bluuebunny/crossref_metadata_2025 huggingface dataset:
Preferences for long‐acting pre‐exposure prophylaxis among gay, bisexual and other men who have sex with men in Taiwan: findings from the 2021 HEART Survey
Authors: Hsu Jing‐Hao , Ku Stephane Wen‐Wei , Chen Tsai‐Wei , Li Chia‐Wen , Huang Poyao , Wu Huei‐Jiuan , Bourne Adam , Strong Carol
Published: September 2023

Introduction

While various antiretrovirals have been studied as potential candidates for long‐acting pre‐exposure prophylaxis (PrEP), the bimonthly injectable cabotegravir—the first long‐acting form of PrEP—was approved in 2021. Event‐driven (ED) PrEP has been the most prevalent dosing regimen among gay, bisexual and other men who have sex with men (GBMSM) in Taiwan, providing a unique setting to observe the preferences for long‐acting PrEP in a community where the daily regimen is not the mainstream method. This study aimed to determine the preferences for the different forms and dosing intervals of long‐acting PrEP that are currently in the development pipeline.

Methods

We conducted a survey in 2021 by convenience sampling the users of social networking applications for GBMSM in Taiwan. Our survey included questions on sexual behaviours, current PrEP regimens and the preferences for potential candidates of long‐acting PrEP, such as implants, intramuscular and subcutaneous injections. We compared the Likert‐scale preference ratings for potential long‐acting options, and conducted logistic regression analysis to examine the factors associated with a preference for bimonthly intramuscular injections (2M IM) over ED and daily PrEP regimens, respectively.

Results

A total of 1728 responses were eligible for analysis. Three percent of respondents (n = 52) were daily PrEP users; 11.5% (n = 198) were ED PrEP users. When not considering cost, current PrEP users—regardless of their original dosing regimen—were most likely to express preferences for monthly oral PrEP, followed by a 6‐month subcutaneous injectable (6M SC) and 2M IM. However, among non‐current PrEP users, monthly oral PrEP was the most preferred form, followed by ED, daily oral and 6M SC injectable. Multivariable logistic regression revealed that current daily users, those willing to take PrEP in the next 6 months and those with more sex partners in the last 12 months had a significant correlation with preferences for the 2M IM injectable over the ED PrEP.

Conclusions

The monthly oral form was the most preferable long‐acting PrEP among GBMSM in Taiwan. Current daily PrEP users preferred the 2M IM injectable over the ED PrEP, which made the 2M IM injectable a potential alternative. Further studies should focus on how the cost and delivery affect PrEP preferences and their actual uptake.
Sexual and drug use risk behaviour trajectories among people treated for recent HCV infection: the REACT study
Authors: Carson Joanne M. , Barbieri Sebastiano , Cunningham Evan , Mao Eric , van der Valk Marc , Rockstroh Jürgen K. , Hellard Margaret , Kim Arthur , Bhagani Sanjay , Feld Jordan J. , Gane Ed , Thurnheer Maria C. , Bruneau Julie , Tu Elise , Dore Gregory J. , Matthews Gail V. , Martinello Marianne ,   the REACT study group
Published: September 2023

Introduction

Exploration of sexual and drug use behaviours following treatment for recent hepatitis C virus (HCV) is limited. This analysis modelled behavioural trajectories following treatment for recent HCV and assessed reinfection.

Methods

Participants treated for recent HCV in an international trial (enrolled 2017–2019) were followed at 3‐monthly intervals for up to 2 years to assess longitudinal behaviours. Population‐averaged changes were assessed using generalized estimating equations. Distinct behavioural trajectories were identified using group‐based trajectory modelling. HCV reinfection incidence was calculated using person‐years (PY) of observation.

Results

During the follow‐up of 212 participants (84% gay and bisexual men [GBM]; 69% HIV; 26% current injecting drug use [IDU]), behavioural trajectories for IDU and stimulant use (past month) did not change. However, population‐averaged decreases in the likelihood of daily IDU (adjusted odds ratio [AOR] 0.83; 95% CI 0.72, 0.95) and opioid use (AOR 0.84; 95% CI 0.75, 0.93) were observed. Among GBM, behavioural trajectories for chemsex did not change. Population‐averaged decreases in condomless anal intercourse with casual male partners (CAI‐CMP) (AOR 0.95; 95% CI 0.90, 0.99) and group‐sex (AOR 0.86; 95% CI 0.80, 0.93) were observed, but masked distinct trajectories. While a proportion had a decreased probability of CAI‐CMP (23%) and group‐sex (59%) post‐treatment, a substantial proportion retained a high probability of these behaviours. High HCV reinfection incidence was observed for the sustained high probability IDU (33.0/100 PY; 95% CI 17.7, 61.3) and chemsex (23.3/100 PY; 95% CI 14.5, 37.5) trajectories.

Conclusions

Limited sexual and drug use behavioural change was observed following treatment for recent HCV, supporting access to surveillance and (re)treatment.
Quantitative Analysis of Whole‐Body MRI for Accessing the Degree of Diffuse Infiltration Patterns and Identifying High Risk Cases of Newly Diagnosed Multiple Myeloma
Authors: Sun Mengtian , Wang Linlin , Wang Chong , Ma Jie , Wang Weimin , Lin Liangjie , Ren Cuiping , Zhang Yong , Cheng Jingliang
Published: September 2023

Background

Accurate identification of high‐risk multiple myeloma (HRMM) is important for prognostication. The degree of diffuse infiltration patterns on magnetic resonance imaging (MRI) is associated with patient prognosis in multiple myeloma. However, objective indexes to determine the degree of diffuse infiltration patterns are unavailable.

