bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the feasibility and effectiveness of a modular treatment program for children and adolescents with depression and interpersonal problems: study protocol of a quasi-experimental pilot feasibility trial (CBASP@YoungAge)
Authors: Dippel N. , In-Albon T. , Schneider S. , Christiansen H. , Brakemeier E.-L. 
Published: July 2022

AbstractBackgroundDepression is a serious disorder in childhood and adolescence. Affected children and adolescents show significant impairments in various aspects of life. Studies on the effectiveness or efficacy of psychotherapy in depressed children and adolescents are qualitatively very heterogeneous and reveal small effect sizes. There is thus a need to better tailor psychotherapy approaches to these age groups to improve outcomes like parent-child relationship, symptomatology, or quality of life.To address this gap, we designed a modular, individualized treatment program for children and adolescents based on the Cognitive Behavioral Analysis System of Psychotherapy (CBASP) including caregiver involvement.MethodThis quasi-experimental pilot feasibility trial is a phase 1 to phase 2 study investigating the feasibility and effectiveness of CBASP@YoungAge by including an intervention group (CBASP@YoungAge) and a treatment-as-usual control group. The treatment of depressive symptoms as well as interpersonal problems with primary caregivers are the main targets of CBASP@YoungAge. Personalization is ensured concerning the treatment course, caregivers’ involvement, and the patient’s age. The primary outcome relates to two areas: the feasibility of the CBASP@YoungAge treatment program in an outpatient context and a change in patients' depressive symptomatology from before to after treatment. We conduct a brief process evaluation after each session in the intervention group to closely monitor the treatment process and examine feasibility from the therapists' and patients' perspectives and mechanisms of symptom change. In addition, we consider interpersonal behavior between children and caregivers, parenting behavior, and monitor the global-health-index in children and parents as secondary outcomes. Pre-, post-, and follow-up data are evaluated.DiscussionThis is the first study of a modular-based intervention program for children and adolescents with depression and a clear focus on the interpersonal problems between the depressed young patient and her/his caregiver. It will provide important knowledge on the feasibility and effectiveness of the program and potential benefits of including caregivers in psychotherapy. Based on this study’s results, we plan a multicenter, randomized, controlled trial whose long-term aim is to improve the psychotherapeutic care of young patients with depression while preventing persistent courses of depressive disorders.Trial registrationGerman Clinical Trials Register, DRKS (identifierDRKS00023281). Registered 17 November 2020–Retrospectively registered
COVID-19 as a putative trigger of anti-MDA5-associated dermatomyositis with acute respiratory distress syndrome (ARDS) requiring lung transplantation, a case report
Authors: Anderle Karolina , Machold Klaus , Kiener Hans P. , Bormann Daniel , Hoetzenecker Konrad , Geleff Silvana , Prosch Helmut , Laccone Franco , Heil Peter M. , Petzelbauer Peter , Aletaha Daniel , Blüml Stephan , Kastrati Kastriot 
Published: July 2022

Abstract
Background
Autoimmune disease following COVID-19 has been studied intensely since the beginning of the pandemic. Growing evidence indicates that SARS-CoV-2 infection, by virtue of molecular mimicry can lead to an antigen-mediated cross-reaction promoting the development of a plethora of autoimmune spectrum diseases involving lungs and extrapulmonary tissues alike. In both COVID-19 and autoimmune disease, the immune self-tolerance breaks, leading to an overreaction of the immune system with production of a variety of autoantibodies, sharing similarities in clinical manifestation, laboratory, imaging, and pathology findings. Anti-Melanoma Differentiation-Associated gene 5 dermatomyositis (anti-MDA5 DM) comprises a rare subtype of systemic inflammatory myopathies associated with characteristic cutaneous features and life-threatening rapidly progressive interstitial lung disease (RP-ILD). The production of anti-MDA5 autoantibodies was proposed to be triggered by viral infections.

Case presentation
A 20-year-old male patient with polyarthritis, fatigue and exertional dyspnea was referred to our department. An elevated anti-MDA5 autoantibody titer, myositis on MRI, ground glass opacifications on lung CT and histological features of Wong-type dermatomyositis were confirmed, suggesting the diagnosis of an anti-MDA5 DM. Amid further diagnostic procedures, a serologic proof of a recent SARS-CoV-2 infection emerged. Subsequently, the patient deteriorated into a fulminant respiratory failure and an urgent lung transplantation was performed, leading to remission ever since (i.e. 12 months as of now).

