tbuckley/cabot-search huggingface dataset:
Asymmetric Amyloid Deposition as an Early Sign of Progression in Mild Cognitive Impairment Due to Alzheimer Disease
Authors: Hai-Jeon Yoon, Bom Sahn Kim, Jee Hyang Jeong, Geon Ha Kim, Hee Kyung Park, Min Young Chun
Journal: Clinical Nuclear Medicine (2021)

Purpose In typical Alzheimer disease with dementia (ADD), amyloid pathologies affect both cerebral hemispheres symmetrically. However, the spatial distribution of amyloid-β (Aβ) in the early stage of ADD or over the course of disease has not been investigated. Therefore, we explored asymmetric pattern of Aβ deposition in both hemispheres according to the ADD continuum using 18 F-florbetaben PET. Methods Sixty-eight subjects, including 15 Aβ-negative normal controls, 28 Aβ-positive mild cognitive impairment (Aβ + MCI), and 25 Aβ-positive ADD (Aβ + ADD) subjects, were enrolled. Differences in the asymmetry index and SUV ratio in each of the 6 target regions (4 cortical lobes, cingulate, precuneus) plus composite region between groups were explored. Results The composite and target regional asymmetry indices were significantly different between groups and was highest in Aβ + MCI (composite, occipital, and temporal, P &lt; 0.001; frontal, P = 0.004). The composite and target regional SUV ratios were significantly different according to 3 groups with gradual increase and were highest in Aβ + ADD (composite and all target regions, P &lt; 0.001). Conclusions The asymmetric pattern of amyloid deposition was distinct between Aβ-negative normal controls and Aβ + MCI. This pattern disappeared as the disease progressed. These data indicate that asymmetric amyloid deposition may be an early sign of MCI over the course of ADD.
Update: COVID-19 Pandemic–Associated Changes in Emergency Department Visits — United States, December 2020–January 2021
Authors: Jennifer Adjemian, Kathleen P. Hartnett, Aaron Kite-Powell, Jourdan DeVies, Roseric Azondekon, Lakshmi Radhakrishnan, Katharina L. van Santen, Loren Rodgers
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

During March 29-April 25, 2020, emergency department (ED) visits in the United States declined by 42% after the declaration of a national emergency for COVID-19 on March 13, 2020. Among children aged ≤10 years, ED visits declined by 72% compared with prepandemic levels (1). To assess the continued impact of the COVID-19 pandemic on EDs, CDC examined trends in visits since December 30, 2018, and compared the numbers and types of ED visits by patient demographic and geographic factors during a COVID-19 pandemic period (December 20, 2020-January 16, 2021) with a prepandemic period 1 year earlier (December 15, 2019-January 11, 2020). After an initial decline during March-April 2020 (1), ED visits increased through July 2020, but at levels below those during the previous year, until December 2020-January 2021 when visits again fell to 25% of prepandemic levels. During this time, among patients aged 0-4, 5-11, 12-17, and ≥18 years, ED visits were lower by 66%, 63%, 38%, and 17%, respectively, compared with ED visits for each age group during the same period before the pandemic. Differences were also observed by region and reasons for ED visits during December 2020-January 2021; more visits during this period were for infectious diseases or mental and behavioral health-related concerns and fewer visits were for gastrointestinal and upper-respiratory-related illnesses compared with ED visits during December 2019-January 2020. Although the numbers of ED visits associated with socioeconomic factors and mental or behavioral health conditions are low, the increased visits by both adults and children for these concerns suggest that health care providers should maintain heightened vigilance in screening for factors that might warrant further treatment, guidance, or intervention during the COVID-19 pandemic.
Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccination
Authors: Kate-Lynn Muir, Avyakta Kallam, Scott A Koepsell, Krishna Gundabolu
Journal: New England Journal of Medicine (2021)

