tbuckley/cabot-search huggingface dataset:
Variation in Pleiotropic Hub Gene Expression Is Associated with Interspecific Differences in Head Shape and Eye Size in <i>Drosophila</i>
Authors: Elisa Buchberger, Anıl Bilen, Sanem Ayaz, David Salamanca, Cristina Matas de las Heras, Armin Niksic, Isabel Almudi, Montserrat Torres-Oliva, Fernando Casares, Nico Posnien
Journal: Molecular Biology and Evolution (2020)

Revealing the mechanisms underlying the breathtaking morphological diversity observed in nature is a major challenge in Biology. It has been established that recurrent mutations in hotspot genes cause the repeated evolution of morphological traits, such as body pigmentation or the gain and loss of structures. To date, however, it remains elusive whether hotspot genes contribute to natural variation in the size and shape of organs. As natural variation in head morphology is pervasive in Drosophila, we studied the molecular and developmental basis of differences in compound eye size and head shape in two closely related Drosophila species. We show differences in the progression of retinal differentiation between species and we applied comparative transcriptomics and chromatin accessibility data to identify the GATA transcription factor Pannier (Pnr) as central factor associated with these differences. Although the genetic manipulation of Pnr affected multiple aspects of dorsal head development, the effect of natural variation is restricted to a subset of the phenotypic space. We present data suggesting that this developmental constraint is caused by the coevolution of expression of pnr and its cofactor u-shaped (ush). We propose that natural variation in expression or function of highly connected developmental regulators with pleiotropic functions is a major driver for morphological evolution and we discuss implications on gene regulatory network evolution. In comparison to previous findings, our data strongly suggest that evolutionary hotspots are not the only contributors to the repeated evolution of eye size and head shape in Drosophila.
Monitoring Trends of COVID-19 Among ESKD Patients in a Large Dialysis Organization
Authors: Kristine Kubisiak, Eric D. Weinhandl, Norma J. Ofsthun, Jeffrey L. Hymes, Robert J. Kossmann, Lorien S. Dalrymple
Journal: Journal of the American Society of Nephrology (2020)

