tbuckley/cabot-search huggingface dataset:
COVID-19: learning as an interdependent world
Authors: None The Lancet
Journal: The Lancet (2021)

There were some grounds for hope that the COVID-19 pandemic would be under control by now. Huge scientific advances have been made in our understanding of COVID-19, as well as its countermeasures. Countries have had 18 months to understand which policies work, and to develop strategies accordingly. Yet the pandemic is at a dangerous and shifting stage. Almost 10 000 deaths are reported globally every day. National responses to COVID-19 range from the complete lifting of restrictions in Denmark, to new state-wide lockdowns in Australia, and a growing political and public health crisis in the USA.
93P Patient-reported outcomes (PROs) with cemiplimab or placebo plus platinum-doublet chemotherapy (chemo) for first-line (1L) treatment of advanced non-small cell lung cancer (aNSCLC): EMPOWER-Lung 3 trial
Authors: T. Makharadze, R.G. Quek, T. Melkadze, M. Gogishvili, C. Ivanescu, D. Giorgadze, M. Dvorkin, K. Penkov, K. Laktionov, G. Nemsadze, M. Nechaeva, I. Rozhkova, E. Kalinka, C. Gessner, B. Moreno-Jaime, R. Passalacqua, G. Konidaris, P. Rietschel, G. Gullo
Journal: Annals of Oncology (2021)
Incorrect Affiliation and Address
Authors: John Mccarthy, Diane Liu, Frederick Kaskel
Journal: JAMA Pediatrics (2021)

periods, but also to indirect factors, such as how people respond to stress.Smoking, poorer nutrition, disordered sleep, and less exercise are common stress responses, and each can contribute to negative prenatal and perinatal outcomes, potentially leading to long-term health outcomes as well. 3,4 Attention has also been paid to the impact of pregnancyspecific stressors, 4 which is particularly salient with respect to our research.Becoming ill with a dangerous yet relatively unknown virus in the midst of a pandemic could be a substantial stressor, not only out of a mother's concern for her own well-being, but for that of her child as well.Any impact that COVID-19 infection may have on fetal development (and any potential long-term impact) could be compounded by the additional stress the mother may feel out of concern for the effect of COVID-19 on the pregnancy.We noted in our article 1 that this pandemic has not affected all demographic groups equally.Research has suggested that disparities in health care, poverty, and other socioeconomic factors can increase the burden of COVID-19 infection.In studies of children and adolescents, social vulnerabilities have been found to increase risk of death, emphasizing the impact of such factors. 5 It is reasonable to assume that these could affect COVID-19-related stress as well and should be considered in future studies.The effect of pandemic-related stress on long-term fetal outcomes is worth investigating.Not only does pandemicrelated stress serve as a potential confounder in determining the impact of maternal COVID-19 infection on long-term fetal health, but it represents a potential public health issue by itself.More mothers were impacted by pandemic-related stressors than were infected with COVID-19 during pregnancy, so the impacts have a much wider reach.Just as impacts of maternal COVID-19 infection are worth studying, so too is the impact of pandemic-related stressors.Provenzi and Grumi make a salient point, and we appreciate their response.
Transformation and outcome of nodular lymphocyte predominant Hodgkin lymphoma: a Finnish Nationwide population-based study
Authors: Ilja Kalashnikov, Tomas Tanskanen, Janne Pitkäniemi, Nea Malila, Sirkku Jyrkkiö, Sirpa Leppä
Journal: Blood Cancer Journal (2021)

