bluuebunny/crossref_metadata_2025 huggingface dataset:
Spinal Muscular Atrophy: A Rare but Treatable Disease of the Nervous System
Authors: Sleigh James N. , Christie-Brown Vanessa , Ryburn Liz , Yáñez-Muñoz Rafael J.
Published: August 2023

When something is rare it means that it happens very infrequently. Did you know that most diseases are rare? There are more than 6,000 known rare diseases, each affecting fewer than 1 in every 2,000 people. But if we put all the rare diseases together, they affect about 1 in 17 of us! Given that they are individually uncommon, rare diseases are often poorly understood. However, rare diseases have a large impact on families and society, thus they require increased attention. In this article, we will explore a rare disease of the nervous system called spinal muscular atrophy (SMA). We will tell you about the symptoms of SMA and explain how it is inherited. SMA has led the way in the discovery of treatments for rare diseases. Finding treatments for rare diseases requires intensive research and commitment from many people, but the success of SMA treatments highlights the importance of studying other rare conditions.
Tacrolimus Exposure Before and After a Switch From Twice-Daily Immediate-Release to Once-Daily Prolonged Release Tacrolimus: The ENVARSWITCH Study
Authors: Monchaud Caroline , Woillard Jean-Baptiste , Crépin Sabrina , Tafzi Naïma , Micallef Ludovic , Rerolle Jean-Philippe , Dharancy Sébastien , Conti Filomena , Choukroun Gabriel , Thierry Antoine , Buchler Matthias , Salamé Ephrem , Garrouste Cyril , Duvoux Christophe , Colosio Charlotte , Merville Pierre , Anglicheau Dany , Etienne Isabelle , Saliba Faouzi , Mariat Christophe , Debette-Gratien Marilyne , Marquet Pierre
Published: August 2023

LCP-tacrolimus displays enhanced oral bioavailability compared to immediate-release (IR-) tacrolimus. The ENVARSWITCH study aimed to compare tacrolimus AUC0–24 h in stable kidney (KTR) and liver transplant recipients (LTR) on IR-tacrolimus converted to LCP-tacrolimus, in order to re-evaluate the 1:0.7 dose ratio recommended in the context of a switch and the efficiency of the subsequent dose adjustment. Tacrolimus AUC0–24 h was obtained by Bayesian estimation based on three concentrations measured in dried blood spots before (V2), after the switch (V3), and after LCP-tacrolimus dose adjustment intended to reach the pre-switch AUC0–24 h (V4). AUC0–24 h estimates and distributions were compared using the bioequivalence rule for narrow therapeutic range drugs (Westlake 90% CI within 0.90–1.11). Fifty-three KTR and 48 LTR completed the study with no major deviation. AUC0–24 h bioequivalence was met in the entire population and in KTR between V2 and V4 and between V2 and V3. In LTR, the Westlake 90% CI was close to the acceptance limits between V2 and V4 (90% CI = [0.96–1.14]) and between V2 and V3 (90% CI = [0.96–1.15]). The 1:0.7 dose ratio is convenient for KTR but may be adjusted individually for LTR. The combination of DBS and Bayesian estimation for tacrolimus dose adjustment may help with reaching appropriate exposure to tacrolimus rapidly after a switch.
YOLO-Based Model for Automatic Detection of Broiler Pathological Phenomena through Visual and Thermal Images in Intensive Poultry Houses
Authors: Elmessery Wael M. , Gutiérrez Joaquín , Abd El-Wahhab Gomaa G. , Elkhaiat Ibrahim A. , El-Soaly Ibrahim S. , Alhag Sadeq K. , Al-Shuraym Laila A. , Akela Mohamed A. , Moghanm Farahat S. , Abdelshafie Mohamed F.
Published: August 2023

The increasing broiler demand due to overpopulation and meat imports presents challenges in poultry farming, including management, disease control, and chicken observation in varying light conditions. To address these issues, the development of AI-based management processes is crucial, especially considering the need for detecting pathological phenomena in intensive rearing. In this study, a dataset consisting of visual and thermal images was created to capture pathological phenomena in broilers. The dataset contains 10,000 images with 50,000 annotations labeled as lethargic chickens, slipped tendons, diseased eyes, stressed (beaks open), pendulous crop, and healthy broiler. Three versions of the YOLO-based algorithm (v8, v7, and v5) were assessed, utilizing augmented thermal and visual image datasets with various augmentation methods. The aim was to develop thermal- and visual-based models for detecting broilers in complex environments, and secondarily, to classify pathological phenomena under challenging lighting conditions. After training on acknowledged pathological phenomena, the thermal YOLOv8-based model demonstrated exceptional performance, achieving the highest accuracy in object detection (mAP50 of 0.988) and classification (F1 score of 0.972). This outstanding performance makes it a reliable tool for both broiler detection and pathological phenomena classification, attributed to the use of comprehensive datasets during training and development, enabling accurate and efficient detection even in complex environmental conditions. By employing both visual- and thermal-based models for monitoring, farmers can obtain results from both thermal and visual viewpoints, ultimately enhancing the overall reliability of the monitoring process.
Development of a Lactic Bacteria Starter for Amaranth Silage and Investigation of Its Influence on Silage Quality
Authors: Anokhina Ekaterina , Obraztsova Svetlana , Tolkacheva Anna , Cherenkov Dmitrii , Sviridova Tatyana , Korneeva Olga
Published: August 2023

