bluuebunny/crossref_metadata_2025_split huggingface dataset:
SNPs in apolipoproteins contribute to sex-dependent differences in blood lipids before and after a high-fat dietary challenge in healthy U.S. adults
Authors: Wang Yining E. , Kirschke Catherine P. , Woodhouse Leslie R. , Bonnel Ellen L. , Stephensen Charles B. , Bennett Brian J. , Newman John W. , Keim Nancy L. , Huang Liping 
Published: September 2022

Abstract
Background
The effect of genetic polymorphisms on fasting blood lipid levels have been widely studied but the effects of these within the context of a high-fat meal challenge remain less characterized. The current study aimed to investigate the association of SNPs in lipoprotein-related genes with blood lipid profiles in healthy adults in the U.S.

Methods
Subjects (n = 393) between 18–66 years of age with BMIs ranging from 18.5–45 kg/m2 were enrolled the cross-sectional Nutritional Phenotyping Study. Among them, 349 subjects (men: 48%; women: 52%) gave consent for genotyping. SNPs in APOA5, APOB, APOC3, APOE, and LDLR were assessed. The association between lipid markers and genotypes was tested separately for each SNP with analysis of variance (ANOVA), adjusted for sex, age, and BMI. We also examined two-factor interactions between SNPs and sex, age, or BMI.

Results
Women carrying the C allele of rs3135506 in APOA5 or men carrying the C allele of rs429358 in APOE had reduced HDL-cholesterol levels during fasting and postprandially. The C allele in APOE was also correlated to increased LDL-C levels. The TT genotype of rs2854116 in APOC3 was associated with elevated total cholesterol. Additive effect of the risk alleles of APOA5 and APOE or APOC3 and APOE was detected. Nevertheless, the tested SNPs had little impact on the postprandial triglyceride responses to the high-fat challenge meal. We found no significant effects of SNPs in APOB (rs1042034) or LDLR (rs2228671) on triglycerides, cholesterol, or free fatty acid levels.

Conclusions
In healthy adults, fasting and postprandial cholesterol levels are strongly correlated with the tested APOA5, APOE, and APOC3 genotypes. Sex contributes to the genetic impact of the tested SNPs on lipid profiles.

Trial registration
ClinicalTrials.gov, NCT02367287. Registered February 20, 2015, https://clinicaltrials.gov/ct2/show/NCT02367287.
Translanguaging at a Saudi University: discrepancy between English language teachers’ attitudes and self-reported pedagogical practices
Authors: Almayez Mayez 
Published: September 2022

Abstract‘Translanguaging’ has recently become a buzzword in TESOL scholarship, serving as both a theoretical concept to decribe the ways in which langauge learners fluidly use their whole linguistic repertoires to communicate and convey meaning as well as a pedagogical tool to leverage those repertoires as valuable learning resources. Over the past two decades, numerous empirical studies have been conducted in many corners of the world to investigate pedagogical translingual practices inside language learning classrooms. Yet, little is known about this phenomenon within the context of KSA, wherein TESOL policies ban the use of students’ native langauge(s) and render them as an impediment to language learning. This study addresses this lacuna as it firstly explores English language teachers’ attitudes towards pedagogical translanguaging, and secondly examines the extent to which those attitudes are reflected into their reoprted pedagogical practices. 101 mono-, bi-, and multilingual English language teachers at a Saudi unveristiy voluntarily participated in this study. By drawing on survey data, the findings showcase a considerable discrepancy between teachers’ stated attitudes and reported pedagogical practices. The findings also illuminate the constraints that hindered the participants’ adoption of pedagogical translanguaging in their teaching. The study finally concludes with pedagogical and policy implications.
Endovascular treatment of acute M1 occlusions due to underlying intracranial atherosclerotic severe stenosis
Authors: Yan Yazhou , Du Li , He Xiliang , Huang Qinghai , Pan Yuan , Xin Tao 
Published: September 2022

Abstract
Background
Endovascular treatment (EVT) for acute ischemic stroke with an occlusion of the M1 segment due to intracranial atherosclerotic severe stenosis (ICASS) remains challenging. This study aimed to evaluate the safety and efficacy of EVT for ICASS-related M1 acute occlusion.

Methods
We retrospectively reviewed all patients with an ICASS-related M1 acute occlusion who underwent EVT at our institution between January 2015 and December 2020. Clinical presentation, baseline characteristics, angiographic and clinical results, technical feasibility, perioperative complications, and follow-up results were evaluated.

