bluuebunny/crossref_metadata_2025 huggingface dataset:
Effective coping strategies utilised by medical students for mental health disorders during undergraduate medical education-a scoping review
Authors: Sattar Kamran , Yusoff Muhamad Saiful Bahri , Arifin Wan Nor , Yasin Mohd Azhar Mohd , Nor Mohd Zarawi Mat
Published: February 2022

Background

Coping denotes cognitive, emotional and behavioural struggles to tackle a troubled person-environment association. Therefore, coping strategies (CSs) are vital for mental well-being. Widespread research studies have explored this domain, targeting caregivers, nurses, physicians and medical teachers, but limited research has been done to explore the common CSs utilised by medical students at the undergraduate medical education level. Therefore, we aimed to identify the frequently occurring CSs and their effects on mental health disorders (MHDs) through the evidence available in the existing literature.

Methods

For this scoping review, we searched the available literature (articles published from January 1, 1986, to March 31, 2021) on CSs at Google Scholar, PubMed and Scopus using the terms coping, medical students and undergraduate medical education. We included in our search all peer-reviewed journal articles whose central topics were the CSs employed by undergraduate medical students of any age, nationality, race and gender.

Results

From among the 2,134 articles that were found, 24 were ultimately included in the study. The articles were authored in 14 countries, allowing us to gather broader data to answer our research question. The first identified theme (MHDs) had four subthemes: stress (55% of the articles), depression (30%), anxiety (25%) and burnout (15%). The second theme (CSs), on the other hand, had eight subthemes: support seeking (60%), active coping (40%), acceptance (40%), avoidance/denial (40%), substance abuse (35%), faith/religion (25%), sports (25%) and miscellaneous (40%).

Conclusions

Themes and subthemes were identified about the most common CSs utilised by undergraduate medical students to tackle common MHDs in the context of medical education. Among the most used CSs was support (social and emotional) seeking. Teaching medical students how to cope with challenging times is essential.
Assessing the impact of public transfer payments on the vulnerability of rural households to healthcare poverty in China
Authors: Li Yali , Huang Lei
Published: February 2022

Background

China completed the task of eliminating absolute poverty, following the 18th National Congress. However, after 2020, rural poverty in China has entered a new stage that is characterised by transformational secondary poverty and relative poverty; thus, the poverty vulnerable group is the new target group. Public transfer payments play a vital role in reducing the vulnerability of rural households to healthcare poverty. Assessing the effectiveness of public transfer payments in rural households can improve the vulnerability of rural households to healthcare poverty.

Methods

In total, 5754 rural households were included each year, which accounted for a total of 16,722 rural households during the three-year study period. The multidimensional poverty and the vulnerability to healthcare poverty of rural households were assessed and compared. Two series of multivariate logistic regression models were further used to assess the effects of public transfer payments on improving the vulnerability of rural households to healthcare poverty.

Results

When the poverty line was set at $1.90 and $3.20, rural households in all the three study years exhibited a higher vulnerability to healthcare poverty than the actual incidence of multidimensional poverty in healthcare, and the Eastern regions exhibited higher vulnerability to poverty than the Western regions of China. The series of multivariate logistic models employed to evaluate the effects of public transfer payments on the rural households’ vulnerability to healthcare poverty indicated that considering the differences in rural households’ demands for healthcare is vital for the government to fulfill the effects of public transfer payments. When income elasticity indicators for health care needs were included, the effect of public transfer payments on improving the vulnerability of rural households changed from less significant in 2014 and 2016. In 2018, however, the effect of public transfers on improving the vulnerability of rural households has increased compared to the non-inclusion elasticity.

Conclusions

The imbalance of development between urban and rural areas in China is increasing, and rural households with heavy economic burdens are facing the risk of low healthcare services. Our findings highlight the importance of government departments in improving public transfer payments to reduce rural households’ vulnerability to healthcare poverty.
Exploring the readiness of senior doctors and nurses to assess and address patients’ social needs in the hospital setting
Authors: Lake Katherine J. , Boyd Mark A. , Smithers Lisa , Howard Natasha J. , Dawson Anna P.
Published: February 2022

Background

Adverse social circumstances are a key factor in health outcomes. Hospitals are an opportune setting for assessing and addressing the unmet social needs of patients, however, the readiness of healthcare workers in hospitals to undertake such tasks requires further exploration in the Australian context. This study aimed to generate a theory of doctors’ and nurses’ readiness to assess and address patients’ social needs in a hospital setting.

Methods

A constructivist grounded theory methodology was applied, with purposive and theoretical sampling used to gather diverse perspectives of readiness during semi-structured interviews with twenty senior doctors and nurses from a variety of clinical specialties working in hospitals serving communities experiencing inequitable social and health outcomes. Line-by-line coding, memo writing, and diagramming were used in analysis to construct an interpretive theory of readiness. Application of constant comparison analytic processes were used to test the robustness of the theory.

Results

The readiness of doctors and nurses varies across individuals and departments, and is founded upon a state of being comfortable and confident to assess social need as determined by a range of personal attributes (e.g. knowledge of social need; skills to assess social need); a state of being willing and prepared to assess and address social need facilitated by supportive environments (e.g. departmental culture); and enabling characteristics of the clinical encounter (e.g. time, rapport).

