tbuckley/cabot-search huggingface dataset:
Phase II Study of Combination Obinutuzumab, Ibrutinib, and Venetoclax in Treatment-Naïve and Relapsed or Refractory Chronic Lymphocytic Leukemia
Authors: Kerry A. Rogers, Ying Huang, Amy S. Ruppert, Lynne V. Abruzzo, Barbara L. Andersen, Farrukh T. Awan, Seema A. Bhat, Allison Dean, Margaret Lucas, Christin Banks, Cara Grantier, Nyla A. Heerema, Gerard Lozanski, Kami J. Maddocks, Thomas R. Valentine, David M. Weiss, Jeffrey A. Jones, Jennifer A. Woyach, John C. Byrd
Journal: Journal of Clinical Oncology (2020)

The development of highly effective targeted agents for chronic lymphocytic leukemia offers the potential for fixed-duration combinations that achieve deep remissions without cytotoxic chemotherapy.This phase II study tested a combination regimen of obinutuzumab, ibrutinib, and venetoclax for a total of 14 cycles in both patients with treatment-naïve (n = 25) and relapsed or refractory (n = 25) chronic lymphocytic leukemia to determine the response to therapy and safety.The primary end point was the rate of complete remission with undetectable minimal residual disease by flow cytometry in both the blood and bone marrow 2 months after completion of treatment, which was 28% in both groups. The overall response rate at that time was 84% in treatment-naïve patients and 88% in relapsed or refractory patients. At that time, 67% of treatment-naïve patients and 50% of relapsed or refractory patients had undetectable minimal residual disease in both the blood and marrow. At a median follow-up of 24.2 months in treatment-naïve patients and 21.5 months in relapsed or refractory patients, the median progression-free and overall survival times were not yet reached, with only 1 patient experiencing progression and 1 death. Neutropenia and thrombocytopenia were the most frequent adverse events, followed by hypertension. Grade 3 or 4 neutropenia was experienced by 66% of patients, with more events in the relapsed or refractory cohort. There was only 1 episode of neutropenic fever. A favorable impact on both perceived and objective cognitive performance during treatment was observed.The combination regimen of obinutuzumab, ibrutinib, and venetoclax offers time-limited treatment that results in deep remissions and is now being studied in phase III cooperative group trials.
Advancements in the co-formulation of biologic therapeutics
Authors: Veeren M. Chauhan, Hongyu Zhang, Paul A. Dalby, Jonathan W. Aylott
Journal: Journal of Controlled Release (2020)

Biologic therapeutics are the medicines of the future and are destined to transform the approaches by which the causes and symptoms of diseases are cured and alleviated. These approaches will be accelerated through the development of novel strategies that target multiple pharmacologically active sites using a combination of different biologics, or mixtures of biologics and small molecule therapeutics. However, for this potential to be realised, advancements in co-formulation strategies for biologic therapeutics must be established. This review describes the current and emerging developments within this field and highlights the challenges and potential solutions, that will pave-the-way towards their clinical translation.
Autosomal recessive hypotrichosis with loose anagen hairs associated with <i>TKFC</i> mutations*
Authors: A. Onoufriadis, A. Cabezas, J.C.F. Ng, J. Canales, M.J. Costas, J.M. Ribeiro, J.R. Rodrigues, M.A. McAleer, L. Castelo‐Soccio, M.A. Simpson, F. Fraternali, A.D. Irvine, J.C. Cameselle, J.A. McGrath
Journal: British Journal of Dermatology (2020)

