bluuebunny/crossref_metadata_2025 huggingface dataset:
Transcriptome, metabolome and suppressor analysis reveal an essential role for the ubiquitin-proteasome system in seedling chloroplast development
Authors: Talloji Prabhavathi , Nehlin Lilian , Hüttel Bruno , Winter Nikola , Černý Martin , Dufková Hana , Hamali Bulut , Hanczaryk Katarzyna , Novák Jan , Hermanns Monika , Drexler Nicole , Eifler Karolin , Schlaich Nikolaus , Brzobohatý Břetislav , Bachmair Andreas
Published: April 2022

Background

Many regulatory circuits in plants contain steps of targeted proteolysis, with the ubiquitin proteasome system (UPS) as the mediator of these proteolytic events. In order to decrease ubiquitin-dependent proteolysis, we inducibly expressed a ubiquitin variant with Arg at position 48 instead of Lys (ubK48R). This variant acts as an inhibitor of proteolysis via the UPS, and allowed us to uncover processes that are particularly sensitive to UPS perturbation.

Results

Expression of ubK48R during germination leads to seedling death. We analyzed the seedling transcriptome, proteome and metabolome 24 h post ubK48R induction and confirmed defects in chloroplast development. We found that mutations in single genes can suppress seedling lethality, indicating that a single process in seedlings is critically sensitive to decreased performance of the UPS. Suppressor mutations in phototropin 2 (PHOT2) suggest that a contribution of PHOT2 to chloroplast protection is compromised by proteolysis inhibition.

Conclusions

Overall, the results reveal protein turnover as an integral part of a signal transduction chain that protects chloroplasts during development.
Machine learning models outperform deep learning models, provide interpretation and facilitate feature selection for soybean trait prediction
Authors: Gill Mitchell , Anderson Robyn , Hu Haifei , Bennamoun Mohammed , Petereit Jakob , Valliyodan Babu , Nguyen Henry T. , Batley Jacqueline , Bayer Philipp E. , Edwards David
Published: April 2022

Recent growth in crop genomic and trait data have opened opportunities for the application of novel approaches to accelerate crop improvement. Machine learning and deep learning are at the forefront of prediction-based data analysis. However, few approaches for genotype to phenotype prediction compare machine learning with deep learning and further interpret the models that support the predictions. This study uses genome wide molecular markers and traits across 1110 soybean individuals to develop accurate prediction models. For 13/14 sets of predictions, XGBoost or random forest outperformed deep learning models in prediction performance. Top ranked SNPs by F-score were identified from XGBoost, and with further investigation found overlap with significantly associated loci identified from GWAS and previous literature. Feature importance rankings were used to reduce marker input by up to 90%, and subsequent models maintained or improved their prediction performance. These findings support interpretable machine learning as an approach for genomic based prediction of traits in soybean and other crops.
Early supported discharge for older adults admitted to hospital with medical complaints: a systematic review and meta-analysis
Authors: Williams Susan , Morrissey Ann-Marie , Steed Fiona , Leahy Aoife , Shanahan Elaine , Peters Catherine , O’Connor Margaret , Galvin Rose , O’Riordan Cliona
Published: April 2022

Introduction

Early supported discharge (ESD) aims to link acute and community care, allowing hospital inpatients to return home and continue to receive the necessary input from healthcare professionals that they would otherwise receive in hospital. The concept has shown reduced length of stay and improved functional outcomes in stroke patients. This systematic review aims to explore the totality of evidence for the use of early supported discharge in older adults hospitalised with medical complaints.

Methods

A literature search of CINAHL in EBSCO, Cochrane Central Register of Controlled Trials in the Cochrane Library (CENTRAL), EMBASE and MEDLINE in EBSCO was carried out. Randomised controlled trials or quasi-randomised controlled trials were included. The Cochrane Risk of Bias Tool 2.0 was used for quality assessment. The primary outcome measure was hospital length of stay. Secondary outcomes included mortality, function, health related quality of life, hospital readmissions, long-term care admissions and cognition. A pooled meta-analysis was conducted using RevMan software 5.4.1.

Results

Five studies met the inclusion criteria. All studies were of some concern in terms of their risk of bias. Statistically significant effects favouring ESD interventions were only seen in terms of length of stay (REM, MD = -6.04, 95% CI -9.76 to -2.32, I2 = 90%, P = 0.001). No statistically significant effects favouring ESD interventions were established in secondary outcomes.

Conclusion

ESD interventions can have a statistically significant impact on the length of stay of older adults admitted to hospital for medical reasons. There is a need for further higher quality research in the area, with standardised interventions and outcome measures used.
Pyrexia in a young infant – is height of fever associated with serious bacterial infection?
Authors: Tan Victoria Shi Rui , Ong Gene Yong-Kwang , Lee Khai Pin , Ganapathy Sashikumar , Chong Shu-Ling
Published: April 2022

Background

Febrile infants ≤ 90 days old make up a significant proportion of patients seeking care in the emergency department (ED). These infants are vulnerable to serious bacterial infections (SBIs) and early identification is required to initiate timely investigations and interventions. We aimed to study if height of an infant’s temperature on presentation to the ED is associated with SBI.

