bluuebunny/crossref_metadata_2025 huggingface dataset:
Centering Diverse Communities within Mindful Parenting Interventions in the U.S.: A Narrative Literature Review
Authors: Williams J. Corey , Bravo Noel , Kota Preeti , Hawkins Janaire , Greene Katherine
Published: October 2024

Background: While mindfulness-based interventions targeted toward parents (and families) in the U.S. offer promise for the treatment and prevention of youth psychological disorders, current research has established the underrepresentation of diverse participants in the research literature. The full extent of inequalities in the demographics of participation in parent mindfulness intervention is less understood. Objective: This study aimed to utilize a narrative literature review approach to examine and describe the degree to which research on mindful parenting interventions is inclusive of BIPOC (Black, Indigenous, and People of Color) communities, non-clinical samples (no diagnosed disorder), cultural adaptions, and skills specific to parenting. Methods: An electronic database search of US-based studies was undertaken for empirical studies that primarily focused on parent mindfulness interventions, which reported outcomes related to either parenting behaviors or child mental health outcomes. After a full-text review, the search resulted in 34 articles. A narrative literature review of the 34 studies was conducted to assess the inclusion of BIPOC communities, non-clinical samples, cultural adaptions, and skills specific to parenting. Results: This review found notable gaps in the degree to which mindful parenting research (1) included BIPOC populations in study samples; (2) focused on non-clinical samples; (3) adapted interventions to align with the cultural needs of participants; and (4) included the application of mindfulness to enhancing knowledge, skills, and behaviors specific to parenting. Conclusions: Given these gaps in the parent mindfulness literature, greater research attention is needed on mindful parenting interventions targeted toward BIPOC communities with no clinical diagnoses, interventions optimized by cultural adaptations, and explicit applications to parenting.
Targeting Oxidative Phosphorylation with a Novel Thiophene Carboxamide Increases the Efficacy of Imatinib against Leukemic Stem Cells in Chronic Myeloid Leukemia
Authors: Kusaba Kana , Watanabe Tatsuro , Kidoguchi Keisuke , Yamamoto Yuta , Tomoda Ayaka , Hoshiko Toshimi , Kojima Naoto , Nakata Susumu , Kimura Shinya
Published: October 2024

Patients with chronic myeloid leukemia (CML) respond to tyrosine kinase inhibitors (TKIs); however, CML leukemic stem cells (LSCs) exhibit BCR::ABL kinase-independent growth and are insensitive to TKIs, leading to disease relapse. To prevent this, new therapies targeting CML-LSCs are needed. Rates of mitochondria-mediated oxidative phosphorylation (OXPHOS) in CD34+CML cells within the primitive CML cell population are higher than those in normal undifferentiated hematopoietic cells; therefore, the inhibition of OXPHOS in CML-LSCs may be a potential cure for CML. NK-128 (C33H61NO5S) is a structurally simplified analog of JCI-20679, the design of which was based on annonaceous acetogenins. NK-128 exhibits antitumor activity against glioblastoma and human colon cancer cells by inhibiting OXPHOS and activating AMP-activated protein kinase (AMPK). Here, we demonstrate that NK-128 effectively suppresses the growth of CML cell lines and that the combination of imatinib and NK-128 is more potent than either alone in a CML xenograft mouse model. We also found that NK-128 inhibits colony formation by CD34+ CML cells isolated from the bone marrow of untreated CML patients. Taken together, these findings suggest that targeting OXPHOS is a beneficial approach to eliminating CML-LSCs, and may improve the treatment of CML.
Molecular Engineering of Virus Tropism
Authors: He Bo , Wilson Belinda , Chen Shih-Heng , Sharma Kedar , Scappini Erica , Cook Molly , Petrovich Robert , Martin Negin P.
Published: October 2024

Engineered viral vectors designed to deliver genetic material to specific targets offer significant potential for disease treatment, safer vaccine development, and the creation of novel biochemical research tools. Viral tropism, the specificity of a virus for infecting a particular host, is often modified in recombinant viruses to achieve precise delivery, minimize off-target effects, enhance transduction efficiency, and improve safety. Key factors influencing tropism include surface protein interactions between the virus and host-cell, the availability of host-cell machinery for viral replication, and the host immune response. This review explores current strategies for modifying the tropism of recombinant viruses by altering their surface proteins. We provide an overview of recent advancements in targeting non-enveloped viruses (adenovirus and adeno-associated virus) and enveloped viruses (retro/lentivirus, Rabies, Vesicular Stomatitis Virus, and Herpesvirus) to specific cell types. Additionally, we discuss approaches, such as rational design, directed evolution, and in silico and machine learning-based methods, for generating novel AAV variants with the desired tropism and the use of chimeric envelope proteins for pseudotyping enveloped viruses. Finally, we highlight the applications of these advancements and discuss the challenges and future directions in engineering viral tropism.
The Effect of Lower Limb Combined Neuromuscular Electrical Stimulation on Skeletal Muscle Cross-Sectional Area and Inflammatory Signaling
Authors: Alharbi Amal , Li Jia , Womack Erika , Farrow Matthew , Yarar-Fisher Ceren
Published: October 2024