Conclusions

We found that the readiness of doctors and nurses is dynamic and impacted by a complex interplay of personal attributes along with contextual and situational factors. These findings indicate that any efforts to strengthen the readiness of doctors and nurses to assess and address social needs must target personal capabilities in addition to characteristics of the working environment.
Verticillium dahliae CFEM proteins manipulate host immunity and differentially contribute to virulence
Authors: Wang Dan , Zhang Dan-Dan , Song Jian , Li Jun-Jiao , Wang Jun , Li Ran , Klosterman Steven J. , Kong Zhi-Qiang , Lin Fa-Zhuang , Dai Xiao-Feng , Subbarao Krishna V. , Chen Jie-Yin
Published: February 2022

Background

Verticillium dahliae is a fungal pathogen that causes a vascular wilt on many economically important crops. Common fungal extracellular membrane (CFEM) domain proteins including secreted types have been implicated in virulence, but their roles in this pathogen are still unknown.

Results

Nine secreted small cysteine-rich proteins (VdSCPs) with CFEM domains were identified by bioinformatic analyses and their differential suppression of host immune responses were evaluated. Two of these proteins, VdSCP76 and VdSCP77, localized to the plant plasma membrane owing to their signal peptides and mediated broad-spectrum suppression of all immune responses induced by typical effectors. Deletion of either VdSCP76 or VdSCP77 significantly reduced the virulence of V. dahliae on cotton. Furthermore, VdSCP76 and VdSCP77 suppressed host immunity through the potential iron binding site conserved in CFEM family members, characterized by an aspartic acid residue in seven VdSCPs (Asp-type) in contrast with an asparagine residue (Asn-type) in VdSCP76 and VdSCP77. V. dahliae isolates carrying the Asn-type CFEM members were more virulent on cotton than those carrying the Asp-type.

Conclusions

In the iron-insufficient xylem, V. dahliae is likely to employ the Asp-type CFEM members to chelate iron, and Asn-type CFEM members to suppress immunity, for successful colonization and propagation in host plants.
High polygenic predisposition for ADHD and a greater risk of all-cause mortality: a large population-based longitudinal study
Authors: Ajnakina Olesya , Shamsutdinova Diana , Wimberley Theresa , Dalsgaard Søren , Steptoe Andrew
Published: February 2022

Background

Attention deficit hyperactivity disorder (ADHD) is a highly heritable, neurodevelopmental disorder known to associate with more than double the risk of death compared with people without ADHD. Because most research on ADHD has focused on children and adolescents, among whom death rates are relatively low, the impact of a high polygenic predisposition to ADHD on accelerating mortality risk in older adults is unknown. Thus, the aim of the study was to investigate if a high polygenetic predisposition to ADHD exacerbates the risk of all-cause mortality in older adults from the general population in the UK.

Methods

Utilising data from the English Longitudinal Study of Ageing, which is an ongoing multidisciplinary study of the English population aged ≥ 50 years, polygenetic scores for ADHD were calculated using summary statistics for (1) ADHD (PGS-ADHDsingle) and (2) chronic obstructive pulmonary disease and younger age of giving first birth, which were shown to have a strong genetic correlation with ADHD using the multi-trait analysis of genome-wide association summary statistics; this polygenic score was referred to as PGS-ADHDmulti-trait. All-cause mortality was ascertained from the National Health Service central register that captures all deaths occurring in the UK.

Results

The sample comprised 7133 participants with a mean age of 64.7 years (SD = 9.5, range = 50–101); of these, 1778 (24.9%) died during a period of 11.2 years. PGS-ADHDsingle was associated with a greater risk of all-cause mortality (hazard ratio [HR] = 1.06, 95% CI = 1.02–1.12, p = 0.010); further analyses showed this relationship was significant in men (HR = 1.07, 95% CI = 1.00–1.14, p = 0.043). Risk of all-cause mortality increased by an approximate 11% for one standard deviation increase in PGS-ADHDmulti-trait (HR = 1.11, 95% CI = 1.06–1.16, p < 0.001). When the model was run separately for men and women, the association between PGS-ADHDmulti-trait and an increased risk of all-cause mortality was significant in men (HR = 1.10, 95% CI = 1.03–1.18, p = 0.003) and women (HR = 1.11, 95% CI = 1.04–1.19, p = 0.003).

Conclusions

A high polygenetic predisposition to ADHD is a risk factor for all-cause mortality in older adults. This risk is better captured when incorporating genetic information from correlated traits.
Comparison of chromosomal status in reserved multiple displacement amplification products of embryos that resulted in miscarriages or live births: a blinded, nonselection case–control study
Authors: Yang Guoxia , Xu Yan , Zeng Yanhong , Guo Jing , Pan Jiafu , Zhou Canquan , Xu Yanwen
Published: February 2022

Objective

To analyze chromosomal status in reserved multiple displacement amplification (MDA) products of embryos that result in miscarriages or live births.

Methods

Patients who underwent preimplantation genetic testing for monogenic disorders (PGT-Ms) without aneuploidy screening were included. The case group included 28 cycles that resulted in miscarriages. Controls included 56 cycles with live births. Comprehensive chromosomal screening (CCS) using next-generation sequencing (NGS) was performed on reserved MDA products from previous blastocyst trophectoderm biopsies. The incidence and type of chromosomal abnormalities in embryos resulting in miscarriages or live births were analyzed.