Thrombotic Thrombocytopenia after Ad26.COV2.S Vaccine A 48-year-old woman presented with a 3-day history of fatigue and abdominal pain 2 weeks after receiving the Ad26.COV2.S vaccine. She had a low...
ヒト補体副経路媒介疾患の治療における新規C3d標的化C3/C5転換酵素阻害剤,TT30のデザインと開発
Authors: Fridkis-Hareli Masha, Storek Michael, Mazsaroff Istvan, M Risitano Antonio, S Lundberg Ante, J Horvath Christopher, Holers V. Michael
Journal: Blood (2011)
Myanmar coup regime targets striking doctors with bullets, arrests, and erasures
Authors: Owen Dyer
Journal: BMJ (2021)

Myanmar’s doctors, prominent in the civil disobedience movement that sprang up following the military’s 1 February seizure of power, are being hunted with arrest warrants if they express opposition to the coup, and face losing their licences, the regime has said.

Others have been shot or beaten when they treat protesters, with soldiers sometimes lying in wait to fire on those who come to the aid of the wounded. Hundreds of physicians are in hiding.

Each day new names are added to the “charge list against doctors” announced daily by the regime, with more than 160 charged since 13 April under incitement laws, according to Physicians for Human Rights.1 “Attempts to arrest those who have been charged are now under way,” the announcement …
Radiation-induced abscopal reproductive effect is driven by TNF-α/p38 MAPK/Rac1 axis in Sertoli cells
Authors: Songling Hu, Lin Zhu, Yimeng Song, Xinrui Zhao, Qianping Chen, Yan Pan, Jianghong Zhang, Yang Bai, Haowen Zhang, Chunlin Shao
Journal: Theranostics (2021)

Rationale: Radiotherapy has become a mainstay for tumor management, and more than 50% of patients with thoracic tumor need to be treated with radiotherapy. However, the potential adverse effects of thoracic radiotherapy on the reproductive system remain elusive. Methods: Western blot analysis, immunofluorescence assay and transmission electron microscopy (TEM) analysis were performed to investigate the integrity of blood-testis barrier (BTB) in male mice after hypofractionated irradiation (IR) on the right thorax. RNA sequencing, co-immunoprecipitation (IP), Duolink PLA and inhibitor experiments were carried out to demonstrate the molecular mechanisms of the BTB dynamics changes and the subsequent reproductive effect. Results: It was found that the hypofractionated IR on right thorax evoked ultrastructural destruction in distant testes, and thus caused radiation-induced abscopal reproductive effect (RIARE) in male mice. Mechanistically, thoracic IR induced significant nuclear translocation of Rac Family Small GTPase 1 (Rac1) in abscopal Sertoli cells, which closely correlated with the activation of TNF-α/p38 mitogen activated protein kinase (MAPK) pathway. Of note, YWHAZ, a critical polarity protein, was found to be co-localized with Rac1 in Sertoli cells, and this interaction was indispensable for thoracic IR-induced Rac1 nuclear translocation and subsequent degradation of BTB-associated proteins. Conclusions: Our findings imply for the first time that YWHAZ-mediated Rac1 nuclear translocation plays central roles in RIARE, and TNF-α/p38 MAPK/Rac1 axis can be employed as a therapeutic target against RIARE for young male patients receiving hypofractionated radiotherapy.
Peripheral markers of allergen‐specific immune activation predict clinical allergy in eosinophilic esophagitis
Authors: Julianna Dilollo, Eric M. Rodríguez‐López, Leah Wilkey, Elizabeth K. Martin, Jonathan M. Spergel, David A. Hill
Journal: Allergy (2021)

