bluuebunny/crossref_metadata_2025 huggingface dataset:
Regorafenib Combined with BRAF/MEK Inhibitors for the Treatment of Refractory Melanoma Brain Metastases
Authors: Dirven Iris , Pierre Eden , Vander Mijnsbrugge An-Sofie , Vounckx Manon , Kessels Jolien I. , Neyns Bart
Published: December 2024

Background: There are no active treatment options for patients with progressive melanoma brain metastases (MBM) failing immune checkpoint blockade (ICB) and BRAF/MEK inhibitors (BRAF/MEKi). Regorafenib (REGO), an oral multi-kinase inhibitor (incl. RAF-dimer inhibition), can overcome adaptive resistance to BRAF/MEKi in preclinical models. Methods: This is a single-center retrospective case series of patients with refractory MBM treated with REGO plus BRAF/MEKi (compassionate use). Results: A total of 22 patients were identified (18 BRAF-mutant, 4 NRASQ61-mutant; 19 with progressive MBM; 11 on corticosteroids). Thirteen BRAFV600-mutant patients were progressing on BRAF/MEKi at the time of REGO association. BRAF-mutant patients received REGO (40–80 mg once daily) combined with BRAF/MEKi, NRAS-mutant patients were treated with REGO + MEKi (+low-dose BRAFi to mitigate skin-toxicity). Grade 3 TRAE included arterial hypertension (n = 4) and maculopapular rash (n = 3). There were no G4/5 TRAE. In BRAF-mutant patients, overall and intracranial objective response rates (overall ORR and IC-ORR) were 11 and 29%, and overall and intracranial disease control rates (overall DCR and IC-DCR) were 44 and 59%, respectively. In NRAS-mutant patients overall ORR and IC-ORR were 0 and 25% and overall DCR and IC-DCR were 25 and 50%, respectively. The median PFS and OS were, respectively, 7.1 and 16.4 weeks in BRAF-mutant and 8.6 and 10.1 weeks in NRAS-mutant patients. Conclusions: In heavily pretreated patients with refractory MBM, REGO combined with BRAF/MEKi demonstrated promising anti-tumor activity with an acceptable safety profile. In BRAFV600-mutant melanoma patients, responses cannot solely be attributed to BRAF/MEKi rechallenge. Further investigation in a prospective trial is ongoing to increase understanding of the efficacy.
The Effect of the Combination of Two Postbiotics on Anxiety-like Behavior in Animal Models
Authors: Robles Vanesa , Balaguer Ferran , Maicas Miren , Martínez-Vázquez Juan Manuel , Martorell Patricia , Tortajada Marta , Ramón Daniel , Valcarce David G.
Published: December 2024

With increasing evidence showing the connections between the microbiome, neurophysiology, and behavior, our research endeavors to investigate whether the consumption of a combination of two postbiotics with antioxidant effects can affect behavior regulation in model species. Here, we worked with a combination (1:1 ratio) of heat-treated Bifidobacterium longum subsp. longum ES1 (CECT7347) and Lacticaseibacillus rhamnosus BPL15 (CECT8361) as a dietary supplement. To examine the potential benefit of using this formulation to alleviate anxiety-like behavior, we employed two model species, Caenorhabditis elegans and adult Danio rerio. In C. elegans, the postbiotic supplementation reduced the anxiety-related behavior analyzed by means of the octanol avoidance test. In zebrafish, the novel tank test indicated a different swimming pattern 2 and 4 months after the animals were fed with the postbiotic combination. While fish did not exhibit any variance in their locomotion parameters such as pace and speed, they showed a statistically significant preference to spend more time in the upper zone of the water tank, a behavior that is correlated with a lower anxiety-like behavior in these species. Our aim with this study is to present evidence that can be used to develop whole-cell postbiotic-based novel and innovative dietary supplements for anxiety-related conditions.
Towards Clinical Application: Calcium Waves for In Vitro Qualitative Assessment of Propagated Primary Human Corneal Endothelial Cells
Authors: Ng Xiao Yu , Peh Gary , Morales-Wong Fernando , Gabriel Rami , Soong Poh Loong , Lin Kun-Han , Mehta Jodhbir S.
Published: December 2024

Corneal endothelium cells (CECs) regulate corneal hydration between the leaky barrier of the corneal endothelium and the ionic pumps on the surface of CECs. As CECs do not regenerate, loss of CECs leads to poor vision and corneal blindness. Corneal transplant is the only treatment option; however, there is a severe shortage of donor corneas globally. Cell therapy using propagated primary human CECs is an alternative approach to corneal transplantations, and proof of functionality is crucial for validating such CECs. Expression markers like Na-K-ATPase and ZO-1 are typical but not specific to CECs. Assessing the barrier function of the expanded CECs via electrical resistance (i.e., TEER and Ussing’s chamber) involves difficult techniques and is thus impractical for clinical application. Calcium has been demonstrated to affect the paracellular permeability of the corneal endothelium. Its absence alters morphology and disrupts apical junctions in bovine CECs, underscoring its importance. Calcium signaling patterns such as calcium waves affect the rate of wound healing in bovine CECs. Therefore, observing calcium waves in expanded CECs could provide valuable insights into their health and functional integrity. Mechanical or chemical stimulations, combined with Ca2+-sensitive fluorescent dyes and time-lapse imaging, can be used to visualize these waves, which could potentially be used to qualify expanded CECs.
Effect of Self-Measuring Blood Pressure Program on Hypertension Control: Analysis by Diabetes Status, Age, Gender, and Race in Rural Arizona
Authors: Luzingu Joy , Kilungo Aminata , Flores Randall , Baccam Zoe , Turner-Warren Tenneh , Reis Thelma , Okusanya Babasola , Ehiri John
Published: December 2024

