bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rotterdam Transition Test
Authors: van Gaalen Martha A.C. , van Pieterson Merel , van den Brink Gertrude , de Ridder Lissy , Rizopoulos Dimitris , van der Woude C. Janneke , Escher Johanna C. 
Published: August 2021

ABSTRACTObjectives:Disease knowledge is important in adolescents with inflammatory bowel disease (IBD) transitioning to adult care. We developed an IBD‐specific knowledge questionnaire, the Rotterdam Transition Test (RTT), and aimed to validate this tool.Methods:This is a prospective longitudinal validation study. The RTT has 25 open questions on IBD, medication, lifestyle, and transition to adult care. A scoring model was developed, and inter‐rater agreement was assessed. Using a Rasch model, we determined the difficulty and performance of the questions. Cronbach alpha was used to demonstrate reliability. Patient factors (age, disease, education, medication use, illness acceptance, and independence) were correlated to RTT score.Results:A total of 207 RTTs were evaluated in 111 adolescent IBD patients. The scoring model showed a kappa score of >0.61 for all questions. Reliability with Cronbach alpha was good (0.81). Mean total result of the RTT was 58% (girls) and 55% (boys) of maximal score.The RTT discriminated well between the different levels of knowledge. Knowledge scores increased in patients who did repeated RTTs during the transition period. Male sex, low educational level, disease acceptance issues, and dependence on parents associated with a significantly lower total RTT score. Prednisone use within 3 months and treatment without biologics associated with significantly higher RTT scores. Disease activity was not a significant factor.Conclusions:The RTT is a reliable and valid tool to assess IBD knowledge. The RTT can be used to detect and discuss knowledge gaps in adolescents with IBD transitioning to adult healthcare.
CT scans better assess lateral wall morphology of “stable appearing” intertrochanteric (IT) femur fractures and predict early failure of sliding hip screw (SHS) fixation
Authors: Hecht Garin , Saiz Augustine M. , Shelton Trevor J. , Haffner Max R. , Delman Connor , Shieh Alvin , Hallare Jericho , Bhatti Satninderdeep , Wolinsky Philip 
Published: August 2021

Objectives:
To compare the efficacy of plain x-ray images and computed tomography (CT) to assess the morphology of the lateral wall (LW) component of intertrochanteric (IT) femur fractures and determine predictors of early fixation failure.

Design:
Retrospective cohort study.

Setting:
Level-one trauma center.

Patients/Participants:
One hundred forty-two adult patients with IT fractures treated with either a sliding hip screw (SHS) or a cephalomedullary nail (CMN) who had both pre-op plain x-ray images and CT scans with at least 6 weeks of follow-up were reviewed.

Intervention:
Preoperative CT scan and plain radiographs of the affected hip.

Main Outcome Measurements:
Lateral wall assessment based on plain x-rays versus CT imaging in relation to implant failure.

Results:
One hundred forty-two patients met inclusion criteria, 105 patients treated with a CMN, and 37 with a SHS. There was a poor correlation between the assessment of the LW on plain x-ray images and CT scans. Failures in the SHS group were significantly associated with all CT measurements (P < .05) but not with plain film LW assessment (P = .66). Fifteen patients had an early implant failure (6 CMN, 9 SHS). There were no statistically significant associations between any radiographic measurement (plain images and CT) and CMN failures.

Conclusions:
Plain film images are not accurate for assessing lateral wall morphology/integrity and are not predictive of SHS implant failures. Our novel CT measurements were effective at detecting lateral wall patterns at risk for treatment failure with SHS implants.
Level of Evidence: Level III
Biomarkers Obtained by Transcranial Magnetic Stimulation in Neurodevelopmental Disorders
Authors: Jannati Ali , Ryan Mary A. , Kaye Harper L. , Tsuboyama Melissa , Rotenberg Alexander 
Published: August 2021

