bluuebunny/crossref_metadata_2025 huggingface dataset:
Using the Constrained Disorder Principle to Navigate Uncertainties in Biology and Medicine: Refining Fuzzy Algorithms
Authors: Ilan Yaron
Published: October 2024

Uncertainty in biology refers to situations in which information is imperfect or unknown. Variability, on the other hand, is measured by the frequency distribution of observed data. Biological variability adds to the uncertainty. The Constrained Disorder Principle (CDP) defines all systems in the universe by their inherent variability. According to the CDP, systems exhibit a degree of variability necessary for their proper function, allowing them to adapt to changes in their environments. Per the CDP, while variability differs from uncertainty, it can be viewed as a regulated mechanism for efficient functionality rather than uncertainty. This paper explores the various aspects of un-certainties in biology. It focuses on using CDP-based platforms for refining fuzzy algorithms to address some of the challenges associated with biological and medical uncertainties. Developing a fuzzy decision tree that considers the natural variability of systems can help minimize uncertainty. This method can reveal previously unidentified classes, reduce the number of unknowns, improve the accuracy of modeling results, and generate algorithm outputs that are more biologically and clinically relevant.
Unveiling the Interplay—Vitamin D and ACE-2 Molecular Interactions in Mitigating Complications and Deaths from SARS-CoV-2
Authors: Wimalawansa Sunil J.
Published: October 2024

The interaction of the SARS-CoV-2 spike protein with membrane-bound angiotensin-converting enzyme-2 (ACE-2) receptors in epithelial cells facilitates viral entry into human cells. Despite this, ACE-2 exerts significant protective effects against coronaviruses by neutralizing viruses in circulation and mitigating inflammation. While SARS-CoV-2 reduces ACE-2 expression, vitamin D increases it, counteracting the virus’s harmful effects. Vitamin D’s beneficial actions are mediated through complex molecular mechanisms involving innate and adaptive immune systems. Meanwhile, vitamin D status [25(OH)D concentration] is inversely correlated with severity, complications, and mortality rates from COVID-19. This study explores mechanisms through which vitamin D inhibits SARS-CoV-2 replication, including the suppression of transcription enzymes, reduced inflammation and oxidative stress, and increased expression of neutralizing antibodies and antimicrobial peptides. Both hypovitaminosis D and SARS-CoV-2 elevate renin levels, the rate-limiting step in the renin-angiotensin-aldosterone system (RAS); it increases ACE-1 but reduces ACE-2 expression. This imbalance leads to elevated levels of the pro-inflammatory, pro-coagulatory, and vasoconstricting peptide angiotensin-II (Ang-II), leading to widespread inflammation. It also causes increased membrane permeability, allowing fluid and viruses to infiltrate soft tissues, lungs, and the vascular system. In contrast, sufficient vitamin D levels suppress renin expression, reducing RAS activity, lowering ACE-1, and increasing ACE-2 levels. ACE-2 cleaves Ang-II to generate Ang(1–7), a vasodilatory, anti-inflammatory, and anti-thrombotic peptide that mitigates oxidative stress and counteracts the harmful effects of SARS-CoV-2. Excess ACE-2 molecules spill into the bloodstream as soluble receptors, neutralizing and facilitating the destruction of the virus. These combined mechanisms reduce viral replication, load, and spread. Hence, vitamin D facilitates rapid recovery and minimizes transmission to others. Overall, vitamin D enhances the immune response and counteracts the pathological effects of SARS-CoV-2. Additionally, data suggests that widely used anti-hypertensive agents—angiotensin receptor blockers and ACE inhibitors—may lessen the adverse impacts of SARS-CoV-2, although they are less potent than vitamin D.
His Bundle Pacing and Left Bundle Branch Pacing in Patients with Heart Failure
Authors: Paluszkiewicz Patrycja , Martuszewski Adrian , Radziejewska Jadwiga , Zawadzki Jacek , Smereka Jacek , Gajek Jacek
Published: October 2024

Background: His bundle pacing (HBP) and left bundle branch pacing (LBBP) are emerging therapies for patients with heart failure and conduction disorders, offering potential advantages over traditional pacing methods. These approaches aim to restore physiological conduction and improve cardiac function more effectively. Objective: This study aims to evaluate the efficacy and safety of HBP and LBBP in patients with heart failure and conduction disturbances, comparing these techniques to conventional pacing. Methods: A comprehensive review of recent studies and clinical trials was conducted, focusing on the performance of HBP and LBBP in improving cardiac function, reducing QRS duration, and enhancing overall patient outcomes. The analysis includes data on clinical efficacy, procedural safety, and long-term benefits associated with these pacing modalities. Results: Both HBP and LBBP have demonstrated significant improvements in cardiac function and clinical outcomes compared to conventional pacing. HBP effectively restores physiological conduction with improved synchronization and a reduction in QRS duration. LBBP has shown enhanced left ventricular activation, leading to better overall cardiac performance. Both techniques have been associated with a lower incidence of complications and a higher success rate in achieving optimal pacing thresholds. Conclusions: HBP and LBBP offer promising alternatives to traditional pacing for patients with heart failure and conduction disorders. These advanced pacing strategies provide superior clinical outcomes and improved cardiac function with reduced risk of complications. Further research and clinical trials are needed to fully establish the long-term benefits and safety profiles of these techniques in diverse patient populations.
Abbreviated Breast MRI as a Supplement to Mammography in Family Risk History of Breast Cancer within the Croatian National Breast Screening Program
Authors: Šupe Parun Andrea , Brkljačić Boris , Ivanac Gordana , Tešić Vanja
Published: October 2024

