tbuckley/cabot-search huggingface dataset:
The subcortical belly of sleep: New possibilities in neuromodulation of basal ganglia?
Authors: Harutomo Hasegawa, Richard Selway, Valentina Gnoni, Sandor Beniczky, Steve C.R. Williams, Meir Kryger, Luigi Ferini-Strambi, Peter Goadsby, Guy D. Leschziner, Keyoumars Ashkan, Ivana Rosenzweig
Journal: Sleep Medicine Reviews (2020)

Early studies posited a relationship between sleep and the basal ganglia, but this relationship has received little attention recently. It is timely to revisit this relationship, given new insights into the functional anatomy of the basal ganglia and the physiology of sleep, which has been made possible by modern techniques such as chemogenetic and optogenetic mapping of neural circuits in rodents and intracranial recording, functional imaging, and a better understanding of human sleep disorders. We discuss the functional anatomy of the basal ganglia, and review evidence implicating their role in sleep. Whilst these studies are in their infancy, we suggest that the basal ganglia may play an integral role in the sleep-wake cycle, specifically by contributing to a thalamo-cortical-basal ganglia oscillatory network in slow-wave sleep which facilitates neural plasticity, and an active state during REM sleep which enables the enactment of cognitive and emotional networks. A better understanding of sleep mechanisms may pave the way for more effective neuromodulation strategies for sleep and basal ganglia disorders.
Risk-benefit analysis of tuberculosis infection testing for household contact management in high-burden countries: a mathematical modelling study
Authors: Courtney M Yuen, James A Seddon, Salmaan Keshavjee, Peter J Dodd
Journal: The Lancet Global Health (2020)

Preventive therapy for tuberculosis reduces the risk of disease in people who have been infected but who are not sick. Countries with a high burden of tuberculosis that are expanding preventive therapy use must decide how tuberculosis infection testing should be used for risk stratification among household contacts of patients with tuberculosis.
Atrophic and hypertrophic skin photoaging and melanocortin-1 receptor (MC1R): the missing link
Authors: Stefania Guida, Silvana Ciardo, Barbara De Pace, Nathalie De Carvalho, Francesca Farnetani, Claudia Pezzini, Johanna Chester, Kaleci Shaniko, Michele Manganelli, Gabriella Guida, Giovanni Pellacani
Journal: Journal of the American Academy of Dermatology (2020)
Correction to: Effectiveness and safety of opicapone in Parkinson’s disease patients with motor fluctuations: the OPTIPARK open-label study
Authors: Heinz Reichmann, Andrew Lees, José-Francisco Rocha, Diogo Magalhães, Patrício Soares-da-Silva
Journal: Translational Neurodegeneration (2020)

An amendment to this paper has been published and can be accessed via the original article.
Prevalence of Barrett’s esophagus in obese patients undergoing pre-bariatric surgery evaluation: a systematic review and meta-analysis
Authors: Bashar Qumseya, Sherif Gendy, Alexander Wallace, Dennis Yang, Davis Estores, Alexander Ayzengart, Peter V. Draganov
Journal: Endoscopy (2020)

Abstract Introduction Obesity is a known risk factor for gastroesophageal reflux disease (GERD), Barrett’s esophagus (BE), and esophageal adenocarcinoma (EAC). Obese patients routinely undergo preoperative esophagogastroduodenoscopy (EGD) before bariatric procedures. We aimed to assess the prevalence of BE in this patient population. Methods We conducted a comprehensive literature search ending in March 2019. Search results were imported into covidence.org and screened by two independent reviewers. Heterogeneity was assessed using I 2 and Q statistics and publication bias using funnel plots and the Orwin fail-safe test. Random-effects modeling was used in all analyses. Results Of 4087 citations, 77 were reviewed in full text and 29 were included in the final analysis based on our predetermined inclusion/exclusion criteria. A total of 13 434 patients underwent pre-bariatric surgery EGD. The pooled prevalence of BE using random-effects modeling was 0.9 % (95 % confidence interval [CI] 0.7 % – 1.3 %); P &lt; 0.001; I 2 = 58 %, Q = 67). In meta-regression analyses, controlling for sex and GERD, we found a positive association between mean body mass index (BMI) and the prevalence of BE (β = 0.15 [95 %CI 0.02 – 0.28]; P = 0.03). A linear relationship between the prevalence of BE and the prevalence of GERD was also noted (β = 3.9 [95 %CI 0.4 – 7.5]; P = 0.03). Conclusions Obesity has been postulated as a major risk factor for BE, yet we found that the prevalence of BE in morbidly obese patients undergoing preoperative EGD was very low. Therefore, obesity alone may not be a major risk factor for BE.
Premature Menopause and Risk for Cardiovascular Disease—Reply
Authors: Michael C. Honigberg, Pradeep Natarajan
Journal: JAMA (2020)