Methods

We performed a retrospective chart review on febrile infants ≤ 90 days old presenting to our ED between 31st March 2015 and 28th February 2016. We compared triage temperature of febrile infants with and without SBIs. We presented sensitivity, specificity, positive and negative predictive values (PPV and NPV) of fever thresholds at triage. A multivariable regression was performed to study the association between height of temperature and the presence of SBI, and presented the adjusted odds ratio (aOR) with corresponding 95% confidence intervals (CI).

Results

Among 1057 febrile infants analysed, 207 (19.6%) had a SBI. Mean temperature of infants with a SBI was significantly higher than those without (mean 38.5 °C, standard deviation, SD 0.6 vs. 38.3 °C, SD 0.5, p < 0.005). For temperature ≥ 39 °C, sensitivity, specificity, PPV and NPV for SBI was 15.5% (95%CI 10.8—21.1%), 90.4% (95%CI 88.2—92.3%), 28.1% (95%CI 21.1—36.3%) and 81.4% (95%CI 80.5—82.4%) respectively. The height of fever was consistently associated with SBI after adjusting for age, gender and SIS (aOR 1.76, 95% CI 1.32—2.33, p < 0.001). However, 32 (15.5%) infants with SBIs had an initial triage temperature ≤ 38 °C.

Conclusions

A higher temperature at triage was associated with a higher risk of SBI among febrile infants ≤ 90 days old. However, height of temperature must be used in conjunction with other risk factors to identify SBIs in young infants.
Altered gut microbiota and its association with inflammation in patients with chronic thromboembolic pulmonary hypertension: a single-center observational study in Japan
Authors: Ikubo Yumiko , Sanada Takayuki Jujo , Hosomi Koji , Park Jonguk , Naito Akira , Shoji Hiroki , Misawa Tomoko , Suda Rika , Sekine Ayumi , Sugiura Toshihiko , Shigeta Ayako , Nanri Hinako , Sakao Seiichiro , Tanabe Nobuhiro , Mizuguchi Kenji , Kunisawa Jun , Suzuki Takuji , Tatsumi Koichiro
Published: April 2022

Background

The pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH) is considered to be associated with chronic inflammation; however, the underlying mechanism remains unclear. Recently, altered gut microbiota were found in patients with pulmonary arterial hypertension (PAH) and in experimental PAH models. The aim of this study was to characterize the gut microbiota in patients with CTEPH and assess the relationship between gut dysbiosis and inflammation in CTEPH.

Methods

In this observational study, fecal samples were collected from 11 patients with CTEPH and 22 healthy participants. The abundance of gut microbiota in these fecal samples was assessed using 16S ribosomal ribonucleic acid (rRNA) gene sequencing. Inflammatory cytokine and endotoxin levels were also assessed in patients with CTEPH and control participants.

Results

The levels of serum tumor necrosis factor-α (TNF-α), interleukin (IL)-6, IL-8, and macrophage inflammatory protein (MIP)-1α were elevated in patients with CTEPH. Plasma endotoxin levels were significantly increased in patients with CTEPH (P < 0.001), and were positively correlated with TNF-α, IL-6, IL-8, and MIP-1α levels. The 16S rRNA gene sequencing and the principal coordinate analysis revealed the distinction in the gut microbiota between patients with CTEPH (P < 0.01) and control participants as well as the decreased bacterial alpha-diversity in patients with CTEPH. A random forest analysis for predicting the distinction in gut microbiota revealed an accuracy of 80.3%.

Conclusion

The composition of the gut microbiota in patients with CTEPH was distinct from that of healthy participants, which may be associated with the elevated inflammatory cytokines and endotoxins in CTEPH.
Obesity is associated with subclinical hypothyroidism in the presence of thyroid autoantibodies: a cross-sectional study
Authors: Yan Yuerong , Xu Mingtong , Wu Muchao , Wang Xiaoyi , Li Feng , Zhang Jin , You Lili , Pan Xiaofang , Feng Weilian , Wu Jiayun , Chen Caixia , Li Xiaohui , Yan Li
Published: April 2022

Background

Both obesity and subclinical hypothyroidism (SCH) have adverse effects on human body, but the relationship between these two conditions remains inconsistent. The presence of thyroid autoantibodies influences thyroid hormone levels, and may further mediate the interaction between obesity and SCH. This study aimed to explore the association among obesity, SCH and thyroid autoantibodies.

Methods

This study was a cross-sectional survey of 2505 subjects. Obesity was defined as a body mass index ≥28 kg/m2. Serum concentrations of thyroid hormones, thyroid peroxidase antibody (TPO-Ab) and thyroglobulin antibody (Tg-Ab) were examined. Logistic analysis was used to explore the relation among obesity, SCH and thyroid autoantibodies.

Results

A proportion of 11.54% (289/2505) subjects were obese, and 165 subjects had SCH. The positive rates of thyroid autoantibodies, TPO-Ab and Tg-Ab were 17.64% (442/2505), 11.02% (276/2505) and 14.13% (354/2505), respectively. The proportion of SCH was significantly higher in obese than nonobese subjects among those with positive thyroid autoantibodies [22.41% (13/58) vs. 11.72% (45/384), p = 0.025, χ2 test]. Moreover, obesity was significantly associated with SCH in the presence of thyroid autoantibodies after adjusting for confounding factors (OR 2.212, 95% CI 1.103 to 4.433, p = 0.025). A higher proportion of subjects with obesity had Tg-Ab positivity [17.99% (52/289) vs. 13.63% (302/2216), p = 0.045, χ2 test], and obesity remained significantly associated with Tg-Ab positivity by multiple logistic analysis (OR 1.504, 95% CI 1.077 to 2.101, p = 0.017).