Summary:
Transcranial magnetic stimulation (TMS) is a method for focal brain stimulation that is based on the principle of electromagnetic induction where small intracranial electric currents are generated by a powerful fluctuating magnetic field. Over the past three decades, TMS has shown promise in the diagnosis, monitoring, and treatment of neurological and psychiatric disorders in adults. However, the use of TMS in children has been more limited. We provide a brief introduction to the TMS technique; common TMS protocols including single-pulse TMS, paired-pulse TMS, paired associative stimulation, and repetitive TMS; and relevant TMS-derived neurophysiological measurements including resting and active motor threshold, cortical silent period, paired-pulse TMS measures of intracortical inhibition and facilitation, and plasticity metrics after repetitive TMS. We then discuss the biomarker applications of TMS in a few representative neurodevelopmental disorders including autism spectrum disorder, fragile X syndrome, attention-deficit hyperactivity disorder, Tourette syndrome, and developmental stuttering.
Cognitive Biomarkers in the Clinic: Lessons From Presurgical fMRI
Authors: Benjamin Christopher F. A. 
Published: August 2021

Summary:
Cognitive biomarkers are vital and uniquely challenging clinical tools. There has been marked growth in neuroimaging-based cognitive biomarkers across the past 40 years with more in development (e.g., clinical cognitive EEG). The challenges involved in developing cognitive biomarkers and key milestones in their development are reviewed here using clinical functional MRI's evolution as a case study. It is argued that indexing cognition is uniquely challenging because it requires patients to consistently use specific cognitive processes, and it is difficult or impossible to independently verify this occurred. This limitation can be successfully managed through careful analysis of standardized protocols for acquisition and interpretation, and ensuring the clinical application of biomarkers integrates disciplines with complementary expertise. Factors beneficial to the adoption of a novel cognitive biomarker include a clinical need and inadequate alternatives. Key milestones in the development of functional MRI included (1) demonstration that its performance was equivalent to its predecessor; (2) demonstration it predicted a clinically meaningful outcome; and (3) the establishment of infrastructure for both its execution and billing. Review of functional MRI and its predecessors suggest a cycle whereby successful cognitive biomarkers are validated, experience widespread adoption and customization/fragmentation, go through a period of review, and finally are refined and standardized. Those applying future cognitive biomarkers in the clinic can avoid some of the failures of clinical functional MRI by defining the skills and disciplines the method requires and routinely evaluating patient outcomes.
Optimized Flow Cytometric Detection of Transient Receptor Potential Vanilloid-1 (TRPV1) in Human Hematological Malignancies
Authors: Omari Sofia A , Geraghty Dominic P , Khalafallah Alhossain A , Venkat Pooja , Shegog Yvette M , Ragg Scott J , de Bock Charles E. , Adams Murray J 
Published: August 2021

AbstractThe ectopic overexpression of transient receptor potential vanilloid-1 (TRPV1) has been detected in numerous solid cancers including breast, prostate, pancreatic, and tongue epithelium cancer. However, the expression of TRPV1 in hematological malignancies remains unknown. Here we show through in silico analysis that elevated TRPV1 mRNA expression occurs in a range of hematological malignancies and present an optimized flow cytometry method to rapidly assess TRPV1 protein expression for both cell lines and primary patient samples. Three anti-TRPV1 antibodies were evaluated for intracellular TRPV1 detection using flow cytometry resulting in an optimized protocol for the evaluation of TRPV1 in hematological malignant cell lines and patients’ peripheral blood mononuclear cells (PBMC). Overexpression of TRPV1 was observed in THP-1 (acute monocytic leukemia) and U266B1 (multiple myeloma, MM), but not U937 (histiocytic lymphoma) compared to healthy PBMC. TRPV1 was also detected in all 49 patients (including B-cell non-Hodgkin’s lymphoma (B-NHL), MM and others, and 20 healthy controls. TRPV1 expression was increased in 8% of patients (MM=2, B-NHL=2). In conclusion, we provide an optimized flow cytometry method for routine expression analysis of clinical samples and show that TRPV1 is increased in 8% of patients with hematological malignancies.
Physiological pattern of cognitive aging
Authors: Novotný Jan S. , Gonzalez-Rivas Juan P. , Vassilaki Maria , Krell-Roesch Janina , Geda Yonas E. , Stokin Gorazd B. 
Published: August 2021

