tbuckley/cabot-search huggingface dataset:
A New Ethical Framework for Assessing the Unique Challenges of Fetal Therapy Trials
Authors: Saskia Hendriks, Christine Grady, David Wasserman, David Wendler, Diana W. Bianchi, Benjamin E. Berkman
Journal: The American Journal of Bioethics (2021)

New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk-benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research (e.g., only for life-threatening conditions). Instead, we propose that the individual risks for the pregnant woman
AB0823 MINIMAL DISEASE ACTIVITY IN PSORIATIC ARTHRITIS IS ASSOCIATED WITH LOW IMPACT OF DISEASE ON PSAID12 QUESTIONAIRE
Authors: J. A. Mosquera Martínez, C. García-Porrúa, L. Fernández-Dominguez, J. L. Guerra-Vazquez, J. Pinto-Tasende
Journal: Annals of the Rheumatic Diseases (2020)

Background: Psoriatic arthritis (PsA) has a prevalence of 0.58% in Spain and patients suffer this disease have significant impact on daily life due to articular, dermatological and psychological symptoms. To reach minimal disease activity (MDA) is a therapeutic goal recommended by EULAR for clinical practice. Objectives: Our aim was to assess the relationship between MDA and PsAID questionnaire in routine clinical practice. Methods: We performed a cross-sectional study of patient and physician reported outcomes. We obtained clinical information of patients with PsA attending clinic from October 2018 to October 2019. Data were collected from clinical records concerning age, gender, disease duration, joint counts, dactylitis, enthesitis, body surface area (BSA) of psoriasis, laboratory results (ESR and CRP), HAQ, PsAID12, pain and global assessment from patient with numerical rating scale (NRS) and MDA status. Data were analysed using SPSS21. Logistic regression was used to assess patient reported outcomes which were associated with achieving MDA. Results: Data were available for 210 patient visits, 57% males. MDA 5/7 was reached in 118 patients (56.2%) and MDA7/7 in 58 (27.6%). Age and gender were not associated with reach MDA. Higher disease duration was associated with MDA, OR 1.062 (1.012-1.114, 95% CI), p 0.015. PsAID12 was evaluated in 156 patients and all components were associated with reach MDA. Patients in MDA had significantly lower PsAID12 than those were not in MDA (mean 1.5 ± SD 1.5 vs. 3.8 ± 2.1), p&lt; 0.0001. PsAID12 of less than 4 is considered a good outcome and individual components of PsAID12 (Figure 1, mean values for NRS) were less than 4 in patients with MDA. Figure 1. All components of PsAID12 were associated with MDA on univariate analysis but only pain and functional capacity remained independent predictors on multiple regression analysis (p&lt; 0.0001 and p0.008 respectively). Percentage of BSA was associated with skin component of PsAID12 (p&lt;0.0001) and with shame component (p0.001). Conclusion: In these PsA patients, MDA was reached mainly in patients with higher disease duration. MDA is a relevant treatment target in PsA, with markedly lower PsAID12 in patients in MDA. Pain and functional discapacity are dominant symptoms in patients with psoriatic arthritis, even in those in MDA. Skin affection is associated with skin and shame components on the PsAID12. References: [1]Queiro R et al. Arthritis Res Ther. 2017 Mar 29;19(1):72. Acknowledgments: SOGARE Disclosure of Interests: José Antonio Mosquera Martínez: None declared, Carlos García-Porrúa: None declared, Luis Fernández-Dominguez: None declared, Jose L. Guerra-Vazquez: None declared, Jose Pinto-Tasende Consultant of: Janssen, Novartis, Speakers bureau: Lilly, Janssen, Novartis, BMS, Pfizer, Celgene
Pair consensus decoding improves accuracy of neural network basecallers for nanopore sequencing
Authors: Jordi Silvestre-Ryan, Ian Holmes
Journal: Genome biology (2021)

Abstract We develop a general computational approach for improving the accuracy of basecalling with Oxford Nanopore’s 1D 2 and related sequencing protocols. Our software PoreOver ( https://github.com/jordisr/poreover ) finds the consensus of two neural networks by aligning their probability profiles, and is compatible with multiple nanopore basecallers. When applied to the recently-released Bonito basecaller, our method reduces the median sequencing error by more than half.