In individuals with a spinal cord injury (SCI), rapid skeletal muscle atrophy and metabolic dysfunction pose profound rehabilitation challenges, often resulting in substantial loss of muscle mass and function. This study evaluates the effect of combined neuromuscular electrical stimulation (Comb-NMES) on skeletal muscle cross-sectional area (CSA) and inflammatory signaling within the acute phase of SCI. We applied a novel Comb-NMES regimen, integrating both high-frequency resistance and low-frequency aerobic protocols on the vastus lateralis muscle, to participants early post-SCI. Muscle biopsies were analyzed for CSA and inflammatory markers pre- and post-intervention. The results suggest a potential preservation of muscle CSA in the Comb-NMES group compared to a control group. Inflammatory signaling proteins such as TLR4 and Atrogin-1 were downregulated, whereas markers associated with muscle repair and growth were modulated beneficially in the Comb-NMES group. The study’s findings suggest that early application of Comb-NMES post-SCI may attenuate inflammatory pathways linked to muscle atrophy and promote muscle repair. However, the small sample size and variability in injury characteristics emphasize the need for further research to corroborate these results across a more diverse and extensive SCI population.
Proximal Co-Translation Facilitates Detection of Weak Protein-Protein Interactions
Authors: Kordonsky Alina , Gabay Matan , Rosinoff Aurelia , Avishid Reut , Flornetin Amir , Deouell Noam , Abd Alkhaleq Taimaa , Efron Noa , Milshtein Shoham , Shifman Julia M. , Gal Maayan , Prag Gali
Published: October 2024

Ubiquitin (Ub) signals are recognized and decoded into cellular responses by Ub-receptors, proteins that tether the Ub-binding domain(s) (UBDs) with response elements. Typically, UBDs bind mono-Ub in highly dynamic and weak affinity manners, presenting challenges in identifying and characterizing their binding interfaces. Here, we report the development of a new approach to facilitate the detection of these weak interactions using split-reporter systems where two interacting proteins are proximally co-translated from a single mRNA. This proximity significantly enhances the readout signals of weak protein–protein interactions (PPIs). We harnessed this system to characterize the ultra-weak UBD and ENTH (Epsin N-terminal Homology) and discovered that the yeast Ent1-ENTH domain contains two Ub-binding patches. One is similar to a previously characterized patch on STAM1(signal-transducing adaptor molecule)-VHS (Vps27, Hrs, and STAM), and the other was predicted by AlphaFold. Using a split-CAT selection system that co-translates Ub and ENTH in combination with mutagenesis, we assessed and confirmed the existence of a novel binding patch around residue F53 on ENTH. Co-translation in the split-CAT system provides an effective tool for studying weak PPIs and offers new insights into Ub-receptor interactions.
Expression Profiles of Fatty Acid Transporters and the Role of n-3 and n-6 Polyunsaturated Fatty Acids in the Porcine Endometrium
Authors: Blitek Agnieszka , Szymanska Magdalena
Published: October 2024

Fatty acids (FAs) are important for cell membrane composition, eicosanoid synthesis, and metabolic processes. Membrane proteins that facilitate FA transport into cells include FA translocase (also known as CD36) and FA transporter proteins (encoded by SLC27A genes). The present study aimed to examine expression profiles of FA transporters in the endometrium of cyclic and early pregnant gilts on days 3 to 20 after estrus and the possible regulation by conceptus signals and polyunsaturated FAs (PUFAs). The effect of PUFAs on prostaglandin (PG) synthesis and transcript abundance of genes related to FA action and metabolism, angiogenesis, and immune response was also determined. Day after estrus and reproductive status of animals affected FA transporter expression, with greater levels of CD36, SLC27A1, and SLC27A4 observed in pregnant than in cyclic gilts. Conceptus-conditioned medium and/or estradiol-17β stimulated SLC27A1 and CD36 expression. Among PUFAs, linoleic acid decreased SLC27A1 and SLC27A6 mRNA expression, while arachidonic, docosahexaenoic, and eicosapentaenoic acids increased SLC27A4 transcript abundance. Moreover, arachidonic acid stimulated ACOX1, CPT1A, and IL1B expression and increased PGE2 and PGI2 secretion. In turn, α-linolenic acid up-regulated VEGFA, FGF2, FABP4, and PPARG mRNA expression. These results indicate the presence of an active transport of FAs in the porcine endometrium and the role of PUFAs as modulators of the uterine activity during conceptus implantation.
GABA Signaling in Health and Disease in the Nervous System
Authors: Kihara Alexandre Hiroaki
Published: October 2024

Throughout development, gamma-aminobutyric acid, or GABA, plays a role in the proliferation, migration, and differentiation of neural progenitor cells [...]
Molecular Structure and Properties of Resistant Dextrins from Potato Starch Prepared by Microwave Heating
Authors: Kapusniak Kamila , Wojcik Malwina , Rosicka-Kaczmarek Justyna , Miśkiewicz Karolina , Pacholczyk-Sienicka Barbara , Juszczak Leslaw
Published: October 2024

The dextrinization of potato starch was performed using a sophisticated single-mode microwave reactor with temperature and pressure control using 10 cycles of heating with stirring between cycles. Microwave power from 150 to 250 W, a cycle time from 15 to 25 s, and two types of vessels with different internal diameters (12 and 24 mm) and therefore different thicknesses of the heated starch layer were used in order to estimate the impact of vessel size used for microwave dextrinization. The characteristics of resistant dextrins (RD) including solubility in water, total dietary fiber (TDF) content, color parameters, the share of various glycosidic bonds, and pasting and rheological properties were carried out. The applied conditions allowed us to obtain RDs with water solubility up to 74% at 20 °C, as well as TDF content up to 47%, with a predominance of low-molecular-weight soluble fiber fraction, with increased content of non-starch glycosidic bonds, negligible viscosity, and a slightly beige color. The geometry of the reaction vessel influenced the properties of dextrins obtained under the same heating power, time, and repetition amounts. Among the conditions used, the most favorable conditions were heating 10 times for 20 s at 200 W in a 10 mL vessel and the least favorable were 15 s cycles.
Phytochemical Analysis and Antioxidant, Antimicrobial, and Antibiofilm Effects of a New Himalayan Lichen Placidium deosaiense Usman and Khalid Growing in Pakistan
Authors: Manojlović Anja , Khalid Abdul Nasir , Usman Muhammad , Stefanović Olgica , Đukić Nevena , Manojlović Nedeljko , Tomović Jovica
Published: October 2024