Conclusions

Obesity was associated with SCH in the presence of thyroid autoantibodies. Examination of SCH is recommended in obese subjects with thyroid autoantibody positivity.
Dose–response relationship of pulmonary disorders by inhalation exposure to cross-linked water-soluble acrylic acid polymers in F344 rats
Authors: Takeda Tomoki , Yamano Shotaro , Goto Yuko , Hirai Shigeyuki , Furukawa Yusuke , Kikuchi Yoshinori , Misumi Kyohei , Suzuki Masaaki , Takanobu Kenji , Senoh Hideki , Saito Misae , Kondo Hitomi , Daghlian George , Hong Young-Kwon , Yoshimatsu Yasuhiro , Hirashima Masanori , Kobashi Yoichiro , Okamoto Kenzo , Kishimoto Takumi , Umeda Yumi
Published: April 2022

Background

In Japan, six workers handling cross-linked water-soluble acrylic acid polymer (CWAAP) at a chemical plant suffered from lung diseases, including fibrosis, interstitial pneumonia, emphysema, and pneumothorax. We recently demonstrated that inhalation of CWAAP-A, one type of CWAAP, causes pulmonary disorders in rats. It is important to investigate dose–response relationships and recoverability from exposure to CWAAPs for establishing occupational health guidelines, such as setting threshold limit value for CWAAPs in the workplace.

Methods

Male and female F344 rats were exposed to 0.3, 1, 3, or 10 mg/m3CWAAP-A for 6 h/day, 5 days/week for 13 weeks using a whole-body inhalation exposure system. At 1 h, 4 weeks, and 13 weeks after the last exposure the rats were euthanized and blood, bronchoalveolar lavage fluid, and all tissues including lungs and mediastinal lymph nodes were collected and subjected to biological and histopathological analyses. In a second experiment, male rats were pre-treated with clodronate liposome or polymorphonuclear leukocyte-neutralizing antibody to deplete macrophages or neutrophils, respectively, and exposed to CWAAP-A for 6 h/day for 2 days.

Results

CWAAP-A exposure damaged only the alveoli. The lowest observed adverse effect concentration (LOAEC) was 1 mg/m3and the no observed adverse effect concentration (NOAEC) was 0.3 mg/m3. Rats of both sexes were able to recover from the tissue damage caused by 13 weeks exposure to 1 mg/m3CWAAP-A. In contrast, tissue damage caused by exposure to 3 and 10 mg/m3was irreversible due to the development of interstitial lung lesions. There was a gender difference in the recovery from CWAAP-A induced pulmonary disorders, with females recovering less than males. Finally, acute lung effects caused by CWAAP-A were significantly reduced by depletion of alveolar macrophages.

Conclusions

Pulmonary damage caused by inhalation exposure to CWAAP-A was dose-dependent, specific to the lung and lymph nodes, and acute lung damage was ameliorated by depleting macrophages in the lungs. CWAAP-A had both a LOAEC and a NOAEC, and tissue damage caused by exposure to 1 mg/m3CWAAP-A was reversible: recovery in female rats was less than for males. These findings indicate that concentration limits for CWAAPs in the workplace can be determined.

Graphical Abstract
Non-linear relationship of gamma-glutamyl transpeptidase to lymphocyte count ratio with the recurrence of hepatocellular carcinoma with staging I–II: a retrospective cohort study
Authors: Li Zeping , Liang Lili , Duan Wen , Zhou Chengmao , Yang Jian-Jun
Published: April 2022

Background

High recurrence rate was a major factor for the poor postoperative prognosis of hepatocellular carcinoma (HCC) patients. The present study was intended to evaluate the association of gamma-glutamyl transpeptidase to lymphocyte count ratio (GLR) and the recurrence of HCC with staging I–II in Chinese.

Methods

The retrospective cohort data was derived from the First Affiliated Hospital of Zhengzhou University from January 2014 to December 2018 on 496 patients who underwent radical resection of HCC with staging I–II. Multivariable Cox regression models were used to determine hazard ratios (HR) and 95% confidence interval (CI) for the recurrence of HCC with staging I–II of each GLR tertile category. The restricted cubic spline model was used to find out the threshold effect.

Results

With the low tertile of GLR as the reference, multivariable-adjusted HR and 95% CI of the middle and high tertile categories were 1.748 (1.170–2.612) and 2.078 (1.339–3.227). In addition, there was a positive correlation (HR 1.002; 95% CI 1.001–1.004) and a non-liner relationship was found, whose point was 27.5. When the GLR was less than 27.5, the risk of recurrence increased, obviously with the increase in GLR levels (HR 1.041; 95% CI 1.014–1.068).

Conclusions

The GLR was independently associated with the recurrence of HCC patients with staging I–II. Furthermore, the relationship was positive and no-linear.
Addressing recall bias in (post-)conflict data collection and analysis: lessons from a large-scale health survey in Colombia
Authors: Moreno-Serra Rodrigo , Anaya-Montes Misael , León-Giraldo Sebastián , Bernal Oscar
Published: April 2022

Background

Much applied research on the consequences of conflicts for health suffers from data limitations, particularly the absence of longitudinal data spanning pre-, during- and post-conflict periods for affected individuals. Such limitations often hinder reliable measurement of the causal effects of conflict and their pathways, hampering also the design of effective post-conflict health policies. Researchers have sought to overcome these data limitations by conducting ex-post surveys, asking participants to recall their health and living standards before (or during) conflict. These questions may introduce important analytical biases due to recall error and misreporting.