SAT0081 Effect of body mass index and bone mineral density on knee osteoarthritis
Authors: A Bilgici, O Kuru, G Alayli, N Yildiz
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> <h3>Objectives</h3> The aim of this study was to investigate the influence of the bone mineral density (BMD) and body mass index (BMI) on the knee osteoarthritis (OA). <h3>Methods</h3> Seventyfive patients were taken in this study. BMD was measured using dual X-ray absorptiometry (Dexa). Measurements of the spine were made at L1-L4 and of the hip at three sites (femoral neck, Ward's region and trochanter). The BMI, an indicator of obesity was calculated as the weight divided by the height squared (kg/m<sup>2</sup>). The knee OA was assessed from a weight-bearing anteroposterior radiograph. Osteophytes and joint space narrowing were evaluated seperately. Individual radiographic features (IRF) rating method was used for grading of osteophytes (0–3) and joint space narrowing (0–3). <h3>Results</h3> The mean age of the women was 67 years (48–75) and of the 23 men was 61 years (45–66). There was a highly positive correlation between BMD and OA with BMI(p &lt; 0.01, p &lt; 0.01 respectively). The density of the lumbar spine and the 3 proximal femur sites was significantly larger in men than in women. Mean femoral BMD was correlated with joint space narrowing but not with osteophytosis (p &lt; 0.05). There was no relationship between the density of the lumbar spine with knee OA. <h3>Conclusion</h3> There is a clear link between BMD and BMI with the knee OA. These results suggest that mechanical factors are important in the pathophysiology of these diseases.
Abstract 18310: NT-proBNP for Predicting Exercise Capacity in Phenotypes of Left Ventricular Hypertrophy - Results From the MyoVasc Study
Authors: Felix Müller, Jürgen H Prochaska, Sebastian Göbel, Andreas Stöhr, Sven O Tröbs, Sören Schwuchow, Mobin Dib, Andreas Schulz, Simon Diestelmeier, Tina Herholz, Jaume L Monteverde, Stefanie Kurz, Karl J Lackner, Tommaso Gori, Thomas Münzel, Philipp S Wild
Journal: Circulation (2017)

Background: Evidence on the relationship between NT-proBNP and exercise tolerance in sub-patterns of left ventricular (LV) hypertrophy is limited. Methods: A sample of 2,000 participants of the Myo...
Analytical and clinical validation of the TruCheck platform for diagnostic triaging of symptomatic cases suspected of colorectal cancer.
Authors: Dadasaheb B Akolkar, Darshana Patil, Pradip Fulmali, Pooja Fulmali, Revati Patil, Kiran Bendale, Archana Adhav, Shoeb Patel, Shabista Khan, Raja Dhasarathan, Vishal Rajan, Rohit Chougule, Pradyumna Shejwalkar, Akshay Ainwale, Mohini Garte, Rahul Sonawane, Madhav Purane, Yogeshwar Chaudhari, Prajakta Sagar, Shubhangi Nerkar
Journal: Journal of Clinical Oncology (2021)

24 Background: Trucheck is a non-invasive approach for diagnostic triaging of symptomatic individuals who are suspected of Colorectal Cancer (CRC) and have been advised an invasive biopsy. Trucheck evaluates blood samples for presence of Circulating Ensembles of Tumor Associated Cells (C-ETACs: EpCAM + , Pan-CK + , CD45 ± ) originating from a primary Colorectal Adenocarcinoma (CR-AD: CDX-2, CK-20, Muc2); such C-ETACs are unexpected in asymptomatic individuals as well as in individuals with benign Colorectal conditions. Methods: For Analytical Validation, spike-recovery analysis was performed using control cells / cell lines for EpCAM (SKBR-3), Pan-CK (SKBR-3), CD45 (PBMCs), CDX2 (CaCO2), CK20 (HCT15) and MUC2 (SW620) to determine the Sensitivity, Specificity, Accuracy, Limit of Detection, Linearity and Precision. Clinical Validations were performed using 15 mL blood samples from 587 participants. An initial Retrospective Clinical Pre-validation was based on blood samples from 350 known cases of CR-AD and 20 cases of non-CRC. The