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Abstract Nanostructures are tiny objects at the molecular and microscopic scale, with carbon nanotubes being the most notable among them. The elements possess exceptional microelectronic properties and other unique characteristics. Researchers have recently focused on the mathematical features of these materials. Molecular descriptors are crucial in mathematical chemistry, particularly in QSAR and QSPR modeling. Topological indices hold a significant position among them. This study presents the precise formulation of the ten most crucial topological indices for a benzene ring positioned on a P-type surface within the highly symmetric 2D lattice $$\hbox {BCZ}_{48}$$ BCZ 48 . We have incorporated the computed indices to develop a predictive model for the graph energy of the 2D lattice and, in addition, provided the NMR patterns and the HOMO-LUMO gap.

A carbon-based material with a broad scope of favourable developments is called graphene. Recently, a graphene nanoribbon with cove-edged was integrated by utilizing a bottom-up liquid-phase procedure, and it can be geometrically viewed as a hybrid of the armchair and the zigzag edges. It is indeed a type of nanoribbon containing asymmetric edges made up of sequential hexagons with impressive mechanical and electrical characteristics. Topological indices are numerical values associated with the structure of a chemical graph and are used to predict various physical, chemical, and biological properties of molecules. They are derived from the graph representation of molecules, where atoms are represented as vertices and bonds as edges. In this article, we derived the exact topological expressions of cove-edged graphene nanoribbons based on the graph-theoretical structural measures that help reduce the number of repetitive laboratory tasks necessary for studying the physicochemical characteristics of graphene nanoribbons with curved edges.

Background Female genital dermatoses (FGD) or vulvar dermatoses are a group of disorders that affect the vulva and contiguous parts. Most of the FGDs can be chronic or recurrent. Effects on Quality of life (QoL) in patients having dermatological conditions are well studied but this is not the case in vulvar dermatoses. Aims We aimed to study the etiology of genital dermatoses in females attending the Dermatology Out Patient Department (OPD) and to assess QoL in females with chronic FGD (>6 weeks duration). Settings and Design This was an observational study on female patients with vulvar complaints presenting to dermatology OPD. Both venereal and nonvenereal dermatoses were enrolled. QoL was assessed in females with chronic FGD using a self-administered Dermatological Life Quality Index (DLQI) questionnaire. Statistical Analysis Sample size was calculated using the formula Categorical variables were presented as numbers and percentages (%) and continuous variables were presented as mean ± standard deviation (SD) and median. The normality of the data was tested by the Kolmogorov-Smirnov test or non-parametric test. A t-test was used for the estimation of the mean. Results Ninety-seven patients were included in our study; Vulvovaginal candidiasis was the most common dermatoses (22.6%); Lichen simplex chronicus (11.3%) the commonest non-venereal dermatoses. 57 (58.7%) had chronic FGD, among whom 43 (75.4%) had significant QoL impairment. Conclusions Infectious etiologies predominated. There was significant impairment in QoL in females with chronic FGD.

Abstract Enhancing the efficacy of immunotherapy in brain metastases (BrM) requires an improved understanding of the immune composition of BrM and how this is affected by radiation and dexamethasone. Our two-arm pilot study (NCT04895592) allocated 26 patients with BrM to either low (Arm A) or high (Arm B) dose peri-operative dexamethasone followed by pre-operative stereotactic radiosurgery (pSRS) and resection (n= 13 per arm). The primary endpoint, a safety analysis at 4 months, was met. The secondary clinical endpoints of overall survival, distant brain failure, leptomeningeal disease and local recurrence at 12-months were 66%, 37.3%, 6%, and 0% respectively and were not significantly different between arms (p= 0.7739, p= 0.3884, p= 0.3469). Immunological data from two large retrospective BrM datasets and confirmed by correlates from both arms of this pSRS prospective trial revealed that BrM CD8 T cells were composed of predominantly PD1+ TCF1+ stem-like and PD1+ TCF1-TIM3+ effector-like cells. Clustering of TCF1+ CD8 T cells with antigen presenting cells in immune niches was prognostic for local control, even without pSRS. Following pSRS, CD8 T cell and immune niche density were transiently reduced compared to untreated BrM, followed by a rebound 6+ days post pSRS with an increased frequency of TCF1- effector-like cells. In sum, pSRS is safe and therapeutically beneficial, and these data provide a framework for how pSRS may be leveraged to maximize intracranial CD8 T cell responses.

