bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Diabetic Ketoacidosis on Executive Function in Children With Type 1 Diabetes: Evidence From Wisconsin Card Sorting Test Performance
Authors: He Jing , Zhu Jiang , Xie Yuting , Du Hongyu , Li Shichen , Li Sihui , He Wenjuan , Li Xia , Zhou Zhiguang , Zhu Xiongzhao 
Published: May 2020

ABSTRACT

Objective
Diabetic ketoacidosis (DKA) in patients with type 1 diabetes mellitus (T1DM) is known to affect memory function, but little is known about its impact on executive function. This study aimed to determine whether a history of DKA was associated with changes in executive function in children with T1DM.

Methods
The sample consisted of 99 patients with T1DM with histories of DKA, 82 patients with T1DM without DKA, and 100 healthy controls aged 7 to 18 years. Neuropsychological function and emotion assessments were performed in all participants. The Wisconsin Card Sorting Test (WCST) was used to assess executive function.

Results
Compared with healthy controls, the DKA group (but not the non-DKA group) had a significantly lower mean intelligence quotient (IQ; p = .006, Cohen d = 0.528) and a significantly higher rate of WCST perseverative errors (p = .006, Cohen d = 0.475). In the DKA group, the age at DKA onset was significantly associated with the IQ (p = .001) and the number of completed WCST categories (p = .046). Higher hemoglobin A1c levels were associated significantly with lower IQ (p < .001), increased rate of WCST perseverative errors (p = .015), and completion of fewer WCST categories (p = .027).

Conclusions
DKA has implications for executive function in children with T1DM. These findings emphasize the importance of DKA prevention in patients with known T1DM, especially younger children with newly diagnosed T1DM.
Intensive Care Unit-Acquired Weakness: Neuropathology
Authors: Swash Michael , de Carvalho Mamede 
Published: May 2020

Summary:
There is extensive evidence in the literature that both peripheral nerve fibers and muscle fibers are affected in the course of intensive care unit-acquired weakness. Peripheral nerve lesion is characterized by axonal degeneration, without inflammatory changes. Muscle fiber involvement is characterized by muscle fiber atrophy and loss of thick filaments, predominantly involving type 2 fibers, but myonecrosis (“acute necrotizing myopathy of intensive care”) has also been reported. Steroids can precipitate thick myofilament damage, probably to some extent also triggered by immobilization and neuromuscular junction blockade. Sepsis and a systemic inflammatory response cause muscle fiber injury because of the release of cytokines and chemokines that modulate enzymatic reactions related to proteolysis. Regarding axonal injury, hyperglycemia, hypoalbuminemia, inflammatory response, and hypoperfusion are accepted risk factors. Nerve and muscle biopsy are the best methods for detection of structural abnormalities, but these are invasive investigations; although not suitable for repeated studies, in selected cases, biopsies may have a role in diagnosis.
Left ventricular mass index and subendocardial myocardial function in children with chronic kidney disease, a transmural strain and three-dimensional echocardiographic study
Authors: El Tantawy Amira Esmat , Fadel Fatina , Abdelrahman Safaa M. , Nabhan Marwa , Ibrahim Reem , Fattouh Aya M. , Sayed Shaimaa , ElKhashab Khaled Mohamed , Afdal Peter , AbdelMassih Antoine Fakhry 
Published: May 2020

Introduction
Left ventricular hypertrophy (LVH) is the commonest myocardial response to chronic kidney disease (CKD); this response has been regarded detrimental as it impairs the blood flow to the deepest layers of the myocardium causing progressive myocardial dysfunction. The aim of these series is to assess the determinants of LVH in CKD patients and its impact on subendocardial function in such patients.

Methods
This study has been conducted on 40 CKD patients (Group 1) and 40 age-matched controls, both groups were assessed by transmural echocardiography to determine the subepicardial and subendocardial global longitudinal strain (GLS) as an expression of the systolic function of each of those layers. LVH was assessed by calculation of left ventricle mass index (LVMI). Both groups underwent ambulatory blood pressure monitoring. Group 1 was assessed as regards lipid profile and insulin resistance by homeostasis model assessment of insulin resistance (HOMA-IR).

