tbuckley/cabot-search huggingface dataset:
Selection on Phalanx Development in the Evolution of the Bird Wing
Authors: Merijn A G de Bakker, Wessel van der Vos, Kaylah de Jager, Wing Yu Chung, Donald A Fowler, Esther Dondorp, Stephan N F Spiekman, Keng Yih Chew, Bing Xie, Rafael Jiménez, Constanze Bickelmann, Shigeru Kuratani, Radim Blazek, Peter Kondrashov, Marilyn B Renfree, Michael K Richardson
Journal: Molecular Biology and Evolution (2021)

The frameshift hypothesis is a widely accepted model of bird wing evolution. This hypothesis postulates a shift in positional values, or molecular-developmental identity, that caused a change in digit phenotype. The hypothesis synthesized developmental and paleontological data on wing digit homology. The "most anterior digit" (MAD) hypothesis presents an alternative view based on changes in transcriptional regulation in the limb. The molecular evidence for both hypotheses is that the MAD expresses Hoxd13 but not Hoxd11 and Hoxd12. This digit I "signature" is thought to characterize all amniotes. Here, we studied Hoxd expression patterns in a phylogenetic sample of 18 amniotes. Instead of a conserved molecular signature in digit I, we find wide variation of Hoxd11, Hoxd12, and Hoxd13 expression in digit I. Patterns of apoptosis, and Sox9 expression, a marker of the phalanx-forming region, suggest that phalanges were lost from wing digit IV because of early arrest of the phalanx-forming region followed by cell death. Finally, we show that multiple amniote lineages lost phalanges with no frameshift. Our findings suggest that the bird wing evolved by targeted loss of phalanges under selection. Consistent with our view, some recent phylogenies based on dinosaur fossils eliminate the need to postulate a frameshift in the first place. We suggest that the phenotype of the Archaeopteryx lithographica wing is also consistent with phalanx loss. More broadly, our results support a gradualist model of evolution based on tinkering with developmental gene expression.
Severe toxicity free survival: physician-derived definitions of unacceptable long-term toxicities following acute lymphocytic leukaemia
Authors: Liv Andrés-Jensen, Andishe Attarbaschi, Edit Bardi, Shlomit Barzilai-Birenboim, Deepa Bhojwani, Melanie M Hagleitner, Christina Halsey, Arja Harila-Saari, Raphaele R L van Litsenburg, Melissa M Hudson, Sima Jeha, Motohiro Kato, Leontien Kremer, Wojciech Mlynarski, Anja Möricke, Rob Pieters, Caroline Piette, Elizabeth Raetz, Leila Ronceray, Claudia Toro, Maria Grazia Valsecchi, Lynda M Vrooman, Sigal Weinreb, Naomi Winick, Kjeld Schmiegelow, Andishe Attarbaschi, Madeline R Adams, Liv Andres-Jensen, Edit Bardi, Shlomit Barzilai-Birenboim, Katja Baust, Deepa Bhojwani, Tineke Boesten, Gabriele Calaminus, Rachel Conyers, Anne-Sophie Darlington, Maëlle de Ville, Gabriele Escherich, Melanie Hagleitner, Christina Halsey, Arja Harila-Saari, Jen-Yin Hou, Ting-Huan Huang, Melissa Hudson, Sima Jeha, Meriel Jenney, Motohiro Kato, Maryna Krawczuk-Rybak, Leontine Kremer, Melchior Lautem, Hse-Che Liu, Elixabet Lopez Lopez, Marion Mateos, Wojciech Mlynarski, Anja Möricke, Katarzyna Muszynska-Roslan, Riitta Niinimaki, Rob Pieters, Caroline Piette, Elizabeth Raetz, Leila Ronceray, Kjeld Schmiegelow, Claudia Toro, Toby Trahair, Maria Grazia Valsecchi, Inge van der Sluis, Raphaële van Litsenburg, Lynda Vrooman, Sigal Weinreb, Andreas Wiener, Naomi Winick, Michihiro Yano, Ting-Chi Yeh, Ester Zapotocka
Journal: The Lancet Haematology (2021)
Respiratory disease, and treatment / thematic poster session impact of the uk lockdown on early copd
Authors: G. C. Donaldson, A. I. Ritchie, F. McLean, B. King, K. Yip, A. S. Beech, A. Bikov, A. R. Jenkins, A. Deans, C. E. Bolton, P. M. Calverley, G. Choudhury, L. McGarvey, E. Sapey, J. Vestbo, J. A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

