bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Preliminary Report on the Variation of Respiratory Blood Pressure during Sleep in Patients with Hypertension
Authors: Wang Jinan , Sun Xingguo , Tai Wenqi , Zhou Qingqing , Zhang Yanfang 
Published: May 2022

ObjectiveExplore whether the blood pressure of hypertensive patients changes periodically with respiration.MethodsThis study analyzed 8 patients with hypertension without sleep apnea who performed cardiopulmonary exercise testing (CPET), polysomnography (PSG), continuous fingertip pulse wave and electrocardiogram (ECG), and compared with 8 normal subjects evaluated in the same period. Calculate the number of respiratory cycles (Bn), average respiratory cycle time (Bn‐T) and other respiratory parameters as well as systolic blood pressure (SBP), diastolic blood pressure (DBP), blood pressure variation cycles (BPV‐n), average blood pressure variation cycle time (BPV‐T) and other blood pressure variability parameters. Continuous variables within and between groups were compared by independent‐sample t test, and data calculated by different methods in the same group were compared by paired‐sample t test.ResultsThe core parameters of CPET such as peak oxygen uptake (72.82±10.07%Pred) and anaerobic threshold (59.69±6.66%Pred) of hypertensive patients without sleep apnea were significantly lower than those of normal subjects (P<0.05). The fingertip pulse wave calculation of SBPV‐n (7000.25±1404.78) and DBPV‐n (6949.25±1407.98) in hypertensive patients were basically the same, similar to the results of normal subjects, and there was no statistically significant difference between the two groups (P>0.05); SBPV‐T, DBPV‐T, SBPV rate and DBPV rate (4.34±0.72 s, 4.37±0.70 s, 14.22±2.39 bpm, 14.10±2.34 bpm) were not statistically different from normal subjects (P>0.05); Bn/SBPV‐n (1.00±0.03) and Bn/DBPV‐n (1.01±0.02) are basically the same as normal subjects (P>0.05), and both are close to 1.SBPV‐n (2464.75±1318.38) and DBPV‐n (936.00±132.18) calculated based on pulse transit time during sleep were significantly lower than the fingertip pulse wave calculation parameter (P<0.01). The systolic blood pressure variation amplitude (2.96±0.83 mmHg) and diastolic blood pressure variation amplitude (2.57±0.38 mmHg) were greater than those of normal subjects, but the difference was not statistically significant.ConclusionThe variability of blood pressure during sleep in hypertensive patients without sleep apnea is similar to variability of respiration, and the change trend is consistent with normal subjects, both blood pressure variability is caused by respiration.
Metabolic Effects of Sodium Fluorocitrate and Potential Treatments on Saccharomyces Cerevisiae: Changes in Oxygen Consumption
Authors: Racine Michelle , DeLey Cox Vanessa E. , Pueblo Erin , Jennings Laura , Tressler Justin , McCranor Bryan 
Published: May 2022

Sodium fluoroacetate (1080) is a colorless, odorless, tasteless, water‐soluble metabolic poison. In the body, fluoroacetate is converted to fluorocitrate (FC) which blocks the citric acid cycle and drastically decreases ATP production. Symptoms of exposure include nausea, vomiting, abdominal pains, salivation, irrational fear, weakness, tachypnea, cyanosis, sweating, increased temperature, and death. Signs and symptoms of 1080 poisoning are nonspecific, further complicating the diagnosis. 1080 is tightly regulated within the United States, but it is commonly used in Australia, New Zealand, Mexico, Japan, South Korea, and Israel as a rodenticide to control invasive and predatory species. An eco‐terrorist scare in New Zealand (2015) and findings reported by the CIA (2007) have led 1080 to being identified as a potential terrorist weapon.To identify potential countermeasures against 1080 poisoning, a Saccharomyces cerevisiae (yeast) model was selected to assess the impact of FC on cellular respiration and to screen candidate therapeutics. In response to FC, yeast showed depressed mitochondrial activity as measured by oxygen consumption rate (OCR). Potential treatments, thonzonium bromide, nifuroxazide, pyrvinium pamoate, menadione, mefloquine, clemastine fumarate, bisacodyl, L‐ascorbic acid, thiethylperazine and vinpocitine, were examined in this study. All treatments are approved by the Food and Drug Administration. Toxicity of each treatment was also assessed.Assays were performed in yeast extract peptone galactose media, a metabolically restrictive media. To assess the effect of FC on OCR, cells were exposed to 50 µM, 100 µM, and 200 µM FC in liquid culture for 1, 4, or 24 hours. After incubation, mitochondrial respiration was assessed via the MitoXpress assay (Agilent), a fluorescence‐based assay that measures OCR. Once established as a viable model, yeasts were then used to screen therapeutics to improve cellular respiration. Yeast was co‐incubated with fluorocitrate (200 µM), and potential treatments at three increasing concentrations for 4 hours and the effects on mitochondrial respiration were assessed via the MitoXpress assay.Following the decreased OCR in yeast exposed to FC, 6 of the 10 treatments successfully restored the mitochondrial function of yeast as demonstrated by an increase in OCR. As a result, the compounds nifuroxazide, pyrvinium pamoate, vinpocitine, clemastine fumarate, bisacodyl, and L‐ascorbic acid are moving forward for further testing in cardiomyocytes and hepatic spheroids, with potential in vivo assessment, to characterize their effectiveness against 1080 poisoning. Future studies will continue to use yeast as a valuable screening method to identify other potential treatments for sodium fluoroacetate.
