tbuckley/cabot-search huggingface dataset:
Early and late stage gene therapy interventions for inherited retinal degenerations
Authors: Catherine Botto, Marco Rucli, Müge Defne Tekinsoy, Juliette Pulman, José-Alain Sahel, Deniz Dalkara
Journal: Progress in Retinal and Eye Research (2021)

Inherited and age-related retinal degeneration is the hallmark of a large group of heterogeneous diseases and is the main cause of untreatable blindness today. Genetic factors play a major pathogenic role in retinal degenerations for both monogenic diseases (such as retinitis pigmentosa) and complex diseases with established genetic risk factors (such as age-related macular degeneration). Progress in genotyping techniques and back of the eye imaging are completing our understanding of these diseases and their manifestations in patient populations suffering from retinal degenerations. It is clear that whatever the genetic cause, the majority of vision loss in retinal diseases results from the loss of photoreceptor function. The timing and circumstances surrounding the loss of photoreceptor function determine the adequate therapeutic approach to use for each patient. Among such approaches, gene therapy is rapidly becoming a therapeutic reality applicable in the clinic. This massive move from laboratory work towards clinical application has been propelled by the advances in our understanding of disease genetics and mechanisms, gene delivery vectors, gene editing systems, and compensatory strategies for loss of photoreceptor function. Here, we provide an overview of existing modalities of retinal gene therapy and their relevance based on the needs of patient populations suffering from inherited retinal degenerations.
Correction: Targeting of PYK2 Synergizes with EGFR Antagonists in Basal-like TNBC and Circumvents HER3-Associated Resistance via the NEDD4–NDRG1 Axis
Authors: Nandini Verma, Anna-Katharina Müller, Charu Kothari, Effrosini Panayotopoulou, Amir Kedan, Michael Selitrennik, Gordon B. Mills, Lan K. Nguyen, Sungyoung Shin, Thomas Karn, Uwe Holtrich, Sima Lev
Journal: Cancer Research (2020)
POS0465 DIFFERENT CLINICAL RELEVANCE OF ANTI-CITRULLINATED PROTEINS ANTIBODIES IN RA PATIENTS
Authors: A. Avdeeva, M. Cherkasova, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2021)

Background: Anti-citrullinated proteins antibodies (ACPA) are a broad group of antibodies, including antibodies to citrullinated fibrinogen, antibodies to cyclic citrullinated peptide (anti-CCP), antibodies to modified citrullinated vimentin (anti-MCV), antibodies to citrullinated α-enolase. Objectives: To find a potential relationship between ACPA and disease activity, bone destruction, and ACPAs responses to various therapeutic regimens. Methods: The study included 232 patients (pts) with rheumatoid arthritis (RA); 90 pts (74 women, Me;IQR age 53.0 (38.0–58.5) years had early RA, with mean disease duration 5.0 (4.0–9.0) months, DAS 28 5.3 (4.4–6.1)); 142 pts had advanced stage of the disease (123 women, median age 51.0 (43.0–60.0) years, disease duration 56.0 (24.0–96.0) months, DAS 28 6.2 (5.5–6.8)). Pts with early RA received methotrexate (MTX) subcutaneously at average 17.5 mg dose once weekly. Pts with advanced RA received the following anti-B-cell therapy: 34 pts - rituximab (RTX); 20 pts - RTX biosimilar; 43 pts - tocilizumab (TCZ) in combination with conventional DMARDs. Serum anti-CCP and anti-MCV concentrations were measured using ELISA. Results: 77 (85.6%) pts with early RA were high positive for anti-CCP, and 29 (70.7%) pts - high positive for anti-MCV. A positive correlation was found between anti-MCV and DAS 28 (r=0.4, p =0.04). As for advanced RA, 78 (80.4%) pts were high positive for anti-CCP, and 70 (79.5%) - for anti-MCV. There was a positive correlation between anti-MCV concentration and SDAI (r=0.4, p =0.02), as well as CDAI (r=0.4, p =0.02). No significant correlations were found between the anti-CCP levels and activity indices, anti-CCP and acute-phase parameters in both early and advanced RA groups. Higher total Sharp scores (96.5 (65.0-122.0)) were found in pts high positive for anti-MCV (n=79), compared to low-positive/negative (57.0 (31.0–88.0), respectively, (n=27, p &lt;0.05). anti-MCV levels dropped significantly in pts on RTX and TCZ therapy at weeks 12 and 24 after initiation of treatment, while high anti-CCP concentration persisted throughout the treatment (Table 1) Conclusion: anti-MCV levels correlated with inflammatory activity and development of bone destruction, and were decreasing in pts on treatment. Anti-CCP was less responsive, showed minor changes during treatment, therefore its’ thorough monitoring was not feasible. Disclosure of Interests: None declared
David Oliver: The pandemic has delivered clinical service innovations worth keeping
Authors: David Oliver
Journal: BMJ (2021)

