tbuckley/cabot-search huggingface dataset:
Knee extensor muscle weakness is a risk factor for the development of knee osteoarthritis: an updated systematic review and meta-analysis including 46 819 men and women
Authors: Britt Elin Øiestad, Carsten B Juhl, Adam G Culvenor, Bjørnar Berg, Jonas Bloch Thorlund
Journal: British Journal of Sports Medicine (2021)

Objective To update a systematic review on the association between knee extensor muscle weakness and the risk of incident knee osteoarthritis in women and men. Design Systematic review and meta-analysis. Data sources Systematic searches in PubMed, EMBASE, SPORTDiscus, CINAHL, AMED and CENTRAL in May 2021. Eligible criteria for selecting studies Longitudinal studies with at least 2 years follow-up including baseline measure of knee extensor muscle strength, and follow-up measure of symptomatic or radiographic knee osteoarthritis. Studies including participants with known knee osteoarthritis at baseline were excluded. Risk of bias assessment was conducted using six criteria for study validity and bias. Grading of Recommendations Assessments, Development and Evaluation assessed overall quality of evidence. Meta-analysis estimated the OR for the association between knee extensor muscle weakness and incident knee osteoarthritis. Results We included 11 studies with 46 819 participants. Low quality evidence indicated that knee extensor muscle weakness increased the odds of symptomatic knee osteoarthritis in women (OR 1.85, 95% CI 1.29 to 2.64) and in adult men (OR 1.43, 95% CI 1.14 to 1.78), and for radiographic knee osteoarthritis in women: OR 1.43 (95% CI 1.19 to 1.71) and in men: OR 1.39 (95% CI 1.07 to 1.82). No associations were identified for knee injured populations except for radiographic osteoarthritis in men. Discussion There is low quality evidence that knee extensor muscle weakness is associated with incident symptomatic and radiographic knee osteoarthritis in women and men. Optimising knee extensor muscle strength may help to prevent knee osteoarthritis. PROSPERO registration number CRD42020214976.
Alterations in Biomarkers Related to Glycemia, Lipid Metabolism, and Inflammation up to 20 Years Before Diagnosis of Type 1 Diabetes in Adults: Findings From the AMORIS Cohort
Authors: Katharina Herzog, Tomas Andersson, Valdemar Grill, Niklas Hammar, Håkan Malmström, Mats Talbäck, Göran Walldius, Sofia Carlsson
Journal: Diabetes Care (2021)

Type 1 diabetes is described to have an acute onset, but autoantibodies can appear several years preceding diagnosis. This suggests a long preclinical phase, which may also include metabolic parameters. Here we assessed whether elevations in glycemic, lipid, and other metabolic biomarkers were associated with future type 1 diabetes risk in adults.We studied 591,239 individuals from the Swedish AMORIS cohort followed from 1985-1996 to 2012. Through linkage to national patient, diabetes, and prescription registers, we identified incident type 1 diabetes. Using Cox regression models, we estimated hazard ratios for biomarkers at baseline and incident type 1 diabetes. We additionally assessed trajectories of biomarkers during the 25 years before type 1 diabetes diagnosis in a nested case-control design.We identified 1,122 type 1 diabetes cases during follow-up (average age of patient at diagnosis: 53.3 years). The biomarkers glucose, fructosamine, triglycerides, the ratio of apolipoprotein (apo)B to apoA-I, uric acid, alkaline phosphatase, and BMI were positively associated with type 1 diabetes risk. Higher apoA-I was associated with lower type 1 diabetes incidence. Already 15 years before diagnosis, type 1 diabetes cases had higher mean glucose, fructosamine, triglycerides, and uric acid levels compared with control subjects.Alterations in biomarker levels related to glycemia, lipid metabolism, and inflammation are associated with clinically diagnosed type 1 diabetes risk, and these may be elevated many years preceding diagnosis.
Strengthening public health for a Healthy China
Authors: None The Lancet Public Health
Journal: The Lancet Public Health (2021)

China's rapid socioeconomic and demographic changes will profoundly affect the health and wellbeing of its population. Preparing the health system and public health responses to old threats and new challenges will be crucial for the country to deliver on its promises—Healthy China 2030. This issue of The Lancet Public Health is dedicated to the health of the 1·4 billion people in China, featuring the best research from China and highlighting the most pressing public health issues.
Corrigendum to: Receptivity to a Nurse-Led Symptom Management Intervention among Highly Symptomatic Patients with Cance
Journal: JNCI Journal of the National Cancer Institute (2021)

