bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of Facile RP-HPLC Method for Simultaneous Determination of Timolol Maleate, Moxifloxacin Hydrochloride, Diclofenac Sodium and Dexamethasone in Plasma, Aqueous Humor and Pharmaceutical Products
Authors: Shahzad Aqeel , Arshad Sohail , Zubair Faryal , Shahzad Shakeel , Batool Farzana , Fu Qiang 
Published: July 2022

Abstract
The present study aimed to develop a validated RP-HPLC method for the simultaneous determination of timolol maleate (TM), moxifloxacin hydrochloride (MOXI), diclofenac sodium (DS) and dexamethasone (DEXA) in human plasma, bovine aqueous humor and pharmaceutical preparations. The chromatographic separation was studied using the C18 column. The chromatographic conditions, such as composition, pH, the flow rate of mobile phase, the temperature of column, wavelength of absorption and injection volume of the sample, were studied. The method was validated to confirm specificity, linearity and accuracy in accordance with an International Conference on Harmonization guidelines. The optimum conditions for separation included mobile phase 0.05 M monobasic phosphate buffer: acetonitrile (65:35 v/v), pH of buffer adjusted to 6.2 and the flow rate of 1 mL/minute. The optimum temperature of the column was found to be 35°C, absorption wavelength 265 nm and injection volume 50 μL. The baseline separation of all four drugs with good sensitivity, resolution, and a less than 15 min run time was achieved. The retention time of TM, MOXI, DS and DEXA were 4.3,5.7,9.9 and 13.5 minutes respectively. The limit of detection (LOD) values were 6.2, 4.8, 0.8 and 1.2 ng/mL for TM, MOXI, DS and DEXA, respectively, whereas their respective limit of quantification (LOQ) values was: were 42.6, 26.8, 5.6 and 6.2 ng/mL. The coefficient of variation for intra-day and inter-day were in the range of 0.32–1.57 and 1.29–3.07%, respectively. The method was found to be sensitive, precise and accurate in human plasma and bovine aqueous humor and can be applied for the quantification of these compounds in plasma, aqueous humor and pharmaceuticals.
An Effective Chromatographic Method for Simultaneous Quantification of Antidiabetic Drugs Alogliptin Benzoate and Pioglitazone HCl in Their Tablet Dosage Form: Implementation toIn vitroDissolution Studies and Uniformity of Dosage Unit
Authors: Mohamed Mahmoud A 
Published: July 2022

AbstractIn patients with Type 2 diabetes, a combination of Alogliptin and Pioglitazone medications, together with diet and physical activity, are used to improve glycemic control. Eco-friendly, cost-effective, and precise stability-indicating RP-HPLC method was developed and validated for the identification and quantification of Alogliptin and Pioglitazone in their tablet dosage form, as well as implementation to in vitro dissolution studies and uniformity of dosage unit. Isocratic separation is conducted at ambient temperature on the InertSustain C18 Analytical Column (150 × 4.6 mm, 5 μm) using mobile phase comprising 50 mM of ammonium dihydrogen phosphate and 5.0 mM of heptane sulfonic acid:acetonitrile (45:55, v/v) at a flow rate of 1.3 mL/minute. Calibration curves are conducted in the linearity range of 1–40 μg/mL of Alogliptin and 2.5–75 μg/mL of Pioglitazone with a correlation value &gt;0.9995 and satisfactory recovery findings between 99 and 100%. The degraded samples are analyzed under relevant stress conditions as acidity, alkalinity, thermal and oxidation. The active components in finished products were subjected to a content uniformity test, which showed that they achieved the declared claim’s acceptance standards (85–115%). Comparative in vitro dissolution studies are performed for generic products Inhibazone 12.5/30 mg FCT and Inhibazone 25/15 mg FCT against innovator products Oseni 12.5/30 mg FCT and Oseni 25/15 mg FCT at suitable FDA dissolution medium and different USP dissolution media and the results are similar. The metrics of the designed method were assessed according to ICH requirements, and all metrics, such as system suitability, linearity, recovery, robustness, LOD, LOQ, specificity and precision, were found to be within required tolerances and no overlapping was found for degradation peaks. Thence, the method can be used in quality control for the analysis of raw material, bulk, finish and stability.
Incidence and Clearance of Anal Human Papillomavirus Infection in 16 164 Individuals, According to Human Immunodeficiency Virus Status, Sex, and Male Sexuality: An International Pooled Analysis of 34 Longitudinal Studies
Authors: Wei Feixue , Goodman Marc T , Xia Ningshao , Zhang Jun , Giuliano Anna R , D’Souza Gypsyamber , Hessol Nancy A , Schim van der Loeff Maarten F , Dai Jianghong , Neukam Karin , de Pokomandy Alexandra , Poynten I Mary , Geskus Ronald B , Burgos Joaquin , Etienney Isabelle , Moscicki Anna-Barbara , Donà Maria Gabriella , Gillison Maura L , Nyitray Alan G , Nowak Rebecca G , Yunihastuti Evy , Zou Huachun , Hidalgo-Tenorio Carmen , Phanuphak Nittaya , Molina Jean-Michel , Schofield Alice M , Kerr Stephen , Fan Song , Lu Yong , Ong Jason J , Chikandiwa Admire T , Teeraananchai Sirinya , Squillace Nicola , Wiley Dorothy J , Palefsky Joel M , Georges Damien , Alberts Catharina J , Clifford Gary M 
Published: July 2022

