bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol for a 15-week randomised controlled trial assessing the independent effects of high-cholesterol and high-saturated fat diets on LDL cholesterol
Authors: Carter Sharayah , Hill Alison M , Yandell Catherine , Buckley Jonathan D , Coates Alison M 
Published: January 2024

IntroductionPrevious research has associated high dietary cholesterol intake with raised low-density lipoprotein cholesterol (LDL-C) and thus increased risk for cardiovascular disease (CVD). Emerging research suggests that it is saturated fat, not dietary cholesterol, associated with increased CVD risk. Despite being high in cholesterol, eggs, low in saturated fat, are not adversely associated with blood lipids or CVD risk. This paper describes a randomised controlled counter-balanced, cross-over trial assessing the effects of a high-cholesterol/low-saturated fat (egg) diet and a low-cholesterol/high-saturated fat diet (egg free) on blood lipids and lipoproteins, while accounting for physical activity levels which can also influence these parameters. The primary aim is to demonstrate that high cholesterol intake (from eggs) within a healthy, low-saturated fat diet does not adversely affect blood lipid levels and lipoprotein profiles. Instead, we propose that adverse effects on these parameters are mediated by saturated fat intake. The secondary aim is to explore relationships between changes in blood lutein and zeaxanthin concentrations and alterations in physical activity, examining whether changes in physical activity mediate effects on blood lipids and lipoproteins.Methods and analysisFifty-two adults aged 18–60 years with LDL-C less than 3.5 mmol/L will be randomly allocated to three isocaloric diets for 5 weeks each: a high-cholesterol (600 mg)/low-saturated fat (6%) (egg) diet, a low-cholesterol (300 mg)/high-saturated fat (12%) (egg free) diet and a control diet that is high in both cholesterol (600 mg) and saturated fat (12%). Lipid and lipoprotein levels, lipoprotein size and concentrations, blood pressure, blood glucose, physical activity levels, and plasma lutein and zeaxanthin concentrations will be measured. Treatment effects will be analysed using linear mixed effects models.Ethics and disseminationEthics approval was obtained from the University of South Australia Human Research Ethics Committee no. 204 327. Results will be disseminated through peer-reviewed journals and national and international presentations.Trial registration numberNCT05267522
Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness—a protocol for a randomised controlled trial (ASTUTE trial)
Authors: Hazell Mae , Reeves Barnaby , Rogers Chris A , Pike Katie , Culliford Lucy , Baos Sarah , Lui Mandy P Y , Beare Nicholas A V , Pavesio Carlos , Denniston Alastair K , Wordsworth Sarah , Keane Pearse A , Wilson Robert , Folkard Annie , Peto Tunde , Sharma Srilakshmi M , Dick Andrew 
Published: January 2024

IntroductionAdalimumab is an effective treatment for autoimmune non-infectious uveitis (ANIU), but it is currently only funded for a minority of patients with ANIU in the UK as it is restricted by the National Institute for Health and Care Excellence guidance. Ophthalmologists believe that adalimumab may be effective in a wider range of patients. The Adalimumab vs placebo as add-on to Standard Therapy for autoimmune Uveitis: Tolerability, Effectiveness and cost-effectiveness (ASTUTE) trial will recruit patients with ANIU who do and do not meet funding criteria and will evaluate the effectiveness and cost-effectiveness of adalimumab versus placebo as an add-on therapy to standard care.Methods and analysisThe ASTUTE trial is a multicentre, parallel-group, placebo-controlled, pragmatic randomised controlled trial with a 16-week treatment run-in (TRI). At the end of the TRI, only responders will be randomised (1:1) to 40 mg adalimumab or placebo (both are the study investigational medicinal product) self-administered fortnightly by subcutaneous injection. The target sample size is 174 randomised participants. The primary outcome is time to treatment failure (TF), a composite of signs indicative of active ANIU. Secondary outcomes include individual TF components, retinal morphology, adverse events, health-related quality of life, patient-reported side effects and visual function, best-corrected visual acuity, employment status and resource use. In the event of TF, open-label drug treatment will be restarted as per TRI for 16 weeks, and if a participant responds again, allocation will be switched without unmasking and treatment with investigational medicinal product restarted.Ethics and disseminationThe trial received Research Ethics Committee (REC) approval from South Central – Oxford B REC in June 2020. The findings will be presented at international meetings, by peer-reviewed publications and through patient organisations and newsletters to patients, where available.Trial registrationISRCTN31474800. Registered 14 April 2020.
Mitigating Debugger-based Attacks to Java Applications with Self-debugging
Authors: Pizzolotto Davide , Berlato Stefano , Ceccato Mariano 
Published: January 2024

