bluuebunny/crossref_metadata_2025_split huggingface dataset:
A transcriptomic analysis of cerebral microvessels reveals the involvement of Notch1 signaling in endothelial mitochondrial-dysfunction-dependent BBB disruption
Authors: Lee Min Joung , Zhu Jiebo , An Jong Hun , Lee Seong Eun , Kim Tae Yeon , Oh Eungseok , Kang Yea Eun , Chung Woosuk , Heo Jun Young 
Published: August 2022

AbstractBackgroundEndothelial cells (ECs) in cerebral vessels are considered the primary targets in acute hemorrhagic brain injuries. EC dysfunction can aggravate neuronal injuries by causing secondary inflammatory responses and blood–brain barrier (BBB) disruption. Previous studies have reported that enhancement of mitochondrial function within ECs may reduce BBB disruption and decrease the severity of acute brain injuries. However, the molecular signaling pathways through which enhanced EC mitochondrial function is enhanced to exert this BBB protective effect have not been fully elucidated.MethodsTo identify signaling pathways involved in linking EC-specific mitochondrial dysfunction and BBB disruption, we first performed RNA sequencing using isolated cerebral vessels from TEKCRIF1 KO mice, a mouse strain that displays EC-specific mitochondrial dysfunction. After identification, we assessed the significance of candidate signaling pathways using an intracerebral hemorrhage (ICH) mouse model. BBB integrity was assessed using an IgG leakage assay, and symptomatic changes were evaluated using behavioral assays.ResultsTranscriptome analyses of the TEKCRIF1 KO mouse revealed significant changes in Notch1 signaling, a pathway intimately involved in BBB maintenance. We also observed a decrease in Notch1 signaling and expression of the mitochondrial oxidative phosphorylation (OxPhos) complex in the ICH mouse model, which also exhibits BBB disruption. To further assess the function of Notch1 signaling in relation to BBB disruption, we injected ICH model mice with adropin, a protein that interacts with the Notch1 ligand NB-3 and activates Notch1 signaling. We found that adropin prevented BBB disruption and reduced the extent (area) of the injury compared with that in vehicle controls, in association with alteration of mitochondrial function.ConclusionThese results suggest that the Notch1 signaling pathway acts as an upstream regulator of DEGs and can be a target to regulate the changes involved with endothelial mitochondrial dysfunction-dependent BBB disruption. Thus, treatment methods that activate Notch1 may be beneficial in acute brain injuries by protecting BBB integrity.
Doctors on the move 2: a qualitative study on the social integration of middle eastern physicians following their migration to Germany
Authors: Schumann Marwa , Sepke Maria , Peters Harm 
Published: August 2022

Abstract
Background
The integration of immigrating physicians has become a challenge for many societies and health care systems worldwide. Facilitating the integration process may benefit both the uptaking country and the immigrating physicians. Previous studies have approached this problem from a system integration perspective. The present study explores the degree of social integration of an exemplary group of Middle Eastern physicians following their migration to Germany from an individual perspective.

Methods
Based on social constructivist epistemology, a series of fifteen interviews and two focus groups with immigrated Middle Eastern physicians (n = 23, purposively sampled) were conducted between 2017 and 2020 in Germany. The audio recordings were transcribed, translated into English and analysed deductively based on Esser’s model of social integration, consisting of four dimensions: acculturation, positioning, interaction and identification.

Results
The social integration of the participants showed a multifaceted picture. The early phase was characterized by disorientation and trial and error. Cultural differences were of major importance. Acculturation was facilitated by German language acquisition and increased over time, although some cultural difficulties remained. Professional positioning was facilitated by the need for physicians and a relatively low-hurdle relicensing procedure. Interaction and identification depended on the efforts of the individual physicians.