Background: Rural areas face numerous health challenges, including workforce shortages, limited training opportunities, and delayed care. These disparities can be mitigated by self-management interventions for diseases such as hypertension. This study assessed the implementation of a Self-Measuring Blood Pressure (SMBP) program in rural Arizona, documenting its barriers and patient experiences. Methods: In this before-after study, participants were loaned a digital device which they used to self-measure and record blood pressure (BP) over 1 week or more for hypertension diagnosis or 4 weeks or more for monitoring. Blood pressure (BP) control was assessed per the guidelines of the American Heart Association and American Diabetes Association. BP changes between baseline and post-program were assessed using paired-Student t tests. Effect modification by diabetes was analyzed using stratification. Results: Among 740 participants, significant associations were found with gender, age, and controlled BP among non-diabetic patients. Post-intervention, 63.4% of diabetic patients showed controlled BP, and 25.7% of non-diabetic patients had controlled BP, with higher control rates among females and older age groups (60–79 years). Baseline mean SBP was 148.3 ± 19.6 mmHg, improving to 133.9 ± 14.6 mmHg; baseline DBP was 88.5 ± 33.6 mmHg, improving to 83.4 ± 9.6 mmHg. Conclusions: The SMBP program effectively controlled BP, highlighting the value of combining clinical care with telemonitoring.
Potential Benefits from Physical Exercise in Advanced Cancer Patients Undergoing Systemic Therapy? A Narrative Review of the Randomized Clinical Trials
Authors: Bozzetti Federico
Published: December 2024

Design. The purpose of this review is the analysis of the literature concerning the effects of physical exercise in cancer patients undergoing medical oncologic treatment. Papers were retrieved from the scrutiny of 15 reviews/meta-analyses published in the last 2 years, which, however, pooled different populations of patients (surgical and medical patients, receiving or not an oncologic therapy, harboring a cancer, or being survivors). Results. We reviewed the data of 35 RCTs on the use of physical exercise in cancer patients, distinguishing well-nourished from malnourished patients. The conclusions of our study are the following: No major difference between well-nourished and malnourished patients as regards compliance/adherence with physical exercise and outcomes. Compliance with physical exercise was reported in about 70% of the studies. Compared with a control group receiving the usual care, in patients who practiced physical exercise, a benefit in some parameters of physical function and quality of life and lean body mass (LBM) was reported in 61%, 47%, and 12%, respectively, of the studies in non-malnourished patients, and in 50%, 100%, and 36%, respectively, of the studies in malnourished patients. The benefit in LBM was more frequently reported in weight-losing patients. There was no strict association among the results of different outcomes (muscle function vs. quality of life vs. LBM). There are still some ill-defined issues, including the optimal physical regimen (with some authors favoring high-intensity interval training and resistance) and the place of exercising (patients usually preferring home exercises, which, however, have been proved less efficacious).
Features of the Nurse-Patient Relationship: Insights from a Qualitative Review Using Artificial Intelligence Interpretation
Authors: Vitale Elsa , Conte Luana , Lupo Roberto , Botti Stefano , Fanizzi Annarita , Massafra Raffaella , De Nunzio Giorgio
Published: December 2024

Introduction: This qualitative literature review explored the intersection of art, creativity, and the nurse–patient relationship in the context of oncology nursing. It delved into the perceptions and reflections of nurses as captured by Generative Artificial Intelligence (GAI) analysis from two specialized nursing databases. Methods: The protocol was registered on the Open Science Framework (OSF) Platform. A comprehensive search was conducted in CINAHL, the British Nursing Database, and the Nursing & Allied Health Database, using keywords related to art, cancer, creativity, nursing, and relationships. The extracted qualitative research studies were then analyzed using GAI to identify key themes and insights. Results: The analysis revealed profound considerations regarding the role of nurses in oncology and palliative patient care. Nurses acknowledged the spiritual dimension through religious and spiritual practices, while emphasizing authentic presence and empathic communication. They actively addressed patient concerns, adapted to challenges, and engaged in continuous professional development. The insights from the GAI interpretation underscored the significance of empathy, creativity, and artistry in nurturing meaningful nurse–patient connections. Conclusions: The GAI-enabled exploration provided valuable insights into several dimensions of care, emphasizing the importance of spiritual sensitivity, empathic communication, and ongoing professional growth. As technology and human care converge, integrating artistry into the nurse–patient relationship could enhance patient experiences, improve outcomes, and enrich the oncology nursing practice.
Braf-Mutant Melanomas: Biology and Therapy
Authors: Pelosi Elvira , Castelli Germana , Testa Ugo
Published: December 2024