Results
Twenty-two patients with ICASS-related M1 acute occlusion were included. Eight patients (36.4%) received bridging therapy, and the other 14 patients (63.6%) directly underwent EVT. Fifteen patients (68.2%) treated with balloon dilations and stenting as rescue treatment. Six patients (27.3%) received single balloon angioplasty, and 5 of these patients were treated with staged stenting. One case (4.5%) failed recanalization at the first EVT, and successful revascularization was achieved a month later. The mean procedure time was 67.2 ± 20.8 min. Successful revascularization (mTICI ≥ 2b) was achieved in 95.5% (21/22) of patients. Perioperative complications developed in two patients (9.1%) including one hemorrhagic event and one thromboembolic event. Angiographic follow-up was available in 20 patients (90.9%) at an average of 8.6 ± 3.0 months. The degree of stenosis was worse (10–30%) in 6 cases (30%) compared with the initial outcomes. The favorable outcomes (mRS ≤ 2) at 3-month follow-up was achieved in 19 patients (86.4%).

Conclusions
ICASS-related occlusion in the M1 segment often required a rescue therapy including balloon angioplasty with/without stenting, and this treatment strategy was safe and effective. But single balloon angioplasty at the first EVT generally cannot achieve satisfactory results and often needed staged stenting treatment.
Analyzing appropriate autonomous vessel for South-East Asian route: from the view of seafarers
Authors: Rahman Bornali 
Published: September 2022

AbstractThe development of autonomous vessel has achieved tremendous interest across the world for the safe navigation and economic benefits. Numerous alternatives are constructed in the autonomous vessel development projects, the alternatives of MUNIN and NYK project are combined for this study; these are - Manned autonomous vessel, Remotely controlled vessel, Autonomous and Partially remote-controlled vessel, and Full autonomous vessel. As the statistics of UNCTAD shows that South-East Asia is a highly dense region and has the busiest international maritime connectivity, this research tried to select the appropriate autonomous vessels from the four alternatives to ensure safe navigation in this traffic congested maritime route. For this study, 311 accident reports are investigated to find out the most frequent casualty and its cause. The data are collected from the global integrated shipping information system of the international maritime organization's website. The decision tree of R-studio demonstrates that the most frequent accidents are- Collision, Grounding, Fire, and listing. Afterwards a survey was made on 65 experienced seafarers to determine which autonomous vessel criteria would be compatible to avoid the casualty. This research adopts AHP (analytical hierarchy process) to conduct the analysis. AHP is a multi-criteria decision analysis method for solving any decision problem. The research shows that ‘Manned autonomous vessel’ and ‘Autonomous and Partially remote-controlled vessel’ are the appropriate alternatives for safe navigation in the South-East Asian region. This study will help the researcher who is working in autonomous vessel development, mainly working for Asian water.
Design of a 2-DOF-PID controller using an improved sine–cosine algorithm for load frequency control of a three-area system with nonlinearities
Authors: Gupta Neelesh Kumar , Kar Manoj Kumar , Singh Arun Kumar 
Published: September 2022

AbstractThis paper proposes an improved sine–cosine algorithm (ISCA) based 2-DOF-PID controller for load frequency control. A three-area test system is built for study, while some physical constraints (nonlinearities) are considered for the investigation of a realistic power system. The proposed method is used as the parameter optimizer of the LFC controller in different scenarios. The 2-DOF-PID controllers are used because of their capability of fast disturbance rejection without significant increase of overshoot in set-point tracking. The 2-DOF-PID controllers’ efficacy is observed by examining the responses with the outcomes obtained with PID and FOPID controllers. The simulation results with the suggested scheme are correlated with some of the existing algorithms, such as SCA, SSA, ALO, and PSO in three different scenarios, i.e., a disturbance in two areas, in three areas, and in the presence of physical constraints. In addition, the study is extended to a four-area power system. Statistical analysis is performed using the Wilcoxon Sign Rank Test (WSRT) on 20 independent runs. This confirms the supremacy of the proposed method.
CAMFuzz: Explainable Fuzzing with Local Interpretation
Authors: Shi Ji , Zou Wei , Zhang Chao , Tan Lingxiao , Zou Yanyan , Peng Yue , Huo Wei 
Published: September 2022

