bluuebunny/crossref_metadata_2025_split huggingface dataset:
Melanin and Neuromelanin: Linking Skin Pigmentation and Parkinson's Disease
Authors: Krainc Talia , Monje Mariana H.G. , Kinsinger Morgan , Bustos Bernabe I. , Lubbe Steven J. 
Published: November 2022

AbstractNeuromelanin‐containing dopaminergic neurons in the substantia nigra pars compacta (SNpc) are the most vulnerable neurons in Parkinson's disease (PD). Recent work suggests that the accumulation of oxidized dopamine and neuromelanin mediate the convergence of mitochondrial and lysosomal dysfunction in patient‐derived neurons. In addition, the expression of human tyrosinase in mouse SNpc led to the formation of neuromelanin resulting in the degeneration of nigral dopaminergic neurons, further highlighting the importance of neuromelanin in PD. The potential role of neuromelanin in PD pathogenesis has been supported by epidemiological observations, whereby individuals with lighter pigmentation or cutaneous malignant melanoma exhibit higher incidence of PD. Because neuromelanin and melanin share many functional characteristics and overlapping biosynthetic pathways, it has been postulated that genes involved in skin pigmentation and melanin formation may play a role in the susceptibility of vulnerable midbrain dopaminergic neurons to neurodegeneration. Here, we highlight potential mechanisms that may explain the link between skin pigmentation and PD, focusing on the role of skin pigmentation genes in the pathogenesis of PD. We also discuss the importance of genetic ancestry in assessing the contribution of pigmentation‐related genes to risk of PD. © 2022 International Parkinson and Movement Disorder Society.
Intake of Pro‐ and/or Prebiotics as a Promising Approach for Prevention and Treatment of Colorectal Cancer
Authors: Wang Huijuan , Chen Ke , Ning Mengge , Wang Xin , Wang Zhouli , Yue Yuan , Yuan Yahong , Yue Tianli 
Published: November 2022

AbstractColorectal cancer (CRC) is the third most common type of cancer, posing a serious threat to human life. It is widely believed that dietary factors may be crucial modifiers of CRC risk, with pro‐and/or prebiotics being especially promising. In this review, a synthesis of CRC prevention and treatment of strategies relying on usage of pro‐ and/or prebiotics supplements is given, as well as discuss mechanisms underlying the contribution of pro‐and/or prebiotics to the suppression of colonic carcinogenesis. Furthermore, a framework for personalizing such supplements according to the composition of an individual's gut microbiome is suggested. Various factors including diversity of one's intestinal microflora, integrity of their intestinal barrier, and the presence of mutagenic/carcinogenic/genotoxic and beneficial compounds are known to have a prominent influence on the development of CRC; thus, clarifying the role of pro‐ and/or prebiotics will yield valuable insight toward optimizing interventions for enhanced patient outcomes in the future.
J‐modulated 19F‐ and 1H‐detected dual‐optimized inverted 1JCC 1,n‐ADEQUATE: A universal ADEQUATE experiment
Authors: Crouch Ronald C. , Pelmuş Marius , Raab Jeffrey G. , Tischenko Evgeny , Frey Michael , Wang Yunyi , Reibarkh Mikhail , Williamson R. Thomas , Martin Gary E. 
Published: November 2022

AbstractThe recently reported 19F‐detected dual‐optimized inverted 1JCC 1,n‐ADEQUATE experiment and the previously reported 1H‐detected version have been modified to incorporate J‐modulation, making it feasible to acquire all 1,1‐ and 1,n‐ADEQUATE correlations as well as 1JCC and nJCC homonuclear scalar couplings in a single experiment. The experiments are demonstrated using N,N‐dimethylamino‐2,5,6‐trifluoro‐3,4‐phthalonitrile and N,N‐dimethylamino‐3,4‐phthalonitrile.
Piloting a new model of personalised care for people with fibromyalgia in primary care with secondary care multidisciplinary support
Authors: Stellman Selena , Ellis Benjamin , Dawson Helen , Kocsis Agnes , Mundra Jag , Hill Cameron , Sahota Kalwant , Douglas Sarah 
Published: November 2022