The incidence of melanoma, the most lethal form of skin cancer, has increased mainly due to ultraviolet exposure. The molecular characterization of melanomas has shown a high mutational burden led to the identification of some recurrent genetic alterations. BRAF gene is mutated in 40–50% of melanomas and its role in melanoma development is paramount. BRAF mutations confer constitutive activation of MAPK signalling. The large majority (about 90%) of BRAF mutations occur at amino acid 600; the majority are BRAFV600E mutations and less frequently BRAFv600K, V600D and V600M. The introduction of drugs that directly target BRAF-mutant protein (BRAF inhibitors) and of agents that stimulate immune response through targeting of immune check inhibitor consistently improved the survival of melanoma BRAFV600-mutant patients with unresectable/metastatic disease. In parallel, studies in melanoma stage II-III patients with resectable disease have shown that adjuvant therapy with ICIs and/or targeted therapy improves PFS and RFS, but not OS compared to placebo; however, neoadjuvant therapy plus adjuvant therapy improved therapeutic response compared to adjuvant therapy alone.
Oncologic and Operative Outcomes of Robotic Staging Surgery Using Low Pelvic Port Placement in High-Risk Endometrial Cancer
Authors: Kim Jeeyeon , Paek Jiheum
Published: December 2024

Upper para-aortic lymph node dissection (PALND) is one of the most challenging gynecologic robotic procedures. This study aimed to evaluate the oncologic and operative outcomes of robotic staging surgery, including upper PALND, using low pelvic port placement (LP3) in 22 patients with high-risk endometrial cancer. High-risk was defined as patients who showed deep myometrial invasion with grade III, cervical involvement, or high-risk histology. The mean patient age and body mass index were 58 years and 24 kg/m2. The mean operative time was 263 min. The mean number of total LNs and upper PALNs obtained was 31 and 10. Two patients received lymphangiography to reduce the amount of drained lymphatic fluid after surgery. The recurrence rate was 13.6% (3/22). There were two LN recurrences and one at the peritoneum in the intra-abdominal cavity. Robotic staging surgery using LP3 was feasible for performing PALND as well as procedures in the pelvic cavity simultaneously. It provides important techniques for performing optimal surgical procedures when surgeons decide to perform comprehensive PALND in instances of isolated recurrence or unexpected LN enlargement as well as high-risk endometrial cancer. Consequently, surgeons can achieve surgical consistency and reproducibility for PALND, leading to improved operative and survival outcomes in high-risk endometrial cancer.
Comparison of Modified Labor Induction Strategies for Pregnant Women at a Single Tertiary Center Before and During the COVID-19 Pandemic
Authors: Tan Yi-Sin , Tsai Ching-Chang , Cheng Hsin-Hsin , Lai Yun-Ju , Lee Pei-Fang , Hsu Te-Yao , Huang Kun-Long
Published: December 2024

Background: The COVID-19 pandemic has substantially impacted healthcare systems and obstetric practices worldwide. Labor induction is a common procedure for preventing obstetric complications in high-risk populations. This study evaluated perinatal outcomes of labor induction using a modified management protocol in a tertiary care center during the COVID-19 pandemic. Methods: We conducted a retrospective study by reviewing electronic structured delivery records of women who underwent elective labor induction between June 2020 and October 2022. We analyzed maternal characteristics, maternal outcomes, and neonatal outcomes during the pre-pandemic (June 2020 to May 2021) and pandemic periods (May 2021 to October 2022). Results: The study included 976 cases: 325 pregnancies in the pre-pandemic group and 651 in the pandemic group. The pandemic group showed earlier gestational age at delivery (39 vs. 40 weeks, p < 0.01) and lower body mass index (27.1 vs. 27.5 kg/m2, p = 0.03). During the pandemic period, we observed a significant increase in labor induction cases and a decrease in cesarean sections. Neonatal outcomes, including Apgar scores and intensive care admissions, showed no significant differences between groups. Subgroup analysis identified advanced maternal age (OR = 1.08; 95% CI = 1.03–1.14; p < 0.01) and primiparity (OR = 5.24; 95% CI = 2.75–9.99; p < 0.01) as independent risk factors for cesarean delivery. Conclusions: Even under modified protocols for labor induction during the COVID-19 pandemic, more pregnancies underwent labor induction while achieving a significant reduction in cesarean sections. Advanced maternal age and primiparity were identified as independent risk factors associated with cesarean delivery.
Instrument-Free Point-of-Care Diagnostic for Leishmania Parasites
Authors: Wiggins Taralyn J. , Peng Ruonan , Bushnell Ruth V. , Tobin John K. , MacLeod David A. , Du Ke , Tobin Gregory J. , Dollery Stephen J.
Published: December 2024

Background/Objective: Leishmaniasis is the second deadliest parasitic disease in the world, after malaria, with an estimated 1.6 million new cases each year. While cutaneous leishmaniasis can result in permanent scars from lesions after treatment, the mucocutaneous and visceral diseases can result in life-altering and life-threatening complications. Accurate species diagnosis is critical for treatment and follow-up, and while PCR-based diagnostics can provide sensitive parasite detection and species identification, they are slow, expensive, and not suitable for low-resource settings. In this publication, we describe our efforts to develop a simple, affordable, and instrument-free Leishmania DNA diagnostic that can be used in both high-tech settings and the field. Methods: Computational biology was utilized to design region-targeted RPA oligos and the corresponding CRISPR guides for the detection of all Leishmania species as well as the specific identification of L. (V.) panamensis as a predictor of mucocutaneous disease. Then, we executed systematic approaches for parasite lysis, RPA amplification of DNA, and fluorescent CRISPR crRNA detection. Results: We have demonstrated the ability to detect single-digit parasites without compromising the specificity in identifying single species as the proof of concept for a point-of-care diagnostic. Individual assays were carried out in succession, culminating in an unquenched fluorescent signal quantifiable over negative control. Conclusions: The described work is the foundation which will be implemented into a three-track [all Leishmania, mucocutaneous or visceral only, and a human positive control] assay that we plan to utilize in a Funnel Adapted Sensing Tube (FAST) single use, instrument-free, and affordable diagnostic.
Research on Fault Feature Extraction Method for Hydroelectric Generating Unit Based on Improved FMD and CDEI
Authors: Wu Tao , Gong Haipeng , Geng Zaiming , Deng Jian , Yuan Fang
Published: December 2024