Results
HOMA-IR proved to be a more important determinant of LV hypertrophy than SBP and DBP with a P of 0.01. Moreover subendocardial GLS was negatively correlated with LVMI with r = 0.69 and P < 0.01 denoting the negative effect. LVH plays on subendocardial function probably by impairing myocardial perfusion.

Conclusion
This study points toward the importance of insulin resistance in aggravation of myocardial remodeling in CKD patients; more studies are warranted to examine the role of insulin Sensitizers in reversing such remodeling and restoring subendocardial function in such important systemic disorder.
Specifications of the ACMG/AMP variant interpretation guidelines for germline TP53 variants
Authors: Fortuno Cristina , Lee Kristy , Olivier Magali , Pesaran Tina , Mai Phuong L. , de Andrade Kelvin C. , Attardi Laura D. , Crowley Stephanie , Evans D. Gareth , Feng Bing-Jian , Major Foreman Ann Katherine , Frone Megan N. , Huether Robert , James Paul A. , McGoldrick Kelly , Mester Jessica , Seifert Bryce A. , Slavin Thomas P. , Witkowski Leora , Zhang Liying , Plon Sharon E. , Spurdle Amanda B. , Savage Sharon A. 
Published: May 2020

ABSTRACTGermline pathogenic variants in TP53 are associated with Li-Fraumeni syndrome (LFS), an autosomal dominant cancer predisposition disorder associated with high risk of malignancy, including early onset breast cancers, sarcomas, adrenocortical carcinomas and brain tumors. Intense cancer surveillance for individuals with TP53 germline pathogenic variants has been shown to decrease mortality; therefore, accurate and consistent classification of variants across clinical and research laboratories is crucial to patient care. Here, we describe the work performed by the Clinical Genome Resource TP53 Variant Curation Expert Panel (ClinGen TP53 VCEP) focused on specifying the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) guidelines for germline variant classification to the TP53 gene. Specifications were applied to twenty ACMG/AMP criteria while nine were deemed not applicable. The original strength level for ten criteria was also adjusted due to current evidence. Use of the TP53-specific guidelines and sharing of clinical data amongst experts and clinical laboratories led to a decrease in variants of uncertain significance from 28% to 12% in comparison with the original guidelines. The ClinGen TP53 VCEP recommends the use of these TP53-specific ACMG/AMP guidelines as the standard strategy for TP53 germline variant classification.
Genomic epidemiology ofCampylobacter jejuniassociated with asymptomatic pediatric infection in the Peruvian Amazon
Authors: Pascoe Ben , Schiaffino Francesca , Murray Susan , Méric Guillaume , Bayliss Sion C. , Hitchings Matthew D. , Mourkas Evangelos , Calland Jessica K. , Burga Rosa , Peñataro Yori Pablo , Jolley Keith A. , Cooper Kerry K. , Parker Craig T. , Olortegui Maribel Paredes , Kosek Margaret N. , Sheppard Samuel K. 
Published: May 2020