Phytochemical composition and antimicrobial, antibiofilm, and antioxidant effects of a newly described Himalayan lichen Placidium deosaiense Usman and Khalid growing in Pakistan were investigated. HPLC–DAD methods were used for identification of secondary metabolites in acetone and methanol extracts. The total phenolics content was measured using a spectrophotometric method. The study investigated the antioxidant (DPPH-scavenging activity assay and reducing-power assay), antibacterial (minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC)), and antibiofilm (inhibition of biofilm formation and reduction in mature biofilm) activities of extracts of the lichen P. deosaiense and isolated parietin. The chemical constituents olivetol, olivetolic acid, haematommic acid, fallacinol, and parietin were identified as major compounds in the tested extracts of the lichen. Parietin was isolated from the acetone extract on a separation column. The methanol extract had higher values of TPC (21.67 mg GAE/g) than the acetone extract. Isolated parietin showed the best antioxidant activity measures, according to the DPPH-scavenging activity assay (IC50 = 51.616 μg/mL) and reducing-power assay. Although the extracts showed the best antibacterial activity (especially against Proteus mirabilis ATCC 12453), parietin demonstrated superior antibiofilm activity (especially against Staphylococcus aureus ATCC 25923). This is the first report on the phytochemical composition of the lichen Placidium deosaiense and the first description of the chemical composition of some of the 45 species of the genus Placidium. This research will pave the way for further exploration of new activities of this lichen and its metabolites, which are important for medicine and pharmacy.
Identification and Copy Number Variant Analysis of Enhancer Regions of Genes Causing Spinocerebellar Ataxia
Authors: Ghorbani Fatemeh , de Boer Eddy N. , Fokkens Michiel R. , de Boer-Bergsma Jelkje , Verschuuren-Bemelmans Corien C. , Wierenga Elles , Kasaei Hamidreza , Noordermeer Daan , Verbeek Dineke S. , Westers Helga , van Diemen Cleo C.
Published: October 2024

Currently, routine diagnostics for spinocerebellar ataxia (SCA) look for polyQ repeat expansions and conventional variations affecting the proteins encoded by known SCA genes. However, ~40% of the patients still remain without a genetic diagnosis after routine tests. Increasing evidence suggests that variations in the enhancer regions of genes involved in neurodegenerative disorders can also cause disease. Since the enhancers of SCA genes are not yet known, it remains to be determined whether variations in these regions are a cause of SCA. In this pilot project, we aimed to identify the enhancers of the SCA genes ATXN1, ATXN3, TBP and ITPR1 in the human cerebellum using 4C-seq, publicly available datasets, reciprocal 4C-seq, and luciferase assays. We then screened these enhancers for copy number variants (CNVs) in a cohort of genetically undiagnosed SCA patients. We identified two active enhancers for each of the four SCA genes. CNV analysis did not reveal any CNVs in the enhancers of the four SCA genes in the genetically undiagnosed SCA patients. However, in one patient, we noted a CNV deletion with an unknown clinical significance near one of the ITPR1 enhancers. These results not only reveal elements involved in SCA gene regulation but can also lead to the discovery of novel SCA-causing genetic variants. As enhancer variations are being increasingly recognized as a cause of brain disorders, screening the enhancers of ATXN1, ATXN3, TBP and ITPR1 for variations other than CNVs and identifying and screening enhancers of other SCA genes might elucidate the genetic cause in undiagnosed patients.
Oncolytic Coxsackievirus B3 Strain PD-H Is Effective Against a Broad Spectrum of Pancreatic Cancer Cell Lines and Induces a Growth Delay in Pancreatic KPC Cell Tumors In Vivo
Authors: Geisler Anja , Dieringer Babette , Elsner Leslie , Klopfleisch Robert , Kurreck Jens , Fechner Henry
Published: October 2024

Pancreatic cancer is one of the deadliest cancers globally, with limited success from existing therapies, including chemotherapies and immunotherapies like checkpoint inhibitors for patients with advanced pancreatic ductal adenocarcinoma (PDAC). A promising new approach is the use of oncolytic viruses (OV), a form of immunotherapy that has been demonstrated clinical effectiveness in various cancers. Here we investigated the potential of the oncolytic coxsackievirus B3 strain (CVB3) PD-H as a new treatment for pancreatic cancer. In vitro, PD-H exhibited robust replication, as measured by plaque assays, and potent lytic activity, as assessed by XTT assays, in most pancreatic tumor cell lines, outperforming two other coxsackievirus strains tested, H3N-375/1TS and CVA21. Thus, H3N-375/1TS showed efficient replication and lytic efficiency in distinctly fewer tumor cell lines, while most tumor cells were resistant to CVA21. The oncolytic efficiency of the three OV largely correlated with mRNA expression levels of viral receptors and their ability to induce apoptosis, as measured by cleaved caspase 3/7 activity in the tumor cells. In a syngeneic mouse model with subcutaneous pancreatic tumors, intratumoral administration of PD-H significantly inhibited tumor growth but did not completely stop tumor progression. Importantly, no virus-related side effects were observed. Although pancreatic tumors respond to PD-H treatment, its therapeutic efficacy is limited. Combining PD-H with other treatments, such as those aiming at reducing the desmoplastic stroma which impedes viral infection and spread within the tumor, may enhance its efficacy.
Immune Marker and C-Reactive Protein Dynamics and Their Prognostic Implications in Modulated Electro-Hyperthermia Treatment in Advanced Pancreatic Cancer: A Retrospective Analysis
Authors: Dobos Nikolett Kitti , Garay Tamas , Herold Magdolna , Simon Alexandra , Madar-Dank Viktor , Balka Gyula , Gajdacsi Jozsef , Dank Magdolna , Szasz Attila Marcell , Herold Zoltan
Published: October 2024

