participate in rehabilitation. Example quotes are provided for each theme to provide context and the patient’s voice.

Conclusions

This qualitative investigation identified key aspects of a patient's rehabilitation in which they encounter a variety of barriers and facilitators of ACL reconstruction rehabilitation. These aspects, such as the rehabilitation characteristics, service delivery, psychological and physiological factors, and interactions with others, were consistently identified by this cohort as factors which affected their rehabilitation. The themes may provide targets for clinicians to improve rehabilitation and deliver patient-centred care. However, the themes must be evaluated in future trials to assess whether interventions to remove barriers or enhance facilitators improves subsequent outcomes such as return to sport and re-injury rates.
Maternal age, autistic-like traits and mentalizing as predictors of child autistic-like traits in a population-based cohort
Authors: Sari Novika Purnama , Jansen Pauline W. , Blanken Laura M. E. , Ruigrok Amber N. V. , Prinzie Peter , Tiemeier Henning , Baron-Cohen Simon , van IJzendoorn Marinus H. , White Tonya
Published: June 2022

Background

Many empirical studies suggest that higher maternal age increases the likelihood of having an autistic child. However, little is known about factors that may explain this relationship or if higher maternal age is related to the number of autistic-like traits in offspring. One possibility is that mothers who have a higher number of autistic-like traits, including greater challenges performing mentalizing skills, are delayed in finding a partner. The goal of our study is to assess the relationship between maternal age, mentalizing skills and autistic-like traits as independent predictors of the number of autistic-like traits in offspring.

Methods

In a population-based study in the Netherlands, information on maternal age was collected during pre- and perinatal enrolment. Maternal mentalizing skills and autistic-like traits were assessed using the Reading the Mind in the Eyes Test and the Autism Spectrum Quotient, respectively. Autistic-like traits in children were assessed with the Social Responsiveness Scale. A total of 5718 mother/child dyads had complete data (Magechild = 13.5 years; 50.2% girls).

Results

The relationship between maternal age and autistic-like traits in offspring best fits a U-shaped curve. Furthermore, higher levels of autistic features in mothers are linked to higher levels of autistic-like traits in their children. Lower mentalizing performance in mothers is linked to higher levels of autistic-like traits in their children.

Limitations

We were able to collect data on both autistic-like traits and the mentalizing skills test in a large population of mothers, but we did not collect these data in a large number of the fathers.

Conclusions

The relationships between older and younger mothers may have comparable underlying mechanisms, but it is also possible that the tails of the U-shaped curve are influenced by disparate mechanisms.
Chemical characterization, antimicrobial, antioxidant, and cytotoxic potentials of Swietenia mahagoni
Authors: Syame Sohier M. , Mohamed Samy M. , Elgabry E. A. , Darwish Yousof A. A. , Mansour Asmaa S.
Published: June 2022

Infectious diseases are the most important cause of death worldwide. Many of these diseases show great resistance to drugs and antibiotics with long-term use. Extracts of some medicinal plants have antimicrobial properties, which can treat and overcome these diseases. Meliaceae is a family of timber trees used extensively in treating many bacterial and fungal diseases, especially Swietenia mahagoni (L.) Jacq. In this study, phytochemical screening, gas chromatography/mass spectrometry (GC/MS) analysis, and antimicrobial, antioxidant, and antitumor activities of the methanolic extract of S. mahagoni (L.) leaves were performed. Phytochemical screening exhibited the presence of alkaloids, flavonoids, saponins, phenols, triterpenoids, glycosides, and tannins. GC/MS analysis exhibited 40 compounds, mainly 7-hexadecene, (Z)-, imidazole-4,5-d2, and 1-acetyl-4,4-bis[4-(3-bromopropoxy)-3,5-dimethoxyphenyl] piperidine. The antibacterial and antifungal potentials of the methanolic extract of S. mahagoni (L.) leaves was investigated using the agar well diffusion technique. Potent antibacterial activity against Staphylococcus aureus, Escherichia coli, Salmonella enterica, Enterobacter aerogenes, and Proteus vulgaris and antifungal activity against Aspergillus flavus, Aspergillus niger, and Candida albicans were found. The minimum inhibitory concentration and minimum bactericidal and fungicidal concentrations ranged from 12.5 to 25 mg/mL. Antioxidant activity was studied using the free radical scavenging assay, and the IC50 value of the leaf extract was 69.9 µg/mL. Cytotoxic activity was screened using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, and the IC50 value was 44.2 µg/mL. These findings suggested the importance of this plant in treating some bacterial and fungal infections and cancer.
A canine-derived chimeric antibody with high neutralizing activity against canine parvovirus-2
Authors: Zhou Lixuan , Wu Hongchao , Du Mengmeng , Song Huanhuan , Huo Ningning , Chen Xiao , Su Xiaorui , Li Weiguo , Wang Lulu , Wang Jie , Huang Baicheng , Tan Feifei , Tian Kegong
Published: June 2022