Conclusions
This study provides a comprehensive picture of the individual social integration of Middle Eastern physicians in Germany. Language and cultural adaptation are identified as being of primary importance. Social integration can be facilitated through orientation programmes or cross-cultural training that benefits the uptaking countries as well as the immigrating physicians.
Barriers and facilitators to opioid agonist therapy in rural and remote communities in Canada: an integrative review
Authors: Pijl Em M. , Alraja Abeer , Duff Elsie , Cooke Carol , Dash Stephen , Nayak Nichole , Lamoureux Jesse , Poulin Ginette , Knight Erin , Fry Ben 
Published: August 2022

AbstractBackgroundPeople living in rural and remote communities in Canada are often disproportionately impacted by opioid use disorder. When compared to urban centres, rural and remote populations face additional barriers to treatment, including geographical distance as well as chronic shortages of health care professionals. This integrative review of the literature was conducted to explore the facilitators and barriers of OAT in rural and remote Canadian communities.MethodsA search of the literature identified relevant studies published between 2001 and 2021.ResultsThe search strategy yielded 26 scholarly peer-reviewed publications, which explored specific barriers and facilitators to rural and remote OAT in Canada, along with two reports and one fact sheet from the grey literature. Most of the scholarly articles were descriptive studies (n = 14) or commentaries (n = 9); there were only three intervention studies. Facilitators and barriers to OAT programs were organized into six themes: intrapersonal/patient factors, social/non-medical program factors, family/social context factors (including community factors), infrastructure/environmental factors, health care provider factors, and system/policy factors.ConclusionsAlthough themes in the literature resembled the social-ecological framework, most of the studies focused on the patient-provider dyad. Two of the most compelling studies focused on community factors that positively impacted OAT success and highlighted a holistic approach to care, nested in a community-based holistic model. Further research is required to foster OAT programs in rural and remote communities.
Results of a multi-site pragmatic hybrid type 3 cluster randomized trial comparing level of facilitation while implementing an intervention in community-dwelling disabled and older adults in a Medicaid waiver
Authors: Spoelstra Sandra L. , Schueller Monica , Basso Viktoria , Sikorskii Alla 
Published: August 2022

AbstractBackgroundEvidence-based interventions that optimize physical function for disabled and older adults living in the community who have difficulty with daily living tasks are available. However, uptake has been limited, particularly in resource-constrained (Medicaid) settings. Facilitation may be an effective implementation strategy. This study’s aim was to compare internal facilitation (IF) versus IF and external facilitation (EF) on adoption and sustainability of an intervention in a Medicaid home and community-based waiver.MethodsIn a hybrid type 3 trial, waiver sites (N= 18) were randomly assigned to implement the intervention using a bundle of strategies with either IF or IF and EF. Adoption and sustainability were assessed via Stages of Implementation Completion (SIC) for each site. Clinician attitudes toward evidence-based practice and self-efficacy were evaluated among 539 registered nurses, social workers, and occupational therapists. Medicaid beneficiary outcomes of activities of daily living, depression, pain, falls, emergency department visits, and hospitalizations were evaluated in a sample ofN= 7030 as reflected by electronic health records data of the Medicaid waiver program. Linear mixed-effects models were used to compare outcomes between trial arms while accounting for cluster-randomized design.ResultsThe mean SIC scores were 72.22 (standard deviation [SD] = 16.98) in the IF arm (9 sites) and 61.33 (SD= 19.29) in the IF + EF arm (9 sites). The difference was not statistically significant but corresponded to the medium clinically important effect size Cohen’sd= 0.60. Clinician implementation outcomes of attitudes and self-efficacy did not differ by trial arm. Beneficiary depression was reduced significantly in the IF + EF arm compared to the IF arm (p= .04, 95% confidence interval for the difference [0.01, 0.24]). No differences between trial arms were found for other beneficiary outcomes.ConclusionsLevel of facilitation did not enhance capacity for adoption and sustainability of an evidence-based intervention in a Medicaid setting that cares for disabled and older adults. Improved beneficiary depression favored use of IF and EF compared to IF alone, and no differences were found for other outcomes. These findings also suggest level of facilitation may not have impacted beneficiary outcomes.Trial registrationClinicalTrials.gov,NCT03634033; date registered August 16, 2018.
A comparison of neuromuscular blockade and reversal using cisatricurium and neostigmine with rocuronium and sugamadex on the quality of recovery from general anaesthesia for percutaneous closure of left atria appendage
Authors: Li Qiongzhen , Yao Haixia , Wu Jingxiang , Xu Meiying , Xie Hong , Wu Dongjin 
Published: August 2022