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Ancient Genomes Reveal the Evolutionary History and Origin of Cashmere-Producing Goats in China
Authors: Yudong Cai, Weiwei Fu, Dawei Cai, Rasmus Heller, Zhuqing Zheng, Jia Wen, Hui Li, Xiaolong Wang, Akil Alshawi, Zhouyong Sun, Siqi Zhu, Juan Wang, Miaomiao Yang, Songmei Hu, Yan Li, Zhirui Yang, Mian Gong, Yunan Hou, Tianming Lan, Kui Wu, Yulin Chen, Yu Jiang, Xihong Wang
Journal: Molecular Biology and Evolution (2020)

Goats are one of the most widespread farmed animals across the world; however, their migration route to East Asia and local evolutionary history remain poorly understood. Here, we sequenced 27 ancient Chinese goat genomes dating from the Late Neolithic period to the Iron Age. We found close genetic affinities between ancient and modern Chinese goats, demonstrating their genetic continuity. We found that Chinese goats originated from the eastern regions around the Fertile Crescent, and we estimated that the ancestors of Chinese goats diverged from this population in the Chalcolithic period. Modern Chinese goats were divided into a northern and a southern group, coinciding with the most prominent climatic division in China, and two genes related to hair follicle development, FGF5 and EDA2R, were highly divergent between these populations. We identified a likely causal de novo deletion near FGF5 in northern Chinese goats that increased to high frequency over time, whereas EDA2R harbored standing variation dating to the Neolithic. Our findings add to our understanding of the genetic composition and local evolutionary process of Chinese goats.
Measurement properties of the Rajka–Langeland severity score in children and adults with atopic dermatitis*
Authors: J.I. Silverberg, D. Lei, M. Yousaf, S.R. Janmohamed, P.P. Vakharia, R. Chopra, R. Chavda, S. Gabriel, K.R. Patel, V. Singam, R. Kantor, Derek Y. Hsu
Journal: British Journal of Dermatology (2020)

Multiple atopic dermatitis (AD) severity scales exist, with no gold standard for use in clinical practice.To determine the measurement properties of the Rajka-Langeland score and compare it with other clinician-reported outcomes in adults and children with AD.We performed a prospective dermatology practice-based study using questionnaires and evaluation by a dermatologist (n = 427).Rajka-Langeland had good concurrent validity with the Eczema Area and Severity Index (Spearman rho = 0·63), SCORing AD (SCORAD) (rho = 0·61), objective-SCORAD (rho = 0·52) and body surface area (rho = 0·51); good convergent validity with the numeric rating scale average-itch (rho = 0·60) and worst-itch (rho = 0·59), Patient-Oriented Eczema Measure (rho = 0·57), Dermatology Life Quality Index (rho = 0·53), Patient-Reported Outcomes Measurement Information System Itch Questionnaire (rho = 0·35-0·55) in adults and/or children; fair discriminant validity for patient- and physician-reported global AD severity; good responsiveness to change of severity of AD and itch; good reliability; internal consistency; with no floor or ceiling effects. Interpretability bands (3, clear/almost clear; 4-5, mild; 6-7, moderate; 8-9, severe) and minimal clinically important difference (1 point) were established.The Rajka-Langeland score showed good construct validity, reliability, internal consistency and responsiveness in adults and children with AD.
Covid-19: Leading statistician slams UK’s reporting of swab tests as “travesty of science”
Authors: Jacqui Wise
Journal: BMJ (2020)

A leading statistician has criticised the UK government’s daily reporting of covid-19 swab test results, saying that no inference can be drawn reliably and that the failure to report by sample date could lead to serious misrepresentation of the pattern of the epidemic.

“The UK’s data collection and reporting of swab testing is a travesty of statistical science, as you can draw no inferences whatsoever about the evolution of the epidemic,” said Sheila Bird, former programme leader at the MRC Biostatistics Unit, Cambridge Institute of Public Health. “Politicians only seem to be interested in the number of tests performed rather than what is actually happening in the epidemic,” she told The BMJ .

