tbuckley/cabot-search huggingface dataset:
Examining COVID-19 preventivebehaviors among cancer survivors in the United States:An analysis of the COVID-19 Impact Survey
Authors: J. Y. Islam, M. Camacho-Rivera, D. C. Vidot
Journal: Clinical Cancer Research (2020)

Background: Cancer survivors are at high risk of contracting severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), the infection that leads to COVID-19, as they are generally older and cancer therapies frequentlylead to immunosuppression  Recently, to mitigate exposure the CDC recommended avoiding nonessential doctorappointments, which may lead to barriers in effective continuity of care and surveillance of cancer survivors duringthe COVID-19 pandemic  The patterns of COVID-19 preventive behaviors practiced by cancer survivors areunknown, including practices related to canceling doctors' appointments  Objective: Our objective was to evaluate COVID-19-related preventive behaviors among cancer survivors in theUnited States (US)  We further examined behaviors related to canceling or postponing activities, specifically doctors'appointments  Methods: We utilized nationally representative weighted data from a sample of 4,428 US adults from the COVID-19Impact Survey collected during Week 1 (April 20-26, 2020) and Week (May 4-10, 2020)  We defined cancersurvivors as those with a self-reported prior diagnosis of cancer  We presented frequencies and used χ2 tests tocompare COVID-19-related preventive behaviors among cancer survivors to other adults  We calculated prevalenceratios with 95% confidence intervals using Poisson regression and robust estimation of standard errors to estimatedeterminants of canceling doctors' appointments among cancer survivors  Results: Cancer survivors were mostly over the age of 60 years (62%), female (53%), non-Hispanic White (62%), and resided in urban areas (72%)  Cancer survivors adhered to most recommended COVID-19-related preventivebehaviors and were more likely to maintain social distancing (92%, χ2 p-value=0 005), wear a face mask (89%, χ2p-value=0 001), and avoid crowded areas (84%, χ2 p-value=0 048) compared to other adults  Additionally, we foundthat cancer survivors are more likely to cancel their doctors' appointments (44%, χ2 p-value=0 001) whereas they were less likely to cancel other social activities such as work (20%, χ2 p-value=0 001) and school-related (12%, χ2p-value=0 002) activities, even among those below the age of 60  However, cancer survivors were more likely toreport symptoms in the last 7 days, including muscle or body aches (χ2 p-value=0 003)  The proportion of cancerpatients who have canceled doctors' appointments due to COVID-19 rose from the month of April (35%) to May(52%)  Younger adults aged 18-29 years, females, and rural cancer survivors were more likely to cancel theirdoctors' appointments, whereas NH-Blacks are less likely to cancel a doctor's appointment when compared to NH-Whites  Conclusion: Cancer survivors are adhering to recommended preventive behaviors  Cancer survivors' continuity ofcare may be impacted by COVID-19, specifically young adults, females, and rural residents
Hepatocyte ATF3 protects against atherosclerosis by regulating HDL and bile acid metabolism
Authors: Yanyong Xu, Yuanyuan Li, Kavita Jadhav, Xiaoli Pan, Yingdong Zhu, Shuwei Hu, Shaoru Chen, Liuying Chen, Yong Tang, Helen H. Wang, Ling Yang, David Q.-H. Wang, Liya Yin, Yanqiao Zhang
Journal: Nature Metabolism (2021)
Impaired complex I repair causes recessive Leber’s hereditary optic neuropathy
Authors: Sarah L. Stenton, Natalia L. Sheremet, Claudia B. Catarino, Natalia A. Andreeva, Zahra Assouline, Piero Barboni, Ortal Barel, Riccardo Berutti, Igor Bychkov, Leonardo Caporali, Mariantonietta Capristo, Michele Carbonelli, Maria L. Cascavilla, Peter Charbel Issa, Peter Freisinger, Sylvie Gerber, Daniele Ghezzi, Elisabeth Graf, Juliana Heidler, Maja Hempel, Elise Heon, Yulya S. Itkis, Elisheva Javasky, Josseline Kaplan, Robert Kopajtich, Cornelia Kornblum, Reka Kovacs-Nagy, Tatiana D. Krylova, Wolfram S. Kunz, Chiara La Morgia, Costanza Lamperti, Christina Ludwig, Pedro F. Malacarne, Alessandra Maresca, Johannes A. Mayr, Jana Meisterknecht, Tatiana A. Nevinitsyna, Flavia Palombo, Ben Pode-Shakked, Maria S. Shmelkova, Tim M. Strom, Francesca Tagliavini, Michal Tzadok, Amelie T. van der Ven, Catherine Vignal-Clermont, Matias Wagner, Ekaterina Y. Zakharova, Nino V. Zhorzholadze, Jean-Michel Rozet, Valerio Carelli, Polina G. Tsygankova, Thomas Klopstock, Ilka Wittig, Holger Prokisch
Journal: Journal of Clinical Investigation (2021)

