tbuckley/cabot-search huggingface dataset:
COVID-19 in Correctional and Detention Facilities — United States, February–April 2020
Authors: Megan Wallace, Liesl Hagan, Kathryn G. Curran, Samantha P. Williams, Senad Handanagic, Adam Bjork, Sherri L. Davidson, Robert T. Lawrence, Joseph McLaughlin, Marilee Butterfield, Allison E. James, Naveen Patil, Kimberley Lucas, Justine Hutchinson, Lynn Sosa, Amanda Jara, Phillip Griffin, Sean Simonson, Catherine M. Brown, Stephanie Smoyer, Meghan Weinberg, Brittany Pattee, Molly Howell, Matthew Donahue, Soliman Hesham, Ellen Shelley, Grace Philips, David Selvage, E. Michele Staley, Anthony Lee, Mike Mannell, Orion McCotter, Raul Villalobos, Linda Bell, Abdoulaye Diedhiou, Dustin Ortbahn, Joshua L. Clayton, Kelsey Sanders, Hannah Cranford, Bree Barbeau, Katherine G. McCombs, Caroline Holsinger, Natalie A. Kwit, Julia C. Pringle, Sara Kariko, Lara Strick, Matt Allord, Courtney Tillman, Andrea Morrison, Devin Rowe, Mariel Marlow
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

An estimated 2.1 million U.S. adults are housed within approximately 5,000 correctional and detention facilities† on any given day (1). Many facilities face significant challenges in controlling the spread of highly infectious pathogens such as SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19). Such challenges include crowded dormitories, shared lavatories, limited medical and isolation resources, daily entry and exit of staff members and visitors, continual introduction of newly incarcerated or detained persons, and transport of incarcerated or detained persons in multiperson vehicles for court-related, medical, or security reasons (2,3). During April 22-28, 2020, aggregate data on COVID-19 cases were reported to CDC by 37 of 54 state and territorial health department jurisdictions. Thirty-two (86%) jurisdictions reported at least one laboratory-confirmed case from a total of 420 correctional and detention facilities. Among these facilities, COVID-19 was diagnosed in 4,893 incarcerated or detained persons and 2,778 facility staff members, resulting in 88 deaths in incarcerated or detained persons and 15 deaths among staff members. Prompt identification of COVID-19 cases and consistent application of prevention measures, such as symptom screening and quarantine, are critical to protecting incarcerated and detained persons and staff members.
Highly stable semiconducting polymer nanoparticles for multi-responsive chemo/photothermal combined cancer therapy
Authors: Yu Xu, Xue Zhai, Peng Su, Tianqi Liu, Luyao Zhou, Jingjing Zhang, Biqing Bao, Lianhui Wang
Journal: Theranostics (2020)

Rationale: Structural stability and size controllability are critical issues to semiconducting polymer nanoparticles (SPNs), which currently show great potential for theranostic applications. Methods: Herein, multi-responsive semiconducting polymer semi-interpenetrating nanoparticles (PDPP3T@PNIPAMAA IPNs) with highly stable structure and uniform size have been successfully designed by semi-interpenetrating technique. Results: It is proposed for the first time that PDPP3T@PNIPAMAA IPNs were prepared with "reinforced concrete" particle structure, which is even resistant to organic solvent such as ethanol and THF. By adjusting the polymerization time, the obtained PDPP3T@PNIPAMAA IPNs exhibit uniform and controllable particle size with extremely low polydispersity index (~0.037) at 1 h of reaction time. The presence of pH/light/GSH multi-responsive semi-interpenetrating network in PDPP3T@PNIPAMAA IPNs dramatically increase their drug loading efficiency (92.64%), which is significantly higher than previously reported comparable SPNs-based drug delivery systems. Additionally, PDPP3T@PNIPAMAA-DOX IPNs further provide improved therapeutic efficacy by the combination of chemotherapy and photothermal therapy with controllably regulated release of doxorubicin (DOX). In vitro and in vivo results indicate that PDPP3T@PNIPAMAA-DOX IPNs are able to release drugs at controlled rate by pH/light/GSH regulation and offer PAI-guided chemo/photothermal combined therapy with excellent therapeutic efficacy. Conclusions: The semi-interpenetrating network method may be generally extended for the preparation of a wide range of organic polymer nanoparticles to achieve ultrahigh structural stability, precise particle size controllability and excellent drug loading capacity.
OTU-02 Per-oral Endoscopic Myotomy (POEM) for oesophageal motility disorders: predictors of treatment success from 103 procedures
Authors: Mehul Patel, Shraddha Gulati, Nishmi Gunasingam, Amyn Haji, Bu’Hussain Hayee
Journal: Endoscopy (2019)

