tbuckley/cabot-search huggingface dataset:
Impact of calorie restriction and intermittent fasting on periodontal health
Authors: Sameena Parveen
Journal: Periodontology 2000 (2021)

Abstract The scientific evidence indicates that calorie restriction and intermittent fasting are among the appropriate strategies targeting factual causative factors of various inflammatory and lifestyle‐related disorders. Periodontitis is a common oral inflammatory disease leading to bone loss that is associated with various systemic problems. Previous studies suggest that calorie restriction may dampen inflammation and concomitant tissue damage under inflammatory conditions, such as periodontal diseases in nonhuman primates. However, insufficient research has been carried out to assess the effects of a calorie‐restricted diet on the initiation and progression of periodontal disease in humans. This review of the literature aims to describe the general concepts of calorie restriction, its clinical implications, and related therapeutic potential in controlling periodontal inflammation. The review shows that fasting regimen groups have shown lesser bone loss because of an increase in osteoprogenitor cells than non‐fasting groups. Calorie restriction dampens the inflammatory response and reduces circulating inflammatory mediators like tumor necrosis factor‐alpha, interleukin‐6, matrix metalloproteinase‐8, matrix metalloproteinase‐9, and interleukin‐1‐beta in gingival crevicular fluid. However, the incorporation of this form of dietary intervention continues to be challenging in our current society, in which obesity is a major public concern. Calorie restriction and intermittent fasting can play a key role in the cost‐effective resolution of periodontal inflammation as a primary prevention strategy for the management of chronic inflammatory diseases, including periodontal diseases.
Improving Appendicitis Care for All Patients
Authors: Anupam B. Kharbanda
Journal: JAMA Network Open (2021)

Kenneth A. Michelson, MD, MPH; Scott D. Reeves, MD; Joseph A. Grubenhoff, MD, MSCS; Andrea T. Cruz, MD, MPH; Pradip P. Chaudhari, MD; Arianna H. Dart, BA; Jonathan A. Finkelstein, MD, MPH; Richard G. Bachur, MD
High-dose IL-2/CD25 fusion protein amplifies vaccine-induced CD4<sup>+</sup>and CD8<sup>+</sup>neoantigen-specific T cells to promote antitumor immunity
Authors: Rosmely Hernandez, Kathryn M LaPorte, Sunnie Hsiung, Alicia Santos Savio, Thomas R Malek
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Immunization with tumor neoantigens is a promising vaccine approach to promote antitumor immunity due to their high immunogenicity, lack of expression in normal tissue, and preferential induction of tumor neoantigen-specific T cells, which are central mediators of the anti-cancer response. A drawback to targeting tumor neoantigen-specific T cells is that these cells are found at a low frequency in patients with cancer, limiting their therapeutic benefit. Interleukin-2 (IL-2) promotes expansion and persistence of tumor-reactive T cells. However, its clinical use has been hampered by toxicities arising from its multiple cellular targets. Thus, new engineered IL-2 receptor (IL-2R) agonists with distinctive cell type selectivity have been designed to harness the potential of IL-2 for tumor immunotherapy. Methods We investigated the potential to amplify neoantigen-specific CD4 + and CD8 + T cell immune responses to promote antitumor immunity through vaccination with tumor neoantigens. Following T cell receptor (TCR)-mediated induction of the high-affinity IL-2R on these T cells, amplification of the neoantigen-specific T cell response was achieved using a high dose of the mouse IL-2/CD25 (mIL-2/CD25) fusion protein, an IL-2R agonist with more favorable pharmacokinetics and pharmacodynamics than IL-2 and selectivity toward the high-affinity IL-2R. Results Administration of a high dose of mIL-2/CD25 shortly after antigen-dependent induction of the high-affinity IL-2R amplified the numbers and function of TCR transgenic tumor-reactive tyrosinase-related protein-1 (TRP-1) CD4 + T cells, leading to antitumor immunity to B16-F10 melanoma. This approach was adapted to amplify endogenous polyclonal B16-F10 neoantigen-specific T cells. Maximal expansion of these cells required prime/boost neoantigen vaccinations, where mIL-2/CD25 was optimal when administered only after the boosting steps. The ensuing mIL-2/CD25-driven immune response supported antitumor immunity to B16-F10 and was more effective than treatment with a similar amount of IL-2. Optimal antitumor effects required amplification of CD4 + and CD8 + neoantigen-specific T cells. High-dose mIL-2/CD25 supported a tumor microenvironment with higher numbers of CD4 + and CD8 + T effectors cells with increased granzyme B expression and importantly a more robust expansion of neoantigen-specific T cells. Conclusion These results indicate that neoantigen-based vaccines are optimized by potentiating IL-2R signaling in CD4 + and CD8 + neoantigen-reactive T cells by using high-dose mIL-2/CD25, leading to more effective tumor clearance.
Oncogene Concatenated Enriched Amplicon Nanopore Sequencing for rapid, accurate, and affordable somatic mutation detection
Authors: Deepak Thirunavukarasu, Lauren Y. Cheng, Ping Song, Sherry X. Chen, Mitesh J. Borad, Lawrence Kwong, Phillip James, Daniel J. Turner, David Yu Zhang
Journal: Genome biology (2021)

