bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease
Authors: Griese Matthias , Kappler Matthias , Stehling Florian , Schulze Johannes , Baden Winfried , Koerner-Rettberg Cordula , Carlens Julia , Prenzel Freerk , Nährlich Lutz , Thalmeier Andreas , Sebah Daniela , Kronfeld Kai , Rock Hans , Ruckes Christian ,   the HCQ-study group, Olivier Margarete , Zielen Stefan , Bagheri-Potthof Azadeh , Thome Ulrich , Gebhardt Julia , Mehl Anna , Lau Susanne Gabriele , Philipp Utz , Kopp Matthias , Stichtenoth Guido , Sommerburg Olaf , Stahl Mirjam , Kitz Richard , Rietschel Christoph , Stock Philippe , Ahrens Frank , Hebestreit Helge , Segerer Florian , Brinkmann Folke , Anne Schlegtendal , Eismann Claudia , Neuner Dörthe , Witt Sabine , Hengst Meike , Feilcke Maria , Babl Jürgen , Stauffer Gabriele , Nickolay Tanja , Gorbulev Stanislav , Anthony Gisela , Stöhr Linda , Vieweg Laura , Strenge-Hesse Anke , Wetzke Martin , Seidl Elias , Schwerk Nicolaus 
Published: July 2022

Abstract
Background
No results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks.

Results
26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O2-saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O2-saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ.

Conclusions
Acknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu, registered 02.07.2013).
Registration The study was registered on 2 July 2013 (Eudra-CT Number: 2013-003714-40), whereas the approval by BfArM was received 24.11.2014, followed by the approval by the lead EC of the University Hospital Munich on 20.01.2015. At clinicaltrials.gov the trial was additionally registered on November 8, 2015 (NCT02615938).
Renal phenotypes correlate with genotypes in unrelated individuals with tuberous sclerosis complex in China
Authors: Luo Cong , Zhang Ye , Zhang Yu-shi , Zhang Ming-Xin , Ning Jun , Chen Min-Feng , Li Yuan , Qi Lin , Zu Xiong-Bing , Li Yang-Le , Cai Yi 
Published: July 2022

AbstractPurposeTo explore the relationship between the genotype and renal phenotype in a Chinese cohort and guide clinical decision-making for treating tuberous sclerosis complex (TSC).Materials and methodsWe reviewed 173 patients with definite TSC at three centers in China from September 2014 to September 2020. All the patients underwentTSC1andTSC2genetic testing as well as renal phenotypic evaluation. All analyses were performed using the SPSS software, version 19.0, with a cut-offPvalue of 0.05 considered statistically significant.ResultsWe identified variants in 93% (161/173) cases, including 16%TSC1and 77%TSC2variants. Analysis of the relationship between the genotype and renal phenotype, revealed that those withTSC2variants were more likely to develop severe renal AML (> 4) (P = 0.044). In terms of treatment,TSC2variants were more likely to undergo nephrectomy/partial nephrectomy (P = 0.036) and receive mTOR medication such as everolimus (P < 0.001). However, there was no significant difference between the two groups in terms of their response to the everolimus treatment.ConclusionPatients withTSC2variants exhibit more severe renal phenotypes, especially those associated with renal angiomyolipomas (AML), and they often require nephrectomy/partial nephrectomy or mTOR medication. Detection of the genotype is helpful in TSC management.
Clusters of clinical and immunologic features in patients with bullous systemic lupus erythematosus: experience from a single-center cohort study in China
Authors: Qiao Lin , Zhang Bingjie , Zheng Wenjie , Li Mengtao , Zhao Yan , Zeng Xiaofeng , Zhang Fengchun , Wang Li , Li Li 
Published: July 2022

Abstract
Background
Bullous systemic lupus erythematosus (BSLE) is a rare subtype of systemic lupus erythematosus (SLE) that is clinically characterized by subepidermal tense vesicles or bullae. We aimed to investigate the clinical and laboratory features of patients with BSLE.

Methods
We retrospectively reviewed all patients who fulfilled the diagnostic criteria for BSLE in our institution from 2015 to 2021. Cutaneous lesions, systemic manifestations, treatment options, and outcomes were evaluated. For each case of BSLE, four controls were randomly selected from patients with single SLE. Major clinical and laboratory characteristics were compared between the two groups.

