bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comprehensive Analysis of Human Epidermal Growth Factor Receptor 2 Through DNA, mRNA, and Protein in Diverse Malignancies
Authors: Shayeb Akram Mesleh , Kurzrock Razelle , Adashek Jacob J. , Kato Shumei 
Published: July 2023

PURPOSE Human epidermal growth factor receptor 2 (HER2) expression (protein immunohistochemistry [IHC] or gene amplification [copy-number variation, CNV]) predicts anti-HER2 therapy responsiveness, although recently it was shown that even low HER2-expressing breast cancers benefit from trastuzumab-deruxtecan. Little is known about HER2 transcriptomic (mRNA) expression, and comparisons between genomic, mRNA, and protein HER2 assays. METHODS HER2 status was evaluated using clinical-grade IHC (protein), quantitative reverse transcription polymerase chain reaction (mRNA), and next-generation sequencing (NGS; amplifications). RESULTS Multi-institutional HER2 testing was performed on 5,305 diverse cancers including non–small-cell lung (n = 1,175), breast (n = 1,040), and colon cancers (n = 566; N = 3,926 tested for CNV; N = 1,848, mRNA; N = 2,533, IHC). Overall, 4.1% (161/3,926) had NGS HER2 amplification; 33.3% (615/1,848) had mRNA overexpression; and 9.3% (236/2,533) were IHC-positive. In 723 patients with all three tests (CNV/mRNA/IHC), various amplification/expression patterns occurred: 7.5% (54/723) had all three HER2 tests positive; 62.8% (454/723) had all three tests negative. Discrepant patterns between amplification and overexpression emerged. For instance, 20% (144/723) of patients had mRNA overexpression alone with negative CNV and IHC. A range in values for only mRNA+ cases occurred in different tumor types (eg, 16.9%, breast; 5%, hepatobiliary). There were 53 patients with various tumors from our institution who had all three assays attempted; 22 tested positive for HER2, and seven received anti-HER2 therapy: two patients achieved response: one (esophageal cancer), complete response (≥42 months); one (cholangiocarcinoma), who only had HER2 mRNA positivity (tissue was inadequate for IHC and CNV assessment), partial response (≥24 months) on HER2-based regimens. CONCLUSION We demonstrate variability of HER2 (protein and mRNA) expression and amplification using comprehensive assays (CNV, mRNA, and IHC) among diverse cancers. As HER2-targeted therapy indications expand, the relative importance of these modalities merits further evaluation.
Does Elevated High-Density Lipoprotein Cholesterol Protect Against Cardiovascular Disease?
Authors: Razavi Alexander C , Jain Vardhmaan , Grandhi Gowtham R , Patel Parth , Karagiannis Angelos , Patel Nidhi , Dhindsa Devinder S , Liu Chang , Desai Shivang R , Almuwaqqat Zakaria , Sun Yan V , Vaccarino Viola , Quyyumi Arshed A , Sperling Laurence S , Mehta Anurag 
Published: July 2023

AbstractHigh-density lipoprotein (HDL) contributes to reverse cholesterol transport, which is 1 of the main explanations for the described inverse association between HDL-cholesterol (HDL-C) and atherosclerotic cardiovascular disease (ASCVD) risk. However, efforts to therapeutically raise HDL-C levels with niacin, fibrates, or cholesteryl ester transfer protein inhibitors have not demonstrated a reduction in ASCVD events when compared with placebo among individuals treated with statins. Furthermore, mendelian randomization studies suggest that HDL-C is unlikely to be a direct biologic variable impacting ASCVD risk. More recently, observations from well-conducted epidemiologic studies have indicated a nonlinear U-shaped relationship between HDL-C and subclinical atherosclerosis, and that very high HDL-C (≥80 mg/dL in men, ≥100 mg/dL in women) is paradoxically associated with higher all-cause and ASCVD-related mortality. These observations suggest that HDL-C is not a universal protective factor for atherosclerosis. Thus, there are several opportunities for reframing the contribution of HDL-C to ASCVD risk and related clinical calculators. Here, we examine our growing understanding of HDL-C and its role in ASCVD risk assessment, treatment, and prevention. We discuss the biological functions of HDL-C and its normative values in relation to demographics and lifestyle markers. We then summarize original studies that observed a protective association between HDL-C and ASCVD risk and more recent evidence indicating an elevated ASCVD risk at very high HDL-C levels. Through this process, we advance the discussion regarding the future role of HDL-C in ASCVD risk assessment and identify knowledge gaps pertaining to the precise role of HDL-C in atherosclerosis and clinical ASCVD.
Epigenetic Causes of Overgrowth Syndromes
Authors: Lui Julian C , Baron Jeffrey 
Published: July 2023

