tbuckley/cabot-search huggingface dataset:
FRI0004 Vitamin d3 analogue – alphacalcidiol decreases il1, tnf and antioxydant enzymes activity in ra and jra patients
Authors: J Vojinovic, N Pejnovic, A Stankovic, M Cosic
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In recent years immunomodulatory action of vitamin D3 was clearly confirmed, when its used in high doses. 1-alpha (OH) vitamin D3 (alphacalcidiol) analogue was shown to induce less hypercalcemic side effects. <h3>Objectives</h3> We organised open-label therapeutical trial in 20 RA and 15 JRA patients who have had three months active disease on basic therapy. Therapy regime remained unchanged but alphacalcidiol in high oral dose was added during next three months (2μgr/day in RA or 0,05μgr/kg/day in JRA pts.). <h3>Methods</h3> Spontaneous and PMA stimulated IL1 and TNF production was measured in all patients before and after the trial by ELISA method in PB mononuclear cells after 24 h cultures. GSH-Px (glutation-peroxidase) and SOD (superoxide-dismutase) activity was measured by RANDOX kits. <h3>Results</h3> Three months high oral dose therapy significantly improved clinical signs of disease activity in correlation with parameters we evaluated. Increased IL1 and TNF production was significantly lowered after the trial and riched values in healthy controls. GSH-Px and SOD activity were lowered in all patients before entering into the stady. Alphacalcidiol therapy induced significant increase of GSH-Px and, on contrary, decrease of SOD activity. Positive correlation trends among this enzymes during disease activity were turned into negative according to disease improvement after the trial finished. <h3>Conclusion</h3> High dose alphacalcidiol is powerful immunomodulatory agent as it is shown for other vitamin D3 analogues. Its main function seem to be stabilisation of impared immunoregulation in RA and JRA which could be of benefit as possible therapeutic agent.
Too little, too late: social media companies’ failure to tackle vaccine misinformation poses a real threat
Authors: Claire Wardle, Eric Singerman
Journal: BMJ (2021)

As the world looks to the new covid-19 vaccines with hope, there are major worries about how social media will affect uptake. <b>Claire Wardle</b> and <b>Eric Singerman</b> ask what the companies in charge should be doing to stem the misinformation tide
Impact of COVID-19 in patients awaiting liver transplantation
Authors: I. Kounis, T. Breard, L. Duhaut, E. De Martin, R. Sobesky, C. Feray, O. Ciacio, A. M. Roque-Afonso, D. Samuel, P. Ichai, A. Coilly
Journal: Hepatology (2020)

Background: During the SARS-CoV2 pandemic, health authorities employed multiple interventions to prevent the spread of the disease Despite these measures, liver transplantation (LT) has never been suspended during this period However, care for patients awaiting LT had to be sometimes delayed The objective of this study was to assess the impact of COVID-19 in patients awaiting LT, the number of patients infected, the risk factors for infection, and the patients' experience during the crisis Methods: This is a mono-center French study, based on anonymous questionnaire completed by patients active on waiting list (WL) of the Paul Brousse hospital on April 2020 Patients were divided into two groups: non-suspect for COVID-19, and suspect or confirmed  Suspect patients were defined: presence of at least one of the following clinical manifestations: fever, chills, aches, dyspnea, anosmia, agueusia, diarrhea, cough  Confirmed COVID-19 patients were defined as SARS-CoV-2 positive PCR or typical COVID-19 images on the chest CT scan Results: Ninety patients were included in the study Indication of LT was cirrhosis for 45 (49%) patients and hepatocellular carcinoma (HCC) for 32 (35%) patients Thirty-one (34%) patients had signs of decompensated cirrhosis Fourteen (15%) patients were suspected for COVID-19 The PCR test was performed in 17 (19%) patients and was positive for 2 (12%) patients A chest CT scan was performed in 29 (32%) patients and was positive for 1 (3 6%) patient  The 3 confirmed patients (3 3%) were hospitalized in a conventional unit, while 2 patients were transferred on ICU In multivariate analysis, the independent factors associated with a suspected or confirmed COVID-19 infection were the use of corticosteroids (OR 7 30, IC = 1 52;35 7, p = 0 011) and the use of aspirin (OR -9 87, IC = 1 92;56 7, p - 0 01) Sixty (71%) patients declared as feeling more at risk for COVID-19 than the general population and 86 (97%) patients respected confinement to the letter  Conclusion: Few active patients on WL for LT had a suspected (15 3%) or confirmed (3 3%) COVID-19  This can be explained by the global respect of confinement  The use of aspirin and corticosteroids were independent factors of suspected or confirmed COVID-19 in this population
Therapy-Induced Transdifferentiation Promotes Glioma Growth Independent of EGFR Signaling
Authors: Hwanhee Oh, Inah Hwang, Ja-Young Jang, Lingxiang Wu, Dongqing Cao, Jun Yao, Haoqiang Ying, Jian Yi Li, Yu Yao, Baoli Hu, Qianghu Wang, Hongwu Zheng, Jihye Paik
Journal: Cancer Research (2021)