Abstract We develop the Oncogene Concatenated Enriched Amplicon Nanopore Sequencing (OCEANS) method, in which variants with low variant allele frequency (VAFs) are amplified and subsequently concatenated for Nanopore Sequencing. OCEANS allows accurate detection of somatic mutations with VAF limits of detection between 0.05 and 1%. We construct 4 distinct multi-gene OCEANS panels targeting recurrent mutations in acute myeloid leukemia, melanoma, non-small- cell lung cancer, and hepatocellular carcinoma and validate them on clinical samples. By demonstrating detection of low VAF single nucleotide variant mutations using Nanopore Sequencing, OCEANS is poised to enable same-day clinical sequencing panels.
Profiling the responsiveness of focal adhesions of human cardiomyocytes to extracellular dynamic nano-topography
Authors: Huaiyu Shi, Xiangjun Wu, Shiyang Sun, Chenyan Wang, Zacharias Vangelatos, Ariel Ash-Shakoor, Costas P. Grigoropoulos, Patrick T. Mather, James H. Henderson, Zhen Ma
Journal: Bioactive Materials (2021)

Focal adhesion complexes function as the mediators of cell-extracellular matrix interactions to sense and transmit the extracellular signals. Previous studies have demonstrated that cardiomyocyte focal adhesions can be modulated by surface topographic features. However, the response of focal adhesions to dynamic surface topographic changes remains underexplored. To study this dynamic responsiveness of focal adhesions, we utilized a shape memory polymer-based substrate that can produce a flat-to-wrinkle surface transition triggered by an increase of temperature. Using this dynamic culture system, we analyzed three proteins (paxillin, vinculin and zyxin) from different layers of the focal adhesion complex in response to dynamic extracellular topographic change. Hence, we quantified the dynamic profile of cardiomyocyte focal adhesion in a time-dependent manner, which provides new understanding of dynamic cardiac mechanobiology.
Impossible but true: complete transection of common bile duct treated with ERCP/percutaneous biliodigestive rendezvous
Authors: Valeria DʼOvidio, Valentina Pompa, Nicola Maltzeff, Giulio Sodani, Roberto Cancellieri, Marco Emilio Bazuro
Journal: Endoscopy (2021)

Bile duct injuries after laparoscopic cholecystectomy have been reported even after surgical procedures performed by expert surgeons. Mean rates have plateaued in the past 10 years (0.30 %–0.60 %). The Hannover classification (2015) is a modification of the Strasberg–Bismuth classification and allows a distinction between small injuries (bile leakage from the cystic duct or aberrant right sectoral branch) and serious injuries inflicted during laparoscopic cholecystectomy [1] [2]. The Hannover classification also provides discriminators for the localization of tangentially or completely transected bile ducts above or below the bifurcation of the hepatic duct, which is a major drawback of other classification systems.
RETRACTED ARTICLE: Facial expressions can detect Parkinson’s disease: preliminary evidence from videos collected online
Authors: Mohammad Rafayet Ali, Taylor Myers, Ellen Wagner, Harshil Ratnu, E. Ray Dorsey, Ehsan Hoque
Journal: npj Digital Medicine (2021)

One of the symptoms of Parkinson's disease (PD) is hypomimia or reduced facial expressions. In this paper, we present a digital biomarker for PD that utilizes the study of micro-expressions. We analyzed the facial action units (AU) from 1812 videos of 604 individuals (61 with PD and 543 without PD, mean age 63.9 yo, sd 7.8 ) collected online using a web-based tool (www.parktest.net). In these videos, participants were asked to make three facial expressions (a smiling, disgusted, and surprised face) followed by a neutral face. Using techniques from computer vision and machine learning, we objectively measured the variance of the facial muscle movements and used it to distinguish between individuals with and without PD. The prediction accuracy using the facial micro-expressions was comparable to those methodologies that utilize motor symptoms. Logistic regression analysis revealed that participants with PD had less variance in AU6 (cheek raiser), AU12 (lip corner puller), and AU4 (brow lowerer) than non-PD individuals. An automated classifier using Support Vector Machine was trained on the variances and achieved 95.6% accuracy. Using facial expressions as a biomarker for PD could be potentially transformative for patients in need of physical separation (e.g., due to COVID) or are immobile.
Monoethanolamine-induced glucose deprivation promotes apoptosis through metabolic rewiring in prostate cancer
Authors: Chakravarthy Garlapati, Shriya Joshi, Ravi Chakra Turaga, Manjari Mishra, Michelle D Reid, Shobhna Kapoor, Liana Artinian, Vincent Rehder, Ritu Aneja
Journal: Theranostics (2021)

