bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transduction of Sympathetic Nerve Activity to Blood Pressure in Type 2 Diabetes Patients
Authors: Young Ben E , Vranish Jennifer R , Holwerda Seth W , Newby Chase E , Keller David M , Hart Emma C , Fadel Paul J 
Published: November 2023

The technique of microneurography has been used extensively to obtain direct recordings of muscle sympathetic nerve activity (MSNA) in both healthy and diseased populations. Much less commonly studied, however, is the transduction of MSNA into changes in arterial blood pressure. Recently, several methodologies have been developed to begin to better understand sympathetic transduction. Herein, we compared two methodologies and their ability to detect group differences in sympathetic transduction between Type 2 Diabetes (T2D) patients (N=15; age=47±2.0 years; 9 women) and age‐and BMI‐matched controls (CON: N=11; age=47±2.4 years; 8 women). T2D patients were of interest since previous work has reported enhanced α‐adrenergic sensitivity in this group. We tested the hypothesis that T2D patients would exhibit an enhanced sympathetic transduction to spontaneous changes in resting MSNA. MSNA, heart rate (ECG), and beat‐to‐beat arterial blood pressure (finger photoplethysmography) were continuously recorded during a 10‐minute resting baseline. Transduction of MSNA was assessed using two distinct methodologies. First, signal averaging was used to characterize the peak change in diastolic blood pressure over the subsequent 10 cardiac cycles following MSNA bursts. Normalized MSNA burst heights were divided into quartiles, and the associated peak diastolic blood pressures were used to derive a slope. Second, diastolic blood pressures were associated with normalized MSNA burst areas at a lag of 6–8 cardiac cycles, and binned into 1%·sec bins. Linear regression of these binned areas provided a slope. Resting MSNA, and diastolic blood pressure (CON: 78±2 mmHg, T2D: 81±3, p=0.28) were not different between groups. There was no difference in transduction slopes between groups using burst height quartiles (CON: 0.73±0.11 mmHg/AU, T2D: 0.53±0.09 mmHg/AU, p=0.18). Indeed, signal averaging of MSNA bursts produced a similar peak increase in diastolic blood pressure in CON (1.7±0.3 mmHg) and T2D patients (1.9±0.3 mmHg; p=0.68). Likewise, transduction slopes derived from binned MSNA areas were also not different between groups (CON: 0.29±0.03 mmHg/%·sec, T2D: 0.23±0.03 mmHg/%·sec, p=0.28). These preliminary findings suggest that, despite enhanced α‐adrenergic sensitivity in T2D, resting sympathetic transduction to arterial blood pressure is not different between T2D patients and healthy CON subjects. This finding was independent of the transduction analysis methodology employed.Support or Funding InformationSupported by AHA Grant In Aid 20160072.
Progression of experimental autoimmune encephalomyelitis is associated with up‐regulation of major sodium transporters in the mouse kidney cortex under a normal salt diet
Authors: Zhou Xiaoming , Packialakshmi Balamurugan , Xiao Yao , Nurmukhambetova Saule , Lees Jason R 
Published: November 2023

Multiple sclerosis is an auto‐immune disease. Experimental autoimmune encephalomyelitis (EAE) is a popular animal model to study the pathophysiology of the disease. Recent repeated demonstrations of the exacerbation of EAE by high salt diets suggest a critical role of Na in the progression of EAE. This discovery has prompted us to study whether EAE stimulates renal absorption of Na even under a normal NaCl diet. The renal cortex is the primary site to absorb Na. In the kidney cortex, Na enters the epithelial cells mainly through the apical Na‐H exchanger NHE3, NaCl co‐transporter NCC and Na channel ENaC and then exits the cells exclusively through the basolateral Na,K‐ATPase. Here we report that as EAE progressed from mild to severe stage, there were parallel increases in the protein abundance of NHE3 and αENaC but not in the protein levels of βENaC, γENaC or NCC. Severe EAE also correlated with augmentation of the Na,K‐ATPase activity with an affiliated elevation of its β1‐subunit protein. These effects cannot be explained alone by EAE‐associated dehydration or anorexia. To determine how NHE3, αENaC and Na,K‐ATPase are up‐regulated during severe EAE, we examined their up‐stream stimulators. We have identified that the protein levels of the kinase SGK1 and scaffold NHERF2 and phosphorylation of ERK1/2 were increased during severe EAE, whereas the protein level of SGK2 or NHERF1 was not. We conclude that severe EAE is associated with up‐regulation of NHE3, αENaC and Na,K‐ATPase, which is most likely contributed by increased expression of SGK1 and NHERF2 and activation of ERK1/2. These data suggest that severe EAE increases Na absorption by the renal cortex.Support or Funding InformationNational Multiple Sclerosis Society PP3448
Human and Murine Precision‐Cut Kidney Slices as a Tool to Study the Inflammatory Pathogenesis of Renal Disease
Authors: Mutsaers Henricus A.M. , Stribos Elisabeth G.D. , Nørregaard Rikke , Olinga Peter 
Published: November 2023