Results

Of 28 embryos resulting in miscarriages in the case group, the rate of chromosomal abnormalities was 53.6%, which was significantly greater than 14.3% for those resulting in live births in control group (P < 0.001). Whole-chromosome aneuploidy was not found in the control group but was noted in 25.0% of embryos in the case group. Although the rates of segmental abnormality and mosaicism were also greater in the case group, no significant differences were detected. One chaotic embryo in the control group progressed to live birth.

Conclusion

Chromosomal abnormalities were the main reason leading to early pregnancy loss. However, abnormalities, such as segmental aneuploidy and mosaicism, should be managed cautiously, considering their undermined reproductive potential.
A Japanese single-center experience of the efficacy and safety of asfotase alfa in pediatric-onset hypophosphatasia
Authors: Sugiyama Yohei , Watanabe Taijiro , Tajika Makiko , Matsuhashi Tetsuro , Shimura Masaru , Fushimi Takuya , Ichimoto Keiko , Matsunaga Ayako , Ebihara Tomohiro , Tsuruoka Tomoko , Akiyama Tomoyuki , Murayama Kei
Published: February 2022

Background

Hypophosphatasia (HPP) is a rare inherited metabolic disorder caused by mutations in the ALPL gene, which encodes tissue nonspecific alkaline phosphatase. The severity of HPP is widely diverse from the perinatal form to the adult mild form. The former represents the most severe form and was earlier associated with high mortality due to pneumonia which was caused by severe hypomineralization of the bones—such as chest deformity and fractured ribs—and muscle weakness. Enzyme replacement therapy using asfotase alfa (AA) was approved in 2015 in Japan for treating patients with HPP and has improved their pulmonary function and life prognosis. There are several practical and ethical challenges related to using orphan drugs for a rare disorder in a publicly funded healthcare system. Sharing experiences about their application is essential towards formulating guidelines to assist clinicians with decisions about their initiation and withdrawal. We report the details of AA experience in ten cases of pediatric-onset HPP in nine families from January 2015 to November 2019 (median [interquartile range] age 11.0 [7.6–12.5] years; 60% male). This is a study of a single-center cohort describing the clinical course of patients with HPP, mainly consisting of the mild childhood form of HPP, treated with AA in Japan.

Results

One case of perinatal form of HPP, two cases of benign prenatal form, and seven cases of childhood form were observed. The most common symptom at onset was pain. All patients had low serum alkaline phosphatase levels as compared to the age-matched reference range before the commencement of AA. All HPP patients seem to have responded to AA treatment, as evidenced by pain alleviation, increased height standard deviation, improvement in respiratory condition and 6-min walk test result improvement, disappearance of kidney calcification, alleviation of fatigue, and/or increases in bone mineralization. There were no serious adverse events, but all patients had an injection site reaction and skin changes at the injection sites. Genetic analysis showed that eight out of ten patients had compound heterozygosity.

Conclusions

AA may be effective in patients with mild to severe pediatric-onset forms of HPP.
Healthcare resource utilization, total costs, and comorbidities among patients with myotonic dystrophy using U.S. insurance claims data from 2012 to 2019
Authors: Howe Sarah J. , Lapidus David , Hull Michael , Yeaw Jason , Stevenson Tanya , Sampson Jacinda B.
Published: February 2022

Background

Myotonic dystrophy (DM) is a rare, inherited disorder with multi-systemic effects that impact the skeletal muscles, eyes, heart, skin and gastrointestinal, endocrine, respiratory, and central nervous systems. DM is divided into two subtypes: DM1 can present from early childhood through adulthood and also has a congenital form (cDM) while DM2 typically manifests during mid-adulthood. Both forms are progressive with no approved treatments, and unmet need for disease-modifying therapies remains high. This study interrogated health insurance claims data to explore the clinical experience, healthcare resource utilization (HCRU), and all-cause costs for DM.

Results

A total of 8541 patients with DM and 242 patients with cDM and their matched controls were selected from a database of over 200 million claimants. HCRU and all-cause costs, including pharmacy, outpatient, and inpatient services, were analyzed across four years in 12-month follow-up periods. Mean all-cause costs per DM patient were high in each of the four periods (range $14,640–$16,704) and showed a steady increase from 13 to 23 months on, while the control group mean costs declined from $9671 in the first 12 months after the index event, to approach the US population average ($5193) over time. For cDM, the highest mean costs were in the first 12-months ($66,496 vs. $2818 for controls), and remained high (above $17,944) across all subsequent periods, while control mean costs approached $0. For DM and cDM, HCRU was higher compared to controls across all study periods and all-cause healthcare costs were mostly driven by inpatient and outpatient encounters. Analysis of all diagnosis codes over the study period (comorbidities) demonstrated an elevated comorbidity profile consistent with the clinical profile of DM.

Conclusions

This study is among the first to utilize claims data to increase understanding of the clinical experience and health economic outcomes associated with DM. The markedly elevated HCRU patterns and comorbidity profile presented here add to the broad body of scientific and clinical knowledge on DM. These insights can inform clinical care and support the development of disease modifying and/or symptom-targeting therapies that address the multi-systemic, progressive nature of DM.
Wilson disease in Northern Portugal: a long-term follow-up study
Authors: Garrido Isabel , Marques Margarida , Liberal Rodrigo , Cardoso Hélder , Lopes Susana , Macedo Guilherme
Published: February 2022

Introduction

Wilson disease is an autosomal recessive disease of liver copper metabolism with predominant hepatic and neurological manifestations. Long-term data on the clinical follow-up and treatment efficacy are limited due to the low frequency of the disease. We evaluated a large cohort of Wilson disease patients from Northern Portugal during a 20-year follow-up period.