Results
Among 4221 patients with SLE, 12 developed BSLE. Vesiculobullous lesions were the first sign in five of the BSLE patients (5/12, 41.7%) and appeared after SLE diagnosis in the remaining seven patients (7/12, 58.3%), with a median duration from SLE onset of 36 months (4–115 months). The most common BSLE-affected sites were the head and neck (10/12, 83.3%), extremities (9/12, 75.0%), trunk (7/12, 58.3%), and mucosae (6/12, 50.0%). All patients with BSLE had extra-cutaneous involvement. The SLE disease activity index score exceeded 5 in 10/12 (83.3%) patients, which indicated high disease activity. Patients in the BSLE group had significantly higher incidences of proteinuria (83.3% vs. 47.9%, P = 0.027), hematuria (75% vs. 31.3%, P = 0.006), hemolytic anemia (33.3% vs. 0%, P = 0.000), and leukopenia (66.7% vs. 25.0%, P = 0.006) than those in the control group. The use of systemic corticosteroids, immunosuppressants, dapsone, and skin care was effective in controlling disease.

Conclusions
Vesiculobullous lesions may be the first manifestation and indicate a high disease activity in patients with BSLE. Early diagnosis using clinical, histopathological, and immunological evaluations can lead to appropriate treatment of this progressive disease and improve prognosis.
Does inter-border conflict influence the views of task sharing among community health volunteers in Nigeria? A qualitative study
Authors: Lar Luret , Stewart Martyn , Isiyaku Sunday , Dean Laura , Ozano Kim , Mpyet Caleb , Theobald Sally 
Published: July 2022

Abstract
Background
Volunteer community health workers are increasingly being engaged in Nigeria, through the World Health Organization’s task sharing strategy. This strategy aims to address gaps in human resources for health, including inequitable distribution of health workers. Recent conflicts in rural and fragile border communities in northcentral Nigeria create challenges for volunteer community health workers to meet their community's increasing health needs. This study aimed to explore the perception of volunteers involved in task sharing to understand factors affecting performance and delivery in such contexts.

Methods
This was a qualitative study conducted in fragile border communities in north central Nigeria. Eighteen audio recorded, semi-structured interviews with volunteers and supervisors were performed. Their perceptions on how task sharing and allocation of tasks affect performance and delivery were elucidated. The transactional social framework was applied during the thematic analysis process to generate an explanatory account of the research data, which was analysed using NVivo software.

Results
Promotive and preventive tasks were shared among the predominantly agrarian respondents. There was a structured task allocation process that linked the community with the health system and mainly cordial relationships were in place. However, there were barriers related to ethnoreligious crises and current conflict, timing of task allocations, gender inequities in volunteerism, shortage of commodities, inadequate incentives, dwindling community support and negative attitudes of some volunteers.

Conclusion
The perception of task sharing was mainly positive, despite the challenges, especially the current conflict. In this fragile context, reconsideration of non-seasonal task allocations within improved community-driven selection and security systems should be encouraged. Supportive supervision and providing adequate and timely renumeration will also be beneficial in this fragile setting.
Knockdown of myorg leads to brain calcification in zebrafish
Authors: Zhao Miao , Lin Xiao-Hong , Zeng Yi-Heng , Su Hui-Zhen , Wang Chong , Yang Kang , Chen Yi-Kun , Lin Bi-Wei , Yao Xiang-Ping , Chen Wan-Jin 
Published: July 2022

AbstractPrimary familial brain calcification (PFBC) is a neurogenetic disorder characterized by bilateral calcified deposits in the brain. We previously identified that MYORG as the first pathogenic gene for autosomal recessive PFBC, and established a Myorg-KO mouse model. However, Myorg-KO mice developed brain calcifications until nine months of age, which limits their utility as a facile PFBC model system. Hence, whether there is another typical animal model for mimicking PFBC phenotypes in an early stage still remained unknown. In this study, we profiled the mRNA expression pattern of myorg in zebrafish, and used a morpholino-mediated blocking strategy to knockdown myorg mRNA at splicing and translation initiation levels. We observed multiple calcifications throughout the brain by calcein staining at 2–4 days post-fertilization in myorg-deficient zebrafish, and rescued the calcification phenotype by replenishing myorg cDNA. Overall, we built a novel model for PFBC via knockdown of myorg by antisense oligonucleotides in zebrafish, which could shorten the observation period and replenish the Myorg-KO mouse model phenotype in mechanistic and therapeutic studies.
A large-scale polygenic risk score analysis identified candidate proteins associated with anxiety, depression and neuroticism
Authors: Cheng Bolun , Yang Xuena , Cheng Shiqiang , Li Chun’e , Zhang Huijie , Liu Li , Meng Peilin , Jia Yumeng , Wen Yan , Zhang Feng 
Published: July 2022

