tbuckley/cabot-search huggingface dataset:
Catalytic‐Enhanced Lactoferrin‐Functionalized Au‐Bi<sub>2</sub>Se<sub>3</sub> Nanodots for Parkinson's Disease Therapy via Reactive Oxygen Attenuation and Mitochondrial Protection
Authors: Lihua Li, Yao Lu, Xingyi Xu, Xianfeng Yang, Lingling Chen, Chengming Jiang, Yu Wang, Wenyan Hu, Xiaoming Wei, Zhongmin Yang
Journal: Advanced Healthcare Materials (2021)

Abstract Overexpression of reactive oxygen species in the substantia nigra pars compacta destroys dopaminergic neurons and accelerates the pathological process of Parkinson's disease (PD). In this study, a new hydrophilic nano‐bioconjugate, lactoferrin (Lf)‐modified Au‐Bi 2 Se 3 nanodot (ND) for efficient PD therapy is developed. In particular, the Lf‐Au‐Bi 2 Se 3 NDs exhibit strong blood‐brain barrier (BBB) permeation. The Lf‐Au‐Bi 2 Se 3 NDs can also serve as multiple enzymes such as superoxide dismutase, catalase, glutathione peroxidase, and peroxide. These NDs are located close to the mitochondria and thus maintain the mitochondrial membrane potential as well as control the cellular ROS level. In vivo results further demonstrate that the NDs can improve the memory and mobility of PD mice; permeation of the BBB, protection of mitochondria, and suppression of dopaminergic neuron loss in the substantia nigra pars compacta are also observed. It is anticipated that these new Lf‐Au‐Bi 2 Se 3 NDs with excellent biocompatibility, multienzyme functionality, and BBB permeability will open new opportunities for PD therapy.
Prognostic Significance of Blood-Based Multi-cancer Detection in Plasma Cell-Free DNA
Authors: Xiaoji Chen, Zhao Dong, Earl Hubbell, Kathryn N. Kurtzman, Geoffrey R. Oxnard, Oliver Venn, Collin Melton, Christina A. Clarke, Rita Shaknovich, Ting Ma, Gerry Meixiong, Michael V. Seiden, Eric A. Klein, Eric T. Fung, Minetta C. Liu
Journal: Clinical Cancer Research (2021)

Purpose:. We recently reported the development of a cell-free DNA (cfDNA) targeted methylation (TM)-based sequencing approach for a multi-cancer early detection (MCED) test that includes cancer signal origin prediction. Here, we evaluated the prognostic significance of cancer detection by the MCED test using longitudinal follow-up data.Experimental Design:. As part of a Circulating Cell-free Genome Atlas (CCGA) substudy, plasma cfDNA samples were sequenced using a TM approach, and machine learning classifiers predicted cancer status and cancer signal origin. Overall survival (OS) of cancer participants in the first 3 years of follow-up was evaluated in relation to cancer detection by the MCED test and clinical characteristics.Results:. Cancers not detected by the MCED test had significantly better OS (P < 0.0001) than cancers detected, even after accounting for other covariates, including clinical stage and method of clinical diagnosis (i.e., standard-of-care screening or clinical presentation with signs/symptoms). Additionally, cancers not detected by the MCED test had better OS than was expected when data were adjusted for age, stage, and cancer type from the Surveillance, Epidemiology, and End Results (SEER) program. In cancers with current screening options, the MCED test also differentiated more aggressive cancers from less aggressive cancers (P < 0.0001).Conclusions:. Cancer detection by the MCED test was prognostic beyond clinical stage and method of diagnosis. Cancers not detected by the MCED test had better prognosis than cancers detected and SEER-based expected survival. Cancer detection and prognosis may be linked by the underlying biological factor of tumor fraction in cfDNA.
AB0098 ASSOCIATED FACTORS IN ONE-YEAR MORTALITY IN PATIENTS WITH SMALL VESSEL SYSTEMIC VASCULITIS
Authors: E. M. Escudero Tepale, M. A. Saavedra, D. Miranda, Z. Castro, M. J. R. Arriga Torres
Journal: Annals of the Rheumatic Diseases (2021)

