tbuckley/cabot-search huggingface dataset:
Historical Introgression from Wild Relatives Enhanced Climatic Adaptation and Resistance to Pneumonia in Sheep
Authors: Yin-Hong Cao, Song-Song Xu, Min Shen, Ze-Hui Chen, Lei Gao, Feng-Hua Lv, Xing-Long Xie, Xin-Hua Wang, Hua Yang, Chang-Bin Liu, Ping Zhou, Peng-Cheng Wan, Yun-Sheng Zhang, Jing-Quan Yang, Wen-Hui Pi, EEr Hehua, Donagh P Berry, Mario Barbato, Ali Esmailizadeh, Maryam Nosrati, Hosein Salehian-Dehkordi, Mostafa Dehghani-Qanatqestani, Arsen V Dotsev, Tatiana E Deniskova, Natalia A Zinovieva, Gottfried Brem, Ondřej Štěpánek, Elena Ciani, Christina Weimann, Georg Erhardt, Joram M Mwacharo, Abulgasim Ahbara, Jian-Lin Han, Olivier Hanotte, Joshua M Miller, Zijian Sim, David Coltman, Juha Kantanen, Michael W Bruford, Johannes A Lenstra, James Kijas, Meng-Hua Li
Journal: Molecular Biology and Evolution (2020)

Abstract How animals, particularly livestock, adapt to various climates and environments over short evolutionary time is of fundamental biological interest. Further, understanding the genetic mechanisms of adaptation in indigenous livestock populations is important for designing appropriate breeding programs to cope with the impacts of changing climate. Here, we conducted a comprehensive genomic analysis of diversity, interspecies introgression, and climate-mediated selective signatures in a global sample of sheep and their wild relatives. By examining 600K and 50K genome-wide single nucleotide polymorphism data from 3,447 samples representing 111 domestic sheep populations and 403 samples from all their seven wild relatives (argali, Asiatic mouflon, European mouflon, urial, snow sheep, bighorn, and thinhorn sheep), coupled with 88 whole-genome sequences, we detected clear signals of common introgression from wild relatives into sympatric domestic populations, thereby increasing their genomic diversities. The introgressions provided beneficial genetic variants in native populations, which were significantly associated with local climatic adaptation. We observed common introgression signals of alleles in olfactory-related genes (e.g., ADCY3 and TRPV1) and the PADI gene family including in particular PADI2, which is associated with antibacterial innate immunity. Further analyses of whole-genome sequences showed that the introgressed alleles in a specific region of PADI2 (chr2: 248,302,667–248,306,614) correlate with resistance to pneumonia. We conclude that wild introgression enhanced climatic adaptation and resistance to pneumonia in sheep. This has enabled them to adapt to varying climatic and environmental conditions after domestication.
Antibiotics for paediatric community-acquired pneumonia in resource-constrained settings
Authors: Amy Sarah Ginsburg, Keith P. Klugman
Journal: European Respiratory Journal (2020)

Despite Streptococcus pneumoniae and Haemophilus influenzae type b vaccination strategies, pneumonia remains the leading infectious cause of child mortality. Greater access to appropriate treatment is critical; however, defining "appropriate" is problematic. World Health Organization (WHO) guidelines recommend diagnosing pneumonia using clinical signs and a non-specific, pragmatic case definition: fast breathing or chest indrawing (pneumonia) and presence of WHO danger signs (severe pneumonia) in children with cough or difficulty breathing [1]. It is unclear whether all "pneumonia" using these definitions needs to be treated with antibiotics, and if so, for how long. 3 days of amoxicillin may be sufficient to treat most non-severe community-acquired paediatric pneumonia in resource-constrained settings <https://bit.ly/3jmQSTX>
Same Day Bilateral Cataract Surgery—Who Benefits?
Authors: Samuel Masket
Journal: Ophthalmology (2020)