Abstract

Background
Understanding the natural history of anal high-risk human papillomavirus (hrHPV) infection is key for designing anal cancer prevention programs but has not been systematically characterized.

Methods
We reanalyzed data from 34 studies including 16 164 individuals in 6 risk groups defined by human immunodeficiency virus (HIV) status, sex, and male sexuality: men who have sex with men (MSM) and people with HIV (MSMWH), HIV-negative MSM, women with HIV (WWH), HIV-negative women, men who have sex with women (MSW) with HIV (MSWWH), and HIV-negative MSW. We used Markov models to estimate incidence and clearance of 13 hrHPV types and their determinants.

Results
Human papillomavirus (HPV) 16 had the highest incidence-clearance ratio of the hrHPV types. MSMWH had the highest hrHPV incidence (eg, 15.5% newly HPV-16 infected within 2 years), followed by HIV-negative MSM (7.5%), WWH (6.6%), HIV-negative women (2.9%), MSWWH (1.7%), and HIV-negative MSW (0.7%). Determinants of HPV-16 incidence included HIV status and number of sexual partners for MSM, women, and MSW, and anal sex behavior for MSM only. HPV-16 clearance was lower for people with HIV (PWH) and lower for prevalent than incident infection. Among MSM, increasing age was associated with lower clearance of prevalent, but not incident, HPV-16 infection.

Conclusions
This robust and unifying analysis of anal hrHPV natural history is essential to designing and predicting the impact of HPV vaccination and HPV-based screening programs on anal cancer prevention, particularly in MSM and PWH. Importantly, it demonstrates the higher carcinogenic potential of longstanding anal prevalent hrHPV infection than more recent incident infection.
LAM: Scrutinizing Leading APIs For Detecting Suspicious Call Sequences
Authors: Alam Shahid 
Published: July 2022

Abstract
The proliferation of smartphones has given exponential rise to the number of new mobile malware. These malware programs are employing stealthy obfuscations to hide their malicious activities. To perform malicious activities a program must make application programming interface (API) calls. Unlike dynamic, static analysis can find all the API call paths but have some issues: large number of features; higher false positives when features reduced; and lowering false positives increases the detection rate. Certain Android API calls, e.g. android.app.Activity:boolean requestWindowFeature(int) enable malware programs to call other APIs to hide their activities. We call them leading APIs as they can lead to malicious activities. To overcome these issues, we propose new heuristics and feature groupings for building a Leading API-call Map, named LAM. We create LAM from a dominant (leading) API call tree. Dominance is a transitive relation and hence enumerates all the call sequences that a leading API leads to. LAM substantially reduces the number and improves the quality of features for combating obfuscations and detecting suspicious call sequences with few false positives. For the dataset used in this paper, LAM reduced the number of features from 509 607 to 29 977. Using 10-fold cross-validation, LAM achieved an accuracy of 97.9% with 0.4% false positives.
Multimodality delineation of a fistulous ruptured sinus of Valsalva aneurysm: a teaching case report
Authors: Zhou Ruihai , Yeung Michael , Sharma Mahesh S 
Published: July 2022