Objective: To evaluate the diagnostic performance of abbreviated breast MRI compared with mammography in women with a family history of breast cancer included in the Croatian National Breast Screening Program. Methods: 178 women with a family history of breast cancer aged 50 to 69 underwent abbreviated breast MRI and mammography. Radiological findings for each method were categorized according to the BI-RADS classification. The gold standard for assessing the diagnostic accuracy of breast MRI and mammography, in terms of suspicious BI-RADS 4 and BI-RADS 5 findings, was the histopathological diagnosis. Performance measures, including cancer detection rates, specificity, sensitivity, and positive and negative predictive values, were calculated for both imaging methods. Results: Twelve new cases of breast cancer were detected, with seven (58.3%) identified only by abbreviated breast MRI, four (33.3%) detected by both mammography and breast MRI, and one (8.3%) diagnosed only by mammography. Diagnostic accuracy parameters for abbreviated breast MRI were 91.67% sensitivity, 94.58% specificity, 55.0% positive predictive value (PPV), and 99.37% negative predictive value (NPV), while for mammography, the corresponding values were 41.67%, 96.39%, 45.46%, and 95.81%, respectively. Conclusions: Abbreviated breast MRI is a useful supplement to screening mammography in women with a family history of breast cancer. Considering the results of the conducted research, it is recommended to assess whether women with a family history of breast cancer have an increased risk and subsequently provide annual abbreviated breast MRI in addition to mammography for early detection of breast cancer.
Effects of Chitosan and N-Succinyl Chitosan on Metabolic Disorders Caused by Oral Administration of Olanzapine in Mice
Authors: Shagdarova Balzhima , Melnikova Viktoria , Kostenko Valentina , Konovalova Mariya , Zhuikov Vsevolod , Varlamov Valery , Svirshchevskaya Elena
Published: October 2024

Background: The issue of human mental health is gaining more and more attention nowadays. However, most mental disorders are treated with antipsychotic drugs that cause weight gain and metabolic disorders, which include olanzapine (OLZ). The search for and development of natural compounds for the prevention of obesity when taking antipsychotic drugs is an urgent task. The biopolymer chitosan (Chi) and its derivatives have lipid-lowering and anti-diabetic properties, which makes them potential therapeutic substances for use in the treatment of metabolic disorders. The purpose of this work was to analyze the effect of the natural biopolymer Chi, its derivative N-succinyl chitosan (SuChi), and Orlistat (ORL) as a control on the effects caused by the intake of OLZ in a mouse model. Methods: Mice were fed with pearl barley porridge mixed with OLZ or combinations OLZ + Chi, OLZ + SuChi, or OLZ + ORL for 2 months. The weight, lipid profile, blood chemokines, expression of genes associated with appetite regulation, and behavior of the mice were analyzed in dynamics. Results: For the first time, data were obtained on the effects of Chi and SuChi on metabolic changes during the co-administration of antipsychotics. Oral OLZ increased body weight, food and water intake, and glucose, triglyceride, and cholesterol levels in blood. ORL and SuChi better normalized lipid metabolism than Chi, decreasing triglyceride and cholesterol levels. OLZ decreased the production of all chemokines tested at the 4th week of treatment and increased CXCL1, CXCL13, and CCL22 chemokine levels at the 7th week. All of the supplements corrected the level of CXCL1, CXCL13, and CCL22 chemokines but did not recover suppressed chemokines. SuChi and ORL stimulated the expression of satiety associated proopiomelanocortin (POMC) and suppressed the appetite-stimulating Agouti-related protein (AgRP) genes. All supplements improved the locomotion of mice. Conclusions: Taken collectively, we found that SuChi more than Chi possessed an activity close to that of ORL, preventing metabolic disorders in mice fed with OLZ. As OLZ carries positive charge and SuChi is negatively charged, we hypothesized that SuChi’s protective effect can be explained by electrostatic interaction between OLZ byproducts and SuChi in the gastrointestinal tract.
Blood Extracellular Vesicles Beyond Circulating Tumour Cells: A Valuable Risk Stratification Biomarker in High-Risk Non-Muscle-Invasive Bladder Cancer Patients
Authors: Magri Valentina , Marino Luca , Del Giudice Francesco , De Meo Michela , Siringo Marco , De Berardinis Ettore , Gandini Orietta , Santini Daniele , Nicolazzo Chiara , Gazzaniga Paola
Published: October 2024

Non-muscle-invasive bladder cancer (NMIBC) prognosis varies significantly due to the biological and clinical heterogeneity. High-risk stage T1-G3, comprising 15–20% of NMIBCs, involves the lamina propria and is associated with higher rates of recurrence, progression, and cancer-specific mortality. In the present study, we have evaluated the enumeration of tumour-derived extracellular vesicles (tdEVs) and circulating tumour cells (CTCs) in high-risk NMIBC patients and their correlation with survival outcomes such as time to progression (TTP), and cancer-specific survival (CSS). Eighty-three high-risk T1-G3 NMIBC patients treated between September 2010 and January 2013 were included. Blood samples were collected before a transurethral resection of the bladder (TURB) and analysed using the CellSearch® system. The presence of at least one CTC was associated with a shorter TTP and CSS. Extending follow-up to 120 months and incorporating automated tdEV evaluation using ACCEPT software demonstrated that tdEV count may additionally stratify patient risk. Combining tdEVs and CTCs improves risk stratification for NMIBC progression, suggesting that tdEVs could be valuable biomarkers for prognosis and disease monitoring. Further research is needed to confirm these findings and establish the clinical significance of tdEVs in early-stage cancers.
Characteristics of Gut Microbiome in the Murine Model of Pancreatic Cancer with Damp-Heat Syndrome
Authors: Tong Yangbo , Han Fang , Liu Mengyao , Xu Tianyu , Zhang Aiqin , Qin Jiangjiang , Zhang Yuhua , Qian Xiang
Published: October 2024