Unequal and Unique contribution of Different Adverse Childhood Experiences to Metabolic Disease Risk in a Multiracial Cohort
Authors: Leachman Jacqueline R. , Heier Kory , Lei Feitong , Ahmed Nermin , Dalmasso Carolina , Duncan Meredith S. , Loria Analia S. 
Published: May 2022

Adverse childhood experiences (ACEs) are an independent risk factor for chronic disease, including obesity and metabolic syndrome. Therefore, we sought to determine the association of ACEs with BMI and plasma metabolic biomarkers affecting a multiracial cohort. Total ACE score was calculated in 38,353 non‐Hispanic Black and White men and women who participated in the second follow‐up of the Southern Community Cohort Study (2012‐2015). We used regression analyses to assess whether total ACE score or individual ACE components were associated with BMI and included interaction terms to evaluate if the association differed by sex or race, and for female participants, we accounted for menopause status. Total ACE score was associated with BMI (non‐linear p‐value=0.0026) and differed by sex and race (interaction p‐value<0.0001), but not menopause status. BMI steadily increased with cumulative ACEs among Black women. Among White women, BMI sharply increased from 0 to 1 ACEs, and steadily increased thereafter. In White men, BMI increased as ACEs increased from 0 to 3 and remained relatively stable among individuals with >4 ACEs. In Black men, BMI decreased with cumulative ACEs. Among Black women, emotional and sexual abuse were associated with higher BMI (p<0.05). Including both Black women and men, having an incarcerated family member was associated with lower BMI. Physical abuse was associated with increased BMI in Black and White men, while emotional neglect was associated with increased BMI in White women (p<0.05). In addition, regression analysis revealed an association between total ACE score and waist circumference, totalcholesterol, the ratio of leptin to adiponectin, HbA1c, and insulin. Furthermore, with increasing number of ACEs, Black men were the most affected in waist circumference, showing a 6 cm overall increase; however, they showed reduced BMI. This data indicates increased visceral fat deposition which is an indicator of metabolic syndrome and insulin resistance. Using a mouse model of postnatal neglect, and in line with this data, we have found that female mice, and not male mice, develop exacerbated adiposity. Specifically, female mice display increased whitening of adipose tissue via the actions of the mineralocorticoid receptor on lipid storage and adipocyte differentiation. Overall, ACEs are associated with BMI, but each ACE component has a unique contribution to this effect that varies based on sex and race. Future pre‐clinical studies should aim to model sex‐ and race‐specific effect of ACE on the development of obesity to provide insights on potential personalized therapies for people undergoing these health disparities.