Background: The highest mortality rates in patients with small vessel systemic vasculitis occur within the first year after the diagnosis, however associated factors have been scarcely studied in our population. Objectives: To identify mortality associated factors at the time of diagnosis in patients with small vessel systemic vasculitis. Methods: Retrospective cohort (2009-2020) involving 81 patients diagnosed with systemic small vessel vasculitis. Demographic, clinical and biochemical parameters were studied as potential factors associated with one-year mortality. Results: Of the total of patients (n=81), 36 (44.4%) had generalized granulomatosis with polyangiitis, 32 (39.5%) had localized granulomatosis with polyangiitis and 5 (6.2%) had early systemic granulomatosis with polyangiitis, 7 (8.6%) had microscopic polyangiitis and 1 (1.25%) had eosinophilic granulomatosis with polyangiitis. Twenty-two deaths (27%) were observed, 14 of them (63.6%) happened within the first year of diagnosis. The leading cause of death was infection (64%). Patients who died within the first year of diagnosis had a higher frequency of hypoalbuminemia (p=0.05) and also presented hemoglobin lower than 10.8 g/dL (p=0.035) in comparison with those who died after the first year of diagnosis. Remission induction treatment did not differ between both groups. Conclusion: Our study suggests that hypoalbuminemia and anemia are factors associated with a higher mortality within the first year after the diagnosis in patients with systemic small vessel vasculitis which contrast with previously reported data. The study design and the reduced number of patients are two major limitations of the study. References: [1]Flossmann O, Berden A, Groot K, et al. Long-term patient survival in ANCA-associated vasculitis. Ann Rheum Dis. 2011;70:488-94. Disclosure of Interests: None declared
Real-World Treatment Patterns and Clinical Outcomes in Patients With Stage III NSCLC: Results of KINDLE, a Multicountry Observational Study
Authors: Abdul Rahman Jazieh, Huseyin Cem Onal, Daniel Shao Weng Tan, Ross A. Soo, Kumar Prabhash, Amit Kumar, Reto Huggenberger, Stephen Robb, Byoung-Chul Cho
Journal: Journal of Thoracic Oncology (2021)

Stage III NSCLC is a heterogeneous disease requiring a multimodal management approach. We conducted a real-world, global study to characterize patients, treatment patterns, and their associated clinical outcomes for stage III NSCLC.KINDLE was a retrospective study in patients with stage III NSCLC (American Joint Committee on Cancer, seventh edition) diagnosed between January 2013 and December 2017, with at least 9 months of documented follow-up since index diagnosis. In addition to descriptive statistics, Kaplan-Meier methodology evaluated survival estimates; two-sided 95% confidence interval was computed. Cox proportional hazards model was used for univariate and multivariate analyses.A total of 3151 patients from more than 100 centers across 19 countries from Asia, Middle East, Africa, and Latin America were enrolled. Median age was 63.0 years (range: 21.0-92.0); 76.5% were males, 69.2% had a smoking history, 53.7% had adenocarcinoma, and 21.4% underwent curative resection. Of greater than 25 treatment regimens, concurrent chemoradiotherapy was the most common (29.4%). The overall median progression-free survival (95% confidence interval) and median overall survival (mOS) were 12.5 months (12.06-13.14) and 34.9 months (32.00-38.01), respectively. Significant associations (p < 0.05) were observed for median progression-free survival and mOS with respect to sex, region, smoking status, stage, histology, and Eastern Cooperative Oncology Group status. In univariate and multivariate analyses, younger age, stage IIIA, better Eastern Cooperative Oncology Group status, concurrent chemoradiotherapy, and surgery as initial therapy predicted better mOS.KINDLE reveals the diversity in treatment practices and outcomes in stage III NSCLC in a real-world setting in the preimmuno-oncology era. There is a high unmet medical need, necessitating novel approaches to optimize outcomes.
Pharmacokinetics of Treosulfan in Patients with Thalassemia Major Undergoing Allogeneic Hematopoietic Stem Cell Transplantation — a Comparison of Two Formulations and Correlation with Clinical Outcomes
Authors: Alok Srivastava, Ezhilpavai Mohanan, Raveen Stephen Stallon Illangeswaran, Carl Panetta, Kavitha M Lakshmi, Anu Korula, Aby Abraham, Biju George, Vikram Mathews, Poonkuzhali Balasubramanian
Journal: Blood (2017)
AB0543 CHARACTERISTICS AND TREATMENT CHANGES IN PATIENTS WITH PSORIATIC ARTHRITIS SEEN IN A COMBINED DERMATOLOGY-RHEUMATOLOGY CLINIC
Authors: K. Klavdianou, M. Stavropoulou, P. Panagakis, M. Papoutsaki, A. Panagiotopoulos, C. Koutsianas, A. Stratigos, D. Rigopoulos, D. Vassilopoulos
Journal: Annals of the Rheumatic Diseases (2021)

