tbuckley/cabot-search huggingface dataset:
Onset, duration and unresolved symptoms, including smell and taste changes, in mild COVID-19 infection: a cohort study in Israeli patients
Authors: Hadar Klein, Kim Asseo, Noam Karni, Yuval Benjamini, Ran Nir-Paz, Mordechai Muszkat, Sarah Israel, Masha Y. Niv
Journal: Clinical Microbiology and Infection (2021)

ObjectivesTo characterize longitudinal symptoms of mild coronavirus disease 2019 (COVID-19) patients for a period of 6 months, to potentially aid in disease management.MethodsPhone interviews were conducted with 103 patients with mild COVID-19 in Israel over a 6-month period (April 2020 to October 2020). Patients were recruited via social media and word to mouth and were interviewed up to 4 times, depending on reports of their unresolved symptoms. Inclusion criteria required participants to be residents of Israel aged 18 years or older, with positive COVID-19 real-time PCR results and nonsevere symptoms. The onset, duration, severity and resolution of symptoms were analysed.ResultsA total of 44% (45/103), 41% (42/103), 39% (40/103) and 38% (39/103) of patients experienced headache, fever, muscle ache and dry cough as the first symptom respectively. Smell and taste changes were experienced at 3.9 ± 5.4 and 4.6 ± 5.7 days (mean ± standard deviation (SD)) after disease onset respectively. Among prevalent symptoms, fever had the shortest duration (5.8 ± 8.6 days), and taste and smell changes were the longest-lasting symptoms (17.2 ± 17.6 and 18.9 ± 19.7 days; durations censored at 60 days). Longer recovery of the sense of smell correlated with the extent of smell change. At the 6-month follow-up, 46% (47/103) of the patients had at least one unresolved symptom, most commonly fatigue (22%, 23/103), smell and taste changes (15%, 15/103 and 8%, 8/103 respectively) and breathing difficulties (8%, 8/103).ConclusionsLong-lasting effects of mild COVID-19 manifested in almost half of the participants reporting at least one unresolved symptom after 6 months.
A multicenter blinded preclinical randomized controlled trial on Jak1/2 inhibition in MRL/MpJ-Fas mice with proliferative lupus nephritis predicts low effect size
Authors: Yutian Lei, Bettina Sehnert, Reinhard E. Voll, Conxita Jacobs-Cachá, Maria Jose Soler, Maria D. Sanchez-Niño, Alberto Ortiz, Roman D. Bülow, Peter Boor, Hans-Joachim Anders
Journal: Kidney International (2021)
Serum milk fat globule-EGF factor 8 protein as a potential biomarker for metabolic syndrome
Authors: Han Ah Lee, Jihwan Lim, Hyung Joon Joo, Young-Sun Lee, Young Kul Jung, Ji Hoon Kim, Hyunggin An, Hyung Joon Yim, Yoon Tae Jeen, Jong Eun Yeon, Do-Sun Lim, Kwan Soo Byun, Yeon Seok Seo
Journal: Clinical and Molecular Hepatology (2021)