Chronic Exposure to Sublethal Concentrations of Aquatic Nitrite Change Nose and Gut Morphology and Associated Microbiomes in Channel Catfish
Authors: Franklin Ashley , Ortiz Whitney , Matthews Michael , Prangnell David , Carlos‐Shanley Camila , Huertas Mar 
Published: May 2022

Nitrite is a common pollutant that can enter waterways via agricultural runoff or build up in aquaculture ponds when nitrogenous waste is converted to nitrite. Preliminary studies by the Huertas lab found that exposure to sublethal concentrations of aquatic nitrite alters the microbiome of goldfish and bioaccumulates in the olfactory epithelia, gills and brain. These studies also showed a negative impact on the olfactory tissue of exposed fish, which could lead to higher susceptibility to nasal pathogens. Our objective is to assess nitrite bioaccumulation in tissues and the alteration of the microbiome in the key aquaculture species channel catfish (Ictalurus punctatus). We hypothesize that the relative abundance and diversity of bacteria in the nose and gut microbiomes of channel catfish will be altered due to elevated nitrite exposure and that nitrite will bioaccumulate in tissues.Channel catfish were exposed to 0 mM (control), 0.2 mM, and 2 mM concentrations of nitrite. A total of six 500 liter tanks were used in a two‐phase experiment. For phase one, 16 fish per tank were placed into three 0 mM nitrite tanks and three 2 mM nitrite tanks. The 2 mM fish were kept for 12 hours before sampling. For phase two, 24 of the phase one control fish were placed into three 0.2 mM tanks and the remaining 24 control fish were left in the three control tanks for a total of 8 fish per tank. Phase two lasted 30 days with sub‐samplings at day five and 30. All fish were sampled for nose, gut, muscle, gill, brain, blood, liver, and kidney tissues for biochemical, microbial, or histological analysis. Upon dissection, fish from the 2 mM tanks exhibited marked methemoglobinemia due to nitrite‐induced oxidation of hemoglobin. The mortality rates were 0.04%, 0.08%, and 92% for the control, 0.2 mM, and 2 mM treatments respectively. The nose and gut microbiomes will be sequenced using whole genome shotgun sequencing to determine the microbial composition and measure changes in relative abundance. Histological analysis showed oxidative damage in all tissues from individuals exposed to 2 mM and partial damage in tissues of the 0.2 mM treatment.Because the microbiome is a powerful barrier against pathogens, disruption of the microbiome could lead to higher rates of disease infection and transmission in fish. Alteration of the nasal microbiome may increase mortality from the bacteria that cause septicemia in catfish, Edwardsiella ictaluri, whose common routes of infection are the nose or gut. Changes to the microbiome could be the missing link between nitrite and increased susceptibility to E. ictaluri infections in intensive farming. In the long term, this research aims to provide guidelines for water quality management in order to decrease the rate of bacterial infection and transmission in aquaculture systems.
Non‐invasive, Spatiotemporal Characterization of Muscle Activation Patterns from Vagus Nerve Stimulation in Human Subjects
Authors: Feucht Maria , Gupta Anita , Sabau Dragos , Nowak Thomas , Coimbatore Rama , Powley Terry , Ward Matthew 
Published: May 2022

Background and HypothesisVagus nerve stimulation (VNS) is used for treatment of epilepsy in over 100,000 patients worldwide and is a potential treatment for inflammatory disorders such as rheumatoid arthritis, diabetes, and sepsis. VNS‐evoked compound nerve action potentials (CNAPs) may have applications as a biomarker of VNS treatment efficacy, but transcutaneous measurement of this activity is obscured by laryngeal muscle artifacts during cervical VNS. Our objective is to develop a more precise understanding of muscle activation patterns that could improve recording and analysis protocols for isolating the vagus nerve (VN) CNAP from EMG artifacts. We hypothesize that analyzing multi‐electrode array (MEA) surface recordings overlying the VN will allow us to characterize this muscle artifact.MethodsTwelve patients undergoing VNS therapy for epilepsy were enrolled in a clinical study at Indiana University School of Medicine (IRB #2006075899). The anatomical dimensions of the neck were recorded for seven of the twelve subjects. A custom‐made MEA with a grid of 32 soft foam electrodes was placed on the skin overlying the VN on each side of the neck with the short axis parallel to the sternocleidomastoid muscle and the midpoint at the level of the laryngeal prominence. Surface potentials were recorded for approximately 20 minutes at the patient’s established device settings.ResultsVNS‐evoked potentials were visualized in nine subjects (three subjects were excluded due to insufficient data). Two probable muscle artifacts were identified, defined as non‐propagating features in the mean response to n > 600 pulses of VNS. The first had an onset latency of ~1‐3 ms, and the second had a latency of ~7‐10 ms. Both artifacts appeared primarily in the electrodes overlying the laryngeal muscles. In one subject, propagating activity at an approximate velocity of 70‐110 m/s was visualized between 1‐2 ms latency.ConclusionThe short latency of the first muscle artifact suggests stimulus signal leakage activating the superior laryngeal nerve. The propagating activity visualized in one subject may show the activity of the external branch of the superior laryngeal nerve, which stimulates the cricothyroid muscle to contract, creating the first muscle artifact. The second artifact with longer latency is likely caused by the recurrent laryngeal nerve, which causes contraction of intrinsic laryngeal muscles such as the posterior cricoarytenoids. Previous analyses may have mischaracterized the first muscle artifact as nerve activity [Usami, K., Kawai, K., Sonoo, M., and Saito, N. (2013). Brain Stimul. 6(4), 615‐623]. The use of MEA‐based recordings clarifies our understanding of the VN’s response to VNS, which may lead to better treatment efficacy and the eventual development of personalized VNS therapies for epilepsy and a range of inflammatory disorders.
