bluuebunny/crossref_metadata_2025 huggingface dataset:
From Guidelines to Lifelines—An Ethnographic Study of How Diabetes Management Is Emplotted During Clinical Encounters with Young Adults with Type 1 Diabetes
Authors: Schønning Signe Hellung , Wahlberg Ayo , Hommel Eva , Grabowski Dan
Published: February 2025

Background/Objectives: Working with young adults with T1D in outpatients clinic entails achieving a delicate balance between maintaining trust and improving diabetes management. By looking at the interactions between healthcare professionals and young adults with T1D as narrative emplotment, this article seeks to investigate how illness narratives are part of and actively worked on in consultations. Methods: Based on ethnographic observations of fourteen consultations with young adults 18–23 years of age, three narrative strategies to promote better diabetes management among the young adults were identified: (1) replacing sub-optimal practice with technology, (2) encouraging enhanced autonomy, and (3) setting realistic standards for diabetes care. Each strategy works to create a meaningful explanation for experienced challenges, formingas a basis for improved diabetes self-management. Results: Consultations were found to create a space where the meaning of living with an illness can be discussed between the healthcare professionals and the patients. Conclusions: Looking at how this meaning is negotiated in the consultations is an important aspect of understanding how daily diabetes management is made practicable, especially when working with young adults who are constituting their identities and often live with sub-optimal glycaemic control.
Implementation and Evaluation of a Training Program to Improve Patient Navigators’ Competencies: A Quasi-Experiment at a Public Tertiary Hospital in China
Authors: Liu Shuo , Tang Weiwei , Chang Qing , Lei Jueming , Yue Haitao , Hou Linjie , Morlock Laura
Published: February 2025

Background/Objectives: Patient navigation is vital for improving healthcare accessibility and patient experience in China’s public hospitals, where high patient demand meets limited medical resources. Patient navigators (PNs) assist patients through the complex healthcare system, but the lack of standardized training and evaluation hampers their ability to meet patient needs. This study piloted a Competencies Improvement Training Program (CITP) in a tertiary hospital to clarify PN competencies, design a feasible curriculum, assess its efficacy, and share insights with peer hospitals. Methods: The CITP used the Plan–Do–Check–Act (PDCA) framework and designed a curriculum with Miller’s Pyramid Model. Over 6 months, eight sessions were conducted, including theory, case studies, etc. The quasi-experimental design compared PN competencies and patient satisfaction before and after. Multiple instruments measured baseline competencies and program efficacy with a 6-month post-training follow-up. Results: A total of 75 PNs (75%) participated and completed all sessions. A total of 1189 patients were surveyed before training, 495 in the first month after training, and 502 in the 6-month follow-up. The CITP significantly boosted PN competency scores from 90.259 to 95.453, though it dipped to 92.721 by 6 months. Patient satisfaction with PN services improved modestly over 6 months. Challenges in applying theoretical knowledge to practical skills were noted, suggesting differentiated training based on navigator demographics. Patient satisfaction for aspects like politeness and tone was linked to patient age and education. Conclusions: The CITP enhanced PN core competencies and provided an evidence-based curriculum model. Future research should involve larger multi-center populations with longer-term follow-ups to validate the program’s effectiveness across diverse settings.
Perceived Harm to Pet Health Associated with Human Quality of Life After a Public Health Disaster
Authors: Haggerty Diana K. , Wahl Robert , Jones Nicole , LaChance Jenny , Hanna Mona
Published: February 2025

This study’s goal was to evaluate associations of human exposure to unfiltered tap water during the Flint water crisis (FWC) with perceived harm to pets from exposure to contaminated water. We also explored the associations of perceived pet harm with participants’ self-reported general, physical, and mental health, as well as quality of life. Adult (n = 3264) pet owners from a public health registry reported unfiltered tap water exposure, perceived pet health, and general health/quality of life at baseline, as well as health/quality of life 1 year later (n = 1172). Using frequencies, percentages, and odds ratios, we evaluated associations of unfiltered tap water consumption with perceived pet health (cross-sectional) and perceived pet health with general health and quality of life (cross-sectional and longitudinal). Daily unfiltered tap water drinkers were 3.12 (95% CI: 2.33–4.23) times more likely to report the FWC had made their pet ill compared to participants who never drank unfiltered water. Participants who reported Flint water made their pet ill had approximately a two-fold increase in odds of reporting poor/fair across all four health/quality-of-life measures compared to those who did not. Both animals and humans were exposed and impacted by the FWC. This study supports the interconnectedness between human and animal health, especially regarding environmental disaster exposure and outcomes.
“Sometimes We Can’t Afford the Healthy Stuff”: Perceptions of Cardiovascular Disease Risk and Healthy Food Accessibility Among Black Women Living in Public Housing
Authors: Sullivan Alisia , Smith India M. , Blue Chanel D. , White Brandi M.
Published: February 2025

African American women living in public housing carry a heavy burden of cardiovascular disease. Eating a heart-healthy diet is crucial to achieving optimal heart health, yet this health disparity population encounters major barriers to healthy eating. This study explored their perceptions of healthy eating and cardiovascular disease. Participants were recruited from public housing in a mid-sized city. Six 2-h focus groups with 32 women were conducted. Focus groups were analyzed using deductive coding. The major focus group findings focused on a limited access to affordable healthy foods. Participants also discussed the use of cost control measures to maximize household food budgets to access healthy foods and the ability to eat healthily. Our findings indicate that food insecurity persists for the populations most at-risk for cardiovascular disease. Plant-based diets may offer a culturally sensitive, innovative, and sustainable approach to reducing heart health risks, alleviating food insecurity, and promoting optimal health outcomes.
Financial Markets Effect on Cryptocurrency Volatility: Pre- and Post-Future Exchanges Collapse Period in USA and Japan
Authors: Alsulami Faizah , Raza Ali
Published: February 2025