Purpose: Murine models of pancreatic cancer with damp-heat syndrome were established based on two methods to explore the differences in the composition of intestinal flora and to seek characteristic genera with potential for model evaluation. Methods: In our study, thirty-four C57BL/6J male mice were randomly divided into a control group (Con), a model group (Mod), a classic damp-heat syndrome group (CDHS), and a climate-chamber group (CC). CDHS and CC groups were fed with a high-fat diet and glucose water, while the CDHS group was given 2.4 g/kg alcohol by gavage for 10 days, and the CC group was placed in a climatic chamber with a set temperature of (32 ± 1) °C and humidity of (92 ± 2)% for 10 days. The Mod group, CDHS group, and CC group underwent tumor-building experiments on day 11. Tumorigenicity was then assessed twice a week. After 4 weeks, feces, colon tissue, and tumor tissue were taken from the mice and were tested, and the mice were euthanized afterwards. Results: Mice in the CDHS and CC groups showed symptoms similar to the clinical damp-heat syndrome observed in traditional Chinese medicine (TCM), and exhibited a worse general condition and more rapid tumor growth trend than those in the Mod group. The pathological examination indicated that inflammation was prevalent in the CDHS and CC groups. Both groups had a disrupted intestinal barrier and an overgrowth of pathogenic bacteria such as c_Gammaproteobacteria, o_Enterobacteriales, and g_Bacteroides. Their microbiota composition showed greater diversity. Conclusions: Intestinal flora may have a promising future in the discovery of indicators for evaluating a model of damp-heat syndrome in pancreatic cancer.
Systemic Innate Immune System Restoration as a Therapeutic Approach for Neurodegenerative Disease: Effects of NP001 on Amyotrophic Lateral Sclerosis (ALS) Progression
Authors: McGrath Michael S. , Zhang Rongzhen , Bracci Paige M. , Azhir Ari , Forrest Bruce D.
Published: October 2024

Background/objective: Amyotrophic lateral sclerosis (ALS) is a diagnosis that incorporates a heterogeneous set of neurodegenerative processes into a single progressive and uniformly fatal disease making the development of a uniformly applicable therapeutic difficult. Recent multinational ALS natural history incidence studies have identified systemic chronic activation of the innate immune system as a major risk factor for developing ALS. Persistent immune activation in patients with ALS leads to loss of muscle and lowering of serum creatinine. The goal of the current study was to test whether the slowing of nerve and muscle destruction in NP001-treated ALS patients compared with controls in phase 2 studies would lead to extension of survival. Methods: Phase 2 clinical studies with NP001, an intravenously administered form of the innate immune system regulator NaClO2, are now reporting long-term survival benefits for drug recipients vs. placebo controls after only six months of intermittent treatment. As a prodrug, NP001 is converted by macrophages to taurine chloramine, a long-lived regulator of inflammation. We performed a pooled analysis of all patients who had completed the studies in two six-month NP001 phase 2 trials. Changes in respiratory vital capacity and the muscle mass product, creatinine, defined treated patients who, compared to placebo, had up to a year of extended survival. Conclusions: The observed longer survival in ALS patients with the greatest inflammation-associated muscle loss provides further evidence that ALS is a disease of ongoing innate immune dysfunction and that NP001 is a disease-modifying drug with sustained clinical activity.
Current Applications of Raman Spectroscopy in Intraoperative Neurosurgery
Authors: Rivera Daniel , Young Tirone , Rao Akhil , Zhang Jack Y. , Brown Cole , Huo Lily , Williams Tyree , Rodriguez Benjamin , Schupper Alexander J.
Published: October 2024

Background: Neurosurgery demands exceptional precision due to the brain’s complex and delicate structures, necessitating precise targeting of pathological targets. Achieving optimal outcomes depends on the surgeon’s ability to accurately differentiate between healthy and pathological tissues during operations. Raman spectroscopy (RS) has emerged as a promising innovation, offering real-time, in vivo non-invasive biochemical tissue characterization. This literature review evaluates the current research on RS applications in intraoperative neurosurgery, emphasizing its potential to enhance surgical precision and patient outcomes. Methods: Following PRISMA guidelines, a comprehensive systematic review was conducted using PubMed to extract relevant peer-reviewed articles. The inclusion criteria focused on original research discussing real-time RS applications with human tissue samples in or near the operating room, excluding retrospective studies, reviews, non-human research, and other non-relevant publications. Results: Our findings demonstrate that RS significantly improves tumor margin delineation, with handheld devices achieving high sensitivity and specificity. Stimulated Raman Histology (SRH) provides rapid, high-resolution tissue images comparable to traditional histopathology but with reduced time to diagnosis. Additionally, RS shows promise in identifying tumor types and grades, aiding precise surgical decision-making. RS techniques have been particularly beneficial in enhancing the accuracy of glioma surgeries, where distinguishing between tumor and healthy tissue is critical. By providing real-time molecular data, RS aids neurosurgeons in maximizing the extent of resection (EOR) while minimizing damage to normal brain tissue, potentially improving patient outcomes and reducing recurrence rates. Conclusions: This review underscores the transformative potential of RS in neurosurgery, advocating for continued innovation and research to fully realize its benefits. Despite its substantial potential, further research is needed to validate RS’s clinical utility and cost-effectiveness.
Comparisons of Intradialytic Exercise Versus Home-Based Exercise in Hemodialysis Patients: A Narrative Review
Authors: Lee Chao-Lin , Wang Ping-Chen , Chen Yi-Ling , Chen Zen-Yong , Uen Ching-Cherng , Lai Hsien-Yung , Shiao Chih-Chung
Published: October 2024