Background: Data on patients with Psoriasis (PSO) referred to a combined Dermatology-Rheumatology outpatient Clinic (Derm-Rheum) with suspected psoriatic arthritis (PsA) are limited. Objectives: To assess patient characteristics and treatment changes in PsA patients referred to a Derm-Rheum Clinic. Methods: Prospective study of PSO patients referred to a combined Derm - Rheum Clinic from February 2018 to June 2020 in a Tertiary University Hospital. Results: Among 151 patients with PSO referred to the Clinic, 129 (85%) with a final diagnosis of PsA were included. In 73% of patients (n=94) PsA was diagnosed there for the 1 st time. 56% were females with a mean age of 55 years and a median disease duration of 14.2 years. At initial evaluation, 95% had peripheral arthritis, 45% nail involvement, 23% axial involvement, 12% enthesitis and 6% dactylitis with a median DAPSA score of 20.5 and PASI score of 1.6, respectively. 31% of the patients were not receiving any systemic treatment, 45% were on biologics (30% as monotherapy, 15% in combination with non-biologics), 29% were on non-biologics (14% as monotherapy, 15% in combination with biologics or targeted synthetic agents] and 10% were on targeted synthetic (ts) agents. At last visit (median follow-up: 15 months) only 8% did not receive any systemic therapy (p&lt;0.001 compared to 1 st visit), 62% were on biologics (39% monotherapy – 23% in combination with non-biologics, p=0.009), 46% were on non-biologics (20% as monotherapy – 26% in combination with biologics or ts agents, p=0.01) and 10% of the patients were on apremilast. The median DAPSA and PASI scores at last visit were 5.3 and 0, respectively. Conclusion: About 2/3 of patients with PSO referred to a combined Derm - Rheum Clinic with suspicious musculoskeletal complaints were diagnosed for the 1 st time as PsA. During follow-up the percentage of PsA patients who started or continued systemic therapy significantly increased with significant improvement of disease activity indices. These data emphasize the value of combined Derm - Rheum Clinics for earlier diagnosis and more efficacious treatment of PsA patients. Acknowledgements: This work was supported by research grants from the Special Account for Research Grants (S.A.R.G.), National and Kapodistrian University of Athens, Athens, Greece. Disclosure of Interests: None declared.
Ab-Externo MicroShunt versus Trabeculectomy in Primary Open-Angle Glaucoma
Authors: N. Douglas Baker, Howard S. Barnebey, Marlene R. Moster, Michael C. Stiles, Steven D. Vold, Anup K. Khatana, Brian E. Flowers, Davinder S. Grover, Nicholas G. Strouthidis, Joseph F. Panarelli
Journal: Ophthalmology (2021)

To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG).One-year results from a 2-year, prospective, randomized, multicenter, noninferiority study (NCT01881425) conducted in the United States and Europe.Eligible patients were aged 40-85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy.Patients were randomized 3:1 to undergo stand-alone MicroShunt implantation or trabeculectomy, both performed with adjunctive mitomycin C (0.2 mg/ml for 2 minutes).The primary effectiveness end point was surgical success, defined as ≥20% reduction in mean diurnal IOP from baseline (no medication washout) at year 1 without increasing the number of glaucoma medications. Secondary effectiveness end points at year 1 were the mean IOP change from baseline and requirement for postoperative intervention. Additional end points included glaucoma medication use and adverse events.Overall, 395 (MicroShunt) and 132 (trabeculectomy) patients were randomized (mean Humphrey visual field mean deviation, -12.34 decibels [dB]). At year 1, probability of success was lower in the MicroShunt group compared with the trabeculectomy group (53.9% vs. 72.7%, respectively; P < 0.01). In the MicroShunt group, mean IOP ± standard deviation decreased from 21.1 ± 4.9 mmHg at baseline to 14.3 ± 4.3 mmHg (-29.1%; P < 0.01) at year 1, with a mean of 0.6 ± 1.1 glaucoma medications (baseline 3.1 ± 1.0; P < 0.01). In the trabeculectomy group, mean IOP decreased from 21.1 ± 5.0 mmHg to 11.1 ± 4.3 mmHg (-45.4%; P < 0.01), with a mean of 0.3 ± 0.9 glaucoma medications (baseline 3.0 ± 0.9; P < 0.01). Postoperative interventions, including laser suture lysis, were reported in 40.8% (MicroShunt) versus 67.4% (trabeculectomy) of patients (P < 0.01). Reported incidence of transient hypotony was higher in the trabeculectomy group versus the MicroShunt group (49.6% vs. 28.9%; P < 0.01). Vision-threatening complications were uncommon and reported in 1.0% of MicroShunt versus 0.8% of trabeculectomy patients.Probability of success was lower with MicroShunt compared with trabeculectomy. Although reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.
What went wrong in the UK’s covid-19 response?
Authors: Martin McKee
Journal: BMJ (2021)