The following amendments to text within the Discussion section have been made online:"statistically significantly more willing to receive nursing phone calls, but because they were small in number compared with those with scores of 7-8, severe sleep dysfunction was not a statistically significant predictor of receptivity to receive an RN SCM phone call" should read: "statistically significantly more willing to receive nursing phone calls, unlike those with scores of 7-8, and severe sleep dysfunction was a statistically significant predictor of receptivity to receive an RN SCM phone call".
Abstract 9439: Invasive Evaluation of Left Ventricular Hemodynamics with Veno-Arterial Extracorporeal Membrane Oxygenation
Authors: Rajat Kalra, Tamas Alexy, Jason Bartos, Andrea M Elliott, Anthony Prisco, Marinos Kosmopoulos, Valmiki Maharaj, Santiago Garcia, Ganesh Raveendran, Demetris Yannopoulos
Journal: Circulation (2021)

Introduction: Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is a frequently used hemodynamic support strategy, but considerable debate exists about its hemodynamic effects. We evaluated changes in left ventricular (LV) function, volumes, and work in patients treated with VA-ECMO using invasive LV catheterization and three-dimensional echocardiographic volumes. Methods: In this case series, patients underwent evaluation due to persistent vasoplegia or poor LV function despite treatment with VA-ECMO. Hemodynamic parameters were reported as medians with interquartile ranges. Paired comparisons were done to evaluate hemodynamics at the baseline (highest) and lowest tolerated levels of VA-ECMO support. Results: Six patients aged 53.5 (41.8, 57.8) years were included. Three patients received VA-ECMO for refractory cardiogenic shock and three patients for extracorporeal cardiopulmonary resuscitation. The baseline LV ejection fraction was 22.1% (19.0%, 24.7%). The baseline and lowest VA-ECMO flows were 4.0 (4.0, 4.0) L/min and 1.0 (1.0, 1.5) L/min, respectively. Compared to the lowest flow, full VA-ECMO support reduced LV end-diastolic volume [116 (90, 153) versus 94 (58, 119) mL, p=0.03], LV end-diastolic pressure [16 (12, 24) versus 14 (9,15) mmHg, p=0.03], LV stroke work [2640 (1800, 4275) versus 1953 (759, 2179) mL*mmHg, p=0.03], and pressure-volume area [6864 (4038, 7715) versus 4575 (3142, 5888) mL*mmHg; p=0.046], respectively. The pressure-volume curves at the highest and lowest VA-ECMO flows are represented in blue and red, respectively ( Figure ). Mean arterial pressure and heart rate were similar at the lowest and highest flows (p=0.17 and p=0.60, respectively). All patients were decannulated from VA-ECMO. Four survived the index hospitalization. Conclusion: High flow VA-ECMO support significantly reduced LV end-diastolic volume, end-diastolic pressure, stroke work, and pressure-volume area compared to low flow.
Profiling of Circulating Tumor DNA for Noninvasive Disease Detection, Risk Stratification, and MRD Monitoring in Patients with CNS Lymphoma
Authors: Jurik Andreas Mutter, Stefan Alig, Eliza Maria Lauer, Mohammad Shahrokh Esfahani, Jan Mitschke, David M. Kurtz, Julia Kühn, Sabine Bleul, Mari Olsen, Chih Long Liu, Michael C. Jin, Charles Macaulay, Nicolas Noel Neidert, Timo Volk, Sebastian Rauer, Dieter Henrik Heiland, Jürgen Finke, Justus Duyster, Julius Wehrle, Marco Prinz, Gerald Illerhaus, Peter C. Reinacher, Elisabeth Schorb, Maximilian Diehn, Ash A. Alizadeh, Florian Scherer
Journal: Blood (2021)
Abstract 13412: Gender Based Differences in Duration of Cardiopulmonary Resuscitation in the Inpatient Setting
Authors: Anna Baillie, Rebecca Sell, Victoria Speck, Gabriel Wardi
Journal: Circulation (2021)