The Department of Health and Social Care publishes the number of patients who have been tested for coronavirus and the number of positive tests. These are broken down into categories …
Treg activation and their role in different subtypes of chronic rhinosinusitis
Authors: Caroline Mann, Irene Schmidtmann, Tobias Bopp, Juergen Brieger, Kai Fruth
Journal: Allergy (2020)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Intraosseous Medullary Fat Necrosis on 99mTc-MDP Bone Scan of Patient With Acute Pancreatitis
Authors: Avinash Tupalli, Meivel Angamuthu, Arun Prashanth, Roma Singh, Rakesh Kumar
Journal: Clinical Nuclear Medicine (2020)

Abstract Pancreatic disease can be associated with polyarthritis and panniculitis in a small number of patients, and this triad constitutes PPP syndrome. Early diagnosis is critical as it has high morbidity and mortality. Panniculitis can occur in fat present anywhere in the body. Involvement of fat in bone marrow is relatively uncommon, and radiologic imaging shows osteolytic lesions involving long bones. Here we present a case of acute pancreatitis, referred to our department for evaluation of severe joint pain and multiple bone pain. 99m Tc-MDP scan with SPECT/CT has been done, which showed medullary expansion with heterogenous tracer uptake, that is, moth-eaten appearance.
Effect of raxibacumab on immunogenicity of Anthrax Vaccine Adsorbed: a phase 4, open-label, parallel-group, randomised non-inferiority study
Authors: Nancy Skoura, Jie Wang-Jairaj, Oscar Della Pasqua, Vijayalakshmi Chandrasekaran, Julia Billiard, Anne Yeakey, William Smith, Helen Steel, Lionel K Tan
Journal: The Lancet Infectious Diseases (2020)
Characteristics of novel Ti–10Mo-xCu alloy by powder metallurgy for potential biomedical implant applications
Authors: Wei Xu, Chenjin Hou, Yuxuan Mao, Lei Yang, Maryam Tamaddon, Jianliang Zhang, Xuanhui Qu, Chaozong Liu, Bo Su, Xin Lu
Journal: Bioactive Materials (2020)

When biomaterials are implanted in the human body, the surfaces of the implants become favorable sites for microbial adhesion and biofilm formation, causing peri-implant infection which frequently results in the failure of prosthetics and revision surgery. Ti-Mo alloy is one of the commonly used implant materials for load-bearing bone replacement, and the prevention of infection of Ti-Mo implants is therefore crucial. In this study, bacterial inhibitory copper (Cu) was added to Ti-Mo matrix to develop a novel Ti-Mo-Cu alloy with bacterial inhibitory property. The effects of Cu content on microstructure, tensile properties, cytocompatibility, and bacterial inhibitory ability of Ti-Mo-Cu alloy were systematically investigated. Results revealed that Ti-10Mo-1Cu alloy consisted of α and β phases, while there were a few Ti2Cu intermetallic compounds existed for Ti-10Mo-3Cu and Ti-10Mo-5Cu alloys, in addition to α and β phases. The tensile strength of Ti-10Mo-xCu alloy increased with Cu content while elongation decreased. Ti-10Mo-3Cu alloy exhibited an optimal tensile strength of 1098.1 MPa and elongation of 5.2%. Cytocompatibility study indicated that none of the Ti-10Mo-xCu alloys had a negative effect on MC3T3-E1 cell proliferation. Bacterial inhibitory rates against S. aureus and E. coli increased with the increase in Cu content of Ti-10Mo-xCu alloy, within the ranges of 20-60% and 15-50%, respectively. Taken together, this study suggests that Ti-10Mo-3Cu alloy with high strength, acceptable elongation, excellent cytocompatibility, and the bacterial inhibitory property is a promising candidate for biomedical implant applications.
Extensive Ethnolinguistic Diversity in Vietnam Reflects Multiple Sources of Genetic Diversity
Authors: Dang Liu, Nguyen Thuy Duong, Nguyen Dang Ton, Nguyen Van Phong, Brigitte Pakendorf, Nong Van Hai, Mark Stoneking
Journal: Molecular Biology and Evolution (2020)

