bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insulin and Cinnamon Polyphenol Extract Regulated Diacylglycerol Acyltransferase and Tristetraprolin Gene Expression in Cultured Mouse Adipocytes and Macrophages
Authors: Cao Heping , Anderson Richard A 
Published: June 2021

Diacylglycerol acyltransferases (DGATs) are integral membrane proteins that catalyze the last step of triacylglycerols (TAGs) biosynthesis in eukaryotic organisms. Plants and animals deficient in DGATs accumulate less TAGs and over‐expression of DGATs increases TAGs. DGAT knockout mice are resistant to diet‐induced obesity and lack milk secretion. Previous studies showed that cinnamon is beneficial to people with insulin resistance due in part to the insulin‐like activity of the cinnamon polyphenol extract (CPE), which also induces anti‐inflammatory zinc‐finger protein 36 (Zfp36)/tristetraprolin (Ttp) gene expression in both cultured adipocytes and macrophages. This study tested if Dgat gene expression is regulated by insulin and CPE using cultured mouse 3T3‐L1 adipocytes and RAW264.7 macrophages. The pre‐adipocytes were induced to oil‐droplet‐filled adipocytes and subsequently treated with insulin (0, 10 and 100 nM) and CPE (0, 10 and 100 μg/ml) for 0, 30, 60, 90 and 120 min. RAW macrophages were treated with CPE (100 μg/ml), insulin (100 nM) and lipopolysaccharides (LPS, 0.1 μg/ml) for 0, 30, 60, 120 and 240 min. Total RNAs were extracted from the cells and converted into cDNAs. TaqMan quantitative real‐time PCR was used to evaluate mRNA levels of mouse Dgat1, Dgat2 and Zfp36/Ttp genes using Rpl32 and Ubqln3 as internal references. Results showed that Dgat mRNA levels were generally decreased and Zfp36/Ttp mRNA levels were modestly increased by insulin and CPE in adipoctyes. Insulin and CPE effects on Dgat2 and Zfp36/Ttp gene expression were modestly increased but LPS increased Zfp36/Ttp mRNA levels up to 50‐fold in macrophages. Our results support the idea that CPE has insulin‐like effects and suggest a potential positive effect of CPE in reducing fat biosynthesis in adipocytes and increasing anti‐inflammatory activities in macrophages. The significance of this study is that CPE could be potentially useful for obesity prevention.Support or Funding InformationUSDA‐ARS Quality and Utilization of Agricultural Products Research Program 306 through CRIS 6054‐41000‐103‐00D
A Global Survey of Patient and Caregiver Experiences Throughout Care for Developmental Dysplasia of the Hip
Authors: Gibbard Marissa , Zivkovic Irena , Jivraj Bejaan , Schaeffer Emily , Robillard Julie M. , Mulpuri Kishore 
Published: June 2021

Background:
Diagnosis and treatment for developmental dysplasia of the hip (DDH) varies greatly depending on condition severity, age at diagnosis, and professional opinion. Little is known about patient experiences across the globe. We aimed to characterize global patient and caregiver experiences during DDH care and to highlight patient-identified priorities.

Methods:
We developed a cross-sectional survey in collaboration with 7 DDH outreach organizations. DDH patients and/or their caregivers (above 18 y old) were invited to complete an international online survey about their experiences. Participants were recruited through web media of all collaborating organizations. Data collection took place over 3 months. Descriptive statistics were used to analyze quantitative results. Qualitative content analysis was used to categorize open-ended responses.

Results:
A total of 739 participants completed the survey, representing 638 (86.3%) parents/guardians of DDH patients, and 101 (13.7%) patients. Three hundred eighty-six (52.2%) participants received diagnosis by 3 months of age; mean age of diagnosis was 15.96 months (90% confidence interval=12.04, 19.91). Of 211 participants with family history of DDH, 68 (32.3%) did not receive DDH screening. Of 187 patients born breech, 82 (43.9%) did not receive DDH screening. In total, 36/94 (38.3%) participants with both family history and breech birth did not receive DDH screening. Most participants reported treatment (696/730, 95.3%), including bracing (n=461) surgery (n=364), and/or closed reduction (n=141). A total of 144 patients reported >1 surgery; 82 reported >3 surgeries. Participants reported a range of 1 to 400 visits to health care professionals for DDH care across 1 to 66 years. Lack of information and resources on treatment practicalities and timelines, along with emotional burden of diagnosis, were greatest challenges reported.

