tbuckley/cabot-search huggingface dataset:
Proinflammatory Cytokines, Insulin Resistance, and Insulin Secretion in Chronic Hepatitis C patients
Authors: Albert Lecube, Cristina Hernández, Joan Genescà, Rafael Simó
Journal: Diabetes Care (2006)

OBJECTIVE—The purpose of this study was to explore the initial pathogenic mechanisms of diabetes associated with hepatitis C virus (HCV) infection. RESEARCH DESIGN AND METHODS—Insulin resistance, proinflammatory cytokines, and β-cell function were evaluated in a case-control study. A total of 28 consecutive nondiabetic patients with chronic hepatitis C were included in the study (anti-HCV+). Fourteen patients with chronic hepatitis other than HCV infection served as the control group (anti-HCV−). Both groups were closely matched by the main clinical variables associated with insulin resistance and the degree of liver fibrosis. In addition, there were no differences between groups regarding hepatic insulin extraction measured by calculating the ratio between C-peptide and insulin. Serum levels of proinflammatory cytokines (tumor necrosis factor [TNF]-α, soluble TNF receptor [sTNFR] 1, soluble TNFR2, and interleukin-6) were measured by enzyme-linked immunosorbent assay. Insulin resistance (homeostasis model assessment [HOMA] of insulin resistance [HOMA-IR]) and insulin secretion at baseline (HOMA-β) and after various stimulus (oral glucose tolerance test, standard food intake, and intravenous glucagon) were determined by previously validated mathematic indexes. RESULTS—HOMA-IR was higher in anti-HCV+ than in anti-HCV− patients (4.35 ± 2.27 vs. 2.58 ± 1.74; P = 0.01). All the proinflammatory cytokines analyzed were significantly higher in anti-HCV+ patients than in anti-HCV− patients. In addition, sTNFR1 and sTNFR2 were directly correlated to HOMA-IR. HOMA-β as well as insulin and C-peptide responses after the intravenous glucagon test were significantly higher in anti-HCV+ patients than in anti-HC− patients. CONCLUSIONS—Insulin resistance mediated by proinflammatory cytokines, but not a deficit in insulin secretion, could be the primary pathogenic mechanism involved in the development of diabetes associated with HCV infection.
John Borthwick Macdonald
Authors: Elspeth Macdonald
Journal: BMJ (2021)

Having secured a scholarship, John Borthwick Macdonald went up to Cambridge to read natural sciences, then medicine. He had a student placement at the Medical Research Council Laboratories in the Gambia. John used his vacation time to travel widely; this included helping with voter registration in Georgia, USA. He published his first article on medical ethics in the Lancet as an undergraduate and his last in his retirement. John trained in respiratory medicine in London and Cardiff, where he met his future wife, Elspeth, also a doctor. He then went to Nottingham before taking up a consultant post in Kilmarnock in 1979, the same year he was awarded his MD on the origin of treatment failure in tuberculosis. …
Impact of SarsCov2 pandemic on vascular liver diseases
Authors: A. Baiges, E. C. Reyes, C. Amicone, T. Luis, A. Puente, E. Llop, E. Alvarado, F. Rocha, L. Orts, O. Ros, P. Vizcarra, M. J. Serrano, M. A. Falga, M. Magaz, P. Olivas, F. B. Sanchez, V. Perez, F. Turon, P. Audrey, O. Goria, R. Pe, V. Hernandez-Gea, A. Plessier, J. C. G. Pagan, J. I. Fortea
Journal: Journal of Hepatology (2021)
Author Correction: Genomic evidence consistent with antagonistic pleiotropy may help explain the evolutionary maintenance of same-sex sexual behaviour in humans
Authors: Brendan P. Zietsch, Morgan J. Sidari, Abdel Abdellaoui, Robert Maier, Niklas Långström, Shengru Guo, Gary W. Beecham, Eden R. Martin, Alan R. Sanders, Karin J. H. Verweij
Journal: Nature Human Behaviour (2021)
Mapping Mechanical Properties of the Tumor Microenvironment by Laser Speckle Rheological Microscopy
Authors: Zeinab Hajjarian, Elena F. Brachtel, Diane M. Tshikudi, Seemantini K. Nadkarni
Journal: Cancer Research (2021)

