bluuebunny/crossref_metadata_2025 huggingface dataset:
Scale-up of the Internet-based Professional Learning to help teachers promote Activity in Youth (iPLAY) intervention: a hybrid type 3 implementation-effectiveness trial
Authors: Lubans D R , Sanders T , Noetel M , Parker P , McKay H , Morgan PJ , Salmon J , Kirwan M , Bennie A , Peralta L , Cinelli R , Moodie M , Hartwig T , Boyer J , Kennedy S G , Plotnikoff R C , Hansen V , Vasconcellos D , Lee J , Antczak D , Lonsdale C
Published: December 2022

Background

Whole-of-school programs have demonstrated success in improving student physical activity levels, but few have progressed beyond efficacy testing to implementation at-scale. The purpose of our study was to evaluate the scale-up of the ‘Internet-based Professional Learning to help teachers promote Activity in Youth’ (iPLAY) intervention in primary schools using the RE-AIM framework.

Methods

We conducted a type 3 hybrid implementation-effectiveness study and collected data between April 2016 and June 2021, in New South Wales (NSW), Australia. RE-AIM was operationalised as: (i) Reach: Number and representativeness of students exposed to iPLAY; (ii) Effectiveness: Impact of iPLAY in a sub-sample of students (n = 5,959); (iii) Adoption: Number and representativeness of schools that received iPLAY; (iv) Implementation: Extent to which the three curricular and three non-curricular components of iPLAY were delivered as intended; (v) Maintenance: Extent to which iPLAY was sustained in schools. We conducted 43 semi-structured interviews with teachers (n = 14), leaders (n = 19), and principals (n = 10) from 18 schools (11 from urban and 7 from rural locations) to determine program maintenance.

Results

Reach: iPLAY reached ~ 31,000 students from a variety of socio-economic strata (35% of students were in the bottom quartile, almost half in the middle two quartiles, and 20% in the top quartile). Effectiveness: We observed small positive intervention effects for enjoyment of PE/sport (0.12 units, 95% CI: 0.05 to 0.20, d = 0.17), perceptions of need support from teachers (0.26 units, 95% CI: 0.16 to 0.53, d = 0.40), physical activity participation (0.28 units, 95% CI: 0.10 to 0.47, d = 0.14), and subjective well-being (0.82 units, 95% CI: 0.32 to 1.32, d = 0.12) at 24-months. Adoption: 115 schools received iPLAY. Implementation: Most schools implemented the curricular (59%) and non-curricular (55%) strategies as intended. Maintenance: Based on our qualitative data, changes in teacher practices and school culture resulting from iPLAY were sustained.

Conclusions

iPLAY had extensive reach and adoption in NSW primary schools. Most of the schools implemented iPLAY as intended and effectiveness data suggest the positive effects observed in our cluster RCT were sustained when the intervention was delivered at-scale.

Trial registration

ACTRN12621001132831.
Effectiveness of interventions to increase device-measured physical activity in pregnant women: systematic review and meta-analysis of randomised controlled trials
Authors: Sharp Kayleigh J. , Sherar Lauren B. , Kettle Victoria E. , Sanders James P. , Daley Amanda J.
Published: December 2022

Background

Interventions that provide pregnant women with opportunities to access and participate in physical activity have been shown to be beneficial to their health. Much of this evidence however has been based on self-reported physical activity data, which may be prone to inflated effects due to recall bias and social desirability bias. No previous synthesis of randomised controlled trials has assessed the effectiveness of these interventions using only device measured data, to assess their health benefits more accurately in pregnant women. This systematic review and meta-analysis aimed to address this evidence gap.

Data sources

Cochrane Central Register of Controlled Trials, Medline, SportDiscus, APA PsycINFO, Embase and Web of Science databases were queried from inception up to December 2, 2021. An updated search of PubMed was conducted on May 16, 2022.

Study eligibility criteria

Randomised controlled trials that recruited pregnant women, participating in any physical activity intervention (excluding interventions aimed entirely at body conditioning), compared with standard antenatal care (comparators), using device-measured total physical activity as an outcome were eligible for inclusion.

Methods

3144 titles and abstracts were screened for eligibility, and 18 met the inclusion criteria. Data were analysed using random effect models, (standardised mean difference and mean difference), using data from baseline to last available follow-up (primary end point), and until between 24 to 30 weeks gestation. Gestational weight gain was also assessed at these timepoints in the included trials.

Results

No significant differences between the groups were found for total physical activity at last available follow-up or 24 to 30 weeks gestation (95% CI 0.03 to 0.27,p = 0.10: 95% CI -0.05 to 0.33,p = 0.15) respectively. On average, pregnant women randomised to a physical activity intervention completed 435 and 449 more steps per day than comparators at last available follow-up and at 24 to 30 weeks gestation (95% CI -0.5-870.6,p = 0.05: 95% CI 5.5-892.7,p = 0.05) respectively. Intervention participants also gained 0.69 kg less (95% CI -1.30 to -0.08,p = 0.03) weight than comparators.

Conclusion

Based on device-measured data, interventions to promote physical activity during pregnancy have small but important effects on increasing physical activity and managing excessive gestational weight gain.
Development and psychometric evaluation of the High-Risk Pregnancy Well-Being Index in Mashhad: a methodological study
Authors: Mirzakhani Kobra , Khadivzadeh Talat , Faridhosseini Farhad , Ebadi Abbas
Published: December 2022

Background

Assessment of well-being in high-risk pregnancy (HRP) is the key to achieve positive maternal and fetal outcomes. Although there are a wide range of instruments for well-being assessment, none of them is comprehensive for well-being assessment in HRP. The present study aimed at the development and psychometric evaluation of the High-Risk Pregnancy Well-Being Index (HRPWBI).