The NHS’s response to the covid-19 pandemic has shown how necessity can be the mother of innovation. Although plenty has gone wrong in national policy,1 and while frontline services have experienced considerable difficulties,2 the crisis has also accelerated and enabled the adoption of some practices we might actually like to keep.

Telephone and online consulting : Infection control measures left us with no option but to make far greater use of this. It was already done in primary care and some secondary care clinics, but it became the default for many routine appointments where physically being in the same room wasn’t necessary.3 It does raise some concerns, including patient preference, exclusion of patients unable to use digital technology, and the ongoing need for hands-on examination and same room discussions. But …
AB0136 ASSESSING THE RELATIONSHIP AMONG OBESITY, GENETIC POLYMORPHISM, AND CLINICAL PARAMETERS IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: K. Yoshida, S. Hatachi, S. Takahashi, N. Amano, M. Katayama, M. Sibata, T. Saito, S. Kumagai
Journal: Annals of the Rheumatic Diseases (2021)

Background: Several study suggested body mass index(BMI) may influence development of rheumatoid arthritis(RA). There are conflicting reports concerning the impact of high BMI on development of RA, but several reports of obese on drug resistance and functional impairment. The relationship of genetic polymorphism on obesity is unclear in RA. Objectives: To examine the relationship among BMI, genetic polymorphism of obesity, disease activity of RA, laboratory parameters, and therapeutic agent of RA. Methods: We have carried out a retrospective observational study by systematically analyzing medical records of total 289 patients diagnosed with RA in Shinko Hospital between March 2016 and December 2019. We also conducted genotyping single nucleotide polymorphisms (SNPs) including FTO (rs1558902 and rs9939609), UCP1 (rs1800592), ADR2(rs1042713) and ADR3(rs4994) after informed consent. Obesity was defined as BMI over than 25 and patients were divided between obese (“Ob”) and non-obese (“non-Ob”). These SNPs, DAS28CRP, laboratory parameters, methotrexate dose, use of biological DMARDs were compared between Ob and non-Ob patients. Results: Of these 289 patients, 82.7% was female, mean age was 61.9 years and BMI was 22.4. Univariate logistic regression showed differences (p&lt;0.1) between Ob and non Ob groups in UCP1 gene mutation(63.6% vs 78%, P=0.018), DAS(2.24 vs 1.99, P=0.033),triglyceride abnormality(23.8% vs 9.3%, P=0.021), HDL(56 vs 71, P=0.00009), HbA1c abnormality(26.5% vs 12.1%, P=0.019),γGTP(32 vs 21, P=0.00037), ALP (253 vs 230, P=0.0058), ALT (26.5 vs 20, P=0.029),and MTX dose(6 vs 8, P=0.066). Multivariate logistic regression showed that Ob group was significantly associated with HDL(OR=0.976, 95%CI 0.958 to 0.995), UCP1 gene mutation(OR=0.446, 95%CI 0.202 to 0.984), γGTP(OR=2.321, 95%CI 1.269 to 4.245), and MTX dose(OR=0.866, 0.784 to 0.957). Conclusion: Obesity in patients with RA had significant positive correlation with γGTP, and negative correlation with HDL, UCP gene mutation and MTX dose. Disclosure of Interests: None declared
Differential Impact of Conditioning Intensity on Post-Transplant Outcome of FLT3 -Mutated and FLT3 Wild Type AML in First Remission, a Report from Taiwan Bone Marrow Transplant Registry (TBMTR)
Authors: Su-Peng Yeh, Ming Yao, Jih-Luh Tang, Jin-Hwang Liu, Tzeon-Jye Chiou, Tran-Der Tan, Po-Nan Wang, Yeu-Chin Chen, Wen-Li Hwang, Ciyuan-jheng Wang, Tsai-Yun Chen, TA-Chih Liu, Ming-Sun Yu, Tso-Fu Wang
Journal: Blood (2017)
POS0486 FACTORS ASSOCIATED WITH CHRONOTROPIC RESPONSE IN PEOPLE WITH RHEUMATOID ARTHRITIS
Authors: A. Osailan
Journal: Annals of the Rheumatic Diseases (2021)