Introduction: The decision to terminate cardiopulmonary resuscitation (CPR) prior to return of spontaneous circulation (ROSC) may be impacted by resuscitation parameters or by patient demographics. Studies show that longer resuscitation efforts have a higher likelihood of ROSC and survival to discharge. It is unclear if gender of the code leader and the patient may be associated with duration of unsuccessful CPR attempt. Methods: Retrospective chart review of inpatient CA that occurred at the UC San Diego Health System between 2011-2019. All adult inpatients with an index cardiac arrest who expired within three days of admission were included. Exclusion criteria included patients who achieved ROSC, CA that occurred outside of the wards or ICU, those with active pre-arrest DNR status, and patients with CA &gt; 3 days after admission (done to minimize provider bias based on prior knowledge of the patient). Data were identified from an internal cardiac arrest quality improvement database. Patient gender was self-reported and code leader gender was identified. Primary outcome was duration of resuscitation efforts. To determine differences in duration of CPR between code leader and patient gender a one-sided ANOVA test was used. A p value &lt; 0.05 was considered statistically significant. Results: We identified 91 patients between 2011 and 2019 that met inclusion criteria. Thirty-eight patients (41.8%) identified as female, fifty-three identified as male (58.2%), the average age was 62.7 years old, and seventeen (18.7%) had initial shockable rhythm. Thirty (33%) of the code leaders identified as female and sixty-one (67%) identified as male. Average duration of CPR was 31.6 minutes (2 - 135 minutes) for male patients with male code leader, 32.2 minutes (9 - 71 minutes) for male patients with female code leader, 27.0 minutes (7 - 60 minutes) for female patients with female code leader, and 33.7 minutes (10 - 73 minutes) for female patients with male code leader. No significant difference in duration of unsuccessful CPR attempt associated with gender of code leader and gender of patient in ANOVA analysis was found (p = 0.512). Conclusions: We did not identify a significant association between code leader and patient gender on duration of CPR in the inpatient setting.
People critically ill with COVID-19 exhibit peripheral immune profiles predictive of mortality and reflective of SARS-CoV-2 lung viral burden
Authors: Anthony R. Cillo, Ashwin Somasundaram, Feng Shan, Carly Cardello, Creg J. Workman, Georgios D. Kitsios, Ayana T. Ruffin, Sheryl Kunning, Caleb Lampenfeld, Sayali Onkar, Stephanie Grebinoski, Gaurav Deshmukh, Barbara Methe, Chang Liu, Sham Nambulli, Lawrence P. Andrews, W. Paul Duprex, Alok V. Joglekar, Panayiotis V. Benos, Prabir Ray, Anuradha Ray, Bryan J. McVerry, Yingze Zhang, Janet S. Lee, Jishnu Das, Harinder Singh, Alison Morris, Tullia C. Bruno, Dario A.A. Vignali
Journal: Cell Reports Medicine (2021)

Despite extensive analyses, there remains an urgent need to delineate immune cell states that contribute to mortality in people critically ill with COVID-19. Here, we present high-dimensional profiling of blood and respiratory samples from people with severe COVID-19 to examine the association between cell-linked molecular features and mortality outcomes. Peripheral transcriptional profiles by single-cell RNA sequencing (RNA-seq)-based deconvolution of immune states are associated with COVID-19 mortality. Further, persistently high levels of an interferon signaling module in monocytes over time lead to subsequent concerted upregulation of inflammatory cytokines. SARS-CoV-2-infected myeloid cells in the lower respiratory tract upregulate
Cevostamab Monotherapy Continues to Show Clinically Meaningful Activity and Manageable Safety in Patients with Heavily Pre-Treated Relapsed/Refractory Multiple Myeloma (RRMM): Updated Results from an Ongoing Phase I Study
Authors: Suzanne Trudel, Adam D Cohen, Amrita Y. Krishnan, Rafael Fonseca, Andrew Spencer, Jesús G. Berdeja, Alexander Lesokhin, Peter A Forsberg, Jacob P. Laubach, Luciano J. Costa, Paula Rodriguez-Otero, Rayan Kaedbey, Joshua Richter, Maria-Victoria Mateos, Sheeba K Thomas, Chihunt Wong, Mengsong Li, Voleak Choeurng, Anjali Vaze, Divya Samineni, Teiko Sumiyoshi, James Cooper, Simon J Harrison
Journal: Blood (2021)
Effects of County-Level Opioid Dispensing Rates on Individual-Level Patterns of Prescription Opioid and Heroin Consumption: Evidence From National U.S. Data
Authors: Mike Vuolo, Brian C. Kelly
Journal: American Journal of Psychiatry (2021)