Abstract Background Eosinophilic esophagitis (EoE) is a T‐cell‐mediated disease that is caused by specific foods and results in esophageal dysfunction. Existing allergy testing modalities are not helpful when attempting to identify EoE‐causal foods necessitating empiric food elimination and recurrent endoscopy. The goal of this study was to identify and compare allergen‐specific immune features that can be assayed in a minimally invasive manner to predict clinical food allergy in EoE. Methods We obtained blood samples from control subjects ( n = 17), subjects with clinical EoE milk allergy ( n = 17), and subjects with immunoglobulin E‐mediated milk allergy ( n = 9). We measured total and milk‐specific plasma immunoglobulin G (IgG)4 levels and peripheral memory CD4 + T helper (T H ) cell proliferation and cytokine production after stimulation with endotoxin‐depleted milk proteins. Sensitivity and specificity for predicting clinical EoE milk allergy were calculated and compared between approaches. Results Total and milk‐specific IgG4 levels were not significantly different between control subjects and subjects with clinical EoE milk allergy. Stimulation with milk proteins caused T H lymphocytes from subjects with clinical EoE milk allergy to proliferate more (%P1 of 38.3 ± 4.6 vs. 12.7 ± 2.8, p &lt; 0.0001), and produce more type 2 cytokines (%IL‐4 + of 33.7 ± 2.8 vs. 6.9 ± 1.6, p &lt; 0.0001) than cells from control subjects. Milk‐dependent memory T H ‐cell proliferation (sensitivity and specificity of 88% and 82%, respectively) and interleukin 4 (IL‐4) production (sensitivity and specificity of 100%) most strongly predicted clinical EoE milk allergy. Conclusions Peripheral markers of allergen‐specific immune activation may be useful in identifying EoE‐causal foods. Assaying milk‐dependent IL‐4 production by circulating memory T H lymphocytes most accurately predicts clinical EoE milk allergy.
Urinary peptides in heart failure: a link to molecular pathophysiology
Authors: Tianlin He, Michaela Mischak, Andrew L. Clark, Ross T. Campbell, Christian Delles, Javier Díez, Gerasimos Filippatos, Alexandre Mebazaa, John J.V. McMurray, Arantxa González, Julia Raad, Rafael Stroggilos, Helle S. Bosselmann, Archie Campbell, Shona M. Kerr, Colette E. Jackson, Jane A. Cannon, Morten Schou, Nicolas Girerd, Patrick Rossignol, Alex McConnachie, Kasper Rossing, Joost P. Schanstra, Faiez Zannad, Antonia Vlahou, William Mullen, Vera Jankowski, Harald Mischak, Zhenyu Zhang, Jan A. Staessen, Agnieszka Latosinska
Journal: European Journal of Heart Failure (2021)

Abstract Aims Heart failure (HF) is a major public health concern worldwide. The diversity of HF makes it challenging to decipher the underlying complex pathological processes using single biomarkers. We examined the association between urinary peptides and HF with reduced (HFrEF), mid‐range (HFmrEF) and preserved (HFpEF) ejection fraction, defined based on the European Society of Cardiology guidelines, and the links between these peptide biomarkers and molecular pathophysiology. Methods and results Analysable data from 5608 participants were available in the Human Urinary Proteome database. The urinary peptide profiles from participants diagnosed with HFrEF, HFmrEF, HFpEF and controls matched for sex, age, estimated glomerular filtration rate, systolic and diastolic blood pressure, diabetes and hypertension were compared applying the Mann–Whitney test, followed by correction for multiple testing. Unsupervised learning algorithms were applied to investigate groups of similar urinary profiles. A total of 577 urinary peptides significantly associated with HF were sequenced, 447 of which (77%) were collagen fragments. In silico analysis suggested that urinary biomarker abnormalities in HF principally reflect changes in collagen turnover and immune response, both associated with fibrosis. Unsupervised clustering separated study participants into two clusters, with 83% of non‐HF controls allocated to cluster 1, while 65% of patients with HF were allocated to cluster 2 ( P &lt; 0.0001). No separation based on HF subtype was detectable. Conclusions Heart failure, irrespective of ejection fraction subtype, was associated with differences in abundance of urinary peptides reflecting collagen turnover and inflammation. These peptides should be studied as tools in early detection, prognostication, and prediction of therapeutic response.
EndoSLAM dataset and an unsupervised monocular visual odometry and depth estimation approach for endoscopic videos
Authors: Kutsev Bengisu Ozyoruk, Guliz Irem Gokceler, Taylor L. Bobrow, Gulfize Coskun, Kagan Incetan, Yasin Almalioglu, Faisal Mahmood, Eva Curto, Luis Perdigoto, Marina Oliveira, Hasan Sahin, Helder Araujo, Henrique Alexandrino, Nicholas J. Durr, Hunter B. Gilbert, Mehmet Turan
Journal: Medical Image Analysis (2021)
Abstract PR-008: Identification and characterization of the molecular mechanisms of SCLC chemo-radiation resistance
Authors: Francesca Anna Carrieri, Nick Connis, Eloise Grasset, Eddie Luidy-Imada, Andrew Ewald, Luigi Marchionni, Christine Hann, Phuoc T. Tran
Journal: Clinical Cancer Research (2021)