The use of amaranth green mass as an alternative source of protein and fiber for canned feed for ruminants is very promising because of several reasons, including a high concentration of crude protein and dry matter digestibility, lower water requirement compared to corn, and a high yield. The purpose of this work is to develop a silage starter from lactic acid bacteria and study its effect on the quality of fermentation and the chemical composition of the silage. The selection of strains of lactic acid bacteria in the composition of the starter was carried out, taking into account their antibacterial activity against opportunistic microorganisms Staphylococcus aureus and Escherichia coli. Amaranth was treated with the developed silage starter (MPF) before ensiling. The study of the composition of the microflora and the acidity of the silage was carried out periodically during the amaranth ensiling process and after 45 days of storage. The use of MPF starter provided a rapid decrease in pH and, on the 10th day, reached a value of 4.2. Silage with the use of MPF starter was characterized by the largest amount of lactic acid—75.1%, the lowest content of acetic acid—24.9%, and the absence of butyric acid. The use of the MPF starter compared to other treatments resulted in the retention of crude protein up to 90%, which improved the quality of amaranth silage. Amaranth silage, in comparison with corn silage traditionally used in fodder production, was characterized by an increased content of all essential amino acids; in terms of lysine content, it exceeded corn silage 2.5 times. Based on the data obtained, it can be concluded that the developed silage starter can significantly improve the quality of amaranth silage.
The Impact of Pediatric Neutering in Dogs and Cats—A Retrospective Study
Authors: Oliveira-Martins Mariana , Portugal Mariana , Cardoso Luís , Martins-Bessa Ana
Published: August 2023

Surgical sterilization is a common procedure in veterinary practice; yet, the age at which to perform said procedure is still a controversial topic since the common practice of performing this surgery at the “conventional” age of 6 months is not supported by concrete scientific data. Therefore, it leaves space for veterinary professionals to opt for pediatric neutering, especially in the context of shelter medicine, since it allows the adoption of younger animals and is an important tool used to combat the overpopulation of stray animals by preventing their reproduction, even though some of the studies regarding the long-term effects of this approach seem to have contradictory results. Consequently, the present study aims to evaluate the impact of pediatric neutering on the occurrence of obesity, behavioral changes and urinary and joint diseases by posing an inquiry by means of telephone questionnaire to 105 owners of cats and dogs neutered and adopted from Coimbra Municipal Animal Shelter. The analysis of the gathered data did not show any statistically significant relationship between age of neutering and the presence of any of the aforementioned conditions in the animals under study.
Prevalence of Toxoplasma gondii in Endangered Wild Felines (Felis silvestris and Lynx pardinus) in Spain
Authors: Matas Méndez Pablo , Fuentes Corripio Isabel , Montoya Matute Ana , Bailo Barroso Begoña , Grande Gómez Rebeca , Apruzzese Rubio Ariadna , Ponce Gordo Francisco , Mateo Barrientos Marta
Published: August 2023

The wildcat (Felis silvestris) and the Iberian lynx (Lynx pardinus) are important species in Spain, considered as near-threatened and endangered, respectively. Both can be infected by Toxoplasma gondii, a parasite that can cause morbidity and mortality in transplacentally-infected or immunocompromised mammals. The data on the prevalence of this parasite in wild populations of these species in Spain are outdated. The objective of this study was to update information and evaluate the role of these felines in parasite epidemiology and the potential impact of the parasite on their conservation. Blood and fecal samples were collected from captured animals, as well as the tongue, diaphragm, and spleen, from animals killed in road accidents in central Spain. An indirect fluorescent antibody test (IFAT) was used to detect parasite antibodies in serum, microscopy and molecular analysis were used to detect oocysts in feces, and molecular analysis was used to determine the existence of tissue cysts. Seroprevalence was 85% in wildcats and 45% in lynx, and parasite DNA was detected in the feces of one wildcat and in tissue samples from 10 wildcats and 11 Iberian lynxes. These results highlight the epidemiological importance and high risk of T. gondii infection in animals and humans in the studied areas. Considering feline susceptibility to infection, monitoring programs are needed to assess the health status of wild felines.
Exogenous CFH Modulates Levels of Pro-Inflammatory Mediators to Prevent Oxidative Damage of Retinal Pigment Epithelial Cells with the At-Risk CFH Y402H Variant
Authors: Velazquez-Soto Henry , Groman-Lupa Sergio , Cruz-Aguilar Marisa , Salazar Alberto L. , Zenteno Juan C. , Jimenez-Martinez Maria C.
Published: August 2023

Age-related macular degeneration (AMD) is a complex, progressive degenerative retinal disease. Retinal pigment epithelial (RPE) cells play an important role in the immune defense of the eye and their dysfunction leads to the progressive irreversible degeneration of photoreceptors. Genetic factors, chronic inflammation, and oxidative stress have been implicated in AMD pathogenesis. Oxidative stress causes RPE injury, resulting in a chronic inflammatory response and cell death. The Y402H polymorphism in the complement factor H (CFH) protein is an important risk factor for AMD. However, the functional significance of CFH Y402H polymorphism remains unclear. In the present study, we investigated the role of CFH in the pro-inflammatory response using an in vitro model of oxidative stress in the RPE with the at-risk CFH Y402H variant. ARPE-19 cells with the at-risk CFH Y402H variant were highly susceptible to damage caused by oxidative stress, with increased levels of inflammatory mediators and pro-apoptotic factors that lead to cell death. Pretreatment of the ARPE-19 cell cultures with exogenous CFH prior to the induction of oxidative stress prevented damage and cell death. This protective effect may be related to the negative regulation of pro-inflammatory cytokines. CFH contributes to cell homeostasis and is required to modulate the pro-inflammatory cytokine response under oxidative stress in the ARPE-19 cells with the at-risk CFH Y402H variant.
Wave-Current Loads on a Super-Large-Diameter Pile in Deep Water: An Experimental Study
Authors: Hong Chenkai , Lyu Zhongda , Wang Fei , Zhao Zhuo , Wang Lei
Published: August 2023

