bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of deleterious variants associated with male infertility genes in a cohort of idiopathic hypospermatogenesis patients
Authors: Sharma Nisha , Halder Ashutosh , Kaushal Seema , Kumar Manoj , Jain Manish
Published: January 2025

Introduction

Hypospermatogenesis is a common histopathological subtype of non-obstructive azoospermia and is characterized by a decrease in the total number of germ cells within the seminiferous tubule as a result of spermatogenic failure. Determination of genetic factors before intracytoplasmic sperm injection can prevent the inheritance of these factors, as hypospermatogenesis patients gives high successful sperm retrieval rate. This study aimed to identify the structural variants associated with idiopathic hypospermatogenesis (iHS) by analyzing patient cohorts diagnosed with azoospermia using whole exome sequencing.

Methods

It is a hospital-based observational study in which patients reporting with azoospermia due to spermatogenic failure were recruited prospectively. Comprehensive clinical history, blood samples, semen analysis parameters, and reproductive endocrine evaluation reports of 51 hypospermatogenesis patients were collected. The known genetic causes were investigated using XY fluorescent in situ hybridization and Yq microdeletion for exclusion. Whole exome sequencing was performed, and the data of 42 iHS patients was analyzed to identify single nucleotide variants associated with diagnostically important male infertility genes.

Results

Genomic analysis of SNVs identified rare deleterious candidate variants in CFTR (c.1265C>T; p.Ser422Phe), CYP21A2 (c.955C>T; p.Gln319Glu), SRD5A2 (c.737G>A; p.Arg245Gln), LHCGR (c.378A>C; p.Lys126Asn) and AR (c.2179C>A; p.Arg727Ser) genes associated with 7/42 idiopathic hypospermatogenesis patients. In silico analysis of variants shows deleterious and probably damaging effects on canonical transcripts of the genes.

Discussion

This exploratory genomic analysis conducted on idiopathic hypospermatogenesis patients shows prevalence of rare deleterious candidate variants in genes associated with human male infertility. The candidate variants in idiopathic hypospermatogenesis patients are heterozygous and genotypically associated with syndromic male infertility. The symptomatic heterozygosity leading to mild spermatogenic failure resulting in hypospermatogenesis points towards a multifactorial etiology of the disease. This study justifies the importance of genetic screening of idiopathic hypospermatogenesis patients for the presence of structural variants in known human male infertility genes.
Impact of Entrepreneurship Support on Entrepreneurship Performance: A Sequential Exploratory Study
Authors: Xiong Rui , Sun Hongyi
Published: January 2025

Entrepreneurship support is undoubtedly necessary but often fails to meet expectations. To investigate the reasons behind this, a sequential exploratory methodology, with both qualitative and quantitative data, was used in this research. Within the Entrepreneurship Ecosystem (EE) paradigm, a conceptual model linking the macro environment, support system, support received, and entrepreneurship performance was developed based on qualitative data from 56 entrepreneurs’ responses and three in-depth interviews in Study 1. Then empirical data from a survey of 244 entrepreneurs was used to validate the model in Study 2. The findings identified two reasons for the ineffectiveness of entrepreneurship policies. One is the constraint imposed by the macro environment, which presents significant challenges for improvement, and the other arises from the policies themselves, which are improvable and require targeted attention. The research reminds policymakers to consider not only the quantity of support but also its quality. Our study refines the EE Microfoundation theory, particularly the causal and mediating mechanisms linking entrepreneurs to their EE.
Study on the Influencing Factors of Green Agricultural Subsidies on Straw Resource Utilization Technology Adopted by Farmers in Heilongjiang Province, China
Authors: Guo Cheng , Li Meng , Chen Hong
Published: January 2025

Due to climate, resource endowment, planting habits, policy publicity, subsidies, and constraints, there have been many problems in the utilization of straw resources in the cold, main grain-producing areas in northern China. Based on the theory of value perception, an analytical framework was constructed, and the ordered logistic model was used to form an empirical analysis of the questionnaire data of more than 60 townships in 7 cities of Heilongjiang Province, trying to analyze the problems existing in the utilization of straw resources. The results show that the external factors include policy subsidy, policy punishment, and transportation convenience. Among the internal reasons, farmers’ personal characteristics, production habits, and perception of technical effectiveness and convenience have a significant impact on the application of straw resource utilization technology. Therefore, improving the intensity and precision of subsidies, strengthening the intensity of punishment, improving the popularization of technology, strengthening the ideological education of farmers to clarify the ecological value of straw resource utilization, and strengthening the construction of infrastructure to improve the convenience of transportation are effective means to promote straw resource utilization technology and promote the green transformation of agriculture.
Community Readiness for Agro Living Lab (ALL) Projects: Factors Influencing Engagement of Young Urban Residents
Authors: Sroka Wojciech , Król Karol , Kulesza Jakub , Stanuch Marcin , Lisek Sławomir
Published: January 2025