<h3>Introduction</h3> Per-oral endoscopic myotomy (POEM) has gained acceptance as an effective treatment for achalasia and other oesophageal motility disorders but may not be seen as a 'first-line' intervention. Many patients referred for POEM to our institution had, therefore, undergone other therapies and little is known about the influence of this or other factors on treatment outcomes. This study provides an overview of treatment success and safety from our institution. <h3>Methods</h3> All patients undergoing POEM since 2013 have been recorded in a registry for baseline characteristics: demographic data, disease classification, previous treatments, manometry, symptoms scores, length of stay (LOS) and procedure parameters. Treatment success was defined as Eckardt score ≤3 and/or reduction by 4 points. Following POEM patients underwent periodic follow-up assessment for: symptoms scores, manometry+pH studies and complications. <h3>Results</h3> 103 procedures were performed (98 achalasia, 5 other motility disorders; median disease duration 3.0 y (range 0.3 – 25.0), 46(44.2%) with prior therapy. Median procedure time was 75 min and LOS 2 nights. Success was achieved in 82/91 procedures (90.1%) at 3 months, with significant improvement in median Eckardt scores (8 vs 1, p&lt;0.001) and mean lower oesophageal sphincter pressures (24.9 vs 10.1 mmHg, p&lt;0.001). Success was more likely in those without previous myotomy (93.7% vs 73.4%, p&lt;0.05) with non-significant trends for entirely treatment naïve patients (95.0% vs 82.9%, p=0.077) and duration of disease &lt;2 y (97% vs 83.7%, p=0.058). Adverse event rate was 1.9% (surgical emphysema and periprocedural bradycardic episode). One patient had prolonged hospital admission (12d) due to premature opening of the mucosal entry site. <h3>Conclusions</h3> POEM is an effective and safe treatment modality for achalasia and other oesophageal motility disorders. Treatment success is affected by previous myotomy and may be influenced by duration of disease and previous other therapies, making a case for earlier intervention. To better understand predictors of outcome, patient selection factors and long-term outcomes we will be implementing a European registry for POEM to guide referrers and practitioners.
Abstract 210: Goal-Directed CPR is Less Effective With an Increased Interval From Cardiac Arrest Onset to Initiation of Chest Compressions
Authors: Pavel Hala, Matias Caceres, Aaron Prater, Josh Jung, Jensyn VanZalen, Brendan M McCracken, Mohamad H Tiba, Cindy H Hsu, Stephen Harvey, Alyssa Enciso, Jake Pitcher, Brandon C Cummings, Robert H Bartlett, Alvaro Rojas-Pena, Robert W Neumar
Journal: Circulation (2018)