Java bytecode is a quite high-level language and, as such, it is fairly easy to analyze and decompile with malicious intents, e.g., to tamper with code and skip license checks. Code obfuscation was a first attempt to mitigate malicious reverse-engineering based on static analysis. However, obfuscated code can still be dynamically analyzed with standard debuggers to perform step-wise execution and to inspect (or change) memory content at important execution points, e.g., to alter the verdict of license validity checks. Although some approaches have been proposed to mitigate debugger-based attacks, they are only applicable to binary compiled code and none address the challenge of protecting Java bytecode.
In this article, we propose a novel approach to protect Java bytecode from malicious debugging. Our approach is based on automated program transformation to manipulate Java bytecode and split it into two binary processes that debug each other (i.e., a self-debugging solution). In fact, when the debugging interface is already engaged, an additional malicious debugger cannot attach. To be resilient against typical attacks, our approach adopts a series of technical solutions, e.g., an encoded channel is shared by the two processes to avoid leaking information, an authentication protocol is established to avoid Man-in-the-middle attacks, and the computation is spread between the two processes to prevent the attacker to replace or terminate either of them.
We test our solution on 18 real-world Java applications, showing that our approach can effectively block the most common debugging tasks (either with the Java debugger or the GNU debugger) while preserving the functional correctness of the protected programs. While the final decision on when to activate this protection is still up to the developers, the observed performance overhead was acceptable for common desktop application domains.
Systematic Review and Meta‐Analysis of Endovascular Therapy Effectiveness for Unruptured Saccular Intracranial Aneurysms
Authors: Pineda‐Castillo Sergio A. , Jones Evan R. , Laurence Keely A. , Thoendel Lauren R. , Cabaniss Tanner L. , Zhao Yan D. , Bohnstedt Bradley N. , Lee Chung‐Hao 
Published: January 2024

Background
Currently, endovascular treatment of intracranial aneurysms is limited by low complete occlusion rates. The advent of novel endovascular technology has expanded the applicability of endovascular therapies; however, the superiority of novel embolic devices over the traditional Guglielmi detachable coils is still debated. We performed a systematic review of literature that reported the Raymond–Roy occlusion classification (RROC) rates of modern endovascular devices to determine their immediate and follow‐up occlusion effectivenesses for the treatment of unruptured saccular intracranial aneurysms.

Methods
A search was conducted using electronic databases (PUBMED, Cochrane, ClinicalTrials.gov, and Web of Science). We retrieved studies published between 2000 and 2022, reporting immediate and follow‐up RROC rates of subjects treated with different endovascular intracranial aneurysm therapies. We extracted demographic information of the treated patients and their reported angiographic RROC rates.

Results

A total of 80 studies from 15 countries were included for data extraction. The RROC rates determined from angiogram were obtained for 21 331 patients (72.5% women, pooled mean age: 58.2 [95% CI]: 56.8–59.6), harboring 22 791 aneurysms. The most frequent aneurysm locations were the internal carotid artery (46.4%, 95% CI: 41.9%–50.9%), the anterior communicating artery (26.4%, 95% CI: 22.5%–30.8%), the middle cerebral artery (24.5%, 95% CI: 19.2%–30.8%), and the basilar tip (14.4%, 95% CI: 11.3%–18.3%). The
complete
occlusion probability (RROC‐I) was analyzed for Guglielmi detachable coils, the Woven EndoBridge, and flow diverters. The RROC‐I rate was the highest in balloon‐assisted coiling (73.9%, 95% CI: 65.0%–81.2%) and the lowest in the Woven EndoBridge (27.8%, 95% CI: 13.2%–49.2%). The follow‐up RROC‐I probability was homogenous in all analyzed devices.