As core pieces of equipment in hydropower generation, the operational condition of critical components such as the rotor and thrust bearing is crucial for the stability of hydropower units. The essence of fault diagnosis for hydroelectric generating units is pattern recognition. To achieve high recognition accuracy, it is necessary to maximize the distinguishability of different fault features. However, traditional time–frequency signal processing methods seldom consider this issue during the decomposition process, resulting in low sensitivity of the extracted features to different fault types. To address this issue, this paper proposes a fault feature extraction method for hydroelectric generating units based on Feature Modal Decomposition (FMD) and the Comprehensive Distance Evaluation Index (CDEI). By improving the FMD algorithm, the objective function for selecting modal components during the FMD decomposition process is set as the CDEI, which can measure the sensitivity of fault features, thereby enhancing the distinguishability of the obtained fault features. Next, the Distance Evaluation Index (DEI) is used to measure the sensitivity of the obtained features, and the most sensitive features are selected. Experiments using a rotor test bench and actual signals before and after thrust bearing horizontal adjustment from a hydroelectric generating unit were conducted and compared with related methods. The results show that the proposed method can effectively improve the sensitivity of the obtained fault features and achieve accurate fault diagnosis for hydroelectric generating units.
Mutual Influences Among the Electricity Market, Carbon Emission Market, and Renewable Energy Certificate Market
Authors: Zou Hongbo , Luo Yuhong , Wen Fushuan , Chen Jiehao , Yang Jinlong , Yang Changhua
Published: December 2024

With the advancement and development of the electricity market (EM), carbon emission market (CEM), and renewable energy certificate market (RECM), promoting the integration and growth of the EM alongside carbon emission trading, renewable energy certificate trading, and other related markets is becoming increasingly important for high-quality development of the power industry. Analyzing the intrinsic connections among these three types of markets can facilitate their coordinated development. In this study, we selected monthly data on European Union (EU) carbon emission futures, French electricity trading prices, and the price of Guarantees of Origin (GO) in France from March 2019 to March 2024 and utilized the Bayesian time-varying stochastic volatility vector autoregression model (TVP-SV-VAR) with time-varying parameters to effectively capture the dynamic changes among the three markets and to analyze the relationships and characteristics of the EM, CEM, and RECM across different historical contexts. Simulation results showed that the influences of the EM and CEM on the RECM were relatively low, with more pronounced short-term effects and relatively stable medium- and long-term effects. In contrast, the influences of the CEM and RECM on the EM were significant, with more pronounced short-term effects and stable medium- and long-term effects. The influences of the EM and RECM on the CEM were significant in the short term.
Electrification of Public Urban Transport: Funding Opportunities, Bus Fleet, and Energy Use Forecasts for Poland
Authors: Batóg Jacek , Batóg Barbara , Mojsiewicz Magdalena , Pluskota Przemysław
Published: December 2024

Diverse measures related to the electrification of transport fleets have been implemented in many countries due to the increasing consumption of fossil fuels and their negative impact on the climate and human health. Such transformation is effective if electric energy is sourced from renewable sources. The rate of transport electrification is determined mainly by legislative and financial incentives, charging infrastructure density, and fuel price. The main aims of the study are to present financial support for investments in low-emission transport infrastructure and to provide forecasts of the fleet of urban electric buses and the expected demand for electricity consumed by them in Poland. The main source of data was statistical reports published by Statistics Poland. Because the available sample was short, basic statistical models were used. The results obtained indicate the stable growth of investments in regional low-emission transport infrastructure, characterized by strong heterogeneity. The foreseen number of electric buses in urban public transport in the realistic variants ranges between 1486 and 1626. In the optimistic variants, the forecast values are significantly higher. However, they can only be achieved if there is a significant increase in investment. The electricity demand forecast for the realistic variant shows a demand of 341,266.50 MWh.
Distributed Dispatch and Profit Allocation for Parks Using Co-Operative Game Theory and the Generalized Nash Bargaining Approach
Authors: Wang Hanwen , Li Xiang , Hu Haojun , Zhou Yizhou
Published: December 2024

To improve the regulatory capacity of distributed resources within the park and enhance the flexibility of market transactions, this paper introduces a distributed dispatch and profit allocation method grounded in cooperative game theory and the generalized Nash bargaining framework. Initially, models for individual park equipment are established. Subsequently, a distributed dispatch model is constructed, followed by the development of a profit allocation strategy based on contribution levels, using the generalized Nash bargaining method. The model is solved using the alternating direction method of multipliers. The results show that the proposed approach achieves fast convergence, optimizes resource sharing and mutual support within the park, lowers operational costs, ensures a fairer distribution of profits, and promotes increased cooperation among park entities.
Dynamics of Aboveground Carbon Across Karst Terrestrial Ecosystems in China from 2015 to 2021
Authors: Shi Jinan , Yu Ling , Fang Hongqian , Zhang Ke , Wigneron Jean-Pierre , Li Xiaojun , Cui Tianxiang , Liu Can , Jiao Yue , Wang Dacheng
Published: December 2024