There was a time when decision making in health care followed a simple credo: If the treatment process was good for the patient, it was good for the doctor and good for the healthcare industry. That was a different day; times have changed. We are presently in an era when concerns about costs and convenience of healthcare delivery and third-party profit margins may, and sometimes do, seemingly exceed the interests of the individual patient. To my sense, routine simultaneous same-day bilateral cataract surgery (SDBCS) is emblematic of that shifting paradigm.
The Intersection of Mechanotransduction and Regenerative Osteogenic Materials
Authors: Anthony A. Bertrand, Sri Harshini Malapati, Dean T. Yamaguchi, Justine C. Lee
Journal: Advanced Healthcare Materials (2020)

Abstract Mechanical signals play a central role in cell fate determination and differentiation in both physiologic and pathologic circumstances. Such signals may be delivered using materials to generate discrete microenvironments for the purposes of tissue regeneration and have garnered increasing attention in recent years. Unlike the addition of progenitor cells or growth factors, delivery of a microenvironment is particularly attractive in that it may reduce the known untoward consequences of the former two strategies, such as excessive proliferation and potential malignant transformation. Additionally, the ability to spatially modulate the fabrication of materials allows for the creation of multiple microenvironments, particularly attractive for regenerating complex tissues. While many regenerative materials have been developed and tested for augmentation of specific cellular responses, the intersection between cell biology and material interactions have been difficult to dissect due to the complexity of both physical and chemical interactions. Specifically, modulating materials to target individual signaling pathways is an avenue of interdisciplinary research that may lead to a more effective method of optimizing regenerative materials. In this work, the aim is to summarize the major mechanotransduction pathways for osteogenic differentiation and to consolidate the known materials and material properties that activate such pathways.
Response to Comment on Chen et al. Clinical Characteristics and Outcomes of Patients With Diabetes and COVID-19 in Association With Glucose-Lowering Medication. Diabetes Care 2020;43:1399–1407
Authors: Yuchen Chen, Dong Yang, Chen Yang, Ling Zheng, Kun Huang
Journal: Diabetes Care (2020)

We appreciate the comments by Cariou et al. (1) regarding our investigation (2) and their intermediate analysis of the CORONADO (CORONAvirus SARS-CoV-2 and Diabetes Outcomes) study (3), and we thank them for sharing important points. Currently, joint early efforts reveal that patients with diabetes and coronavirus disease 2019 (COVID-19) undergo more severe inflammation and worse prognosis, and no evidence suggests the need for stopping any glucose-lowering therapy (2,3), since high blood glucose during hospitalization has also been suggested as a risk factor for poor outcomes in patients with diabetes with COVID-19 (4).

We acknowledge Cariou et al. for sharing additional independent predictive factors associating with early death on day …
The authors reply
Authors: Rimda Wanchoo, Maria Louise Barilla-LaBarca, Kenar D. Jhaveri
Journal: Kidney International (2020)

