bluuebunny/crossref_metadata_2025 huggingface dataset:
How practice setting affects family physicians’ views on genetic screening: a qualitative study
Authors: Fok Rose Wai-Yee , Ong Cheryl Siow Bin , Lie Désirée , Ishak Diana , Fung Si Ming , Tang Wern Ee , Sun Shirley , Smith Helen , Ngeow Joanne Yuen Yie
Published: July 2021

Background

Genetic screening (GS), defined as the clinical testing of a population to identify asymptomatic individuals with the aim of providing those identified as high risk with prevention, early treatment, or reproductive options. Genetic screening (GS) improves patient outcomes and is accessible to the community. Family physicians (FPs) are ideally placed to offer GS. There is a need for FPs to adopt GS to address anticipated genetic specialist shortages.

Objective

To explore FP attitudes, perceived roles, motivators and barriers, towards GS; and explore similarities and differences between private and public sector FPs.

Methods

We developed a semi-structured interview guide using existing literature. We interviewed private and public sector FPs recruited by purposive, convenience and snowballing strategies, by telephone or video to theme saturation. All sessions were audio-recorded, transcribed and coded for themes by two independent researchers with an adjudicator.

Results

Thirty FPs were interviewed (15 private, 15 public). Theme saturation was reached for each group. A total of 12 themes (6 common, 3 from private-practice participants, 3 public-employed participants) emerged. Six common major themes emerged: personal lack of training and experience, roles and relevance of GS to family medicine, reluctance and resistance to adding GS to practice, FP motivations for adoption, patient factors as barrier, and potential solutions. Three themes (all facilitators) were unique to the private group: strong rapport with patients, high practice autonomy, and high patient literacy. Three themes (all barriers) were unique to the public group: lack of control, patients’ lower socioeconomic status, and rigid administrative infrastructure.

Conclusion

FPs are motivated to incorporate GS but need support for implementation. Policy-makers should consider the practice setting when introducing new screening functions. Strategies to change FP behaviours should be sensitive to their sense of autonomy, and the external factors (either as facilitators or as barriers) shaping FP practices in a given clinical setting.
The PROMOTe study: targeting the gut microbiome with prebiotics to overcome age-related anabolic resistance: protocol for a double-blinded, randomised, placebo-controlled trial
Authors: Ni Lochlainn Mary , Nessa Ayrun , Sheedy Alyce , Horsfall Rachel , García María Paz , Hart Deborah , Akdag Gulsah , Yarand Darioush , Wadge Samuel , Baleanu Andrei-Florin , Whelan Kevin , Steves Claire
Published: July 2021

Background

Loss of skeletal muscle mass and strength occurs with increasing age and is associated with loss of function, disability, and the development of sarcopenia and frailty. Dietary protein is essential for skeletal muscle function, but older adults do not anabolise muscle in response to protein supplementation as well as younger people, so called ‘anabolic resistance’. The aetiology and molecular mechanisms for this are not understood, however the gut microbiome is known to play a key role in several of the proposed mechanisms. Thus, we hypothesise that the gut microbiome may mediate anabolic resistance and therefore represent an exciting new target for ameliorating muscle loss in older adults.

This study aims to test whether modulation of the gut microbiome using a prebiotic, in addition to protein supplementation, can improve muscle strength (as measured by chair-rise time) versus protein supplementation alone.

Methods

The study is a randomised, double-blinded, placebo-controlled trial, with two parallel arms; one will receive prebiotic and protein supplementation, and the other will receive placebo (maltodextrin) and protein supplementation. Participants will be randomised as twin pairs, with one twin from each pair in each arm. Participants will be asked to take supplementation once daily for 12 weeks in addition to resistance exercises. Every participant will receive a postal box, containing their supplements, and the necessary equipment to return faecal, urine, saliva and capillary blood samples, via post. A virtual visit will be performed using online platform at the beginning and end of the study, with measures taken over video. Questionnaires, food diary and cognitive testing will be sent out via email at the beginning and end of the study.

Discussion

This study aims to provide evidence for the role of the gut microbiome in anabolic resistance to dietary protein. If those who take the prebiotic and protein supplementation have a greater improvement in muscle strength compared with those who take protein supplementation alone, this would suggest that strategies to modify the gut microbiome may reduce anabolic resistance, and therefore potentially mitigate sarcopenia and frailty in older adults.

Trial registration

Clinicaltrials.gov:NCT04309292. Registered on the 2nd May 2020.
Quantitative assessment of the effectiveness of joint measures led by Fangcang shelter hospitals in response to COVID-19 epidemic in Wuhan, China
Authors: Jiang Hui , Song Pengfei , Wang Siyi , Yin Shuangshuang , Yin Jinfeng , Zhu Chendi , Cai Chao , Xu Wangli , Li Weimin
Published: July 2021

Objective

To quantitatively evaluate the effectiveness of Fangcang shelter hospitals, designated hospitals, and the time interval from illness onset to diagnosis toward the prevention and control of the COVID-19 epidemic.

Methods

We used SEIAR and SEIA-CQFH warehouse models to simulate the two-period epidemic in Wuhan and calculate the time dependent basic reproduction numbers (BRNs) of symptomatic infected individuals, asymptomatic infected individuals, exposed individuals, and community-isolated infected individuals. Scenarios that varied in terms of the maximum numbers of open beds in Fangcang shelter hospitals and designated hospitals, and the time intervals from illness onset to hospitals visit and diagnosis were considered to quantitatively assess the optimal measures.