Methods

This methodological study was conducted using the Waltz’s four-step method. The dimensions of well-being in HRP were determined based on a conceptual model and the blueprint and the item pool of HRPWBI were developed. Then, the face and the content validity were assessed and item analysis was performed. Construct validity was also assessed through exploratory factor analysis with principal component analysis on the data obtained from 376 women with HRP in Mashhad, Iran. Finally, internal consistency, test–retest stability, sensitivity, and interpretability of HRPWBI were assessed.

Results

The scale- content validity index (SCVI) of HRPWBI was 0.91. In factor analysis, 33 items were loaded on seven factors which explained 53.77% of the total variance. Internal consistency, relative stability, absolute stability, sensitivity, and interpretability of HRPWBI were confirmed with a Cronbach’s alpha of 0.84, a test–retest intraclass correlation coefficient of 0.97, a standard error of measurement of 0.92, a minimal detectable change of 8.09, and a minimal important change of 2.92, respectively.

Conclusion

HRPWBI is a valid and reliable instrument for well-being assessment among women with HRP. It can be used to assess well-being and the effects of well-being improvement interventions on well-being among women with HRP.
CRISPR/Cas9: a tool to eradicate HIV-1
Authors: Bhowmik Ruchira , Chaubey Binay
Published: December 2022

The development of antiretroviral therapy (ART) has been effective in suppressing HIV replication. However, severe drug toxicities due to the therapy and its failure in targeting the integrated proviral genome have led to the introduction of a new paradigm of gene-based therapies. With its effective inhibition and high precision, clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein-9 nuclease (Cas9) or CRISPR/Cas9 has emerged as an effective genome editing tool in the last decade. Mediated by guide RNAs (gRNAs), Cas9 endonuclease acts like genetic scissors that can modify specific target sites. With this concept, CRISPR/Cas9 has been used to target the integrated proviral HIV-1 genome both in in vitro as well as in vivo studies including non-human primates. The CRISPR has also been tested for targeting latent HIV-1 by modulating the proviral transcription with the help of a specialized Cas9 mutant. Overcoming the limitations of the current therapy, CRISPR has the potential to become the primary genome editing tool for eradicating HIV-1 infection. In this review, we summarize the recent advancements of CRISPR to target the proviral HIV-1 genome, the challenges and future prospects.
Identification of a neutralizing linear epitope within the VP1 protein of coxsackievirus A10
Authors: Zhu Hanyu , Liu Xin , Wu Yue , He Yunyi , Zheng Huanying , Liu Hongbo , Liu Qiliang
Published: December 2022

Background

Coxsackievirus A10 (CV-A10) is a leading cause of hand, foot, and mouth disease (HFMD). It is necessary to identify neutralizing epitopes to investigate and develop an epitope-based vaccine against CV-A10. The viral protein VP1 is the immunodominant capsid protein and contains the critical neutralizing epitope. However, neutralizing epitopes within VP1 protein of CV-A10 have not been well characterized.

Methods

Bioinformatics techniques were applied to predict linear epitopes on the CV-A10 VP1 protein. The advanced structural features of epitopes were analyzed by three-dimensional (3D) modeling. The anticipated epitope peptides were synthesized and used to immunize mice as antigens. ELISA and micro-neutralization assay were used to determine the specific IgG antibody and neutralizing antibody titers. The protective efficacy of the epitope peptides in vivo was evaluated using a passive immunization/challenge assay.

Results

Three linear epitopes (EP3, EP4, and EP5) were predicted on CV-A10 VP1, all spatially exposed on the capsid surface, and exhibited adequate immunogenicity. However, only EP4, corresponding to residues 162–176 of VP1, demonstrated potent neutralization against CV-A10. To determine the neutralizing capacity of EP4 further, EP4 double-peptide was synthesized and injected into mice. The mean neutralizing antibody titer of the anti-EP4 double-peptide sera was 1:50.79, which provided 40% protection against lethal infection with CV-A10 in neonatal mice. In addition, sequence and advanced structural analysis revealed that EP4 was highly conserved among representative strains of CV-A10 and localized in the EF loop region of VP1, like EV-A71 SP55 or CV-A16 PEP55.

Conclusions

These data demonstrate that EP4 is a specific linear neutralizing epitope on CV-A10 VP1. Its protective efficacy can be enhanced by increasing its copy number, which will be the foundation for developing a CV-A10 epitope-based vaccine.
A family-based study of genetic and epigenetic effects across multiple neurocognitive, motor, social-cognitive and social-behavioral functions
Authors: Nudel Ron , Zetterberg Richard , Hemager Nicoline , Christiani Camilla A. J. , Ohland Jessica , Burton Birgitte K. , Greve Aja N. , Spang Katrine S. , Ellersgaard Ditte , Gantriis Ditte L. , Bybjerg-Grauholm Jonas , Plessen Kerstin J. , Jepsen Jens Richardt M. , Thorup Anne A. E. , Werge Thomas , Mors Ole , Nordentoft Merete
Published: December 2022