Background/Aims: Useful biomarkers for metabolic syndrome have been insufficient. We investigated the performance of serum milk fat globule-EGF factor-8 (MFG-E8), the key mediator of inflammatory pathway, in diagnosis of metabolic syndrome.Methods: Subjects aged between 30 and 64 years were prospectively enrolled in the Seoul Metabolic Syndrome cohort. Serum MFG-E8 levels were measured at baseline.Results: A total of 556 subjects were included, comprising 279 women (50.2%) and 277 men (49.8%). Metabolic syndrome was diagnosed in 236 subjects (42.4%), and the mean MFG-E8 level of subjects with metabolic syndrome was significantly higher than that of subjects without metabolic syndrome (P&lt;0.001). MFG-E8 level was significantly correlated with all metabolic syndrome components and pulse wave velocity (all P&lt;0.05). Subjects were categorized into two groups according to the best MFG-E8 cut-off value as follows: group 1, MFG-E8 level &lt;4,745.1 pg/mL (n=401, 72.1%); and group 2, MFG-E8 level ≥4,745.1 (n=155, 27.9%). At baseline, metabolic syndrome in group 2 was significantly more prevalent than in group 1 (63.9% vs. 34.2%, P&lt;0.001). During median follow-up of 17 months, metabolic syndrome developed in 122 (38.1%) subjects among 320 subjects without it at baseline. The incidence of metabolic syndrome in group 2 was significantly higher than that in group 1 (55.4% vs. 34.5%, P=0.003). On multivariate analysis, MFG-E8 level ≥4,745.1 pg/mL was an independent predictor for diagnosis and development of metabolic syndrome after adjusting other factors (all P&lt;0.05).Conclusions: Serum MFG-E8 level is a potent biomarker for the screening and prediction of metabolic syndrome.
Long-term maturation of human cortical organoids matches key early postnatal transitions
Authors: Aaron Gordon, Se-Jin Yoon, Stephen S. Tran, Christopher D. Makinson, Jin Young Park, Jimena Andersen, Alfredo M. Valencia, Steve Horvath, Xinshu Xiao, John R. Huguenard, Sergiu P. Pașca, Daniel H. Geschwind
Journal: Nature Neuroscience (2021)
Recurrent COVID-19 including evidence of reinfection and enhanced severity in thirty Brazilian healthcare workers
Authors: Letícia Adrielle dos Santos, Pedro Germano de Góis Filho, Ana Maria Fantini Silva, João Victor Gomes Santos, Douglas Siqueira Santos, Marília Marques Aquino, Rafaela Mota de Jesus, Maria Luiza Dória Almeida, João Santana da Silva, Daniel M. Altmann, Rosemary J. Boyton, Cliomar Alves dos Santos, Camilla Natália Oliveira Santos, Juliana Cardoso Alves, Ianaline Lima Santos, Lucas Sousa Magalhães, Emilia M.M.A. Belitardo, Danilo J.P.G. Rocha, João P.P. Almeida, Luis G.C. Pacheco, Eric R.G.R. Aguiar, Gubio Soares Campos, Silvia Inês Sardi, Rejane Hughes Carvalho, Amélia Ribeiro de Jesus, Karla Freire Rezende, Roque Pacheco de Almeida
Journal: Journal of Infection (2021)

There is growing concern about individuals reported to suffer repeat COVID-19 disease episodes, these in a small number of cases characterised as de novo infections with distinct sequences, indicative of insufficient protective immunity even in the short term.
Chronic rhinosinusitis with nasal polyps is associated with impaired TMEM16A-mediated epithelial chloride secretion
Authors: Johanna J. Salomon, Tobias Albrecht, Simon Y. Graeber, Heike Scheuermann, Simone Butz, Jolanthe Schatterny, Heimo Mairbäurl, Ingo Baumann, Marcus A. Mall
Journal: Journal of Allergy and Clinical Immunology (2021)
Abstract PS16-10: Tao kinase 3 augment the resistance to microtubule-disrupting agents in breast cancer cells
Authors: Chih-Yeu Fang, Tsung-Ching Lai, Michael Hsiao
Journal: Cancer Research (2021)

Abstract Breast cancer is the leading type of cancer in women worldwide. It is a heterogeneous disease that contains several subtypes with substantial differences in pathology and clinical outcome. With the advancements in imaging and targeted therapy, many patients with early stages of this disease have a great opportunity to be cured. However, recurrence or metastasis of tumor still occurs in patients even after successful primary treatment. Chemotherapy remains one of the most important treatment for advanced breast cancer. Anti-microtubule agents including taxanes, eribulin and vinca-alkaloids constitutes the major anti-breast cancer chemotherapeutic category, while chemoresistance remains a thorny issue for advanced disease. We aimed to discover novel candidate regulators for chemoresistance in breast cancer. A lentiviral-based, high-throughput shRNA platform was developed for screening the variation of global kinome to find new therapeutic targets in paclitaxel-resistant breast cancer cells. The underlying molecular mechanisms was further explored by global phosphoprotein array and expression microarray. The serine/threonine kinase, TAO Kinase 3 (TAOK3), was identified from 724 kinase genes. Knockdown of TAOK3 exhibited the most profound reduction of IC50 values in response to paclitaxel treatment in breast cancer cells. High expression of TAOK3 was related to poor prognosis in breast cancer patients after adjuvant chemotherapy. Furthermore, the expression of TAOK3 also decreased the sensitivity to other anti-microtubule drugs, including eribulin and vinorelbine. Expression microarray analysis revealed that NF-κB signaling plays the major regulation roles in TAOK3-associated resistance. Taken together, our results showed that TAOK3 increases resistance to anti-microtubule drug through upregulating the NF-κB signaling in breast cancer. Inhibitors that disrupt TAOK3 and NF-κB signaling pathway may overcome the drug resistance for patients treated with anti-microtubule agents. Citation Format: Chih-Yeu Fang, Tsung-Ching Lai, Michael Hsiao. Tao kinase 3 augment the resistance to microtubule-disrupting agents in breast cancer cells [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS16-10.
Eprenetapopt Plus Azacitidine in <i>TP53</i>-Mutated Myelodysplastic Syndromes and Acute Myeloid Leukemia: A Phase II Study by the Groupe Francophone des Myélodysplasies (GFM)
Authors: Thomas Cluzeau, Marie Sebert, Ramy Rahmé, Stefania Cuzzubbo, Jacqueline Lehmann-Che, Isabelle Madelaine, Pierre Peterlin, Blandine Bève, Habiba Attalah, Fatiha Chermat, Elsa Miekoutima, Odile Beyne Rauzy, Christian Recher, Aspasia Stamatoullas, Lise Willems, Emmanuel Raffoux, Céline Berthon, Bruno Quesnel, Michael Loschi, Antoine F. Carpentier, David A. Sallman, Rami Komrokji, Anouk Walter-Petrich, Sylvie Chevret, Lionel Ades, Pierre Fenaux
Journal: Journal of Clinical Oncology (2021)