Abstract EGFR is frequently amplified, mutated, and overexpressed in malignant gliomas. Yet the EGFR-targeted therapies have thus far produced only marginal clinical responses, and the underlying mechanism remains poorly understood. Using an inducible oncogenic EGFR-driven glioma mouse model system, our current study reveals that a small population of glioma cells can evade therapy-initiated apoptosis and potentiate relapse development by adopting a mesenchymal-like phenotypic state that no longer depends on oncogenic EGFR signaling. Transcriptome analyses of proximal and distal treatment responses identified TGFβ/YAP/Slug signaling cascade activation as a major regulatory mechanism that promotes therapy-induced glioma mesenchymal lineage transdifferentiation. Following anti-EGFR treatment, TGFβ secreted from stressed glioma cells acted to promote YAP nuclear translocation that stimulated upregulation of the pro-mesenchymal transcriptional factor SLUG and subsequent glioma lineage transdifferentiation toward a stable therapy-refractory state. Blockade of this adaptive response through suppression of TGFβ-mediated YAP activation significantly delayed anti-EGFR relapse and prolonged animal survival. Together, our findings shed new insight into EGFR-targeted therapy resistance and suggest that combinatorial therapies of targeting both EGFR and mechanisms underlying glioma lineage transdifferentiation could ultimately lead to deeper and more durable responses. Significance: This study demonstrates that molecular reprogramming and lineage transdifferentiation underlie anti-EGFR therapy resistance and are clinically relevant to the development of new combinatorial targeting strategies against malignant gliomas with aberrant EGFR signaling.
Truncated YY1 interacts with BASP1 through a 339KLK341 motif in YY1 and suppresses vascular smooth muscle cell growth and intimal hyperplasia after vascular injury
Authors: Fernando S Santiago, Yue Li, Ling Zhong, Mark J Raftery, Laurence Lins, Levon M Khachigian
Journal: Cardiovascular Research (2021)

