tbuckley/cabot-search huggingface dataset:
Enhanced osseointegration of three-dimensional supramolecular bioactive interface through osteoporotic microenvironment regulation
Authors: Haotian Bai, Yue Zhao, Chenyu Wang, Zhonghan Wang, Jincheng Wang, Hou Liu, Yubin Feng, Quan Lin, Zuhao Li, He Liu
Journal: Theranostics (2020)

: Osteoporosis is more likely to cause serious complications after joint replacement, mainly due to physiological defects of endogenous osteogenic cells and the pathological osteoclast activity. It is a feasible solution to design a prosthetic surface interface that specifically addresses this troublesome situation.
Treatment of Patients with Therapy-Refractory Acute GvHD with the Novel MSC Product MSC-Ffm Resulted in Excellent Response and Low Mortality: Post-Approval Observational Data from 69 Consecutive Patients
Authors: Peter Bader, Selim Kuci, Zyrafete Kuci, Shahrzad Bakhtiar, Oliver Basu, Gesine Bug, Michael Dennis, Johann Greil, Aniko Barta, Krisztián Kallay, Peter J. Lang, Giovanna Lucchini, Raj Pol, Ansgar S. Schulz, Karl-Walter Sykora, Irene Teichert von Luettichau, Grit Herter-Sprie, Mohammad Ashab Uddin, Philip Jenkin, Abdulrahman S. Alsultan, Jochen Büchner, Jerry Stein, Agnes Kelemen, Shankaranarayana Paneesha, Andrea Jarisch, Jan Soerensen, Emilia Salzmann-Manrique, Erhard Seifried, Thomas Klingebiel, Halvard Bonig
Journal: Blood (2017)
More Evidence in the Treatment of Subcutaneous Abdominal Wound Healing Impairment
Authors: Adam C. Fields, Kamal M. F. Itani
Journal: JAMA Surgery (2020)

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Impact of Neoadjuvant Durvalumab with or without Tremelimumab on CD8+ Tumor Lymphocyte Density, Safety, and Efficacy in Patients with Oropharynx Cancer: CIAO Trial Results
Authors: Renata Ferrarotto, Diana Bell, Maria L. Rubin, Katherine A. Hutcheson, Jason M. Johnson, Ryan P. Goepfert, Jack Phan, Yasir Y. Elamin, Danice K. Torman, Carla L. Warneke, Amy C. Hessel, Adam S. Garden, Jeffrey N. Myers, Faye M. Johnson, J. Jack Lee, Andrew G. Sikora, Maura L. Gillison, Bonnie S. Glisson, Neil D. Gross
Journal: Clinical Cancer Research (2020)

In oropharyngeal squamous cell carcinoma (OPC), high CD8+ tumor-infiltrating lymphocyte (CD8+TIL) density confers improved prognosis. We compared neoadjuvant durvalumab (PD-L1 inhibitor) with durvalumab + tremelimumab (CTLA-4 inhibitor) in terms of impact on CD8+TIL density, safety, and efficacy in patients with OPC.Patients with newly diagnosed stage II-IVA OPC or locoregionally recurrent OPC amenable to resection were included. Patients were randomized to two cycles of durvalumab or durvalumab + tremelimumab before surgery. The primary endpoint was change between baseline and resection specimen in CD8+TIL density between arms. Secondary endpoints included safety, response rate per RECIST, major pathologic response (MPR; ≤10% viable tumor cells) rate, and patient-reported outcomes.Of 28 eligible patients (14/arm), 20 (71%) had newly diagnosed OPC, and 24 (86%) were p16-positive. The posttreatment to pretreatment median CD8+TIL density ratio was 1.31 for durvalumab and 1.15 for combination treatment (P = 0.97; 95% CI: -1.07-2.28). In each group, 6 patients (43%, 95% CI: 17.66-71.14) had a response. Eight patients (29%) had a MPR at the primary tumor and/or nodal metastases. Neither baseline CD8+TIL density nor PD-L1 expression level correlated with overall response, but a trend toward greater CD8+TIL change in patients with a MPR was seen (P = 0.059; 95% CI: -0.33-3.46). Four patients (14%) had grade ≥3 adverse events. At median follow-up time of 15.79 months, all patients were alive, and one had an additional recurrence.Durvalumab + tremelimumab did not increase CD8+TIL density more than durvalumab alone did. The observed safety and activity support further investigation of neoadjuvant checkpoint inhibitor for OPC.
On the Alert for Cytokine Storm: Immunopathology in <scp>COVID</scp>‐19
Authors: Lauren A. Henderson, Scott W. Canna, Grant S. Schulert, Stefano Volpi, Pui Y. Lee, Kate F. Kernan, Roberto Caricchio, Shawn Mahmud, Melissa M. Hazen, Olha Halyabar, Kacie J. Hoyt, Joseph Han, Alexei A. Grom, Marco Gattorno, Angelo Ravelli, Fabrizio De Benedetti, Edward M. Behrens, Randy Q. Cron, Peter A. Nigrovic
Journal: Arthritis & Rheumatology (2020)