Abstract Small cell lung cancer (SCLC) is among the most aggressive form of lung malignancies and accounts for 15-20% of all lung cancers. It has the tendency to metastasize early, thus limited-stage SCLC patients still receive systemic treatment with chemo-radiotherapy (chemoXRT) for their localized disease. SCLC is exceptionally sensitive to chemoXRT and exhibits high response rates; however, the recurrence rate is almost 100% and patients relapse with tumors that resist further treatments. Elucidating mechanisms of chemoXRT resistance in SCLC is needed to develop improved therapies and positively impact patient outcomes. To better interrogate mechanisms of chemoXRT resistance, we developed a SCLC patient-derived xenograft (PDX) in vivo system for the major molecular subtypes of SCLC (classic and variant). Briefly, PDX tumor bearing mice were treated with: 1) vehicle control; 2) cisplatin plus etoposide (EP); 3) radiotherapy (XRT); and 4) both EP/XRT. A major response was observed within the EP/XRT arm compared to vehicle or single therapy arms. Whole transcriptome profiling among all treatment arms revealed molecular pathways and biological processes associated with chemoXRT resistance. Also, by comparing our data with two previous SCLC patient cohort studies, we identified gene candidates for functional validation of chemoXRT resistance (i.e. ST6GAL1, TNIK and SOHLH2). To enable real-time cellular and molecular analysis of PDX behavior ex vivo and to validate SCLC chemoXRT resistance candidate genes, we established a novel PDX organoid (PDO) model to study the molecular underpinnings of XRT resistance in SCLC. Classic and variant SCLC PDOs still retained the cellular, DNA and RNA markers consistent with their parental PDX molecular subtype classification using array comparative genomic hybridization and RNA-sequencing. We aim to utilize our novel SCLC PDX/PDO models as a tool to identify and validate candidates for chemoXRT resistance to be used as biomarkers and targets to combat chemoXRT resistance in SCLC. Citation Format: Francesca Anna Carrieri, Nick Connis, Eloise Grasset, Eddie Luidy-Imada, Andrew Ewald, Luigi Marchionni, Christine Hann, Phuoc T. Tran. Identification and characterization of the molecular mechanisms of SCLC chemo-radiation resistance [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr PR-008.
Towards the elimination of Plasmodium vivax malaria: Implementing the radical cure
Authors: Kamala Thriemer, Benedikt Ley, Lorenz von Seidlein
Journal: PLoS Medicine (2021)