Abstract Aims In-stent restenosis and late stent thrombosis are complications associated with the use of metallic and drug-coated stents. Strategies that inhibit vascular smooth muscle cell (SMC) proliferation without affecting endothelial cell (EC) growth would be helpful in reducing complications arising from percutaneous interventions. SMC hyperplasia is also a pathologic feature of graft stenosis and fistula failure. Our group previously showed that forced expression of the injury-inducible zinc finger (ZNF) transcription factor, yin yang-1 (YY1), comprising 414 residues inhibits neointima formation in carotid arteries of rabbits and rats. YY1 inhibits SMC proliferation without affecting EC growth in vitro. Identifying a shorter version of YY1 retaining cell-selective inhibition would make it more amenable for potential use as a gene therapeutic agent. Methods and results We dissected YY1 into a range of shorter fragments (YY1A-D, YY1Δ) and found that the first two ZNFs in YY1 (construct YY1B, spanning 52 residues) repressed SMC proliferation. Receptor binding domain analysis predicts a three-residue (339KLK341) interaction domain. Mutation of 339KLK341 to 339AAA341 in YY1B (called YY1Bm) abrogated YY1B’s ability to inhibit SMC but not EC proliferation and migration. Incubation of recombinant GST-YY1B and GST-YY1Bm with SMC lysates followed by precipitation with glutathione–agarose beads and mass spectrometric analysis identified a novel interaction between YY1B and BASP1. Overexpression of BASP1, like YY1, inhibited SMC but not EC proliferation and migration. BASP1 siRNA partially rescued SMC from growth inhibition by YY1B. In the rat carotid balloon injury model, adenoviral overexpression of YY1B, like full-length YY1, reduced neointima formation, whereas YY1Bm had no such effect. CD31+ immunostaining suggested YY1B could increase re-endothelialization in a 339KLK341-dependent manner. Conclusion These studies identify a truncated form of YY1 (YY1B) that can interact with BASP1 and inhibit SMC proliferation, migration, and intimal hyperplasia after balloon injury of rat carotid arteries as effectively as full length YY1. We demonstrate the therapeutic potential of YY1B in vascular proliferative disease.
The dose-optimisation of lenvatinb for patients with unresectable hepatocellular carcinoma in clinical practice: A retrospective analysis of real-world evidence in China.
Authors: Lan Zhang, Yanhong Wang, Ningling Ge, Yu-Hong Gan, ZhengGang Ren, Yi Chen
Journal: Journal of Clinical Oncology (2021)

280 Background: Lenvatinib has become available as first-line therapy in patients with unresectable hepatocellular carcinoma (u-HCC). Although 8mg or 12mg/day is the standard starting dose according to weight, the high rate of adverse events (AEs) leading to dose reduction often limits its application. Various dosing schedules are used clinically to alleviate toxicities in practice. This study evaluated the safety and antitumor activity of two dosing strategies for lenvatinib administrations. Methods: Patients administered lenvatinib for u-HCC between April 2018 and July 2019 were enrolled. The dose-escalation strategy was conducted as follow, starting dose 4mg/day orally with biweekly escalation (As common AE always occurred within 2 weeks after administered), per 4 mg increment, to 8 or 12mg finally per body weight if no significant drug-related (no more than G2) adverse events occurred. Patients with a standard-dose strategy (8/12mg/day orally per body weight) were also included for comparison.Objective response rate(ORR) and progression-free survival (PFS) were assessed according to RECIST1.1 criteria. Dose-reduction rate was recorded and treatment-related adverse events (TRAE) was evaluated according to the CTCAE 5.0. Results: Totally 56 patients were included (37 in dose-escalation group and 19 in standard-dose group). The mean weight was 64.79±1.66 kg in dose-escalation group and 58.76±2.45 kg in standard-dose group, BCLC stage C proportion was 51.4% and 63.2%, Child-pugh B proportion was 16.2% and 5.3% respectively. Baseline demographic parameters were comparable between two groups (P&gt;0.05). There was no significant difference in response rate (32.43% vs 42.1%, P=0.335), disease control rate (86.4% vs 84.2%, P=0.686) and PFS (P=0.631). The proportion of patients who reached the full dose (per weight) was also similar (48.6% vs 63.2%, p=0.399). Dose reduction rate was significantly higher in standard-dose group than dose-escalation group (36.8%vs 13.5%,p=0.044). Although, no difference in grade 3/4 adverse events was found between two groups (P=0.083), patients in standard-dose group(36.8%,7/19) have a higher incidence trend of G3/4 AEs than those of dose-escalation group(16.2%,6/37). Conclusions: The dose-escalation strategy may be an alternative approach to prolong lenvatinib treatment period, with comparable efficacy and more tolerance. More data are needed to confirm the long-term efficacy and safety of the dose-escalation strategy.
A Purpuric Rash
Authors: Kevin D. He, Ken He, Paul B. Cornia
Journal: JAMA (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Androgen Misuse and Abuse
Authors: David J Handelsman
Journal: Endocrine Reviews (2021)