AbstractPsychiatric disorders and neuroticism are closely associated with central nervous system, whose proper functioning depends on efficient protein renewal. This study aims to systematically analyze the association between anxiety / depression / neuroticism and each of the 439 proteins. 47,536 pQTLs of 439 proteins in brain, plasma and cerebrospinal fluid (CSF) were collected from recent genome-wide association study. Polygenic risk scores (PRS) of the 439 proteins were then calculated using the UK Biobank cohort, including 120,729 subjects of neuroticism, 255,354 subjects of anxiety and 316,513 subjects of depression. Pearson correlation analyses were performed to evaluate the correlation between each protein and each of the mental traits by using calculated PRSs as the instrumental variables of protein. In general population, six correlations were identified in plasma and CSF such as plasma protease C1 inhibitor (C1-INH) with neuroticism score (r = − 0.011, P = 2.56 × 10− 9) in plasma, C1-INH with neuroticism score (r = -0.010, P = 3.09 × 10− 8) in CSF, and ERBB1 with self-reported depression (r = − 0.012, P = 4.65 × 10− 5) in CSF. C1-INH and ERBB1 may induce neuroticism and depression by affecting brain function and synaptic development. Gender subgroup analyses found that BST1 was correlated with neuroticism score in male CSF (r = − 0.011, P = 1.80 × 10− 5), while CNTN2 was correlated with depression score in female brain (r = − 0.013, P = 6.43 × 10− 4). BST1 and CNTN2 may be involved in nervous system metabolism and brain health. Six common candidate proteins were associated with all three traits (P < 0.05) and were confirmed in relevant proteomic studies, such as C1-INH in plasma, CNTN2 and MSP in the brain. Our results provide novel clues for revealing the roles of proteins in the development of anxiety, depression and neuroticism.
Genetic subtypes and phenotypic characteristics of 110 patients with Prader-Willi syndrome
Authors: Zhang Lu , Liu Xiaoliang , Zhao Yunjing , Wang Qingyi , Zhang Yuanyuan , Gao Haiming , Zhang Bijun , Cui Wanting , Zhao Yanyan 
Published: July 2022

Abstract
Background
Prader-Willi syndrome (PWS) is a complex disorder caused by impaired paternally expressed genes on chromosome 15q11-q13. Variable findings have been reported about the phenotypic differences among PWS genetic subtypes.

Methods
A total of 110 PWS patients were diagnosed from 8,572 pediatric patients included from July 2013 to December 2021 by MLPA and MS-MLPA assays. Atypical deletions were defined by genomic CNV-sequencing. Maternal uniparental disomy (UPD) was subgrouped by microsatellite genotyping. Clinical data were collected for phenotype-genotype associations. Twenty-one patients received growth hormone (GH) treatment, and the anthropometric and laboratory parameters were evaluated and compared.

Results
Genetically, the 110 patients with PWS included 29 type I deletion, 56 type II deletion, 6 atypical deletion, 11 heterodisomy UPD, and 8 isodisomy UPD. The UPD group had significantly higher maternal age (31.4 ± 3.4 vs 27.8 ± 3.8 years), more anxiety (64.29% vs 26.09%) and autistic traits (57.14% vs 26.09%), and less hypopigmentation (42.11% vs 68.24%) and skin picking (42.86% vs 71.01%) than the deletion group. The type I deletion group was diagnosed at earlier age (3.7 ± 3.3 vs 6.2 ± 3.2 years) and more common in speech delay (95.45% vs 63.83%) than the type II. The isodisomy UPD group showed a higher tendency of anxiety (83.33% vs 50%) than the heterodisomy. GH treatment for 1 year significantly improved the SDS of height (− 0.43 ± 0.68 vs − 1.32 ± 1.19) and IGF-I (− 0.45 ± 0.48 vs − 1.97 ± 1.12). No significant changes were found in thyroid function or glucose/lipid metabolism.