INTRODUCTION: Public health measures to reduce the transmission of COVID-19 have required various changes in life-style, including loss or risk to employment and social isolation. We wished to assess how these measured effected 30-45 year old smokers at risk of COPD participating in the BLF Early COPD cohort study METHODS: At enrolment, participants were aged 30-45 years, tobacco smokers with >10 pack-year smoking history, FEV1=>80% predicted and a BMI < 35kg/m2. Participants were seen face-to-face in clinic pre-COVID. During lock-down, they were posted questionnaires and contacted by telephone. The last clinic visit took place on the 12 March 2020, remote visits took place between 16 April and 28 Sep. 260 individuals at six sites (25 Belfast, 38 Birmingham, 25 Edinburgh, 101 London, 27 Manchester and 44 Nottingham) were asked about smoking habits. The MRC chronic bronchitis questionnaire, COPD Assessment test (CAT), Leicester cough questionnaire, Hospital Anxiety and Depression questionnaire were completed in writing by the participant and returned by post or photographed and returned by email. At enrolment, the post-BD FEV1 was 3.81 (SD 0.8) litres, 101% (11) of GLI predicted. Comparisons were made by paired t-tests and chi-squared tests. RESULTS: Level of anxiety increased from 6.74 (SD 4.4) to 7.37 (SD 4.7, n=233;p=0.010) during lock-down;depression scores increased from 4.30 (3.9) to 5.14 (SD 4.1;n=233;p<0.001). Anxiety increased in 78/233 and depression in 89/233 participants by 2 or more units, 2 units is considered the minimally important (MCID) in bronchiectasis, COPD and ILD (Wynne, 2020) Figure 1 shows that during lock-down, the proportion of participants not smoking increased from 31/259 (12.0%) to 62/259 (23.9%;p<0.001). In those who continued to smoke, cigarettes per day (p=0.59) and rolling tobacco consumption (g/week) (p=0.92) were unchanged. Participants reported less chronic bronchitis defined as “do you bring up phlegm like this on most days (or nights) as much as three months each year”, fell from 83/260 (31.9%) participants to 74/259 (28.6%;p<0.001). CAT scores fell from 10.5 (SD 6.4) to 9.6 (SD 6.3;n=233;p=0.007) and total cough score improved from 18.7 (SD 2.7) to 19.1 (2.6;n=204;p=0.007). CONCLUSIONS: Despite increased anxiety and depression, participants quit smoking and those that continued to smoke, did not smoke more. Respiratory symptoms of chronic bronchitis, cough and CAT scores improved. REFERENCES:Wynne SC, et al. Chron Respir Dis. 2020 Jan-Dec;17:1479973120933292. doi: 10.1177/1479973120933292. .
Serum uric acid control for prevention of gout flare in patients with asymptomatic hyperuricaemia: a retrospective cohort study of health insurance claims and medical check-up data in Japan
Authors: Ruriko Koto, Akihiro Nakajima, Hideki Horiuchi, Hisashi Yamanaka
Journal: Annals of the Rheumatic Diseases (2021)

