tbuckley/cabot-search huggingface dataset:
Altered pulmonary capillary blood volume in childhood sickle cell disease
Authors: Plamen Bokov, Priscilla Boizeau, Jade Pautrat, Florence Missud, Aissatou Ba, Zinédine Haouari, André Denjean, Christophe Delclaux, Malika Benkerrou
Journal: European Respiratory Journal (2020)

It has consistently been shown that patients with sickle cell disease (SCD) exhibit a compensatory increase in pulmonary capillary blood volume (PCBV), at least in a specific subgroup of patients [1]. This increase in PCBV could be related to the anaemia-induced increase in cardiac output [2]. Chaudry et al. [3] showed that SCD patients failed to recruit and dilate their pulmonary capillary bed to the same extent as control subjects for a given rise in effective pulmonary blood flow. One may therefore hypothesise that PCBV is already maximally recruited at rest; however, this has yet to be confirmed. Furthermore, it is not clear whether this potential defective pulmonary vascular recruitment is related to SCD history. Children with sickle cell disease have a pulmonary capillary blood volume that is already dilated at rest and that may initiate a restrictive defect <https://bit.ly/2MRaqkc> P. Bokov and C. Delclaux thank Nicole Beydon for initiating the subject of the present study.
Drugs That Regulate Local Cell Signaling: AKAP Targeting as a Therapeutic Option
Authors: Paula J. Bucko, John D. Scott
Journal: The Annual Review of Pharmacology and Toxicology (2020)

Cells respond to environmental cues by mobilizing signal transduction cascades that engage protein kinases and phosphoprotein phosphatases. Correct organization of these enzymes in space and time enables the efficient and precise transmission of chemical signals. The cyclic AMP-dependent protein kinase A is compartmentalized through its association with A-kinase anchoring proteins (AKAPs). AKAPs are a family of multivalent scaffolds that constrain signaling enzymes and effectors at subcellular locations to drive essential physiological events. More recently, it has been recognized that defective signaling in certain endocrine disorders and cancers proceeds through pathological AKAP complexes. Consequently, pharmacologically targeting these macromolecular complexes unlocks new therapeutic opportunities for a growing number of clinical indications. This review highlights recent findings on AKAP signaling in disease, particularly in certain cancers, and offers an overview of peptides and small molecules that locally regulate AKAP-binding partners.
ガッリ-ガッリ病はダウリング-デゴス病の棘融解異型である:ドイツの家族における付加的DNA鑑定による証拠
Authors: Schmieder Astrid, Leverkus Martin, M Pasternack Sandra, C Betz Regina, Krahl Dieter
Journal: Journal of the American Academy of Dermatology (2012)
MGMT Promoter Methylation as a Target In Metastatic Colorectal Cancer: Rapid Turnover and Use of Folates Alter its Study—Letter
Authors: Alessandro Ottaiano, Michele Caraglia
Journal: Clinical Cancer Research (2020)

We read with great interest the work by Pietrantonio and colleagues ([1][1]). O6 methyl-guanine methyltransferase (MGMT) is one of the most important biomarkers in glioblastomas showing predictive and prognostic power and its epigenetic silencing has a critical role in many other cancers ([2][2]).
Self-eating: friend or foe? The emerging role of autophagy in fibrotic diseases
Authors: Yajing Li, Runping Liu, Jianzhi Wu, Xiaojiaoyang Li
Journal: Theranostics (2020)

Fibrosis occurs in most human organs including the liver, lung, heart and kidney, and is crucial for the progression of most chronic diseases. As an indispensable catabolic process for intracellular quality control and homeostasis, autophagy occurs in most mammalian cells and is implicated in many biological processes including fibrogenesis. Although advances have been made in understanding autophagy process, the potential role of autophagy in fibrotic diseases remains controversial and has recently attracted a great deal of attention. In the current review, we summarize the commonalities of autophagy affecting different types of fibrosis in different organs, including the liver, lung, heart, and kidney as well as in cystic fibrosis, systematically outline the contradictory results and highlight the distinct role of autophagy during the various stages of fibrosis. In summary, the exact role autophagy plays in fibrogenesis depends on specific cell types and different stimuli, and identifying and evaluating the pathogenic contribution of autophagy in fibrogenesis will promote the discovery of novel therapeutic strategies for the clinical management of these fibrotic diseases.
Distal Symmetric Polyneuropathy in 2020
Authors: Brian C. Callaghan, Ray S. Price, Eva L. Feldman
Journal: JAMA (2020)