Abstract
Human overgrowth disorders are characterized by excessive prenatal and/or postnatal growth of various tissues. These disorders often present with tall stature, macrocephaly, and/or abdominal organomegaly and are sometimes associated with additional phenotypic abnormalities such as intellectual disability and increased cancer risk. As the genetic etiology of these disorders have been elucidated, a surprising pattern has emerged. Multiple monogenic overgrowth syndromes result from variants in epigenetic regulators: variants in histone methyltransferases NSD1 and EZH2 cause Sotos syndrome and Weaver syndrome, respectively, variants in DNA methyltransferase DNMT3A cause Tatton-Brown-Rahman syndrome, and variants in chromatin remodeler CHD8 cause an autism spectrum disorder with overgrowth. In addition, very recently, a variant in histone reader protein SPIN4 was identified in a new X-linked overgrowth disorder. In this review, we discuss the genetics of these overgrowth disorders and explore possible common underlying mechanisms by which epigenetic pathways regulate human body size.
Dual Aldosterone- and Cortisol-Secreting Adrenal Cortical Carcinoma: Pre- and Perioperative Evaluation and Management
Authors: Rosenberg Rebecca , Raeburn Christopher D , Clay Michael R , Wierman Margaret E 
Published: July 2023

Abstract
Adrenal cortical carcinoma (ACC) is a rare cancer (1-2/million) that presents with hormone overproduction in 60% of cases. Presentation of ACC with multiple hormone syndromes from different adrenal zones is rare. We present a case of dual-secreting ACC with hyperaldosteronism and cortisol excess. The previously healthy patient was noted to have new-onset hypertension and hypokalemia during a primary care visit. On hormonal evaluation, he was found to have evidence of hyperaldosteronism and adrenocorticotropic hormone (ACTH)-independent cortisol excess. Imaging revealed a 2.7 × 3.1 × 3.5 cm left adrenal mass with indeterminant computed tomography characteristics. He underwent laparoscopic adrenalectomy and required glucocorticoid replacement for adrenal insufficiency postoperatively. Pathology revealed stage T2N0M0 ACC. His hypokalemia resolved and glucocorticoids were stopped within a month. This case stresses the importance of routine screening for cortisol excess in all adrenal masses detected on imaging. Avoidance of postoperative adrenal insufficiency in patients with cortisol excess without overt Cushing syndrome is paramount.
Emerging Potential of Microwave Ablation for Primary Aldosteronism Resulting From Unilateral Aldosterone-producing Adenoma
Authors: Mills Edouard G , Palazzo Fausto F , Leen Edward , Wernig Florian 
Published: July 2023

Abstract
Primary aldosteronism (PA) is the most prevalent form of secondary hypertension and is most commonly caused by an adrenal adenoma or bilateral adrenal hyperplasia. Minimally invasive adrenalectomy is the treatment of choice for unilateral disease. Here, we report the case of a 57-year-old man with previous bladder cancer who was referred for evaluation of resistant hypertension and hypokalemia. Diagnostic workup indicated PA with computed tomography imaging revealing a left adrenal adenoma and adrenal venous sampling lateralizing to the left adrenal. He was therefore referred for a left adrenalectomy using a retroperitoneoscopic approach. However, surgery was complicated by significant perinephritis related to previous bladder cancer immunotherapy and, in view of an identifiable adrenal adenoma, a partial adrenalectomy was performed. Despite histology confirming removal of an adrenal adenoma, he remained hypertensive and hypokalemic with persistent PA. He underwent a computed tomography-guided percutaneous thermal (microwave) ablation of the residual adrenal nodule with immediate biochemical reversal of PA. Six years postprocedure, he remains biochemically and clinically cured from PA. This article presents the details of the case and reviews the literature on long-term outcomes for patients undergoing thermal ablation and adrenalectomy, suggesting that thermal ablation may be a viable alternative for selected patients.
The Effect of Specific Bioactive Collagen Peptides on Tendon Remodeling during 15 wk of Lower Body Resistance Training
Authors: BALSHAW THOMAS G. , FUNNELL MARK P. , MCDERMOTT EMMET J. , MADEN-WILKINSON THOMAS M. , MASSEY GARRY J. , ABELA SEAN , QUTEISHAT BTOOL , EDSEY MAX , JAMES LEWIS J. , FOLLAND JONATHAN P. 
Published: July 2023