Purpose

To investigate whether qualitative and quantitative evaluations of diffuse infiltration patterns on MRI could identify HRMM.

Study Type

Retrospective.

Subjects

Totally, 180 patients (79 HRMM and 101 standard‐risk MM) were assessed. The presence of del(17p), t(4;14), t(14;16), t(14;20), gain 1q, and/or p53 mutations was considered to indicate HRMM.

Field Strength/Sequence

3.0 T/diffusion‐weighted whole‐body imaging with background body signal suppression (DWIBS), modified Dixon chemical‐shift imaging Quant (mDIXON Quant), and short TI inversion recovery (STIR).

Assessment

Qualitative analysis involved assessing the degree of diffuse marrow infiltration (mild, moderate, or severe), and quantitative analysis involved evaluating apparent diffusion coefficient (ADC), fat fraction (FF), and T2* values. Clinical data such as sex, age, hemoglobin, serum albumin, serum calcium, serum creatinine, serum lactate dehydrogenase, β2‐microglobulin, and bone marrow plasma cells (BMPCs) were also included.

Statistical Tests

Univariate and multivariate analyses, receiver operating characteristic (ROC) curve. P < 0.05 was considered statistically significant.

Results

The high‐risk group had significantly higher ADC and T2* and lower FF compared with the standard‐risk group. Multivariate analysis indicated BMPCs as a significant independent risk factor for HRMM (odds ratio (OR) = 1.019, 95% CI 1.004–1.033), while FF was a significant independent protective factor associated with HRMM (OR = 0.972, 95% CI 0.946–0.999). The combination of BMPCs and FF achieved the highest areas under the curve (AUC) of 0.732, with sensitivity and specificity of 70.9% and 68.3%, respectively.

Data Conclusion

Compared with qualitative analysis, FF value was independently associated with HRMM. The quantitative features of diffuse marrow infiltration on MRI scans are more effective in detecting HRMM.

Level of Evidence

3

Technical Efficacy

Stage 2
Noninvasive Assessment of Diabetic Kidney Disease With MRI: Hype or Hope?
Authors: Zhao Kaixuan , Seeliger Erdmann , Niendorf Thoralf , Liu Zaiyi
Published: September 2023

Owing to the increasing prevalence of diabetic mellitus, diabetic kidney disease (DKD) is presently the leading cause of chronic kidney disease and end‐stage renal disease worldwide. Early identification and disease interception is of paramount clinical importance for DKD management. However, current diagnostic, disease monitoring and prognostic tools are not satisfactory, due to their low sensitivity, low specificity, or invasiveness. Magnetic resonance imaging (MRI) is noninvasive and offers a host of contrast mechanisms that are sensitive to pathophysiological changes and risk factors associated with DKD. MRI tissue characterization involves structural and functional information including renal morphology (kidney volume (TKV) and parenchyma thickness using T1‐ or T2‐weighted MRI), renal microstructure (diffusion weighted imaging, DWI), renal tissue oxygenation (blood oxygenation level dependent MRI, BOLD), renal hemodynamics (arterial spin labeling and phase contrast MRI), fibrosis (DWI) and abdominal or perirenal fat fraction (Dixon MRI). Recent (pre)clinical studies demonstrated the feasibility and potential value of DKD evaluation with MRI. Recognizing this opportunity, this review outlines key concepts and current trends in renal MRI technology for furthering our understanding of the mechanisms underlying DKD and for supplementing clinical decision‐making in DKD. Progress in preclinical MRI of DKD is surveyed, and challenges for clinical translation of renal MRI are discussed. Future directions of DKD assessment and renal tissue characterization with (multi)parametric MRI are explored. Opportunities for discovery and clinical break‐through are discussed including biological validation of the MRI findings, large‐scale population studies, standardization of DKD protocols, the synergistic connection with data science to advance comprehensive texture analysis, and the development of smart and automatic data analysis and data visualization tools to further the concepts of virtual biopsy and personalized DKD precision medicine. We hope that this review will convey this vision and inspire the reader to become pioneers in noninvasive assessment and management of DKD with MRI.

Level of Evidence

1

Technical Efficacy

Stage 2
A comparison of bolus track and test bolus computed tomography pulmonary angiography and the implications on pulmonary and aortic vessel enhancement, effective dose and suboptimal scan rate
Authors: Murphy Aoife , White Helen
Published: September 2023

Introduction

Bolus track and test bolus are the most commonly used contrast timing protocols to undertake computed tomography pulmonary angiography (CTPA). The aim of this study was to compare test bolus and bolus track contrast enhancement protocols in terms of enhancement of the pulmonary vessels and aorta, radiation dose and suboptimal scan rate to determine the optimal technique for CTPA.

Methods

A total of 200 CTPA examinations (100 using each protocol) performed between January and February 2021 were assessed retrospectively. All scans were performed on a 2x128 Dual Source Siemens Drive Scanner. CT attenuation was measured in Hounsfield Units (HU), with measurements taken from the main pulmonary trunk, right pulmonary artery and left pulmonary artery, ascending and descending aorta. The mean effective dose was calculated from the dose‐length product (DLP). The suboptimal scan rate was calculated as the percentage of examinations below 210HU.