Efforts to control Plasmodium vivax malaria have been less successful than for Plas-modiumAU : PerCSE; iftwodifferentspeciessharethesamegenus; thegenusofthesecondspeciesshoulds falciparum, resulting in higher prevalence of P. vivax malaria in most coendemic regions.One of the key differences between the 2 species is the ability of P. vivax to form hypnozoites causing relapses which facilitate transmission.Preventing P. vivax relapses is key for the elimination of P. vivax malaria.• The widescale use of the radical cure to clear hypnozoites has been underutilized in most endemic countries.Two breakthroughs have increased the likelihood that the radical cure will be rolled out in P. vivax endemic regions: To clear hypnozoites, primaquine can be administered in short, high-dose regimens or a single dose of the recently licensed tafenoquine is administered.Novel technologies allow measurement of glucose-6-phosphate dehydrogenase (G6PD) activity at the point of care.Identifying patients with low G6PD activity, not eligible for these novel regimens, is a precondition for their safe administration.• Novel approaches to P. vivax elimination such as mass drug administrations of antimalarial drugs including 8-aminoquinolines require considerable resources and carry safety risks.• A safe and protective P. vivax vaccine would be an asset in the elimination of P. vivax malaria but is unlikely to be available in the near future.• Case management that includes a radical cure is currently the most promising approach to P. vivax elimination.New regimens for radical cure and the possibility to minimise the risk of haemolysis through novel G6PD tests bring up operational challenges, but if deployed wisely could have sufficient impact to eliminate if not eradicate P. vivax malaria.
Microtissue Geometry and Cell‐Generated Forces Drive Patterning of Liver Progenitor Cell Differentiation in 3D
Authors: Ian C. Berg, Erfan Mohagheghian, Krista Habing, Ning Wang, Gregory H. Underhill
Journal: Advanced Healthcare Materials (2021)

3D microenvironments provide a unique opportunity to investigate the impact of intrinsic mechanical signaling on progenitor cell differentiation. Using a hydrogel-based microwell platform, arrays of 3D, multicellular microtissues in constrained geometries, including toroids and cylinders are produced. These generated distinct mechanical profiles to investigate the impact of geometry and stress on early liver progenitor cell fate using a model liver development system. Image segmentation allows the tracking of individual cell fate and the characterization of distinct patterning of hepatocytic makers to the outer shell of the microtissues, and the exclusion from the inner diameter surface of the toroids. Biliary markers are distributed throughout the interior regions of micropatterned tissues and are increased in toroidal tissues when compared with those in cylindrical tissues. Finite element models of predicted stress distributions, combined with mechanical measurements, demonstrates that intercellular tension correlates with increased hepatocytic fate, while compression correlates with decreased hepatocytic and increased biliary fate. This system, which integrates microfabrication, imaging, mechanical modeling, and quantitative analysis, demonstrates how microtissue geometry can drive patterning of mechanical stresses that regulate cell differentiation trajectories. This approach may serve as a platform for further investigation of signaling mechanisms in the liver and other developmental systems.
Mesenchymal stromal cell therapy for pancreatitis: Progress and challenges
Authors: Zhilong Ma, Jia Zhou, Tingsong Yang, Wangcheng Xie, Guodong Song, Zhenshun Song, Ji Chen
Journal: Medicinal Research Reviews (2021)

Abstract Pancreatitis is a common gastrointestinal disease with no effective therapeutic options, particularly for cases of severe acute and chronic pancreatitis (CP). Mesenchymal stromal cells (MSCs) are multipotent cells with diverse biological properties, including directional migration, paracrine, immunosuppressive, and antiinflammatory effects, which are considered an ideal candidate cell type for repairing tissue damage caused by various pathogenies. Several researchers have reported significant therapeutic efficacy of MSCs in animal models of acute and CP. However, the specific underlying mechanisms are yet to be clarified and clinical application of MSCs as pancreatitis therapy has rarely been reported. This review mainly focuses on the potential and challenges in clinical application of MSCs for treatment of acute and CP, along with discussion of the underlying molecular mechanisms.
Abstract 10876: Nosocomial Infections Are Associated With Increased Hospital Readmissions, Mortality, and Cost in Patients Hospitalized With Heart Failure
Authors: Esther E Oh, Yuna H Bae-Shaaw, Geoffrey Joyce, Emi Minejima, Tien M Ng
Journal: Circulation (2018)