The authors examined directly whether county-level changes in opioid dispensing rates affect individual-level prescription opioid misuse, frequency of use, and dependence, as well as the same outcomes for heroin.Using data from the restricted-access National Survey on Drug Use and Health, the Centers for Disease Control and Prevention's retail opioid prescription database, the Prescription Drug Abuse Policy System, and the U.S. Census, the authors applied fixed-effects models to determine whether county-level dispensing rates affected prescription opioid outcomes as intended and whether changes in rates adversely affected heroin use outcomes. Bayes factors were used to confirm evidence for null findings.The sample included 748,800 respondents age 12 and older from 2006 to 2016. The odds of prescription opioid misuse, increased frequency of misuse, and dependence were 7.2%, 3.5%, and 10.4% higher, respectively, per standard deviation increase in the county-level opioid dispensing rate per 100 persons. There was no evidence for any association between opioid dispensing rates and the three heroin outcomes. The odds ratio was nonsignificant according to frequentist techniques in fixed-effects models, and Bayesian techniques confirmed very strong support for the null hypothesis.County-level opioid dispensing rates are directly associated with individual-level prescription opioid misuse, frequency of misuse, and dependence. Changes in dispensing were not associated with population shifts in heroin use. Reductions in opioid dispensing rates have contributed to stemming prior increases in prescription opioid misuse while not adversely affecting heroin use. Physicians and other health care providers can take action to minimize opioid dispensing for tangible benefits regarding prescription opioid misuse without adverse effects on heroin use.
Selected Articles from This Issue
Journal: Clinical Cancer Research (2021)

Carboplatin is commonly used for treating many solid cancers, but many patients develop resistance, necessitating combination treatment. Preclinical studies have shown that the combination of ceralasertib, an ATR inhibitor, and carboplatin may hold clinical promise. Here, Yap and colleagues report the results of a multicenter phase I study of ceralasertib plus carboplatin in patients with advanced solid cancers. This combination was well tolerated and showed potential clinical activity, with 18 of 34 patients showing stable disease. Two patients with absent or low ATM or SLFN11 protein expression achieved confirmed partial responses. Further clinical study is necessary to validate the clinical utility of this combination.The randomized phase III coBRIM study (NCT01689519) demonstrated that the addition of cobimetinib to vemurafenib improved progression-free survival (PFS) and overall survival (OS) in patients with previously untreated BRAFV600-positive advanced melanoma. Ascierto and colleagues report long-term follow-up of this study. Over at least 5 years of follow-up. results of PFS and OS benefits remain for cobimetinib plus vemurafenib compared with vemurafenib monotherapy. Normal baseline lactate dehydrogenase levels, low tumor burden, and a complete response were associated with extended OS and PFS. These results confirm the clinical utility of this combination.The combined targeting of PD-1 and CTLA-4 has provided benefit to patients with advanced melanoma, but toxicity has been a challenge, primarily due to ipilimumab. To further tailor dosing of ipilimumab, Long and colleagues conducted a clinical trial assessing standard-dose pembrolizumab plus alternative ipilimumab dosing regimens in patients with advanced melanoma. All patients received pembrolizumab at 200 mg every 3 weeks plus ipilimumab at either 50 mg (PEM200+IPI50) every 6 weeks or 100 mg (PEM200+IPI100) every 12 weeks. The PEM200+IPI50 regimen reduced both treatment-related adverse events and immune-mediated adverse events compared to PEM200+IPI100. The ORR was 55% in PEM200+IPI50 and 61% in PEM200+IPI100. Based on these data, further clinical trials of PD-1 inhibitors with alternative ipilimumab dosing are warranted.Adoptive cell transfer of tumor-infiltrating lymphocytes (ACT-TIL) can mediate durable complete responses in patients with metastatic melanoma after a single treatment. To evaluate ACT-TIL in the era of checkpoint inhibition and targeted molecular therapy, Seitter and colleagues analyzed a cohort of 226 patients treated as part of ACT-TIL clinical trials. Patients who had received PD-1 blockade or MAPK inhibitors prior to ACT-TIL demonstrated a lower objective response rate and shorter melanoma-specific survival after ACT-TIL than patients who were naïve to those treatments. These data suggest a potential role for ACT-TIL as a front-line therapy for eligible patients.
CSIG-20. CANNABIDIOL CONVERTS NFKB INTO A TUMOR SUPPRESSOR IN GLIOBLASTOMA WITH DEFINED ANTIOXIDATIVE PROPERTIES
Authors: Marie Volmar, Grace Cheng, Joel Schick, Roland Kälin, Rainer Glass
Journal: Neuro-Oncology (2021)