AbstractObjectiveAn estimated 5.5 million people in England have high‐impact chronic pain, which is severe pain associated with significant disability. Current models of healthcare often fail to address their broad range of symptoms and address their complex non‐medical needs.MethodsA pilot project was designed with the aim of improving the quality of care and addressing unmet needs of patients high‐impact musculoskeletal (MSK) pain through providing a personalised approach to their pain and wider psychosocial needs. The model comprised a longer initial appointment with a general practitioner, a later follow‐appointment, and support of the multidisciplinary team (MDT) (informally and through a formal MDT meeting) with both primary care clinicians and specialists based in secondary care.ResultsForty six patients were seen using this model, with prominent themes of consultations including self‐management, social needs, mental health and understanding their diagnosis. Evaluation of the pilot demonstrated improvements in MSK and non‐MSK symptoms, together with improved patient confidence in self‐management and knowledge and understanding of their condition. Multidisciplinary working proved to be invaluable in addressing patients' wider needs but also upskilling and supporting primary care clinicians. Primary care staff also found it to be a satisfying way to care for patients, and developed increasing skills and confidence in supporting patients with chronic pain.ConclusionThis model of care appears to be an effective way to help primary care teams to provide more holistic personalised care to a group of patients who are highly complex and so often forgotten.
A transition scheme from diffusive to discrete crack topologies at finite strain during the course of a staggered iterative procedure
Authors: Han Jike , Shintaku Yuichi , Moriguchi Shuji , Terada Kenjiro 
Published: November 2022

AbstractThis study presents a novel transition scheme that can trace an actual crack path as closely as possible and stably update its explicit crack tip even in a large deformation regime. The crack initiation and propagation processes are determined from an energy minimization problem with respect to the displacement field and crack phase‐field, and the predicted path represented by a diffuse crack topology is replaced by a discrete path by applying the finite cover method. By developing a technique for determining explicit crack tips, the crack topology is updated from diffusive to discrete intermittently during the course of the staggered iterative procedure. Therefore, even a curved crack path that evolves significantly within a single time increment can be explicitly captured. Additionally, to stably update an explicit crack tip within the finite strain framework, we introduce a stabilization technique. Specifically, pseudo‐stiffness is applied to severely damaged elements around the discrete crack path to prevent excessively large deformations, and the corrector of the displacement increment in the global Newton–Raphson iterative procedure is intentionally diminished so that the discrete crack opens in a gradual and stable manner. After describing the individual techniques devised in the proposed scheme for achieving these features based on their algorithmic aspects, we present several representative numerical examples to demonstrate the performance and capability of the developed approach.
A meta‐analysis comparing the effectiveness of alternate day fasting, the 5:2 diet, and time‐restricted eating for weight loss
Authors: Elortegui Pascual Paloma , Rolands Maryann R. , Eldridge Alison L. , Kassis Amira , Mainardi Fabio , Lê Kim‐Anne , Karagounis Leonidas G. , Gut Philipp , Varady Krista A. 
Published: November 2022

AbstractObjectiveThe objective of this meta‐analysis was to compare the effectiveness of different intermittent fasting (IF) regimens on weight loss, in the general population, and compare these to traditional caloric energy restriction (CER).MethodsThree databases were searched from 2011 to June 2021 for randomized controlled trials (RCTs) that assessed weight loss and IF, including alternate day fasting (ADF), the 5:2 diet, and time‐restricted eating (TRE). A random effect network analysis was used to compare the effectiveness between the three regimens. Meta‐regression analysis was presented as weighted mean differences of body weight loss.ResultsThe exploratory random effects network analysis of 24 RCTs (n = 1768) ranked ADF as the most effective, followed by CER and TRE. The meta‐analysis showed that IF regimens resulted in similar weight loss to CER (mean difference 0.26 kg, 95% CI: –0.31 to 0.84; p = 0.37). Compliance was generally high (>80%) in trials shorter than 3 months.ConclusionsThe present meta‐analysis concludes that IF is comparable to CER and a promising alternative for weight loss. Among the three regimens, ADF showed the highest effectiveness for weight loss, followed by CER and TRE. Further well‐powered RCTs with longer durations of intervention are required to draw solid conclusions.
Improvement of compatibility, mechanical, thermal and dielectric properties of poly(lactic acid) and poly(butylene adipate‐co‐terephthalate) blends and their composites with porous clay heterostructures from mixed surfactant systems
Authors: Chotiradsirikun Suchinda , Than‐ardna Bhumin , Guo RuYan , Bhalla Amar S. , Manuspiya Hathaikarn 
Published: November 2022