Conclusion
We explored the physical, psychological and behavioral phenotype-genotype associations as well as the GH treatment effect on PWS from a large cohort of Chinese pediatric patients. Our data might promote pediatricians' recognition and early diagnosis of PWS.
Explore the attitudes of children and adolescent parents towards the vaccination of COVID-19 in China
Authors: Wang Lin , Wen Wen , Chen Chen , Tang Jiake , Wang Chunyi , Zhou Mengyun , Cheng Yongran , Zhang Xingwei , Wang Mingwei , Feng Zhanhui , Wang Weiqian 
Published: July 2022

Abstract
Background
With the increasing incidence of asymptomatic carriers or milder symptoms, children and adolescents are likely to become a silent source of infection. In view of the efficacy and safety of vaccines in the treatment of novel Coronavirus pneumonia, population-wide vaccination will be an inevitable trend to control the spread of COVID-19. However, there is no survey on the attitudes of Chinese parents of children and adolescents towards their children’s COVID-19 vaccination.

Methods
We used online questionnaires to find out the attitudes of Chinese parents toward their children’s immunization against COVID-19. Logistic regression was used to explore the influencing factors.

Results
A total of 2019 parents participated in the survey. Overall, 74.38% parents said they would actively get vaccinated, 8.90% refused to get vaccinated, 4.60% said they would delay vaccination and 12.12% were still undecided.

Conclusions
In general, Chinese parents have a high desire to be vaccinated against COVID-19, and most parents have a positive attitude towards their children’s vaccination. However, many people still hesitate or even refuse to be vaccinated. Education background, attitudes towards children’s vaccination, children’s age, recent illness and other factors have a certain impact on Chinese parents of children and adolescents towards their children’s COVID-19 vaccination.
Different AHO phenotype in a Chinese family with a novel GNAS missense variant: a case report
Authors: Zhou Qing , Liang Bin , Fu Qing-Xian , Liu Hui , Zou Chao-Chun 
Published: July 2022

Abstract
Background
Albright’s hereditary osteodystrophy (AHO) is an inherited disorder which is caused by an inactivating variant in the GNAS gene. AHO appears associated to either pseudohypoparathyroidism 1a (PHP1a) when GNAS gene is maternally inherited or to pseudo-pseudohypoparathyroidism (PPHP) when it is paternally inherited. We describe the clinical and biochemical characteristics of two patients, a boy and his mother with a novel heterozygous missense variant of GNAS gene.

Case presentation
The boy presented with typical AHO phenotype (early-onset obesity, round face, short neck, shortened fifth metacarpal bone, developmental retardation, but without short stature and subcutaneous calcifications), multiple hormone resistance including PTH, TSH and ACTH, and mild calcification in the right basal ganglia. The mother only presented with brachydactyly and short stature, without hormone resistance and other signs of AHO. Whole-exome sequencing identified in the son and his mother a novel heterozygous missense variant (p. Val375Leu) in exon 13 of GNAS gene. The diagnosis of PHP-1a for the son and PPHP for the mother were confirmed.

Conclusion
This study further expands the spectrum of known GNAS pathogenic variants, and also demonstrates the heterogeneous phenotype of AHO due to a novel GNAS pathogenic variant.
Unravelling genetic variants of a swedish family with high risk of prostate cancer
Authors: Barilla Serena , Lindblom Annika , Helgadottir Hafdis T. 
Published: July 2022

Abstract
Background
Prostate cancer is the most prevalent cancer in men worldwide. It is a polygenic disease with a substantial proportion of heritability. Identification of novel candidate biomarkers is crucial for clinical cancer prevention and the development of therapeutic strategies. Here, we describe the analysis of rare and common genetic variants that can predispose to the development of prostate cancer.

Methods
Whole-genome sequencing was performed on germline DNA of five Swedish siblings which were diagnosed with prostate cancer. The high-risk variants were identified setting the minor allele frequency < 0.01, CADD > 10 and if tested in PRACTICAL, OR > 1.5, while the low-risk variants were identified minor allele frequency > 0.01, CADD > 10 and if tested in PRACTICAL, OR > 1.1.

Results
We identified 38 candidate high-risk gene variants and 332 candidate low-risk gene variants, where 2 and 14 variants were in coding regions, respectively, that were shared by the brothers with prostate cancer.