Abstract The transcription factor NFKB drives neoplastic progression of many cancers including primary brain tumors (glioblastoma; GBM). Precise therapeutic modulation of NFKB activity can suppress central oncogenic signalling pathways in GBM, but clinically applicable compounds to achieve this goal have remained elusive. In a pharmacogenomics study with a panel of transgenic glioma cells we observed that NFKB can be converted into a tumor suppressor by the non-psychotropic cannabinoid Cannabidiol (CBD). Subsequently, we investigated the anti-tumor effects of CBD, which is used as an anticonvulsive drug (Epidiolex) in pediatric neurology, in a larger set of human primary GBM stem-like cells (hGSC). For this study we performed pharmacological assays, gene expression profiling, biochemical and cell-biological experiments. We validated our findings using orthotopic in vivo models and bioinformatics analysis of human GBM-datasets. We found that CBD promotes DNA binding of the NFKB subunit RELA and simultaneously prevents RELA-phosphorylation on serine-311, a key residue which permits genetic transactivation. Strikingly, sustained DNA binding by RELA lacking phospho-serine 311 was fully sufficient to mediate hGSC cytotoxicity. Widespread sensitivity to CBD was observed in a cohort of hGSC defined by low levels of reactive oxygen-species (ROS), while high ROS-content in other tumors blocked CBD induced hGSC death. Consequently, ROS levels served as predictive biomarker for CBD-sensitive tumors. This evidence demonstrates how a clinically approved drug can convert NFKB into a tumor suppressor and suggests a promising repurposing option for GBM-therapy
Insulin signalling in tanycytes gates hypothalamic insulin uptake and regulation of AgRP neuron activity
Authors: Marta Porniece Kumar, Anna Lena Cremer, Paul Klemm, Lukas Steuernagel, Sivaraj Sundaram, Alexander Jais, A. Christine Hausen, Jenkang Tao, Anna Secher, Thomas Åskov Pedersen, Markus Schwaninger, F. Thomas Wunderlich, Bradford B. Lowell, Heiko Backes, Jens C. Brüning
Journal: Nature Metabolism (2021)

Abstract Insulin acts on neurons and glial cells to regulate systemic glucose metabolism and feeding. However, the mechanisms of insulin access in discrete brain regions are incompletely defined. Here we show that insulin receptors in tanycytes, but not in brain endothelial cells, are required to regulate insulin access to the hypothalamic arcuate nucleus. Mice lacking insulin receptors in tanycytes (IR ∆Tan mice) exhibit systemic insulin resistance, while displaying normal food intake and energy expenditure. Tanycytic insulin receptors are also necessary for the orexigenic effects of ghrelin, but not for the anorexic effects of leptin. IR ∆Tan mice exhibit increased agouti-related peptide (AgRP) neuronal activity, while displaying blunted AgRP neuronal adaptations to feeding-related stimuli. Lastly, a highly palatable food decreases tanycytic and arcuate nucleus insulin signalling to levels comparable to those seen in IR ∆Tan mice. These changes are rooted in modifications of cellular stress responses and of mitochondrial protein quality control in tanycytes. Conclusively, we reveal a critical role of tanycyte insulin receptors in gating feeding-state-dependent regulation of AgRP neurons and systemic insulin sensitivity, and show that insulin resistance in tanycytes contributes to the pleiotropic manifestations of obesity-associated insulin resistance.
Twelve lateral flow immunoassays (LFAs) to detect SARS-CoV-2 antibodies
Authors: Sophie I. Owen, Christopher T. Williams, Gala Garrod, Alice J. Fraser, Stefanie Menzies, Lisa Baldwin, Lottie Brown, Rachel L. Byrne, Andrea M. Collins, Ana I. Cubas-Atienzar, Margaretha de Vos, Thomas Edwards, Camille Escadafal, Daniela M. Ferreira, Tom Fletcher, Angela Hyder-Wright, Grant A. Kay, Konstantina Kontogianni, Jenifer Mason, Elena Mitsi, Tim Planche, Jilian A. Sacks, Joseph Taylor, Stacy Todd, Caroline Tully, Luis E. Cuevas, Emily R. Adams
Journal: Journal of Infection (2021)

There are an abundance of commercially available lateral flow assays (LFAs) that detect antibodies to SARS-CoV-2. Whilst these are usually evaluated by the manufacturer, externally performed diagnostic accuracy studies to assess performance are essential. Herein we present an evaluation of 12 LFAs.
To PEGylate or not to PEGylate: Immunological properties of nanomedicine’s most popular component, polyethylene glycol and its alternatives
Authors: Da Shi, Damian Beasock, Adam Fessler, Janos Szebeni, Julia Y. Ljubimova, Kirill A. Afonin, Marina A. Dobrovolskaia
Journal: Advanced Drug Delivery Reviews (2021)
Response to ‘The role of curettage as an intervention for basal cell carcinoma’. Re. ‘Interventions for basal cell carcinoma: abridged Cochrane systematic review and <scp>GRADE</scp> assessments’: reply from the authors
Authors: J. Thomson, S. Hogan, J. Leonardi‐Bee, H.C. Williams, F.J. Bath‐Hextall
Journal: British Journal of Dermatology (2021)

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