bluuebunny/crossref_metadata_2025_split huggingface dataset:
Molecular evaluation of hepatitis B virus infection and predominant mutations of pre-core, basal core promoter and S regions in an Iranian population with type 2 diabetes mellitus: a case–control study
Authors: Farshadpour Fatemeh , Taherkhani Reza , Saberi Fatemeh 
Published: June 2022

Abstract
Background
This study was designed to evaluate the prevalence, genotypic patterns, and predominant mutations of hepatitis B virus (HBV) infection among diabetic patients.

Methods
Serum samples were obtained from 733 patients with type 2 diabetes mellitus and 782 non-diabetic controls. The presence of HBsAg and HBcAb was determined by ELISA. Nested PCR, targeting S and pre-core regions of the HBV genome, followed by sequencing was carried out to determine HBV genotypes and predominant mutations in the S, basal core promoter (BCP), and pre-core regions of the HBV genome.

Results
Of 733 diabetic patients, 94 cases (12.82%) were positive for HBcAb, 28 cases (3.82%) were positive for HBsAg, and 19 cases (2.59%) had HBV-DNA with genotype D, sub-genotype D1/D3 and subtype ayw2. An occult HBV infection was found in one of the HBV DNA-positive samples, which was positive for HBcAb but negative for HBsAg. P120T/G145R, G1896A/G1899A, and A1762T/G1764T were the most frequent point substitution mutations detected in the S, pre-core, and BCP regions of the HBV genome, respectively. P120T and G145R mutations were associated with low levels or undetectable levels of HBsAg in serum. Therefore, routine tests based on HBsAg detection cannot detect HBsAg-negative infected patients.

Conclusions
Relatively high prevalence of HBV infection was found in diabetic patients, while all of the HBV-infected patients were unaware of their infection. Therefore, screening for HBV infection should be included in the management program of diabetes for timely diagnosis and treatment of infected but asymptomatic patients.
Neuropsychiatric lupus erythematosus with neurogenic pulmonary edema and anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor limbic encephalitis: a case report
Authors: Li Rongqi , Wang Yingai , Wu Xiuhua , Wang Junping , Wei Wei , Li Xin 
Published: June 2022

Abstract
Background
Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune inflammatory disease predominantly found in women of child-bearing age. Neurogenic pulmonary edema (NPE) is a recalcitrant complication that occurs after injury to the central nervous system and has an acute onset and rapid progression. Limbic encephalitis is an inflammatory encephalopathy caused by viruses, immune responses, or other factors involving the limbic system. NPE caused by SLE is rare.

Case presentation
Here, we report a case of a 21-year-old woman with SLE who experienced five episodes of generalized tonic–clonic seizure after headache and dyspnea. Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) 2 antibody was tested positive in the serum and cerebrospinal fluid. Electrocardiography (EEG) indicated paroxysmal or sporadic medium amplitude theta activity. In addition, chest computed tomography (CT) showed multiple diffuse consolidations and ground-glass opacities. We finally considered a diagnosis of NPE and AMPAR limbic encephalitis. The patient's symptoms improved obviously after methylprednisolone pulse therapy and antiepileptic treatment.

Conclusions
NPE can be a complication of neuropsychiatric lupus erythematosus (NPSLE). AMPAR2 antibodies may be produced in NPSLE patients, especially in those with high polyclonal IgG antibody titers. More basic and clinical studies are required to confirm these observations and elucidate the pathogenicity of encephalitis-related autoantibodies in SLE patients.
Frequency and duration of extreme hypoxemic and hyperoxemic episodes during manual and automatic oxygen control in preterm infants: a retrospective cohort analysis from randomized studies
Authors: Bachman Thomas E. , Onland Wes , van Kaam Anton H. , Roubik Karel , Hummler Helmut D. , Lal Mithilesh , Lista Gianluca , Fajardo Carlos A. 
Published: June 2022

Abstract
Objective
Neonatal exposure to episodic hypoxemia and hyperoxemia is highly relevant to outcomes. Our goal was to investigate the differences in the frequency and duration of extreme low and high SpO2 episodes between automated and manual inspired oxygen control.