Results

The average HU of the pulmonary arteries was 358 HU ± SD 129.2 in the test bolus group and increased to 394 HU ± SD 133.9 in the bolus track group with a P value of ≤0.05. The average HU of the aorta was 235 HU ± SD 82.8 in the test bolus group and increased to 319 HU ± SD 91.8 in the bolus track group with a P value of <0.001. Although not statistically significant, the mean effective dose was reduced by 4.2% for the bolus track protocol (2.4 mSv vs. 2.5 mSv, P > 0.05). Fewer suboptimal scans were performed with the bolus track protocol (5 scans <210HU Bolus Track vs. 9 scans <210HU Test Bolus).

Conclusion

The bolus track protocol results in increased enhancement of the pulmonary arteries and aorta, with the added benefits of a lower suboptimal scan rate and lower effective dose.
Ethno‐demographic disparities in humoral responses to the COVID‐19 vaccine among healthcare workers
Authors: Ahluwalia Pankaj , Vashisht Ashutosh , Singh Harmanpreet , Sahajpal Nikhil Shri , Mondal Ashis K. , Jones Kimya , Farmaha Jaspreet , Bloomquist Ryan , Carlock Caroline Marie , Fransoso Drew , Sun Christina , Day Tyler , Prah Comfort , Vuong Trinh , Ray Patty , Bradshaw Danielle , Galvis Marisol Miranda , Fulzele Sadanand , Raval Girindra , Moore Justin Xavier , Cortes Jorge , James Jeffrey N. , Kota Vamsi , Kolhe Ravindra
Published: September 2023

The COVID‐19 pandemic had a profound impact on global health, but rapid vaccine administration resulted in a significant decline in morbidity and mortality rates worldwide. In this study, we sought to explore the temporal changes in the humoral immune response against SARS‐CoV‐2 healthcare workers (HCWs) in Augusta, GA, USA, and investigate any potential associations with ethno‐demographic features. Specifically, we aimed to compare the naturally infected individuals with naïve individuals to understand the immune response dynamics after SARS‐CoV‐2 vaccination. A total of 290 HCWs were included and assessed prospectively in this study. COVID status was determined using a saliva‐based COVID assay. Neutralizing antibody (NAb) levels were quantified using a chemiluminescent immunoassay system, and IgG levels were measured using an enzyme‐linked immunosorbent assay method. We examined the changes in antibody levels among participants using different statistical tests including logistic regression and multiple correspondence analysis. Our findings revealed a significant decline in NAb and IgG levels at 8−12 months postvaccination. Furthermore, a multivariable analysis indicated that this decline was more pronounced in White HCWs (odds ratio [OR] = 2.1, 95% confidence interval [CI] = 1.07−4.08, p = 0.02) and IgG (OR = 2.07, 95% CI = 1.04−4.11, p = 0.03) among the whole cohort. Booster doses significantly increased IgG and NAb levels, while a decline in antibody levels was observed in participants without booster doses at 12 months postvaccination. Our results highlight the importance of understanding the dynamics of immune response and the potential influence of demographic factors on waning immunity to SARS‐CoV‐2. In addition, our findings emphasize the value of booster doses to ensure durable immunity.
Exploring the mechanisms of long COVID: Insights from computational analysis of SARS‐CoV‐2 gene expression and symptom associations
Authors: Das Sanisha , Kumar Suresh
Published: September 2023

Long coronavirus disease (COVID) has emerged as a global health issue, affecting a substantial number of people worldwide. However, the underlying mechanisms that contribute to the persistence of symptoms in long COVID remain obscure, impeding the development of effective diagnostic and therapeutic interventions. In this study, we utilized computational methods to examine the gene expression profiles of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection and their associations with the wide range of symptoms observed in long COVID patients. Using a comprehensive data set comprising over 255 symptoms affecting multiple organ systems, we identified differentially expressed genes and investigated their functional similarity, leading to the identification of key genes with the potential to serve as biomarkers for long COVID. We identified the participation of hub genes associated with G‐protein‐coupled receptors (GPCRs), which are essential regulators of T‐cell immunity and viral infection responses. Among the identified common genes were CTLA4, PTPN22, KIT, KRAS, NF1, RET, and CTNNB1, which play a crucial role in modulating T‐cell immunity via GPCR and contribute to a variety of symptoms, including autoimmunity, cardiovascular disorders, dermatological manifestations, gastrointestinal complications, pulmonary impairments, reproductive and genitourinary dysfunctions, and endocrine abnormalities. GPCRs and associated genes are pivotal in immune regulation and cellular functions, and their dysregulation may contribute to the persistent immune responses, chronic inflammation, and tissue abnormalities observed in long COVID. Targeting GPCRs and their associated pathways could offer promising therapeutic strategies to manage symptoms and improve outcomes for those experiencing long COVID. However, the complex mechanisms underlying the condition require continued study to develop effective treatments. Our study has significant implications for understanding the molecular mechanisms underlying long COVID and for identifying potential therapeutic targets. In addition, we have developed a comprehensive website (https://longcovid.omicstutorials.com/) that provides a curated list of biomarker‐identified genes and treatment recommendations for each specific disease, thereby facilitating informed clinical decision‐making and improved patient management. Our study contributes to the understanding of this debilitating disease, paving the way for improved diagnostic precision, and individualized therapeutic interventions.
Reprocessable Vanillin‐Based Schiff Base Vitrimers: Tuning Mechanical and Thermomechanical Properties by Network Design
Authors: Klein Florian C. , Vogt Malte , Abetz Volker
Published: September 2023