Conclusion:
Results demonstrate that DDH diagnosis and treatment can pose significant burden on patients and caregivers. Reliable public information is needed to support those affected. Global educational efforts are needed to raise awareness of DDH risk factors, signs, and symptoms among care providers, to increase awareness and improve identification, screening, and monitoring of at-risk children.
Epidemiologic and Clinical Characteristics of Clostridioides difficile Infections in Hospitalized and Outpatient Pediatric Oncology and Hematopoietic Stem Cell Transplant Patients
Authors: Barbar Ruba , Hayden Randall , Sun Yilun , Tang Li , Hakim Hana 
Published: June 2021

Background:
The epidemiology and clinical course of Clostridioides difficile infection (CDI) in children, especially with cancer, are poorly defined. We aim to describe the epidemiology, clinical features and outcomes of CDI and to identify risk factors for recurrence in a pediatric oncology center.

Methods:
This is a retrospective cohort study of CDI in pediatric oncology and hematopoietic stem cell transplant (HSCT) patients in 2016 and 2017. CDI cases were identified by positive C. difficile test in symptomatic patients. CDI episodes were classified as incident, duplicate or recurrent and community-onset, hospital-onset or community-onset healthcare facility-associated. Data about clinical course and outcomes were abstracted. Risk factors for CDI recurrence were assessed by logistic regression.

Results:
One hundred seventy-eight patients 1 year of age and older developed 291 CDI episodes; 78% were incident and 22% recurrent. Underlying diagnoses were leukemia/lymphoma (57%) and solid/brain tumors (41%); 30% were HSCT recipients. Antibiotics, chemotherapy, antacids, steroids and laxatives were received by 96%, 82%, 70%, 47% and 15%, respectively. Half of the patients were neutropenic. Twenty-two percent of outpatients with CDI required hospitalization. Chemotherapy was delayed in 25%. There were no intensive care unit admissions nor deaths due to CDI. Exposure to H2-antagonists was identified as an independent risk factor for CDI recurrence.

Conclusions:
Although CDI in pediatric oncology and HSCT patients was associated with chemotherapy delay and hospitalization in approximately a quarter of patients, it was not associated with morbidity or mortality because patients had no attributable intensive care unit admission nor death. H2-antagonists are independent risk factors for CDI recurrence.
Trajectories of pain during pregnancy predict symptoms of postpartum depression
Authors: Mathur Vani A. , Nyman Tristin , Nanavaty Namrata , George Nevita , Brooker Rebecca J. 
Published: June 2021

Abstract

Introduction:
Postpartum depression imparts a significant and long-lasting burden on maternal and child health. Successful prevention or early detection of postpartum depression will rely on the identification of early risk factors. Pain during pregnancy (before childbirth) is a key potential predictor of postpartum depression risk. However, longitudinal studies characterizing pregnancy pain, its normal trajectory over time, and its prospective relations with symptoms of postpartum depression are lacking.

Methods:
We used data from a longitudinal study of maternal emotion that included assessments of pain and depressive symptoms at 3 time points—during the second and third trimester of pregnancy and at 4 months postpartum. Structural equation modelling was used to estimate longitudinal patterns of change in maternal pain over time. Latent growth curve parameters were tested as predictors of symptoms of postpartum depression.

Results:
Ninety-three healthy pregnant women enrolled in this study. Although the sample comprised women with relatively low-risk pregnancies, more than 90% of participants experienced pregnancy pain. Greater linear increases and less negative quadratic change in maternal pain over time were associated with greater levels of postpartum depression, even when controlling for prenatal depressive symptoms. Interpreting both parameters together, pain that increased in late pregnancy, when normative patterns had either levelled off or begun to decline, was associated with greater levels of postpartum depression.