Poor outcomes in COVID-19 correlate with clinical and laboratory features of cytokine storm syndrome. Broad screening for cytokine storm and early, targeted antiinflammatory therapy may prevent immunopathology and could help conserve limited health care resources. While studies are ongoing, extrapolating from clinical experience in cytokine storm syndromes may benefit the multidisciplinary teams caring for patients with severe COVID-19.
CRISPR/CAS9-mediated knockout of Abi1 inhibits p185Bcr-Abl-induced leukemogenesis and signal transduction to ERK and PI3K/Akt pathways
Authors: James Faulkner, Peixin Jiang, Delaney Farris, Ryan Walker, Zonghan Dai
Journal: Journal of Hematology & Oncology (2020)

Abstract Background Abl interactor 1 (Abi1) is a downstream target of Abl tyrosine kinases and a component of the WAVE regulatory complex (WRC) that plays an important role in regulating actin cytoskeleton remodeling and membrane receptor signaling. While studies using short hairpin RNA (shRNA) have suggested that Abi1 plays a critical role in Bcr-Abl-induced leukemogenesis, the mechanism involved is not clear. Methods In this study, we knocked out Abi1 expression in p185 Bcr-Abl -transformed hematopoietic cells using CRISPR/Cas9-mediated gene editing technology. The effects of Abi1 deficiency on actin cytoskeleton remodeling, the Bcr-Abl signaling, IL-3 independent growth, and SDF-induced chemotaxis in these cells were examined by various in vitro assays. The leukemogenic activity of these cells was evaluated by a syngeneic mouse transplantation model. Results We show here that Abi1 deficiency reduced the IL3-independent growth and SDF-1α-mediated chemotaxis in p185 Bcr-Abl -transformed hematopoietic cells and inhibited Bcr-Abl-induced abnormal actin remodeling. Depletion of Abi1 also impaired the Bcr-Abl signaling to the ERK and PI3 kinase/Akt pathways. Remarkably, the p185 Bcr-Abl -transformed cells with Abi1 deficiency lost their ability to develop leukemia in syngeneic mice. Even though these cells developed drug tolerance in vitro after prolonged selection with imatinib as their parental cells, the imatinib-tolerant cells remain incapable of leukemogenesis in vivo. Conclusions Together, this study highlights an essential role of Abi1 in Bcr-Abl-induced leukemogenesis and provides a model system for dissecting the Abi1 signaling in Bcr-Abl-positive leukemia.
Consensus guidelines for management of hyperammonaemia in paediatric patients receiving continuous kidney replacement therapy
Authors: Rupesh Raina, Jirair K. Bedoyan, Uta Lichter-Konecki, Philippe Jouvet, Stefano Picca, Nicholas Ah Mew, Marcel C. Machado, Ronith Chakraborty, Meghana Vemuganti, Manpreet K. Grewal, Timothy Bunchman, Sidharth Kumar Sethi, Vinod Krishnappa, Mignon McCulloch, Khalid Alhasan, Arvind Bagga, Rajit K. Basu, Franz Schaefer, Guido Filler, Bradley A. Warady
Journal: Nature Reviews Nephrology (2020)