The aim of this research is to analyze the drivers of young urban residents’ readiness to actively participate in agro living lab (ALL) projects, contributing to sustainable and resilient urban systems. This study is based on a literature review and a survey conducted among students from selected universities in Kraków. Using factor analysis and regression trees, the profiles of the individuals most inclined to participate in ALL projects were identified. The analysis included a wide range of variables, such as education, proximity to agriculture, perception of urban agriculture, and various sociodemographic characteristics. These findings indicate that readiness to engage in ALL projects is strongly associated with respondents’ field of study, interests, and individual experiences. Moreover, participants with positive attitudes toward urban agriculture and personal relationships with farmers were more likely to express a readiness to participate in ALLs. These results provide new insights into the social conditions influencing ALL participation and offer valuable guidance for developing strategies to promote the active engagement of urban populations in sustainable food initiatives.
Effects of Purple and Green-Colored Bottle Traps on Captures of Ambrosia Beetles in Ornamental Nurseries
Authors: Govindaraju Ramkumar , Joseph Shimat V.
Published: January 2025

The granulate ambrosia beetle, Xylosandrus crassiusculus (Motschulsky), and the black stem borer, Xylosandrus germanus (Blandford), are important pests in ornamental nurseries. The effects of monitoring trap color in capturing adult X. crassiusculus and X. germanus are mixed in the literature. Because the colorless bottle trap is commonly used to monitor ambrosia beetles in ornamental nurseries, it is unclear if adding purple or green, commonly used for collecting cerambycids and buprestids, would improve adult X. crassiusculus and X. germanus captures. Thus, the objective of this study was to compare the effect of purple or green-colored bottle traps with colorless bottle traps on captures of adult X. crassiusculus and X. germanus in ornamental nurseries. In 2023 and 2024, experiments were conducted using bottle traps baited with AgBio low-release ethanol lure (LR ethanol lure). Adding purple or green to the bottle trap did not improve captures of adult X. crassiusculus and X. germanus. Adult X. germanus captures were reduced in the green-bottle trap than in the colorless trap. The purple bottle trap did not collect more numbers of adult X. crassiusculus and X. germanus than the colorless bottle trap with LR ethanol lure. This suggests that adding purple or green to bottle traps did not provide additional value in monitoring ambrosia beetles in ornamental nurseries for management decisions.
Plasma Cardiac Troponin-I Concentration in Normal Horses and in Horses with Cardiac Abnormalities
Authors: Foreman Jonathan H. , Tennent-Brown Brett S. , Oyama Mark A. , Sisson D. David
Published: January 2025

Cardiac troponin-I (cTnI) is a highly sensitive and specific marker of myocardial injury detectable in plasma by immunoassay techniques. Inclusion criteria over a 3-year period required a diagnosis of cardiac disease accompanied by electrocardiographic (ECG) and cardiac ultrasound examinations (n = 23) in adult horses (≥2 years of age). A second group of normal adult ponies (n = 12) was studied as a reference group. Heparinized jugular venous blood samples were collected and centrifuged within 30 min, and the plasma was separated and frozen at −70 °C for subsequent batched cTnI analysis. The lower limit of detection was 0.01 ng/mL, and the upper limit was 100 ng/mL of plasma. Normal equine plasma cTnI concentrations ranged from 0.01 to 0.03 ng/mL (n = 12). Horses with non-arrhythmogenic murmurs (n = 4) included tricuspid (0.05 ng/mL cTnI), mitral (0.07), and aortic insufficiencies (0.01, 0.02). Horses with benign atrial fibrillation (n = 8) had a cTnI range of <0.01–0.09 ng/mL, with four horses having cTnI concentrations falling slightly outside the reference range (0.04, 0.05, 0.06, and 0.09). Horses with ventricular arrhythmias (ventricular premature contractions or ventricular tachycardia) and documentable myocardial toxicities or immunological reactions (n = 5) had cTnI concentrations of 0.05, 0.21, 0.31, 15.18, and >100 ng/mL. Horses with ventricular arrhythmias but no documentation of myocardial toxicity (n = 3) had cTnI concentrations of 0.34, 0.46, and 80.42 ng/mL. When grouped by arrhythmia type and compared using the Mann–Whitney Rank Sum Test, the median ventricular arrhythmia cTnI (0.40 ng/mL) was significantly higher than the median atrial fibrillation cTnI (0.04 ng/mL, p < 0.001). It was concluded that horses with myocardial toxicities and ventricular arrhythmias often had severe elevations in plasma cTnI.
Viperin and Its Effect on SVCV Replication in Common Carp, Cyprinus carpio
Authors: Meng Yan , Hu Xi , Jiang Nan , Fan Yuding , Li Yiqun , Xue Mingyang , Xu Chen , Liu Wenzhi , Zhou Yong
Published: January 2025