Recently, the diameters and construction water depths of the pile foundations of planned and newly built sea-crossing bridges have been increasing greatly. Hydrodynamic loads are the key control factors in the design of super-large-diameter piles. However, most of the previous studies focused on the inline force on the pile with a small diameter, and there were few cases to consider the impact of the transverse force on the hydrodynamic load of the pile under wave-current actions. In this study, to understand the hydrodynamic loads on such deep-water super-large-diameter piles, the prototype was one of the 6.3-m piles used in the Xihoumen Rail-cum-Road Bridge, and 1:60-scale model tests were carried out in an experimental tank, with the actions of regular waves and waves combined with currents used as loads. The influence of the current velocity and static wave height on the inline and transverse forces on the pile was measured and analyzed. The experimental results indicate that with increasing current velocity, the fluctuation characteristics of the wave-current-induced inline and transverse forces change significantly, and their peak values increase obviously compared to those induced by only waves. In particular, the peak transverse force increases tens of times and can become equivalent to the inline force. The modified Morison formula and Kutta–Joukowski formula are used to derive the correlations between the drag coefficient CD, inertia coefficient CM, lift coefficient CL, and redefined Keulegan–Carpenter number KC*. Under wave-current action, the transverse force contributes quite significantly to the hydrodynamic load on a super-large-diameter pile, making it easier to trigger extreme structural loads. The results presented herein are an important reference for the engineering designs of such super-large-diameter piles.
Geochemical Characteristics of Elements and Main Controlling Factors of Organic Matter Enrichment in Shale from Wufeng Formation to Submember Long-11 in Southern Sichuan
Authors: Xiong Rong , Zhong Quan , Ren Zhenxing
Published: August 2023

A total of 70 shale samples from seven core holes, namely, N203, N208, N209, N210, N211, N215 and N217, in Changning area, south Sichuan, were analyzed for major and trace elements. Based on an analysis of longitudinal variation characteristics of major and trace elements, the REDOX conditions, paleoproductivity, relative sea level height and terrigenous detrital injection amount of gas-bearing shale in Wufeng Formation–Submember Long-11 in the Changning area were studied. And, the main controlling factors of organic matter enrichment in Wufeng Formation–Submember Long-11 were discussed. The results show the following: (1) Trace elements Mo, U, Ba and Ni are relatively enriched in the shale of Wufeng Formation–Submember Long-11 in the Changning area, while the Co element is deficient. The flat distribution pattern of rare earth in Wufeng Formation–Submember Long-11 shows that the shale deposits are weakly influenced by terrigenous materials. The amount of terrigenous injection in Wufeng Formation is higher than that in Submember Long-11, and the amount of terrigenous injection increased gradually from the lower part of Bed Long-111 to the lower part of Bed Long-114. (2) The REDOX environment discrimination indexes such as U/Th, Ni/Co, V/Sc and δU show that the water REDOX conditions of Wufeng Formation–Submember Long-11 in the Changning area have changed many times during the shale sedimentary period, and the overall REDOX conditions are dominated by an anaerobic environment. The REDOX indexes at the boundary between Long-111 and Wufeng Formation are relatively small and in the oxidizing environment range. The REDOX index from Bed Long-111 to Bed Long-114 decreases gradually, and the anaerobic environment of Bed Long-111 and Bed Long-112 gradually changes to the oxygen-poor environment of Bed Long-113; and, the REDOX index of Bed Long-114 is the lowest, which is generally oxygen rich. (3) Organic matter enrichment in Wufeng Formation Submember Long11 in the Changning area is mainly controlled by REDOX conditions. Low terrigenous injection and a relatively high sea level have positive effects on organic matter enrichment, but there is no obvious relationship between the paleoproductivity and organic matter enrichment.
Temporal and Spatial Evolution Laws of Freezing Temperature Field in the Inclined Shaft of Water-Rich Sand Layers
Authors: Zhang Jie , Wang Bin , Rong Chuanxin , Long Wei , Yu Shengmin
Published: August 2023