Conclusion

We observed that the coil‐based endovascular therapy provides acceptable rates of complete occlusion, and these rates are improved in balloon‐assisted coils. Out of the analyzed devices, the Woven EndoBridge exhibited the shortest time to achieve >90% probability of follow‐up complete occlusion (∼18 months). Overall, the Guglielmi detachable coils remain the
gold standard
for endovascular treatment of unruptured saccular aneurysms.
Patterns of Care in the Diagnosis and Management of Intracranial Atherosclerosis‐Related Large‐Vessel Occlusion: The Rescue‐LVO Survey
Authors: Siddiqui Fazeel M. , Fletcher Jeffrey J. , Elias Augusto E. , Dandapat Sudeepta , Kale Sushant P. , Heiferman Daniel , Riedy Loren , Farooqui Mudassir , Rodriguez‐Calienes Aaron , Vivanco‐Suarez Juan , Pandey Aditya S. , Ortega‐Gutierrez Santiago 
Published: January 2024

Background
We aimed to determine the current practice patterns among neurointerventional practitioners frequently involved in treating intracranial atherosclerosis‐related large‐vessel occlusion (ICAS‐LVO) during mechanical thrombectomy.

Methods
We conducted an international online survey of neurointerventionalist members of the Society of Vascular and Interventional Neurology and Society of Neurointerventional Surgery. The 28‐question poll evaluated the preferences on diagnosis, treatment, and endovascular approach to ICAS‐LVO.

Results
A total of 184 individual survey responses were obtained from practicing neurointerventional physicians. Overall, 38.3% reported an incidence of 6% to 10% of ICAS‐LVO during mechanical thrombectomy. Most neurointerventionalists (91%) diagnose ICAS‐LVO after a continued or recurrent occlusion or by the presence of fixed focal stenosis after multiple mechanical thrombectomy attempts. Most respondents (86%) preferred acute treatment of ICAS‐LVO with rescue stenting (RS)±angioplasty. However, in patients who achieved recanalization with a severe fixed focal stenosis, most (58%) recommended primary medical management. The preferred medication during acute RS was intravenous antiplatelet therapy (65%), and after acute RS, it was dual oral antiplatelet therapy (65%). Fear of hemorrhagic complications (74%) was the most compelling reason not to perform RS±angioplasty. Of respondents, 24% were hesitant to randomize patients to acute RS versus medical therapy in a future randomized trial because of the lack of sensitive and specific biomarkers to diagnose ICAS‐LVO before mechanical thrombectomy treatment.

Conclusions
The findings of this survey highlight the variations in practice in the medical and endovascular management of ICAS‐LVO. In addition, it informs the situation of equipoise in the treatment decision in ICAS‐LVO, which can then be incorporated into the design of future randomized clinical trials.
Informed Down-Sampled Lexicase Selection: Identifying Productive Training Cases for Efficient Problem Solving
Authors: Boldi Ryan , Briesch Martin , Sobania Dominik , Lalejini Alexander , Helmuth Thomas , Rothlauf Franz , Ofria Charles , Spector Lee 
Published: January 2024

Abstract
Genetic Programming (GP) often uses large training sets and requires all individuals to be evaluated on all training cases during selection. Random down-sampled lexicase selection evaluates individuals on only a random subset of the training cases, allowing for more individuals to be explored with the same number of program executions. However, sampling randomly can exclude important cases from the down-sample for a number of generations, while cases that measure the same behavior (synonymous cases) may be overused. In this work, we introduce Informed Down-Sampled Lexicase Selection. This method leverages population statistics to build down-samples that contain more distinct and therefore informative training cases. Through an empirical investigation across two different GP systems (PushGP and Grammar-Guided GP), we find that informed down-sampling significantly outperforms random down-sampling on a set of contemporary program synthesis benchmark problems. Through an analysis of the created down-samples, we find that important training cases are included in the down-sample consistently across independent evolutionary runs and systems. We hypothesize that this improvement can be attributed to the ability of Informed Down-Sampled Lexicase Selection to maintain more specialist individuals over the course of evolution, while still benefiting from reduced per-evaluation costs.
Bian Que’s Twelve Channels?
Authors: Li Jianmin , Yang Dolly 
Published: January 2024