Loose anagen hair is a rare form of impaired hair anchorage in which anagen hairs that lack inner and outer root sheaths can be gently and painlessly plucked from the scalp. This condition usually occurs in children and is often self-limiting. A genetic basis for the disorder has been suggested but not proven. A better understanding the aetiology of loose anagen hair may improve prevention and treatment strategies.To identify a possible genetic basis of loose anagen hair using next-generation DNA sequencing and functional analysis of variants identified.In this case study, whole-exome sequencing analysis of a pedigree with one affected individual with features of loose anagen hair was performed.The patient was found to be compound heterozygous for two single-nucleotide substitutions in TKFC resulting in the following missense mutations: c.574G> C (p.Gly192Arg) and c.682C> T (p.Arg228Trp). Structural analysis of human TKFC showed that both mutations are located near the active site cavity. Kinetic assays of recombinant proteins bearing either of these amino acid substitutions showed almost no dihydroxyacetone kinase or D-glyceraldehyde kinase activity, and FMN cyclase activity reduced to just 10% of wildtype catalytic activity.TKFC missense mutations may predispose to the development of loose anagen hairs. Identification of this new biochemical pathobiology expands the metabolic and genetic basis of hypotrichosis.
Re: Vasilis Stavrinides, Francesco Giganti, Bruce Trock, et al. Five-year Outcomes of Magnetic Resonance Imaging-based Active Surveillance for Prostate Cancer: A Large Cohort Study. Eur Urol 2020;78:443–51
Authors: Carissa E. Chu, Peter E. Lonergan, Peter R. Carroll
Journal: European Urology (2020)
Abstract 17072: Discordance Between Lactic Acid Elevation and Invasive Hemodynamics in Decompensated Heart Failure
Authors: Nikhil Narang, Bow Chung, Ann Nguyen, Teruhiko Imamura, Sara Kalantari, Bryan Smith, Gene H Kim, Jayant Raikhelkar, Nitasha Sarswat, Valluvan Jeevanandam, Gabriel T Sayer, Nir Uriel
Journal: Circulation (2018)

Introduction: Elevated lactic acid (LA) levels carry a poor prognosis in patients admitted with shock. Data is lacking on the association of LA level with the severity of decompensated heart failure (HF). This study assesses the relationship between LA levels, invasive hemodynamics and clinical outcomes. Methods: Patients presenting to the cardiac care unit with decompensated HF between 2015-18 were prospectively enrolled into an invasive hemodynamics study. LA (normal 0.7-2.1 mmol/L) levels were obtained within 12 hours prior to right heart catheterization (RHC). No significant changes in therapy were made in the time between LA level collection &amp; RHC. Patients were divided into 4 groups: 1) normal pulmonary capillary wedge pressure (PCWP) (&lt; 18 mmHg)/ normal Fick cardiac index (CI) (≥ 2.2 L/min/m 2 ), 2) normal PCWP/ low CI (&lt; 2.2 L/min/m 2 ) 3) elevated PCWP (≥ 18 mmHg )/ normal CI, 4) elevated PCWP / low CI. Results: 80 patients were enrolled. Mean age 58±14 years; 78% male, left ventricular ejection fraction was 24±4%. Prior to RHC, 55% patients were on vasoactives and/or inotropes. Mean (SD) PCWP was 26 ± 8.8 mmHg and mean CI was 2.06 ± 0.61 L/min/m 2 . Overall 48 (60%) of the patients had high PCWP and low CI (group 4). 81% had normal LA (≤2.1 mmol/L) prior to RHC. There was no correlation between LA level and PCWP (R=0.12; p=0.30); there was a moderate inverse correlation between LA level and CI (R=-0.40; p&lt;0.01). Only 25% of patients with the highest risk hemodynamic profile (elevated PCWP/low CI) had an elevated LA level (Figure A). 90- day all cause mortality was 33% When LA was stratified by tertile, there was no significant difference in mortality between the tertiles (Figure B). Conclusion: In patients with decompensated HF, normal LA levels do not exclude the presence of cardiogenic shock with profoundly impaired cardiac output. Invasive assessment of hemodynamics should not be delayed based on LA level alone.
Improving handwashing habits and household air quality in Africa after COVID-19
Authors: Adeladza K Amegah
Journal: The Lancet Global Health (2020)