AbstractIn this study, nanocomposite poly(lactic acid) and poly(butylene adipate‐co‐terephthalate) (PLA/PBAT) blends were prepared through polymer blending in the presence of multi‐functional epoxy as a compatibilizer that could react with epoxy group and terminated end group of two phases to increase interfacial adhesion between PLA and PBAT and improve the toughness of PLA. The effects of porous clay heterostructure from mixed CTAB:CTAC surfactant in the mole ratio of 1:2 (B1C2‐PCH) were also investigated. The elongation at break of the blends reached 38%, which was eight times that of neat PLA. The cryo‐fractured surface demonstrated the interfacial adhesion caused by the interaction of the epoxy group of the reactive compatibilizer with the terminal carboxyl and hydroxyl groups of PLA and PBAT. Moreover, PBAT reduced the crystallization rate and percent crystallinity of the PLA matrix and further decreased when compatibilizer was used. Alternatively, B1C2‐PCH accelerated the heterogeneous nucleation and crystallization of the nanocomposite films. After adding small amount of B1C2‐PCH, the nanocomposite films demonstrated excellent dielectric properties. Therefore, the improvement of PLA/PBAT nanocomposite blends are capable to be further developed as polymeric capacitor films.
Direct measurement and verification of cohesive zone model parameters for basalt/PProds using the transverse tensile test and virtual double cantilever beam test
Authors: Tobata Yuta , Naito Kimiyoshi , Tanks Jonathon 
Published: November 2022

AbstractTo further our understanding of failure in thermoplastic‐based composite rods, the mode I‐governed cohesive zone model parameter of a basalt fiber reinforced polypropylene composite rod is evaluated. The relations between stress and strain, the maximum normal traction and final separation displacement are examined using a transverse tensile test method. The measured traction is verified by three‐dimensional finite element analysis of rod‐shaped double cantilever beam specimens. The numerical results show the close relation between the crack length and cube root of compliance, and yields a representative value of the mode I‐governed critical fracture energy.
High‐performance nano‐biocomposite ionic soft actuators based on microfibrillated cellulose/ionic liquid electrolyte membrane
Authors: Wang Fan , Wang Lei , Shen Fangfang , Wang Donghai , Shen Wenhao 
Published: November 2022

AbstractHigh‐performance electro‐responsive ionic soft actuators with low actuation voltage, large bending strain, and ecofriendly functionalities have received great interest in soft robots, biomimetic robots, biomedical devise, flexible electronics, and wearable devices. Herein, we report a novel ionic soft actuator using biofriendly microfibrillated cellulose (MFC) and PEDOT:PSS, which exhibited a large peak‐to‐peak displacement (11.21 mm) mm under a sinusoidal excitation of 1.5 V at 0.1 Hz, low actuation voltage, wide driving frequency, excellent actuation durability (98% retention for 2 h), and excellent controllability, due to the strong ionic interactions of MFC fibers with cations and anions of ionic liquid (IL). Furthermore, the helical MFC‐IL ionic actuator was successfully designed, displaying that the radical displacements of the helical actuator could be controlled by changing the applied frequency and voltage. Therefore, the proposed ionic actuator as well as its helical design will offer an available pathway for guiding the development of artificial muscles, biomedical active devices, soft robots, flexible electronics, and soft electronics.
Designing of smart nanogels based on tragacanth gum for cisplatin delivery
Authors: Verma Chetna , Pathania Deepak , Negi Poonam , Gupta Piyush Kumar , Verma Rama Shanker , Gupta Bhuvanesh 
Published: November 2022