Vietnam features extensive ethnolinguistic diversity and occupies a key position in Mainland Southeast Asia. Yet, the genetic diversity of Vietnam remains relatively unexplored, especially with genome-wide data, because previous studies have focused mainly on the majority Kinh group. Here, we analyze newly generated genome-wide single-nucleotide polymorphism data for the Kinh and 21 additional ethnic groups in Vietnam, encompassing all five major language families in Mainland Southeast Asia. In addition to analyzing the allele and haplotype sharing within the Vietnamese groups, we incorporate published data from both nearby modern populations and ancient samples for comparison. In contrast to previous studies that suggested a largely indigenous origin for Vietnamese genetic diversity, we find that Vietnamese ethnolinguistic groups harbor multiple sources of genetic diversity that likely reflect different sources for the ancestry associated with each language family. However, linguistic diversity does not completely match genetic diversity: There have been extensive interactions between the Hmong-Mien and Tai-Kadai groups; different Austro-Asiatic groups show different affinities with other ethnolinguistic groups; and we identified a likely case of cultural diffusion in which some Austro-Asiatic groups shifted to Austronesian languages during the past 2,500 years. Overall, our results highlight the importance of genome-wide data from dense sampling of ethnolinguistic groups in providing new insights into the genetic diversity and history of an ethnolinguistically diverse region, such as Vietnam.
Two multi-fragment recombination events resulted in the β-lactam-resistant serotype 11A-ST6521 related to Spain9V-ST156 pneumococcal clone spreading in south-western Europe, 2008 to 2016
Authors: Aida González-Díaz, Miguel P Machado, Jordi Càmara, José Yuste, Emmanuelle Varon, Miriam Domenech, María Del Grosso, José María Marimón, Emilia Cercenado, Nieves Larrosa, María Dolores Quesada, Dionisia Fontanals, Assiya El-Mniai, Meritxell Cubero, João A Carriço, Sara Martí, Mario Ramirez, Carmen Ardanuy
Journal: Eurosurveillance (2020)

Background The successful pneumococcal clone Spain 9V -ST156 (PMEN3) is usually associated with vaccine serotypes 9V and 14. Aim Our objective was to analyse the increase of a serotype 11A variant of PMEN3 as cause of invasive pneumococcal disease (IPD) in Spain and its spread in south-western Europe. Methods We conducted a prospective multicentre study of adult IPD in Spain (2008–16). Furthermore, a subset of 61 penicillin-resistant serotype 11A isolates from France, Italy, Portugal and Spain were subjected to whole genome sequencing (WGS) and compared with 238 genomes from the European Nucleotide Archive (ENA). Results Although the incidence of serotype 11A in IPD was stable, a clonal shift was detected from CC62 (penicillin-susceptible) to CC156 (penicillin-resistant). By WGS, three major 11A-CC156 lineages were identified, linked to ST156 (n = 5 isolates; France, Italy and Portugal), ST166 (n = 4 isolates; France and Portugal) and ST838/6521 (n = 52 isolates; France, Portugal and Spain). Acquisition of the 11A capsule allowed to escape vaccine effect. AP200 (11A-ST62) was the donor for ST156 and ST838/6521 but not for ST166. In-depth analysis of ST838/6521 lineage showed two multi-fragment recombination events including four and seven fragments from an 11A-ST62 and an NT-ST344 representative, respectively. Conclusion The increase in penicillin-resistant serotype 11A IPD in Spain was linked to the spread of a vaccine escape PMEN3 recombinant clone. Several recombination events were observed in PMEN3 acquiring an 11A capsule. The most successful 11A-PMEN3 lineage spreading in south-western Europe appeared after two multi-fragment recombination events with representatives of two major pneumococcal clones (11A-ST62 and NT-ST344).
Online management of rheumatoid arthritis during COVID-19 pandemic
Authors: Yang Zhang, Jian Wang, Liang Zhao, Jun Xiao, Zhanjun Shi
Journal: Annals of the Rheumatic Diseases (2020)

We have read with great interest the recent article from Figueroa-Parra et al 1 entitled ‘Are my patients with rheumatic diseases at higher risk of COVID-19?’ We agree that patients with rheumatic diseases are at higher risk of communicable diseases such as COVID-19, and protective measures are required.