Objectives In patients with gout, treating to target serum uric acid levels (sUA) of ≤6.0 mg/dL is universally recommended to prevent gout flare. However, there is no consensus on asymptomatic hyperuricaemia. Using Japanese health insurance claims data, we explored potential benefits of sUA control for preventing gout flare in subjects with asymptomatic hyperuricaemia. Methods This retrospective cohort study analysed the JMDC Claims Database from April 2012 through June 2019. Subjects with sUA ≥8.0 mg/dL were identified, and disease status (prescriptions for urate-lowering therapy (ULT), occurrence of gout flare, sUA) was investigated for 1 year. Time to first onset and incidence rate of gout flare were determined by disease status subgroups for 2 years or more. The relationship between gout flare and sUA control was assessed using multivariable analysis. Results The analysis population was 19 261 subjects who met eligibility criteria. We found fewer occurrences of gout flare, for both gout and asymptomatic hyperuricaemia, in patients who achieved sUA ≤6.0 mg/dL with ULT than in patients whose sUA remained &gt;6.0 mg/dL or who were not receiving ULT. In particular, analysis by a Cox proportional-hazard model for time to first gout flare indicated that the HR was lowest, at 0.45 (95% CI 0.27 to 0.76), in subjects with asymptomatic hyperuricaemia on ULT (5.0&lt;sUA ≤ 6.0 mg/dL), compared with untreated subjects (sUA ≥8.0 mg/dL). Conclusions Occurrences of gout flare were reduced by controlling sUA at ≤6.0 mg/dL in subjects with asymptomatic hyperuricaemia as well as in those with gout. Trial registration number UMIN000039985.
Determining the Association of Preoperative Controlled Prescription Medication Use With Outcomes After Total Knee Arthroplasty
Authors: Kevin X. Farley, Jacob M. Wilson
Journal: JAMA Network Open (2021)

Ahmed K. Emara, MD; Daniel Santana, BS; Daniel Grits, BS; Alison K. Klika, MS; Viktor E. Krebs, MD; Robert M. Molloy, MD; Nicolas S. Piuzzi, MD
Applicability and Prognostic Significance of Flow Cytometric Cerebrospinal Fluid Investigation in Children with Acute Lymphoblastic Leukemia
Authors: Alexander Popov, Tatiana Verzhbitskaya, Julia Roumiantseva, Svetlana Lagoiko, Grigory Tsaur, Olga Khlebnikova, Olga Streneva, Alexander Karachunsky, Larisa Fechina
Journal: Blood (2017)
Clinical utility of whole-genome sequencing in precision oncology
Authors: Richard Rosenquist, Edwin Cuppen, Reinhard Buettner, Carlos Caldas, Helene Dreau, Olivier Elemento, Geert Frederix, Sean Grimmond, Torsten Haferlach, Vaidehi Jobanputra, Manja Meggendorfer, Charles G. Mullighan, Sarah Wordsworth, Anna Schuh
Journal: Seminars in Cancer Biology (2021)
Helpful technical notes for intraperitoneal natural orifice transluminal endoscopic surgery (NOTES) salvage in a failed EUS-guided gastroenterostomy scenario
Authors: Joan B. Gornals, Claudia F. Consiglieri, Sandra Maisterra, Albert Garcia-Sumalla, Julio G. Velasquez-Rodriguez, Carme Loras
Journal: Endoscopy (2021)

The main reasons for dislodgement of the distal flange of a lumen-apposing metal stent (LAMS) into the peritoneum during endoscopic ultrasound (EUS)-guided gastroenterostomy are that the delivery catheter pushes away the small bowel without entering it, or else that advancement of a preloaded guidewire tents away the jejunal loop (in both cases, the EUS window is lost).
Infographic. Exercise-based prevention programmes for non-contact musculoskeletal injuries in football (soccer)
Authors: Italo Ribeiro Lemes, Thales R Souza, Danilo De Oliveira Silva, Vitor N Lage, Bárbara A B Roch, Evert Verhagen, Caroline Bolling, Cecilia Ferreira Aquino, Sérgio T Fonseca, Rafael Zambelli Pinto
Journal: British Journal of Sports Medicine (2021)

