tbuckley/cabot-search huggingface dataset:
THU0340 DURATION AND SYSTEMIC SCLEROSIS SUBTYPE ARE ASSOCIATED WITH DIFFERENT GUT MICROBIOME PROFILES
Authors: Y. Braun-Moscovici, S. Ben Simon, K. Dolnikov, S. Giryes, D. Markovits, Y. Tavor, K. Toledano, A. Balbir-Gurman, O. Koren
Journal: Annals of the Rheumatic Diseases (2020)

Background: A growing body of evidence suggests that the gut microbiota plays a significant role in the development of autoimmune diseases. Altered microbiota composition was associated with gastrointestinal and extraintestinal features in systemic sclerosis (SSc) patients. Objectives: To look for differences in gut microbiota between SSc patients regarding disease duration, disease subset and occurrence of digital ulcers (DU). Methods: SSc patients seen at our center were recruited in a prospective study. The exclusion criteria included antibiotic or probiotic treatment during the month prior to recruitment, recent hospitalization, BMI&gt;30, diabetes mellitus or concomitant inflammatory bowel disease. Fecal samples were processed and 16S rRNA gene sequences were analyzed using the QIIME2 packageWeighted (quantitative) and unweighted (qualitative) UniFrac distances, alpha diversity for richness and homogeneity, taxa plots for species and phyla and ANCOM analyses were performed. Results: During July 2018-May 2019, 26 SSc patients (mean age [SD] 53[12.7] years) and disease duration 8.8 [7.1] years) fulfilled the criteria and were willing to participate in the study. Thirteen patients had diffuse SSc, 16 patients had active DU, 8 patients had Raynaud’s phenomenon only without DU, 2 patients had past DU. The microbiota was significantly more similar between patients without active DU compared to those with active DU (P=0.024), but species richness did not differ. Patients with SSc duration less than 6 years had significantly different microbiota compared to long-lasting SSc (unweighted PCoA – q=0.031). Significant variations concerning quantitative and qualitative UniFrac distances (q=0.063, q=0.005) and species richness (q=0.009) were found among patients with diffuse compared to limited SSc. Limited SSc was associated with greater species richness. Taxa plot analysis revealed higher relative abundance of Firmicutes in diffuse disease and of Actinobacteria and Bacteroidetes in limited SSc. Conclusion: Disease duration, disease subset and active DU were associated with shifts in the microbiome of SSc patients. The impact of these changes on disease progression needs further elucidation. Figure: Disclosure of Interests: Yolanda Braun-Moscovici: None declared, Shira Ben Simon: None declared, Katya Dolnikov: None declared, Sami Giryes: None declared, Doron Markovits: None declared, Yonit Tavor: None declared, Kohava Toledano: None declared, Alexandra Balbir-Gurman Consultant of: Novartis, Omry Koren: None declared
Recent developments in the medicinal chemistry of single boron atom-containing compounds
Authors: Shu Song, Ping Gao, Lin Sun, Dongwei Kang, Jacob Kongsted, Vasanthanathan Poongavanam, Peng Zhan, Xinyong Liu
Journal: Acta Pharmaceutica Sinica B (2021)

Various boron-containing drugs have been approved for clinical use over the past two decades, and more are currently in clinical trials. The increasing interest in boron-containing compounds is due to their unique binding properties to biological targets; for example, boron substitution can be used to modulate biological activity, pharmacokinetic properties, and drug resistance. In this perspective, we aim to comprehensively review the current status of boron compounds in drug discovery, focusing especially on progress from 2015 to December 2020. We classify these compounds into groups showing anticancer, antibacterial, antiviral, antiparasitic and other activities, and discuss the biological targets associated with each activity, as well as potential future developments.
Optimization of a transmural care pathway for allergen immunotherapy to primary care by an integrated personal eHealth environment
Authors: Johanna P.M. van der Valk, Jasper H. Kappen, Sanne Ruikes‐Mertens, Maurits S. van Maaren, Patrick J.E. Bindels, Roy Gerth van Wijk, G. J. Braunstahl
Journal: Allergy (2021)

Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Impact of primary tumor size/horizontal extent on survival in colorectal cancer.
Authors: Olatunji B. Alese, Wei Zhou, Renjian Jiang, Katerina Mary Zakka, Walid Labib Shaib, Christina Wu, Maria Diab, Mehmet Akce, Bassel F. El-Rayes
Journal: Journal of Clinical Oncology (2021)