Results

The BRN decreased from 4.50 on Jan 22, 2020 to 0.18 on March 18, 2020. Without Fangcang shelter hospitals, the cumulative numbers of cases and deaths would increase by 18.58 and 51.73%, respectively. If the number of beds in the designated hospitals decreased by 1/2 and 1/4, the number of cumulative cases would increase by 178.04 and 92.1%, respectively. If the time interval from illness onset to hospital visit was 4 days, the number of cumulative cases and deaths would increase by 2.79 and 6.19%, respectively. If Fangcang shelter hospitals were not established, the number of beds in designated hospitals reduced 1/4, and the time interval from visiting hospitals to diagnosis became 4 days, the cumulative number of cases would increase by 268.97%.

Conclusion

The declining BRNs indicate the high effectiveness of the joint measures. The joint measures led by Fangcang shelter hospitals are crucial and need to be rolled out globally, especially when medical resources are limited.
Childhood abuse and borderline personality disorder features in Chinese undergraduates: the role of self-esteem and resilience
Authors: Xie Guo-Die , Chang Jun-Jie , Yuan Meng-Yuan , Wang Geng-Fu , He Yang , Chen Shan-Shan , Su Pu-Yu
Published: July 2021

Background

Although childhood abuse is considered to be related to borderline personality disorder (BPD), few studies have elaborated on the mediating role of self-esteem and resilience in it. Thus, the present study aimed to explore the potential mediating role of resilience and self-esteem between childhood abuse and BPD.

Methods

This cross-sectional study was conducted with 4034 college students in Anhui Province, China. Participants were asked to complete Chinese versions of the following instruments: Childhood Trauma Questionnaire–Short Form (CTQ-SF), Mclean Screening Instrument for Borderline Personality Disorder (MSI-BPD), Connor-Davidson Resilience Scale (CD-RISC), and Rosenberg Self-Esteem Scale (RSES). Structural equation modeling (SEM) was used to test the mediation effects.

Results

Resilience and self-esteem were found to be mediators of all three types of childhood abuse (emotional abuse, physical abuse and sexual abuse) when the types were examined separately; however, when all three types of childhood abuse were entered into the model simultaneously, neither the indirect effects nor direct effects of physical abuse or sexual abuse were found to be significant, only the association between emotional abuse and BPD features was partially mediated by resilience and self-esteem.

Conclusions

Self-esteem and resilience mediate the links between childhood abuse and BPD features, and emotional abuse is uniquely associated with BPD features.
Racial and socioeconomic disparities in multimorbidity and associated healthcare utilisation and outcomes in Brazil: a cross-sectional analysis of three million individuals
Authors: Hone Thomas , Stokes Jonathan , Trajman Anete , Saraceni Valeria , Coeli Claudia Medina , Rasella Davide , Durovni Betina , Millett Christopher
Published: July 2021

Background

Evidence is limited on racial/ethnic group disparities in multimorbidity and associated health outcomes in low- and middle-income countries hampering effective policies and clinical interventions to address health inequalities.

Methods

This study assessed race/ethnic and socioeconomic disparities in the prevalence of multimorbidity and associated healthcare utilisation, costs and death in Rio de Janeiro, Brazil. A cross-sectional analysis was carried out of 3,027,335 individuals registered with primary healthcare (PHC) services. Records included linked data to hospitalisation, mortality, and welfare-claimant (Bolsa Família) records between 1 Jan 2012 and 31 Dec 2016. Logistic and Poisson regression models were carried out to assess the likelihood of multimorbidity (two or more diagnoses out of 53 chronic conditions), PHC use, hospital admissions and mortality from any cause. Interactions were used to assess disparities.

Results

In total 13,509,633 healthcare visits were analysed identifying 389,829 multimorbid individuals (13%). In adjusted regression models, multimorbidity was associated with lower education (Adjusted Odds Ratio (AOR): 1.26; 95%CI: 1.23,1.29; compared to higher education), Bolsa Família receipt (AOR: 1.14; 95%CI: 1.13,1.15; compared to non-recipients); and black race/ethnicity (AOR: 1.05; 95%CI: 1.03,1.06; compared to white). Multimorbidity was associated with more hospitalisations (Adjusted Rate Ratio (ARR): 2.75; 95%CI: 2.69,2.81), more PHC visits (ARR: 3.46; 95%CI: 3.44,3.47), and higher likelihood of death (AOR: 1.33; 95%CI: 1.29,1.36). These associations were greater for multimorbid individuals with lower educational attainment (five year probability of death 1.67% (95%CI: 1.61,1.74%) compared to 1.13% (95%CI: 1.02,1.23%) for higher education), individuals of black race/ethnicity (1.48% (95%CI: 1.41,1.55%) compared to 1.35% (95%CI: 1.31,1.40%) for white) and individuals in receipt of welfare (1.89% (95%CI: 1.77,2.00%) compared to 1.35% (95%CI: 1.31,1.38%) for non-recipients).

Conclusions

The prevalence of multimorbidity and associated hospital admissions and mortality are greater in individuals with black race/ethnicity and other deprived socioeconomic groups in Rio de Janeiro. Interventions to better prevent and manage multimorbidity and underlying disparities in low- and middle-income country settings are needed.
Association of indoor microbial aerosols with respiratory symptoms among under-five children: a systematic review and meta-analysis
Authors: Fakunle Adekunle Gregory , Jafta Nkosana , Naidoo Rajen N. , Smit Lidwien A. M.
Published: July 2021

Background

Despite the recognition of the importance of indoor microbial exposures on children’s health, the role of different microbial agents in development and aggravation of respiratory symptoms and diseases is only poorly understood. This study aimed to assess whether exposure to microbial aerosols within the indoor environment are associated with respiratory symptoms among children under-5 years of age.

