tbuckley/cabot-search huggingface dataset:
Empirical Anti-MRSA vs Standard Antibiotic Therapy and Risk of 30-Day Mortality in Patients Hospitalized for Pneumonia
Authors: Barbara Ellen Jones, Jian Ying, Vanessa Stevens, Candace Haroldsen, Tao He, McKenna Nevers, Matthew A. Christensen, Richard E. Nelson, Gregory J. Stoddard, Brian C. Sauer, Peter M. Yarbrough, Makoto M. Jones, Matthew Bidwell Goetz, Tom Greene, Matthew H. Samore
Journal: JAMA Internal Medicine (2020)

Use of empirical broad-spectrum antibiotics for pneumonia has increased owing to concern for resistant organisms, including methicillin-resistant Staphylococcus aureus (MRSA). The association of empirical anti-MRSA therapy with outcomes among patients with pneumonia is unknown, even for high-risk patients.
Inequalities in 2020: time for a health strategy that unites the country
Authors: Michael Craig Watson, Patricia Owen
Journal: BMJ (2020)

Peter English is right to stress the importance of tackling the ubiquitous problem of inequalities and to highlight interventions that could make a significant improvement to the country’s health.1 A wealth of evidence linking deprivation with poor health has now accumulated and the excellent Lancet study adds further weight to this research.2

Doctors, nurses, and health visitors have considerable roles to play …
Thalamus Modulates Consciousness via Layer-Specific Control of Cortex
Authors: Michelle J. Redinbaugh, Jessica M. Phillips, Niranjan A. Kambi, Sounak Mohanta, Samantha Andryk, Gaven L. Dooley, Mohsen Afrasiabi, Aeyal Raz, Yuri B. Saalmann
Journal: Neuron (2020)
An Emerging Paradigm for Germline Testing in Pancreatic Ductal Adenocarcinoma and Immediate Implications for Clinical Practice
Authors: Michael Rainone, Isha Singh, Erin E. Salo-Mullen, Zsofia K. Stadler, Eileen M. O’Reilly
Journal: JAMA Oncology (2020)

Pancreatic ductal adenocarcinoma (PDAC) is a malignant neoplasm with a rising incidence and is a leading public health challenge. Pancreatic ductal adenocarcinoma has been well characterized genomically, with findings of therapeutic actionability that have substantive implications for clinical practice based on recent high-level evidence.Pathogenic germline alterations (PGAs) are relatively common in individuals with PDAC, as evidenced in multiple recent data sets, with a frequency of approximately 10%. The most common PGAs are in BRCA1, BRCA2, and ATM and more rarely in PALB2, MLH1, MSH2, MSH6, PMS2, CDKN2A, and TP53, among others, with an aggregate frequency of 3.8% to 9.7%. These PGAs are of key interest owing to therapeutic actionability and the downstream identification of at-risk family members and possible hereditary cancer syndromes. Approximately 3% to 7% of individuals with PDAC harbor a BRCA1 or BRCA2 mutation, which are among the most frequently mutated genes in PDAC. Recent updates to the American Society of Clinical Oncology and the National Comprehensive Cancer Network guidelines recommend risk assessment for all individuals with PDAC irrespective of personal or family history or ethnicity. Treatment implications include the use of checkpoint inhibitor therapy for mismatch repair-deficient PDAC and the validation of poly-ADP (adenosine diphosphate)-ribose polymerase inhibitor (PARPi) therapy as a maintenance strategy in platinum-sensitive PDAC.With increasing evidence and slow improvement of outcomes, PDAC has entered the era of precision medicine. Germline mutations have been identified in key genes with an aggregate frequency of 3.8% to 9.7%, several of which are therapeutically actionable with platinum, PARPi, and checkpoint inhibitor therapy. Potential therapeutic targets need to be actively sought and identified.
The efficacy and safety of topical rapamycin–calcitriol for facial angiofibromas in patients with tuberous sclerosis complex: a prospective, double‐blind, randomized clinical trial
Authors: P.L. Chen, J.B. Hong, L.J. Shen, Y.T. Chen, S.J. Wang, Y.H. Liao
Journal: British Journal of Dermatology (2020)