Design
Post-hoc analysis of a cohort from prospective randomized cross-over studies.

Setting
Seven tertiary care neonatal intensive care units.

Patients
Fifty-eight very preterm neonates (32 or less weeks PMA) receiving respiratory support and supplemental oxygen participating in an automated versus manual oxygen control cross-over trial.

Main measures
Extreme hypoxemia was defined as a SpO2 < 80%, extreme hyperoxemia as a SpO2 > 98%. Episode duration was categorized as < 5 seconds, between 5 to < 30 seconds, 30 to < 60 seconds, 60 to < 120 seconds, and 120 seconds or longer.

Results
The infants were of a median postmenstrual age of 29 (28-31) weeks, receiving a median FiO2 of 0.28 (0.25-0.32) with mostly receiving non-invasive respiratory support (83%). While most of the episodes were less than 30 seconds, longer episodes had a marked effect on total time exposure to extremes. The time differences in each of the three longest durations episodes (30, 60, and 120 seconds) were significantly less during automated than during manual control (p < 0.001). Nearly two-third of the reduction of total time spent at the extremes between automated and manual control (3.8 to 2.1% for < 80% SpO2 and 3.0 to 1.6% for > 98% SpO2) was seen in the episodes of at least 60 seconds.

Conclusions
This study shows that the majority of episodes preterm infants spent in SpO2 extremes are of short duration regardless of manual or automated control. However, the infrequent longer episodes not only contribute the most to the total exposure, but also their reduction in frequency to the improvement associated with automated control.
Information extraction from free text for aiding transdiagnostic psychiatry: constructing NLP pipelines tailored to clinicians’ needs
Authors: Turner Rosanne J. , Coenen Femke , Roelofs Femke , Hagoort Karin , Härmä Aki , Grünwald Peter D. , Velders Fleur P. , Scheepers Floortje E. 
Published: June 2022

Abstract
Background
Developing predictive models for precision psychiatry is challenging because of unavailability of the necessary data: extracting useful information from existing electronic health record (EHR) data is not straightforward, and available clinical trial datasets are often not representative for heterogeneous patient groups. The aim of this study was constructing a natural language processing (NLP) pipeline that extracts variables for building predictive models from EHRs. We specifically tailor the pipeline for extracting information on outcomes of psychiatry treatment trajectories, applicable throughout the entire spectrum of mental health disorders (“transdiagnostic”).

Methods
A qualitative study into beliefs of clinical staff on measuring treatment outcomes was conducted to construct a candidate list of variables to extract from the EHR. To investigate if the proposed variables are suitable for measuring treatment effects, resulting themes were compared to transdiagnostic outcome measures currently used in psychiatry research and compared to the HDRS (as a gold standard) through systematic review, resulting in an ideal set of variables. To extract these from EHR data, a semi-rule based NLP pipeline was constructed and tailored to the candidate variables using Prodigy. Classification accuracy and F1-scores were calculated and pipeline output was compared to HDRS scores using clinical notes from patients admitted in 2019 and 2020.

Results
Analysis of 34 questionnaires answered by clinical staff resulted in four themes defining treatment outcomes: symptom reduction, general well-being, social functioning and personalization. Systematic review revealed 242 different transdiagnostic outcome measures, with the 36-item Short-Form Survey for quality of life (SF36) being used most consistently, showing substantial overlap with the themes from the qualitative study. Comparing SF36 to HDRS scores in 26 studies revealed moderate to good correlations (0.62—0.79) and good positive predictive values (0.75—0.88). The NLP pipeline developed with notes from 22,170 patients reached an accuracy of 95 to 99 percent (F1 scores: 0.38 – 0.86) on detecting these themes, evaluated on data from 361 patients.