TP53-mutated (TP53m) myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) have very poor outcome irrespective of the treatment received, including 40% responses (20% complete remission [CR]) with azacitidine (AZA) alone, short response duration, and a median overall survival (OS) of approximately 6 months. Eprenetapopt (APR-246), a novel first-in-class drug, leads to p53 protein reconformation and reactivates its proapoptotic and cell-cycle arrest functions.This phase II study assessed the safety and efficacy of eprenetapopt in combination with AZA in untreated high or very high International Prognostic Scoring System-R TP53m MDS and AML patients.Fifty-two TP53m patients (34 MDS, 18 AML [including seven with more than 30% blasts]) were enrolled. In MDS, we observed an overall response rate (ORR) of 62%, including 47% CR, with a median duration of response at 10.4 months. In AML, the ORR was 33% including 17% CR (27% and 0% CR in AML with less than and more than 30% marrow blasts, respectively). Seventy-three percent of responders achieved TP53 next-generation sequencing negativity (ie, variant allele frequency < 5%). The main treatment-related adverse events were febrile neutropenia (36%) and neurologic adverse events (40%), the latter correlating with a lower glomerular filtration rate at treatment onset (P < .01) and higher age (P = .05), and resolving with temporary drug interruption without recurrence after adequate eprenetapopt dose reduction. With a median follow-up of 9.7 months, median OS was 12.1 months in MDS, and 13.9 and 3.0 months in AML with less than and more than 30% marrow blasts, respectively.In this very high-risk population of TP53m MDS and AML patients, eprenetapopt combined with AZA was safe and showed potentially higher ORR and CR rate, and longer OS than reported with AZA alone.
Experimental Models of SARS-CoV-2 Infection: Possible Platforms to Study COVID-19 Pathogenesis and Potential Treatments
Authors: Sareh Pandamooz, Benjamin Jurek, Carl-Philipp Meinung, Zahra Baharvand, Alireza Sahebi Shahem-abadi, Silke Haerteis, Jaleel A. Miyan, James Downing, Mehdi Dianatpour, Afshin Borhani-Haghighi, Mohammad Saied Salehi
Journal: The Annual Review of Pharmacology and Toxicology (2021)

In December 2019, a novel coronavirus crossed species barriers to infect humans and was effectively transmitted from person to person, leading to a worldwide pandemic. Development of effective clinical interventions, including vaccines and antiviral drugs that could prevent or limit theburden or transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a global health priority. It is thus of utmost importance to assess possible therapeutic strategies against SARS-CoV-2 using experimental models that recapitulate aspects of the human disease. Here, we review available models currently being developed and used to study SARS-CoV-2 infection and highlight their application to screen potential therapeutic approaches, including repurposed antiviral drugs and vaccines. Each identified model provides a valuable insight into SARS-CoV-2 cellular tropism, replication kinetics, and cell damage that could ultimately enhance understanding of SARS-CoV-2 pathogenesis and protective immunity.
Therapeutic activity of an inhaled potent SARS-CoV-2 neutralizing human monoclonal antibody in hamsters
Authors: Michael S. Piepenbrink, Jun-Gyu Park, Fatai S. Oladunni, Ashlesha Deshpande, Madhubanti Basu, Sanghita Sarkar, Andreas Loos, Jennifer Woo, Phillip Lovalenti, Derek Sloan, Chengjin Ye, Kevin Chiem, Christopher W. Bates, Reuben E. Burch, Nathaniel B. Erdmann, Paul A. Goepfert, Vu L. Truong, Mark R. Walter, Luis Martinez-Sobrido, James J. Kobie
Journal: Cell Reports Medicine (2021)