Abstract Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a rare B-cell malignancy associated with excellent survival. However, some patients experience histological transformation into aggressive large B-cell lymphoma. Population-based data on transformation in patients with NLPHL is limited. We conducted a nationwide population-based study to estimate the risk of transformation and relative survival in patients diagnosed with NLPHL in Finland between 1995 and 2018. We identified a total of 453 patients (median age, 48 years; 76% males) with the incident NLPHL from the Finnish Cancer Registry. The cumulative incidence of transformation was 6.3% (95% CI, 4.2-9.6) at 10 years. After adjusting for sex, age and year of diagnosis, transformation was associated with a substantially increased risk of death (HR 8.55, 95% CI 4.49−16.3). Ten-year relative survival was 94% (95% CI, 89%‒100%). The patients diagnosed at a later calendar year had lower excess risk of death (HR, 0.38 per 10-year increase; 95% CI, 0.15‒0.98). We conclude that while the 10-year relative survival for the patients with NLPHL was excellent in this large population-based cohort for the entire study period, transformation resulted in a substantially increased mortality compared with the patients without transformation. Our results also suggest a reduction in excess mortality over time.
The Survival Impact of Second Primary Lung Cancer in Patients With Lung Cancer
Authors: Eunji Choi, Sophia J Luo, Jacqueline V Aredo, Leah M Backhus, Lynne R Wilkens, Chloe C Su, Joel W Neal, Loïc Le Marchand, Iona Cheng, Heather A Wakelee, Summer S Han
Journal: JNCI Journal of the National Cancer Institute (2021)

Lung cancer survivors have a high risk of developing second primary lung cancer (SPLC), but little is known about the survival impact of SPLC diagnosis.We analyzed data from 138 969 patients in the Surveillance, Epidemiology, and End Results (SEER), who were surgically treated for initial primary lung cancer (IPLC) in 1988-2013. Each patient was followed from the date of IPLC diagnosis to SPLC diagnosis (for those with SPLC) and last vital status through 2016. We performed multivariable Cox regression to evaluate the association between overall survival and SPLC diagnosis as a time-varying predictor. To investigate potential effect modification, we tested interaction between SPLC and IPLC stage. Using data from the Multiethnic Cohort Study (MEC) (n = 1540 IPLC patients with surgery), we evaluated the survival impact of SPLC by smoking status. All statistical tests were 2-sided.A total of 12 115 (8.7%) patients developed SPLC in SEER over 700 421 person-years of follow-up. Compared with patients with single primary lung cancer, those with SPLC had statistically significantly reduced overall survival (hazard ratio [HR] = 2.12, 95% confidence interval [CI] = 2.06 to 2.17; P < .001). The effect of SPLC on reduced survival was more pronounced among patients with early stage IPLC vs advanced-stage IPLC (HR = 2.14, 95% CI = 2.08 to 2.20, vs HR = 1.43, 95% CI = 1.21 to 1.70, respectively; Pinteraction < .001). Analysis using MEC data showed that the effect of SPLC on reduced survival was statistically significantly larger among persons who actively smoked at initial diagnosis vs those who formerly or never smoked (HR = 2.31, 95% CI = 1.48 to 3.61, vs HR = 1.41, 95% CI = 0.98 to 2.03, respectively; Pinteraction = .04).SPLC diagnosis is statistically significantly associated with decreased survival in SEER and MEC. Intensive surveillance targeting patients with early stage IPLC and active smoking at IPLC diagnosis may lead to a larger survival benefit.
Abstract 13649: Asymmetric Cerebral Perfusion in Comatose Extracorporeal Membrane Oxygenation Patients
Authors: Imad Khan, Thomas Johnson, Irfaan Dar, Kelly Donohue, Yan Xu, Esmeralda Santiago, Emily Loose, Olga Selioutski, Mark Marinescu
Journal: Circulation (2021)