Over the past half-century, environmental degradation and human disturbances have threatened the aboveground biomass carbon (AGC) in China’s karst ecosystems. However, recent ecological programs have led to environmental improvements, leaving it unclear whether China’s karst ecosystems act as an AGC sink or AGC source. In this study, we utilized L-band vegetation optical depth to quantify the dynamics of AGC across the karst regions of China from 2015 to 2021. We observed an increase in AGC density of 0.73 Mg C ha−1 yr−1, suggesting that karst ecosystems in China functioned as an AGC sink throughout the research period. The largest increase in AGC density, 1.29 Mg C ha−1 yr−1, was observed in Central China, indicating an AGC sink capacity stronger than that of other regions. Among the different land-use types, forests played a dominant role, exhibiting the largest net change in AGC density at 1.03 Mg C ha−1 yr−1. Furthermore, using the random forest model, temperature, soil clay content, and altitude were identified as the primary factors driving AGC changes. Our results enhance the understanding of the role of China’s karst terrestrial ecosystem in the global carbon cycle, emphasizing its contribution to the global carbon sink.
The Newborn Screening Programme Revisited: An Expert Opinion on the Challenges of Rett Syndrome
Authors: Singh Jatinder , Santosh Paramala
Published: December 2024

Genomic sequencing has the potential to revolutionise newborn screening (NBS) programmes. In 2024, Genomics England began to recruit for the Generation Study (GS), which uses whole genome sequencing (WGS) to detect genetic changes in 500 genes in more than 200 rare conditions. Ultimately, its purpose is to facilitate the earlier identification of rare conditions and thereby improve health-related outcomes for individuals. The adoption of rare conditions into the GS was guided by four criteria: (1) the gene causing the condition can be reliably detected; (2) if undiagnosed, the rare condition would have a serious impact; (3) early or presymptomatic testing would substantially improve outcomes; and (4) interventions for conditions screened are accessible to all. Rett syndrome (RTT, OMIM 312750), a paediatric neurodevelopment disorder, was not included in the list of rare conditions in the GS. In this opinion article, we revisit the GS and discuss RTT from the perspective of these four criteria. We begin with an introduction to the GS and then summarise key points about the four principles, presenting challenges and opportunities for individuals with RTT. We provide insight into how data could be collected during the presymptomatic phase, which could facilitate early diagnosis and improve our understanding of the prodromal stage of RTT. Although many features of RTT present a departure from criteria adopted by the GS, advances in RTT research, combined with advocacy from parent-based organisations, could facilitate its entry into future newborn screening programmes.
Temperature and Photoperiod Control of Shoot Growth and Floral Bud Initiation in Biennial-Fruiting Blackberries
Authors: Sønsteby Anita , Sadojevic Mirjana , Heide Ola M.
Published: December 2024

Growth and flower bud initiation (FBI) were studied in single-stem plants of four biennial-fruiting cultivars in a controlled environment and under field conditions at 60°40′ N. Shoot growth varied widely among the cultivars but was significantly enhanced by high temperature (20 °C) in all cultivars, whereas photoperiod had a subordinate growth effect. FBI data from bud dissection after 6 weeks of cultivation in the phytotron were used to calculate FBI indices for the various cultivars and environment conditions. The indices also varied much among the cultivars but were enhanced by elevated temperature, being highest in ‘Natchez’ and ‘Sweet Royalla’, while ‘Natchez’ was the only cultivar in which FBI was significantly enhanced by short days. The non-vigorous and erect growing ‘Ouachita’ remained vegetative at both temperatures but flowered in spring after overwintering at 0.5 °C. The field experiment confirmed the superior growth vigor of ‘Loch Ness’ and ‘Sweet Royalla’ as well as the photoperiodic sensitivity of ‘Natchez’. The results also confirmed that floral initiation starts in lateral buds located 10–20 nodes below the apex, and from there it progresses in both acropetal and basipetal direction. We conclude that temperature is at least as important as the photoperiod for the control of FBI in biennial-fruiting blackberries.
RETRACTED: El-Far et al. Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats’ Brain and Heart. Int. J. Mol. Sci. 2021, 22, 6839
Authors: El-Far Ali H. , Elewa Yaser H. A. , Abdelfattah Elsayeda-Zeinab A. , Alsenosy Abdel-Wahab A. , Atta Mustafa S. , Abou-Zeid Khalid M. , Jaouni Soad K. Al , Mousa Shaker A. , Noreldin Ahmed E.
Published: December 2024

The International Journal of Molecular Sciences retracts the article “Thymoquinone and Curcumin Defeat Aging-Associated Oxidative Alterations Induced by D-Galactose in Rats’ Brain and Heart” [...]
Genome-Wide Association Study of Grape Texture Based on Puncture
Authors: Lin Meiling , Sun Lei , Liu Xuewei , Fan Xiucai , Zhang Ying , Jiang Jianfu , Liu Chonghuai
Published: December 2024