Viperin is an interferon-stimulated gene (ISG) that plays an important role in the congenital antiviral immunity of vertebrates. In this study, the common carp viperin (cc-viperin) gene is characterized, and we determine whether it has the ability to inhibit spring viremia of carp virus (SVCV) replication in EPC cells. The results showed that the full-length cDNA of the cc-viperin gene was 1044 bp and it encoded 348 amino acids. The cc-viperin sequence contained a leucine zipper in the N-terminal, a CxxxCxxC motif in the SAM domain, and a conservative C-terminus. The cc-viperin gene’s nucleotide and amino acid sequence alignment revealed that cc-viperin displayed relatively high sequence identity compared with other species. Phylogenetic analysis displayed the close relation of cc-viperin with Carassius auratus and Mylopharyngodon piceus. Subcellular localization analysis indicated that the cc-viperin protein was located in the cytoplasm. The gene expression results showed that cc-viperin was expressed in all of the tissues tested. Its expression level significantly increased in EPC cells after 24 h to 72 h compared to the control during SVCV infection. Moreover, cc-viperin significantly inhibited SVCV replication when it was overexpressed, whereas it increased SVCV replication when it had reduced expression in EPC cells, respectively. To summarize, the results obtained in this work show that cc-viperin shares similar sequence characteristics with other vertebrates, and it could inhibit SVCV replication in EPC cells, displaying an antiviral effect in common carp.
Comparative Outcomes of Meropenem–Vaborbactam vs. Ceftazidime–Avibactam Among Adults Hospitalized with an Infectious Syndrome in the US, 2019–2021
Authors: Zilberberg Marya D. , Nathanson Brian H. , Redell Mark A. , Sulham Kate , Shorr Andrew F.
Published: January 2025

Background/Objectives: Meropenem–vaborbactam (MEV) and ceftazidime–avibactam (CZA) are active against “urgent threat” pathogens like carbapenem-resistant Enterobacterales (CRE). However, few studies have compared outcomes between them. Methods: To explore comparative outcomes of MEV vs. CZA, we conducted a multicenter retrospective cohort study of all adult hospitalized patients with a serious infection (sepsis, urinary tract infection [UTI], complicated intraabdominal [cIAI] infection, or pneumonia) within the PINC AI Database, 2019–2021. Descriptive statistics compared the two groups along demographic and clinical characteristics, and multiple regression derived adjusted outcomes. Results: Among 1,989,765 patients who met enrollment criteria, 455 received MEV and 2320 CZA. Compared to CZA, patients on MEV were more commonly Caucasian (68.1% vs. 63.6%, p = 0.032) or Hispanic (21.8% vs. 12.8%, p < 0.001). Their mean [SD] Charlson comorbidity scores did not differ (3.6 [2.5] vs. 3.5 [2.5], p = 0.403). The most common index infection in both groups was pneumonia, though it was less prevalent in the MEV- than the CZA-treated group (48.1% vs. 56.8%, p = 0.001). Fewer than one-third of all patients received the respective drug within 2 days of the onset of the index infection (30.6% MEV vs. 33.0% CZA, p = 0.313). Fewer patients on MEV than CZA required mechanical ventilation (35.0% vs. 41.4%, p = 0.010). MEV treatment was associated with lower adjusted mortality (17.0% [95% CI 13.6%, 20.3%] vs. 20.6% [95% CI 19.0%, 22.2%], p = 0.048) relative to CZA. Conclusions: In this cohort of hospitalized patients treated with either MEV or CZA for their infectious syndrome, MEV was associated with lower adjusted hospital mortality, although the confidence intervals around the values overlapped.
Neurotoxic Effect of Myricitrin in Copper-Induced Oxidative Stress Is Mediated by Increased Intracellular Ca2+ Levels and ROS/p53/p38 Axis
Authors: Vlašić Ignacija , Krstačić-Galić Antonio , Horvat Anđela , Oršolić Nada , Sadžak Anja , Mandić Lucija , Šegota Suzana , Jazvinšćak Jembrek Maja
Published: January 2025

Although commonly appreciated for their anti-oxidative and neuroprotective properties, flavonoids can also exhibit pro-oxidative activity, potentially reducing cell survival, particularly in the presence of metal ions. Disrupted copper homeostasis is a known contributor to neuronal dysfunction through oxidative stress induction. This study investigated the effects of myricitrin (1–20 μg/mL) on copper-induced toxicity (0.5 mM CuSO4) in the neuroblastoma SH-SY5Y cell line. At non-toxic concentrations, myricitrin exacerbated copper’s toxic effects. The myricitrin-induced decrease in survival was accompanied with increased reactive oxygen species (ROS) production, reduced superoxide dismutase activity, and a lower GSH/GSSG ratio. In combination with copper, myricitrin also activated caspase-3/7, promoted nuclear chromatin changes, and compromised membrane integrity. At the protein level, myricitrin upregulated p53 and PUMA expression. The toxic effects of myricitrin were alleviated by the p38 inhibitor SB203580, the intracellular calcium chelator BAPTA-AM, and the NMDA receptor blocker MK-801, highlighting the significant role of the ROS/p53/p38 axis in cell death and the critical involvement of calcium ions in apoptosis induction. The atomic force microscopy was used to assess the surface morphology and nanomechanical properties of SH-SY5Y cells, revealing changes following myricitrin treatment. This research highlights the toxic potential of myricitrin and emphasizes the need for caution when considering flavonoid supplementation in conditions with elevated copper levels.
Learning-Based Model Predictive Control for Legged Robots with Battery–Supercapacitor Hybrid Energy Storage System
Authors: Shu Boyu , Huang Zhiwu , Ren Wanwan , Wu Yue , Li Heng
Published: January 2025