Handwashing with soap under running water is a key intervention for preventing the spread of COVID-19. However, in Africa, before the COVID-19 pandemic, this simple and effective intervention for preventing sanitation-related diseases such as cholera, diarrhoea, dysentery, typhoid, and soil-transmitted helminth infections was not practised by many people, especially in communities in rural areas and low-income urban settlements. Only 15% of the population in sub-Saharan Africa have access to basic handwashing facilities with soap and water.
Amoeba Genome Reveals Dominant Host Contribution to Plastid Endosymbiosis
Authors: Duckhyun Lhee, JunMo Lee, Khaoula Ettahi, Chung Hyun Cho, Ji-San Ha, Ya-Fan Chan, Udi Zelzion, Timothy G Stephens, Dana C Price, Arwa Gabr, Eva C M Nowack, Debashish Bhattacharya, Hwan Su Yoon
Journal: Molecular Biology and Evolution (2020)

Abstract Eukaryotic photosynthetic organelles, plastids, are the powerhouses of many aquatic and terrestrial ecosystems. The canonical plastid in algae and plants originated &amp;gt;1 Ga and therefore offers limited insights into the initial stages of organelle evolution. To address this issue, we focus here on the photosynthetic amoeba Paulinella micropora strain KR01 (hereafter, KR01) that underwent a more recent (∼124 Ma) primary endosymbiosis, resulting in a photosynthetic organelle termed the chromatophore. Analysis of genomic and transcriptomic data resulted in a high-quality draft assembly of size 707 Mb and 32,361 predicted gene models. A total of 291 chromatophore-targeted proteins were predicted in silico, 208 of which comprise the ancestral organelle proteome in photosynthetic Paulinella species with functions, among others, in nucleotide metabolism and oxidative stress response. Gene coexpression analysis identified networks containing known high light stress response genes as well as a variety of genes of unknown function (“dark” genes). We characterized diurnally rhythmic genes in this species and found that over 49% are dark. It was recently hypothesized that large double-stranded DNA viruses may have driven gene transfer to the nucleus in Paulinella and facilitated endosymbiosis. Our analyses do not support this idea, but rather suggest that these viruses in the KR01 and closely related P. micropora MYN1 genomes resulted from a more recent invasion.
Disparities in Incidence of COVID-19 Among Underrepresented Racial/Ethnic Groups in Counties Identified as Hotspots During June 5–18, 2020 — 22 States, February–June 2020
Authors: Jazmyn T. Moore, Jessica N. Ricaldi, Charles E. Rose, Jennifer Fuld, Monica Parise, Gloria J. Kang, Anne K. Driscoll, Tina Norris, Nana Wilson, Gabriel Rainisch, Eduardo Valverde, Vladislav Beresovsky, Christine Agnew Brune, Nadia L. Oussayef, Dale A. Rose, Laura E. Adams, Sindoos Awel, Julie Villanueva, Dana Meaney-Delman, Margaret A. Honein, Gregory Bautista, Janet Cowins, Charles Edge, Gail Grant, Robbie Gray, Sean Griffing, Nikki Hayes, Laura Hughes, Rene Lavinghouze, Sarah Leonard, Robert Montierth, Krishna Palipudi, Victoria Rayle, Andrew Ruiz, Malaika Washington, Sherri Davidson, Jennifer Dillaha, Rachel Herlihy, Carina Blackmore, Thomas Troelstrup, Laura Edison, Ebony Thomas, Caitlin Pedati, Farah Ahmed, Catherine Brown, Sarah Lyon Callo, Kathryn Como-Sabetti, Paul Byers, Victor Sutton, Zackary Moore, Sietske de Fijter, Alexia Zhang, Linda Bell, John Dunn, Stephen Pont, Keegan McCaffrey, Emily Stephens, Ryan Westergaard
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