Methods

A systematic literature search was conducted on PubMed, Web of Science, GreenFILE, ScienceDirect, EMBASE and Cochrane library through February 2020. Studies that investigated the exposure–response relationship between components of the indoor microbial communities and respiratory symptoms among under-five children were eligible for inclusion. A random-effect meta-analysis was applied to estimate pooled relative risk (RR) and 95% confidence interval (CI) for study specific high versus low microbial exposures. The potential effect of individual studies on the overall estimate was evaluated using leave-one-out analysis, while heterogeneity was evaluated byI2statistics using RevMan 5.3.

Results

Fifteen studies were eligible for inclusion in a meta-analysis. The pooled risk estimate suggested that increased microbial exposure was associated with an increased risk of respiratory symptoms [pooled relative risk (RR): 1.24 (1.09, 1.41),P = 0.001]. The association was strongest with exposure to a combination ofAspergillus,Penicillium, Cladosporium and Alternariaspecies [pooled RR: 1.73 (1.30, 2.31),P = 0.0002]. Stratified analysis revealed an increased risk of wheeze [pooled RR: 1.20 (1.05, 1.37),P = 0.007 and allergic rhinitis [RR: 1.18 (0.94, 1.98),P = 0.16] from any microbial exposure.

Conclusions

Microbial exposures are, in general, associated with risk of respiratory symptoms. Future studies are needed to study the indoor microbiome more comprehensively, and to investigate the mechanism of these associations.
Bayesian optimization with evolutionary and structure-based regularization for directed protein evolution
Authors: Frisby Trevor S. , Langmead Christopher James
Published: July 2021

Background

Directed evolution (DE) is a technique for protein engineering that involves iterative rounds of mutagenesis and screening to search for sequences that optimize a given property, such as binding affinity to a specified target. Unfortunately, the underlying optimization problem is under-determined, and so mutations introduced to improve the specified property may come at the expense of unmeasured, but nevertheless important properties (ex. solubility, thermostability, etc). We address this issue by formulating DE as a regularized Bayesian optimization problem where the regularization term reflects evolutionary or structure-based constraints.

Results

We applied our approach to DE to three representative proteins, GB1, BRCA1, and SARS-CoV-2 Spike, and evaluated both evolutionary and structure-based regularization terms. The results of these experiments demonstrate that: (i) structure-based regularization usually leads to better designs (and never hurts), compared to the unregularized setting; (ii) evolutionary-based regularization tends to be least effective; and (iii) regularization leads to better designs because it effectively focuses the search in certain areas of sequence space, making better use of the experimental budget. Additionally, like previous work in Machine learning assisted DE, we find that our approach significantly reduces the experimental burden of DE, relative to model-free methods.

Conclusion

Introducing regularization into a Bayesian ML-assisted DE framework alters the exploratory patterns of the underlying optimization routine, and can shift variant selections towards those with a range of targeted and desirable properties. In particular, we find that structure-based regularization often improves variant selection compared to unregularized approaches, and never hurts.
Cemented versus uncemented hemiarthroplasty for femoral neck fractures in patients with neuromuscular diseases: a minimum of 2 years’ follow-up study
Authors: Wang Yuchuan , Wang Zhongzheng , Tian Siyu , Tan Zhanchao , Zhu Yanbin , Chen Wei , Zhang Yingze
Published: July 2021

Background

The aim of this study was to compare the outcomes of cemented and uncemented hemiarthroplasty for femoral neck fractures in patients with neuromuscular disease.

Methods

We reviewed 156 patients with neuromuscular disease who underwent hemiarthroplasty between June 2015 and December 2019. Patients were divided into cemented group (n= 105) and uncemented group (n= 51), with a minimum follow-up of 2 years. Factors including preoperative features, duration of surgery, intraoperative blood loss, complications, pain, Harris hip scores (HHS), and quality of life were compared across groups, and Kaplan–Meier curves were used to estimate survival.

Results

In the uncemented group, the mean duration of surgery was 16.0 min. shorter (p= 0.001) and the mean intraoperative blood loss was 71.1 mL less (p= 0.01). Visual analog scales (VAS), HHS, and European Quality of Life-5 Dimensions (EQ-5D) scores were not different between the groups. Despite a few potential trends, we did not observe a difference in complications such as periprosthetic fractures and dislocations. The rates of mortality were similar between groups (p=0.821).

Conclusions

Both arthroplasties may be used with good medium-term results in the treatment of femoral neck fractures in patients with neuromuscular diseases.
Clinical characteristics and genetic spectrum of 26 individuals of Chinese origin with primary ciliary dyskinesia
Authors: Zhao Xinyue , Bian Chun , Liu Keqiang , Xu Wenshuai , Liu Yaping , Tian Xinlun , Bai Jing , Xu Kai-Feng , Zhang Xue
Published: July 2021

Background

Primary ciliary dyskinesia (PCD) is a rare, highly heterogeneous genetic disorder involving the impairment of motile cilia. With no single gold standard for PCD diagnosis and complicated multiorgan dysfunction, the diagnosis of PCD can be difficult in clinical settings. Some methods for diagnosis, such as nasal nitric oxide measurement and digital high-speed video microscopy with ciliary beat pattern analysis, can be expensive or unavailable. To confirm PCD diagnosis, we used a strategy combining assessment of typical symptoms with whole-exome sequencing (WES) and/or low-pass whole-genome sequencing (WGS) as an unbiased detection tool to identify known pathogenic mutations, novel variations, and copy number variations.

