tbuckley/cabot-search huggingface dataset:
Depression in Older Adults
Authors: Amy Fiske, Julie Loebach Wetherell, Margaret Gatz
Journal: Annual Review of Clinical Psychology (2009)

Depression is less prevalent among older adults than among younger adults, but it can have serious consequences. More than half of cases represent a first onset in later life. Although suicide rates in the elderly are declining, they are still higher than in younger adults and are more closely associated with depression. Depressed older adults are less likely to endorse affective symptoms and more likely to display cognitive changes, somatic symptoms, and loss of interest than are depressed younger adults. Risk factors leading to the development of late-life depression likely comprise complex interactions among genetic vulnerabilities, cognitive diathesis, age-associated neurobiological changes, and stressful events. Insomnia is an often overlooked risk factor for late-life depression. We suggest that a common pathway to depression in older adults, regardless of which predisposing risks are most prominent, may be curtailment of daily activities. Accompanying self-critical thinking may exacerbate and maintain a depressed state. Offsetting the increasing prevalence of certain risk factors in late life are age-related increases in psychological resilience. Other protective factors include higher education and socioeconomic status, engagement in valued activities, and religious or spiritual involvement. Treatments including behavioral therapy, cognitive-behavioral therapy, cognitive bibliotherapy, problem-solving therapy, brief psychodynamic therapy, and life review/reminiscence therapy are effective but are too infrequently used with older adults. Preventive interventions including education for individuals with chronic illness, behavioral activation, cognitive restructuring, problem-solving skills training, group support, and life review have also received support.
Aging and Diabetes: Shifting the Risk Trajectory With High-Sensitivity Cardiac Troponins
Authors: Ian J. Neeland, James A. de Lemos
Journal: Diabetes Care (2020)

Diabetes is a serious health challenge for the aging population, contributing to morbidity and mortality primarily through increased risk for ischemic heart disease, heart failure, and stroke (1). Approximately 25–30% of adults over the age of 65 years have diabetes (2,3), and this proportion is expected to increase rapidly in the coming decades (4). Older individuals with diabetes also have higher rates of comorbidities including functional disability, accelerated muscle loss, chronic kidney disease, and coexisting cardiovascular risk factors compared with those without diabetes (3). Since multiple comorbidity among older adults with diabetes is common, individualized risk assessment to guide therapy using standard risk stratification tools has proven to be challenging. Therefore, new strategies are needed to improve risk assessment and inform use of novel and emerging therapies for patients with diabetes given important risk/benefit trade-offs between efficacy and adverse effects in the older adult population.

Incorporation of high-sensitivity cardiac troponin (hs-cTn) into risk stratification and treatment decision algorithms is one such strategy that has the potential to improve personalized diabetes care. hs-cTn–based risk stratification (using both the hs-cTnT and hs-cTnI isoforms) has been extensively investigated in multiple population settings and for multiple outcomes including coronary artery disease, heart failure, stroke, and mortality (5–8). The association is strongest for heart failure and mortality and weakest for ischemic events (6). When measured in ambulatory individuals without cardiac symptoms, hs-cTn is a measure of subclinical myocardial injury and provides independent, additional prognostic information beyond other cardiac biomarkers and diagnostic tests such as electrocardiographic left ventricular hypertrophy, N-terminal pro B-type natriuretic peptide, and coronary artery calcium (9,10). Importantly, although hs-cTn is commonly elevated beyond the detectable threshold in older adults (∼2/3 will have a level …
Depression and Mortality
Authors: Barry W. Rovner
Journal: JAMA (1991)

To determine the prevalence rates of major depressive disorder and of depressive symptoms and their relationship to mortality in nursing homes, research psychiatrists examined 454 consecutive new admissions and followed them up longitudinally for 1 year. Major depressive disorder occurred in 12.6% and 18.1% had depressive symptoms; the majority of cases were unrecognized by nursing home physicians and were untreated. Major depressive disorder, but not depressive symptoms, was a risk factor for mortality over 1 year independent of selected physical health measures and increased the likelihood of death by 59%. Because depression is a prevalent and treatable condition associated with increased mortality, recognition and treatment in nursing homes is imperative. (<i>JAMA</i>. 1991;265:993-996)
Narratives of transphobic violence in the Mexican province of Colima: A psychosocial analysis
Authors: Antar Martínez-Guzmán, Katherine Johnson
Journal: International Journal of Transgender Health (2020)