AbstractThe present work deals with the development of smart nanogels with a coating of a lipid layer, which synergized the triggered delivery of the anticancer drug cisplatin (CP). In the first step, the chemical initiation method was used for the grafting of poly(itaconic acid) on tragacanth gum (TG). Subsequently, this grafted TG matrix was used for the synthesis of nanoparticles. Nanoemulsion process was followed to prepare CP‐loaded grafted TG–lecithin (GTG‐LC) nanogels using dioctyl sulfosuccinate as the surfactant. These nanoparticles were characterized for size, morphology, elemental composition and crystallinity. Transmission electron microscopy images of the GTG‐LC nanogels with varying concentrations of CP demonstrate an irregular polygonal shape of the nanoparticles which is strongly influenced by the CP concentration. The smart nanogels exhibit a unique structure, nano‐within‐nano, a structure where nanosized CP is encapsulated within the GTG‐LC nanogel. Grafted nanogels have a high carboxyl functionality and exhibit pH‐sensitive behavior leading to pH‐responsive drug release behavior. These nanogels show required biocompatibility and offer interesting material for nanomedicines in chemotherapy. © 2022 Society of Industrial Chemistry.
Mass spectrometry‐based high‐throughput proteomics and its role in biomedical studies and systems biology
Authors: Messner Christoph B. , Demichev Vadim , Wang Ziyue , Hartl Johannes , Kustatscher Georg , Mülleder Michael , Ralser Markus 
Published: November 2022

AbstractThere are multiple reasons why the next generation of biological and medical studies require increasing numbers of samples. Biological systems are dynamic, and the effect of a perturbation depends on the genetic background and environment. As a consequence, many conditions need to be considered to reach generalizable conclusions. Moreover, human population and clinical studies only reach sufficient statistical power if conducted at scale and with precise measurement methods. Finally, many proteins remain without sufficient functional annotations, because they have not been systematically studied under a broad range of conditions. In this review, we discuss the latest technical developments in mass spectrometry (MS)‐based proteomics that facilitate large‐scale studies by fast and efficient chromatography, fast scanning mass spectrometers, data‐independent acquisition (DIA), and new software. We further highlight recent studies which demonstrate how high‐throughput (HT) proteomics can be applied to capture biological diversity, to annotate gene functions or to generate predictive and prognostic models for human diseases.
Portable mass spectrometry system: instrumentation, applications, and path to ‘omics analysis
Authors: Wang Jing , Pursell Madison E. , DeVor Amanda , Awoyemi Olanrewaju , Valentine Stephen J. , Li Peng 
Published: November 2022

AbstractMass spectrometry (MS) is an information rich analytical technique and plays a key role in various ‘omics studies. Standard mass spectrometers are bulky and operate at high vacuum, which hinder their adoption by the broader community and utility in field applications. Developing portable mass spectrometers can significantly expand the application scope and user groups of MS analysis. This review discusses the basics and recent advancements in the development of key components of portable mass spectrometers including ionization source, mass analyzer, detector, and vacuum system. Further, major areas where portable mass spectrometers are applied are also discussed. Finally, a perspective on the further development of portable mass spectrometers including the potential benefits for ‘omics analysis is provided.
Clearing up the smoke: Physical and mental health considerations regarding cannabis use in adolescents with cystic fibrosis
Authors: Ince H. Yavuz , Phan Hanna , Nasr Samya Z. , Pierce Jessica M. , Malas Nasuh 
Published: November 2022

AbstractThe cannabis plant is the most used federally illegal drug in the United States and is widely used by adolescents. Cannabis has complex effects on the body and mind. All health professionals who take care of adolescents with cystic fibrosis (CF) should be aware of the factors impacting cannabis use in CF. Given limited evidence regarding the benefits of cannabis and the significant risks, clinicians have the responsibility to identify risk of cannabis use early, counsel patients about the risks, provide a safe space for ongoing conversations about cannabis use in the context of CF care, and deliver evidence‐based interventions.
Regional inequalities in life expectancy and lifespan variation by educational attainment in Spain, 2014–2018
Authors: Bramajo Octavio , Permanyer Iñaki , Blanes Amand 
Published: November 2022

AbstractTwo important sources of inequality in mortality are regional variation and individuals' socioeconomic status. While many studies have investigated the effect that each of these two factors might have had on mortality levels separately, they have rarely been studied simultaneously. Using linked data from the Spanish National Institute of Statistics, we study regional levels of life expectancy and lifespan inequality by sex and educational attainment in contemporary Spain (2014–2018). In all regions, life expectancy was higher (and lifespan variation lower) for individuals with higher educational attainment and among women. We find a negative relationship between life expectancy and lifespan inequality across subnational regions among all sex‐education groups. However, the relationship is much weaker among the highly educated. These findings suggest that spatial conditions still matter as health determinants, but even more among individuals with disadvantaged socioeconomic positions, not only in terms of lower life expectancy but also of higher lifespan variation.
Disease trajectory of SLE clinical endpoints and covariates affecting disease severity and probability of response: Analysis of pooled patient‐level placebo (Standard‐of‐Care) data to enable model‐informed drug development
Authors: Goteti Kosalaram , French Jonathan , Garcia Ramon , Li Ying , Casset‐Semanaz Florence , Aydemir Aida , Townsend Robert , Mateo Cristina Vazquez , Studham Matthew , Guenther Oliver , Kao Amy , Gastonguay Marc , Girard Pascal , Benincosa Lisa , Venkatakrishnan Karthik 
Published: November 2022