Delayed Reperfusion of the Renal Outer Medulla Attenuates Ischemia Reperfusion‐Induced Vascular Congestion
Authors: McLarnon Sarah R. , Sun Jingping , O'Connor Paul M. 
Published: May 2022

Vascular congestion, or red blood cell (RBC) trapping, of the renal outer medulla (OM) is a common finding in acute tubular necrosis caused by ischemia reperfusion (IR). Work from our laboratory suggests that vascular congestion originates in the renal venous vasculature of the cortex and OM during the ischemic phase. Following reperfusion, RBCs then fill the OM plexus capillaries as the venous drainage vessels of this region remain blocked. We have also previously reported that pretreatment with low dose lipopolysaccharide (LPS) attenuates IR‐induced vascular congestion, however the mechanisms remain unknown. In the current study, we hypothesized that pretreatment with LPS prevents vascular congestion by delayed reperfusion of blood to the OM following ischemia.To test this hypothesis, WKY rats (male, 12 weeks) were pretreated (i.p) with 1mg/kg LPS (n=6) or saline control (n=7) once daily for 3 days. Rats were then anesthetized, and Transonic Laser Doppler probes were inserted in the renal cortex and OM. Doppler flux, as a determinate of regional kidney blood flow was then measured over 10 minutes of baseline, 45 minutes of renal artery clamping and 30 minutes of reperfusion.We found no differences in baseline blood flow of the cortex (pTREATMENT=0.0543) or OM (pTREATMENT=0.5085) between rats pretreated with low dose LPS or saline control. Following removal of the renal artery clamp, the return of blood flow to the cortex was gradual over the first several minutes of reperfusion (pTIME<0.0001), reaching a plateau following 10 minutes of reperfusion in both treatment groups (pINTERACTION=0.9999) (Fig. A). The reperfusion of blood to the OM, however, rapidly returned to baseline levels within 1 minute of reperfusion in control animals (1 min: 0 to 0.43AU) (Fig. B). In contrast, OM blood flow returned slowly in LPS treated rats (1 min: 0 to ‐0.08AU) and did not return to baseline levels during the 30‐minute reperfusion period (pINTERACTION=0.0127) (Fig. B).These data indicate that LPS pretreatment, paradoxically, delayed early reperfusion of the renal OM via a regional vasoconstriction response. We speculate that delayed reperfusion of the OM attenuates medullary plexus congestion by allowing time for the RBCs in the shared venous circulation to clear. These findings support the hypothesis that reperfusion of the renal outer medullary plexus before cortical perfusion is restored, is responsible for the development of prolonged vascular congestion. New therapeutics focused on renal hemodynamics to prevent congestion after ischemia may prevent much of the injury associated with acute kidney injury.