Abstract Altered mechanical properties of the tumor matrix have emerged as both the cause and consequence of breast carcinogenesis. Increased tumor stiffness has traditionally provided a viable metric to screen for malignancies via palpation or imaging. Previous studies have demonstrated that the microscale mechanical properties of the cell substrate influence tumor proliferation and invasive migration in vitro. Nevertheless, the association of the mechanical microenvironment with clinical hallmarks of aggressiveness in human breast tumors, including histopathological subtype, grade, receptor expression status, and lymph node involvement is poorly understood. This is largely due to the lack of tools for mapping tumor viscoelastic properties in clinical specimens with high spatial resolution over a large field of view (FoV). Here we introduce laser Speckle rHEologicAl micRoscopy (SHEAR) that for the first time enables mapping the magnitude viscoelastic or shear modulus, |G*(x,y,ω)|, over a range of frequencies (ω = 1–250 rad/second) in excised tumors within minutes with a spatial resolution of approximately 50 μm, over multiple cm2 FoV. Application of SHEAR in a cohort of 251 breast cancer specimens from 148 patients demonstrated that |G*(x,y,ω)| (ω = 2π rad/second) closely corresponds with histological features of the tumor, and that the spatial gradient of the shear modulus, |∇|G*(x,y,ω)||, is elevated at the tumor invasive front. Multivariate analyses established that the metrics, (|G* |) and (|∇|G* ||), measured by SHEAR are associated with prognosis. These findings implicate the viscoelastic properties of the tumor microenvironment in breast cancer prognosis and likely pave the path for identifying new modifiable targets for treatment. Significance: Laser speckle rheological microscopy establishes the links between microscale heterogeneities of viscoelasticity and histopathological subtype, tumor grade, receptor expression, as well as lymph node status in breast carcinoma.
Lack of Transparency and Potential Bias in Artificial Intelligence Data Sets and Algorithms
Authors: Roxana Daneshjou, Mary P. Smith, Mary D. Sun, Veronica Rotemberg, James Zou
Journal: JAMA Dermatology (2021)

<h3>Importance</h3> Clinical artificial intelligence (AI) algorithms have the potential to improve clinical care, but fair, generalizable algorithms depend on the clinical data on which they are trained and tested. <h3>Objective</h3> To assess whether data sets used for training diagnostic AI algorithms addressing skin disease are adequately described and to identify potential sources of bias in these data sets. <h3>Data Sources</h3> In this scoping review, PubMed was used to search for peer-reviewed research articles published between January 1, 2015, and November 1, 2020, with the following paired search terms:<i>deep learning</i>and<i>dermatology</i>,<i>artificial intelligence</i>and<i>dermatology</i>,<i>deep learning</i>and<i>dermatologist</i>, and<i>artificial intelligence</i>and<i>dermatologist</i>. <h3>Study Selection</h3> Studies that developed or tested an existing deep learning algorithm for triage, diagnosis, or monitoring using clinical or dermoscopic images of skin disease were selected, and the articles were independently reviewed by 2 investigators to verify that they met selection criteria. <h3>Consensus Process</h3> Data set audit criteria were determined by consensus of all authors after reviewing existing literature to highlight data set transparency and sources of bias. <h3>Results</h3> A total of 70 unique studies were included. Among these studies, 1 065 291 images were used to develop or test AI algorithms, of which only 257 372 (24.2%) were publicly available. Only 14 studies (20.0%) included descriptions of patient ethnicity or race in at least 1 data set used. Only 7 studies (10.0%) included any information about skin tone in at least 1 data set used. Thirty-six of the 56 studies developing new AI algorithms for cutaneous malignant neoplasms (64.3%) met the gold standard criteria for disease labeling. Public data sets were cited more often than private data sets, suggesting that public data sets contribute more to new development and benchmarks. <h3>Conclusions and Relevance</h3> This scoping review identified 3 issues in data sets that are used to develop and test clinical AI algorithms for skin disease that should be addressed before clinical translation: (1) sparsity of data set characterization and lack of transparency, (2) nonstandard and unverified disease labels, and (3) inability to fully assess patient diversity used for algorithm development and testing.
Optimal Thyroid Hormone Replacement
Authors: Jacqueline Jonklaas
Journal: Endocrine Reviews (2021)