Electrically driven legged robots have become popular in recent years. However, the development of reliable energy supply systems and effective energy management strategies for legged robots with dramatically varying power requirements still needs to be explored. This article proposes a learning-based model predictive control (MPC) energy management strategy for legged robots with battery–supercapacitor hybrid energy storage systems containing a power prediction unit and an MPC with learning-based adaptive weights. Firstly, the mathematical model of the legged robot is established, and a dual-layer long short-term memory network is constructed to predict the load power demand, providing the model and measurable disturbance for the MPC. Secondly, a multi-objective optimization objective function is established for the MPC-based energy management strategy. Three normalized terms, battery capacity loss, battery power fluctuation, and supercapacitor state-of-charge regulation, are balanced in the objective function. Finally, a deep learning algorithm is proposed to adaptively adjust the three weighting factors to meet the diverse operation conditions. Hardware-in-the-loop experimental implementations demonstrate that the proposed method can improve the kinematic performance of the legged robot by maintaining the supercapacitor state of charge at a relatively high level and reducing the battery capacity loss by 12.7% compared with the conventional MPC method.
A Novel Dual-Function Drone Landing Gear with Ultra-Fast Grasping Capability Enabled by a Quick-Release Mechanism
Authors: Wang Chang , Kong Lingrui , Zhao Yan , Liu Chao , Liu Xuan , Zhang Jianhua
Published: January 2025

To simplify the grasping mechanism of drones, this paper presents a dual-function landing gear with an actively closing mechanism, designed for coaxial drones. The proposed design integrates self-locking and clutch mechanisms, enabling the landing gear to be actuated by a single motor. This novel approach eliminates the need for additional actuators, optimizing the drone’s takeoff, landing, and grasping capabilities while reducing energy consumption compared to traditional designs. Kinematic and static analyses, along with experimental evaluations, were conducted to assess the grasping performance of the mechanism. Experimental results demonstrate that the landing gear can close within 0.2 s and provide a grasping force exceeding 10 N. Compared to conventional designs, this solution offers a reliable and energy-efficient approach for dual-function drone operations.
Evaluation of Digital Asset Investment Platforms: A Case Study of Non-Fungible Tokens (NFTs)
Authors: Lee Ming-Fang , Li Jian-Ting , Lin Wan-Rung , Wang Yi-Hsien
Published: January 2025

According to the latest data from CryptoSlam, as of November 2024, NFT sales have approached USD 7.43 billion, with trading profits exceeding USD 33.303 million. In the buyer–seller market, the potential demand for NFT transactions continues to grow, leading to rapid development in the NFT market and giving rise to various issues, such as price manipulation, counterfeit products, hacking of investment platforms, identity verification errors, data leaks, and wallet security failures, all of which have caused significant financial losses for investors. Currently, the NFT investment market faces challenges such as legal uncertainty, information security, and high price volatility due to speculation. This study conducted expert interviews and adopted a two-stage research methodology to analyze the most common risk factors when selecting NFT investments. It employed the Decision-Making Trial and Evaluation Laboratory (DEMATEL) and the Analytic Network Process (ANP) to explore risk factors such as legal issues, security concerns, speculation, and price volatility, aiming to understand how these factors influence investors in choosing the most suitable NFT investment platform. The survey was conducted between February and June 2023, targeting professionals and scholars with over 10 years of experience in the financial market or financial research, with a total of 13 participants. The empirical results revealed that speculation had the greatest impact compared to legal issues, security concerns, and NFT price volatility. Speculation and price volatility directly influenced other risk factors, potentially increasing the risks faced by NFT investment platforms. In contrast, legal and security issues had less influence on other factors and were more affected by them, indicating a relatively lower likelihood of occurrence. Thus, investors must be cautious of short-term speculation, particularly when dealing with rare NFTs. The best approach is to set an exit price to minimize potential losses if the investment does not proceed as planned.
A Possible Solution to the Black Hole Information Paradox
Authors: Arraut Ivan
Published: January 2025

The information paradox suggests that the black hole loses information when it emits radiation. In this way, the spectrum of radiation corresponds to a mixed (non-pure) quantum state even if the internal state generating the black hole is expected to be pure in essence. In this paper we propose an argument solving this paradox by developing an understanding of the process by which spontaneous symmetry breaks when a black hole selects one of the many possible ground states and emits radiation as a consequence of it. Here, the particle operator number is the order parameter. This mechanism explains the connection between the density matrix, corresponding to the pure state describing the black hole state, and the density matrix describing the spectrum of radiation (mixed quantum state). From this perspective, we can recover black hole information from the superposition principle, applied to the different possible order parameters (particle number operators).
Characterization and Atmospheric Drivers of Nocturnal Ozone Enhancement in Putian City, China
Authors: Fang Chunsheng , Zhou Xiaowei , Cai Yuxuan , Wang Ju
Published: January 2025