Many psychiatric and neurodevelopmental disorders are known to be heritable, but studies trying to elucidate the genetic architecture of such traits often lag behind studies of somatic traits and diseases. The reasons as to why relatively few genome-wide significant associations have been reported for such traits have to do with the sample sizes needed for the detection of small effects, the difficulty in defining and characterizing the phenotypes, partially due to overlaps in affected underlying domains (which is especially true for cognitive phenotypes), and the complex genetic architectures of the phenotypes, which are not wholly captured in traditional case–control GWAS designs. We aimed to tackle the last two issues by performing GWASs of eight quantitative neurocognitive, motor, social-cognitive and social-behavioral traits, which may be considered endophenotypes for a variety of psychiatric and neurodevelopmental conditions, and for which we employed models capturing both general genetic association and parent-of-origin effects, in a family-based sample comprising 402 children and their parents (mostly family trios). We identified 48 genome-wide significant associations across several traits, of which 3 also survived our strict study-wide quality criteria. We additionally performed a functional annotation of implicated genes, as most of the 48 associations were with variants within protein-coding genes. In total, our study highlighted associations with five genes (TGM3, CACNB4, ANKS1B, CSMD1 and SYNE1) associated with measures of working memory, processing speed and social behavior. Our results thus identify novel associations, including previously unreported parent-of-origin associations with relevant genes, and our top results illustrate new potential gene → endophenotype → disorder pathways.
Children’s inhibition skills are associated with their P3a latency—results from an exploratory study
Authors: Linnavalli Tanja , Lahti Outi , Törmänen Minna , Tervaniemi Mari , Cowley Benjamin Ultan
Published: December 2022

Background

The P3a response is thought to reflect involuntary orienting to an unexpected stimulus and has been connected with set-shifting and inhibition in some studies. In our exploratory study, we investigated if the amplitude and the latency of the P3a response were associated with the performance in a modified flanker task measuring inhibition and set-shifting in 10-year-old children (N = 42). Children participated in electroencephalography (EEG) measurement with an auditory multifeature paradigm including standard, deviating, and novel sounds. In addition, they performed a separate flanker task requiring inhibition and set-shifting skills.

Results

The P3a latencies for deviant sounds were associated with the reaction time reflecting inhibition: the shorter the response latencies were, the faster the reaction time was. The P3a latencies for novel sounds were not linked to the reaction times reflecting either inhibition or set-shifting. In addition, the magnitude of the P3a response was not associated with the performance in the flanker task.

Conclusions

Our results suggest that P3a response latency and reaction speed reflecting inhibitory skills are based on shared neural mechanism. Thus, the present study brings new insight to the field investigating the associations between behavior and its neural indices.
Efficacy and safety of percutaneous endoscopic cervical discectomy for cervical disc herniation: a systematic review and meta-analysis
Authors: Zhang Jinjie , Zhou Qiujun , Yan Yan , Ren Jianlei , Wei Shenyu , Zhu Haijia , Song Zhoufeng
Published: December 2022

Background

Since there are currently no systematic evidence-based medical data on the efficacy and safety of PECD, this meta-analysis pooled data from studies that reported the efficacy or safety of PECD for cervical disc herniation to examine the efficacy, recurrence and safety of using PECD to treat cervical disc herniation.

Methods

We searched the PubMed, EMBASE and Cochrane Library databases for studies published from inception to July 2022. Nine nonrandomized controlled trials (non-RCTs) that reported the efficacy or safety of percutaneous endoscopic cervical discectomy for cervical disc herniation were included. We excluded duplicate publications, studies without full text, studies with incomplete information, studies that did not enable us to conduct data extraction, animal experiments and reviews. STATA 15.1 software was used to analyse the data.

Results

The proportions of excellent and good treatment results after PECD for CDH were 39% (95% CI: 31–48%) and 47% (95% CI: 34–59%), respectively. The pooled results showed that the VAS scores at 1 week post-operatively (SMD = −2.55, 95% CI: − 3.25 to − 1.85) and at the last follow-up (SMD = − 4.30, 95% CI: − 5.61 to − 3.00) after PECD for cervical disc herniation were significantly lower than the pre-operative scores. The recurrence rate of neck pain and the incidence of adverse events after PECD for cervical disc herniation were 3% (95% CI: 1–6%) and 5% (95% CI: 2–9%), respectively. Additionally, pooled results show that the operative time (SMD = − 3.22, 95% CI: − 5.21 to − 1.43) and hospital stay (SMD = − 1.75, 95% CI: − 2.67to − 0.84) were all significantly lower for PECD than for ACDF. The pooled results also showed that the proportion of excellent treatment results was significantly higher for PECD than for ACDF (OR = 2.29, 95% CI: 1.06–4.96).

Conclusion

PECD has a high success rate in the treatment of CHD and can relieve neck pain, and the recurrence rate and the incidence of adverse events are low. In addition, compared with ACDF, PECD has a higher rate of excellent outcomes and a lower operative time and hospital stay. PECD may be a better option for treating CHD.
Factors affecting titanium mesh cage subsidence in single-level anterior cervical corpectomy and fusion for ossification of the posterior longitudinal ligament
Authors: Tang Yifan , Geng Xiangwu , Li Fengning , Sun Yanqing , Jia Lianshun , Zhou Shengyuan , Chen Xiongsheng
Published: December 2022

Purpose

To analyze risk factors of titanium mesh cage (TMC) subsidence in single-level anterior cervical corpectomy and fusion (ACCF) for cervical ossification of the posterior longitudinal ligament (OPLL).

Methods

TMC subsidence is defined as the reduction of the adjacent vertebral bodies by ≥ 2 mm. Patients with cervical OPLL who were treated with single-level ACCF between January 2019 and May 2021 were retrospectively analyzed in two groups: patients with TMC subsidence as Group S and patients with no TMC subsidence as Group N during the one-year follow-up period. The degree of distraction of surgical segment and correction of the cervical curvature was measured to analyze their relationship with TMC subsidence.