Methods

We investigate how to implement ex-post health surveys that collect recall data, for conflict-affected populations, which is reliable for empirical analysis via standard quantitative methods. We propose two complementary strategies based on methods developed in the psychology and psychometric literatures—the Flashbulb and test-retest approaches—to identify and address recall bias in ex-post health survey data. We apply these strategies to the case study of a large-scale health survey which we implemented in Colombia in the post-peace agreement period, but that included recall questions referring to the conflict period.

Results

We demonstrate how adapted versions of the Flashbulb and test-retest strategies can be used to test for recall bias in (post-)conflict survey responses. We also show how these test strategies can be incorporated into post-conflict health surveys in their design phase, accompanied by further ex-ante mitigation strategies for recall bias, to increase the reliability of survey data analysis—including by identifying the survey modules, and sub-populations, for which empirical analysis is likely to yield more reliable causal inference about the health consequences of conflict.

Conclusions

Our study makes a novel contribution to the field of applied health research in humanitarian settings, by providing practical methodological guidance for the implementation of data collection efforts in humanitarian contexts where recall information, collected from primary surveys, is required to allow assessments of changes in health and wellbeing. Key lessons include the importance of embedding appropriate strategies to test and address recall bias into the design of any relevant data collection tools in post-conflict or humanitarian contexts.
Design of the PERSPECTIVE study: PERsonalized SPEeCh Therapy for actIVE conversation in Parkinson’s disease (randomized controlled trial)
Authors: Maas J. J. L. , De Vries N. M. , Bloem B. R. , Kalf J. G.
Published: April 2022

Objective

To evaluate the effectiveness of personalized and home-based speech therapy on quality of life, intelligibility, and social participation for people with Parkinson’s disease (PD) who have a reduced intelligibility of speech.

Background

Speech problems in PD have a profound negative impact on social interaction and quality of life. Evidence for speech therapy in PD is growing, but more work remains needed to explore its full potential. Efficacy exists for highly intensive standardized speech treatment programs, but not all patients can comply with this rather intense intervention, especially the more severely affected ones. Here, we aim to study the effectiveness of personalized and home-based (remote) speech therapy in PD on quality of life and speech. The intervention will be supported by a dedicated speech training app. We expect that this approach will improve speech intelligibility and quality of life in patients irrespective of disease stage.

Methods

We will perform a single blind, randomized controlled trial, comparing 8 weeks of speech therapy to no intervention using a waiting list design. A total of 215 PD patients with problems in intelligibility will be recruited by 12 highly experienced speech therapists. All patients will be measured at baseline and after 8 weeks (primary endpoint). Additionally, the experimental group will be re-assessed one more time, after a wash-out period of 24 weeks. The control group will receive deferred treatment after 8 weeks, but without additional follow-up assessments. Our primary outcome is quality of life (as measured with PDQ-39). Secondary outcomes include speech and voice quality, intelligibility, severity of voice and speech complaints, and caregiver burden.

Results

The inclusion of participants has started on March 1, 2019, and is expected to be finalized on April 1, 2021. We expect to have the first results in January 2022.

Conclusions

We will investigate the effectiveness of speech therapy in PD. Particular strengths of our study include a randomized and single-blinded design, the personalized treatment approach, the inclusion of PD patients irrespective of disease stage or severity of the speech complaint, the long-term follow-up, the adequate power, and the use of a patient-relevant primary endpoint. This will allow us to draw firm conclusions about the effectiveness of personalized and remote speech therapy for PD patients in all disease stages.

Trial registration

ClinicalTrials.govNCT03963388. Registered on May 24, 2019
Safety, tolerability, and efficacy of monoclonal CD38 antibody felzartamab in late antibody-mediated renal allograft rejection: study protocol for a phase 2 trial
Authors: Mayer Katharina A. , Budde Klemens , Halloran Philip F. , Doberer Konstantin , Rostaing Lionel , Eskandary Farsad , Christamentl Anna , Wahrmann Markus , Regele Heinz , Schranz Sabine , Ely Sarah , Firbas Christa , Schörgenhofer Christian , Kainz Alexander , Loupy Alexandre , Härtle Stefan , Boxhammer Rainer , Jilma Bernd , Böhmig Georg A.
Published: April 2022

Background

Antibody-mediated rejection (ABMR) is a cardinal cause of renal allograft loss. This rejection type, which may occur at any time after transplantation, commonly presents as a continuum of microvascular inflammation (MVI) culminating in chronic tissue injury. While the clinical relevance of ABMR is well recognized, its treatment, particularly a long time after transplantation, has remained a big challenge. A promising strategy to counteract ABMR may be the use of CD38-directed treatment to deplete alloantibody-producing plasma cells (PC) and natural killer (NK) cells.