Leber's hereditary optic neuropathy (LHON) is the most frequent mitochondrial disease and was the first to be genetically defined by a point mutation in mitochondrial DNA (mtDNA). A molecular diagnosis is achieved in up to 95% of cases, the vast majority of which are accounted for by 3 mutations within mitochondrial complex I subunit–encoding genes in the mtDNA (mtLHON). Here, we resolve the enigma of LHON in the absence of pathogenic mtDNA mutations. We describe biallelic mutations in a nuclear encoded gene, DNAJC30, in 33 unsolved patients from 29 families and establish an autosomal recessive mode of inheritance for LHON (arLHON), which to date has been a prime example of a maternally inherited disorder. Remarkably, all hallmarks of mtLHON were recapitulated, including incomplete penetrance, male predominance, and significant idebenone responsivity. Moreover, by tracking protein turnover in patient-derived cell lines and a DNAJC30-knockout cellular model, we measured reduced turnover of specific complex I N-module subunits and a resultant impairment of complex I function. These results demonstrate that DNAJC30 is a chaperone protein needed for the efficient exchange of complex I subunits exposed to reactive oxygen species and integral to a mitochondrial complex I repair mechanism, thereby providing the first example to our knowledge of a disease resulting from impaired exchange of assembled respiratory chain subunits.
Ameliorative Effects of Intranasal AntagomiR-125b in AD
Authors: Xiao Chun, Chauhan Neelima
Journal: Alzheimers Disease & Dementia (2020)

Alzheimer's disease (AD) is a global public health crisis. Currently, there are no treatments to prevent or halt the disease. Given the precedence of chronic neuroinflammation in triggering AD-like neurodegeneration and an observed upregulation of NFkB-driven miRs i.e. mir-125b positively correlating with AD, silencing specific micro-RNA with antisense-microRNA (antagomir) to miR-125b was undertaken to evaluate its efficacy in ameliorating AD-like neurodegeneration in 5XFAD transgenic mice modeling AD.
Simulating SARS-CoV-2 epidemics by region-specific variables and modeling contact tracing app containment
Authors: Alberto Ferrari, Enrico Santus, Davide Cirillo, Miguel Ponce-de-Leon, Nicola Marino, Maria Teresa Ferretti, Antonella Santuccione Chadha, Nikolaos Mavridis, Alfonso Valencia
Journal: npj Digital Medicine (2021)

Abstract Targeted contact-tracing through mobile phone apps has been proposed as an instrument to help contain the spread of COVID-19 and manage the lifting of nation-wide lock-downs currently in place in USA and Europe. However, there is an ongoing debate on its potential efficacy, especially in light of region-specific demographics. We built an expanded S I R model of COVID-19 epidemics that accounts for region-specific population densities, and we used it to test the impact of a contact-tracing app in a number of scenarios. Using demographic and mobility data from Italy and Spain, we used the model to simulate scenarios that vary in baseline contact rates, population densities, and fraction of app users in the population. Our results show that, in support of efficient isolation of symptomatic cases, app-mediated contact-tracing can successfully mitigate the epidemic even with a relatively small fraction of users, and even suppress altogether with a larger fraction of users. However, when regional differences in population density are taken into consideration, the epidemic can be significantly harder to contain in higher density areas, highlighting potential limitations of this intervention in specific contexts. This work corroborates previous results in favor of app-mediated contact-tracing as mitigation measure for COVID-19, and draws attention on the importance of region-specific demographic and mobility factors to achieve maximum efficacy in containment policies.
Ingestion-time differences in the pharmacodynamics of hypertension medications: Systematic review of human chronopharmacology trials
Authors: Ramón C. Hermida, Ramón G. Hermida-Ayala, Michael H. Smolensky, Artemio Mojón, José R. Fernández
Journal: Advanced Drug Delivery Reviews (2021)

Pharmacokinetics of hypertension medications is significantly affected by circadian rhythms that influence absorption, distribution, metabolism and elimination. Furthermore, their pharmacodynamics is affected by ingestion-time differences in kinetics and circadian rhythms comprising the biological mechanism of the 24 h blood pressure (BP) pattern. However, hypertension guidelines do not recommend the time to treat patients with medications. We conducted a systematic review of published evidence regarding ingestion-time differences of hypertension medications and their combinations on ambulatory BP-lowering, safety, and markers of target organ pathology. Some 153 trials published between 1976 and 2020, totaling 23,869 hypertensive individuals, evaluated 37 different single and 14 dual-fixed combination therapies. The vast (83.7%) majority of the trials report clinically and statistically significant benefits - including enhanced reduction of asleep BP without inducing sleep-time hypotension, reduced prevalence of the higher cardiovascular disease risk BP non-dipping 24 h profile, decreased incidence of adverse effects, improved renal function, and reduced cardiac pathology - when hypertension medications are ingested at-bedtime/evening rather than upon-waking/morning. Non-substantiated treatment-time difference in effects by the small proportion (16.3%) of published trials is likely explained by deficiencies of study design and conduct. Systematic and comprehensive review of the literature published the past 45 years reveals no single study reported significantly better benefit of the still conventional, yet unjustified by medical evidence, upon-waking/morning hypertension treatment schedule.
Targeting and clearance of senescent foamy macrophages and senescent endothelial cells by antibody-functionalized mesoporous silica nanoparticles for alleviating aorta atherosclerosis
Authors: Le Minh Pham, Eok-Cheon Kim, Wenquan Ou, Cao Dai Phung, Tien Tiep Nguyen, Thanh Tung Pham, Kishwor Poudel, Milan Gautam, Hanh Thuy Nguyen, Jee-Heon Jeong, Chul Soon Yong, So-Young Park, Jae-Ryong Kim, Jong Oh Kim
Journal: Biomaterials (2021)
Initial triple therapy in pulmonary arterial hypertension: coming of age and rejuvenated
Authors: Harm Jan Bogaard, Olivier Sitbon
Journal: European Respiratory Journal (2021)

A rare condition in children and adults alike, pulmonary arterial hypertension (PAH) is progressive and carries a poor prognosis [1, 2]. Therapeutically, three pathways are being targeted to induce vasodilation, inhibit vascular proliferation and reduce the load on the right heart: the endothelin, nitric oxide and prostacyclin (PGI2) pathways [3]. Incident adult patients with severe PAH ( i.e. with a high, >10% risk of 1-year mortality) are preferably treated with a parenteral PGI2 analogue, while the double oral combination of a phosphodiesterase type-5 (PDE-5) inhibitor and an endothelin receptor antagonist (ERA) is considered standard of care for most other patients with mild to moderate PAH [1, 2, 4]. On the basis of the landmark AMBITION trial [5], PDE-5 inhibitor/ERA combination treatment is preferably started right after diagnosis (initial combination therapy). One small retrospective study in treatment-naïve, incident patients with severe PAH suggested exceptional benefit from initial triple combination therapy, consisting of a PDE-5 inhibitor, an ERA and intravenous epoprostenol [6]. This result was recently confirmed in a similar observational study of severe incident PAH patients treated with a combination including the subcutaneous PGI2 analogue treprostinil [7]. The more recently developed prostacyclin receptor (IP) agonist selexipag was shown to improve outcomes in prevalent patients on initial mono- or combination therapy [8]. However, the benefit of initial triple combination therapy in treatment-naïve, mild-to-moderate PAH patients has not been established. Initial triple therapy benefits severe PAH patients across the ages <https://bit.ly/3o9vB1G>
Abstract 14007: Advancing Age is a Stronger Predictor of Increasing Valvular Heart Disease Hospitalizations Than Variations in Gender, Race or Ethnicity
Authors: Phyllis G Supino, Ofek Y Hai, Jeffrey S Borer
Journal: Circulation (2017)