Results

A total of 128 patients were included in Group S, and 138 patients were included in Group N. There was no significant difference in patient demographics and complications between the two groups. The degree of distraction in Group S was significantly higher than that in Group N (11.4% ± 7.6% vs. 4.7% ± 9.7%, P < 0.01). The change of C2 to C7 Cobb angle (α) in Group S was significantly greater than that in Group N (5.7 ± 2.7 vs. 1.4 ± 4.7, P < 0.01), and the change of interspinous process distance (SPD) in Group S was also significantly greater than that in Group N (7.0 ± 4.2 vs. 4.1 ± 2.7, P < 0.01). The JOA score and JOA recovery rate were not statistically different between the two groups.

Conclusions

Intraoperative selection of overlength TMC in single-level ACCF for OPLL, over-distraction and excessive correction of the cervical curvature may cause TMC subsidence after surgery. No significant impact of TMC subsidence on the surgical outcome was observed during the 1-year follow-up period.
Efficacy of electroacupuncture in assisting postoperative healing of distal radius fractures: study protocol for a randomized controlled trial
Authors: Fu Jiani , Cai Xiaowen , Ouyang Huailiang , Gong Chunzhu , Huang Yong
Published: December 2022

Background

Manual reduction and surgical treatment are common methods for distal radius fractures (DRFs). The existing literature suggests that postoperative combined rehabilitation treatment and medication are effective for the healing of DRFs. However, the side effects of these treatments remain to be solved. Previous studies have shown that electroacupuncture (EA) can effectively relieve wrist swelling and improve the joint function in patients with DRFs, but more evidence is needed to prove the effectiveness of EA. This trial aims to explore the efficiency and feasibility of combined EA treatment in postoperative treatment of DRFs compared with routine treatment.

Methods

This is a parallel randomized controlled trial. A total of 222 patients diagnosed with moderate DRFs will be recruited and randomly assigned to an EA group or a routine treatment group at a ratio of 1:1. Routine treatment group will receive medication and rehabilitation. Yangxi (LI 5), Yangchi (TE 4), Yanggu (SI 5), Hegu (LI 4), and Taiyuan (LU 9) will be selected in the EA group for intervention three times a week on the basis of routine treatment. Both groups will receive 8 weeks of treatment and 4 weeks of follow-up. The primary outcome will be ulnar positive variance. The secondary outcomes will include radiographic healing rate, bone strength, hemorheological indices, serum biochemical indicators and inflammatory factors, grip strength, wrist swelling score, patient-rated wrist evaluation, disabilities of arm, shoulder and hand, and visual analogue scale. Outcomes will be evaluated at baseline, postoperative 3rd day, 2nd, 4th, 6th, 8th, and 12th weeks.

Discussion

The results of this study will help establish a more optimized scheme to treat patients with DRFs.

Trial registration Chinese Clinical Trial Registry ChiCTR2200062857. Registered on 21 August 2022, www.chictr.org.cn/com/25/showproj.aspx?proj=175567.
Personalization of IVF-ICSI workflow based on patient characteristics improves IVF laboratory outcomes and embryo ploidy by PGT-A
Authors: Wyse Brandon A. , Fuchs Weizman Noga , Montbriand Janice , Kharonsky Rima , Antes Ran , Abramov Rina , Madjunkova Svetlana , Librach Clifford L.
Published: December 2022

Background

Intracytoplasmic sperm injection (ICSI) has become a common method of fertilization in assisted reproduction worldwide. However, there are still gaps in knowledge of the ideal IVF-ICSI workflow including the optimal duration of time between induction of final oocyte maturation, oocyte denudation and ICSI. The aim of this study was to examine outcomes following different workflow protocols in IVF-ICSI procedures in blastocysts that have undergone undisturbed incubation and preimplantation genetic testing for aneuploidy (PGT-A) prior to transfer.

Methods

Retrospective secondary analysis of 113 patients (179 IVF cycles, 713 embryos), all of whom have gone through IVF-ICSI and PGT-A using undisturbed culture. Predictive test variables were the length of time from: trigger to OPU, OPU to denudation, and denudation to ICSI. Outcome metrics assessed were: maturation, fertilization, blastulation and euploid rates. Generalized Estimated Equations Linear Model was used to examine the relationship between key elements of a given cycle and continuous outcomes and LOESS curves were used to determine the effect over time.

Results

In a paired multi-regression analysis, where each patient served as its own control, delaying OPU in patients with unexplained infertility improved both maturation and blastulation rates (b = 29.7, p < 0.0001 and b = 9.1, p = 0.06, respectively). Longer incubation with cumulus cells (CCs) significantly correlated with improved ploidy rates among patients under 37, as well as among patients with unexplained infertility (r = 0.22 and 0.29, respectively), which was also evident in a multiple regression analysis (b = 6.73, p < 0.05), and in a paired analysis (b = 6.0, p < 0.05). Conversely, among patients with a leading infertility diagnosis of male factor, longer incubation of the denuded oocyte prior to ICSI resulted in a significantly higher euploid rate (b = 15.658, p < 0.0001).