AbstractSystemic lupus erythematosus (SLE) is an autoimmune disease affecting multiple organ systems. Many investigational agents have failed or shown only modest effects when added to standard of care (SoC) therapy in placebo‐controlled trials, and only two therapies have been approved for SLE in the last 60 years. Clinical trial outcomes have shown discordance in drug effects between clinical endpoints. Herein, we characterized longitudinal disease activity in the SLE population and the sources of variability by developing a latent disease trajectory model for SLE component endpoints (Systemic Lupus Erythematosus Disease Activity Index [SLEDAI], Physician's Global Assessment [PGA], British Isles Lupus Assessment Group Index [BILAG]) and composite endpoints (Systemic Lupus Erythematosus Responder Index [SRI], BILAG‐based Composite Lupus Assessment [BICLA], and Lupus Low Disease Activity State [LLDAS]) using patient‐level historical SoC data from nine phase II and III studies. Across all endpoints, in predictions up to 52 weeks from the final disease trajectory model, the following baseline covariates were associated with a greater decrease in SLE disease activity and higher response to placebo + SoC: Hispanic ethnicity from Central/South America, absence of hypocomplementemia, recent SLE diagnosis, and high baseline disease activity score using SLEDAI and BILAG separately. No discernible differences were observed in the trajectory of response to placebo + SoC across different SoC medications (antimalarial and immunosuppressant such as mycophenolate, methotrexate, and azathioprine). Across all endpoints, disease trajectory showed no difference in Asian versus non‐Asian patients, supporting Asia‐inclusive global SLE drug development. These results describe the first population approach to support a model‐informed drug development framework in SLE.
Plantamajoside attenuates cardiac fibrosis via inhibiting AGEs activated‐RAGE/autophagy/EndMT pathway
Authors: Zhang Lu , Guo Yi‐Ning , Liu Jing , Wang Lin‐Hai , Wu Han‐Qin , Wang Ting , Deng Bo , Wang Jun‐Yan , Lu Lu , Chen Zi‐Xin , He Jia‐qi , Liang Bi‐Rong , Li Huan , Huang Yu‐Sheng , Yang Zhong‐Qi , Xian Shao‐Xiang , Wang Ling‐Jun , Ye Xiao‐Han 
Published: November 2022

AbstractAdvanced glycation end products (AGEs) have been identified to transduce fibrogenic signals via inducing the activation of their receptor (RAGE)‐mediated pathway. Recently, disrupting AGE‐RAGE interaction has become a promising therapeutic strategy for chronic heart failure (CHF). Endothelial‐to‐mesenchymal transition (EndMT) is close to the cardiac fibrosis pathological process. Our previous studies have demonstrated that knockout RAGE suppressed the autophagy‐mediated EndMT, and thus alleviated cardiac fibrosis. Plantamajoside (PMS) is the major bioactive compound of Plantago Asiatica, and its activity of anti‐fibrosis has been documented in many reports. However, its effect on CHF and the underlying mechanism remains elusive. Thus, we tried to elucidate the protective role of PMS in CHF from the viewpoint of the AGEs/RAGE/autophagy/EndMT axis. Herein, PMS was found to attenuate cardiac fibrosis and dysfunction, suppress EndMT, reduce autophagy levels and serum levels of AGEs, yet did not affect the expression of RAGE in CHF mice. Mechanically, PMS possibly binds to the V‐domain of RAGE, which is similar to the interaction between AGEs and RAGE. Importantly, this competitive binding disturbed AGEs‐induced the RAGE‐autophagy‐EndMT pathway in vitro. Collectively, our results indicated that PMS might exert an anti‐cardiac fibrosis effect by specifically binding RAGE to suppress the AGEs‐activated RAGE/autophagy/EndMT pathway.