Abstract Hypothyroidism is a common endocrinopathy, and levothyroxine is frequently prescribed. Despite the basic tenets of initiating and adjusting levothyroxine being agreed on, there are many nuances and complexities to consistently maintaining euthyroidism. Understanding the impact of patient weight and residual thyroid function on initial levothyroxine dosage and consideration of age, comorbidities, thyrotropin goal, life stage, and quality of life as levothyroxine is adjusted can be challenging and continually evolving. Because levothyroxine is a lifelong medication, it is important to avoid risks from periods of overtreatment or undertreatment. For the subset of patients not restored to baseline health with levothyroxine, causes arising from all aspects of the patient’s life (coexistent medical conditions, stressors, lifestyle, psychosocial factors) should be broadly considered. If such factors do not appear to be contributing, and biochemical euthyroidism has been successfully maintained, there may be benefit to a trial of combination therapy with levothyroxine and liothyronine. This is not supported by the majority of randomized clinical trials, but may be supported by other studies providing lower-quality evidence and by animal studies. Given this discrepancy, it is important that any trial of combination therapy be continued only as long as a patient benefit is being enjoyed. Monitoring for adverse effects, particularly in older or frail individuals, is necessary and combination therapy should not be used during pregnancy. A sustained-release liothyronine preparation has completed phase 1 testing and may soon be available for better designed and powered studies assessing whether combination therapy provides superior therapy for hypothyroidism.
Clonal hematopoiesis in sickle cell disease
Authors: Thomas Pincez, Simon S. K. Lee, Yann Ilboudo, Michael Preuss, Anne-Laure Pham Hung d’Alexandry d’Orengiani, Pablo Bartolucci, Frédéric Galactéros, Philippe Joly, Daniel E. Bauer, Ruth J. F. Loos, R. Coleman Lindsley, Guillaume Lettre
Journal: Blood (2021)
Revealing novel, latent subsets of patients with morphoea through principal component analysis
Authors: L.F. Abbas, A.K. Joseph, S. Prasad, J.L. Zhu, K.S. Fitch, R. Haley, K.S. Torok, H.T. Jacobe
Journal: British Journal of Dermatology (2021)

The clinical features and patient impact of morphea, an inflammatory disorder of the skin and soft tissue, remain poorly characterized. While numerous clinical classification schemes are in use, there is little work systematically examining latent clinical and quality of life features within these clinical subtypes. In an effort to address this gap, prior work from our group revealed that the Padua Criteria performed best in grouping patients into consistent subtypes, however we did not perform in depth analysis of subsets that may exist within these subtypes.
Short Sleep Duration Among Infants, Children, and Adolescents Aged 4 Months–17 Years — United States, 2016–2018
Authors: Anne G. Wheaton, Angelika H. Claussen
Journal: MMWR Morbidity and Mortality Weekly Report (2021)