Conclusions
This study expanded the knowledge of potential risk factor candidates involved in hereditary and familial prostate cancer. Our findings can be beneficial when applying targeted screening in families with a high risk of developing the disease.
Rationale and methods of the Antioxidant and NMDA receptor blocker Weans Anoxic brain damage of KorEa OHCA patients (AWAKE) trial
Authors: Choi Jin-Ho , Chun Byeong Jo , Yeom Seok Ran , Chung Sung Phil , Lee Young Hwan , Kim Yun-Hee , Lee Ji Sung , Lee Jin Hwan , Lee Hwan Goo , Jin Jing Yu , An Chun San , Gwag Byoung Joo 
Published: July 2022

Abstract
Background
Ischemic brain injury is a major hurdle that limits the survival of resuscitated out-of-hospital cardiac arrest (OHCA).

Methods
The aim of this study is to assess the feasibility and potential for reduction of ischemic brain injury in adult OHCA patients treated with high- or low-dose Neu2000K, a selective blocker of N-methyl-d-aspartate (NMDA) type 2B receptor and also a free radical scavenger, or given placebo. This study is a phase II, multicenter, randomized, double-blinded, prospective, intention-to-treat, placebo-controlled, three-armed, safety and efficacy clinical trial. This trial is a sponsor-initiated trial supported by GNT Pharma. Successfully resuscitated OHCA patients aged 19 to 80 years would be included. The primary outcome is blood neuron-specific enolase (NSE) level on the 3rd day. The secondary outcomes are safety, efficacy defined by study drug administration within 4 h in > 90% of participants, daily NSE up to 5th day, blood S100beta, brain MRI apparent diffusion coefficient imaging, cerebral performance category (CPC), and Modified Rankin Scale (mRS) at 5th, 14th, and 90th days. Assuming NSE of 42 ± 80 and 80 ± 80 μg/L in the treatment (high- and low-dose Neu2000K) and control arms with 80% power, a type 1 error rate of 5%, and a 28% of withdrawal prior to the endpoint, the required sample size is 150 patients.

Discussion
The AWAKE trial explores a new multi-target neuroprotectant for the treatment of resuscitated OHCA patients.

Trial registration
ClinicalTrials.gov NCT03651557. Registered on August 29, 2018.
Supporting families to achieve a healthy weight development for their child with overweight/obesity using the STARKIDS intervention: study protocol for a cluster-randomized controlled trial
Authors: Ziser Katrin , Junne Florian , Herschbach Anne , Martus Peter , Jacoby Johann , Stuber Felicitas , Rahmani Azad Zahra , Mack Isabelle , Weiland Alisa , Krauß Inga , Greule Constanze , Sudeck Gorden , Kastner Lydia , Zurstiege Guido , Hoell Andreas , Bethge Wolfgang , Sammet Torben , Schliesing Olaf , Zipfel Stephan , Ehehalt Stefan , Giel Katrin E. 
Published: July 2022

Abstract
Background
Childhood and adolescent overweight and obesity are among the most serious health challenges today. Structured weight reduction programs can be helpful to reduce severe health consequences but evidence is partly scarce. The STARKIDS program aims to improve on some of these limitations and is designed to be a structured, stepwise, digitally supported intervention program for the whole family. It is divided into two intervention steps spanning over 1.5 years and aims at promoting a healthy weight development of children/adolescents with overweight/obesity and an increase in quality of life.

Methods
The STARKIDS intervention is evaluated in a cluster-randomized study design by comparing it with a control group receiving a one-time structured counselling in the pediatric practice. The study aims to include 1000 families with children/adolescents with overweight/obesity from 100 pediatric practices. The main outcomes are reduction in body mass index percentiles and improvements in children’s/adolescent’s quality of life, secondary outcomes refer to the contents of the intervention such as diet, physical activity, stress, and media habits. All outcomes are measured on three measurement time points: (T0) at baseline/inclusion in the study, (T1) baseline + 12 months which is the end of step 1 of the STARKIDS intervention, and (T2) baseline + 18 months which is the end of step 2 of the STARKIDS intervention.

Discussion
The stepwise, e-health-supported STARKIDS program is a low-threshold intervention program for families with children/adolescents with overweight/obesity. With the proof of concept, STARKIDS provides the potential to be implemented as a standard care tool for the prevention and intervention of childhood/adolescence obesity in the German health system.

Trial registration
German Clinical Trials Register (DRKS) DRKS00022813 (acknowledged primary register of the World Health Organization). Registered on 27 November 2020 (Universal Trial Number U1111-1254-9536).