Bio‐based polymer building blocks derived from abundant biomass represent a promising class of monomers for the synthesis of sustainable high‐performance polymers. Lignin‐derived vanillin is used as a bio‐based, aromatic molecular platform for chemical modifications. The use of vanillin aldehyde derivatives as monomers with different alkyl chain length, cured with bio‐based and less‐toxic di‐ and triamines, leads to covalent adaptable Schiff base networks and thus enables sustainable and thermally reprocessable high‐performance materials without using highly toxic amines. A process is presented to prepare homogeneous films of crosslinked materials that are thermally reprocessable while maintaining their mechanical performance. The network structures, mechanical properties, and thermal stability of the obtained polymeric sheets are characterized in detail. By systematically adjusting the composition of the network building blocks, the mechanical properties could be varied from tough materials with a high elastic modulus of 1.6 GPa to materials with high flexibility and elastomeric behavior with an elongation at break of 400%. Furthermore, the stress–relaxation behavior of stoichiometric and nonstoichiometric Schiff base vitrimers is investigated. The combination of bio‐based building blocks and the degradability of Schiff base networks under acidic conditions resulted in sustainable, environmentally friendly, chemically and thermomechanically recyclable vitrimers with self‐healing and shape‐memory properties.
Purine and purinergic receptors in health and disease
Authors: Ai Yanling , Wang Hengyi , Liu Lu , Qi Yulin , Tang Shiyun , Tang Jianyuan , Chen Nianzhi
Published: September 2023

Purines and purinergic receptors are widely distributed throughout the human body. Purine molecules within cells play crucial roles in regulating energy metabolism and other cellular processes, while extracellular purines transmit signals through specific purinergic receptors. The ubiquitous purinergic signaling maintains normal neural excitability, digestion and absorption, respiratory movement, and other complex physiological activities, and participates in cell proliferation, differentiation, migration, and death. Pathological dysregulation of purinergic signaling can result in the development of various diseases, including neurodegeneration, inflammatory reactions, and malignant tumors. The dysregulation or dysfunction of purines and purinergic receptors has been demonstrated to be closely associated with tumor progression. Compared with other subtypes of purinergic receptors, the P2X7 receptor (P2X7R) exhibits distinct characteristics (i.e., a low affinity for ATP, dual functionality upon activation, the mediation of ion channels, and nonselective pores formation) and is considered a promising target for antitumor therapy, particularly in patients with poor response to immunotherapy This review summarizes the physiological and pathological significance of purinergic signaling and purinergic receptors, analyzes their complex relationship with tumors, and proposes potential antitumor immunotherapy strategies from tumor P2X7R inhibition, tumor P2X7R overactivation, and host P2X7R activation. This review provides a reference for clinical immunotherapy and mechanism investigation.
Prediagnostic Blood Metal Levels and the Risk of Parkinson's Disease: A Large European Prospective Cohort
Authors: Zhao Yujia , Ray Anushree , Broberg Karin , Kippler Maria , Lill Christina M. , Vineis Paolo , Katzke Verena A. , Rodriguez‐Barranco Miguel , Chirlaque María‐Dolores , Guevara Marcela , Gómez Jesús‐Humberto , Hansen Johnni , Panico Salvatore , Middleton Lefkos T. , Masala Giovanna , Pala Valeria , Vinagre‐Aragon Ana , Zibetti Maurizio , Vermeulen Roel , Peters Susan
Published: September 2023

Background

Metals have been postulated as environmental concerns in the etiology of Parkinson's disease (PD), but metal levels are typically measured after diagnosis, which might be subject to reverse causality.

Objective

The aim of this study was to investigate the association between prediagnostic blood metal levels and PD risk.

Methods

A case‐control study was nested in a prospective European cohort, using erythrocyte samples collected before PD diagnosis.

Results

Most assessed metals were not associated with PD risk. Cadmium has a suggestive negative association with PD (odds ratio [95% confidence interval] for the highest quartile, 0.70 [0.42–1.17]), which diminished among never smokers. Among current smokers only, lead was associated with decreased PD risk (0.06 [0.01–0.35]), whereas arsenic showed associations toward an increased PD risk (1.85 [0.45–7.93]).

Conclusions

We observe no strong evidence to support a role of metals in the development of PD. In particular, smoking may confound the association with tobacco‐derived metals. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
Threshold secret sharing with geometric algebras
Authors: Silva David , Harmon Luke , Delavignette Gaetan
Published: September 2023