AbstractBackgroundRuptured sinus of Valsalva (SOV) is a rare cardiac anomaly with poor prognosis if untreated. Early diagnosis with accurate delineation of its anatomy is critical for timely treatment and choice of surgical vs. percutaneous intervention. Here we report a case of fistulous rupture of SOV; the preoperative multimodality studies including echocardiography, cardiac magnetic resonance and cardiac catheterization provided teaching and learning points.Case summaryA 48-year-old man with history of heart murmur and hypertension presented with a 5-day history of shortness of breath and peripheral oedema. He was diagnosed with rapid atrial flutter. The transthoracic and transesophageal echocardiography showed severe biventricular systolic dysfunction with a left-to-right shunt from ruptured SOV. The colour Doppler by transthoracic and transesophageal echocardiography and cardiac magnetic resonance revealed a swaying shunt flow exiting in direction to the right atrium (RA) and basal right ventricle (RV) during systole and diastole with no myocardial scaring. The left and right heart catheterization showed elevated right-sided pressures, pulmonary capillary wedge pressure, and left ventricular end-diastolic pressure. There was no difference in O2 saturation between venae cavae and RA but a misleading step-up in O2 saturation between RA and RV. Owing to rupture anatomy with uncertainty, the patient underwent surgical intervention. The ruptured SOV tunnelled through the base of tricuspid annulus to the RA very close to the basal RV.DiscussionEven with multimodality studies it can still be challenging to delineate the anatomy of a ruptured SOV without uncertainty preoperatively.
Effects of a comprehensive lifestyle intervention on cardiovascular health: the TANSNIP-PESA trial
Authors: Garcia-Lunar Ines , van der Ploeg Hidde P , Fernández Alvira Juan Miguel , van Nassau Femke , Castellano Vázquez Jose Maria , van der Beek Allard J , Rossello Xavier , Fernández-Ortiz Antonio , Coffeng Jennifer , van Dongen Johanna M , Mendiguren Jose Maria , Ibáñez Borja , van Mechelen Willem , Fuster Valentin 
Published: July 2022

Abstract

Aims
To investigate the effectiveness of a 3-year worksite lifestyle intervention on cardiovascular metrics and to study whether outcomes are influenced by baseline subclinical atherosclerosis (SA) by non-invasive imaging.

Methods and results
A randomized controlled trial was performed to compare a lifestyle intervention with standard of care in asymptomatic middle-aged subjects, stratified by SA. The intervention consisted of nine motivational interviews during the first year, followed by three further sessions between Years 1 and 3. The primary outcome was the change in a pre-specified adaptation of the Fuster-BEWAT score (Blood pressure, Exercise, Weight, Alimentation, and Tobacco) between baseline and follow-up Years 1–3. A total of 1020 participants (mean age 50 ± 4 years) were enrolled, of whom 510 were randomly assigned to the intervention and 510 to the control group. The baseline adapted Fuster-BEWAT score was 16.2 ± 3.7 points in the intervention group and 16.5 ± 3.5 points in the control group. At Year 1, the score improved significantly in intervention participants compared with controls [estimate 0.83 (95% CI 0.52–1.15) points]. However, intervention effectiveness decreased to non-significant levels at Year 3 [0.24 (95% CI –0.10 to 0.59) points]. Over the 3-year period, the intervention was effective in participants having low baseline SA [0.61 (95% CI 0.30–0.93) points] but not in those with high baseline SA [0.19 (95% CI –0.26 to 0.64) points].

Conclusion
In middle-aged asymptomatic adults, a lifestyle intervention was associated with a significant improvement in cardiovascular health and behavioural metrics. The effect attenuated after 1 year as the intensity of the intervention was reduced.

Trial registration
ClinicalTrials.gov (NCT02561065).
Phenotyping the hypertensive heart
Authors: Tadic Marijana , Cuspidi Cesare , Marwick Thomas H 
Published: July 2022

Abstract
Arterial hypertension remains the most frequent cardiovascular (CV) risk factor, and is responsible for a huge global burden of disease. Echocardiography is the first-line imaging method for the evaluation of cardiac damage in hypertensive patients and novel techniques, such as 2D and D speckle tracking and myocardial work, provide insight in subclinical left ventricular (LV) impairment that would not be possible to detect with conventional echocardiography. The structural, functional, and mechanical cardiac remodelling that are detected with imaging are intermediate stages in the genesis of CV events, and initiation or intensification of antihypertensive therapy in response to these findings may prevent or delay progressive remodelling and CV events. However, LV remodelling—especially LV hypertrophy—is not specific to hypertensive heart disease (HHD) and there are circumstances when other causes of hypertrophy such as athlete heart, aortic stenosis, or different cardiomyopathies need exclusion. Tissue characterization obtained by LV strain, cardiac magnetic resonance, or computed tomography might significantly help in the distinction of different LV phenotypes, as well as being sensitive to subclinical disease. Selective use of multimodality imaging may therefore improve the detection of HHD and guide treatment to avoid disease progression. The current review summarizes the advanced imaging tests that provide morphological and functional data about the hypertensive cardiac injury.
Local genetic covariance between serum urate and kidney function estimated with Bayesian multitrait models
Authors: Lupi Alexa S , Sumpter Nicholas A , Leask Megan P , O’Sullivan Justin , Fadason Tayaza , de los Campos Gustavo , Merriman Tony R , Reynolds Richard J , Vazquez Ana I 
Published: July 2022

