bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dietary nitrate prevents progression of carotid subclinical atherosclerosis through blood pressure‐independent mechanisms in patients with or at risk of type 2 diabetes mellitus
Authors: Morselli Franca , Faconti Luca , Mills Charlotte E. , Morant Steven , Chowienczyk Philip J. , Yeung Joshua Au , Cavarape Alessandro , Cruickshank J. Kennedy , Webb Andrew J. 
Published: May 2021

AimsTo test if 6 months' intervention with dietary nitrate and spironolactone could affect carotid subclinical atherosclerosis and stiffness, respectively, vs. placebo/doxazosin, to control for blood pressure (BP).MethodsA subgroup of participants in our double‐blind, randomized‐controlled, factorial VaSera trial had carotid imaging. Patients with hypertension and with/at risk of type 2 diabetes were randomized to active nitrate‐containing beetroot juice or placebo nitrate‐depleted juice, and spironolactone or doxazosin. Vascular ultrasound for carotid diameter (CD, mm) and intima–media thickness (CIMT, mm) was performed at baseline, 3‐ and 6‐months. Carotid local stiffness (CS, m/s) was estimated from aortic pulse pressure (Arteriograph) and carotid lumen area. Data were analysed by modified intention to treat and using mixed‐model effect, adjusted for confounders.ResultsIn total, 93 subjects had a baseline evaluation and 86% had follow‐up data. No statistical interactions occurred between the juice and drug arms and BP was similar between the juices and between the drugs. Nitrate‐containing vs. placebo juice significantly lowered CIMT (−0.06 [95% confidence interval −0.12, −0.01], P = .034), an overall difference of ~8% relative to baseline; but had no effect on CD or CS. Doxazosin appeared to reduce CS from baseline (−0.34 [−0.62, −0.06]) however, no difference was detected vs. spironolactone (−0.15 [−0.46, 0.16]). No differences were detected between spironolactone or doxazosin on CIMT and CD.ConclusionsOur results show that 6 months' intervention with dietary nitrate influences vascular remodelling, but not carotid stiffness or diameter. Neither spironolactone nor doxazosin had a BP‐independent effect on carotid structure and function.
Implementation of oral anticoagulation treatment guidelines in patients with newly diagnosed atrial fibrillation
Authors: Arbel Anat , Abu‐Ful Zomoroda , Preis Meir , Cohen Shai , Saliba Walid 
Published: May 2021

AimsOral anticoagulants (OACs) are considered the mainstay in preventing stroke in atrial fibrillation (AF). OAC treatment remains suboptimal among AF patients, even after the introduction of direct oral anticoagulants (DOACs). We aimed to assess trends overtime and current implementation of OAC treatment guidelines in AF, using a large dataset of real world data from Israel.MethodsThis is a retrospective cohort study that includes all adult members of Clalit Health Services, the largest healthcare provider in Israel, with newly diagnosed nonvalvular AF between January 2014 and December 2019 with CHA2DS2‐VASc score ≥2. OAC treatment rates were calculated and multivariate regression models were used to identify predictors of OACs initiation.ResultsOverall, 46 531 patients were included in the study. The 3‐months cumulative OAC treatment rates increased consistently over the years: 46.9% (95% confidence interval, 46.1–47.7%), 54.9% (54.1–55.6%) and 61.7% (60.9–62.4%) during 2014–2015, 2016–2017 and 2018–2019, respectively. DOACs constituted 51.3% of prescribed OACs in 2014–2015 and increased to 95.1% during 2018–2019. On multivariate analyses, the likelihood of OACs initiation among AF patients increased across the years and across higher socioeconomic classes, and was more likely among females, Jews, statins users and patients previously screened for colorectal cancer, but less likely among smokers and patients with impaired renal function. The likelihood of treatment increased with higher CHA2DS2‐VASc score and decreased with higher HAS‐BLED score.ConclusionDespite the increasing OAC treatment rates among high‐risk AF patients, mainly attributed to the expanding DOAC use, OAC treatment scope is still far from optimal.
Negative interpretations of ambiguous ‘psychosis‐like’ and ‘anxiety‐like’ experiences in recovery from psychosis or anxiety
Authors: Sired Rebecca , Griffith Emma , Jamalamadaka Taruna , Salkovskis Paul 
Published: May 2021