Asymmetric cerebral perfusion can occur when extracorporeal membrane oxygenation (ECMO) flow competes with native cardiac circulation. It is unclear whether this phenomenon associates with brain injury. Diffuse correlation spectroscopy (DCS) provides continuous, laser-based, non-invasive, bedside monitoring of relative cerebral blood flow (rCBF). This study measured rCBF in ECMO patients via DCS to determine whether comatose patients experience asymmetric cerebral perfusion. Adults receiving ECMO for any indication were prospectively recruited from 12/2019-3/2021. Patients with prior neurologic injury, scalp/facial lacerations, and SARS-CoV-2 infection were excluded. DCS monitoring was performed daily during ECMO support with sensors placed on bilateral foreheads. Mean arterial pressure (MAP) was continuously recorded from the bedside monitor. The Glasgow Coma Scale (GCS) was assessed by clinical staff multiple times daily with sedation pauses, if possible, per standard of care. rCBF was calculated by comparing continuous cerebral blood flow (CBF) measurements to the daily median CBF, then averaged at each MAP value. Daily rCBF asymmetry was calculated by summing the absolute difference of rCBF between the two hemispheres at each MAP value, normalized for the total MAP range experienced by the patient that day. Twelve subjects were enrolled in this study (ages 21-78, 6 with cardiac arrest, 4 with acute heart failure, 2 with ARDS) and grouped by maximum GCS motor (GCS-M) score during ECMO, with 3 “comatose” subjects (GCS-M ≤ 4), and 9 “awake” subjects (GCS-M &gt; 4). DCS was performed over 66 sessions with a mean duration of 131.83 ± 1.13 minutes. Comatose subjects exhibited more rCBF asymmetry than awake subjects (0.28 ± 0.06 mmHg-1 vs. 0.10 ± 0.001 mmHg-1, p=0.045). No difference in asymmetry was noted between patients with or without cardiac arrest. We found that comatose ECMO subjects exhibited higher inter-hemispheric rCBF asymmetry over a range of blood pressures than awake subjects. Though our comatose sample is small, further validation of this finding and its causes, such as cerebrovascular dysregulation, is warranted.
Targeting radiation-tolerant persister cells as a strategy for inhibiting radioresistance and recurrence in glioblastoma
Authors: Jintao Gu, Nan Mu, Bo Jia, Qingdong Guo, Luxiang Pan, Maorong Zhu, Wangqian Zhang, Kuo Zhang, Weina Li, Meng Li, Lichun Wei, Xiaochang Xue, Yingqi Zhang, Wei Zhang
Journal: Neuro-Oncology (2021)

Compelling evidence suggests that glioblastoma (GBM) recurrence results from the expansion of a subset of tumor cells with robust intrinsic or therapy-induced radioresistance. However, the mechanisms underlying GBM radioresistance and recurrence remain elusive. To overcome obstacles in radioresistance research, we present a novel preclinical model ideally suited for radiobiological studies. With this model, we performed a screen and identified a radiation-tolerant persister (RTP) subpopulation. RNA sequencing was performed on RTP and parental cells to obtain mRNA and miRNA expression profiles. The regulatory mechanisms among NF-κB, YY1, miR-103a, XRCC3, and FGF2 were investigated by transcription factor activation profiling array analysis, chromatin immunoprecipitation, western blot analysis, luciferase reporter assays, and the MirTrap system. Transferrin-functionalized nanoparticles (Tf-NPs) were employed to improve blood–brain barrier permeability and RTP targeting. RTP cells drive radioresistance by preferentially activating DNA damage repair and promoting stemness. Mechanistic investigations showed that continual radiation activates the NF-κB signaling cascade and promotes nuclear translocation of p65, leading to enhanced expression of YY1, the transcription factor that directly suppresses miR-103a transcription. Restoring miR-103a expression under these conditions suppressed the FGF2–XRCC3 axis and decreased the radioresistance capability. Moreover, Tf-NPs improved radiosensitivity and provided a significant survival benefit. We suggest that the NF-κB–YY1–miR-103a regulatory axis is indispensable for the function of RTP cells in driving radioresistance and recurrence. Thus, our results identified a novel strategy for improving survival in patients with recurrent/refractory GBM.
Immunogenicity and safety of a third dose of CoronaVac, and immune persistence of a two-dose schedule, in healthy adults: interim results from two single-centre, double-blind, randomised, placebo-controlled phase 2 clinical trials
Authors: Gang Zeng, Qianhui Wu, Hongxing Pan, Minjie Li, Juan Yang, Lin Wang, Zhiwei Wu, Deyu Jiang, Xiaowei Deng, Kai Chu, Wen Zheng, Lei Wang, Wanying Lu, Bihua Han, Yuliang Zhao, Fengcai Zhu, Hongjie Yu, Weidong Yin
Journal: The Lancet Infectious Diseases (2021)
Increasing risk of breakthrough COVID-19 in outbreaks with high attack rates in European long-term care facilities, July to October 2021
Authors: Carl Suetens, Pete Kinross, Pilar Gallego Berciano, Virginia Arroyo Nebreda, Eline Hassan, Clémentine Calba, Eugenia Fernandes, Andre Peralta-Santos, Pedro Casaca, Nathalie Shodu, Sara Dequeker, Flora Kontopidou, Lamprini Pappa, Oliver Kacelnik, Anita Wang Børseth, Lois O’Connor, Patricia Garvey, Rasa Liausedienė, Rolanda Valintelienė, Corinna Ernst, Joël Mossong, Mária Štefkovičová, Zuzana Prostináková, Ann Caroline Danielsen, Aikaterini Mougkou, Favelle Lamb, Orlando Cenciarelli, Dominique L. Monnet, Diamantis Plachouras
Journal: Eurosurveillance (2021)

