tbuckley/cabot-search huggingface dataset:
THU0090 Tap1 and tap2 gene polymorphism in rheumatoid arthritis in eastern french population
Authors: S Zhang, J Chabod, A Penfornis, P Tiberghien, D Wendling, E Toussirot
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> The Transporter associated with antigen processing (TAP) gene products are involved in the processing of endogenous peptides that bind to human leukocyte antigen (HLA) class I molecules and polymorphism within these genes could alter the immune responses, the phenomenon relevant to the development of autoimmunes diseases. <h3>Objectives</h3> In this study, we examined the polymorphism of TAP1 and TAP2 genes in patients with rheumatoid arthritis (RA). <h3>Methods</h3> TAP1 and TAP2 typing was performed in 138 white RA patients and 100 healthy controls, all of them originating from Eastern France. TAP1 polymorphic residues at position 333 and 637 and amino acid variants 379, 565, 651 and 665 in TAP2 gene were determined using amplification refractory mutation system (ARMS)- PCR. This method enabled us to determine 4 TAP1 alleles (TAP1A to TAP1D) and 8 TAP2 alleles (TAP2A to TAP2H). All patients and controls had been HLA DRB1* genotyped. <h3>Results</h3> The polymorphic residues TAP1/333 and TAP1/637 did not show any difference in their distribution between patients and controls. Similar findings were observed for TAP2/379 and TAP2/665. However, we found an increased frequency of Thr homozygosity and heterozygosity at position 565 in TAP2 gene (RA vs Controls: 25.3% vs 14%; p: 0.032;OR: 2.09;CI: 1.01–4.38). Similarly, the prevalence of subjects who were homozygote and heterozygote for Cys/651 was increased in the RA group (RA vs Controls: 22.4% vs 11%; p:0.02). The frequency of TAP2F was higher in RA patients (24.5%) as compared with controls (11.3%), without significance after correction (p:0.029; p corr: 0.17). Finally, we found no linkage disequilibrium between DRB1* associated -alleles and amino acid substitution Thr/665 whereas Cys/651 was not independent of DRB1*04, a strongly RA-linked allele. Only a few patients expressing Thr at position 565 in TAP2 gene were associated with severe clinical manifestations. <h3>Conclusion</h3> We evidenced in this study an association between a particular amino acid residue, namely Thr/665 in TAP2 gene, and RA. This association was found to be weak and did not seem to be a predictor for the severity of the disease.
Pressurized Intraperitoneal Aerosol Chemotherapy: The Road from Promise to Proof
Authors: Loek A.W. de Jong, Nielka P. van Erp, Lana Bijelic
Journal: Clinical Cancer Research (2021)

Abstract Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is an innovative drug delivery technique invented to be used for the treatment of peritoneal metastasis. Its application gained popularity over the past years. Several prospective clinical trials are being conducted to determine efficacy and safety. At this moment, there remain many challenges to overcome before PIPAC can be widely adopted in clinical practice. See related article by Kim et al., p. 1875
SAT0113 Total metacarpo-pharangeal arthroplasty in ra
Authors: N Murata, M Saito, S Wakitani, K Imoto, K Masada, M Goto, Y Komatsubara
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> It is no exaggeration to say that most of the patients with rheumatoid arthritis (RA) suffer from finger's sysfunction. Although the total arthroplasty for hip joint and knee joint have brout great benefit for RA patients, total arthroplasty for the upper tremity has not be developed enough. We have contrived new total metacarpo-phrangeal arthroplasty (TMPA) for 4 years and half. <h3>Objectives</h3> TMPA have been done in 126 patients (136 hands);106 RA, 16 post-injury, 4 others. <h3>Methods</h3> TMP joint is composed with the metacarpal head made of titanium and polyethylene socket with stem. Socket stem is capable to slide into titanium sleeve that is fixed in basal pharangeal cavity with cement. <h3>Results</h3> In RA patients TMPA have been done in 106 patients, 114 hands (85 right hands and 29 left hands), 14 thumbs and 291 fingers. Revision was done in 5 patients and removal of TMP joint was done in 6 patients for technical errors in most cases. But the cause of revision in 2 cases is breakage of the polyethylene stem, so we are amending it now. <h3>Conclusion</h3> We have contrived new TMP joint and have done TMPA in 106 RA patients, 114 hands, 14 thumbs and 291 fingers. Polyethylene breakage occurred in 2 fingers, so reinforcement of polyethylene stem is necessary.
Long-term effectiveness of faecal immunochemical test screening for proximal and distal colorectal cancers
Authors: Han-Mo Chiu, Grace Hsiao-Hsuan Jen, Ying-Wei Wang, Jean Ching-Yuan Fann, Chen-Yang Hsu, Ya-Chung Jeng, Amy Ming-Fang Yen, Sherry Yueh-Hsia Chiu, Sam Li-Sheng Chen, Wen-Feng Hsu, Yi-Chia Lee, Ming-Shiang Wu, Chien-Yuan Wu, Yann-Yuh Jou, Tony Hsiu-Hsi Chen
Journal: Gut (2021)