Abstract
Hyperuricemia (serum urate &gt;6.8 mg/dl) is associated with several cardiometabolic and renal diseases, such as gout and chronic kidney disease. Previous studies have examined the shared genetic basis of chronic kidney disease and hyperuricemia in humans either using single-variant tests or estimating whole-genome genetic correlations between the traits. Individual variants typically explain a small fraction of the genetic correlation between traits, thus the ability to map pleiotropic loci is lacking power for available sample sizes. Alternatively, whole-genome estimates of genetic correlation indicate a moderate correlation between these traits. While useful to explain the comorbidity of these traits, whole-genome genetic correlation estimates do not shed light on what regions may be implicated in the shared genetic basis of traits. Therefore, to fill the gap between these two approaches, we used local Bayesian multitrait models to estimate the genetic covariance between a marker for chronic kidney disease (estimated glomerular filtration rate) and serum urate in specific genomic regions. We identified 134 overlapping linkage disequilibrium windows with statistically significant covariance estimates, 49 of which had positive directionalities, and 85 negative directionalities, the latter being consistent with that of the overall genetic covariance. The 134 significant windows condensed to 64 genetically distinct shared loci which validate 17 previously identified shared loci with consistent directionality and revealed 22 novel pleiotropic genes. Finally, to examine potential biological mechanisms for these shared loci, we have identified a subset of the genomic windows that are associated with gene expression using colocalization analyses. The regions identified by our local Bayesian multitrait model approach may help explain the association between chronic kidney disease and hyperuricemia.
Spatial and temporal control of expression with light-gated LOV-LexA
Authors: Ribeiro Inês M A , Eßbauer Wolfgang , Kutlesa Romina , Borst Alexander 
Published: July 2022

Abstract
The ability to drive expression of exogenous genes in different tissues and cell types, under the control of specific enhancers, has been crucial for discovery in biology. While many enhancers drive expression broadly, several genetic tools were developed to obtain access to isolated cell types. Studies of spatially organized neuropiles in the central nervous system of fruit flies have raised the need for a system that targets subsets of cells within a single neuronal type, a feat currently dependent on stochastic flip-out methods. To access the same cells within a given expression pattern consistently across fruit flies, we developed the light-gated expression system LOV-LexA. We combined the bacterial LexA transcription factor with the plant-derived light, oxygen, or voltage photosensitive domain and a fluorescent protein. Exposure to blue light uncages a nuclear localizing signal in the C-terminal of the light, oxygen, or voltage domain and leads to the translocation of LOV-LexA to the nucleus, with the subsequent initiation of transcription. LOV-LexA enables spatial and temporal control of expression of transgenes under LexAop sequences in larval fat body and pupal and adult neurons with blue light. The LOV-LexA tool is ready to use with GAL4 and Split-GAL4 drivers in its current form and constitutes another layer of intersectional genetics that provides light-controlled genetic access to specific cells across flies.
Neuropsychological Correlates of Changes in Driving Behavior Among Clinically Healthy Older Adults
Authors: Aschenbrenner Andrew J , Murphy Samantha A , Doherty Jason M , Johnson Ann M , Bayat Sayeh , Walker Alexis , Peña Yasmin , Hassenstab Jason , Morris John C , Babulal Ganesh M 
Published: July 2022

Abstract

Objectives
To determine the extent to which cognitive domain scores moderate change in driving behavior in cognitively healthy older adults using naturalistic (Global Positioning System-based) driving outcomes and to compare against self-reported outcomes using an established driving questionnaire.

Methods
We analyzed longitudinal naturalistic driving behavior from a sample (N = 161, 45% female, mean age = 74.7 years, mean education = 16.5 years) of cognitively healthy, nondemented older adults. Composite driving variables were formed that indexed “driving space” and “driving performance.” All participants completed a baseline comprehensive cognitive assessment that measured multiple domains as well as an annual self-reported driving outcomes questionnaire.