Conclusions
The NLP pipeline developed in this study extracts outcome measures from the EHR that cater specifically to the needs of clinical staff and align with outcome measures used to detect treatment effects in clinical trials.
A prediction model for xerostomia in locoregionally advanced nasopharyngeal carcinoma patients receiving radical radiotherapy
Authors: Li Minying , Zhang Jingjing , Zha Yawen , Li Yani , Hu Bingshuang , Zheng Siming , Zhou Jiaxiong 
Published: June 2022

AbstractBackgroundThis study was to evaluate the predictors of xerostomia and Grade 3 xerostomia in locoregionally advanced nasopharyngeal carcinoma (NPC) patients receiving radical radiotherapy and establish prediction models for xerostomia and Grade 3 xerostomia based on the predictors.MethodsTotally, 365 patients with locoregionally advanced NPC who underwent radical radiotherapy were randomly divided into the training set (n = 255) and the testing set (n = 110) at a ratio of 7:3. All variables were included in the least absolute shrinkage and selection operator regression to screen out the potential predictors for xerostomia as well as the Grade 3 xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The random forest (RF), a decision tree classifier (DTC), and extreme-gradient boosting (XGB) models were constructed. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), area under the curve (AUC) and accuracy were analyzed to evaluate the predictive performance of the models.ResultsIn the RF model for predicting xerostomia, the sensitivity was 1.000 (95%CI 1.000–1.000), the PPV was 0.990 (95%CI 0.975–1.000), the NPV was 1.000 (95%CI 1.000–1.000), the AUC was 0.999 (95%CI 0.997–1.000) and the accuracy was 0.992 (95%CI 0.981–1.000) in the training set. The sensitivity was 0.933 (95%CI 0.880–0.985), the PPV was 0.933 (95%CI 0.880–0.985), and the AUC was 0.915 (95%CI 0.860–0.970) in the testing set. Hypertension, age, total radiotherapy dose, dose at 50% of the left parotid volume, mean dose to right parotid gland, mean dose to oral cavity, and course of induction chemotherapy were important variables associated with the risk of xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy. The AUC of DTC model for predicting xerostomia was 0.769 (95%CI 0.666–0.872) in the testing set. The AUC of the XGB model for predicting xerostomia was 0.834 (0.753–0.916) in the testing set. The RF model showed the good predictive ability with the AUC of 0.986 (95%CI 0.972–1.000) in the training set, and 0.766 (95%CI 0.626–0.905) in the testing set for identifying patients who at high risk of Grade 3 xerostomia in those with high risk of xerostomia.ConclusionsAn RF model for predicting xerostomia in locoregionally advanced NPC patients receiving radical radiotherapy and an RF model for predicting Grade 3 xerostomia in those with high risk of xerostomia showed good predictive ability.
Learning from errors? The impact of erroneous example elaboration on learning outcomes of medical statistics in Chinese medical students
Authors: Wang Chengwei , Li Junyi , Li Haiyan , Xia Yijing , Wang Xiaoyu , Xie Yufei , Wu Jinyang 
Published: June 2022

Abstract
Background
Constructivism theory has suggested that constructing students’ own meaning is essential to successful learning. The erroneous example can easily trigger learners’ confusion and metacognition, which may “force” students to process the learning material and construct meaning deeply. However, some learners exhibit a low level of elaboration activity and spend little time on each example. Providing instructional scaffolding and elaboration training may be an efficient method for addressing this issue. The current study conducted a randomized controlled trial to examine the effectiveness of erroneous example elaboration training on learning outcomes and the mediating effects of metacognitive load for Chinese students in medical statistics during the COVID-19 pandemic.

Methods
Ninety-one third-year undergraduate medical students were randomly assigned to the training group (n = 47) and the control group (n = 44). Prerequisite course performance and learning motivation were collected as covariates. The mid-term exam and final exam were viewed as posttest and delayed-test to make sure the robustness of the training effect. The metacognitive load was measured as a mediating variable to explain the relationship between the training and academic performance.

Results
The training significantly improved both posttest and delayed-test performance compared with no training (Fposttest = 26.65, p < 0.001, Partial η2 = 0.23; Fdelayed test = 38.03, p < 0.001, Partial η2 = 0.30). The variation trend in metacognitive load in the two groups was significantly different (F = 2.24, p < 0.05, partial η2 = 0.20), but metacognitive load could not explain the positive association between the treatment and academic performance (β = − 0.06, se = 0.24, 95% CI − 0.57 to 0.43).