There are ~250 million people worldwide playing football (soccer). Despite the health benefits of playing sports, there is an inherent risk of sustaining injuries. Non-contact musculoskeletal injuries account for up to 66% of all muscle and joint/ligament injuries in football.1 Identifying effective strategies to reduce the occurrence of non-contact injuries in football is crucial for athletes and their teams. Previous reviews suggest that exercise-based prevention programmes reduce the risk of overall injuries by 22%–25% among women and recreational football players.2 3 However, there was no study summarising the effects of …
Abstract 419: Conserved Age-associated Cytoskeletal Remodeling Improves Cardiac Function and Lifespan
Authors: Gaurav Kaushik, Alice Spenlehauer, Ayla O Sessions, Adriana S Trujillo, Alexander Fuhrmann, Zongming Fu, Vidya Venkatraman, Danielle Pohl, Jeremy Tuler, Mingyi Wang, Edward G Lakatta, Karen Ocorr, Rolf Bodmer, Sanford I Bernstein, Jennifer E Van Eyk, Anthony Cammarato, Adam J Engler
Journal: Circulation Research (2016)

The human heart is capable of functioning for decades despite minimal cell turnover or regeneration, suggesting that molecular alterations help sustain heart function with age. However, identification of compensatory remodeling events in the aging heart remains elusive. We present the cardiac proteomes of young and old rhesus monkeys and rats, from which we show that certain age-associated remodeling events within the cardiomyocyte cytoskeleton are highly conserved and beneficial rather than deleterious. Targeted transcriptomic analysis in Drosophila confirmed conservation and implicated vinculin as a unique molecular regulator of cardiac function during aging. Cardiac-restricted vinculin overexpression reinforced the cortical cytoskeleton and enhanced myofilament organization, leading to improved contractility and hemodynamic stress tolerance in healthy and myosindeficient fly hearts. Moreover, cardiac-specific vinculin overexpression increased median life span by more than 150% in flies and preserved their physical activity. A broad array of potential therapeutic targets and regulators of age-associated modifications, specifically for vinculin, are presented and suggest altered metabolism as a system mechanism for lifespan extension. These findings suggest that the heart has molecular mechanisms to sustain performance and promote longevity, which may be assisted by therapeutic intervention to ameliorate the decline of function in aging patient hearts.
Gender Disparities in Journal Citations—Another Metric of Inequity in Academia
Authors: Helen R. Burstin, Vineet M. Arora
Journal: JAMA Network Open (2021)

While women are increasingly represented in the medical profession, they continue to face significant barriers to advancement in academic medicine.Research consistently demonstrates disparities for women in academic promotion, journal authorship, research funding, leadership roles, and compensation.A recent article 1 demonstrated that the gap for women to advance to associate professor, full professor, or department chair has not narrowed over time and has likely worsened during the pandemic.Elsewhere in JAMA Network Open, Chatterjee and Werner 2 describe a novel metric of gender inequity that may offer another reason for the lagging advancement of women in academic medicine-a disparity in citations of women's research in high-impact journals.The timely and important article demonstrates two important findings: women are less likely to be published in highimpact journals, and they are less likely to have their research cited by others.The combination of men primary and senior authors was most frequently cited, while women primary and senior authors were less likely to be cited.While others have previously noted disparities in publication in highimpact journals, 3 this article goes further by demonstrating that even after achieving the goal of publication in a high-impact journal, women's research is less likely to be cited and amplified.The authors note that research citations are often used in promotion and academic advancement as a proxy for scholarly impact.Although women researchers increasingly publish in prestigious journals, advancement can be
The European Medicines Agency Review of Crizanlizumab for the Prevention of Recurrent Vaso-Occlusive Crises in Patients With Sickle Cell Disease
Authors: Julio Delgado, Caroline Voltz, Milena Stain, Tuomo Lapveteläinen, Susanne Urach, Johanna Lähteenvuo, Karri Penttilä, Christian Gisselbrecht, Harald Enzmann, Francesco Pignatti
Journal: HemaSphere (2021)

