bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chondroitin sulfate-AuNRs electroactive scaffolds for on-demand release of biofactors
Authors: Malki Maayan , Shapira Assaf , Dvir Tal 
Published: January 2022

AbstractControlled release systems are often integrated into polymeric scaffolds to supply essential biofactors to trigger physiological processes in engineered tissues. Here, we report the modification of chondroitin sulfate (CS) electroactive polymer with gold nanorods (AuNRs) to create hybrid macroporous scaffolds for enhanced on-demand release of growth factors and cytokines. The mechanical properties, porosity and degradation of the hybrid scaffolds were evaluated, and the viability and functionality of seeded cardiac cells were assessed. Following, the ability to control the release of the enzyme lysozyme, and the cytokine, stromal cell-derived factor 1 (SDF-1) by applying electrical stimulation, was demonstrated. The AuNRs were able to increase the current through the scaffolds, providing an efficient on–off release profile of SDF-1, which resulted in higher migration of cells expressing CXCR4 receptor. Finally, the engineered scaffolds were transplanted in rats and SDF-1 was released daily by electrical stimulation, promoting blood vessel-forming cell infiltration and vascularization. We envision that gold nanoparticles and other conducting nanomaterials can be incorporated into different electroactive materials to improve their capabilities not only for tissue engineering applications, but for a variety of biomedical applications, where enhanced electrical stimulation is needed.
Graphical Abstract
Novel insights into PORCN mutations, associated phenotypes and pathophysiological aspects
Authors: Arlt Annabelle , Kohlschmidt Nicolai , Hentschel Andreas , Bartels Enrika , Groß Claudia , Töpf Ana , Edem Pınar , Szabo Nora , Sickmann Albert , Meyer Nancy , Schara-Schmidt Ulrike , Lau Jarred , Lochmüller Hanns , Horvath Rita , Oktay Yavuz , Roos Andreas , Hiz Semra 
Published: January 2022

Abstract
Background
Goltz syndrome (GS) is a X-linked disorder defined by defects of mesodermal- and ectodermal-derived structures and caused by PORCN mutations. Features include striated skin-pigmentation, ocular and skeletal malformations and supernumerary or hypoplastic nipples. Generally, GS is associated with in utero lethality in males and most of the reported male patients show mosaicism (only three non-mosaic surviving males have been described so far). Also, precise descriptions of neurological deficits in GS are rare and less severe phenotypes might not only be caused by mosaicism but also by less pathogenic mutations suggesting the need of a molecular genetics and functional work-up of these rare variants.

Results
We report two cases: one girl suffering from typical skin and skeletal abnormalities, developmental delay, microcephaly, thin corpus callosum, periventricular gliosis and drug-resistant epilepsy caused by a PORCN nonsense-mutation (c.283C > T, p.Arg95Ter). Presence of these combined neurological features indicates that CNS-vulnerability might be a guiding symptom in the diagnosis of GS patients. The other patient is a boy with a supernumerary nipple and skeletal anomalies but also, developmental delay, microcephaly, cerebral atrophy with delayed myelination and drug-resistant epilepsy as predominant features. Skin abnormalities were not observed. Genotyping revealed a novel PORCN missense-mutation (c.847G > C, p.Asp283His) absent in the Genome Aggregation Database (gnomAD) but also identified in his asymptomatic mother. Given that non-random X-chromosome inactivation was excluded in the mother, fibroblasts of the index had been analyzed for PORCN protein-abundance and -distribution, vulnerability against additional ER-stress burden as well as for protein secretion revealing changes.

Conclusions
Our combined findings may suggest incomplete penetrance for the p.Asp283His variant and provide novel insights into the molecular etiology of GS by adding impaired ER-function and altered protein secretion to the list of pathophysiological processes resulting in the clinical manifestation of GS.
Aerobic capacity and skeletal muscle characteristics in glycogen storage disease IIIa: an observational study
Authors: Hennis Philip J. , Murphy Elaine , Meijer Rick I. , Lachmann Robin H. , Ramachandran Radha , Bordoli Claire , Rayat Gurinder , Tomlinson David J. 
Published: January 2022

Abstract
Background
Individuals with glycogen storage disease IIIa (GSD IIIa) (OMIM #232400) experience muscle weakness and exercise limitation that worsen through adulthood. However, normative data for markers of physical capacity, such as strength and cardiovascular fitness, are limited. Furthermore, the impact of the disease on muscle size and quality is unstudied in weight bearing skeletal muscle, a key predictor of physical function. We aim to produce normative reference values of aerobic capacity and strength in individuals with GSD IIIa, and to investigate the role of muscle size and quality on exercise impairment.

