tbuckley/cabot-search huggingface dataset:
Safety and Tolerability of Transdermal Cannabidiol Gel in Children With Developmental and Epileptic Encephalopathies
Authors: Ingrid E. Scheffer, Joe Hulihan, John Messenheimer, Shayma Ali, Ngaire Keenan, Jim Griesser, Donna L. Gutterman, Terri Sebree, Lynette G. Sadleir
Journal: JAMA Network Open (2021)

<h3>Importance</h3> Developmental and epileptic encephalopathies (DEEs) are the most severe group of drug-resistant epilepsies. Alternatives to oral therapies are urgently needed to reduce seizures and improve developmental outcomes and comorbidities in this medically complex population. <h3>Objective</h3> To assess the safety and tolerability of cannabidiol (CBD) transdermal gel in children with DEEs and to evaluate seizure frequency, sleep, and quality of life. <h3>Design, Setting, and Participants</h3> This nonrandomized controlled trial was conducted in 2 centers in Australia and New Zealand from April 2018 to July 2019. Children and adolescents aged 3 to 18 years with DEEs who were receiving a stable regimen of 1 to 4 antiseizure medications were eligible for this study. After 1-month baseline and titration periods, patients entered a 5.5-month flexible-dosing maintenance period for a total of 6.5 months of treatment. Data were analyzed throughout the 6.5-month treatment period. <h3>Interventions</h3> Twice-daily applications of CBD transdermal gel at doses of 125 to 500 mg for 6.5 months. <h3>Main Outcomes and Measures</h3> Safety and tolerability assessments included adverse events (AEs) and examination of skin. The outcome for seizures was the median percentage change from baseline in monthly (28-day) seizure frequency of focal impaired awareness seizures (FIAS) and tonic-clonic seizures (TCS) over 6.5 months. <h3>Results</h3> Of 48 patients (mean [SD] age, 10.5 [3.8] years; 26 [54%] boys), 29 (60%) had at least 1 treatment-related AE over 6.5 months; 44 of 46 treatment-related AEs (96%) were mild or moderate. Treatment-related AEs that occurred in at least 5% of patients were application-site dryness, application-site pain, and somnolence (each reported by 4 patients [8%]). The only treatment-related gastrointestinal AE was diarrhea, reported in a single patient. CBD treatment was associated with reductions in FIAS and TCS frequency. Analysis of the 33 patients with FIAS and TCS showed a median (interquartile range) monthly reduction in seizures of 58% (−5.3% to 81.8%) at 5 months and 43.5% (−23.8% to 57.5%) over the entire 6.5-month study period. Parents and caregivers noted improvements in social or interpersonal engagement and irritability (33 of 43 [77%] participants); alertness, energy, and sleep (23 of 43 [53%]); and cognition or concentration (20 of 43 [47%]). <h3>Conclusions and Relevance</h3> In this study, CBD transdermal gel was safe, well tolerated, and was associated with reductions in FIAS and TCS frequency and disease burden. <h3>Trial Registration</h3> ClinicalTrials.gov Identifier:ACTRN12618000516280
A Clinical PET Imaging Tracer ([18F]DASA-23) to Monitor Pyruvate Kinase M2–Induced Glycolytic Reprogramming in Glioblastoma
Authors: Corinne Beinat, Chirag B. Patel, Tom Haywood, Surya Murty, Lewis Naya, Jessa B. Castillo, Samantha T. Reyes, Megan Phillips, Pablo Buccino, Bin Shen, Jun Hyung Park, Mary Ellen I. Koran, Israt S. Alam, Michelle L. James, Dawn Holley, Kim Halbert, Harsh Gandhi, Joy Q. He, Monica Granucci, Eli Johnson, Daniel Dan Liu, Nobuko Uchida, Rahul Sinha, Pauline Chu, Donald E. Born, Geoffrey I. Warnock, Irving Weissman, Melanie Hayden-Gephart, Mehdi Khalighi, Tarik F. Massoud, Andrei Iagaru, Guido Davidzon, Reena Thomas, Seema Nagpal, Lawrence D. Recht, Sanjiv Sam Gambhir
Journal: Clinical Cancer Research (2021)

Pyruvate kinase M2 (PKM2) catalyzes the final step in glycolysis, a key process of cancer metabolism. PKM2 is preferentially expressed by glioblastoma (GBM) cells with minimal expression in healthy brain. We describe the development, validation, and translation of a novel PET tracer to study PKM2 in GBM. We evaluated 1-((2-fluoro-6-[
Noncoding Variation and Transcriptional Plasticity Promote Thermal Adaptation in Oysters by Altering Energy Metabolism
Authors: Ao Li, Li Li, Ziyan Zhang, Shiming Li, Wei Wang, Ximing Guo, Guofan Zhang
Journal: Molecular Biology and Evolution (2021)