Methods

This investigator-initiated trial is planned as a randomized, placebo-controlled, double-blind, parallel-group, multi-center phase 2 trial designed to assess the safety and tolerability (primary endpoint), pharmacokinetics, immunogenicity, and efficacy of the fully human CD38 monoclonal antibody felzartamab (MOR202) in late ABMR. The trial will include 20 anti-HLA donor-specific antibody (DSA)-positive renal allograft recipients diagnosed with active or chronic active ABMR ≥ 180 days post-transplantation. Subjects will be randomized 1:1 to receive felzartamab (16 mg/kg per infusion) or placebo for a period of 6 months (intravenous administration on day 0, and after 1, 2, 3, 4, 8, 12, 16, and 20 weeks). Two follow-up allograft biopsies will be performed at weeks 24 and 52. Secondary endpoints (preliminary assessment) will include morphologic and molecular rejection activity in renal biopsies, immunologic biomarkers in the blood and urine, and surrogate parameters predicting the progression to allograft failure (slope of renal function; iBOX prediction score).

Discussion

Based on the hypothesis that felzartamab is able to halt the progression of ABMR via targeting antibody-producing PC and NK cells, we believe that our trial could potentially provide the first proof of concept of a new treatment in ABMR based on a prospective randomized clinical trial.

Trial registration

EU Clinical Trials Register (EudraCT) 2021-000545-40. Registered on 23 June 2021. ClinicalTrials.gov NCT05021484. Registered on 25 August 2021
Trial of Early Antiviral Therapies during Non-hospitalized Outpatient Window (TREAT NOW) for COVID-19: a summary of the protocol and analysis plan for a decentralized randomized controlled trial
Authors: Kaizer Alexander M. , Wild Jessica , Lindsell Christopher J. , Rice Todd W. , Self Wesley H. , Brown Samuel , Thompson B. Taylor , Hart Kimberly W. , Smith Clay , Pulia Michael S. , Shapiro Nathan I. , Ginde Adit A.
Published: April 2022

Background

Coronavirus disease 2019 (COVID-19) has a heterogeneous outcome in individuals from remaining asymptomatic to death. In a majority of cases, mild symptoms are present that do not require hospitalization and can be successfully treated in the outpatient setting, though symptoms may persist for a long duration. We hypothesize that drugs suitable for decentralized study in outpatients will have efficacy among infected outpatients

Methods

The TREAT NOW platform is designed to accommodate testing multiple agents with the ability to incorporate new agents in the future. TREAT NOW is an adaptive, blinded, multi-center, placebo-controlled superiority randomized clinical trial which started with two active therapies (hydroxychloroquine and lopinavir/ritonavir) and placebo, with the hydroxychloroquine arm dropped shortly after enrollment began due to external evidence. Each arm has a target enrollment of 300 participants who will be randomly assigned in an equal allocation to receive either an active therapy or placebo twice daily for 14 days with daily electronic surveys collected over days 1 through 16 and on day 29 to evaluate symptoms and a modified COVID-19 ordinal outcome scale. Participants are enrolled remotely by telephone and consented with a digital interface, study drug is overnight mailed to study participants, and data collection occurs electronically without in-person interactions.

Discussion

If effective treatments for COVID-19 can be identified for individuals in the outpatient setting before they advance to severe disease, it will prevent progression to more severe disease, reduce the need for hospitalization, and shorten the duration of symptoms. The novel decentralized, “no touch” approach used by the TREAT NOW platform has distinction advantages over traditional in-person trials to reach broader populations and perform study procedures in a pragmatic yet rigorous manner.

Trial registration

ClinicalTrials.gov NCT04372628. Registered on April 30, 2020. First posted on May 4, 2020.
The development of theory-informed participant-centred interventions to maximise participant retention in randomised controlled trials
Authors: Newlands Rumana , Duncan Eilidh , Treweek Shaun , Elliott Jim , Presseau Justin , Bower Peter , MacLennan Graeme , Ogden Margaret , Wells Mary , Witham Miles D. , Young Bridget , Gillies Katie
Published: April 2022

Background

A failure of clinical trials to retain participants can influence the trial findings and significantly impact the potential of the trial to influence clinical practice. Retention of participants involves people, often the trial participants themselves, performing a behaviour (e.g. returning a questionnaire or attending a follow-up clinic as part of the research). Most existing interventions that aim to improve the retention of trial participants fail to describe any theoretical basis for the potential effect (on behaviour) and also whether there was any patient and/or participant input during development. The aim of this study was to address these two problems by developing theory- informed, participant-centred, interventions to improve trial retention.

Methods

This study was informed by the Theoretical Domains Framework and Behaviour Change Techniques Taxonomy to match participant reported determinants of trial retention to theoretically informed behaviour change strategies. The prototype interventions were described and developed in a co-design workshop with trial participants. Acceptability and feasibility (guided by (by the Theoretical Framework of Acceptability) of two prioritised retention interventions was explored during a focus group involving a range of trial stakeholders (e.g. trial participants, trial managers, research nurses, trialists, research ethics committee members). Following focus group discussions stakeholders completed an intervention acceptability questionnaire.

Results

Eight trial participants contributed to the co-design of the retention interventions. Four behaviour change interventions were designed: (1) incentives and rewards for follow-up clinic attendance, (2) goal setting for improving questionnaire return, (3) participant self-monitoring to improve questionnaire return and/or clinic attendance, and (4) motivational information to improve questionnaire return and clinic attendance. Eighteen trial stakeholders discussed the two prioritised interventions. The motivational information intervention was deemed acceptable and considered straightforward to implement whilst the goal setting intervention was viewed as less clear and less acceptable.