Abstract
Background
There is a growing interest in minimally invasive left atrial appendage closure therapies. However, for successful catheter surgery, it is necessary to achieve high-quality postoperative recovery. The aim of the study is to comparison of neuromuscular blockade and reversal using cisatricurium and neostigmine with rocuronium and sugamadex on the quality of recovery from general anaesthesia for percutaneous closure of left atria appendage.

Methods
Eighty-four patients who received percutaneous LAAC were randomly placed into two groups, general anesthesia and endotracheal intubation with either propofol-remifentanil-cisatracurium-neostigmine (group C) or propofol-remifentanil-rocuronium-sugammadex (group S). The QoR-40 questionnaire was used to assess recovery quality 6 h after surgery, and the time of spontaneous respiration, the time of consciousness recovery, the time of extubation, the duration in the postanaesthesia care unit (PACU), and the adverse events after awakening were collected.

Results
Compared with the group C, the group S demonstrated significantly higher individual QoR-40 dimension scores, a significantly shorter recovery time for spontaneous respiration and consciousness, time of extubation, and duration in the PACU, and a lower incidence of transient hypoxemia, agitation, nausea and vomiting and urinary retention. There was a non-significant trend for the length of stay in the hospital in both groups.

Conclusions
General anesthesia and endotracheal intubation with propofol-remifentanil-rocuronium-sugammadex provided better quality of recovery, shorter anaesthesia duration, and lower incidence of hypoxemia and agitation. Neuromuscular blockade and reversal using rocuronium and sugamadex is better than with cisatricurium and neostigmine on the quality of recovery from general anaesthesia for percutaneous closure of left atria appendage.
Trial registration: chictr.org, ChiCTR2000031857. Registered on April 12, 2020.
Esophageal carcinosarcoma comprising undifferentiated pleomorphic sarcoma and squamous cell carcinoma: a case report
Authors: Fang Ziyao , Xia Tian , Pan Shu , Xu Chun , Ju Sheng , Shen Ziqing , Zhao Jun 
Published: August 2022

Abstract
Background
Esophageal carcinosarcoma (ECS) is a rare malignant tumor that often presents as an intraluminal polypoid lesion in the esophageal lumen. The pathogenesis of esophageal carcinosarcoma is not clear and its etiology is still being discussed.

Case presentation
We report the case of a 68-year-old male who had dysphagia for approximately three months. Contrast-enhanced computed tomography showed an irregular enhancing mass in the lower esophagus. Endoscopy showed a gray-white mass with a smooth surface that almost filled the esophageal lumen at a location 28 cm from the incisor tooth. Considering the location of the tumor, we opted for Ivor-Lewis esophagectomy with intrathoracic anastomosis through a 5-port laparoscope and uniport video-assisted thoracic surgery (VATS). Pathological analysis showed that the mass comprised carcinoma in situ and pleomorphic sarcoma, without lymphatic metastasis. The postoperative pathological stage was T1bN0M0, stage I (Japanese Classification of Esophageal Cancer 11th Edition). The latest follow-up of the patient was 14 months after the surgery, and no signs of recurrence or metastasis were found.

Conclusion
This case demonstrates a rare esophageal malignancy with a peculiar histological composition. Successful VATS esophagectomy with intrathoracic anastomosis was conducted without recurrence or metastasis at the 14-month follow-up.
Aripiprazole treatment for temper outbursts in Prader–Willi syndrome
Authors: Deest Maximilian , Wieting Jelte , Jakob Maximilian Michael , Deest-Gaubatz Stephanie , Groh Adrian , Seifert Johanna , Toto Sermin , Bleich Stefan , Frieling Helge , Eberlein Christian K. 
Published: August 2022

Abstract
Background
Prader–Willi syndrome (PWS) is a rare neurodevelopmental disorder based on a loss of paternally expressed genes in chromosome segment 15q11-13. Behavioral traits such as temper outbursts, stereotypic, and ritualistic behavior, as well as an increased risk of psychosis accompany the syndrome, representing a major issue in the treatment of adults with PWS. Up to now, no treatment guideline for these conditions in PWS exist. This study aimed to retrospectively analyze the effect and adverse effects of treatment with aripiprazole for temper outbursts in 10 adults with PWS.