With the increasing prevalence of end-stage kidney disease, the number of patients requiring hemodialysis (HD) continues to rise. While life-sustaining, HD is often associated with adverse effects such as muscle loss, physical deconditioning, fatigue, and compromised health-related quality of life (HRQoL). Recent research suggests that intradialytic exercise (IDE) and home-based exercise (HBE) may mitigate these adverse effects and improve patient outcomes. However, the existing literature mainly focuses on the outcomes of both exercises, whereas the comparison of types is often omitted. Hence, this review consolidates findings from studies investigating the effectiveness, implementation, safety, feasibility, and adherence of different types of IDE and HBE in HD patients. Overall, the current literature bolsters the significance of IDE and HBE for improving health in HD patients. IDE and HBE enhance physical function, cardiopulmonary capacity, HRQoL, and cognitive well-being. Some research proposed an indirect link between IDE and survival rates. Despite these benefits, challenges remain in implementing these exercise modalities, including patient adherence and the feasibility of routine exercise during HD sessions. Integrating these exercises into routine care allows healthcare providers to enhance outcomes for HD patients. Further research is suggested to optimize exercise protocols and explore long-term effects and cost-effectiveness.
Bedside Neuromodulation of Persistent Pain and Allodynia with Caloric Vestibular Stimulation
Authors: Ngo Trung T. , Barsdell Wendy N. , Law Phillip C. F. , Arnold Carolyn A. , Chou Michael J. , Nunn Andrew K. , Brown Douglas J. , Fitzgerald Paul B. , Gibson Stephen J. , Miller Steven M.
Published: October 2024

Background: Caloric vestibular stimulation (CVS) is a well-established neurological diagnostic technique that also induces many phenomenological modulations, including reductions in phantom limb pain (PLP), spinal cord injury pain (SCIP), and central post-stroke pain. Objective: We aimed to assess in a variety of persistent pain (PP) conditions (i) short-term pain modulation by CVS relative to a forehead ice pack cold-arousal control procedure and (ii) the duration and repeatability of CVS modulations. The tolerability of CVS was also assessed and has been reported separately. Methods: We conducted a convenience-based non-randomised single-blinded placebo-controlled study. Thirty-eight PP patients were assessed (PLP, n = 8; SCIP, n = 12; complex regional pain syndrome, CRPS, n = 14; non-specific PP, n = 4). Patients underwent 1–3 separate-day sessions of iced-water right-ear CVS. All but four also underwent the ice pack procedure. Analyses used patient-reported numerical rating scale pain intensity (NRS-PI) scores for pain and allodynia. Results: Across all groups, NRS-PI for pain was significantly lower within 30 min post-CVS than post-ice pack (p < 0.01). Average reductions were 24.8% (CVS) and 6.4% (ice pack). CRPS appeared most responsive to CVS, while PLP and SCIP responses were less than expected from previous reports. The strongest CVS pain reductions lasted hours to over three weeks. CVS also induced substantial reductions in allodynia in three of nine allodynic CRPS patients, lasting 24 h to 1 month. As reported elsewhere, only one patient experienced emesis and CVS was widely rated by patients as a tolerable PP management intervention. Conclusions: Although these results require interpretative caution, CVS was found to modulate pain relative to an ice pack control. CVS also modulated allodynia in some cases. CVS should be examined for pain management efficacy using randomised controlled trials.
Mitochondrial Creatine Kinase 2 (Ckmt2) as a Plasma-Based Biomarker for Evaluating Reperfusion Injury in Acute Myocardial Infarction
Authors: Lang Alexander , Oehler Daniel , Benkhoff Marcel , Reinders Yvonne , Barcik Maike , Shahrjerdi Khatereh , Kaldirim Madlen , Sickmann Albert , Dannenberg Lisa , Polzin Amin , Pfeiler Susanne , Kelm Malte , Grandoch Maria , Jung Christian , Gerdes Norbert
Published: October 2024