Conclusions

In this study we have demonstrated that different IVF-ICSI workflows affect patients differently, depending on their primary infertility diagnosis. Thus, ideally, the IVF-ICSI workflow should be tailored to the individual patient based on the primary infertility diagnosis. This study contributes to our understanding surrounding the impact of IVF laboratory procedures and highlights the importance of not only tracking “classic” IVF outcomes (maturation, fertilization, blastulation rates), but highlights the importance that these procedures have on the ploidy of the embryo.
Prophylactic surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC CO2) versus standard surgery for gastric carcinoma at high risk of peritoneal carcinomatosis: short and long-term outcomes (GOETH STUDY)—a collaborative randomized controlled trial by ACOI, FONDAZIONE AIOM, SIC, SICE, and SICO
Authors: Di Giorgio A. , Gerardi C. , Abatini C. , Melotti G. , Bonavina L. , Torri V. , Santullo F. , Garattini S. , De Luca M. , Rulli Erica , Rulli Eliana , Pacelli F. ,   GOETH Investigators
Published: December 2022

Introduction

At the time of diagnosis, 15–20% of gastric carcinomas are in stage T4 or T4b. Furthermore, 5–20% of patients undergoing potentially curative surgery suffer from synchronous or metachronous peritoneal metastases. To date, neither surgery nor systemic chemotherapy successfully controls peritoneal dissemination, offering a limited impact on survival. Peritoneal metastases are in fact responsible for death in around 60% of gastric cancer patients.

Several Eastern studies in the past have focused on hyperthermic intraperitoneal chemotherapy (HIPEC) as a prophylactic measure in patients with serosal extension, nodal involvement, and positive peritoneal fluid cytology. Therefore, a new multimodal therapeutic strategy based on aggressive surgery plus new locoregional treatment may prolong survival in this particular clinical scenario.

Methods

This study compares the efficacy of prophylactic surgery (radical gastric resection, appendectomy, resection of the round ligament of the liver, and bilateral adnexectomy) plus hybrid CO2 HIPEC system versus standard surgery in patients with T3-T4 N0-N + gastric adenocarcinoma. Patients will be randomly assigned (1:1 ratio) to the experimental arm or standard surgery. The primary endpoint is to establish the difference in disease-free survival between the groups. The secondary objective is to compare the safety and tolerability of prophylactic surgery plus HIPEC CO2 versus standard surgery.

Discussion

Considering the poor prognosis of patients with peritoneal dissemination from gastric cancer, a prophylactic strategy to prevent peritoneal metastases may be beneficial. In patients with gastric cancer at high risk of peritoneal carcinomatosis, we propose aggressive surgical treatment with radical gastrectomy, removal of organs at risk of harbouring tumour cells, and HIPEC.

Trial registration

ClinicalTrials.gov NCT03917173. Registered on 16 April 2019.

Protocol version: v1, March 27, 2019.

Protocol number: IRFMN-GCC-7813.

EudraCT number: 2019–001478-27.
An explorative epigenome-wide association study of plasma renin and aldosterone concentration in a Ghanaian population: the RODAM study
Authors: van der Linden Eva L. , Halley Adrienne , Meeks Karlijn A. C. , Chilunga Felix , Hayfron-Benjamin Charles , Venema Andrea , Garrelds Ingrid M. , Danser A. H. Jan , van den Born Bert-Jan , Henneman Peter , Agyemang Charles
Published: December 2022

Background

The epigenetic regulation of the renin–angiotensin–aldosterone system (RAAS) potentially plays a role in the pathophysiology underlying the high burden of hypertension in sub-Saharan Africans (SSA). Here we report the first epigenome-wide association study (EWAS) of plasma renin and aldosterone concentrations and the aldosterone-to-renin ratio (ARR).

Methods

Epigenome-wide DNA methylation was measured using the Illumina 450K array on whole blood samples of 68 Ghanaians. Differentially methylated positions (DMPs) were assessed for plasma renin concentration, aldosterone, and ARR using linear regression models adjusted for age, sex, body mass index, diabetes mellitus, hypertension, and technical covariates. Additionally, we extracted methylation loci previously associated with hypertension, kidney function, or that were annotated to RAAS-related genes and associated these with renin and aldosterone concentration.

Results

We identified one DMP for renin, ten DMPs for aldosterone, and one DMP associated with ARR. Top DMPs were annotated to the PTPRN2, SKIL, and KCNT1 genes, which have been reported in relation to cardiometabolic risk factors, atherosclerosis, and sodium-potassium handling. Moreover, EWAS loci previously associated with hypertension, kidney function, or RAAS-related genes were also associated with renin, aldosterone, and ARR.

Conclusion

In this first EWAS on RAAS hormones, we identified DMPs associated with renin, aldosterone, and ARR in a SSA population. These findings are a first step in understanding the role of DNA methylation in regulation of the RAAS in general and in a SSA population specifically. Replication and translational studies are needed to establish the role of these DMPs in the hypertension burden in SSA populations.
Rehabilitation in the long-term care insurance domain: a scoping review
Authors: Shinohara Hiroshi , Mikami Yukio , Kuroda Rumi , Asaeda Makoto , Kawasaki Takashi , Kouda Ken , Nishimura Yukihide , Ohkawa Hiroyuki , Uenishi Hiroyasu , Shimokawa Toshio , Mikami Yasuo , Tajima Fumihiro , Kubo Toshikazu
Published: December 2022

Purpose

Since the enactment of the long-term care insurance (LTCI) act in 2000, the number of LTCI users has increased annually. However, evidence regarding what is being carried out as rehabilitation treatment under LTCI is lacking. In this study, a scoping review was performed to bridge this knowledge gap.

Methods

Articles related to rehabilitation in connection with LTCI published between April 2000 and November 2020 were searched for in PubMed, CINAHL, CENTRAL (Cochrane Central Register of Controlled Trials), Ichushi Web Ver.5, and CiNii and randomized controlled trials (RCTs) of rehabilitation provided under LTCI were examined.

Results

Of the 15,572 publications identified, 15 RCTs, including rehabilitation treatment by physiatrists and therapists, met the eligibility criteria of our review and were included. The rehabilitation trials in the 15 RCTs varied and included balance training, exercise therapy, cognitive tasks, and activities such as singing and dancing. The results allowed us to focus on three categories: fall prevention, dementia, and theory and tools interventions related to occupational therapy practice.