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AB0856 CHRONIC INTESTINAL PSEUDO-OBSTRUCTION WITH HYDRONEPHROSIS: A CASE REPORT ON SUCH DISABLING AND RARE COMPLICATION OF LUPUS
Authors: C. S. Ng, S. L. Kan, A. L. Lim
Journal: Annals of the Rheumatic Diseases (2021)

Background: Chronic intestinal pseudo-obstruction can be a rare complication of systemic lupus erythematosus. It is often late to be identified in contrast to other commoner organs involvement in systemic lupus erythematosus such as nervous system, joint and kidney. Objectives: To report a case of uncommon gastrointestinal complication of lupus, with associated hydronephrosis at the ureter, with treatment delay. Methods: We report a case of chronic intestinal pseudo-obstruction. Results: A 34 year old, with ten-year history of lupus nephritis, presented with recurrent abdominal pain and diarrhoea past nine months. The patient had just been diagnosed as end-stage renal failure a year ago, on regular haemodialysis. For the past ten years, the patient was not able to tolerate immunosuppressant due to the multiple episodes of infections, including shin carbuncle, herpes zoster, breast abscess and catheter-related candida/bacterial infections. However, the patient did not have any other major organs manifestations of lupus for the past ten years. The patient was apyretic. Multiple stool cultures were negative including Clostridium difficile. The abdominal radiography showed dilated small bowel with diffuse thickening of large and small bowels on computed tomography. Bilateral uretero-hydronephrosis was also noted without any evidence of obstructive uropathy on imaging. Ileocolic resection was done for presumed intestinal obstruction and the ileocolic biopsy did not reveal any granuloma, malignancy or vasculitis except for non-specific inflammation of cecum. Cytomegalovirus inclusion body was absent as well. Tuberculosis culture was negative. Oesophagoduodenoscopy and colonoscopy were offered in view of persistent unexplained loose stool and abdominal pain. But unremarkable findings were noted from multiple biopsy specimens of the small and large bowels. Second relook of the initial hemicolectomy specimen with special actin immunostain on the smooth muscle revealed degenerative changes of the muscularis propria. These were evidenced by cytoplasmic vacuolation, atrophy and pyknotic nucleus of the smooth muscle cells with surrounding oedema. Smooth muscle dysmotility could be the underlying pathology of this patient presentation. The patient responded well to intravenous immunoglobulin followed by azathioprine in addition to prednisolone and prokinetic agent. Conclusion: Prompt recognition is pivotal in this case could have prevented the unnecessary surgical intervention earlier. It is potentially reversible. Long term prognosis of this rare entity is, however, varying. Disclosure of Interests: None declared
COVID‐19‐associated multisystem inflammatory syndrome in adults with Kawasaki disease‐like cutaneous manifestations
Authors: M. Razmi T, T.P. Afra, T.P. Mohammed, P.T.M. Ashik, E. Sukesh
Journal: British Journal of Dermatology (2021)

DEAR EDITOR, A 40-year-old Indian women, with normal vital observations, was referred to us for suspected drug rash.The rash appeared within a day of fever associated with unilateral cervical lymphadenopathy.Examination revealed strawberry tongue (a) and brightly erythematous acral skin that later peeled off (b, c).Blood investigation revealed lymphopenia, eosinophilia, abnormal liver function, raised C-reactive protein (224 mg L -1 ) and erythrocyte sedimentation rate (39 mm h -1 ).COVID-19 IgM was positive with negative IgG and reverse-transcription polymerase chain reaction.Radiological evaluations and echocardiograph were noncontributory.With oral steroids, she had an uneventful hospital stay.Our patient had features of Kawasaki disease along with evidence of recent COVID-19 infection, hepatic dysfunction and raised inflammatory markers fulfilling the Centers for Disease Control and Prevention criteria 1 for multisystem inflammatory syndrome in adults (MIS-A).Cutaneous findings (morbilliform, maculopapular and erythroderma) along with Kawasaki disease-like features 2 in adults in this pandemic scenario should prompt dermatologists to suspect MIS-A.
Health‐related quality of life with fixed‐duration venetoclax‐obinutuzumab for previously untreated chronic lymphocytic leukemia: Results from the randomized, phase 3 <scp>CLL14</scp> trial
Authors: Othman Al‐Sawaf, Brittany Gentile, Jacob Devine, Can Zhang, Kavita Sail, Maneesh Tandon, Anna‐Maria Fink, Nadine Kutsch, Clemens‐Martin Wendtner, Barbara Eichhorst, Michael Hallek, Kirsten Fischer
Journal: American Journal of Hematology (2021)