https://www.cdc.gov/coronavirus/2019-ncov/cases-in-us.html.† Hotspot counties are defined as those meeting all of the following baseline criteria: 1) >100 new COVID-19 cases in the most recent 7 days, 2) an increase in the most recent 7-day COVID-19 incidence over the preceding 7-day incidence, 3) a decrease of <60% or an increase in the most recent 3-day COVID-19 incidence over the preceding 3-day incidence, and 4) the ratio of 7-day incidence to 30-day incidence exceeds 0.31.In addition, hotspots must have met at least one of the following criteria: 1) >60% change in the most recent 3-day COVID-19 incidence, or 2) >60% change in the most recent 7-day incidence.Abbreviations: AI/AN = American Indian/Alaska Native; COVID-19 = coronavirus disease 2019; NHPI = Native Hawaiian/other Pacific Islanders.* Disparities were defined as percentage difference of ≥5% between the proportion of cases and the proportion of the population or a ratio ≥1.5 for the proportion of cases to the proportion of the population) for underrepresented racial/ethnic groups in each county.† Counties with race/ethnicity data available for ≥50% of cases.§ Racial/ethnic groups are not mutually exclusive in a given county.
Chilblains and COVID‐19: why SARS‐CoV‐2 endothelial infection is questioned
Authors: M. Baeck, D. Hoton, L. Marot, A. Herman
Journal: British Journal of Dermatology (2020)

histological and immunostaining of skin biopsies of seven cases of 'epidemic chilblains' with negative SARS-CoV-2 reverse transcription polymerase chain reaction (RT-PCR) testing and repeated serology was similar to those of a historical series of 11 cases of chilblains lupus, notably for high expression of CD123 and MxA [a type-I interferon (IFN-I)-induced protein] in both groups. 3Thus, they hypothesized that chilblains observed during the COVID-19 outbreak are linked to a high IFN response to SARS-CoV-2, leading to both negative RT-PCR and serology due to this effective antiviral response and that development of chilblains is due to IFN production.Their hypothesis is notably based on recent publications showing that impaired IFN response is observed in patients who are critically ill with COVID-19. 4,5ven though we agree that it cannot be absolutely excluded, there is no evidence that their reported cases without RT-PCR or serological confirmation are really related to the infection.In our series, where most cases were negative for SARS-CoV-2 both by PCR and serology, it is highly unlikely that they are false-negatives as serology was performed an average of 3 weeks after the onset of manifestation.Secondly, their hypothesis warranted further exploration, notably to confirm the high IFN production in patients with chilblains and negative serology and PCR.Testing of IFN levels was performed in blood samples in two patients in our series and showed a low level of IFN production.In addition, to extrapolate that high IFN production would lead to negative PCR and serology, starting from the findings that profoundly impaired IFN-I response characterized by low interferon production is observed in critically ill patients, is a very speculative hypothesis.Indeed, such high IFN response could be expected to cause other clinical manifestations in addition to chilblains.Finally, it was previously shown that CD123 immunostaining is not different between chilblain lupus erythematosus and idiopathic chilblains. 6So, the fact of observing this expression in 'epidemic chilblain' is not an argument for attributing them to SARS-CoV-2.We also observed in five cases a high expression of CD123 in patients with negative serology and without any associated infectious signs.
Do oncologists engage in bereavement practices? A survey of the Israeli Society of Clinical Oncology and Radiation Therapy (ISCORT)
Authors: B. W. Corn, E. Shabtai, O. Merimsky, M. Inbar, E. Rosenbaum, A. Meerovitz, R. Tamir, I. Wexler
Journal: Journal of Clinical Oncology (2009)