This study is the first to scientifically investigate stock indices and currency exchanges that affect crypto price volatility pre and post the FTX (Future Exchanges) collapse event. Weekly series from 1 January 2020 to 31 December 2024 were utilized for the analysis. The ARDL model suggests positive symmetric short- and long-term effects of USA stock indices on Bitcoin and Ethereum prices (p < 0.10), while Japanese stock indices and currency exchanges have negative symmetric short- and long-term effects on Bitcoin and Ethereum price volatility (p < 0.10). The global index MSCI has no symmetric effect. The asymmetric approach NARDL suggests positive and negative asymmetric short- and long-term effects of USA and Japanese stock indices and currency exchanges on Bitcoin and Ethereum price volatility (p < 0.05). This research helps exchange brokers and crypto traders diversify their holdings, reduce stock index and currency exchange risk, and accurately predict Bitcoin and Ethereum price variations.
Regulation of the H1 Type VI Secretion System by the Transcriptional Regulator NfxB in Pseudomonas aeruginosa
Authors: Liu Shuhui , Wu Ziyuan , Yan Wenbo , Liu Qian , Zhao Yuanli , Gao Tingting , Yang Yiming , Cao Linke , Tao Ruixue , Li Meng , Liu Lijun , Zhang Yani , Wang Tietao
Published: February 2025

The type VI secretion system (T6SS) is a widely distributed molecular apparatus found in most Gram-negative bacteria. Studies show that T6SSs have functions in bacterial virulence, inter- and intra-bacterial competition, and environmental adaptation. Pseudomonas aeruginosa, an opportunistic pathogen, harbors three T6SS gene clusters that perform diverse roles in clinical infection. Herein, using DNA affinity chromatography of the H1-T6SS promoter, the fluoroquinolone antibiotic resistance regulator NfxB was identified. Further studies demonstrated that NfxB negatively regulates the expression of H1-T6SS by directly binding to its promoter region. T6SS expression and effector secretion are regulated by the fluoroquinolone antibiotic via NfxB, which enhances inter-bacterial competition in the complex bacterial ecology. Meanwhile, the deletion of nfxB alters carbenicillin resistance through an unknown pathway. This study provides new insights into the regulation of T6SS by environmental signals, and it provides data support for antibiotic resistance and inter-bacterial competition due to T6SSs.
Immunophenotypic Implications of Reverse-Circadian Glucocorticoid Treatment in Congenital Adrenal Hyperplasia
Authors: Nowotny Hanna F. , Choi Hannah , Ziegler Selina , Doll Natalie , Bäuerle Ariane , Welp Ann-Christin , Dubinski Ilja , Schiergens Katharina , Neumann Uta , Tschaidse Lea , Auer Matthias K. , Rothenfusser Simon , Schmidt Heinrich , Reisch Nicole
Published: February 2025

Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH) requires lifelong glucocorticoid replacement to manage cortisol deficiency and excessive androgen production. Conventional circadian treatment (CT) tries to mimic natural cortisol rhythms, whereas reverse-circadian treatment (RC) prioritizes the suppression of adrenal androgen excess overnight through evening dosing. Limited data exist on the immunological impact of these regimens. A bi-centric study was conducted, including 41 pediatric and adolescent CAH patients. Peripheral blood samples were collected from patients on conventional treatment (n = 38) or RC (n = 16), with 11 RC patients switching to conventional treatment. Immune cell phenotypes, cytokine profiles, and natural killer (NK) cell cytotoxicity were assessed. Patients receiving RC showed lower percentages of CD4+CD25+ T cells (p = 0.0139). After the switch, patients with RC presented with a higher percentage of non-classical monocytes (p = 0.0255) and a lower percentage of Th17 cells (p = 0.0195). A lower expression of CD107 was observed with RC (p < 0.0001), as well as a higher percentage of NKp30 (p = 0.0189). Comparing patients after the switch from RC to HC, patients with RC presented with a lower NKG2D expression (p = 0.0420). Both conventional treatment and RC exhibited distinct immunological impacts, with CT showing modest advantages in normalizing immune phenotypes. These findings suggest that CT may offer immunological benefits for managing young patients with congenital adrenal hyperplasia.
Dynamic Impacts of Stock Enhancement on Kaluga Sturgeon (Huso dauricus): Novel Conservation Strategy Insights from the Gut Microbe Composition and Gene Expression Mode
Authors: Li Yutao , Wang Ruoyu , Zhai Cunhua , Cao Dingchen , Sun Zhipeng , Zhang Ying , Ma Bo
Published: February 2025