125 Background: Pathologic staging in colorectal cancer (CRC) is crucial in patient management. Data regarding the impact of size/horizontal tumor extent is limited, contradictory and currently excluded from the American Joint Committee on Cancer (AJCC) staging model. However, a previously published SEER analysis showed that AJCC stages I and IIIA have similar 2- and 5- year survival rates, and worse rates for stage II. Using the largest cohort to date, we report the impact of primary tumor size on CRC survival. Methods: Data were obtained from all US hospitals that contributed to the National Cancer Database (NCDB) between 2010 and 2015. Univariate and multivariate analyses were performed to identify factors associated with patient outcome. Kaplan-Meier analysis and Cox proportional hazards models were used to assess the association between tumor/patient characteristics and overall survival (OS). Results: A total of 61,145 patients were identified with a similar gender distribution (M/F:50.9%/49.1%). The mean age was 62.7years (SD+/-14.1) and 82% were non-Hispanic Whites. Majority had colon primary (82.7%) and 82.4% had microsatellite stable (MSS) disease. Distribution across stages I-IV was 20.1%, 32.1%, 34.7% and 13.2% respectively. Among the total study population, AJCC stage correlated closely with OS on multivariate analysis (HR 1.49, 2.29, 8.38 for stages II to IV compared to stage I), while the distinguishing power for tumor size was relatively mild (HR 1.19 and 1.33 for 5-10 cm and &gt;5cm compared to &lt;5cm). Among patients with stage II disease, tumors &gt;10cm were associated with worse survival compared to those &lt;5cm (HR 1.2; 1.03-1.39; p=0.22). Stage III disease also had differential survival rates; patients with tumors 5-10cm (HR 1.21; 1.14-1.28; p&lt;0.001) and &gt;10cm (HR 1.57; 1.37-1.80; p&lt;0.001) had worse survival than those &lt;5cm. Patients with stage II who did not receive adjuvant chemotherapy (CTX) had worse survival outcomes (HR 1.29; 1.08-1.55; p=0.005) compared to stage III disease who did. Accounting for tumor size, there was no statistically significant survival differences between stage I patients and stages II and III patients who received adjuvant chemotherapy. Conclusions: Tumors larger than 10cm have inferior outcomes among patients in the same AJCC stages. Stage II patients without adjuvant CTX did worse than stage III with CTX. Further studies are needed to clarify the role of tumor size in staging models. [Table: see text]
dadi.CUDA: Accelerating Population Genetics Inference with Graphics Processing Units
Authors: Ryan N Gutenkunst
Journal: Molecular Biology and Evolution (2020)

dadi is a popular but computationally intensive program for inferring models of demographic history and natural selection from population genetic data. I show that running dadi on a Graphics Processing Unit can dramatically speed computation compared with the CPU implementation, with minimal user burden. Motivated by this speed increase, I also extended dadi to four- and five-population models. This functionality is available in dadi version 2.1.0, https://bitbucket.org/gutenkunstlab/dadi/.
Abstract 12268: Conductive Biomaterial Polypyrrole-Chitosan Hydrogel Can Influence Our Resistant Fibrotic Scar Tissue Model to Perform Electrically Like Healthy Heart Tissue
Authors: Daniel Ramnath, Yu Sun, Richard D Weisel, Ren-Ke Li
Journal: Circulation (2018)

Introduction: After myocardial infarction, necrosed cardiomyocytes are replaced with fibrotic tissue (FT) which dampens electrical activity and impedes impulse conduction in the heart, increasing t...
Genomic characterization of <i>ATM</i> alterations in advanced pancreatic ductal adenocarcinoma (PDAC).
Authors: Sheron Perera, Robert Edward Denroche, Spring Holter, Deirdre Kelly, Amy Zhang, Yifan Wang, Anna Dodd, Stephanie Ramotar, Shawn Hutchinson, Mustapha Tehfe, Ravi Ramjeesingh, James Joseph Biagi, Julie Wilson, Faiyaz Notta, Sandra Fischer, George Zogopoulos, Robert C Grant, Steven Gallinger, Jennifer J. Knox, Grainne M. O'Kane
Journal: Journal of Clinical Oncology (2021)