The efficacy of topical rapamycin is well documented for tuberous sclerosis complex (TSC)-related facial angiofibromas (FAs). Calcitriol has been shown to lessen skin fibrosis and may be therapeutically beneficial to FAs.To evaluate whether topical rapamycin-calcitriol combination is an effective and safe treatment for TSC-related FAs.Fifty-two patients with TSC with FAs were enrolled in this prospective study including three 12-week periods. In period 1, either topical rapamycin 0·1% or calcitriol 0·0003% single-agent therapy vs. their combination was applied in a double-blind, left-right-randomized, split-face comparison. The primary outcome was the reduction of modified Facial Angiofibroma Severity Index (mFASI) at week 12. In period 2, the patients were reassigned to use on both cheeks the ointment that resulted in the better primary outcome in period 1. The treatment was discontinued in period 3 (week 25-36) and a follow-up mFASI was scored to evaluate the degree of recurrence.The mean changes in mFASI at week 12 compared with baseline were -0·92, -0·44 and -1·09 for rapamycin (P ≤ 0·001), calcitriol (P = 0·039) and rapamycin-calcitriol combination (P ≤ 0·001), respectively. Although rapamycin-calcitriol combination and rapamycin had similar statistically significant decreases of mFASI at week 12, rapamycin-calcitriol combination resulted in faster improvement in erythema, greater reduction of papule elevation and longer durability after discontinuing treatment than rapamycin alone. The treatments were well tolerated.This randomized clinical trial demonstrates that topical rapamycin-calcitriol combination therapy is an effective and safe regimen for TSC-related FAs. What is already known about this topic? Facial angiofibromas (FAs) cause substantial psychological distress in individuals with tuberous sclerosis complex (TSC), but invasive procedural treatments are not applicable to all patients. Topical rapamycin has been demonstrated as an effective and safe treatment regimen for TSC-related FAs. What does this study add? Compared with baseline (day 0), both topical rapamycin 0·1% and rapamycin 0·1%-calcitriol 0·0003% combination ointment achieved statistically significant reductions in modified Facial Angiofibroma Severity Index at week 12. Compared with rapamycin alone, extended use of the rapamycin-calcitriol combination regimen until week 24 showed more effectiveness in decreasing papule elevation and could maintain a longer therapeutic effect after treatment discontinuation. Linked Comment: Lee. Br J Dermatol 2020; 183:604-606.
Abstract P6-06-16: Resveratrol enhanced chemosensitivity by reversing macrophage polarization in breast cancer
Authors: Isabella Wai Yin Cheuk, Jiawei Chen, Man Ting Siu, Sau Wing Lam, Jue Wang, Vivian Yvonne Shin, Ava Kwong
Journal: Cancer Research (2020)