Genetic variation and phenotypic plasticity are both important to adaptive evolution. However, how they act together on particular traits remains poorly understood. Here, we integrated phenotypic, genomic, and transcriptomic data from two allopatric but closely related congeneric oyster species, Crassostrea angulata from southern/warm environments and Crassostrea gigas from northern/cold environments, to investigate the roles of genetic divergence and plasticity in thermal adaptation. Reciprocal transplantation experiments showed that both species had higher fitness in their native habitats than in nonnative environments, indicating strong adaptive divergence. The southern species evolved higher transcriptional plasticity, and the plasticity was adaptive, suggesting that increased plasticity is important for thermal adaptation to warm climates. Genome-wide comparisons between the two species revealed that genes under selection tended to respond to environmental changes and showed higher sequence divergence in noncoding regions. All genes under selection and related to energy metabolism exhibited habitat-specific expression with genes involved in ATP production and lipid catabolism highly expressed in warm/southern habitats, and genes involved in ATP consumption and lipid synthesis were highly expressed in cold/northern habitats. The gene for acyl-CoA desaturase, a key enzyme for lipid synthesis, showed strong selective sweep in the upstream noncoding region and lower transcription in the southern species. These results were further supported by the lower free fatty acid (FFA) but higher ATP content in southern species and habitat, pointing to significance of ATP/FFA trade-off. Our findings provide evidence that noncoding variation and transcriptional plasticity play important roles in shaping energy metabolism for thermal adaptation in oysters.
Intertriginous Xanthomas—Pathognomonic Cutaneous Markers of Homozygous Familial Hypercholesterolemia
Authors: Abheek Sil, Dibyendu Bikash Bhanja, Surajit Kumar Biswas
Journal: JAMA Dermatology (2021)

This case report describes yellow papules coalescing into plaques involving the medial and lateral canthi of eyes, finger web spaces of both hands, antecubital fossae, and nodular swellings over the elbows.
Development of a three-layer consecutive gene delivery system for enhanced bone regeneration
Authors: Hye Jin Kim, Sujin Lee, Jong Min Park, Hui Bang Cho, Ji-In Park, Ji Sun Park, Keun-Hong Park
Journal: Biomaterials (2021)

This study developed a three-layer consecutive gene delivery system (T-CGDS) for timely gene delivery into human mesenchymal stem cells (hMSCs). The timing of transcription factor expression is important to effectively induce bone differentiation. Therefore, a three-layered nanocomposite was fabricated using differently sized gold nanoparticles to promote bone regeneration and osteogenic differentiation. The core layer comprised 80 nm gold nanoparticles coupled with ATF4 pDNA. Following coating with heparin-conjugated Pluronic F-127 (HP-F127), 50 nm gold nanoparticles coupled with SP7 pDNA were added to fabricate a bi-layer system. After further coating with HP-F127, 20 nm gold nanoparticles combined with RUNX2 pDNA were added. Consequently, a T-CGDS measuring 350-450 nm was fabricated. Genes were released for more than 8 days, while the size of the T-CGDS decreased over time. When the T-CGDS was applied to hMSCs, the gene in the outer layer (RUNX2) was expressed first, followed by those in the middle (SP7) and core (ATF4) layers. The T-CGDS effectively induced bone differentiation and regeneration in vitro and in vivo. Timely delivery of the ATF4 gene to stem cells via the T-CGDS can greatly assist osteogenic differentiation involved in bone regeneration.
Diagnostic accuracy of helical computed tomographic scanning (CT), digital substraction angiography (DSA), and CT following intrahepatic arterial injection of ionidized oil (lipiodol CT) in patients with hepatocellular carcinoma (HCC).
Authors: Imamura H, Nakayama A, Kitamura H, Miyagawa Si, Kawasaki S
Journal: Hepatology (1999)
Apolipoprotein E and Alzheimer's Disease: Findings, Hypotheses, and Potential Mechanisms
Authors: Nicole Koutsodendris, Maxine R. Nelson, Antara Rao, Yadong Huang
Journal: Annual Review of Pathology Mechanisms of Disease (2021)