Results
Peak oxygen uptake (V̇O2peak) was lower in the individuals with GSD IIIa than predicted based on demographic data (17.0 (9.0) ml/kg/min, 53 (24)% of predicted, p = 0.001). Knee extension maximum voluntary contraction (MVC) was also substantially lower than age matched predicted values (MVC: 146 (116) Nm, 57% predicted, p = 0.045), though no difference was found in MVC relative to body mass (1.88 (2.74) Nm/kg, 61% of predicted, p = 0.263). There was a strong association between aerobic capacity and maximal leg strength (r = 0.920; p = 0.003). Substantial inter-individual variation was present, with a high physical capacity group that had normal leg strength (MVC), and relatively high V̇O2peak, and a low physical capacity that display impaired strength and substantially lower V̇O2peak. The higher physical capacity sub-group were younger, had larger Vastus Lateralis (VL) muscles, greater muscle quality, undertook more physical activity (PA), and reported higher health-related quality of life.

Conclusions
V̇O2peak and knee extension strength are lower in individuals with GSD IIIa than predicted based on their demographic data. Patients with higher physical capacity have superior muscle size and structure characteristics and higher health-related quality of life, than those with lower physical capacity. This study provides normative values of these important markers of physical capacity.
Barriers and facilitators to implementing the HEADSS psychosocial screening tool for adolescents living with HIV/AIDS in teen club program in Malawi: health care providers perspectives
Authors: Kip Esther C. , Udedi Michael , Kulisewa Kazione , Go Vivian F. , Gaynes Bradley N. 
Published: January 2022

Abstract
Background
Adolescents living with HIV (ALHIV) are at high risk of experiencing mental health problems. Depression is a major contributor to the burden of HIV-related disease amongst ALHIV and is significantly linked to non-adherence to anti-retroviral therapy (ART), yet it is under-recognized. In 2015, the Baylor College of Medicine International Pediatric AIDS Initiative (BIPAI) recommended that the psychosocial screening tool Home, Education, Activities, Drugs, Sexuality, Suicide/Depression (HEADSS) be used to screen ALHIV in Malawi who were part of an adolescent antiretroviral therapy program termed “Teen Club”. However, the HEADSS tool has been substantially under-utilized. This study assessed barriers and facilitators to implementing HEADSS for ALHIV attending Teen Club Program in four selected health facilities in Malawi.

Methods
We conducted a qualitative study using semi-structured interviews at four program sites (one district hospital and one health center each in two districts) between April and May 2019. Twenty key informants were purposively selected to join this study based on their role and experiences. We used the five domains of the Consolidated Framework for Implementation Research (CFIR) to guide the development of the interview guides, analysis and interpretation of results.

Results
Barriers included inadequate planning for integration of the HEADSS approach; concerns that the HEADSS tool was too long, time consuming, lacked appropriate cultural context, and increased workload; and reports by participants that they did not have knowledge and skills to screen ALHIV using this tool. Facilitators to implementing the screening were that health care providers viewed screening as a guide to better systematic counselling, believed that screening could build better client provider relationship, and thought that it could fit into the existing work practice since it is not complex.