Infants, children, and adolescents who do not get sufficient sleep are at increased risk for injuries, obesity, type 2 diabetes, poor mental health, attention and behavior problems, and poor cognitive development (1).The American Academy of Sleep Medicine (AASM) provides age-specific sleep duration recommendations to promote optimal health (1).CDC analyzed data from the 2016-2018 National Survey of Children's Health (NSCH) to assess the prevalence of short sleep duration among persons in the United States aged 4 months-17 years.Overall, on the basis of parent report, 34.9% of persons aged 4 months-17 years slept less than recommended for their age.The prevalence of short sleep duration was higher in southeastern states and among racial and ethnic minority groups, persons with low socioeconomic status, and those with special health care needs.The prevalence of short sleep duration ranged from 31.2% among adolescents aged 13-17 years to 40.3% among infants aged 4-11 months.Persons aged 4 months-17 years with a regular bedtime were more likely to get enough sleep.Public health practitioners, educators, and clinicians might advise parents on the importance of meeting recommended sleep duration and implementing a consistent bedtime for healthy development.NSCH is a population-based, nationally representative online and paper survey of parents or primary caregivers (parents) of noninstitutionalized U.S. persons aged ≤17 years.The survey is conducted by the U.S. Census Bureau under the direction of the Health Resources and Services Administration's Maternal and Child Health Bureau.*NSCH asks parents about the physical and emotional health of one person aged ≤17 years selected at random from the household, as well as * https://mchb.hrsa.gov/
Variable implementation of optimal therapeutic strategies in metastatic colorectal cancer: Reviewing rates of liver resection and triplet chemotherapy across Australian hospitals as potential quality indicators.
Authors: Catherine Dunn, Lucy Gately, Jeanne Tie, Louise M. Nott, Belinda Lee, Shehara Ramyalini Mendis, Jeremy David Shapiro, Vanessa Wong, Matthew E. Burge, Rachel Wong, Suzanne Kosmider, Margaret Lee, Ross Jennens, Peter Gibbs
Journal: Journal of Clinical Oncology (2021)

248 Background: Quality indicators (QI) are essential to monitor the efficacy of cancer care and to guide quality improvement, however many are derived from ‘expert consensus’ and are not validated against outcomes. Moreover, the majority of oncological QI are defined in the surgical setting, with only a paucity of QI for the treatment of metastatic disease. We aimed to define and validate novel QI for metastatic colorectal cancer (mCRC) based on therapeutic approaches associated with a proven survival benefit. Methods: Data was analysed from TRACC, a multisite Australian registry collecting prospective demographic, tumour, treatment and outcome data for mCRC. We identified all patients diagnosed across 11 hospitals and explored variation by site with regards to patient and tumour characteristics, first-line chemotherapy administration and resection of oligometastatic disease. Log-rank testing and Kaplan-Meier curves compare overall survival (OS) between sites, and Pearson correlation was used to assess associations with each QI. Results: We examined data from 3132 patients diagnosed with mCRC between July 2009 – April 2021. Median age was 66 years (range 62 – 71 years by site), ECOG 0-1 81% (range 69 – 96% by site), and Charlson Comorbidity Index ≤2 43% (33 – 59% by site). Multivariate analysis confirmed association of known adverse prognostic factors with inferior OS (poor ECOG, right sided primary, KRAS or BRAF mutation, all p &lt;0.05). Median OS for entire cohort was 26.2 months (95%CI 24.9 – 27.3 months), and varied by hospital site from 20.1 – 36.1 months (p&lt;0.001). Of the QI evaluated, rate of triplet chemotherapy (FOLFOXIRI) administration (2.8 – 13.2% by site) was very strongly correlated with OS (R 2 = 0.851), rate of liver resection (9.8 – 23.2% by site) was moderately correlated (R 2 = 0.523), and rates of active treatment with first-line chemotherapy (63 - 90% by site) were weakly correlated (R 2 = 0.209). Other proposed QI such as rates of lung metastases resection or chemotherapy administration in the elderly showed significant variation by site, but did not correlate with survival. Conclusions: There is significant variation in OS for patients with mCRC in these Australian hospitals, with major differences in treatment approaches. Treatment strategies known to improve survival outcomes, such as triplet FOLFOXIRI chemotherapy and resection of liver metastases, may be potential QI to benchmark and track quality improvement over time. Further analysis will determine the impact of baseline patient populations between sites, and to correlate these QI with other quality measures.
In vivo somatic cell base editing and prime editing
Authors: Gregory A. Newby, David R. Liu
Journal: Molecular Therapy (2021)