This study investigated the distribution and evolution characteristics of the temperature field during the freezing and excavation of inclined shafts, with the freezing open-excavation section of Shengfu Mine’s main inclined shaft (located in Shaanxi Province) as the project background. Utilizing field-measured data and the finite element software COMSOL Multiphysics, a 3D freezing temperature-field numerical calculation model was constructed to examine the temporal and spatial evolutions of the temperature field during the construction of the inclined shaft. The findings showed that after 88 days of freezing, the average temperature of the frozen wall in the open-excavation section was below −12 °C. The frozen wall thickness in the sidewalls of different layers exceeded 4 m, and the thickness at the bottom plate exceeded 5 m, meeting the excavation design requirements. For the same freezing time, the average temperature of the frozen wall in the fine sand layer was 0.28 to 2.39 °C lower than that of the frozen wall in the medium sand layer, and its effective thickness was 0.36 to 0.59 m greater than that in the medium sand layer. When the soil was excavated, and the well side was exposed, a phenomenon known as “heat flow erosion” occurred in the soil at the well-side position, causing the well-side temperature to rise. Nevertheless, this increase was generally limited, and when continuous cooling was applied, the well side could maintain a very low negative temperature level. Consequently, there was no spalling phenomenon. The effective thickness of the frozen wall during excavation did not decrease, with the average temperature remaining below −10 °C. Consequently, there was no large-scale “softening” of the frozen wall during excavation, thus ensuring construction safety. The numerical calculation model in this paper can be used to predict the development law of the freezing temperature field of the water–rich sandy layers in Shengfu Mine and adjust the on–site cooling plan in real time according to the construction progress. This research provides valuable theoretical insights for the optimal design and safe construction of freezing inclined-shaft sinking projects.
Photobiomodulation as a Therapeutic Strategy in Burning Mouth Syndrome: A Scoping Review
Authors: Spadari Francesco , Pulicari Federica , Ghizzoni Martina , Porrini Massimo , Bosotti Moreno , Pellegrini Matteo
Published: August 2023

Burning mouth syndrome (BMS) is considered an atypical oral clinical-symptomatological condition because its etiopathogenesis is not yet fully clarified. It is mainly characterized by the symptom of burning, which occurs chronically and with various intensities. It is essential for making a diagnosis of BMS, clinical negativities, and instrumental investigations. It mainly affects the female sex, in the pre-post-climactic phases. A peripheral neuropathic matrix of the pain symptoms has been repeatedly demonstrated. However, this subjectivity is associated with personalities with anxiety-depressive traits, affective-behavioral difficulties, and disorders of the psycho-algogenic sphere. Numerous treatments are reported in the literature, which have rarely met lasting healing parameters. In this clinical landscape, photobiomodulation therapy (PBMT) can be considered a possible therapeutic alternative. Our study aims to present a scoping review of how photobiomodulation is used in BMS therapy and to analyze the outcome of the therapy. A literature review focused on the photobiomodulation treatment for burning mouth syndrome was conducted in the main scientific databases: PubMed, SCOPUS, and Web of Science. The results of our research highlight encouraging results regarding photobiomodulation, as in all studies, there is a reduction in symptoms.
Combination of Pioglitazone and Metformin Actions on Liver Lipid Metabolism in Obese Mice
Authors: Liu Jieying , Wang Dongmei , Xie Ziyan , Ding Lu , Li Shunhua , Ma Xuemei , Liu Jing , Ren Jing , Xiao Cheng , Yang Chunru , Xiao Xinhua
Published: August 2023

Background: Despite the increasing prevalence rate of nonalcoholic fatty liver disease (NAFLD) worldwide, efficient pharmacotherapeutic regimens against NAFLD still need to be explored. Previous studies found that pioglitazone and metformin therapy could partly ameliorate NAFLD, but their combination therapy effects have not been researched. In the present study, we assessed the protective effects of metformin and pioglitazone combination therapy on liver lipid metabolism in high-fat diet (HFD)-fed mice and investigated the molecular mechanism. Methods: Male C57BL/6 mice were divided into five groups: normal control; HFD control; metformin monotherapy; pioglitazone monotherapy and combined therapy. After 8 weeks of pharmacological intervention, glucose and lipid metabolism characteristics, hepatic histology, lipidomics profiling and RNA-seq analysis were performed. Results: The combination of pioglitazone and metformin significantly ameliorated HFD-induced metabolic disturbance and the hepatic oil red O area. A lipidomics analysis showed that combined therapy could significantly reduce the high levels of free fatty acids (FFA), diacylglycerol and triglycerides, while a set of glycerophospholipids and sphingolipids were increased in the combined therapy group. Consistently, an RNA-seq analysis also showed a remarkable reduction in genes associated with FFA uptake and de novo lipogenesis, including Cd36, Fads1, Fads2, Fasn, Scd1, Elovl5 and Pklr in the combined therapy group. Conclusions: Pioglitazone and metformin might have a synergistic protective effect on NAFLD by improving hepatic lipid profiles in HFD-induced mice. Further studies are needed to verify the clinical effects.
Fatty Acid-Activated Proton Transport by Bisaryl Anion Transporters Depolarises Mitochondria and Reduces the Viability of MDA-MB-231 Breast Cancer Cells
Authors: York Edward , McNaughton Daniel A. , Duman Meryem-Nur , Gale Philip A. , Rawling Tristan
Published: August 2023

In respiring mitochondria, the proton gradient across the inner mitochondrial membrane is used to drive ATP production. Mitochondrial uncouplers, which are typically weak acid protonophores, can disrupt this process to induce mitochondrial dysfunction and apoptosis in cancer cells. We have shown that bisaryl urea-based anion transporters can also mediate mitochondrial uncoupling through a novel fatty acid-activated proton transport mechanism, where the bisaryl urea promotes the transbilayer movement of deprotonated fatty acids and proton transport. In this paper, we investigated the impact of replacing the urea group with squaramide, amide and diurea anion binding motifs. Bisaryl squaramides were found to depolarise mitochondria and reduce MDA-MB-231 breast cancer cell viability to similar extents as their urea counterpart. Bisaryl amides and diureas were less active and required higher concentrations to produce these effects. For all scaffolds, the substitution of the bisaryl rings with lipophilic electron-withdrawing groups was required for activity. An investigation of the proton transport mechanism in vesicles showed that active compounds participate in fatty acid-activated proton transport, except for a squaramide analogue, which was sufficiently acidic to act as a classical protonophore and transport protons in the absence of free fatty acids.
Challenges and Opportunities in Developing Targeted Therapies for Triple Negative Breast Cancer
Authors: Chapdelaine Abygail G. , Sun Gongqin
Published: August 2023

