tbuckley/cabot-search huggingface dataset:
Additional Barriers to Methadone Use in Hospitals and Skilled Nursing Facilities—Reply
Authors: Jarratt D. Pytell, Joshua M. Sharfstein, Yngvild Olsen
Journal: JAMA Internal Medicine (2020)

In Reply Starting January 1, 2020, as a result of the 2018 Substance Use-Disorder Prevention that Promotes Opioid Recovery and Treatment for Patients and Communities Act, Medicare Part B has provided a bundled payment for opioid addiction treatment in an opioid treatment program.1
Evaluation of the Effectiveness and Tolerability of Mycophenolate Mofetil and Mycophenolic Acid for the Treatment of Morphea
Authors: Megan Arthur, Nicole M. Fett, Emile Latour, Heidi Jacobe, Elaine Kunzler, Stephanie Florez-Pollack, Jacob Houser, Shivani Sharma, Smriti Prasad, Alisa Femia, Marleigh J. Stern, Lisa K. Pappas-Taffer, Rebecca Gaffney, Anthony P. Fernandez, Daniel Knabel, Adela Rambi Cardones, Nicole Leung, Anne Laumann, Jeong Min Yu, Jeffrey Zhao, Ruth Ann Vleugels, Elizabeth Tkachenko, Kelly Lo
Journal: JAMA Dermatology (2020)

<h3>Importance</h3> First-line systemic therapy for morphea includes methotrexate with or without systemic corticosteroids. When this regimen is ineffective, not tolerated, or contraindicated, a trial of mycophenolate mofetil (MMF) or mycophenolic acid (MPA)—referred to herein as<i>mycophenolate</i>—is recommended; however, evidence to support this recommendation remains weak. <h3>Objective</h3> To evaluate the effectiveness and tolerability of mycophenolate for the treatment of morphea. <h3>Design, Setting, and Participants</h3> A retrospective cohort study was conducted from January 1, 1999, to December 31, 2018, among 77 patients with morphea from 8 institutions who were treated with mycophenolate. <h3>Main Outcomes and Measures</h3> The primary outcome was morphea disease activity, severity, and response at 0, 3 to 6, and 9 to 12 months of mycophenolate treatment. A secondary outcome was whether mycophenolate was a well-tolerated treatment of morphea. <h3>Results</h3> There were 61 female patients (79%) and 16 male patients (21%) in the study, with a median age at disease onset of 36 years (interquartile range, 16-53 years) and median diagnostic delay of 8 months (interquartile range, 4-14 months). Generalized morphea (37 [48%]), pansclerotic morphea (12 [16%]), and linear morphea of the trunk and/or extremities (9 [12%]) were the most common subtypes of morphea identified. Forty-one patients (53%) had an associated functional impairment, and 49 patients (64%) had severe disease. Twelve patients received initial treatment with mycophenolate as monotherapy or combination therapy and 65 patients received mycophenolate after prior treatment was ineffective (50 of 65 [77%]) or poorly tolerated (21 of 65 [32%]). Treatments prior to mycophenolate included methotrexate (48 of 65 [74%]), systemic corticosteroids (42 of 65 [65%]), hydroxychloroquine (20 of 65 [31%]), and/or phototherapy (14 of 65 [22%]). After 3 to 6 months of mycophenolate treatment, 66 of 73 patients had stable (n = 22) or improved (n = 44) disease. After 9 to 12 months of treatment, 47 of 54 patients had stable (n = 14) or improved (n = 33) disease. Twenty-seven patients (35%) achieved disease remission at completion of the study. Treatments received in conjunction with mycophenolate were frequent. Mycophenolate was well tolerated. Gastrointestinal adverse effects were the most common (24 [31%]); cytopenia (3 [4%]) and infection (2 [3%]) occurred less frequently. <h3>Conclusions and Relevance</h3> This study suggests that mycophenolate is a well-tolerated and beneficial treatment of recalcitrant, severe morphea.
Human behavior, not race or geography, is the strongest predictor of microbial succession in the gut bacteriome of infants
Authors: Candice Quin, Deanna L. Gibson
Journal: Gut Microbes (2020)