Objective To measure the effects of faecal immunochemical test (FIT) for colorectal cancer (CRC) screening on overall and site-specific long-term effectiveness of population-based organised service screening. Design A prospective cohort study of Taiwanese nationwide biennial FIT screening was performed. A total of 5 417 699 eligible subjects were invited to attend screening from 2004 through 2009 and were followed up until 2014. We estimated the adjusted relative rates (aRRs) on the effectiveness of reducing advanced-stage CRC (stage II+) and CRC death by Bayesian Poisson regression models with the full adjustment for a cascade of self-selection factors (including the screening rate and the colonoscopy rate) and the completeness of colonoscopy together with demographic features. Results FIT screening (exposed vs unexposed) reduced the incidence of advanced-stage CRC (48.4 vs 75.7 per 100 000) and mortality (20.3 vs 41.3 per 100 000). Statistically significant reductions of both incidence of advanced-stage CRCs (aRR=0.66, 95% CI 0.63 to 0.70) and deaths from CRC (aRR=0.60, 95% CI 0.57 to 0.64) were noted. FIT screening was more effective in reducing distal advanced-stage CRCs (aRR=0.61, 95% CI 0.58 to 0.64) and CRC mortality (aRR=0.56, 95% CI 0.53 to 0.69) than proximal advanced CRCs (aRR=0.84, 95% CI 0.77 to 0.92) and CRC mortality (aRR=0.72, 95% CI 0.66 to 0.80). Conclusion A large-scale population-based biennial FIT screening demonstrates 34% significant reduction of advanced-stage CRCs and 40% reduction of death from CRC with larger long-term effectiveness in the distal colon than the proximal colon. Our findings provide a strong and consistent evidence-based policy for supporting a sustainable population-based FIT organised service screening worldwide. The disparity of site-specific long-term effectiveness also provides an insight into the remedy for lower effectiveness of FIT screening in the proximal colon.
AB0106 The morphological and functional changes of microcirculatory vessels in systemic sclerosis
Authors: RT Alekperov, ES Match, NG Guseva
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> Systemic sclerosis (SSc) is characterised by the proof deterioration of microcirculation and the large structural changes of the microcirculatory vessels. The aim of the study was to investigate the relationship between functional and structural abnormalities of skin microcirculation in patients with systemic sclerosis (SSc). <h3>Methods</h3> Thirty patients with SSc aged 16 to 68 years (mean age 47,46 + 2,41 yrs) were included in the study. Nineteen pts had limited cutaneous SSc (lSSc), and eleven – diffuse cutaneous SSc (dSSc). The morphological changes of skin capillaries were estimated by the nailfold capillary microscopy. The skin microcirculation was evaluated by laser Doppler flowmetry (LDF). <h3>Results</h3> All studied patients showed an abnormal nailfold capillary pattern: enlargement of the capillary loop (dilated capillaries) and the loss of capillaries either diffusely or in limited areas. Depending on a degree of the nailfold capillaries changes the patients were divided into 3 groups: with mild (17 pts), moderate (14 pts) and severe (9 pts) changes. The level of basal skin blood flow in first group of the patients was 0,624 + 0,031v. In second group of the patients basal skin blood flow was 0,361 + 0,050v and there was also significantly below, when compared with first group of patients (p = 0,002). The lowest level of basal skin blood flow 0,212 + 0,063v was observed in the patients of third groups and also was significantly smaller than in the patients of first group (p &lt; 0,001). There wasn't a statistically significant difference in basal skin blood flow levels between 2nd and 3rd groups of the patients. The level of basal skin blood flow closely correlated with number of capillaries (r = 0,73; p &lt; 0,001). In the patients with dSSc the greater decrease of number of capillaries was observed, than in the patients with lSSc. Basal skin blood flow in dSSc was considerably below, than in lSSc (0,438 + 0,040v and 0,250 + 0,063v respectively; p = 0,02). <h3>Conclusion</h3> Thus, the microcirculation abnormalities closely correlated with structural changes of capillaries in SSc.
Antibody persistence in the first 6 months following SARS-CoV-2 infection among hospital workers: a prospective longitudinal study
Authors: Arnaud G. L'Huillier, Benjamin Meyer, Diego O. Andrey, Isabelle Arm-Vernez, Stephanie Baggio, Arnaud Didierlaurent, Christiane S. Eberhardt, Isabella Eckerle, Carole Grasset-Salomon, Angela Huttner, Klara M. Posfay-Barbe, Irene Sabater Royo, Jacques A. Pralong, Nicolas Vuilleumier, Sabine Yerly, Claire-Anne Siegrist, Laurent Kaiser
Journal: Clinical Microbiology and Infection (2021)
Which Genes for Hereditary Breast Cancer?
Authors: Steven A. Narod
Journal: New England Journal of Medicine (2021)