ABSTRACT

Purpose
Collagen peptide supplementation has been reported to enhance synthesis rates or growth in a range of musculoskeletal tissues and could enhance tendinous tissue adaptations to resistance training (RT). This double-blind placebo-controlled study aimed to determine if tendinous tissue adaptations, size (patellar tendon cross-sectional area (CSA) and vastus lateralis (VL) aponeurosis area), and mechanical properties (patellar tendon), after 15 wk of RT, could be augmented with collagen peptide (CP) versus placebo (PLA) supplementation.

Methods
Young healthy recreationally active men were randomized to consume either 15 g of CP (n = 19) or PLA (n = 20) once every day during a standardized program of lower-body RT (3 times a week). Measurements pre- and post-RT included patellar tendon CSA and VL aponeurosis area (via magnetic resonance imaging), and patellar tendon mechanical properties during isometric knee extension ramp contractions.

Results
No between-group differences were detected for any of the tendinous tissue adaptations to RT (ANOVA group–time, 0.365 ≤ P ≤ 0.877). There were within-group increases in VL aponeurosis area (CP, +10.0%; PLA, +9.4%), patellar tendon stiffness (CP, +17.3%; PLA, +20.9%) and Young’s modulus (CP, +17.8%; PLA, +20.6%) in both groups (paired t-tests (all), P ≤ 0.007). There were also within-group decreases in patellar tendon elongation (CP, −10.8%; PLA, −9.6%) and strain (CP, −10.6%; PLA, −8.9%) in both groups (paired t-tests (all), P ≤ 0.006). Although no within-group changes in patellar tendon CSA (mean or regional) occurred for CP or PLA, a modest overall time effect (n = 39) was observed for mean (+1.4%) and proximal region (+2.4%) patellar tendon CSA (ANOVA, 0.017 ≤ P ≤ 0.048).

Conclusions
In conclusion, CP supplementation did not enhance RT-induced tendinous tissue remodeling (either size or mechanical properties) compared with PLA within a population of healthy young men.
Práticas de modelos de gestão de pessoas em laboratórios acreditados e sua influência sobre o número de não-conformidades na norma ABNT NBR ISO/IEC 17025
Authors: Maia Andreia Queiroz de Almeida , Fermam Ricardo Kropf Santos , Da Costa Felix Rodrigo Pereira Barretto 
Published: July 2023

O cenário atual é de mudança permanente no ambiente organizacional das empresas devido à concorrência cada vez mais acirrada e à inovação tecnológica. O objetivo deste trabalho de pesquisa é analisar a influência da seleção do Modelo de Gestão de Pessoas (MGP) sobre a competência dos laboratórios de ensaios e calibração acreditados. Referencial teórico. A gestão de pessoas é um tema de relevância para as empresas devido às mudanças nos negócios e ao intenso desenvolvimento tecnológico, o que deu origem a um achado significativo nas organizações: as pessoas se tornam a principal vantagem competitiva no mundo organizacional. Metodologia. Foi desenvolvido um questionamento para identificar a adesão dos laboratórios aos MGP e sua relação com o número de não conformidades no item 6.2 (Pessoal) da ABNT NBR ISO/IEC 17025:2017. Um questionário foi aplicado aos gestores das empresas. Resultados. Os laboratórios estão em diferentes níveis de maturidade para o comportamento humano e gestão de pessoal. É preciso olhar além dos requisitos da norma para permanecer no mercado e abrir novos desafios de negócios. Pesquisa, implicações práticas e sociais. Os resultados são válidos para laboratórios que atendem aos requisitos da ISO/IEC 17025:2017. Originalidade/valor. Os laboratórios acreditados precisam olhar para a equipe além dos requisitos das normas. Vale ressaltar que profissionais de laboratório qualificados fomentam novos mercados.
Estimated direct and indirect health care costs of severe infectious keratitis by cultured organisms in Thailand: An 8-year retrospective study
Authors: Chantra Somporn , Jittreprasert Supachase , Chotcomwongse Peranut , Amornpetchsathaporn Anyarak 
Published: July 2023

