tbuckley/cabot-search huggingface dataset:
Treating tuberculosis in low-resource settings: practice pragmatically
Authors: Xiaohui Sun, Najib M Rahman, Abdel Douiri
Journal: Thorax (2020)

Tuberculosis (TB) remains a long-standing life-threatening contagious disease and claimed approximately 1.5 million lives worldwide in 2018. Regional variations occur extensively with polarised incidence rates between low and high TB burden countries.1 TB is a social disease in partnership with poverty. TB burden fluctuates with the rises and falls of socioeconomic development despite the advancements in healthcare.2 Poverty-related components such as poor living conditions and malnutrition, which do not merely increase individual’s susceptibility to infection, but affect healthcare expenditure and loss of income associated with TB infection amplify the effect of poverty on TB treatment and prevention. Therefore, combating TB contributes to reducing impoverishment, meanwhile fighting impoverishment assists TB control efforts especially in restricted resource settings.3

A pragmatic …
Abstract P165: Comparing Grip Strength, Weakness, And Frailty Based On Comorbidity And Laboratory Data Among Patients With Cardiovascular Disease
Authors: Gloria Kim, Arati A Gangadharan, Matthew A Corriere
Journal: Circulation (2020)

Introduction: Some approaches to frailty screening use diagnostic or laboratory data that may be incomplete. Grip strength can identify weakness, a component of phenotype-based frailty assessment. We compared grip strength as a reductionist, phenotype-based approach to frailty screening with comorbidity and laboratory-based alternatives. Hypothesis: Grip strength and categorical weakness are correlated with the modified frailty index-5 (mFI-5) and lab values associated with frailty. Methods: Weakness based on grip, BMI, and gender was compared with mFI-5 comorbidities and lab values. Patients with at least 3/5 mFI-5 comorbidities were considered frail. Lab data collected within 6 months of grip measurement was assessed. Associations were evaluated using multivariable models and kappa. Methods: 2,597 patients had grip strength measured over 5 months. Mean age was 64.4±14.6, mean BMI was 29.5±6.9;46% were women, and 87% white. Prevalent comorbidities included hypertension (28%), CHF (22%), diabetes (29%), and COPD (26%); 9% were functionally dependent. 34% were weak, but only 13% were frail based on mFI-5. Hemoglobin, creatinine, and CRP differed significantly based on weakness ( Table ). Laboratory data were missing for 36%- 95% of patients. Multivariable models identified significant associations between weakness, hemoglobin, and all MFI-5 comorbidities. Categorical agreement between weakness and frailty was limited (kappa =0.09; 95% CL 0.0641-0.1232). Conclusion: Weakness based on grip strength provides a practical, inexpensive approach to risk assessment, especially when incomplete data excludes other approaches. Comorbidity-based assessment categorizes many weak patients as non-frail. Table. Demographic, laboratory values, and comorbidities by categorical weakness based on grip 20 th percentile. Mean values for continuous variables by weakness adjusted for gender and BMI, p-value for T-test; frequency and total percent for categorical variables, p-value represents chi-square test.
[18F]-Alfatide PET imaging of integrin αvβ3 for the non-invasive quantification of liver fibrosis
Authors: Tuo Shao, Zhen Chen, Vasily Belov, Xiaohong Wang, Steve H. Rwema, Viksit Kumar, Hualong Fu, Xiaoyun Deng, Jian Rong, Qingzhen Yu, Lixin Lang, Wenyu Lin, Lee Josephson, Anthony E. Samir, Xiaoyuan Chen, Raymond T. Chung, Steven H. Liang
Journal: Journal of Hepatology (2020)
Health groups criticise EU funded breast cancer screening study as a “missed opportunity”
Authors: Ingrid Torjesen
Journal: BMJ (2020)

Critics have branded an EU funded trial looking at the potential for personalised breast cancer screening “a missed opportunity” for failing to fully evaluate the benefits and harms of screening.

Four groups concerned about women’s health and human rights in research—the UK charity Healthwatch, Belgium’s Group de Recherche et d’Action pour la Sante, the Italian epidemiologists and scientists of No Grazie, and the French group Cancer Rose—identified problems with the EU funded My Personal Breast Screening (MyPeBS) trial, which aims to show non-inferiority to current national screening. Their criticisms are outlined in a letter in the Journal International de Medicine .1

MyPeBS involves 85 000 women aged 40 to 70 in Belgium, France, Israel, Italy, and the UK randomised to breast screening according to their personalised risk or to their national standard screening programme.