Alzheimer's disease (AD) is a multifactorial neurodegenerative disorder that involves dysregulation of many cellular and molecular processes. It is notoriously difficult to develop therapeutics for AD due to its complex nature. Nevertheless, recent advancements in imaging technology and the development of innovative experimental techniques have allowed researchers to perform in-depth analyses to uncover the pathogenic mechanisms of AD. An important consideration when studying late-onset AD is its major genetic risk factor, apolipoprotein E4 (apoE4). Although the exact mechanisms underlying apoE4 effects on AD initiation and progression are not fully understood, recent studies have revealed critical insights into the apoE4-induced deficits that occur in AD. In this review, we highlight notable studies that detail apoE4 effects on prominent AD pathologies, including amyloid-β, tau pathology, neuroinflammation, and neural network dysfunction. We also discuss evidence that defines the physiological functions of apoE and outlines how these functions are disrupted in apoE4-related AD.
Eating disorders through the periodontal lens
Authors: Hélène Rangé, Pierre Colon, Nathalie Godart, Yvonne Kapila, Philippe Bouchard
Journal: Periodontology 2000 (2021)

Abstract People with eating disorders suffer from a mental disorder that negatively affects their physical and/or mental health. The three most frequent eating disorders are binge eating disorder, bulimia nervosa, and anorexia nervosa. Environmental and genetic factors are involved in the pathogenesis of eating disorders in vulnerable persons. Although treatment varies among different types of eating disorders, nutrition, medical care combined with psychotherapy and medications are standard of care. The aim of this review is to give an overview of the oral health impact of eating disorders with a special emphasis on the periodontium. Oral health professionals have a unique role to play in the early diagnosis of eating disorders because of the important impact that eating disorders have on the oral cavity. In vomiting‐associated eating disorders, the risk of erosive tooth wear is mainly localized to the palatal surfaces of the incisors. Emerging evidence also indicates a high frequency of gingivitis and gingival recessions associated with compulsive toothbrushing. A holistic approach, including oral health and functional rehabilitation, should be promoted by physicians, psychiatrists, and dentists for people with eating disorders.
BMA refuses to engage with consultant pay review process amid call for reform
Authors: Elisabeth Mahase
Journal: BMJ (2021)

Consultants in England will not engage with the Review Body on Doctors’ and Dentists’ Remuneration (DDRB) process this year and are instead calling for urgent negotiations with the government, the BMA has said.

The decision came after a BMA survey taken by 6000 consultants found that over 80% believed this year’s pay increase of 3%, which was below inflation, to be inadequate or completely unacceptable, while 91% said it showed that the government did not value the work …
Identifying adults at high-risk for change in weight and BMI in England: a longitudinal, large-scale, population-based cohort study using electronic health records
Authors: Michail Katsoulis, Alvina G Lai, Karla Diaz-Ordaz, Manuel Gomes, Laura Pasea, Amitava Banerjee, Spiros Denaxas, Kostas Tsilidis, Pagona Lagiou, Gesthimani Misirli, Krishnan Bhaskaran, Goya Wannamethee, Richard Dobson, Rachel L Batterham, Dimitra-Kleio Kipourou, R Thomas Lumbers, Lan Wen, Nick Wareham, Claudia Langenberg, Harry Hemingway
Journal: The Lancet Diabetes & Endocrinology (2021)

Targeted obesity prevention policies would benefit from the identification of population groups with the highest risk of weight gain. The relative importance of adult age, sex, ethnicity, geographical region, and degree of social deprivation on weight gain is not known. We aimed to identify high-risk groups for changes in weight and BMI using electronic health records (EHR).
2mm径の小血管に薬剤溶出性ステント(DES)は留置可能か?-SESおよびPESの小血管留置に関する実験的研究-
Authors: 堀田祐紀, 玉直人, 福岡良太, 寺井英伸, 土谷武嗣, 池田正寿, 名村正伸
Journal: Circulation (2009)
Prediction of ventilator-associated pneumonia outcomes according to the early microbiological response: a retrospective observational study
Authors: Adrian Ceccato, Cristina Dominedò, Miquel Ferrer, Ignacio Martin-Loeches, Enric Barbeta, Albert Gabarrús, Catia Cillóniz, Otavio T. Ranzani, Gennaro De Pascale, Stefano Nogas, Pierluigi Di Giannatale, Massimo Antonelli, Antoni Torres
Journal: European Respiratory Journal (2021)