Renal disease is a major global health problem and the 9th leading cause of death in the United States. Inflammation is one of the driving forces in acute and chronic kidney diseases, and cytokines act as both mediators and initiators of injury. Currently, there is a lack of good translational models to study the inflammatory basis of kidney disorders, hindering the search for therapeutic targets. The objective of our study was to investigate the inflammatory process in an in vitro model that reflects the cellular diversity as well as architecture of the kidney, namely precision‐cut kidney slices (PCKS).PCKS were successfully prepared from both human and murine kidneys, and cultured up to 96 hours. Viability of PCKS was assessed by the ATP content of the slices. Furthermore, gene expression of several inflammatory markers was determined by quantitative PCR.Human and murine PCKS remained viable during culture up to 72h. During culture of human PCKS we observed a marked increase in the gene levels of interleukin (IL)‐6, IL‐8, and IL‐1β, peaking at 3–24h. Afterwards, gene expression decreased but remained elevated as compared to control slices (0h). Conversely, expression of COX‐2 increased at 3h and remained high. Interestingly, a similar expression profile was observed in murine PCKS. During culture, gene levels of IL‐6 and CXCL1 spiked at 3h, after which gene expression decreased, while both IL‐1β and COX‐2 greatly increased at 3h and plateaued. Noteworthy, long‐term incubation (72–96h) induced fibrogenesis in PCKS, possibly driven by ILs. The impact of COX‐2 inhibitors on the inflammatory and fibrotic response in PCKS is currently being evaluated.Thus, PCKS can be used to study the inflammatory pathogenesis of renal disease and identify therapeutic targets. Moreover, the model is useful to reveal species differences in disease development and progression.Support or Funding InformationNA
ngPalmPISC: A Sensitive Method for Proteome‐wide Characterization of S‐acylation
Authors: Zhou Bo , Yan Yiwu , Freeman Michael R , Yang Wei 
Published: November 2023

Protein S‐acylation (palmitoylation) reversibly modulates protein localization, and thus regulates protein activity, stability, and complex formation. Accumulating evidence suggests that S‐acylation plays a key role in the development and progression of various diseases, such as cancer and neurodegenerative diseases. Previously, we established an S‐acylproteomics method termed Palmitoyl‐protein Identification and Site Characterization (PalmPISC), and identified 67 known and 331 novel candidate S‐acylated proteins from human prostate cancer DU145 cells (Yang et al., Mol Cell Proteomics, 2010, 9: 54–70). In this study, we developed a next‐generation PalmPISC (ngPalmPISC) method that enables proteome‐wide characterization of S‐acylated proteins. Using ngPalmPISC, we identified 2,063 high‐confidence and 528 medium‐confidence candidate S‐acylated proteins from human prostate cancer LNCaP cells. Of these, 1,174 (56.9%) high‐confidence and 242 (45.8%) medium‐confidence candidates are contained in the SwissPalm database, corroborating the effectiveness of our ngPalmPISC method in identifying S‐acylated proteins. In addition, 1,191 and 457 cysteine residues were identified as candidate S‐acylation sites with high and medium confidence, respectively. To our knowledge, this represents the first proteome‐wide characterization of human S‐acylated proteins, with a proteomic coverage of almost an order of magnitude greater than any other single S‐acylproteomics study. Gene ontology analysis of the high‐confidence candidates indicates that S‐acylated proteins are highly significantly enriched in subcellular organelles including mitochondria, endoplasmic reticulum, Golgi apparatus, nucleolus, ribosome, and peroxisome, as well as in biological processes like rRNA processing, translation, and fatty acid beta‐oxidation. Interestingly, many candidate prostate cancer biomarkers, such as prostate‐specific antigen, prostate‐specific membrane antigen, and alpha‐methylacyl‐CoA racemase, are S‐acylated in LNCaP cells. This suggests that S‐acylation may play an important role in prostate cancer progression, and that the S‐acylproteome is a rich source for prostate cancer biomarker discovery. In summary, our ngPalmPISC method opens up a new avenue for proteome‐wide analysis of S‐acylated proteins in cells and clinical specimens, and its application reveals that S‐acylation is more prevalent than we previously thought.Support or Funding InformationDoD PCRP W81XWH‐15‐1‐0167Steve Spielberg Cancer Discovery Foundation (CSR205927)
Inserting Quantitative Literacy into the Human Physiology Lab Curriculum
Authors: Krontiris‐Litowitz Johanna 
Published: November 2023