e20588 Background: What happens to the patient-physician relationship after the patient succumbs to the illness? To begin answering this question, we determined the extent to which oncologists are involved in bereavement rituals for their patients. Methods: An e-mail survey was sent to ISCORT oncologists querying them as to their involvement in bereavement rituals including funerals, visitations (e.g., shiva), condolence phone calls, and condolence letters. Results were described using summary statistics, Wilcoxon, and Fisher's exact test. Results: The survey response rate was 69% (126/182). Median age of respondents was 49 y and the male:female ratio was 2:1. Generally, only 2% of oncologists attend funeral services and 1% visit the family. A higher number telephoned the surviving family members (27%) or sent written condolences (18%). When a ‘special bond‘ developed between doctor and patient, there was a significant increase in those who attended the funeral (8%), participated in a visitation (18%), or made phone calls (54%), p &lt; .0001 for all three rituals. There was no higher likelihood to participate in bereavement practices as a function of subspecialty (Medical v. Radiation v. Surgical Oncologist), gender, religiosity, or personal death anxiety. The rank ordered reasons for not participating in bereavement activities are lack of time, fear of burnout, need to maintain boundaries, and death anxiety. Males, more often than females, indicated that time constraints were the most important factor in determining their participation (P = .025). There was a weakly significant association between the physician's spirituality and participation in specific bereavement rituals. Interestingly, 11% of oncologists indicated that they would participate in bereavement visits if compensated for their time. Conclusions: Most oncologists do not engage in bereavement rituals for their deceased patients. When they do, they are less likely to attend a funeral or visit the family, and more likely to send a condolence card or call. No significant financial relationships to disclose.
Risk of hydroxychloroquine alone and in combination with azithromycin in the treatment of rheumatoid arthritis: a multinational, retrospective study
Authors: Jennifer C E Lane, James Weaver, Kristin Kostka, Talita Duarte-Salles, Maria Tereza F Abrahao, Heba Alghoul, Osaid Alser, Thamir M Alshammari, Patricia Biedermann, Juan M Banda, Edward Burn, Paula Casajust, Mitchell M Conover, Aedin C Culhane, Alexander Davydov, Scott L DuVall, Dmitry Dymshyts, Sergio Fernandez-Bertolin, Kristina Fišter, Jill Hardin, Laura Hester, George Hripcsak, Benjamin Skov Kaas-Hansen, Seamus Kent, Sajan Khosla, Spyros Kolovos, Christophe G Lambert, Johan van der Lei, Kristine E Lynch, Rupa Makadia, Andrea V Margulis, Michael E Matheny, Paras Mehta, Daniel R Morales, Henry Morgan-Stewart, Mees Mosseveld, Danielle Newby, Fredrik Nyberg, Anna Ostropolets, Rae Woong Park, Albert Prats-Uribe, Gowtham A Rao, Christian Reich, Jenna Reps, Peter Rijnbeek, Selva Muthu Kumaran Sathappan, Martijn Schuemie, Sarah Seager, Anthony G Sena, Azza Shoaibi, Matthew Spotnitz, Marc A Suchard, Carmen O Torre, David Vizcaya, Haini Wen, Marcel de Wilde, Junqing Xie, Seng Chan You, Lin Zhang, Oleg Zhuk, Patrick Ryan, Daniel Prieto-Alhambra
Journal: The Lancet Rheumatology (2020)

Hydroxychloroquine, a drug commonly used in the treatment of rheumatoid arthritis, has received much negative publicity for adverse events associated with its authorisation for emergency use to treat patients with COVID-19 pneumonia. We studied the safety of hydroxychloroquine, alone and in combination with azithromycin, to determine the risk associated with its use in routine care in patients with rheumatoid arthritis.
A Notch3-Marked Subpopulation of Vascular Smooth Muscle Cells Is the Cell of Origin for Occlusive Pulmonary Vascular Lesions
Authors: Lea C. Steffes, Alexis A. Froistad, Adam Andruska, Mario Boehm, Madeleine McGlynn, Fan Zhang, Wenming Zhang, David Hou, Xuefei Tian, Lucile Miquerol, Kari Nadeau, Ross J. Metzger, Edda Spiekerkoetter, Maya E. Kumar
Journal: Circulation (2020)