AbstractCampylobacteris the leading bacterial cause of gastroenteritis worldwide and its incidence is especially high in low- and middle-income countries (LMIC). Disease epidemiology in LMICs is different compared to high income countries like the USA or in Europe. Children in LMICs commonly have repeated and chronic infections even in the absence of symptoms, which can lead to deficits in early childhood development. In this study, we sequenced and characterizedC. jejuni(n=62) from a longitudinal cohort study of children under the age of 5 with and without diarrheal symptoms, and contextualized them within a globalC. jejunigenome collection. Epidemiological differences in disease presentation were reflected in the genomes, specifically by the absence of some of the most common global disease-causing lineages. As in many other countries, poultry-associated strains were a major source of human infection but almost half of local disease cases (15 of 31) were attributable to genotypes that are rare outside of Peru. Asymptomatic infection was not limited to a single (or few) human adapted lineages but resulted from phylogenetically divergent strains suggesting an important role for host factors in the cryptic epidemiology of campylobacteriosis in LMICs.Author summaryCampylobacteris the leading bacterial cause of gastroenteritis worldwide and despite high incidence in low- and middle-income countries (LMICs), where infection can be fatal, culture based isolation is rare and the genotypes responsible for disease have not broadly been identified. The epidemiology of disease is different to that in high income countries, where sporadic infection associated with contaminated food consumption typically leads to acute gastroenteritis. In some LMICs infection is endemic among children and common asymptomatic carriage is associated with malnutrition, attenuated growth in early childhood, and poor cognitive and physical development. Here, we sequenced the genomes of isolates sampled from children in the Peruvian Amazon to investigate genotypes associated with varying disease severity and the source of infection. Among the common globally circulating genotypes and local genotypes rarely seen before, no single lineage was responsible for symptomatic or asymptomatic infection – suggesting an important role for host factors. However, consistent with other countries, poultry-associated strains were a major source of infection. This genomic surveillance approach, that integrates microbial ecology with population based studies in humans and animals, has considerable potential for describing cryptic epidemiology in LMICs and will inform work to improve infant health worldwide.
Using the COVID-19 to influenza ratio to estimate the numbers of symptomatic COVID-19 cases in Wuhan prior to the lockdown
Authors: Du Zhanwei , Cowling Benjamin J. , Meyers Lauren Ancel 
Published: May 2020

AbstractA recent study tested 45 throat swabs taken from adults over age 30 who sought outpatient care at one of two central Wuhan hospitals for influenza-like-illness between December 30, 2019 and January 19, 2020. Although none were confirmed COVID-19 cases, nine retrospectively tested positive for the virus. Using the fact that Wuhan has 393 other hospitals, we extrapolate the total number of undetected cases of symptomatic COVID-19 in adults during this period. we estimate that there were 5,558 [95% CI: 2,761-9,864] adults with symptomatic COVID-19 infections in Wuhan between December 30th and January 19th, 2020.
A first study on the impact of containment measure on COVID-19 spread in Morocco
Authors: Hammoumi Aayah , Qesmi Redouane 
Published: May 2020

AbstractBackgroundSince the appearance of the first case of COVID-19 in Morocco, the cumulative number of reported infectious cases continues to increase and, consequently, the government imposed the containment measure within the country. Our aim is to predict the impact of the compulsory containment on COVID-19 spread. Earlier knowledge of the epidemic characteristics of COVID-19 transmission related to Morocco will be of great interest to establish an optimal plan-of-action to control the epidemic.MethodUsing a Susceptible-Asymptomatic-Infectious model and the data of reported cumulative confirmed cases in Morocco from March 2nd to April 9, 2020, we determined the basic and control reproduction numbers and we estimated the model parameter values. Furthermore, simulations of different scenarios of containment are performed.ResultsEpidemic characteristics are predicted according to different rates of containment. The basic reproduction number is estimated to be 2.9949, with CI(2.6729–3.1485). Furthermore, a threshold value of containment rate, below which the epidemic duration is postponed, is determined.ConclusionOur findings show that the basic reproduction number reflects a high speed of spread of the epidemic. Furthermore, the compulsory containment can be efficient if more than 73% of population are confined. However, even with 90% of containment, the end-time is estimated to happen on July 4th which can be harmful and lead to consequent social-economic damages. Thus, containment need to be accompanied by other measures such as mass testing to reduce the size of asymptomatic population. Indeed, our sensitivity analysis investigation shows that the COVID-19 dynamics depends strongly on the asymptomatic duration as well as the contact and containment rates. Our results can help the Moroccan government to anticipate the spread of COVID-19 and avoid human loses and consequent social-economic damages as well.
Clinical-grade whole genome sequencing of colorectal cancer and 3’ transcriptome analysis demonstrate targetable alterations in the majority of patients
Authors: Stodolna Agata , He Miao , Vasipalli Mahesh , Kingsbury Zoya , Becq Jennifer , Stockton Joanne D , Dilworth Mark P , James Jonathan , Sillo Toju , Blakeway Daniel , Ward Stephen T , Ismail Tariq , Ross Mark T. , Beggs Andrew D. 
Published: May 2020