Abstract Hyperammonaemia in children can lead to grave consequences in the form of cerebral oedema, severe neurological impairment and even death. In infants and children, common causes of hyperammonaemia include urea cycle disorders or organic acidaemias. Few studies have assessed the role of extracorporeal therapies in the management of hyperammonaemia in neonates and children. Moreover, consensus guidelines are lacking for the use of non-kidney replacement therapy (NKRT) and kidney replacement therapies (KRTs, including peritoneal dialysis, continuous KRT, haemodialysis and hybrid therapy) to manage hyperammonaemia in neonates and children. Prompt treatment with KRT and/or NKRT, the choice of which depends on the ammonia concentrations and presenting symptoms of the patient, is crucial. This expert Consensus Statement presents recommendations for the management of hyperammonaemia requiring KRT in paediatric populations. Additional studies are required to strengthen these recommendations.
Case for continuing community NIV and CPAP during the COVID-19 epidemic
Authors: Jillian G Baker, Milind Sovani
Journal: Thorax (2020)

Dear Editor,

Recent clinical guidelines regarding the use of home non-invasive ventilation (NIV) and continuous positive airway pressure (CPAP) during the COVID-19 epidemic have tried to balance the risks of stopping NIV or CPAP against the unknown potential risk of increased aerosol-related transmission to family and carers.1 2 We read with interest views put forward by Barker et al 3 but feel that wider aspects need consideration, and for NIV and CPAP separately.

NIV use: NIV is primarily used for those with previous, or at risk from, hypercapnic respiratory failure (neuromuscular disorders, chest wall deformity, obesity or underlying lung disease, for example, COPD). Stopping home NIV risks the return of symptoms (lethargy, headache, dyspnoea and confusion), increased patient and family anxiety and precipitating life-threatening acute hypercapnia, which is likely to result in hospital admission, patient exposure to …
PTPROt aggravates inflammation by enhancing NF-κB activation in liver macrophages during nonalcoholic steatohepatitis
Authors: Kangpeng Jin, Yang Liu, Yuze Shi, Haitian Zhang, YuanYuan Sun, Guangyan Zhangyuan, Fei Wang, Weiwei Yu, Jincheng Wang, Xuewen Tao, Xin Chen, Wenjie Zhang, Beicheng Sun
Journal: Theranostics (2020)

Rationale: Inflammation plays a crucial role in the progression of nonalcoholic steatohepatitis (NASH). Protein tyrosine phosphatase receptor type O truncated isoform (PTPROt) is an integral membrane protein that has been identified in osteoclasts, macrophages, and B lymphocytes. However, its relationship between inflammation and NASH is largely unknown. Herein, we aimed to study the function of PTPROt in NASH progression. Methods: We established a NASH mouse model in wild-type (WT), PTPRO knockout mice by western diet (WD) and methionine-choline-deficient diet (MCD). In addition, MCD-induced NASH model was established in BMT mice. Moreover, we determined the expression of PTPROt in liver macrophages in human subjects without steatosis, with simple steatosis, and with NASH to confirm the relationship between PTPROt and NASH. In vitro assays were also performed to study the molecular role of PTPROt in NASH progression. Results: Human samples and animal model results illustrated that PTPROt is increased in liver macrophages during NASH progression and is positively correlated with the degree of NASH. Our animal model also showed that PTPROt in liver macrophages can enhance the activation of the NF-κB signaling pathway, which induces the transcription of genes involved in the inflammatory response. Moreover, PTPROt promotes the transcription of pro-oxidant genes and inhibits antioxidant and protective genes via increased activation of the NF-κB signaling pathway, thereby causing an increased level of reactive oxygen species (ROS) and damaged mitochondria. This triggers the NLRP3-IL1β axis and causes a heightened inflammatory response. Notably, PTPROt partially limits inflammation and ROS production by promoting mitophagy, which participates in a negative feedback loop in this model. Conclusions: Our data strongly indicate that PTPROt plays a dual role in inflammation via the NF-κB signaling pathway in liver macrophages during NASH. Further studies are required to explore therapeutic strategies and prevention of this common liver disease through PTPROt.
The challenges of the COVID‐19 pandemic: Approaches for the elderly and those with Alzheimer's disease
Authors: Qing Zhang, Weihong Song
Journal: MedComm (2020)