The sturgeon population has experienced strict threats due to inordinate human activities in the last decade and has been classified into the Red List of Threatened Species in recent years. Stock enhancement is one effective practice for the conservation of wild sturgeons. However, the survival conditions for sturgeon were not satisfactory after they were directly restocked into their natural habitat. Huso dauricus is an important protected sturgeon species, and finding an appropriate conservation strategy for the wild population is urgent. To clarify the dynamic adaptability of Huso dauricus to its wild environment, 1000 individuals were released into a natural river. On the 0th, 7th, 14th, and 30th days, five recaptured individuals were used to evaluate the dynamic trends in biochemical biomarkers, intestinal histomorphology, gut microbe taxon composition, and transcription profile over 30 days of stock enhancement. Our results indicated that Huso dauricus individuals still had a physiological stress status on the seventh day and then gradually adapted to the wild habitat 14 days after reintroduction based on the serum cortisol level. Meanwhile, the feeding habitat, organ function indicators, and growth performance showed similar dynamic changes within 30 days. Interestingly, their gut bacterial diversity and taxon structure also fluctuated over the 30 days after restocking, and they were accompanied by dynamic changes in intestinal pathological injury and tight junction protein expression in this period. The transcriptome analysis revealed the dynamic adaptability of Huso dauricus to wild habitats associated with the expression modes of genes related to the FoxO family, immune system, cytochrome family, and ATP metabolism. Taken together, the findings of the present research demonstrated that artificial reintroduction had dynamic impacts on the health condition of Huso dauricus and that 14 days of wilderness training might be essential for sturgeon restocking practices. Our study revealed the adaption mechanism of Huso dauricus at the molecular level during the restocking period and shed light on the theoretical guidelines for wild sturgeon conservation.
Single-Cell RNA Sequencing in Unraveling Acquired Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: New Perspectives
Authors: Peng Lin , Deng Siyou , Li Jinjie , Zhang Yujie , Zhang Li
Published: February 2025

Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) have demonstrated remarkable efficacy in treating non-small cell lung cancer (NSCLC), but acquired resistance greatly reduces efficacy and poses a significant challenge to patients. While numerous studies have investigated the mechanisms underlying EGFR-TKI resistance, its complexity and diversity make the existing understanding still incomplete. Traditional approaches frequently struggle to adequately reveal the process of drug resistance development through mean value analysis at the overall cellular level. In recent years, the rapid development of single-cell RNA sequencing technology has introduced a transformative method for analyzing gene expression changes within tumor cells at a single-cell resolution. It not only deepens our understanding of the tumor microenvironment and cellular heterogeneity associated with EGFR-TKI resistance but also identifies potential biomarkers of resistance. In this review, we highlight the critical role of single-cell RNA sequencing in lung cancer research, with a particular focus on its application to exploring the mechanisms of EGFR-TKI-acquired resistance in NSCLC. We emphasize its potential for elucidating the complexity of drug resistance mechanism and its promise in informing more precise and personalized treatment strategies. Ultimately, this approach aims to advance NSCLC treatment toward a new era of precision medicine.
Direct Cloning and Heterologous Expression of the Dmxorosin Biosynthetic Gene Cluster from Streptomyces thermolilacinus SPC6, a Halotolerant Actinomycete Isolated from the Desert in China
Authors: Dong Maoxing , Feng Huyuan , Zhang Wei , Ding Wei
Published: February 2025

Streptomyces thermolilacinus SPC6 is a halotolerant strain isolated from the Linze Desert in China. It has a very high growth rate and short life cycle compared to other Streptomycetes, including the model organism Streptomyces coelicolor. The one strain–many compounds fermentation approach and global natural products investigation revealed that Streptomyces thermolilacinus SPC6 exhibits impressive productivity of secondary metabolites. Genome mining uncovered 20 typical secondary metabolic biosynthetic gene clusters (BGC), with a BGC dmx identified as completely silent. Subsequently, this cryptic BGC was successfully directly cloned and heterologously expressed in Streptomyces hosts, resulting in the discovery of a new lanthipeptide, dmxorosin. Notably, the proposed biosynthetic pathway indicates its potential as a basis for the synthetic biology of new lanthipeptide.
Cytotoxicity and Antibacterial Activity of Protonated Diallylammonium Polymers: Influence of End Groups and Molecular Weight
Authors: Timofeeva Larisa M. , Simonova Yulia A. , Eremenko Ivan V. , Filatova Marina P. , Topchiy Maxim A. , Kozobkova Nataliya V. , Shleeva Margarita O. , Eropkin Mikhail Yu.
Published: February 2025

A series of antimicrobial protonated diallylammonium polymers, poly(diallylammonium trifluoroacetate) (PDAATFA), were synthesized by classical polymerization, using an especially elaborated method for preparation of polymers with low molecular weight (MW), and by RAFT polymerization, with different end groups in a range of MW values of (8–43) × 103 g∙mol−1. Cytotoxicity relative to eukaryotic cells (epithelioid lines A-549 and MA-104) and bactericidal activity of the polymers (relative to Pseudomonas aeruginosa and Staphylococcus aureus) are investigated. The effect of the end groups and MW on toxicity and bactericidal activity is shown. Dependence of the activity and, most of all, cytotoxicity on MW is preserved even at a small difference in MW values in the MW range of (18–40) × 103 g·mol−1. A clear dependence of the studied properties on the nature of the terminal group is revealed. Sulfate -O-S(=O)2-O¯ end group has a noticeable effect on the bactericidal efficiency and smaller influence on toxicity, while dithiocarbonyl end group -S-C(=S)-O-CH2-CH3 has a significant effect on efficiency and especially toxicity, drastically increasing the latter. Overall, based on the results obtained, polymers PDAATFA of low MW are considered promising antimicrobial agents for the creation of new transdermal drugs.
Evaluation of Small-Molecule Candidates as Modulators of M-Type K+ Currents: Impacts on Current Amplitude, Gating, and Voltage-Dependent Hysteresis
Authors: Lu Te-Ling , Liutkevičienė Rasa , Rovite Vita , Gao Zi-Han , Wu Sheng-Nan
Published: February 2025