396 Background: BRCA1/2 and PALB2 are genes critical to the faithful repair of double strand breaks through the homologous recombination repair (HRR) pathway. Alterations in these genes serve as predictive biomarkers to both platinum and PARP inhibitors. Ataxia-telangiectasia mutated ( ATM) is also indirectly involved in HRR; however, its role as a predictive biomarker to DNA damage response agents is debated. Herein we evaluated the genomic characteristics and clinical outcomes of patients with ATM alterations on the Comprehensive Molecular Characterization of Advanced Ductal Pancreas Adenocarcinoma for Better Treatment Selection (COMPASS) trial. Methods: Patients on this study undergo a biopsy for whole genome sequencing (WGS) and RNA sequencing prior to chemotherapy; those with germline variants in ATM were reviewed by a genetics counsellor and defined as pathogenic, likely pathogenic, variant of unknown significance (VUS) or benign/likely benign. Genomic characteristics were reviewed and published classifiers of homologous recombination deficiency (HRD) were applied to all cases and included the percentage of substitution base signature (SBS) 3, the HRDetect score, the computed algorithm of large scale transitions, telomeric allelic imbalances and loss of heterozygosity (LOH), otherwise known as the genomic instability score (GIS). Results: As of January 2020, 304 patients were enrolled and 245 patients had both WGS and clinical data available. 86 germline variants in ATM were present in 70 patients. The majority of these (80%) were classified as benign or likely benign. 10 VUS were detected and 4 patients (2%) had pathogenic/likely pathogenic variants (PV). Of these 4 patients, LOH or a second somatic hit was evident in 1 case. Upon review of the PVs and VUS, SBS were consistent with typical PDAC and tumour mutational burden was low. HRDetect scores were low ( &lt; 0.1) for 13/14 cases with either a VUS or PV; one VUS without biallelic loss, had a high HRDetect score, with presence of SBS 3 and a high GIS. This particular case was also found to have a tandem duplicator phenotype. None of the 4 cases with PV had evidence of HRD. Furthermore all four were treated with platinum based regimens without evidence of response. Conclusions: In a large series of sequenced pancreatic cancers, the presence of pathogenic germline variants in ATM was rare, with none of the cases demonstrating evidence of HRD. This suggests that this population is unlikely to benefit from PARP inhibition.
SAT0174 Bone health in young women: a population study
Authors: DJ Pattison, J Catterick, CW Pritchard, SA New, AD Woolf
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Peak bone mass is determined by the genetic potential as modified by nutrition, exercise, hormonal status and disease. Osteoporosis may be prevented by identifying and modifying risk factors in younger age groups. This paper reports on the distribution of bone density (BMD) and prevalence of risk factors in 225, of a target 300. <h3>Objectives</h3> The aims of this study were to identify the frequency of osteoporosis and identify the key associates of low bone density in young women in 2 regions of England. <h3>Methods</h3> Women (excluding pregnant) aged 20–29 were selected at random from 9 GP practices (6 in Cornwall [C]and 3 in Surrey [S]) in a 2 stage random sampling process, and invited by letter to participate. Demographic, lifestyle and anthropometric data were collected by questionnaire, 7-day food diary and examination. BMD was measured at the lumbar spine (LS) and femoral neck (FN) using dual-energy X-ray absorptiometry (DXA). <h3>Results</h3> The main demographic and anthropometric data are given in Table 1. No differences were found between the 2 groups. However, a lower BMD was found in C at the FN (t = 2.13, p = 0.03). Although the meaning of t-score is uncertain in women of this age, osteopenia (t-score &lt;-1.0 and &gt;-2.5) was found in 21% women at LS and 11% at FN. Osteoporosis (t-score &lt;-2.5) was found in 2(1%) cases at the LS only, both in C. Various risk factors were identified in the total group. Amenorrhoea &gt;6 months duration in 29(13%), BMI &lt;19 in 13(6%), history of smoking in 134(59%). 74(33%) women had a history of fracture however none fulfilled the standard criteria for low trauma fracture. 18(8%) women reported a history of possible or definite eating disorder. In analysing the association between risk factors and BMD weight had the predominant effect at FN (r2 = 0.181 B = 0.425 p &lt; 0.001) and LS (r2 = 0.112 B = 0.334 p &lt; 0.001). Risk factors significantly associated with BMD were history of smoking (t = -2.31 p = 0.02) and amenorrhoea (t = -2.09 p = 0.04). Associations between self-reported milk intake and BMD were analysed using the GL Model. Those with a current consumption of 1 pint/day or more had BMD.094 (SD.043 p = 0.03) greater than those who drank milk less than once/week. Both adolescent and current low consumption of milk was associated with a lower BMD for weight than expected. <h3>Conclusion</h3> The prevalence of osteoporosis was low in young UK women but 25% were osteopenic. BMD measurement may be of limited use at this age for predicting future osteoporotic fracture in the normal population. The overall prevalence of identified risk factors was low but smoking and body weight are both modifiable thus health promotion messages should aim to target these risk factors.
Distinct metabolic programs established in the thymus control effector functions of γδ T cell subsets in tumor microenvironments
Authors: Noella Lopes, Claire McIntyre, Stefania Martin, Mathilde Raverdeau, Nital Sumaria, Ayano C. Kohlgruber, Gina J. Fiala, Leandro Z. Agudelo, Lydia Dyck, Harry Kane, Aaron Douglas, Stephen Cunningham, Hannah Prendeville, Roisin Loftus, Colleen Carmody, Philippe Pierre, Manolis Kellis, Michael Brenner, Rafael J. Argüello, Bruno Silva-Santos, Daniel J. Pennington, Lydia Lynch
Journal: Nature Immunology (2021)
Corrigendum to: Tie2-dependent knockout of HIF-1 impairs burn wound vascularization and homing of bone marrow-derived angiogenic cells
Authors: K Sarkar, S Rey, X Zhang, R Sebastian, G P Marti, K Fox-Talbot, A V Cardona, J Du, Y S Tan, L Liu, F Lay, F J Gonzalez, J W Harmon, G L Semenza
Journal: Cardiovascular Research (2021)
Prevalence of Systemic Lupus Erythematosus in the United States: Estimates From a Meta‐Analysis of the Centers for Disease Control and Prevention National Lupus Registries
Authors: Peter M. Izmirly, Hilary Parton, Lu Wang, W. Joseph McCune, S. Sam Lim, Cristina Drenkard, Elizabeth D. Ferucci, Maria Dall'Era, Caroline Gordon, Charles G. Helmick, Emily C. Somers
Journal: Arthritis & Rheumatology (2021)