Introduction: Several studies suggest that valvular heart disease (VHD) incidence is increasing. Advancing age has been proposed as one explanatory factor but its relative importance vs. other demo...
Impairment of Proteasome Function in Podocytes Leads to CKD
Authors: Shin-ichi Makino, Naritoshi Shirata, Juan Alejandro Oliva Trejo, Kanae Yamamoto-Nonaka, Hiroyuki Yamada, Takafumi Miyake, Kiyoshi Mori, Takahiko Nakagawa, Yoshitaka Tashiro, Hirofumi Yamashita, Motoko Yanagita, Ryosuke Takahashi, Katsuhiko Asanuma
Journal: Journal of the American Society of Nephrology (2020)

Significance Statement The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal system (APLS) are major intracellular protein degradation mechanisms. The importance of the APLS in podocytes is established, but the role of the UPS is not well understood. The first mouse model of podocyte-specific proteasome impairment revealed that UPS plays important roles in podocyte homeostasis, inducing p53-mediated apoptosis and mTOR-mediated autophagy suppression. The podocytes with impaired proteasomes exhibited characteristic features of aging and increase in a marker of aging. Our data suggest that proteasome impairment in podocytes leads to CKD and show that antioxidants and autophagy activators could be therapeutic agents for age-dependent CKD. Background The ubiquitin-proteasome system (UPS) and the autophagy-lysosomal system (APLS) are major intracellular degradation procedures. The importance of the APLS in podocytes is established, but the role of the UPS is not well understood. Methods To investigate the role of the UPS in podocytes, mice were generated that had deletion of Rpt3 ( Rpt3 pdKO ), which encodes an essential regulatory subunit required for construction of the 26S proteasome and its deubiquitinating function. Results Rpt3 pdKO mice showed albuminuria and glomerulosclerosis, leading to CKD. Impairment of proteasome function caused accumulation of ubiquitinated proteins and of oxidative modified proteins, and it induced podocyte apoptosis. Although impairment of proteasome function normally induces autophagic activity, the number of autophagosomes was lower in podocytes of Rpt 3 pdKO mice than in control mice, suggesting the autophagic activity was suppressed in podocytes with impairment of proteasome function. In an in vitro study, antioxidant apocynin and autophagy activator rapamycin suppressed podocyte apoptosis induced by proteasome inhibition. Moreover, rapamycin ameliorated the glomerular injury in the Rpt3 pdKO mice. The accumulation of ubiquitinated proteins and of oxidative modified proteins, which were detected in the podocytes of Rpt3 pdKO mice, is a characteristic feature of aging. An aging marker was increased in the podocytes of Rpt3 pdKO mice, suggesting that impairment of proteasome function promoted signs of aging in podocytes. Conclusions Impairment of proteasome function in podocytes led to CKD, and antioxidants and autophagy activators can be therapeutic agents for age-dependent CKD.
Exploring cancer clinical trial participation in the new normal of COVID-19: The patient perspective.
Authors: Martha Ann Raymond, Margaret-Ann Simonetta
Journal: Journal of Clinical Oncology (2021)

461 Background: The impact of coronavirus (COVID-19) has significantly affected cancer patients seeking to enroll in a clinical trial. The pandemic has led to an unprecedented disruption across the cancer research community pausing trial operations. Data from the National Institute of Health and the National Library of Medicine indicates 988 cancer clinical trials were suspended from March  September 1 , 2020, with 60% of institutions enrolling patients at a lower rate. Our research underscores the patient perspective of clinical trial participation amid COVID-19. Methods: July  September 2020 Nationwide eight-week online survey and interviews. Research goals: gain a better understanding of barriers and cultural attitudes of ethnically diverse communities regarding trial participation; learn the enhanced safety measures needed for patients to feel comfortable returning to the clinic; better understand the importance of effective patient-clinician communication. Results: 511 patient participants reported the following insights: 86% reported their healthcare team had not discussed trial participation; 99% reported being comfortable with telehealth visits for pre-screening and monitoring; 82% receive care at community-based hospitals. Barriers to enrollment and additional safety considerations include gaps in outreach and education services for ethnically diverse communities; absence of cultural sensitivity and disregard of historical perspective; financial insecurity and travel; and the need for increased COVID-19 testing, enhanced safety protocols and a proven vaccine. Participants identified their ethnicity as 38% Caucasian; 24% Black/African American; 19% Hispanic/Latino; 16% Asian; 2% Native American/Pacific Islander. Conclusions: Clinical trials provide patients access to the newest treatments, and yet only 2%-3% of adult cancer patients enroll in a trial. Common barriers to trial participation have been widely researched, but now amongst the coronavirus pandemic, additional barriers are evident. Based on our research, our call to action is clear: work with key opinion leaders in ethnically diverse populations to help build trust and mutual respect when discussing research studies; and engage patients and clinicians to openly discuss clinical trial enrollment working toward patient-centered communication. The coronavirus pandemic is a devastating public health threat, and it will take a collective effort from the entire cancer community to minimize the effect of COVID-19 on cancer clinical trial participation.
Gastrointestinal cancer mortality rate global trends over the last century.
Authors: Ravina Sidhu, Perneet Powar, Ritu Priya Calla, Dinesh Vyas
Journal: Journal of Clinical Oncology (2021)