Methods

Twenty-four patients, diagnosed from 1975 to 2020 in a tertiary care center in Portugal, were retrospectively evaluated according to their clinical presentation, therapies and outcomes.

Results

Most of the patients were males (54%), with a median age at diagnosis of 19 years old (interquartile range 15–25). The main manifestations of Wilson disease were hepatic (71%) and neurological (25%). Family history was positive in 5 (21%) patients. Four patients (17%) presented with acute liver failure and fifteen (63%) individuals had cirrhosis at diagnosis. Penicillamine therapy was used by 11 (46%) patients, while trientine and zinc were given to 8 (33%) and 1 (4%) patient, respectively. Ten (42%) individuals underwent liver transplantation. The majority of patients (83%) had stable disease or improved outcomes during follow-up.

Conclusion

This is the largest cohort of adult patients with Wilson disease reported in Northern Portugal. We show that Wilson disease has favorable outcomes with long overall survival, assuming adherence to therapy and lack of other insults to their liver.
SKP2 drives the sensitivity to neddylation inhibitors and cisplatin in malignant pleural mesothelioma
Authors: Salaroglio Iris Chiara , Belisario Dimas Carolina , Bironzo Paolo , Ananthanarayanan Preeta , Ricci Luisa , Digiovanni Sabrina , Fontana Simona , Napoli Francesca , Sandri Alberto , Facolmatà Chiara , Libener Roberta , Comunanza Valentina , Grosso Federica , Gazzano Elena , Leo Francesco , Taulli Riccardo , Bussolino Federico , Righi Luisella , Papotti Mauro Giulio , Novello Silvia , Scagliotti Giorgio Vittorio , Riganti Chiara , Kopecka Joanna
Published: February 2022

Background

The combination of pemetrexed and cisplatin remains the reference first-line systemic therapy for malignant pleural mesothelioma (MPM). Its activity is moderate because of tumor aggressiveness, immune-suppressive environment and resistance to chemotherapy-induced immunogenic cell death (ICD). Preliminary and limited findings suggest that MPM cells have deregulated ubiquitination and proteasome activities, although proteasome inhibitors achieved disappointing clinical results.

Methods

Here, we investigated the role of the E3-ubiquitin ligase SKP/Cullin/F-box (SCF) complex in cell cycle progression, endoplasmic reticulum (ER)/proteostatic stress and ICD in MPM, and the therapeutic potential of the neddylation/SCF complex inhibitor MLN4924/Pevonedistat.

Results

In patient-derived MPM cultures and syngenic murine models, MLN4924 and cisplatin showed anti-tumor effects, regardless of MPM histotype and BAP1 mutational status, increasing DNA damage, inducing S- and G2/M-cell cycle arrest, and apoptosis. Mechanistically, by interfering with the neddylation of cullin-1 and ubiquitin-conjugating enzyme UBE2M, MLN4924 blocks the SCF complex activity and triggers an ER stress-dependent ICD, which activated anti-MPM CD8+T-lymphocytes. The SKP2 component of SCF complex was identified as the main driver of sensitivity to MLN4924 and resistance to cisplatin. These findings were confirmed in a retrospective MPM patient series, where SKP2 high levels were associated with a worse response to platinum-based therapy and inferior survival.

Conclusions

We suggest that the combination of neddylation inhibitors and cisplatin could be worth of further investigation in the clinical setting for MPM unresponsive to cisplatin. We also propose SKP2 as a new stratification marker to determine the sensitivity to cisplatin and drugs interfering with ubiquitination/proteasome systems in MPM.
Assessing lead time bias due to mammography screening on estimates of loss in life expectancy
Authors: Syriopoulou Elisavet , Gasparini Alessandro , Humphreys Keith , Andersson Therese M.-L.
Published: February 2022

Background

An increasingly popular measure for summarising cancer prognosis is the loss in life expectancy (LLE), i.e. the reduction in life expectancy following a cancer diagnosis. The proportion of life lost (PLL) can also be derived, improving comparability across age groups as LLE is highly age-dependent. LLE and PLL are often used to assess the impact of cancer over the remaining lifespan and across groups (e.g. socioeconomic groups). However, in the presence of screening, it is unclear whether part of the differences across population groups could be attributed to lead time bias. Lead time is the extra time added due to early diagnosis, that is, the time from tumour detection through screening to the time that cancer would have been diagnosed symptomatically. It leads to artificially inflated survival estimates even when there are no real survival improvements.

Methods

In this paper, we used a simulation-based approach to assess the impact of lead time due to mammography screening on the estimation of LLE and PLL in breast cancer patients. A natural history model developed in a Swedish setting was used to simulate the growth of breast cancer tumours and age at symptomatic detection. Then, a screening programme similar to current guidelines in Sweden was imposed, with individuals aged 40–74 invited to participate every second year; different scenarios were considered for screening sensitivity and attendance. To isolate the lead time bias of screening, we assumed that screening does not affect the actual time of death. Finally, estimates of LLE and PLL were obtained in the absence and presence of screening, and their difference was used to derive the lead time bias.