The practice of biology involves collection and interpretation of data sets that frequently require mathematical analysis or statistical tests. Therefore, it is important for students to build the skill set that enables them to analyze data, develop predicative numeric relationships, create models mathematical models the mimic physiological events and communicate ideas about data. Educators have identified a gap in the quantitative literacy (QL) or mathematical and computational preparation of future scientists. These skills are not part of the learning outcomes of traditional college math courses, however, they can be taught in the contextual situations found in discipline‐specific lab courses.The objective of this study was to: 1) identify a set of QL learning objectives that could be embedded in a physiology lab curriculum and 2) develop pre‐test that could be used to probe student QL skill level. A set of five QL learning objectives framed the curriculum of a one semester undergraduate human physiology laboratory course (n=33). On the first day of class students were given a 7 question pretest that evaluated their understanding of quantitative scale, ability to develop computational strategies, capacity to communicate quantitative ideas in a text or tabular format, and their proficiency in extracting information and trends from graphs. For the remainder of the course, students performed lab protocols that supported content and QL learning objectives. At the end of the course student learning was assessed by comparing the results of the pre‐test to student performance on the lab notebooks and final exam. Analysis of the pre‐test scores showed that the instrument identified gaps in basic QL skills. Approximately 20–30 % of the students could not apply concepts of scale in order to correctly answer a question, extract information or inferences from a complex graph, or readily develop a computational strategy for a rate calculation. Analysis of student performance at the end of the course showed learning gains in these areas. These results indicate that the pretest was effective at disclosing disparities in student QL skills and serving as a benchmark for evaluating student learning gains.
Understanding how we understand: promoting research literacy during PhUn Week
Authors: Crecelius Anne R 
Published: November 2023

Physiology Understanding (PhUn) Week is an outreach program that encourages connections between scientists and their local schools. Students (n=23) enrolled in a combined undergraduate and graduate Research in Sport and Health Science course served as visiting scientist teachers for a high school anatomy course at a non‐traditional charter school (24 participants). University students identified an original research article in the literature and a popular press source that mentioned that primary source and brought these to the classroom. The university students also designed a brief lesson to address: 1) the components of the primary research article, and 2) how well the popular press source translated the findings to a lay audience. Pairings of high school students spent approximately 30 min each with two different sets of university students. High school students were given a worksheet to record knowledge gained and university students were anonymously surveyed after the experience. Based on these quantitative survey results, university students enjoyed the experience, did not find it difficult to translate knowledge to an age‐appropriate level, learned something about themselves from the experience, and thought the high school students enjoyed and learned from the activity. Open‐ended responses supported these findings and addressed the willingness of the high school students to engage in conversations about the research process and future career plans. These results suggest that activities designed to promote research literacy can be enjoyable and engaging in this setting. Future work should address the effectiveness of this type of programing. In addition, this project successfully piloted PhUn Week activities into a non‐physiology specific course.Support or Funding InformationThe American Physiological Society provided PhUn Week promotional materials.
The Mechanisms of Gut‐dependent Protection against Cardiac Injury
Authors: Pier Marissa Lopez 
Published: November 2023