Conclusions
We report a unique case of a patient with a new-onset anti-MDA5 DM with fulminant ARDS emerging in a post-infectious stage of COVID-19, who underwent a successful lung transplantation and achieved remission. Given the high mortality of anti-MDA5 DM associated RP-ILD, we would like to highlight that the timely recognition of this condition and urgent therapy initiation are of utmost importance.
Nephroblastoma Treatment and Outcomes in a Low-Income Setting
Authors: Shyirambere Cyprien , Villaverde Chandler , Nguyen Cam , Ruhangaza Deogratias , Umwizerwa Aline , Nsanzimana Oscar , Mujyuwisha Louis , Iradukunda Esperance , Shulman Lawrence N. , Lehmann Leslie 
Published: July 2022

PURPOSE Nephroblastoma is a highly curable pediatric cancer that requires multidisciplinary care. Few reports have assessed long-term treatment outcomes in low-resource settings using a task-shifting model of care. We report outcomes of a large cohort and factors associated with survival. METHODS We performed a retrospective chart review of all patients with nephroblastoma presenting to the Butaro Cancer Center of Excellence in Rwanda between July 2012 and June 2018. RESULTS In total, 136 patients were identified and treated according to International Society of Pediatric Oncology guidelines for low-income settings. Median age at diagnosis was 39.7 months (interquartile range, 25.3-61.8 months); 56.6% were female. Sixty-one (44.9%) patients presented with stage I-III disease, 35 (25.7%) with stage IV disease, and 6 (4.4%) with stage V disease; the remainder were unstaged (n = 34; 25.0%). Most patients completed surgery (n = 97; 71.3%) and postoperative chemotherapy (n = 82; 60.2%); 17 patients received radiotherapy. With a median follow-up time of 18.1 months, 44.9% of patients were alive, 41.9% had died, 8.8% were lost to follow-up, and 4.4% were referred for palliative care or declined further care at the end of the study. Three-year overall survival was 57.5% (95% CI, 48.1 to 65.8) for the entire cohort, and 80.1% (95% CI, 66.8 to 88.5) and 44.0% (95% CI, 26.8 to 60.0) for stages I-III and IV-V, respectively. CONCLUSION We demonstrate that patients with nephroblastoma can be successfully treated in a low-resource setting. Survival remains lower than in high-income countries, in part due to early deaths, contributing to approximately 30% of patients not being medically able to receive surgical intervention. Next steps include the development of strategies that focus on earlier diagnosis, supportive care during the early phases of therapy, and efficient and timely transitions between specialties for multimodal care.
Comparison of Titer and Signal to Noise (S/N) for Determination of Anti-drug Antibody Magnitude Using Clinical Data from an Industry Consortium
Authors: Starcevic Manning Marta , Hassanein Mohamed , Partridge Michael A. , Jawa Vibha , Mora Johanna , Ryman Josiah , Barker Breann , Braithwaite Christian , Carleton Kevin , Hay Laura , Hottenstein Charles , Kubiak Robert J. , Devanarayan Viswanath 
Published: July 2022

AbstractDuring biotherapeutic drug development, immunogenicity is evaluated by measuring anti-drug antibodies (ADAs). The presence and magnitude of ADA responses is assessed using a multi-tier workflow where samples are screened, confirmed, and titered. Recent reports suggest that the assay signal to noise ratio (S/N) obtained during the screening tier correlates well with titer. To determine whether S/N could more broadly replace titer, anonymized ADA data from a consortium of sponsors was collected and analyzed. Datasets from clinical programs with therapeutics of varying immunogenicity risk levels (low to high), common ADA assay platforms (ELISA and MSD) and formats (bridging, direct, solid-phase extraction with acid dissociation), and titration approaches (endpoint and interpolated) were included in the analysis. A statistically significant correlation between S/N and titer was observed in all datasets, with a strong correlation (Spearman’s r > 0.8) in 11 out of 15 assays (73%). For assays with available data, conclusions regarding ADA impact on pharmacokinetics and pharmacodynamics were similar using S/N or titer. Subject ADA kinetic profiles were also comparable using the two measurements. Determination of antibody boosting in patients with pre-existing responses could be accomplished using similar approaches for titer and S/N. Investigation of factors that impacted the accuracy of ADA magnitude measurements revealed advantages and disadvantages to both approaches. In general, S/N had superior precision and ability to detect potentially low affinity/avidity responses compared to titer. This analysis indicates that S/N could serve as an equivalent and in some cases preferable alternative to titer for assessing ADA magnitude and evaluation of impact on clinical responses.
Graphical Abstract
PILS proteins provide a homeostatic feedback on auxin signaling output
Authors: Feraru Elena , Feraru Mugurel I. , Moulinier-Anzola Jeanette , Schwihla Maximilian , Ferreira Da Silva Santos Jonathan , Sun Lin , Waidmann Sascha , Korbei Barbara , Kleine-Vehn Jürgen 
Published: July 2022