We thank Hasbal for the concern expressed1Hasbal N.B. Thrombotic microangiopathy: COVID-19 or hydroxychloroquine?.Kidney Int. 2020; 98: 1619-1620Abstract Full Text Full Text PDF PubMed Scopus (6) Google Scholar regarding hydroxychloroquine (HCQ) as the cause of the thrombotic microangiopathy (TMA) in our published case titled "Thrombotic Microangiopathy in a Patient With COVID-19."2Jhaveri K.D. Meir L.R. Flores Chang B.S. et al.Thrombotic microangiopathy in a patient with COVID-19.Kidney Int. 2020; 98: 509-512Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar An immune-mediated thrombotic microangiopathy usually requires ongoing exposure to the drug. In our case, the patient mentioned was on HCQ for a duration of 5 days. The initial 2 doses were prior to admission, and the drug was continued during the initial 3 days of hospitalization. The findings of hemolysis and TMA developed on day 17 of the admission, which was 2 weeks after the drug had been discontinued. In reports from both Fromm et al.3Fromm L.M. Suspected hydroxychloroquine-induced thrombotic thrombocytopenic purpura.J Pharm Pract Res. 2018; 48: 72-75Crossref Scopus (7) Google Scholar and Mar et al.4Mar N. Mendoza Ladd A. Acquired thrombotic thrombocytopenic purpura: puzzles, curiosities and conundrums.J Thromb Thrombolysis. 2011; 31: 119-121Crossref PubMed Scopus (5) Google Scholar that were mentioned, TMA developed during the duration of treatment with HCQ. In addition, the most commonly used indication for HCQ is systemic lupus erythematosus, and we have to keep in mind that systemic lupus erythematosus can also lead to systemic TMA.5Song D. Wu L.H. Wang F.M. et al.The spectrum of renal thrombotic microangiopathy in lupus nephritis.Arthritis Res Ther. 2013; 15: R12Crossref PubMed Scopus (169) Google Scholar In our case, the short course of HCQ, the stability of lactate dehydrogenase, anemia, and platelets for 2 weeks, and the delayed development of TMA, weeks after the drug was discontinued, suggest against the possibility of HCQ-related TMA. KDJ serves as a consultant for Astex Pharmaceuticals and Natera. All the other authors declared no competing interests. Thrombotic microangiopathy in a patient with COVID-19Kidney InternationalVol. 98Issue 2PreviewWe describe a patient with coronavirus disease 2019 (COVID-19) and clinically significant kidney biopsy-proven thrombotic microangiopathy. Full-Text PDF Thrombotic microangiopathy: COVID-19 or hydroxychloroquine?Kidney InternationalVol. 98Issue 6PreviewI read with great interest the letter to the editor by Jhaveri et al. reporting the first published case report of thrombotic microangiopathy in a patient with coronavirus disease 2019 (COVID-19).1 Although there was a clear temporal relationship between the presentation with COVID-19 and development of thrombotic microangiopathy, I wonder whether the authors considered the possibility of a drug-induced thrombotic microangiopathy, in particular hydroxychloroquine, which was introduced on day 1 of admission. Full-Text PDF
Antibiotic prescribing for lower UTI in elderly patients in primary care and risk of bloodstream infection: A cohort study using electronic health records in England
Authors: Laura Shallcross, Patrick Rockenschaub, Ruth Blackburn, Irwin Nazareth, Nick Freemantle, Andrew Hayward
Journal: PLoS Medicine (2020)

Background Research has questioned the safety of delaying or withholding antibiotics for suspected urinary tract infection (UTI) in older patients. We evaluated the association between antibiotic treatment for lower UTI and risk of bloodstream infection (BSI) in adults aged ≥65 years in primary care. Methods and findings We analyzed primary care records from patients aged ≥65 years in England with community-onset UTI using the Clinical Practice Research Datalink (2007–2015) linked to Hospital Episode Statistics and census data. The primary outcome was BSI within 60 days, comparing patients treated immediately with antibiotics and those not treated immediately. Crude and adjusted associations between exposure and outcome were estimated using generalized estimating equations. A total of 147,334 patients were included representing 280,462 episodes of lower UTI. BSI occurred in 0.4% (1,025/244,963) of UTI episodes with immediate antibiotics versus 0.6% (228/35,499) of episodes without immediate antibiotics. After adjusting for patient demographics, year of consultation, comorbidities, smoking status, recent hospitalizations, recent accident and emergency (A&E) attendances, recent antibiotic prescribing, and home visits, the odds of BSI were equivalent in patients who were not treated with antibiotics immediately and those who were treated on the date of their UTI consultation (adjusted odds ratio [aOR] 1.13, 95% CI 0.97–1.32, p-value = 0.105). Delaying or withholding antibiotics was associated with increased odds of death in the subsequent 60 days (aOR 1.17, 95% CI 1.09–1.26, p-value < 0.001), but there was limited evidence that increased deaths were attributable to urinary-source BSI. Limitations include overlap between the categories of immediate and delayed antibiotic prescribing, residual confounding underlying differences between patients who were/were not treated with antibiotics, and lack of microbiological diagnosis for BSI. Conclusions In this study, we observed that delaying or withholding antibiotics in older adults with suspected UTI did not increase patients' risk of BSI, in contrast with a previous study that analyzed the same dataset, but mortality was increased. Our findings highlight uncertainty around the risks of delaying or withholding antibiotic treatment, which is exacerbated by systematic differences between patients who were and were not treated immediately with antibiotics. Overall, our findings emphasize the need for improved diagnostic/risk prediction strategies to guide antibiotic prescribing for suspected UTI in older adults.
Synaptopodin Is Dispensable for Normal Podocyte Homeostasis but Is Protective in the Context of Acute Podocyte Injury
Authors: Liang Ning, Hani Y. Suleiman, Jeffrey H. Miner
Journal: Journal of the American Society of Nephrology (2020)