Background/Objectives: Acute myocardial infarction (AMI), characterized by irreversible heart muscle damage and impaired cardiac function caused by myocardial ischemia, is a leading cause of global mortality. The damage associated with reperfusion, particularly mitochondrial dysfunction and reactive oxygen species (ROS) formation, has emerged as a crucial factor in the pathogenesis of cardiac diseases, leading to the recognition of mitochondrial proteins as potential markers for myocardial damage. This study aimed to identify differentially expressed proteins based on the type of cardiac injury, in particular those with and without reperfusion. Methods: Male C57Bl/6J mice were either left untreated, sham-operated, received non-reperfused AMI, or reperfused AMI. Twenty-four hours after the procedures, left ventricular (LV) function and morphological changes including infarct size were determined using echocardiography and triphenyl tetrazolium chloride (TTC) staining, respectively. In addition, plasma was isolated and subjected to untargeted mass spectrometry and, further on, the ELISA-based validation of candidate proteins. Results: We identified mitochondrial creatine kinase 2 (Ckmt2) as a differentially regulated protein in plasma of mice with reperfused but not non-reperfused AMI. Elevated levels of Ckmt2 were significantly associated with infarct size and impaired LV function following reperfused AMI, suggesting a specific involvement in reperfusion damage. Conclusions: Our study highlights the potential of plasma Ckmt2 as a biomarker for assessing reperfusion injury and its impact on cardiac function and morphology in the acute phase of MI.
A Globally Guided Dual-Arm Reactive Motion Controller for Coordinated Self-Handover in a Confined Domestic Environment
Authors: Geng Zihang , Yang Zhiyuan , Xu Wei , Guo Weichao , Sheng Xinjun
Published: October 2024

Future humanoid robots will be widely deployed in our daily lives. Motion planning and control in an unstructured, confined, and human-centered environment utilizing dexterity and a cooperative ability of dual-arm robots is still an open issue. We propose a globally guided dual-arm reactive motion controller (GGDRC) that combines the strengths of global planning and reactive methods. In this framework, a global planner module with a prospective task horizon provides feasible guidance in a Cartesian space, and a local reactive controller module addresses real-time collision avoidance and coordinated task constraints through the exploitation of dual-arm redundancy. GGDRC extends the start-of-the-art optimization-based reactive method for motion-restricted dynamic scenarios requiring dual-arm cooperation. We design a pick–handover–place task to compare the performances of these two methods. Results demonstrate that GGDRC exhibits accurate collision avoidance precision (5 mm) and a high success rate (84.5%).
Age-Friendly Environment Design of High-Speed Railway Stations from a Healthy Ageing Perspective: A Case Implementation in Nanjing, China
Authors: Cao Ying , Li Danming , Gao Xuewen , Bi Shibo , Yu Kexin , Zhou Di
Published: October 2024

China stands out as one of the countries with the largest and fastest-growing elderly populations. Elderly requirements for the quality of high-speed railway stations environment are increasing. The relationship between the built environment of high-speed railway stations and elderly health has become an urgent problem to be solved. The challenge necessitates a systematic approach to age-friendly design. Based on the practical experience of the authors in an age-friendly design of an indoor environment at Nanjing South Railway Station, questionnaire surveys and user interviews were employed to profile four types of typical elderly passengers. Data collection methods were used to create behavior maps. (1) This study identifies the age-friendly needs of elderly passengers, pinpointing the key environment issues. (2) It proposes age-friendly design strategies for various functional areas of Nanjing South Railway Station. (3) It introduces an age-friendly module combination design system, which including basic type I, enhanced type II, and optimized type III, in order to meet the demands for six levels of high-speed railway stations in China. This study promotes the age-friendly transformation of environments at a high-speed railway station, offering theoretical foundations and methodological references for constructing an age-friendly environment from a healthy ageing perspective.
Stacking Fault Nucleation in Films of Vertically Oriented Multiwall Carbon Nanotubes by Pyrolysis of Ferrocene and Dimethyl Ferrocene at a Low Vapor Flow Rate
Authors: Taallah Ayoub , Wang Shanling , Odunmbaku Omololu , Zhang Lin , Guo Xilong , Dai Yixin , Li Wenkang , Ye Huanqing , Wu Hansong , Song Jiaxin , Guo Jian , Wen Jiqiu , He Yi , Boi Filippo S.
Published: October 2024

Recent observations of superconductivity in low-dimensional systems composed of twisted, untwisted, or rhombohedral graphene have attracted significant attention. One-dimensional moiré superlattices and flat bands have interestingly been identified in collapsed chiral carbon nanotubes (CNTs), opening up new avenues for the tunability of the electronic properties in these systems. The nucleation of hexagonal moiré superlattices and other types of stacking faults has also been demonstrated in partially collapsed and uncollapsed carbon nano-onions (CNOs). Here, we report a novel investigation on the dynamics of stacking fault nucleation within the multilayered lattices of micrometer-scale vertically oriented films of multiwall CNTs (MWCNTs), resulting from the pyrolysis of molecular precursors consisting of ferrocene or dimethyl ferrocene, at low vapor flow rates of ~5–20 mL/min. Interestingly, local nucleation of moiré-like superlattices (as stacking faults) was found when employing dimethyl ferrocene as the pyrolysis precursor. The morphological and structural properties of these systems were investigated with the aid of scanning and transmission electron microscopies, namely SEM, TEM, and HRTEM, as well as X-ray diffraction (XRD) and Raman point/mapping spectroscopy. Deconvolution analyses of the Raman spectra also demonstrated a local surface oxidation, possibly occurring on defect-rich interfaces, frequently identified within or in proximity of bamboo-like graphitic caps. By employing high-temperature Raman spectroscopy, we demonstrate a post-growth re-graphitization, which may also be visualized as an alternative way of depleting the oxygen content within the MWCNTs’ interfaces through recrystallization.
Proton Therapy in Uveal Melanoma
Authors: Chan Adrian Wai , Lin Haibo , Yacoub Irini , Chhabra Arpit M. , Choi J. Isabelle , Simone Charles B.
Published: October 2024