Grapes are grown extensively around the world and play a crucial role in overall fruit production globally. The quality of the grape is largely determined by the texture of the flesh, making it a key focus for grape breeders. Our study was conducted on 437 grape accessions using a puncture method to analyze berry texture characteristics. The results reveal strong correlations among the five texture parameters of grape accessions. Following the GWAS analysis using 2,124,668 population SNPs, 369 significant SNP locations linked to the grape berry texture were discovered. Through the process of gene annotation and expression analysis in the localization regions, several genes potentially linked to berry texture were identified, including E13A, FIS1A, CML35, AGL2, and AGL62. E13A, FIS1A, and CML35 were identified as potentially more relevant to grape berry texture based on gene expression analysis. Further investigation through transient transformation demonstrated that overexpressing E13A and CML35 resulted in notable changes in grape pulp texture. During this study, the berry textures of 437 grape accessions were comprehensively evaluated, and several important candidate genes were screened based on GWAS and analysis of gene function. This discovery paves the way for future research and breeding initiatives related to grape berry texture.
Interactions of VMAT2 with CDCrel-1 and Parkin in Methamphetamine Neurotoxicity
Authors: Chauhan Heli , Carruthers Nicholas J. , Stemmer Paul M. , Schneider Bernard L. , Moszczynska Anna
Published: December 2024

In recent years, methamphetamine (METH) misuse in the US has been rapidly increasing, and there is no FDA-approved pharmacotherapy for METH use disorder (MUD). In addition to being dependent on the drug, people with MUD develop a variety of neurological problems related to the toxicity of this drug. A variety of molecular mechanisms underlying METH neurotoxicity has been identified, including the dysfunction of the neuroprotective protein parkin. However, it is not known whether parkin loss of function within striatal dopaminergic (DAergic) terminals translates into decreased DA storage capacity. This study examined the relationship between parkin, its substrate cell division cycle related-1 (CDCrel-1) associated with synaptic vesicles, and vesicular monoamine transporter-2 (VMAT2) responsible for packaging DA in an in vivo model of METH neurotoxicity. To assess the individual differences in response to METH’s neurotoxic effects, a large group of male Sprague Dawley rats were treated with binge METH or saline and sacrificed 1 h or 24 h later. This study is the first to show that CDCrel-1 interacts with VMAT2 in the rat striatum and that binge METH can alter this interaction as well as the levels and subcellular localization of CDCrel-1. The proteomic analysis of VMAT-2-associated proteins revealed the upregulation of several proteins involved in the exocytosis/endocytosis cycle and responses to stress. The results suggest that DAergic neurons are engaged in counteracting METH-induced toxic effects, including attempts to increase endocytosis and autophagy at 1 h after the METH binge, with the responses varying widely between individual rats. Studying CDCrel-1, VMAT2, and other proteins in large groups of outbred rats can help define individual genetic and molecular differences in responses to METH neurotoxicity, which, in turn, may aid treating humans suffering from MUD and its neurological consequences.
Single-Cell RNA Sequencing of PBMCs Identified Junction Plakoglobin (JUP) as Stratification Biomarker for Endometriosis
Authors: Andrieu Thomas , Duo Angelo , Duempelmann Lea , Patzak Magdalena , Saner Flurina Annacarina Maria , Skrabalova Jitka , Donato Cinzia , Nestorov Peter , Mueller Michael D.
Published: December 2024

This study aimed to identify unique characteristics in the peripheral blood mononuclear cells (PBMCs) of endometriosis patients and develop a non-invasive early diagnostic tool. Using single-cell RNA sequencing (scRNA-seq), we constructed the first single-cell atlas of PBMCs from endometriosis patients based on 107,964 cells and 25,847 genes. Within CD16+ monocytes, we discovered JUP as a dysregulated gene. To assess its diagnostic potential, we measured peritoneal fluid (PF) and serum JUP levels in a large cohort of 199 patients including 20 women with ovarian cancer (OC). JUP was barely detectable in PF but was significantly elevated in the serum of patients with endometriosis and OC, with levels 1.33 and 2.34 times higher than controls, respectively. Additionally, JUP was found in conditioned culture media of CD14+/CD16+ monocytes aligning with our scRNA-seq data. Serum JUP levels correlated with endometriosis severity and endometrioma presence but were unaffected by dysmenorrhea, menstrual cycle, or adenomyosis. When combined with CA125 (cancer antigen 125) JUP enhanced the specificity of endometriosis diagnosis from 89.13% (CA125 measured alone) to 100%. While sensitivity remains a challenge at 19%, our results suggest that JUP’s potential to enhance diagnostic accuracy warrants additional investigation. Furthermore, employing serum JUP as a stratification marker unlocked the potential to identify additional endometriosis-related genes, offering novel insights into disease pathogenesis.
AEmiGAP: AutoEncoder-Based miRNA–Gene Association Prediction Using Deep Learning Method
Authors: Yoon Seungwon , Yoon Hyewon , Cho Jaeeun , Lee Kyuchul
Published: December 2024

MicroRNAs (miRNAs) play a crucial role in gene regulation and are strongly linked to various diseases, including cancer. This study presents AEmiGAP, an advanced deep learning model that integrates autoencoders with long short-term memory (LSTM) networks to predict miRNA–gene associations. By enhancing feature extraction through autoencoders, AEmiGAP captures intricate, latent relationships between miRNAs and genes with unprecedented accuracy, outperforming all existing models in miRNA–gene association prediction. A thoroughly curated dataset of positive and negative miRNA–gene pairs was generated using distance-based filtering methods, significantly improving the model’s AUC and overall predictive accuracy. Additionally, this study proposes two case studies to highlight AEmiGAP’s application: first, a top 30 list of miRNA–gene pairs with the highest predicted association scores among previously unknown pairs, and second, a list of the top 10 miRNAs strongly associated with each of five key oncogenes. These findings establish AEmiGAP as a new benchmark in miRNA–gene association prediction, with considerable potential to advance both cancer research and precision medicine.
An Update on Microbial Interventions in Autism Spectrum Disorder with Gastrointestinal Symptoms
Authors: Moreno Rachel J. , Ashwood Paul
Published: December 2024

