tbuckley/cabot-search huggingface dataset:
Pre-existing Thyroid Autoimmunity and Risk of Papillary Thyroid Cancer: A Nested Case-Control Study of US Active-Duty Personnel
Authors: Donald S.A. McLeod, Sheryl A. Bedno, David S. Cooper, Susan M. Hutfless, Silvia Ippolito, Susan J. Jordan, Peter G. Matos, Rachel E. Neale, Elena Sabini, David C. Whiteman, Paul W. Ladenson, Patrizio Caturegli
Journal: Journal of Clinical Oncology (2022)

Thyroid autoimmunity has been associated with differentiated thyroid cancer although multiple potential biases might have influenced the results of previous studies.We conducted a case-control study nested within the cohort of US active-duty personnel 1996-2014 to assess the association between thyroid autoimmunity, defined by serology, and thyroid cancer diagnosis. The primary exposure was thyroid peroxidase (TPO) antibody status 7-10 years before the thyroid cancer index date. We also assessed whether diagnosis of thyroid autoimmunity mediated any associations identified and if thyroid cancer features differed by autoimmunity status.Among 451 incident cases of papillary thyroid cancer and matched controls (median age 36 years, 61.4% men), TPO antibody positivity (v negative) 7-10 years prediagnosis was associated with thyroid cancer (odds ratio [OR] 1.90 [95% CI, 1.33 to 2.70]). Exploratory analyses suggested an increasing risk of thyroid cancer with higher TPO antibody titer (TPO antibody 550-1,399 IU/mL: OR 2.95 [95% CI, 1.37 to 6.36]; and ≥ 1,400 IU/mL: OR 3.91 [95% CI, 1.66 to 9.24]). Positive TPO antibody status remained associated with thyroid cancer after those with diagnosed autoimmunity were excluded, and the association was not mediated by diagnosis of thyroid autoimmunity. Among the cases with diagnosed autoimmunity, 58% thyroid cancers were ≤ 10 mm diameter.Longstanding prior thyroid autoimmunity up to 10 years before thyroid cancer diagnosis was associated with papillary thyroid cancer risk. The results could not be fully explained by diagnosis of thyroid autoimmunity although when autoimmunity had been identified, thyroid cancers were diagnosed at a very early stage.
TCTAP C-082 One Moment Percutaneous Treatment of Heavily Calcific Subocclusive Left Main Stenosis and Triple Coronary Artery Disease With Concomitant Severe Aortic Stenosis: Valvuloplasty for Impella Implantation and All Stenosis Treatment
Authors: Bernardo Cortese, Elisabetta Iardino, Gaetano Di Palma, Farhat Fouladvand
Journal: Journal of the American College of Cardiology (2022)
Altered adult neurogenesis and gliogenesis in patients with mesial temporal lobe epilepsy
Authors: Aswathy Ammothumkandy, Kristine Ravina, Victoria Wolseley, Alexandria N. Tartt, Pen-Ning Yu, Luis Corona, Naibo Zhang, George Nune, Laura Kalayjian, J. John Mann, Gorazd B. Rosoklija, Victoria Arango, Andrew J. Dwork, Brian Lee, J. A. D. Smith, Dong Song, Theodore W. Berger, Christianne Heck, Robert H. Chow, Maura Boldrini, Charles Y. Liu, Jonathan J. Russin, Michael A. Bonaguidi
Journal: Nature Neuroscience (2022)
How Would You Treat This Patient With Acute and Chronic Pain From Sickle Cell Disease?
Authors: Zahir Kanjee, Maureen Okam Achebe, Wally R. Smith, Risa B. Burns
Journal: Annals of Internal Medicine (2022)