AbstractIntroductionClinical grade whole genome sequencing (cWGS) has the potential to become standard of care within the clinic because of its breadth of coverage and lack of bias towards certain regions of the genome. Colorectal cancer presents a difficult treatment paradigm, with over 40% of patients presenting at diagnosis with metastatic disease. We hypothesised that cWGS coupled with 3’ transcriptome analysis would give new insights into colorectal cancer.MethodsPatients underwent PCR-free whole genome sequencing and alignment and variant calling using a standardised pipeline to output SNVs, indels, SVs and CNAs. Additional insights into mutational signatures and tumour biology were gained by the use of 3’ RNAseq.ResultsFifty-four patients were studied in total. Driver analysis identified the Wnt pathway gene APC as the only consistently mutated driver in colorectal cancer. Alterations in the PI3K/mTOR pathways were seen as previously observed in CRC. Multiple private CNAs, SVs and gene fusions were unique to individual tumours. Approximately 20% of patients had a tumour mutational burden of >10 mutations/Mb of DNA, suggesting suitability for immunotherapy.ConclusionsClinical whole genome sequencing offers a potential avenue for identification of private genomic variation that may confer sensitivity to targeted agents and offer patients new options for targeted therapies.
A Fundamental Inconsistency in the SIR Model Structure and Proposed Remedies
Authors: Nikolaou Michael 
Published: May 2020

AbstractThe susceptible-infectious-removed (SIR) compartmental model structure and its variants are a fundamental modeling tool in epidemiology. As typically used, however, this tool may introduce an inconsistency by assuming that the rate of depletion of a compartment is proportional to the content of that compartment. As mentioned in the seminal SIR work of Kermack and McKendrick, this is an assumption of mathematical convenience rather than realism. As such, it leads to underprediction of the infectious compartment peaks by a factor of about two, a problem of particular importance when dealing with availability of resources during an epidemic. To remedy this problem, we develop the dSIR model structure, comprising a single delay differential equation and associated delay algebraic equations. We show that SIR and dSIR fully agree in assessing stability and long-term values of a population through an epidemic, but differ considerably in the exponential rates of ascent and descent as well as peak values during the epidemic. The novel Padé-SIR structure is also introduced as a approximation of dSIR by ordinary differential equations. We rigorously analyze the properties of these models and present a number of illustrative simulations, particularly in view of the recent coronavirus epidemic. Suggestions for further study are made.
Pooled testing with replication: a mass testing strategy for the COVID-19 pandemics
Authors: Žilinskas Julius , Lančinskas Algirdas , Guarracino Mario R. 
Published: May 2020

AbstractIn absence of a vaccine or antiviral drugs for the COVID-19 pandemic, it becomes urgent to test for positiveness to the virus as many people as possible, in order to detect early outbreaks of the infection. Present testing solutions are based on the extraction of RNA from patients using oropharyngeal (OP) and nasopharyngeal (NP) swabs, and then testing with real-time PCR for the presence of specific RNA filaments identifying the virus. This approach is limited by the availability of reactants, trained technicians and laboratories. To speed up the testing procedures, some attempts have been done on group testing, which means that the swabs of multiple patients are grouped together and tested. Here we propose to use this technique in conjunction with a combinatorial replication scheme in which each patient is allocated in two or more groups to reduce total numbers of tests and to allow testing of even larger numbers of people. Under mild assumptions, a 13× average reduction of tests can be achieved.
Causal effects of senescence through intrinsic epigenetic age acceleration on age-related diseases: a Mendelian randomization study
Authors: Gatto F. , Ueda P. 
Published: May 2020