Results

The largest absolute bias for LLE was 0.61 years for a high screening sensitivity scenario and assuming perfect screening attendance. The absolute bias was reduced to 0.46 years when the perfect attendance assumption was relaxed to allow for imperfect attendance across screening visits. Bias was also present for the PLL estimates.

Conclusions

The results of the analysis suggested that lead time bias influences LLE and PLL metrics, thus requiring special consideration when interpreting comparisons across calendar time or population groups.
Meta-analysis defines predominant shared microbial responses in various diseases and a specific inflammatory bowel disease signal
Authors: Abbas-Egbariya Haya , Haberman Yael , Braun Tzipi , Hadar Rotem , Denson Lee , Gal-Mor Ohad , Amir Amnon
Published: February 2022

Background

Gut microbial alteration is implicated in inflammatory bowel disease but is noted in other diseases. Systematic comparison to define similarities and specificities is hampered since most studies focus on a single disease.

Results

We develop a pipeline to compare between disease cohorts starting from the raw V4 16S amplicon sequence variants. Including 12,838 subjects, from 59 disease cohorts, we demonstrate a predominant shared signature across diseases, indicating a common bacterial response to different diseases. We show that classifiers trained on one disease cohort predict relatively well other diseases due to this shared signal, and hence, caution should be taken when using such classifiers in real-world scenarios, where diseases are intermixed. Based on this common signature across a large array of diseases, we develop a universal dysbiosis index that successfully differentiates between cases and controls across various diseases and can be used for prioritizing fecal donors and samples with lower disease probability. Finally, we identify a set of IBD-specific bacteria, which can direct mechanistic studies and design of IBD-specific microbial interventions.

Conclusions

A robust non-specific general response of the gut microbiome is detected in a large array of diseases. Disease classifiers may confuse between different diseases due to this shared microbial response. Our universal dysbiosis index can be used as a tool to prioritize fecal samples and donors. Finally, the IBD-specific taxa may indicate a more direct association to gut inflammation and disease pathogenesis, and those can be further used as biomarkers and as future targets for interventions.
Neighbourhood characteristics related to mental health service use among adults with diabetes: a population-based cohort study in New Brunswick, Canada
Authors: Gupta Neeru , Crouse Dan Lawson , Foroughi Ismael
Published: February 2022

Objective

It has been postulated that social and economic inequalities may shape the distributions of comorbid diabetes and mental illness. This observational cohort study using linked population-based administrative and geospatial datasets aimed to describe associations between neighbourhood socioenvironments and disorder-specific mental health service use among adults with diabetes in the province of New Brunswick, Canada.

Results

A baseline cohort of 66,275 persons aged 19 and over living with diabetes was identified. One-quarter (26.3%) had used healthcare services for mood and anxiety disorders at least once during the six-year follow-up period 2012/2013–2017/2018. Based on Cox proportional hazards models, the risk of mental health service contacts was significantly higher among those residing in the most materially deprived neighbourhoods [HR: 1.07 (95% CI: 1.01–1.14)] compared to those in the least so, and those in areas characterized with the highest residential instability [HR: 1.13 (95% CI: 1.05–1.22)] compared to those in areas with the lowest instability. Among adults with incident diabetes (N = 4410), age and sex but not neighbourhood factors were related to differential help-seeking behaviours for mental health problems. These findings underscored the gap between theoretical postulations and population-based observations in delineating the syndemics of neighbourhood socioenvironments and mental health outcomes in populations with high diabetes prevalence.
Competition age: does it matter for swimmers?
Authors: Born Dennis-Peter , Stäcker Ina , Romann Michael , Stöggl Thomas
Published: February 2022

Objective

To establish reference data on required competition age regarding performance levels for both sexes, all swimming strokes, and race distances and to determine the effect of competition age on swimming performance in the context of other common age metrics. In total, 36,687,573 race times of 588,938 swimmers (age 14.2 ± 6.3 years) were analyzed. FINA (Fédération Internationale de Natation) points were calculated to compare race times between swimming strokes and race distances. The sum of all years of race participation determined competition age.

Results

Across all events, swimmers reach top-elite level, i.e. > 900 FINA points, after approximately 8 years of competition participation. Multiple-linear regression analysis explained up to 40% of variance in the performance level and competition age showed a stable effect on all race distances for both sexes (β = 0.19 to 0.33). Increased race distance from 50 to 1500 m, decreased effects of chronological age (β = 0.48 to − 0.13) and increased relative age effects (β = 0.02 to 0.11). Reference data from the present study should be used to establish guidelines and set realistic goals for years of competition participation required to reach certain performance levels. Future studies need to analyze effects of transitions between various swimming strokes and race distances on peak performance.
Two neuroanatomical subtypes of males with autism spectrum disorder revealed using semi-supervised machine learning
Authors: Liu Guanlu , Shi Liting , Qiu Jianfeng , Lu Weizhao
Published: February 2022

Background

Clinical and etiological varieties remain major obstacles to decompose heterogeneity in autism spectrum disorders (ASD). Recently, neuroimaging raised new hope to identify neurosubtypes of ASD for further understanding the biological mechanisms behind the disorder.