Sickle cell disease is prevalent in large numbers of patients in the United States and has a significant global impact. Its complications span numerous organs and lead to reduced life expectancy. Acute and chronic sickle cell pain is a common cause of patient suffering. The American Society of Hematology published updated guidelines on management of acute and chronic pain from sickle cell disease in 2019. Several of the recommendations are conditional and leave specific decisions to the treating physician. These include conditional recommendations about the use of ketamine for acute pain and the initiation and discontinuation of long-term opioid therapy for chronic pain. Here, 2 hematologists discuss these guidelines and make contrasting recommendations for the management of acute and chronic pain for a patient with sickle cell disease.
Investigation of immune response induction by Japanese encephalitis live‐attenuated and chimeric vaccines in mice
Authors: Enyue Fang, Xinyu Liu, Xiaohui Liu, Ming Li, Ling Wang, Miao Li, Zelun Zhang, Yuhua Li, Yongxin Yu
Journal: MedComm (2022)

The Japanese encephalitis (JE) live-attenuated vaccine SA14-14-2 and the chimeric vaccine IMOJEV (JE-CV) are two kinds of vaccines available for use worldwide. JE-CV was previously known as ChimeriVax-JE, that consists of yellow fever vaccine 17D (YFV-17D) from which the structural genes (prM/E) have been replaced with those of SA14-14-2. This study aimed to investigate the neutralizing antibody, protection efficacy, and specific T-cell response elicited by both vaccines in mice. The neutralizing antibodies produced by JE-CV were slightly lower than those produced by SA14-14-2, but the protection conferred by JE-CV was considerably lower in the low vaccine dose immunization group. Furthermore, the JE-CV did not induce a specific T-cell response against JEV NS3, while it did induce a potent antigen-specific T-cell response against the viral backbone vaccine YFV. In conclusion, this study is the first detailed investigation of the cellular immune response to the two vaccines. Enzyme-linked immunospot (ELISPOT) and flow staining suggest a more potent specific T-cell response against the JEV antigen was elicited in mice immunized with SA14-14-2 but not JE-CV. Using heterologous flaviviruses as a live-attenuated vaccine backbone may unlikely generate an optimal T-cell response against the vaccine strain virus and might affect the protective efficacy.
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Authors: Neil Goldenberg, Leonardo Brandão, Christoph Male
Journal: JAMA (2022)

Also, additional surveillance imaging may have exposed patients to more procedural sedation, ionizing radiation, and cost and would have required patients to spend extra time undergoing additional testing.However, change in thrombus burden at 3 months will be evaluated in a subsequent exploratory analysis.Third, Abdelmonem and colleagues inquire as to why the period for adverse event collection in the study was from randomization through 94 days after diagnosis of index venous thromboembolism.Given that the trial was designed to evaluate duration of therapy using currently prescribed anticoagulants rather than investigational drugs, an adverse event collection time frame was selected to optimize relevance to the study intervention; accordingly, this was defined in the trial protocol and the safety plan as the time from randomization to completion of the longer of the 2 randomized durations of anticoagulation.Nevertheless, data on recurrent venous thromboembolism and bleeding events were collected through 2 years.Fourth, Abdelmonem and colleagues note that the secondary outcome was driven by occurrences of postthrombotic syndrome, which developed in approximately 25% of patients younger than 21 years of age with extremity deep venous thrombosis and is consistent with prior literature in pediatric and adult populations.We agree that further study of prognostic factors for postthrombotic syndrome in patients younger than 21 years of age is warranted.Through clinical and translational research, 4-6 including the use of banked plasma from the Kids-DOTT trial, investigators in the field of pediatric venous thromboembolism should continue to investigate this important issue.
TCTAP C-166 Percutaneous Pulmonic Balloon Valvuloplasty in Carcinoid Heart Disease With Bioprosthetic Tricuspid Valve
Authors: Bryan Rene Toledano, Kristy Brillantes Garganera, Jessielyn Sia, Luis Martin Icasiano Habana, Timothy Dy
Journal: Journal of the American College of Cardiology (2022)
Covid-19: Ending free testing is a mistake
Authors: Trevor Pickersgill
Journal: BMJ (2022)