The increasingly severe nocturnal ozone enhancement (NOE) event pollution is widely concerning. Therefore, based on the observed hourly O3 concentrations from 2015 to 2023, this study analyzes the characteristics of NOE events over Putian City. The analysis results show that the frequency of NOE events over Putian City is high, at about 127 days annually, with a high frequency in April and a low frequency in July and August. Most NOE events corresponded to a nocturnal O3 peak concentration (NOP) of <120 μg/m3. Moreover, they mainly occurred between 1:00–3:00 and 7:00. The physicochemical processes over Putian City in April, October, and November 2020 were simulated using the Weather Research and Forecasting (WRF, version 4.3.3) model coupled with the Community Multiscale Air Quality (CMAQ, version 5.4) model. The results suggest that O3 transport, especially horizontal transport from the eastern sea and Zhejiang Province and vertical transport from the upper atmosphere, could be the major cause of NOE events over Putian City. Furthermore, the nocturnal movement of the pollution zone, along with the aggregation of O3 due to weakened dry deposition and the influence of a stable boundary layer obstructed by mountain terrain, significantly influenced the overall O3 concentration. Thus, NOE events over Putian City stem from the interaction among these physicochemical processes. The study results emphasize the importance of O3 control in Putian City and suggest the implementation of strict joint regional control measures for to improve air quality.
Nonrelativistic Approximation in the Theory of a Spin-2 Particle with Anomalous Magnetic Moment
Authors: Ivashkevich Alina , Red’kov Viktor , Ishkhanyan Artur
Published: January 2025

We start with the 50-component relativistic matrix equation for a hypothetical spin-2 particle in the presence of external electromagnetic fields. This equation is hypothesized to describe a particle with an anomalous magnetic moment. The complete wave function consists of a two-rank symmetric tensor and a three-rank tensor that is symmetric in two indices. We apply the general method for performing the nonrelativistic approximation, which is based on the structure of the 50×50 matrix Γ0 of the main equation. Using the 7th-order minimal equation for the matrix Γ0, we introduce three projective operators. These operators permit us to decompose the complete wave function into the sum of three parts: one large part and two smaller parts in the nonrelativistic approximation. We have found five independent large variables and 45 small ones. To simplify the task, by eliminating the variables related to the 3-rank tensor, we have derived a relativistic system of second-order equations for the 10 components related to the symmetric tensor. We then take into account the decomposition of these 10 variables into linear combinations of large and small ones. In accordance with the general method, we separate the rest energy in the wave function and specify the orders of smallness for different terms in the arising equations. Further, after performing the necessary calculations, we derive a system of five linked equations for the five large variables. This system is presented in matrix form, which has a nonrelativistic structure, where the term representing additional interaction with the external magnetic field through three spin projections is included. The multiplier before this interaction contains the basic magnetic moment and an additional term due to the anomalous magnetic moment. The latter characteristic is treated as a free parameter within the hypothesis.
Ethanol Disrupts the Protective Crosstalk Between Macrophages and HBV-Infected Hepatocytes
Authors: Ganesan Murali , Pathania Anup S. , Bybee Grace , Kharbanda Kusum K. , Poluektova Larisa Y. , Osna Natalia A.
Published: January 2025

About 296 million people worldwide are living with chronic hepatitis B viral (HBV) infection, and outcomes to end-stage liver diseases are potentiated by alcohol. HBV replicates in hepatocytes, but other liver non-parenchymal cells can sense the virus. In this study, we aimed to investigate the regulatory effects of macrophages on HBV marker and interferon-stimulated genes (ISGs) expressions in hepatocytes. This study was performed on HBV-replicating HepG2.2.15 cells and human monocyte-derived macrophages (MDMs). We found that exposure of HepG2.2.15 cells to an acetaldehyde-generating system (AGS) increased HBV RNA, HBV DNA, and cccDNA expressions and suppressed the activation of ISGs, APOBEC3G, ISG15, and OAS1. Supernatants collected from IFNα-activated MDMs decreased HBV marker levels and induced ISG activation in AGS-treated and untreated HepG2.215 cells. These effects were reversed by exposure of MDMs to ethanol and mimicked by treatment with exosome release inhibitor GW4869. We conclude that exosome-mediated crosstalk between IFN-activated macrophages and HBV-replicating hepatocytes plays a protective role via the up-regulation of ISGs and suppression of HBV replication. However, ethanol exposure to macrophages breaks this protection.
The Relationship Between the Modulation of Intestinal Microbiota and the Response to Immunotherapy in Patients with Cancer
Authors: Radoš Laura , Golčić Marin , Mikolašević Ivana
Published: January 2025

The intestinal microbiota is an important part of the human body, and its composition can affect the effectiveness of immunotherapy. In the last few years, the modulation of intestinal microbiota in order to improve the effectiveness of immunotherapy has become a current topic in the scientific community, but there is a lack of research in this area. In this review, the goal was to analyze the current relevant literature related to the modulation of intestinal microbiota and the effectiveness of immunotherapy in the treatment of cancer. The effects of antibiotics, probiotics, diet, and fecal microbial transplantation were analyzed separately. It was concluded that the use of antibiotics, especially broad-spectrum types or larger quantities, causes dysbiosis of the intestinal microbiota, which can reduce the effectiveness of immunotherapy. While dysbiosis could be repaired by probiotics and thus improve the effectiveness of immunotherapy, the use of commercial probiotics without evidence of intestinal dysbiosis has not yet been sufficiently tested to confirm its safety for cancer for immunotherapy-treated cancer patients. A diet consisting of sufficient amounts of fiber, as well as a diet with higher salt content positively correlates with the success of immunotherapy. Fecal transplantation is a safe and realistic adjuvant option for the treatment of cancer patients with immunotherapy, but more clinical trials are necessary. Modulating the microbiota composition indeed changes the effectiveness of immunotherapy, but in the future, more human studies should be organized to precisely determine the types and procedures of microbiota modulation.
Advances in Cell and Immune Therapies for Melanoma
Authors: Timis Tanase , Buruiana Sanda , Dima Delia , Nistor Madalina , Muresan Ximena Maria , Cenariu Diana , Tigu Adrian-Bogdan , Tomuleasa Ciprian
Published: January 2025