457 Gastrointestinal Cancer Mortality Rate Global Trends Over the Last Century Background: Global gastroenterology cancer mortality trends have drastically changed over past decades due to alterations in risk factors such as diet, populations, exposures, and medical advancements. This study investigates specifically how meat consumption, the biggest evolving risk factor for GI cancer mortality, has influenced various gastrointestinal incidence rates globally. Although the correlation between meat consumption and cancer risk has been investigated, a global temporal study investigating the national mortality rates of gastrointestinal cancers relating to meat production remains unexplored. We researched causes for the trends between meat production and GI cancer mortality in the USA, Canada, Japan, France, and Singapore. Methods: Cancer mortality data was collected from the WHO Cancer Mortality Database, specifically the IARC database. Meat consumption data was unavailable between the 1960s-2010, so meat production data was used and obtained from the FAOSTAT. Results: The pancreatic cancer mortality rate increased in each country except Canada. This spike is due to increased meat consumption, obesity, lack of screening modalities, poor prognosis, and late diagnosis of the disease. Canada’s 1% drop in mortality rate can be attributed to a decreased smoking rate amongst men (62% to 16% from 1965-2017) as well as a decline in meat consumption. The mortality rates of gastric and colorectal cancer (CRC) have decreased despite a meat production increase. Decreased H. pylori prevalence (Europe: 48.8% to 39.8%, North America: 42.4% to 26.6%, and Western Asia: 53.6% to 54.3%) , better food preservation, and improvement in environmental conditions have lowered gastric cancer incidence. The CRC mortality rate in the USA, Canada, Japan, and France decreased mostly due to colonoscopy screening measures, better treatment, and decreased red meat consumption. In Singapore, increased obesity and high caloric diets account for an increased CRC mortality rate despite decreased meat production. This rate is exacerbated by lower screening rates due to decreased CRC risk awareness. Conclusions: Gastric and CRC mortality rates decreased despite increased meat production, while pancreatic cancer incidence rates have increased. These trends are further investigated and necessary to understand to lower the mortality rates of GI cancers on a global scale.
2D Nanomaterials for Tissue Engineering and Regenerative Nanomedicines: Recent Advances and Future Challenges
Authors: Yuanyuan Zheng, Xiangqian Hong, Jiantao Wang, Longbao Feng, Taojian Fan, Rui Guo, Han Zhang
Journal: Advanced Healthcare Materials (2021)

Abstract Regenerative medicine has become one of the hottest research topics in medical science that provides a promising way for repairing tissue defects in the human body. Due to their excellent physicochemical properties, the application of 2D nanomaterials in regenerative medicine has gradually developed and has been attracting a wide range of research interests in recent years. In particular, graphene and its derivatives, black phosphorus, and transition metal dichalcogenides are applied in all the aspects of tissue engineering to replace or restore tissues. This review focuses on the latest advances in the application of 2D‐nanomaterial‐based hydrogels, nanosheets, or scaffolds that are engineered to repair skin, bone, and cartilage tissues. Reviews on other applications, including cardiac muscle regeneration, skeletal muscle repair, nerve regeneration, brain disease treatment, and spinal cord healing are also provided. The challenges and prospects of applications of 2D nanomaterials in regenerative medicine are discussed.