Abstract This is an interim analysis of the Beta-blocker (Propranolol) use in traumatic brain injury (TBI) based on the high-sensitive troponin status (BBTBBT) study. The BBTBBT is an ongoing double-blind placebo-controlled randomized clinical trial with a target sample size of 771 patients with TBI. We sought, after attaining 50% of the sample size, to explore the impact of early administration of beta-blockers (BBs) on the adrenergic surge, pro-inflammatory cytokines, and the TBI biomarkers linked to the status of high-sensitivity troponin T (HsTnT). Patients were stratified based on the severity of TBI using the Glasgow coma scale (GCS) and HsTnT status (positive vs negative) before randomization. Patients with positive HsTnT (non-randomized) received propranolol (Group-1; n = 110), and those with negative test were randomized to receive propranolol (Group-2; n = 129) or placebo (Group-3; n = 111). Propranolol was administered within 24 h of injury for 6 days, guided by the heart rate (> 60 bpm), systolic blood pressure (≥ 100 mmHg), or mean arterial pressure (> 70 mmHg). Luminex and ELISA-based immunoassays were used to quantify the serum levels of pro-inflammatory cytokines (Interleukin (IL)-1β, IL-6, IL-8, and IL-18), TBI biomarkers [S100B, Neuron-Specific Enolase (NSE), and epinephrine]. Three hundred and fifty patients with comparable age (mean 34.8 ± 9.9 years) and gender were enrolled in the interim analysis. Group 1 had significantly higher baseline levels of IL-6, IL-1B, S100B, lactate, and base deficit than the randomized groups (p = 0.001). Group 1 showed a significant temporal reduction in serum IL-6, IL-1β, epinephrine, and NSE levels from baseline to 48 h post-injury (p = 0.001). Patients with severe head injuries had higher baseline levels of IL-6, IL-1B, S100B, and HsTnT than mild and moderate TBI (p = 0.01). HsTnT levels significantly correlated with the Injury Severity Score (ISS) (r = 0.275, p = 0.001), GCS (r = − 0.125, p = 0.02), and serum S100B (r = 0.205, p = 0.001). Early Propranolol administration showed a significant reduction in cytokine levels and TBI biomarkers from baseline to 48 h post-injury, particularly among patients with positive HsTnT, indicating the potential role in modulating inflammation post-TBI. Trial registration: ClinicalTrials.gov NCT04508244. It was registered first on 11/08/2020. Recruitment started on 29 December 2020 and is ongoing. The study was partly presented at the 23rd European Congress of Trauma and Emergency Surgery (ECTES), April 28–30, 2024, in Estoril, Lisbon, Portugal.