In the intervention group, women’s personal risk is estimated using factors such as breast density, genetic profile, personal and family history, and age. Those deemed low risk will receive a mammogram at the end of the study after four years while average …
SCOTCERV: A phase II trial of docetaxel and gemcitabine as second-line chemotherapy in cervical cancer
Authors: R. Symonds, S. Davidson, S. Chan, N. Reed, T. McMahon, J. Paul
Journal: Journal of Clinical Oncology (2007)

5548 Background: Concurrent Cisplatin chemotherapy along with radiotherapy is standard therapy for locally advanced cervical cancer. There is no established second line regimen. Taxanes and Gemcitabine are not thought to share drug resistance with Cisplatin. In combination they are reasonably tolerated; myelosuppression is the dose limiting toxicity. Response is more likely in recurrences outside the irradiated area. Methods: This was a multi-centre phase II trial of Docetaxel (75mg/m 2 d1) and Gemcitabine (1,000 mg/m 2 d1,d8) in relapsed patients (pts) after treatment with cisplatin alone or in combination (excluding with taxanes) and/or radiotherapy. A Gehan two-stage design was used (minimum response rate requirement 25%). Pts had to have disease assessable by RECIST outside the irradiated pelvis and adequate organ function. After 12 pts the Docetaxel dose was reduced to 60 mg/m 2 . Results: 26 eligible pts were recruited to the study; information is available currently for 24. The median age is 43 years (range 30–62) and the median time from prior treatment is 12 months (1–55). 23 pts had prior chemoradiotherapy. Performance status: 0 (15) or 1 (9). Histology: squamous 17, adenoCa (6) mixed (1). Major metastatic sites were lung (11) and para-aortic nodes (11). The principal toxicity was neutropenia (gd 3 (8), gd 4 (8)) with 4 pts experiencing grade 3 febrile neutropenia. Dose reductions occurred in 29% of pts (Docetaxel) and 25% of pts (Gemcitabine), primarily for neutropenic fever. Haematological toxicity resulted in d8 Gemcitabine being omitted in 41% of cycles. 1 patient had gd3 SOB and 1 patient gd 3 diarrhoea. Reduction of Docetaxel dose did not reduce haematological toxicity. 5 pts have not, as yet, had response reported. In 19 pts (16 completed therapy) there was 1 CR, 4 PR, 6 stable disease, 7 progressions and 1 unevaluable. The overall response rate is 26% (95% ci 9%-51%). Conclusions: This preliminary data shows this combination has activity against platinum resistant metastatic cervical cancer, although the ability to deliver d8 Gemcitabine is compromised. Final results will be available for the meeting. [Table: see text]
First heterozygous <i>NOP10</i> mutation in familial pulmonary fibrosis
Authors: Caroline Kannengiesser, Effrosyni D. Manali, Patrick Revy, Isabelle Callebaut, Ibrahima Ba, Adrien Borgel, Claire Oudin, Aggeliki Haritou, Lykourgos Kolilekas, Katerina Malagari, Raphael Borie, Elodie Lainey, Catherine Boileau, Bruno Crestani, Spyros A. Papiris
Journal: European Respiratory Journal (2020)

<b>We provide first evidence that a heterozygous <i>NOP10</i> mutation (c.17A&gt;G,p.Tyr6Cys) identified in a large family co-segregates with adult-onset familial PF and predisposes to short telomere syndrome (familial PF, liver, haematological diseases)</b>http://bit.ly/2wvXsUd
Abstract P222: Sex Moderates Treatment Effects in Integrated Behavior Therapy for Comorbid Obesity and Depression
Authors: Nan Lv, Lan Xiao, Lisa Goldman Rosas, Elizabeth Venditti, Mark Snowden, Megan Lewis, Leanne Williams, Joshua Smyth, Olusola Ajilore, Ben Gerber, Jun Ma
Journal: Circulation (2020)