Coronavirus disease 2019 (COVID-19) is an infectious disease that since its outbreak in December 2019 has become a global pandemic. COVID-19 is caused by the previously unknown coronavirus SARS-CoV-2. The elderly are the most vulnerable to COVID-19, and have the highest mortality of the afflicted. Similar patterns have been observed in epidemics and pandemics throughout the 20th and the beginning of the 21st centuries. In this article, we review some unique challenges the elderly and people with Alzheimer's disease face during the COVID-19 pandemic and suggest approaches that could be taken from healthcare and social approaches to better handle this pandemic.
Assessing the risks of ‘infodemics’ in response to COVID-19 epidemics
Authors: Riccardo Gallotti, Francesco Valle, Nicola Castaldo, Pierluigi Sacco, Manlio De Domenico
Journal: Nature Human Behaviour (2020)

During COVID-19, governments and the public are fighting not only a pandemic but also a co-evolving infodemic—the rapid and far-reaching spread of information of questionable quality. We analysed more than 100 million Twitter messages posted worldwide during the early stages of epidemic spread across countries (from 22 January to 10 March 2020) and classified the reliability of the news being circulated. We developed an Infodemic Risk Index to capture the magnitude of exposure to unreliable news across countries. We found that measurable waves of potentially unreliable information preceded the rise of COVID-19 infections, exposing entire countries to falsehoods that pose a serious threat to public health. As infections started to rise, reliable information quickly became more dominant, and Twitter content shifted towards more credible informational sources. Infodemic early-warning signals provide important cues for misinformation mitigation by means of adequate communication strategies. An analysis of news shared on Twitter estimates the level of infodemic risk associated with COVID-19 across countries. Epidemic spread and infodemic risk co-evolve, with reliable information becoming more dominant as infection rates rise locally.
Targeting ceramide synthase 6–dependent metastasis-prone phenotype in lung cancer cells
Authors: Motoshi Suzuki, Ke Cao, Seiichi Kato, Yuji Komizu, Naoki Mizutani, Kouji Tanaka, Chinatsu Arima, Mei Chee Tai, Kiyoshi Yanagisawa, Norie Togawa, Takahiro Shiraishi, Noriyasu Usami, Tetsuo Taniguchi, Takayuki Fukui, Kohei Yokoi, Keiko Wakahara, Yoshinori Hasegawa, Yukiko Mizutani, Yasuyuki Igarashi, Jin-ichi Inokuchi, Soichiro Iwaki, Satoshi Fujii, Akira Satou, Yoko Matsumoto, Ryuichi Ueoka, Keiko Tamiya-Koizumi, Takashi Murate, Mitsuhiro Nakamura, Mamoru Kyogashima, Takashi Takahashi
Journal: Journal of Clinical Investigation (2019)

