bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of polyunsaturated fatty acid (PUFA) administration on the microbiome-gut-brain axis in adolescents with anorexia nervosa (the MiGBAN study): study protocol for a longitudinal, double-blind, randomized, placebo-controlled trial
Authors: Keller Lara , Dempfle Astrid , Dahmen Brigitte , Schreiber Samira , Adan Roger A. H. , Andreani Nadia Andrea , Danner Unna N. , Eisert Albrecht , Fetissov Sergueï , Fischmeister Florian Ph. S. , Karwautz Andreas , Konrad Kerstin , Kooij Karlijn L. , Trinh Stefanie , van der Vijgh Benny , van Elburg Annemarie A. , Zeiler Michael , Baines John , Seitz Jochen , Herpertz-Dahlmann Beate 
Published: July 2022

Abstract
Background
Anorexia nervosa (AN) is a severe psychiatric disease that often takes a chronic course due to insufficient treatment options. Emerging evidence on the gut-brain axis offers the opportunity to find innovative treatments for patients with psychiatric disorders. The gut microbiome of patients with AN shows profound alterations that do not completely disappear after weight rehabilitation. In previous studies, the administration of polyunsaturated fatty acids (PUFA) resulted in effects that might be beneficial in the treatment of AN, affecting the microbiome, body weight and executive functions. Therefore, the MiGBAN study aims to examine the effects of a nutritional supplementation with PUFA on the gut microbiome and body mass index (BMI) in patients with AN.

Methods
This is a longitudinal, double-blind, randomized, placebo-controlled trial. Within 2 years, 60 adolescent patients aged 12 to 19 years with AN will receive either PUFA or placebo for 6 months additional to treatment as usual. After 1 year, the long-term effect of PUFA on the gut microbiome and consecutively on BMI will be determined. Secondary outcomes include improvement of gastrointestinal symptoms, eating disorder psychopathology, and comorbidities. Additionally, the interaction of the gut microbiome with the brain (microbiome-gut-brain axis) will be studied by conducting MRI measurements to assess functional and morphological changes and neuropsychological assessments to describe cognitive functioning. Anti-inflammatory effects of PUFA in AN will be examined via serum inflammation and gut permeability markers. Our hypothesis is that PUFA administration will have positive effects on the gut microbiota and thus the treatment of AN by leading to a faster weight gain and a reduction of gastrointestinal problems and eating disorder psychopathology.

Discussion
Due to previously heterogeneous results, a systematic and longitudinal investigation of the microbiome-gut-brain axis in AN is essential. The current trial aims to further analyse this promising research field to identify new, effective therapeutic tools that could help improve the treatment and quality of life of patients. If this trial is successful and PUFA supplementation contributes to beneficial microbiome changes and a better treatment outcome, their administration would be a readily applicable additional component of multimodal AN treatment.

Trial registration
German Clinical Trials Register DRKS00017130. Registered on 12 November 2019.
Clinical features and outcomes of patients with wheat-dependent exercise-induced anaphylaxis: a retrospective study
Authors: Du Zhirong , Gao Xiang , Li Junda , Li Lun , Liu Juan , Yin Jia 
Published: July 2022

Abstract
Background
Wheat-dependent exercise-induced anaphylaxis (WDEIA) is a serious and potentially life-threatening form of wheat allergy. Further episodes can only be prevented by avoiding wheat ingestion or avoiding exercise after wheat intake. Anaphylaxis may recur in some patients post-diagnosis. This study aimed to analyze the clinical features and management/outcomes of WDEIA in China.

Methods
We retrospectively analyzed the clinical characteristics, and laboratory testing of 197 patients with WDEIA. After diagnosis, the patients were followed up as outpatients to evaluate dietary/exercise choice and clinical outcomes.

Results
Among the 197 WDEIA patients (median age, 37 years), 53.8% were male and 28.4% had other allergic disorders. The median duration of anaphylaxis before diagnosis was 16 months. Significant delays in diagnosis (> 1 years) were recorded in 52.7% of the patients, which has not decreased by years (P = 0.064). Exercise (83.8%), alcohol (12.2%), and nonsteroidal anti-inflammatory drugs (7.1%) were the most common cofactors. The most common clinical features were urticaria (100%), loss of consciousness (82.7%), dyspnea (50.8%), and hypotension (47.2%). Of the 197 eligible patients, 155 responded (78.7%), and 124 (80.0%) of which had no anaphylaxis post-diagnosis. A wheat-free diet prevented future anaphylaxis in 91.7% of the patients, followed by the avoidance of wheat combined with exercise (87%) and reduced wheat intake combined with exercise avoidance (80.5%).