Introduction: Obesity and depression often co-occur, especially in women. Efficacious treatments exist for both conditions, but treatment outcomes vary. Assessing sex-specific responses to integrated therapy of these conditions could inform opportunities for tailoring. Hypothesis: Sex will significantly moderate the effects of an integrated collaborative care intervention on weight loss and depression outcomes through 24 months. Short-term treatment response at 6 months will reliably predict 12- and 24-month outcomes by sex. Methods: We conducted secondary analyses using data from the RAINBOW trial, which demonstrated efficacy of an integrated collaborative care intervention at reducing weight (BMI) and depression severity (SCL-20) at 12 months relative to usual care in adults with obesity and depression. Linear mixed models were used to assess treatment effects by sex, an a priori hypothesized biological moderator, on BMI and SCL-20 at 6, 12, and 24 months. Areas under the receiver operating characteristic curves (AUCs) based on logistic regressions were used to assess sex-specific thresholds of weight loss (%) and SCL-20 reduction at 6 months that reliably predicted clinically significant weight loss (i.e., ≥5% of baseline weight) and depression response (i.e., ≥50% decrease in SCL-20 scores) at 12 and 24 months. Results: Sex significantly moderated the treatment effects on BMI and SCL-20. Compared with women, men achieved significantly greater reductions in BMI at 6, 12, and 24 months in the intervention relative to usual care. Compared with men, women achieved significantly greater reductions in SCL-20 at 12 months only in the intervention relative to usual care. AUCs in the logistic models were similar for both sexes: &gt;0.82 at 12 months and &gt;0.65 at 24 months predicting clinically significant weight loss; &gt;0.70 at 12 months and &gt;0.67 at 24 months predicting clinically significant depression response. With 80% specificity to ensure good probability of correctly identifying participants not achieving longer-term outcomes of clinical significance, women who lost 2.5-3.0% weight and men who lost 3.4-4.1% weight at 6 months were likely to achieve ≥5% weight loss at 12 and 24 months. Similarly, women who reduced SCL-20 by 0.70 and men who reduced by 0.60-0.65 were likely to achieve ≥50% decrease in SCL-20 at 12 and 24 months. Conclusions: The treatment effects of this integrated intervention for obesity and depression differed significantly by sex, with men showing greater weight loss and women showing greater depression reduction. Sex-specific short-term responses at 6 months were identified for predicting clinically significant weight loss and depression outcomes at 12 and 24 months. Results suggest that sex may be an important tailoring variable when designing collaborative care interventions.
Abstract P537: Reduced Cardiovascular Regenerative Capacity is Associated With Enhanced Inflammatory Response to Acute Psychological Stress
Authors: Zakaria Almuwaqqat, Jeong Hwan Kim, Muhammad Hammadah, Shabatun Islam, Bruno B Lima, Iraj Hesaroieh, Ali Mokhtari, OLEKSIY LEVANTSEVYCH, Kiran Ejaz, Amit J Shah, J Douglas Bremner, Edmund Waller, Viola Vaccarino, Arshed A QUYYUMI
Journal: Circulation (2020)

Background: Bone marrow-derived progenitor cells (PCs) are involved in vascular regeneration and correlate with vascular function and cumulative cardiovascular risk. Systemic inflammation is associated with increased mobilization and differentiation of circulating PCs (CPCs) which may ultimately lead to exhaustion of vascular regenerative capacity. Individuals with coronary artery disease (CAD) exhibit a pro-inflammatory response to a mental stress challenge that has been associated with an elevated risk of adverse outcomes. We sought to determine whether subjects with reduced numbers of circulating PCs (CPCs) are at higher risk of a pro-inflammatory response to acute mental stress. Methods: 500 outpatients with stable CAD were enrolled into the Mental Stress Ischemia Prognosis study and underwent a laboratory-based mental stress protocol. Mononuclear cells expressing CD45med, CD34 and CXCR4 epitopes, known to be enriched for hematopoietic PCs, were enumerated using flow cytometry. Interleukin-6 (IL6) and C-Reactive Protein (CRP) levels were measured before and after mental stress. Baseline and changes in IL6 levels were compared across CPC tertiles using linear regression after adjusting for patient characteristics. Results: Mean age was 63± 9 years, 77% male, 70% white. Median CD34+ CPC count was 1.64 (1.02-2.43 cells/μL. CPC levels were not associated with either the baseline IL6 level (Beta= 0.071 95%CI, -0.091, 0.23) or CRP levels (Beta, 0.60, 95%CI, -0.25, 0.44). However, independent of demographics, CAD risk factors and baseline IL6 levels, lower CD34+/CXCR4+ CPC counts were associated with a higher inflammatory response during mental stress, measured as a rise in IL6 level (Beta= -0.11, 95%CI, -0.20, -0.028). Conclusions: Patients with reduced CPC levels have a greater pro-inflammatory response to mental stress. Thus, the observed higher risk in subjects with impaired regenerative capacity might be at least partly due to a higher stress-related pro-inflammatory response.
mRNA modification orchestrates cancer stem cell fate decisions
Authors: Weicheng Liang, Zexiao Lin, Cong Du, Dongbo Qiu, Qi Zhang
Journal: Molecular Cancer (2020)