Introduction: The interval from cardiac arrest (CA) to initiation of chest compressions (no-flow time) plays an important role in outcome of CA. The purpose of this study was to evaluate impact of no-flow time on the effectiveness of a goal-direct CPR strategy during prolonged cardiac arrest. Hypothesis: The effectiveness of goal-directed CPR declines with increased no-flow time. Methods: Porcine model of CA was utilized with a period of untreated ventricular fibrillation of 4 or 8 min (groups CA-4, CA-8, n=5/group) followed by a goal-directed CPR protocol for up to 40 minutes. Manual and mechanical chest compressions with impedance threshold device were used sequentially to achieve PetCO2 goal &gt;20 mmHg. Epinephrine infusion and boluses were adjusted with the goal of achieving an arterial diastolic blood pressure &gt;35 mmHg. Hemodynamic parameters were collected throughout the protocol, averaged in 5-minute intervals and compared between groups by an unpaired t-test. Results: A higher average DBP was achieved in the CA-4 vs. CA-8 group during CPR (19 ± 11 mmHg vs. 12 ± 9 mmHg: p&lt;0.04) with stronger responses to epinephrine boluses (max increase 23 vs. 11 mmHg). Brain perfusion through internal carotid artery during CPR relative to baseline averaged 24 ± 34 % vs. 10 ± 12 % in the CA-4 vs. CA-8 group respectively (p&lt;0.006). PetCO2 remained above 20 mmHg 71 ± 35 % vs. 31 ± 13 % of time during CPR in the CA-4 vs. CA-8 group respectively (p&lt;0.001). Conclusion: In this swine model of prolonged VF cardiac arrest, increased no-flow time limits the effectiveness of a goal-directed CPR strategy. Moreover, the response to standard dose of epinephrine was higher after shorter no-flow time.
Homoharringtonine in Combination with Cytarabine and Aclarubicin in the Treatment of Refractory/Relapsed Acute Myeloid Leukemia: a Single-Center Experience
Authors: Wenjuan Yu, Liping Mao, Jiejing Qian, Wenbin Qian, Haitao Meng, Wenyuan Mai, Hongyan Tong, Yin Tong, Jie Jin
Journal: Blood (2011)
Исследование железодефицитных состояний у больных глютензависимыми заболеваниями, находящихся на аглиадиновой диете
Authors: O.Yu. Gubska, А.A. Kuzminets, O.A. Naumova, I.A. Rodionova, O.A. Dolko
Journal: GASTROENTEROLOGY (2020)

Актуальность. Железодефицитная анемия (ЖДА) — это наиболее частый внекишечный симптом при целиакии у взрослых. Исследований наличия или отсутствия железодефицита, в том числе скрытого, у пациентов, имеющих как целиакию, так и непереносимость глютена без цели­акии (НГБЦ), ранее в нашей стране не проводилось. Цель исследования: изучить и проанализировать общеклинические и биохимические показатели крови, отражающие наличие анемии и/или железодефицита у больных целиакией и непереносимостью глютена без целиакии, находящихся на АГД. Материалы и методы. В исследование были включены 38 взрослых с диагностированными ранее основными видами непереносимости злаков — целиакией и НГБЦ. Все они находились на диете с полным исключением глютена. Всем исследуемым определялись гематологические показатели: общая железосвязывающая способность сыворотки, содержание эритроцитов, гемоглобина, ферритина, железа и трансферрина крови. Результаты. В результате обследования 38 пациентов, находящихся на аглиадиновой диете продолжительностью 6,5 (IQR 4–12) года, выявлено наличие ЖДА легкой степени у 13,16 % обследованных, при этом латентный железодефицит выявлялся у 18,42 % обследованных. Снижение концентрации сывороточного железа крови отмечено у 23,08 % больных общей группы, но частота железодефицита (в том числе латентного) в обследованной группе по анализу показателей концентрации сывороточного ферритина достигла 31,58 %, превалируя над частотой выявления ЖДА почти вдвое. При этом содержание эритроцитов было нормальным у 100 % обследованных. Среди пациентов с железодефицитом лица с целиакией встречаются чаще, чем среди пациентов с НГБЦ (83,3 и 16,7 % соответственно). Выводы. Больные целиакией и НГБЦ остаются в группе риска по развитию ЖДА, несмотря на то, что они находятся на аглиадиновой диете. Изолированный показатель эритроцитов не является информативным для диагностики не только скрытого железодефицита, но и ЖДА. Изолированный сывороточный уровень железа также не является показательным для диагностики данных состояний. В этом отношении именно ферритин становится наиболее показательным маркером железодефицита. Необходимо целенаправленное наблюдение за этой группой больных с целью выявления скрытых форм микронутриентного дефицита, в частности железа, и осуществления обоснованной, индивидуализированной коррекции их последствий.
Complement factor H–deficient mice develop spontaneous hepatic tumors
Authors: Jennifer Laskowski, Brandon Renner, Matthew C. Pickering, Natalie J. Serkova, Peter M. Smith-Jones, Eric T. Clambey, Raphael A. Nemenoff, Joshua M. Thurman
Journal: Journal of Clinical Investigation (2020)