We collected data from 10 EU/EEA countries on 240 COVID-19 outbreaks occurring from July-October 2021 in long-term care facilities with high vaccination coverage. Among 17,268 residents, 3,832 (22.2%) COVID-19 cases were reported. Median attack rate was 18.9% (country range: 2.8-52.4%), 17.4% of cases were hospitalised, 10.2% died. In fully vaccinated residents, adjusted relative risk for COVID-19 increased with outbreak attack rate. Findings highlight the importance of early outbreak detection and rapid containment through effective infection prevention and control measures.
Medical adhesive allergens: Retrospective analysis of cross-sectional data from the North American Contact Dermatitis Group, 2001-2018
Authors: Amber Reck Atwater, Raina Bembry, Beiyu Liu, Erin M. Warshaw, Joel G. DeKoven, Jonathan I. Silverberg, James S. Taylor, Kathryn A. Zug, Marie-Claude Houle, Donald V. Belsito, Howard I. Maibach, Margo J. Reeder, Denis Sasseville, Cory Dunnick, Joseph F. Fowler, Melanie D. Pratt, Vincent A. DeLeo
Journal: Journal of the American Academy of Dermatology (2021)
Characterization of Primary Mitral Regurgitation With Flail Leaflet and/or Wall-Impinging Flow
Authors: Seth Uretsky, Donna Chelle V. Morales, Lillian Aldaia, Anuj Mediratta, Konstantinos Koulogiannis, Leo Marcoff, Sakul Sakul, Steven D. Wolff, Linda D. Gillam
Journal: Journal of the American College of Cardiology (2021)
Water, sanitation, and hygiene for control of trachoma in Ethiopia (WUHA): a two-arm, parallel-group, cluster-randomised trial
Authors: Solomon Aragie, Dionna M Wittberg, Wondyifraw Tadesse, Adane Dagnew, Dagnachew Hailu, Ambahun Chernet, Jason S Melo, Kristen Aiemjoy, Mahteme Haile, Taye Zeru, Zerihun Tadesse, Sarah Gwyn, Diana L Martin, Benjamin F Arnold, Matthew C Freeman, Scott D Nash, E Kelly Callahan, Travis C Porco, Thomas M Lietman, Jeremy D Keenan
Journal: The Lancet Global Health (2021)
Abstract 17180: Complications Of A Severe Case Of Multisystem Inflammatory Syndrome In Children
Authors: Danielle Sganga, Shiraz A Maskatia
Journal: Circulation (2021)