This JAMA Insights Clinical Update reviews the diagnosis and management of distal symmetric neuropathy, including control of risk factors (eg, high glucose in type 1 diabetes, weight loss) and use of nonpharmacologic and pharmacologic therapies (eg, SNRIs, tricyclic antidepressants, gabapentinoids).
Association of Medicaid Expansion Under the Affordable Care Act With Breast Cancer Stage at Diagnosis
Authors: Justin M. Le Blanc, Danielle R. Heller, Ann Friedrich, Donald R. Lannin, Tristen S. Park
Journal: JAMA Surgery (2020)

<h3>Importance</h3> The expansion of Medicaid sought to fill gaps in insurance coverage among low-income Americans. Although coverage has improved, little is known about the relationship between Medicaid expansion and breast cancer stage at diagnosis. <h3>Objective</h3> To review the association of Medicaid expansion with breast cancer stage at diagnosis and the disparities associated with insurance status, age, and race/ethnicity. <h3>Design, Setting, and Participants</h3> This cohort study used data from the National Cancer Database to characterize the relationship between breast cancer stage and race/ethnicity, age, and insurance status. Data from 2007 to 2016 were obtained, and breast cancer stage trends were assessed. Additionally, preexpansion years (2012-2013) were compared with postexpansion years (2015-2016) to assess Medicaid expansion in 2014. Data were analyzed from August 12, 2019, to January 19, 2020. The cohort included a total of 1 796 902 patients with primary breast cancer who had private insurance, Medicare, or Medicaid or were uninsured across 45 states. <h3>Main Outcomes and Measures</h3> Percent change of uninsured patients with breast cancer and stage at diagnosis, stratified by insurance status, race/ethnicity, age, and state. <h3>Results</h3> This study included a total of 1 796 902 women. Between 2012 and 2016, 71 235 (4.0%) were uninsured or had Medicaid. Among all races/ethnicities, in expansion states, there was a reduction in uninsured patients from 22.6% (4771 of 21 127) to 13.5% (2999 of 22 150) (<i>P</i> &lt; .001), and in nonexpansion states, there was a reduction from 36.5% (5431 of 14 870) to 35.6% (4663 of 13 088) (<i>P</i> = .12). Across all races, there was a reduction in advanced-stage disease from 21.8% (4603 of 21 127) to 19.3% (4280 of 22 150) (<i>P</i> &lt; .001) in expansion states compared with 24.2% (3604 of 14 870) to 23.5% (3072 of 13 088) (<i>P</i> = .14) in nonexpansion states. In African American patients, incidence of advanced disease decreased from 24.6% (1017 of 4136) to 21.6% (920 of 4259) (<i>P</i> &lt; .001) in expansion states and remained at approximately 27% (27.4% [1220 of 4453] to 27.5% [1078 of 3924];<i>P</i> = .94) in nonexpansion states. Further analysis suggested that the improvement was associated with a reduction in stage 3 diagnoses. <h3>Conclusions and Relevance</h3> In this cohort study, expansion of Medicaid was associated with a reduced number of uninsured patients and a reduced incidence of advanced-stage breast cancer. African American patients and patients younger than 50 years experienced particular benefit. These data suggest that increasing access to health care resources may alter the distribution of breast cancer stage at diagnosis.
Possible Protective Effect of Renin-Angiotensin System Inhibitors in COVID-19 Induced Acute Kidney Injury
Authors: Chia Siang Kow, Syed Shahzad Hasan
Journal: Journal of the American Society of Nephrology (2020)