Conclusions

This is the first study to develop interventions to improve trial retention that are based on the accounts of trial participants and also conceptualised and developed as behaviour change interventions (to encourage attendance at trial research visit or return a trial questionnaire). Further testing of these interventions is required to assess effectiveness.
Effect of core stabilization exercises in addition to conventional therapy in improving trunk mobility, function, ambulation and quality of life in stroke patients: a randomized controlled trial
Authors: Mahmood Wajeeha , Ahmed Burq Hafiz Syed Ijaz , Ehsan Sarah , Sagheer Basita , Mahmood Tahir
Published: April 2022

Background

Stroke is a major cause of disability with mainly affecting trunk mobility and function. The purpose of this study is to determine the effectiveness of core stabilization exercises versus conventional therapy on trunk mobility, function, ambulation, and quality of life of stroke patients.

Design

Assessor blinded randomized control trial.

Setting

Ibrahim polyclinic—Shadman, Ch Muhammad Akram teaching hospital-Raiwind, Rasheed hospital-Defence.

Subjects

Chronic ischemic stroke patients.

Intervention

Control group (n = 21) underwent conventional treatment for stroke for 40 min/ day, 5 times/ week for 8 weeks. Experimental group (n = 20) received core stability training for additional 15 min along with conventional treatment.

Main measures

Main outcome measures were Trunk impairment scale (TIS), functional ambulation category (FAC), stroke specific quality of life (SSQOL) and trunk range of motion (ROM).

Results

The differences between the control group and experimental group post-treatment were statistically significant for trunk impairment, functional ambulation, quality of life, and frontal plane trunk motion (p-value < 0.05) with higher mean values for core stabilization training. The frontal plane trunk mobility and rotation showed non-significant differences post-treatment (p-value > 0.05).

Conclusion

This study concluded that core stabilization training is better as compared to the conventional physical therapy treatment for improving trunk impairments, functional ambulation and quality of life among patients of stroke. The core stabilization training is also more effective in improving trunk mobility in sagittal plane. This study is registered in Iranian Registry of Clinical Trials IRCT20210614051578N1 and was approved by the local research ethics committee of Riphah International University.
The assessment of a novel lower body resistance garment as a mechanism to increase the training stimulus during running: a randomised cross-over study
Authors: Hoffmann Samantha M. , Di Domenico Isaiah , Collins Paul K.
Published: April 2022

Background

This study examined the physiological and perceived impact of wearing a novel lower body resistance garment during exercise and recovery.

Methods

Using a randomised cross-over design, 15 recreationally-active males performed 2 × 10-min steady-state runs followed by a 10-min passive recovery with concomitant monitoring of oxygen consumption (V̇O2), heart rate (HR) and rating of perceived exertion (RPE; exercise portion only), wearing either the resistance garment (experimental) or running shorts (control).

Results

During exercise, there was a trend for V̇O2 and RPE to be higher (4.5% and 7.7% respectively) in experimental than control (V̇O2: r = 0.24, p > 0.05; RPE: r = 0.32, p > 0.05) and for HR to be lower (− 0.4%, r = − 0.05, p > 0.05). During recovery, V̇O2 and HR tended to be lower (4.7% and 4.3% respectively) in experimental than control (V̇O2: r = − 0.32, p > 0.05; HR: r = − 0.27, p > 0.05).

Conclusions

Though effects were trivial to small, and not statistically significant, these findings provide proof of concept and suggest that this garment design may increase the training stimulus during running and aid post-exercise recovery.
Epigenetics of early-life adversity in youth: cross-sectional and longitudinal associations
Authors: Sumner Jennifer A. , Gambazza Simone , Gao Xu , Baccarelli Andrea A. , Uddin Monica , McLaughlin Katie A.
Published: April 2022

Background

Altered DNA methylation (DNAm) may be one pathway through which early-life adversity (ELA) contributes to adverse mental and physical health outcomes. This study investigated whether the presence versus absence of ELA experiences reflecting the dimensions of threat and deprivation were associated with epigenome-wide DNAm cross-sectionally and longitudinally in a community-based sample of children and adolescents.

Methods

In 113 youths aged 8–16 years with wide variability in ELA, we examined associations of abuse (physical, sexual, emotional; indicating threat-related experiences) and neglect (emotional, physical; indicating deprivation-related experiences) with DNAm assessed with the Illumina EPIC BeadChip array, with DNA derived from saliva. In cross-sectional epigenome-wide analyses, we investigated associations of lifetime abuse and neglect with DNAm at baseline. In longitudinal epigenome-wide analyses, we examined whether experiencing abuse and neglect over an approximately 2-year follow-up were each associated with change in DNAm from baseline to follow-up.

Results

In cross-sectional analyses adjusting for lifetime experience of neglect, lifetime experience of abuse was associated with DNAm for four cytosine-phosphodiester-guanine (CpG) sites (cg20241299: coefficient = 0.023, SE = 0.004; cg08671764: coefficient = 0.018, SE = 0.003; cg27152686: coefficient = − 0.069, SE = 0.012; cg24241897: coefficient = − 0.003, SE = 0.001; FDR < .05). In longitudinal analyses, experiencing neglect over follow-up was associated with an increase in DNAm for one CpG site, adjusting for abuse over follow-up (cg03135983: coefficient = 0.036, SE = 0.006; FDR < .05).