The core subunits of the KV7.2, KV7.3, and KV7.5 channels, encoded by the KCNQ2, KCNQ3, and KCNQ5 genes, are expressed across various cell types and play a key role in generating the M-type K+ current (IK(M)). This current is characterized by an activation threshold at low voltages and displays slow activation and deactivation kinetics. Variations in the amplitude and gating kinetics of IK(M) can significantly influence membrane excitability. Notably, IK(M) demonstrates distinct voltage-dependent hysteresis when subjected to prolonged isosceles-triangular ramp pulses. In this review, we explore various small-molecule modulators that can either inhibit or enhance the amplitude of IK(M), along with their perturbations on its gating kinetics and voltage-dependent hysteresis. The inhibitors of IK(M) highlighted here include bisoprolol, brivaracetam, cannabidiol, nalbuphine, phenobarbital, and remdesivir. Conversely, compounds such as flupirtine, kynurenic acid, naringenin, QO-58, and solifenacin have been shown to enhance IK(M). These modulators show potential as pharmacological or therapeutic strategies for treating certain disorders linked to gain-of-function or loss-of-function mutations in M-type K+ (KV7x or KCNQx) channels.
Nigrostriatal Degeneration Underpins Sensorimotor Dysfunction in an Inducible Mouse Model of Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS)
Authors: Kul Emre , Santos Mónica , Stork Oliver
Published: February 2025

Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder caused by moderately expanded CGG trinucleotide repeats in the 5′ untranslated region (UTR) of the FMR1 gene. Characterized by motor deficits such as action tremor and cerebellar gait ataxia, FXTAS is further distinguished by ubiquitin-positive intranuclear inclusions in neurons and glia. However, its clinical spectrum often overlaps with other neurodegenerative conditions such as Parkinson’s disease (PD). Sensorimotor gating deficits, commonly associated with disorders affecting the nigrostriatal pathway such as PD, have been reported in FXTAS, but the underlying connection between these two phenotypes remains undetermined. In this study, we used the P90CGG mouse model of FXTAS, which expresses 90 CGG repeats upon doxycycline induction, to investigate sensorimotor gating deficits and their relationship to nigrostriatal degeneration. After induction, the P90CGG model exhibited late-onset impairments in prepulse inhibition (PPI), a cross-species measure of sensorimotor gating. These deficits coincided with pronounced nigrostriatal degeneration but occurred without evidence of inclusion formation in the substantia nigra. Our findings highlight nigrostriatal degeneration, which has not previously been reported in animal models of FXTAS, and suggest a potential link to sensorimotor gating dysfunction within the context of the disorder.
Review of Elevated Para-Cresol in Autism and Possible Impact on Symptoms
Authors: Flynn Christina K. , Adams James B. , Krajmalnik-Brown Rosa , Khoruts Alexander , Sadowsky Michael J. , Nirmalkar Khemlal , Takyi Evelyn , Whiteley Paul
Published: February 2025

Para-cresol (p-cresol), and its primary human metabolite p-cresol sulfate (pCS), are among the most studied gut-derived metabolites relevant to autism spectrum disorder (ASD). P-cresol is produced by bacterial modification of phenylalanine or tyrosine and is one of many potentially deleterious metabolites produced by the gut microbiota. Seventeen studies have observed p-cresol and/or p-cresol sulfate as being higher in the urine of children with autism spectrum disorder (ASD) vs. controls. P-cresol has harmful effects on the body, including within the gut, brain, kidneys, liver, immune system, and mitochondria. Some of these effects may contribute to autism and comorbid symptoms. In the gut, p-cresol acts as an antibiotic, altering the gut microbiome to favor the bacteria that produce it. In the mitochondria, p-cresol disrupts ATP production and increases oxidative stress, which is also common in autism. In the brain, p-cresol impairs neuronal development. P-cresol inactivates dopamine beta-hydroxylase, which converts dopamine to noradrenaline. P-cresol sulfate impairs kidney function and is linked to chronic kidney disease (CKD), which is more common in ASD adults. P-cresol also interferes with immune function. Three animal studies have demonstrated that p-cresol causes autism-related symptoms in mice, and that mice can be recovered by the administration of fecal microbiota transplant from healthy mice. Similarly, it was found that microbiota transplant therapy treatment in children with ASD significantly reduced p-cresol sulfate levels to normal and led to significant improvements in gastrointestinal (GI) and ASD symptoms. In summary, p-cresol and pCS likely contribute to ASD core symptoms in a substantial subset of children with ASD.
Vitisin A Outperforms Cyanidin-3-O-Glucoside in Triglyceride Reduction by Modulating Hepatic Lipogenesis and Fatty Acid β-Oxidation
Authors: Li Yawen , Li Xusheng , Liu Jia , Jayavanth Pallavi , Bai Weibin , Jiao Rui
Published: February 2025