Triple negative breast cancer (TNBC) is a heterogeneous group of breast cancers characterized by their lack of estrogen receptors, progesterone receptors, and the HER2 receptor. They are more aggressive than other breast cancer subtypes, with a higher mean tumor size, higher tumor grade, the worst five-year overall survival, and the highest rates of recurrence and metastasis. Developing targeted therapies for TNBC has been a major challenge due to its heterogeneity, and its treatment still largely relies on surgery, radiation therapy, and chemotherapy. In this review article, we review the efforts in developing targeted therapies for TNBC, discuss insights gained from these efforts, and highlight potential opportunities going forward. Accumulating evidence supports TNBCs as multi-driver cancers, in which multiple oncogenic drivers promote cell proliferation and survival. In such multi-driver cancers, targeted therapies would require drug combinations that simultaneously block multiple oncogenic drivers. A strategy designed to generate mechanism-based combination targeted therapies for TNBC is discussed.
Quantification of Non-Motor Symptoms in Parkinsonian Cynomolgus Monkeys
Authors: Bao Yu , Gan Chaoning , Chen Zuyue , Qi Zhongquan , Meng Zhiqiang , Yue Feng
Published: August 2023

Background: Parkinson’s disease (PD) is a neurodegenerative disorder that features motor and non-motor deficits. The use of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopamine neuron degeneration has been widely practiced to produce reliable animal models of PD. However, most previous preclinical studies focused on motor dysfunction, and few non-motor symptoms were evaluated. Thus far, there is a lack of comprehensive investigations of the non-motor symptoms in animal models. Objectives: In this study, we aim to use a battery of behavioral methods to evaluate non-motor symptoms in MPTP-induced non-human primate PD models. Methods: Cognitive function, sleep, and psychiatric behaviors were evaluated in MPTP-treated cynomolgus monkeys. The tests consisted of a delayed matching-to-sample (DMTS) task, the use of a physical activity monitor (PAM), an apathy feeding task (AFT), the human intruder test (HIT), novel fruit test (NFT), and predator confrontation test (PCT). In addition, we tested whether the dopamine receptor agonist pramipexole (PPX) can improve these non-motor symptoms. Results: The present results show that the MPTP-treated monkeys exhibited cognitive deficits, abnormal sleep, and anxiety-like behaviors when compared to the control monkeys. These symptoms were relieved partially by PPX. Conclusions: These results suggest that MPTP-induced PD monkeys displayed non-motor symptoms that were similar to those found in PD patients. PPX treatment showed moderate therapeutic effects on these non-motor symptoms. This battery of behavioral tests may provide a valuable model for future preclinical research.
Network Analysis of Anxiety Symptoms in Front-Line Medical Staff during the COVID-19 Pandemic
Authors: Wu Lin , Ren Lei , Li Fengzhan , Shi Kang , Fang Peng , Wang Xiuchao , Feng Tingwei , Wu Shengjun , Liu Xufeng
Published: August 2023

Background: This research analyses the relations between anxiety symptoms from the network perspective to deepen the understanding of anxiety in front-line medical staff during the COVID-19 pandemic and can also provide a reference for determining potential goals of clinical interventions. Methods: A convenience sampling was adopted, and the Generalized Anxiety Disorder 7-item scale (GAD-7) was administered to front-line medical staff through online platforms. A regularized partial correlation network of anxiety was constructed and then we evaluated its accuracy and stability. The expected influence and predictability were used to describe the relative importance and the controllability, using community detection to explore community structure. The gender-based differences and the directed acyclic graph were implemented. Results: The connections between A1 “Feeling nervous, anxious or on edge” and A2 “Not being able to stop or control worrying”, A6 “Becoming easily annoyed or irritable” and A7 “Feeling afraid as if something awful might happen”, etc., were relatively strong; A2 “Not being able to stop or control worrying” and A3 “Worrying too much about different things” had the highest expected influence, and A2 “Not being able to stop or control worrying” had the highest predictability. The community detection identified two communities. The results of the gender network comparison showed the overall intensity of the anxiety network in women was higher than that in men; DAG indicated that A2 “Not being able to stop or control worrying” had the highest probabilistic priority; the lines from A2 “Not being able to stop or control worrying” to A1 “Feeling nervous, anxious or on edge” and A2 “Not being able to stop or control worrying” to A7 “Feeling afraid as if something awful might happen” represented the most important arrows. Conclusion: There exist broad interconnections among anxiety symptoms of front-line medical staff on the GAD-7. A2 “Not being able to stop or control worrying” might be the core symptom and a potential effective intervention target. It was possible to bring an optimal result for the entire GAD symptom network by interfering with A2 “Not being able to stop or control worrying”. GAD may have two “subsystems”. The modes of interconnection among anxiety may be consistent between genders.
How China’s Great Bay Area Policies Affect the National Identity of Hong Kong Youth—A Study of a Quasi-Natural Experiment Based on the Difference-in-Differences Model
Authors: Fu Chengzhe , Liao Liao , Mo Tingyang , Chen Xiaoqing
Published: August 2023