Objective:. We aimed to determine whether n-butyl-2-cyanoacrylate (NB2C) adhesive is a safe and effective mechanism for nonpenetrating mesh and peritoneal fixation during laparoscopic groin hernia repair. Background:. Chronic pain after laparoscopic groin hernia repair has been associated with penetrating fixation, but there had been no US Food and Drug Administration–approved devices for nonpenetrating fixation in this context. Methods:. Patients undergoing laparoscopic transabdominal preperitoneal (TAP) or totally extraperitoneal (TEP) groin hernia repair with mesh at 1 of 5 academic medical centers were randomized to mesh (TAP/TEP) and peritoneal (TAP) fixation with NB2C adhesive or absorbable tacks. The primary outcome was improvement in pain (visual analog scale [VAS]) at 6 months. The noninferiority margin was 0.9 (α = 0.025; β = 80%). Recurrence, successful use of the device, quality of life, and rates of adverse events (AEs) were secondary outcomes. Results:. From 2019 to 2021, 284 patients were randomized to either NB2C adhesive or absorbable tacks (n = 142/142). Patient and hernia characteristics were comparable, and 65% were repaired using a TAP approach. The difference in VAS improvement at 6 months with NB2C adhesive was not inferior to absorbable tacks in intention-to-treat and per-protocol analyses, respectively (0.25 [95% CI, −0.33 to 0.82]; P = 0.013; 0.22 [95% CI, −0.36 to 0.80], noninferiority P = 0.011). There were no differences in secondary outcomes including recurrence, successful use of each device to fixate the mesh and peritoneum, quality of life, and additional VAS pain scores. Rates of adverse and serious AEs were also comparable. Conclusions:. NB2C adhesive is safe and effective for mesh fixation and peritoneal closure during laparoscopic groin hernia repair.

Abstract Non-melanoma skin cancer (NMSC), encompassing basal and squamous cell carcinoma, is the most prevalent cancer in the United States. While surgical removal remains the conventional therapy with a 95% 5-year cure rate, there is a growing interest in exploring alternative treatment strategies. In this study, we investigated the role of Bortezomib (BTZ), a proteasome inhibitor, in NMSC. Using two NMSC cell lines (A431 and A388), we examined the effects of BTZ treatment. Our results demonstrated that 48 h of BTZ treatment led to downregulating Skp2 expression in both A431 and A388 cells while upregulating p53 expression, specifically in A388 cells. These alterations resulted in impaired cellular growth and caspase-dependent cell death. Silencing Skp2 in A388 cells with siRNA confirmed the upregulation of p53 as a direct target. Furthermore, BTZ treatment increased the Bax to Bcl-2 ratio, promoting mitochondrial permeability and the subsequent release of cytochrome C, thereby activating caspases. We also found that BTZ exerted its antitumor effects by generating reactive oxygen species (ROS), as blocking ROS production significantly reduced BTZ-induced apoptotic cell death. Interestingly, BTZ treatment induced autophagy, which is evident from the increased expression of microtubule-associated proteins nucleoporin p62 and LC-3A/B. In addition to cell lines, we assessed the impact of BTZ in an in vivo setting using Caenorhabditis elegans (C. elegans). Our findings demonstrated that BTZ induced germline apoptosis in worms even at low concentrations. Notably, this increased apoptosis was mediated through the activity of CEP-1, the worm’s counterpart to mammalian p53. In summary, our study elucidated the molecular mechanism underlying BTZ-induced apoptosis in NMSC cell lines and C. elegans. By targeting the skp2/p53 axis, inducing mitochondrial permeability, generating ROS, and promoting autophagy, BTZ demonstrates promising anti-cancer activity in NMSC. These findings provide novel insights into potential therapeutic strategies for controlling the unregulated growth of NMSC.

Abstract With improvements in survival for patients with metastatic cancer, long-term local control of brain metastases has become an increasingly important clinical priority. While consensus guidelines recommend surgery followed by stereotactic radiosurgery (SRS) for lesions >3 cm, smaller lesions (≤3 cm) treated with SRS alone elicit variable responses. To determine factors influencing this variable response to SRS, we analyzed outcomes of brain metastases ≤3 cm diameter in patients with no prior systemic therapy treated with frame-based single-fraction SRS. Following SRS, 259 out of 1733 (15%) treated lesions demonstrated MRI findings concerning for local treatment failure (LTF), of which 202 /1733 (12%) demonstrated LTF and 54/1733 (3%) had an adverse radiation effect. Multivariate analysis demonstrated tumor size (>1.5 cm) and melanoma histology were associated with higher LTF rates. Our results demonstrate that brain metastases ≤3 cm are not uniformly responsive to SRS and suggest that prospective studies to evaluate the effect of SRS alone or in combination with surgery on brain metastases ≤3 cm matched by tumor size and histology are warranted. These studies will help establish multi-disciplinary treatment guidelines that improve local control while minimizing radiation necrosis during treatment of brain metastasis ≤3 cm.