AbstractThe effect of aging on cognition in cognitively healthy adult populations remains poorly investigated. Given that cognition evolves in time and thus, during aging, and becomes eroded in several disorders, some of which have recently acquired biological definitions, it is imperative to understand the process of cognitive aging. To determine the association of aging with cognitive performance in a cognitively healthy population, we studied cognitive performance in population-based cohort of 673 adults (aged 25-89). We found a gradual decline in cognitive performance across the lifespan, which requires two decades to demonstate significant change. This age-related decline was not significantly altered by either gender or education. These findings contribute to understand cognitive aging and provide essential data on physiological cognition for more precise diagnostics and timely intervention of early changes in cognition.
Drug-resistant focal epilepsy in children is associated with increased modal controllability of the whole brain and epileptogenic regions
Authors: Chari Aswin , Seunarine Kiran , He Xiaosong , Tisdall Martin , Clark Christopher A , Bassett Danielle S , Scott Rodney C , Rosch Richard E 
Published: August 2021

AbstractNetwork control theory provides a framework by which neurophysiological dynamics of the brain can be modelled as a function of the structural connectome constructed from diffusion MRI. Average controllability describes the ability of a region to drive the brain to easy-to-reach neurophysiological states whilst modal controllability describes the ability of a region to drive the brain to difficult-to-reach states.In this study, we identify increases in mean average and modal controllability in children with drug-resistant epilepsy compared to healthy controls. Using simulations, we purport that these changes may be a result of increased thalamocortical connectivity. At the node level, we demonstrate decreased modal controllability in the thalamus and posterior cingulate regions. In those undergoing resective surgery, we also demonstrate increased modal controllability of the resected parcels, a finding specific to patients who were rendered seizure free following surgery.Changes in controllability are a manifestation of brain network dysfunction in epilepsy and may be a useful construct to understand the pathophysiology of this archetypical network disease. Understanding the mechanisms underlying these controllability changes may also facilitate the design of network-focussed interventions that seek to normalise network structure and function.
COVID-19 Outcomes Among Users of CD20 Inhibitors for Immune-Mediated Diseases: A Comparative Cohort Study
Authors: Patel Naomi J. , D’Silva Kristin M. , Hsu Tiffany Y-T. , DiIorio Michael , Fu Xiaoqing , Cook Claire , Prisco Lauren , Martin Lily , Vanni Kathleen M.M. , Zaccardelli Alessandra , Zhang Yuqing , Sparks Jeffrey A. , Wallace Zachary S. 
Published: August 2021

AbstractObjectivePatients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes due to impaired humoral immunity, but differences versus the general population are unknown.MethodsWe identified patients with immune-mediated diseases who received CD20 inhibitors within one year prior to the index date of PCR-confirmed COVID-19 between January 31, 2020, and January 31, 2021. Comparators with COVID-19 were matched up to 5:1 by age, sex, and PCR date. Hazard ratios (HRs) and 95% confidence intervals (CIs) for hospitalization, mechanical ventilation, and death in CD20 inhibitor users versus comparators were estimated using Cox regression.ResultsWe identified 114 cases with COVID-19 who had received CD20 inhibitors for immune-mediated diseases (mean age 55 years, 70% female) and 559 matched comparators with COVID-19 (mean age 54 years, 70% female). CD20 inhibitor-treated cases had higher mortality (aHR 2.16; 95% CI: 1.03 to 4.54) than matched comparators. Risks of hospitalization (aHR 0.88; 95% CI: 0.62 to 1.26) and mechanical ventilation (aHR 0.82; 95% CI: 0.36 to 1.87) were similar. Similar trends were seen in analyses according to type of indication (e.g., rheumatic or neurologic disease) and duration of CD20 inhibitor use (<1 or ≥1 year), and after excluding patients with interstitial lung disease, cancer, and those on glucocorticoids prior to COVID-19 diagnosis.ConclusionsPatients who received CD20 inhibitors for immune-mediated diseases prior to COVID-19 had higher mortality following COVID-19 than matched comparators, highlighting the urgent need to mitigate excess risks in CD20 inhibitor users during the ongoing pandemic.Key MessagesWhat is already known about this subject?Patients with immune-mediated diseases treated with CD20 inhibitors may have worse COVID-19 outcomes than those treated with other immunomodulatory medications, but differences compared to the general population are unknown.What does this study add?CD20 inhibitor-treated cases had over two-fold higher risk of mortality than matched general population comparators, although risks of hospitalization and mechanical ventilation were similar.How might this impact on clinical practice or future developments?There is an urgent need for risk mitigation strategies, such as SARS-CoV-2 monoclonal antibodies or booster vaccinations, for patients with immune-mediated diseases treated with CD20 inhibitors during the ongoing COVID-19 pandemic.
Internet Use impact on Physical Health during COVID-19 pandemic in Bangladesh: A Web-based Cross-sectional study
Authors: Abir Tanvir , Osuagwu Uchechukwu Levi , Nur–A Yazdani Dewan Muhammad , Mamun Abdullah Al , Kakon Kaniz , Salamah Anas A. , Zainol Noor Raihani , Khanam Mansura , Agho Kingsley Emwinyore 
Published: August 2021