The incidence rate of cutaneous melanoma is on the rise worldwide, due to increased exposure to UV radiation, aging populations, and exposure to teratogen agents. However, diagnosis is more precise, and the increased number of new cases is related to the improved diagnosis tools. Despite better early diagnosis and better therapies, melanoma has remained a significant public health challenge because of its aggressive behavior and high potential for metastasis. In 2020, cutaneous melanoma constituted approximately 1.3% of all cancer deaths that occurred within the European Union, thereby highlighting the necessity for effective prevention, timely diagnosis, and sustainable treatment measures, especially as a growing number of cases occur among younger patients. Melanoma is regarded as one of the most inflamed cancers due to its high immune cell presence and strong response to immunotherapy, fueling the need for development of immune-driven innovative treatments. Approved therapies, including immune checkpoint inhibitors (e.g., anti-PD-1 and anti-CTLA-4), have notably improved survival rates in melanoma. However, the limitations of the PD-1/PD-L1 and CTLA-4 axes inhibitors, such as low response rates, treatment resistance, and toxicity, have driven the need for continued research and advancements in treatment strategies. Current clinical trials are exploring various combinations of immune checkpoint inhibitors with costimulatory receptor agonists, chemotherapy, targeted therapies, and other immunotherapies, with the goal of improving outcomes and reducing side effects for melanoma patients. Emerging approaches, including adoptive cell therapy with tumor-infiltrating lymphocytes (TILs) and oncolytic virotherapy, are showing promise. While CAR-T cell therapy has been less successful in melanoma compared to blood cancers, ongoing research is addressing challenges like the tumor microenvironment and antigen specificity. This review provides an overview of the requirement for advances in these medications, to mark a significant step forward in melanoma management, set to bring a fresh breath of hope for patients.
Deep Convolutional Framelets for Dose Reconstruction in Boron Neutron Capture Therapy with Compton Camera Detector
Authors: Didonna Angelo , Ramos Lopez Dayron , Iaselli Giuseppe , Amoroso Nicola , Ferrara Nicola , Pugliese Gabriella Maria Incoronata
Published: January 2025

Background: Boron neutron capture therapy (BNCT) is an innovative binary form of radiation therapy with high selectivity towards cancer tissue based on the neutron capture reaction 10B(n,α)7Li, consisting in the exposition of patients to neutron beams after administration of a boron compound with preferential accumulation in cancer cells. The high linear energy transfer products of the ensuing reaction deposit their energy at the cell level, sparing normal tissue. Although progress in accelerator-based BNCT has led to renewed interest in this cancer treatment modality, in vivo dose monitoring during treatment still remains not feasible and several approaches are under investigation. While Compton imaging presents various advantages over other imaging methods, it typically requires long reconstruction times, comparable with BNCT treatment duration. Methods: This study aims to develop deep neural network models to estimate the dose distribution by using a simulated dataset of BNCT Compton camera images. The models pursue the avoidance of the iteration time associated with the maximum-likelihood expectation-maximization algorithm (MLEM), enabling a prompt dose reconstruction during the treatment. The U-Net architecture and two variants based on the deep convolutional framelets framework have been used for noise and artifact reduction in few-iteration reconstructed images. Results: This approach has led to promising results in terms of reconstruction accuracy and processing time, with a reduction by a factor of about 6 with respect to classical iterative algorithms. Conclusions: This can be considered a good reconstruction time performance, considering typical BNCT treatment times. Further enhancements may be achieved by optimizing the reconstruction of input images with different deep learning techniques.
New Insights in Microplastic Cellular Uptake Through a Cell-Based Organotypic Rainbow-Trout (Oncorhynchus mykiss) Intestinal Platform
Authors: Verdile Nicole , Cattaneo Nico , Camin Federica , Zarantoniello Matteo , Conti Federico , Cardinaletti Gloriana , Brevini Tiziana A. L. , Olivotto Ike , Gandolfi Fulvio
Published: January 2025

Microplastics (MPs) in fish can cross the intestinal barrier and are often bioaccumulated in several tissues, causing adverse effects. While the impacts of MPs on fish are well documented, the mechanisms of their cellular internalization remain unclear. A rainbow-trout (Oncorhynchus mykiss) intestinal platform, comprising proximal and distal intestinal epithelial cells cultured on an Alvetex scaffold, was exposed to 50 mg/L of MPs (size 1–5 µm) for 2, 4, and 6 h. MP uptake was faster in RTpi-MI compared to RTdi-MI. Exposure to microplastics compromised the cellular barrier integrity by disrupting the tight-junction protein zonula occludens-1, inducing significant decreases in the transepithelial-electrical-resistance (TEER) values. Consequently, MPs were internalized by cultured epithelial cells and fibroblasts. The expression of genes related to endocytosis (cltca, cav1), macropinocytosis (rac1), and tight junctions’ formation (oclna, cldn3a, ZO-1) was analyzed. No significant differences were observed in cltca, oclna, and cldn3a expression, while an upregulation of cav1, rac1, and ZO-1 genes was detected, suggesting macropinocytosis as the route of internalization, since also cav1 and ZO-1 are indirectly related to this mechanism. The obtained results are consistent with data previously reported in vivo, confirming its validity for identifying MP internalization pathways. This could help to develop strategies to mitigate MP absorption through ingestion.
TGFβ1 Restores Energy Homeostasis of Human Trophoblast Cells Under Hyperglycemia In Vitro by Inducing PPARγ Expression, AMPK Activation, and HIF1α Degradation
Authors: Khiat Nihad , Girouard Julie , Kana Tsapi Emmanuelle Stella , Vaillancourt Cathy , Van Themsche Céline , Reyes-Moreno Carlos
Published: January 2025