Conclusions
Erroneous example learning and metacognitive demonstrations are effective for academic performance in the domain of medical statistics, but their underlying mechanism merits further study.
Evaluation of an experiential clinical learning option during pandemic teaching suspensions
Authors: Canfield Jules , Truong Ve , Bereznicka Agata , Lunze Karsten 
Published: June 2022

Abstract
Background
As students’ direct patient contact was suspended because of COVID-19-related restrictions, we revised our clinical addiction medicine curriculum for students to learn about the different multidisciplinary clinical models delivered at our hospital and in community settings. Our aim was to provide an overview of clinical modalities and familiarize learners with clinician and patient experiential perspectives.

Methods
We implemented a multi-pronged approach, offering an overview of clinical care programs through remote panels involving care providers at the clinics where students had previously been scheduled for in-person rotations. This included inpatient and office-based addiction services, addiction treatment program for adolescents and young adults, integrated addiction care and HIV primary care clinic, and opioid use urgent care clinic. Beyond having them join outpatient telehealth clinic visits, students also participated in an online panel involving patients in recovery to gain familiarity with their care perspectives; and joined a panel with recovery coaches to get further insights into patient challenges in clinical settings. Students further participated in remote opioid treatment trainings and observed clinical rounds of inpatient addiction consults and adolescent clinic team meetings.

Results
With this revised curriculum, students learned about the variety of clinical modalities at the height of our hospital’s COVID-19 pandemic burden. The evaluation suggested that students appreciated the authenticity of accounts from patients and providers about their challenges and satisfaction related to clinical care. While in a remote learning setting, students overall wished for more personal interaction with patients and providers. They also noted a lack of group cohesion and connection that they felt would otherwise have been met in an in-person program.

Conclusions
Remote learning allowed our program to connect trainees to the multidisciplinary field of addiction medicine despite the COVID-19 pandemic. In future program iterations, we will consider hybrid formats of in-person learning experiences with direct patient and faculty contact where possible, combined with online provider and patient panels possibly, in addition to virtual breakout formats to facilitate more personal student-patient and student-faculty interactions.
Dysferlinopathy misdiagnosed with juvenile polymyositis in the pre-symptomatic stage of hyperCKemia: a case report and literature review
Authors: Contreras-Cubas Cecilia , Barajas-Olmos Francisco , Frayre-Martínez Maria Inés , Siordia-Reyes Georgina , Guízar-Sánchez Claudia C. , García-Ortiz Humberto , Orozco Lorena , Baca Vicente 
Published: June 2022

Abstract
Background
Dysferlinopathy encompasses a group of rare muscular dystrophies caused by recessive mutations in the DYSF gene. The phenotype ranges from asymptomatic elevated serum creatine kinase (hyperCKemia) to selective and progressive involvement of the proximal and/or distal muscles of the limbs. Bohan and Peter criteria are the most widely used for the diagnosis of polymyositis, but they have limitations and can misclassify muscular dystrophies with inflammation as polymyositis. Most dysferlinopathy patients have muscle biopsies with inflammation and thus are vulnerable to misdiagnosis with polymyositis and inappropriate treatment with steroids and immunosuppressors.

Case presentation
We describe a 14 years-old male patient who was referred for assessment of asymptomatic hyperCKemia (26,372 IU/L). An X-linked dystrophinopathy initially was ruled out by direct genetic testing. Juvenile polymyositis was considered based on muscle biopsy, creatine kinase levels, and electromyography changes. Corticosteroid treatment triggered proximal lower limb muscular weakness, and no full muscular strength recovery was observed after corticosteroid withdrawal. Based on these observations, a limb-girdle muscular dystrophy (LGMD) was suspected, and LGMDR2 was confirmed by whole exome sequencing.