Background/Objectives: Uveal melanoma is the most common primary intraocular malignancy in adults. Treatment options for localized, early-stage disease include enucleation, brachytherapy, and proton beam therapy. This review aims to evaluate the role of proton therapy in the definitive management of uveal melanoma, focusing on its physics, radiobiology, treatment techniques, and associated outcomes. Methods: This narrative review synthesizes current literature on proton therapy for uveal melanoma, emphasizing case selection, treatment efficacy, and side effects. Results: Proton therapy offers significant advantages for thicker uveal melanomas (over 8 mm) due to its unique physical properties, including a rapid dose fall-off that protects critical structures like the retina and optic nerve. Proton therapy may have benefits in tumor control for ocular melanomas given its increased relative biological effectiveness relative to photon therapy for these typically more radioresistant melanomas. Proton therapy may also hold special value for uveal melanomas in close proximity to the optic nerve, as patients are at high risk of visual toxicities with brachytherapy. The review discusses the efficacy of proton therapy across small, medium, and large tumors, along with strategies for improving patient survival through combined systemic therapy. Additionally, the potential of ocular reirradiation with proton therapy is addressed. Conclusions: Proton therapy is an effective treatment for uveal melanoma. It offers advantages over brachytherapy for large tumors, tumors that are close to the optic nerve or insertion of extra-ocular muscles.
Quantitative Multi-Parametric MRI of the Prostate Reveals Racial Differences
Authors: Chatterjee Aritrick , Fan Xiaobing , Slear Jessica , Asare Gregory , Yousuf Ambereen N. , Medved Milica , Antic Tatjana , Eggener Scott , Karczmar Gregory S. , Oto Aytekin
Published: October 2024

Purpose: This study investigates whether quantitative MRI and histology of the prostate reveal differences between races, specifically African Americans (AAs) and Caucasian Americans (CAs), that can affect diagnosis. Materials and Methods: Patients (98 CAs, 47 AAs) with known or suspected prostate cancer (PCa) underwent 3T MRI (T2W, DWI, and DCE-MRI) prior to biopsy or prostatectomy. Quantitative mpMRI metrics: ADC, T2, and DCE empirical mathematical model parameters were calculated. Results: AAs had a greater percentage of higher Gleason-grade lesions compared to CAs. There were no significant differences in the quantitative ADC and T2 values between AAs and CAs. The cancer signal enhancement rate (α) on DCE-MRI was significantly higher for AAs compared to CAs (AAs: 13.3 ± 9.3 vs. CAs: 6.1 ± 4.7 s−1, p < 0.001). The DCE signal washout rate (β) was significantly lower in benign tissue of AAs (AAs: 0.01 ± 0.09 s−1 vs. CAs: 0.07 ± 0.07 s−1, p < 0.001) and significantly elevated in cancer tissue in AAs (AAs: 0.12 ± 0.07 s−1 vs. CAs: 0.07 ± 0.08 s−1, p = 0.02). DCE significantly improves the differentiation of PCa from benign in AAs (α: 52%, β: 62% more effective in AAs compared to CAs). Histologic analysis showed cancers have a greater proportion (p = 0.04) of epithelium (50.9 ± 12.3 vs. 44.7 ± 12.8%) and lower lumen (10.5 ± 6.9 vs. 16.2 ± 6.8%) in CAs compared to AAs. Conclusions: This study shows that AAs have different quantitative DCE-MRI values for benign prostate and prostate cancer and different histologic makeup in PCa compared to CAs. Quantitative DCE-MRI can significantly improve the performance of MRI for PCa diagnosis in African Americans but is much less effective for Caucasian Americans.
Oxidation of Geraniol on Vermiculite—The Influence of Selected Parameters on the Oxidation Process
Authors: Gajewska Sylwia , Wróblewska Agnieszka , Fajdek-Bieda Anna , Kamińska Adrianna , Sreńscek-Nazzal Joanna , Miądlicki Piotr , Michalkiewicz Beata
Published: October 2024

Geraniol is a compound belonging to the group of monoterpenes that finds many applications in organic syntheses, medicine and cosmetics. The following properties of geraniol and its derivatives are of particular interest in medicine: its anti-inflammatory, antioxidant, antimicrobial and anticancer effects. The geraniol oxidation process was carried out using a mineral of natural origin—vermiculite. Vermiculite is a catalyst that perfectly fits into modern trends in the organic industry, where the aim is to use cheap, renewable and relatively easily available catalytic materials (vermiculite is found on continents including Africa, North America, South America, Australia and Asia). Preliminary studies on the oxidation process of geraniol on vermiculite was carried out in a glass apparatus using molecular oxygen supplied by means of a bubbler and magnetic stirrer with a heating function. During the oxidation process of geraniol on vermiculite, the influence of the following parameters was examined: the temperature, amount of catalyst and reaction time. The main parameters of the process, on the basis of which the most favorable process conditions were selected, were the selectivity of the transformation to 2,3-epoxygeraniol, citral and 2,3-epoxycitral, and the conversion of geraniol. The composition of the post-reaction mixtures was determined qualitatively and quantitatively using the gas chromatography method. In addition, vermiculite was subjected to instrumental tests, such as XRD, SEM, EDX, FTIR and UV-VIS. Moreover, the specific surface area, pore volume and pore volume distribution were estimated on the basis of N2 sorption at −196 °C and also the acid-site concentration in vermiculite was established.
Spirobifluorene-Based D-A Type Conjugated Polymer Photocatalysts for Water Splitting
Authors: Zhao Hao , Sun Pengyao , Xu Hui , Xiao Xinyi , Kong Zhiyuan , Song Shige , Li Weihao , Liu Luzun , Wang Jiadong , Pan Xiaobo
Published: October 2024