Recent advances in genome editing technologies have magnified the prospect of single-dose cures for many genetic diseases. For most genetic disorders, precise DNA correction is anticipated to best treat patients. To install desired DNA changes with high precision, our laboratory developed base editors (BEs), which can correct the four most common single-base substitutions, and prime editors, which can install any substitution, insertion, and/or deletion over a stretch of dozens of base pairs. Compared to nuclease-dependent editing approaches that involve double-strand DNA breaks (DSBs) and often result in a large percentage of uncontrolled editing outcomes, such as mixtures of insertions and deletions (indels), larger deletions, and chromosomal rearrangements, base editors and prime editors often offer greater efficiency with fewer byproducts in slowly dividing or non-dividing cells, such as those that make up most of the cells in adult animals. Both viral and non-viral in vivo delivery methods have now been used to deliver base editors and prime editors in animal models, establishing that base editors and prime editors can serve as effective agents for in vivo therapeutic genome editing in animals. This review summarizes examples of in vivo somatic cell (post-natal) base editing and prime editing and prospects for future development. Recent advances in genome editing technologies have magnified the prospect of single-dose cures for many genetic diseases. For most genetic disorders, precise DNA correction is anticipated to best treat patients. To install desired DNA changes with high precision, our laboratory developed base editors (BEs), which can correct the four most common single-base substitutions, and prime editors, which can install any substitution, insertion, and/or deletion over a stretch of dozens of base pairs. Compared to nuclease-dependent editing approaches that involve double-strand DNA breaks (DSBs) and often result in a large percentage of uncontrolled editing outcomes, such as mixtures of insertions and deletions (indels), larger deletions, and chromosomal rearrangements, base editors and prime editors often offer greater efficiency with fewer byproducts in slowly dividing or non-dividing cells, such as those that make up most of the cells in adult animals. Both viral and non-viral in vivo delivery methods have now been used to deliver base editors and prime editors in animal models, establishing that base editors and prime editors can serve as effective agents for in vivo therapeutic genome editing in animals. This review summarizes examples of in vivo somatic cell (post-natal) base editing and prime editing and prospects for future development.
Recovery of a quality improvement project during the COVID pandemic.
Authors: Melanie Lynn Powis, Alyssa Macedo, Monika K. Krzyzanowska, Vishal Kukreti, Lucy Xiaolu Ma, Saidah Hack, Celina Dara
Journal: Journal of Clinical Oncology (2021)

246 Background: Prior to COVID we undertook a QI project with the aim improving the documentation of a best possible medication history (BPMH) or medication reconciliation (MedRec) for patients initiating systemic therapy (ST) in ambulatory oncology, where care spans multiple providers and patients may be at increased risk of adverse drug events. While initial improvements were realized (16.7% and 3.9% increases for BPMH and MedRec, respectively), completion rates returned to baseline following the start of the COVID pandemic. Methods: Guided by the four-phase Quality Implementation Framework we sought to recover implementation of MedRec. We initially undertook a purposeful re-examination of the MedRec process (Phase 1) to identify barriers to conducting MedRec during COVID. This guided the tailored selection of Expert Recommendations for Implementing Change (ERIC) implementation strategies utilized during the successive phase of the project. During each phase the proportion of patients with documented BPMH or MedRec within 30 days of initiating ST out of those eligible was calculated. Results: Major barriers to conducting MedRec during COVID included reduced resources (time, human resources and physical resources), loss of dedicated staff, and change in workflow/ clinical models brought on by the introduction of virtual care. This informed our strategy to improve capacity to conduct MedRec (Phase 2) through the development and distribution of educational materials, revisions of professional roles, and creation of a new dedicated clinical team consisting of existing modified duty nurses to conduct MedRec. To support ongoing implementation (Phase 3), additional implementation strategies included the staged implementation scale-up, conduct of educational meetings/ outreach visits, facilitation, and provision of clinical supervision. The impact of each phase of implementation on BPMH and MedRec completion rates is summarized in Table. Conclusions: Recovery of a quality improvement intervention during COVID was realized through the utilization of a structured, implementation process model approach to identify and address barriers to implementation. Future work will focus on improvement of MedRec completion rates by clinicians, and on embedding processes into practice (Phase 4) to support sustainability of the intervention.[Table: see text]
A Review of the Diagnosis and Management of Headache—Reply
Authors: Matthew S. Robbins
Journal: JAMA (2021)

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