Conclusion:
A developmental trajectory of pain experience that did not subside after childbirth was associated with greater postpartum depressive symptoms, suggesting that atypical trajectories of pain may be a risk factor for postpartum depression.
Highly sensitive scent-detection of COVID-19 patients in vivo by trained dogs
Authors: Vesga Omar , Agudelo Maria , Valencia-Jaramillo Andrés F. , Mira-Montoya Alejandro , Ossa-Ospina Felipe , Ocampo Esteban , Čiuoderis Karl , Pérez Laura , Cardona Andrés , Aguilar Yudy , Agudelo Yuli , Hernández-Ortiz Juan P. , Osorio Jorge E. 
Published: June 2021

AbstractTimely and accurate diagnostics are essential to fight the COVID-19 pandemic, but no test satisfies both conditions. Dogs can scent-identify the unique odors of the volatile organic compounds generated during infection by interrogating specimens or, ideally, the body of a patient. After training 6 dogs to detect SARS-CoV-2 in human respiratory secretions (in vitro scent-detection), we retrained 5 of them to diagnose the infection by scenting the patient directly (in vivo scent-detection). Then, efficacy trials were designed to compare the diagnostic performance of the dogs against that of the rRT-PCR in 848 human subjects: 269 hospitalized patients (COVID-19 prevalence 30.1%), 259 hospital staff (prevalence 2.7%), and 320 government employees (prevalence 1.25%). The limit of detection in vitro was lower than 10-12 copies ssRNA/mL. In vivo, all dogs detected 92 COVID-19 patients present among the 848 study subjects. Detection was immediate, and independent of prevalence, time post-exposure, or presence of symptoms, with 95.2% accuracy and high sensitivity (95.9%; 95% C.I. 93.6-97.4), specificity (95.1%; 94.4-95.8), positive predictive value (69.7%; 65.9-73.2), and negative predictive value (99.5%; 99.2-99.7). To determine real-life performance, we waited 75 days to carry out an effectiveness assay among the riders of the Metro System of Medellin, deploying the human-canine teams without previous training or announcement. Three dogs (one of each breed) scent-interrogated 550 citizens who volunteered for simultaneous canine and rRT-PCR testing. Negative predictive value remained at 99.0% (95% C.I. 98.3-99.4), but positive predictive value dropped to 28.2% (95% C.I. 21.1-36.7). Canine scent-detection in vivo is a highly accurate screening test for COVID-19, and it detects more than 99% of infected individuals independently of the key variables. However, real-life conditions increased substantially the number of false positives, indicating the necessity of training a threshold for the limit of detection to discriminate environmental odoriferous contamination from infection.
Biallelic and de novo variants in ATP6V0A1 cause progressive myoclonus epilepsy and developmental and epileptic encephalopathy
Authors: Bott Laura C , Forouhan Mitra , Lieto Maria , Sala Ambre J , Ellerington Ruth , Johnson Janel O , Speciale Alfina A , Criscuolo Chiara , Filla Alessandro , Chitayat David , Nemeth Andrea H ,   Italian Undiagnosed Diseases Network, Angelucci Francesco , Lim Wooi Fang , Striano Pasquale , Zara Federico , Helbig Ingo , Muona Mikko , Courage Carolina , Lehesjoki Anna-Elina , Berkovic Samuel F ,   V-ATPase Consortium, Fischbeck Kenneth H , Brancati Francesco , Morimoto Richard I , Wood Matthew JA , Rinaldi Carlo 
Published: June 2021

AbstractThe vacuolar H+-ATPase is a large multi-subunit proton pump, composed of an integral membrane V0 domain, involved in proton translocation, and a peripheral V1 domain, catalysing ATP hydrolysis. This complex is widely distributed on the membrane of various subcellular organelles, such as endosomes and lysosomes, and plays a critical role in cellular processes ranging from autophagy to protein trafficking and endocytosis. Variants in ATP6V0A1, the brain-enriched isoform in the V0 domain, have been recently associated with developmental delay and epilepsy in four individuals. Here we identified 17 individuals from 14 unrelated families with both with new and previously characterised variants in this gene, representing the largest cohort to date. Five affected subjects with biallelic variants in this gene presented with a phenotype of early-onset progressive myoclonus epilepsy with ataxia, while 12 individuals carried de novo missense variants and showed severe developmental and epileptic encephalopathy. The R740Q mutation, which alone accounts for almost 50% of the mutations identified among our cases, leads to failure of lysosomal hydrolysis by directly impairing acidification of the endolysosomal compartment, causing autophagic dysfunction and severe developmental defect in C. elegans. Altogether, our findings further expand the neurological phenotype associated with variants in this gene and provide a direct link with endolysosomal acidification in the pathophysiology of ATP6V0A1-related conditions.
Type 2 Diabetes and Risk of Early-Onset Colorectal Cancer
Authors: Li Zitong , Chen Hanyu , Fritz Cassandra D.L , Zheng Xiaobin , Zong Xiaoyu , Nickel Katelin B. , Tipping Andrew , Nguyen Long H. , Chan Andrew T. , Giovannucci Edward L. , Colditz Graham A. , Olsen Margaret A. , Campbell Peter T. , Davidson Nicholas O. , Fields Ryan C. , Cao Yin 
Published: June 2021