Background: Monitoring real-time acceleration, plateaus, and deceleration of infection rates is important for healthcare planning during a pandemic  We implemented methodology to continuously monitor daily cases and changes of COVID-19 case rates among individuals with ESKD receiving care in a large dialysis organization  Methods: We identified patients with ESKD receiving dialysis in a Fresenius Medical Care North America (FMCNA) dialysis facility who tested positive for COVID-19  We fit a loess curve to the daily cumulative number of identified cases and computed the first and second derivative of the fitted curve to assess rate of change and change in rate of change, respectively, over time  We used these visualization techniques to monitor trends in case rates at the national and state levels  Results: By May 15, 2020, there were 5,513 confirmed COVID-19 cases among patients receiving dialysis in an FMCNA facility  Mean age was 63 6 years, 57% were male, and 71% of confirmed cases had diabetes  Nationally, during the peak infection period in early April, new cases routinely exceeded 150 per day and there was a steady acceleration in growth of cases until the second week of April  As of May 15, 2020, among states with sufficient data, 2 states demonstrated continued acceleration, 10 demonstrated deceleration, and 13 plateaued in rate of growth  Conclusions: The timing of the acceleration in growth of COVID-19 cases among individuals with ESKD followed national trends in the general population  Varying patterns of plateauing and deceleration of cases at the state level were observed in the ESKD population  Real-time monitoring of disease rates in high-risk populations, such as individuals with ESKD, is needed to plan for continuously changing healthcare demands during a pandemic
Natural history of monoclonal B-cell lymphocytosis among relatives in CLL families
Authors: Susan L. Slager, Mark C. Lanasa, Gerald E. Marti, Sara J. Achenbach, Nicola J. Camp, Fatima Abbasi, Neil E. Kay, Celine M. Vachon, James R. Cerhan, James B. Johnston, Timothy G. Call, Kari G. Rabe, Geffen Kleinstern, Nicholas J. Boddicker, Aaron D. Norman, Sameer A. Parikh, Jose F. Leis, Versha Banerji, Danielle M. Brander, Martha Glenn, Alessandra Ferrajoli, Karen Curtin, Esteban Braggio, Tait D. Shanafelt, Mary L. McMaster, J. Brice Weinberg, Curtis A. Hanson, Neil E. Caporaso
Journal: Blood (2020)
Genomic and phenotypic insights from an atlas of genetic effects on DNA methylation
Authors: Josine L. Min, Gibran Hemani, Eilis Hannon, Koen F. Dekkers, Juan Castillo-Fernandez, René Luijk, Elena Carnero-Montoro, Daniel J. Lawson, Kimberley Burrows, Matthew Suderman, Andrew D. Bretherick, Tom G. Richardson, Johanna Klughammer, Valentina Iotchkova, Gemma Sharp, Ahmad Al Khleifat, Aleksey Shatunov, Alfredo Iacoangeli, Wendy L. McArdle, Karen M. Ho, Ashish Kumar, Cilla Söderhäll, Carolina Soriano-Tárraga, Eva Giralt-Steinhauer, Nabila Kazmi, Dan Mason, Allan F. McRae, David L. Corcoran, Karen Sugden, Silva Kasela, Alexia Cardona, Felix R. Day, Giovanni Cugliari, Clara Viberti, Simonetta Guarrera, Michael Lerro, Richa Gupta, Sailalitha Bollepalli, Pooja Mandaviya, Yanni Zeng, Toni-Kim Clarke, Rosie M. Walker, Vanessa Schmoll, Darina Czamara, Carlos Ruiz-Arenas, Faisal I. Rezwan, Riccardo E. Marioni, Tian Lin, Yvonne Awaloff, Marine Germain, Dylan Aïssi, Ramona Zwamborn, Kristel van Eijk, Annelot Dekker, Jenny van Dongen, Jouke-Jan Hottenga, Gonneke Willemsen, Cheng-Jian Xu, Guillermo Barturen, Francesc Català-Moll, Martin Kerick, Carol Wang, Phillip Melton, Hannah R. Elliott, Jean Shin, Manon Bernard, Idil Yet, Melissa Smart, Tyler Gorrie-Stone, Chris Shaw, Ammar Al Chalabi, Susan M. Ring, Göran Pershagen, Erik Melén, Jordi Jiménez-Conde, Jaume Roquer, Deborah A. Lawlor, John Wright, Nicholas G. Martin, Grant W. Montgomery, Terrie E. Moffitt, Richie Poulton, Tõnu Esko, Lili Milani, Andres Metspalu, John R. B. Perry, Ken K. Ong, Nicholas J. Wareham, Giuseppe Matullo, Carlotta Sacerdote, Salvatore Panico, Avshalom Caspi, Louise Arseneault, France Gagnon, Miina Ollikainen, Jaakko Kaprio, Janine F. Felix, Fernando Rivadeneira, Henning Tiemeier, Marinus H. van IJzendoorn, André G. Uitterlinden, Vincent W. V. Jaddoe, Chris Haley, Andrew M. McIntosh, Kathryn L. Evans, Alison Murray, Katri Räikkönen, Jari Lahti, Ellen A. Nohr, Thorkild I. A. Sørensen, Torben Hansen, Camilla S. Morgen, Elisabeth B. Binder, Susanne Lucae, Juan Ramon Gonzalez, Mariona Bustamante, Jordi Sunyer, John W. Holloway, Wilfried Karmaus, Hongmei Zhang, Ian J. Deary, Naomi R. Wray, John M. Starr, Marian Beekman, Diana van Heemst, P. Eline Slagboom, Pierre-Emmanuel Morange, David-Alexandre Trégouët, Jan H. Veldink, Gareth E. Davies, Eco J. C. de Geus, Dorret I. Boomsma, Judith M. Vonk, Bert Brunekreef, Gerard H. Koppelman, Marta E. Alarcón-Riquelme, Rae-Chi Huang, Craig E. Pennell, Joyce van Meurs, M. Arfan Ikram, Alun D. Hughes, Therese Tillin, Nish Chaturvedi, Zdenka Pausova, Tomas Paus, Timothy D. Spector, Meena Kumari, Leonard C. Schalkwyk, Peter M. Visscher, George Davey Smith, Christoph Bock, Tom R. Gaunt, Jordana T. Bell, Bastiaan T. Heijmans, Jonathan Mill, Caroline L. Relton
Journal: Nature Genetics (2021)
Advanced Liver Fibrosis Is Common in Patients With Type 2 Diabetes Followed in the Outpatient Setting: The Need for Systematic Screening
Authors: Romina Lomonaco, Eddison Godinez Leiva, Fernando Bril, Sulav Shrestha, Lydia Mansour, Jeff Budd, Jessica Portillo Romero, Siegfried Schmidt, Ku-Lang Chang, George Samraj, John Malaty, Katherine Huber, Pierre Bedossa, Srilaxmi Kalavalapalli, Jonathan Marte, Diana Barb, Danielle Poulton, Nada Fanous, Kenneth Cusi
Journal: Diabetes Care (2020)

Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM).A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m2; and HbA1c: 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis.The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI).Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT.
Ketones in Pregnancy: Why Is It Considered Necessary to Avoid Them and What Is the Evidence Behind Their Perceived Risk?
Authors: Helen L. Tanner, Marloes Dekker Nitert, Leonie K. Callaway, Helen L. Barrett
Journal: Diabetes Care (2020)

Current dietary advice for women with gestational diabetes mellitus is to avoid diets that result in elevated ketone levels. This guidance stems from a concern that maternal ketones are associated with poor fetal and childhood outcomes, including reduced childhood intelligence quota. The evidence behind these guidelines is conflicting and inconsistent. Given that dietary counseling is the initial treatment strategy for women with diabetes in pregnancy, it is important that clinicians understand the concern regarding maternal ketones. This review examines the physiology of ketogenesis in pregnancy, the prevalence of elevated maternal ketone levels, and the relationship between maternal ketones and fetal and childhood outcomes.
“You’re on mute:” How to organise a virtual medical conference
Authors: Nikki Nabavi, Patricia Vinchenzo, Derek K Tracy
Journal: BMJ (2020)

Coronavirus disease 2019 (covid-19) has sparked a rapid transformation in learning and how information is delivered. In July 2020 we ran a virtual educational event, the National Psychiatry Summer School, with sponsorship from the Royal College of Psychiatrists. This free event over two days comprised eminent speakers, hundreds of attendees, and international participation. It highlighted the challenges and opportunities digital conferences can offer. We hope our reflections and learning will inspire others to create and run high quality, accessible virtual events. Virtual learning is here to stay—not to replace but to enhance opportunities for medical education.

Organising a successful conference (whether online or face to face) requires commitment. Consider carefully who you will work with and allocate the workload across this reliable, enthusiastic team who share your vision. Establish roles with set responsibilities and timelines, agreed from the outset. Collaborating with institutions or individuals outside your existing network can increase creativity, reduce individual workload, and divide costs to produce a high quality event. In a virtual setting, organising committees can be from across the world, allowing collaboration with non-UK based universities, societies, charities, or special interest groups. Diversity can be increased at all levels—from representation of speakers and voices to breaking down traditional barriers of geography.

Be clear about the aims of your event—namely, what it is for and who might attend. Create a theme for the event and invite speakers who fit. Think, has this been done before? If so, why is yours different, and why is it needed? Set the date of your conference. Although we prepared ours in a month, it would be better to plan as far ahead as possible. Find out what is taking place near the proposed date to avoid clashes with established events, examinations, and holidays.