Case Presentation: A 10 year old male with prior COVID-19 exposure presented with 7 days of fever, rash, cough, vomiting, and hypotension. Laboratory evaluation was notable for SARS-CoV2 antibodies, elevated cardiac enzymes, BNP, and inflammatory markers. Initial echocardiogram showed normal cardiac function and a small LAD coronary aneurysm. He was diagnosed with Multisystemic Inflammatory Syndrome in Children (MIS-C) and given methylprednisolone and IVIG. Within 24 hours, he developed severe LV dysfunction and progressive cardiorespiratory failure requiring VA-ECMO cannulation and anticoagulation with bivalirudin. Cardiac biopsy demonstrated lymphocytic infiltration consistent with myocarditis. On VA-ECMO, he had transient periods of complete AV block. With immunomodulator treatment (anakinra, infliximab) and 5 days of plasmapheresis, inflammatory symptoms and cardiac function improved. He weaned off ECMO, and anticoagulation was transitioned to enoxaparin. He had left sided weakness 5 days later, and brain MRI revealed an MCA infarct. Ten days later, he had focal right sided weakness and repeat MRI showed multiple hemorrhagic cortical lesions, thought to be thromboembolic with hemorrhagic conversion secondary to an exaggerated inflammatory response to an MSSA bacteremia in the setting of MIS-C. Enoxaparin was discontinued. After continued recovery and a slow anakinra and steroid wean, he has normal coronary arteries, cardiac function, and baseline ECG but requires ongoing neurorehabilitation. Discussion: COVID-19 infection in children is often mild, but MIS-C is an evolving entity that can present with a wide range of features and severity. This case highlights two concepts. While first degree AV block is often reported in MIS-C, there is potential for progression to advanced AV block. Close telemetry monitoring is critical, especially if there is evidence of myocarditis. MIS-C shares features with Kawasaki disease, with a notable difference being a higher likelihood of shock and cardiac dysfunction in MIS-C. In MIS-C patients with cardiovascular collapse requiring ECMO, there is a risk for stroke. There should be a low threshold for neuroimaging and multidisciplinary effort to guide anticoagulation in these complex cases.
Hypoglycaemia following JAK inhibitor treatment in patients with diabetes
Authors: Jette A van Lint, Florence P A M van Hunsel, Sander W Tas, Harald E Vonkeman, Frank Hoentjen, Martijn B A van Doorn, Renske C F Hebing, Michael T Nurmohamed, Bart J F van den Bemt, Eugene P van Puijenbroek, Naomi T Jessurun
Journal: Annals of the Rheumatic Diseases (2021)
Renal Neoplasia in Polycystic Kidney Disease: An Assessment of Tuberous Sclerosis Complex–associated Renal Neoplasia and PKD1/TSC2 Contiguous Gene Deletion Syndrome
Authors: Sounak Gupta, Christine M. Lohse, Ross Rowsey, Michael R. McCarthy, Wei Shen, Loren Herrera-Hernandez, Stephen A. Boorjian, R. Houston Thompson, Rafael E. Jimenez, Bradley C. Leibovich, John C. Cheville
Journal: European Urology (2021)
Meet EBE: The Development of an Evidence-Based Endoscopy Simulator
Authors: Raj Shah, Sagarika Satyavada, Michael Kurin, Mayada Ismail, Zachary L. Smith, Perica Davitkov, Gerard Isenberg, Gottumukkala S. Raju, Ashley Faulx, Yngve Falck-Ytter, Amitabh Chak
Journal: Clinical Gastroenterology and Hepatology (2021)
Abstract 17117: Hyperhomocysteinemia Associated St Elevation Myocardial Infarction In A Young Male
Authors: Omar Sheikh, Jennifer Mustard, Muhammad Osman, Harsh Golwala
Journal: Circulation (2021)

Case Presentation: A 24-year-old male with a medical history of Crohn’s on mesalamine presented to the emergency room with crushing substernal chest pain at rest. Electrocardiogram revealed ST elevations in Lead V2-V5 (Figure-1a). He was taken emergently to the catheterization laboratory and had 100% thrombotic occlusion of his proximal left anterior descending coronary artery (LAD) (Figure-1b). Intravascular ultrasound (IVUS) confirmed the presence of soft atheromatous lipid-rich plaque in the proximal LAD with heavy thrombus burden (Figure-1c/d). He underwent aspiration thrombectomy and IVUS guided percutaneous coronary intervention with a 4.5 mm x 32 mm drug-eluting stent. Echocardiogram revealed an akinetic anterior wall with an ejection fraction of 35% without a patent foramen ovale. Hypercoagulable workup was initiated and showed a significantly elevated homocysteine level of 84.4 umol/L (normal:3.5-10.4). Family history, drug screen, hemoglobin A1C, and lipid profile were unremarkable. Discussion: The differential diagnosis in a young male presenting with a STEMI includes thromboembolism versus plaque rupture. IVUS showed clear evidence of a lipid-rich plaque demonstrating premature atherosclerotic vascular disease rather than a thromboembolic event. His most striking risk factor was hyperhomocysteinemia with a level of 84.4 umol/L. Elevations in homocysteine plasma concentration has been identified as an independent risk factor for atherosclerosis due to its atherogenic and prothrombotic properties. To date lowering homocysteine levels with folate and additional therapies have not shown to reduce the risk of coronary disease. Our case stresses the importance of intravascular imaging, especially in atypical cases such as a young male presenting with a STEMI to differentiate plaque rupture versus thromboembolism. Further studies are needed to identify risk modifying therapies for hyperhomocysteinemia associated vascular disease.
New insights in hidradenitis suppurativa from a population‐based Dutch cohort: prevalence, smoking behaviour, socioeconomic status and comorbidities*
Authors: Lisette M. Prens, Klasiena Bouwman, Lisa D. Troelstra, Errol P. Prens, Behrooz Z. Alizadeh, Barbara Horváth
Journal: British Journal of Dermatology (2021)