Abstract Background The purpose of this study was to evaluate the effect of nanoparticles (NPs) of a plant extract on implant osseointegration in vivo. NPs of the Cissus quadrangularis (CQ) extract were synthesized. Twenty Wistar rats were included in the study. The test group (n = 5) had NPs-incorporated, the control group (n = 5) had no incorporation of NPs, and the sham group (n = 5) did not have implants placed. The toxicity profile of NPs was carried out by biochemical analysis before and after the implant placement. The rate of integration was assessed using Cone Beam Computed Tomography (CBCT), Digital X-ray, histology, and scanning electron microscopy (SEM) at intervals of 2, 4, and 6 weeks. Statistical significance between the groups was determined by Analysis of Variance (ANOVA) (p

Summary: Intra-tumoral phenotypic heterogeneity promotes tumor relapse and therapeutic resistance and remains an unsolved clinical challenge. Decoding the interconnections among different biological axes of plasticity is crucial to understand the molecular origins of phenotypic heterogeneity. Here, we use multi-modal transcriptomic data—bulk, single-cell, and spatial transcriptomics—from breast cancer cell lines and primary tumor samples, to identify associations between epithelial-mesenchymal transition (EMT) and luminal-basal plasticity—two key processes that enable heterogeneity. We show that luminal breast cancer strongly associates with an epithelial cell state, but basal breast cancer is associated with hybrid epithelial/mesenchymal phenotype(s) and higher phenotypic heterogeneity. Mathematical modeling of core underlying gene regulatory networks representative of the crosstalk between the luminal-basal and epithelial-mesenchymal axes elucidate mechanistic underpinnings of the observed associations from transcriptomic data. Our systems-based approach integrating multi-modal data analysis with mechanism-based modeling offers a predictive framework to characterize intra-tumor heterogeneity and identify interventions to restrict it.

Background: The glucocorticoid receptor (GR) is frequently expressed in breast cancer (BC), and its prognostic implications are contingent on estrogen receptor (ER) status. To address conflicting reports and explore therapeutic potential, a GR signature (GRsig) independent of ER status was developed. We also investigated cell type-specific GR protein expression in BC tumor epithelial cells and infiltrating lymphocytes. Methods: GRsig was derived from Dexamethasone treated cell lines through a bioinformatic pipeline. Immunohistochemistry assessed GR protein expression. Associations between GRsig and tumor phenotypes (proliferation, cytolytic activity (CYT), immune cell distribution, and epithelial-to-mesenchymal transition (EMT) were explored in public datasets. Single-cell RNA sequencing data evaluated context-dependent GR roles, and a cell type-specific prognostic role was assessed in an independent BC cohort. Results: High GRsig levels were associated with a favorable prognosis across BC subtypes. Tumor-specific high GRsig correlated with lower proliferation, increased CYT, and anti-tumorigenic immune cells. Single-cell data analysis revealed higher GRsig expression in immune cells, negatively correlating with EMT while a positive correlation was observed with EMT primarily in tumor and stromal cells. Univariate and multivariate analyses demonstrated the robust and independent predictive capability of GRsig for favorable prognosis. GR protein expression on immune cells in triple-negative tumors indicated a favorable prognosis. Conclusion: This study underscores the cell type-specific role of GR, where its expression on tumor cells is associated with aggressive features like EMT, while in infiltrating lymphocytes, it predicts a better prognosis, particularly within TNBC tumors. The GRsig emerges as a promising independent prognostic indicator across diverse BC subtypes.