Hepatocellular carcinoma (HCC) is difficult to detect, carries a poor prognosis, and is one of few cancers with an increasing yearly incidence. Molecular defects in complement factor H (CFH), a critical regulatory protein of the complement alternative pathway (AP), are typically associated with inflammatory diseases of the eye and kidney. Little is known regarding the role of CFH in controlling complement activation within the liver. While studying aging CFH-deficient (fH–/–) mice, we observed spontaneous hepatic tumor formation in more than 50% of aged fH–/– males. Examination of fH–/– livers (3–24 months) for evidence of complement-mediated inflammation revealed widespread deposition of complement-activation fragments throughout the sinusoids, elevated transaminase levels, increased hepatic CD8+ and F4/80+ cells, overexpression of hepatic mRNA associated with inflammatory signaling pathways, steatosis, and increased collagen deposition. Immunostaining of human HCC biopsies revealed extensive deposition of complement fragments within the tumors. Investigating the Cancer Genome Atlas also revealed that increased CFH mRNA expression is associated with improved survival in patients with HCC, whereas mutations are associated with worse survival. These results indicate that CFH is critical for controlling complement activation in the liver, and in its absence, AP activation leads to chronic inflammation and promotes hepatic carcinogenesis.
Salmonella Typhoid Toxin PltB Subunit and Its Non-typhoidal Salmonella Ortholog Confer Differential Host Adaptation and Virulence
Authors: Sohyoung Lee, Yi-An Yang, Shawn K. Milano, Tri Nguyen, Changhwan Ahn, Ji Hyun Sim, Andrew J. Thompson, Eric C. Hillpot, Gyeongshik Yoo, James C. Paulson, Jeongmin Song
Journal: Cell Host & Microbe (2020)
Acquired EGFr TKI resistance associated with mutation of the EGFr.
Authors: Joyce E. Ohm, Joseph M. Amann, David P. Carbone
Journal: Cancer Research (2004)

2464  Lung cancer is the leading cause of cancer death in the United States, with cure rates of less than 15%. Even though most non-small cell lung cancer tumors express the epidermal growth factor receptor (EGFr), significant clinical responses to the specific tyrosine kinase inhibitor (TKI) gefitinib are seen in only about 10% of NSCLC patients. This has led to some question as to whether the EGFr is even the target of these drugs in responding patients. In addition, even dramatic responders eventually relapse and the mechanism of acquired resistance is unclear. We evaluated the sequence of the EGFr in a patient who demonstrated a near-complete response to gefitinib after relentless progression through four chemotherapeutic regimens. This response was sustained for 18 months during which the patient had a completely normal quality of life before relapsing with rapid regrowth of tumor at one of the original sites of disease. A surgical biopsy was obtained from the tumor at the time of relapse and DNA and RNA prepared for analysis. The EGFr genomic sequence was aligned with the abl kinase domain in which point mutations have been identified as a cause for acquired TKI resistance in CML and exons analogous to those involved in abl TKI resistance were identified. This region of the kinase domain was PCR amplified and sequenced from tumor genomic DNA, and an in-frame 15-nucleotide deletion was identified within exon 19. This mutation was not present in somatic DNA and is expressed in RNA isolated from the tumor at the time of relapse. This mutation is predicted to result in the deletion of 5 amino acid residues within the drug-binding pocket and immediately adjacent to a key lysine residue known to be important for drug binding. We have cloned this receptor into expression constructs and are in the process of evaluating the functional consequences of this mutation in vitro. If this mutation is confirmed to underlie the acquisition of resistance to EGFr TKIs in additional patients, this finding will strongly support EGFr as the physiologically important target of gefitinib in patients with dramatic responses. Additionally, these data suggest that non-TKI EGFr targeting agents such as anti-receptor antibodies might be efficacious after acquired resistance to a TKI.
How to stop prednisone in SLE in remission?: Response to: ‘Withdrawal of low-dose prednisone in inactive SLE patients: is there another alternative?’ by Sabio
Authors: Alexis Mathian, Micheline Pha, Zahir Amoura
Journal: Annals of the Rheumatic Diseases (2020)