Background Mexico has the second-highest index of crimes motivated by transphobia in the world. Transphobic violence manifests in a pervasive and complex manner in a country where violence permeates all aspects of social life. Some progress has been made to improve transgender rights and fight discrimination, but this has had an unequal impact in different geopolitical and cultural contexts within the country, particularly outside of metropolitan centers.Aim The study explores how transphobia is experienced in the conservative province of Colima and how transphobic practices play a part in shaping transgender subjective experience and identity construction. A psychosocial theoretical framework is adopted to attend to the relationship between cultural, institutional and interpersonal practices in this process.Methods A qualitative approach is used to explore how different forms of transphobic violence are experienced by trans women in Colima. A purposive sample of 12 trans women, aged 22-38 years took part in narrative interviews which were analyzed thematically. Findings: The analysis is organized into three themes: (a) narratives of gender identity construction (b) gender expression and experiences of transphobic violence in Colima (c) sites for social support and change.Discussion We argue that the psychosocial processes related to transphobia are context-specific shaping transgender identities and limiting and regulating gender expression. Family, education, LGBT community and the police were identified as key sites for support against or source of transphobic violence.Conclusion Despite the challenging socio-political context interventions are needed in policy and institutional practices to tackle stigma, transphobia and, trans-misogyny and improve the lives of transgender people living in regional areas in the global south.
Calcitriol‐Loaded Dual‐pH‐Sensitive Micelle Counteracts Pro‐Metastasis Effect of Paclitaxel in Triple‐Negative Breast Cancer Therapy
Authors: Zhong Zheng, Tianqun Lang, Xin Huang, Guanru Wang, Robert J. Lee, Lesheng Teng, Qi Yin, Yaping Li
Journal: Advanced Healthcare Materials (2020)

Abstract The therapy of triple‐negative breast cancer (TNBC) relies on chemotherapy basing on cytotoxic agents, including paclitaxel (PTX). Unfortunately, PTX will facilitate the invasion of cancer cells and the formation of metastases. To counteract pro‐metastasis of PTX in TNBC therapy, in this work, calcitriol (CTL) is delivered along with PTX by a dual‐pH‐sensitive micelle. The PTX/CTL‐co‐loaded dual‐pH‐sensitive micelle (PCDM) can switch its surface charge from negative to positive at the tumor tissue and release PTX and CTL inside the lysosomes because of the structure change of the polymers composing PCDM under the acidic condition. This property makes PCDM able to escape from mononuclear‐phagocyte system clearance and easy to enter tumor cells. PCDM efficiently suppresses the 4T1 primary tumor growth in mice and inhibits lung metastasis, due to downregulation of matrix metalloproteinase‐9 and BCL‐2 levels, upregulation of E‐cadherin level, and counteracting the PTX‐induced elevation of C‐C motif chemokine ligand 2 (CCL2) and Ly6C + monocytes levels by CTL. PCDM shows good biocompatibility without promoting the serum calcium level. Therefore, the combination of PTX and CTL based on this pH‐sensitive micelle is promising for the TNBC treatment.
125P Prognostic factors in phyllodes tumours (PT) of the breast: A single-institution cohort
Authors: E. Di Liso, M. Bottosso, V. Tsvetkova, M. Lo Mele, M.V. Dieci, C. Falci, G. Faggioni, G. Tasca, C.A. Giorgi, T. Giarratano, E. Mioranza, A.P. Dei Tos, V. Guarneri, P.F. Conte
Journal: Annals of Oncology (2020)
Venous thromboembolism in adults: summary of updated NICE guidance on diagnosis, management, and thrombophilia testing
Authors: Terry McCormack, Marie C Harrisingh, Daniel Horner, Susan Bewley
Journal: BMJ (2020)

### What’s new in this guidance?

Venous thromboembolic (VTE) disease is a continuing global health burden with serious mortality, morbidity, and health economic consequences.1 The one year case fatality rate of definite or probable VTE has been estimated at 23%.2 Approximately 1 to 2 of every 1000 adults in the worldwide population will be diagnosed with VTE annually, with higher incidence rates in those over 70 (2 to 7/1000) and over 80 (3 to 12/1000).13