ObjectivesFear of relapse (FOR) after experiencing psychosis has been found to predict actual relapse; however, potential mechanisms underlying this relationship have not been investigated. Negative appraisals of ‘prodromal symptoms’ are believed to play an important role in both psychosis and mental health anxiety (MHA). This study aimed to explore whether people in recovery from psychosis or anxiety disorders show an enduring tendency to negatively interpret ambiguous experiences both related and less related to their previous mental health difficulty relative to controls.DesignCross‐sectional between‐groups questionnaire design.MethodsParticipants self‐reported as in recovery from psychosis (n = 33) or anxiety (n = 77) or without previous experience of mental health problems (n = 61) were recruited online or via NHS services. Interpretations of psychosis‐like, anxiety‐like, and external‐control experiences were measured using the newly developed Experiences Interpretation Questionnaire (EIQ). MHA and FOR were measured using self‐report questionnaires.ResultsPeople in recovery from psychosis interpreted psychosis‐like experiences significantly more negatively than the other groups. Negative interpretations of anxiety‐like experiences were greater than controls but comparable between mental health groups. Contrary to predictions, FOR was not significantly different between the mental health groups. MHA and FOR did not significantly predict negative interpretations of psychosis‐like items in the psychosis group, however, MHA predicted negative interpretations of anxiety‐like items in the anxiety group. The EIQ subscales demonstrated good test–retest reliability.ConclusionsPeople in self‐defined recovery from psychosis or anxiety are more likely to negatively interpret ambiguous experiences relating to their previous mental health difficulties. Clinical and future research implications are outlined.Practitioner points

People in recovery from psychosis or anxiety appraise possible symptoms of their previous difficulties negatively/catastrophically (as indicating relapse) relative to those without prior MH problems.

Clinicians should consider attending to how people in recovery appraise possible symptoms when encouraging early signs monitoring as part of relapse prevention. This may be important to ensure that self‐monitoring leads to helpful responses rather than being counterproductive, with catastrophic interpretations leading to anxiety and thus increasing the risk of relapse.

Interventions drawing on CBT principles to address catastrophic interpretations of possible symptoms may potentially be a useful addition to relapse prevention work; in psychosis this may also include symptoms of anxiety.
The timing of 30‐month stay expirations and generic entry: A cohort study of first generics, 2013–2020
Authors: Kannappan Sunand , Darrow Jonathan J. , Kesselheim Aaron S. , Beall Reed F. 
Published: May 2021

AbstractBefore the first generic version of a drug is marketed, patent litigation often occurs. The process begins when generic manufacturers notify the US Food and Drug Administration (FDA) of their intent to market a generic copy of a brand‐name drug protected by patents, which they allege to be invalid or not infringed (called a Paragraph IV certification). Assuming the brand‐name manufacturer responds with litigation within 45 days, a 30‐month stay period is triggered, which bars the FDA from authorizing generic entry until the stay period expires or litigation is resolved in favor of the generic manufacturer. To understand whether 30‐month stays delay generic entry, we examined the timing of major legal events leading to generic entry for a cohort of 46 generic drugs, including the timing of Paragraph IV certification filings, stay period expirations, the FDA approvals of generics, and generic product launches. We found Paragraph IV certifications were filed a median of 5.2 years after the brand drug’s FDA approval. There was a median of 3.2 years between the stay period expiration and subsequent generic launch. Because stay periods generally expire well in advance of when generic entry typically occurs, 30‐month stays are unlikely to delay the timing of generic entry. Patent litigation could begin even earlier, however, if litigation was allowed to start immediately following a brand‐name drug’s FDA approval; but by law currently, the soonest this can begin is 4 years after the brand drug’s FDA approval.
Study Highlights

WHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?

Before generic versions of new drugs reach the market, patent litigation often occurs. Once litigation has been initiated, a 30‐month regulatory stay period is triggered that bars the US Food and Drug Administration (FDA) from approving the generic application until litigation resolves or the stay period expires.

WHAT QUESTION DID THIS STUDY ADDRESS?
What is the timing of key legal events in the regulatory approval process for generic drugs in relation to the eventual launch of the generic product?

WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?
We identified the typical timing of the initiation of patent litigation and expiration of the 30‐month stay period prior to the eventual launch of generic products. Litigation is often initiated as soon as legally possible (i.e., 4 years after the launch of the brand product), and stay periods typically expire well before generic entry occurs.

HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?
Stay periods are unlikely to delay generic entry directly because stay expirations often occur well before the time of generic launch. Allowing the submission of generic drug applications immediately following a brand drug’s FDA approval would facilitate earlier patent dispute resolution and prevent unnecessary delays in the anticipated generic product launch date.
Sweet syndrome with perifollicular involvement because of koebnerization from facial hair plucking
Authors: Flanagan Kelly E. , Krueger Steven , Amano Shinya , Auerbach Amanda , St. John Jessica , Deng April 
Published: May 2021

AbstractSweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an uncommon skin eruption characterized by fever, leukocytosis, and tender erythematous papules, nodules, and plaques. Histopathologically, SS lesions are characterized by marked superficial papillary edema with a dense neutrophilic infiltrate. SS is known to demonstrate both the Koebner phenomenon and pathergy. The majority of reported cases of these phenomena occur following significant cutaneous injury (e.g., biopsies, burns) rather than minor trauma such as pressure and friction. Here, we present the first known reported case of SS koebnerization secondary to minor grooming‐related hair plucking. In addition, this is also the first reported case to our knowledge of SS with perifollicular involvement on histopathology.
The level of agreement between rapid‐on‐site evaluation of endoscopic ultrasound fine needle aspirate and surgical histological diagnosis in gastrointestinal lesions
Authors: Khoury Tawfik , Sbeit Wisam 
Published: May 2021

AbstractObjectiveEndoscopic ultrasound (EUS) is the main tool for biopsy via fine needle aspiration (FNA) from gastrointestinal (GI) lesions including pancreatic, upper gastrointestinal, and adjacent lesions. The variable diagnostic yield and delay until the final pathological results can affect treatment planning and cause patient anxiety. We aimed to assess the agreement of rapid on‐site evaluation (ROSE) of EUS‐FNA with the surgical histological diagnosis of patients who underwent resection.MethodA retrospective study was performed including all patients 18 years or older who underwent EUS‐FNA with ROSE for GI lesions. For patients who underwent surgical resection, the correlation between ROSE and the surgical histological diagnosis was evaluated with the kappa coefficient.ResultsOverall, 73 patients who underwent EUS‐FNA with ROSE were included, of whom 22 (30.1%) had curative resection. The final pathological diagnosis from surgery showed 17 malignant and 5 benign lesions. Among the benign lesions, ROSE correctly identified 2 (diagnostic accuracy of 40%), while among the malignant lesions, ROSE correctly identified 14 (diagnostic accuracy of 82.4%), yielding a fair kappa coefficient of 0.366 (95% CI 0.035‐0.697). When classifying the lesions as either malignant vs benign or suspicious of malignancy, the kappa coefficient increased to 0.58 (95% CI 0.180‐0.975) for the subgroup of pancreatic lesions, with diagnostic accuracy of 81.2% for the malignant category.ConclusionsA high level of agreement for malignancy was found between FNA‐EUS with ROSE and the final surgical histological diagnosis. ROSE can be used as an adjuvant diagnostic tool to optimise patient management and decrease delay‐related anxiety.
Problems in using Beals' index to detect species trends in incomplete floristic monitoring data (Reply to Bruelheide et al. (2020))
Authors: Christensen Erik , Christensen Björn , Christensen Sören 
Published: May 2021

AbstractBruelheide et al. (Diversity and Distributions, 26, 2020, 782) explored repeated habitat mapping data to identify floristic changes over time on the basis of two surveys. Because of the incompleteness of the data, they utilized the Beals' index based on the aggregated data from both surveys as a statistical tool for the analysis. The aim of this note is to illustrate problems of this approach, which in particular is shown to produce a systematic underestimation of species decrease (and—potentially less relevant in practice—increase). A specific set of model cases will be introduced to show the effects of unjustified usage of the Beals' index in this specific form.
Supporting treatment adherence regimens in children with epilepsy: A randomized clinical trial
Authors: Modi Avani C. , Guilfoyle Shanna M. , Glauser Tracy A. , Mara Constance A. 
Published: May 2021