In this work, we propose a geometric algebra‐based variation of a well‐known threshold secret‐sharing scheme introduced by Adi Shamir in 1979. Secret sharing is a cryptographic primitive which allows a secret input to be divided into multiple shares which are then sent to a collection of parties. The shares are generated so that only “authorized” sets of shares can reconstruct the secret. In Shamir's scheme, any sufficiently large set of shares can reconstruct the secret. The minimum number of shares which can obtain the secret is called the threshold, and any number of shares smaller than the threshold reveals nothing about the secret. The shares are generated such that each party can perform computations, generating a new set of shares that, when reconstructed, are equivalent to performing those exact computations directly on the secret input data. Our variant changes the domain from which secrets are taken: A finite field with prime order is replaced by a geometric algebra over a finite field of prime order. This change preserves the important security properties of Shamir's scheme, namely, idealness (secrets and shares are chosen from the same space) and perfectness (“unauthorized” sets of shares learn nothing about the secret). Our scheme allows secret sharing to be seamlessly added to the arsenal of GA‐based applications. Our extension of Shamir's secret scheme was first worked out for geometric algebras. It appears, however, that in fact it works for other algebras, a situation worthy to be explored in future work. For definiteness, in this paper, we restrict the analysis to the case of geometric algebras.
A spot‐specific range uncertainty framework for robust optimization of proton therapy treatments
Authors: Cohilis Marie , Souris Kevin , Buti Gregory , Chang Chih‐Wei , Lin Liyong , Lee John A. , Sterpin Edmond
Published: September 2023

Purpose

An accurate estimation of range uncertainties is essential to exploit the potential of proton therapy. According to Paganetti's study, a value of 2.4% (1.5 standard deviation) is currently recommended for planning robust treatments with Monte Carlo dose engines. This number is based on a dominant contribution from the mean excitation energy of tissues. However, it was recently shown that expressing tissues as a mixture of water and “dry” material in the CT calibration process allowed for a significant reduction of this uncertainty. We thus propose an adapted framework for pencil beam scanning robust optimization. First, we move towards a spot‐specific range uncertainty (SSRU) determination. Second, we use the water‐based formalism to reduce range uncertainties and, potentially, to spare better the organs at risk.

Methods

The stoichiometric calibration was adapted to provide a molecular decomposition (including water) of each voxel of the CT. The SSRU calculation was implemented in MCsquare, a fast Monte Carlo dose engine dedicated to proton therapy. For each spot, a ray‐tracing method was used to propagate molecular I‐values uncertainties and obtain the corresponding effective range uncertainty. These were then combined with other sources of range uncertainties, according to Paganetti's study of 2012. The method was then assessed on three head‐and‐neck patients. Two plans were optimized for each patient: the first one with the classical 2.4% flat range uncertainty (FRU), the second one with the variable range uncertainty. Both plans were then compared in terms of target coverage and OAR mean dose reduction. Robustness evaluations were also performed, using the SSRU for both plans in order to simulate errors as realistically as possible.

Results

For patient 1, it was found that the median SSRU was 1.04% (1.5 standard deviation), yielding, therefore, a very large reduction from the 2.4% FRU. All three SSRU plans were found to have a very good robustness level at a 90% confidence interval while sparing OAR better than the classical plan. For instance, in nominal cases, average reductions in the mean dose of 15.7, 8.4, and 13.2% were observed in the left parotid, right parotid, and pharyngeal constrictor muscle, respectively. As expected, the classical plans showed a higher but unnecessary level of robustness.

Conclusions

Promising results of the SSRU framework were observed on three head‐and‐neck cases, and more patients should now be considered. The method could also benefit to other tumor sites and, in the long run, the variable part of the range uncertainty could be generalized to other sources of uncertainty in order to move towards more and more patient‐specific treatments.
A demand‐responsive feeder service with a maximum headway at mandatory stops
Authors: Galarza Montenegro Bryan David , Sörensen Kenneth , Vansteenwegen Pieter
Published: September 2023

Public transportation out of suburban or rural areas is crucial. Feeder transportation services offer a solution by transporting passengers to areas where more options for public transport are available. On one hand, fully flexible demand‐responsive feeder services (DRFSs) efficiently tailor their service to the needs of the passengers. On the other hand, traditional feeder services provide predictability and easier cost control. In this article, a semi‐flexible DRFS is considered, which combines positive characteristics of both traditional services as well as fully flexible services. This feeder service has two types of bus stops: mandatory bus stops and optional bus stops. Mandatory bus stops are guaranteed to be visited by a bus within a certain time interval. Optional stops are only visited when there is demand for transportation nearby. The performance of this feeder service is optimized with the use of a new type of metaheuristic framework, which we denote as parameter space search. Experimental results on small benchmark instances indicate that the heuristic performs on average 12.42% better than LocalSolver, a commercial optimization solver, with an average runtime of 2.1 s. Larger instances can also be solved, typically within 2 min.
Preparation of polymer‐stabilized cholesteric liquid crystal films capable of broadband reflection using a three‐layer system of self‐diffusion
Authors: Liu Yutong , Zhang Xuetao , Cao Yue , Han Rui , Li Hui , Zhao Xiaohui , He Wanli , Yang Zhou , Wang Dong , Cao Hui , Wang Huihui , Zhou Hui
Published: September 2023