Abstract Androgens are potent drugs requiring prescription for valid medical indications but are misused for invalid, unproven, or off-label reasons as well as being abused without prescription for illicit nonmedical application for performance or image enhancement. Following discovery and first clinical application of testosterone in the 1930s, commercialization of testosterone and synthetic androgens proliferated in the decades after World War II. It remains among the oldest marketed drugs in therapeutic use, yet after 8 decades of clinical use, the sole unequivocal indication for testosterone remains in replacement therapy for pathological hypogonadism, organic disorders of the male reproductive system. Nevertheless, wider claims assert unproven, unsafe, or implausible benefits for testosterone, mostly representing wishful thinking about rejuvenation. Over recent decades, this created an epidemic of testosterone misuse involving prescription as a revitalizing tonic for anti-aging, sexual dysfunction and/or obesity, where efficacy and safety remains unproven and doubtful. Androgen abuse originated during the Cold War as an epidemic of androgen doping among elite athletes for performance enhancement before the 1980s when it crossed over into the general community to become an endemic variant of drug abuse in sufficiently affluent communities that support an illicit drug industry geared to bodybuilding and aiming to create a hypermasculine body physique and image. This review focuses on the misuse of testosterone, defined as prescribing without valid clinical indications, and abuse of testosterone or synthetic androgens (androgen abuse), defined as the illicit use of androgens without prescription or valid indications, typically by athletes, bodybuilders and others for image-oriented, cosmetic, or occupational reasons.
Covid-19: South Africa variant found in the US as Biden expands health coverage
Authors: Janice Hopkins Tanne
Journal: BMJ (2021)

<h3>Introduction:</h3> This study examined the attitudes and perceptions of family medicine educators with regards to COVID-19’s impact on both career thinking and work intentions. <h3>Methods:</h3> We surveyed 949 Family Medicine educators and practicing physicians as part of the 2021 Council of Academic Family Medicine’s (CAFM) Educational Research Alliance (CERA) survey. <h3>Results:</h3> Changes in thinking about their nonwork lives (<i>P &lt; .001</i>, OR = 2.82), changes in life priorities (<i>P &lt; .001</i>, OR = 2.07), along with recent changes to the educator job that are perceived as less enjoyable (<i>P &lt; .001</i>, OR = 1.31), are associated with career thinking changes. Perception of being treated fairly (<i>P = .002</i>, OR = 0.83), changes in thinking about nonwork lives (<i>P = .003</i>, OR = 1.29), changes in life priorities (<i>P &lt; .001</i>, OR = 1.65), and recent less enjoyable changes to the educator job (<i>P &lt; .001</i>, OR = 1.26), are associated with an intent to reduce work hours. Perception of being treated fairly (<i>P &lt; .001</i>, OR = 0.81), changes in life priorities (<i>P &lt; .001</i>, OR = 1.31), recent work changes that are less enjoyable (<i>P &lt; .001</i>, OR = 1.38), and workload increases (<i>P = .02</i>, OR = 0.87), are associated with increased thoughts of doing something different in 5 years. Older participants were more likely to intent to reduce hours (<i>P &lt; .001</i>, OR = 1.05) and have increased thoughts of doing something different in 5 years (<i>P &lt; .001</i>, OR = 1.04). Meanwhile, women were more likely to experience career thinking changes (<i>P = .02</i>, OR = 1.42). <h3>Discussion:</h3> Our findings suggest that the career thinking and work intentions of family medicine educators have been greatly impacted by the pandemic. There may be consequences for how they think about and approach their careers and jobs in the future. Additional research is needed to determine what these actual consequences mean. In addition, employers should carefully assess these types of changes, identify which educator subgroups they may affect the most, and act accordingly, particularly in areas like recruitment and retention.
Case 2-2021: A 26-Year-Old Pregnant Woman with Ventricular Tachycardia and Shock
Authors: Nandita S. Scott, Sunu S. Thomas, Doreen DeFaria Yeh, Andrew S. Fox, R. Neal Smith
Journal: New England Journal of Medicine (2021)