AbstractGrey-box fuzzing techniques have been widely used in software bug finding. In general, there are many decisions to make in the fuzzing process, including which code block in the target program should be explored first, which bytes of an input seed should be mutated to reach the target code block, and how to mutate the chosen input bytes. However, existing solutions usually rely on random exploration or certain heuristics to choose where and how to fuzz, which limits the efficiency of fuzzing. In this paper, we propose a novel solution CAMFuzz to guide the fuzzing process with explainable decisions in explainable artificial intelligence (XAI). First, we propose a dynamic weight adjustment algorithm, which considers both the difficulty of reaching a block and the number of unvisited blocks nearby, to find code blocks worthy to explore first. Second, we utilize a widely used local interpretation technique, i.e., class activation mapping (CAM), to recognize which part of an input seed should be mutated to reach a given target code block. Therefore, CAMFuzz can distinguish which part of code in the program is more important and which positions in the input file should be mutated first, in order to achieve a better code coverage and bug finding efficiency. Third, to further help the fuzzer increase fuzzing efficiency, we leverage a lightweight static program analysis to help the fuzzer identify magic values. We implement a prototype of CAMFuzz and evaluate it on 13 real-world programs (including 11 open source targets, 2 closed-source commercial products including a Microsoft component and Hancom Office) Results show that CAMFuzz outperforms state-of-the-art fuzzers in both code coverage and bug finding. To detail, CAMFuzz on average achieves 2.07$$\times$$
×
more bugs and 1.17$$\times$$
×
coverage improvements. In total, it found 19 previously unknown vulnerabilities, of which 6 have been assigned by CVE so far.
Relative bradycardia in patients with COVID-19
Authors: Jung Lae-Young , Kim Jae-Min , Ryu Sukhyun , Lee Chang-Seop 
Published: September 2022

Abstract
Introduction
Relative bradycardia(RB) is a relatively low heart rate response to rise in body temperature that occurs in several infectious diseases and can be an important clinical sign. In previous case reports, RB was presented in some patients with Coronavirus disease 2019 (COVID-19) COVID-19.

Objective and Methods
To investigate the correlation between temperature and heart rate, we retrospectively reviewed 249 febrile patients with documented COVID-19 patients. RB was defined as a rise in the heart rate from a basal heart rate of less than 10 beats/minute/°C rise in temperature.

Results
In this study, the prevalence of RB in patients with COVID-19 was 60.6%. When the HR at peak temperatures for patients with COVID-19 were compared with reference valve (general temperature-heart rate response in infectious disease), our findings demonstrate a relatively lower heart rate at all peak temperatures recorded. Despite differences in heart rate response, there were not significant differences in clinical outcomes (pulmonary manifestation, intensive care unit admission, Death).

Conclusions
Most patients with COVID-19 are associated with relative bradycardia, not related to clinical outcomes. RB in COVID-19 can be considered as the clinical features for differential diagnosis from other febrile conditions.
A review of current practices in periprosthetic joint infection debridement and revision arthroplasty
Authors: Mian Humza M. , Lyons Joseph G. , Perrin Joshua , Froehle Andrew W. , Krishnamurthy Anil B. 
Published: September 2022

Abstract
Background
Periprosthetic joint infection remains a significant challenge for arthroplasty surgeons globally. Over the last few decades, there has been much advancement in terms of treatment and diagnosis, however, the fight rages on. As management of periprosthetic joint infections continues to evolve, it is critical to reflect back on current debridement practices to establish common ground as well as identify areas for future research and improvement.

Body
In order to understand the debridement techniques of periprosthetic joint infections, one must also understand how to diagnose a periprosthetic joint infection. Multiple definitions have been elucidated over the years with no single consensus established but rather sets of criteria. Once a diagnosis has been established the decision of debridement method becomes whether to proceed with single vs two-stage revision based on the probability of infection as well as individual patient factors. After much study, two-stage revision has emerged as the gold standard in the management of periprosthetic infections but single-stage remains prominent with further and further research.

