tbuckley/cabot-search huggingface dataset:
Coronavirus Disease 2019 and Effects of School Closure for Children and Their Families
Authors: Michele Poletti, Andrea Raballo
Journal: JAMA Pediatrics (2020)

Coronavirus Disease 2019 and Effects of School Closure for Children and Their FamiliesTo the Editor Risks for mental health of children and adolescents in the era of the coronavirus disease 2019 (COVID-19) pandemic, owing to school closure and quarantine, have been delineated by Golberstein et al. 1 We further extend their implications of school closure for children and their families, an issue that undergoes a deafening silence in the public debate.Mental health of children and adolescents undergoes a sudden stress test during quarantine 1 that causes a complete, sudden, and unprepared loss of direct social relationships with peers, representing a significant human need and stimulus for well-being, socioemotional development, and self-identity in this age range.Direct social relationships are limited to family members, with increased risks of loneliness; especially in the absence of home outdoor spaces, school closure significantly increases the risks for (1) physical health; (2) addiction to video games and binge watching (clearly exceeding daily time limits of screen exposure indicated by pediatric guidelines); and (3) alteration of circadian rhythms.Moreover, compulsory coexistence with family members may increase the risk of direct or assisted verbal or physical domestic violence.Finally, school closure may have profound effect on academic achievement, especially in the youngest children and in children of families with low socioeconomic status. 2,3If school closure will be confirmed for the remaining months and also summer camps will be impeded, the well-known summer learning gap will be amplified, 4 especially for children of families at low socioeconomic status and for children with preexisting neurodevelopmental or mental health conditions of vulnerability.Families with low socioeconomic status have less available possibilities in terms of suitable places to do homework, electronic devices, internet access, and owned books 2,3 ; parents themselves in the case of low socioeconomic status, exemplified by the immigrant parent-child acculturation gap, 5 may be less able to motivate and help them in this new experience of online schooling.Therefore, educational systems should plan and finance extraordinary ad hoc interventions to reduce long-lasting effects of prolonged school closures, especially for more disadvantaged children, focused but not limited to learning.Moreover, school closure is a serious and impeding problem also for working parents if they are allowed to return to work, considering that other family members who can provide resources, such as grandparents, are probably quarantined themselves.In conclusion, medical, educational, and economic competencies should implement strategic plans for a progressive restart of educational activities that may ensure a calculated trade-off between risk of COVID-19 infection, reduction of learning gap, and restart of working for parents.
Cost-effectiveness of point-of-care testing with task-shifting for HIV care in South Africa: a modelling study
Authors: Monisha Sharma, Edinah Mudimu, Kate Simeon, Anna Bershteyn, Jienchi Dorward, Lauren R Violette, Adam Akullian, Salim S Abdool Karim, Connie Celum, Nigel Garrett, Paul K Drain
Journal: The Lancet HIV (2020)
Multiple Endocrine Neoplasia Type 1: Latest Insights
Authors: Maria Luisa Brandi, Sunita K Agarwal, Nancy D Perrier, Kate E Lines, Gerlof D Valk, Rajesh V Thakker
Journal: Endocrine Reviews (2020)

Abstract Multiple endocrine neoplasia type 1 (MEN1), a rare tumor syndrome that is inherited in an autosomal dominant pattern, is continuing to raise great interest for endocrinology, gastroenterology, surgery, radiology, genetics, and molecular biology specialists. There have been 2 major clinical practice guidance papers published in the past 2 decades, with the most recent published 8 years ago. Since then, several new insights on the basic biology and clinical features of MEN1 have appeared in the literature, and those data are discussed in this review. The genetic and molecular interactions of the MEN1-encoded protein menin with transcription factors and chromatin-modifying proteins in cell signaling pathways mediated by transforming growth factor β/bone morphogenetic protein, a few nuclear receptors, Wnt/β-catenin, and Hedgehog, and preclinical studies in mouse models have facilitated the understanding of the pathogenesis of MEN1-associated tumors and potential pharmacological interventions. The advancements in genetic diagnosis have offered a chance to recognize MEN1-related conditions in germline MEN1 mutation–negative patients. There is rapidly accumulating knowledge about clinical presentation in children, adolescents, and pregnancy that is translatable into the management of these very fragile patients. The discoveries about the genetic and molecular signatures of sporadic neuroendocrine tumors support the development of clinical trials with novel targeted therapies, along with advancements in diagnostic tools and surgical approaches. Finally, quality of life studies in patients affected by MEN1 and related conditions represent an effort necessary to develop a pharmacoeconomic interpretation of the problem. Because advances are being made both broadly and in focused areas, this timely review presents and discusses those studies collectively.
277P Tegafur/uracil, platinum and cetuximab (UPEx) as first line treatment in frail patients with recurrent or metastatic head and neck squamous cell carcinoma
Authors: M-C. Hsieh, C-C. Wang, C-C. Yang, S-A. Yeh, C-F. Lien, C-C. Wang, Y-C. Shih, Y-F. Tsai, T-Z. Hwang
Journal: Annals of Oncology (2020)
Abstract PO-22: Compromised counterselection by FAS creates a lethal subtype of germinal center lymphoma
Authors: Raud Razzaghi, Shreya Agarwal, Nikita Kotlov, Olga Plotnikova, Krystle Nomie, Da Wei Huang, George W. Wright, Moyi Li, Katsuyoshi Takata, Chen Yao, John J. O'Shea, James D. Phelan, Stefania Pittaluga, David W. Scott, Jagan R. Muppidi
Journal: Blood Cancer Discovery (2020)

Abstract Fas is highly expressed on germinal center (GC) B cells, and mutations of FAS have been reported in diffuse large B-cell lymphoma (DLBCL); however, the function of Fas in the GC remains controversial. Although GC-derived DLBCL has better overall outcomes to therapy than other DLBCL types, some cases are refractory and the molecular basis for this is often unknown. We show that Fas is a strong cell-intrinsic regulator of GC B cells that promotes B-cell death in the light zone likely via T follicular helper (Tfh) cell-derived Fas ligand. In the absence of Fas, GCs were more clonally diverse due to an accumulation of cells that did not demonstrably bind antigen. We found that FAS alterations occurred most commonly in the GC-derived genetic subtype of DLBCL, EZB. FAS alterations in EZB were associated with inferior outcomes and an enrichment of Tfh cells. Alterations in FAS co-occurred with deficiency in HVEM and PD-1 ligands that regulate the Tfh-B cell interaction and were associated with increased diversity of B-cell receptor variable genes across samples. This work shows that Fas is critically required for GC homeostasis and suggests that loss of Tfh-mediated counterselection in the GC contributes to lethality in a distinct subtype of GC-derived lymphoma. Citation Format: Raud Razzaghi, Shreya Agarwal, Nikita Kotlov, Olga Plotnikova, Krystle Nomie, Da Wei Huang, George W. Wright, Moyi Li, Katsuyoshi Takata, Chen Yao, John J. O'Shea, James D. Phelan, Stefania Pittaluga, David W. Scott, Jagan R. Muppidi. Compromised counterselection by FAS creates a lethal subtype of germinal center lymphoma [abstract]. In: Proceedings of the AACR Virtual Meeting: Advances in Malignant Lymphoma; 2020 Aug 17-19. Philadelphia (PA): AACR; Blood Cancer Discov 2020;1(3_Suppl):Abstract nr PO-22.
EMT Transcription Factor ZEB1 Represses the Mutagenic POLθ-Mediated End-Joining Pathway in Breast Cancers
Authors: Mélanie K. Prodhomme, Roxane M. Pommier, Camille Franchet, Frédérique Fauvet, Valérie Bergoglio, Pierre Brousset, Anne-Pierre Morel, Anne-Cécile Brunac, Mojgan Devouassoux-Shisheboran, Virginie Petrilli, Caroline Moyret-Lalle, Jean-Sébastien Hoffmann, Alain Puisieux, Agnès Tissier
Journal: Cancer Research (2020)

Abstract A characteristic of cancer development is the acquisition of genomic instability, which results from the inaccurate repair of DNA damage. Among double-strand break repair mechanisms induced by oncogenic stress, the highly mutagenic theta-mediated end-joining (TMEJ) pathway, which requires DNA polymerase theta (POLθ) encoded by the POLQ gene, has been shown to be overexpressed in several human cancers. However, little is known regarding the regulatory mechanisms of TMEJ and the consequence of its dysregulation. In this study, we combined a bioinformatics approach exploring both Molecular Taxonomy of Breast Cancer International Consortium and The Cancer Genome Atlas databases with CRISPR/Cas9-mediated depletion of the zinc finger E-box binding homeobox 1 (ZEB1) in claudin-low tumor cells or forced expression of ZEB1 in basal-like tumor cells, two triple-negative breast cancer (TNBC) subtypes, to demonstrate that ZEB1 represses POLQ expression. ZEB1, a master epithelial-to-mesenchymal transition–inducing transcription factor, interacted directly with the POLQ promoter. Moreover, downregulation of POLQ by ZEB1 fostered micronuclei formation in TNBC tumor cell lines. Consequently, ZEB1 expression prevented TMEJ activity, with a major impact on genome integrity. In conclusion, we showed that ZEB1 directly inhibits the expression of POLQ and, therefore, TMEJ activity, controlling both stability and integrity of breast cancer cell genomes. Significance: These findings uncover an original mechanism of TMEJ regulation, highlighting ZEB1 as a key player in genome stability during cancer progression via its repression of POLQ. See related commentary by Carvajal-Maldonado and Wood, p. 1441
The Use of B-Type Natriuretic Peptides in Coronary Artery Disease: Utile or Futile?⁎⁎Editorials published in the Journal of the American College of Cardiologyreflect the views of the authors and do not necessarily represent the views of JACCor the American College of Cardiology.
Authors: Christian Mueller
Journal: Journal of the American College of Cardiology (2007)
13624 Thyroid dysfunction in psoriasis: Higher prevalence of thyroid dysfunction in patients with generalized pustular psoriasis
Authors: Kaoru Namiki, Masahiro Kamata, Mayumi Nagata, Saki Fukaya, None aki Fukaya, Kotaro Hayashi, Atsuko Fukuyasu, Takamitsu Tanaka, Takeko Ishikawa, Takamitsu Ohnishi, Yayoi Tada
Journal: Journal of the American Academy of Dermatology (2020)
Infection Control of COVID-19
Authors: Ayah Adel Nawwar, Julie Searle, Christopher Green, Iain Douglas Lyburn
Journal: Clinical Nuclear Medicine (2020)

Abstract In accordance with published international COVID-19 pandemic guidance (American College of Nuclear Medicine, British Nuclear Medicine Society, and European Association of Nuclear Medicine), the use of face masks has become an essential part of infection control for both patients and staff. A 56-year-old man with mantle cell lymphoma underwent staging FDG PET/CT, which demonstrated avid lymphadenopathy below the diaphragm and an unusual diffuse FDG uptake projected over the face, raising the suspicion of cutaneous lymphomatous involvement. On reflection of the clinical scenario and scanning conditions, cutaneous involvement was discounted; the pattern of uptake and lack of CT correlate were supportive of a cutaneous artifact related to the presence of the patient's mask.
Abstract 15354: CRT versus RV Pacing--Can We Reduce Readmissions in HFpEF Through Better Device Selection?
Authors: Esseim Sharma, Michael Wu, Wasiq Sheikh, Anshul Parulkar, Brian D McCauley, Malik B Ahmed, Lauren Rousseau, Antony F Chu
Journal: Circulation (2019)

Introduction: Cardiac resynchronization therapy (CRT) reduces hospital admissions and 30-day readmissions in systolic heart failure in appropriately selected patients. Recently published data sugge...
Timing of Introduction of Complementary Foods — United States, 2016–2018
Authors: Katelyn V. Chiang, Heather C. Hamner, Ruowei Li, Cria G. Perrine
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

The American Academy of Pediatrics (AAP) recommends introducing complementary foods (i.e., any solid or liquid other than breast milk or infant formula) to infants at approximately age 6 months (1). Although a consensus on ideal timing is lacking, most experts agree that introduction of complementary foods before age 4 months is too early because of infant gastrointestinal and motor immaturity (1,2). In addition, early introduction prevents exclusively breastfed infants from reaching the recommended 6 months of exclusive breastfeeding (1) and might be associated with increased risk for overweight and obesity (3). Nationally representative data on complementary feeding are limited; state-level estimates have been previously unavailable. CDC analyzed 2016-2018 data from the National Survey of Children's Health (NSCH) (N = 23,927) to describe timing of complementary feeding introduction and prevalence of early introduction of complementary foods before age 4 months (early introduction) among children aged 1-5 years. Prevalence of early introduction was 31.9% nationally and varied geographically and across sociodemographic and infant feeding characteristics. These estimates suggest that many infants are introduced to complementary foods before they are developmentally ready. Efforts by health care providers and others who might influence infant feeding practices could help decrease the number of infants who are introduced to complementary foods too early.
T型カルシウムチャンネルインヒビターである塩酸エホニジピンの交感神経活動に対する臨床効果 123 I-メタヨードベンジルグアニジン心筋シンチグラフィー及び心拍/血圧変動性のスペクトル分析を用いた試験
Authors: Harada K, Nomura M, Nishikado A, Uehara K, Nakaya Y, Ito S
Journal: Circulation (2003)
Abstract 15938: Sex-Specific Impact of S-Nitrosoglutathione Reductase (gsnor) on Ventricular Remodeling and Function Following Myocardial Infarction in Mice
Authors: Shathiyah Kulandavelu, Raul A Dulce, Amarylis A Wanschel, Lauro Takeuchi, Wayne Balkan, Joshua M Hare
Journal: Circulation (2018)

Introduction: Female hearts are less susceptible to injury following myocardial infarction (MI) likely due to estrogen working through the nitric oxide (NO) pathway. NO exerts effects largely via S...
Randomized Trial Replication Using Observational Data for Comparative Effectiveness of Secukinumab and Ustekinumab in Psoriasis
Authors: Zenas Z. N. Yiu, Kayleigh J. Mason, Philip J. Hampton, Nick J. Reynolds, Catherine H. Smith, Mark Lunt, Christopher E. M. Griffiths, Richard B. Warren
Journal: JAMA Dermatology (2020)

Treatments for psoriasis may be less effective in everyday practice than in clinical trials. Emulating a target trial using data from the British Association of Dermatologists Biologics and Immunomodulators Register (BADBIR) can provide treatment effect estimates that are robust and can inform both clinicians and regulatory bodies.To assess the comparative effectiveness of ustekinumab and secukinumab in patients with psoriasis, and to test whether the relative effectiveness estimate of the CLEAR trial, a randomized clinical trial that compared secukinumab with ustekinumab for psoriasis, can be replicated.This comparative effectiveness research study used a target trial emulation approach and was performed between November 2007 and August 2019. Data were obtained from BADBIR, a multicenter longitudinal pharmacovigilance register of patients with moderate to severe psoriasis in the United Kingdom and Republic of Ireland. Participants had chronic plaque psoriasis, were 18 years or older, and had at least 1 record of a Psoriasis Area and Severity Index (PASI) of 12 or higher before their initiation to secukinumab or ustekinumab. Propensity score (PS) 1:1 matched analysis and inverse probability treatment weighted analysis were performed.The primary outcomes were the risk ratio (RR) and the risk difference (RD) for achieving PASI of 2 or lower after 12 months of therapy for secukinumab compared with ustekinumab. Methods to account for missing outcome data were complete case analysis, nonresponder imputation, last observation carried forward, inverse probability of censoring weighting, and multiple imputation. Regulatory and estimate agreement metrics were used to benchmark the effect estimates in this study against those in the CLEAR trial.A total of 1231 patients were included in the analysis, with 917 receiving ustekinumab and 314 receiving secukinumab. Secukinumab was superior to ustekinumab in all analyses, except under the nonresponder imputation method, in the proportion of participants achieving a PASI of 2 or lower (PS-weighted complete case analysis: RR, 1.28 [95% CI, 1.06-1.55]; RD, 11.9% [1.6-22.1]). All analyses, except for nonresponder imputation, reached regulatory agreement in both PS-matching and PS-weighted analyses.This comparative effectiveness study found that secukinumab resulted in more patients achieving a PASI of 2 or lower after 12 months of therapy compared with ustekinumab in patients with psoriasis. Target trial emulation in this study resulted in regulatory and estimate agreement with the CLEAR randomized clinical trial; further such studies may help fill the evidence gap when comparing other systemic therapies for psoriasis.
15261 Lack of tuberculosis reactivation in 12,319 patients with psoriasis, psoriatic arthritis, or ankylosing spondylitis treated with secukinumab: An ad hoc analysis of pooled safety data from 28 clinical trials
Authors: Boni Elewski, John W. Baddley, Atul Deodhar, Marina Magrey, Phoebe Rich, Enrique Soriano, Jennifer Soung, Weibin Bao, Manmath Patekar, Mark Lebwohl, Abhishek Sharma
Journal: Journal of the American Academy of Dermatology (2020)
What to Do With Sideline Guilt
Authors: Henry S. Kahn
Journal: JAMA Internal Medicine (2020)