Abstract Introduction Functional brain templates are often used in the analysis of clinical functional MRI (fMRI) studies. However, these templates are mostly built based on anatomy or fMRI of healthy subjects, which have not been fully vetted in clinical cohorts. Our aim was to evaluate language templates by comparing with primary language areas (PLAs) detected from presurgical fMRI of brain tumor patients. Methods Four language templates (A–D) based on anatomy, task‐based fMRI, resting‐state fMRI, and meta‐analysis, respectively, were compared with PLAs detected by fMRI with word generation and sentence completion paradigms. For each template, the fraction of PLA activations enclosed by the template (positive inclusion fraction, [PIF]), the fraction of activations within the template but that did not belong to PLAs (false inclusion fraction, [FIF]), and their Dice similarity coefficient (DSC) with PLA activations were calculated. Results For anterior PLAs, Template A had the greatest PIF (median, 0.95), whereas Template D had both the lowest FIF (median, 0.074), and the highest DSC (median, 0.30), which were all significant compared to other templates. For posterior PLAs, Templates B and D had similar PIF (median, 0.91 and 0.90, respectively) and DSC (both medians, 0.059), which were all significantly higher than that of Template C. Templates B and C had significantly lower FIF (median, 0.061 and 0.054, respectively) compared to Template D. Conclusion This study demonstrated significant differences between language templates in their inclusiveness of and spatial agreement with the PLAs detected in the presurgical fMRI of the patient cohort. These findings may help guide the selection of language templates tailored to their applications in clinical fMRI studies.

Cancer is caused by a complex interaction of factors that interrupt the normal growth and division of cells. At the center of this process is the intricate relationship between DNA damage and the cellular mechanisms responsible for maintaining genomic stability. When DNA damage is not repaired, it can cause genetic mutations that contribute to the initiation and progression of cancer. On the other hand, the DNA damage response system, which involves the phosphorylation of the histone variant H2AX (γH2AX), is crucial in preserving genomic integrity by signaling and facilitating the repair of DNA double-strand breaks. This review provides an explanation of the molecular dynamics of H2AX in the context of DNA damage response. It emphasizes the crucial role of H2AX in recruiting and localizing repair machinery at sites of chromatin damage. The review explains how H2AX phosphorylation, facilitated by the master kinases ATM and ATR, acts as a signal for DNA damage, triggering downstream pathways that govern cell cycle checkpoints, apoptosis, and the cellular fate decision between repair and cell death. The phosphorylation of H2AX is a critical regulatory point, ensuring cell survival by promoting repair or steering cells towards apoptosis in cases of catastrophic genomic damage. Moreover, we explore the therapeutic potential of targeting H2AX in cancer treatment, leveraging its dual function as a biomarker of DNA integrity and a therapeutic target. By delineating the pathways that lead to H2AX phosphorylation and its roles in apoptosis and cell cycle control, we highlight the significance of H2AX as both a prognostic tool and a focal point for therapeutic intervention, offering insights into its utility in enhancing the efficacy of cancer treatments.

Triple Negative Breast Cancer (TNBC) is the most aggressive type of breast cancer (BC). Despite advances in the clinical management of TNBC, recurrence-related mortality remains a challenge. The stem-like phenotype of TNBC plays a significant role in the persistence of minimal disease residue after therapy. Individuals exhibiting stem-like characteristics are particularly prone to inducing malignant relapse accompanied by strong resistance. Therefore, stem-like traits have been broadly proposed as therapeutic vulnerabilities to treat TNBC and reduce recurrence. However, heterogeneity within TNBC often generally restricts the stability of the therapeutic efficacy. To understand the heterogeneity and manage TNBC more precisely, multiple TNBC subtyping categories have been reported, providing the basis for profile-according therapeutic regimens. To provide more insight into targeting stem-like traits to ablate TNBC and reduce recurrence in the context of heterogeneity, this paper reviewed the molecular subtyping of TNBC, identified the consensus subtypes with distinct stem-like phenotypes, characterized the stemness hierarchy of TNBC, outlined the biological models for stem-like TNBC subtypes, summarized the therapeutic vulnerabilities in stem-like traits of the subtypes, and proposed potential therapeutic regimens targeting stem-like characteristics to improve TNBC prognosis.