ABSTRACTObjectiveEarly-onset colorectal cancer (CRC) is increasing in many developed countries. Type 2 diabetes mellitus has increased substantially in younger adults; however, its role in early-onset CRC remains unidentified.DesignWe conducted a claims-based nested case-control study using IBM® MarketScan® Commercial Database (2006-2015). Incident early-onset CRC diagnosed at ages 18-49 were identified by ICD-9-CM diagnosis code, and the first coded diagnostic pathology date was assigned as the index date. Controls were frequency matched with cases. Type 2 diabetes, stratified by severity, was identified through ICD-9-CM using the Klabunde algorithm. Multivariate logistic regressions were used to estimate odds ratios (ORs) and 95% confidence intervals (Cls).ResultsA total of 6001 early-onset CRC and 52104 controls were included. Type 2 diabetes was associated with an increased risk of early-onset CRC (5.0% in cases vs. 3.7% in controls; OR 1.24; 95% CI 1.09 to 1.41). The positive association was more pronounced for uncontrolled (OR 1.37; 95% CI 1.12 to 1.67) or complicated (OR 1.59; 95% CI 1.08-2.35) type 2 diabetes compared to controlled diabetes (OR 1.13; 95% CI 0.94 to 1.36). The positive association was driven by proximal (OR 1.35; 95% CI 1.03 to 1.77) and distal (OR 1.67; 95% CI 1.30 to 2.15) colon cancer but not rectal cancer.ConclusionsIndividuals with type 2 diabetes have a higher risk of early-onset CRC, with stronger associations for uncontrolled/complicated diabetes. The rising prevalence of type 2 diabetes among younger adults in the US may partially contribute to the increasing incidence of early-onset CRC.
Tracking deaths from hitherto undetected infections can be an indicator of latent sars-cov-2 cases
Authors: Rangayyan Yashaswini Mandayam , Kidambi Sriram , Raghavan Mohan 
Published: June 2021

ABSTRACTBackgroundWith countries across the world facing repeated epidemic waves, it becomes critical to monitor, mitigate and prevent subsequent waves. Common indicators like active case numbers can flatter to deceive in the presence of systemic inefficiencies like insufficient testing or contact tracing. Test positivity rates are sensitive to testing strategies and cannot estimate the extent of undetected cases. Reproductive numbers estimated from logarithms of new incidences are inaccurate in dynamic scenarios and not sensitive enough to capture changes in efficiencies. Systemic fatigue results in lower testing, inefficient tracing and quarantining thereby precipitating the onset of the epidemic wave.MethodsWe propose a novel indicator for detecting the slippage of test-trace efficiency based on the numbers of deaths/hospitalizations resulting from known and hitherto unknown infections. This can also be used to forecast an epidemic wave that is advanced or exacerbated due to drop in efficiency.ResultsUsing a modified SEIRD epidemic simulator we show that (i) Ratio of deaths/hospitalizations from an undetected infection to total deaths converges to a measure of systemic test-trace inefficiency. (ii) This index forecasts the slippage in efficiency earlier than other known metrics. (iii) Mitigation triggered by this index helps reduce peak active caseload and eventual deaths.ConclusionsDeaths/hospitalizations accurately track the systemic inefficiencies and detect latent cases. Based on these results we make a strong case that administrations use this metric in the ensemble of indicators. Further hospitals may need to be mandated to distinctly register deaths/hospitalizations due to previously undetected infections.Key MessagesDeaths or Hospitalizations are unmissable events in an epidemic and this paper proposes a metric Dratio based on these numbers to monitor the inefficiencies in test-track-trace performance.The ratio of deaths(or hospitalizations) resulting from undetected infections to total deaths (or hospitalizations) detect the onset of laxity in regulations earlier than other conventional metrics like daily increase in active cases, daily deaths or even reproductive number estimates.Mitigation by tracking the Dratio reduces or truncates the epidemic wave intensity or delays it sufficiently.
Classifying Texas counties using ARIMA Models on COVID-19 daily confirmed cases: the impact of political affiliation and face covering orders
Authors: Jiang Hao , Pulins Brigitta , Thiele Aurélie C. 
Published: June 2021