Through a simple and effective method for preparing broadband reflective liquid crystal films, the advantages of the three‐layer system are expanded based on the two‐layer system. The cholesteric liquid crystals form a prepolymerized layer after semi‐curing. In the design of the top prepolymerization layer, there is less content of the chiral compound R5011, which results in the formation of cholesteric liquid crystal molecules with a larger pitch. Mainly by controlling the content of polymerizable monomers and UV‐absorbing dyes in cholesteric liquid crystals (CLCs), a polymer network with density gradient distribution suitable for substance diffusion is formed, and the oleophobic substrate on one side of the low‐density polymer network is more likely to be peeled off. In the design of the lowest prepolymerization layer, the content of R5011 is higher, which results in the formation of cholesteric liquid crystals with a larger pitch. One side substrate of two cholesteric liquid crystal cassettes is peeled off and merged into a new liquid crystal cassette whose left and right sides are stacked with septum pads (20 μm), and the nematic liquid crystals are poured into the middle layer to form a three‐layer integrated film. The polymer network of the polymer‐stabilized cholesteric liquid crystals (PSCLCs) itself in the bilayer was used as a diffusion channel. Chiral compounds and UV‐absorbing dyes were diffused from the cholesteric liquid crystal layer to the intermediate nematic liquid crystal layer by diffusion gradient method, resulting in liquid crystal films with arbitrary wavelength bands and ultrawide broadband reflection.
Natural angiotensin converting enzyme inhibitors: A safeguard against hypertension, respiratory distress syndrome, and chronic kidney diseases
Authors: Khaled Aya , Ahmed Esraa , Mamdouh Mohamed , Saad Hager , Mohamed Aya , Sobhy Marina , Piatti Diletta , Sabry Miral , Saad Muhammed A. , Sabry Omar M. , Caprioli Giovanni
Published: September 2023

Hypertension is a serious concern as it is one of the causes of kideny failure and pulmonary fibrosis. An important therapeutic strategy for treating chronic hypertension is to inhibit the angiotensin converting enzyme (ACE). ACE inhibition reduces kidney damage, pulmonary artery pressure, and high blood pressure. Due to their high efficacy and low risk of side effects, natural renin‐angiotensin system inhibitors have drawn increasing attention over the past decades. Alkaloids, amino acids, anthocyanidins, flavonoids, glucosinolates, isoflavonoids, phenolic acids, polyphenolics, and triterpenoids are among the bioactive metabolites pocessing an impressive ACE inhibitory activity. Many herbs including Rosmarinus officinalis, Hibiscus sabdariffa, Curcuma longa, Rauwolfia serpentina, Emblica officinalis, Cynara scolymus, Punica granatum, Mucuna pruriens, Capsicum annuum, and Moringa olifera were found having ACE inhibitory activities comparable to captopril and enalpril. These enticing natural ACE inhibitors deserve to be a safeguard medicine against hypertension, respiratory distress syndrome, and chronic kidney diseases. More clinical trials are required before new natural compounds and herbs can be used to treat chronic hypertension and its ramifications, such as respiratory distress syndrome and kidney failure.
High‐performance liquid chromatography‐based assay optimization for the detection of plasma amino acids for applications in metabolic disorders in developing countries
Authors: Wasim Muhammad , Khan Haq Nawaz , Tawab Abdul , Habib Fazal e , Iqbal Mazhar , Awan Fazli Rabbi
Published: September 2023

Plasma amino acids are generally analyzed through ion exchange chromatography, a reproducible but time‐consuming method. Here, we report the optimization of a reverse‐phase‐high‐performance liquid chromatography with fluorescence detector (RP‐HPLC‐FLD) assay for the detection and quantification of plasma amino acids for potential applications in metabolic disorders (e.g., aminoacidopathies, a rare group of Inborn Errors of Metabolism). For assay development, initially standard amino acids were derivatized with ortho‐phthalaldehyde‐3‐mercaptopropionic acid (OPA‐3‐MPA) and filtered through a 0.20 μm syringe filter. The excitation and emission wavelengths of 240–450 nm (λex—λem) were used for the detection of amino acids. Chromatographic separation was achieved by gradient RP‐HPLC‐FLD through C18 symmetry column (150 × 4.6 mm, particle size 3.5 μm). HPLC assay was successfully optimized and was able to detect amino acids in the range of 10–400 ng/mL and good linearity (R2 > 0.98) was achieved in the mixture for each standard amino acid. Moreover, the current assay showed great efficiency with two additional advantages: the use of low‐cost mobile phases, and the detection and quantification of amino acids at low level (ng/mL) concentration in biofluids. This assay could be applied for the analysis of human plasma to identify aminoacidopathies in newborn screening programs, and other metabolic disorders.
On transforming model‐based tests into code: A systematic literature review
Authors: Ferrari Fabiano C. , Durelli Vinicius H. S. , Andler Sten F. , Offutt Jeff , Saadatmand Mehrdad , Müllner Nils
Published: September 2023

Model‐based test design is increasingly being applied in practice and studied in research. Model‐based testing (MBT) exploits abstract models of the software behaviour to generate abstract tests, which are then transformed into concrete tests ready to run on the code. Given that abstract tests are designed to cover models but are run on code (after transformation), the effectiveness of MBT is dependent on whether model coverage also ensures coverage of key functional code. In this article, we investigate how MBT approaches generate tests from model specifications and how the coverage of tests designed strictly based on the model translates to code coverage. We used snowballing to conduct a systematic literature review. We started with three primary studies, which we refer to as the initial seeds. At the end of our search iterations, we analysed 30 studies that helped answer our research questions. More specifically, this article characterizes how test sets generated at the model level are mapped and applied to the source code level, discusses how tests are generated from the model specifications, analyses how the test coverage of models relates to the test coverage of the code when the same test set is executed and identifies the technologies and software development tasks that are on focus in the selected studies. Finally, we identify common characteristics and limitations that impact the research and practice of MBT:(i) some studies did not fully describe how tools transform abstract tests into concrete tests,(ii) some studies overlooked the computational cost of model‐based approaches and (iii) some studies found evidence that bears out a robust correlation between decision coverage at the model level and branch coverage at the code level. We also noted that most primary studies omitted essential details about the experiments.
Role of PLC/IP3/IP3R axis in excess molybdenum exposure induced apoptosis in duck renal tubular epithelial cells
Authors: Guo Huiling , Zhang Caiying , Pu Wenjing , Chu Xuesheng , Huang Gang , Cui Ting , Huang Bingyan , Liu Hang , Dai Xueyan
Published: September 2023