Results
Aripiprazole was prescribed for temper outbursts (n = 10). Treatment outcome was assessed using the Clinical Global Impression-Severity (CGI-S) and -Improvement Scale (CGI-I).
Treatment success (CGI-I < 3) was observed in 70% of cases, with adverse effects from mild to partly serious extent in 60% of cases. The major adverse effect observed was increased daytime sleepiness. In total, 50% of the individuals were treated successfully for temper outbursts. The BMI did not change significantly in the successfully treated group after 6 months of treatment.

Conclusions
Aripiprazole can be a treatment option for temper outbursts in people with PWS. Although a high rate of side effects was detected, their severity led to discontinuation in only 20% of the cases. Furthermore, the absence of weight gain makes aripiprazole interesting especially for the PWS population.
Estimation of hereditary fructose intolerance prevalence in the Chinese population
Authors: Tang Meiling , Chen Xiang , Ni Qi , Lu Yulan , Wu Bingbing , Wang Huijun , Yin Zhaoqing , Zhou Wenhao , Dong Xinran 
Published: August 2022

Abstract
Background
Hereditary fructose intolerance (HFI) caused by aldolase B reduction or deficiency that results in fructose metabolism disorder. The disease prevalence in the Chinese population is unknown, which impedes the formulation of HFI screening and diagnosis strategies.

Materials and methods
By searching a local cohort (Chinese Children’s Rare Disease Genetic Testing Clinical Collaboration System, CCGT) and public databases (ClinVar and Human Gene Mutation Database) and reviewing HFI-related literature, we manually curated ALDOB pathogenic or likely pathogenic (P/LP) variants according to ACMG guidelines. Allele frequency (AF) information from the local database CCGT and the public databases HuaBiao and gnomAD for ALDOB P/LP variants was used to estimate and the HFI prevalence in the Chinese population and other populations by the Bayesian framework. We collected the genotype and clinical characteristics of HFI patients from the CCGT database and published literature to study genotype–phenotype relationships.

Result
In total, 81 variants of ALDOB were curated as P/LP. The estimated Chinese HFI prevalence was approximately 1/504,678, which was much lower than that for non-Finland European (1/23,147), Finnish in Finland (1/55,539), admixed American (1/132,801) and Ashkenazi Jewish (1/263,150) populations. By analyzing the genetic characteristics of ALDOB in the Chinese population, two variants (A338V, A338G) had significantly higher AFs in the Chinese population than in the non-Finland European population from gnomAD (all P values < 0.05). Five variants (A150P, A175D, N335K, R60*, R304Q) had significantly lower AFs (all P values < 0.1). The genotype–phenotype association analyses were based on 68 reported HFI patients from a literature review and the CCGT database. The results showed that patients carrying homozygous variant sites (especially A150P) were more likely to present nausea, and patients carrying two missense variant sites were more likely to present aversion to sweets and fruit (all P values < 0.05). Our research reveals that some gastrointestinal symptoms seem to be associated with certain genotypes.

Conclusion
The prevalence of HFI in the Chinese population is extremely low, and there is no need to add HFI testing to the current newborn screening programs if medical costs are considered. A genetic testing strategy is suggested for early diagnosis of HFI.
Measurement of perceived needs in humanitarian contexts using the HESPER scale: a scoping study with reflections on the collaboration between researchers and humanitarian actors
Authors: Hugelius Karin 
Published: August 2022

Abstract
Background
Needs assessment is one of the fundamental humanitarian responses to sudden-onset or long-lasting emergencies. The Humanitarian Emergency Settings Perceived Needs Scale (HESPER)/ HESPER Web are valid scales for identifying perceived needs among humanitarian or disaster-affected populations, both in humanitarian practice and in science. This scoping review aimed to determine the scientific use of HESPER or HESPER Web, report on previously published perceived needs in humanitarian emergencies, and discuss how scientific and humanitarian actors can work together in a partnership in needs assessment in humanitarian settings.