In the United States, autism spectrum disorder (ASD) affects 1 in 33 children and is characterized by atypical social interactions, communication difficulties, and intense, restricted interests. Microbial dysbiosis in the gastrointestinal (GI) tract is frequently observed in individuals with ASD, potentially contributing to behavioral manifestations and correlating with worsening severity. Moreover, dysbiosis may contribute to the increased prevalence of GI comorbidities in the ASD population and exacerbate immune dysregulation, further worsening dysbiosis. Over the past 25 years, research on the impact of microbial manipulation on ASD outcomes has gained substantial interest. Various approaches to microbial manipulation have been preclinically and clinically tested, including antibiotic treatment, dietary modifications, prebiotics, probiotics, and fecal microbiota transplantation. Each method has shown varying degrees of success in reducing the severity of ASD behaviors and/or GI symptoms and varying long-term efficacy. In this review, we discuss these microbiome manipulation methods and their outcomes. We also discuss potential microbiome manipulation early in life, as this is a critical period for neurodevelopment.
Green Synthesized Silver Nanoparticles Induced Accumulation of Biomass and Secondary Metabolites in Hairy Roots of Rehmannia glutinosa
Authors: Zhu Yunhao , Hu Xiangxiang , Dong Le , Yang Han , Zhou Danning , Liu Xiangnan , Dong Chengming , Yue Xiule , Zhao Le
Published: December 2024

The hairy roots of Rehmannia glutinosa (Gaertn.) Libosch. ex Fisch. & C. A. Mey. are capable of producing active compounds such as iridoid glycoside, and phenylethanoid glycosides, which have potential applications in the pharmaceutical industry. Silver nanoparticles (AgNPs) have been used as novel elicitors in the induced cultivation of hairy roots, but there is a lack of research regarding their effects on R. glutinosa hairy roots. In the present study, silver nanoparticles (Pp-AgNPs) synthesized by the endophytic fungus Penicillium polandii PG21 were adopted to elicit hairy roots of R. glutinosa, to investigate their influences on the biomass, color, secondary metabolites, antioxidant activity, sucrose metabolism, and phytohormone-related gene expression. The results revealed that the dry weight and fresh weight of R. glutinosa hairy roots were both higher in the treated group than in the control group after addition of 2 mg/L Pp-AgNPs for 20 d. The content of verbascoside, total phenylethanol glycosides and total cycloartenoid in the treatment group reached the highest level at 20 d, which were 1.75, 1.51, 1.44 times more than those in the control group, respectively. Pp-AgNPs significantly stimulated the enzyme activities of catalase (CAT), superoxide dismutase (SOD), and peroxidase (POD). The growth-promoting effect of Pp-AgNPs may be accomplished by increasing sucrose metabolism, and regulating the synthesis and signal transduction of gibberellin (GA) and indoleacetic acid (IAA). Moreover, expressed sequence tags-simple sequence repeat (EST-SSR)-based genetic diversity analyses indicated that there was little possibility of genetic variation among samples under different treatment conditions. In conclusion, the appropriate concentration of Pp-AgNPs can be used as an effective elicitor to improve the biomass and secondary metabolites content in R. glutinosa hairy roots.
Macrostomum lignano Complements the Portfolio of Simple Animal Models Used for Marine Toxicological Studies
Authors: Ma Yuanyuan , Roeder Thomas
Published: December 2024

Macrostomum lignano is gaining increasing recognition as a model organism for toxicological studies in marine ecosystems and expands the range of simple animal models currently used. Water pollution caused by human activities not only endangers environmental integrity but also affects human health, underlining the need to monitor water pollution effectively. This review describes the distinctive characteristics of M. lignano, including its rapid reproductive cycle, increased sensitivity to environmental variability, and remarkable regenerative abilities. Over the last thirty years, M. lignano has been used in various research areas, particularly molecular biology and toxicology. This endeavor has benefited from significant advances in genome and transcriptome technologies. Recent investigations have revealed its sensitivity to various pollutants and highlighted its potential for assessing toxicological effects at the physiological and molecular levels. Furthermore, the ecological versatility and stable microbiome of M. lignano make it an exemplary model for research into pollutant interactions in marine ecosystems. Despite challenges associated with its complex genomic architecture, ongoing genomic efforts are promising to significantly enhance its utility in toxicological research. This review underscores the pivotal role of M. lignano in advancing environmental health studies and outlines future research directions to maximize its potential as a model organism.
Assessment of Changes in the Expression of Genes Involved in Insulin Signaling and Glucose Transport in Leukocytes of Women with Gestational Diabetes During Pregnancy and in the Postpartum Period
Authors: Zieleniak Andrzej , Zurawska-Klis Monika , Laszcz Karolina , Bulash Krystsina , Pacyga Dagmara , Cypryk Katarzyna , Wozniak Lucyna , Wojcik Marzena
Published: December 2024