Pulmonary arterial hypertension (PAH) is a fatal disease characterized by profound vascular remodeling in which pulmonary arteries narrow because of medial thickening and occlusion by neointimal lesions, resulting in elevated pulmonary vascular resistance and right heart failure. Therapies targeting the neointima would represent a significant advance in PAH treatment; however, our understanding of the cellular events driving neointima formation, and the molecular pathways that control them, remains limited. We comprehensively map the stepwise remodeling of pulmonary arteries in a robust, chronic inflammatory mouse model of pulmonary hypertension. This model demonstrates pathological features of the human disease, including increased right ventricular pressures, medial thickening, neointimal lesion formation, elastin breakdown, increased anastomosis within the bronchial circulation, and perivascular inflammation. Using genetic lineage tracing, clonal analysis, multiplexed in situ hybridization, immunostaining, deep confocal imaging, and staged pharmacological inhibition, we define the cell behaviors underlying each stage of vascular remodeling and identify a pathway required for neointima formation. Neointima arises from smooth muscle cells (SMCs) and not endothelium. Medial SMCs proliferate broadly to thicken the media, after which a small number of SMCs are selected to establish the neointima. These neointimal founder cells subsequently undergoing massive clonal expansion to form occlusive neointimal lesions. The normal pulmonary artery SMC population is heterogeneous, and we identify a Notch3-marked minority subset of SMCs as the major neointimal cell of origin. Notch signaling is specifically required for the selection of neointimal founder cells, and Notch inhibition significantly improves pulmonary artery pressure in animals with pulmonary hypertension. This work describes the first nongenetically driven murine model of pulmonary hypertension (PH) that generates robust and diffuse occlusive neointimal lesions across the pulmonary vascular bed and does so in a stereotyped timeframe. We uncover distinct cellular and molecular mechanisms underlying medial thickening and neointima formation and highlight novel transcriptional, behavioral, and pathogenic heterogeneity within pulmonary artery SMCs. In this model, inflammation is sufficient to generate characteristic vascular pathologies and physiological measures of human PAH. We hope that identifying the molecular cues regulating each stage of vascular remodeling will open new avenues for therapeutic advancements in the treatment of PAH.
AB0226 Prevalence of radiographic hip osteoarthritis in turkey
Authors: B Goker
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The prevalence of hip osteoarthritis (OA) varies greatly across different geographic locations and population groups. Limited data exist about the prevalence of radiographic hip OA in Turkey. <h3>Objectives</h3> The aim of the study was to assess the prevalence of radiographic hip OA in Turkish population. <h3>Methods</h3> The radiographs kept at the files of the Department of Urology at Gazi University/Ankara were accessed. Patients aged 25 and over were included (range:25–97). Plain supine abdominal radiographs and intravenous pyelographies were evaluated. A hip joint was included in the study only if the entire femoral head and acetabulum were visible. Kellgren and Lawrence (K&amp;L) grading system for OA was utilised. <h3>Results</h3> 1249 hips in 682 (205F, 477M) patients were evaluated. Overall, 8.8% of the hips evaluated had radiographic hip OA (K&amp;L grade 2 and above). In 566 patients, both hips were included, and of these, 11.7% had radiographic hip OA in either one or both hips (9.4% of women and 12.7% of men). 51.5% of the cases had bilateral findings. The prevalence of radiographic hip OA increased with age. It was 1.9%, 16.1%, and 21.6% for age ranges 25–39, 40–54 and &gt;54, respectively. In the majority of the patients the radiographic findings indicated only mild disease (K&amp;L grade 2). There were 3 patients with grade 3 (moderate) disease and only 1 patient (aged 68) had K&amp;L grade 4 (severe) OA. <h3>Conclusion</h3> The results suggest that, K&amp;L grade 2 OA changes emphasising osteophytes at the hip joints are not uncommon in Turkish population, especially among aged 40 and over, but moderate-to-severe radiographic OA is not frequent.