AbstractObjectiveThis study was undertaken to examine the efficacy of a family‐tailored education and problem‐solving behavioral intervention, Supporting Treatment Adherence Regimens (STAR), in young children (2–12 years old) with new onset epilepsy compared to an attention control (i.e., education only [EO]) intervention. Participants randomized to the STAR intervention were hypothesized to demonstrate significantly improved adherence at postintervention and 3‐, 6‐, and 12‐month follow‐up visits compared to the EO intervention. Seizure and health‐related quality of life (HRQOL) outcomes were also examined.MethodsTwo hundred children with new onset epilepsy and their caregivers were recruited during routine epilepsy clinic visits. Baseline questionnaires were completed, and electronic adherence monitors were provided. Participants with adherence less than 95% during the run‐in period were randomized to either STAR or EO intervention. Active intervention was provided to both groups for 4 months. Questionnaires were completed at conclusion of the active intervention phase and three follow‐up time points (3, 6, and 12 months). Group differences in adherence, seizure outcomes, and HRQOL were examined using regression‐based analyses of covariance and longitudinal mixed effect linear or logistical models.ResultsAdherence at 12‐month follow‐up was significantly different between the STAR (mean = 82.34, SD = 21.29) and EO intervention groups (mean = 61.77, SD = 28.29), with the STAR group demonstrating 20.6% greater adherence (b = 19.11, p = .04, 95% confidence interval = 1.00–37.22, d = .83). No significant differences were found between groups in seizure and HRQOL outcomes.SignificanceA family‐based behavioral adherence intervention demonstrated sustained adherence improvements 1 year following epilepsy diagnosis compared to an epilepsy‐specific education intervention. STAR is an efficacious adherence intervention that can easily be implemented into routine epilepsy care.
Minimum wage, firm dynamics, and wage inequality: Theory and evidence​
Authors: Chao Chi‐Chur , Ee Mong Shan , Nguyen Xuan , Yu Eden S. H. 
Published: May 2021

AbstractThis paper investigates the distributive and welfare impacts of increasing minimum wage in an economy with imperfect competition. In the short run without entry/exit of manufacturing firms, an increase in the urban minimum wage reduces the skilled–unskilled wage gap but worsens unemployment and welfare in the economy. In the long run, a higher minimum wage induces firms to exit the urban manufacturing sector, thereby releasing capital to the rural agricultural sector. This can yield double dividends by further narrowing wage inequality and improving social welfare. Empirical results based on data from 43 selected countries confirm our theoretical findings.
Adaptation of the Quality of Life Adolescent Cleft Questionnaire for Spanish children and adolescents with cleft lip and/or palate
Authors: Ruiz‐Guillén Ana , Suso‐Ribera Carlos , Romero‐Maroto Martín , Gallardo Carmen , Peñacoba Cecilia 
Published: May 2021

AbstractBackgroundThe Quality of Life Adolescent Cleft Questionnaire is a measure of quality of life in cleft lip/palate (CL/P) and includes items on pre‐treatment and post‐treatment status. Items, however, were originally organized in a factor structure that prevents a formal pre‐treatment to post‐treatment comparison. Additionally, the questionnaire was tested in older patients.AimWe aimed to explore a factor structure that allows a comparison of pre‐ to post‐treatment status in children and adolescents with CL/P.DesignThe sample comprised 60 children and adolescents with CL/P. The scale was divided into two groups of items (24 comparing pre‐treatment and post‐treatment status and 26 measuring current quality of life). Two different exploratory and confirmatory analyses were conducted (one for each group of items). Sources of criterion validity were investigated with measures of self‐esteem and self‐efficacy.ResultsThe results supported a 6‐factor structure for the pre‐treatment and post‐treatment items. In the second group of items, 9 items were removed due to inadequate functioning and a final 4‐factor solution was obtained. The criterion validity of factors was good.ConclusionThe proposed factor solution might be more useful to detect the perceived satisfaction in different areas and can be used in younger patients.
Cobalt‐containing spherical glass nanoparticles for therapeutic ion release
Authors: Barrioni Breno R. , de Carvalho Sandhra M. , Naruphontjirakul Parichart , Norris Elizabeth , Kelly Nicole L. , Hanna John V. , Jones Julian R. , Pereira Marivalda de M. 
Published: May 2021