ABSTRACT
Multiple internal and external signals modulate the metabolism, intercellular transport and signaling of the phytohormone auxin. Considering this complexity, it remains largely unknown how plant cells monitor and ensure the homeostasis of auxin responses. PIN-LIKES (PILS) intracellular auxin transport facilitators at the endoplasmic reticulum are suitable candidates to buffer cellular auxin responses because they limit nuclear abundance and signaling of auxin. We used forward genetics to identify gloomy and shiny pils (gasp) mutants that define the PILS6 protein abundance in a post-translational manner. Here, we show that GASP1 encodes an uncharacterized RING/U-box superfamily protein that impacts on auxin signaling output. The low auxin signaling in gasp1 mutants correlates with reduced abundance of PILS5 and PILS6 proteins. Mechanistically, we show that high and low auxin conditions increase and reduce PILS6 protein levels, respectively. Accordingly, non-optimum auxin concentrations are buffered by alterations in PILS6 abundance, consequently leading to homeostatic auxin output regulation. We envision that this feedback mechanism provides robustness to auxin-dependent plant development.
Drying-Induced Surface Wrinkles Generated on Chitosan Films Having Polyion Complex Skin Layers: Effects of Physical Properties of Skin Layers and Substrates on Surface Wrinkling upon Drying
Authors: Izawa Hironori , Ishisaka Shota , Saimoto Hiroyuki , Ifuku Shinsuke 
Published: July 2022

Abstract
The effects of the physical properties of skin layers and substrates on drying-induced surface wrinkling are investigated with a system using chitosan films having polyion complex (PIC) skin layers. The PIC layers are fabricated with diverse anionic polymers having similar molecular weights on a chitosan (CS) film surface, and the films are dried. In all cases, surface wrinkles form but their sizes vary widely depending on the molecular structure. In particular, wrinkles formed with ligninsulfonate are much larger than those formed with the others. The skin layers differ significantly in surface hardness but not in thickness, indicating that wrinkle sizes induced by PIC skin layers are predominately determined by the hardness of the layers or by physical properties affected by hardness, such as shrinkage volume. The effects of the elastic moduli and shrinkage volume of the substrates are evaluated with higher molecular weight CS and surface-deacetylated chitin nanofiber composite CS films that have different elastic moduli but show very similar swelling–drying behaviors. The wrinkle sizes and skin layer thicknesses also suggest that wrinkle size in this system depends on the hardness of the skin layers or on the physical properties affecting the hardness.
Substrate-Specific Activation and Long-Range Olefin Migration Catalysis at the Pd Centers in a Porous Metal-Macrocycle Framework
Authors: Han Mengying , Tashiro Shohei , Shiraogawa Takafumi , Ehara Masahiro , Shionoya Mitsuhiko 
Published: July 2022

Abstract
Developing catalysts comparable to natural enzymes that achieve only specific reactions has long been a key challenge in the field of molecular synthesis. Long-range olefin migration reactions have attracted great interest as molecular transformation reactions that can realize remote re-functionalization of a molecule with high atom economy. Herein we report that linear alkenyl alcohols of a certain chain length can chemically activate Pd centers precisely arranged in a porous metal-macrocycle framework (MMF), thereby promoting substrate-specific, catalytic long-range olefin migration reactions that produce aldehydes or ketones. Furthermore, MMF can be chemically activated by highly reactive alkenyl alcohol substrates, converting another olefinic substrate that normally would not react with nonactivated MMF into an olefin-migrated product at a high conversion. These reaction specificities are discussed in relation to the arrangement mode of the Pd active centers in the confined space.
Does pre-operative breast MRI have an impact on surgical outcomes in high-grade DCIS?
Authors: Healy Nuala A. , Parag Yethiksha , Soppelsa Giorgia , Wignarajah Primee , Benson John R. , Agrawal Amit , Forouhi Parto , Kilburn-Toppin Fleur , Gilbert Fiona J. 
Published: July 2022

Objectives:
High-grade DCIS (HG DCIS) is associated with upgrade to invasive disease but few studies evaluate the role of MRI in this subset of DCIS. This study compared surgical outcomes of females with HG DCIS on biopsy who had pre-operative MRI with those that proceeded directly to surgery.