Covid-19: Ending free testing is a mistakeIn light of escalating rates of infection, hospital admissions, and rising sickness absence rates, the UK government should reconsider the end to free covid-19 testing Trevor Pickersgill BMA treasurer and consultant neurologist Helpfully, in the UK, we now have nine more "official" symptoms to consider when deciding if we might have covid-19.What we do not have is universally free testing so many people are left to make up their own minds about whether they have a cold, hay fever, normal aches and pains, or indeed covid-19.If they can afford to, and can find stocks, they can buy a lateral flow test.
Local euchromatin enrichment in lamina-associated domains anticipates their repositioning in the adipogenic lineage
Authors: Julia Madsen-Østerbye, Mohamed Abdelhalim, Marie-Odile Baudement, Philippe Collas
Journal: Genome biology (2022)

Interactions of chromatin with the nuclear lamina via lamina-associated domains (LADs) confer structural stability to the genome. The dynamics of positioning of LADs during differentiation, and how LADs impinge on developmental gene expression, remains, however, elusive.
Genetic heterogeneity on sleep disorders in Parkinson’s disease: a systematic review and meta-analysis
Authors: Jingxuan Huang, Yangfan Cheng, Chunyu Li, Huifang Shang
Journal: Translational Neurodegeneration (2022)

Abstract A growing amount of evidence has indicated contributions of variants in causative genes of Parkinson’s disease (PD) to the development of sleep disturbance in PD and prodromal PD stages. In this article, we aimed to investigate the role of genetics in sleep disorders in PD patients and asymptomatic carriers at prodromal stage of PD. A systematic review and meta-analysis of observational studies was conducted based on the MEDLINE, EMBASE and PsychINFO databases. A pooled effect size was calculated by odds ratio (OR) and standard mean difference (SMD). Forty studies were selected for quantitative analysis, including 17 studies on glucocerebrosidase ( GBA ), 25 studies on Leucine-rich repeat kinase 2 ( LRRK2 ) and 7 on parkin ( PRKN ) genes, and 3 studies on alpha-synuclein gene ( SNCA ) were used for qualitative analysis. Patients with PD carrying GBA variants had a significantly higher risk for rapid-eye-movement behavior disorders (RBD) (OR, 1.82) and higher RBD Screening Questionnaire scores (SMD, 0.33). Asymptomatic carriers of GBA variants had higher severity of RBD during follow-up. Patients with PD carrying the LRRK2 G2019S variant had lower risk and severity of RBD compared with those without LRRK2 G2019S. Variants of GBA , LRRK2 and PRKN did not increase or decrease the risk and severity of excessive daytime sleepiness and restless legs syndrome in PD. Our findings suggest that the genetic heterogeneity plays a role in the development of sleep disorders, mainly RBD, in PD and the prodromal stage of PD.
Multimarker synaptic protein cerebrospinal fluid panels reflect TDP-43 pathology and cognitive performance in a pathological cohort of frontotemporal lobar degeneration
Authors: Alba Cervantes González, David J. Irwin, Daniel Alcolea, Corey T. McMillan, Alice Chen-Plotkin, David Wolk, Sònia Sirisi, Oriol Dols-Icardo, Marta Querol-Vilaseca, Ignacio Illán-Gala, Miguel Angel Santos-Santos, Juan Fortea, Edward B. Lee, John Q. Trojanowski, Murray Grossman, Alberto Lleó, Olivia Belbin
Journal: Molecular Neurodegeneration (2022)