Results

A total of 26 individuals of Chinese origin with a confirmed PCD diagnosis aged 13 to 61 years (median age, 24.5 years) were included. Biallelic pathogenic mutations were identified in 19 of the 26 patients, including 8 recorded HGMD mutations and 24 novel mutations. The detection rate reached 73.1%. DNAH5 was the most frequently mutated gene, and c.8383C > T was the most common mutated variant, but it is relatively rare in PCD patients from other ethnic groups.

Conclusion

This study demonstrates the practical clinical utility of combining WES and low-pass WGS as a no-bias detecting tool in adult patients with PCD, showing a clinical characteristics and genetic spectrum of Chinese PCD patients.
CACNA1C is a prognostic predictor for patients with ovarian cancer
Authors: Chang Xiaohan , Dong Yunxia
Published: July 2021

Background

CACNA1C, as a type of voltage-dependent calcium ion transmembrane channel, played regulatory roles in the development and progress of multiple tumors. This study was aimed to analyze the roles of CACNA1C in ovarian cancer (OC) of overall survival (OS) and to explore its relationships with immunity.

Methods

Single gene mRNA sequencing data and corresponding clinical information were obtained from The Cancer Genome Atlas Database (TCGA) and the International Cancer Genome Consortium (ICGC) datasets. Gene set enrichment analysis (GSEA) was used to identify CACNA1C-related signal pathways. Univariate and multivariate Cox regression analyses were applied to evaluate independent prognostic factors. Besides, associations between CACNA1C and immunity were also explored.

Results

CACNA1C had a lower expression in OC tumor tissues than in normal tissues (P < 0.001), with significant OS (P = 0.013) and a low diagnostic efficiency. We further validated the expression levels of CACNA1C in OC by means of the ICGC dataset (P = 0.01), qRT-PCR results (P < 0.001) and the HPA database. Univariate and multivariate Cox hazard regression analyses indicated that CACNA1C could be an independent risk factor of OS for OC patients (both P < 0.001). Five significant CACNA1C-related signaling pathways were identified by means of GSEA. As for genetic alteration analysis, altered CACNA1C groups were significantly associated with OS (P = 0.0169), progression-free survival (P = 0.0404), disease-free survival (P = 0.0417) and disease-specific survival (P = 9.280e-3), compared with unaltered groups in OC. Besides, CACNA1C was dramatically associated with microsatellite instability (MSI) and immunity.

Conclusions

Our results shed light on that CACNA1C could be a prognostic predictor of OS in OC and it was closely related to immunity.
Severe onset of inflammatory myositis in a child: think to paraneoplastic myositis
Authors: Benvenuto Simone , Gortani Giulia , Bussani Rossana , Poropat Federico , Murru Flora Maria , Carrozzi Marco , Tommasini Alberto , Taddio Andrea
Published: July 2021

Background

Juvenile idiopathic inflammatory myopathies (JIIMs) are a group of heterogenous, acquired, autoimmune disorders that affect the muscle. While the association between IIMs and malignancy has been widely reported in adults, cancer-associated myositis (CAM) is rare in children, so that routine malignancy screening is not generally performed. This report shows a case of severe CAM in a child.

Case presentation

An 11-years-old girl presented with worsening dyspnea after a 3-weeks history of progressive proximal weakness, myalgia, dysphagia, and weight loss. Her past history was remarkable for a type I Arnold-Chiari malformation associated with an anterior sacral meningocele. Physical examination showed severe hypotony and hypotrophy. Pulse oximetry and blood test showed a type II respiratory failure (SpO2 88%, pCO2 68 mmHg) and increased muscle enzyme levels (CPK 8479 U/L, AST 715 U/L, ALT 383 U/L, LDH 1795 U/L). The patient needed invasive mechanical ventilation. Inflammatory myositis was considered and treatment with intravenous methylprednisolone (30 mg/Kg/day for 3 days followed by 2 mg/Kg/day) and IVIG (1 g/kg/day for 2 days) was started. Muscle biopsy showed endomysial and perimysial necrosis and inflammation. The presence of serum anti-TIF1-γ antibody positivity led to a malignancy screening. Whole-body MRI showed a mature teratoma underneath sacral meningocele and both lesions were surgically removed.

Given the histological and clinical severity of the myopathy, mycophenolate (500 mg twice a day) and rituximab (360 mg/m2, 4 weekly infusions) were added. Due to extreme muscular wasting, severe malnutrition and intolerance to enteral feeding the patient needed a transient tracheostomy and parenteral nutrition, followed by physiotherapy, speech therapy and nocturnal non-invasive ventilation. A complete remission was achieved 3 months after.

Conclusions

Among cancer-associated autoantibodies (CAAs) in adult patients, anti-TIF1-γ carries the highest risk of CAM, which recognizes with a high likelihood a paraneoplastic pathogenesis. In children, anti-TIF1-γ antibody has been associated with severe cutaneous disease, lipodystrophy, and chronic disease course, but not with CAM, which is overall rare in younger patients. Severe onset of a JIIM, especially if anti-TIF1-γ antibody positive, should prompt suspect of a CAM and lead to a screening for malignancy.
Jacobsen syndrome and neonatal bleeding: report on two unrelated patients
Authors: Serra Gregorio , Memo Luigi , Antona Vincenzo , Corsello Giovanni , Favero Valentina , Lago Paola , Giuffrè Mario
Published: July 2021

Introduction

In 1973, Petrea Jacobsen described the first patient showing dysmorphic features, developmental delay and congenital heart disease (atrial and ventricular septal defect) associated to a 11q deletion, inherited from the father. Since then, more than 200 patients have been reported, and the chromosomal critical region responsible for this contiguous gene disorder has been identified.