As a virtual conference usually costs less …
Comment on “Low dose oral minoxidil for treating alopecia: A 3-year North American retrospective case series”: Adding further evidence about side effects
Authors: Daniel Ortega-Quijano, Juan Jimenez-Cauhe, Diego Fernandez-Nieto, David Saceda-Corralo, Sergio Vaño-Galvan
Journal: Journal of the American Academy of Dermatology (2021)
Effects of dapagliflozin in heart failure with reduced ejection fraction and chronic obstructive pulmonary disease: an analysis of <scp>DAPA‐HF</scp>
Authors: Pooja Dewan, Kieran F. Docherty, Olof Bengtsson, Rudolf A. de Boer, Akshay S. Desai, Jaroslaw Drozdz, Nathaniel M. Hawkins, Silvio E. Inzucchi, Masafumi Kitakaze, Lars Køber, Mikail N. Kosiborod, Anna Maria Langkilde, Daniel Lindholm, Felipe A. Martinez, Béla Merkely, Mark C. Petrie, Piotr Ponikowski, Marc S. Sabatine, Morten Schou, Mikaela Sjöstrand, Scott D. Solomon, Subodh Verma, Pardeep S. Jhund, John J.V. McMurray
Journal: European Journal of Heart Failure (2020)

Chronic obstructive pulmonary disease (COPD) is an important comorbidity in heart failure (HF) with reduced ejection fraction (HFrEF), associated with worse outcomes and often suboptimal treatment because of under-prescription of beta-blockers. Consequently, additional effective therapies are especially relevant in patients with COPD. The aim of this study was to examine outcomes related to COPD in a post hoc analysis of the Dapagliflozin And Prevention of Adverse-outcomes in Heart Failure (DAPA-HF) trial.We examined whether the effects of dapagliflozin in DAPA-HF were modified by COPD status. The primary outcome was the composite of an episode of worsening HF or cardiovascular death. Overall, 585 (12.3%) of the 4744 patients randomized had a history of COPD. Patients with COPD were more likely to be older men with a history of smoking, worse renal function, and higher baseline N-terminal pro B-type natriuretic peptide, and less likely to be treated with a beta-blocker or mineralocorticoid receptor antagonist. The incidence of the primary outcome was higher in patients with COPD than in those without [18.9 (95% confidence interval 16.0-22.2) vs. 13.0 (12.1-14.0) per 100 person-years; hazard ratio (HR) for COPD vs. no COPD 1.44 (1.21-1.72); P < 0.001]. The effect of dapagliflozin, compared with placebo, on the primary outcome, was consistent in patients with [HR 0.67 (95% confidence interval 0.48-0.93)] and without COPD [0.76 (0.65-0.87); interaction P-value 0.47].In DAPA-HF, one in eight patients with HFrEF had concomitant COPD. Participants with COPD had a higher risk of the primary outcome. The benefit of dapagliflozin on all pre-specified outcomes was consistent in patients with and without COPD.ClinicalTrials.gov ID NCT03036124.
Formulation and efficacy of ECO/pRHO-ABCA4-SV40 nanoparticles for nonviral gene therapy of Stargardt disease in a mouse model
Authors: Da Sun, Wenyu Sun, Song-Qi Gao, Cheng Wei, Amirreza Naderi, Andrew L. Schilb, Josef Scheidt, Sangjoon Lee, Timothy S. Kern, Krzysztof Palczewski, Zheng-Rong Lu
Journal: Journal of Controlled Release (2020)
A randomised controlled trial of the effect of a connected inhaler system on medication adherence in uncontrolled asthmatic patients
Authors: Alison Moore, Andrew Preece, Raj Sharma, Liam G. Heaney, Richard W. Costello, Robert A. Wise, Andrea Ludwig-Sengpiel, Giselle Mosnaim, Jamie Rees, Ryan Tomlinson, Ruth Tal-Singer, David A. Stempel, Neil Barnes
Journal: European Respiratory Journal (2020)