Conclusions
A culturally adapted screening tool, especially one that can be used by non-clinicians such as lay health workers, would improve the ability to address mental health needs of ALHIV in many primary care and social service settings where resources for professional mental health staff are limited. These findings are a springboard for efforts to culturally adapt the HEADSS screening tool for detection of mental and risky behaviors among ALHIV attending ART program in Malawi.
TRPM7 silencing modulates glucose metabolic reprogramming to inhibit the growth of ovarian cancer by enhancing AMPK activation to promote HIF-1α degradation
Authors: Chen Yongchang , Liu Lu , Xia Longzheng , Wu Nayiyuan , Wang Ying , Li He , Chen Xue , Zhang Xiaoye , Liu Zhaoyi , Zhu Miaochen , Liao Qianjin , Wang Jing 
Published: January 2022

Abstract
Background
Tumor cell metabolic reprogramming is crucial for the malignant behavior of cancer cells by promoting their proliferation. However, little is known on how transient receptor potential 7 (TRPM7) modulates metabolic reprogramming in ovarian cancer.

Methods
The effects of TRPM7 silencing on transcriptome profile, glucose uptake, lactic acid production, extracellular acidification rate (ECAR), oxygen consumption rate (OCR), intracellular ROS and ATP levels, and NAD+/NADH ratios in ovarian cancer cells were examined. The impacts of TRPM7 silencing on the levels of glycolysis-related HK2, PDK1 and oxidative phosphorylation (OXPHOS)-related IDH3B and UQCRC1, HIF-1α expression and AMPK phosphorylation were determined in ovarian cancer. The effect of AMPK activity on HIF-1α ubiquitination degradation was investigated in ovarian cancer cells.

Results
Compared with the control, TRPM7 silencing suppressed the proliferation of ovarian cancer cells by shifting preferable glycolysis to OXPHOS. In parallel, TRPM7 silencing decreased the glucose uptake of tumor-bearing mice and TRPM7 levels were negatively correlated with IDH3B and UQCRC1, but positively with HK2 and PDK1 expression in ovarian cancer tissues. Mechanistically, TRPM7 silencing significantly increased AMPK phosphorylation and decreased HIF-1α protein levels in ovarian cancer, particularly in HIF-1α silencing cells. The shifting from glycolysis to OXPHOS by TRPM7 silencing was abrogated by HIF-1α over-expression and impaired by inhibiting AMPK activity in ovarian cancer cells. Moreover, enhanced AMPK activation inhibited glycolysis, which was abrogated by HIF-1α over-expression in ovarian cancer cells. Moreover, the enhanced AMPK activation promoted HIF-1α ubiquitination degradation.

Conclusions
TRPM7 silencing enhanced AMPK activation to shift glycolysis to oxidative phosphorylation by promoting HIF-1α ubiquitination degradation in ovarian cancer. Hence, TRPM7 may be a therapeutic target for intervention of ovarian cancer.
DUDE - a universal prevention program for non-suicidal self-injurious behavior in adolescence based on effective emotion regulation: study protocol of a cluster-randomized controlled trial
Authors: Buerger Arne , Emser Theresa , Seidel Alexandra , Scheiner Christin , von Schoenfeld Cornelia , Ruecker Viktoria , Heuschmann Peter U. , Romanos Marcel 
Published: January 2022

Abstract
Background
Non-suicidal self-injury (NSSI) has become a substantial public health problem. NSSI is a high-risk marker for the development and persistence of mental health problems, shows high rates of morbidity and mortality, and causes substantial health care costs. Thus, there is an urgent need for action to develop universal prevention programs for NSSI before adolescents begin to show this dangerous behavior. Currently, however, universal prevention programs are lacking.

Methods
The main objective of the present study is to evaluate a newly developed universal prevention program (“DUDE – Du und deine Emotionen / You and your emotions”), based on a skills-based approach in schools, in 3200 young adolescents (age 11–14 years). The effectiveness of DUDE will be investigated in a cluster-randomized controlled trial (RCT) in schools (N = 16). All groups will receive a minimal intervention called “Stress-free through the school day” as a mental health literacy program to prevent burnout in school. The treatment group (N = 1600; 8 schools) will additionally undergo the universal prevention program DUDE and will be divided into treatment group 1 (DUDE conducted by trained clinical psychologists; N = 800; 4 schools) and treatment group 2 (DUDE conducted by trained teachers; N = 800; 4 schools). The active control group (N = 1600; 8 schools) will only receive the mental health literacy prevention. Besides baseline assessment (T0), measurements will occur at the end of the treatment (T1) and at 6- (T2) and 12-month (T3) follow-up evaluations. The main outcome is the occurrence of NSSI within the last 6 months assessed by a short version of the Deliberate Self-Harm Inventory (DSHI-9) at the 1-year follow-up (primary endpoint; T3). Secondary outcomes are emotion regulation, suicidality, health-related quality of life, self-esteem, and comorbid psychopathology and willingness to change.