Patients’ presentation

We report on two unrelated newborns observed in Italy affected by Jacobsen syndrome (JBS, also known as 11q23 deletion). Both patients presented prenatal and postnatal bleeding, growth and developmental delay, craniofacial dysmorphisms, multiple congenital anomalies, and pancytopenia of variable degree. Array comparative genomic hybridization (aCGH) identified a terminal deletion at 11q24.1-q25 of 12.5 Mb and 11 Mb, in Patient 1 and 2, respectively. Fluorescent in situ hybridization (FISH) analysis of the parents documented a de novo origin of the deletion for Patient 1; parents of Patient 2 refused further genetic investigations.

Conclusions

Present newborns show the full phenotype of JBS including thrombocytopenia, according to their wide 11q deletion size. Bleeding was particularly severe in one of them, leading to a cerebral hemorrhage. Our report highlights the relevance of early diagnosis, genetic counselling and careful management and follow-up of JBS patients, which may avoid severe clinical consequences and lower the mortality risk. It may provide further insights and a better characterization of JBS, suggesting new elements of the genotype-phenotype correlations.
Cauchy type means for some generalized convex functions
Authors: Mehreen Naila , Anwar Matloob
Published: July 2021

In this paper, we establish Jensen’s inequality for s-convex functions in the first sense. By using Jensen’s inequalities, we obtain some Cauchy type means for p-convex and s-convex functions in the first sense. Also, by using Hermite–Hadamard inequalities for the respective generalized convex functions, we find new generalized Cauchy type means.
Optimization of an analytical HPLC-DAD method for detecting hydroxycinnamic acid derivatives from mixtures of Saussurea grandifolia and Taraxacum coreanum
Authors: Lee Hak-Dong , Paje Leo Adrianne , Lee Sullim , Kang Ki Sung , Hong Kyungki , Kwon Hyukjin , Lee Sanghyun
Published: July 2021

An analytical method was established to identify and quantify hydroxycinnamic acids, such as 1,5-dicaffeoylquinic acid (DCQA) and chicoric acid (CA), in mixtures of Saussurea grandifolia and Taraxacum coreanum (MST) by using reverse-phase high-performance liquid chromatography coupled with diode array detector (HPLC-DAD). Analyses were carried out by using an INNO C18 column with a gradient elution system, and different parameters were used to validate our optimized method. Results demonstrated limits of detection and quantification of 5.46 × 10–3 and 16.54 × 10–3 mg/mL for DCQA and 0.37 × 10–3 and 1.14 × 10–3 mg/mL for CA, respectively. The calibration curves for DCQA and CA showed good linearity over the concentration ranges of 0.025–0.4 and 0.00625–0.1 mg/mL, respectively, and both exhibited r2 = 1.0000. In the accuracy test, high recovery rates were obtained ranging from 101.16–104.18% for DCQA and 97.55–108.49% for CA, while the precision values were ≤ 1.00% for DCQA and ≤ 1.21% for CA. The values obtained from our analyses support the use of this analytical method for the accurate identification and quantification of DCQA and CA from MST. Our methodology could be used further to determine the content of hydroxycinnamic acid derivatives in routine analyses and large-scale extraction processes.
Psychological therapy for mood instability within bipolar spectrum disorder: a randomised, controlled feasibility trial of a dialectical behaviour therapy-informed approach (the ThrIVe-B programme)
Authors: Wright Kim , Dodd Alyson L. , Warren Fiona C. , Medina-Lara Antonieta , Dunn Barnaby , Harvey Julie , Javaid Mahmood , Jones Steven H. , Owens Christabel , Taylor Rod S. , Duncan Deborah , Newbold Alexandra , Norman Shelley , Warner Faith , Lynch Thomas R.
Published: July 2021

Background

A subgroup of those with bipolar spectrum disorders experience ongoing mood fluctuations outside of full episodes. We conducted a randomised, controlled feasibility study of a Dialectical Behavioural Therapy-informed approach for bipolar mood fluctuations (Therapy for Inter-episode mood Variability in Bipolar [ThrIVe-B]). Our study aimed to examine the feasibility and acceptability of a future definitive trial evaluating the clinical and cost effectiveness of the ThrIVe-B programme. Participants were required to meet diagnostic criteria for a bipolar spectrum disorder and report frequent mood swings outside of acute episodes. They were randomised to treatment as usual (control arm) or the ThrIVe-B intervention plus treatment as usual (intervention arm). Follow-up points were at 3, 6, 9 and 15 months after baseline, with 9 months as the primary end point. To evaluate feasibility and acceptability we examined recruitment and retention rates, completion rates for study measures, adverse events and feedback from participants on their experience of study participation and therapy.

Results

Of the target 48 participants, 43 were recruited (22 in the intervention arm; 21 in the control arm), with a recruitment rate of 3.9 participants per month. At 9 months 74% of participants engaged in research follow-up assessment, exceeding the pre-specified criterion of 60%. There were no serious concerns about the safety of the research procedures or the intervention. On one of the four candidate primary outcome measures, the 95% CI for the between-group mean difference score excluded the null effect and included the minimal clinically important difference, favouring the intervention arm, whilst on no measure was there evidence of deterioration in the intervention arm relative to the control arm. Attendance of the intervention (50% attending at least half of the mandatory sessions) was below the pre-specified continuation criterion of 60%, and qualitative feedback from participants indicated areas that may have hampered or facilitated engagement.