Background: People with rheumatoid arthritis (RA) are at high risk for cardiovascular diseases (CVD) and CVD mortality. Reduced Chronotropic response (CR), which produces exercise intolerance, is known as a contributing factor to CVD and mortality. Studies have shown that people with RA have reduced CR. However, knowledge about the factors associated with CR in people with RA is limited. Objectives: To explore the factors associated with CR including CVD risk factors, inflammatory markers and cardiorespiratory fitness (VO 2 peak). Methods: 106 people with RA completed a treadmill exercise tolerance test while heart rate (HR) was monitored via 12 leads ECG. CR was defined as the percentage of [(achieved peak HR minus resting HR) divided by (age-predicted maximum HR minus resting HR)]. Serological CVD risk factors and inflammatory markers including lipids profile, markers of insulin resistance and sensitivity (HOMA, QUICKi), high sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate (ESR), fibrinogen and white blood cells (WBC) were examined via a fasted blood sample. VO 2 peak was assessed via breath-by-breath gas analysis. Results: 34% had reduced CR based on the cut-off value (≤ 80%) and the average CR was 86.2 ± 21%. Body mass index (r=-0.33, p=.001), HOMA (r=-0.26, p=.009), hsCRP (r=-0.23, p=.02), ESR (r=-0.21, p=.04), fibrinogen (r=-0.2, p=.05), WBC (r=-0.21, p=.04) were inversely associated with CR, whereas, high density lipoprotein (HDL) (r=0.43, p&lt;.001), QUICKi (r=0.31, p=.002), and VO 2 peak (r=0.4, p&lt;.001) were positively associated with CR. When all the variables were entered into a stepwise linear regression, HDL (p&lt;.001) and VO 2 peak (p=.009) were independently associated with CR. Conclusion: The current findings suggest that CR in RA was associated with many CVD risk factors, inflammatory markers, and cardiorespiratory fitness. Among all the varibales, HDL and cardiorespiratory fitness were moderately and independently associated with CR. Future studies should investigate the effect of improving these associated variables on CR in people with RA via exercise training programes. Acknowledgements: Thanks to physical activity in Rheumatoid arthritis research team and Research department in Dudley Hospital. Sincere appreciation and gratitude to Dr Jet Veldhuizen van Zanten, Prof. Joan Duda, and Prof. George Kitas from the University of Birmingham and Prof. George Metsios from the University of Wolverhampton. Disclosure of Interests: None declared
Immunotherapy in association with stereotactic radiotherapy for non-small cell lung cancer brain metastases: results from a multicentric retrospective study on behalf of AIRO
Authors: Silvia Scoccianti, Emanuela Olmetto, Valentina Pinzi, Mattia Falchetto Osti, Rossella Di Franco, Saverio Caini, Paola Anselmo, Paolo Matteucci, Davide Franceschini, Cristina Mantovani, Giancarlo Beltramo, Francesco Pasqualetti, Alessio Bruni, Paolo Tini, Emilia Giudice, Patrizia Ciammella, Anna Merlotti, Sara Pedretti, Marianna Trignani, Marco Krengli, Niccolò Giaj-Levra, Isacco Desideri, Guido Pecchioli, Paolo Muto, Ernesto Maranzano, Laura Fariselli, Pierina Navarria, Umberto Ricardi, Vieri Scotti, Lorenzo Livi
Journal: Neuro-Oncology (2021)