Discussion
DUDE is tailored to diminish the incidence of NSSI and to prevent its possible long-term consequences (e.g., suicidality) in adolescents. It is easy to access in the school environment. Furthermore, DUDE is a comprehensive approach to improve mental health via improved emotion regulation.

Trial registration
German Clinical Trials Register (DRKS) DRKS00018945. Registered on 01 April 2020, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00018945
Effects of acupuncture treatment on postoperative gastrointestinal dysfunction in colorectal cancer: study protocol for randomized controlled trials
Authors: Liu Xueyan , Wang Zhijie , Yao Hao , Yang Yanrong , Cao Huijuan , Toh Zhanhao , Zheng Ruwen , Ren Yi 
Published: January 2022

Abstract
Background
Postoperative gastrointestinal dysfunction (PGID) is a common complication arising from colorectal cancer surgery. Attributing factors, such as anesthesia, surgical retraction, and early intake of water, can inhibit gastrointestinal motility, causing constipation, reduction or absence of bowel sounds, nausea, vomiting, and other symptoms. Delayed recovery in gastrointestinal function can lead to intestinal obstructions or paralysis, anastomotic leaks, and other complications, affecting the patient’s recovery and quality of life negatively. Due to its complex pathophysiology, treatment for PGID in colorectal patients has remained a challenge. Acupuncture is an alternative therapy commonly used for postoperative recovery. This study aims to evaluate the therapeutic efficacy and safety of acupuncture on PGID. Through the complementation of acupuncture and enhanced recovery after surgery (ERAS) protocols, the advantages of acupuncture treatments could be demonstrated to promote its application in future clinical practice.

Methods
The study design is a prospective randomized controlled trial (RCT). One hundred sixty postoperative colorectal cancer patients will be recruited from Cancer Hospital Chinese Academy of Medical Sciences (CICAMS). Subjects who fulfill inclusion criteria will be randomly assigned into the acupuncture group (AG) (n = 80) or control group (CG) (n = 80). AG will receive acupuncture treatment and perioperative care guided by ERAS protocols, and CG will only receive perioperative care guided by ERAS protocols. The intervention will begin on the first day post-surgery, continuing for 4 days, with a follow-up assessment in a month. Time of first postoperative flatus would be the primary outcome measure. Secondary outcome measures include the time of first postoperative defecation, time of first fluid intake, time of first ambulation, postoperative hospital stay, gastrointestinal reaction score, acupuncture sensation evaluation scale, laboratory tests, postoperative quality of life, readmission rate, and postoperative complications. All results are evaluated from baseline, post-treatment, and upon follow-up.

Discussion
The results of the study would help elucidate evidence of the therapeutic effects of acupuncture on the recovery of postoperative gastrointestinal function. The objective of the study aims for the eventual inclusion of acupuncture in the ERAS protocol, allowing for wider application in clinical practice.

Trial registration
ClinicalTrials.gov ChiCTR2000036351. Registered on August 22, 2020
Molecular and functional characterization of a conserved odorant receptor from Aedes albopictus
Authors: Yan Ru , Xu Zhanyi , Qian Jiali , Zhou Qiaoling , Wu Huiming , Liu Yahui , Guo Yirong , Zhu Guonian , Chen Mengli 
Published: January 2022