Conclusions

It is broadly feasible to conduct a trial of this design within the population of people with frequent bipolar mood swings. Changes should be made to the therapy to increase uptake, such as simplifying content and considering individual rather than group delivery.

Trial registrationISRCTN: ISRCTN54234300. Registered 14th July 2017,http://www.isrctn.com/ISRCTN54234300
The relevance of science-policy-practice dialogue. Exploring the urban climate resilience governance in Italy
Authors: Caldarice Ombretta , Tollin Nicola , Pizzorni Maria
Published: July 2021

The concept of resilience has been developed for over 40 years in different disciplines. The academic discussion on defining resilience is thriving to create interdisciplinary understandings and meanings. Simultaneously, resilience has firmly entered into planning practice to address vulnerabilities and cities' exposure facing to present and future hazards particularly related to climate change effects. In the last twenty years, a growing number of cities are adopting local climate actions, and urban resilience is also gradually a crucial part of international and national policies worldwide. Despite the increasing attention to urban resilience, its implementation at the local scale and the required increasing ambition are still lagging, also due to a lack of dialogue among researchers (the scientific level), policy-makers (the normative level) and practitioners (the operational level). Following the 2018 CitiesIPCC Research and Action Agenda recommendations, this paper contributes to improving understanding barriers, opportunities, and needs for science-policy-practice dialogue for urban climate resilience. The paper analyses the urban climate resilient strategiesstrategies of the Italian metropolitan cities, concluding that a science-policy-practice dialogue is lacking in implementing evidence-based climate change resilience policies and actions actions at the local scale. Starting from the Italian case study, the paper suggests an iterative process to unlock the science-policy-practice dialogue for contributing to operationalise urban climate resilience fostering thanks to a multiscalar governance approach.
Designing and validating an evaluation inventory for assessing teachers’ professional accountability
Authors: Rahmatollahi Maryam , Mohamadi Zenouzagh Zohre
Published: July 2021

Research has already established the boundless potential of teachers in assisting effective learning processes, and there is still a need to expand research to illustrate interrelation and connection between the construct of teachers’ professional accountability which moderates and directs student learning. To this end, a comprehensive review of the literature was conducted by the researchers to explore and extract relevant theoretical constructs to teacher accountability. A literature review was followed by structured interviews with 20 administrators, teachers, students, and parents to record perceived concepts related to teacher accountability. Content analysis of recorded interviews and thematic network analysis of literature resulted in a 30-item Likert scale. The researcher-made questionnaire was subject to reliability and validity issues. Thus, in the second phase, the questionnaire was piloted with 142 male and female EFL in-service teachers selected on the basis of the convenient sampling method. Factor analysis on data collected through this reduced the items to 29 and indicated that data on teacher accountability loaded on five components including accountability towards students (N: 7 items), parents (N: 5 items), school leadership (N: 5 items), society (N: 7 items), and the profession (N: 5 items). The results also indicated that the questionnaire enjoys sound psychometric properties of reliability (α: 0.88 ˂0.5). The upshots of this study could provide a better understanding of the concept and lead teachers to be more coherent and accountable.
Effects of polymorphic cytochrome P450 2A6 genotypes on chemoprevention against colorectal tumors in single Japanese cohort using daily low-dose aspirin: insights into future personalized treatments
Authors: Yamazaki Hiroshi , Shimizu Makiko , Otani Takahiro , Mizugaki Ami , Mure Kanae , Suzuki Sadao , Ishikawa Hideki
Published: July 2021

Background

A chemopreventive effect of low-dose aspirin against colorectal tumors was previously found in participants of two Japanese multicenter, double-blind, randomized, placebo-controlled clinical trials investigating the effects of daily aspirin (100 mg/day) for 0.7–2 years on tumor recurrence in colorectal cancer patients whose tumors were excised endoscopically.

Methods

In the current study, chemopreventive data from single-center subsets having daily aspirin (100 mg/day) were reanalyzed with respect to variations in polymorphic cytochrome P450 2A6 (CYP2A6). From the J-CAPP study, 56 of 311 participants (47 men, 9 women; excluding patients with familial adenomatous polyposis) were genotyped for CYP2A6*1, *4 (whole-gene deletion), *7 (amino acid substitution), and *9 (upstream mutation), and from the J-FAPP IV study, 81 of 102 participants (43 men, 38 women; including patients with familial adenomatous polyposis) were also genotyped.

Results

The chemopreventive effects of daily aspirin were found to be inversely dependent on the predicted enzyme activity of the CYP2A6 phenotype [based on normal genotypes (CYP2A6*1/*1,*7,*9) and impaired genotypes (CYP2A6*4,*7,*9/*4,*7,*9 and CYP2A6*1/*4)] among a nonsmoker Japanese cohort without familial adenomatous polyposis.

Conclusions

The CYP2A6 wild-type allele could be a candidate biomarker for reduced chemopreventive effects of daily aspirin in a population with wide-ranging CYP2A6 phenotypes with a high frequency of impaired activities resulting from variations and whole-gene deletions. The CYP2A6 genotypes could be applicable to future personalized treatments for colorectal tumor chemoprevention with daily aspirin.
Utility of 24-hour ambulatory blood pressure monitoring in potential living kidney donors
Authors: Aslam Nabeel , Memon Sobia H. , Wadei Hani , Lesser Elizabeth R. , Niazi Shehzad K.
Published: July 2021

Introduction

Hypertension (HTN) is a risk factor for cardiovascular disease; therefore, it is imperative to risk stratify potential kidney donors during evaluation. Clinic blood pressure (CBP) measurement is inaccurate in assessing presence or absence of HTN. There is paucity of data about utility of 24-h ambulatory blood pressure monitoring (ABPM) during kidney donor evaluation.