Prospective Clinical Validation was performed on blood samples collected prior to any invasive procedures from 217 symptomatic cases suspected of CRC. Results: Analytical Validation indicated 100% Sensitivity, 100% Specificity, 100% Accuracy, 90% Precision and significant linearity (R 2 ≥0.98) for all ICC markers. Clinical Pre-validation indicated 84.9 % Sensitivity and 100% Specificity for CR-AD v/s non-CRC. In the Prospective Clinical Validation cohort, histopathological evaluation (HPE) of biopsied tumor tissue indicated benign Colorectal conditions in 10 cases and CR-AD 207 of the 217 suspected cases. Based on HPE as the standard, the Trucheck approach had 90.3% Sensitivity, 100% Specificity and 95.2% Accuracy. Conclusions: Symptomatic individuals suspected of CRC may benefit from the sensitive and specific non-invasive Trucheck approach. Individuals positive for CR-AD-specific C-ETACs can be prioritized for further clinical procedures while C-ETAC negative individuals can be considered for alternate diagnoses. The Trucheck approach can eliminate the need for (and risks associated with) invasive colon biopsies in a significant proportion of suspected cases and is especially useful where
Few-shot learning creates predictive models of drug response that translate from high-throughput screens to individual patients
Authors: Jianzhu Ma, Samson H. Fong, Yunan Luo, Christopher J. Bakkenist, John Paul Shen, Soufiane Mourragui, Lodewyk F. A. Wessels, Marc Hafner, Roded Sharan, Jian Peng, Trey Ideker
Journal: Nature Cancer (2021)
FRI0088 Poly(adp-ribose) polymerase (parp) polymorphism in spanish systemic lupus erythematosus (sle) patients
Authors: T Martin-Donaire, MJ Citores, S Rosado-Garcia, I Rua-Figueroa, I Garcia-Laorden, C Rodriguez-Lozano, P Perez-Aciego, C Rodriguez-Gallego, A Durantez
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> PARP is a DNA-binding protein that catalyses the covalent addition of ADP-ribose to many nuclear proteins. It is involved in DNA repair and apoptosis, processes that have been implicated as causative factors for SLE. It has been shown that patients suffering SLE have decreased PARP mRNA levels and a low enzime activity. The PARP gene is located at 1q41-q42 and contains a microsatellite (CA)n polymorphism in the promoter region that probably affects the transcription and mRNA levels. A recent study found preferential transmission of the allele containing 12 CA repeats to affected offspring in Caucasian SLE families. <h3>Objectives</h3> To investigate the association between PARP polymorphism and SLE susceptibility in Spaniards. <h3>Methods</h3> 76 unrelated SLE patients from Canary Islands (Spain) fulfilling at least four of the ACR criteria and 79 sex-matched healthy donors were included. A segment of the PARP gene containing the microsatellite was amplified by PCR and the resulting products were electrophoresed in denaturing polyacrilamide gels. Chi-square test was used for statistical analysis. <h3>Results</h3> Allelic distributions of PARP polymorphism showed no statistical differences between SLE patients and controls. But considering particular clinical features we found several associations with specific alleles: a) homozygotes for 11rep. allele suffered more lymphopenia (p = 0.04) but less hypocomplementemia (p = 0.03), b) autoantibodies anti-Ro/La were more frequent (p = 0.02) in carriers of 15rep., c) carriers of 16rep. allele presented more malar rash (p = 0.03) and seizures (p = 0.04), and finally d) carriers of 17rep. allele showed a reduced risk of production of several autoantibodies as anti-Sm (p = 0.007) and anti-Ro/La (p = 0.04). <h3>Conclusion</h3> Although PARP alleles seem not to influence susceptibility to SLE in Spaniards, some of them may be related to the presence of several clinical and analytical manifestations of the disease.