Pyranoanthocyanins exhibit greater bioactivity compared to monomeric anthocyanins, yet the lipid-lowering effects of pyranoanthocyanin Vitisin A, a primary derivative found in aged red wines, have not been extensively studied in vivo. This study evaluated the triglyceride-lowering effects of Vitisin A and its anthocyanin counterpart Cyanidin-3-O-glucoside (C3G) in both free fatty acid -induced HepG2 cells and high-fat diet-fed ApoE-/- mice, with a focus on their roles in lipid metabolism. In vitro, Vitisin A significantly reduced triglyceride levels and lipid accumulation in HepG2 cells compared to C3G at equivalent concentrate. In vivo, dietary supplementation with 100 mg/kg of Vitisin A reduced body weight gain and plasma triglyceride levels by 19.6% and 29.5%, respectively, whereas no significant effects were observed with C3G. Mechanistically, Vitisin A markedly inhibited hepatic de novo lipogenesis (DNL) by activating the AMPK/ACC signaling pathway and downregulating FASN expression. Concurrently, Vitisin A enhanced fatty acid β-oxidation more robustly than C3G by upregulating CPT-1A via AMPK/SIRT1/PGC-1α and PPAR-α/PGC-1α pathways. Both Vitisin A and C3G driving peroxisomal β-oxidation of very-long-chain fatty acids. In summary, Vitisin A demonstrated superior triglyceride-lowering effects compared to C3G, primarily through dual mechanisms of inhibiting hepatic DNL and enhancing fatty acid β-oxidation.
Liquid Chromatography Quadrupole Time-of-Flight Tandem Mass Spectrometry Characterization of Ethyl Acetate Fraction from Sargassum pallidum and Its Anti-Melanogenesis Effect in B16F10 Melanoma Cells and Zebrafish Model
Authors: Kim Wook-Chul , Kang Hyeon , Lee Seung-Hong
Published: February 2025

Melanin overproduction causes various skin diseases, such as spots, freckles, and wrinkles, resulting in the requirement of melanin synthesis inhibitors like 1-phenyl-2-thiourea (PTU) and kojic acid, which have been commonly used in the pharmaceutical industry. However, these inhibitors can cause side effects such as skin irritation and allergies. Therefore, it is necessary to develop safe and effective melanin inhibitors from natural resources. The purpose of this study was to investigate a whitening agent from natural substances using B16F10 melanoma cells and zebrafish model. We investigated the melanogenesis-inhibiting activities of the fractions from Sargassum pallidum extract. The ethyl acetate fraction from S. pallidum extract (SPEF) significantly decreased tyrosinase activity. SPEF also significantly reduced α-melanocyte stimulating hormone (MSH)-induced intracellular tyrosinase activity and melanin content in B16F10 cells. Moreover, SPEF inhibited the expression levels of key melanogenic proteins such as tyrosinase, TRP-1, TRP-2, and MITF by downregulating the phosphorylation levels of CREB and PKA in α-MSH-stimulated melanoma cells. Furthermore, SPEF significantly suppressed melanin synthesis in the zebrafish model with no developmental toxicity. LC-Q-TOF-MS/MS analysis identified that SPEF was composed of 12 phytochemical compounds, including diterpenes, which were the dominant metabolites. These results altogether show that SPEF effectively suppresses melanogenesis in B16F10 melanoma cells and in a zebrafish model, with potential for usage in pharmaceuticals and cosmeceuticals.
Small Heat Shock Proteins: Protein Aggregation Amelioration and Neuro- and Age-Protective Roles
Authors: Albinhassan Tahani H. , Alharbi Bothina Mohammed , AlSuhaibani Entissar S. , Mohammad Sameer , Malik Shuja Shafi
Published: February 2025

Protein misfolding, aggregation, and aberrant aggregate accumulation play a central role in neurodegenerative disease progression. The proteotoxic factors also govern the aging process to a large extent. Molecular chaperones modulate proteostasis and thereby impact aberrant-protein-induced proteotoxicity. These chaperones have a diverse functional spectrum, including nascent protein folding, misfolded protein sequestration, refolding, or degradation. Small heat shock proteins (sHsps) possess an ATP-independent chaperone-like activity that prevents protein aggregation by keeping target proteins in a folding-competent state to be refolded by ATP-dependent chaperones. Due to their near-universal upregulation and presence in sites of proteotoxic stress like diseased brains, sHsps were considered pathological. However, gene knockdown and overexpression studies have established their protective functions. This review provides an updated overview of the sHsp role in protein aggregation amelioration and highlights evidence for sHsp modulation of neurodegenerative disease-related protein aggregation and aging.
Mechanistic Insights into CYP199A4-Catalyzed α-Hydroxyketone Formation and Hydrogen Bond-Assisted C–C Bond Cleavage Catalyzed by the CYP199A4 F182L Mutant
Authors: Yuan Chang , Xu Jiaqi , Wang Shun , Fang Ye-Guang , Tan Hongwei
Published: February 2025

CYP199A4 is a cytochrome P450 and can catalyze the hydroxylation of 4-propionylbenzoic acid (4-pIBA) to generate α-hydroxyketone with high stereoselectivity. The F182L mutant of CYP199A4 (F182L-CYP199A4) has been shown to support the cleavage of the C–C bond between the carbonyl and hydroxyl groups of α-hydroxyketone, whereas wild-type CYP199A4 cannot. To uncover how the Phe182 regulates substrate reactivity, we conducted classical molecular dynamics (MD) and quantum mechanics/molecular mechanics (QM/MM) MD simulations on these systems. The results predicted that the formation of α-hydroxyketone preferentially led to the (S)-enantiomer. Moreover, the findings revealed that the F182L-CYP199A4 facilitated the formation of a hydrogen bond between the α-hydroxyketone and the reactive peroxoanion (POA) species. This interaction stabilized the α-hydroxyketone near POA and promoted the subsequent C–C bond cleavage. The mechanism of α-hydroxyketone formation and the subsequent C–C bond cleavage were elucidated by employing the hybrid density functional theory (DFT). The α-hydroxyketone formation mechanism involved C–H hydroxylation of 4-pIBA with a rate-limiting energy barrier of 17.1 kcal/mol. The C–C bond cleavage of α-hydroxyketone catalyzed by F182L-CYP199A4 occurred via a radical attack mechanism.
Anemia Classification System Using Machine Learning
Authors: Gómez Jorge Gómez , Parra Urueta Camilo , Álvarez Daniel Salas , Hernández Riaño Velssy , Ramirez-Gonzalez Gustavo
Published: February 2025