Objective To evaluate real-world treatment patterns and clinical outcomes in recurrent/advanced endometrial cancer patients who progressed following prior systemic therapy in clinical practice in Europe.Design Endometrial Cancer Health Outcomes-Europe (ECHO-EU) is a retrospective patient chart review study.Setting ECHO-EU is a multicentre study conducted in the UK, Germany, Italy, France and Spain.Participants Patients with recurrent/advanced endometrial cancer who progressed between 1 July 2016 and 30 June 2019 following prior first-line systemic therapy were eligible and data were collected until last available follow-up through November 2021.Primary and secondary outcome measures Data collected included patient demographics, clinical and treatment characteristics, and clinical outcomes. Kaplan-Meier analyses were performed since initiation of second-line therapy to estimate time to treatment discontinuation, real-world progression-free survival (rwPFS) and overall survival (OS).Results A total of 475 patients were included from EU5 countries. Median age was 69 years at advanced endometrial cancer diagnosis, 78.7% had stage IIIB–IV disease, 45.9% had Eastern Cooperative Oncology Group status ≥2 at second-line therapy initiation. In second line, a majority of patients initiated either non-platinum-based chemotherapy (55.6%) or endocrine therapy (16.2%). Physician-reported real-world overall response rate (classified as complete or partial response) to second-line therapy was 34.5%, median rwPFS was 7.4 months (95% CI 6.2 to 8.0) and median OS was 11.0 months (95% CI 9.9 to 12.3).Conclusions Patients had poor clinical outcomes with a median OS of

In the current study, Neosetophomone B (NSP–B) was investigated for its anti-cancerous potential using network pharmacology, quantum polarized ligand docking, molecular simulation, and binding free energy calculation. Using SwissTarget prediction, and Superpred, the molecular targets for NSP-B were predicted while cancer-associated genes were obtained from DisGeNet. Among the total predicted proteins, only 25 were reported to overlap with the disease-associated genes. A protein-protein interaction network was constructed by using Cytoscape and STRING databases. MCODE was used to detect the densely connected subnetworks which revealed three sub-clusters. Cytohubba predicted four targets, i.e., fibroblast growth factor , FGF20, FGF22, and FGF23 as hub genes. Molecular docking of NSP-B based on a quantum-polarized docking approach with FGF6, FGF20, FGF22, and FGF23 revealed stronger interactions with the key hotspot residues. Moreover, molecular simulation revealed a stable dynamic behavior, good structural packing, and residues’ flexibility of each complex. Hydrogen bonding in each complex was also observed to be above the minimum. In addition, the binding free energy was calculated using the MM/GBSA (Molecular Mechanics/Generalized Born Surface Area) and MM/PBSA (Molecular Mechanics/Poisson-Boltzmann Surface Area) approaches. The total binding free energy calculated using the MM/GBSA approach revealed values of −36.85 kcal/mol for the FGF6-NSP-B complex, −43.87 kcal/mol for the FGF20-NSP-B complex, and −37.42 kcal/mol for the FGF22-NSP-B complex, and −41.91 kcal/mol for the FGF23-NSP-B complex. The total binding free energy calculated using the MM/PBSA approach showed values of −30.05 kcal/mol for the FGF6-NSP-B complex, −39.62 kcal/mol for the FGF20-NSP-B complex, −34.89 kcal/mol for the FGF22-NSP-B complex, and −37.18 kcal/mol for the FGF23-NSP-B complex. These findings underscore the promising potential of NSP-B against FGF6, FGF20, FGF22, and FGF23, which are reported to be essential for cancer signaling. These results significantly bolster the potential of NSP-B as a promising candidate for cancer therapy.