A 26-year-old pregnant woman presented at 32 weeks of gestation with cardiogenic shock after cardiac arrest. The troponin T level was markedly elevated, an electrocardiogram showed right bundle-branch block, and echocardiography revealed severe left ventricular hypokinesis. Extracorporeal membrane oxygenation was performed. A diagnosis and management decisions were made.
Clinical Responsiveness to All-trans Retinoic Acid Is Potentiated by LSD1 Inhibition and Associated with a Quiescent Transcriptome in Myeloid Malignancies
Authors: Mina M. Tayari, Helena G. Dos Santos, Deukwoo Kwon, Terrence J. Bradley, Amber Thomassen, Charles Chen, Yvonne Dinh, Aymee Perez, Arthur Zelent, Lluis Morey, Luisa Cimmino, Ramin Shiekhattar, Ronan T. Swords, Justin M. Watts
Journal: Clinical Cancer Research (2021)

Abstract Purpose: In preclinical studies, the lysine-specific histone demethylase 1A (LSD1) inhibitor tranylcypromine (TCP) combined with all-trans retinoic acid (ATRA) induces differentiation and impairs survival of myeloid blasts in non-acute promyelocytic leukemia acute myeloid leukemia (AML). We conducted a phase I clinical trial (NCT02273102) to evaluate the safety and activity of ATRA plus TCP in patients with relapsed/refractory AML and myelodysplasia (MDS). Patients and Methods: Seventeen patients were treated with ATRA and TCP (three dose levels: 10 mg twice daily, 20 mg twice daily, and 30 mg twice daily). Results: ATRA-TCP had an acceptable safety profile. The MTD of TCP was 20 mg twice daily. Best responses included one morphologic leukemia-free state, one marrow complete remission with hematologic improvement, two stable disease with hematologic improvement, and two stable disease. By intention to treat, the overall response rate was 23.5% and clinical benefit rate was 35.3%. Gene expression profiling of patient blasts showed that responding patients had a more quiescent CD34+ cell phenotype at baseline, including decreased MYC and RARA expression, compared with nonresponders that exhibited a more proliferative CD34+ phenotype, with gene expression enrichment for cell growth signaling. Upon ATRA-TCP treatment, we observed significant induction of retinoic acid–target genes in responders but not nonresponders. We corroborated this in AML cell lines, showing that ATRA-TCP synergistically increased differentiation capacity and cell death by regulating the expression of key gene sets that segregate patients by their clinical response. Conclusions: These data indicate that LSD1 inhibition sensitizes AML cells to ATRA and may restore ATRA responsiveness in subsets of patients with MDS and AML.
Lung Perfusion Scintigraphy in Pulmonary Vein Occlusion After Radiofrequency Ablation
Authors: Kamlesh Jobanputra, Orhan K. Oz
Journal: Clinical Nuclear Medicine (2021)

We describe functional and anatomical imaging findings in an 86-year-old woman who was treated for paroxysmal atrial fibrillation 5 years ago with radiofrequency ablation. She had been symptom-free for 4 years. Five years after the ablation, she presented with exertional dyspnea of several months' duration. She had left bundle branch block and aortic insufficiency with normal ejection fraction on 2-dimensional echocardiogram, none of which explained her symptoms. A CT coronary angiogram showed no obstructive coronary artery disease: Coronary Artery Disease Reporting and Data System category 1. Complete occlusion of the left superior pulmonary vein was, however, noted at its origin. Lung perfusion scintigraphy was obtained to evaluate differential perfusion.
Prenatal Opioid Exposure and Motor Cortex Volume—Reply
Authors: Micah L. Hartwell, Julie M. Croff
Journal: JAMA Pediatrics (2021)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Pediatrics HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Pediatrics journal