Synaptopodin (Synpo) is an actin-associated protein in podocytes and dendritic spines. Many functions in regulating the actin cytoskeleton via RhoA and other pathways have been ascribed to Synpo, yet no pathogenic mutations in the SYNPO gene have been discovered in patients. Naturally occurring Synpo isoforms are known (Synpo-short and -long), and a novel truncated version (Synpo-T) is upregulated in podocytes from Synpo mutant mice. Synpo-T maintains some Synpo functions, which may prevent a podocyte phenotype from emerging in unchallenged mutant mice.Novel mouse models were generated to further investigate the functions of Synpo. In one, CRISPR/Cas9 deleted most of the Synpo gene, preventing production of any detectable Synpo protein. Two other mutant strains made truncated versions of the protein. Adriamycin injections were used to challenge the mice, and Synpo functions were investigated in primary cultured podocytes.Mice that could not make detectable Synpo (Synpo-/- ) did not develop any kidney abnormalities up to 12 months of age. However, Synpo-/- mice were more susceptible to Adriamycin nephropathy. In cultured primary podocytes from mutant mice, the absence of Synpo caused loss of stress fibers, increased the number and size of focal adhesions, and impaired cell migration. Furthermore, loss of Synpo led to decreased RhoA activity and increased Rac1 activation.In contrast to previous findings, podocytes can function normally in vivo in the absence of any Synpo isoform. Synpo plays a protective role in the context of podocyte injury through its involvement in actin reorganization and focal adhesion dynamics.
Asymptomatic COVID-19 Infection Detected on 18F-FDG PET/CT Scan Done for Multiple Myeloma
Authors: Ravishankar Pillenahalli Maheshwarappa, Michael Moore Graham
Journal: Clinical Nuclear Medicine (2020)

A 69-year-old woman with multiple myeloma came to our department for F-FDG PET/CT scan for routine surveillance. The patient denied any history of fever, cough, shortness of breath, or body aches. F-FDG PET/CT scan from vertex to knees was performed. PET/CT images revealed extensive peripheral ground-glass opacities showing intense FDG uptake (SUVmax 12) involving bilateral lower lobes. Possibility of an infective etiology including novel coronavirus (COVID-19) infection was raised. The patient's oropharyngeal swab for COVID-19 by polymerase chain reaction amplification test came back positive for COVID-19 infection. The patient and her husband were advised home quarantine for 14 days.
Poly-IC enhances the effectiveness of cancer immunotherapy by promoting T cell tumor infiltration
Authors: Hussein Sultan, Juan Wu, Valentyna I Fesenkova, Aaron E Fan, Diane Addis, Andres M Salazar, Esteban Celis
Journal: Journal for ImmunoTherapy of Cancer (2020)