Elevated glucose levels at the fetal–maternal interface are associated with placental trophoblast dysfunction and increased incidence of pregnancy complications. Trophoblast cells predominantly utilize glucose as an energy source, metabolizing it through glycolysis in the cytoplasm and oxidative respiration in the mitochondria to produce ATP. The TGFβ1/SMAD2 signaling pathway and the transcription factors PPARγ, HIF1α, and AMPK are key regulators of cell metabolism and are known to play critical roles in extravillous trophoblast cell differentiation and function. While HIF1α promotes glycolysis over mitochondrial respiration, PPARγ and AMPK encourage the opposite. However, the interplay between TGFβ1 and these energy-sensing regulators in trophoblast cell glucose metabolism remains unclear. This study aimed to investigate whether and how TGFβ1 regulates energy metabolism in trophoblast cells exposed to normal and high glucose conditions. The trophoblast JEG-3 cells were incubated in normal (5 mM) and high (25 mM) glucose conditions for 24 h in the absence and the presence of TGFβ1. The protein expression levels of phosphor (p)-SMAD2, GLUT1/3, HIF1α, PPARγ, p-AMPK, and specific OXPHOS protein subunits were determined by western blotting, and ATP and lactate production by bioluminescent assay kits. JEG-3 cells exposed to 25 mM glucose decreased ATP production but did not affect lactate production. These changes led to a reduction in the expression levels of GLUT1/3, mitochondrial respiratory chain proteins, and PPARγ, coinciding with an increase in HIF1α expression. Conversely, TGFβ1 treatment at 25 mM glucose reduced HIF1α expression while enhancing the expression levels of GLUT1/3, PPARγ, p-AMPK, and mitochondrial respiratory chain proteins, thereby rejuvenating ATP production. Our findings reveal that high glucose conditions disrupt cellular glucose metabolism in trophoblast cells by perturbing mitochondrial oxidative respiration and decreasing ATP production. Treatment with TGFβ1 appears to counteract this trend, probably by enhancing both glycolytic and mitochondrial metabolism, suggesting a potential regulatory role of TGFβ1 in placental trophoblast cell glucose metabolism.
Schwann Cells in Neuromuscular Disorders: A Spotlight on Amyotrophic Lateral Sclerosis
Authors: Moss Kathryn R. , Saxena Smita
Published: January 2025

Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disease primarily affecting motor neurons, leading to progressive muscle atrophy and paralysis. This review explores the role of Schwann cells in ALS pathogenesis, highlighting their influence on disease progression through mechanisms involving demyelination, neuroinflammation, and impaired synaptic function. While Schwann cells have been traditionally viewed as peripheral supportive cells, especially in motor neuron disease, recent evidence indicates that they play a significant role in ALS by impacting motor neuron survival and plasticity, influencing inflammatory responses, and altering myelination processes. Furthermore, advancements in understanding Schwann cell pathology in ALS combined with lessons learned from studying Charcot–Marie–Tooth disease Type 1 (CMT1) suggest potential therapeutic strategies targeting these cells may support nerve repair and slow disease progression. Overall, this review aims to provide comprehensive insights into Schwann cell classification, physiology, and function, underscoring the critical pathological contributions of Schwann cells in ALS and suggests new avenues for targeted therapeutic interventions aimed at modulating Schwann cell function in ALS.
Evaluating Genioplasty Procedures: A Systematic Review and Roadmap for Future Investigations
Authors: Dalmeijer Sebastiaan W. R. , Riet Tom C. T. van , Ho Jean-Pierre T. F. , Becking Eddy (A. G.)
Published: January 2025

Study design: Systematic review. Objective: This systematic review examines the existing literature concerning the objective and subjective evaluations of osseous genioplasty outcomes. Methods: A comprehensive search was conducted in databases including PubMed, Embase, and Web of Science, yielding 2563 references, which were screened by two independent reviewers. We included 105 articles originating from 25 different countries. Data were systematically extracted, categorized, and documented. Results: Genioplasty was performed in 5218 patients, either independently (3560 cases) or in combination with other orthognathic procedures (1696 cases), with a predominant focus on female patients (64%). Objective evaluation primarily focused on surgical accuracy, relapse, and neurosensory disturbance, while subjective assessments were largely related to aesthetics and patient satisfaction. Despite significant advancements in three-dimensional surgical planning and assessment, the review highlights a lack of standardized methods for evaluating isolated genioplasty outcomes. Conclusions: The findings emphasize the need for improved and validated instruments that specifically assess the functional and aesthetic results of genioplastic surgery. Future research should prioritize patient-centered prospective studies and the development of assessment tools to ensure more comprehensive and reliable outcome evaluations.
Tara Gum Nanochitosan-Based Coatings to Extend Guava Shelf-Lives
Authors: Schlogl Andersen Escobar , Bianchi Jhonatan Rafael de Oliveira , Gonçalves Liliane de Paula , Magalhães George Lucas da Silva , Aguiar Ana Claudia Arcanjo da Silva , Lopes Ranieli Paiva , de Oliveira Junior Ênio Nazaré , Coimbra Jane Sélia dos Reis , Santos Igor José Boggione
Published: January 2025