Abstract Despite their small numbers, cancer stem cells play a central role in driving cancer cell growth, chemotherapeutic resistance, and distal metastasis. Previous studies mainly focused on how DNA or histone modification determines cell fate in cancer. However, it is still largely unknown how RNA modifications orchestrate cancer cell fate decisions. More than 170 distinct RNA modifications have been identified in the RNA world, while only a few RNA base modifications have been found in mRNA. Growing evidence indicates that three mRNA modifications, inosine, 5-methylcytosine, and N 6 -methyladenosine, are essential for the regulation of spatiotemporal gene expression during cancer stem cell fate transition. Furthermore, transcriptome-wide mapping has found that the aberrant deposition of mRNA modification, which can disrupt the gene regulatory network and lead to uncontrollable cancer cell growth, is widespread across different cancers. In this review, we try to summarize the recent advances of these three mRNA modifications in maintaining the stemness of cancer stem cells and discuss the underlying molecular mechanisms, which will shed light on the development of novel therapeutic approaches for eradicating cancer stem cells.
Audit of excisional breast biopsies in a Nigeria teaching hospital
Authors: C. A. Adisa
Journal: Journal of Clinical Oncology (2007)

1553 Background: Excision biopsy is an accurate method for diagnosis of breast tumors especially where facilities for needle biopsies like tru cut needle biopsy or aspiration cytology method are not readily available. We report a 10-year prospective study of the clinical and pathological characteristics of excised breast masses in our centre. Methods: Clinical records and pathological results of all excised breast masses of consecutive patients referred to the Breast Clinic of the Abia State University Teaching Hospital, Aba, Nigeria were studied from January 1994 to December 2003. We present the outcome of the histology reports from breast biopsy for a period of 10 years (1994–2003) in Abia State University Teaching Hospital. Results: A total of 421 patients had breast masses excised. The age ranged from 12 years to 80 years. 79% of the patients with cancer of the breast were 50 years old or younger and the youngest patient was 14 years. Malignancies were discovered in 24% of the cases and the predominant histological type was infiltrating ductal carcinoma (NOS). 79% of the breast cancers occur in pre menopausal women and the majorities (85%) were late stages. Conclusions: Majority of breast masses in Nigerian women are benign. The preponderance of late staged tumors and pre menopausal patients call for early detection, public awareness and improved screening methods. No significant financial relationships to disclose.
Abstract P503: Continuous Diurnal Patterns of Atrial Fibrillation Onset by Chronic Kidney Disease Status: The Atherosclerosis Risk in Communities (aric) Study
Authors: Esther Kim, Vadim Zipunnikov, Elsayed Z Soliman, Josef Coresh, Kunihiro Matsushita, Lin Y Chen
Journal: Circulation (2020)