Background Ventilator-associated pneumonia (VAP) is a leading infectious cause of morbidity in critically ill patients, yet current guidelines offer no indications for follow-up cultures. We aimed to evaluate the role of follow-up cultures and microbiological response 3 days after diagnosing VAP as predictors of short- and long-term outcomes. Methods We performed a retrospective analysis of a cohort prospectively collected from 2004 to 2017. VAP was diagnosed based on clinical, radiographical and microbiological criteria. For microbiological identification, a tracheobronchial aspirate was performed at diagnosis and repeated after 72 h. We defined three groups when comparing the two tracheobronchial aspirate results: persistence, superinfection and eradication of causative pathogens. Results 157 patients were enrolled in the study, among whom microbiological persistence, superinfection or eradication was present in 67 (48%), 25 (16%) and 65 (41%), respectively, after 72 h. Those with superinfection had the highest mortalities in the intensive care unit (p=0.015) and at 90 days (p=0.036), while also having the fewest ventilator-free days (p=0.019). Multivariable analysis revealed shock at VAP diagnosis (OR 3.43, 95% CI 1.25–9.40), Staphylococcus aureus isolation at VAP diagnosis (OR 2.87, 95% CI 1.06–7.75) and hypothermia at VAP diagnosis (OR 0.67, 95% CI 0.48–0.95, per +1°C) to be associated with superinfection. Conclusions Our retrospective analysis suggests that VAP short- and long-term outcomes may be associated with superinfection in follow-up cultures. Follow-up cultures may help guide antibiotic therapy and its duration. Further prospective studies are necessary to verify our findings.
Omega-3 polyunsaturated fatty acids and FADS genotype: is personalised prevention of asthma on the horizon?
Authors: Vanessa Garcia-Larsen
Journal: European Respiratory Journal (2021)

<b>Findings replicated in two cohort studies showed that in children with a common fatty acid desaturase (<i>FADS</i>) variant, a higher intake of omega</b><b>-3 fatty acids EPA and DHA was associated with a lower risk of asthma incidence in adolescence</b>https://bit.ly/3fJT5b3
Genomic temporal heterogeneity of circulating tumour DNA in unresectable metastatic colorectal cancer under first-line treatment
Authors: Feng Wang, You-Sheng Huang, Hao-Xiang Wu, Zi-Xian Wang, Ying Jin, Yi-Chen Yao, Yan-Xing Chen, Qi Zhao, Shifu Chen, Ming-Ming He, Hui-Yan Luo, Miao-Zhen Qiu, De-shen Wang, Feng-Hua Wang, Mingyan Xu, Yu-Hong Li, Rui-Hua Xu
Journal: Gut (2021)

Objective Circulating tumour DNA (ctDNA) sequencing is increasingly used in the clinical management of patients with colorectal cancer. However, the genomic heterogeneity in ctDNA during treatments and its impact on clinical outcomes remain largely unknown. Design We conducted a prospective cohort study ( NCT04228614 ) of 171 patients with unresectable metastatic colorectal cancer (mCRC) who underwent first-line treatment and prospectively collected blood samples with or without tumour samples from patients at baseline and sequentially until disease progression or last follow-up. Results The RAS/BRAF alterations in paired baseline tissue and plasma samples from 63 patients displayed a favourable concordance (81.0%, 51/63). After a period of first-line treatment (median time between baseline and last liquid biopsy, 4.67 months), 42.6% (26/61) of RAS-mutant patients showed RAS clearance and 50.0% (5/10) of BRAF-mutant patients showed BRAF clearance, while 3.6% (3/84) and 0.7% (1/135) of patients showed new RAS or BRAF mutations in ctDNA. Patients with plasma RAS/BRAF clearance showed similar progression-free survival (PFS) and overall survival (OS) with patients who remained RAS/BRAF wild-type, while much better outcomes than those who remained RAS/BRAF mutant. Patients who gained new RAS/BRAF mutations showed similar prognosis as those who maintained RAS/BRAF mutations, and shorter PFS and OS than those who remained RAS/BRAF wild-type. Conclusion This prospective, serial and large-scale ctDNA profiling study reveals the temporal heterogeneity of mCRC-related somatic variants, which should be given special attention in clinical practice, as evidenced by the finding that the shift in plasma RAS/BRAF mutational status can yield a drastic change in survival outcomes.
Neutralizing antibodies for the prevention and treatment of COVID-19
Authors: Lanying Du, Yang Yang, Xiujuan Zhang
Journal: Cellular and Molecular Immunology (2021)