Active packaging has emerged as a promising technological alternative for coating fruits and extending their shelf life. In this study, we developed a Tara gum and chitosan nanostructure-based coating, assessing its effects on guava shelf life and antifungal activity. In vitro analyses showed that nanochitosan suspension concentrations between 4.5 and 5.625 mg·mL−1 completely inhibited the growth of the fungus Colletotrichum gloeosporioides and reduced the growth of Puccinia psidii. In in vivo tests, guavas coated with a 1.5% (w/v) Tara gum coating with 0.5% (v/v) nanochitosan exhibited significantly delayed or no lesion growth, unlike the control group, where lesions developed continuously. Beyond antifungal results, the Tara gum and nanochitosan coatings maintained the guava’s luminescence for up to 16 days, reduced weight loss, and preserved firmness compared to the control group. Firmness tests indicated that Tara gum, both pure and at 0.1% and 0.3% (v/v) concentrations, was effective in preserving this characteristic. Chemically, the coating also contributed to increased pH and acidity of the guavas, although a reduction in reducing and total sugars was observed in all groups. These findings confirm that the Tara gum with nanochitosan-based coating is an effective nanotechnological biomaterial to extend the shelf life of seasonal fruits, acting as a physical and biological barrier against pathogens and supporting post-harvest preservation.
From Integer Programming to Machine Learning: A Technical Review on Solving University Timetabling Problems
Authors: Gu Xin , Krish Muralee , Sohail Shaleeza , Thakur Sweta , Sabrina Fariza , Fan Zongwen
Published: January 2025

Solving the university timetabling problem is crucial as it ensures efficient use of resources, minimises scheduling conflicts, and enhances overall productivity. This paper presents a comprehensive review of university timetabling problems using integer programming algorithms. This study explores various integer programming techniques and their effectiveness in optimising complex scheduling requirements in higher education institutions. We analysed 95 integer programming-based models developed for solving university timetabling problems, covering relevant research from 1990 to 2023. The goal is to provide insights into the evolution of these algorithms and their impact on improving university scheduling. We identify that the implementation rate of models using integer programming is 98%, which is much higher than 34% implementation rates using meta-heuristics algorithms from the existing review. The integer programming models are analysed by the problem types, solutions, tools, and datasets. For three types of timetabling problems including course timetabling, class timetabling, and exam timetabling, we dive deeper into the commercial solvers CPLEX (47), Gurobi (11), Lingo (5), Open Solver (4), C++ GLPK (4), AIMMS (2), GAMS (2), XPRESS (2), CELCAT (1), AMPL (1), and Google OR-Tools CP-SAT (1) and identify that CPLEX is the most frequently used integer programming solver. We explored the uses of machine learning algorithms and the hybrid solutions of combining the integer programming and machine learning algorithms in higher education timetabling solutions. We also identify areas for future work, which includes an emphasis on using integer programming algorithms in other industrial areas, and using machine learning models for university timetabling to allow data-driven solutions.
Quantum Chemical Topological Analysis of [2Fe2S] Core in Novel [FeFe]-Hydrogenase Mimics
Authors: Matczak Piotr
Published: January 2025

Synthetic mimics of the active site of [FeFe]-hydrogenase enzymes are important in the context of catalytic hydrogen production for future energetic applications. Providing a detailed quantum chemical description of the catalytic center of such mimics contributes to a better understanding of their behavior in hydrogen production processes. In this work, the analysis of bonds in the butterfly [2Fe2S] core in a series of complexes based on recently synthesized [FeFe]-hydrogenase mimics has been carried out using a wide range of quantum chemical topological methods. This series includes hexacarbonyl diiron dithiolate-bridged complexes with the bridging ligand bearing a five-membered carbon ring functionalized with diverse groups. The quantum theory of atoms in molecules (QTAIM) and the electron localization function (ELF) provided detailed characteristics of Fe–Fe and Fe–S bonds in the [2Fe2S] core of the complexes. A relatively small amount of strongly delocalized electron charge is attributed to the Fe–Fe bond. It was established how the topological parameters of the Fe–Fe and Fe–S bonds are affected by the five-membered carbon ring and its functionalization in the bridging dithiolate ligand. Next, one of the first applications of the interacting quantum atoms (IQA) method to [FeFe]-hydrogenase mimics was presented. The pairwise interaction between the metal centers in the [2Fe2S] core turns out to be destabilizing in contrast to the Fe–S interactions responsible for the stabilization of the entire core.