Methods

24-h ABPM is performed on all kidney donors at Mayo Clinic Florida. We conducted retrospective review of 264 consecutive potential kidney donors from 1/1/2012 to 12/31/2017. Demographic, comorbid conditions, laboratory results and 24-h ABPM data were collected. Subjects were divided into two groups: Group1: Subjects with no prior history of HTN and new diagnosis of HTN using 24-h ABPM; Group 2: Subjects with no prior history of hypertension and normal BP on 24-h ABPM.

Results

Baseline demographic included mean age 46.40 years, 39% males, 78.4% Caucasians, and mean BMI was 26.94. Twenty one subjects (8.0%) had prior diagnosis of HTN. Among 243 subjects without prior HTN, 62 (25.5%) were newly diagnosed with HTN using 24-h ABPM. CBP was high only in 27 out of 62 (43.6%) of newly diagnosed HTN subjects. Thirty-five subjects (14.4%) had masked HTN and 14 subjects (5.8%) had white-coat HTN. Newly diagnosed hypertensive subjects were more likely to be males as compared to Group 2 (53.2% vs 34.3% P = 0.008). There was a trend of more non-Caucasians subjects (30.6% vs 19.9% P = 0.08) and more active smokers (17.7% vs 11.6%, P = 0.054) in Group1 as compared to Group 2. Only 17 (27.4%) out of 62 newly diagnosed hypertensive subjects were deemed suitable for kidney donation as compared to 105 (58.0%) out of 181 normotensive subjects (P < 0.001).

Conclusion

In our cohort, use of ABPM resulted in new diagnosis of HTN in 1 out of 4 potential kidney donors. Newly diagnosed HTN was more common in men, those with non-Caucasian race, and in active smokers. There was a significantly reduced acceptance rate for kidney donation among newly diagnosed HTN subjects. Further studies are needed to determine the value of 24-h ABPM among these high risk groups.
Multiomic technologies for analyses of inborn errors of immunity: from snapshot of the average cell to dynamic temporal picture at single-cell resolution
Authors: Kawashima Yusuke , Nishikomori Ryuta , Ohara Osamu
Published: July 2021

Advances in DNA sequencing technology have significantly impacted human genetics; they have enabled the analysis of genetic causes of rare diseases, which are usually pathogenic variants in a single gene at the nucleotide sequence level. However, since the quantity of data regarding the relationship between genotype and phenotype is insufficient to diagnose some rare immune diseases definitively, genetic information alone cannot help obtain a mechanistic understanding of the disease etiology. For such cases, exploring the molecular phenotype using multiomic analyses could be the approach of choice. In this review, we first overview current technologies for multiomic analysis, particularly focusing on RNA and protein profiling of bulk cell ensembles. We then discuss the measurement modality and granularity issue because it is critical to design multiomic experiments properly. Next, we illustrate the importance of bioimaging by describing our experience with the analysis of an autoinflammatory disease, cryopyrin-associated periodic fever syndrome, which could be caused by low-frequency somatic mosaicism and cannot be well characterized only by multiomic snapshot analyses of an ensemble of many immune cells. We found it powerful to complement the multiomic data with bioimaging data that can provide us with indispensable time-specific dynamic information of every single cell in the “immune cell society.” Because we now have many measurement tools in different modalities and granularity to tackle the etiology of rare hereditary immune diseases, we might gain a deeper understanding of the pathogenic mechanisms of these diseases by taking full advantage of these tools in an integrated manner.
Metagenomics analysis revealed the distinctive ruminal microbiome and resistive profiles in dairy buffaloes
Authors: Sun Hui-Zeng , Peng Ke-Lan , Xue Ming-Yuan , Liu Jian-Xin
Published: July 2021

Background

Antimicrobial resistance poses super challenges in both human health and livestock production. Rumen microbiota is a large reservoir of antibiotic resistance genes (ARGs), which show significant varations in different host species and lifestyles. To compare the microbiome and resistome between dairy cows and dairy buffaloes, the microbial composition, functions and harbored ARGs of rumen microbiota were explored between 16 dairy cows (3.93 ± 1.34 years old) and 15 dairy buffaloes (4.80 ± 3.49 years old) using metagenomics.

Results

Dairy buffaloes showed significantly different bacterial species (LDA > 3.5 & P < 0.01), enriched KEGG pathways and CAZymes encoded genes (FDR < 0.01 & Fold Change > 2) in the rumen compared with dairy cows. Distinct resistive profiles were identified between dairy cows and dairy buffaloes. Among the total 505 ARGs discovered in the resistome of dairy cows and dairy buffaloes, 18 ARGs conferring resistance to 16 antibiotic classes were uniquely detected in dairy buffaloes. Gene tcmA (resistance to tetracenomycin C) presented high prevalence and age effect in dairy buffaloes, and was also highly positively correlated with 93 co-expressed ARGs in the rumen (R = 0.98 & P = 5E-11). In addition, 44 bacterial species under Lactobacillus genus were found to be associated with tcmA (R > 0.95 & P < 0.001). L. amylovorus and L. acidophilus showed greatest potential of harboring tcmA based on co-occurrence analysis and tcmA-containing contigs taxonomic alignment.