Conclusions

In this study, we identified examples of epigenetic patterns associated with ELA experiences of threat and deprivation that were already observable in youth. We provide novel evidence for change in DNAm over time in relation to ongoing adversity and that experiences reflecting distinct ELA dimensions may be characterized by unique epigenetic patterns.
Clinical trial of insulin-like growth factor-1 in Phelan-McDermid syndrome
Authors: Kolevzon A. , Breen M. S. , Siper P. M. , Halpern D. , Frank Y. , Rieger H. , Weismann J. , Trelles M. P. , Lerman B. , Rapaport R. , Buxbaum J. D.
Published: April 2022

Background

Phelan-McDermid syndrome (PMS) is caused by haploinsufficiency of the SHANK3 gene and is characterized by global developmental delays and autism spectrum disorder (ASD). Based on several converging lines of preclinical and clinical evidence supporting the use of insulin-like growth factor-1 (IGF-1) in PMS, this study aims to follow-up a previous pilot study with IGF-1 to further evaluate this novel therapeutic for core symptoms of ASD in children with PMS.

Methods

Ten children aged 5–9 with PMS were enrolled. Participants were randomized to receive IGF-1 or placebo (saline) using a 12-week, double-blind, crossover design. Efficacy was assessed using the primary outcome of the Aberrant Behavior Checklist—Social Withdrawal (ABC-SW) subscale as well as secondary outcome measures reflecting core symptoms of ASD. To increase power and sample size, we jointly analyzed the effect of IGF-1 reported here together with results from our previous controlled trail of IGF-1 in children with PMS (combined N = 19).

Results

Results on the ABC-SW did not reach statistical significance, however significant improvements in sensory reactivity symptoms were observed. In our pooled analyses, IGF-1 treatment also led to significant improvements in repetitive behaviors and hyperactivity. There were no other statistically significant effects seen across other clinical outcome measures. IGF-1 was well tolerated and there were no serious adverse events.

Limitations

The small sample size and expectancy bias due to relying on parent reported outcome measures may contribute to limitations in interpreting results.

Conclusion

IGF-1 is efficacious in improving sensory reactivity symptoms, repetitive behaviors, and hyperactivity  in children with PMS.

Trial registration NCT01525901.
Renal functional and interstitial fibrotic assessment with non-Gaussian diffusion kurtosis imaging
Authors: Li Anqin , Yuan Guanjie , Hu Yao , Shen Yaqi , Hu Xuemei , Hu Daoyu , Li Zhen
Published: April 2022

Objectives

To evaluate the application value of diffusion kurtosis imaging (DKI) for monitoring renal function and interstitial fibrosis.

Methods

Forty-two patients suspected of having primary nephropathy, hypertension or diabetes with impaired renal function were examined with DKI. DKI metrics of renal cortex and medulla on both sides of each patient were measured, including mean kurtosis (MK), axial kurtosis (Ka), radial kurtosis (Kr), mean diffusivity (MD) and fractional anisotropy (FA). The differences in DKI metrics between stable and impaired estimated glomerular filtration rate (eGFR) patients as well as between mild and severe interstitial fibrosis patients were compared. Correlations of DKI metrics with clinical indicators and pathology were analyzed. Diagnostic performance of DKI to assess the degree of renal dysfunction was analyzed.

Results

Cortical MK, parenchymal Ka, MD and medullary FA were different in stable vs impaired eGFR patients and mild vs severe interstitial fibrosis patients (all p < .05). Negative correlation was found between Ka and eGFR (cortex: r = − 0.579; medulla: r = − 0.603), between MD and interstitial fibrosis (cortex: r = − 0.899; medulla: r = − 0.770), and positive correlation was found between MD and eGFR (cortex: r = 0.411; medulla: r = 0.344), between Ka and interstitial fibrosis (cortex: r = 0.871; medulla: r = 0.844) (all p < .05). DKI combined with mean arterial blood pressure (MAP) and urea showed good diagnostic power for assessing the degree of renal dysfunction (sensitivity: 90.5%; specificity: 89.5%).

Conclusions

Noninvasive DKI has certain application value for monitoring renal function and interstitial fibrosis.
Association of acute hepatitis B and acute myopathy: a case report
Authors: Zangeneh Mehrangiz , Mesgarian Masoomeh , Khosravani-Nezhad Yasamin
Published: April 2022

Background

Hepatitis B virus infection is a global public health problem. Although hepatitis B virus primarily affects hepatocytes, it sometimes develops disease manifestations outside the liver, such as myopathy, which is commonly caused by chronic hepatitis B.

Case presentation

This case report describes a 57-year-old Iranian woman admitted to the hospital with jaundice, fever, body itching, abdominal pain, progressive muscle weakness, icteric sclera, right upper quadrant pain, and decreased muscle force. Examination on the first day of admission revealed that the patient was negative for hepatitis D antibody, positive for hepatitis B core (IgM) antibody, positive for hepatitis B surface antigen, and negative for hepatitis B e antibody but positive for hepatitis B e antigen. Moreover, she showed high levels of hepatitis B virus DNA viral load, creatine kinase, lactate dehydrogenase, serum glutamic-oxaloacetic transaminase, serum glutamic-pyruvic transaminase, total bilirubin, direct bilirubin, and alkaline phosphatase, and electromyography/nerve conduction velocity showed acute myopathic process.