Background: Previous research has suggested that modulated electro-hyperthermia (mEHT) can be used to induce anti-tumor immune effects and to extend patient survival. The use of mEHT in advanced pancreatic cancer is beneficial; however, its immune-mediating effects were never investigated. Methods: A retrospective observational study was conducted. Leukocyte counts, C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), and granulocyte-to-lymphocyte ratio (GLR) were measured at baseline, midpoint, and after mEHT treatment. Results: A total of 73 mEHT treated pancreatic cancer patients were included. The time elapsed between tumor diagnosis and the first mEHT treatment was 4.40 ± 5.70 months. While no change could be observed between the baseline and the first follow-up visits, the total white blood cell (WBC), neutrophil, and granulocyte count, CRP, NLR, and GLR were significantly higher at the second follow-up compared to both previous visits. Higher levels of the latter parameters following the last mEHT treatment were signaling significantly poor prognostic signs, and so were their longitudinal changes. Conclusions: After the initiation of mEHT, immune markers stabilize with the treatment, but this positive effect is eroded over time by progressive disease. Monitoring the changes in these markers and the occurrence of their increase is a prognostic marker of shorter survival.
Alexithymia and Bipolar Disorder: Virtual Reality Could Be a Useful Tool for the Treatment and Prevention of These Conditions in People with a Physical Comorbidity
Authors: Sancassiani Federica , Perra Alessandra , Galetti Alessia , Di Natale Lorenzo , De Lorenzo Valerio , Lorrai Stefano , Kalcev Goce , Pintus Elisa , Cantone Elisa , Nonnis Marcello , Nardi Antonio Egidio , Montisci Roberta , Primavera Diego
Published: October 2024

Background: Alexithymia, a predictor in chronic illnesses, like cardiovascular and bipolar disorder (CD–BD), could be improved with a virtual reality (VR) cognitive remediation program. This secondary analysis of a previous randomized controlled trial (RCT) evaluates alexithymia improvement and its factors in an experimental group versus a control group, exploring extensions to individuals with comorbid non-psychiatric chronic conditions. Methods: A feasibility cross-over RCT (ClinicalTrials.gov NCT05070065) enrolled individuals aged 18–75 with mood disorders (BD, DSM-IV), excluding those with relapses, epilepsy, or severe eye conditions due to potential risks with VR. Alexithymia levels were measured using the Toronto Alexithymia Scale with 20 items (TAS-20). Results: The study included 39 individuals in the experimental group and 25 in the control group, with no significant age or sex differences observed. Significantly improved alexithymia scores were noted in the experimental group compared to controls (F = 111.9; p < 0.0001) and in subgroups with chronic non-psychiatric comorbidities (F = 4.293, p = 0.048). Scores were particularly improved for difficulty in identifying feelings (F = 92.42; p < 0.00001), communicating feelings (F = 61.34; p < 0.00001), and externally oriented thinking (F = 173.12; p < 0.00001). Conclusions: The findings highlight alexithymia enhancement in BD, even with comorbid non-psychiatric chronic diseases. Given its impact on BD progression and related conditions, like CD, developing and evaluating VR-based tools in this context is suggested by these findings.
CT-Derived Patient-Specific Computer Simulation of the Novel Self-Expanding Evolut FX Implantation: A Case Series
Authors: Hegeman Romy R. M. J. J. , van Putten Simon E. , Timmers Leo , Rensing Benno J. W. M. , Sonker Uday , Laengle Severin , Andreas Martin , Swaans Martin J. , ten Berg Jurriën M. , Klein Patrick
Published: October 2024

Background/Objectives: Paravalvular leak and permanent pacemaker implantation remain relevant issues after transcatheter aortic valve implantation (TAVI). Novel device development as well as adequate preprocedural device selection can contribute to optimal outcomes. Methods: Computed tomography-based patient-specific computer anatomical analysis and simulation were used in addition to standard preprocedural preparation in three of the first Evolut FX cases in our center. Procedural and follow-up echocardiographic outcomes are presented. Results: Computed tomography-based computer simulation of Evolut FX resulted in implantation of a different size in one of three cases. In three cases of severe aortic valve stenosis, procedural as well as follow-up outcomes were satisfactory and in line with the simulated results of the chosen strategy. Conclusions: Preprocedural patient-specific computer simulation predicts and guides decision-making in TAVI with the Evolut FX platform. The combination of advanced preprocedural technology and novel technologies continues to contribute to the optimization of TAVI outcomes.
Associations Between High-Density Lipoprotein Cholesterol Efflux and Brain Grey Matter Volume
Authors: Giacona John M. , Wang Jijia , Zhang Rong , Kelley Brendan J. , Hajjar Ihab , Thomas Binu P. , Yu Fang F. , de Lemos James A. , Rohatgi Anand , Vongpatanasin Wanpen
Published: October 2024