AbstractBioactive glass nanoparticles (BGNPs) can be internalized by cells, allowing the intracellular release of dissolution products with therapeutic benefit. Different therapeutic ions can be incorporated into the glass network that can promote angiogenesis via simulation of hypoxia conditions and consequent activation of pro‐angiogenic genes. Here, novel monodispersed spherical dense BGNPs were obtained by a modified Stöber method with the SiO2–CaO–CoO composition, with diameters of 92 ± 1 nm, with cobalt as the pro‐angiogenic ion. The presence of Co2+ species and the role of Co and Ca as network modifiers in the silica glass were confirmed by X‐ray photoelectron spectroscopy and 29Si solid‐state magic‐angle spinning nuclear magnetic resonance, respectively. Controlled Co2+ ion release was observed in culture media, and no cytotoxicity was observed by (4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl tetrazolium bromide cell viability assay on human osteosarcoma cells in direct contact with the nanoparticles. This study demonstrated that Co2+ ions can be incorporated into dense and spherical BGNPs, and these materials exhibit great potential as intracellular ion delivery systems with therapeutic properties.
Targeting LIMK1 with luteolin inhibits the growth of lung cancer in vitro and in vivo
Authors: Zhang Man , Wang Rui , Tian Jie , Song Mengqiu , Zhao Ran , Liu Kangdong , Zhu Feng , Shim Jung‐Hyun , Dong Zigang , Lee Mee‐Hyun 
Published: May 2021

AbstractLung cancer is the leading cause of cancer‐related deaths. LIM domain kinase (LIMK) 1 is a member of serine/threonine kinase family and highly expressed in various cancers. Luteolin, a polyphenolic plant flavonoid, has been reported to suppress tumour proliferation through inducing apoptosis and autophagy via MAPK activation in glioma. However, the mechanism of luteolin on suppressing lung cancer growth is still unclear. We found that luteolin targeted LIMK1 from the in silico screening and significantly inhibited the LIMK1 kinase activity, which was confirmed with pull‐down binding assay and computational docking models. Treatment with luteolin inhibited lung cancer cells anchorage‐independent colony growth and induced apoptosis and cell cycle arrest at G1 phase. Luteolin also decreased the expression of cyclin D1 and increased the levels of cleaved caspase‐3 by down‐regulating LIMK1 signalling related targets, including p‐LIMK and p‐cofilin. Furthermore, luteolin suppressed the lung cancer patient‐derived xenograft tumour growth by decreasing Ki‐67, p‐LIMK and p‐cofilin expression in vivo. Taken together, these results provide insight into the mechanism that underlies the anticancer effects of luteolin on lung cancer, which involved in down‐regulation of LIMK1 and its interaction with cofilin. It also provides valuable evidence for translation towards lung cancer clinical trials with luteolin.
The preferences of people with asthma or chronic obstructive pulmonary disease for self‐management support: A qualitative descriptive study
Authors: O'Connell Selena , McCarthy Vera J. C. , Queally Michelle , Savage Eileen 
Published: May 2021

AbstractAims and objectivesThe aim of this study was to explore and describe the self‐management support (SMS) preferences of adults with asthma and/or chronic obstructive pulmonary disease (COPD).BackgroundSelf‐management support interventions have had beneficial outcomes for people with asthma and people with COPD, though challenges remain in their implementation. Increased understanding of the support preferences of people with asthma/COPD can help inform the development of future interventions to address patients' preferences.DesignA qualitative descriptive design was used.MethodsSemi‐structured focus group and individual interviews were conducted with 20 adult participants who had asthma and/or COPD in Ireland. Qualitative content analysis was used to analyse interviews. The SRQR reporting guideline was used.ResultsThree themes were identified. Support accessibility included having access to routine and unscheduled support from healthcare professionals with specialist knowledge. Consultation content described the need for comprehensive and person‐centred support. The person–provider relationship described the value of healthcare professionals acknowledging patient concerns, noted as a challenge for people with asthma, and continuity in relationships over time.ConclusionsRoutine support for people with asthma/COPD needs to be comprehensive in addressing the individual patient's challenges. Access to timely advice during exacerbations was a priority for people with asthma/COPD, suggesting that flexible access to services as well as routine review may be optimal for supporting self‐management of asthma/COPD. Feeling listened to regarding symptoms experienced may be of intrinsic value to people with asthma/COPD.Relevance to clinical practiceThe study emphasises the importance of continued training in communications skills for healthcare professionals supporting people with asthma/COPD, particularly acknowledging the patient's concerns in the context of symptom changes/flare‐up. A respiratory nurse specialist was valued as being a care coordinator who could support routine management as well as managing exacerbations, having specialist knowledge and knowing the patient over time.