Rationale: Cancer cells rely on glucose metabolism for fulfilling their high energy demands. We previously reported that monoethanolamine (Etn), an orally deliverable lipid formulation, reduced intracellular glucose and glutamine levels in prostate cancer (PCa). Glucose deprivation upon Etn treatment exacerbated metabolic stress in PCa, thereby enhancing cell death. Moreover, Etn was potent in inhibiting tumor growth in a PCa xenograft model. However, the precise mechanisms underlying Etn-induced metabolic stress in PCa remain elusive. The purpose of the present study was to elucidate the mechanisms contributing to Etn-mediated metabolic rewiring in PCa. Methods: Glucose transporters (GLUTs) facilitate glucose transport across the plasma membrane. Thus, we assessed the expression of GLUTs and the internalization of GLUT1 in PCa. We also evaluated the effects of Etn on membrane dynamics, mitochondrial structure and function, lipid droplet density, autophagy, and apoptosis in PCa cells. Results: Compared to other GLUTs, GLUT1 was highly upregulated in PCa. We observed enhanced GLUT1 internalization, altered membrane dynamics, and perturbed mitochondrial structure and function upon Etn treatment. Etn-induced bioenergetic stress enhanced lipolysis, decreased lipid droplet density, promoted accumulation of autophagosomes, and increased apoptosis. Conclusion: We provide the first evidence that Etn alters GLUT1 trafficking leading to metabolic stress in PCa. By upregulating phosphatidylethanolamine (PE), Etn modulates membrane fluidity and affects mitochondrial structure and function. Etn also induces autophagy in PCa cells, thereby promoting apoptosis. These data strongly suggest that Etn rewires cellular bioenergetics and could serve as a promising anticancer agent for PCa.
AIforCOVID: Predicting the clinical outcomes in patients with COVID-19 applying AI to chest-X-rays. An Italian multicentre study
Authors: Paolo Soda, Natascha Claudia D’Amico, Jacopo Tessadori, Giovanni Valbusa, Valerio Guarrasi, Chandra Bortolotto, Muhammad Usman Akbar, Rosa Sicilia, Ermanno Cordelli, Deborah Fazzini, Michaela Cellina, Giancarlo Oliva, Giovanni Callea, Silvia Panella, Maurizio Cariati, Diletta Cozzi, Vittorio Miele, Elvira Stellato, Gianpaolo Carrafiello, Giulia Castorani, Annalisa Simeone, Lorenzo Preda, Giulio Iannello, Alessio Del Bue, Fabio Tedoldi, Marco Alí, Diego Sona, Sergio Papa
Journal: Medical Image Analysis (2021)

Recent epidemiological data report that worldwide more than 53 million people have been infected by SARS-CoV-2, resulting in 1.3 million deaths. The disease has been spreading very rapidly and few months after the identification of the first infected, shortage of hospital resources quickly became a problem. In this work we investigate whether artificial intelligence working with chest X-ray (CXR) scans and clinical data can be used as a possible tool for the early identification of patients at risk of severe outcome, like intensive care or death. Indeed, further to induce lower radiation dose than computed tomography (CT), CXR is a simpler and faster radiological technique, being also more widespread. In this respect, we present three approaches that use features extracted from CXR images, either handcrafted or automatically learnt by convolutional neuronal networks, which are then integrated with the clinical data. As a further contribution, this work introduces a repository that collects data from 820 patients enrolled in six Italian hospitals in spring 2020 during the first COVID-19 emergency. The dataset includes CXR images, several clinical attributes and clinical outcomes. Exhaustive evaluation shows promising performance both in 10-fold and leave-one-centre-out cross-validation, suggesting that clinical data and images have the potential to provide useful information for the management of patients and hospital resources.
Electrogenic sodium bicarbonate cotransporter NBCe1 regulates pancreatic β cell function in type 2 diabetes
Authors: Matthew R. Brown, Heather Holmes, Kuntol Rakshit, Naureen Javeed, Tracy K. Her, Alison A. Stiller, Satish Sen, Gary E. Shull, Y.S. Prakash, Michael F. Romero, Aleksey V. Matveyenko
Journal: Journal of Clinical Investigation (2021)