Objective: High-density lipoprotein cholesterol efflux function may prevent brain amyloid beta deposition and neurodegeneration. However, the relevance of this finding has not been established in the diverse middle-aged population. Methods: We examined 1826 adults (47% Black adults) who participated in the Dallas Heart Study to determine associations between high-density lipoprotein (HDL) measures and brain structure and function. White matter hyperintensities (WMH) and whole-brain grey matter volume (GMV) were measured using brain MRI, and the Montreal Cognitive Assessment (MoCA) was used to measure neurocognitive function. HDL cholesterol efflux capacity (HDL-CEC) was assessed using fluorescence-labeled cholesterol efflux from J774 macrophages, and HDL particle size measures were assessed using nuclear magnetic resonance (NMR) spectroscopy (LipoScience). Multivariable linear regressions were performed to elucidate associations between HDL-CEC and brain and cognitive phenotypes after adjustment for traditional risk factors such as age, smoking status, time spent in daily physical activity, and education level. Results: Higher HDL-CEC and small HDL particle (HDL-P) concentration were positively associated with higher GMV normalized to total cranial volume (TCV) (GMV/TCV) after adjustment for relevant risk factors (β = 0.078 [95% CI: 0.029, 0.126], p = 0.002, and β = 0.063 [95% CI: 0.014, 0.111], p = 0.012, respectively). Conversely, there were no associations between HDL measures and WMH or MoCA (all p > 0.05). Associations of HDL-CEC and small HDL-P with GMV/TCV were not modified by ApoE-ε4 status or race/ethnicity. Interpretation: Higher HDL cholesterol efflux and higher plasma concentration of small HDL-P were associated with higher GMV/TCV. Additional studies are needed to explore the potential neuroprotective functions of HDL.
Weighted-Incidence Syndromic Combination Antibiogram (WISCA) to Support Empirical Antibiotic Therapy Decisions in Infected Ischemic Leg Ulcers—A Feasibility Study
Authors: Salm Jonas , Ikker Franziska , Noory Elias , Beschorner Ulrich , Kramer Tobias Siegfried , Westermann Dirk , Zeller Thomas
Published: October 2024

Objective: Patients with peripheral artery occlusive disease (PAD) are at risk of developing foot ulcers, which can subsequently lead to foot infections and an increased risk of amputation. In cases of severe ischemic foot infections (IFIs), the empirical use of antibiotics can be limb-saving. However, there is currently no evidence-based guidance on the choice of empirical antibiotic therapy for IFI. Methods and Design: This retrospective single-center cohort study included 216 hospitalized patients with severe IFI undergoing endovascular revascularization. Weighted-Incidence Syndromic Combination Antibiograms (WISCAs) were calculated to guide empirical antibiotic choice. Results: The two most common causative pathogens for IFI were S. aureus and P. aeruginosa, with frequencies of 19.8% and 6.1%, respectively. The calculation of WISCAs revealed a low empirical coverage of amoxicillin (AMX) or clindamycin (CLN) with 21.6% and 27.7%, respectively. The empirical coverage of amoxicillin/clavulanic-acid (AMC), trimethoprim/sulfmethoxazole (SXT), and ciprofloxacin (CIP) was 50.6%, 53.1%, and 55.4%, respectively. Piperacillin/tazobactam (PT) exhibited the highest empirical coverage, with 82.5% as calculated by WISCAs. The calculated WISCAs did not significantly alter when stratified by the clinical characteristics of the patients. Conclusions: The empirical antibiotic coverage of CLN and AMX was low. SXT represents a promising empirical alternative in the case of IFI, irrespective of comorbidities and the WIfI score. WISCAs can assist in the decision-making process regarding empirical antibiotic therapy choices in cases of IFI.
Ultralow Prostate-Specific Antigen (PSA) Levels and Improved Oncological Outcomes in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) Patients Treated with Apalutamide: A Real-World Multicentre Study
Authors: López-Abad Alicia , Belmonte Mario , Ramírez Backhaus Miguel , Server Gómez Gerardo , Cao Avellaneda Enrique , Moreno Alarcón Cristóbal , López Cubillana Pedro , Yago Giménez Pablo , de Pablos Rodríguez Pedro , Juan Fita María José , Climent Durán Miguel Ángel , Guardiola Ruiz Iris , Vidal Crespo Natalia , Moreno Avilés Juan , Guzmán Martínez-Valls Pablo Luis , López González Pedro Ángel
Published: October 2024

Background/Objectives: Androgen receptor-targeted agents have significantly improved the prognosis of metastatic hormone-sensitive prostate cancer (mHSPC). Prostate-specific antigen (PSA) levels are key prognostic markers, with rapid and deep reductions associated with better outcomes. This study aims to assess the association between the new PSA cut-offs and survival in mHSPC patients treated with Apalutamide. Methods: We conducted a multicentre, retrospective analysis of mHSPC patients treated with Apalutamide between March 2021 and January 2023. Overall survival (OS) and radiographic progression-free survival (rFPS) were analyzed and stratified by the following PSA ranges: <0.02 ng/mL (ultralow), 0.02–0.2 ng/mL, and >0.2 ng/mL. Cox regression was applied to identify variables associated with OS and rPFS. Results: Among 193 patients, 34.2% had de novo mHSPC, with the majority classified as M1b. A total of 58.2% (110) of our cohort achieved ultralow PSA levels, with 20.6% between 0.02 and 0.2 ng/mL, and 21.2% of PSA levels > 0.2 ng/mL. Most patients reached ultralow PSA within six months. Low-volume, metachronous, and M1a subgroups displayed a higher prevalence of patients reaching ultralow PSA levels. At 18 months, OS was 100% in the ultralow PSA group, 94.4% for the 0.02–0.2 ng/mL group, and 67.7% in the >0.2 ng/mL group. Similarly, rPFS at 18 months was 100%, 93.5%, and 50.7%, respectively. Cox regression revealed that both ultralow PSA levels and ISUP grade had a significant impact on OS (HR of 8.256 and 0.164, respectively). For rPFS, only ultralow PSA levels had a significant impact (HR = 0.085). Conclusions: This real-world study of mHSPC patients treated with Apalutamide plus ADT revealed that achieving ultralow PSA levels is strongly associated with better oncological outcomes.
Influence of Transperineal Ultrasound on the POP-Q System in the Surgical Indication of Symptomatic Pelvic Organ Prolapse
Authors: García-Mejido José Antonio , Hurtado-Guijosa Ana , Fernández-Gomez Alfonso , Fernández-Palacín Fernando , Lao-Peña Carolina , Sainz-Bueno José Antonio
Published: October 2024