Abstract Chronic lymphocytic leukemia (CLL)‐related symptoms impair the well‐being of patients, making improvement of health‐related quality of life (QoL) a goal of treatment. The CLL14 trial demonstrated higher efficacy of fixed‐duration venetoclax‐obinutuzumab (Ven‐Obi) compared to chlorambucil‐obinutuzumab (Clb‐Obi) in patients with previously untreated CLL. To assess patients' QoL, the following patient‐reported outcomes (PRO) measures were assessed: the M.D. Anderson Symptom Inventory (MDASI) core instrument and CLL module and the EORTC Quality of Life Questionnaire Core 30 (EORTC QLQ‐C30). At treatment start, physical functioning (mean 75.9 [standard deviation (SD) ± 20.1] in the Clb‐Obi arm and 76.9 [±19.4] in the Ven‐Obi arm), role functioning (73.6 [±27.86] and 72.6 [±26.9]) and GHS/QoL (63.6 [±21.0] and 60.3 [±20.5]) were comparable between treatment arms per EORTC QLQ‐C30 scale scores. Baseline levels of physical and role functioning were maintained throughout treatment and follow‐up, with no relevant improvement or deterioration. On average, patients treated with Ven‐Obi showed a meaningful improvement of GHS/QoL during treatment and follow‐up by at least eight points at cycle three, whereas improvement was delayed until cycle eight with Clb‐Obi. According to MDASI scores, CLL symptoms (1.5 [±1.2] and 1.6 [±1.3]), core cancer symptoms (1.5 [±1.4] and 1.8 [±1.7]) and symptom interference (2.1 [±2.3] and 2.3 [±2.3]) were generally low and comparable between treatment arms at baseline and were maintained throughout treatment and follow‐up. This analysis demonstrates that the higher efficacy of Ven‐Obi is not associated with QoL impairment and that Ven‐Obi achieves early relief of CLL‐related symptoms in elderly unfit patients.
Medical Heredity. Distinguished Children of Physicians (United States, to 1910).
Journal: JAMA (1926)

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Influence of pig farming on human Gut Microbiota: role of airborne microbial communities
Authors: Julia Moor, Tsering Wüthrich, Suzanne Aebi, Nadezda Mostacci, Gudrun Overesch, Anne Oppliger, Markus Hilty
Journal: Gut Microbes (2021)

It has been hypothesized that both genetics and diet influence the composition of the human cecal microbiota. However, it remains unclear whether and how occupational exposure to microbes impacts the microbial communities in human guts. Using a One Health approach, we visited pig farms (n = 26) and collected stool specimens from pig workers (n = 59), pig barn air samples (n = 19), and rectal swabs from pigs at three different growth stages (n = 144). Stool samples from cattle workers were included as a control group (n = 22). Each sample's microbiota was characterized using 16S rRNA gene sequencing and the DADA2 pipeline.We obtained a significantly different clustering of the microbial compositions of pig and cattle workers by permutational multivariate analysis of variance (PERMANOVA; P < .001). Workers primarily exposed to pigs had higher relative abundances of Prevotellaceae and less Bacteroidaceae than workers exposed to cattle. We also found that the microbial compositions of pig workers' stool samples shared extensive fractions with the samples from their pigs. We also identified amplicon sequencing variants (ASVs) in the airborne microbiota which were likely involved in zoonotic transmission events.We hypothesize that ASVs originating from pig feces are aerosolized and, through breathing, get trapped in the pig farm workers' upper respiratory tract from where they can get swallowed. Consequently, some of the animal associated ASVs are transferred into the gastrointestinal tracts (GITs) which leads to changes in the composition of the human gut microbiota. The importance of this finding for human health must be investigated further.