Methods

In this study, brain structural MRI data and clinical measures of 221 male subjects with ASD and 257 healthy controls were selected from 7 independent sites from the Autism Brain Image Data Exchange database (ABIDE). Heterogeneity through discriminative analysis (HYDRA), a recently-proposed semi-supervised clustering method was utilized to divide individuals with ASD into several neurosubtypes by regional volumetric measures of gray matter, white matter, and cerebrospinal fluid. Voxel-wise volume, clinical measures, dynamic resting-state functional magnetic resonance imaging (R-fMRI) measures among different neurosubtypes of ASD were explored. In addition, support vector machine (SVM) model was applied to test whether the neurosubtyping of ASD could improve diagnostic accuracy of ASD.

Results

Two neurosubtypes of ASD with different voxel-wise volumetric patterns were revealed. The full-scale intelligence quotient (IQ), verbal IQ, Autism Diagnostic Observation Schedule (ADOS) total scores and ADOS severity scores were significantly different between the two neurosubtypes, the total intracranial volume was correlated with performance IQ in Subtype 1 and was correlated with ADOS communication score and ADOS social score in Subtype 2. Compared with Subtype 2, Subtype 1 showed lower dynamic R-fMRI measures, lower dynamic functional architecture stability, higher mean and lower standard deviation (SD) of concordance among dynamic R-fMRI measures in cerebellum. In addition, classification accuracies between ASD neurosubtypes and healthy controls were significantly improved compared with classification accuracy between entire ASD group and healthy controls.

Limitations

The present study excluded female subjects and left-handed subjects, which limited the ability to investigate the associations between these factors and the heterogeneity of ASD.

Conclusions

The two distinct neuroanatomical subtypes of ASD validated by other data modalities not only adds reliability of the result, but also bridges from brain phenomenology to clinical behavior. The current neurosubtypes of ASD could facilitate understanding the neuropathology of this disorder and could be potentially used to improve clinical decision-making process and optimize treatment.
Important role of the SDF-1/CXCR4 axis in the homing of systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) to ovaries in rats with chemotherapy-induced premature ovarian insufficiency (POI)
Authors: Ling Li , Hou Jiying , Liu Dandan , Tang Dongyuan , Zhang Yanqin , Zeng Qianru , Pan Heng , Fan Ling
Published: February 2022

Background

Chemotherapy can induce premature ovarian insufficiency (POI). POI causes multiple sequelae and is currently incurable. As shown in our previous studies, systemically transplanted human amnion-derived mesenchymal stem cells (hAD-MSCs) home to ovaries with chemotherapy-induced POI and subsequently reduce ovarian injury and improve ovarian function in rats with POI. However, the cellular mechanisms that direct the migration and homing of hAD-MSCs to ovaries with chemotherapy-induced POI are incompletely understood. This study investigated the role of the SDF-1/CXCR4 axis in the migration and homing of systemically transplanted hAD-MSCs to ovaries with chemotherapy-induced POI and its relevant downstream signalling pathways.

Methods

CXCR4 expression in hAD-MSCs was assessed using Western blotting and immunofluorescence staining. hAD-MSC migration was tested using Transwell migration assays. SDF-1 levels were detected using ELISA. Seventy-two female SD rats were randomly divided into the control, POI, hAD-MSCs and hAD-MSCs + AMD3100 groups. Cyclophosphamide was used to establish rat POI models. For inhibitor treatment, hAD-MSCs were pretreated with AMD3100 before transplantation. PKH26-labeled hAD-MSCs were injected into the tail vein of POI rats 24 h after chemotherapy. After hAD-MSC transplantation, the homing of hAD-MSCs to ovaries and ovarian function and pathological changes were examined. We further investigated the molecular mechanisms by detecting the PI3K/Akt and ERK1/2 signalling pathways.

Results

hAD-MSCs expressed CXCR4. SDF-1 induced hAD-MSC migration in vitro. SDF-1 levels in ovaries and serum were significantly increased in rats with chemotherapy-induced POI, and ovaries with POI induced the homing of hAD-MSCs expressing CXCR4. Blocking the SDF-1/CXCR4 axis with AMD3100 significantly reduced the number of hAD-MSCs homing to ovaries with POI and further reduced their efficacy in POI treatment. The binding of SDF-1 to CXCR4 activated the PI3K/Akt signalling pathway, and LY294002 significantly inhibited hAD-MSC migration induced by SDF-1 in vitro. Moreover, inhibition of the PI3K/Akt signalling pathway significantly reduced the number of systemically transplanted hAD-MSCs homing to chemotherapy-induced ovaries in rats with POI.

Conclusions

SDF-1/CXCR4 axis partially mediates the migration and homing of systemically transplanted hAD-MSCs to the ovaries of rats with chemotherapy-induced POI, and the PI3K/Akt signalling pathway might be involved in the migration and homing of hAD-MSCs mediated by the SDF-1/CXCR4 axis.
State of the Art and Uses for the Biopharmaceutics Drug Disposition Classification System (BDDCS): New Additions, Revisions, and Citation References
Authors: Bocci Giovanni , Oprea Tudor I. , Benet Leslie Z.
Published: February 2022

The Biopharmaceutics Drug Disposition Classification system (BDDCS) is a four-class approach based on water solubility and extent of metabolism/permeability rate. Based on the BDDCS class to which a drug is assigned, it is possible to predict the role of metabolic enzymes and transporters on the drug disposition of a new molecular entity (NME) prior to its administration to animals or humans. Here, we report a total of 1475 drugs and active metabolites to which the BDDCS is applied. Of these, 379 are new entries, and 1096 are revisions of former classification studies with the addition of references for the approved maximum dose strength, extent of the systemically available drug excreted unchanged in the urine, and lowest solubility over the pH range 1.0–6.8 when such information is available in the literature. We detail revised class assignments of previously misclassified drugs and the literature analyses to classify new drugs. We review the process of solubility assessment for NMEs prior to drug dosing in humans and approved dose classification, as well as the comparison of Biopharmaceutics Classification System (BCS) versus BDDCS assignment. We detail the uses of BDDCS in predicting, prior to dosing animals or humans, disposition characteristics, potential brain penetration, food effect, and drug-induced liver injury (DILI) potential. This work provides an update on the current status of the BDDCS and its uses in the drug development process.