At the request of the corresponding author, the JCI is retracting this article.Following an institutional investigative review of errors in the article, it was determined that the data reported in Figure 1B were an analysis of E2F1 expression rather than CERS6 expression, as originally reported.The correct data do not show a difference in CERS6 expression with invasion status in human lung adenocarcinomas.In addition, errors were noted in Supplemental Figure 2, Supplemental Figure 3B, and Supplemental Table 1.The institutional review found no evidence of intention to falsify results.The authors apologize for these errors.
The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice
Authors: Kunpeng Wu, Yan Yuan, Huihui Yu, Xin Dai, Shu Wang, Zhengxu Sun, Fen Wang, He Fei, Qiwang Lin, Hua Jiang, Tong Chen
Journal: Blood (2020)
Update to U.S. Medical Eligibility Criteria for Contraceptive Use, 2016: Updated Recommendations for the Use of Contraception Among Women at High Risk for HIV Infection
Authors: Naomi K. Tepper, Kathryn M. Curtis, Shanna Cox, Maura K. Whiteman
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

"U.S. Medical Eligibility Criteria for Contraceptive Use" (U.S. MEC) 2016 provides evidence-based guidance for the safe use of contraceptive methods among U.S. women with certain characteristics or medical conditions (1). The U.S. MEC is adapted from global guidance from the World Health Organization (WHO) and kept up to date through continual review of published literature (1). CDC recently evaluated the evidence and the updated WHO guidance on the risk for human immunodeficiency virus (HIV) acquisition among women using hormonal contraception and intrauterine devices (IUDs) (2). After careful review, CDC adopted WHO's 2019 updated guidance for inclusion in the U.S. MEC guidance; CDC's updated guidance states that progestin-only injectable contraception (including depot medroxyprogesterone acetate [DMPA]) and IUDs (including levonorgestrel-releasing and copper-bearing) are safe for use without restriction among women at high risk for HIV infection (U.S. MEC category 1 [previously U.S. MEC category 2, advantages outweigh risks]) (Box). CDC's guidance also adds an accompanying clarification for women who wish to use IUDs, which states "Many women at a high risk for HIV infection are also at risk for other sexually transmitted diseases (STDs). For these women, refer to the recommendations in the 'U.S. Medical Eligibility Criteria for Contraceptive Use' for women with other factors related to STDs, and the 'U.S. Selected Practice Recommendations for Contraceptive Use' on STD screening before IUD insertion" (1,3). Recommendations for other hormonal contraceptive methods (including combined hormonal methods, implants, and progestin-only pills) remain the same; there is also no restriction for their use among women at high risk for HIV infection (U.S. MEC category 1). Finally, CDC clarified that the U.S. MEC recommendations for concurrent use of hormonal contraceptives or IUDs and antiretroviral use for treatment of HIV infection also apply to use of antiretrovirals for prevention of HIV acquisition (preexposure prophylaxis [PrEP]).
Man is jailed for hitting emergency department doctor in the face
Authors: Clare Dyer
Journal: BMJ (2020)

A man has been jailed for six months for punching an emergency department doctor who was dealing with patients with covid-19 at a hospital in which around half the emergency department consultants and nurses have tested positive for the virus.

Gareth Rudge, 34, of no fixed address, hit the doctor in the face and head outside the emergency department at Royal Gwent Hospital in the early hours of Friday 10 …
Polygenic and clinical risk scores and their impact on age at onset and prediction of cardiometabolic diseases and common cancers
Authors: Nina Mars, Jukka T. Koskela, Pietari Ripatti, Tuomo T. J. Kiiskinen, Aki S. Havulinna, Joni V. Lindbohm, Ari Ahola-Olli, Mitja Kurki, Juha Karjalainen, Priit Palta, Benjamin M. Neale, Mark Daly, Veikko Salomaa, Aarno Palotie, Elisabeth Widén, Samuli Ripatti
Journal: Nature Medicine (2020)
CDC Recommendations for Hepatitis C Screening Among Adults — United States, 2020
Authors: Sarah Schillie, Carolyn Wester, Melissa Osborne, Laura Wesolowski, A. Blythe Ryerson
Journal: MMWR Recommendations and Reports (2020)