Conclusion
Despite decades of data, there is no single treatment algorithm for periprosthetic joint infections and subsequent debridement technique. Our review touches on the goals of debridement while providing a perspective as to diagnosis and the particulars of how intraoperative factors such as intraarticular irrigation can play pivotal roles in infection eradication. By providing a perspective on current debridement practices, we hope to encourage future study and debate on how to address periprosthetic joint infections best.
Sequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial
Authors: Ascierto Paolo A. , Mandalà Mario , Ferrucci Pier Francesso , Guidoboni Massimo , Rutkowski Piotr , Ferraresi Virginia , Arance Ana , Guida Michele , Maiello Evaristo , Gogas Helen , Richtig Erika , Fierro Maria Teresa , Lebbè Celeste , Helgadottir Hildur , Queirolo Paola , Spagnolo Francesco , Tucci Marco , Del Vecchio Michele , Gonzales Cao Maria , Minisini Alessandro Marco , De Placido Sabino , Sanmamed Miguel F. , Mallardo Domenico , Curvietto Marcello , Melero Ignacio , Palmieri Giuseppe , Grimaldi Antonio M. , Giannarelli Diana , Dummer Reinhard , Chiarion Sileni Vanna 
Published: September 2022

PURPOSE Limited prospective data are available on sequential immunotherapy and BRAF/MEK inhibition for BRAFV600-mutant metastatic melanoma. METHODS SECOMBIT is a randomized, three-arm, noncomparative phase II trial (ClinicalTrials.gov identifier: NCT02631447 ). Patients with untreated, metastatic BRAFV600-mutant melanoma from 37 sites in nine countries were randomly assigned to arm A (encorafenib [450 mg orally once daily] plus binimetinib [45 mg orally twice daily] until progressive disease [PD] -> ipilimumab plus nivolumab [ipilimumab 3 mg/kg once every 3 weeks and nivolumab 1 mg/kg once every 3 weeks × four cycles -> nivolumab 3 mg/kg every 2 weeks]), arm B [ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib], or arm C (encorafenib plus binimetinib for 8 weeks -> ipilimumab plus nivolumab until PD -> encorafenib plus binimetinib). The primary end point was overall survival (OS) at 2 years. Secondary end points included total progression-free survival, 3-year OS, best overall response rate, duration of response, and biomarkers in the intent-to-treat population. Safety was analyzed throughout sequential treatment in all participants who received at least one dose of study medication. RESULTS A total of 209 patients were randomly assigned (69 in arm A, 71 in arm B, and 69 in arm C). At a median follow-up of 32.2 (interquartile range, 27.9-41.6) months, median OS was not reached in any arm and more than 30 patients were alive in all arms. Assuming a null hypothesis of median OS of ≤ 15 months, the OS end point was met for all arms. The 2-year and 3-year OS rates were 65% (95% CI, 54 to 76) and 54% (95% CI, 41 to 67) in arm A, 73% (95% CI, 62 to 84) and 62% (95% CI, 48 to 76) in arm B, and 69% (95% CI, 59 to 80) and 60% (95% CI, 58 to 72) in arm C. No new safety signals emerged. CONCLUSION Sequential immunotherapy and targeted therapy provide clinically meaningful survival benefits for patients with BRAFV600-mutant melanoma.
Comparing a Bayesian Approach (BEST) with the Two One-Sided t-Tests (TOSTs) for Bioequivalence Studies
Authors: Peck Carl , Campbell Gregory , Yoo Isaac , Feng Kairui , Hu Meng , Zhao Liang 
Published: September 2022

AbstractThe two one-sided t-tests (TOST) procedure has been used to evaluate average bioequivalence (BE). As a regulatory standard, it is crucial that TOST distinguish BE from not-BE (NBE) when BE data are not lognormal. TOST was compared with a Bayesian procedure (BEST by Kruschke) in simulated datasets of test/reference ratios (T/R) which were BE and NBE, wherein (1) log(T/R) or T-R were normally distributed, (2) sample sizes ranged 10–50, and (3) extreme log(T/R) or T-R values were randomly included in datasets. The 90% “credible interval” (CrI) from BEST is a Bayesian alternative of the 90% confidence interval (CI) of TOST and it can be derived from a posterior distribution that is more reflective of the observed mean log(T/R) distribution that often deviates from normality. In the absence of extreme T/R values, both methods agreed BE when observed T/R were lognormal. BEST more accurately concluded BE or NBE, while requiring fewer subjects, when observed log(T/R) or T-R were normal in the presence of extreme values. Overall, TOST and BEST perform comparably on lognormal T/R, while BEST is more accurate, requiring fewer subjects when datasets are normal for T-R or contain extreme values. Of note, the normally distributed datasets only rarely contain extreme values. Our results imply that when BEST and TOST yield different BE assessment results from bioequivalent products, TOST may disadvantage applicants when T/R are not lognormal and/or include extreme T/R values. Application of BEST can address the situation when T/R are not lognormal or include extreme data values. Application of BEST to BE data can be considered a useful alternative to TOST for evaluation of BE and for efficient development of BE formulations.
RhoB Promotes Endometrial Stromal Cells Decidualization Via Semaphorin3A/PlexinA4 Signaling in Early Pregnancy
Authors: Xu Ling , Li Yan-Hong , Zhao Wei-Jie , Sang Yi-Fei , Chen Jia-Jia , Li Da-Jin , Du Mei-Rong 
Published: September 2022