Graphical abstract
Optimization of robustness based on reinforced nodes in a modular network
Authors: Kfir-Cohen Yael , Vaknin Ben Porath Dana , Havlin Shlomo
Published: February 2022

Many networks such as critical infrastructures exhibit a modular structure. One approach to increase the robustness of these systems is to reinforce a fraction of the nodes so that the reinforced nodes provide additional needed sources for themselves as well as for their nearby neighborhood. Since reinforcing a node can be expensive, the efficiency of the decentralization process by reinforced nodes is vital. Here we develop a model which combines both modularity and reinforced nodes and study the robustness of the system. Using tools from percolation theory, we derive an analytical solution for the robustness resulting from any partition of reinforced nodes; between nodes that have links that connect between modules and nodes which have links only within modules. We find that near the critical percolation threshold the robustness is greatly affected by the partition. In particular, we find a partition of reinforced nodes that yields optimal robustness and we show that the optimal partition remains constant for high average degrees.
Tandem C2 domains mediate dynamic organelle targeting of a DOCK family guanine nucleotide exchange factor
Authors: Mallery Eileen L. , Yanagisawa Makoto , Zhang Chunhua , Lee Youngwoo , Robles Linda M. , Alonso Jose M. , Szymanski Daniel B.
Published: February 2022

Multicellular organisms use dedicator of cytokinesis (DOCK) family guanine nucleotide exchange factors (GEFs) to activate Rac/Rho-of-plants small GTPases and coordinate cell shape change. In developing tissues, DOCK signals integrate cell-cell interactions with cytoskeleton remodeling, and the GEFs cluster reversibly at specific organelle surfaces to orchestrate cytoskeletal reorganization. The domain organizations among DOCK orthologs are diverse, and the mechanisms of localization control are poorly understood. Here, we use combinations of transgene complementation and live-cell imaging assays to uncover an evolutionarily conserved and essential localization determinant in the DOCK-GEF named SPIKE1. The SPIKE1-DHR3 domain is sufficient for organelle association in vivo, and displays a complicated lipid-binding selectivity for both phospholipid head groups and fatty acid chain saturation. SPIKE1-DHR3 is predicted to adopt a C2-domain structure and functions as part of a tandem C2 array that enables reversible clustering at the cell apex. This work provides mechanistic insight into how DOCK GEFs sense compositional and biophysical membrane properties at the interface of two organelle systems.
Multimodality imaging of breast hematomas and their mimickers
Authors: Molière Sébastien
Published: February 2022

While breast hematomas are common, their imaging features are often underrecognized or mistaken for other conditions.

Diagnosis of acute hematomas is generally easy when associated with a recent history of breast trauma, surgery, or percutaneous biopsy. However, minor trauma might not always be remembered, and breast hematoma might have longlasting imaging manifestations when associated with fat necrosis. Also, because of the increasing use of breast MRI and FDG-PET/CT, breast hematomas are increasingly detected as incidentalomas and may mimic malignancies.

Conversely, breast hematomas may also be associated with authentic malignant processes.

In this pictorial review, we present the natural history of breast hematomas, their various imaging features, as well as their differential diagnoses, highlighting the situations requiring histopathological correlation.
Interobserver variation in the interpretation of magnetic resonance enterography in Crohn’s disease
Authors: Bhatnagar Gauraang , Mallett Sue , Quinn Laura , Beable Richard , Bungay Helen , Betts Margaret , Greenhalgh Rebecca , Gupta Arun , Higginson Anthony , Hyland Rachel , Ilangovan Rajapandian , Lambie Hannah , Mainta Evgenia , Patel Uday , Pilcher James , Plumb Andrew , Porté François , Sidhu Harbir , Slater Andrew , Tolan Damian , Zealley Ian , Halligan Steve , Taylor Stuart
Published: February 2022

Objectives:

To evaluate interobserver variability for diagnosis of disease presence and extent of small bowel and colonic Crohn’s disease using MR enterography (MRE)

Methods:

Data from the first 73 consecutive patients (mean age 32, 33F, 28 new diagnosis, 45 suspected relapse) recruited to a multicentre, prospective diagnostic accuracy trial evaluating MRE for small bowel Crohn’s disease were each read independently by three (from a pool of 20) radiologists. Radiologists documented presence and segmental location of small bowel Crohn’s disease and recorded morphological mural/extramural parameters for involved segments. Per patient percentage agreement for disease presence and extent were calculated against an outcome-based construct reference standard (averaged between pairs of readers). Prevalence-adjusted bias-adjusted κ (PABAK) was calculated.