Results
Across an average of 24 months of naturalistic driving, our results showed that attentional control, broadly defined as the ability to focus on relevant aspects of the environment and ignore distracting or competing information as measured behaviorally with tasks such as the Stroop color naming test, moderated change in driving space scores over time. Specifically, individuals with lower attentional control scores drove fewer trips per month, drove less at night, visited fewer unique locations, and drove in smaller spaces than those with higher attentional control scores. No cognitive domain predicted driving performance such as hard braking or sudden acceleration.

Discussion
Attentional control is a key moderator of change over time in driving space but not driving performance in older adults. We speculate on mechanisms that may relate attentional control ability to modifications of driving behaviors.
Enhanced volatile emissions and anti-herbivore functions mediated by the synergism between jasmonic acid and salicylic acid pathways in tea plants
Authors: Jiao Long , Bian Lei , Luo Zongxiu , Li Zhaoqun , Xiu Chunli , Fu Nanxia , Cai Xiaoming , Chen Zongmao 
Published: July 2022

Abstract
The interaction between jasmonic acid (JA) and salicylic acid (SA) pathways, which affects plant stress resistance, is mainly considered to be antagonistic. Using an established theoretical model, we investigated how tea plant (Camellia sinensis) volatiles induced by exogenous elicitors of the JA and SA pathways are affected by the sequence of elicitor application, elicitor identity, and the applied concentrations. We also examined the effects of the volatiles mediated by the JA–SA synergistic interaction on the behaviors of a tea leaf-chewing herbivore (Ectropis grisescens) and its parasitic wasp (Apanteles sp.). The JA and SA pathway interactions were almost always reciprocally synergistic when the two pathways were elicited at different times, except at high JA elicitor concentrations. However, the JA pathway antagonized the SA pathway when they were elicited simultaneously. The elicitor identity affected the degree of JA–SA interaction. The volatiles induced by the JA pathway in the JA–SA reciprocal synergism treatments included up to 11 additional compounds and the total amount of volatiles was up to 7.9-fold higher. Similarly, the amount of emitted volatiles induced by the SA pathway in the reciprocal synergism treatments increased by up to 4.2-fold. Compared with the volatiles induced by either pathway, the enriched volatiles induced by the JA–SA reciprocal synergism similarly repelled E. grisescens, but attracted Apanteles sp. more strongly. Thus, non-simultaneous activation is important for optimizing the JA–SA reciprocal synergism. This reciprocal synergism enables plants to induce multifarious responses, leading to increased biotic stress resistance.
Susceptibility factor StEXA1 interacts with StnCBP to facilitate potato virus Y accumulation through the stress granule-dependent RNA regulatory pathway in potato
Authors: Chen Ruhao , Tu Zhen , He Changzheng , Nie Xianzhou , Li Kun , Fei Sitian , Song Botao , Nie Bihua , Xie Conghua 
Published: July 2022

Abstract
Plant viruses recruit multiple host factors for translation, replication, and movement in the infection process. The loss-of-function mutation of the susceptibility genes will lead to the loss of susceptibility to viruses, which is referred to as ‘recessive resistance’. Essential for potexvirus Accumulation 1 (EXA1) has been identified as a susceptibility gene required for potexvirus, lolavirus, and bacterial and oomycete pathogens. In this study, EXA1 knockdown in potato (StEXA1) was found to confer novel resistance to potato virus Y (PVY, potyvirus) in a strain-specific manner. It significantly compromised PVYO accumulation but not PVYN:O and PVYNTN. Further analysis revealed that StEXA1 is associated with the HC-Pro of PVY through a member of eIF4Es (StnCBP). HC-ProO and HC-ProN, two HC-Pro proteins from PVYO and PVYN, exhibited strong and weak interactions with StnCBP, respectively, due to their different spatial conformation. Moreover, the accumulation of PVYO was mainly dependent on the stress granules (SGs) induced by StEXA1 and StnCBP, whereas PVYN:O and PVYNTN could induce SGs by HC-ProN independently through an unknown mechanism. These results could explain why StEXA1 or StnCBP knockdown conferred resistance to PVYO but not to PVYN:O and PVYNTN. In summary, our results for the first time demonstrate that EXA1 can act as a susceptibility gene for PVY infection. Finally, a hypothetical model was proposed for understanding the mechanism by which StEXA1 interacts with StnCBP to facilitate PVY accumulation in potato through the SG-dependent RNA regulatory pathway.