Methods:
This single-centre retrospective, observational study identified patients with pure HG DCIS on pre-operative biopsy from the pathology database. Surgical outcomes, clinicopathological and radiological features were obtained for all patients.

Results:
From August 2015 to February 2020, 217 patients had HG DCIS on biopsy. Pre-operative MRI was performed in 40 (MRI group) and not in 88 (No MRI group) patients. Initial mastectomy was performed in 25/40 (63%) women in the MRI group and 20/88 (23%) women in the no MRI group (p &lt; 0.0001). No difference was observed in re-operation rate between the two groups, 15% in MRI group vs 22% in No MRI group (p = 0.4749). Mean tumour size on histology was larger in mastectomy cases in the MRI group (73.4 mm, range 6–140 mm), than the total MRI group, (58.3 mm, range 0–140 mm) or no MRI group (30.7 mm, range 0–130 mm) (p &lt; 0.0001).

Conclusions:
Pre-operative MRI in HG DCIS is associated with higher mastectomy rates, possibly due to patient selection for MRI, as tumours on final histology were significantly larger. Fewer re-operations were observed in the MRI group although this was not significant.

Advances in knowledge:
Breast MRI performed pre-operatively in HG DCIS is associated with higher mastectomy rates and fewer re-operation rates.
Breast calcification micromorphology classification
Authors: Scott Robert , Lyburn Iain , Cornford Eleanor , Bouzy Pascaline , Stone Nicholas , Greenwood Charlene , Bouybayoune Ihsanne , Pinder Sarah , Rogers Keith 
Published: July 2022

Objectives: The importance of consistent terminology in describing the appearance of breast calcifications in mammography is well recognised. Imaging of calcifications using electron microscopy is a globally growing field of research. We therefore suggest that the time is ripe to develop a lexicon of terms for classifying the micromorphology of breast calcifications. Methods: Calcifications within a wide range of histological sections of breast tissue, both benign and malignant, were imaged by Scanning Electron Microscopy (SEM). These images were examined, and the micromorphology of calcifications present was grouped to create a classification system. Results: Based on the appearance of the calcifications observed, we propose five main categories for classification of the micromorphology of breast calcifications, namely, Dense Homogenous, Punctulate, Banded, Spongy and Aggregate. Conclusions: Use of the descriptive categories outlined here will help to ensure consistency and comparability of published observations on the micromorphology of breast calcifications. Advances in knowledge: This is the first time a lexicon and classification system has been proposed for the micromorphology of breast calcifications, as observed by scanning electron microscopy of histological sections. This will facilitate comparability of observed relationships between micromorphology, mammographic appearance, chemistry and pathology.
Viral load and gastrointestinal inflammation in COVID-19 patients
Authors: Syafei Aditya Riadi , Sugihartono Titong , Nusi Iswan Abbas , Setiawan Poernomo Boedi , Purbayu Herry , Maimunah Ummi , Kholili Ulfa , Widodo Budi , Thamrin Husin , Vidyani Amie , Maulahela Hasan , Yamaoka Yoshio , Miftahussurur Muhammad 
Published: July 2022

