bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of mitochondrial DNA quantity and quality in the human aged and Alzheimer’s disease brain
Authors: Klein Hans-Ulrich , Trumpff Caroline , Yang Hyun-Sik , Lee Annie J. , Picard Martin , Bennett David A. , De Jager Philip L. 
Published: November 2021

Abstract
Background
Mitochondrial dysfunction is a feature of neurodegenerative diseases, including Alzheimer’s disease (AD). Changes in the mitochondrial DNA copy number (mtDNAcn) and increased mitochondrial DNA mutation burden have both been associated with neurodegenerative diseases and cognitive decline. This study aims to systematically identify which common brain pathologies in the aged human brain are associated with mitochondrial recalibrations and to disentangle the relationship between these pathologies, mtDNAcn, mtDNA heteroplasmy, aging, neuronal loss, and cognitive function.

Methods
Whole-genome sequencing data from n = 1361 human brain samples from 5 different regions were used to quantify mtDNAcn as well as heteroplasmic mtDNA point mutations and small indels. Brain samples were assessed for 10 common pathologies. Annual cognitive test results were used to assess cognitive function proximal to death. For a subset of samples, neuronal proportions were estimated from RNA-seq profiles, and mass spectrometry was used to quantify the mitochondrial protein content of the tissue.

Results
mtDNAcn was 7–14% lower in AD relative to control participants. When accounting for all 10 common neuropathologies, only tau was significantly associated with lower mtDNAcn in the dorsolateral prefrontal cortex. In the posterior cingulate cortex, TDP-43 pathology demonstrated a distinct association with mtDNAcn. No changes were observed in the cerebellum, which is affected late by pathologies. Neither age nor gender was associated with mtDNAcn in the studied brain regions when adjusting for pathologies. Mitochondrial content and mtDNAcn independently explained variance in cognitive function unaccounted by pathologies, implicating complex mitochondrial recalibrations in cognitive decline. In contrast, mtDNA heteroplasmy levels increased by 1.5% per year of life in the cortical regions, but displayed no association with any of the pathologies or cognitive function.

Conclusions
We studied mtDNA quantity and quality in relation to mixed pathologies of aging and showed that tau and not amyloid-β is primarily associated with reduced mtDNAcn. In the posterior cingulate cortex, the association of TDP-43 with low mtDNAcn points to a vulnerability of this region in limbic-predominant age-related TDP-43 encephalopathy. While we found low mtDNAcn in brain regions affected by pathologies, the absence of associations with mtDNA heteroplasmy burden indicates that mtDNA point mutations and small indels are unlikely to be involved in the pathogenesis of late-onset neurodegenerative diseases.
The promise of microRNA-based therapies in Alzheimer’s disease: challenges and perspectives
Authors: Walgrave Hannah , Zhou Lujia , De Strooper Bart , Salta Evgenia 
Published: November 2021

AbstractMulti-pathway approaches for the treatment of complex polygenic disorders are emerging as alternatives to classical monotarget therapies and microRNAs are of particular interest in that regard. MicroRNA research has come a long way from their initial discovery to the cumulative appreciation of their regulatory potential in healthy and diseased brain. However, systematic interrogation of putative therapeutic or toxic effects of microRNAs in (models of) Alzheimer’s disease is currently missing and fundamental research findings are yet to be translated into clinical applications. Here, we review the literature to summarize the knowledge on microRNA regulation in Alzheimer’s pathophysiology and to critically discuss whether and to what extent these increasing insights can be exploited for the development of microRNA-based therapeutics in the clinic.
Development of colonic transit time and ultrasound imaging tools as objective indicators for assessing abnormal defecation associated with food intake: a narrative review based on previous scientific knowledge
Authors: Okawa Yohei 
Published: November 2021

Abstract
Background
Functional gastrointestinal disorders (FGIDs) involve chronic or persistent gastrointestinal symptoms. Laboratory tests show no organic lesions, and the symptoms are due to dysfunction. The most typical FGID is irritable bowel syndrome (IBS). In IBS patients, defecation disorders are common and have adverse effects on daily life. The proper evaluation and analysis of colonic transit are important for the management of defecation disorders in IBS patients. In addition, dietary intake and lifestyle affect colonic transit. An accurate assessment of such factors can guide management, leading to improvements in colonic transit and the resolution of defecation disorders.