Abstract Background Synapse degeneration is an early event in pathological frontotemporal lobar degeneration (FTLD). Consequently, a surrogate marker of synapse loss could be used to monitor early pathologic changes in patients with underlying FTLD. The aim of this study was to evaluate the relationship of antemortem cerebrospinal fluid (CSF) levels of 8 synaptic proteins with postmortem global tau and TDP-43 burden and cognitive performance and to assess their diagnostic capacity in a neuropathological FTLD cohort. Methods We included patients with a neuropathological confirmation of FTLD-Tau ( n = 24, mean age-at-CSF 67 years ± 11), FTLD-TDP ( n = 25, 66 years ± 9) or AD ( n = 25, 73 years ± 6) as well as cognitively normal controls ( n = 35, 69 years ± 7) from the Penn FTD Center and ADRC. We used a semi-quantitative measure of tau and TDP-43 inclusions to quantify pathological burden across 16 brain regions. Statistical methods included Spearman rank correlations, one-way analysis of covariance, ordinal regression, step-wise multiple linear regression and receiver-operating characteristic curves. Result CSF calsyntenin-1 and neurexin-2a were correlated in all patient groups ( r s = .55 to .88). In FTLD-TDP, we observed low antemortem CSF levels of calsyntenin-1 and neurexin-2a compared to AD (.72-fold, p = .001, .77-fold, p = .04, respectively) and controls (.80-fold, p = .02, .78-fold, p = .02, respectively), which were inversely associated with post-mortem global TDP-43 burden (regression r 2 = .56, p = .007 and r 2 = .57, p = .006, respectively). A multimarker panel including calsyntenin-1 was associated with TDP-43 burden ( r 2 = .69, p = .003) and MMSE score ( r 2 = .19, p = .03) in FTLD. A second multimarker synaptic panel, also including calsyntenin-1, was associated with MMSE score in FTLD-tau ( r 2 = .49, p = .04) and improved diagnostic performance to discriminate FTLD-Tau and FTLD-TDP neuropathologic subtypes (AUC = .83). Conclusion These synaptic panels have potential in the differential diagnosis of FTLD neuropathologic subtypes and as surrogate markers of cognitive performance in future clinical trials targeting TDP-43 or tau.
TCTAP C-165 Real-Time Hybrid Visualization Modality Combining Fluoroscopy and Segmented CT-Scan Facilitates Transcatheter Left Atrial Appendage Closure Procedure
Authors: Igor V. Buzaev, Tagir Aminov, Vladimir Plechev, Irina Evgenievna Nikolaeva, Naufal Zagidullin, Eustaquio M. Onorato
Journal: Journal of the American College of Cardiology (2022)
HIV, STI and renal function testing frequency and STI history among current users of self-funded HIV pre-exposure prophylaxis, a cross-sectional study, Germany, 2018 and 2019
Authors: Uwe Koppe, Janna Seifried, Ulrich Marcus, Stefan Albrecht, Klaus Jansen, Heiko Jessen, Barbara Gunsenheimer-Bartmeyer, Viviane Bremer
Journal: Eurosurveillance (2022)

IntroductionUsers of pre-exposure prophylaxis (PrEP) require periodic testing for HIV, sexually transmitted infections (STI) and renal function. Before PrEP was made free of charge through statutory health insurance in late 2019, PrEP users in Germany had to pay for testing themselves.AimWe investigated self-reported HIV, STI and renal function testing frequencies among self-funded PrEP users in Germany, factors associated with infrequent testing, and STI diagnoses.MethodsA cross-sectional anonymous online survey in 2018 and 2019 recruited current PrEP users via dating apps for men who have sex with men (MSM), a PrEP community website, anonymous testing sites and friends. We used descriptive methods and logistic regression for analysis.ResultsWe recruited 4,848 current PrEP users. Median age was 37 years (interquartile range (IQR): 30-45), 88.7% identified as male, and respectively 26.3%, 20.9% and 29.2% were tested less frequently for HIV, STI and renal function than recommended. Participants with lower STI testing frequency were significantly less likely to report STI diagnoses during PrEP use, especially among those with many partners and inconsistent condom use. Factors most strongly associated with infrequent testing included not getting tested before starting PrEP, using PrEP from informal sources and on-demand/intermittent PrEP use.DiscussionIn a setting of self-funded PrEP, many users obtained medical tests less frequently than recommended, which can lead to missed diagnoses. Barriers to testing should be addressed to enable proper medical supervision. The suitability of testing frequencies to PrEP users with less frequent risk exposures needs to be evaluated.
Mitochondrial Calcium Uniporter Drives Metastasis and Confers a Targetable Cystine Dependency in Pancreatic Cancer
Authors: Xiuchao Wang, Yunzhan Li, Zekun Li, Shengchen Lin, Hongwei Wang, Jianwei Sun, Chungen Lan, Liangliang Wu, Dongxiao Sun, Chongbiao Huang, Pankaj K. Singh, Nadine Hempel, Mohamed Trebak, Gina M. DeNicola, Jihui Hao, Shengyu Yang
Journal: Cancer Research (2022)

Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with few effective treatments. Here we show that the mitochondrial calcium uniporter (MCU) promotes PDAC cell migration, invasion, metastasis, and metabolic stress resistance by activating the Keap1-Nrf2 antioxidant program. The cystine transporter SLC7A11 was identified as a druggable target downstream of the MCU-Nrf2 axis. Paradoxically, despite the increased ability to uptake cystine, MCU-overexpressing PDAC demonstrated characteristics typical of cystine-deprived cells and were hypersensitive to cystine deprivation-induced ferroptosis. Pharmacologic inhibitors of SLC7A11 effectively induced tumor regression and abrogated MCU-driven metastasis in PDAC. In patient-derived organoid models in vitro and patient-derived xenograft models in vivo, MCU-high PDAC demonstrated increased sensitivity to SLC7A11 inhibition compared with MCU-low tumors. These data suggest that MCU is able to promote resistance to metabolic stress and to drive PDAC metastasis in a cystine-dependent manner. MCU-mediated cystine addiction could be exploited as a therapeutic vulnerability to inhibit PDAC tumor growth and to prevent metastasis.
Vertical transmission and humoral immune response following maternal infection with SARS-CoV-2: a prospective multicenter cohort study
Authors: Manal Massalha, Enav Yefet, Orit Rozenberg, Sofia Soltsman, Jamal Hasanein, Tatiana Smolkin, Adi Alter, Yuri Perlitz, Zohar Nachum
Journal: Clinical Microbiology and Infection (2022)
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Journal: JAMA Dermatology (2022)

Samuel Der Sarkissian, MD; Schapoor Hessam, MD, PhD; Joslyn S. Kirby, MD; Michelle A. Lowes, MBBS, PhD; Dillon Mintoff, MD, MSc; Haley B. Naik, MD; Hans Christian Ring, MD, PhD; Nisha Suyien Chandran, MD; John W. Frew, MBBS, PhD
TCTAP A-073 Murray Law-Based Quantitative Flow Ratio for Assessment of Left Main Bifurcation Derived From a Single Fluoroscopic Angiographic View as Compared to FFRCT
Authors: Nozomi Kotoku, Daixin Ding, Kai Ninomiya, Shinichiro Masuda, Shigetaka Kageyama, William Wijns, Shengxian Tu, Yoshinobu Onuma, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2022)
The Role of Tissue Biopsy in the Management of Immune Checkpoint Inhibitor Toxicity
Authors: Leslie A. Fecher, Shrinivas Bishu, Robert J. Fontana, Salim S. Hayek, Bryan J. Schneider
Journal: Journal of the National Comprehensive Cancer Network (2022)

Immune checkpoint inhibitors have revolutionized the treatment of cancer and are now omnipresent. However, immune-related adverse events can present with varying phenotypes and timing, which can pose diagnostic and therapeutic challenges for the treating oncologist as well as subspecialty consultants. Biopsies of affected organs may provide insight into biologic mechanisms as well as potentially guide management in certain circumstances.
TCTAP A-050 Calcified Plaque Detected on Optical Coherence Tomography With Deep Learning and Cross-Validated With Optical and Ultrasonic Signals: A Complementary Appraisal and Preamble to the Use of Combined IVUS-OCT Catheter
Authors: Jiayue Huang, Kai Ninomiya, Shengxian Tu, Shinichiro Masuda, Jouke Dijkstra, Miao Chu, Daixin Ding, Sean O. Hynes, Neil O’Leary, William Wijns, Yoshinobu Onuma, Patrick W. Serruys
Journal: Journal of the American College of Cardiology (2022)
The potential for indoor fans to change air conditioning use while maintaining human thermal comfort during hot weather: an analysis of energy demand and associated greenhouse gas emissions
Authors: Arunima Malik, Coen Bongers, Bonnie McBain, Olivier Rey-Lescure, Richard de Dear, Anthony Capon, Manfred Lenzen, Ollie Jay
Journal: The Lancet Planetary Health (2022)