In this study, a system was developed to predict anemia using blood count data and supervised learning algorithms. Anemia, a common condition characterized by low levels of red blood cells or hemoglobin, affects oxygenation and often causes symptoms, such as fatigue and shortness of breath. The diagnosis of anemia often requires laboratory tests, which can be challenging in low-resource areas where anemia is common. We built a supervised learning approach and trained three models (Linear Discriminant Analysis, Decision Trees, and Random Forest) using an anemia dataset from a previous study by Sabatini in 2022. The Random Forest model achieved an accuracy of 99.82%, highlighting its capability to subclassify anemia types (microcytic, normocytic, and macrocytic) with high precision, which is a novel advancement compared to prior studies limited to binary classification (presence/absence of anemia) of the same dataset.
Efficient Sequestration of Heavy Metal Cations by [Mo2S12]2− Intercalated Cobalt Aluminum-Layered Double Hydroxide
Authors: Roy Subrata Chandra , Donley Carrie L. , Islam Saiful M.
Published: February 2025

Heavy metal cations such as Ag+, Pb2+, and Hg2+ can accumulate in living organisms, posing severe risks to biological systems, including humans. Therefore, removing heavy metal cations from wastewater is crucial before discharging them to the environment. However, trace levels and high-capacity removal of the heavy metals remain a critical challenge. This work demonstrates the synthesis and characterization of [Mo2S12]2− intercalated cobalt aluminum-layered double hydroxide, CoAl―Mo2S12―LDH (CoAl―Mo2S12), and its remarkable sorption properties for heavy metals. This material shows high efficiency for removing over 99.9% of Ag+, Cu2+, Hg2+, and Pb2+ from 10 ppm aqueous solutions with a distribution constant, Kd, as high as 107 mL/g. The selectivity order for removing these ions, determined from the mixed ion state experiment, was Pb2+ < Cu2+ ≪ Hg2+ < Ag+. This study also suggests that CoAl―Mo2S12 is not selective for Ni2+, Cd2+, and Zn2+ cations. CoAl―Mo2S12 is an efficient sorbent for Ag+, Cu2+, Hg2+, and Pb2+ ions at pH~12, with the removal performance of both Ag+ and Hg2+ cations retaining > 99.7% across the pH range of ~2 to 12. Our study also shows that the CoAl―Mo2S12 is a highly competent silver cation adsorbent exhibiting removal capacity (qm) as high as ~918 mg/g compared with the reported data. A detailed mechanistic analysis of the post-treated solid samples with Ag+, Hg2+, and Pb2+ reveals the formation of Ag2S, HgS, and PbMoO4, respectively, suggesting the precipitation reaction mechanism.
Effect of Boron and Iron at Various Concentrations on the Catalytic Graphitization of the Polyacrylonitrile Derived from the Polymerization of Acrylonitrile
Authors: Kim Taewoo , Kim Byoung-Suhk , Ko Tae Hoon , Kim Hak Yong
Published: February 2025

In this study, a novel and facile approach of catalytic graphitization was adopted for the preparation of graphitized polyacrylonitrile (PAN)-derived carbon. Pure PAN and boron-introduced PAN were derived from the monomer acrylonitrile using a polymerization technique. Iron nitrate nonahydrate at different concentrations (2.5%, 5%, and 10%) was added to the boronated PAN and carbonized at 1250 °C. The effect of iron and boron on the catalytic graphitization of PAN was comprehensively analyzed. The results showed that the boronated PAN containing a 5% Fe salt was more graphitized due to the optimized amount of the metallic iron, which promoted the rate of conversion of the amorphous carbon to graphitic carbon containing carbon nanotube (CNT) by rearranging the nearby carbon and reducing the energy barrier for the transformation. Furthermore, the in situ formed iron boron carbide within the graphitized carbon provided a nucleation site and stabilized the catalytic activity of the metallic iron at high temperature. This work presents a promising approach for obtaining a highly graphitic PAN-derived carbon by adopting a strategy of catalytic graphitization using the born and iron as catalytic agents.
Psychometric Properties of the Athletic Shoulder Test in Adolescent Tennis Players
Authors: Paliouras Achilleas , Porgiopoulou Marina , Varverakis Giorgos , Stavrakakis Giorgos , Strimpakos Nikolaos , Kapreli Eleni
Published: February 2025