Novel and Effective: ECG Utilization for MI Confirmation in Mouse Models
Authors: Broughton Philip , Troncoso Miguel , DeLeon‐Pennell Kristine 
Published: May 2022

IntroductionElectrocardiography measures the electrical activity of the heart to generate an electrocardiogram (ECG) through a non‐invasive process that involves placing electrodes on strategic points on the body. When an MI occurs, the lack of contractility induces changes to the ECG, visualized by a prolonged QRS wave and amplification of the R wave. Previously, we identified the area under the QRS wave, 1 min after permanent ligation in a mouse model of myocardial infarction (MI) determined surgical success. The purpose of this study was to further demonstrate in a second cohort that the previous ECG parameters identified accurately confirmed that an MI has been administered by left anterior coronary artery ligation in real‐time.Methods and ResultsPermanent coronary artery ligation was performed on WT and CD8atmak1 (CD8‐/‐) mice (n=9/genotype); an ECG was recorded using a surgical monitoring platform and was analyzed on iWorkx LabScribe Data Acquisition and Analysis software. Previous analysis of the first dataset indicated no differences between sexes so both males and females were used in the second cohort. A receiver operating characteristic (ROC) curve was used to link changes in the QRS complex at the 1‐min mark with MI surgical success. By ROC analysis, the area under the QRS complex had an area under the curve (AUC) of 0.94 (p=0.01) indicating a strong association with MI success. To remove any potential effect of surgical platform variability, we normalized the 1 min data to pre‐MI values to determine fold‐change in the area under the QRS complex. ROC analysis of the normalized data also indicated a strong sensitivity and specificity for MI success with an AUC value of 0.90 (p=0.02). Mice in the second cohort were divided into two groups based on a cut‐off point for either the area under the QRS complex (≥0.003 mV/sec) or the normalized data (≥ 3.1 fold change in the QRS complex) to distinguish the two groups. Using the non‐normalized data alone, there was an 84% success rate with 2 false positives and 1 false negative. Analysis using the normalized data alone had an 74% success rate, with 2 false positives and 3 false negatives. None of these false positives or negatives were linked to genotype or sex.ConclusionOur data indicates that while changes in the QRS complex 1‐min after ligation may be useful for confirming MI surgical success, there are potential limitations that could skew the data. One possible explanation for the false positives could be variation between ECG boards. To remove this, we normalized post‐MI data to pre‐MI values but, this seemed to decrease effectiveness. It is also important to note that many of the false negatives were due to anomalies within the ECG such as the presence of R‐prime waves. For this reason, users must be consistent when analyzing the ECG data points to minimize variation. In summary, using the ECG data 1 min after ligation had a fairly strong prediction rate for MI surgical success.
Recognition and Cleavage of Human tRNA Methyltransferase TRMT1 by the SARS‐CoV‐2 Main Protease
Authors: D'Oliviera Angel , Geissler Evan P. , Mugridge Jeffrey S. 
Published: May 2022

The SARS‐CoV‐2 main protease (MPro) is responsible for cleaving viral polypeptides to generate functional viral proteins, but like other viral proteases, MPro may also actively target and cleaave endogenous human host proteins during infection. Here we show that a human tRNA methyltransferase, TRMT1, can be recognized and cleaved by SARS‐CoV‐2 MPro. TRMT1 is a SAM‐dependent methyltransferase that installs the N2,N2‐dimethylguanosine (m2,2G) modification onto position G26 of human tRNAs. This abundant m2,2G modification is important for global protein synthesis, cellular redox homeostasis, and has been linked to neurodevelopmental defects. Early in the COVID‐19 pandemic, a host‐virus protein interaction map identified a putative interaction between SARS‐CoV‐2 MPro and human TRMT1. We carried out kinetic assays that show both a short peptide sequence in TRMT1 as well as endogenous, full‐length TRMT1 are actively cleaved by recombinant SARS‐CoV‐2 MPro in vitro. Cleavage of full‐length TRMT1 results in loss of its C‐terminal zinc finger domain thought to be critical for tRNA binding. Furthermore, we determined the co‐crystal structure of the human TRMT1 peptide in complex with SARS‐CoV‐2 MPro, which shows that the bound TRMT1 peptide substrate adopts a unique conformation in the protease active site. These results suggest that tRNA methyltransferase TRMT1 is a viable substrate for SARS‐CoV‐2 MPro, provide new structural insights into the diverse substrate recognition properties of the viral protease, and raise the possibility that TRMT1 cleavage during SARS‐CoV‐2 infection could contribute to downregulation of host protein synthesis or other phenotypes of viral infection.