Main topic
The Rome IV diagnostic criteria for IBS are based on subjective symptoms, which must be communicated and explained by the patient, limiting their application. Colonic transit time and ultrasonography are objective tools that can be used to diagnose IBS. In particular, previous studies used colonic transit to accurately distinguish between constipation and normal stool passage and to assess delayed gastrointestinal motility. Diet and lifestyle modifications can improve colonic transit and ameliorate bowel dysfunction.

Conclusion
Colonic transit can be improved by modifying lifestyle factors. Defecation disorders in IBS patients may be resolved by focusing on such factors. In the future, methods of visualizing defecation disorders due to impaired gastrointestinal motility and objective indicators of the associated abdominal symptoms need to be investigated.
Estimating the number of children in households with substance use disorders in Germany
Authors: Kraus Ludwig , Uhl Alfred , Atzendorf Josefine , Seitz Nicki-Nils 
Published: November 2021

Abstract
Background
Parental substance misuse is reported to endanger the health and psychological development of children and adolescents. The aim of the present study was to address conceptual and methodological problems in estimating the number of children affected by parental substance misuse (CaPSM) and offer a novel approach based on survey data.

Methods
Data came from the 2018 German Epidemiological Survey of Substance Abuse (ESA) among 18- to 64-year-olds (n = 9267) and from population statistics. DSM-IV diagnostic criteria were used to assess substance use disorder (SUD) related to tobacco, alcohol, cannabis, cocaine or amphetamine. Based on the number of household members, the number of children below age 18 years and the information on SUD status of the respondent living in this household, the number of children currently living in households with at least one member with SUD was estimated.

Results
In 2018, there were 13,597,428 children younger than 18 years living in Germany. Of these, 6.9–12.3% (935,522–1,673,103) were estimated to currently live in households where at least one adult had a tobacco use disorder, 5.1–9.2% (688,111–1,257,345) in households where at least one adult had an alcohol use disorder and 0.6–1.2% (87,817–158,401) in households where at least one adult had a disorder related to the use of illicit drugs. The total number of children currently living with SUD adults in their household was estimated at 11.2–20.2% (1,521,495–2,751,796).

Conclusions
Available estimates are difficult to interpret and to compare due to a lack of clear case definitions and methodological approaches with various biases and limitations. Future estimates need to provide precise case definitions and standard approaches.
Prenatal diagnosis of complete paternal uniparental isodisomy for chromosome 3: a case report
Authors: Bu Xiufen , Li Xu , Zhou Shihao , Shi Liangcheng , Jiang Xuanyu , Peng Can , Li Hongyu , He Jun 
Published: November 2021

Abstract
Background
Uniparental disomy (UPD) is defined as an inheritance of two chromosomes from only one of the parents with no representative copy from the other. Paternal-origin UPD of chromosome 3 is a very rare condition, with only five cases of paternal UPD(3) reported.

Case presentation
Here, we report a prenatal case that is only the second confirmed paternal UPD(3) reported with no apparent disease phenotype. The fetus had a normal karyotype and normal ultrasound features throughout gestation. Copy neutral regions of homozygosity on chromosome 3 were identified by single nucleotide polymorphism (SNP) array. Subsequent SNP array data of parent–child trios showed that the fetus carried complete paternal uniparental isodisomy (isoUPD) of chromosome 3. The parents decided to continue with the pregnancy after genetic counseling, and the neonate had normal physical findings at birth and showed normal development after 1.5 years.