A recent article by Batlle et al.1 entitled "AKI in COVID-19: Emerging Evidence of a Distinct Pathophysiology" has discussed comprehensively the possible pathophysiology of AKI in novel coronavirus disease 2019 (COVID-19), a complication of COVID-19 that many have largely ignored. Although the authors were right to avoid speculating about specific interventions until a full picture has been obtained, we feel that sound hypotheses with evidence extrapolated from the COVID-19 population may help in the design of clinical trials or even prospective studies to better understand what works and what does not, since in the field of medicine it is always about testing hypotheses (without causing harm), especially amid this COVID-19 pandemic where many lives have been claimed due to complications in such a short period of time. It has now been established that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative pathogen for COVID-19, gains entry into host cells through an angiotensin-converting enzyme 2 (ACE2) protein, which is also abundantly expressed in the kidney. Authors have speculated about direct viral infection of the kidney, where SARS-CoV-2 gains entry through the ACE2 protein of the proximal tubule. In this sense, the use of renin-angiotensin system (RAS) inhibitors, including ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs), may be protective toward kidney injury. Firstly, ARBs could compete with SARS-CoV-2 for ACE2-expressing proximal tubular cells, block the binding, and hence the attachment of SARS-CoV-2 to ACE2, thereby inhibiting its entry into the cells. In this way, there may be less entry, if not entirely of no entry, of SARS-CoV-2 into proximal tubular cells. Thus, the proximal tubular cells at risk may be limited, and tubular function of the kidney may be better preserved. Secondly, downregulation of ACE2 upon viral invasion and subsequent increased production of angiotensin II seems to drive the occurrence of kidney injury.2 Both ACE inhibitors and ARBs could block the physiologic effect of angiotensin II. The protective ability of RAS inhibitors may have been hinted in a prospective cohort study of 701 patients with COVID-19. Cheng et al.3 investigated the association between in-hospital medications (on admission and during hospitalization) and the development of AKI among patients with COVID-19. It was noted that none of the patients who were taking RAS inhibitors on admission or during hospitalization for COVID-19 developed AKI. In contrast, almost all patients with COVID-19 who had AKI were receiving antibiotics (35/36; 97%), a well known causative agent for AKI.4 Disclosures All authors have nothing to disclose. Funding None.
Single-Cell Transcriptional Archetypes of Airway Inflammation in Cystic Fibrosis
Authors: Jonas C. Schupp, Sara Khanal, Jose L. Gomez, Maor Sauler, Taylor S. Adams, Geoffrey L. Chupp, Xiting Yan, Sergio Poli, Yujiao Zhao, Ruth R. Montgomery, Ivan O. Rosas, Charles S. Dela Cruz, Emanuela M. Bruscia, Marie E. Egan, Naftali Kaminski, Clemente J. Britto
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Cystic fibrosis (CF) is a life-shortening, multisystem hereditary disease caused by abnormal chloride transport. CF lung disease is driven by innate immune dysfunction and exaggerated inflammatory responses that contribute to tissue injury. To define the transcriptional profile of this airway immune dysfunction, we performed the first single-cell transcriptome characterization of CF sputum.
SR4R: An Integrative SNP Resource for Genomic Breeding and Population Research in Rice
Authors: Jun Yan, Dong Zou, Chen Li, Zhang Zhang, Shuhui Song, Xiangfeng Wang
Journal: Genomics Proteomics & Bioinformatics (2020)