Epidemiologic data on systemic lupus erythematosus (SLE) are limited, particularly for racial/ethnic subpopulations in the US. This meta-analysis leveraged data from the Centers for Disease Control and Prevention (CDC) National Lupus Registry network of population-based SLE registries to estimate the overall prevalence of SLE in the US.
A phase II open-label study in adult and adolescent patients (pts) with advanced solid tumors harboring fibroblast growth factor receptor (<i>FGFR</i>) gene alterations.
Authors: Shubham Pant, Josep Tabernero, Christophe Massard, Gopa Iyer, Olaf Witt, Toshihiko Doi, Shukui Qin, Christine Lu-Emerson, Darren R. Hargrave, Javier García-Corbacho, Shonda Marie Little, Qi Xia, Ademi E. Santiago-Walker, Christopher Moy, Constance Hammond, Hussein Sweiti, Martin H. Schuler
Journal: Journal of Clinical Oncology (2021)

TPS480 Background: The pan- FGFR tyrosine kinase inhibitor erdafitinib is approved by the US Food and Drug Administration for adults with locally advanced or metastatic urothelial carcinoma and susceptible FGFR3/2 genetic alterations who have progressed during or after ≥ 1 line of prior platinum-containing chemotherapy. FGFR gene alterations are potential oncogenic drivers that have been reported in many solid tumors in adult and pediatric pts. Because of limited response to standard of care options in pts failing systemic therapy, there is strong rationale to assess the safety and efficacy of erdafitinib in adolescent and adult pts with advanced solid tumors and FGFR alterations. Methods: This phase 2, open-label study (RAGNAR/42756493CAN2002; NCT04083976) will include pts aged ≥ 12 years with histologically confirmed unresectable, locally advanced, or metastatic solid tumors (except urothelial tumors) harboring predefined FGFR mutations or fusions. Eligibility screening includes molecular screening for FGFR alterations by central or local next-generation sequencing assays, and other clinical criteria. Pts will enroll into either a broad panel cohort (BPC) of target FGFR alterations or an exploratory cohort (EC) for FGFR alterations that do not meet criteria for BPC. Approximately 280 pts (BPC, n = 240; EC, n = 40) will be enrolled. The primary efficacy end point is overall response rate (ORR) as assessed by the independent review committee. Secondary end points include investigator-assessed ORR, duration of response, disease control rate, progression-free survival, overall survival, safety, pharmacokinetics, and health-related quality of life. Safety assessments include adverse events, vital signs, electrocardiograms, physical examinations, laboratory tests, performance status assessment, growth assessments in adolescents, and ophthalmologic examination. As of December 2019, pts are being enrolled at ~158 sites in 15 countries. Results of this study will provide efficacy and safety data for erdafitinib across multiple solid tumors with FGFR alterations and evaluate the potential benefit of targeting the underlying altered biology of FGFR irrespective of tumor histology in adult and adolescent pts. Clinical trial information: NCT04083976.
Household transmission of SARS-CoV-2 and risk factors for susceptibility and infectivity in Wuhan: a retrospective observational study
Authors: Fang Li, Yuan-Yuan Li, Ming-Jin Liu, Li-Qun Fang, Natalie E Dean, Gary W K Wong, Xiao-Bing Yang, Ira Longini, M Elizabeth Halloran, Huai-Ji Wang, Pu-Lin Liu, Yan-Hui Pang, Ya-Qiong Yan, Su Liu, Wei Xia, Xiao-Xia Lu, Qi Liu, Yang Yang, Shun-Qing Xu
Journal: The Lancet Infectious Diseases (2021)
Acute liver injury in COVID-19: Risk factors in a large pediatric cohort
Authors: A. Perez, A. Cantor, J. Miller, D. Kogan-Liberman, B. Rudolph, K. G. Margolis, Q. Gao, B. DaSilva, M. Martinez, N. Ovchinsky
Journal: Hepatology (2020)