Conclusion
The diagnosis of WDEIA is frequently delayed. Therefore, when patients present with unexplained anaphylaxis, the possibility of WDEIA should be considered. A wheat-free diet or avoiding wheat combined with exercise or reduced wheat combined with exercise avoidance helps to significantly reduce the onset of future anaphylaxis. However, approximately one-fifth of patients continue to experience anaphylaxis post-diagnosis. Thus, these patients must always carry epinephrine autoinjectors.
The longitudinal bidirectional relationship between autistic traits and brain morphology from childhood to adolescence: a population-based cohort study
Authors: Durkut Melisa , Blok Elisabet , Suleri Anna , White Tonya 
Published: July 2022

Abstract
Objective
Autistic traits are associated with alterations in brain morphology. However, the anatomic location of these differences and their developmental trajectories are unclear. The primary objective of this longitudinal study was to explore the bidirectional relationship between autistic traits and brain morphology from childhood to adolescence.

Method
Participants were drawn from a population-based cohort. Cross-sectional and longitudinal analyses included 1950 (mean age 13.5) and 304 participants (mean ages 6.2 and 13.5), respectively. Autistic traits were measured with the Social Responsiveness Scale. Global brain measures and surface-based measures of gyrification, cortical thickness and surface area were obtained from T1-weighted MRI scans. Cross-sectional associations were assessed using linear regression analyses. Cross-lagged panel models were used to determine the longitudinal bidirectional relationship between autistic traits and brain morphology.

Results
Cross-sectionally, higher levels of autistic traits in adolescents are associated with lower gyrification in the pars opercularis, insula and superior temporal cortex; smaller surface area in the middle temporal and postcentral cortex; larger cortical thickness in the superior frontal cortex; and smaller cerebellum cortex volume. Longitudinally, both autistic traits and brain measures were quite stable, with neither brain measures predicting changes in autistic traits, nor vice-versa.

Limitations
Autistic traits were assessed at only two time points, and thus we could not distinguish within- versus between-person effects. Furthermore, two different MRI scanners were used between baseline and follow-up for imaging data acquisition.

Conclusions
Our findings point to early changes in brain morphology in children with autistic symptoms that remain quite stable over time. The observed relationship did not change substantially after excluding children with high levels of autistic traits, bolstering the evidence for the extension of the neurobiology of autistic traits to the general population.
Waardenburg syndrome type 4 coexisting with open-angle glaucoma: a case report
Authors: Zhang Li , Wan Yue , Wang Ningli 
Published: July 2022

Abstract
Background
Waardenburg syndrome is an autosomal dominant disorder with varying degrees of sensorineural hearing loss as well as abnormal pigmentation in hair, skin, and iris. There are four types of Waardenburg syndrome (1–4) with different characteristics. Mutations in six genes have been identified to be associated with the various types. Herein, we describe a case of Waardenburg syndrome type 4 combined with open-angle glaucoma.

Case presentation
A 43-year-old Han Chinese man had undergone trabeculectomy due to progression of visual field impairment and unstable intraocular pressure in both eyes. Slit-lamp examination revealed diffuse iris hypopigmentation in the left eye and hypopigmentation of part of the iris in the right eye. Fundus examination showed red, sunset-like fundus due to a lack of pigmentation in the retinal pigment epithelium layer, diffuse loss of the nerve fiber layer, and an excavated optic nerve head with advanced-stage glaucoma. Imaging was performed using anterior segment optical coherence tomography to detect the iris configuration. In the heterochromic iris portion, the normal part of the iris showed a clear hyperreflective signal of the anterior border layer, while atrophy of the pigmented anterior border layer showed a hyporeflective area of the anterior surface resulting in reduced light absorption. Two mutations of the endothelin receptor type B gene were recognized in this study. The first (c.1111G>A on exon 7) leads to an amino acid change from glycine to serine at codon 371. Sanger verification revealed that this mutation is inherited from the mother. The other mutation (c.553G>A) leads to an amino acid change from valine to methionine at codon 185. Sanger verification showed that this mutation was inherited from the father.