Pancreatic β cell failure in type 2 diabetes mellitus (T2DM) is attributed to perturbations of the β cell's transcriptional landscape resulting in impaired glucose-stimulated insulin secretion. Recent studies identified SLC4A4 (a gene encoding an electrogenic Na+-coupled HCO3– cotransporter and intracellular pH regulator, NBCe1) as one of the misexpressed genes in β cells of patients with T2DM. Thus, in the current study, we set out to test the hypothesis that misexpression of SLC4A4/NBCe1 in T2DM β cells contributes to β cell dysfunction and impaired glucose homeostasis. To address this hypothesis, we first confirmed induction of SLC4A4/NBCe1 expression in β cells of patients with T2DM and demonstrated that its expression was associated with loss of β cell transcriptional identity, intracellular alkalinization, and β cell dysfunction. In addition, we generated a β cell–selective Slc4a4/NBCe1-KO mouse model and found that these mice were protected from diet-induced metabolic stress and β cell dysfunction. Importantly, improved glucose tolerance and enhanced β cell function in Slc4a4/NBCe1-deficient mice were due to augmented mitochondrial function and increased expression of genes regulating β cell identity and function. These results suggest that increased β cell expression of SLC4A4/NBCe1 in T2DM plays a contributory role in promotion of β cell failure and should be considered as a potential therapeutic target.
Outcomes of endoscopic resection for superficial duodenal tumors: 10 years’ experience in 18 Japanese high volume centers
Authors: Motohiko Kato, Yoji Takeuchi, Shu Hoteya, Tsuneo Oyama, Satoru Nonaka, Shoichi Yoshimizu, Naomi Kakushima, Ken Ohata, Hironori Yamamoto, Yuko Hara, Hisashi Doyama, Osamu Dohi, Yasushi Yamasaki, Hiroya Ueyama, Kengo Takimoto, Koichi Kurahara, Tomoaki Tashima, Nobutsugu Abe, Atsushi Nakayama, Ichiro Oda, Naohisa Yahagi
Journal: Endoscopy (2021)

Abstract Background Data on endoscopic resection (ER) for superficial duodenal epithelial tumors (SDETs) are insufficient owing to their rarity. There are two main ER techniques for SDETs: endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). In addition, modified EMR techniques, such as underwater EMR (UEMR) and cold polypectomy, are becoming popular. We conducted a large-scale retrospective multicenter study to clarify the detailed outcomes of duodenal ER. Methods Patients with SDETs who underwent ER at 18 institutions from January 2008 to December 2018 were included. The rates of en bloc resection and delayed adverse events (AEs; defined as delayed bleeding or perforation) were analyzed. Local recurrence was analyzed using the Kaplan–Meier method. Results In total, 3107 patients (including 1017 undergoing ESD) were included. En bloc resection rates were 79.1 %, 78.6 %, 86.8 %, and 94.8 %, and delayed AE rates were 0.5 %, 2.2 %, 2.8 %, and 6.8 % for cold polypectomy, UEMR, EMR and ESD, respectively. The delayed AE rate was significantly higher in the ESD group than in non-ESD groups for lesions &lt; 19 mm (7.4 % vs. 1.9 %; P &lt; 0.001), but not for lesions &gt; 20 mm (6.1 % vs. 7.1 %; P = 0.64). The local recurrence rate was significantly lower in the ESD group than in the non-ESD groups (P &lt; 0.001). Furthermore, for lesions &gt; 30 mm, the cumulative local recurrence rate at 2 years was 22.6 % in the non-ESD groups compared with only 1.6 % in the ESD group (P &lt; 0.001). Conclusions ER outcomes for SDETs were generally acceptable. ESD by highly experienced endoscopists might be an option for very large SDETs.
The hallmark of COVID-19 cancer disparities: Cellular sequelae
Authors: E. McGhee, M. T. Li, Y. L. Lin, N. Carr, C. Njubigbo, R. Sadeghi, B. Su-Velez, J. Handler, A. Handler, J. Okoro, S. Afework, J. Vadgama
Journal: Cancer Research (2021)
Bone sarcomas: ESMO–EURACAN–GENTURIS–ERN PaedCan Clinical Practice Guideline for diagnosis, treatment and follow-up
Authors: S.J. Strauss, A.M. Frezza, N. Abecassis, J. Bajpai, S. Bauer, R. Biagini, S. Bielack, J.Y. Blay, S. Bolle, S. Bonvalot, I. Boukovinas, J.V.M.G. Bovee, K. Boye, B. Brennan, T. Brodowicz, A. Buonadonna, E. de Álava, A.P. Dei Tos, X. Garcia del Muro, A. Dufresne, M. Eriksson, F. Fagioli, A. Fedenko, V. Ferraresi, A. Ferrari, N. Gaspar, S. Gasperoni, H. Gelderblom, F. Gouin, G. Grignani, A. Gronchi, R. Haas, A.B. Hassan, S. Hecker-Nolting, N. Hindi, P. Hohenberger, H. Joensuu, R.L. Jones, C. Jungels, P. Jutte, L. Kager, B. Kasper, A. Kawai, K. Kopeckova, D.A. Krákorová, A. Le Cesne, F. Le Grange, E. Legius, A. Leithner, A. López Pousa, J. Martin-Broto, O. Merimsky, C. Messiou, A.B. Miah, O. Mir, M. Montemurro, B. Morland, C. Morosi, E. Palmerini, M.A. Pantaleo, R. Piana, S. Piperno-Neumann, P. Reichardt, P. Rutkowski, A.A. Safwat, C. Sangalli, M. Sbaraglia, S. Scheipl, P. Schöffski, S. Sleijfer, D. Strauss, K. Sundby Hall, A. Trama, M. Unk, M.A.J. van de Sande, W.T.A. van der Graaf, W.J. van Houdt, T. Frebourg, R. Ladenstein, P.G. Casali, S. Stacchiotti
Journal: Annals of Oncology (2021)
Covid-19: Hospital may cease giving patient ivermectin, US court rules, as prescriptions soar
Authors: Owen Dyer
Journal: BMJ (2021)