Abstract
The name Bian Que, like that of the Yellow Emperor (Huangdi), has reverberated through the development of Chinese medicine since the time of the Warring States. The discovery of a human figurine showing channels and strategic points, together with a number of medical texts, during the excavation of the Laoguanshan Han tomb in Chengdu, Sichuan, in 2012–13 has reignited controversies about whether it is correct to speak of a specific Bian Que school, or whether, as this paper argues, these texts were written by the Han physicians who used Bian Que as a mouthpiece to record their own medical expositions. The paper begins by examining the main characteristics of the Laoguanshan human figurine and discusses what this excavated artifact reveals about the early history of Chinese medicine. It questions the existence of the so-called Bian Que school and, obliquely, the suggested relationships between the school and the figurine and between the school and medical texts found in the same tomb. The paper shows how diverse the disjointed knowledge of medicine was and that the idea of a “school” does not accurately reflect what was happening in the transmission of medical knowledge during the Warring States, Qin, and Han periods (475 BCE–220 CE).
Looms of Life
Authors: Lo Vivienne 
Published: January 2024

Abstract
The classics of Chinese medicine are redolent with allusions to weaving as they describe a new imperial anatomy and physiology of the medical body. The superior physician in the Yellow Emperor’s corpus manipulated ji 機, the trigger mechanisms at strategic points on the surface of the body, which provided remote relief from the symptoms of illness. Through stimulating these points, medical practice with needle and moxibustion could control the many spirits that inhabited the body, weaving them into a numinous fabric. This paper explores the spatiotemporal geographies of meaning expressed in the manuscripts and artifacts excavated at the Laoguanshan tomb sites. In particular, an analysis of the medical texts, models of mechanical pattern shaft looms, and a tiny lacquered medical figurine recovered there suggest that local translational knowledge transfer between medicine, weaving, and water technologies occurred in the upper reaches of the Yangzi Valley. The resulting innovations were at the heart of a new imperial Chinese medicine.
Preliminary Translation of the Tianhui Laoguanshan Manuscript on Piercing as Therapy
Authors: Lo Vivienne 
Published: January 2024

Abstract
This translation forms a triptych with the following two articles in this double special issue: Gu Man, Zhou Qi, and Liu Changhua, “Techniques for Piercing the Mai Recorded in the Laoguanshan Han Tomb Bamboo Slips” and Zhou Qi, “Research on the Lacquered Channel Figurine Excavated from a Han Tomb in Tianhui.” Here you can read an entire Tianhui Laoguanshan text in translation on the subject of therapeutic piercing. The contribution by Gu, Zhou, and Liu positions the therapy in relation to ideas and techniques in other manuscript texts contemporary to the one translated here and the printed classics of Chinese medicine. These articles are accompanied by opinion pieces written by current practitioners of Chinese medicine as expert witnesses to the evolution of the techniques and their relevance, or not, to modern practice. Together, we present an interdisciplinary analysis that we hope will engage the reader actively in the process of multifocal interpretation. The text here is introduced by a translator’s introduction that reflects broadly on the unique challenges of rendering this fascinating work into English.
Observed 10–20-Day Deep-Current Variability at 5°N, 90.5°E in the Eastern Indian Ocean
Authors: Wang Jinghong , Shu Yeqiang , Wang Dongxiao , Chen Ju , Yang Yang , Wang Weiqiang , Guo Binbin , Huang Ke , He Yunkai 
Published: January 2024

Abstract
In the eastern off-equatorial Indian Ocean, deep current intraseasonal variability within a typical period of 10–20 days was revealed by a mooring at 5°N, 90.5°E, accounting for over 50% of the total bottom subtidal velocity variability. The 10–20-day oscillations were more energetic in the cross-isobathic direction (STD = 3.02 cm s−1) than those in the along-isobathic direction (STD = 1.50 cm s−1). The oscillations were interpreted as topographic Rossby waves (TRWs) because they satisfied the TRWs dispersion relation that considered the smaller Coriolis parameter and stronger β effect at low latitude. Further analysis indicated significant vertical coupling between the deep cross-slope oscillations and cross-isobathic 10–20-day perturbations at the depth of 300–950 m. The 10–20-day TRWs were generated by cross-isobathic motions under the potential vorticity conservation adjustment. The Mercator Ocean output reproduced the generation of kinetic energy (KE) of deep current variability. The associated diagnostic analysis of multiscale energetics showed that the KE of TRWs was mainly supplied by vertical pressure work. In the seamount region (2°–10°N, 89°–92°E), vertical and horizontal pressure works were identified to be the dominant energy source (contributing to 94% of the total KE source) and sink (contributing to 98% of the total KE sink) of the deep current variability, transporting energy downward and redistributing energy horizontally, respectively.
An Assessment of Dropsonde Sampling Strategies for Atmospheric River Reconnaissance
Authors: Zheng Minghua , Torn Ryan , Delle Monache Luca , Doyle James , Ralph Fred Martin , Tallapragada Vijay , Davis Christopher , Steinhoff Daniel , Wu Xingren , Wilson Anna , Papadopoulos Caroline , Mulrooney Patrick 
Published: January 2024