PurposeTo evaluate the economic impact of treating severe infectious keratitis (IK) at one tertiary referral center in Thailand by analyzing the direct costs of treatment and estimating the indirect costs, and to determine whether cultured organisms had any effect on treatment expenditure.MethodsA retrospective study was conducted of patients with severe IK who had been hospitalized between January 2014 and December 2021 in Rajavithi Hospital. Data from medical records were collected from the time of the patients’ admission until the point at which they were discharged and treated in the outpatient department and their IK was completely healed, or until evisceration/enucleation was performed. The direct costs of treatment included fees for services, medical professionals and investigation, as well as for operative and non-operative treatment. The indirect costs consisted of patients’ loss of wages, and costs of travel and food.ResultsA total of 335 patients were studied. The median direct, indirect and total costs were US$65.2, range US$ 6.5–1,119.1, US$314.5, range US$50.8–1,067.5, and US$426.1, range 57.5–1,971.5 respectively. There was no statistically significant difference between direct, indirect, or total treatment costs for culture-negative and culture-positive patients. Among those who were positive, fungal infections entailed the highest total cost of treatment, and this difference was statistically significant (p<0.001). In terms of direct and indirect costs, patients with fungal infections had the greatest direct costs, and this figure was statistically significant (p = 0.001); however, those with parasitic infections had the highest indirect treatment costs, and this was also statistically significant (p<0.001).ConclusionSevere IK can cause serious vision impairment or blindness. Indirect costs represented the majority of the expense at 73.8%. There was no difference between direct, indirect, and total treatment costs for patients who were culture-negative or positive. Among the latter, fungal infections resulted in the highest total cost of treatment.
Vaccine related crowdfunding on a ‘Freedom Fundraising’ platform
Authors: Snyder Jeremy , Zenone Marco 
Published: July 2023

Introduction
Donation-based crowdfunding was heavily used during the COVID-19 pandemic. While most of these campaigns were uncontroversial, others spread misinformation or undermined public health. In response, mainstream crowdfunding platforms like GoFundMe restricted what campaigns they would host. This led some campaigns to shift to lesser-known and less restrictive crowdfunding platforms. While research on health-related misinformation on mainstream crowdfunding platforms is increasing, less is known about crowdfunding on less restrictive platforms like GiveSendGo. The aim of this study is to review vaccine-related crowdfunding campaigns on the GiveSendGo platform to better understand: 1) how vaccines are portrayed on GiveSendGo; and 2) how successful these campaigns have been at attracting financial support.

Methods
We searched the GiveSendGo crowdfunding platform for campaigns including “vaccine” or “vaccination”. This process yielded 907 unique results which were then scraped for their campaign text and fundraising data. The authors reviewed these campaigns for fundraisers whose aims related to vaccines for humans and assigned campaigns as being for 1) Accessing vaccines; 2) creating Spaces for the unvaccinated; 3) helping Unvaccinated Individuals); 4) Advocacy about vaccines; 5) supporting Anti-Mandate actions; and 6) responding to Vaccine Injuries.

Findings
We identified 765 crowdfunding campaigns that raised $6,814,817 and requested $838,578,249. Anti-Mandate campaigns were most common, followed by Unvaccinated Individuals, Vaccine Injuries, Advocacy, Access, and Spaces. Only Access campaigns took a positive or neutral view toward vaccines. Themes of freedom and religion cut across campaign types with campaigns critical of vaccines invoking bodily autonomy and religious freedom as justifying their fundraisers.

Discussion
Very few of these fundraisers met their goals. With the exception of Access campaigns, they frequently contained highly polarizing language advocating against public health mandates, misinformation about vaccine safety, and language from bioethics and reproductive choice advocates. Restrictions on vaccine-related campaigns on the GoFundMe platform likely drove campaign creation on GiveSendGo.
Using Artificial Intelligence to Predict Cirrhosis From Computed Tomography Scans
Authors: Mazumder Nikhilesh R. , Enchakalody Binu , Zhang Peng , Su Grace L. 
Published: July 2023

INTRODUCTION:
Undiagnosed cirrhosis remains a significant problem. In this study, we developed and tested an automated liver segmentation tool to predict the presence of cirrhosis in a population of patients with paired liver biopsy and computed tomography (CT) scans.