Patients with rheumatic diseases need frequent doctor appointments to get tailored and individualised therapies.2 However, during the COVID-19 pandemic, most outpatient services were cancelled to avoid cross-infection. Besides, visiting hospitals puts these patients at higher risk of being infected, in consideration of their advanced age and comorbidities. …
Identification of a Small-Molecule Inhibitor That Disrupts the SIX1/EYA2 Complex, EMT, and Metastasis
Authors: Hengbo Zhou, Melanie A. Blevins, Jessica Y. Hsu, Deguang Kong, Matthew D. Galbraith, Andrew Goodspeed, Rachel Culp-Hill, Michael U.J. Oliphant, Dominique Ramirez, Lingdi Zhang, Jennyvette Trinidad-Pineiro, Lesley Mathews Griner, Rebecca King, Elena Barnaeva, Xin Hu, Noel T. Southall, Marc Ferrer, Daniel L. Gustafson, Daniel P. Regan, Angelo D'Alessandro, James C. Costello, Samarjit Patnaik, Juan Marugan, Rui Zhao, Heide L. Ford
Journal: Cancer Research (2020)

Abstract Metastasis is the major cause of mortality for patients with cancer, and dysregulation of developmental signaling pathways can significantly contribute to the metastatic process. The Sine oculis homeobox homolog 1 (SIX1)/eyes absent (EYA) transcriptional complex plays a critical role in the development of multiple organs and is typically downregulated after development is complete. In breast cancer, aberrant expression of SIX1 has been demonstrated to stimulate metastasis through activation of TGFβ signaling and subsequent induction of epithelial–mesenchymal transition (EMT). In addition, SIX1 can induce metastasis via non-cell autonomous means, including activation of GLI-signaling in neighboring tumor cells and activation of VEGFC–induced lymphangiogenesis. Thus, targeting SIX1 would be expected to inhibit metastasis while conferring limited side effects. However, transcription factors are notoriously difficult to target, and thus novel approaches to inhibit their action must be taken. Here we identified a novel small molecule compound, NCGC00378430 (abbreviated as 8430), that reduces the SIX1/EYA2 interaction. 8430 partially reversed transcriptional and metabolic profiles mediated by SIX1 overexpression and reversed SIX1-induced TGFβ signaling and EMT. 8430 was well tolerated when delivered to mice and significantly suppressed breast cancer–associated metastasis in vivo without significantly altering primary tumor growth. Thus, we have demonstrated for the first time that pharmacologic inhibition of the SIX1/EYA2 complex and associated phenotypes is sufficient to suppress breast cancer metastasis. Significance: These findings identify and characterize a novel inhibitor of the SIX1/EYA2 complex that reverses EMT phenotypes suppressing breast cancer metastasis.
Abstract AP13: GENOME-SCALE CRISPR KNOCKOUT SCREEN IDENTIFIES TIGAR AS A MODIFIER OF PARP INHIBITOR SENSITIVITY
Authors: Pingping Fang, Kay Minn, Jeremy Chien
Journal: Clinical Cancer Research (2019)

Abstract A key challenge is to understand the mechanisms that contribute to “BRCAness” and hence sensitivity to poly (ADP-ribose) polymerase (PARP) inhibitors. Using the sensitivity to PARP inhibitor olaparib as a surrogate for “BRCAness”, we performed a CRISPR/Cas9-based genome-scale loss-of-function screen and identified TIGAR as a modifier of olaparib response. TIGAR knockdown increases the level of intracellular reactive oxygen species, induces more DNA damage after olaparib treatment, and causes “BRCAness” by downregulating BRCA1 and genes in the Fanconi anemia pathway. Further, TIGAR knockdown induces senescence, reduces spheroid tumor cell growth, and enhances the cytotoxic effect of olaparib. Finally, TIGAR is amplified in ovarian cancer and a higher expression of TIGAR is associated with poor overall survival in high-grade serous ovarian cancer. Our study shows that TIGAR knockdown causes extensive transcriptional reprogramming and enhances sensitivity to PARP inhibitor, demonstrating that TIGAR is a relevant therapeutic target for treating ovarian cancer. Citation Format: Pingping Fang, Kay Minn, Jeremy Chien. GENOME-SCALE CRISPR KNOCKOUT SCREEN IDENTIFIES TIGAR AS A MODIFIER OF PARP INHIBITOR SENSITIVITY [abstract]. In: Proceedings of the 12th Biennial Ovarian Cancer Research Symposium; Sep 13-15, 2018; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2019;25(22 Suppl):Abstract nr AP13.