Development of a Model to Estimate the Association Between Delay in Cancer Treatment and Local Tumor Control and Risk of Metastases
Authors: John Ng, Yael R. Stovezky, David J. Brenner, Silvia C. Formenti, Igor Shuryak
Journal: JAMA Network Open (2021)

<h3>Importance</h3> The coronavirus disease 2019 (COVID-19) pandemic has led to treatment delays for many patients with cancer. While published guidelines provide suggestions on which cases are appropriate for treatment delay, there are no good quantitative estimates on the association of delays with tumor control or risk of new metastases. <h3>Objectives</h3> To develop a simplified mathematical model of tumor growth, control, and new metastases for cancers with varying doubling times and metastatic potential and to estimate tumor control probability (TCP) and metastases risk as a function of treatment delay interval. <h3>Design, Setting, and Participants</h3> This decision analytical model describes a quantitative model for 3 tumors (ie, head and neck, colorectal, and non–small cell lung cancers). Using accepted ranges of tumor doubling times and metastatic development from the clinical literature from 2001 to 2020, estimates of tumor growth, TCP, and new metastases were analyzed for various treatment delay intervals. <h3>Main Outcomes and Measures</h3> Risk estimates for potential decreases in local TCP and increases in new metastases with each interval of treatment delay. <h3>Results</h3> For fast-growing head and neck tumors with a 2-month treatment delay, there was an estimated 4.8% (95% CI, 3.4%-6.4%) increase in local tumor control risk and a 0.49% (0.47%-0.51%) increase in new distal metastases risk. A 6-month delay was associated with an estimated 21.3% (13.4-30.4) increase in local tumor control risk and a 6.0% (5.2-6.8) increase in distal metastases risk. For intermediate-growing colorectal tumors, there was a 2.1% (0.7%-3.5%) increase in local tumor control risk and a 2.7% (2.6%-2.8%) increase in distal metastases risk at 2 months and a 7.6% (2.2%-14.2%) increase in local tumor control risk and a 24.7% (21.9%-27.8%) increase in distal metastases risk at 6 months. For slower-growing lung tumors, there was a 1.2% (0.0%-2.8%) increase in local tumor control risk and a 0.19% (0.18%-0.20%) increase in distal metastases risk at 2 months, and a 4.3% (0.0%-10.6%) increase in local tumor control risk and a 1.9% (1.6%-2.2%) increase in distal metastases risk at 6 months. <h3>Conclusions and Relevance</h3> This study proposed a model to quantify the association of treatment delays with local tumor control and risk of new metastases. The detrimental associations were greatest for tumors with faster rates of proliferation and metastasis. The associations were smaller, but still substantial, for slower-growing tumors.
FRI0130 Relationship between presence of neurological symptoms and activity of systemic lupus erythematosus
Authors: L Ostanek, K Honczarenko, K Fischer, I Fiedorowicz-Fabrycy
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> According to many authors presence of neurological symptoms are features of disease activity in patients with systemic lupus erythematosus. Clinical observations very often do not confirm this hypothesis. <h3>Objectives</h3> To assess if neurological symptoms correlate with disease activity in patients with systemic lupus erythematosus. <h3>Methods</h3> The study was performed on 83 patients with SLE (77 women and 6 men), age 17–63 years mean age 33,8 yrs), disease duration was 1–30 years (mean 9,05 yr). Every subject was assessed at least two times by rheumatologist and neurologist during different stages of SLE activity. SLE activity was assess according to SLEDAI scale. Haematological, biochemistry and coagulation tests were performed for everyone. In some cases histopatolgical assessment of tissue samples were done. Electrophysiological tests (EEM, EMG, BAEP, VEP) and cerebral CT, MRI and SPECT scans were performed in subjects with neurological symptoms. All the subjects were tested for the presence of antinuclear antibodies, (ANA), anticardiolipin antibodies (aCL), anti-B2-glycoprotein antibodies and antiendothelial antibodies (AECA). Results of the mentioned tests were statistically evaluated. <h3>Results</h3> No association has been found between presence of neurological symptoms and disease activity in patients with systemic lupus erythematosus Neurological symptoms were found significantly more frequently in subjects with high titer of IgG anticardiolipin antibodies and in patients with secondary antiphospholipid syndrome. There was a tendency for neurological symptoms to occur in patients with vascular complications. <h3>Conclusion</h3>
FRI0060 Successful treatment of active rheumatoid arthritis with chimeric monoclonal antibody to tumour necrosis factor (infliximab): an open study
Authors: KA Boki, VA Vassiliou, G Linardaki, HM Moutsopoulos