To define efficacy and toxicity of Immunotherapy (IT) with stereotactic radiotherapy (SRT) including radiosurgery (RS) or hypofractionated SRT (HFSRT) for brain metastases (BM) from non-small cell lung cancer (NSCLC) in a multicentric retrospective study from AIRO (Italian Association of Radiotherapy and Clinical Oncology).NSCLC patients with BM receiving SRT + IT and treated in 19 Italian centers were analyzed and compared with a control group of patients treated with exclusive SRT.One hundred patients treated with SRT + IT and 50 patients treated with SRT-alone were included. Patients receiving SRT + IT had a longer intracranial Local Progression-Free Survival (iLPFS) (propensity score-adjusted P = .007). Among patients who, at the diagnosis of BM, received IT and had also extracranial progression (n = 24), IT administration after SRT was shown to be related to a better overall survival (OS) (P = .037). A multivariate analysis, non-adenocarcinoma histology, KPS = 70 and use of HFSRT were associated with a significantly worse survival (P = .019, P = .017 and P = .007 respectively). Time interval between SRT and IT ≤7 days (n = 90) was shown to be related to a longer OS if compared to SRT-IT interval >7 days (n = 10) (propensity score-adjusted P = .008). The combined treatment was well tolerated. No significant difference in terms of radionecrosis between SRT + IT patients and SRT-alone patients was observed. The time interval between SRT and IT had no impact on the toxicity rate.Combined SRT + IT was a safe approach, associated with a better iLPFS if compared to exclusive SRT.
NCCN Guidelines® Insights: Breast Cancer, Version 4.2021
Authors: William J. Gradishar, Meena S. Moran, Jame Abraham, Rebecca Aft, Doreen Agnese, Kimberly H. Allison, Sarah L. Blair, Harold J. Burstein, Chau Dang, Anthony D. Elias, Sharon H. Giordano, Matthew P. Goetz, Lori J. Goldstein, Sara A. Hurvitz, Steven J. Isakoff, Rachel C. Jankowitz, Sara H. Javid, Jairam Krishnamurthy, Marilyn Leitch, Janice Lyons, Jennifer Matro, Ingrid A. Mayer, Joanne Mortimer, Ruth M. O'Regan, Sameer A. Patel, Lori J. Pierce, Hope S. Rugo, Amy Sitapati, Karen Lisa Smith, Mary Lou Smith, Hatem Soliman, Erica M. Stringer-Reasor, Melinda L. Telli, John H. Ward, Kari B. Wisinski, Jessica S. Young, Jennifer L. Burns, Rashmi Kumar
Journal: Journal of the National Comprehensive Cancer Network (2021)

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer–focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor–positive, HER2-negative breast cancer.
POS0269-HPR CONTENT VALIDITY OF A MULTIPLE LANGUAGES QUESTIONNAIRE FOR MEASURING FLARE IN KNEE AND HIP OA: DEVELOPMENT OF THE FLARE-OA
Authors: F. Guillemin, A. Barcenilla-Wong, M. Vitaloni, L. Adarmouch, M.T. Duruöz, J. Epstein, M. Sebbani, Y. Traore, C. Rutherford, M. Cross, B. Fautrel, T. Buttel, G.A. Hawker, L. March, D. Hunter, E. Spitz
Journal: Annals of the Rheumatic Diseases (2021)

Background: Flare in osteoarthritis (OA) of the knee and hip (KHOA) is an important outcome for patients’ daily life and clinical research. A definition of a flare was set, and a core set of domains was recently endorsed by OMERACT/OARSI. No patient reported outcome (PRO) yet focusses on flare in OA specifically. Objectives: To develop a self-reporting instrument measuring flare in 5 languages, using qualitative methods and international Delphi consensus. Methods: We generated items using a dual-language (English and French) approach involving patients with OA from Australia, France and the United States and health care professionals (HCP) from international societies (OARSI, SFR, OMERACT). Item generation relied on semi-structured individual interviews conducted with OA patients and HCP and one focus group with patients. Content analysis allowed for identifying verbatim statements that were meaningful for patients and HCP. A Delphi consensus method was used to select the most relevant items, according to core domains set (OMERACT). A cross-cultural approach using current guidelines (1) was applied to produce Spanish (in Spain), Turkish and classical Arabic (in Morocco) versions using independent translation and expert committee to preserve its content validity. Results: From semi-structured interviews with 29 patients and 16 HCPs and one focus group with 10 patients, 180 statements in French (106) and English (77) were generated. Based on similarity or redundancy, 50 items with equivalent meaning in both languages were retained by an expert committee. After two Delphi rounds involving 50 patients and 116 HCPs from 17 countries on four continents, it was reduced to 33 items (response 0=not at all, to 10=absolutely) in five domains (pain, swelling, stiffness, consequences of symptoms and psychological aspects). This questionnaire was cross-culturally adapted into Spanish, Turkish and classical Arabic. The Spanish version uncovered one inappropriate item in the original questionnaire that was amended accordingly in all 5 languages. Conclusion: Flare is more than just an exacerbation of pain. The Flare-OA questionnaire includes all OMERACT recommended core domains. High content validity was seen in 2 original and 3 cross-culturally adapted languages. The Flare-OA should be considered as fit for purpose and evaluation of responsiveness in clinical studies in 5 languages. Disclosure of Interests: None declared
RNA:m5c/Methyltransferases Mediate Chromatin Organization and 5-Azacytidine Response/Resistance in Leukemia
Authors: Jason Cheng, Li Chen, Yuan Li, Ming Yue, Adam Cloe, Jamile M. Shammo, Richard A. Larson, Chuan He, Michelle M. Le Beau, James W. Vardiman
Journal: Blood (2017)
Reply to Borrelli <i>et al.</i>: Novel Drug Targets for Central Apneas in Heart Failure: On the Road
Authors: Jeremy E. Orr, M. Safwan Badr
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