Results of two large case–control studies that analyzed the associations between a number of putative cancer susceptibility genes and breast cancer risk are now reported in the Journal. The study by Dorling et al.1 included 34 genes and 113,000 women from 25 countries, and the study by Hu et al.2 included 28 genes and 64,000 women from the United States. Variants in 8 genes — BRCA1, BRCA2, PALB2, BARD1, RAD51C, RAD51D, ATM, and CHEK2 — had a significant association with breast cancer risk in both studies. In addition, there was a significant association for variants in MSH6 in the international . . .
Pharyngoesophageal perforation during introduction of an echoendoscope treated with a fully covered self-expandable metal stent
Authors: Ignacio Couto-Worner, Germán Charquero-Martínez, José Souto-Ruzo, Emilio Estévez-Prieto, Benito González-Conde, Pedro Alonso-Aguirre
Journal: Endoscopy (2021)

A 69-year-old woman with a history of renal transplantation was investigated for biliary duct dilation. She was receiving treatment with prednisone and tacrolimus.
Effects of Metformin, Metformin Plus Rosiglitazone, and Metformin Plus Lifestyle on Insulin Sensitivity and [Beta]-Cell Function in TODAY: TODAY STUDY GROUP
Authors: Silva Arslanian, Laura Pyle, Marisa Payan, Fida Bacha, Sonia Caprio, Morey W. Haymond, Lynne Levitsky, Robin S. Goland, Neil H. White, Will Sm
Journal: Diabetes Care (2013)

OBJECTIVE-The Treatment Options for type 2 Diabetes in Adolescents and Youth (TODAY) trial demonstrated that combination therapy with metformin plus rosiglitazone provided superior durability of glycemic control compared with metformin alone, with significantly lower treatment failure rates (38.6 vs. 51.7%), and metformin plus lifestyle was intermediate. Herein we describe the temporal changes in measures of s-cell function and insulin sensitivity over a 4-year period among the three treatments.

RESEARCH DESIGN AND METHODS-TODAY participants (699) were tested periodically with an oral glucose tolerance test to determine insulin sensitivity (1/fasting insulin [1/I^sub F^]), insulinogenic index (?I^sub 30^/?G^sub 30^) or C-peptide index (?C^sub 30^/?G^sub 30^), and s-cell function relative to insulin sensitivity (oral disposition index [oDI]).

RESULTS-During the first 6 months, metformin plus rosiglitazone exhibited a significantly greater improvement in insulin sensitivity and oDI versus metformin alone and versus metformin plus lifestyle; these improvements were sustained over 48 months of TODAY. Irrespective of treatment, those who failed to maintain glycemic control had significantly lower s-cell function (~50%), higher fasting glucose concentration, and higher HbA^sub 1c^ at randomization compared with those who did not fail.

CONCLUSIONS-The beneficial change in insulin sensitivity and the resultant lower burden on s-cell function achieved in the first 6 months with metformin plus rosiglitazone appear to be responsible for its superior glycemic durability over metformin alone and metformin plus lifestyle. However, initial s-cell reserve and HbA^sub 1c^ at randomization are independent predictors of glycemic durability. Therefore, efforts to preserve s-cell function before significant loss occurs and to reduce HbA^sub 1c^ may be beneficial in the treatment of youth with type 2 diabetes.
Author Correction: Tau molecular diversity contributes to clinical heterogeneity in Alzheimer’s disease
Authors: Simon Dujardin, Caitlin Commins, Aurelien Lathuiliere, Pieter Beerepoot, Analiese R. Fernandes, Tarun V. Kamath, Mark B. De Los Santos, Naomi Klickstein, Diana L. Corjuc, Bianca T. Corjuc, Patrick M. Dooley, Arthur Viode, Derek H. Oakley, Benjamin D. Moore, Kristina Mullin, Dinorah Jean-Gilles, Ryan Clark, Kevin Atchison, Renee Moore, Lori B. Chibnik, Rudolph E. Tanzi, Matthew P. Frosch, Alberto Serrano-Pozo, Fiona Elwood, Judith A. Steen, Matthew E. Kennedy, Bradley T. Hyman
Journal: Nature Medicine (2021)
Shaping the slow waves of sleep: A systematic and integrative review of sleep slow wave modulation in humans using non-invasive brain stimulation
Authors: Kristoffer D. Fehér, Marina Wunderlin, Jonathan G. Maier, Elisabeth Hertenstein, Carlotta L. Schneider, Christian Mikutta, Marc A. Züst, Stefan Klöppel, Christoph Nissen
Journal: Sleep Medicine Reviews (2021)