Background/Objectives: The Athletic Shoulder Test (ASH) has been described as one of the most promising upper-extremity tests to assess performance in overhead athletes. Its high reliability rates, short testing period, and applicability in any environment with portable and cheap equipment have been highlighted as some of the advantages of the test. However, it has yet to be evaluated in a non-adult athletic population. Therefore, the aim of this study was to investigate the ASH test’s psychometric properties in a sample of young tennis players. Methods: A total of 33 adolescent tennis players were evaluated among two sessions with a week interval. Intra-rater, inter-rater, and test-retest reliability were investigated. Additionally, possible correlations with measures of rotational shoulder strength and upper-extremity performance were examined. Two novice physiotherapists performed all the measurements following appropriate training. Results: The relative reliability scores, as calculated by intraclass correlation coefficient (ICC) indices, were found to be excellent (ICC = 0.924–0.988). Standard error of measurement and minimal detectable change scores have been estimated per position (SEM = 2.74–7.06 N, MDC = 7.55–19.42N). Test-retest reliability provided slightly higher SEM and MDC scores on average (SEM = 3.33–6.47, MDC = 9.32–18.04) than intra-rater and inter-rater reliability. Associations between ASH and the two tests were found to be moderate to strong (r = 0.584–0.856), with the dominant arm providing higher correlation scores (r = 0.605–0.856) than the non-dominant one (r = 0.584–0.823). Absolute values were collected and are provided for all three upper-limb tests; normalized values were calculated for ASH and rotational strength and peak torque only for the ASH measurements. Conclusions: The excellent reliability rates establish the ASH test as a highly recommended testing protocol for adolescent tennis players.
A Systematic Review of Disappearing Colorectal Liver Metastases: Resection or No Resection?
Authors: Papakonstantinou Menelaos , Fantakis Antonios , Torzilli Guido , Donadon Matteo , Chatzikomnitsa Paraskevi , Giakoustidis Dimitrios , Papadopoulos Vasileios N. , Giakoustidis Alexandros
Published: February 2025

Background: Colorectal cancer is the second most common type of cancer and a leading cause of cancer-related deaths worldwide. Approximately 15% of the patients with colorectal cancer will already have liver metastases (CRLMs) at diagnosis. Luckily, the advances in chemotherapy regimens during the past few decades have led to increased rates of disease regression that could even render an originally unresectable disease resectable. In certain patients with CRLMs, the hepatic lesions are missing on preoperative imaging after neoadjuvant chemotherapy. These patients can undergo surgery with or without resection of the sites of the disappearing liver metastases (DLMs). In this systematic review, we assess the recurrence rate of the DLMs that were left unresected as well as the complete pathologic response of those resected. Methods: A literature search was conducted in PubMed for studies including patients with CRLMs who received neoadjuvant chemotherapy and had DLMs in preoperative imaging. Two independent reviewers completed the search according to the PRISMA checklist. Results: Three hundred and twenty-six patients with 1134 DLMs were included in our review. A total of 47 out of 480 DLMs (72.29%) that were removed had viable tumor cells in postoperative histology. One hundred and forty-five tumors could not be identified intraoperatively and were removed based on previous imaging, with thirty (20.69%) of them presenting viable cancer cells. Four hundred and sixty-five lesions could not be identified and were left in place. Of them, 152 (32.69%) developed local recurrence within 5 years. Of note, 34 DLMs could not be categorized as viable or non-viable tumors. Finally, DLMs that were identifiable intraoperatively had a higher possibility of viable tumors compared to non-identifiable ones (72.29% vs. 20.69%, respectively). Conclusions: Disappearing liver metastases that are left unresected have an increased possibility of recurrence. Patients receiving neoadjuvant treatment for CRLMs may have better survival chances after resecting all the DLM sites, either identifiable intraoperatively or not.
Fathers’ Cocaine Use and Parent–Child Feeding Interactions
Authors: Cerniglia Luca , Maremmani Angelo Giovanni Icro , Cimino Silvia
Published: February 2025

Background: Limited research has explored father–child interactions during feeding in dyads where fathers use cocaine, despite the critical role these interactions play in infant development. Methods: This study aimed to evaluate whether paternal cocaine use, psychopathology (measured via the SCL-90/R), and difficult child temperament (assessed using the QUIT) are linked to lower-quality father–child feeding interactions (evaluated through the SVIA) compared to dyads with non-substance-using fathers. Results: Father–child feeding interactions in the substance-using (SU) group were significantly poorer in quality than those in the non-substance-using (NSU) group. Fathers using cocaine displayed elevated SCL-90/R scores, particularly in hostility, anxiety, and depression. Maternal anxiety exacerbated interactional conflict during feeding. Furthermore, in the SU group, higher paternal psychoticism predicted lower-quality feeding interactions (as indicated by three SVIA subscales) but only when combined with higher levels of children’s Negative Emotionality. Conclusions: This study highlights the significant challenges faced by substance-using fathers in maintaining high-quality feeding interactions, emphasizing the detrimental impact of paternal psychopathology, maternal anxiety, and child temperament on caregiving dynamics.
Peak Eccentric Cycling Exercise and Cardiorespiratory Responses to Normobaric Hypoxia Versus Normobaric Normoxia in Healthy Adults: A Randomized, Controlled Crossover Trial
Authors: Wick Carmen , Constam Esther , Schneider Simon R. , Titz Anna , Furian Michael , Lichtblau Mona , Ulrich Silvia , Müller Julian
Published: February 2025