AbstractBackgroundThe Asian tiger mosquitoAedes albopictusis a competent vector of several viral arboviruses including yellow fever, dengue fever, and chikungunya. Several vital mosquito behaviors (e.g., feeding, host-seeking, mating, and oviposition) are primarily dependent on the olfactory system for semiochemicals detection and discrimination. However, the limited number of studies hampers our understanding of the relationships between theAe. albopictusolfactory system and the complex chemical world.MethodsWe performed RT-qPCR assay on antennae ofAe. albopictusmosquitoes of different sexes, ages and physiological states, and found odorant receptor 11 (AalbOr11) enriched in non-blood-fed female mosquitoes. Then, we examined the odorant preference with a panel of physiologically and behaviorally relevant odorants inXenopusoocytes.ResultsThe results indicated that AalbOr11 could be activated by ten aromatics, seven terpenes, six heterocyclics, and three alcohols. Furthermore, using post-RNA interference (RNAi) hand-in-cage assay, we found that reducing the transcript level of AalbOr11 affected the repellency activity mediated by (+)-fenchone at a lower concentration (0.01% v/v).ConclusionsUsing in vitro functional characterization, we found that AalbOr11 was a broadly tuned receptor. Moreover, we found that AalbOr11 shared a conserved odorant reception profile with homologousAnopheles gambiaeOr11. In addition, RNAi and bioassay suggested that AablOr11 might be one of the receptors mediating (+)-fenchone repellency activity. Our study attempted to link odor-induced behaviors to odorant reception and may lay the foundation for identifying active semiochemicals for monitoring or controlling mosquito populations.Graphical Abstract
Lessons learned in allergy and immunology training: a survey analysis
Authors: Cyr Chloe , Cyr Michael , Quirt Jaclyn , Connors Lori 
Published: January 2022

Abstract
Background
There is currently little Canadian data to assess how well traditional time-based residency training programs have prepared residents for careers in Clinical Immunology and Allergy (CIA). This study aims to identify the perceived preparedness of residents in various areas of practice upon the completion of a Canadian CIA residency training program.

Methods
In the summer of 2020, an electronic survey was sent to 2018 and 2019 graduates of Canadian CIA training programs by the Canadian Society of Allergy and Clinical Immunology (CSACI).

Results
Former residents felt well prepared in most Medical Expert areas. Residents felt less prepared for the intrinsic roles of Leader, Communicator, Collaborator, Health Advocate, Scholar, and Professional. The majority of the intrinsic competencies were learned through mentorship and on the job after finishing training.

Conclusions
Upon completion of training, Canadian CIA residents felt well prepared for many competencies, particularly in Medical Expert areas. Training programs may wish to focus on various intrinsic competencies in order to better prepare residents for transition to practice. Academic half-day was not identified as a primary learning centre for intrinsic competencies, suggesting that new teaching strategies may be required.
Structure-based knowledge acquisition from electronic lab notebooks for research data provenance documentation
Authors: Schröder Max , Staehlke Susanne , Groth Paul , Nebe J. Barbara , Spors Sascha , Krüger Frank 
Published: January 2022

AbstractBackgroundElectronic Laboratory Notebooks (ELNs) are used to document experiments and investigations in the wet-lab. Protocols in ELNs contain a detailed description of the conducted steps including the necessary information to understand the procedure and the raised research data as well as to reproduce the research investigation. The purpose of this study is to investigate whether such ELN protocols can be used to create semantic documentation of the provenance of research data by the use of ontologies and linked data methodologies.MethodsBased on an ELN protocol of a biomedical wet-lab experiment, a retrospective provenance model of the raised research data describing the details of the experiment in a machine-interpretable way is manually engineered. Furthermore, an automated approach for knowledge acquisition from ELN protocols is derived from these results. This structure-based approach exploits the structure in the experiment’s description such as headings, tables, and links, to translate the ELN protocol into a semantic knowledge representation. To satisfy the Findable, Accessible, Interoperable, and Reuseable (FAIR) guiding principles, a ready-to-publish bundle is created that contains the research data together with their semantic documentation.ResultsWhile the manual modelling efforts serve as proof of concept by employing one protocol, the automated structure-based approach demonstrates the potential generalisation with seven ELN protocols. For each of those protocols, a ready-to-publish bundle is created and, by employing the SPARQL query language, it is illustrated that questions about the processes and the obtained research data can be answered.ConclusionsThe semantic documentation of research data obtained from the ELN protocols allows for the representation of the retrospective provenance of research data in a machine-interpretable way. Research Object Crate (RO-Crate) bundles including these models enable researchers to easily share the research data including the corresponding documentation, but also to search and relate the experiment to each other.