Abstract Background: Resveratrol is a naturally occurring polyphenolic compound in Polygonum cuspidatum and is well known for its antitumor effect by targeting several cancer-related inflammatory pathways. However, limited data is available on the effect of resveratrol in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant leukocyte population within the tumors and are associated with poor prognosis in over 80% of breast cancer cases. This study aimed to investigate the effect of resveratrol on TAM polarization in breast cancer progression. Methods: The antitumor effect of resveratrol was examined in MDA-MB-231(MB231), cisplatin resistance MDA-MB-231 (cisR) cells, and T47D by cell proliferation assay using MTT. Gene expressions of M1 and M2 markers in macrophages derived from THP-1 cells were examined by qPCR and immunofluorescence staining after treated with tumor-conditioned medium (TCM) with or without resveratrol (25μM). Cytokine profile of TCM was examined by Qiagen Multi-Analyte ELISArray and expression of cytokines in TCM was validated by qPCR and ELISA. The effect of resveratrol and its downstream targets on macrophage polarization were investigated by supplementing resveratrol with interferon gamma (IFN-γ, 20ng/ml) and lipopolysaccharide (LPS, 100ng/ml) for M1 macrophage polarization or IL-4 (20ng/ml) and IL-13 (20ng/ml)for M2 macrophage polarization. NOD/SCID mice were used to investigate the potential use of resveratrol in treating breast cancer and chemotherapy as complementary treatment in vivo. Results: Our preliminary data demonstrated that resveratrol significantly reduced cell proliferation and enhanced chemosensitivity in MB231, cisR, and T47D cells. Resveratrol inhibited CD163 (M2 marker) and increased CXCL10 (M1 marker) expression. In addition, resveratrol decreased exogenous IL-6 levels in TCM, thus inhibited breast cancer cell proliferation by promoting M1/M2 macrophage polarization ratio and supressing IL-6/pSTAT3 pathway. Combined use of resveratrol and cisplatin significantly decreased tumor size in vivo. Conclusion: Our data demonstrated that resveratrol enhanced chemosensitivity in vivo and in vitro by promoting M1/M2 macrophage polarization ratio and supressing STAT3 activation through reducing exogenous IL-6 levels. This study revealed a novel mechanism on resveratrol-mediated macrophage polarization on breast cancer progression. Correspondence: akwong@asiabreastregistry.com Citation Format: Isabella Wai Yin Cheuk, Jiawei Chen, Man Ting Siu, Sau Wing Lam, Jue Wang, Vivian Yvonne Shin, Ava Kwong. Resveratrol enhanced chemosensitivity by reversing macrophage polarization in breast cancer [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P6-06-16.
Health Resource Utilisation (HRU) in Europe Associated with Skeletal-Related Events (SRES): Results from a Retrospective Study
Authors: J. Body, J. Pereira, H. Sleeboom, N. Maniadakis, E. Terpos, J. Finek, O. Gunther, G. Hechmati, T. Mossman, R. von Moos
Journal: Annals of Oncology (2012)
Clozapine-Associated Obsessive-Compulsive Symptoms and Their Management: A Systematic Review and Analysis of 107 Reported Cases
Authors: David D. Kim, Alasdair M. Barr, Cynthia Lu, S. Evelyn Stewart, Randall F. White, William G. Honer, Ric M. Procyshyn
Journal: Psychotherapy and Psychosomatics (2020)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; It is not uncommon to find obsessive-compulsive symptoms (OCS) in patients treated with clozapine. These symptoms are attributed to anti-serotonergic effects of clozapine. The objective of this study was to conduct a systematic review of reported cases of clozapine-associated OCS to better understand the nature and management of these symptoms. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; MEDLINE, Embase, and PsycINFO databases were searched with no publication year or language restrictions. Studies reporting cases of clozapine-associated OCS, either de novo or exacerbation of preexisting OCS, were included. The final search date was July 11, 2019. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; Fifty-seven studies, involving 107 cases (75 de novo, 32 exacerbated OCS), were included. Clozapine triggered moderate-severe OCS at varying doses (100–900 mg/day) and treatment durations (median 6 months, interquartile range 2–24 months). Higher severity was significantly associated with preexisting OCS, poorer insight into OCS, and active psychosis at the time of OCS. Common strategies to treat clozapine-associated OCS included adding selective serotonin reuptake inhibitors, clomipramine, or aripiprazole, often accompanied by clozapine dose reduction. The rate of response to antidepressants was 49% (29/59), where younger age, shorter duration of underlying illness, shorter cloza­pine treatment duration, better insight into OCS, and presence of taboo thoughts were significantly associated with antidepressant response. Subsequent clozapine dose reduction was effective in many non-responders, where aripiprazole was simultaneously added in 50% (8/16). &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Clozapine can trigger severe OCS. Adding aripiprazole with/without clozapine dose reduction may be a good alternative to antidepressants for managing clozapine-associated OCS. Clinicians should be more vigilant about these adverse effects and administer appropriate treatments.
Coronavirus: online GP bookings should be stopped because of safety risks, warns BMA
Authors: Elisabeth Mahase
Journal: BMJ (2020)

<b>Background: </b> The role of apolipoprotein E (APOE) polymorphism has been well recognized in other cognitive neurodegenerative disorders, such as Alzheimer disease. Its role in multiple sclerosis (MS) is less clear, though studies indicate that 40% to 60% of patients with MS have evidence of cognitive impairment. <b>Objective: </b> To determine whether there is an association between APOE ε4 and cognitive deficits in MS. <b>Methods: </b> We performed a standardized battery of neuropsychological tests investigating the four cognitive domains commonly impaired in MS and assessed the association of the presence of APOE ε4 with cognition in MS. <b>Results: </b> A strong association was found between the presence of APOE ε4 and cognitive deficits in patients with MS, particularly in the domains of learning and memory. This association was strongest in our youngest cohort (age 31 to 40) of patients with MS. <b>Conclusions: </b> APOE ε4 is significantly associated with cognitive impairment in patients with multiple sclerosis (MS). However, the modest effects do not justify APOE genotyping of patients with MS in clinical practice.
Physical activity and body image: Intertwined health priorities identified by transmasculine young people in a non-metropolitan area
Authors: Michelle Teti, L. A. Bauerband, Abigail Rolbiecki, Cole Young
Journal: International Journal of Transgender Health (2020)