Background: Chronic kidney disease (CKD) is associated with atrial fibrillation (AF); however, most studies have looked at its presence or occurrence as a dichotomous outcome, and diurnal patterns of AF by CKD status have not yet been characterized. Methods: Of 2257 adults (71-94 years) who underwent 2 weeks of non-invasive continuous heart rhythm monitoring using the Zio XT Patch, we examined 61 participants with paroxysmal AF and characterized the probability of AF onset over the course of 24 hours using a generalized function-on-scalar regression model. CKD status was defined using eGFR and albuminuria. Results: The median device wear-time was 13.7 (12.6, 13.9) days, and the majority (57%) had CKD. In non-CKD, the probability of AF onset fluctuated over 24 hours with two nadir periods occurring in late morning (~10am) and late evening (~10pm), and somewhat prominent peaks occurring in early morning (~8am) and early evening (~6pm) [figure] . Overall, CKD had a higher probability of AF compared to non-CKD. CKD also demonstrated a less pronounced nadir in late evening, and was significantly more likely to experience AF during this time (OR 2.80; 95% CI 1.05, 11.94) compared to non-CKD. This observation was consistent even after adjusting for various potential confounders such as age, sex, race, diabetes, and a history of cardiovascular disease. Conclusion: Based on 2-week monitoring, AF onset seems to exhibit a diurnal pattern throughout the day with peaks in the early morning and evening, and nadir in late morning and evening. Compared to those without CKD, those with CKD are more likely to experience AF in late evening, suggesting a potential high-risk time window for monitoring. Further studies are needed to evaluate prognostic value of AF diurnal patterns.
AB0078 Pulse methylprednisolone and cyclophosphamide therapy in three systemic lupus erythematosus patients with bronchiolitis obliterans organising pneumonia as the initial manifestation
Authors: JC Tseng, HH Cheng, RJ Hu, LY Lu
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Diverse pleuropulmonary manifestations are common in patients with systemic lupus erythematosus (SLE). Bronchiolitis obliterans organising pneumonia (BOOP) is a pathologic entity characterised by the formation of fibrous plugs within terminal bronchioles and alveolar ducts. Although BOOP has been associated with several connective tissue disorders, there are rare reports of BOOP in patients with SLE as the initial manifestation. <h3>Objectives</h3> We describe three SLE patients with open lung biopsy-proved BOOP as the initial manifestation. <h3>Methods</h3> All three cases presented with acute/subacute chest symptoms of fever, cough and dyspnea. Chest radiographs and CT scan of lung revealed bilateral pulmonary infiltrates. BOOP was confirmed by open lung biopsy. Pulmonary vasculitis was also demonstrated in lung histopathology in one case. The pulmonary lesions and respiratory illnesses responded to pulse intravenous methylprednisolone and cyclophosphamide therapy. <h3>Results</h3> <h3>Conclusion</h3> <h3>References</h3> Otsuka F, Amano T, Hashimoto N, Takahashi M, Hayakawa N, Makino H, Ota Z, Ogura T. Bronchiolitis obliterans organizing peumonia associated with systemic lupus erythematosus with antiphospholipid antibody. Intern Med. 1996;35(4):341–4 Imasaki T, Yoshii A, Tanaka S, Ogura T, Ishikawa A, Takahashi T. Polymyositis and Sjogren's syndrome associated with bronchiolitis obliterans organizing pneumonia. Intern Med. 1996;35(3):231–5 Min JK, Hong YS, Park SH, Park JH, Lee SH, Lee YS, Kim HH, Cho CS, Kim HY. Bronchiolitis obliterans organizing pneumonia as an initial manifestation with systemic lupus erythematosus. J Rheumatol. 1997;24(11):2254–7 Shinohara T, Hidaka T, Matsuki Y, Ishizuka T, Takamizawa M, Kawakami M, Kikuma H. Rapidly progressive interstitial lung disease associated with dermatomyositis responding to intravenous cyclophosphamide pulse therapy. Intern Med. 1997;36(7):519–23
Prediction of stress and drug craving ninety minutes in the future with passively collected GPS data
Authors: David H. Epstein, Matthew Tyburski, William J. Kowalczyk, Albert J. Burgess-Hull, Karran A. Phillips, Brenda L. Curtis, Kenzie L. Preston
Journal: npj Digital Medicine (2020)

Abstract Just-in-time adaptive interventions (JITAIs), typically smartphone apps, learn to deliver therapeutic content when users need it. The challenge is to “push” content at algorithmically chosen moments without making users trigger it with effortful input. We trained a randomForest algorithm to predict heroin craving, cocaine craving, or stress (reported via smartphone app 3x/day) 90 min into the future, using 16 weeks of field data from 189 outpatients being treated for opioid-use disorder. We used only one form of continuous input (along with person-level demographic data), collected passively: an indicator of environmental exposures along the past 5 h of movement, as assessed by GPS. Our models achieved excellent overall accuracy—as high as 0.93 by the end of 16 weeks of tailoring—but this was driven mostly by correct predictions of absence. For predictions of presence, “believability” (positive predictive value, PPV) usually peaked in the high 0.70s toward the end of the 16 weeks. When the prediction target was more rare, PPV was lower. Our findings complement those of other investigators who use machine learning with more broadly based “digital phenotyping” inputs to predict or detect mental and behavioral events. When target events are comparatively subtle, like stress or drug craving, accurate detection or prediction probably needs effortful input from users, not passive monitoring alone. We discuss ways in which accuracy is difficult to achieve or even assess, and warn that high overall accuracy (including high specificity) can mask the abundance of false alarms that low PPV reveals.