China’s Bay Area policies are important for integrating Hong Kong (HK) and Macao youth into China’s overall development. However, their effect on national identity is still mostly theoretical, lacking objective and scientific empirical evaluations. From a cultural adaptation perspective, interactions between social groups with different cultural backgrounds can promote cultural and political identity transformation. Therefore, guided by China’s Bay Area policies, which encourage various cross-border exchanges via economic cooperation, HK youth can keep in touch with such Mainland Chinese cultural values as “responsible government”, facilitating “political socialization”, and political–cultural adaptation, helping to promote their psychological inclusion into society, contributing to a positive attitude towards the mainland government, and achieving the policy effect of building national identity. A quasi-natural experiment based on the regional differences in the first stages of China’s Bay Area policies can help to evaluate their effects on HK youth’s national identity. This study defines the initial stage of the Bay Area policy implementation as from 2016, when the 13th Five-Year Plan advocated building the “Great Bay Area of Guangdong, Hong Kong and Macao”, to 2019, when the Outline was published. The policies issued at this stage were the so-called “early policies”. Due to data limitations, it is difficult to obtain post-2019 survey data; therefore, the study mainly focuses on the policy effects at the beginning of the Bay Area’s construction. Four groups of cross-sectional data from the World Value Survey 6 (WVS6) (2010–2014) and World Value Survey 7 (WVS7) (2017–2020), with HK and the mainland (the non-Guangdong region) included, are used to examine the policy effect under the Difference-in-Differences (DID) Model. The research shows that the policies significantly enhanced HK youth’s national identity, and their trust in the mainland government played an intermediary role in the policy effect mechanism. However, the effect was uneven, benefiting the national identities of HK youth working in the for-profit private sector more than their unemployed or public sector peers. Therefore, this research proposes several policy implications to facilitate policy decision making related to youth in China’s Bay Area.
Mapping the Barriers of Big Data Process in Construction: The Perspective of Construction Professionals
Authors: Atuahene Bernard Tuffour , Kanjanabootra Sittimont , Gajendran Thayaparan
Published: August 2023

This study identifies, maps and thematizes the barriers to the big data process in the construction industry from the perspective of construction professionals. Australian construction professionals with varying experiences in the big data process were interviewed. Qualitative data analysis identified forty barriers in the big data process and five themes: people, knowledge, technology, data, and environment. The barriers were further mapped, with some transcending more than one stage in the big data process. Many of the barriers have not been empirically identified in previous studies. By implication, mapping the barriers across the big data process enables professionals/construction firms to visualize the potential lapses before and/or during implementation. Therefore, the study offers professionals/construction firms strategic insights and operational perspectives for planning and deploying big data processes.
Determining the Factors Influencing Construction Project Management Performance Improvement through Earned Value-Based Value Engineering Strategy: A Delphi-Based Survey
Authors: Nejatyan Esmaeil , Sarvari Hadi , Hosseini Seyed Abbas , Javanshir Hassan
Published: August 2023

Proper planning and management of construction projects have long been regarded as a necessity. The ability to make sound decisions and solve problems using appropriate performance reports related to the project implementation process are the two most key factors in controlling the performance of construction project management. Even though these factors considerably contribute to controlling precise project performance, previous research has failed to investigate them to their fullest potential. Therefore, this research seeks to fill the existing gap by determining the influential factors on construction project management performance through earned value-based value engineering strategy. In this line, a comprehensive literature analysis was undertaken to extract the influential factors on construction project management performance. Then, three rounds of a Delphi survey were conducted to consolidate the influential factors. There were a total of 39 factors that were grouped into four categories. The identified influential factors were then evaluated through the analysis of quantitative data. The findings showed that the dimension of “Engineering economics” was ranked first in terms of importance, followed by “Project management performance”, “Value engineering approach”, and “Earned value management” at the second to fourth ranks, respectively. The overall ranking of the factors placed “Project Stakeholder Management” in the first position and “Project Management Software” in the bottom place. It is anticipated that the key findings and effective recommendations of this study will considerably contribute to the improvement of decisions on project planning and improve the performance of construction project management while enhancing different stakeholders’ understanding of the most influential factors on the performance of construction project management.
Theoretical and Numerical Studies of Elastic Buckling and Load Resistance of a Shuttle-Shaped Double-Restrained Buckling-Restrained Brace
Authors: Shi Jun , Jin Shuangshuang , Xu Lueqin , Liu Yangqing , Zhang Ruijie
Published: August 2023