SARS-CoV-2 infection results in viral burden in the respiratory tract, enabling transmission and leading to substantial lung pathology. The 1212C2 fully human monoclonal antibody was derived from an IgM memory B cell of a COVID-19 patient, has high affinity for the Spike protein receptor binding domain, neutralizes SARS-CoV-2, and exhibits in vivo prophylactic and therapeutic activity in hamsters when delivered intraperitoneally, reducing upper and lower respiratory viral burden and lung pathology. Inhalation of nebulized 1212C2 at levels as low as 0.6 mg/kg, corresponding to 0.03 mg/kg lung-deposited dose, reduced the viral burden below the detection limit and mitigated lung pathology. The therapeutic efficacy of an exceedingly low dose of inhaled 1212C2 supports the rationale for local lung delivery for dose-sparing benefits, as compared to the conventional parenteral route of administration. These results suggest that the clinical development of 1212C2 formulated and delivered via inhalation for the treatment of SARS-CoV-2 infection should be considered.
A comprehensive analysis of classification methods in gastrointestinal endoscopy imaging
Authors: Debesh Jha, Sharib Ali, Steven Hicks, Vajira Thambawita, Hanna Borgli, Pia H. Smedsrud, Thomas de Lange, Konstantin Pogorelov, Xiaowei Wang, Philipp Harzig, Minh-Triet Tran, Wenhua Meng, Trung-Hieu Hoang, Danielle Dias, Tobey H. Ko, Taruna Agrawal, Olga Ostroukhova, Zeshan Khan, Muhammad Atif Tahir, Yang Liu, Yuan Chang, Mathias Kirkerød, Dag Johansen, Mathias Lux, Håvard D. Johansen, Michael A. Riegler, Pål Halvorsen
Journal: Medical Image Analysis (2021)

Gastrointestinal (GI) endoscopy has been an active field of research motivated by the large number of highly lethal GI cancers. Early GI cancer precursors are often missed during the endoscopic surveillance. The high missed rate of such abnormalities during endoscopy is thus a critical bottleneck. Lack of attentiveness due to tiring procedures, and requirement of training are few contributing factors. An automatic GI disease classification system can help reduce such risks by flagging suspicious frames and lesions. GI endoscopy consists of several multi-organ surveillance, therefore, there is need to develop methods that can generalize to various endoscopic findings. In this realm, we present a comprehensive analysis of the Medico GI challenges: Medical Multimedia Task at MediaEval 2017, Medico Multimedia Task at MediaEval 2018, and BioMedia ACM MM Grand Challenge 2019. These challenges are initiative to set-up a benchmark for different computer vision methods applied to the multi-class endoscopic images and promote to build new approaches that could reliably be used in clinics. We report the performance of 21 participating teams over a period of three consecutive years and provide a detailed analysis of the methods used by the participants, highlighting the challenges and shortcomings of the current approaches and dissect their credibility for the use in clinical settings. Our analysis revealed that the participants achieved an improvement on maximum Mathew correlation coefficient (MCC) from 82.68% in 2017 to 93.98% in 2018 and 95.20% in 2019 challenges, and a significant increase in computational speed over consecutive years.
Importance of Intestinal Environment and Cellular Plasticity of Islets in the Development of Postpancreatectomy Diabetes
Authors: Tatsuya Fukuda, Ryotaro Bouchi, Takato Takeuchi, Kikuko Amo-Shiinoki, Atsushi Kudo, Shinji Tanaka, Minoru Tanabe, Takumi Akashi, Kazuhiro Hirayama, Toshitaka Odamaki, Miki Igarashi, Ikuo Kimura, Katsuya Tanabe, Yukio Tanizawa, Tetsuya Yamada, Yoshihiro Ogawa
Journal: Diabetes Care (2021)