We thank Dr Sabio et al for his interest in our study.1 2 Dr Sabio in his letter suggests that the one-time withdrawal of 5 mg/day of prednisone is too abrupt and could have favoured the appearance of systemic lupus erythematosus (SLE) flares. Dr Sabio describes the practice of his unit which is to decrease by 1.25 mg of prednisone every 2 to 3 months until a complete stop. In the event of a relapse or flare, an effective dose is maintained for a longer period of time and then slowly lowered. The opinion that an abrupt cessation of a very …
ボツリヌス毒素Aによる下部尿路疾患の最新の管理:ボトックス(onabotulinumtoxinA)とディスポート(abobotulinumtoxinA)の系統的レビュー | 文献情報 | J-GLOBAL 科学技術総合リンクセンター
Authors: Mangera Altaf, Chapple Chris, Andersson Karl-Erik, Apostolidis Apostolos, Dasgupta Prokar, Giannantoni Antonella, Gravas Stavros, Madersbacher Stephan
Journal: European Urology (2011)
Prostaglandin E1 Inhibits <i>GLI2</i> Amplification–Associated Activation of the Hedgehog Pathway and Drug Refractory Tumor Growth
Authors: Fujia Wu, Chenze Zhang, Chen Zhao, Hao Wu, Zhaoqian Teng, Tao Jiang, Yu Wang
Journal: Cancer Research (2020)

Aberrant activation of the Hedgehog (HH) signaling pathway underlines the initiation and progression of a multitude of cancers. The effectiveness of the leading drugs vismodegib (GDC-0449) and sonidegib (LDE225), both Smoothened (SMO) antagonists, is compromised by acquisition of mutations that alter pathway components, notably secondary mutations in SMO and amplification of GLI2, a transcriptional mediator at the end of the pathway. Pharmacologic blockade of GLI2 activity could ultimately overcome these diversified refractory mechanisms, which would also be effective in a broader spectrum of primary tumors than current SMO antagonists. To this end, we conducted a high-content screening directly analyzing the ciliary translocation of GLI2, a key event for GLI2 activation in HH signal transduction. Several prostaglandin compounds were shown to inhibit accumulation of GLI2 within the primary cilium (PC). In particular, prostaglandin E1 (PGE1), an FDA-approved drug, is a potent GLI2 antagonist that overcame resistance mechanisms of both SMO mutagenesis and GLI2 amplification. Consistent with a role in HH pathway regulation, EP4 receptor localized to the PC. Mechanistically, PGE1 inhibited HH signaling through the EP4 receptor, enhancing cAMP-PKA activity, which promoted phosphorylation and degradation of GLI2 via the ubiquitination pathway. PGE1 also effectively inhibited the growth of drug refractory human medulloblastoma xenografts. Together, these results identify PGE1 and other prostaglandins as potential templates for complementary therapeutic development to circumvent resistance to current generation SMO antagonists in use in the clinic. SIGNIFICANCE: These findings show that PGE1 exhibits pan-inhibition against multiple drug refractory activities for Hedgehog-targeted therapies and elicits significant antitumor effects in xenograft models of drug refractory human medulloblastoma mimicking GLI2 amplification.
Glycoside scutellarin enhanced CD-MOF anchoring for laryngeal delivery
Authors: Kena Zhao, Tao Guo, Caifen Wang, Yong Zhou, Ting Xiong, Li Wu, Xue Li, Priyanka Mittal, Senlin Shi, Ruxandra Gref, Jiwen Zhang
Journal: Acta Pharmaceutica Sinica B (2020)