Conclusions
These findings provided further evidence to confirm that there were no important imprinted genes on paternal chromosome 3 that caused serious diseases and a reference for the prenatal diagnosis and genetic counseling of UPD(3) in the future.
Contradictory roles of lipid metabolism in immune response within the tumor microenvironment
Authors: Yu Weina , Lei Qingyang , Yang Li , Qin Guohui , Liu Shasha , Wang Dan , Ping Yu , Zhang Yi 
Published: November 2021

AbstractComplex interactions between the immune system and tumor cells exist throughout the initiation and development of cancer. Although the immune system eliminates malignantly transformed cells in the early stage, surviving tumor cells evade host immune defense through various methods and even reprogram the anti-tumor immune response to a pro-tumor phenotype to obtain unlimited growth and metastasis. The high proliferation rate of tumor cells increases the demand for local nutrients and oxygen. Poorly organized vessels can barely satisfy this requirement, which results in an acidic, hypoxic, and glucose-deficient tumor microenvironment. As a result, lipids in the tumor microenvironment are activated and utilized as a primary source of energy and critical regulators in both tumor cells and related immune cells. However, the exact role of lipid metabolism reprogramming in tumor immune response remains unclear. A comprehensive understanding of lipid metabolism dysfunction in the tumor microenvironment and its dual effects on the immune response is critical for mapping the detailed landscape of tumor immunology and developing specific treatments for cancer patients. In this review, we have focused on the dysregulation of lipid metabolism in the tumor microenvironment and have discussed its contradictory roles in the tumor immune response. In addition, we have summarized the current therapeutic strategies targeting lipid metabolism in tumor immunotherapy. This review provides a comprehensive summary of lipid metabolism in the tumor immune response.
Chronic respiratory diseases other than asthma in children: the COVID-19 tsunami
Authors: Di Cicco Maria , Tozzi Maria Giulia , Ragazzo Vincenzo , Peroni Diego , Kantar Ahmad 
Published: November 2021

AbstractCoronavirus disease 2019 (COVID-19) affects all components of the respiratory system, including the neuromuscular breathing apparatus, conducting and respiratory airways, pulmonary vascular endothelium, and pulmonary blood flow. In contrast to other respiratory viruses, children have less severe symptoms when infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A minority of children experience a post-infectious inflammatory syndrome, the pathology and long-term outcomes of which are poorly understood. The reason for the lower burden of symptomatic disease in children is not yet clear, but several pathophysiological characteristics are postulated. The SARS-CoV-2 pandemic has brought distinct challenges to the care of children globally. Proper recommendations have been proposed for a range of non-asthmatic respiratory disorders in children, including primary ciliary dyskinesia and cystic fibrosis. These recommendations involve the continuation of the treatment during this period and ways to maintain stability. School closures, loss of follow-up visit attendance, and loss of other protective systems for children are the indirect outcomes of measures to mitigate the COVID-19 pandemic. Moreover, COVID-19 has reshaped the delivery of respiratory care in children, with non-urgent and elective procedures being postponed, and distancing imperatives have led to rapid scaling of telemedicine. The pandemic has seen an unprecedented reorientation in clinical trial research towards COVID-19 and a disruption in other trials worldwide, which will have long-lasting effects on medical science. In this narrative review, we sought to outline the most recent findings on the direct and indirect effects of SARS-CoV-2 pandemic on pediatric respiratory chronic diseases other than asthma, by critically revising the most recent literature on the subject.
Compounded glycopyrrolate is a compelling choice for drooling children: five years of facility experience
Authors: Zanon Davide , Tumminelli Cristina , Galimberti Anna Maria Chiara , Torelli Lucio , Maestro Alessandra , Barbi Egidio , Maximova Natalia 
Published: November 2021

Abstract
Background
Describe the efficacy of a galenic glycopyrrolate formulation and its impact on patients with sialorrhea Quality of Life (QoL), including costs analysis.

Methods
We performed a retrospective observational study on 21 patients who received a custom-formulated galenic glycopyrrolate syrup for sialorrhea for an average period of 14.3 months. We analyzed the telephone interviews with elaborated and validated questionnaires and the therapy costs comparing the brand marketed drug with the galenic formulation.

Results
Overall, 16 out of 21 patients (76.2%) reported a significant improvement in sialorrhea and QoL. In 14 subjects (66.7%), there was a remarkable decrease in the drooling severity; 10 individuals (47.6%) reported a reduction in drooling frequency. Nine patients experienced at least one adverse effect of glycopyrrolate therapy, and three of them stopped the treatment. No severe side effects were observed. The galenic drug significantly reduced costs for patients.

Conclusions
An oral glycopyrrolate solution easily administered to children with brain injuries is not commercially available in many European countries. This study demonstrates the efficacy of a compounded glycopyrrolate syrup on drooling severity, frequency and ensures a better QoL in patients and their caregivers.
The negative effects of new screens on the cognitive functions of young children require new recommendations
Authors: Eric Osika 
Published: November 2021

AbstractTelevision studies have shown that some negative effects of screens could depend on exposure time, but more importantly on the characteristics of the child, the type of content viewed, and the context in which it is viewed. Studies on newer screens show that these factors are still valid but new ones now play a negative role: portable screens increase the duration of exposure and lowered the age at which exposure begins. More worryingly, new screen persuasive designs and dark patterns largely used incite more frequent use, attracting the attention of children and parents, resultantly interfering deeply in parent/child relationships. In this text we suggest that current academic recommendations have to be more broadly shared but also that new recommendations are needed: especially to advise parents not to let their screen interactions compete with real interactions with their child which are the core of learnings (especially language) and emotional regulations but also of their security.
Psychoeducation focused on family accommodation: a practical intervention for parents of children and adolescents with obsessive-compulsive disorder
Authors: Demaria Francesco , Pontillo Maria , Tata Maria Cristina , Gargiullo Prisca , Mancini Francesco , Vicari Stefano 
Published: November 2021

AbstractObsessive-compulsive disorder (OCD) is a neuropsychiatric disorder that is frequently diagnosed in children and adolescents. In pediatric OCD, family plays an important role in the development and maintenance of the disease. In this relationship, both genetic and behavioral factors, such as parental modeling and family accommodation, are significant. Parental modeling concerns the daily enactment of dysfunctional behavioral patterns by a parent with OCD, which may influence children. Family accommodation, in contrast, describes the direct participation of parents in their child’s compulsive rituals, by modifying daily routines or by facilitating avoidance of OCD triggers, to decrease the child’s distress and time spent executing compulsions. Approximately 80–90% of the relatives of OCD patients actively participate in patients’ rituals. The literature demonstrates that a high level of family accommodation is associated with OCD symptom severity, reduced response to cognitive-behavioral treatment (CBT), and a higher risk of therapy dropout.Despite this, no studies have aimed at delineating practical guidance for psychotherapists to support parents in reducing family accommodation.The main aim of this paper is to propose a psychoeducation intervention focused on cognitive-behavioral strategies to help families to manage their child’s OCD behaviors without enacting dysfunctional family accommodation behaviors in order to support their child’s successful therapy.
Efficacy of abdomen-rubbing qigong exercise for chronic insomnia: study protocol for a randomized controlled trial
Authors: Guan Chong , Cheng Ziji , Xie Fangfang , Wang Ruiping , Zhang Jing , Yao Fei , Fang Min 
Published: November 2021

Abstract
Background
Insomnia is a common sleeping disorder which affects the quality of life which can bring harms to physical and mental health of human beings and even economic development. Traditional Chinese medicine (TCM) plays an outstanding role in treating chronic diseases and alleviating their symptoms. Therefore, the purpose of this study is to assess the treatment efficacy in patients with insomnia treated with abdomen-rubbing qigong exercise (ARQE). In addition, the brain function changes of patients will be explored by resting state functional magnetic resonance imaging (rs-fMRI).

Method/design
This trial is a randomized, single-blind, controlled study planned to transpire between July 1, 2020, and July 31, 2021. A sample size of 114 participants (57 per group) with chronic insomnia will be randomly assigned to receive ARQE or CBTI for 8 weeks. The study duration will be 13 weeks, including a 1-week screening period, 8 weeks of intervention, and another 4 weeks of follow-up. The primary outcome is the Pittsburgh sleep quality index scores. Secondary outcomes include insomnia severity index, gastrointestinal symptom rating scale, the Hamilton Depression Scale, and rs-fMRI scan. The adverse events will be in control.

Discussion
The results of this study will help to clarify the efficacy of ARQE in the treatment of insomnia and try to use rs-fMRI technology to explore the brain function changes of ARQE in improving sleep quality in patients with insomnia disorder. If the results are as expected, this study will provide high-quality evidence for the treatment of insomnia with ARQE.

Trial registration
China Clinical Registration Agency ChiCTR1900028009. Registered on 19 December 2019.
Adding muscle power exercises to a strength training program for people with patellofemoral pain: protocol of a randomized controlled trial
Authors: de Vasconcelos Gabriela Souza , Nunes Guilherme Silva , Barton Christian John , Munhoz Raquel Fantinelli , da Silva Maria Eduarda Chinotti Batista , Pisani Giulia Keppe , Luz Bruna Calazans , Serrão Fábio Viadanna 
Published: November 2021

Abstract
Background
Strong evidence supports the proximal combined with quadriceps strengthening for patellofemoral pain (PFP) rehabilitation. However, most reported rehabilitation programs do not follow specific exercise prescription recommendations or do not provide adequate details for replication in clinical practice. Furthermore, people with PFP have power deficits in hip and knee muscles and it remains unknown whether the addition of power exercises would result in superior or more consistent outcomes. Therefore, this study is designed to verify whether the benefits of a rehabilitation program addressing proximal and knee muscles comprising power and strength exercises are greater than those of a program consisting of strength exercises only.

Method
This study will be a randomized controlled trial that will be conducted at university facilities. A minimum of 74 people with PFP between the ages of 18 and 45 years will be included. The experimental group will engage in a 12-week resistance training program focusing on proximal and knee muscles using power and strength exercises. The control group will engage in a 12-week resistance training program focusing on proximal and knee muscles using strength exercises only. Primary outcomes will be pain intensity and physical function; and secondary outcomes will be kinesiophobia, self-reported improvement, quality of life, peak hip and knee torque, and hip and knee rate of force development. The primary outcomes will be evaluated at baseline, and after 6 weeks, 12 weeks, 3 months, 6 months, and 1 year. The secondary outcomes will be evaluated at baseline and immediately after the interventions. Therapists and participants will not be blinded to group allocation.

Discussion
This randomized clinical trial will investigate if adding power exercises to a progressive resistance training may lead to more consistent outcomes for PFP rehabilitation. The study will provide additional knowledge to support rehabilitation programs for people with PFP.

Trial registration
ClinicalTrials.gov NCT 03985254. Registered on 26 August 2019.
Meeting report: South African Medical Research Council Standard of Care in Clinical Research in Low- And Middle-Income Settings Summit, November 2017
Authors: Miner Maurine D. , Bekker Linda-Gail , Kredo Tamara , Bhagwandin Niresh , Corey Lawrence , Gray Glenda E. 
Published: November 2021

AbstractA cornerstone of HIV prevention clinical trials is providing a combination prevention package to all trial participants. The elements included in that standard of care (SoC) package evolve as new prevention modalities are developed. Pre-exposure prophylaxis (PrEP) was recommended by the World Health Organization for persons at high risk of acquiring HIV, but not all countries immediately adopted those recommendations. The South African Medical Research Council (SAMRC) convened a summit to discuss issues relating to SoC and PrEP in HIV prevention clinical trials taking place in lower- to middle-income countries (LMIC). Policymakers, regulators, ethicists, experts in law, researchers, representatives of advocacy groups, and the HIV Vaccine Trials Network (HVTN) presented a framework within which SoC principles could be articulated. A group of subject matter experts presented on the regulatory, ethical, scientific, and historic framework of SoC in clinical trials, focusing on PrEP in South Africa. Summit participants discussed how and when to include new HIV treatment and prevention practices into existing clinical guidelines and trial protocols, as well as the opportunities for and challenges to scaling up interventions. The summit addressed challenges to PrEP provision, such as inconsistent efficacy amongst different populations and various biological, virological, and immunological explanations for this heterogeneity. Advocates and community members propagated the urgent need for accessible interventions that could avert HIV infection. The meeting recommended supporting access to PrEP in HIV prevention trials by (1) developing PrEP access plans for HIV vaccine trials, (2) creating a PrEP fund that would supply PrEP to sites conducting HIV prevention trials via a central procurement mechanism, and (3) supporting the safety monitoring of PrEP. This report summarizes the presentations and discussions from the summit in order to highlight the importance of SoC in HIV prevention clinical trials.