Background: A dearth of research exists about the health behaviors of transgender young people (TYP). As we seek to learn more about transgender (trans) health, community-based participatory research (CBPR) approaches are crucial for incorporating TYP’s needs into the formulation of research questions and development of health behavior programing.Aim: Explore body image and exercise as priorities among TYP.Methods: Trans masculine young adults (N = 16) in a small city in the Midwest took part in semi-structured interviews about their health behaviors and priorities. Theme analysis was used to capture key patterns in participants’ responses. Specific analysis steps included initial and more specific coding, analytical memos, organizational matrices and reports, and discussion about results with participants.Results: Participants identified exercise and body image as connected primary health concerns. They discussed these issues in terms of three themes: Body shape as motivation for exercise; Poor body image, stigma and fear as exercise barriers, and; Exercise or lack of, as destructive. Participants wanted to exercise to achieve a certain body shape, not for health or as stress relief. They cited gyms as unwelcoming, however. They also worried about discrimination and did not feel sufficiently comfortable with their bodies to exercise. When they could not exercise, they used harmful behaviors, like restricted eating, to achieve a specific male shape.Conclusions: Using participatory methods allowed us to understand the priorities of a group of Transmasculine young people. Our findings suggest that it is important to continue to explore TYP’s body-related motivations for exercise and understand the balance between exercise as a positive health behavior, and a potentially harmful one, in light of TYP’s complex body image concerns. Trans friendly gyms and gym policies could promote safe exercise and continued anti trans discrimination work and policy advocacy can promote the safety of TYP in all spaces.
Abstract ES8-1: Adjuvant endocrine therapy in 2020: It's complicated
Authors: A McCartney, A Di Leo
Journal: Cancer Research (2020)

Abstract Adjuvant endocrine therapy in 2020: It’s complicated Data regarding the use of adjuvant endocrine therapy in patients with hormone receptor-positive early breast cancer has grown over the past decades, and yet still uncertainty remains in management recommendations. In pre-menopausal women, treatment decisions are often driven by estimation of risk of recurrence, measured in terms of clinical and pathological parameters, algorithm-based prognostic modelling derived from breast cancer registries, molecular profiling and gene signature assays. Despite these significant advances, risk of distant disease recurrence is still over-estimated in a significant proportion of women. The addition of ovarian suppression to tamoxifen in pre-menopausal women has been shown to increase rates of both disease-free survival and overall survival than tamoxifen alone, with the use of the steroidal aromatase inhibitor exemestane producing further higher rates of freedom from recurrence. However, the addition of ovarian suppression in this generally low-risk population comes at the cost of increased adverse events and potential to interpose child-bearing years. Further to this, the SOFT/TEXT studies mandated five years of active treatment; little is known as to whether extended treatment beyond those five years would be comparatively equal, better or worse in terms of outcome endpoints. In the post-menopausal population, the updated ASCO Clinical Practice Guideline suggests that all women with node-positive disease should be offered extended therapy including an aromatase inhibitor for a total of ten years, as well as women with node-negative disease possessing high-risk prognostic factors. The question of how best to identify those women who may fare equally well with de-escalated, shorter therapy remains open. The issue of adverse events and drug-related side effects, particularly in the setting of extended therapy, is relevant and may impact negatively on overall treatment compliance and quality of life. As such, the choice of endocrine therapy remains an important consideration, as is evidence that intermittent administration of aromatase inhibitors may be feasible in selected patients. CDK4/6 inhibitors, administered in tandem with endocrine therapy, have radically changed the approach to managing metastatic endocrine receptor-positive disease. There is now much interest in moving these agents forward into the neoadjuvant and adjuvant setting, with a number of phase II and III trials ongoing. If positive data is consistently reported in adjuvant studies, this will undoubtedly create another layer of complexity to the clinical management of endocrine-sensitive disease. Citation Format: A McCartney, A Di Leo. Adjuvant endocrine therapy in 2020: It's complicated [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr ES8-1.
Abstract 15044: Risk of Myocardial Infarction in Carriers of Familial Hypercholesterolemia Mutations is Modified by Common Variant Genetic Background or Adherence to a Healthy Lifestyle
Authors: Akl C Fahed, Minxian Wang, Mark Chaffin, Alexander G Bick, Candace Patterson, Pradeep Natarajan, Matthew Lebo, Puneet Batra, Kenney Ng, Patrick T Ellinor, Anthony A Philippakis, Sekar Kathiresan, Amit V Khera
Journal: Circulation (2019)

Background: Recent genetic studies have highlighted ‘incomplete penetrance’ of DNA sequence variants related to familial hypercholesterolemia mutations - although carriers on average have a three-f...
Ultrasound Brain Stimulation Piloted in Alzheimer Study
Authors: Jennifer Abbasi
Journal: JAMA (2020)