It is essential to develop new carriers for laryngeal drug delivery in light of the lack of therapy in laryngeal related diseases. When the inhalable micron-sized crystals of γ-cyclodextrin metal-organic framework (CD-MOF) was utilized as dry powder inhalers (DPIs) carrier with high fine particle fraction (FPF), it was found in this research that the encapsulation of a glycoside compound, namely, scutellarin (SCU) in CD-MOF could significantly enhance its laryngeal deposition. Firstly, SCU loading into CD-MOF was optimized by incubation. Then, a series of characterizations were carried out to elucidate the mechanisms of drug loading. Finally, the laryngeal deposition rate of CD-MOF was 57.72 ± 2.19% improved by SCU, about two times higher than that of CD-MOF, when it was determined by Next Generation Impactor (NGI) at 65 L/min. As a proof of concept, pharyngolaryngitis therapeutic agent dexamethasone (DEX) had improved laryngeal deposition after being co-encapsulated with SCU in CD-MOF. The molecular simulation demonstrated the configuration of SCU in CD-MOF and its contribution to the free energy of the [email protected], which defined the enhanced laryngeal anchoring. In conclusion, the glycosides-like SCU could effectively enhance the anchoring of CD-MOF particles to the larynx to facilitate the treatment of laryngeal diseases.
The Cholesterol-Raising Factor from Coffee Beans
Authors: R Urgert, M B Katan
Journal: Journal of the Royal Society of Medicine (1996)

Coffee beans and some types of coffee brew—not the regular types of coffee prepared with a paper filter or with soluble coffee granules—contain the diterpenes cafestol and kahweol. Cafestol and kahweol raise the serum concentration of cholesterol and triglycerides in humans, and they also appear mildly to affect the integrity of liver cells. Both effects are transient after withdrawal of the diterpenes, and it is as yet unsure whether these effects are associated. Patients at increased risk of heart disease who drink large amounts of coffee should be advised to select brews low in diterpenes.
When can professional sport recommence safely during the COVID-19 pandemic? Risk assessment and factors to consider
Authors: Sean Carmody, Andrew Murray, Mariya Borodina, Vincent Gouttebarge, Andrew Massey
Journal: British Journal of Sports Medicine (2020)

The COVID-19 pandemic has had, and will have, profound effects on every person on earth. Measures advocated by the WHO and put in place by national governments, businesses and individuals will save millions of lives, but current movement restrictions (ie, various degrees of lockdown) cannot continue indefinitely. The activity restrictions imposed by governments are designed to reduce human-to-human transmission; they buy time and allow international collaboration between governments and internally to build and allocate the resources and systems to 1. Test: every suspected case where testing is merited and available while having effective prevention strategies in place. 2. Trace: follow up all confirmed cases of COVID-19 and contact trace every relevant contact to identify and cut off transmission. 3. Treat: manage all cases effectively, with adequate intensive care unit capacity, ventilators and staff. Rightly, professional sport has been placed on hold during the COVID-19 pandemic. The WHO (#BeActive) and many governments continue to promote certain types of moderate physical activity for the benefits it confers on the immune system and physical and mental health.1–4 Sport has health, social and economic benefits for individuals and society, and when the COVID-19 pandemic is better 'controlled', it may be appropriate to reintroduce community sport and professional sport. In this editorial, we opine on what needs to be in place for professional sport to recommence. The relaxation of movement/activity/business restrictions is likely to happen over a gradual period, and time frames will differ across nations and even within nations. The following is expected5: