bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and Validation of Ultra Performance Liquid Chromatography (UPLC) Method for the Quantitative Estimation of Caffeine in Non-Alcoholic Soft and Energy Drinks
Authors: Ahmad Wasim , Yusuf Mohammad , Ahmad Ayaz , Hassan Yousif Amin , Amir Mohd , Wahab Shadma 
Published: February 2022

Abstract

Background
The popularity of beverages such as cold coffee, iced tea, and energy drinks has risen tremendously among athletes and youths. Energy drinks are used to enhance performance due to the presence of a high amount of caffeine (CFN) and sugars, as well as other constituents such as vitamins, amino acids, taurine, extracts of Ginkgo biloba, ginseng, guarana, and other herbal products. Commercial drinks are promoted as being beneficial to health; thus it is an important concern regarding adverse effects linked with these drinks or products.

Objective
The aim of the study is to develop and validate the ultra performance liquid chromatography-photodiode array detector (UPLC-PDA) method for the estimation of CFN in eight marketed non-alcoholic drinks including two soft drinks and six energy drinks.

Method
The chromatographic separation of CFN was achieved on Acquity UPLC® CSHTM C18 1.7 µm, 2.1 × 100 mm column, using isocratic mode, mobile phase comprising acetonitrile and water (30:70, v/v) at a flow rate 0.3 mL/min using injection volume 1 µL.

Results
The elution of CFN occurred at 1.06 min, and the calibration curve of the CFN was computed from the peak area ratio detected at 273 nm. All the validation parameters were found within the assay variability limits as per ICH guidelines. The obtained results revealed that the soft drinks SD1 and SD2 have 87.21 ± 1.28 and 101.81 ± 1.52% (w/w), whereas CFN concentration in energy drink brands ED1, ED2, ED3, ED4, ED5, and ED6 was 95.90 ± 1.62, 64.0 ± 1.07, 76.68 ± 1.95, 74.97 ± 2.33, 82.09 ± 2.43, and 88.04 ± 2.94% (w/w) of labeled claims, respectively.

Conclusions
The developed UPLC method was found suitable for the quality control of commercial soft and energy drinks containing CFN.

Highlights
The developed chromatographic method is very simple, cost effective and could be utilized for the routine analysis of caffeine in the soft and energy drinks.
Pediatric SARS-CoV-2 Seroprevalence in Arkansas Over the First Year of the COVID-19 Pandemic
Authors: Boehme Karl W , Kennedy Joshua L , Snowden Jessica , Owens Shana M , Kouassi Marianne , Mann Ryan L , Paredes Amairani , Putt Claire , James Laura , Jin Jing , Du Ruofei , Kirkpatrick Catherine , Modi Zeel , Caid Katherine , Young Sean , Zohoori Namvar , Kothari Atul , Boyanton Bobby L , Craig Forrest J 
Published: February 2022

Abstract

Background
Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) seroprevalence studies largely focus on adults, but little is known about spread in children. We determined SARS-CoV-2 seroprevalence in children and adolescents from Arkansas over the first year of the coronavirus disease of 2019 (COVID-19) pandemic.

Methods
We tested remnant serum samples from children ages 1-18 years who visited Arkansas hospitals or clinics for non-COVID-19-related reasons from April 2020 through April 2021 for SARS-CoV-2 antibodies. We used univariable and multivariable regression models to determine the association between seropositivity and participant characteristics.

Results
Among 2357 participants, seroprevalence rose from 7.9% in April/May 2020 (95% CI, 4.9-10.9) to 25.0% in April 2021 (95% CI, 21.5-28.5). Hispanic and black children had a higher association with antibody positivity than non-Hispanic and white children, respectively, in multiple sampling periods.

Conclusions
By spring 2021, most children in Arkansas were not infected with SARS-CoV-2. With the emergence of SARS-CoV-2 variants, recognition of long-term effects of COVID-19, and the lack of an authorized pediatric SARS-CoV-2 vaccine at the time, these results highlight the importance of including children in SARS-CoV-2 public health, clinical care, and research strategies.
Brain uptake and distribution patterns of 2-hydroxypropyl-ß-cyclodextrin after intrathecal and intranasal administration
Authors: Banks William A , Calias Pericles , Hansen Kim M , Bullock Kristin M , Engelke Kory 
Published: February 2022

Abstract

Objectives
Cyclodextrins are increasingly used therapeutically. For example, 2-hydroxypropyl-ß-cyclodextrin (kleptose) is used for the treatment of Niemann–Pick disease. Kleptose crosses the blood–brain barrier poorly, in part because of a central nervous system (CNS)-to-blood (efflux) transporter, and so is administered by the intrathecal (IT) route in the treatment of Niemann–Pick disease.

Methods
Here, we evaluated the uptake and distribution of kleptose by the brain and spinal cord after intranasal (IN) or IT delivery.

Key findings
Kleptose distributed to all regions of the brain and spinal cord after IN administration, with only 3.27% of the administered dose entering the bloodstream. Intrathecal delivery produced levels in the whole brain about 40 times higher than intranasal administration and about 20 times higher than previously found after intravenous administration. About 70–90% of the IT dose rapidly entered the bloodstream, in part because of the previously described efflux transporter. The uptake by CNS after IN and IT was both non-saturable. The uptake by the olfactory bulb, hypothalamus and pons-medulla was favoured by all routes of administration.

Conclusions
Kleptose was taken up by all regions of the CNS after either IN or IT administration, but IN administration resulted in only a fraction of the uptake of the IT route.
‘She Wanted to Listen to her General Practitioner’s Advice…’: Exploring and Explaining Antibiotic Prescribing as a Regulatory Encounter
Authors: Carter David J 
Published: February 2022

Abstract
This article examines the pressing global problem of antimicrobial resistance (AMR), applying motivational posture theory to demonstrate how AMR and the prescribing that drives it can be considered a regulatory challenge. Following an outline of AMR and the threat of the ‘superbugs’ to which it gives rise, the article assesses the regulatory nature of the ‘prescribing encounter’ in the primary care setting. It applies both a responsive regulatory lens and motivational posture theory to analyse over 100 narrative accounts of encounters between a general practitioner and a patient. In so doing, the article examines the discursive repertoires and cultural resources available to primary care patients to explain the prescribing encounter and the dynamics within it. It concludes that patients conceive of prescribers as regulatory authorities and prescribing itself as a regulatory encounter. On this basis, the article argues that applying responsive regulatory theory and practice in response to the AMR challenge is likely to find reasonable patient acceptance, offering a new approach to this currently intractable challenge. This article then offers an analysis of what factors indicate patient drift towards defiance of regulatory aims, and what engagement and support encourage a return to cooperation.
The Toggle Switch Model for Gene Expression Change during the Prenatal-to-Postnatal Transition in Mammals
Authors: Hao Junjun , Hao Wuling , Liu Zhen , Shi Peng 
Published: February 2022

Abstract
The prenatal-to-postnatal transition is a pivotal process in the life cycle whereby an organism shifts from responding to intrauterine cues to undergoing extrauterine stresses with many physiological adaptations. However, the molecular basis underlying the evolutionarily conserved physiological adaptations remains elusive. Here, we analyze the transcriptomes of seven organs across developmental time points from five mammalian species by constructing computational coexpression networks and report a developmental shift of gene expression at the perinatal stage. The low-to-high and high-to-low expressed genes tightly coalesce in the functional categories and gene regulatory pathways that implicate the physiological adaptions during the prenatal-to-postnatal transition, including lipid metabolism, circadian rhythm, immune response, cell cycle, and cell division. The low-to-high and high-to-low expressed genes around the perinatal stage tend to form the mutually inhibitory toggle switch gene pairs linking the gene regulatory networks in response to the environmental changes. We thus propose the toggle switch model for the developmental shift of gene expression as a mechanic framework to investigate how the physiological adaptations occur during the prenatal-to-postnatal transition.
The non-telomeric evolutionary trajectory of TRF2 in zebrafish reveals its specific roles in neurodevelopment and aging
Authors: Ying Yilin , Hu Xuefei , Han Peng , Mendez-Bermudez Aaron , Bauwens Serge , Eid Rita , Tan Li , Pousse Mélanie , Giraud-Panis Marie-Joseph , Lu Yiming , Gilson Eric , Ye Jing 
Published: February 2022

Abstract
The shelterin protein complex is required for telomere protection in various eukaryotic organisms. In mammals, the shelterin subunit TRF2 is specialized in preventing ATM activation at telomeres and chromosome end fusion in somatic cells. Here, we demonstrate that the zebrafish ortholog of TRF2 (encoded by the terfa gene) is protecting against unwanted ATM activation genome-wide. The terfa-compromised fish develop a prominent and specific embryonic neurodevelopmental failure. The heterozygous fish survive to adulthood but exhibit a premature aging phenotype. The recovery from embryonic neurodevelopmental failure requires both ATM inhibition and transcriptional complementation of neural genes. Furthermore, restoring the expression of TRF2 in glial cells rescues the embryonic neurodevelopment phenotype. These results indicate that the shelterin subunit TRF2 evolved in zebrafish as a general factor of genome maintenance and transcriptional regulation that is required for proper neurodevelopment and normal aging. These findings uncover how TRF2 links development to aging by separate functions in gene expression regulation and genome stability control.
ALT-FISH quantifies alternative lengthening of telomeres activity by imaging of single-stranded repeats
Authors: Frank Lukas , Rademacher Anne , Mücke Norbert , Tirier Stephan M , Koeleman Emma , Knotz Caroline , Schumacher Sabrina , Stainczyk Sabine A , Westermann Frank , Fröhling Stefan , Chudasama Priya , Rippe Karsten 
Published: February 2022

AbstractAlternative lengthening of telomeres (ALT) occurs in ∼10% of cancer entities. However, little is known about the heterogeneity of ALT activity since robust ALT detection assays with high-throughput in situ readouts are lacking. Here, we introduce ALT-FISH, a method to quantitate ALT activity in single cells from the accumulation of single-stranded telomeric DNA and RNA. It involves a one-step fluorescent in situ hybridization approach followed by fluorescence microscopy imaging. Our method reliably identified ALT in cancer cell lines from different tumor entities and was validated in three established models of ALT induction and suppression. Furthermore, we successfully applied ALT-FISH to spatially resolve ALT activity in primary tissue sections from leiomyosarcoma and neuroblastoma tumors. Thus, our assay provides insights into the heterogeneity of ALT tumors and is suited for high-throughput applications, which will facilitate screening for ALT-specific drugs.
Mediation of Zinc and Iron Accumulation in Maize by ZmIRT2, a Novel Iron-Regulated Transporter
Authors: Li Suzhen , Song Zizhao , Liu Xiaoqing , Zhou Xiaojin , Yang Wenzhu , Chen Jingtang , Chen Rumei 
Published: February 2022

AbstractIron (Fe) is an essential micronutrient for plant growth. Iron-regulated transporters (IRTs) play important roles in Fe2+ uptake and transport in strategy I plants. Maize (Zea mays) belongs to a strategy II plant, in which mugineic acid (MA)-Fe3+ uptake is mainly carried out by Yellow Stripe 1 (YS1). However, ZmIRT1 was previously identified by our laboratory. In this study, we isolated a novel gene from maize (ZmIRT2), which is highly homologous to OsIRT2 and ZmIRT1. ZmIRT2 was expressed in roots and anther and was induced by Fe and zinc (Zn) deficiencies. ZmIRT2-GFP fusion protein localized to the plasma membrane and endoplasmic reticulum. ZmIRT2 reversed growth defects involving Zn and Fe uptake in mutant yeast. ZmIRT2 overexpression in maize led to elevated Zn and Fe levels in roots, shoots and seeds of transgenic plants. Transcript levels of ZmIRT1 were elevated in roots, while levels of YS1 were reduced in shoots of ZmIRT2 transgenic plants. Our results imply that ZmIRT2 may function solely with ZmIRT1 to mediate Fe uptake in roots. ZmIRT1, ZmIRT2 and ZmYS1 may function in a cooperative manner to maintain Zn and Fe homeostasis in ZmIRT2 overexpressing plants. Furthermore, ZmIRT2 could be used in fortification efforts to elevate Zn and Fe levels in crop plants.
Treating patients with moderate-to-severe psoriasis vulgaris
Authors: Kessler Timothy R. 
Published: February 2022

ABSTRACT
Psoriasis vulgaris is a common inflammatory disease of adults and children. Affected patients often are incorrectly diagnosed, undertreated, or not treated at all. The relapsing course of psoriasis negatively affects a patient's quality of life. The condition is associated with social isolation, anxiety, and depression, and can harm personal relationships and employment status. Psoriasis may have a significant psychologic and socioeconomic effect throughout a patient's life. Skin involvement is the most prominent symptom of this disease; however, understanding that psoriasis is a chronic, multisystem inflammatory disease is essential to proper treatment. Patients with mild-to-moderate psoriasis can control their disease primarily with topical medications or phototherapy. However, when used as monotherapy or combined with phototherapy, topical medication can be inadequate to treat moderate-to-severe psoriasis. Biologic agents offer treatment options with many benefits for controlling psoriasis vulgaris, whether given as monotherapy or combined with topical or systemic medications.
What Role do Mitochondria Have in Diastolic Dysfunction? Implications for Diabetic Cardiomyopathy and Heart Failure With Preserved Ejection Function
Authors: McCandless Martin G. , Altara Raffaele , Booz George W. , Kurdi Mazen 
Published: February 2022

Abstract:
Diastolic dysfunction is common to both diabetic cardiomyopathy and heart failure with preserved ejection fraction (HFpEF). Although commonly attributed to increased fibrosis, alterations in mitochondrial function and associated Ca2+ handling may contribute to impaired cardiac function. With mitochondrial dysfunction, increased reactive oxygen species (ROS), inflammation, and decreased adenosine triphosphate/adenosine diphosphate ratio may lead to increased extracellular matrix and diminished contractile relaxation. In this article, we discuss recent research implicating deficient mitochondria-associated endoplasmic reticulum membranes (MAMs) as it relates to impaired metabolic function and what role that may have in diastolic dysfunction in diabetic cardiomyopathy. The contribution of mitochondrial dysfunction to diastolic dysfunction in HFpEF is less established, but equally credible based on preclinical studies. However, there are notable differences between diabetic cardiomyopathy and HFpEF. Recent evidence implicates impaired endoplasmic reticulum signaling, in particular the unfolded protein response (UPR), in the pathogenesis of HFpEF. With HFpEF, enhanced pressure on the mitochondrial “gas pedal” because of increased cytosolic Ca2+ may perturb mitochondrial homeostasis. For diabetic cardiomyopathy and HFpEF, a better understanding of how altered cellular ion and redox status affect mitochondrial function is needed. Finally, we discuss the implications that mitochondrial dysfunction may have in devising novel therapeutic strategies for diabetic cardiomyopathy and HFpEF.
Effect of Channel Assembly (KCNQ1 or KCNQ1 + KCNE1) on the Response of Zebrafish IKs Current to IKs Inhibitors and Activators
Authors: Haverinen Jaakko , Hassinen Minna , Vornanen Matti 
Published: February 2022

Abstract:
In cardiac myocytes, the slow component of the delayed rectifier K+ current (IKs) ensures repolarization of action potential during beta-adrenergic activation or when other repolarizing K+ currents fail. As a key factor of cardiac repolarization, IKs should be present in model species used for cardiovascular drug screening, preferably with pharmacological characteristics similar to those of the human IKs. To this end, we investigated the effects of inhibitors and activators of the IKs on KCNQ1 and KCNQ1 + KCNE1 channels of the zebrafish, an important model species, in Chinese hamster ovary cells. Inhibitors of IKs, chromanol 293B and HMR-1556, inhibited zebrafish IKs channels with approximately similar potency as that of mammalian IKs. Chromanol 293B concentration for half-maximal inhibition (IC50) of zebrafish IKs was at 13.1 ± 5.8 and 13.4 ± 2.8 µM for KCNQ1 and KCNQ1+KCNE1 channels, respectively. HMR-1556 was a more potent inhibitor of zebrafish IKs channels with IC50 = 0.1 ± 0.1 µM and 1.5 ± 0.8 µM for KCNQ1 and KCNQ1 + KCNE1 channels, respectively. R-L3 and mefenamic acid, generally identified as IKs activators, both inhibited zebrafish IKs. R-L3 almost completely inhibited the current generated by KCNQ1 and KCNQ1 + KCNE1 channels with similar potency (IC50 1.1 ± 0.4 and 1.0 ± 0.4 µM, respectively). Mefenamic acid partially blocked zebrafish KCNQ1 (IC50 = 9.5 ± 4.8 µM) and completely blocked KCNQ1 + KCNE1 channels (IC50 = 3.3 ± 1.8 µM). Although zebrafish IKs channels respond to IKs inhibitors in the same way as mammalian IKs channels, their response to activators is atypical, probably because of the differences in the binding domain of KCNE1 to KCNQ1. Therefore, care must be taken when translating the results from zebrafish to humans.
Exercise and Quality-of-Life Outcomes of Two Versus Three Weekly Sessions of Pulmonary Rehabilitation
Authors: Li Guanhua , Roberts Mary , Wheatley John , Leung Winnie , Harding Elise , Liu Abby , Boehm Christiane , Sausa Christine , Cho Jin-Gun 
Published: February 2022

Purpose:
This study aimed to assess whether there are differences in exercise or health-related quality-of-life (HRQoL) outcomes following twice-weekly supervised sessions of pulmonary rehabilitation (PR) compared with three times weekly over an 8-wk program in patients with chronic obstructive pulmonary disease (COPD).

Methods:
We conducted a quasi-experimental, single-center observational study using 198 subjects who completed two supervised PR sessions (intervention group) compared with 208 historical controls who completed three weekly sessions. We assessed between-group differences in outcomes after balancing groups using inverse probability of treatment weighting (IPTW) of propensity scores, followed by regression adjustment.