Conclusion
Waardenburg syndrome shows a remarkable diversity in clinical presentation and morphology. This disease can also present with open-angle glaucoma. Sequencing analysis revealed two heterozygous mutations in the EDNRB gene in this patient, inherited from his mother and father, respectively. These two sites constitute a compound heterozygous variation.
Feasibility and cost description of highly intensive rehabilitation involving new technologies in patients with post-acute stroke—a trial of the Swiss RehabTech Initiative
Authors: Schuster-Amft Corina , Kool Jan , Möller J. Carsten , Schweinfurther Raoul , Ernst Markus J. , Reicherzer Leah , Ziller Carina , Schwab Martin E. , Wieser Simon , Wirz Markus ,   for the SRTI study group, Menig Alexandra , Paredes Liliana P. , Rosemeier Heike 
Published: July 2022

AbstractBackgroundThere is a need to provide highly repetitive and intensive therapy programs for patients after stroke to improve sensorimotor impairment. The employment of technology-assisted training may facilitate access to individualized rehabilitation of high intensity. The purpose of this study was to evaluate the safety and acceptance of a high-intensity technology-assisted training for patients after stroke in the subacute or chronic phase and to establish its feasibility for a subsequent randomized controlled trial.MethodsA longitudinal, multi-center, single-group study was conducted in four rehabilitation clinics. Patients participated in a high-intensity 4-week technology-assisted trainings consisting of 3 to 5 training days per week and at least 5 training sessions per day with a duration of 45 min each. Feasibility was evaluated by examining recruitment, intervention-related outcomes (adherence, subjectively perceived effort and effectiveness, adverse events), patient-related outcomes, and efficiency gains. Secondary outcomes focused on all three domains of the International Classification of Functioning Disability and Health. Data were analyzed and presented in a descriptive manner.ResultsIn total, 14 patients after stroke were included. Participants exercised between 12 and 21 days and received between 28 and 82 (mean 46 ± 15) technology-assisted trainings during the study period, which corresponded to 2 to 7 daily interventions. Treatment was safe. No serious adverse events were reported. Minor adverse events were related to tiredness and exertion. From baseline to the end of the intervention, patients improved in several functional performance assessments of the upper and lower extremities. The efficiency gains of the trainings amounted to 10% to 58%, in particular for training of the whole body and for walking training in severely impaired patients.ConclusionsHighly intensive technology-assisted training appears to be feasible for in- and outpatients in the subacute or chronic phase after stroke. Further clinical trials are warranted in order to define the most comprehensive approach to highly intensive technology-assisted training and to investigate its efficacy in patients with neurological disorders.Trial registrationClinicalTrials.govIdentifier: NCT03641651 at August 31st 2018
Spatial trends and projections of chronic malnutrition among children under 5 years of age in Ethiopia from 2011 to 2019: a geographically weighted regression analysis
Authors: Seboka Binyam Tariku , Hailegebreal Samuel , Mamo Tizalegn Tesfaye , Yehualashet Delelegn Emwodew , Gilano Girma , Kabthymer Robel Hussen , Ewune Helen Ali , Kassa Reta , Debisa Mary Abera , Yawo Mulugeta Namaro , Endashaw Habtamu , Demeke Abel Desalegn , Tesfa Getanew Aschalew 
Published: July 2022

Abstract
Introduction
Undernutrition is a serious global health issue, and stunting is a key indicator of children's nutritional status which results from long-term deprivation of basic needs. Ethiopia, the largest and most populous country in Sub-Saharan Africa, has the greatest rate of stunting among children under the age of five, yet the problem is unevenly distributed across the country. Thus, we investigate spatial heterogeneity and explore spatial projection of stunting among under-five children. Further, spatial predictors of stunting were assessed using geospatial regression models.

Methods
The Ethiopia Demographic and Health Surveys (EDHS) data from 2011, 2016, and 2019 were examined using a geostatistical technique that took into account spatial autocorrelation. Ordinary kriging was used to interpolate stunting data, and Kulldorff spatial scan statistics were used to identify spatial clusters with high and low stunting prevalence. In spatial regression modeling, the ordinary least square (OLS) model was employed to investigate spatial predictors of stunting and to examine local spatial variations geographically weighted regression (GWR) and multiscale geographically weighted regression (MGWR) models were employed.