Colonization of the gastrointestinal tract with microorganisms during infancy represents a critical control point for shaping life-long immune-mediated disease susceptibility. Abnormal colonization or an imbalance of microbes, termed dysbiosis, is implicated in several diseases. Consequently, recent research has aimed at understanding ways to manipulate a dysbiotic microbiome during infancy to resemble a normal, healthy microbiome. However, one of the fundamental issues in microbiome research is characterizing what a "normal" infant microbiome is based on geography, ethnicity and cultural variations. This review provides a comprehensive account of what is currently known about the infant microbiome from a global context. In general, this review shows that the influence of cultural variations in feeding practices, delivery modes and hygiene are the biggest contributors to microbial variability. Despite geography or race, all humans have similar microbial succession during infancy.
Chest pain: heart or gullet?
Journal: BMJ (1983)

What, then, are our duties towards insulin dependent diabetic patients in relation to home blood glucose monitoring ?Doctors' attitudes will vary, but all patients should be made aware of the technique and, if interested, be given or loaned equipment for a trial period.Those choosing to continue will need further guidance.The choice between a reflectance meter and strips suitable for direct visual reading is an individual one, but whichever method is used the patient's competence should be assessed.There are sources of potential error,21 and repeat checking of technique and accuracy is necessary.Patients will tire quickly of producing large numbers of results if they do not understand or are not told how to use them, so arrangements are needed for individual follow up by a physician.The results may point towards the need for radical changes in insulin treatment, and if these are not undertaken monitoring becomes no more than a record of poor control.All this means that if more patients are to use self monitoring effectively, demands on staff time will increase and efficient schemes will be needed for the education of patients.The emergence of the specialist nursing teacher is a step forward, but all those concerned with diabetic patient care, including family practitioners, can play a part by becoming familiar with self monitoring techniques.What, finally, are the financial implications for patients and the National Health Service ?Reflectance meters cost around £80 and strips retail at about 26p each (NHS cost about 15p each).Blood monitoring equipment is not available on pre- scription, and though some patients receive supplies through hospital pharmacies others bear the full cost.If we believe that near normal blood glucose concentrations are desirable, it seems illogical to provide on prescription urine testing apparatus which, though cheaper, can detect only frank hyperglycaemia and to penalise those who prefer to use blood testing.And, in balancing the costs with the advantages of blood glucose monitoring, we must be aware of patient preferences and needs, which arei not reflected in objective indicators of control.
Aberrant gut microbiota alters host metabolome and impacts renal failure in humans and rodents
Authors: Xifan Wang, Songtao Yang, Shenghui Li, Liang Zhao, Yanling Hao, Junjie Qin, Lian Zhang, Chengying Zhang, Weijing Bian, Li Zuo, Xiu Gao, Baoli Zhu, Xin Gen Lei, Zhenglong Gu, Wei Cui, Xiping Xu, Zhiming Li, Benzhong Zhu, Yuan Li, Shangwu Chen, Huiyuan Guo, Hao Zhang, Jing Sun, Ming Zhang, Yan Hui, Xiaolin Zhang, Xiaoxue Liu, Bowen Sun, Longjiao Wang, Qinglu Qiu, Yuchan Zhang, Xingqi Li, Weiqian Liu, Rui Xue, Hong Wu, DongHua Shao, Junling Li, Yuanjie Zhou, Shaochuan Li, Rentao Yang, Oluf Borbye Pedersen, Zhengquan Yu, Stanislav Dusko Ehrlich, Fazheng Ren
Journal: Gut (2020)