Results:

Agreement for small bowel disease presence for new diagnosis/relapsed patients was 68%(κ = 0.36)/ 78% (κ = 0.56) and 43%(κ = 0.14)/ 53% for disease extent (κ = 0.07), respectively. For disease presence, all three radiologists agreed correctly with the reference standard in 41/59 (69%) of patients with small bowel involvement, and in 8/14 (57%) cases of without small bowel disease. Agreement was highest for multisegment disease, greater than 5 cm in length, with mural thickness>6 mm, and increased mural T2 signal. Agreement for colonic disease presence was 61% (κ = 0.21 fair agreement) for new diagnosis/ 60% (κ = 0.20, slight agreement) for relapsed patients.

Conclusion:

There is a reasonable agreement between radiologists for small bowel disease presence using MRE for newly diagnosed Crohn’s disease, and patients with suspected relapse, respectively. Agreement is lower for disease extent.

Advances in knowledge:

There is reasonable agreement between radiologists for small bowel disease presence using MRE for newly diagnosed (68%) Crohn’s disease, and patients with suspected relapse (78%). Agreement is lower for disease extent (43% new diagnosis and 53% suspected relapse).
Detection of the disease activity with ankylosing spondylitis through intravoxel incoherent motion diffusion-weighted MR imaging of sacroiliac joint
Authors: Liu Li , Zhou Zhimin , Hua Sunyu , Xue Leixi , Zhu Jiangtao , Liu Rong , Li Yong
Published: February 2022

Objective:

To explore the value of the quantitative parameter of intravoxel incoherent motion diffusion (IVIM-DWI) at 3.0 T MRI of the sacroiliac joint in differentiating different disease activity statuses of ankylosing spondylitis (AS) and to compare it with traditional diffusion-weighted imaging (DWI) and Spondyloarthritis Research Consortium of Canada (SPARCC) score.

Methods:

56 AS patients (active group, inactive group) and 24 healthy controls were included. Clinical data, quantitative parameters of IVIM-DWI MR images and the SPARCC scores were collected. The Kruskal–Wallis test was used to compare the differences between the groups. Receiver operating characteristic (ROC) curve analysis of histogram data and the SPARCC scores identified the efficacy of the three groups. The Spearman correlation coefficients were used to analyse the correlation between the quantitative IVIIM-DWI parameters and the SPARCC score.

Results:

The f (10th percentile) and SPARCC score of the active group were significantly higher than those of the inactive group. The f (10th, 25th, 50th percentiles), Dslow (average, entropy, 10th ~ 90 th percentiles), Dfast (kurtosis, skewness), ADC (average, 10th ~ 90 th percentiles) and the SPARCC score of the active group were significantly higher than the control group (p < 0.05). The AUC of the SPARCC score was the highest (0.799) in the identification between the active and inactive groups, and the sensitivity and specificity were 69.23 and 82.35%, respectively, at the cut-off value of 12. The SPARCC score was positively correlated with each percentile and the average value.

Conclusions:

Quantitative IVIIM-DWI parameters are helpful for the identification of different AS disease activity levels and are superior to traditional DWI. IVIM-DWI quantitative parameters had a good correlation with the SPARCC score.

Advances in knowledge:

A new MR technology-quantitative parameters of IVIM-DWI contribute to the identification of AS disease activity. IVIM-DWI quantitative parameters were well correlated with the SPARCC score.
The Pet127 protein is a mitochondrial 5′-to-3′ exoribonuclease from the PD-(D/E)XK superfamily involved in RNA maturation and intron degradation in yeasts
Authors: Łabędzka-Dmoch Karolina , Rażew Michal , Gapińska Marta , Piątkowski Jakub , Kolondra Adam , Salmonowicz Hanna , Wenda Joanna M. , Nowotny Marcin , Golik Paweł
Published: February 2022

Pet127 is a mitochondrial protein found in multiple eukaryotic lineages, but absent from several taxa, including plants and animals. Distant homology suggests that it belongs to the divergent PD-(D/E)XK superfamily which includes various nucleases and related proteins. Earlier yeast genetics experiments suggest that it plays a nonessential role in RNA degradation and 5′ end processing. Our phylogenetic analysis suggests that it is a primordial eukaryotic invention that was retained in diverse groups, and independently lost several times in the evolution of other organisms. We demonstrate for the first time that the fungal Pet127 protein in vitro is a processive 5′-to-3′ exoribonuclease capable of digesting various substrates in a sequence nonspecific manner. Mutations in conserved residues essential in the PD-(D/E)XK superfamily active site abolish the activity of Pet127. Deletion of the PET127 gene in the pathogenic yeast Candida albicans results in a moderate increase in the steady-state levels of several transcripts and in accumulation of unspliced precursors and intronic sequences of three introns. Mutations in the active site residues result in a phenotype identical to that of the deletant, confirming that the exoribonuclease activity is related to the physiological role of the Pet127 protein. Pet127 activity is, however, not essential for maintaining the mitochondrial respiratory activity in C. albicans.
Tożsamość kulturowa współczesnych potomków górali beskidzkich osiadłych w Serbii
Authors: Hajduk-Nijakowska Janina
Published: February 2022

Recenzja: Katarzyna Marcol, Toutowie. Język i pamięć w ustanawianiu wspólnoty Wiślan w Banacie, Wydawnictwo Uniwersytetu Śląskiego, Katowice 2020.