Suboptimal adherence to maintenance therapy contributes to poor asthma control and exacerbations. This study evaluated the effect of different elements of a connected inhaler system (CIS), comprising clip-on inhaler sensors, a patient-facing app and a healthcare professional (HCP) dashboard, on adherence to asthma maintenance therapy. This was an open-label, parallel-group, 6-month, randomised controlled trial in adults with uncontrolled asthma (asthma control test (ACT) score less than 20) on fixed-dose inhaled corticosteroids/long-acting β-agonist maintenance therapy (n=437). All subjects received fluticasone furoate/vilanterol ELLIPTA dry-powder inhalers for maintenance and salbutamol/albuterol metered-dose inhalers for rescue, with a sensor attached to each inhaler. Participants were randomised to one of five CIS study arms (allocation ratio 1:1:1:1:1) reflecting the recipient of the data feedback from the sensors, as follows: 1) maintenance use to participants and HCPs (n=87); 2) maintenance use to participants (n=88); 3) maintenance and rescue use to participants and HCPs (n=88); 4) maintenance and rescue use to participants (n=88); and 5) no feedback (control) (n=86). For the primary endpoint, observed mean± sd adherence to maintenance therapy over months 4–6 was 82.2±16.58% (n=83) in the “maintenance to participants and HCPs” arm and 70.8±27.30% (n=85) in the control arm. The adjusted least squares mean± se was 80.9±3.19% and 69.0±3.19%, respectively (study arm difference: 12.0%, 95% CI 5.2–18.8%; p&lt;0.001). Adherence was also significantly greater in the other CIS arms versus the control arm. The mean percentage of rescue medication free days (months 4–6) was significantly greater in participants receiving data on their rescue use compared with controls. ACT scores improved in all study arms with no significant differences between groups. A CIS can improve adherence to maintenance medication and reduce rescue medication use in patients with uncontrolled asthma.
CKD Patients on Hemodialysis (HD) with COVID-19 Infection: Characteristics and Outcome
Authors: Suresh Sankarasubbaiyan, Mallikarjuna Gowda B. Gowda, Mohammad S. Husain, Satyanarayana R. Puvvada, Vikram A. Sonawane, Kaparaboina K. Kumar, Guruvulu Venkata, Kamal D. Shah
Journal: Journal of the American Society of Nephrology (2020)

Sankarasubbaiyan, Suresh; Gowda, Mallikarjuna Gowda B.; Husain, Mohammad S.; Puvvada, Satyanarayana R.; Sonawane, Vikram A.; Kumar, Kaparaboina K.; Venkata, Guruvulu; Shah, Kamal D. Author Information
Abstract 79: Is Harada Score a Useful Tool in Mexican Childrens with Kawasaki Disease?
Authors: Angel J Flores-Pineda, Fernando Garcia-Rodriguez, Javier E Tomala-Haz, Paola B Lara-Herrera, Diego R Salinas-Encinas, Andres N Rodriguez-Garcia, Maria R Maldonado-Velazquez, Sarbelio Moreno-Espinosa, Enrique Faugier-Fuentes
Journal: Circulation (2015)