Objective Patients with renal failure suffer from symptoms caused by uraemic toxins, possibly of gut microbial origin, as deduced from studies in animals. The aim of the study is to characterise relationships between the intestinal microbiome composition, uraemic toxins and renal failure symptoms in human end-stage renal disease (ESRD). Design Characterisation of gut microbiome, serum and faecal metabolome and human phenotypes in a cohort of 223 patients with ESRD and 69 healthy controls. Multidimensional data integration to reveal links between these datasets and the use of chronic kidney disease (CKD) rodent models to test the effects of intestinal microbiome on toxin accumulation and disease severity. Results A group of microbial species enriched in ESRD correlates tightly to patient clinical variables and encode functions involved in toxin and secondary bile acids synthesis; the relative abundance of the microbial functions correlates with the serum or faecal concentrations of these metabolites. Microbiota from patients transplanted to renal injured germ-free mice or antibiotic-treated rats induce higher production of serum uraemic toxins and aggravated renal fibrosis and oxidative stress more than microbiota from controls. Two of the species, Eggerthella lenta and Fusobacterium nucleatum , increase uraemic toxins production and promote renal disease development in a CKD rat model. A probiotic Bifidobacterium animalis decreases abundance of these species, reduces levels of toxins and the severity of the disease in rats. Conclusion Aberrant gut microbiota in patients with ESRD sculpts a detrimental metabolome aggravating clinical outcomes, suggesting that the gut microbiota will be a promising target for diminishing uraemic toxicity in those patients. Trial registration number This study was registered at ClinicalTrials.gov ( NCT03010696 ).
Metastatic Melanoma Patient–Derived Xenografts Respond to MDM2 Inhibition as a Single Agent or in Combination with BRAF/MEK Inhibition
Authors: Rebecca L. Shattuck-Brandt, Sheau-Chiann Chen, Emily Murray, Christopher Andrew Johnson, Holly Crandall, Jamye F. O'Neal, Rami Nayef Al-Rohil, Caroline A. Nebhan, Vijaya Bharti, Kimberly B. Dahlman, Gregory D. Ayers, Chi Yan, Mark C. Kelley, Rondi M. Kauffmann, Mary Hooks, Ana Grau, Douglas B. Johnson, Anna E. Vilgelm, Ann Richmond
Journal: Clinical Cancer Research (2020)

Abstract Purpose: Over 60% of patients with melanoma respond to immune checkpoint inhibitor (ICI) therapy, but many subsequently progress on these therapies. Second-line targeted therapy is based on BRAF mutation status, but no available agents are available for NRAS, NF1, CDKN2A, PTEN, and TP53 mutations. Over 70% of melanoma tumors have activation of the MAPK pathway due to BRAF or NRAS mutations, while loss or mutation of CDKN2A occurs in approximately 40% of melanomas, resulting in unregulated MDM2-mediated ubiquitination and degradation of p53. Here, we investigated the therapeutic efficacy of over-riding MDM2-mediated degradation of p53 in melanoma with an MDM2 inhibitor that interrupts MDM2 ubiquitination of p53, treating tumor-bearing mice with the MDM2 inhibitor alone or combined with MAPK-targeted therapy. Experimental Design: To characterize the ability of the MDM2 antagonist, KRT-232, to inhibit tumor growth, we established patient-derived xenografts (PDX) from 15 patients with melanoma. Mice were treated with KRT-232 or a combination with BRAF and/or MEK inhibitors. Tumor growth, gene mutation status, as well as protein and protein–phosphoprotein changes, were analyzed. Results: One-hundred percent of the 15 PDX tumors exhibited significant growth inhibition either in response to KRT-232 alone or in combination with BRAF and/or MEK inhibitors. Only BRAFV600WT tumors responded to KRT-232 treatment alone while BRAFV600E/M PDXs exhibited a synergistic response to the combination of KRT-232 and BRAF/MEK inhibitors. Conclusions: KRT-232 is an effective therapy for the treatment of either BRAFWT or PANWT (BRAFWT, NRASWT) TP53WT melanomas. In combination with BRAF and/or MEK inhibitors, KRT-232 may be an effective treatment strategy for BRAFV600-mutant tumors.
Rammya Mathew: Professionalism in a time of crisis
Authors: Rammya Mathew
Journal: BMJ (2020)

In recent years doctors have been accused of lacking professionalism, and many of us have suffered with self-doubt as a result. Now, however, our NHS workforce is witnessing a global pandemic on a scale we haven’t experienced before. We’ve had to plan at length, reorganise structures, and redeploy our staff to ensure that we’re as prepared as we can be for the coming weeks and months.