Background Immunotherapies, such as immune checkpoint inhibitors and adoptive cell therapies, have revolutionized cancer treatment and resulted in complete and durable responses in some patients. Unfortunately, most immunotherapy treated patients still fail to respond. Absence of T cell infiltration to the tumor site is one of the major obstacles limiting immunotherapy efficacy against solid tumors. Thus, the development of strategies that enhance T cell infiltration and broaden the antitumor efficacy of immunotherapies is greatly needed. Methods We used mouse tumor models, genetically deficient mice and vascular endothelial cells (VECs) to study the requirements for T cell infiltration into tumors. Results A specific formulation of poly-IC, containing poly-lysine and carboxymethylcellulose (PICLC) facilitated the traffic and infiltration of effector CD8 T cells into the tumors that reduced tumor growth. Surprisingly, intratumoral injection of PICLC was significantly less effective in inducing tumor T cell infiltration and controlling growth of tumors as compared with systemic (intravenous or intramuscular) administration. Systemically administered PICLC, but not poly-IC stimulated tumor VECs via the double-stranded RNA cytoplasmic sensor MDA5, resulting in enhanced adhesion molecule expression and the production of type I interferon (IFN-I) and T cell recruiting chemokines. Expression of IFNαβ receptor in VECs was necessary to obtain the antitumor effects by PICLC and IFN-I was found to directly stimulate the secretion of T cell recruiting chemokines by VECs indicating that this cytokine-chemokine regulatory axis is crucial for recruiting effector T cells into the tumor parenchyma. Unexpectedly, these effects of PICLC were mostly observed in tumors and not in normal tissues. Conclusions These findings have strong implications for the improvement of all types of T cell-based immunotherapies for solid cancers. We predict that systemic administration of PICLC will improve immune checkpoint inhibitor therapy, adoptive cell therapies and therapeutic cancer vaccines.
18F-FDG PET/CT Findings of an Isolated Splenic Metastasis From Endometrial Adenocarcinoma
Authors: Tingting Xu, Bing Cen, Lin Liu, Yingwei Wang, Yue Chen
Journal: Clinical Nuclear Medicine (2020)

Abstract Splenic metastasis from endometrial carcinoma is rare, especially when the spleen is the sole metastatic site. Herein, we report the case of a 47-year-old woman with a history of endometrial adenocarcinoma diagnosed 1 year ago. At that time, she underwent total abdominal hysterectomy, bilateral salpingo-oophorectomy, and pelvic node dissection. Restaging 18 F-FDG PET/CT demonstrated an isolated splenic mass with elevated FDG activity. There were no other signs of recurrence. The lesion was surgically resected and diagnosed as a metastasis from the endometrial adenocarcinoma.
Audio Interview: Eight Months of Action and Inaction against Covid-19
Authors: Eric J. Rubin, Lindsey R. Baden, Stephen Morrissey
Journal: New England Journal of Medicine (2020)

Eight Months of Action and Inaction against Covid-19 In this audio interview conducted on September 23, 2020, as global deaths near 1 million and U.S. deaths pass 200,000, the editors reflect on 8 ...
The Importance of a Cause-Based Protocol to Approach Cancer-Related Nausea and Vomiting—Reply
Authors: Charles L. Loprinzi, Jennifer G. Le-Rademacher, Rudolph M. Navari
Journal: JAMA Oncology (2020)

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Response to Comment on Misra et al. Homozygous Hypomorphic <i>HNF1A</i> Alleles Are a Novel Cause of Young-Onset Diabetes and Result in Sulfonylurea-Sensitive Diabetes. Diabetes Care 2020;43:909–912
Authors: Shivani Misra, Neelam Hassanali, Amanda J. Bennett, Agata Juszczak, Richard Caswell, Kevin Colclough, Jonathan Valabhji, Sian Ellard, Nicholas S. Oliver, Anna L. Gloyn
Journal: Diabetes Care (2020)

We thank Wu et al. (1) for their correspondence. We agree, low levels of high-sensitivity C-reactive protein (hs-CRP) are characteristic of heterozygous loss-of-function mutations affecting HNF1A (2). Wu et al. query the interpretation of the heterozygous p.A251T variant being pathogenic on the basis of the father’s “‘higher” hs-CRP level; however, this comment is factually incorrect. Our data support that p.A251T is not maturity-onset diabetes of the young (MODY)-causing in the heterozygous state, as evidenced by the hs-CRP level in the heterozygous father who does not have diabetes and, notably, by the lack of response to sulfonylurea therapy and higher BMI in the heterozygous mother, who does have diabetes. We quite agree, and have acknowledged in the article, that there are likely to be other drivers of dysglycemia in the proband’s parents. This very point …