Hidradenitis suppurativa (HS) is a chronic autoinflammatory skin condition and is associated with several comorbidities. Previous studies report variable prevalence rates of HS, depending on the methodology. However, the exact prevalence remains unknown. To estimate the prevalence of HS in a large population‐based cohort in the Northern Netherlands, and to compare patients with HS to the general population, investigate characteristics and identify potential associated comorbidities. Data were collected through a cross‐sectional survey‐based study within the Lifelines Cohort Study (n = 167 729), based on the general population located in the Northern Netherlands. A digital self‐reported questionnaire was developed consisting of validated questions for determining HS. Among 56 084 respondents, the overall prevalence of HS was 2.1% [95% confidence interval (CI) 2.0–2.2]. The respondents with HS had lower socioeconomic status than the controls (P < 0.001) and more frequently currently smoked (P < 0.001). Several new significant associations in patients with HS were revealed, such as fibromyalgia (OR 2.26, 95% CI 1.64–3.11), irritable bowel syndrome (OR 1.63, 95% CI 1.18–2.26), chronic fatigue syndrome (OR 1.72, 95% CI 1.06–2.78) and migraine (OR 1.48, 95% CI 1.11–1.96). Fibromyalgia and chronic fatigue syndrome remained significantly associated with HS in the multivariate analysis after adjusting for age, sex, body mass index, smoking status and socioeconomic status. Our study showed a higher prevalence of HS in the Northern Netherlands compared with the overall estimated prevalence of 1% and identified several new associated comorbidities.
An alternatively spliced STING isoform localizes in the cytoplasmic membrane and directly senses extracellular cGAMP
Authors: Xiaobo Li, Yuanyuan Zhu, Xiao Zhang, Xiang An, Mingjiao Weng, Jiaqi Shi, Song Wang, Caiqi Liu, Shengnan Luo, Tongsen Zheng
Journal: Journal of Clinical Investigation (2021)

It has been revealed that 2'3'-cyclic-GMP-AMP (cGAMP), a second messenger that activates the antiviral stimulator of IFN genes (STING), elicits an antitumoral immune response. Since cGAMP cannot cross the cell membrane, it is not clear how intracellular STING has been activated by extracellular cGAMP until SLC19A1 was identified as an importer to transport extracellular cGAMP into the cytosol. However, SLC19A1-deficient cells also sense extracellular cGAMP, suggesting the presence of mechanisms other than the facilitating transporters for STING sensing extracellular cGAMP. Here, using immunoprecipitation, immunofluorescence, and flow cytometry, we identified an alternatively spliced STING isoform, plasmatic membrane STING (pmSTING), that localized in the plasma membrane with its C-terminus outside the cell, due to a lack of 1 transmembrane domain in its N-terminus compared with canonical STING. Further studies showed that extracellular cGAMP not only promoted the dimerization of pmSTING and interaction of pmSTING with TANK-binding kinase 1 (TBK1) and IFN regulatory factor 3 (IRF3), but also enhanced the phosphorylation of TBK1 and IRF3 and the production of IFN in pmSTING-transfected cells. Additionally, we also identified similar pmSTING isoforms in other species including human. This study suggests a conserved role for pmSTING in sensing extracellular cGAMP and provides insight into the role of cGAMP as an immunotransmitter.