None of this has happened without effort. I see colleagues all around me giving everything they’ve got, often working 20 hour days and making many personal sacrifices to make this …
Engineering Approaches for Addressing Opioid Use Disorder in the Community
Authors: Paul M. Griffin
Journal: Annual Review of Biomedical Engineering (2020)

Many communities in the United States are struggling to deal with the negative consequences of illicit opioid use. Effectively addressing this epidemic requires the coordination and support of community stakeholders in a change process with common goals and objectives, continuous engagement with individuals with opioid use disorder (OUD) through their treatment and recovery journeys, application of systems engineering principles to drive process change and sustain it, and use of a formal evaluation process to support a learning community that continuously adapts. This review presents strategies to improve OUD treatment and recovery with a focus on engineering approaches grounded in systems thinking.
Crizotinib in <i>ROS1</i> and <i>MET</i> Deregulated NSCLC—Response
Authors: Lorenza Landi, Rossella Bruno, Gabriella Fontanini, Federico Cappuzzo
Journal: Clinical Cancer Research (2020)

We thank the authors for their interest in our study and for their comments. Wiesweg and colleagues correctly reported that the minor allele frequency of both p.T1010I and p.R988C MET variants is close to 1% in the European population, but these mutations were described also as somatic (T1010I:
Practice of endoscopy during COVID-19 pandemic: position statements of the Asian Pacific Society for Digestive Endoscopy (APSDE-COVID statements)
Authors: Philip Wai Yan Chiu, Siew C Ng, Haruhiro Inoue, D Nageshwar Reddy, Enqiang Ling Hu, Joo Young Cho, Lawrence KY Ho, David G Hewett, Han-Mo Chiu, Rungsun Rerknimitr, Hsiu-Po Wang, Shiaw Hooi Ho, Dong Wan Seo, Khean-Lee Goh, Hisao Tajiri, Seigo Kitano, Francis K L Chan
Journal: Gut (2020)

Coronavirus-19 (COVID-19) caused by SARS-CoV-2 has become a global pandemic. Risk of transmission may occur during endoscopy and the goal is to prevent infection among healthcare professionals while providing essential services to patients. Asia was the first continent to have a COVID-19 outbreak, and this position statement of the Asian Pacific Society for Digestive Endoscopy shares our successful experience in maintaining safe and high-quality endoscopy practice at a time when resources are limited. Sixteen experts from key societies of digestive endoscopy in Asia were invited to develop position statements, including patient triage and risk assessment before endoscopy, resource prioritisation and allocation, regular monitoring of personal protective equipment, infection control measures, protective device training and implementation of a strategy for stepwise resumption of endoscopy services after control of the COVID-19 outbreak.
Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a population-based cohort study
Authors: Fang-Xiao Zhu, Jing-Yang Huang, Zhizhong Ye, Qing-Qing Wen, James Cheng-Chung Wei
Journal: Annals of the Rheumatic Diseases (2020)

Idiopathic thrombocytopenic purpura (ITP) may play a role in early-stage systemic lupus erythematosus (SLE). The incidence of SLE in patients with ITP and the potential relationship between them is still unclear. This study was performed to provide epidemiological evidence regarding the relationship between ITP and SLE occurrence.In this population-based retrospective cohort study, the risk of SLE was analysed in a cohort of patients newly diagnosed with ITP between 2000 and 2013. Controls were selected at a 1:2 ratio through propensity score matching (PSM) using the greedy algorithm. The Cox proportional hazard model was used to analyse the association between ITP and SLE incidence. There were four different Cox regression models, and the sensitivity analyses were implemented to evaluate the HR of SLE after exposure with ITP.In the age-matched and sex-matched ITP and non-ITP cohort, the average follow-up time was about 80 months in this study. There were 34 (4.70%) and 27 (0.19%) incident cases of SLE in ITP and non-ITP group. The incidence rates were 62.0 (95% CI 44.3 to 86.8) and 2.10 (95% CI 1.44 to 3.06), respectively. The adjusted HR of incidental SLE in the ITP group was 25.1 (95% CI 13.7 to 46.0). The other risk factors for SLE were female sex and Sjogren's syndrome. After PSM, the incidence rate and Kaplan-Meir curves of SLE were consistent with the results for the age-matched and sex-matched population, the HR 17.4 (95% CI 5.28 to 57.4) was estimated by conditional Cox model.This cohort study demonstrated that patients with ITP have a higher risk of SLE. Clinically, patients with ITP should be monitored for incidental lupus.
Tuberculosis and HIV responses threatened by COVID-19
Authors: Paul Adepoju
Journal: The Lancet HIV (2020)