Background: Coronavirus disease 2019 (COVID-19) is associated with acute liver injury in adults, but liver injury has not been well characterized in pediatric patients We aim to describe the prevalence of liver injury in children in the setting of acute severe respiratory syndrome-coronavirus 2 (SARSCoV- 2) infection and to identify risk factors for the development of COVID-19-associated liver disease Methods: This is a retrospective cohort analysis of all patients ≤ 21 years of age with an acute SARS-CoV-2 infection and positive real-time reverse transcription polymerase chain reaction presenting between March 14th to June 30th, 2020 to two tertiary children's hospitals in New York City Institutional Review Board approval was obtained at both institutions Patients without aminotransferase testing or those with multisystem inflammatory syndrome in children were excluded from analysis Acute liver injury was categorized as mild if alanine aminotransferase (ALT) was above the upper limit of normal (ULN) (>30 U/L) and severe if ALT was more than five times ULN Results: A total of 225 patients were evaluated The mean age was 11 years (standard deviation ± 7 years);61% were male, 55% were of Hispanic/Latinx ethnicity, and 21% were black  Obesity was identified in 35% of children;7% had pre-existing liver disease The majority (74%) of patients were hospitalized, while 23% of patients required intensive care unit (ICU) admission and 8% developed multi-organ failure (MOF) Two percent of patients (5/225) died 45% of patients developed acute liver injury (median 67 U/L, [IQR 45-160] U/L), and severe liver injury (median 271 [IQR 193- 389] U/L) was noted in 12% of all children The presence of gastrointestinal symptoms was reported in 54% of patients Factors associated with acute liver injury in univariate analysis included age (p = 0 015), obesity (p = 0 0001), pre-existing liver disease (p = 0 005), elevated inflammatory markers such as ferritin (p < 0 0001), C-reactive protein (CRP) (p < 0 0001), d-dimer (p = 0 002), as well as MOF (p = 0 0009) and ICU admission (p = 0 026) In multivariate regression model, acute liver injury was significantly associated with older age (OR 1 18;p = 0 01), CRP (OR 1 07;p = 0 01) and ICU admission (OR 8 9, p = 0 02) Clinical and laboratory characteristics are listed in the Table 1 Conclusion: Acute liver injury is common in children with SARS-CoV-2 infection but is most often mild Patients who are older and those with higher disease severity may be at risk for more significant liver injury (Table Presented)
Contribution of resident and circulating precursors to tumor-infiltrating CD8 <sup>+</sup> T cell populations in lung cancer
Authors: Paul Gueguen, Christina Metoikidou, Thomas Dupic, Myriam Lawand, Christel Goudot, Sylvain Baulande, Sonia Lameiras, Olivier Lantz, Nicolas Girard, Agathe Seguin-Givelet, Marine Lefevre, Thierry Mora, Aleksandra M. Walczak, Joshua J. Waterfall, Sebastian Amigorena
Journal: Science Immunology (2021)

CD8 + T cells in lung tumors differentiate through convergent pathways to an expanded and actively cycling terminal state.