A new type of shuttle-shaped double-restrained buckling-restrained brace (SDR-BRB) is proposed, which adopts the form of a shuttle-shaped deformation section similar to its bending moment distribution as the external restraining system. The SDR-BRB has the advantages of superlong size, high load-carrying capacity, and lightweight components, and is suitable for use in large-span spatial structures and bridge structures with an exposed BRB. First, the calculation formula of the elastic buckling load of a pin-ended SDR-BRB is derived based on the equilibrium method, which is verified through the eigenvalue buckling analysis method, and the effects of the main geometric parameters on its elastic buckling behavior are evaluated. The effects of multiple key factors on the load-carrying capacity of the SDR-BRB are then studied by parametric analysis. The results show that the restraining ratio, initial imperfection, and gap have significant effects on the ultimate load-carrying capacity and overall stability of the SDR-BRB, while the effect of the diameter–thickness ratio is relatively small. On this basis, the fitting formula of the critical restraining ratio of the SDR-BRB considering the influences of initial imperfection and gap is proposed and verified by finite element analysis. The research lays a foundation for further research into the elastic–plastic hysteretic behavior and design method of an SDR-BRB.
Utilisation of Ceramic Stoneware Tile Waste as Recycled Aggregate in Concrete
Authors: Roig-Flores Marta , Reig Lucía , Albero Vicente , Hernández-Figueirido David , Melchor-Eixea Antonio , Pitarch Ángel M. , Piquer Ana
Published: August 2023

The construction industry has a significant environmental impact and concrete production is responsible for a large part of CO2 emissions and energy consumption. This study focused on the reutilisation of a specific type of tiles ceramic waste (TCW), composed only of stoneware and porcelain stoneware tiles, hereafter referred to as ceramic stoneware (CS), as recycled aggregate in concrete. Natural limestone and CS aggregates (sand and gravel) were characterised (particle size distribution, water absorption, resistance to wear, density and X-ray diffraction analyses) and recycled aggregate concrete (RAC) was prepared by replacing 20, 50 and 100 vol.% of sand and gravel, separately. Concrete workability generally improved with CW addition, especially when replacing natural gravel. Although the compressive strengths of the concrete specimens prepared with recycled sand were slightly lower than those of the reference specimens, similar or better results were recorded with the recycled CS gravel. In consonance, the RAC developed with recycled gravel obtained lower water penetration depths than the reference concrete. No significant variation in tensile strength was observed when varying CS content (values within the 2.33–2.65 MPa range). The study contributes to sustainable construction practices and circular economy by promoting the valorisation and reutilisation of industrial waste and reducing the consumption of natural resources.
Experimental Study on the Dynamic Modulus of an Asphalt Roadbed Grouting Mixture under the Influence of Complex and Multiple Factors
Authors: Ran Wuping , Qiu Hengzheng , Ai Xianchen , Zhang Shanshan , Wang Yaqiang
Published: August 2023

After long-term service, the ground will experience settlement and the stability of the roadbed will be lost. In order to effectively reinforce the roadbed, an asphalt roadbed grouting mixture has been applied to the filling of the roadbed. The rotary compaction method was used to prepare different gradation types of lime composite-modified oil sludge pyrolysis residue asphalt, mixtures Sup13, Sup19, and Sup25. This article takes the dynamic modulus of an asphalt roadbed grouting mixture as the mechanical index, and the uniaxial compression dynamic modulus test is carried out on three kinds of rotary compaction asphalt mixtures, Sup13, Sup19, and Sup25. The dynamic modulus master curves of different gradation composite-modified oil sludge pyrolysis residue asphalt mixtures are fitted to study the dynamic modulus of asphalt mixtures under different nominal maximum particle sizes, loading frequencies, and temperatures. The results show that (1) The dynamic modulus of different gradation composite-modified oil sludge pyrolysis residue asphalt mixtures increases with the decrease in temperature and the increase in frequency; (2) when other conditions are the same, the compound-modified asphalt mixture’s dynamic modulus decreases significantly under low-frequency and high-temperature conditions; (3) in the range of 4.4–37.8 °C and medium loading frequency, the dynamic modulus of the compound-modified asphalt mixture is more affected by temperature and loading frequency; (4) in the low-temperature and high-frequency range, the compound-modified asphalt mixture with a larger nominal maximum particle size has a higher dynamic modulus, and the asphalt mixture with better stability of skeleton structure has a higher dynamic modulus. The research results of this article will provide scientific guidance for the study of the mechanical properties of asphalt roadbed grouting mixtures.
Interruption of p53-MDM2 Interaction by Nutlin-3a in Human Lymphoma Cell Models Initiates a Cell-Dependent Global Effect on Transcriptome and Proteome Level
Authors: Psatha Konstantina , Kollipara Laxmikanth , Drakos Elias , Deligianni Elena , Brintakis Konstantinos , Patsouris Eustratios , Sickmann Albert , Rassidakis George Z. , Aivaliotis Michalis
Published: August 2023

In most lymphomas, p53 signaling pathway is inactivated by various mechanisms independent to p53 gene mutations or deletions. In many cases, p53 function is largely regulated by alterations in the protein abundance levels by the action of E3 ubiquitin-protein ligase MDM2, targeting p53 to proteasome-mediated degradation. In the present study, an integrating transcriptomics and proteomics analysis was employed to investigate the effect of p53 activation by a small-molecule MDM2-antagonist, nutlin-3a, on three lymphoma cell models following p53 activation. Our analysis revealed a system-wide nutlin-3a-associated effect in all examined lymphoma types, identifying in total of 4037 differentially affected proteins involved in a plethora of pathways, with significant heterogeneity among lymphomas. Our findings include known p53-targets and novel p53 activation effects, involving transcription, translation, or degradation of protein components of pathways, such as a decrease in key members of PI3K/mTOR pathway, heat-shock response, and glycolysis, and an increase in key members of oxidative phoshosphorylation, autophagy and mitochondrial translation. Combined inhibition of HSP90 or PI3K/mTOR pathway with nutlin-3a-mediated p53-activation enhanced the apoptotic effects suggesting a promising strategy against human lymphomas. Integrated omic profiling after p53 activation offered novel insights on the regulatory role specific proteins and pathways may have in lymphomagenesis.
A Systematic Review of Short-Term Outcomes of Minimally Invasive Thoracoscopic Surgery for Lung Cancer after Neoadjuvant Systemic Therapy
Authors: Sedighim Shaina , Frank Madelyn I. , Heutlinger Olivia , Lee Carlin , Hachey Stephanie J. , Keshava Hari B.
Published: August 2023