BackgroundIncreasing air conditioner use for cooling indoor spaces has the potential to be a primary driver of global greenhouse gas emissions. Moving indoor air with residential fans can raise the temperature threshold at which air conditioning needs to be turned on to maintain the thermal comfort of building occupants. We investigate whether fans can be used to reduce air conditioner use and associated greenhouse gas emissions.MethodsWe developed an integrated framework, featuring a dynamic adaptive thermal comfort model with a geographical information system-based spatially gridded map of Australia, further complemented with census data. We assessed the change in energy use and associated greenhouse gas emissions for five scenarios of air conditioner and fan use: an air conditioner-only scenario (no fans); and four fan-first scenarios with fans operating at speeds of 0·1 m/s, 0·3 m/s, 0·8 m/s, and 1·2 m/s, with air conditioning used only once the upper temperature threshold for thermal discomfort is exceeded. For each day of the selected case study year, we estimated the upper temperature limit for thermal comfort and the number of hours in which air conditioning would be switched on.FindingsThe thermal comfort threshold was increased by the use of fans compared with air conditioner use alone. We found that widespread indoor fan use had the potential to reduce energy demand and greenhouse gas emissions attributable to air conditioner use, without compromising thermal comfort. Taking an annual perspective, the use of fans with air speeds of 1·2 m/s compared with air conditioner use alone resulted in a 76% reduction in energy use (from 5592 GWh to 1344 GWh) and associated greenhouse gas emissions (5091 kilotonnes to 1208 kilotonnes).InterpretationA common strategy to cope with hot weather is the use of air conditioners, which feed a cycle of high electricity consumption, often delivered by fossil fuel power stations that in turn contribute to further increases in emissions. Moving air with electric fans could serve as a sustainable alternative, reducing air conditioner use and associated greenhouse gas emissions without sacrificing thermal comfort.FundingAustralian Research Council, New South Wales Department of Planning, Industry and Environment, and The University of Sydney.
Political Campaign Contributions of Surgeons in the United States Throughout the 2020 Election Cycle
Authors: Awinita Barpujari, Mehul Mehra, Rohin Singh, Kendra Wang, Benjamin Sherman, Rhea Gopali, Palvasha Deme, Vamsi P. Reddy, David B. Hoyt
Journal: JAMA Surgery (2022)

Political engagement by the physician workforce is necessary to ensure continued representation of their interests in health care legislation. Limited data are available pertaining to the political involvement of US surgeons.To analyze the magnitude and distribution of political donations made by all US surgeons throughout the 2020 election cycle.Partisan and geographical differences in surgeon contributions by aggregating data (January 1 through December 31, 2020) from the US Federal Election Commission database were analyzed. Contributions were labeled as Republican, Democrat, or independent depending on the committee they were designated to.Differences in contributions to Republicans, Democrats, and independent candidates for all US surgeons and for subgroups.For the 2020 election year, a total of 53 944 donations were made by surgeons in the United States, amounting to $9 223 350.68. Among all surgical specialties, the top 5 highest number of contributions were made from orthopedic surgeons (n = 15 081), ophthalmic surgeons (n = 14 836), neurological surgeons (n = 7481), urologists (n = 4544), and plastic surgeons (n = 4060). Of these donations, 59.46% (n = 32 107) were made to the Republican party ($5 420 326), 30.83% (n = 16 644) were made to the Democratic party ($1 612 775), and 9.71% (n = 5243) were made to nonpartisan (ie, independent) organizations ($2 190 250). Overall, pediatric surgeons reported the lowest mean contribution amount of $59.43, whereas thoracic surgeons reported the highest mean contribution amount of $225.19.Health care legislation has an immense impact on how medicine is practiced and utilized. This analysis reveals a high degree of political activity of surgeons across different specialties and geographic regions.