Patients with probable Alzheimer disease (AD) had sustained memory improvements 3 months after ultrasound brain stimulation in a small pilot study. The noninvasive technique, called transcranial pulse stimulation (TPS), is designed to apply ultrashort ultrasound pulses to small brain areas.
Light‐Triggered Cancer Cell Specific Targeting and Liposomal Drug Delivery in a Zebrafish Xenograft Model
Authors: Li Kong, Quanchi Chen, Frederick Campbell, Ewa Snaar‐Jagalska, Alexander Kros
Journal: Advanced Healthcare Materials (2020)

Abstract Cell‐specific drug delivery remains a major unmet challenge for cancer nanomedicines. Here, light‐triggered, cell‐specific delivery of liposome‐encapsulated doxorubicin to xenograft human cancer cells in live zebrafish embryos is demonstrated. This method relies on light‐triggered dePEGylation of liposome surfaces to reveal underlying targeting functionality. To demonstrate general applicability of this method, light‐triggered, MDA‐MB‐231 breast cancer cell specific targeting in vivo (embryonic zebrafish) is shown using both clinically relevant, folate‐liposomes, as well as an experimental liposome‐cell fusion system. In the case of liposome‐cell fusion, the delivery of liposomal doxorubicin direct to the cytosol of target cancer cells results in enhanced cytotoxicity, compared to doxorubicin delivery via either folate‐liposomes or free doxorubicin, as well as a significant reduction in xenograft cancer cell burden within the embryonic fish.
Celecoxib in lymphangioleiomyomatosis: results of a phase I clinical trial
Authors: Souheil El-Chemaly, Angelo Taveira-DaSilva, Shefali Bagwe, Katarzyna Klonowska, Tania Machado, Anthony M. Lamattina, Hilary J. Goldberg, Amanda M. Jones, Patricia Julien-Williams, Rie Maurer, Ivan O. Rosas, Elizabeth P. Henske, Joel Moss, David J. Kwiatkowski
Journal: European Respiratory Journal (2020)

<b>COX2 inhibition is safe in LAM patients with mild disease. In the subset of patients with high VEGF-D (&gt;800 pg per mL) COX2 inhibition appears to cause a decrease in VEGF-D levels and may provide clinical benefit.</b>http://bit.ly/395drXs
Inter- and intratumor DNA methylation heterogeneity associated with lymph node metastasis and prognosis of esophageal squamous cell carcinoma
Authors: Huajing Teng, Meiying Xue, Jialong Liang, Xingxing Wang, Lu Wang, Wenqing Wei, Chao Li, Ze Zhang, Qinglan Li, Xia Ran, Xiaohui Shi, Wanshi Cai, Weihu Wang, Hengjun Gao, Zhongsheng Sun
Journal: Theranostics (2020)

Background: Esophageal squamous cell carcinoma (ESCC), one of the leading causes of cancer mortality worldwide, is a heterogeneous cancer with diverse clinical manifestations. However, little is known about the epigenetic heterogeneity and its clinical relevance for this prevalent cancer. Methods: We generated 7.56 Tb single-base resolution whole-genome bisulfite sequencing data for 84 ESCC and paired paraneoplastic tissues. The analysis identified inter- and intratumor DNA methylation (DNAm) heterogeneity, epigenome-wide DNAm alterations together with the functional regulators involved in the hyper- or hypomethylated regions, and their association with clinical features. We then validated the correlation between the methylation level of specific regions and clinical outcomes of 96 ESCC patients in an independent cohort. Results: ESCC manifested substantial inter- and intratumor DNAm heterogeneity. The high intratumor DNAm heterogeneity was associated with lymph node metastasis and worse overall survival. Interestingly, hypermethylated regions in ESCC were enriched in promoters of numerous transcription factors, and demethylated noncoding regions related to RXR transcription factor binding appeared to contribute to the development of ESCC. Furthermore, we identified numerous DNAm alterations associated with carcinogenesis and lymph node metastasis of ESCC. We also validated three novel prognostic markers for ESCC, including one each in the promoter of CLK1, the 3' untranslated region of ZEB2, and the intergenic locus surrounded by several lncRNAs. Conclusions: This study presents the first population-level resource for dissecting base-resolution DNAm variation in ESCC and provides novel insights into the ESCC pathogenesis and progression, which might facilitate diagnosis and prognosis for this prevalent malignancy.