Background: Minimally invasive surgeries for non-small cell lung cancers (NSCLCs) such as video-assisted thoracoscopic surgeries (VATSs) and robotic-assisted thoracoscopic surgeries (RATSs) have become standard of care for patients needing surgical resection in early stages. The role for neoadjuvant systemic therapy has increased with patients receiving neoadjuvant systemic chemotherapy and immunotherapy. However, there has been some equipoise over the intraoperative and overall outcomes for these patients. Here, we review the current data regarding outcomes of patients undergoing minimally invasive thoracic surgical resection after systemic chemotherapy, immunotherapy, or both. Methods: A systematic literature review of randomized controlled trials and observational studies presenting data on patients with NSCLC that underwent neoadjuvant systemic therapy followed by minimally invasive surgery was performed assessing complications, conversion rates, and lymph node yield. Results: Our search strategy and review of references resulted in 239 publications to screen with 88 full texts assessed and 21 studies included in our final review. VATS had a statistically significant higher lymph node yield in five studies. The reported conversion rates ranged from 0 to 54%. Dense adhesions, bleeding, and difficult anatomy were the most common reported reasons for conversion to open surgeries. The most common complications between both groups were prolonged air leak, arrythmia, and pneumonia. VATS was found to have significantly fewer complications in three papers. Conclusions: The current literature supports VATS as safe and feasible for patients with NSCLC after neoadjuvant systemic treatment. Surgeons should remain prepared to convert to open surgeries in those patients with dense adhesions and bleeding risk.
Significance of Furin Expression in Thyroid Neoplastic Transformation
Authors: Azevedo Maria Teresa , Macedo Sofia , Canberk Sule , Cardoso Luís , Gaspar Tiago Bordeira , Pestana Ana , Batista Rui , Sobrinho-Simões Manuel , Soares Paula
Published: August 2023

Angiotensin-Converting Enzyme 2 (ACE2), Transmembrane Serine Protease 2 (TMPRSS2), and Furin were known to be key players in the SARS-CoV-2 infection, and the thyroid gland was revealed to be one of the relevant targets of the virus. Regardless of the viral infection, the expression of these molecules in the thyroid gland and their putative role in the neoplastic transformation of the thyrocytes has not been thoroughly explored. In this work, we aimed to characterize the mRNA and protein expression pattern of ACE2, TMPRSS2, and Furin in a series of patients with thyroid lesions. Our main results revealed a significantly decreased expression of ACE2 mRNA in the thyroid neoplasms in comparison to normal adjacent tissue. Furin mRNA was significantly increased in thyroid neoplasms when compared to normal adjacent tissue. In addition, a higher Furin mRNA level in thyroid carcinomas was associated with the presence of lymph node metastasis. Furin mRNA expression revealed a high discriminatory power between adjacent tissue and neoplasms. Protein expression of these molecules did not correlate with mRNA expression. Our study shows the mRNA downregulation of ACE2 and overexpression of Furin in thyroid neoplasms. Further studies are required to clarify if Furin expression can be a potential diagnostic indicator in thyroid neoplasia.
MRD as Biomarker for Response to Donor Lymphocyte Infusion after Allogeneic Hematopoietic Cell Transplantation in Patients with AML
Authors: Teich Katrin , Stadler Michael , Gabdoulline Razif , Kandarp Jyoti , Wienecke Clara , Heida Bennet , Klement Piroska , Büttner Konstantin , Venturini Letizia , Wichmann Martin , Puppe Wolfram , Schultze-Florey Christian , Koenecke Christian , Beutel Gernot , Eder Matthias , Ganser Arnold , Heuser Michael , Thol Felicitas
Published: August 2023

Donor lymphocyte infusions (DLIs) can directly target leukemic cells through a graft-versus-leukemia effect and play a key role in the prevention and management of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Predictors of response to DLIs are not well established. We evaluated measurable residual disease (MRD) before, 30 and 90 days after DLI treatment as biomarkers of response. MRD was assessed by next-generation sequencing in 76 DLI-treated acute myeloid leukemia patients. MRD status before DLI treatment was independently prognostic for event-free survival (EFS, p < 0.001) and overall survival (OS, p < 0.001). Within 90 days of DLI treatment, 73% of MRD+ patients converted to MRD− and 32% of patients without remission achieved remission. MRD status 90 days after DLI treatment was independently prognostic for the cumulative incidence of relapse (CIR, p = 0.011) and relapse-free survival (RFS, p = 0.001), but not for OS. To evaluate the role of DLI treatment in MRD− patients, 23 MRD− patients who received DLIs were compared with a control cohort of 68 MRD− patients not receiving DLIs. RFS (p = 0.23) and OS (p = 0.48) were similar between the two cohorts. In conclusion, MRD is prognostic before (EFS, OS) and after (CIR, RFS) DLI treatment and may help in the selection of patients who benefit most from DLIs.