Excess molybdenum (Mo) is harmful to animals, but its nephrotoxicity has not been comprehensively explained. To appraise the influences of excess Mo on Ca homeostasis and apoptosis via PLC/IP3/IP3R axis, primary duck renal tubular epithelial cells were exposed to 480 μM and 960 μM Mo, and joint of 960 μM Mo and 10 μM 2‐APB or 0.125 μM U‐73122 for 12 h (U‐73122 pretreated for 1 h), respectively. The data revealed that the increment of [Ca2+]c induced by Mo mainly originated from intracellular Ca storage. Mo exposure reduced [Ca2+]ER, elevated [Ca2+]mit, [Ca2+]c, and the expression of Ca homeostasis‐related factors (Calpain, CaN, CRT, GRP94, GRP78 and CaMKII). 2‐APB could effectively reverse subcellular Ca2+ redistribution by inhibiting IP3R, which confirmed that [Ca2+]c overload induced by Mo originated from ER. Additionally, PLC inhibitor U‐73122 remarkably mitigated the change, and dramatically reduced the number of apoptotic cells, the expression of Bak‐1, Bax, cleaved‐Caspase‐3/Caspase‐3, and notably increased the expression of Bcl‐xL, Bcl‐2, and Bcl‐2/Bax ratio. Overall, the results confirmed that the Ca2+ liberation of ER via PLC/IP3/IP3R axis was the main cause of [Ca2+]c overload, and then stimulated apoptosis in duck renal tubular epithelial cells.
Advanced wind turbine control development using field test analysis for generator overspeed mitigation
Authors: Phadnis Mandar , Zalkind Daniel , Pao Lucy
Published: September 2023

Turbulent and gusty wind conditions can cause generator overspeed peaks to exceed a threshold that then lead to wind turbine shutdowns, which then decrease the energy production of the wind turbines. We derive so‐called “gust measures” that predict when generator overspeed peaks may occur. These gust measures are then used to develop advanced controllers to mitigate generator overspeed peaks so that wind turbines can operate more robustly in difficult wind conditions without exceeding generator overspeed thresholds that would lead to turbine shutdown events. The advanced controllers are demonstrated in nonlinear aeroelastic simulations using the open‐source wind turbine simulation tool OpenFAST. To increase the realism of the simulations, they are run using field‐replicated wind conditions and a wind turbine model based on data from an experimental field campaign on a downscaled demonstrator of a novel extreme‐scale, two‐bladed, downwind rotor design.
Database Internals: Hardware and Operating System Interactions
Authors: Mendes Felipe Cardeneti , Sarna Piotr , Emelyanov Pavel , Dunlop Cynthia
Published: September 2023

A database’s internal architecture makes a tremendous impact on the latency it can achieve and the throughput it can handle. Being an extremely complex piece of software, a database doesn’t exist in a vacuum, but rather interacts with the environment, which includes the operating system and the hardware.
Processes and Structures for Agile Product Development
Authors: Schuh Günther , Tittel Jonas , Amft André , Apelt Sebastian , Bergs Thomas , Boßmann Carsten , Brecher Christian , Brettel Malte , Briele Kristof , Flemisch Frank , Jacobs Georg , Jagla Patrick , Jansen Nico , Kuhn Maximilian , Meißner Maximilian , Perau Stefan , Piller Frank , Preutenborbeck Michael , Rey Markus , Rumpe Bernhard , Schmitt Robert , Wiesch Marian
Published: September 2023

The work stream CRD-C.I of the Cluster of Excellence Internet of Production focuses on the topic of agile product development in order to enable reduced lead-times as well as exceeded customer and user satisfaction in product development. The main emphasis of the research lies on the associated processes and structures. In the course of the first 3 years of the Internet of Production, answers to relevant research questions of agile product development were developed within and between the research areas of market development, organization, data and engineering as well as production of prototypes. This chapter presents selected focus areas and insights from these research areas.
Introduction
Authors: Reibling Nadine
Published: September 2023

Why write a book on medicalization and psychologization in the welfare state? In this introduction, Reibling points out how the topical issue of research on medialization and psychologization can enter into a much-needed academic dialogue with research on the welfare state. This chapter provides multiple examples of the importance of medicine and psychology across various fields of the welfare state, including unemployment, poverty, homelessness, families, education, and social care. Furthermore, the chapter introduces its central country case—that of Germany—and highlights the fact that this book represents one of the first studies to investigate medicalization and psychologization in social policies in the context of a conservative welfare state.
Winding θ and destructive interference of instantons
Authors: Nguyen Mendel , Tanizaki Yuya , Ünsal Mithat
Published: September 2023