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Infliximab is a chimeric anti-tumour necrosis factor α (anti-TNFα) monoclonal IgG1 antibody, neutralising the soluble cytokine and blocking the membrane bound cytokine that is used successfully for the treatment of active rheumatoid arthritis (RA) not controlled with other disease modified anti-rheumatic drugs (DMARDs). <h3>Objectives</h3> The clinical evaluation of infliximab in the treatment of active RA. <h3>Methods</h3> Twenty-four (24) patients (pts) with active RA (20 women and 4 men), mean age 46.4 ± 10.17 (years), and mean disease duration 9.9 ± 7.77 (years) received infliximab in a combination with Methotrexate 10 mg/week and Prednizolone 7.5–10 mg/day in an open unrandomized trial. Thirteen (13) pts completed three months therapy with infliximab and 11 pts six months. Infliximab was given at a dose of 3 mg/kg of body weight at week 0, 2 and 6 of treatment protocol and then every 8 weeks. All these pts had received combination therapy with DMARDs for more than three months, before enrolling in the study, without sufficient improvement. Active RA was defined by 10 or more swollen joints (10.9 ± 4.7), 12 or more tender joints (13.4 ± 5.11), ESR &gt;28 mm (48.0 ± 19.23 mm) and C-reactive protein &gt;5.0 mg/dl (37.4 ± 12.69 mg/dl). A statistical analysis was done after the third and sixth month of treatment. <h3>Results</h3> At three months, the number of swollen joints was reduced to 3.3 ± 2.73 (p &lt; 0.001) and the number of tender joints was, also, reduced to 4.1 ± 3.17 (p &lt; 0.001), ESR was 29.0 ± 20.5 mm (p &lt; 0.001) and CRP 18.6 ± 13.05 mg/dl (p &lt; 0.001). At six months, statistically significant difference was not observed in any of the parameters of disease activity: swollen joints were 2.8 ± 2.01 (NS), tender joints 5.6 ± 4.3 (NS), ESR 24.6 ± 19.3 mm (NS) and CRP 15.4 ± 12.3 mg/dl (NS). Four female pts were excluded from the study and the statistical analysis: one patient because of unsufficient respond, another patient because of allergic reaction during the 5th infusion, and 2 pts because of uncontrolled urinary track infection after the 3rd infusion. All the pts declare dizziness, light headache, nausea, 2 pts reported abdominal pain after the first infusion and 2 pts increased hairing loss. One patient with alopecia areata universalis reported hair improvement but this result was only for a small period of time. <h3>Conclusion</h3> The initiation of infliximab therapy in patients with active RA resulted in a fast and significant improvement of peripheral articular manifestations and quality of life. Even though major adverse events were not reported, the clinicians should be aware of this possibility.
Health-related quality of life and time from diagnosis among young adult colorectal cancer survivors.
Authors: Kimberly Ann Miller, Julia Stal, Phuong Gallagher, Jonathan N Kaslander, David R. Freyer, Priscilla Marin, Heinz-Josef Lenz, Joel Milam, Afsaneh Barzi
Journal: Journal of Clinical Oncology (2021)

34 Background: Incidence of colorectal cancer (CRC) in patients under 50 years of age is rising. Quality of life in survivorship is not well-described in this population. We compared health-related quality of life (HRQoL) in CRC survivors ≤ 50 years old who were 6-18 months or 19-36 months from initial diagnosis or relapse. Methods: A cross-sectional online survey was administered in collaboration with a national organization for young CRC survivors. The Functional Assessment of Cancer Therapy (FACT-C) was used to measure HRQoL, which assesses HRQoL globally, including a CRC specific scale, and emotional, physical, social, and functional well-being domains. T-tests were conducted to compare HRQoL between survivors who were 6-18 months versus 19-36 months from diagnosis/relapse. Results: This sample (n=308) had a mean age of 33.76 SD±6.68; 201 (65.3%) were male; tumor location was colon or rectal in 41.7% and 58.3%, respectively. The majority (55.23%) were diagnosed with stage 2 disease; 98.0% were non-metastatic. 42.2% experienced relapse; 25% had an ostomy. Most survivors were 6-18 months (N=189; 61.4%) from diagnosis/relapse, and key demographics and disease characteristics did not significantly differ between those who were shorter versus longer time from diagnosis/relapse. The mean global HRQoL score was 67.3 out of a possible score of 136. Across domains, scores were low, with social well-being the highest (15.15/28) and emotional well-being the lowest (11.44/24). Social well-being was significantly higher among survivors who were 6-18 months from diagnosis/relapse compared to those 19-36 months (15.98 for 6-18 months vs. 13.83 for 19-36; p&lt;0.01), as was functional well-being (13.20 for 6-18 months vs. 11.12 for 19-36; p&lt;0.01). Emotional well-being and physical well-being did not significantly differ between groups. Conclusions: Overall HRQoL scores were low among younger CRC survivors, and social and functional well-being were significantly worse for those longer from diagnosis. Appropriate counseling and other targeted interventions are necessary to maintain HRQoL over time in this at-risk population. [Table: see text]