OBJECTIVE To elucidate the pathogenesis of postpancreatectomy diabetes mellitus (PPDM). RESEARCH DESIGN AND METHODS Forty-eight patients without diabetes undergoing either pancreatoduodenectomy (PD) (n = 20) or distal pancreatectomy (DP) (n = 28) were included. A 75-g oral glucose tolerance test was performed every 6 months. Microbiome composition and short-chain fatty acids (SCFAs) in feces were examined before and 6 months after surgery. The association of histological characteristics of the resected pancreas with PPDM was examined. RESULTS During follow-up (median 3.19 years), 2 of 20 PD patients and 16 of 28 DP patients developed PPDM. Proteobacteria relative abundance, plasma glucagon-like peptide 1 (GLP-1), and fecal butyrate levels increased only after PD. Postsurgical butyrate levels were correlated with postsurgical GLP-1 levels. With no significant difference in the volume of the resected pancreas between the surgical procedures, both β-cell and α-cell areas in the resected pancreas were significantly higher in DP patients than in PD patients. In DP patients, the progressors to diabetes showed preexisting insulin resistance compared with nonprogressors, and both increased α- and β-cell areas were predictors of PPDM. Furthermore, in DP patients, α-cell and β-cell areas were associated with ALDH1A3 expression in islets. CONCLUSIONS We postulate that a greater removal of β-cells contributes to the development of PPDM after DP. Islet expansion along with preexisting insulin resistance is associated with high cellular plasticity, which may predict the development of PPDM after DP. In contrast, PD is associated with alterations of gut microbiome and increases in SCFA production and GLP-1 secretion, possibly protecting against PPDM development.
Mesh removal: skills accreditation planned for surgeons who work in new centres
Authors: Clare Dyer
Journal: BMJ (2021)

Surgeons who will work at new specialist mesh centres throughout England hope to establish their competence through credentialing in the field of pelvic mesh removal surgery, in the absence of a recognised training programme.

The seven centres around England for women with complications from mesh inserted for urinary incontinence and vaginal prolapse will begin operating on 1 April.1 Their establishment follows a recommendation in the Cumberlege review, which looked into three avoidable harms from medical treatment, including the after effects of pelvic mesh.2

Women around the world have experienced serious long term effects from the material, which has twisted, moved, …
Subsidiary of US healthcare firm will run more than 50 GP practices after takeover deal
Authors: Gareth Iacobucci
Journal: BMJ (2021)

A subsidiary of a large US healthcare company has taken over the running of one of England’s biggest NHS general practice providers in an expansion of its UK portfolio.

Operose Health1—a subsidiary of US company Centene2—has acquired AT Medics, which operates 37 GP practices across London, mostly under alternative provider medical services (APMS) contracts.

These will add to the 21 GP practices in England that Operose already runs, which were transferred to it last year when Centene Corporation brought together its UK subsidiaries The Practice Group and Simplify Health.3 Operose is owned by MH Services (UK), which is owned by MH Holdings International (UK).

The expansion will likely make Operose the largest primary care provider in …
Ultrasound image reconstruction from plane wave radio-frequency data by self-supervised deep neural network
Authors: Jingke Zhang, Qiong He, Yang Xiao, Hairong Zheng, Congzhi Wang, Jianwen Luo
Journal: Medical Image Analysis (2021)

Image reconstruction from radio-frequency (RF) data is crucial for ultrafast plane wave ultrasound (PWUS) imaging. Compared with the traditional delay-and-sum (DAS) method based on relatively imprecise assumptions, sparse regularization (SR) method directly solves the inverse problem of image reconstruction and has presented significant improvement in the image quality when the frame rate remains high. However, the computational complexity of SR is too high for practical implementation, which is inherently associated with its iterative process. In this work, a deep neural network (DNN), which is trained with an incorporated loss function including sparse regularization terms, is proposed to reconstruct PWUS images from RF data with significantly reduced computational time. It is remarkable that, a self-supervised learning scheme, in which the RF data are utilized as both the inputs and the labels during the training process, is employed to overcome the lack of the "ideal" ultrasound images as the labels for DNN. In addition, it has been also verified that the trained network can be used on the RF data obtained with steered plane waves (PWs), and thus the image quality can be further improved with coherent compounding. Using simulation data, the proposed method has significantly shorter reconstruction time (∼10 ms) than the conventional SR method (∼1-5 mins), with comparable spatial resolution and 1.5-dB higher contrast-to-noise ratio (CNR). Besides, the proposed method with single PW can achieve higher CNR than DAS with 75 PWs in reconstruction of in-vivo images of human carotid arteries.
Effects of tailored telemonitoring on functional status and quality of life in patients with heart failure
Authors: J. Josiane Boyne, A. Gingele, B. Ramaekers, H. P. Brunner La Rocca, G. J. De Weerd, J. Kragten, V. Van Empel, H. J. M. Vrijhoef, A. P. M. Gorgels, G. Cleuren, C. Knackstedt
Journal: European Journal of Heart Failure (2018)