Introduction: Non-cardiac comorbidities are increasingly recognized as potential therapeutic targets in heart failure (HF). Nosocomial infections represent a common modifiable occurrence in patient...
Bimekizumab versus Adalimumab in Plaque Psoriasis
Authors: Richard B. Warren, Andrew Blauvelt, Jerry Bagel, Kim A. Papp, Paul Yamauchi, April Armstrong, Richard G. Langley, Veerle Vanvoorden, Dirk De Cuyper, Christopher Cioffi, Luke Peterson, Nancy Cross, Kristian Reich
Journal: New England Journal of Medicine (2021)

Bimekizumab is a monoclonal IgG1 antibody that selectively inhibits interleukin-17A and interleukin-17F. The efficacy and safety of bimekizumab as compared with the tumor necrosis factor inhibitor adalimumab in patients with moderate-to-severe plaque psoriasis have not been extensively examined.We randomly assigned patients with moderate-to-severe plaque psoriasis in a 1:1:1 ratio to receive subcutaneous bimekizumab at a dose of 320 mg every 4 weeks for 56 weeks; bimekizumab at a dose of 320 mg every 4 weeks for 16 weeks, then every 8 weeks for weeks 16 to 56; or subcutaneous adalimumab at a dose of 40 mg every 2 weeks for 24 weeks, followed by bimekizumab at a dose of 320 mg every 4 weeks to week 56. The primary end points were a 90% or greater reduction from baseline in the Psoriasis Area and Severity Index (PASI) score (PASI 90 response; PASI scores range from 0 to 72, with higher scores indicating worse disease) and an Investigator's Global Assessment (IGA) score of 0 or 1, signifying clear or almost clear skin (scores range from 0 [clear skin] to 4 [severe disease]), at week 16. The analysis of the primary end points tested noninferiority at a margin of -10 percentage points and then tested for superiority.A total of 614 patients were screened, and 478 were enrolled; 158 patients were assigned to receive bimekizumab every 4 weeks, 161 to receive bimekizumab every 4 weeks and then every 8 weeks, and 159 to receive adalimumab. The mean age of the patients was 44.9 years; the mean PASI score at baseline was 19.8. At week 16, a total of 275 of 319 patients (86.2%) who received bimekizumab (both dose groups combined) and 75 of 159 (47.2%) who received adalimumab had a PASI 90 response (adjusted risk difference, 39.3 percentage points; 95% confidence interval [CI], 30.9 to 47.7; P<0.001 for noninferiority and superiority). A total of 272 of 319 patients (85.3%) who received bimekizumab and 91 of 159 (57.2%) who received adalimumab had an IGA score of 0 or 1 (adjusted risk difference, 28.2 percentage points; 95% CI, 19.7 to 36.7; P<0.001 for noninferiority and superiority). The most common adverse events with bimekizumab were upper respiratory tract infections, oral candidiasis (predominantly mild or moderate as recorded by the investigator), hypertension, and diarrhea.In this 56-week trial, bimekizumab was noninferior and superior to adalimumab through 16 weeks in reducing symptoms and signs of plaque psoriasis but was associated with a higher frequency of oral candidiasis and diarrhea. Longer and larger trials are required to determine the efficacy and safety of bimekizumab as compared with other agents in the treatment of plaque psoriasis. (Funded by UCB Pharma; BE SURE ClinicalTrials.gov number, NCT03412747.).
Lumpers and splitters: Birth of Th17 cells
Authors: Brigitta Stockinger
Journal: The Journal of Experimental Medicine (2021)

Th17 cells were born as a new subset of CD4 T cells to complement Th1, Th2, and T reg cells. From their identification as a distinct subset, they quickly became the paradigm for the astonishing plasticity that CD4 T cells can exhibit depending on tissue environment and circumstances.