AbstractBackgroundBangladesh ranked fifth largest internet user in Asia. Past studies on internet use have focused on its impact on mental health, with little known about its impact on the physical health of individuals during COVID-19 pandemic. Hence, this study examines the impact of Internet use frequency on physical health during the Covid-19 lockdown in Bangladesh.MethodsA web-based cross-sectional study on 3242 individuals aged 18 and above was conducted from 2ndAugust – 1stOctober 1, 2020, during the lockdown in Bangladesh. The survey covers demographics, Internet use frequency and physical health questions. Multiple linear regression analyses were used to examine the impact of internet use frequency on physical health.ResultsThe result indicated that 72.5%, 69.9%, 65.1% and 55.3% reported headache, back pain, numbness of the fingers and neck pain, respectively. The multivariable analyses showed increased physical health impact among regular (coefficient β =0.52, 95% confidence interval [CI]: 0.18-0.85,P=0.003), frequent (β = 1.21, 95%CI: 0.88–1.54,P< .001) and intense (β = 2.24, 95%CI: 1.91–2.57,P< .001) internet users. Other factors associated with physical health scores were gender, income (in Taka), occupation, regions, and working status.ConclusionFrequent, intensive, and extensive use of the internet were strong predictors of increased physical health problems, and the study suggests the need for raising awareness of physical health problems triggered by high internet users among the high socioeconomic group in Bangladesh.
Clinical pneumonia in the hospitalised child in Malawi in the post-pneumococcal conjugate vaccine era: a prospective hospital-based observational study
Authors: Iroh Tam Pui-Ying , Chirombo James , Henrion Marc Y. R. , Newberry Laura , Mambule Ivan , Everett Dean , Mwansambo Charles , Cunliffe Nigel A. , French Neil , Heyderman Robert S. , Bar-Zeev Naor ,   the VacSurv Consortium
Published: August 2021

AbstractObjectiveAssess characteristics of clinical pneumonia after introduction of pneumococcal conjugate vaccine (PCV), by HIV exposure status, in children hospitalized in a governmental hospital in Malawi.Methods and findingsWe evaluated 1,139 children ≤5 years old hospitalised with clinical pneumonia: 101 HIV-exposed uninfected (HEU) and 1038 HIV-unexposed, uninfected (HUU). Median age was 11 months (IQR 6-20), 59% were male, median mid-upper arm circumference (MUAC) was 14 cm (IQR 13-15) and mean weight-for-height z score was -0.7 (±2.5). The highest Respiratory Index of Severity in Children (RISC) scores were allocated to 10.4% of the overall cohort, respectively. Only 45.7% had fever, and 37.2% had at least one danger sign at presentation. The most common clinical features were crackles (54.7%), nasal flaring (53.5%), and lower chest wall indrawing (53.2%). Compared to HUU, HEU children were significantly younger (9 months v. 11 months), with lower mean birth weight (2.8 kg v. 3.0 kg) and MUAC (13.6 cm v. 14.0 cm), had higher prevalence of vomiting (32.7% v. 22.0%), tachypnoea (68.4% v. 49.8%), and highest RISC scores (20.0% v. 9.4%). Five children died (0.4%). However, clinical outcomes were similar for both groups.ConclusionsIn this post-PCV setting where prevalence of HIV and malnutrition is high, children hospitalised fulfilling the WHO Integrated Management of Childhood Illness criteria for clinical pneumonia present with heterogeneous features. These vary by HIV exposure status but this does not influence either the frequency of danger signs or mortality. The poor performance of available severity scores in this population and the absence of more specific diagnostics hinder appropriate antimicrobial stewardship and the rational application of other interventions.Strengths and limitations of the studyWe evaluated over 1,100 children hospitalized with pneumonia in a low-income country setting after introduction of PCV.This observational cohort was nested within a prospective hospital-based study of PCV13 effectivenessWe assessed the demographic and clinical characteristics of clinical pneumonia patients and compared HEU vs. HUU children, and computed RISC scores for severe pneumonia
A Machine Learning Model Incorporating Laboratory Blood Tests Discriminates Between SARS-CoV-2 and Influenza Infections at Emergency Department Visit
Authors: Liu Junyi , Westblade Lars F. , Chadburn Amy , Fideli Richard , Craney Arryn , Rand Sophie , Cushing Melissa , Zhao Zhen , Meng Jingjing , Yang He S. 
Published: August 2021

AbstractIntroductionSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza virus are contagious respiratory pathogens with similar symptoms but require different treatment and management strategies. This study investigated whether laboratory blood tests can discriminate between SARS-CoV-2 and influenza infections at emergency department (ED) presentation.Methods723 influenza A/B positive (2018/1/1 to 2020/3/15) and 1,281 SARS-CoV-2 positive (2020/3/11 to 2020/6/30) ED patients were retrospectively analyzed. Laboratory test results completed within 48 hours prior to reporting of virus RT-PCR results, as well as patient demographics were included to train and validate a random forest (RF) model. The dataset was randomly divided into training (2/3) and testing (1/3) sets with the same SARS-CoV-2/influenza ratio. The Shapley Additive Explanations technique was employed to visualize the impact of each laboratory test on the differentiation.ResultsThe RF model incorporating results from 15 laboratory tests and demographic characteristics discriminated SARS-CoV-2 and influenza infections, with an area under the ROC curve value 0.90 in the independent testing set. The overall agreement with the RT-PCR results was 83% (95% CI: 80-86%). The test with the greatest impact on the differentiation was serum total calcium level. Further, the model achieved an AUC of 0.82 in a new dataset including 519 SARS-CoV-2 ED patients (2020/12/1 to 2021/2/28) and the previous 723 influenza positive patients. Serum calcium level remained the most impactful feature on the differentiation.ConclusionWe identified characteristic laboratory test profiles differentiating SARS-CoV-2 and influenza infections, which may be useful for the preparedness of overlapping COVID-19 resurgence and future seasonal influenza.
Elamipretide (SS-31) Treatment Attenuates Age-Associated Post-Translational Modifications of Heart Proteins
Authors: Whitson Jeremy A. , Martín-Pérez Miguel , Zhang Tong , Gaffrey Matthew J. , Merrihew Gennifer E. , Huang Eric , White Collin C. , Kavanagh Terrance J. , Qian Wei-Jun , Campbell Matthew D. , MacCoss Michael J. , Marcinek David J. , Villén Judit , Rabinovitch Peter S. 
Published: August 2021

ABSTRACTIt has been demonstrated that elamipretide (SS-31) rescues age-related functional deficits in the heart but the full set of mechanisms behind this have yet to be determined. We investigated the hypothesis that elamipretide influences post-translational modifications to heart proteins. The S-glutathionylation and phosphorylation proteomes of mouse hearts were analyzed using shotgun proteomics to assess the effects of aging on these post-translational modifications and the ability of the mitochondria-targeted drug elamipretide to reverse age-related changes. Aging led to an increase in oxidation of protein thiols demonstrated by increased S-glutathionylation of cysteine residues on proteins from Old (24 months old at the start of the study) mouse hearts compared to Young (5-6 months old). This shift in the oxidation state of the proteome was almost completely reversed by 8-weeks of treatment with elamipretide. Many of the significant changes that occurred were in proteins involved in mitochondrial or cardiac function. We also found changes in the mouse heart phosphoproteome that were associated with age, some of which were partially restored with elamipretide treatment. Parallel reaction monitoring of a subset of phosphorylation sites revealed that the unmodified peptide reporting for Myot S231 increased with age, but not its phosphorylated form and that both phosphorylated and unphosphorylated forms of the peptide covering cMyBP-C S307 increased, but that elamipretide treatment did not affect these changes. These results suggest that changes to thiol redox state and phosphorylation status are two ways in which age may affect mouse heart function, which can be restored by treatment with elamipretide.