Exploring synthetic pathways for efficient photocatalysts has always been a major goal in catalysis. The performance of organic photocatalysts is affected by a variety of complex factors, and how to understand the structure–effect relationship is the key to designing efficient photocatalysts. This work explored the feasibility of constructing large-specific-surface-area conjugated microporous polymers (CMPs) based on stereoscopic units like spirobifluorene and achieving efficient photocatalytic activity by modulating the donor–acceptor (D-A) ratio with dibenzothiophene sulfone. Crosslinked pore structures were successfully constructed, and the specific surface area increased with the ratio of spirobifluorene. When the molar ratio of D-A was 1:20, polymer Spso-3 showed the highest photocatalytic hydrogen production activity, at 22.4 mmol h–1 g–1. The findings indicate that constructing D-A type CMPs should be a promising approach to improving the performance of photocatalytic water separation. The appropriate push–pull effect of the D-A structure promotes the photo-induced separation of electron–hole pairs, and the porous structure built on steric units offers ample space for catalytic reactions. This work could provide case references for structural design and the structure–effect relationship of efficient polymer photocatalysts.
Kinetic Modelling of Aromaticity and Colour Changes during the Degradation of Sulfamethoxazole Using Photo-Fenton Technology
Authors: Villota Natalia , Duoandicoechea Unai , Lombraña Jose Ignacio , De Luis Ana María
Published: October 2024

Sulfamethoxazole (SMX) is an antibiotic that is extensively used in veterinary medicine, and its occurrence in wastewater and surface water can reach up to 20 μg/L. SMX is categorized as a pollutant of emerging concern by the US EPA due to its persistence and effects on humans and the environment. In this study, photo-Fenton technology is proposed for the removal of SMX. Aqueous solutions of SMX (50.0 mg/L) are treated in a 150 W UV photoreactor, using [Fe2+]0 = 0.5 mg/L and varying [H2O2]0 = 0–3.0 mM. During the reaction, colour (AU) was assessed along with SMX (mg/L), turbidity (NTU), and TC (mg/L). SMX degrades to aromatic intermediates with chromophoric groups, exhibiting colour (yellow to brown) and turbidity. As these intermediates are mineralized into CO2 and H2O, the colour and turbidity of the water lose intensity. Using a molar ratio of 1 mol SMX:10 mol H2O2, the maximum degradation of aromatic species takes place (71% elimination), and colourless water with turbidity < 1 NTU is obtained. A kinetic modelling for aromaticity loss and colour formation as a function of the oxidant concentration has been proposed. The application of this model allows the estimation of oxidant amounts for an efficient removal of SMX under environmentally friendly conditions.
Carbon Materials with Different Dimensions Supported Pt Catalysts for Selective Hydrogenation of 3,4-Dichloronitrobenzene to 3,4-Dichloroaniline
Authors: Zhan Nannan , Xiao Yan , Chen Xingkun , Tan Yuan , Ding Yunjie
Published: October 2024

In this study, carbon materials with different dimensions, including the typical one-dimensional (1D) carbon nanotube (CNT), two-dimensional (2D) graphene (GF), and three-dimensional (3D) activated carbon (AC), were investigated as a support for Pt catalysts for the selective hydrogenation of 3,4-dichloronitrobenzene (3,4-DCNB) to 3,4-dichloroaniline (3,4-DCAN). Notably, the Pt/CNT catalyst with the lowest dimension exhibited the best conversion of 3,4-DCNB under mild reaction conditions, followed by Pt/GF. Comprehensive characterizations, including XRD, TEM, XPS, and in situ CO DRIFTS, reveal that the dimension of carbon supports plays an important role in the particle size and electronic properties of Pt species, consequently affecting the catalytic performances of Pt catalysts. According to the results, electron-deficient Pt particles with small sizes are more favorable for the hydrogenation of 3,4-DCNB to 3,4-DCAN. In addition, dynamic tests and in situ DRIFTS of 3,4-DCNB indicated that the carbonaceous supports will largely influence the adsorption and activation capacity of the Pt catalysts, so that Pt loaded on CNT and GF are superior to that on the AC. We believe this study will provide good guidance for designing efficient carbon-supported metal catalysts for selective hydrogenation.
Immobilization and Kinetic Properties of ß-N-Acetylhexosaminidase from Penicillium oxalicum
Authors: Štefuca Vladimír , Bláhová Mária , Hronská Helena , Rosenberg Michal
Published: October 2024

The application of immobilized enzymes often plays a key role in successfully implementing an economically feasible biocatalytic process at an industrial scale. Designing an immobilized biocatalyst involves solving several tasks, from the selection of the carrier and immobilization method to the characterization of the kinetic properties of the immobilized enzyme. In this study, we focused on the kinetic properties of free and immobilized ß-N-acetylhexosaminidase (Hex), a promising enzyme for application in the field of biotechnology, especially for the synthesis of bioactive carbohydrates. Hex was immobilized via covalent binding in methacrylate particles. The effect of immobilizing Hex from Penicillium oxalicum into porous particles on kinetic properties was investigated, and mathematical and experimental modeling showed that the kinetic behavior of the enzyme was significantly influenced by diffusion in the particles. Along with the study on kinetics, a simple method was developed to investigate the reversible inhibition of the immobilized enzyme in a continuous-flow system. The method is suitable for application in cases where a chromogenic substrate is used, and here it was applied to demonstrate the inhibitory effects of N-acetyl-glucosaminyl thiazoline (NAG-thiazoline) and O-(2-Acetamido-2-deoxy-D-glucopyranosylidene)amino N-phenyl carbamate ((Z)-PugNAc) on Hex.
Cryoprotective Potential of Theobromine in the Improvement of the Post-Thaw Quality of Bovine Spermatozoa
Authors: Benko Filip , Baňas Štefan , Ďuračka Michal , Kačániová Miroslava , Tvrdá Eva
Published: October 2024