The information commons for rice (IC4R) database is a collection of 18 million single nucleotide polymorphisms (SNPs) identified by resequencing of 5152 rice accessions. Although IC4R offers ultra-high density rice variation map, these raw SNPs are not readily usable for the public. To satisfy different research utilizations of SNPs for population genetics, evolutionary analysis, association studies, and genomic breeding in rice, raw genotypic data of these 18 million SNPs were processed by unified bioinformatics pipelines. The outcomes were used to develop a daughter database of IC4R - SnpReady for Rice (SR4R). SR4R presents four reference SNP panels, including 2,097,405 hapmapSNPs after data filtration and genotype imputation, 156,502 tagSNPs selected from linkage disequilibrium-based redundancy removal, 1180 fixedSNPs selected from genes exhibiting selective sweep signatures, and 38 barcodeSNPs selected from DNA fingerprinting simulation. SR4R thus offers a highly efficient rice variation map that combines reduced SNP redundancy with extensive data describing the genetic diversity of rice populations. In addition, SR4R provides rice researchers with a web interface that enables them to browse all four SNP panels, use online toolkits, as well as retrieve the original data and scripts for a variety of population genetics analyses on local computers. SR4R is freely available to academic users at http://sr4r.ic4r.org/.
Chronic Effects of High Fine Particulate Matter Exposure on Lung Cancer in China
Authors: Jianxin Li, Xiangfeng Lu, Fangchao Liu, Fengchao Liang, Keyong Huang, Xueli Yang, Qingyang Xiao, Jichun Chen, Xiaoqing Liu, Jie Cao, Shufeng Chen, Chong Shen, Ling Yu, Fanghong Lu, Xianping Wu, Liancheng Zhao, Xigui Wu, Ying Li, Dongsheng Hu, Jianfeng Huang, Meng Zhu, Yang Liu, Hongbing Shen, Dongfeng Gu
Journal: American Journal of Respiratory and Critical Care Medicine (2020)

Rationale: Limited cohort studies have evaluated chronic effects of high fine particulate matter (particulate matter with an aerodynamic diameter ≤2.5 μm [PM2.5]) exposure on lung cancer.Objectives: To investigate the response pattern of lung cancer associated with high PM2.5 exposure.Methods: A Chinese cohort of 118,551 participants was followed up from 1992 to 2015. By incorporating PM2.5 exposure at 1 km spatial resolution generated using the satellite-based model during 2000-2015, we estimated the association between lung cancer and time-weighted average PM2.5 concentration using Cox proportional hazard models.Measurements and Main Results: A total of 844 incident lung cancer cases were identified during 915,053 person-years of follow-up. Among them, 701 lung cancer deaths occurred later. The exposure-response curves for lung cancer associated with PM2.5 exposure were nonlinear, with steeper slopes at the higher concentrations. Adjusted for age, sex, geographical region, urbanization, education level, smoking status, alcohol consumption, work-related physical activity, and body mass index, participants exposed to the second-fifth quintiles of PM2.5 had higher risk for lung cancer incidence than those exposed to the first quintile, with hazard ratios of 1.44 (95% confidence interval [CI], 1.10-1.88), 1.49 (95% CI, 1.12-1.99), 2.08 (95% CI, 1.42-3.04), and 2.45 (95% CI, 1.83-3.29), respectively. The corresponding hazard ratios for lung cancer mortality were 1.83 (95% CI, 1.33-2.50), 1.80 (95% CI, 1.29-2.53), 2.50 (95% CI, 1.62-3.86), and 2.95 (95% CI, 2.09-4.17), respectively.Conclusions: We provide strong evidence that high PM2.5 exposure leads to an elevated risk of lung cancer incidence and mortality, highlighting that remarkable public health benefits could be obtained from the improvement of air quality in highly polluted regions.
Current understanding of the role of Adipose-derived Extracellular Vesicles in Metabolic Homeostasis and Diseases: Communication from the distance between cells/tissues
Authors: Chun-Jun Li, Qian-Hua Fang, Ming-Lin Liu, Jing-Na Lin
Journal: Theranostics (2020)