Tuberculosis and HIV responses threatened by COVID-19As the first cases of COVID-19 affect Nigeria's health-care workers, will the country's HIV and tuberculosis responses weather the pandemic?Paul Adepoju reports.March 24, 2020, was World Tuberculosis Day 2020, but this year tuberculosis was overshadowed by the COVID-19 pandemic.By the end of that week, COVID-19 had already exceeded 600 000 confirmed cases and about 30 000 deaths worldwide.Before the
The large GTPase Rab44 regulates granule exocytosis in mast cells and IgE-mediated anaphylaxis
Authors: Tomoko Kadowaki, Yu Yamaguchi, Mizuho A. Kido, Takaya Abe, Kohei Ogawa, Mitsuko Tokuhisa, Weiqi Gao, Kuniaki Okamoto, Hiroshi Kiyonari, Takayuki Tsukuba
Journal: Cellular and Molecular Immunology (2020)
Understanding heterogeneity of fetal hemoglobin induction through comparative analysis of F and A erythroblasts
Authors: Eugene Khandros, Peng Huang, Scott A. Peslak, Malini Sharma, Osheiza Abdulmalik, Belinda M. Giardine, Zhe Zhang, Cheryl A. Keller, Ross C. Hardison, Gerd A. Blobel
Journal: Blood (2020)
Unsaturated polyurethane films grafted with enantiomeric polylysine promotes macrophage polarization to a M2 phenotype through PI3K/Akt1/mTOR axis
Authors: Yiyuan Duan, Honghao Zheng, Zehua Li, Yuejun Yao, Jie Ding, Xuemei Wang, Jayachandra Reddy Nakkala, Deteng Zhang, Zhaoyi Wang, Xingang Zuo, Xiaowen Zheng, Jun Ling, Changyou Gao
Journal: Biomaterials (2020)
Phase I Trial of Trametinib with Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer
Authors: Christina Wu, Terence M. Williams, Ryan Robb, Amy Webb, Lai Wei, Wei Chen, Sameh Mikhail, Kristen K. Ciombor, Dana B. Cardin, Cynthia Timmers, Somashekar G. Krishna, Mark Arnold, Alan Harzman, Sherif Abdel-Misih, Sameek Roychowdhury, Tanios Bekaii-Saab, Evan Wuthrick
Journal: Clinical Cancer Research (2020)