Conclusion

The focal points of attention in the rehabilitation treatment of LTCI were identified. However, the physical function, quality of life, and activities of daily living (ADL) of those who “need support” vary from person to person. Therefore, the consolidation of evidence on rehabilitation treatment of LTCI must be continued.
The Systematic Review Toolbox: keeping up to date with tools to support evidence synthesis
Authors: Johnson Eugenie Evelynne , O’Keefe Hannah , Sutton Anthea , Marshall Christopher
Published: December 2022

Background

The Systematic Review (SR) Toolbox was developed in 2014 to collate tools that can be used to support the systematic review process. Since its inception, the breadth of evidence synthesis methodologies has expanded greatly. This work describes the process of updating the SR Toolbox in 2022 to reflect these changes in evidence synthesis methodology. We also briefly analysed included tools and guidance to identify any potential gaps in what is currently available to researchers.

Methods

We manually extracted all guidance and software tools contained within the SR Toolbox in February 2022. A single reviewer, with a second checking a proportion, extracted and analysed information from records contained within the SR Toolbox using Microsoft Excel. Using this spreadsheet and Microsoft Access, the SR Toolbox was updated to reflect expansion of evidence synthesis methodologies and brief analysis conducted.

Results

The updated version of the SR Toolbox was launched on 13 May 2022, with 235 software tools and 112 guidance documents included. Regarding review families, most software tools (N = 223) and guidance documents (N = 78) were applicable to systematic reviews. However, there were fewer tools and guidance documents applicable to reviews of reviews (N = 66 and N = 22, respectively), while qualitative reviews were less served by guidance documents (N = 19). In terms of review production stages, most guidance documents surrounded quality assessment (N = 70), while software tools related to searching and synthesis (N = 84 and N = 82, respectively). There appears to be a paucity of tools and guidance relating to stakeholder engagement (N = 2 and N = 3, respectively).

Conclusions

The SR Toolbox provides a platform for those undertaking evidence syntheses to locate guidance and software tools to support different aspects of the review process across multiple review types. However, this work has also identified potential gaps in guidance and software that could inform future research.
Coordinated transcriptional and post-transcriptional epigenetic regulation during skeletal muscle development and growth in pigs
Authors: Zhang Du , Wu Shumei , Zhang Xinxin , Ren Shuqiang , Tang Zhonglin , Gao Fei
Published: December 2022

Background

N6-methyladenosine (m6A) and DNA 5-methylcytosine (5mC) methylation plays crucial roles in diverse biological processes, including skeletal muscle development and growth. Recent studies unveiled a potential link between these two systems, implicating the potential mechanism of coordinated transcriptional and post-transcriptional regulation in porcine prenatal myogenesis and postnatal skeletal muscle growth.

Methods

Immunofluorescence and co-IP assays were carried out between the 5mC writers and m6A writers to investigate the molecular basis underneath. Large-scale in-house transcriptomic data were compiled for applying weighted correlation network analysis (WGCNA) to identify the co-expression patterns of m6A and 5mC regulators and their potential role in pig myogenesis. Whole-genome bisulfite sequencing (WGBS) and methylated RNA immunoprecipitation sequencing (MeRIP-seq) were performed on the skeletal muscle samples from Landrace pigs at four postnatal growth stages (days 30, 60, 120 and 180).

Results

Significantly correlated expression between 5mC writers and m6A writers and co-occurrence of 5mC and m6A modification were revealed from public datasets of C2C12 myoblasts. The protein-protein interactions between the DNA methylase and the m6A methylase were observed in mouse myoblast cells. Further, by analyzing transcriptome data comprising 81 pig skeletal muscle samples across 27 developmental stages, we identified a 5mC/m6A epigenetic module eigengene and decoded its potential functions in pre- or post-transcriptional regulation in postnatal skeletal muscle development and growth of pigs. Following integrative multi-omics analyses on the WGBS methylome data and MeRIP-seq data for both m6A and gene expression profiles revealed a genome/transcriptome-wide correlated dynamics and co-occurrence of 5mC and m6A modifications as a consequence of 5mC/m6A crosstalk in the postnatal myogenesis progress of pigs. Last, we identified a group of myogenesis-related genes collaboratively regulated by both 5mC and m6A modifications in postnatal skeletal muscle growth in pigs.

Conclusions

Our study discloses a potential epigenetic mechanism in skeletal muscle development and provides a novel direction for animal breeding and drug development of related human muscle-related diseases.
Gut dysbiosis induces the development of mastitis through a reduction in host anti-inflammatory enzyme activity by endotoxemia
Authors: Zhao Caijun , Hu Xiaoyu , Bao Lijuan , Wu Keyi , Zhao Yihong , Xiang Kaihe , Li Shuang , Wang Ying , Qiu Min , Feng Lianjun , Meng Xiangyue , Zhang Naisheng , Fu Yunhe
Published: December 2022

Background

Mounting experimental evidence has shown that the gut microbiota plays a significant role in the pathogenesis of mastitis, and clinical investigations have found that the occurrence of mastitis is correlated with ruminal dysbiosis. However, the underlying mechanism by which the ruminal microbiota participates in the development of mastitis remains unknown.