Background/Objectives: The diagnostic capacity of the preoperative pelvic organ prolapse quantification (POP-Q) system to define surgical pelvic organ prolapse (POP) is sometimes limited. On the other hand, pelvic floor ultrasound can influence the surgical indication for patients with symptomatic POP. Therefore, our objective is to determine how transperineal ultrasound can influence the surgical indication for symptomatic POP. Methods: This is a prospective observational study conducted over two years including patients who underwent corrective surgery for symptomatic POP. All patients underwent a preoperative examination using the POP-Q system to assess POP. Patients in whom the pelvic floor specialist had diagnostic doubts about the stage of POP underwent an ultrasound examination of the POP. Before the surgical procedure and with the patient anesthetized, a new clinical examination was performed using the POP-Q system and surgical correction of the POP was executed when the patient had a decline to stage II or higher. Cohen’s kappa coefficient of agreement was used to assess the agreement. Results: Of the 180 patients who met the inclusion criteria, 167 were included (99 with preoperative clinical examination and 68 with preoperative clinical examination and ultrasound study). The kappa index for the diagnosis of surgical uterine prolapse of the preoperative clinical examination (moderate correlation) was lower than the ultrasound examination (very good correlation) (0.493 p < 0.001 and 0.924 p < 0.001). The kappa index for the diagnosis of cervical elongation without surgical uterine prolapse also showed differences between the preoperative clinical examination (good correlation) and the ultrasound examination (very good correlation) (0.749 p < 0.001 and 0.853 p < 0.001). Conclusions: Transperineal ultrasound has a higher concordance than presurgical clinical examination, based on the POP-Q system, for detecting POP with central compartment surgical indication.
The Role of Natriuretic Peptides in the Management of Heart Failure with a Focus on the Patient with Diabetes
Authors: Vergani Michela , Cannistraci Rosa , Perseghin Gianluca , Ciardullo Stefano
Published: October 2024

Natriuretic peptides (NPs) are polypeptide hormones involved in the homeostasis of the cardiovascular system. They are produced by cardiomyocytes and regulate circulating blood volume and sodium concentration. Clinically, measurements of brain natriuretic peptide (BNP) and N-terminal pro-BNP (NT-proBNP) are recommended by international guidelines as evidence is accumulating on their usefulness. They have a high negative predictive value, and in the setting of low NPs, a diagnosis of heart failure (HF) can be safely excluded in both emergency (BNP < 100 pg/mL, NT-proBNP < 300 pg/mL) and outpatient settings (BNP < 35 pg/mL and NT-proBNP < 125 pg/mL). Moreover, the 2023 consensus from the European Society of Cardiology suggests threshold values for inclusion diagnosis. These values are also associated with increased risks of major cardiovascular events, cardiovascular mortality, and all-cause mortality whether measured in inpatient or outpatient settings. Among patients without known HF, but at high risk of developing it (e.g., in the setting of diabetes mellitus, hypertension, or atherosclerotic cardiovascular disease), NPs may be useful in stratifying cardiovascular risk, optimizing therapy, and reducing the risk of developing overt HF. In the diabetes setting, risk stratification with the use of these peptides can guide the physician to a more informed and appropriate therapeutic choice as recommended by guidelines. Notably, NP levels should be carefully interpreted in light of certain conditions that may affect their reliability, such as chronic kidney disease and obesity, as well as demographic variables, including age and sex. In conclusion, NPs are useful in the diagnosis and prognosis of HF, but they also offer advantages in the primary prevention setting.
Oxidative Processes and Xenobiotic Metabolism in Plants: Mechanisms of Defense and Potential Therapeutic Implications
Authors: Vicidomini Caterina , Palumbo Rosanna , Moccia Maria , Roviello Giovanni N.
Published: October 2024