The experimental study of electroencephalographic slow wave sleep (SWS) stretches over more than half a century and has corroborated its importance for basic physiological processes, such as brain plasticity, metabolism and immune system functioning. Alterations of SWS in aging or pathological conditions suggest that modulating SWS might constitute a window for clinically relevant interventions. This work provides a systematic and integrative review of SWS modulation through non-invasive brain stimulation in humans. A literature search using PubMed, conducted in May 2020, identified 3220 studies, of which 82 fulfilled inclusion criteria. Three approaches have been adopted to modulate the macro- and microstructure of SWS, namely auditory, transcranial electrical and transcranial magnetic stimulation. Our current knowledge about the modulatory mechanisms, the space of stimulation parameters and the physiological and behavioral effects are reported and evaluated. The integration of findings suggests that sleep slow wave modulation bears the potential to promote our understanding of the functions of SWS and to develop new treatments for conditions of disrupted SWS.
PULSE: A randomized phase II open label study of panitumumab rechallenge versus standard therapy after progression on anti-EGFR therapy in patients with <i>RAS</i> wild-type metastatic colorectal cancer (mCRC).
Authors: John H. Strickler, Fang-Shu Ou, Tanios S. Bekaii-Saab, Christine Megerdichian Parseghian, Andrea Cercek, Kimmie Ng, Federico Augusto Sanchez, Sarah Bruggeman, Joseph J. Larson, Gene Grant Finley, Joleen M. Hubbard, Christina Wu, Heinz-Josef Lenz, Scott Kopetz, Ryan Bruce Corcoran
Journal: Journal of Clinical Oncology (2021)

TPS143 Background: Patients with KRAS and NRAS ( RAS) wild-type mCRC benefit from the epidermal growth factor receptor (EGFR) monoclonal antibodies (Abs) panitumumab and cetuximab, but nearly all patients experience resistance. Blood-based profiling of cell free DNA (cfDNA) can identify genomic alterations that drive acquired EGFR Ab resistance. After discontinuation of anti-EGFR Abs, acquired genomic alterations decay over time to undetectable levels. Some studies have suggested clinical benefit from EGFR Ab rechallenge, but there is limited evidence that EGFR Ab rechallenge improves survival compared to standard of care (SOC) therapies. We hypothesize that cfDNA profiling will identify patients appropriate for panitumumab rechallenge, and that these molecularly selected patients will have improved survival compared to current SOC therapies. Methods: This is a randomized phase II, open label study designed to compare the overall survival (OS) of panitumumab rechallenge versus SOC (investigator choice TAS-102 or regorafenib). Secondary objectives include comparisons of progression free survival, objective response rate, clinical benefit rate, and quality of life as measured by the linear analogue self-assessment (LASA) questionnaire. Eligible patients have radiographically measurable KRAS, NRAS, and BRAF codon 600 wild-type mCRC based on tumor tissue testing, and must have experienced progression or intolerance to treatment with a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF Ab, and an anti-PD-1 Ab if the tumor has mismatch repair deficiency or is MSI-H. Progression after at least 4 months treatment with an anti-EGFR Ab is required. All patients must be enrolled in the COLOMATE cfDNA screening protocol (NCT03765736) and meet molecular eligibility based on Guardant360 cfDNA profiling (absence of amplification of ERBB2, KRAS, NRAS, and MET; absence of mutations of BRAF, EGFR, ERBB2, KRAS, NRAS, and MET [mutant allele frequency &gt; 0.5%]). Greater than 90 days must have elapsed between the most recent treatment with an anti-EGFR Ab and cfDNA profiling. Dosing for all study drugs is according to clinical SOC. 120 patients will be randomized 1:1 to panitumumab rechallenge or SOC. With 83 OS events, this study will have 80% power to detect an improvement in median OS from 6.5 to 10 months (HR=0.65; 1-sided α= 0.15). This study began enrollment in 6/2020. Recruitment is ongoing at 16 sites in the Academic and Community Cancer Research United (ACCRU) network (ACCRU-GI-1623). Clinical trial information: NCT03992456.
Collaborating to share evidence-basedCOVID-19 information across lung cancer patientadvocacy groups
Authors: A. C. Moore, J. Freeman-Daily, K. Norris, B. Bunn, J. Baranski, C. Chin, U. B. Roy
Journal: Clinical Cancer Research (2020)