Results
In all, eight papers were found in which the HESPER or HESPER Web had been used in conflict- or post-conflict settings or natural disasters. The study samples varied from 85 to 1000 participants (mean 440). The mean number of perceived needs in all studies was 8, varying from 4.25 to 12.18. The top three needs varied in all the studies. A high number of perceived needs was associated with mental health problems. No paper has reported on how the assessment outcomes were shared between the researchers and humanitarian actors.

Conclusion
Inventorying the needs from the perspective of the affected population is important to tailor the response to each humanitarian emergency. The HESPER scale and the HESPER Web are multisectoral tools that can be used to take inventory of the perceived needs and indicate the mental health problems that arise in conflict-ridden and natural disaster contexts. It is essential that results from a scientific needs inventory are shared with adequate humanitarian stakeholders to not only facilitate a proper response, but also to foster a closer collaboration between scientists, humanitarians, and the affected population. Doing so would increase the development and use of evidence in practice when providing humanitarian aid.
LncRNA MILIP links YBX1 to translational activation of Snai1 and promotes metastasis in clear cell renal cell carcinoma
Authors: Wang Yanliang , Feng Yu Chen , Gan Yujin , Teng Liu , Wang Li , La Ting , Wang Peilin , Gu Yue , Yan Lei , Li Na , Zhang Lina , Wang Limeng , Thorne Rick F. , Zhang Xu Dong , Cao Huixia , Shao Feng-Min 
Published: August 2022

Abstract
Background
Distant metastasis is the major cause of clear cell renal cell carcinoma (ccRCC)-associated mortality. However, molecular mechanisms involved in ccRCC metastasis remain to be fully understood. With the increasing appreciation of the role of long non-coding RNAs (lncRNAs) in cancer development, progression, and treatment resistance, the list of aberrantly expressed lncRNAs contributing to ccRCC pathogenesis is expanding rapidly.

Methods
Bioinformatics analysis was carried out to interrogate publicly available ccRCC datasets. In situ hybridization and qRT-PCR assays were used to test lncRNA expression in human ccRCC tissues and cell lines, respectively. Chromatin immunoprecipitation and luciferase reporter assays were used to examine transcriptional regulation of gene expression. Wound healing as well as transwell migration and invasion assays were employed to monitor ccRCC cell migration and invasion in vitro. ccRCC metastasis was also examined using mouse models in vivo. RNA pulldown and RNA immunoprecipitation were performed to test RNA–protein associations, whereas RNA-RNA interactions were tested using domain-specific chromatin isolation by RNA purification.

Results
MILIP expression was upregulated in metastatic compared with primary ccRCC tissues. The increased MILIP expression in metastatic ccRCC cells was driven by the transcription factor AP-2 gamma (TFAP2C). Knockdown of MILIP diminished the potential of ccRCC cell migration and invasion in vitro and reduced the formation of ccRCC metastatic lesions in vivo. The effect of MILIP on ccRCC cells was associated with alterations in the expression of epithelial-to-mesenchymal transition (EMT) hallmark genes. Mechanistically, MILIP formed an RNA-RNA duplex with the snail family transcriptional repressor 1 (Snai1) mRNA and bound to Y-box binding protein 1 (YBX1). This promoted the association between the YBX1 protein and the Snai1 mRNA, leading to increased translation of the latter. Snai1 in turn played an important role in MILIP-driven ccRCC metastasis.

Conclusions
The TFAP2C-responsive lncRNA MILIP drives ccRCC metastasis. Targeting MILIP may thus represent a potential avenue for ccRCC treatment.