We thank the authors for calling attention to an important recent study on examining the use of pharmacotherapy with buspirone in patients with central sleep apnea related to heart failure with reduced ejection fraction (1) in our recent statement (2).As noted, the study found important decreases in chemoreflex sensitivity to carbon dioxide without changes in sensitivity to oxygen.These findings lend support to emerging evidence that central chemoreceptors play an important role in the pathogenesis of central sleep apnea in those with heart failure and stand in contrast to the traditional view that peripheral chemoreceptors are the sole important drivers in this context (3).Although the reductions in the apnea-hypopnea index in this study were modest, this work provides a foundation for much needed novel clinical investigations in addition to clarifying relevant underlying neurobiology.
Highly Sensitive On‐Skin Temperature Sensors Based on Biocompatible Hydrogels with Thermoresponsive Transparency and Resistivity
Authors: Tae Hyun Park, Seongjin Park, Seunggun Yu, Sangun Park, Junseok Lee, Sunho Kim, Youngmee Jung, Hyunjung Yi
Journal: Advanced Healthcare Materials (2021)

Abstract The development of electrically responsive sensors that interact directly with human skin and at the same time produce a visual indication of the temperature is in great demand. Here, we report a highly sensitive electronic skin (E‐skin) sensor that measures and visualizes skin temperature simultaneously using a biocompatible hydrogel displaying thermoresponsive transparency and resistivity resulting from a temperature dependence of the strength of the hydrogen bonding between its components. This thermoresponsive hydrogel (TRH) showed a temperature dependence of not only the proton conductivity but also of its transmittance of light through a change in polymer conformation. We were able to use our TRH temperature sensor (TRH‐TS) to measure temperature in a wide range of temperatures based on a change in its intrinsic resistivity (−0.0289 °C −1 ) and to visualize the temperature due to its thermoresponsive transmittance (from 7% to 96%). The TRH‐TS exhibited high reliability upon multiple cycles of heating and cooling. The on‐skin TRH‐TS patch is also shown to successfully produce changes in its impedance and optical transparency as a result of changes in skin temperature during cardiovascular exercise. This work has shown that our biocompatible TRH‐TS is potentially suitable as wearable E‐skin for various emerging flexible healthcare monitoring applications.
Rapid suppression and sustained activation of distinct cortical regions for a delayed sensory-triggered motor response
Authors: Vahid Esmaeili, Keita Tamura, Samuel P. Muscinelli, Alireza Modirshanechi, Marta Boscaglia, Ashley B. Lee, Anastasiia Oryshchuk, Georgios Foustoukos, Yanqi Liu, Sylvain Crochet, Wulfram Gerstner, Carl C.H. Petersen
Journal: Neuron (2021)

The neuronal mechanisms generating a delayed motor response initiated by a sensory cue remain elusive. Here, we tracked the precise sequence of cortical activity in mice transforming a brief whisker stimulus into delayed licking using wide-field calcium imaging, multiregion high-density electrophysiology, and time-resolved optogenetic manipulation. Rapid activity evoked by whisker deflection acquired two prominent features for task performance: (1) an enhanced excitation of secondary whisker motor cortex, suggesting its important role connecting whisker sensory processing to lick motor planning; and (2) a transient reduction of activity in orofacial sensorimotor cortex, which contributed to suppressing premature licking. Subsequent widespread cortical activity during the delay period largely correlated with anticipatory movements, but when these were accounted for, a focal sustained activity remained in frontal cortex, which was causally essential for licking in the response period. Our results demonstrate key cortical nodes for motor plan generation and timely execution in delayed goal-directed licking.