On 26 March 2020, the National Institute for Health and Care Excellence (NICE) published NG158,4 an updated version of its guideline on the diagnosis and management of VTE (original version 2012, minor update 2015: National Institute for Health and Care Excellence 2020 venous thromboembolism in adults: diagnosis, management and thrombophilia testing. https://www.nice.org.uk/guidance/ng158). This article summarises the new key recommendations, with a focus on those most relevant to primary care and secondary generalist physicians, and includes existing 2012 or 2015 recommendations that have not been updated where they are relevant to the topic …
Variations between women and men in risk factors, treatments, cardiovascular disease incidence, and death in 27 high-income, middle-income, and low-income countries (PURE): a prospective cohort study
Authors: Marjan Walli-Attaei, Philip Joseph, Annika Rosengren, Clara K Chow, Sumathy Rangarajan, Scott A Lear, Khalid F AlHabib, Kairat Davletov, Antonio Dans, Fernando Lanas, Karen Yeates, Paul Poirier, Koon K Teo, Ahmad Bahonar, Felix Camilo, Jephat Chifamba, Rafael Diaz, Joanna A Didkowska, Vilma Irazola, Rosnah Ismail, Manmeet Kaur, Rasha Khatib, Xiaoyun Liu, Marta Mańczuk, J Jaime Miranda, Aytekin Oguz, Maritza Perez-Mayorga, Andrzej Szuba, Lungiswa P Tsolekile, Ravi Prasad Varma, Afzalhussein Yusufali, Rita Yusuf, Li Wei, Sonia S Anand, Salim Yusuf
Journal: The Lancet (2020)
Response to Open Peer Commentaries “Rethinking the Ethical, Legal, and Clinical Foundations of Informed Consent and Shared Decision-Making for Brain Death Determination”
Authors: Jeremy R. Garrett, Ivor Berkowitz
Journal: The American Journal of Bioethics (2020)

(2020). Response to Open Peer Commentaries "Rethinking the Ethical, Legal, and Clinical Foundations of Informed Consent and Shared Decision-Making for Brain Death Determination". The American Journal of Bioethics: Vol. 20, No. 6, pp. W1-W5.
Vanishing Bone Metastases in 18F-FDG PET/CT
Authors: Alida Ainouche, David Morland, Carole Durot, Christine Hoeffel, Dimitri Papathanassiou
Journal: Clinical Nuclear Medicine (2020)

Abstract A 36-year-old woman with a history of large B-cell lymphoma was referred for the exploration of sclerotic bone thoracic vertebral metastases discovered on a contrast-enhanced CT examination. 18 F-FDG PET showed no pathological uptake in the affected vertebrae, as well as normal vertebral density on the coupled unenhanced CT. After review of the initial contrast-enhanced CT, a left brachiocephalic vein stenosis was noted, leading to a retrograde contrast filling of the accessory hemiazygos vein and the capillary spaces within the vertebrae, mimicking sclerotic metastases.
Multidisciplinary Management of Breast Cancer With Extensive Regional Nodal Involvement
Authors: Benjamin D. Smith, Matthew P. Goetz, Judy C. Boughey
Journal: Journal of Clinical Oncology (2020)

The Oncology Grand Rounds series is designed to place original reports published in the Journal into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in Journal of Clinical Oncology, to patients seen in their own clinical practice.
Universal and Serial Laboratory Testing for SARS-CoV-2 at a Long-Term Care Skilled Nursing Facility for Veterans — Los Angeles, California, 2020
Authors: Amy V. Dora, Alexander Winnett, Lauren P. Jatt, Kusha Davar, Mika Watanabe, Linda Sohn, Hannah S. Kern, Christopher J. Graber, Matthew B. Goetz
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

This report describes how universal, serial reverse transcription–polymerase chain reaction testing of residents in a long-term care skilled nursing facility in Los Angeles, California, helped to interrupt transmission of coronavirus disease 2019 in the facility.
183O Use of physical activity (PA) and supportive care (SC) among patients (pts) with early breast cancer (BC) reporting cancer-related fatigue (CRF)
Authors: A. Di Meglio, C. Charles, E. Martin, J. Havas, A.S. Gbenou, A-L. Martin, S. Everhard, E. Laas, O. Tredan, L. Vanlemmens, C. Jouannaud, C. Levy, O. Rigal, M. Fournier, P. Soulie, A. Dumas, G. Menvielle, F. André, S. Dauchy, I. Vaz-Luis
Journal: Annals of Oncology (2020)
Tumor‐Targeted Inhibition of Monocarboxylate Transporter 1 Improves T‐Cell Immunotherapy of Solid Tumors
Authors: Tongyi Huang, Qiang Feng, Zhaohui Wang, Wei Li, Zhichen Sun, Jonathan Wilhelm, Gang Huang, Tram Vo, Baran D. Sumer, Jinming Gao
Journal: Advanced Healthcare Materials (2020)

Export of lactic acid from glycolytic cancer cells to the extracellular tumor milieu has been reported to enhance tumor growth and suppress antitumor immunity. In this study, a pH-activatable nanodrug is reported for tumor-targeted inhibition of monocarboxylate transporter-1 (MCT1) that reverses lactic acid-induced tumor immunosuppression. The nanodrug is composed of an MCT1 inhibitor (AZD3965) loaded inside the ultra-pH-sensitive nanoparticles (AZD-UPS NPs). AZD-UPS NP is produced by a microfluidics method with improved drug loading efficiency and optimal nanoparticle size over sonication methods. The nanodrug remains as intact micelles at pH 7.4 but rapidly disassembles and releases payload upon exposure to acidic pH. When combined with anti-PD-1 therapy, AZD-UPS NP leads to potent tumor growth inhibition and increases survival in two tumor models over oral administration of AZD3965 at dramatically reduced dose (>200-fold). Safety evaluations demonstrate reduced drug distribution in heart and liver tissues with decrease in toxic biomarkers such as cardiac troponin by the nanodrug. Increased T-cell infiltration and reduced exhaustive PD1
Clinical course and risk factors for mortality of COVID-19 patients with pre-existing cirrhosis: a multicentre cohort study
Authors: Xiaolong Qi, Yanna Liu, Jitao Wang, Jonathan A Fallowfield, Jianwen Wang, Xinyu Li, Jindong Shi, Hongqiu Pan, Shengqiang Zou, Hongguang Zhang, Zhenhuai Chen, Fujian Li, Yan Luo, Mei Mei, Huiling Liu, Zhengyan Wang, Jinlin Li, Hua Yang, Huihua Xiang, Xiaodan Li, Tao Liu, Ming-Hua Zheng, Chuan Liu, Yifei Huang, Dan Xu, Xiaoguo Li, Ning Kang, Qing He, Ye Gu, Guo Zhang, Chuxiao Shao, Dengxiang Liu, Lin Zhang, Xun Li, Norifumi Kawada, Zicheng Jiang, Fengmei Wang, Bin Xiong, Tetsuo Takehara, Don C Rockey
Journal: Gut (2020)

The behavioral effects of nicotine were compared with those of its metabolites, nornicotine and cotinine, in beagle dogs and squirrel monkeys. Subjects responded under a multiple fixed-interval (FI) 300-sec, fixed-ratio (FR) 30 response schedule of food presentation. Nicotine (0.01-1.0 mg/kg i.m.) and nornicotine (0.03-3.0 mg/kg i.m.) produced qualitatively similar effects in both dogs and monkeys. Nicotine produced dose-related increases, then decreases in rates of responding during FI components; rates of responding during FR components were only decreased. Nornicotine produced only dose-dependent decreases in responding during both FI and FR components. In the dogs, cotinine (0.01-10.0 mg/kg i.m.) produced only dose-dependent decreases in rates of responding during both FI and FR components. In the squirrel monkeys, however, cotinine (0.1-3.0 mg/kg i.m.) increased responding during FI components; a high dose of 30.0 mg/kg decreased responding during both FI and FR components. The behavioral effects of cocaine (0.03-3.0 mg/kg i.m.) and its metabolite norcocaine (0.01-1.0 mg/kg i.m.) were compared in the dogs. FI rates of responding first increased and then decreased with increasing doses of each drug, whereas FR rates of responding only decreased in a dose-related manner. Norcocaine was slightly more potent than cocaine in producing these effects on schedule-controlled responding in dogs. These experiments indicate the metabolites of nicotine and cocaine are behaviorally active and may contribute to the pharmacological profile of the parent compounds.
113P Impact of local recurrence on disease-specific survival in breast cancer patients who underwent breast-conserving surgery
Authors: D.G. Tiezzi, L. de Mattos, L.F. Orlandini, F.J. Candido Dos Reis, H.H. Carrara, O.M. Rueda, C. Caldas, J.M.D. Andrade
Journal: Annals of Oncology (2020)
Predicting extubation outcomes using the Heart Rate Characteristics index in preterm infants: a cohort study
Authors: Mallinath Chakraborty, William John Watkins, Katherine Tansey, William E. King, Sujoy Banerjee
Journal: European Respiratory Journal (2020)

A strategy of early extubation to noninvasive respiratory support in preterm infants could be boosted by the availability of a decision support tool for clinicians. Using the Heart Rate Characteristics index (HRCi) with clinical parameters, we derived and validated predictive models for extubation readiness and success. Peri-extubation demographic, clinical and HRCi data for up to 96 h were collected from mechanically ventilated infants in the control arm of a randomised trial involving eight neonatal centres, where clinicians were blinded to the HRCi scores. The data were used to produce a multivariable regression model for the probability of subsequent re-intubation. Additionally, a survival model was produced to estimate the probability of re-intubation in the period after extubation. Of the 577 eligible infants, data from 397 infants (69%) were used to derive the pre-extubation model and 180 infants (31%) for validation. The model was also fitted and validated using all combinations of training (five centres) and test (three centres) centres. The estimated probability for the validation episodes showed discrimination with high statistical significance, with an area under the curve of 0.72 (95% CI 0.71–0.74; p&lt;0.001). Data from all infants were used to derive models of the predictive instantaneous hazard of re-intubation adjusted for clinical parameters. Predictive models of extubation readiness and success in real-time can be derived using physiological and clinical variables. The models from our analyses can be accessed using an online tool available at www.heroscore.com/extubation , and have the potential to inform and supplement the confidence of the clinician considering extubation in preterm infants.
Balancing Past vs Future Values in Decision-Making—Reply
Authors: Claire J. Creutzfeldt, Robert G. Holloway
Journal: JAMA (2020)

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MHC-I genotype and tumor mutational burden predict response to immunotherapy
Authors: Aaron M. Goodman, Andrea Castro, Rachel Marty Pyke, Ryosuke Okamura, Shumei Kato, Paul Riviere, Garrett Frampton, Ethan Sokol, Xinlian Zhang, Edward D. Ball, Hannah Carter, Razelle Kurzrock
Journal: Genome Medicine (2020)

Abstract Background Immune checkpoint blockade (ICB) with antibodies inhibiting cytotoxic T lymphocyte-associated protein-4 (CTLA-4) and programmed cell death protein-1 (PD-1) (or its ligand (PD-L1)) can stimulate immune responses against cancer and have revolutionized the treatment of tumors. The influence of host germline genetics and its interaction with tumor neoantigens remains poorly defined. We sought to determine the interaction between tumor mutational burden (TMB) and the ability of a patient’s major histocompatibility complex class I (MHC-I) to efficiently present mutated driver neoantigens in predicting response ICB. Methods Comprehensive genomic profiling was performed on 83 patients with diverse cancers treated with ICB to determine TMB and human leukocyte antigen-I (HLA-I) genotype. The ability of a patient’s MHC-I to efficiently present mutated driver neoantigens (defined by the Patient Harmonic-mean Best Rank (PHBR) score (with lower PHBR indicating more efficient presentation)) was calculated for each patient. Results The median progression-free survival (PFS) for PHBR score &lt; 0.5 vs. ≥ 0.5 was 5.1 vs. 4.4 months ( P = 0.04). Using a TMB cutoff of 10 mutations/mb, the stable disease &gt; 6 months/partial response/complete response rate, median PFS, and median overall survival (OS) of TMB high/PHBR high vs. TMB high/PHBR low were 43% vs. 78% ( P = 0.049), 5.8 vs. 26.8 months ( P = 0.03), and 17.2 months vs. not reached ( P = 0.23), respectively. These findings were confirmed in an independent validation cohort of 32 patients. Conclusions Poor presentation of driver mutation neoantigens by MHC-I may explain why some tumors (even with a high TMB) do not respond to ICB.