Extracellular vesicles (EVs) including exosomes, microvesicles (MVs), and apoptotic bodies, are small membrane vesicular structures that are released during cell activation, senescence, or programmed cell death, including apoptosis, necroptosis, and pyroptosis.EVs serve as novel mediators for long-distance cell-to-cell communications and can transfer various bioactive molecules, such as encapsulated cytokines and genetic information from their parental cells to distant target cells.In the context of obesity, adipocyte-derived EVs are implicated in metabolic homeostasis serving as novel adipokines.In particular, EVs released from brown adipose tissue or adipose-derived stem cells may help control the remolding of white adipose tissue towards browning and maintaining metabolic homeostasis.Interestingly, EVs may even serve as mediators for the transmission of metabolic dysfunction across generations.Also, EVs have been recognized as novel modulators in various metabolic disorders, including insulin resistance, diabetes mellitus, and non-alcoholic fatty liver disease.In this review, we summarize the latest progress from basic and translational studies regarding the novel effects of EVs on metabolic diseases.We also discuss EV-mediated cross-talk between adipose tissue and other organs/tissues that are relevant to obesity and metabolic diseases, as well as the relevant mechanisms, providing insight into the development of new therapeutic strategies in obesity and metabolic diseases.
Dysfunction of parvalbumin neurons in the cerebellar nuclei produces an action tremor
Authors: Mu Zhou, Maxwell D. Melin, Wei Xu, Thomas C. Südhof
Journal: Journal of Clinical Investigation (2020)

Essential tremor is a common brain disorder affecting millions of people, yet the neuronal mechanisms underlying this prevalent disease remain elusive. Here, we showed that conditional deletion of synaptotagmin-2, the fastest Ca2+ sensor for synaptic neurotransmitter release, from parvalbumin neurons in mice caused an action tremor syndrome resembling the core symptom of essential tremor patients. Combining brain region–specific and cell type–specific genetic manipulation methods, we found that deletion of synaptotagmin-2 from excitatory parvalbumin-positive neurons in cerebellar nuclei was sufficient to generate an action tremor. The synaptotagmin-2 deletion converted synchronous into asynchronous neurotransmitter release in projections from cerebellar nuclei neurons onto gigantocellular reticular nucleus neurons, which might produce an action tremor by causing signal oscillations during movement. The tremor was rescued by completely blocking synaptic transmission with tetanus toxin in cerebellar nuclei, which also reversed the tremor phenotype in the traditional harmaline-induced essential tremor model. Using a promising animal model for action tremor, our results thus characterized a synaptic circuit mechanism that may underlie the prevalent essential tremor disorder.
Outcomes of Embedding Dermatologic Care Within Oncology Practices for Patients With Cancer
Authors: Bernice Y. Kwong
Journal: JAMA Dermatology (2020)

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ZnS@ZIF-8 core-shell nanoparticles incorporated with ICG and TPZ to enable H<sub>2</sub>S-amplified synergistic therapy
Authors: Chao Fang, Dong Cen, Yifan Wang, Yongjun Wu, Xiujun Cai, Xiang Li, Gaorong Han
Journal: Theranostics (2020)

Abnormal tumor microenvironment, such as hypoxia, interstitial hypertension and low pH, leads to unexpected resistance for current tumor treatment.The development of versatile drug delivery systems which present responsive characteristics to tumor microenvironment (TME) has been extensively carried out, but remains challenging.In this study, zeolitic imidazolate framework-8 (ZIF-8) coated ZnS nanoparticles have been designed and prepared for co-delivery of ICG/TPZ molecules, denoted as ZSZIT, for H2S-amplified synergistic therapy.Methods: The ZSZ nanoparticles were characterized using SEM, TEM and XRD.The in vitro viabilities of cancer cells cultured with ZSZIT under normoxia/hypoxia conditions were evaluated by cell counting kit-8 (CCK-8) assay.In addition, in vivo anti-tumor effect was also performed using male Balb/c nude mice as animal model.Results: ZSZIT shows cascade PDT and hypoxia-activated chemotherapeutic effect under an 808nm NIR irradiation.Meanwhile, ZSZIT degrades under tumor acidic environment, and H2S produced by ZnS cores could inhibit the expression of catalase, which subsequently favors the hypoxia and antitumor effect of TPZ drug.Both in vitro and in vivo studies demonstrate the H2S-sensitized synergistic antitumor effect based on cascade PDT/chemotherapy.Conclusion: This cascade H2S-sensitized synergistic nanoplatform has enabled more effective and lasting anticancer treatment.