Crizanlizumab is a monoclonal antibody that binds to P-selectin. On October 28, 2020, a conditional marketing authorization valid through the European Union (EU) was issued for crizanlizumab for the prevention of recurrent vaso-occlusive crises (VOCs) in patients with sickle cell disease aged 16 years or older. Crizanlizumab was evaluated in a phase 2, double-blind, placebo-controlled randomized multicenter trial comparing high-dose (5 mg/kg) crizanlizumab, low-dose (2.5 mg/kg) crizanlizumab and placebo in patients with a history of 2–10 VOCs in the previous year. Patients who were receiving concomitant hydroxycarbamide (HC) as well as those not receiving HC were included in the study. The primary endpoint of the trial was the annual rate of sickle cell-related pain crises as adjudicated by a central review committee. High-dose crizanlizumab led to a 45.3% lower median annual rate of sickle cell-related pain crises compared to placebo ( P = 0.010), with no statistically significant difference for the low dose. Treatment with high-dose crizanlizumab led to similar incidences of adverse events (AEs), grade 3 AEs, and serious AEs compared to placebo. Most frequently observed AEs that occurred more often in the crizanlizumab arm compared to placebo were infusion related reactions (34.8% versus 21%), arthralgia (18.2% versus 8.1%), diarrhea (10.6% versus 3.2%), and nausea (18.2% versus 11.3%). The aim of this article is to summarize the scientific review of the application leading to regulatory approval in the EU.
Covid-19: the last incompetently managed pandemic?
Authors: Steven Ford
Journal: BMJ (2021)

“Make it the last pandemic,” urges the report of the Independent Panel for Pandemic Preparedness and Response.1 Could there be a more fatuous remark?

Pandemics are foreseeable, foreseen, have been with us always, and will, almost certainly, be with us forever. Biology does not negotiate and is inherently capricious and chaotic. Preparation, mitigation, and coordinated global action can be accomplished, but centuries or millennia will pass before “the last pandemic” …
TGM4: an immunogenic prostate-restricted antigen
Authors: Zoila A Lopez-Bujanda, Aleksandar Obradovic, Thomas R Nirschl, Laura Crowley, Rodney Macedo, Alexandros Papachristodoulou, Timothy O’Donnell, Uri Laserson, Jelani C Zarif, Ran Reshef, Tiezheng Yuan, Mithil K Soni, Emmanuel S Antonarakis, Michael C Haffner, H Benjamin Larman, Michael M Shen, Pawel Muranski, Charles G Drake
Journal: Journal for ImmunoTherapy of Cancer (2021)

Background Prostate cancer is the second leading cause of cancer-related death in men in the USA; death occurs when patients progress to metastatic castration-resistant prostate cancer (CRPC). Although immunotherapy with the Food and Drug Administration‐approved vaccine sipuleucel‐T, which targets prostatic acid phosphatase (PAP), extends survival for 2–4 months, the identification of new immunogenic tumor-associated antigens (TAAs) continues to be an unmet need. Methods We evaluated the differential expression profile of castration-resistant prostate epithelial cells that give rise to CRPC from mice following an androgen deprivation/repletion cycle. The expression levels of a set of androgen-responsive genes were further evaluated in prostate, brain, colon, liver, lung, skin, kidney, and salivary gland from murine and human databases. The expression of a novel prostate-restricted TAA was then validated by immunostaining of mouse tissues and analyzed in primary tumors across all human cancer types in The Cancer Genome Atlas. Finally, the immunogenicity of this TAA was evaluated in vitro and in vivo using autologous coculture assays with cells from healthy donors as well as by measuring antigen-specific antibodies in sera from patients with prostate cancer (PCa) from a neoadjuvant clinical trial. Results We identified a set of androgen-responsive genes that could serve as potential TAAs for PCa. In particular, we found transglutaminase 4 (Tgm4) to be highly expressed in prostate tumors that originate from luminal epithelial cells and only expressed at low levels in most extraprostatic tissues evaluated. Furthermore, elevated levels of TGM4 expression in primary PCa tumors correlated with unfavorable prognosis in patients. In vitro and in vivo assays confirmed the immunogenicity of TGM4. We found that activated proinflammatory effector memory CD8 and CD4 T cells were expanded by monocyte-derived dendritic cell (moDCs) pulsed with TGM4 to a greater extent than moDCs pulsed with either PAP or prostate-specific antigen (PSA), and T cells primed with TGM4-pulsed moDCs produce functional cytokines following a prime/boost regiment or in vitro stimulation. An IgG antibody response to TGM4 was detected in 30% of vaccinated patients, while fewer than 8% of vaccinated patients developed antibody responses to PSA or prostate-specific membrane antigen (PSMA). Conclusions These results suggest that TGM4 is an immunogenic, prostate-restricted antigen with the potential for further development as an immunotherapy target.
Abstract 410: Novel Sulfonylhydrazone Derivative Prevents Cardiac and Vascular Remodeling in Rats With Streptozotocin-induced Diabetes
Authors: Roberto T Sudo, Josenildo S Araujo, Ananssa M Silva, Allan K Alencar, Mateus S Delgobbo, Thiago F Silva, Margarete M Trachez, Lidia M Lima, Eliezer J Barreiro, Gisele Zapata-Sudo
Journal: Circulation Research (2016)