Abstract
During a 6-day intensive observing period in January 2021, Atmospheric River Reconnaissance (AR Recon) aircraft sampled a series of atmospheric rivers (ARs) over the northeastern Pacific that caused heavy precipitation over coastal California and the Sierra Nevada. Using these observations, data denial experiments were conducted with a regional modeling and data assimilation system to explore the impacts of research flight frequency and spatial resolution of dropsondes on model analyses and forecasts. Results indicate that dropsondes significantly improve the representation of ARs in the model analyses and positively impact the forecast skill of ARs and quantitative precipitation forecasts (QPF), particularly for lead times > 1 day. Both reduced mission frequency and reduced dropsonde horizontal resolution degrade forecast skill. On the other hand, experiments that assimilated only G-IV data and experiments that assimilated both G-IV and C-130 data show better forecast skill than experiments that only assimilated C-130 data, suggesting that the additional information provided by G-IV data is necessary for improving forecast skill. Although this is a case study, the 6-day period studied encompassed multiple AR events that are representative of typical AR behavior. Therefore, the results indicate that future operational AR Recon missions incorporate daily mission or back-to-back flights, maintain current dropsonde spacing, support high-resolution data transfer capacity on the C-130s, and utilize G-IV aircraft in addition to C-130s.
Documentation of the Patient Characteristics Morbid Obesity and Bariatric Surgery in the Hospital Information System and the Influence on the Number of Medication-Related Problems
Authors: Kingma Jurjen S. , Brenkman Iris A. M. , van den Broek Marcel P. H. , van den Bemt Patricia M. L.A. , Janssen Karin , Knibbe Catherijne A. J. , Burgers Desirée M. T. 
Published: January 2024

Background: As a result of pharmacokinetic changes, individuals with morbid obesity and/or with bariatric surgery may require dose adjustments, additional monitoring or medication should be avoided. Clinical decision support (CDS) may provide automated alerts enabling correct prescribing but requires documentation of these patient characteristics in the Hospital Information System (HIS) to prevent medication-related problems (MRPs). Objective: The primary objective is to determine the proportion of patients with documentation of the patient characteristics morbid obesity and bariatric surgery in the HIS. The secondary objective is to compare the proportion of patients with an MRP in the group with versus without documentation. Also, the type and severity of MRPs and the medication involved are determined. Methods: A prospective cohort study was performed. Patients admitted to the hospital were identified as morbidly obese and/or with bariatric surgery. In the identified patients, the proportion of patients with documentation of the patient characteristics in the HIS was evaluated as primary outcome. Subsequently, patient records were reviewed for MRPs, which were categorized and associated medication was registered. For the primary objective, descriptive statistics was used. For the secondary outcome, the Fisher’s exact test was used. Results: In 43 (21.4%, 95% confidence interval [CI]: 15.7%-27.1%) of 201 included patient (113 morbid obesity, 70 bariatric surgery and 18 both), the patient characteristics were documented. An MRP occurred in 2.3% versus 13.9% ( P = 0.032) of patients with and without documentation, respectively. The most common MRP was underdosing in morbid obesity, while in patients with bariatric surgery it was prescription of contra-indicated medication. Conclusion and relevance: The proportion of patients with documentation of the patient characteristics bariatric surgery and/or morbid obesity in the HIS is low, which appears to be associated with more MRPs. To improve medication safety, it is important to document these patient characteristics.