Epigenetic alterations that lead to differential expression of microRNAs (miRNAs/miR) are known to regulate tumour cell states, epithelial–mesenchymal transition (EMT) and the progression to metastasis in breast cancer. This study explores the key contribution of miRNA-18a in mediating a hybrid E/M cell state that is pivotal to the malignant transformation and tumour progression in the aggressive ER-negative subtype of breast cancer. The expression status and associated effects of miR-18a were evaluated in patient-derived breast tumour samples in combination with gene expression data from public datasets, and further validated in in vitro and in vivo breast cancer model systems. The clinical relevance of the study findings was corroborated against human breast tumour specimens (n = 446 patients). The down-regulated expression of miR-18a observed in ER-negative tumours was found to drive the enrichment of hybrid epithelial/mesenchymal (E/M) cells with luminal attributes, enhanced traits of migration, stemness, drug-resistance and immunosuppression. Further analysis of the miR-18a targets highlighted possible hypoxia-inducible factor 1-alpha (HIF-1α)-mediated signalling in these tumours. This is a foremost report that validates the dual role of miR-18a in breast cancer that is subtype-specific based on hormone receptor expression. The study also features a novel association of low miR-18a levels and subsequent enrichment of hybrid E/M cells, increased migration and stemness in a subgroup of ER-negative tumours that may be attributed to HIF-1α mediated signalling. The results highlight the possibility of stratifying the ER-negative disease into clinically relevant groups by analysing miRNA signatures.

The growing global burden of malignant tumors with increasing incidence and mortality rates underscores the urgent need for more effective and less toxic therapeutic options. Herbal compounds are being increasingly studied for their potential to meet these needs due to their reduced side effects and significant efficacy. Pristimerin (PS), a triterpenoid from the quinone formamide class derived from the Celastraceae and Hippocrateaceae families, has emerged as a potent anticancer agent. It exhibits broad-spectrum anti-tumor activity across various cancers such as breast, pancreatic, prostate, glioblastoma, colorectal, cervical, and lung cancers. PS modulates several key cellular processes, including apoptosis, autophagy, cell migration and invasion, angiogenesis, and resistance to chemotherapy, targeting crucial signaling pathways such as those involving NF-κB, p53, and STAT3, among others. The main objective of this review is to provide a comprehensive synthesis of the current literature on PS, emphasizing its mechanisms of action and molecular targets with the utmost clarity. It discusses the comparative advantages of PS over current cancer therapies and explores the implications for future research and clinical applications. By delineating the specific pathways and targets affected by PS, this review seeks to offer valuable insights and directions for future research in this field. The information gathered in this review could pave the way for the successful development of PS into a clinically applicable anticancer therapy.

Preceding a core-collapse supernova (CCSN), various processes produce an increasing amount of neutrinos of all flavors characterized by mounting energies from the interior of massive stars. Among them, the electron antineutrinos are potentially detectable by terrestrial neutrino experiments such as KamLAND and Super-Kamiokande (SK) via inverse beta decay interactions. Once these pre-supernova (pre-SN) neutrinos are observed, an early warning of the upcoming CCSN can be provided. In light of this, KamLAND and SK, both located in the Kamioka mine in Japan, have been monitoring pre-SN neutrinos since 2015 and 2021, respectively. Recently, we performed a joint study between KamLAND and SK on pre-SN neutrino detection. A pre-SN alert system combining the KamLAND detector and the SK detector was developed and put into operation, which can provide a supernova alert to the astrophysics community. Fully leveraging the complementary properties of these two detectors, the combined alert is expected to resolve a pre-SN neutrino signal from a 15 M _⊙ star within 510 pc of the Earth at a significance level corresponding to a false alarm rate of no more than 1 per century. For a Betelgeuse-like model with optimistic parameters, it can provide early warnings up to 12 hr in advance.