Results:
Both groups achieved clinically and statistically significant improvements in exercise and HRQoL following the PR program. After IPTW and regression adjustment, the intervention group had a lower post-PR 6-min walk time by 1.2: 95% CI, −12.9 to 10.5 m (P = .84), compared with the control group. Although post-PR COPD Assessment Test (CAT) scores decreased in both groups, the intervention group had a higher post-PR CAT score by 1.5: 95% CI, 0.37 to 2.66 a.u. (P = .01), compared with the control group. All other HRQoL measures failed to reach statistical significance. None of the between-group differences reached minimal clinically important differences for COPD.

Conclusions:
Our findings support current international guidelines for twice-weekly supervised PR sessions combined with unsupervised home exercise sessions. We conclude there is no disadvantage in running a PR program for patients with COPD using twice-weekly supervised sessions compared with three times weekly supervised sessions.
Cardiorespiratory Fitness, Inflammation, and Risk of Chronic Obstructive Pulmonary Disease in Middle-Aged Men
Authors: Kunutsor Setor K. , Jae Sae Young , Mäkikallio Timo H. , Laukkanen Jari A. 
Published: February 2022

Purpose:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic lung inflammation. The relationship between cardiorespiratory fitness (CRF) and COPD has not been well characterized. We aimed to evaluate the independent and joint associations of inflammation (high-sensitivity C-reactive protein [hsCRP]) and CRF with COPD risk in a cohort of White men.

Methods:
Among 2274 men aged 42-61 yr at baseline, serum hsCRP level was measured using an immunometric assay and CRF was assessed using a respiratory gas exchange analyzer. The level of hsCRP was categorized as normal and high (≤3 and >3 mg/L, respectively) and CRF as low and high. We corrected for within-person variability in exposures using repeat measurements taken several years apart.

Results:
A total of 116 COPD cases occurred during a median follow-up of 26.0 yr. The age-adjusted regression dilution ratio of hsCRP and CRF was 0.57 (95% CI, 0.50-0.64) and 0.58 (95% CI, 0.53-0.64), respectively. Comparing high versus normal hsCRP levels, the multivariable-adjusted HR for COPD was 1.79 (95% CI, 1.20-2.68). The COPD risk decreased linearly with increasing CRF. The multivariable-adjusted HR for COPD per 1-SD increase in CRF was 0.75 (95% CI, 0.60-0.95). Compared with men with normal hsCRP-low CRF, high hsCRP-low CRF was associated with an increased COPD risk, 1.80 (95% CI, 1.12-2.89), with no evidence of an association for high hsCRP-high CRF and COPD risk, 1.35 (95% CI, 0.68-2.69).

Conclusions:
Both hsCRP and CRF are associated with COPD risk in middle-aged men. However, high CRF levels attenuate the increased COPD risk related to high hsCRP levels.
Tuck-in deep anterior lamellar keratoplasty for the management of post-radial keratotomy keratectasia
Authors: Nagpal Ritu , Sharma Namrata , Bafna Rahul Kumar , Muraleekrishna Manu , Vajpayee Rasik Bihari 
Published: February 2022

Purpose:
To evaluate the outcomes of tuck-in deep anterior lamellar keratoplasty (DALK) for the management of post-radial keratotomy (RK) keratectasia.

Setting:
Institution.

Design:
Retrospective.

Methods:
Medical records of all cases presenting with post-RK keratectasia from January 2012 to December 2019 were included. Data on corrected distance visual acuity (CDVA), refraction, keratometry, ultrasonic pachymetry, corneal topography, endothelial cell count, applanation tonometry, and dilated fundus examination recorded at all follow-up visits were included. Details of surgical steps, including intraoperative and postoperative complications and any secondary procedures performed subsequently, were also recorded.

Results:
7 eyes of 5 patients that developed corneal ectasia after a previous RK procedure underwent DALK with peripheral tuck-in. All eyes had CDVA ≤6/24, preoperatively. The surgical procedure was successfully performed in all eyes without any intraoperative complications. CDVA at the final follow-up ranged between 6/9 and 6/60, with 6 eyes achieving CDVA of 6/18 or better. The median keratometric cylinder reduced from a preoperative value of 7.2 ± 9.27 diopters (D) to 2 ± 1.83 D at the final follow-up. The median central corneal thickness at the final follow-up was 598 ± 40.01 μm, and spherical equivalent ranged between −1.75 D and −3.5 D (median −2 ± 0.57). The percentage of endothelial cell loss ranged between 2.1% and 8.4%. All eyes retained graft clarity, and none showed any evidence of significant interface haze or corneal vascularization.

Conclusions:
Tuck-in DALK could successfully address corneal ectasia developing after RK, achieving visual gains. Moreover, it was able to restore the peripheral corneal thickness with a minimal risk for dehiscence of RK incisions.