To the Editor The Physician Perspective by Reuben 1 on sideline guilt should strike a deep chord for many of us.I am a family physician, 72 years old, 6 years retired after an episode of ill health from which I have recovered.So I have my health, food in the refrigerator, enough money in the bank, and a spouse who still puts up with me.The only hardship we face is that coronavirus disease 2019 (COVID-19) has kept us from seeing our far-flung children and grandchildren and forced us to socialize distantly with our friends.Many of my prepandemic activities-working as a nursing home ombudsman, teaching medical students, serving on hospital committees-have been curtailed completely or relegated to virtual visits.That I, as a noncritical care specialist, could meaningfully replace a frontline worker is a dubious proposition at best.As Reuben 1 points out, staying away from hospitals may be the most constructive thing some of us can do.But beyond the world of medicine, there is so much more to feel guilty about.The COVID-19 pandemic and current events have brought into sharp focus the long-standing racial and class inequities from which I and so many who might read this have undoubtedly benefited in one way or another.I would add 2 suggestions to those Reuben 1 has proposed.First, allow yourself to experience gratitude if you float in the same guilty boat as I do: gratitude that you have the boat.Second, get angry about the state of the world and get motivated.The Viewpoint by Berwick 2 on the moral determinants of health is a good place to start.There is much that those of us who are blessed not to be suffering in these difficult times can do to help make sure the new normal will better than the old.
PODO447: a novel antibody to a tumor-restricted epitope on the cancer antigen podocalyxin
Authors: Diana Canals Hernaez, Michael R Hughes, Pamela Dean, Peter Bergqvist, Ismael Samudio, Ola Blixt, Katharina Wiedemeyer, Yicong Li, Chris Bond, Eric Cruz, Martin Köbel, Blake Gilks, Calvin D Roskelley, Kelly M McNagny
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background The success of new targeted cancer therapies has been dependent on the identification of tumor-specific antigens. Podocalyxin (Podxl) is upregulated on tumors with high metastatic index and its presence is associated with poor outcome, thus emerging as an important prognostic and theragnostic marker in several human cancers. Moreover, in human tumor xenograft models, Podxl expression promotes tumor growth and metastasis. Although a promising target for immunotherapy, the expression of Podxl on normal vascular endothelia and kidney podocytes could hamper efforts to therapeutically target this molecule. Since pathways regulating post-translational modifications are frequently perturbed in cancer cells, we sought to produce novel anti-Podxl antibodies (Abs) that selectively recognize tumor-restricted glycoepitopes on the extracellular mucin domain of Podxl. Methods Splenic B cells were isolated from rabbits immunized with a Podxl-expressing human tumor cell line. Abs from these B cells were screened for potent reactivity to Podxl + neoplastic cell lines but not Podxl + primary endothelial cells. Transcripts encoding heavy and light chain variable regions from promising B cells were cloned and expressed as recombinant proteins. Tumor specificity was assessed using primary normal tissue and an ovarian cancer tissue microarray (TMA). Mapping of the tumor-restricted epitope was performed using enzyme-treated human tumor cell lines and a glycan array. Results One mAb (PODO447) showed strong reactivity with a variety of Podxl+ tumor cell lines but not with normal primary human tissue including Podxl+ kidney podocytes and most vascular endothelia. Screening of an ovarian carcinoma TMA (219 cases) revealed PODO447 reactivity with the majority of tumors, including 65% of the high-grade serous histotype. Subsequent biochemical analyses determined that PODO447 reacts with a highly unusual terminal N-acetylgalactosamine beta-1 (GalNAcβ1) motif predominantly found on the Podxl protein core. Finally, Ab–drug conjugates showed specific efficacy in killing tumor cells in vitro . Conclusions We have generated a novel and exquisitely tumor-restricted mAb, PODO447, that recognizes a glycoepitope on Podxl expressed at high levels by a variety of tumors including the majority of life-threatening high-grade serous ovarian tumors. Thus, tumor-restricted PODO447 exhibits the appropriate specificity for further development as a targeted immunotherapy.
Genes that Escape X-Inactivation in Humans Have High Intraspecific Variability in Expression, Are Associated with Mental Impairment but Are Not Slow Evolving
Authors: Yuchao Zhang, Atahualpa Castillo-Morales, Min Jiang, Yufei Zhu, Landian Hu, Araxi O. Urrutia, Xiangyin Kong, Laurence D. Hurst
Journal: Molecular Biology and Evolution (2015)

We wish to bring to the readers' attention that, owing to a scripting error, column 3 of supplementary table S3 was incorrectly specified.This column described the X-inactivation status of the genes in our sample.We now issue a replacement and augmented supplementary table S3.We are grateful to Mr Kerem Wainer Katsir for bringing this issue to our attention.Previously, we merged our data with that of Park et al. to test for differences between classes in Ka/Ks.Owing to the error in specification of column 3, these merged data are also incorrect.The data presented in Park et al. (2010) are therein said to be derived from Carrel and Willard (2005).It has, however, also come to our attention that the data in Park et al and Carrel and Willard, while similar, are not identical.We now therefore present both of these data sets and a consensus merge of all three.