Results

In the present study, we found that cows with clinical mastitis had marked systemic inflammation, which was associated with significant ruminal dysbiosis, especially enriched Proteobacteria in the rumen. Ruminal microbiota transplantation from mastitis cows (M-RMT) to mice induced mastitis symptoms in recipient mice along with increased mammary proinflammatory signature activation of the TLR4-cGAS-STING-NF-κB/NLRP3 pathways. M-RMT also induced mucosal inflammation and impaired intestinal barrier integrity, leading to increased endotoxemia and systemic inflammation. Moreover, we showed that M-RMT mirrored ruminal microbiota disruption in the gut of recipient mice, as evidenced by enriched Proteobacteria and similar bacterial functions, which were correlated with most proinflammatory parameters and serum lipopolysaccharide (LPS) levels in mice. Recurrent low-grade LPS treatment mirrored gut dysbiosis-induced endotoxemia and caused severe mastitis in mice. Furthermore, we found that gut dysbiosis-derived LPS reduced host alkaline phosphatase activity by activating neuraminidase (Neu), which facilitates low-grade LPS exposure and E. coli-induced mastitis in mice. Conversely, treatment with calf intestinal alkaline phosphatase or the Neu inhibitor zanamivir alleviated low-grade LPS exposure and E. coli-induced mastitis in mice.

Conclusions

Our results suggest that ruminal dysbiosis-derived low-grade endotoxemia can cause mastitis and aggravate pathogen-induced mastitis by impairing host anti-inflammatory enzymes, which implies that regulating the ruminal or gut microbiota to prevent low-grade systemic inflammation is a potential strategy for mastitis intervention.
Celecoxib activates autophagy by inhibiting the mTOR signaling pathway and prevents apoptosis in nucleus pulposus cells
Authors: Chen Weisin , Yasen Miersalijiang , Wang Hanquan , Zhuang Chenyang , Wang Zixiang , Lu Shunyi , Jiang Libo , Lin Hong
Published: December 2022

Background

Intervertebral disc degeneration results from a variety of etiologies, including inflammation and aging. Degenerated intervertebral discs feature down-regulated extracellular matrix synthesis, resulting in losing their ability to retain water and absorb compression. Celecoxib is a well-known selective cyclooxygenase-2 inhibitor for treating arthritis and relieving pain. Nevertheless, the mechanism of Celecoxib for treating inflammation-related intervertebral disc degeneration has not yet been clarified.

Method

Protein synthesis was analyzed by western blot. Fluorescent probes DCFH-DA and MitoSox Red detected reactive oxygen species and were measured by flow cytometry. The activity of the kinase pathway was evaluated by protein phosphorylation. Autophagy was monitored by mRFP-GFP-LC3 transfection and LC3 analysis. Mitochondrial apoptotic proteins were analyzed by western blot and cell membrane integrity was measured by flow cytometry. The autophagic gene was silenced by siRNA.

Results

In this study, interleukin-1β stimulation reduced the synthesis of aggrecan, type I and II collagen and caused excessive production of reactive oxygen species. We looked for a therapeutic window of Celecoxib for nucleus pulposus cells to regain extracellular matrix synthesis and reduce oxidative stress. To look into nucleus pulposus cells in response to stimuli, enhancement of autophagy was achieved by Celecoxib, confirmed by mRFP-GFP-LC3 transfection and LC3 analysis. The mammalian target of rapamycin and a panel of downstream proteins responded to Celecoxib and propelled autophagy machinery to stabilize homeostasis. Ultimately, inhibition of autophagy by silencing autophagy protein 5 disrupted the protective effects of Celecoxib, culminating in apoptosis.

Conclusion

In summary, we have demonstrated a new use for the old drug Celecoxib that treats intervertebral disc degeneration by enhancing autophagy in nucleus pulposus cells and opening a door for treating other degenerative diseases.
Comparison of efficacy and safety of intravitreal ranibizumab and conbercept before vitrectomy in Chinese proliferative diabetic retinopathy patients: a prospective randomized controlled trial
Authors: Li Siying , Guo Lili , Zhou Pingping , Tang Jiyang , Wang Zongyi , Zhang Linqi , Zhao Mingwei , Qu Jinfeng
Published: December 2022

Background

To compare the efficacy and safety of preoperative intravitreal injections of ranibizumab and conbercept in Chinese proliferative diabetic retinopathy (PDR) patients.

Methods

This prospective randomized controlled trial enrolled 90 eyes of 80 patients with PDR. Forty-four eyes of 40 patients that received intravitreal ranibizumab (IVR) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVR group. Forty-six eyes of 40 patients that received intravitreal conbercept (IVC) injections (0.5 mg/0.05 mL) before vitreous surgeries were assigned to the IVC group. Intraoperative and postoperative indices were assessed for further comparison between the two groups.

Results

There were no statistically significant differences in all surgery indices, including intraoperative indices (surgery time, P = 0.225; intraoperative bleeding, P = 0.808; endodiathermy use, P = 0.693; incidence of iatrogenic retinal breaks, P = 0.740; relaxing retinotomy, P = 0.682; retinal reattachment, P = 0.682 and silicone oil tamponade, P = 0.814) and postoperative indices (postoperative vitreous hemorrhage (VH), P = 0.808; neovascular glaucoma (NVG), P = 0.964; recurrent retinal detachment, P = 0.531; postoperative fibrovascular proliferation progression, P = 0.682 and reoperation, P = 0.955) between the two groups. There were no statistically significant differences in best-corrected visual acuity (BCVA) at each follow-up visit (P = 0.939, 0.669, 0.741 and 0.717, respectively) or in central retinal thickness (CRT) (P = 0.976, 0.699, 0.551 and 0.686, respectively). As for safety profile, both groups had no ocular or system adverse events during the observation period.

Conclusions

IVR and IVC as a pretreatment of vitrectomy had similar efficacy and safety profile for Chinese PDR patients.