AbstractOlder age is associated with many diseases. However, it is unclear whether the biological mechanisms underpinning senescense (biological ageing) is a cause of age-related diseases (ARDs). In this Mendelian randomization study, we examined the causal effects of intrinsic epigenetic age acceleration (IEAA) - a process assumed downstream of senescence - on the occurrence of ARDs. In a metanalysis of 18 genome-wide association studies (GWAS) spanning 12 ARDs in ~27 million people of European ancestry (median per GWAS: 17’008 cases vs. 40’940 controls), IEAA-associated SNPs did not significantly increase the risk of ARDs as a group (odds-ratio (OR) = 0.99) nor of any individual ARD (OR range: 0.87-1.04). However, one SNP, rs2736099 on TERT, was significantly associated with 8 of 10 ARDs with increased risk for lung and ovarian cancer, atrial fibrillation, and benign prostatic hyperplasia and lower risk for Alzheimer’s disease, rheumatoid arthritis, cardiovascular artery disease and breast cancer. No associations between rs2736099 and known ARD risk factors were found strengthening the causal role of rs2736099-associated senescence. While IEAA was not found as a unifying cause of ARDs, senescence seems to cause some ARDs while preventing others through a mechanism only partially affecting IEAA and associated with rs2736099.
Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease: A retrospective study
Authors: Mallat Jihad , Hamed Fadi , Balkis Maher , Mohamed Mohamed A. , Mooty Mohamad , Malik Asim , Nusair Ahmad , Bonilla Maria-Fernanda 
Published: May 2020

AbstractBackgroundThere is conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patientsObjectiveTo assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearanceDesignRetrospective observational studySettingCleveland Clinic Abu DhabiParticipantsHospitalized adult patients with confirmed SARS-CoV-2 infectionInterventionNoneMeasurementsThe primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by two negative results using RT-PCR assay with samples obtained 24 hours apartResults34 confirmed COVID-19 patients were included. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ compared to those who did not receive HCQ (17 [13–21] vs. 10 [4–13] days, p=0.023). HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, pneumonia or oxygen therapy) in multivariable linear regression analysis. On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared to 90.9% (10/11) patients who did not receive HCQ (p=0.016).LimitationsSmall sample size and retrospective design with a potential risk of selection biasConclusionHCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.
Notch and TLR signaling coordinate monocyte cell fate and inflammation
Authors: Gamrekelashvili Jaba , Kapanadze Tamar , Sablotny Stefan , Ratiu Corina , Dastagir Khaled , Lochner Matthias , Karbach Susanne , Wenzel Philip , Sitnow Andre , Fleig Susanne , Sparwasser Tim , Kalinke Ulrich , Holzmann Bernhard , Haller Hermann , Limbourg Florian P. 
Published: May 2020

AbstractConventional Ly6Chimonocytes have developmental plasticity for a spectrum of differentiated phagocytes. Here we show, using conditional deletion strategies in a mouse model of Toll-like receptor (TLR) 7-induced inflammation, that the spectrum of developmental cell fates of Ly6Chimonocytes, and the resultant inflammation, is coordinately regulated by TLR and Notch signaling. Cell-intrinsic Notch2 and TLR7-Myd88 pathways independently and synergistically promote Ly6Clopatrolling monocyte development from Ly6Chimonocytes under inflammatory conditions, while impairment in either signaling axis impairs Ly6Clomonocyte development. At the same time, TLR7 stimulation in the absence of functional Notch2 signaling promotes resident tissue macrophage gene expression signatures in monocytes and ectopic differentiation of Ly6Chimonocytes into macrophages and dendritic cells, which appear in the blood stream and infiltrate the spleen and major blood vessels, resulting in unrestrained systemic inflammation. Thus, Notch2 is a master regulator of Ly6Chimonocyte cell fate and inflammation in response to TLR signaling.