The gut is the main location for immunological regulation and is influenced by the flora that reside there. This flora, also known as the gut microbiome, is necessary for maintaining immune health and disruptions in the microbiome result in systemic, metabolic and inflammatory disorders including obesity, diabetes, and cardiovascular disease. Therefore a possible approach to treat these disorders involves modulating the gut microbiome through the administration of probiotics. Probiotics are defined by the World Health Organization as, “live microorganisms that confer a health benefit to the host when consumed in adequate amounts.” Data from our laboratory indicate that a specific strain of probiotic, Bifidobacterium animalis sub‐species lactis 420 (B420), reduces the extent of cardiac injury following ischemia/reperfusion in a mouse model of myocardial infarction. This cardioprotection is attributed to a reduction in cardiac inflammation, however, it is unclear precisely how B420 mediates this effect. Here, we hypothesize that the mechanism of gut‐dependent cardioprotection observed in vivo is through epigenetic and post‐translational regulation of intestinal, epithelial and immune cell function. We further hypothesize that the initiation of this mechanism is not uniform throughout the GI tract, and may be regionally localized. To this end, we developed a system to track the probiotic in the gut to better understand where and how they interact with the gut microbiome. Indocyanine Green (ICG) is a near infrared(NIR) stable aqueous, sterile, fluorescent, and clinically effective agent. In this study we aim to develop an inexpensive and effective method to track B420 bacteria in the gut‐microbiome. ICG was cultured with B420 and analyzed with LagoX imaging software at NIR wavelengths. ICG did not inhibit growth of B420 culture, and was a suitable reagent for labeling B420 bacteria. The ICG‐B420 co‐culture was gavaged in a treatment group of C57BL/6 mice at 2mg/kg, while control mice received B420 only. The GI tract was imaged in vivo and ex vivo bioluminescence. Bacterial genomic DNA from C57BL/6 treated and untreated mice gut epithelia was quantified using B420 primers and quantitative PCR(qPCR), and verified localization of bacteria colonization observed during fluorescent imaging.Support or Funding InformationCardiovascular Training Grant in Biomedical Engineering NIH T32 training grant
Lipid droplets in steatotic liver disease
Authors: Bilson Josh , Scorletti Eleonora 
Published: November 2023

Purpose of review
This review aims to discuss the most recent evidence exploring the role of lipid droplets in steatotic liver disease (SLD). We highlight the breadth of mechanisms by which lipid droplets may contribute to the progression of SLD with a particular focus on the role of lipid droplets as inducers of mechanical stress within hepatocytes and genetic mutations in lipid droplet associated proteins. Finally, this review provides an update on clinical trials exploring the therapeutic potential and strategies targeting lipid droplets.

Recent findings
The size, composition and location of hepatic lipid droplets strongly influence the pathological role of these organelles in SLD. Emerging studies are beginning to elucidate the importance of lipid droplet induced hepatocyte mechanical stress. Novel strategies targeting lipid droplets, including the effects of lipid droplet associated protein mutations, show promising therapeutic potential.

Summary
Much more than a histological feature, lipid droplets are complex heterogenous organelles crucial to cellular metabolism with important causative roles in the development and progression of SLD. Lipid droplet induced mechanical stress may exacerbate hepatic inflammation and fibrogenesis and potentially contribute to the development of a pro-carcinogenic hepatic environment. The integration of advancements in genetics and molecular biology in upcoming treatments aspires to transcend symptomatic alleviation and address the fundamental causes and pathological development of SLD.
Vibrio methylphosphonaticus sp. nov., a methylphosphonate-decomposing bacterium isolated from surface seawater in the Xisha Islands, PR China
Authors: Wang Wei , Liu Mei , Cao Bingbing , Liu Yi , Huang Keyi , Ding Yunqi , Xu Ziqing , Sun Fucheng , Zhang Yunxiao , Niu Wentao , Tian Peng , Huang Dingyong , Wang Xiaolei , Xiao Jiaguang 
Published: November 2023

A Gram-stain-negative, facultative anaerobic, methylphosphonate-decomposing, motile by a polar flagellum and rod-shaped marine bacterium, designated S4B1T, was isolated from the surface seawater collected from the Yongle Atoll (Xisha Islands, PR China). The pairwise alignment showed the highest sequence similarity of 97.5 and 96.6 % to

Vibrio aestuarianus

subsp.