Hepatitis C virus (HCV) infection is a major source of morbidity and mortality in the United States. HCV is transmitted primarily through parenteral exposures to infectious blood or body fluids that contain blood, most commonly through injection drug use. No vaccine against hepatitis C exists and no effective pre- or postexposure prophylaxis is available. More than half of persons who become infected with HCV will develop chronic infection. Direct-acting antiviral treatment can result in a virologic cure in most persons with 8-12 weeks of all-oral medication regimens. This report augments (i.e., updates and summarizes) previously published recommendations from CDC regarding testing for HCV infection in the United States (Smith BD, Morgan RL, Beckett GA, et al. Recommendations for the identification of chronic hepatitis C virus infection among persons born during 1945-1965. MMWR Recomm Rec 2012;61[No. RR-4]). CDC is augmenting previous guidance with two new recommendations: 1) hepatitis C screening at least once in a lifetime for all adults aged ≥18 years, except in settings where the prevalence of HCV infection is <0.1% and 2) hepatitis C screening for all pregnant women during each pregnancy, except in settings where the prevalence of HCV infection is <0.1%. The recommendation for HCV testing that remains unchanged is regardless of age or setting prevalence, all persons with risk factors should be tested for hepatitis C, with periodic testing while risk factors persist. Any person who requests hepatitis C testing should receive it, regardless of disclosure of risk, because many persons might be reluctant to disclose stigmatizing risks.
Diagnosis Rates of Chronic Hepatitis B in Privately Insured Patients in the United States
Authors: Eiichi Ogawa, Yee Hui Yeo, Nolan Dang, Michael H. Le, Donghak Jeong, Sally Tran, Linda Henry, Ramsey Cheung, Mindie H. Nguyen
Journal: JAMA Network Open (2020)

To achieve the World Health Organization goal of viral hepatitis elimination by 2030, it is important to estimate current rates of chronic hepatitis B (CHB) diagnosis and treatment.To provide an accurate accounting of the number of patients with CHB aged 6 years or older who have not yet been diagnosed in the United States.This cross-sectional study used the commercial US Truven Health MarketScan Database (138 634 154 privately insured individuals in January 2007 to December 2014) to identify patients with CHB diagnosis and the National Health and Nutrition Examination Survey to estimate the actual number of privately insured persons with CHB. Based on sex and age distribution derived from the US Census Bureau, we calculated the total population with CHB and the proportion of those who remained undiagnosed among the 198 073 302 privately insured individuals. Next, we identified diagnosed CHB patients who received 1 or more prescription for CHB medications to calculate the treatment rate for those with severe disease states, such as cirrhosis and hepatocellular carcinoma, that would warrant treatment. Analyses were performed from October 2017 to January 2020.The rate and number of patients with CHB who remained undiagnosed and treatment rates for patients with CHB who have cirrhosis or hepatocellular carcinoma.Among the 198 073 302 privately insured individuals (48.55% male; 15.52% aged 6-17 years; 84.48% aged ≥18 years), there were 511 029 (95% CI, 317 733-704 325) individuals with CHB, but only 95 075 of these had been diagnosed, yielding a diagnosis rate of only 18.60% (95% CI, 13.50%-29.92%), meaning that 81.40% (95% CI, 70.08%-86.50%) were undiagnosed. The treatment rates were 34.79% (95% CI, 33.31%-36.27%) for those with cirrhosis and 48.64% (95% CI, 45.59%-51.69%) for those with hepatocellular carcinoma.In this study, only approximately 1 in 5 privately insured patients with CHB had been diagnosed. Only one-third of patients with CHB who had cirrhosis and one-half who had hepatocellular carcinoma received antiviral therapy. Further efforts are needed to improve the current situation of poor connection to care for patients with CHB, especially for those with advanced liver disease.