Conclusion
We report a dysferlinopathy patient who was misdiagnosed with juvenile polymyositis and explore in a literature review how common such misdiagnoses are. With diagnosis based only on routine clinicopathological examinations, distinguishing an inflammatory myopathy from dysferlinopathy is quite difficult. We suggest that before establishing a diagnosis of “definite” or “probable” juvenile polymyositis, according to Bohan and Peter or current ACR/EULAR criteria, a muscular dystrophy must first be ruled out.
Blood gene expression risk profiles and interstitial lung abnormalities: COPDGene and ECLIPSE cohort studies
Authors: Moll Matthew , Hobbs Brian D. , Menon Aravind , Ghosh Auyon J. , Putman Rachel K. , Hino Takuya , Hata Akinori , Silverman Edwin K. , Quackenbush John , Castaldi Peter J. , Hersh Craig P. , McGeachie Michael J. , Sin Don D. , Tal-Singer Ruth , Nishino Mizuki , Hatabu Hiroto , Hunninghake Gary M. , Cho Michael H. 
Published: June 2022

AbstractBackgroundInterstitial lung abnormalities (ILA) are radiologic findings that may progress to idiopathic pulmonary fibrosis (IPF). Blood gene expression profiles can predict IPF mortality, but whether these same genes associate with ILA and ILA outcomes is unknown. This study evaluated if a previously described blood gene expression profile associated with IPF mortality is associated with ILA and all-cause mortality.MethodsIn COPDGene and ECLIPSE study participants with visual scoring of ILA and gene expression data, we evaluated the association of a previously described IPF mortality score with ILA and mortality. We also trained a new ILA score, derived using genes from the IPF score, in a subset of COPDGene. We tested the association with ILA and mortality on the remainder of COPDGene and ECLIPSE.ResultsIn 1469 COPDGene (training n = 734; testing n = 735) and 571 ECLIPSE participants, the IPF score was not associated with ILA or mortality. However, an ILA score derived from IPF score genes was associated with ILA (meta-analysis of test datasets OR 1.4 [95% CI: 1.2–1.6]) and mortality (HR 1.25 [95% CI: 1.12–1.41]). Six of the 11 genes in the ILA score had discordant directions of effects compared to the IPF score. The ILA score partially mediated the effects of age on mortality (11.8% proportion mediated).ConclusionsAn ILA gene expression score, derived from IPF mortality-associated genes, identified genes with concordant and discordant effects on IPF mortality and ILA. These results suggest shared, and unique biologic processes, amongst those with ILA, IPF, aging, and death.
Identification and functional characterization of the first deep intronic GLA mutation (IVS4+1326C>T) causing renal variant of Fabry disease
Authors: Dai Xuantong , Zong Xue , Pan Xiaoxia , Lu Wei , Jiang Geng-Ru , Lin Fujun 
Published: June 2022

Abstract
Background
Fabry disease (FD, OMIM #301500) is an X-linked lysosomal disorder caused by the deficiency of α-galactosidase A (α-GalA), encoded by the GLA gene. Among more than 1100 reported GLA mutations, few were deep intronic mutations which have been linked to classic and cardiac variants of FD.

Methods and results
We report a novel hemizygous deep intronic GLA mutation (IVS4+1326C>T) in a 33-year-old Chinese man with a mild α-GalA deficiency phenotype involving isolated proteinuria and predominant globotriaosylceramide deposits in podocytes. IVS4+1326C>T, which appears to be the first deep intronic GLA mutation associated with renal variant of FD, was identified by Sanger sequencing the entire GLA genomic DNA sequence of the patient’s peripheral mononuclear blood lymphocytes (PBMCs). Further sequencing of cDNA from PBMCs of the patient revealed a minor full-length GLA transcript accounting for about 25% of total GLA transcript, along with two major aberrantly spliced GLA transcripts encoding mutant forms of α-GalA with little enzyme activity characterized by in vitro α-GalA overexpression system in the HEK293T cells. Thus, the combined clinical phenotype, genetic analysis and functional studies verified the pathogenicity of IVS4+1326C>T.

Conclusions
The identification of IVS4+1326C>T establishes a link between deep intronic GLA mutation and the renal variant of FD, which extends the mutation spectrum in GLA gene and justifies further study of how IVS4+1326C>T and potentially other deep intronic GLA mutations contribute to Fabry podocytopathy through aberrant splicing. Future studies should also assess the true incidence of IVS4+1326C>T in patients with different variants of FD, which may improve early genetic diagnosis to allow timely treatment that can prevent disease progression and improve survival.