Trial registration: Registered at ClinicalTrials.gov (NCT05414149).
In vitro evaluation of gentamicin activity against Spanish field isolates of Brachyspira hyodysenteriae
Authors: Vega Clara , Pérez-Pérez Lucía , Argüello Héctor , Gómez-García Manuel , Puente Héctor , Fernández-Usón Ignacio , Rubio Pedro , Carvajal Ana
Published: December 2022

Background

The treatment of swine dysentery (SD) has become constrained in recent years due to the limited availability of effective drugs combined with a rise in antimicrobial resistance. Gentamicin, an aminoglycoside antibiotic, is authorised for the control of this disease in several European countries but has not been extensively used so far. In this study, the in vitro susceptibility of 56 Brachyspira hyodysenteriae field isolates was evaluated against gentamicin using a broth microdilution test. The molecular basis of decreased susceptibility to gentamicin was also investigated by sequencing the 16S rRNA gene and phylogenetic relatedness by multiple-locus variable number tandem-repeat analysis (MLVA).

Results

Most B. hyodysenteriae isolates presented low minimum inhibitory concentration (MIC) values to gentamicin, with a mode of 2 µg/mL, a median or MIC50 of 4 µg/mL and percentile 90 or MIC90 of 16 µg/mL. The distribution of these values over the period studied (2011–2019) did not show a tendency towards the development of resistance to gentamicin. Differences in susceptibility among isolates could be explained by two point-mutations in the 16S rRNA gene, C990T and A1185G, which were only present in isolates with high MICs. These isolates were typed in three different MLVA clusters. Analyses of co-resistance between gentamicin and antimicrobials commonly used for the treatment of SD revealed that resistance to tiamulin and valnemulin was associated with low MICs for gentamicin.

Conclusions

The results provide an accurate characterisation of antimicrobial sensitivity to gentamicin and possible mechanisms of resistance in Spanish B. hyodysenteriae isolates. These findings allow us to propose gentamicin as an alternative in the antibiotic management of SD, particularly in outbreaks caused by pleuromutilin resistant isolates.
Acute ST-segment elevations following paclitaxel administration for uterine cervical cancer: a case report and literature review
Authors: Higami Shota , Tanaka Yusuke , Deguchi Tomomi , Shiraishi Mariko , Shiki Yasuhiko
Published: December 2022

Paclitaxel-induced cardiac ischemia is a rare but life-threatening complication. Although it may be difficult to distinguish from hypersensitivity or infusion reactions, it should not be overlooked. We herein report a rare case of ST-segment elevation following the administration of paclitaxel for uterine cervical cancer and review the literature regarding paclitaxel-induced cardiac ischemia.

A 48-year-old woman with uterine cervical cancer with no cardiovascular risk factors was admitted to our hospital for concurrent chemoradiotherapy (CCRT) and planned to receive weekly paclitaxel and carboplatin for a total of 5 weeks. Just after the completion of the first cycle of paclitaxel infusion, she presented with diaphoresis and her consciousness level decreased. Electrocardiography showed ST elevation, suggesting acute myocardial infarction. Laboratory testing revealed troponin I positivity. Emergency coronary angiography (CAG) revealed a normal coronary artery, suggesting paclitaxel-induced vasospasm. After CAG, the patient was hemodynamically stable and was returned to the gynecologic unit two days after CAG. CCRT without paclitaxel was continued and the patient was uneventfully discharged from hospital.
Mechanisms of Cynarine for treatment of non-alcoholic fatty liver disease based on the integration of network pharmacology, molecular docking and cell experiment
Authors: Sun Chun-Yong , Yang Le-Le , Zhao Pan , Yan Pei-Zheng , Li Jia , Zhao Dong-Sheng
Published: December 2022

Background

Nonalcoholic Fatty Liver Disease (NAFLD) is a chronic Liver Disease prevalent all over the world. It has become more and more common in Japan, China and most western developed countries. The global prevalence rate is 25.24%, and the trend is increasing year by year. Related studies have shown that Cynarine has certain liver protection, lipid lowering and immune intervention effects. So, this study to systematically predict and analyze the mechanism of Cynarine in the treatment of non-alcoholic fatty liver disease (NAFLD) based on the integration of network pharmacology, molecular docking, and cell experiment.

Methods

We performed Heatmap and Venn diagram analyses to identify genes and targets in Cynarine treat NAFLD. The network of Cynarine-therapeutic targets and the protein-protein interaction network (PPI) was constructed. We used gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses to visualize associated functional pathways. The Sybyl tool was used to dock the Cynarine with key therapeutic targets molecularly. Finally, cell experiments were applied to validate the role of Cynarine in the treatment of NAFLD.

Results

The Cynarine could act on 48 targets of NAFLD, and the role of CASP3, TP53, MMP9, ELANE, NOTCH1 were more important. The PPI network showed that immune and inflammation-related targets played a pivotal role. The KEGG analysis found that the PI3K-Akt signaling pathway, cell cycle and MAPK signaling pathway may be the main pathways for Cynarine to prevent and treat NAFLD. Molecular docking studies confirmed that Cynarine has good binding activity with therapeutic targets. Cynarine reduced the fat deposition ability of NAFLD model cells, and effectively reduced the levels of ALT and AST released by liver cells due to excessive lipid accumulation. We also found that Cynarine inhibited the expression of AKT1 and MAPK1.

Conclusions

This study revealed that Cynarine could significantly reduce the fat deposition ability of NAFLD model cells, which may be closely related to the effective regulation of AKT1 and MAPK1 expression by Cynarine.