Objectives: Investigate the effects of LASSBio-1773, a ligand of PPAR-gamma receptor with hypoglycemic activity, in a model of diabetic cardiomyopathy (DC) induced by streptozotocin (STZ). Methods: Male Wistar rats received a single i.v. injection of STZ (60 mg/kg) for diabetes induction. Experimental groups were: control, STZ + vehicle, and STZ + LASSBio-1773 (50 mg/kg/day i.p.). Animals were treated with vehicle or LASSBio-1773 for 7 days after disease onset. Cardiovascular function and plasma biochemistry evaluations were performed by the end of protocol. Findings: Serum glucose, total cholesterol and triglycerides levels were significantly higher in STZ group, and treatment with LASSBio-1773 normalized both hyperglycemia and hypertriglyceridemia (Table 1). Following 8 weeks of STZ injection, echocardiography showed that left ventricular (LV) filling pressures (E/e′) increased in STZ + vehicle group. Treatment with LASSBio-1773 improved diastolic parameters in STZ-injected rats but no changes were observed on LV ejection fraction (Table 1). STZ + vehicle group have developed hypertension which was reduced after treatment with LASSBio-1773 (Table 1). Vascular dysfunction was found by the reduced acetylcholine maximum relaxation (Ach-MR) in isolated aortic rings from STZ + vehicle group which was improved with LASSBio-1773 administration. Conclusions: LASSBio-1773 improved cardiovascular function and lipid profile of diabetic rats, indicating that this novel PPAR-gamma agonist is a promising candidate for the treatment of diabetes-related cardiac complications.
Abstract 446: Availability and Quality of Cardiopulmonary Resuscitation Films Featuring a Female Victim on the Internet: A Cross-Sectional Study
Authors: Carlos Lynes, Lorrel Brown
Journal: Circulation (2019)

Introduction: Bystander cardiopulmonary (CPR) improves survival following out-of-hospital cardiac arrest (OHCA). However, women are less likely than men to receive CPR in public locations. Female-specific issues such as fear of touching breasts have been identified as barriers to performing CPR on women. The purpose of this study was to quantify and evaluate online CPR instructional films featuring a female victim. Methods: Using the search query “how to do CPR” via Google and YouTube, 374 and 500 films (38 and 25 result pages), respectively, were reviewed in May 2019. Exclusion criteria included: non-English, non-instructional, pediatric or animal victim, duplicates, parity, or in-hospital cardiac arrest. We identified 11 films featuring a female victim. These films were scored on 6 key aspects of CPR education: scene safety, check responsiveness, activate Emergency Medical Services, proper hand position, accurate rate, and appropriate depth of compressions. Results: Of the 874 reviewed films, 11 featured a female victim. Just 5 films were high-quality (correctly addressing 5 or 6 key aspects of CPR training, Figure 1). Furthermore, 2 of the 5 high-quality instructional films taught rescue breathing, which is no longer a recommended component of bystander CPR in the U.S. The remaining 3 films were all created outside the U.S. (Australia, New Zealand, England). None of the films explicitly addressed barriers to performing CPR on a female, including fear of touching breasts or concerns about causing harm. Conclusion: Out of the billions of films available online, we identified only 3 high-quality instructional films teaching modern, hands-only CPR featuring a female victim, none of which addressed specific female-related CPR issues. This gender disparity can be addressed with high-quality CPR training films that feature a female victim and explicitly address previously-identified barriers to performing CPR on a female.