The RAS/RAF/MEK/ERK signaling pathway is critical to the development of colorectal cancers, and KRAS, NRAS, and BRAF mutations foster resistance to radiation. We performed a phase I trial to determine the safety of trametinib, a potent MEK1/2 inhibitor, with 5-fluorouracil (5-FU) chemoradiation therapy (CRT) in patients with locally advanced rectal cancer (LARC).Patients with stage II/III rectal cancer were enrolled on a phase I study with 3+3 study design, with an expansion cohort of 9 patients at the MTD. Following a 5-day trametinib lead-in, with pre- and posttreatment tumor biopsies, patients received trametinib and CRT, surgery, and adjuvant chemotherapy. Trametinib was given orally daily at 3 dose levels: 0.5 mg, 1 mg, and 2 mg. CRT consisted of infusional 5-FU 225 mg/m2/day and radiation dose of 28 daily fractions of 1.8 Gy (total 50.4 Gy). The primary endpoint was to identify the MTD and recommended phase II dose. IHC staining for phosphorylated ERK (pERK) and genomic profiling was performed on the tumor samples.Patients were enrolled to all dose levels, and 18 patients were evaluable for toxicities and responses. Treatment was well tolerated, and there was one dose-limiting toxicity of diarrhea, which was attributed to CRT rather than trametinib. At the 2 mg dose level, 25% had pathologic complete response. IHC staining confirmed dose-dependent decrease in pERK with increasing trametinib doses.The combination of trametinib with 5-FU CRT is safe and well tolerated, and may warrant additional study in a phase II trial, perhaps in a RAS/RAF-mutant selected population.
Basolateral Amygdala Drives a GPCR-Mediated Striatal Memory Necessary for Predictive Learning to Influence Choice
Authors: Ashleigh K. Morse, Beatrice K. Leung, Emily Heath, Jesus Bertran-Gonzalez, Elise Pepin, Billy C. Chieng, Bernard W. Balleine, Vincent Laurent
Journal: Neuron (2020)
Outcome of patients with Fanconi anemia developing myelodysplasia and acute leukemia who received allogeneic hematopoietic stem cell transplantation: A retrospective analysis on behalf of <scp>EBMT</scp> group
Authors: Stefano Giardino, Regis P. de Latour, Mahmoud Aljurf, Dirk‐Jan Eikema, Paul Bosman, Yves Bertrand, Abdelghani Tbakhi, Wolfgang Holter, Martin Bornhäuser, Claudia Rössig, Birgit Burkhardt, Marco Zecca, Boris Afanasyev, Gerard Michel, Arnold Ganser, Amal Alseraihy, Mouhab Ayas, Duygu Uckan‐Cetinkaya, Benedicte Bruno, Katharine Patrick, Peter Bader, Maija Itälä‐Remes, Vanderson Rocha, Charlotte Jubert, Miguel A. Diaz, Peter J. Shaw, Luiz G. D. Junior, Franco Locatelli, Nicolaus Kröger, Maura Faraci, Filomena Pierri, Edoardo Lanino, Maurizio Miano, Antonio Risitano, Marie Robin, Carlo Dufour
Journal: American Journal of Hematology (2020)

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is curative for bone marrow failure in patients with Fanconi anemia (FA), but the presence of a malignant transformation is associated with a poor prognosis and the management of these patients is still challenging. We analyzed outcome of 74 FA patients with a diagnosis of myelodysplastic syndrome (n = 35), acute leukemia (n = 35) or with cytogenetic abnormalities (n = 4), who underwent allo-HSCT from 1999 to 2016 in EBMT network. Type of diagnosis, pre-HSCT cytoreductive therapies and related toxicities, disease status pre-HSCT, donor type, and conditioning regimen were considered as main variables potentially influencing outcome. The 5-year OS and EFS were 42% (30-53%) and 39% (27-51%), respectively. Patients transplanted in CR showed better OS compared with those transplanted in presence of an active malignant disease (OS:71%[48-95] vs 37% [24-50],P = .04), while none of the other variables considered had an impact. Twenty-two patients received pre-HSCT cytoreduction and 9/22 showed a grade 3-4 toxicity, without any lethal event or negative influence on survival after HSCT(OS:toxicity pre-HSCT 48% [20-75%] vs no-toxicity 51% [25-78%],P = .98). The cumulative incidence of day-100 grade II-IV a-GvHD and of 5-year c-GvHD were 38% (26-50%) and 40% (28-52%). Non-relapse-related mortality and incidence of relapse at 5-years were 40% (29-52%) and 21% (11-30%) respectively, without any significant impact of the tested variables. Causes of death were transplant-related events in most patients (34 out of the 42 deaths, 81%). This analysis confirms the poor outcome of transformed FA patients and identifies the importance of achieving CR pre-HSCT, suggesting that, in a newly diagnosed transformed FA patient, a cytoreductive approach pre-HSCT should be considered if a donor have been secured.
Antibiotics Do Not Reduce Length of Hospital Stay for Uncomplicated Diverticulitis in a Pragmatic Double-Blind Randomized Trial
Authors: Rebekah Jaung, Sherry Nisbet, Martijn Pieter Gosselink, Angelina Di Re, Celia Keane, Anthony Lin, Tony Milne, Bruce Su’a, Siraj Rajaratnam, Grahame Ctercteko, Li Hsee, David Rowbotham, Andrew Hill, Ian Bissett
Journal: Clinical Gastroenterology and Hepatology (2020)