METHODS:
We used a cohort of 1,590 CT scans within the Morphomics database to train an automated liver segmentation model using 3D-U-Net and Google's DeeplLabv3+. Imaging features were then automatically calculated from an external test cohort of patients with chronic liver disease who had a paired liver biopsy and CT within 6 months of each other in January 2004–2012. Using gradient boosting decision trees, we developed multivariate models to predict the presence of histologic cirrhosis and evaluated with 5-fold cross-validated c-statistic.

RESULTS:
Our cohort had 351 patients; 96 patients had cirrhosis. Of the total cohort, 72 were postliver transplant. Both fibrosis (FIB)-4 and liver morphomics alone performed equally well with area under the receiving operating characteristics of 0.76 (95% confidence interval 0.70–0.81) and 0.71 (95% confidence interval 0.65–0.76), respectively (P = 0.2). However, the combination of liver morphomics with laboratory values or liver morphomics with laboratory and demographic data resulted in significant improved performance with area under the receiving operating characteristics of 0.84 (0.80–0.89) and 0.85 (0.81–0.90), respectively, compared with FIB-4 alone (P < 0.001). In a subgroup analysis, we also examined performance in patients without liver transplantation and saw similar augmentation of FIB-4.

DISCUSSION:
This proof-of-principle study demonstrates that automatically extracted features within CT scans can be combined with classic electronic medical record data to improve the prediction of cirrhosis in patients with liver disease. This tool may be used in both pretransplant and posttransplant patients and has the potential to improve our ability to detect undiagnosed cirrhosis.
Underlying Educational Inequalities in the Global and Fijian Context
Authors: Goundar Prashneel Ravisan 
Published: July 2023

Abstract
The delivery of education and the outcome it produces largely depend on how students are taught, the resources they are exposed to along with the kind of facilities they are provided with. We have to acknowledge that teaching and learning do not occur in the same way across the world due to critical factors. These factors cause hindrances in the education system that create educational inequalities which exist in various forms as this article aims to outline. Some of these include shortage of teachers, poverty learning-gap, distribution of resources, location of schools, access to scholarship, and school curriculum. It is worth comparing Fiji’s education system to the global context using all the three streams of education that is primary, secondary, and higher education. It is prudent that stakeholders in all three education streams are aware of the nature of inconsistencies that affect the students. This will inform and enable policy makers to engage with the current underlying inequalities in education in order to address these that persist in the world and in Fiji. Conversations that revolve around these issues will be fruitful for the education system in Fiji and worldwide.
Non-transient optimum design of nonlinear electromagnetic vibration-based energy harvester using homotopy perturbation method
Authors: Dezhara Aboozar 
Published: July 2023

Abstract
In this paper the coupled differential equations governing the vibration of nonlinear electromagnetic energy harvesters are solved by the homotopy perturbation method. The amplitudes of odd harmonics of displacement of the magnet, coil current, and load voltage are derived up to the 5th harmonic. The frequency response of output power is plotted and it peaks at the linear mechanical resonance frequency. It should be noted that the optimum design of coil and load parameters, optimum electromagnetic coupling coefficient, and optimum vibration frequency of the magnet attached to a non-linear spring resulted in a stationary or non-transient vibration. Paying insufficient attention to this point and using typical parameters instead of optimum ones will result in transient vibration. The research aims at a rigorous semi-analytical method on a nonlinear problem which has previously solely investigated by numerical or experimental method.
Dilemmas and directions of real-time detecting trapped individuals using ultra-wideband radar in building fire rescue
Authors: Wang Song , Weng Wenguo 
Published: July 2023

Abstract
The crucial component of a successful building fire rescue is detecting trapped individuals efficiently and supporting firefighters in planning rescue and evacuation routes simultaneously. Due to its insensitivity to heat flow, great penetration, and high accuracy, Ultra-Wideband radar is widely used in autonomous driving and medical monitoring, but it has not yet been shown its full potential in fire rescue. In light of this, a summary of eight technical challenges for finding and rescuing trapped individuals in typical building fire scenarios is provided, which could be the traction to investigate the capability state of UWB radar technology. Five technological issues that restrict the use of UWB radar for fire rescue scene detection are discussed followed. Finally, 10 important technologies are presented in three directions to deal with the issues at hand, and several advanced technologies are planned in two directions to improve the performance of UWB radar in fire rescue.