Abstract Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) initiates the infection process by binding to the viral cellular receptor angiotensin-converting enzyme 2 through the receptor-binding domain (RBD) in the S1 subunit of the viral spike (S) protein. This event is followed by virus–cell membrane fusion mediated by the S2 subunit, which allows virus entry into the host cell. Therefore, the SARS-CoV-2 S protein is a key therapeutic target, and prevention and treatment of coronavirus disease 2019 (COVID-19) have focused on the development of neutralizing monoclonal antibodies (nAbs) that target this protein. In this review, we summarize the nAbs targeting SARS-CoV-2 proteins that have been developed to date, with a focus on the N-terminal domain and RBD of the S protein. We also describe the roles that binding affinity, neutralizing activity, and protection provided by these nAbs play in the prevention and treatment of COVID-19 and discuss the potential to improve nAb efficiency against multiple SARS-CoV-2 variants. This review provides important information for the development of effective nAbs with broad-spectrum activity against current and future SARS-CoV-2 strains.
Sculpture and haptic deficit in the time of COVID-19
Authors: Colin Martin
Journal: The Lancet Neurology (2021)

"Touch is now more charged than it was when the idea for this exhibition was dreamt up in 2019", said artist and writer Edmund de Waal during an interview on BBC Radio 4 Today programme on May 19, 2021. "We have gone from wanting to touch things to needing desperately to touch." At a studio briefing in February 2020, a month before This Living Hand—the exhibition curated by de Waal—was scheduled to open, few could have imagined how dramatically a nascent viral pandemic would change the world. Opening after a delay of 14 months, the curatorial focus on the sculptor Henry Moore's drawings of hands, the primacy of touch in experiencing sculpture, and in developing haptic knowledge, resonates more deeply than anyone could have anticipated.
Time to resolution of respiratory and systemic coronavirus disease 2019 symptoms in community setting
Authors: Aurélien Dinh, Luc Jaulmes, Agnès Dechartres, Clara Duran, Hélène Mascitti, Xavier Lescure, Youri Yordanov, Patrick Jourdain, Apra Caroline (AC), Jaulmes Luc (JL), Mensch Arthur (MA), Aime-Eusebi Amélie, Apra Caroline, Bleibtreu Alexandre, Debuc Erwan, Dechartres Agnes, Deconinck Laurène, Dinh Aurélien, Jourdain Patrick, Katlama Christine, Lebel Josselin, Lescure François-Xavier, Yordanov Youri, Artigou Yves, Banzet Amélie, Boucheron Elodie, Boudier Christiane, Buzenac Edouard, Chapron Marie-Claire, Chekaoui Dalhia, None De Bastard Laurent, Debuc Erwan, Aurélien Dinh, Grenier Alexandre, Haas Pierre-Etienne, Hody Julien, Jarraya Michèle, Jourdain Patrick, Lacaille Louis, Le Guern Aurélie, Leclert Jeremy, Male Fanny, Marchand-Arvier Jerôme, Martin-Blondet Emmanuel, Nassour Apolinne, Ourahou Oussama, Thomas Penn, Ribardiere Ambre, Robin Nicolas, Rouge Camille, Nicolas Schmidt, Villie Pascaline
Journal: Clinical Microbiology and Infection (2021)
Helen Salisbury: Blood bottles, vaccines, and freight
Authors: Helen Salisbury
Journal: BMJ (2021)

In our clinical work there’s always an element of surprise: we never know when our schedules will be derailed by the urgent needs of a sick child or a patient with psychosis. However, our practice managers are experts in planning and organisation. Over years, they hone skills that include knowing which parts of the complicated business of running a GP surgery need to happen when. These skills are particularly relevant when it comes to the annual flu vaccination campaign: they work out how much vaccine to order in January, plan the clinics, and …
Genetics journal that carried articles helpful to Chinese state surveillance hit by editorial board resignations
Authors: Owen Dyer
Journal: BMJ (2021)

Nine members of the editorial board of the journal Molecular Genetics and Genomic Medicine have resigned after the journal’s editor failed to tackle concerns that it had published articles from China potentially useful in the genetic surveillance of oppressed minorities, such as the Uyghurs of Xinjiang province.

The articles discuss genetic techniques that are also being used to build much broader government databases of China’s population for non-medical purposes, said Yves Moreau, a professor specialising in computational genetics at the Catholic University of Leuven, Belgium.

Moreau initially complained to the journal’s editor in chief, Suzanne Hart, in March. Among the articles he cited was one which analysed the “forensic characteristics” of the “Xinjiang Mongolian group.”1 Another discussed the differentiation of Muslim demographic groups among the Han Chinese …
Development of hepatocellular carcinoma in patients with hepatitis C virus infection and with or without past hepatitis B virus infection.
Authors: Kinoshita H, Kubo S, Kuroki T, Seki S, Shiomi S, Nakajima S, Takeda T, Tamori A, Fukuda K, Nishiguchi S, Minamitani S
Journal: Hepatology (1997)