Canine parvovirus-2 (CPV-2) infection causes serious multisystemic disease in dogs and many animal species worldwide. Previously, a monoclonal antibody (MAb) of CPV-2, 10H4, showed high neutralizing activity and therapeutic effect against CPV-2 in dogs. However, the application of mouse MAb is limited in other animals due to immune rejection. Here, the variable regions of the heavy and light chains of 10H4 were cloned and ligated with constant canine antibody regions to produce a canine-derived chimeric MAb 11D9, in a CHO-S cell expression system. The cell supernatant of the CHO cell line 11D9 exhibited a HI titer of 1:2560 against all the variants of CPV-2 (new CPV-2a, new CPV-2b, and CPV-2c), and had the same average neutralization titer as the new CPV-2a (1:11,046.5) and new CPV-2b (1:11,046.5) variants, which was slightly higher than that of CPV-2c variants (1:10,615.7). In animal experiment, the treatment of chimeric MAb 11D9 had a high therapeutic effect in beagles infected with the new CPV-2a. Overall, the canine-derived chimeric MAb 11D9 produced by CHO-S cells showed a high HI and neutralization titer against CPV-2 and the therapeutic effects against the new CPV-2a in beagles, providing potential for the prevention or treatment of CPV-2 infections in dogs.
Nicotinamide mononucleotide supplementation improves the quality of porcine oocytes under heat stress
Authors: Song Meijie , Li Yu , Zhou Yihang , Yan Jiner , Zhou Xiaohua , Gao Qian , Miao Yilong , Xiong Bo
Published: June 2022

Background

Elevated ambient temperature-caused heat stress is a major concern for livestock production due to its negative impact on animal feed intake, growth, reproduction, and health. Particularly, the germ cells are extremely sensitive to the heat stress. However, the effective approach and strategy regarding how to protect mammalian oocytes from heat stress-induced defects have not been determined.

Methods

Germinal vesicle (GV) porcine oocytes were cultured at 41.5 °C for 24 h to induce heat stress, and then cultured at 38.5 °C to the specific developmental stage for subsequent analysis. Nicotinamide mononucleotide (NMN) was dissolved in water to 1 mol/L for a stock solution and further diluted with the maturation medium to the final concentrations of 10 μmol/L, 20 μmol/L, 50 μmol/L or 100 μmol/L, respectively, during heat stress. Immunostaining and fluorescence intensity quantification were applied to assess the effects of heat stress and NMN supplementation on the key processes during the oocyte meiotic maturation.

Results

Here, we report that NMN supplementation improves the quality of porcine oocytes under heat stress. Specifically, we found that heat stress resulted in oocyte maturation failure by disturbing the dynamics of meiotic organelles, including the cytoskeleton assembly, cortical granule distribution and mitochondrial function. In addition, heat stress induced the production of excessive reactive oxygen species (ROS) and DNA damage, leading to the occurrence of apoptosis in oocytes and subsequent embryonic development arrest. More importantly, we validated that supplementation of NMN during heat stress restored the meiotic defects during porcine oocyte maturation.

Conclusions

Taken together, our study documents that NMN supplementation is an effective approach to improve the quality of oocytes under heat stress by promoting both nuclear and cytoplasmic maturation.