Abstract

While the θ dependence of field theories is 2π periodic, the ground-state wavefunctions at θ and θ + 2π often belong to different classes of symmetry-protected topological states. When this is the case, a continuous change of the θ parameter can introduce an interface that supports a nontrivial field theory localized on the wall. We consider the 2d ℂPN−1 sigma model as an example and construct a weak-coupling setup of this interface theory by considering the small S1 compactification with nonzero winding θ parameter and a suitable symmetry-twisted boundary condition. This system has N classical vacua connected by fractional instantons, but the anomaly constraint tells us that the fractional-instanton amplitudes should vanish completely to have N-fold degeneracy at the quantum level. We show how this happens in this purely bosonic system, uncovering that the integration over the zero modes annihilates the fractional instanton amplitudes, in sharp contrast to what happens when the θ angle is constant. Moreover, we provide another explanation of this selection rule by showing that the N perturbative vacua acquire different charges under the global symmetry with the activation of the winding θ angle. We also demonstrate a similar destructive interference between instanton effects in the ℂPN−1 quantum mechanics with the Berry phase.
Imprints of a supercooled phase transition in the gravitational wave spectrum from a cosmic string network
Authors: Ferrer Francesc , Ghoshal Anish , Lewicki Marek
Published: September 2023

Abstract

A network of cosmic strings (CS), if present, would continue emitting gravitational waves (GW) as it evolves throughout the history of the Universe. This results in a characteristic broad spectrum making it a perfect source to infer the expansion history. In particular, a short inflationary period caused by a supercooled phase transition would cause a drop in the spectrum at frequencies corresponding to that event. However, the impact on the spectrum is similar to the ones caused by an early matter-dominated era or from particle production, making it difficult to disentangle these different physical origins. We point out that, in the case of a short inflationary period, the GW spectrum receives an additional contribution from the phase transition itself. This leads to a characteristic imprint of a peak on top of a wide plateau both visible at future GW observatories.
Evidence for an accumulation of mineral oil saturated hydrocarbons (MOSH) in human tissues: a re-evaluation of biopsy and autopsy data
Authors: Pirow Ralph , Concin Nicole , Grob Koni
Published: September 2023

Consumers are exposed to mineral oil hydrocarbons (MOH) e.g. through foodstuffs and cosmetics. Upon ingestion, MOH follow the absorption pathway of dietary lipids. Analytical chemistry has revealed the presence of the main fraction, designated as mineral oil saturated hydrocarbons (MOSH), in mesenteric lymph nodes (MLNs), liver, spleen, and adipose tissue. Recent results from animal studies raised concerns about a long-term, possibly irreversible accumulation of some MOSH in humans. To address this issue, we performed a statistical re-analysis of published biopsy and autopsy data regarding the age-dependence of MOSH levels in human tissue. MOSH concentrations in MLNs and adipose tissue showed a 1.2–1.4-fold increase per decade, pointing to very long-term accumulation in both tissues. There was no evidence for age-dependent MOSH concentrations in liver and spleen. There was no sex difference in the MOSH concentrations in MLNs, suggesting a similar oral exposure for men and women. On average, women had a 2.2–2.5-fold higher MOSH concentration in the liver, spleen and adipose tissue compared to men. This finding may point to a sex difference in metabolism, in line with animal data. The use of certain cosmetics was a relevant predictor in addition to age. Women that used cosmetics like lipstick, hand cream, and sun cream had an average 2.1-fold higher MOSH concentration in abdominal subcutaneous fat than non-users.
The working life expectancy of American adults experiencing depression
Authors: Dobson Kathleen G. , Gignac Monique A. M. , Mustard Cameron A.
Published: September 2023

Objectives

To estimate the working life expectancies (WLE) of men and women with depression, examining depression by symptom trajectories from the late 20s to early 50s, and to estimate WLE by race/ethnicity and educational attainment.

Methods

Data from 9206 participants collected from 1979 to 2018 in the US National Longitudinal Survey of Youth 1979 cohort were used. Depression was measured using theCenter for Epidemiologic Studies Depression Scale Short Format four time points (age 28–35, age 30–37, age 40, and age 50). Labor force status was measured monthly starting at age 30 until age 58–62. Depressive symptom trajectories were estimated using growth mixture modeling and multistate modeling estimated WLE from age 30–60 for each gender and depressive symptom trajectory.

Results

Five latent symptom trajectories were established: a persistent low symptom trajectory (n = 6838), an episodic trajectory with high symptoms occurring before age 40 (n = 995), an episodic trajectory with high symptoms occurring around age 40 (n = 526), a trajectory with high symptoms occurring around age 50 (n = 570), and a persistent high symptom trajectory (n = 277). The WLE for men at age 30 was 30.3 years for the persistent low symptom trajectory, 22.8 years for the episodic before 40 trajectory, 19.6 years for the episodic around age 40 trajectory, 18.6 years for the episodic around age 50 trajectory, and 13.2 years for the persistent high symptom trajectory. Results were similar for women. WLE disparities between depression trajectories grew when stratified by race/ethnicity and education level.

Conclusions

Roughly a quarter of individuals experienced episodic depressive symptoms. However, despite periods of low depressive symptoms, individuals were expected to be employed ~5–17 years less at age 30 compared to those with low symptoms. Accessible employment and mental health disability support policies and programs across the working life course may be effective in maintaining work attachment and improving WLE among those who experience depression.