Conclusions

The current study revealed distinctive microbiome and unique ARGs in dairy buffaloes compared to dairy cattle. Our results provide novel understanding on the microbiome and resistome of dairy buffaloes, the unique ARGs and associated bacteria will help develop strategies to prevent the transmission of ARGs.
Tocilizumab in management of refractory juvenile idiopathic arthritis, 10 years of experience at tertiary university hospital
Authors: Muzaffer Mohammed A. , Abdelgalil Abobakr A.
Published: July 2021

Background

Juvenile idiopathic arthritis (JIA) is the most prevalent pediatric rheumatic disorder. Progress in modalities of therapy improves the disease outcome. We aimed to determine the efficacy and safety of tocilizumab (TCZ) in the management of systemic (sJIA) and polyarticular (pJIA) in children who are resistant to conventional as well as other biological therapies. In this retrospective study, we selected JIA patients according to the International League of Association for Rheumatology (ILAR) criteria and were treated with TCZ. Response to TCZ was assessed using Juvenile Arthritis Disease Activity Score-10 (JADAS-10) and also outcomes were assessed according to the American College of Rheumatology (ACR) remission criteria. Safety of the drug was assessed by documenting possibly related adverse effects (AE). Statistical analysis using SPSS version 25 with statistical significance is considered if p ≤ 0.05. We included 16 JIA patients aged ≤ 18 years but 2 of them were excluded as they developed severe reaction during the TCZ 1st dose, so finally, 14 patients were included.

Results

The median age of our patients was 12 years. Of these 14 patients, 9 (64.3%) had sJIA and 5 (35.7%) had pJIA. TCZ use led to significant improvement in the JADAS-10 from mean 22.4 (± 7.9) when it was initially assessed and then 3, 6, 12, and 24 months after TCZ initiation with means 5.7 (± 3.9), 4.4 (± 3.7), 3.5 (± 3.1), and 2.7 (± 2.2), (P = 0.001, 0.001, 0.005, 0.012), respectively. Five patients exhibited TCZ possibly expected side effects. Neutropenia and infusion-related reactions were the most frequent AE.

Conclusions

Tocilizumab seems to be generally effective and safe drug in the management of sJIA and pJIA especially in cases refractory to conventional as well as other biologic agents.
Factors associated with hip pain in end-stage renal disease patients on prevalent hemodialysis: a cross-sectional study
Authors: Şenlikci Hüma Bölük , Afşar Sevgi İkbali , Özen Selin , Sayın Cihat Burak
Published: July 2021

Background

Hemodialysis (HD) patients suffer from musculoskeletal disorders. The most reported musculoskeletal problem is arthralgia. Hip arthralgia has been commonly reported in patients undergoing HD. Hip pain can lead to a decrease in levels of physical activity, limitation in joint range of motion, and consequently difficulties in performing activities of daily living (ADL) and impair the quality of life (QoL). The aim of the study is to reveal the prevalence of hip pain and related factors in HD patients. This cross-sectional study included 73 patients on prevalent HD whose ages ranged from 25 to 65 years and who were on HD for more than 6 months. Physical examination and radiological imaging were done to every patient. Visual analog scale, Barthel Index, and Short Form-36 were used to evaluate pain, ADL, and QoL, respectively.

Results

Hip arthralgia was detected in 32 patients. Around 43% of which were diagnosed hip osteoarthritis, 34% greater trochanteric pain syndrome, 15% femoroacetabular impingement, and 6% soft tissue calcifications. Diabetes mellitus and hemodialysis duration were found to be significantly different between the groups of hip pain and without hip pain. Diabetes mellitus was identified as an independent risk factor for hip pain in hemodialysis patients. ADL and QoL were significantly lower in patients with hip pain compared to those without (p < 0.01; p < 0.05, respectively).

Conclusions

The results of our research show that HD patients should be screened for the presence of hip pain and other musculoskeletal disorders and that this is an area which requires further consideration and medical research.
Clinical Utility of Precision Medicine in Pediatric Oncology: A Systematic Review
Authors: Lee Justin , Gillam Lynn , Visvanathan Keshini , Hansford Jordan R. , McCarthy Maria C.
Published: July 2021

PURPOSE

Precision medicine uses advanced molecular techniques to guide the use of targeted therapeutic drugs and is an emerging paradigm in pediatric oncology. Clinical evidence related to the efficacy of many novel targeted drugs, however, is currently very limited given the rarity of pediatric cancer and the lack of published evidence for the use of these drugs in children. This systematic review aimed to evaluate the existing evidence for the feasibility and clinical efficacy of precision medicine in pediatric oncology.

METHODS

A systematic review was conducted using the PubMed, Medline, and Embase databases. Clinical trials and observational studies, which used molecular assays such as whole-exome sequencing to identify molecular targets that guided the allocation of targeted cancer drugs and reported clinical outcomes, were included in this review.

RESULTS

Twenty-one clinical trials and observational studies were identified, collectively enrolling 1,408 pediatric patients across nine countries. Therapeutic targets were found in 647 patients (46.0%); however, only 175 of these patients (27.0%) received a targeted drug. Objective responses were recorded for 73 (41.7%) of these 175 patients, only 5.2% of the total sample. Inconsistent outcome reporting and limited comparison with conventional treatment hindered evaluation of the clinical utility of precision medicine.

CONCLUSION

Precision medicine can feasibly identify molecular targets in a clinical setting. However, the inaccessibility of targeted drugs is a significant barrier, restricting the exploration of its therapeutic potential in pediatric oncology. Future clinical trials should endeavor to link the molecular testing results with access to targeted drugs and standardize outcome reporting to advance understanding of the benefits of this novel paradigm in improving patient outcomes.