AbstractThe aim of this paper is to investigate whether the 254 Texas counties in the United States can be grouped in a meaningful way according to the characteristics of the ARIMA or seasonal ARIMA models fitting the logarithm of daily confirmed cases of the Coronavirus Disease 2019 (COVID-19) for 254 counties in Texas of the United States. We analyze clusters of the model’s non-seasonal parameters (p, d, q), distinguishing between county-level political affiliations and face covering orders, and also consider county-level population and poverty rate. Using data from March 4, 2020 to March 15, 2021, we find that 223 of the total 254 counties are clustered into 23 model parameters (p, d, q), while the number of cases in the remaining 31 counties could not be successfully fitted to ARIMA models. We also find the impact of the county-level infection rate and the county-level poverty rate on clusters of counties with different political affiliations and face covering orders. Further, we find that the infection rate and the poverty rate had a significant high positive correlation, and Democrat-leaning counties, which tend to have large populations, had a higher correlation coefficient between infection rate and poverty rate. We also observe a significant high positive correlation between the infection rate and the number of cumulative cases in Republican counties that had not imposed a face covering order.
Language systems from lesion-symptom mapping in aphasia: A meta-analysis of voxel-based lesion mapping studies
Authors: Na Yoonhye , Jung JeYoung , Tench Christopher , Auer Dorothee P. , Pyun Sung-Bom 
Published: June 2021

AbstractBackgroundAphasia is one of the most common causes of post-stroke disabilities. As the symptoms and impact of post-stroke aphasia are heterogeneous, it is important to understand how topographical lesion heterogeneity in patients with aphasia is associated with different domains of language impairments. Here, we aim to provide a comprehensive overview of neuroanatomical basis in post-stroke aphasia through coordinate based meta-analysis of voxel-based lesion-symptom mapping studies.MethodsWe performed a meta-analysis of lesion-symptom mapping studies in post-stroke aphasia. We obtained coordinate-based functional neuroimaging data for 2,007 individuals with aphasia from 25 studies that met predefined inclusion criteria.ResultsOverall, our results revealed that the distinctive patterns of lesions in aphasia are associated with different language functions and tasks. Damage to the insular-motor areas impaired speech with preserved comprehension and a similar pattern was observed when the lesion covered the insular-motor and inferior parietal lobule. Lesions in the frontal area severely impaired speaking with relatively good comprehension. The repetition-selective deficits only arise from lesions involving the posterior superior temporal gyrus. Damage in the anterior-to-posterior temporal cortex was associated with semantic deficits.ConclusionThe association patterns of lesion topography and specific language deficits provide key insights into the specific underlying language pathways. Our meta-analysis results strongly support the dual pathway model of language processing, capturing the link between the different symptom complexes of aphasias and the different underlying location of damage.
Group Testing Large Populations for SARS-CoV-2
Authors: Zabeti Hooman , Dexter Nick , Lau Ivan , Unruh Leonhardt , Adcock Ben , Chindelevitch Leonid 
Published: June 2021

AbstractGroup testing, the testing paradigm which combines multiple samples within a single test, was introduced in 1943 by Robert Dorfman. Since its original proposal for syphilis screening, group testing has been applied in domains such as fault identification in electrical and computer networks, machine learning, data mining, and cryptography. The SARS-CoV-2 pandemic has led to proposals for using group testing in its original context of identifying infected individuals in a population with few tests. Studies suggest that non-adaptive group testing - in which all the tests are determined in advance - for SARS-CoV-2 could help save 20% to 90% of tests depending on the prevalence. However, no systematic approach for comparing different non-adaptive group testing strategies currently exists.In this paper we develop a software platform for evaluating non-adaptive group testing strategies in both a noiseless setting and in the presence of realistic noise sources, modelled on published experimental observations, which makes them applicable to polymerase chain reaction (PCR) tests, the dominant type of tests for SARS-CoV-2. This modular platform can be used with a variety of group testing designs and decoding algorithms. We use it to evaluate the performance of near-doubly-regular designs and a decoding algorithm based on an integer linear programming formulation, both of which are known to be optimal in some regimes. We find savings between 40% and 91% of tests for prevalences up to 10% when a small error (below 5%) is allowed. We also find that the performance degrades gracefully with noise. We expect our modular, user-friendly, publicly available platform to facilitate empirical research into non-adaptive group testing for SARS-CoV-2.