cardii

12_122_3T3T and

Vibrio atypicus

HHS02T, respectively. Phylogenetic analysis based on 16S rRNA gene and the phylogenomic analysis of single-copy genes showed that strain S4B1T belonged to the genus

Vibrio

and formed a close branch with Vibrio qingdaonensis ZSDZ65T. Growth of strain S4B1T occurred at 4–30 °C (optimum, 28 °C), at pH 6.0–8.0 (optimum, pH 7.0) and in the presence of 2–7 % (w/v) NaCl (optimum, 3 %). The predominant fatty acids (>10 %) were C16 : 0, iso-C16 : 0 and summed feature 3 (C16 : 1

ω7c or/and C16 : 1
ω6c). The DNA G+C content of the assembled genomic sequence was 44.3 mol%. Average nucleotide identity (ANI) values between S4B1T and its reference species were lower than the threshold for species delineation (95–96 %), in which its highest ANI value with V. qingdaonensis ZSDZ65T was 87.0 %. In silico DNA–DNA hybridization further showed that strain S4B1T had less than 70 % similarity to its relatives. On the basis of the polyphasic evidence, strain S4B1T is proposed to represent a novel species of the genus

Vibrio

, for which the name Vibrio methylphosphonaticus sp. nov. is proposed. The type strain is S4B1T (=KCTC 92311T=MCCC 1K06168T).
An online tool for correcting verification bias when validating electronic phenotyping algorithms
Authors: Bhasin Ajay , Bielinski Suzette J. , Kho Abel N. , Larson Nicholas B. , Rasmussen-Torvik Laura 
Published: November 2023

AbstractComputable or electronic phenotypes of patient conditions are becoming more commonplace in quality improvement and clinical research. During phenotyping algorithm validation, standard classification performance measures (i.e., sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) are commonly employed. When validation is performed on a randomly sampled patient population, direct estimates of these measures are valid. However, it is common that studies will sample patients conditional on the algorithm result, leading to a form of bias known as verification bias. The presence of verification bias requires adjustment of performance measure estimates to account for this sampling bias. Herein, we describe the appropriate formulae for valid estimates of sensitivity, specificity, and accuracy to account for verification bias. We additionally present an online tool to adjust algorithm performance measures for verification bias by directly taking the sampling strategy into consideration and recommend use of this tool to properly estimate algorithm performance for phenotyping validation studies.
Predictors of High-grade Squamous Intraepithelial Lesion treatment failure
Authors: Botting-Provost S. , Koushik A. , Trottier H. , Coutlée F. , Mayrand MH 
Published: November 2023

AbstractObjectiveTo estimate the association between several risk factors and high-grade squamous intraepithelial lesions (HSIL) treatment failure in order to identify predictors.MethodsThe study population included 1,548 Canadian women treated for HSIL who participated in a randomized control trial. HSIL treatment failure was the presence of histologically confirmed HSIL or worse during the two-year follow-up period. This nested-case control study included all 101 cases of treatment failure and controls that were matched 1:1 on treatment center and date of failure. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between each potential predictor and HSIL treatment failure. Independent variables that were examined included age, parity, smoking status, number of sexual partners, condom use, method of contraception, margins, number of passes, diagnosis on conisation, genotype, and number of infecting types. Interactions between smoking and margins and genotype were evaluated.ResultsHaving positive vs. negative margins (adjusted OR=4.05, 95% CI 1.57-10.48) and being positive forHuman Papillomavirus(HPV)16 and/or HPV18 vs. any other type (adjusted OR=2.69, 95% CI 1.32-5.49) were predictors of HSIL treatment failure in multivariable models. ORs suggested that older age, more severe lesions, and single-type infections may be at a higher risk of treatment failure but were not statistically significant. The ORs for smoking status, number of sexual partners, condom use, contraception, parity, and number of passes were near the null value. We did not observe any evidence of interaction between smoking and genotype, nor between margins and genotype.ConclusionOnly positive margins and HPV16/18 positivity were predictors for being diagnosed with HSIL or worse within two years of treatment. However, we do not recommend automatic retreatment of those with positive margins because over 90% of those with positive margins did not fail treatment. The predictive value of HPV16 and HPV18 for HSIL treatment failure suggests that high coverage vaccination programs should contribute to a significant reduction in residual/recurrent disease.