Results
Overall, stunting prevalence was decreased from 44.42% [95%, CI: 0.425–0.444] in 2011 to 36.77% [95%, CI: 0.349–0.375] in 2019. Across three waves of EDHS, clusters with a high prevalence of stunting in children under 5 years were consistently observed in northern Ethiopia stretching in Tigray, Amhara, Afar, and Benishangul-Gumuz. Another area of very high stunting incidence was observed in the Southern parts of Ethiopia and the Somali region of Ethiopia. Our spatial regression analysis revealed that the observed geographical variation of under-five stunting significantly correlated with poor sanitation, poor wealth index, inadequate diet, residency, and mothers' education.

Conclusions
In Ethiopia, substantial progress has been made in decreasing stunting among children under the age of 5 years; although disparities varied in some areas and districts between surveys, the pattern generally remained constant over time. These findings suggest a need for region and district-specific policies where priority should be given to children in areas where most likely to exhibit high-risk stunting.
Computational analysis uncovers the deleterious SNPs along with the mutational spectrum of p53 gene and its differential expression pattern in pan-cancer
Authors: Alam Saruar , Sayem Mohammad , Bello Martiniano , Mou Sadia Islam , Faruqui Nairita Ahsan , Hossain Faruk , Hasan Md. Kamrul 
Published: July 2022

Abstract
Background
A variety of accessible data, including those of single-nucleotide polymorphisms (SNPs) on the human p53 gene, are made widely available on a global scale. Owing to this, our investigation aimed to deal with the detrimental SNPs in the p53 gene by executing various valid computational tools, including—Filter, SIFT, PredictSNP, Fathmm, UTRScan, ConSurf, SWISS-MODEL, Amber 16 package, Tm-Adjust, I-Mutant, Task Seek, GEPIA2 after practical and basic appraisal, dissolvable openness, atomic progression, analyzing the energy minimization and assessing the gene expression pattern.

Results
Out of the total 581 p53 SNPs, 420 SNPs were found to be missense or non-synonymous, 435 SNPs were in the three prime UTR, and 112 SNPs were in the five prime UTR from which 16 non-synonymous SNPs (nsSNPs) were predicted to be non-tolerable while PredictSNP package predicted 14. Concentrating on six bioinformatics tools of various dimensions, a combined output was generated, where 14 nsSNPs could exert a deleterious effect. We found 5 missense SNPs in the DNA binding domain's three crucial amino acid positions, using diverse SNP analyzing tools. The underlying discoveries were fortified by microsecond molecular dynamics (MD) simulations, TM-align, I-Mutant, and Project HOPE. The ExPASy-PROSITE tools characterized whether the mutations were located in the functional part of the protein or not. This study provides a decisive outcome, concluding the accessible SNPs' information by recognizing the five unfavorable nsSNPs—rs28934573 (S241F), rs11540652 (R248Q), rs121913342 (R248W), rs121913343 (R273C), and rs28934576 (R273H). By utilizing Heatmapper and GEPIA2, several visualization plots, including heat maps, box plots, and survival plots, were produced.

Conclusions
These plots disclosed differential expression patterns of the p53 gene in humans. The investigation focused on recognizing the detrimental nsSNPs, which augmented the danger posed by various oncogenesis in patients of different populations, including within the genome-wide studies (GWS).
A scoping review on acute gastrointestinal surgical complications in immunocompromised pediatric patients
Authors: Dargham Tarek Bou , Moumneh Mohamad Bahij , Atallah Christine , Zaghal Ahmad 
Published: July 2022

AbstractBackgroundGastrointestinal complications are becoming increasingly more common and pose a significant risk on the health of children with compromised immunity caused by various etiologies such as chemotherapy and posttransplantation immunosuppression. We aim to review abdominal complications in immunocompromised children and their respective management.Main bodyThis is a scoping review of the literature. PubMed, MEDLINE, Google Scholar, and Scopus libraries were searched for relevant articles. Extracted data included the etiologies of immunocompromised immunity, gastrointestinal and abdominal complications in immunocompromised children, diagnosis, and treatment of these pathologies. Examples of gastrointestinal complications in immunocompromised children include, but not limited to, neutropenic enterocolitis, acute appendicitis, bowel perforation, acalculous cholecystitis, and acute pancreatitis. Our literature review showed that bacterial and fungal infections are the major causes of exacerbation and mortality. The main cause of immunosuppression in children with neutropenic enterocolitis and acute pancreatitis is chemotherapy, and management of these pathologies using intravenous fluids, antibiotic therapy, and granulocyte-stimulating factors is the current standard of care. Surgical intervention is uncommon and reserved for complicated cases. That said, in acute appendicitis and bowel perforation, laparoscopy is the mainstay treatment. However, in systemic infections, nonsurgical interventions such as transfusion and bowel rest are the gold standard. As for acalculous cholecystitis, percutaneous cholecystectomy is superior to laparotomy and other surgical interventions.ConclusionTimely diagnosis and management of gastrointestinal complications in the immunocompromised children is key in reducing mortality and morbidity. Both surgical and nonsurgical interventions are needed and should be further studied in order to improve outcomes.
High-throughput Sequencing to Identify Monogenic Etiologies in a Preselected Polycystic Ovary Syndrome Cohort
Authors: Crespo Raiane P , Rocha Thais P , Montenegro Luciana R , Nishi Mirian Y , Jorge Alexander A L , Maciel Gustavo A R , Baracat Edmund , Latronico Ana Claudia , Mendonca Berenice B , Gomes Larissa G 
Published: July 2022