Plants are continuously exposed to environmental challenges, including pollutants, pesticides, and heavy metals, collectively termed xenobiotics. These substances induce oxidative stress by generating reactive oxygen species (ROS), which can damage cellular components such as lipids, proteins, and nucleic acids. To counteract this, plants have evolved complex metabolic pathways to detoxify and process these harmful compounds. Oxidative stress in plants primarily arises from the overproduction of hydrogen peroxide (H2O2), superoxide anions (O2•−), singlet oxygen (1O2), and hydroxyl radicals (•OH), by-products of metabolic activities such as photosynthesis and respiration. The presence of xenobiotics leads to a notable increase in ROS, which can result in cellular damage and metabolic disruption. To combat this, plants have developed a strong antioxidant defense mechanism that includes enzymatic antioxidants that work together to eliminate ROS, thereby reducing their harmful effects. In addition to enzymatic defenses, plants also synthesize various non-enzymatic antioxidants, including flavonoids, phenolic acids, and vitamins. These compounds effectively neutralize ROS and help regenerate other antioxidants, offering extensive protection against oxidative stress. The metabolism of xenobiotic substances in plants occurs in three stages: the first involves modification, which refers to the chemical alteration of xenobiotics to make them less harmful. The second involves conjugation, where the modified xenobiotics are combined with other substances to increase their solubility, facilitating their elimination from the plant. The third stage involves compartmentalization, which is the storage or isolation of conjugated xenobiotics in specific parts of the plant, helping to prevent damage to vital cellular functions. Secondary metabolites found in plants, such as alkaloids, terpenoids, and flavonoids, play a vital role in detoxification and the defense against oxidative stress. Gaining a deeper understanding of the oxidative mechanisms and the pathways of xenobiotic metabolism in plants is essential, as this knowledge can lead to the formulation of plant-derived strategies aimed at alleviating the effects of environmental pollution and enhancing human health by improving detoxification and antioxidant capabilities, as discussed in this review.
Spatiotemporal Dynamics and Driving Factors of Vegetation Greenness in Typical Tourist Region: A Case Study of Hainan Island, China
Authors: Guo Jianchao , Zhang Lin , Qi Shi , Chen Jiadong
Published: October 2024

Vegetation greenness has been one of the most widely utilized indicators to assess the vegetation growth status for the better ecological environment. However, in typical tourist regions, the impact of the geographical environment, socioeconomic development, and tourism development on vegetation greenness changes is still a challenge. To address this challenge, we used the Google Earth Engine (GEE) cloud platform combined with a series of Landsat remote sensing images to calculate the fractional vegetation cover (FVC) which can be used as an indicator to characterize the spatiotemporal evolution of vegetation greenness in Hainan Island from 2000 to 2020. Furthermore, we employed geographic detector and structural equation models to quantify the relative importance and explanatory power of the geographical environment, socioeconomic development, and tourism development on vegetation greenness changes and to clarify the interaction of mechanisms of various factors in Haikou and Sanya. The results show that the annual growth rate of the FVC in Hainan Island was 0.0025/a. In terms of spatial distribution, the trend of the FVC changes was mainly characterized by non-significant and extremely significant improvement, accounting for 35.34% and 29.38% of the study area. Future vegetation greenness was dominated by weak counter-persistent increase and weak persistent increase. The geographical environmental factors were the main factors affecting vegetation greenness in Haikou, followed by the socioeconomic and the tourism development factors, while the geographical environmental factors also dominate in Sanya, followed by the tourism development factors and finally the socioeconomic factors. Specifically, the spatial distribution of vegetation greenness was primarily influenced by land use types, elevation, slope, and travel services. Geographical environmental factors could indirectly affect changes in socioeconomic and tourism development, thereby indirectly affecting the spatial distribution of vegetation greenness. These findings can provide some significant implications to guide the ecological environmental protection for sustainable development in Hainan Island in China.
Using Local Entropy Mapping as an Approach to Quantify Surface Temperature Changes Induced by Urban Parks in Mexico City
Authors: Núñez Juan Manuel , Santamaría Andrea , Avila Leonardo , Perez-De La Mora D. A.
Published: October 2024

Understanding the mechanisms whereby parks contribute to cooling urban settings is critical to effectively addressing the challenges posed by rising temperatures in densely populated cities and ultimately improving the quality of urban life. This study employs a spatial approach with advanced analytical techniques, including local entropy mapping, to quantify surface temperature changes induced by urban parks across different geographical areas. Using satellite imagery to estimate land surface temperature (LST) during a heat wave in Mexico City, the study provides a practical approach to understanding the complex relationship between urban park size and urban heat island intensity within 300 m. The study’s findings indicate that while parks exert a cooling influence on their immediate vicinity, the extent of this effect varies spatially and depends on factors such as the size and location of the park and the nature of the surrounding terrain. Specifically, the results indicate that this relationship is not randomly distributed across the urban landscape. Instead, there is a clear pattern of spatial clustering within the city. Consequently, this research underlines the complexity of the problem, emphasizing the indispensable role of urban design and planning strategies to harness the full potential of parks as cooling agents within cities.
Influencing Factors of Peasant Households’ Willingness to Relocate to Concentrated Residences in Mountainous Areas: Evidence from Rural Southwest China
Authors: Zhong Jia , Cao Qian , Chen Ruiyin , Liu Shaoquan , Lian Zhaoyang , Yu Hui , Zhou Ningchuan
Published: October 2024

Relocating poor people in mountainous areas to centralized settlement sites is an important poverty alleviation policy implemented by China and a key measure to promote stable poverty alleviation and sustainable rural development for the poor. Based on the survey data of 405 peasant households in the Panxi Area in 2021, this study constructed a structural equation model (SEM) to explore the influencing factors of peasant households’ willingness to relocate to a concentrated residence. The results showed the following: (1) Of the 405 peasant households surveyed, 20.98% were unwilling to move to centralized resettlement sites, making it more difficult to carry out the relocation policy for poverty alleviation. (2) Living environment, living conditions, important social groups, the economic benefits, living benefits, and survival benefits brought by concentrated residences, governments, and the village committees significantly influenced the willingness to relocate to a concentrated residence. In contrast, agricultural income, ecological benefits, and value benefits brought by the concentrated residence had little effect on the willingness to relocate to a concentrated residence. (3) Land force, human force, cognitive force, and national force significantly positively affected the peasant households’ willingness to relocate to a concentrated residence. This study is of great significance in promoting the implementation of poverty alleviation and relocation policy, improving the efficiency of relocation and promoting the wellbeing of peasant households.
The Intersectionality Between Amazon and Commodities Production: A Close Look at Sustainability
Authors: Schneider Adriane Terezinha , Dias Rosangela Rodrigues , Deprá Mariany Costa , Dutra Darissa Alves , Machado Richard Luan Silva , de Menezes Cristiano Ragagnin , Zepka Leila Queiroz , Jacob-Lopes Eduardo
Published: October 2024