Theobromine (TBR) is a methylxanthine known for its bronchodilatory and stimulatory effects. This research evaluated the vitality, capacitation patterns, oxidative characteristics, microbial profile and expression of capacitation-associated proteins (CatSper1/2, sodium bicarbonate cotransporter [NBC], protein kinases A [PKA] and C [PKC] and adenylate cyclase 10 [ADCY10]) in cryopreserved bovine spermatozoa (n = 30) in the absence (cryopreserved control [CtrlC]) or presence of different TBR concentrations (12.5, 25, and 50 µM) in egg yolk extender. Fresh ejaculate served as a negative control (CtrlN). Significant post-thaw maintenance of the sperm motility, membrane and DNA integrity and mitochondrial activity (p < 0.001) were recorded following the administration of 25 μM and 50 μM TBR, then compared to CtrlC. All groups supplemented with TBR exhibited a significantly lower percentage of prematurely capacitated spermatozoa (p < 0.001) than CtrlC. Significantly decreased levels of global reactive oxygen species (ROS), hydrogen peroxide and hydroxyl radicals were observed in the presence of 25 μM and 50 μM TBR (p < 0.01). Western blot analysis revealed that supplementation with 50 μM TBR significantly prevented the loss of NBC and ADCY10 (p < 0.01), while all TBR doses stabilized the levels of PKC (p < 0.05 at 50 μM TBR; p < 0.001 at 12.5 μM and 25 μM TBR). In summary, we suggest that TBR is effective in protecting the spermatozoa during the cryopreservation process through its potential to stimulate energy synthesis while preventing ROS overproduction and the loss of proteins involved in the sperm activation process.
Characterization of Tumor-Infiltrating Lymphocyte-Derived Atypical TCRs Recognizing Breast Cancer in an MR1-Dependent Manner
Authors: Hayee Abdul , Kobayashi Eiji , Motozono Chihiro , Hamana Hiroshi , My Ha Thi Viet , Okada Takuya , Toyooka Naoki , Yamaguchi Satoshi , Ozawa Tatsuhiko , Kishi Hiroyuki
Published: October 2024

The MHC class I-related 1 (MR1) molecule is a non-polymorphic antigen-presenting molecule that presents several metabolites to MR1-restricted T cells, including mucosal-associated invariant T (MAIT) cells. MR1 ligands bind to MR1 molecules by forming a Schiff base with the K43 residue of MR1, which induces the folding of MR1 and its reach to the cell surface. An antagonistic MR1 ligand, Ac-6-FP, and the K43A mutation of MR1 are known to inhibit the responses of MR1-restricted T cells. In this study, we analyzed MR1-restricted TCRs obtained from tumor-infiltrating lymphocytes (TILs) from breast cancer patients. They responded to two breast cancer cell lines independently from microbial infection and did not respond to other cancer cell lines or normal breast cells. Interestingly, the reactivity of these TCRs was not inhibited by Ac-6-FP, while it was attenuated by the K43A mutation of MR1. Our findings suggest the existence of a novel class of MR1-restricted TCRs whose antigen is expressed in some breast cancer cells and binds to MR1 depending on the K43 residue of MR1 but without being influenced by Ac-6-FP. This work provides new insight into the physiological roles of MR1 and MR1-restricted T cells.
Prevalence of Antidepressant Prescription in Adolescents Newly Diagnosed with Depression in Germany
Authors: Kaur Nimran , Doege Corinna , Kostev Karel
Published: October 2024

Background: Depression is the most common mental illness in the world, found in nearly three in ten adolescents globally. This study aims to evaluate the prevalence of antidepressant prescriptions and the types of antidepressant therapy administered among adolescents diagnosed with depression in Germany. Methods: This retrospective cohort study, based on data provided by 30 child and adolescent psychiatrists, included adolescents aged 13–17 years with an initial diagnosis of depression between 2010 and 2022 (index date) documented in the IQVIATM Disease Analyzer database. Kaplan–Meier curves were used to investigate the one-year cumulative incidence of antidepressant prescriptions stratified by age, sex, and depression severity. Multivariable Cox regression analyses were used to assess the association between age, sex, depression severity, co-diagnoses, and antidepressant drug prescription. Results: A total of 6338 adolescents (mean age: 16 years, 67% female, 59% with moderate depression) were available. The cumulative incidence of antidepressant prescriptions was 61% and increased with age from 13 years old to 17 years old. Fluoxetine was the most prescribed drug, followed by Sertraline, Escitalopram, Serotonin and Norepinephrine reuptake inhibitors, herbal medications, and Mirtazapine. Obsessive–compulsive disorder and eating disorders were found to be significantly associated with antidepressant prescriptions within the spectrum of co-diagnosed conditions. Conclusions: Higher age, depression severity, and a co-diagnosis of an obsessive–compulsive disorder or eating disorder were significantly positively associated with antidepressant prescriptions in adolescents. Fluoxetine was the most frequently prescribed drug for depression.