Abstract

Context
Polycystic ovary syndrome (PCOS) etiology remains to be elucidated, but familial clustering and twin studies have shown a strong heritable component.

Objective
The purpose of this study was to identify rare genetic variants that are associated with the etiology of PCOS in a preselected cohort.

Methods
This prospective study was conducted among a selected group of women with PCOS. The study’s inclusion criteria were patients with PCOS diagnosed by the Rotterdam criteria with the following phenotypes: severe insulin resistance (IR), normoandrogenic–normometabolic phenotype, adrenal hyperandrogenism, primary amenorrhea, and familial PCOS. Forty-five patients were studied by target sequencing, while 8 familial cases were studied by whole exome sequencing.

Results
Patients were grouped according to the inclusion criteria with the following distribution: 22 (41.5%) with severe IR, 13 (24.5%) with adrenal hyperandrogenism, 7 (13.2%) with normoandrogenic phenotype, 3 (5.7%) with primary amenorrhea, and 8 (15.1%) familial cases. DNA sequencing analysis identified 1 pathogenic variant in LMNA, 3 likely pathogenic variants in INSR, PIK3R1, and DLK1, and 6 variants of uncertain significance level with interesting biologic rationale in 5 genes (LMNA, GATA4, NR5A1, BMP15, and FSHR). LMNA was the most prevalent affected gene in this cohort (3 variants).

Conclusion
Several rare variants in genes related to IR were identified in women with PCOS. Although IR is a common feature of PCOS, patients with extreme or atypical phenotype should be carefully evaluated to rule out monogenic conditions.
Prediction of Metachronous Peritoneal Metastases After Radical Surgery for Colon Cancer: A Scoring System Obtained from an International Multicenter Cohort
Authors: Pedrazzani Corrado , Turri Giulia , Marrelli Daniele , Kim Hye Jin , Park Eun Jung , Spolverato Gaya , Foppa Caterina , Spinelli Antonino , Pucciarelli Salvatore , Baik Seung Hyuk , Choi Gyu Seog 
Published: July 2022

Abstract
Background
Since novel strategies for prevention and treatment of metachronous peritoneal metastases (mPM) are under study, it appears crucial to identify their risk factors. Our aim is to establish the incidence of mPM after surgery for colon cancer (CC) and to build a statistical model to predict the risk of recurrence.

Patients and Methods
Retrospective analysis of consecutive pT3–4 CC operated at five referral centers (2014–2018). Patients who developed mPM were compared with patients who were PM-free at follow-up. A scoring system was built on the basis of a logistic regression model.

Results
Of the 1423 included patients, 74 (5.2%) developed mPM. Patients in the PM group presented higher preoperative carcinoembryonic antigen (CEA) [median (IQR): 4.5 (2.5–13.0) vs. 2.7 (1.5–5.9), P = 0.001] and CA 19-9 [median (IQR): 17.7 (12.0–37.0) vs. 10.8 (5.0–21.0), P = 0.001], advanced disease (pT4a 42.6% vs. 13.5%; pT4b 16.2% vs. 3.2%; P < 0.001), and negative pathological characteristics. Multivariate logistic regression identified CA 19-9, pT stage, pN stage, extent of lymphadenectomy, and lymphovascular invasion as significant predictors, and individual risk scores were calculated for each patient. The risk of recurrence increased remarkably with score values, and the model demonstrated a high negative predictive value (98.8%) and accuracy (83.9%) for scores below five.

Conclusions
Besides confirming incidence and risk factors for mPM, our study developed a useful clinical tool for prediction of mPM risk. After external validation, this scoring system may guide personalized decision-making for patients with locally advanced CC.