An Ohio judge has overturned an earlier court order that forced a hospital to treat a covid-19 patient with the antiparasitic drug ivermectin, popularised by US conservative media.West Chester Hospital was ordered to administer the unproved drug by a county judge on 23 August, after Julie Smith sued on behalf of her husband, Jeffrey Smith, who has been in intensive care since 15 July and on a ventilator since 1 August.Julie Smith launched her lawsuit after the hospital declined to fill a prescription she had obtained from Fred Wagshul, one of three doctors who last year founded the Front Line COVID-19 Critical Care Alliance (FLCCCA), a group that has spread claims of ivermectin's efficacy against the coronavirus.10
Importance of the Assessment Time Window for Intravenous Tranexamic Acid and Thromboembolic Events
Authors: Loïc Sentilhes, Aurélien Mattuizzi, Catherine Deneux-Tharaux
Journal: JAMA Surgery (2021)

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Covid-19 and GPs: the unmeasured goes unnoticed
Authors: Ellen S V Fallows
Journal: BMJ (2021)

Thank you for publishing this important and heartfelt piece about how being listened to and supported by her GP helped one anonymous patient through a traumatic time.1 I’m so grateful she shared her experiences and raised important points about relationship based care and the art that is general practice.

Her point about the unmeasured going unnoticed is critical to protecting what we do as GPs. It isn’t just technology that threatens …
Most Fully Vaccinated Patients With Cancer Have SARS-CoV-2 Antibodies
Authors: Anita Slomski
Journal: JAMA (2021)

Tal Goshen-Lago, PhD; Ithai Waldhorn, MD; Roy Holland, MD; Moran Szwarcwort-Cohen, PhD; Anat Reiner-Benaim, PhD; Yael Shachor-Meyouhas, MD; Khetam Hussein, MD; Liana Fahoum, MSc; Mali Baruch, BSc; Avivit Peer, MD; Yoram Reiter, PhD; Ronit Almog, MD; Michael Halberthal, MD; Irit Ben-Aharon, MD, PhD
A novel method for endoscopic closure of endoscopic submucosal dissection-induced defects in the colorectum: the closure method with an elastic-rubber ring (CMER)
Authors: Yuka Kowazaki, Hisashi Fukuda, Itaru Saito, Toyoaki Sawano, Tomohiro Kurokawa, Norio Kanzaki, Anastasios Manolakis
Journal: Endoscopy (2021)

Endoscopic submucosal dissection (ESD) is a widely used technique associated with high en bloc resection rates for colorectal lesions [1], but at the cost of a higher incidence of adverse events, such as delayed bleeding and perforation, compared with endoscopic mucosal resection [2]. To prevent such complications, closure of ESD-induced mucosal defects is pursued, although this task can become challenging owing to their large size [3]. Herein, we report a new closure method for ESD-induced defects using endoclips and an elastic-rubber ring designed for orthodontics, which we have called the closure method with an elastic-rubber ring (CMER).