Background: ACE-2 receptors are well-known as binding receptors to spike protein of SARS-CoV-2 highly expressed in the gastrointestinal system. The Role of SARS-CoV-2 viral load and its effect on gut inflammation in COVID-19 patients are still not well-understood. This study aims to determine the impact of SARS-CoV-2 viral load on gastrointestinal inflammation. Methods: A total of 44 inpatient subjects who fulfilled eligibility criteria were examined for cycle threshold values from nasopharyngeal swab samples collected from several nucleic levels based on fluorescence signal and calprotectin levels of stool samples using Calprotectin enzyme-linked immunosorbent assay (ELISA) kit. Results: Of 44 subjects, 52.3% were male, with a median age of 52.5 years. Hypertension or diabetes was found in 26 patients. The median cycle threshold value was 31.3 with a value range of 10.9-40.0, median cycle threshold was significantly lower in subjects with comorbidity with P = 0.01. The median fecal calprotectin level was 42 μg/g with a value range of 5.1-1,393.7 μg/g, with median fecal calprotectin significantly higher in subjects with gastrointestinal symptoms with P = 0.008 with a relative risk (RR) of 5.5. There was a significant correlation between cycle threshold and fecal calprotectin in subjects with comorbidity with P <0.05, a coefficient contingency of 0.414. Conclusion: Subjects with comorbidity are prone to have higher viral loads paralleled with gastrointestinal inflammation. Subjects with overt gastrointestinal manifestations had a five-fold higher degree of gut inflammation.
Case Report: Caecal volvulus management from diagnosis to treatment in a young patient
Authors: Abbassi Imed , Triki Wissem , Trigui Racem , Itaimi Ahmed , Ayed Karim , Sebri Hajer , Baraket Oussema , Bouchoucha Sami 
Published: July 2022

Caecal volvulus (CV) is a rare cause of intestinal obstruction, defined by an axial torsion of the caecum, ascending colon, and terminal ileum around the mesenteric vascular pedicles, leading to ischemia and bowel necrosis. A 20-year-old woman, with no significant medical history, was admitted for generalized abdominal pain evolving for three days, along with constipation and abdominal distension, but with no vomiting. Physical examination showed a generalized abdominal tenderness with no rigidity or rebound tenderness, associated with abdominal distension and tympanic upon percussion. Laboratory findings were within normal limits. An abdominal computed tomography scan revealed distension of a loop of the large bowel with its long axis extending from the right lower quadrant to the epigastrium or left upper quadrant. Colonic haustral pattern was absent. An abdominal computed tomography scan showed a rounded focal collection of air-distended bowel with haustral creases in the upper left quadrant. In addition, spiraled loops of the collapsed cecum (giving a whirl sign) were noted, along with low-attenuating fatty mesentery from the twisted bowel. The patient underwent an emergency laparotomy and caecectomy using GEA 80 charges. The patient had no complaints post-operation. CV is a rare cause of bowel obstruction, mainly caused by an exceedingly mobile caecum. Despite its rareness, CV represents the second most common cause of large bowel volvulus, behind sigmoid volvulus. For acute obstruction by CV, it is hard to differentiate it clinically from obstruction of the small bowel; therefore, radiological exams are needed. Surgery is the gold standard treatment for CV. We report a rare case of CV to highlight the rarity of this pathology, specify its diagnostic and therapeutic means, and its clinical and biological evolution.
Automated detection of over- and under-dispersion in baseline tables in randomised controlled trials
Authors: Barnett Adrian 
Published: July 2022

Background: Papers describing the results of a randomised trial should include a baseline table that compares the characteristics of randomised groups. Researchers who fraudulently generate trials often unwittingly create baseline tables that are implausibly similar (under-dispersed) or have large differences between groups (over-dispersed). I aimed to create an automated algorithm to screen for under- and over-dispersion in the baseline tables of randomised trials. Methods: Using a cross-sectional study I examined 2,245 randomised controlled trials published in health and medical journals on PubMed Central. I estimated the probability that a trial's baseline summary statistics were under- or over-dispersed using a Bayesian model that examined the distribution of t-statistics for the between-group differences, and compared this with an expected distribution without dispersion. I used a simulation study to test the ability of the model to find under- or over-dispersion and compared its performance with an existing test of dispersion based on a uniform test of p-values. My model combined categorical and continuous summary statistics, whereas the uniform uniform test used only continuous statistics. Results: The algorithm had a relatively good accuracy for extracting the data from baseline tables, matching well on the size of the tables and sample size. Using t-statistics in the Bayesian model out-performed the uniform test of p-values, which had many false positives for skewed, categorical and rounded data that were not under- or over-dispersed. For trials published on PubMed Central, some tables appeared under- or over-dispersed because they had an atypical presentation or had reporting errors. Some trials flagged as under-dispersed had groups with strikingly similar summary statistics. Conclusions: Automated screening for fraud of all submitted trials is challenging due to the widely varying presentation of baseline tables. The Bayesian model could be useful in targeted checks of suspected trials or authors.