Conclusions

Interestingly, myopathy symptoms improved after improving hepatitis symptoms and decreasing hepatitis B viral load, suggesting a close association between hepatitis B infection and myopathy.
A smooth approximation approach for optimization with probabilistic constraints based on sigmoid function
Authors: Ren Yong H. , Xiong Ying , Yan Yu H. , Gu Jian
Published: April 2022

Many practical problems, such as computer science, communications network, product design, system control, statistics and finance, etc.,can be formulated as a probabilistic constrained optimization problem (PCOP) which is challenging to solve since it is usually nonconvex and nonsmooth. Effective methods for the probabilistic constrained optimization problem mostly focus on approximation techniques, such as convex approximation, D.C. (difference of two convex functions) approximation, and so on. This paper aims at studying a smooth approximation approach. A smooth approximation to the probabilistic constraint function based on a sigmoid function is analyzed. Equivalence of PCOP and the corresponding approximation problem are shown under some appropriate assumptions. Sequential convex approximation (SCA) algorithm is implemented to solve the smooth approximation problem. Numerical results suggest that the smooth approximation approach proposed is effective for optimization problems with probabilistic constraints.
An analysis of the role of HnRNP C dysregulation in cancers
Authors: Mo Liyi , Meng Lijuan , Huang Zhicheng , Yi Lan , Yang Nanyang , Li Guoqing
Published: April 2022

Heterogeneous nuclear ribonucleoproteins C (HnRNP C) is part of the hnRNP family of RNA-binding proteins. The relationship between hnRNP C and cancers has been extensively studied, and dysregulation of hnRNP C has been found in many cancers. According to existing public data, hnRNP C could promote the maturation of new heterogeneous nuclear RNAs (hnRNA s, also referred to as pre-mRNAs) into mRNAs and could stabilize mRNAs, controlling their translation. This paper reviews the regulation and dysregulation of hnRNP C in cancers. It interacts with some cancer genes and other biological molecules, such as microRNAs (miRNAs), long noncoding RNAs (lncRNAs), and double-stranded RNAs (dsRNAs). Even directly binds to them. The effects of hnRNP C on biological processes such as alternative cleavage and polyadenylation (APA) and N6-methyladenosine (m6A) modification differ among cancers. Its main function is regulating stability and level of translation of cancer genes, and the hnRNP C is regarded as a candidate biomarker and might be valuable for prognosis evaluation.
Assessing critical thinking through L2 argumentative essays: an investigation of relevant and salient criteria from raters’ perspectives
Authors: Sato Takanori
Published: April 2022

Although some second language (L2) pedagogical approaches recognize critical thinking (CT) as an important skill, its assessment is challenging because it is not a well-defined construct with varying definitions. This study aimed to identify the relevant and salient features of argumentative essays that allow for the assessment of L2 students’ CT skills. This study implemented a convergent mixed-methods research design, collecting and analyzing both quantitative and qualitative data to collate the results. Five raters assessed 140 causal argumentative essays written by Japanese university students attending Content and Language Integrated Learning courses based on five criteria: Task Achievement, Coherence and Cohesion, Lexical Resource, Grammatical Range and Accuracy, and CT Skills. A standard multiple regression was conducted to examine the relationships among these criteria. Additionally, raters’ written verbal protocols were collected to identify the essay features to be considered when assessing students’ CT skills. The results indicated that raters’ judgments of students’ CT were closely linked to Task Achievement. Furthermore, their assessments were affected by the essay’s relevancy to the question, content development, logicality, and quality of ideas. This study’s findings help to conceptualize CT as a construct and should be incorporated into the assessment criteria of various L2 educational contexts.
Muscle histological changes in a large cohort of patients affected with Becker muscular dystrophy
Authors: Ripolone Michela , Velardo Daniele , Mondello Stefania , Zanotti Simona , Magri Francesca , Minuti Elisa , Cazzaniga Sara , Fortunato Francesco , Ciscato Patrizia , Tiberio Francesca , Sciacco Monica , Moggio Maurizio , Bettica Paolo , Comi Giacomo P.
Published: April 2022

Becker muscular dystrophy (BMD) is a severe X-linked muscle disease. Age of onset, clinical variability, speed of progression and affected tissues display wide variability, making a clinical trial design for drug development very complex. The histopathological changes in skeletal muscle tissue are central to the pathogenesis, but they have not been thoroughly elucidated yet. Here we analysed muscle biopsies from a large cohort of BMD patients, focusing our attention on the histopathological muscle parameters, as fibrosis, fatty replacement, fibre cross sectional area, necrosis, regenerating fibres, splitting fibres, internalized nuclei and dystrophy evaluation. We correlated histological parameters with both demographic features and clinical functional evaluations. The most interesting results of our study are the accurate quantification of fibroadipose tissue replacement and the identification of some histopathological aspects that well correlate with clinical performances. Through correlation analysis, we divided our patients into three clusters with well-defined histological and clinical features. In conclusion, this is the first study that analyses in detail the histological characteristics of muscle biopsies in a large cohort of BMD patients, correlating them to a functional impairment. The collection of these data help to better understand the histopathological progression of the disease and can be useful to validate any pharmacological trial in which the modification of muscle biopsy is utilized as outcome measure.