Not much is currently known about disturbances in insulin signaling and glucose transport in leukocytes of women with gestational diabetes mellitus (GDM) during and after pregnancy. In this study, the expression of insulin signaling (INSR, IRS1, IRS2 and PIK3R1)- and glucose transporter (SLC2A1, SLC2A3 and SLC2A4)-related genes in the leukocytes of 92 pregnant women was assayed using quantitative RT-PCR. The cohort consisted of 44 women without GDM (NGT group) and 48 with GDM (GDM group) at 24–28 weeks of gestation. GDM women were then tested again one year after childbirth (pGDM group: 14 women (29.2%) with abnormal glucose tolerance (AGT) and 34 women (70.8%) with normoglycemia). The GDM and NGT groups were closely matched for gestational age and parameters of obesity, such as pre-pregnancy body mass index (BMI), pregnancy weight, and gestational weight gain (GWG) (p > 0.05). Compared to the NGT group, the GDM and pGDM groups were hyperglycemic, but the GDM group featured a more highly insulin-resistant condition than the pGDM group, as reflected by higher fasting insulin (FI) levels and the values of the homeostasis model assessment for insulin resistance (HOMA-IR) (p < 0.05). In leukocytes from the GDM and pGDM groups, PIK3R1, SLC2A1, and SLC2A3 were upregulated and IRS1 was downregulated, with a larger magnitude in fold change (FC) values for PIK3R1 and IRS1 in the GDM group and for SLC2A1 and SLC2A3 in the pGDM group. The expression of SLC2A4 was unchanged in the GDM group but upregulated in the pGDM group, where it was inversely correlated with HOMA-IR (rho = −0.48; p = 0.007). Although the INSR and IRS2 levels did not significantly differ between the groups, the IRS2 transcript positively correlated with pregnancy weight, fasting plasma glucose, FI, and HOMA-IR in the GDM group. Our findings indicate that pronounced quantitative changes exist between the GDM and pGDM groups with respect to the expression of certain genes engaged in insulin signaling and glucose transport in leukocytes, with insulin resistance of a variable degree. These data also highlight the relationship of leukocyte SLC2A4 expression with insulin resistance in the postpartum period.
High-Yield Preparation and Characterization of Feline Albumin with Antioxidant Properties and In Vivo Safety
Authors: Deng Mengyin , Wu Quanlong , Yang Na , Teng Da , Wang Yexuan , Hao Ya , Lu Haiqiang , Mao Ruoyu , Wang Jianhua
Published: December 2024

To address the limited supply of serum albumin (SA) and potential pathogen contamination, focus has been concentrated on the heterologous expression of human serum albumin (HSA), particularly in Pichia pastoris. However, there are rare studies on feline serum albumin (FSA), which requires a large amount in pet foods and clinical treatment. In this work, the codon-optimized recombinant feline serum albumin (rFSA) sequence was designed and transferred into P. pastoris GS115 for recombinant expression. The high-level expression strain was selected by a high concentration of G418, followed by plate and shaker screening. At the 5 L fermenter level, the total protein concentration reached 3.89 mg/mL after 113 h of induction. At lower concentrations (1–4 μM), rFSA exhibited a potent free radical scavenging capacity, reaching 99% and 60% for ABTS+• and •O2−, respectively, which surpassed that of natural plasma-derived FSA. The secondary structure and stability of rFSA were found to be consistent with those of FSA. Additionally, an in vivo safety assay in mice showed no significant difference between the rFSA group and the normal saline group in terms of body weight changes, complete blood count, serum biochemistry, inflammatory factors, and tissue sections. These results above indicate that P. pastoris is the optimal host for the high preparation of rFSA. Furthermore, rFSA has been demonstrated to be relatively safe, which paves the way for subsequent industrialized production and its application in pet foods and veterinary clinics.
Analysis of Service Quality in Smart Running Applications Using Big Data Text Mining Techniques
Authors: Kim Jongho , Chung Jinwook
Published: December 2024

In the rapidly evolving digital healthcare market, ensuring both the activation of the market and the fulfillment of the product’s social role is essential. This study addresses the service quality of smart running applications by utilizing big data text mining techniques to bridge the gap between user experience and service quality in digital health applications. The research analyzed 264,330 app reviews through sentiment analysis and network analysis, focusing on key service dimensions such as system efficiency, functional fulfillment, system availability, and data privacy. The findings revealed that, while users highly value the functional benefits provided by these applications, there are significant concerns regarding system stability and data privacy. These insights underscore the importance of addressing technical and security issues to enhance user satisfaction and continuous application usage. This study demonstrates the potential of text mining methods in quantifying user experience, offering a robust framework for developing user-centered digital health services. The conclusions emphasize the need for continuous improvement in smart running applications to meet market demands and social expectations, contributing to the broader discourse on the integration of e-commerce and digital health.
Factors Affecting Customer Use Intention of MyData Services in the Fintech Industry
Authors: Yu An-Peng , Xu Chao , Cho Sung-Eui
Published: December 2024

This study investigates the factors affecting customer use intentions of MyData services in the fintech industry, focusing on the mediating role of perceived value across informational, security, and service dimensions. Six independent factors were defined, namely, transparency, controllability, reliability, security, diversity, and personalization, in the context of the abovementioned dimensions, and their associations with perceived value and customer use intention were analyzed. The regression analysis results from a survey of 291 participants reveal that transparency, controllability, security, diversity, and personalization significantly enhance perceived value, whereas transparency, security, and personalization directly impact customer use intentions. Furthermore, perceived value plays a mediating role for all factors, except for reliability. These findings show that the independent and mediating factors identified in this study are meaningful in analyzing the relationship between MyData services and customer use intentions in the fintech industry.