Food production’s environmental, economic, and social challenges should be demystified through quantitative data. Therefore, the objective of this paper was to investigate the ecoregional sustainability of the Amazon biome from the perspective of the environmental life cycle, economic feasibility, and social life cycle analysis, emphasizing the pillars of sustainability in the production of three commodities: soybean, beef cattle, and Brazil nuts. Carbon footprint, net present value, and worker endpoint were the metrics evaluated. According to the results found in this study, the livestock presented greater environmental burdens in terms of carbon balance when compared to the production of Brazil nuts and soybean production with carbon balances in the order of 4.75 tCO2eq/ha, −0.02 tCO2eq/ha, and −1.20 tCO2eq/ha, respectively. From an economic viewpoint, the extractive production of Brazil nuts presented the highest net profit per hectare/year (USD 559.21), followed by the agricultural system (USD 533.94) and livestock (USD 146.19). Finally, in relation to the social aspect of the production systems analyzed, the negative impacts linked to beef cattle production are related to the subcategories of forced labor and equal opportunities, and the positive impacts linked to soybean production are related to the subcategories of salary and benefits. The results highlight a genuine and sustainable balance in Brazil nuts extraction, presenting it as an investment for a sustainable future while demystifying the multifaceted information related to food production as a whole, in order to assist in decision-making and the formulation of public policies.
Various Viewpoints to Investigate the Origins of Life Are Needed
Authors: Jia Tony Z. , Chandru Kuhan
Published: October 2024

How life first arose on Earth is a mystery that humankind has sought to understand for millennia, and includes scientific, philosophical, societal, and religious aspects, amongst others [...]
Using the Radial-Shear Rolling Method for Casted Zirconium Alloy Ingot Structure Improvement
Authors: Arbuz Alexandr , Popov Fedor , Panichkin Alexandr , Kawałek Anna , Lutchenko Nikita , Ozhmegov Kirill
Published: October 2024

In developing materials for the nuclear industry, it is crucial to enhance both alloy composition and processing methods. This study focuses on investigations of applying radial-shear rolling (RSR) to a Zr-1%Nb alloy ingot, aiming to refine its microstructure and improve its properties for nuclear applications. This method, with complex vortex metal flow inside of a casted workpiece, has not been previously tested for processing zirconium ingots, so experimental verification of its applicability is of scientific interest. The 30 mm diameter ingot, produced by vacuum induction melting, was initially rolled to 20 mm at 800 °C to eliminate defects and refine the cast structure. A second rolling stage reduced the diameter to 13 mm at 530 °C, resulting in an ultrafine-grained structure. The RSR method effectively combines structural refinement and defect healing within fewer cycles, making it suitable for producing components for nuclear reactors. This approach demonstrates a potential reduction in traditional processing steps, providing a more efficient route for preparing high-quality materials for nuclear applications.
Overlooked Ionic Contribution of a Chiral Dopant in Cholesteric Liquid Crystals
Authors: Shaban Hassanein , Wu Po-Chang , Jia Yi-Fei , Lee Wei
Published: October 2024

This study focuses on the ionic contribution by a chiral dopant added into a nematic host for preparing cholesteric liquid crystals (CLCs). Chiral structures were designated by individually incorporating two enantiomers, R5011 and S5011, into the nematic E44 to construct right- and left-handed CLCs, respectively. Characterized by the space-charge polarization, the dielectric spectra of the CLCs were investigated in the low-frequency regime, where f  ≤  1 kHz. The role of the individual chiral dopant, R5011 or S5011, at concentrations of 0–4.0 wt.% in altering the ionic properties of the CLC material was analyzed by deducing the electrical conductivity, ion density, and ion diffusivity. Regardless of the cell structure to be antiparallel or twisted by 90°, a significant ionic response was observed in the right-handed CLCs in comparison with the left-handed counterparts, suggesting that excess ions originating from our R5011 were introduced into the mesogenic mixtures. This work alarms the potential contribution of notorious impurity ions by a chiral dopant, which is often ignored in fabricating CLCs for electro-optical applications.
Electro-Spun P(VDF-HFP)/Silica Composite Gel Electrolytes for High-Performance Lithium-Ion Batteries
Authors: Huang Wen , Liu Caiyuan , Fang Xin , Peng Hui , Yang Yonggang , Li Yi
Published: October 2024

This work presents a facile way to fabricate a polymer/ceramics composite gel electrolyte to improve the overall properties of lithium-ion batteries. Lithium salt-grafted silica was synthesized and mixed with P(VDF-HFP) to produce a nanofiber film by the electrostatic spinning method. After coating a layer of SiO2 onto the surface of nanofibers through a sol-gel method, a composite nanofiber film was obtained. It was then immersed in plasticizer until saturation to make a composite gel electrolyte film. Electrochemical test results showed that the obtained gel electrolyte film shows high thermal stability (~450 °C), high ionic conductivity of 1.3 × 10−3 S cm−1 at 25 °C and a lithium-ion transference number of 0.58, and superior cycling stability, providing a new direction for manufacturing secondary batteries with higher safety and performance.