Background/Objectives: Pulmonary rehabilitation clinics are traditionally located at higher altitudes (HAs), where lower PO2 reduces exercise capacity and blood oxygenation. Eccentric cycling exercise (ECC), with its lower cardiorespiratory demand compared to concentric cycling (CON), might therefore be a potential advantageous training modality at HAs, particularly for individuals with reduced exercise capacity. This study aimed to compare the cardiorespiratory responses of ECC while breathing normoxic versus hypoxic gas in healthy participants. Methods: This randomized, controlled crossover trial involved healthy participants performing CON in normoxia (FiO2 = 0.21), followed by two incremental ECC tests until 70–100% of peak exercise, one with normoxia and one with normobaric hypoxia (FiO2 = 0.15), in a randomized order. Oxygen uptake (V’O2) and additional outcomes were measured breath-by-breath. Endpoints were defined at rest, 50%, 70%, peak exercise, and isotime. The trial is registered on clinicaltrails.gov (NCT05185895). Results: Twelve healthy participants (age: 30 ± 11 years, six females) completed the study. During both interventions, V’O2 increased linearly with exercise intensity, with no significant differences between normoxic and hypoxic conditions. At peak exercise, SpO2 and peak work rate were significantly lowered by 5% (95%CI: 3 to 8%, p < 0.001) and by 22 W (95%CI: 8 to 36 W, p = 0.009) in hypoxia compared to normoxia. Other outcomes were unchanged. When comparing CON to ECC in normoxia, the mean differences in V’O2 increased with higher loads. Conclusions: This study demonstrated that V’O2 and other cardiopulmonary parameters remain unchanged when performing ECC in hypoxia compared to normoxia. Comparing CON to ECC in normoxia, participants achieved higher workloads and greater V’O2 consumption during CON compared to ECC at comparable watts, confirming the higher metabolic cost associated with CON. We identified that the optimal submaximal ECC intensities, with the highest difference in V’O2 between CON versus ECC, are around 40% of peak V’O2.
Assessment of the Relationship between Pre-Existing Muscle Atrophy, Subcutaneous Fat Volume, and the Prognosis of COVID-19
Authors: Zarei Fariba , Sepahdar Afrooz , Saeedi-Moghadam Mahdi , Zeinali-Rafsanjani Banafsheh
Published: February 2025

Background: Coronavirus disease 2019 (COVID-19), with its rapid transmission and emergence, has become a major global public health concern. COVID-19 patients are at an increased risk of acute skeletal muscle loss and complications such as muscular weakness, depression, and anxiety. Furthermore, sarcopenia has been linked to COVID-19 vulnerability, hospitalization rates, and severity. This study aims to investigate the relationship between pre-existing sarcopenia, subcutaneous fat, and the prognosis of COVID-19. Methods: Patients over 18 with positive tests who had chest CT scans without underlying conditions were included in this cohort study. The ratio of muscle volume to the total body surface area was calculated. Patients were divided into four subgroups: outpatients, hospitalized, ICU admitted, and deceased. The initial muscle volume for each group was compared. Results: In total, 127 patients were included in the study, 63 (49%) of whom were male. The mean age of the patients was 51.8 ± 18.16 (from 23 to 87 years). In total, 27 patients (21.3%) were treated as outpatients, 49 patients (38.6%) were hospitalized, and 23 (18.1%) were admitted to the ICU. Twenty-eight patients (22%) died. The total muscle/surface area ratio was significantly associated with disease outcome and prognosis. The ratio was significantly lower in dead individuals (p = 0.017). Conclusions: Sarcopenia was discovered to be significantly associated with the severity of COVID-19 and a poor prognosis. Reducing the risk of severe COVID-19 is possible by identifying and managing sarcopenia-related risk factors.
Minimally Invasive Surgery for Spontaneous Intracerebral Hemorrhage: A Review
Authors: Bankole Nourou Dine Adeniran , Kuntz Cyrille , Planty-Bonjour Alexia , Beaufort Quentin , Gaberel Thomas , Cordonnier Charlotte , Pasi Marco , Schlunk Frieder , Nawabi Jawed , Zemmoura Ilyess , Boulouis Grégoire
Published: February 2025

Background: Spontaneous intracerebral hemorrhage (ICH) accounts for approximately 20% of all strokes and is associated with high mortality and disability rates. Despite numerous trials, conventional surgical approaches have not demonstrated consistent improvements in functional outcomes. Minimally invasive surgery (MIS) for ICH evacuation has emerged as a promising alternative, with the potential to improve functional outcomes and reduce mortality. Objectives: This narrative review aims to provide a comprehensive overview of various MIS techniques and their reported impact on functional outcomes in patients with spontaneous ICH while discussing key limitations in the existing literature. Methods: We systematically searched PubMed to identify studies published from 1 January 2010 to 22 March 2024. The search strategy included the following terms: (“minimally*”[All Fields] AND “invasive*”[All Fields] AND “surgery*”[All Fields] AND “intracerebral*”[All Fields] AND “hemorrhage*”[All Fields]) AND (2010:2024[pdat]). This review focuses on randomized controlled trials (RCTs) that evaluate MIS techniques for ICH and their clinical outcomes. Results: Our search identified six RCTs conducted between January 2010 and March 2024, encompassing 2180 patients with a mean age of 58.03 ± 4.5 years. Four trials demonstrated significantly improved functional recovery (mRs ≤ 3), reduced mortality, and fewer adverse events compared with standard medical management or conventional craniotomy. All MIS techniques rely on stereotactic planning and the use of tools such as exoscopes, endoscopes, craniopuncture, or thrombolytic irrigation for precise hematoma evacuation. These approaches reduce brain tissue disruption and improve precision. However, the variability in techniques, costs, and lack of an external validation limit the generalizability of these findings. Conclusions: MIS shows potential as an alternative to conventional management strategies for ICH, offering encouraging evidence for improved functional outcomes and reduced mortality in selected studies. However, these findings remain limited by gaps in the literature, including the need for external validation, significant methodological heterogeneity, and economic challenges. Further rigorous trials are essential to confirm the generalizability and long-term impact of these approaches.