Background: The COVID-19 pandemic has presented an urgent and serious threat to multiple at-risk populations, including those with lung cancer (LC)  This rapidly evolving crisis has seen a growing onslaught of information andguidance from multiple sources, much of which is confusing and conflicting  Thus, LC patient advocacy groups(PAGs) in the USA collaborated to share carefully vetted COVID-19 information for LC patients and caregiversonline  Our goals were to gather evidence-based information that addressed concerns of LC patients andcaregivers, translate it in a manner understandable for the general public, and share it with one voice across all LCnonprofits  This retrospective study examined whether the online LC community found this collaboration valuableand whether the weekly updates addressed useful topics in a trustworthy manner  Methods: The first “Joint Statement on Coronavirus COVID-19 from Lung Cancer Advocacy Groups” was publishedon March 3, 2020  Updates were published most Mondays thereafter  We also produced an IASLC podcast  Anonline survey (conducted over a 5-day period in early June) asked USA LC patients and caregivers (1) if they wereaware of the updates, (2) whether they found the updates useful, (3) which topic areas they found most helpful, and(4) what value they saw in the collaboration across LC advocacy groups  We also collected web statistics for eachPAGs posts of this content  Results: Cumulatively, online posts of the weekly updates received over 34,000 views between March 3 and theend of May and reached over 71,000 on Facebook  The podcast received twice the number of listens compared tothe average of pre-COVID-19 podcasts on the IASLC and Soundcloud sites  Of the 83 LC patients and caregiverswho responded to the online survey, three quarters were dealing with stage III or IV non-small cell LC, and half wereolder than 60  About 2/3 were aware of the weekly updates, and of those, over 80% found the statements helpful The five most helpful topics were (1) effect of the pandemic on LC diagnosis, treatment, and clinical trials;(2) effectof the pandemic on LC research;(3) COVID-19 treatments and vaccines;(4) who is likely to have a severe case ofCOVID-19;and (5) what we know about developing immunity to COVID-19  Based on coding responses from anopen-ended question, the majority of respondents found the collaboration valuable and trustworthy (for example,Increased trust and credibility knowing all orgs are behind it)  The updates were found so valuable that they arealso translated into Spanish by a pan-cancer Latin American PAG for their communities  Conclusions: Lung cancer patients and caregivers, particularly those considered to be at higher risk for severesymptoms or death from COVID-19, found evidence-based, patient-focused collaborative updates about COVID-19from major lung cancer PAGs informative, helpful, and trustworthy
18F-FDG PET/CT Monitoring of Response to Programmed Death Protein 1 Blockade in Metastatic Basal Cell Carcinoma
Authors: Hossein Jadvar, Gino K. In
Journal: Clinical Nuclear Medicine (2021)

A 73-year-old woman with history of metastatic basal cell carcinoma presented with a large spinal mass demonstrating a high mutational burden of 111 mutations/Mb. She underwent T12 corpectomy and T10-L3 posterior spinal fusion followed by adjuvant radiation. After 2 years of surveillance, FDG PET/CT and a contrast-enhanced MRI revealed recurrence, prompting salvage therapy with the hedgehog signaling pathway inhibitor, sonidegib, which only transiently stabilized the disease. An off-label treatment with the programmed death protein 1 inhibitor, pembrolizumab, was initiated. Serial FDG PET/CT showed gradual decline in tumor metabolism over the next 12 months, leading to complete metabolic response.
COVID-19 increased the risk of ICU-acquired bloodstream infections: a case–cohort study from the multicentric OUTCOMEREA network
Authors: Niccolò Buetti, Stéphane Ruckly, Etienne de Montmollin, Jean Reignier, Nicolas Terzi, Yves Cohen, Shidasp Siami, Claire Dupuis, Jean-François Timsit
Journal: Intensive Care Medicine (2021)
Mandatory HPV Vaccination and Political Debate
Authors: Lawrence O Gostin
Journal: JAMA (2011)

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