Abstract
Endometrial decidualization refers to a series of morphological changes and functional remodeling of the uterine endometrium to accept the embryo under the effect of estrogen and progesterone secreted by ovaries after ovulation. During decidualization, endometrial stromal cells (ESCs) proliferate and differentiate into decidual stromal cells, undergoing cytoskeletal rearrangement-mediated morphological changes and expressing decidualization markers, such as insulin-like growth factor-binding protein-1 and prolactin. Ras homology (Rho) proteins, a family of small G proteins, are well known as regulators of cellular morphology and involved in multiple other cellular processes. In this study, we found ras homolog family member B (RHOB) was the most significantly upregulated gene in the Rho protein family after the in vitro decidualization of human primary ESCs. RhoB expression was induced mainly by 3′,5′-cyclic adenosine 5′-monophosphate (cAMP) / protein kinase A (PKA) / cyclic adenosine monophosphate-response element binding protein signaling and partly by progesterone signaling. Knockdown of RhoB in ESCs greatly inhibited actin cytoskeletal rearrangement, cell morphological transformation, and upregulation of insulin-like growth factor-binding protein-1, suggesting an indispensable role of RhoB in decidualization. Mechanistically, the downstream target of RhoB was semaphorin3A (Sema3A), which mediated its signaling via interacting with the receptor, plexinA4. More importantly, decreased expression of RhoB, Sema3A, and plexinA4 were detected in deciduas from patients with unexplained spontaneous miscarriage. Collectively, our results indicate that RhoB/Sema3A/plexinA4 signaling plays a positive role in endometrial decidualization and relates to unexplained spontaneous miscarriage, which is worthy of further exploration so as to provide new insights into therapeutic strategies for pregnancy diseases associated with poor decidualization.
A pilot study of risk-stratified cervical cancer screening
Authors: Wang Jiangrong , Elfström K. Miriam , Borgfeldt Christer , Dillner Joakim 
Published: September 2022

Background: Cervical screening programs target entire populations, although it is well established that cervical cancer risks can vary >100-fold based, in particular, on the woman’s screening history. Since cervical screening switched to Human Papillomavirus (HPV) testing as the primary screening method, the risk differences are even larger as different HPV types may vary in associated cancer risk by 100 times. Furthermore, HPV infections with the most oncogenic types are declining dramatically because of HPV vaccination programs. Tailoring screening intensity based on the known cancer risk of the individual (risk-stratified screening) therefore has great potential to increase both the sensitivity and specificity. Within Horizon 2020 a major project for Risk-stratified Screening for Cervical Cancer (RISCC) has therefore been launched. We performed a pilot study of risk-stratified screening to evaluate feasibility and acceptability of offering vaginal HPV self-sampling tests to women with a higher risk of cervical cancer. Methods: We identified resident women who had had either i) atypical glandular cells in screening tests during the past six years (risk >150/100,000 woman-years) or ii) abnormal screening findings above the age of 50, but without sufficient follow-up (risk >65/100,000). The women were invited, either by short message service (SMS) or physical letters, to order an HPV self-sampling kit via the study web-platform. The returned self-collected samples were tested for HPV. If positive, women were invited for clinical follow-up. Results: Among 920 targeted women, 191 (21%) placed an order and 163 (18%) returned a self-collected sample. Among all tested samples, 19 (12%) were positive for hrHPV and 18 of these women attended clinical follow-up. Conclusions: SMS invitations to high-risk women complemented with physical letters are feasible and result in substantial requests for kits and submission of samples. Future work will focus on improving the efficiency of the procedure and further increasing attendance.