Background/Purpose: In developed countries Kawasaki disease (KD) is the most common cause of acquired heart disease in childhood. Haradascore is one of the most used predictive tool for coronary arteries aneurysms (CAA) development in KD. The aim of the study is to describe clinical data, treatment, and to assess the Harada score in Mexican patients with KD. Methods: We retrospectively indentified all patients evaluated at Hospital Infantil de Mexico Federico Gómez during a 6-yearperiod between 2008 and 2014. We reviewed demographic, clinical, laboratory, echocardiographic, and treatment data;and Harada scores were derived to evaluate efficacy in predicting risk for CAA. Results: In our Institution 34 cases were reported during the study period, 16 (47.1%) males, and median age of 36 (8 - 120)months. Incomplete KD was diagnosed in 6 (17.6%) cases with no significant differences in demographic data, but with alower accuracy in establishing diagnosis at admission compared with complete presentations (100% vs 66.7%, P = 0.027).Most of the patients (76.5%) received at least one antibiotic prior to admission to our Hospital. Patients presented with history of 6 (4 - 16) days with fever and conjunctivitis. Significant differences were observed between complete and incomplete presentations regarding oral changes (100% vs 66.7%, P = .027), strawberry tongue (92.9% vs 33.3%, P = .004), pharyngitis (100% vs 33.3%, P &lt; .001), and rash (71.4% vs 16.7%, P = .021). No significant differences were observed in laboratory results. Seven (20.6%) echocardiograms werereported with CAA, one of them found valve insufficiency, and none identified effusion. Harada score was positive in 23 (67.6%) patients, with high sensitivity (85.7%) and low specificity (37%), OR 1.36 (CI95% 0.89 - 2.06, P = .384). In total, 32 (94.1%) patients received intravenous immunoglobulin (IVIG). Retreatment with IVIG was given in 3 (8.8%) and steroid treatment in 1 (2.9%) patient. All of the patients received aspirin. Conclusions: This study revealed a high incidence of CAA in our population, added to lack of suspicion and antibiotic overuse. As in Japanese and US population, Harada score is a good screening tool to identify risk for CAA development in Mexican patients.
Reducing Dependence on General Anesthesia for Pediatric Oncology Outpatients Undergoing Repeated Lumbar Punctures
Authors: Esther R. Berko, Yahui Wei, Emily Stiglich, Derek Klingman, Julie Vardaro, Sarah K Tasian, Sara McDonough, Katelyn Oranges, Kelly Meyers, Eileen Aber, Miriam Kolb, Lindsay Borel, Nicholas Evageliou, Rebecca Citrin, Jane Minturn, Anne Reilly, Susan R. Rheingold
Journal: Blood (2020)
International Union of Basic and Clinical Pharmacology. CXI. Pharmacology, Signaling, and Physiology of Metabotropic Glutamate Receptors
Authors: Karen J. Gregory, Cyril Goudet
Journal: Pharmacological Reviews (2020)

Metabotropic glutamate (mGlu) receptors respond to glutamate, the major excitatory neurotransmitter in the mammalian brain, mediating a modulatory role that is critical for higher-order brain functions such as learning and memory. Since the first mGlu receptor was cloned in 1992, eight subtypes have been identified along with many isoforms and splice variants. The mGlu receptors are transmembrane-spanning proteins belonging to the class C G protein–coupled receptor family and represent attractive targets for a multitude of central nervous system disorders. Concerted drug discovery efforts over the past three decades have yielded a wealth of pharmacological tools including subtype-selective agents that competitively block or mimic the actions of glutamate or act allosterically via distinct sites to enhance or inhibit receptor activity. Herein, we review the physiologic and pathophysiological roles for individual mGlu receptor subtypes including the pleiotropic nature of intracellular signal transduction arising from each. We provide a comprehensive analysis of the in vitro and in vivo pharmacological properties of prototypical and commercially available orthosteric agonists and antagonists as well as allosteric modulators, including ligands that have entered clinical trials. Finally, we highlight emerging areas of research that hold promise to facilitate rational design of highly selective mGlu receptor-targeting therapeutics in the future. <h3>Significance Statement</h3> The metabotropic glutamate receptors are attractive therapeutic targets for a range of psychiatric and neurological disorders. Over the past three decades, intense discovery efforts have yielded diverse pharmacological tools acting either competitively or allosterically, which have enabled dissection of fundamental biological process modulated by metabotropic glutamate receptors and established proof of concept for many therapeutic indications. We review metabotropic glutamate receptor molecular pharmacology and highlight emerging areas that are offering new avenues to selectively modulate neurotransmission.