The current work advocates the use of Cashew Nut Shell Liquid/Oil (CNSL), an oil extract of the leftover cashew nut shells, as a novel environment-friendly cutting fluid in sustainable machining operations. The tribological characteristics of CNSL obtained on a pin-on-disc tribometer are found to be better compared to the traditionally used cutting fluid. Experiments are conducted on the surface grinder with EN8 material, considering input parameters, such as cutting fluid type, grinder speed and grade, work speed, and depth of cut, with Surface Roughness ( Ra ) and Grinding Temperature ( Temp ) being the responses. Input parameter optimization is performed using Taguchi’s statistical models. A total of 36 investigative and six validation experiments are conducted, and a prediction model is proposed. When Ra and Temp are optimized simultaneously, the prediction value of Ra is 0.071 μm, and the corresponding value of Temp is 31.6 °C for which the experimental values are 0.072 μm and 32 °C respectively. This work also applies the TODIM (TOmada de Decisao Interativa Multicriterio, in the Portuguese language), a multi-attribute decision-making method for ranking the input parameter settings. The study reveals that the performance of CNSL is better than that of a traditional cutting fluid, and the TODIM method can be successfully applied to rank the input parameter settings.

Among multimessenger observations of the next Galactic core-collapse supernova, Super-Kamiokande (SK) plays a critical role in detecting the emitted supernova neutrinos, determining the direction to the supernova (SN), and notifying the astronomical community of these observations in advance of the optical signal. In 2022, SK has increased the gadolinium dissolved in its water target (SK-Gd) and has achieved a Gd concentration of 0.033%, resulting in enhanced neutron detection capability, which in turn enables more accurate determination of the supernova direction. Accordingly, SK-Gd’s real-time supernova monitoring system has been upgraded. SK_SN Notice, a warning system that works together with this monitoring system, was released on 2021 December 13, and is available through GCN Notices. When the monitoring system detects an SN-like burst of events, SK_SN Notice will automatically distribute an alarm with the reconstructed direction to the supernova candidate within a few minutes. In this paper, we present a systematic study of SK-Gd’s response to a simulated Galactic SN. Assuming a supernova situated at 10 kpc, neutrino fluxes from six supernova models are used to characterize SK-Gd’s pointing accuracy using the same tools as the online monitoring system. The pointing accuracy is found to vary from 3° to 7° depending on the models. However, if the supernova is closer than 10 kpc, SK_SN Notice can issue an alarm with three-degree accuracy, which will benefit follow-up observations by optical telescopes with large fields of view.

This study analyzed the metabolite profiles and antioxidant capacities of two waxy and non-waxy Korean red rice accessions newly bred. Fifteen phenolic compounds were detected in the rice samples. Accession1 had high fatty acids, phytosterols, and vitamin E; accession3 had high vitamin E and phytosterol; and accession4 had a high total flavonoid. The correlation analysis findings from this study validated the positive association between all the metabolites and antioxidant activity. in silico results revealed that protocatechuic acid had a docking score of -9.541, followed by luteolin, quercetin, and caffeic acid, all of which had significant docking scores and a significant number of contacts. Similarly, molecular dynamics simulations showed that phytochemicals had root mean square deviation values of <2.8 Å with Keap 1, indicating better stability. This study provides valuable insights into potential directions for future investigations and improvements in the functional qualities of other colored rice varieties., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have influenced the work reported in this study., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: Platinum-based anticancer chemotherapy (PAC) represents a cornerstone in cancer treatment, retaining its status as the gold standard therapy. However, PAC's efficacy is countered by significant toxicities, such as nephrotoxicity, ototoxicity, and neurotoxicity. Recent studies have linked these toxicities to ferroptosis, characterized by iron accumulation, reactive oxygen species generation, and lipid peroxidation. This review explores the mechanisms underlying PAC-induced toxicities, focusing on the involvement of ferroptosis with three major PAC drugs-cisplatin, carboplatin, and oxaliplatin. Further, we provide a comprehensive analysis of the natural product mitigation of PAC-induced ferroptotic toxicity., Key Findings: The mechanistic role of ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, while studies on carboplatin-induced ferroptotic toxicities are lacking. Natural compounds targeting molecular pathways of ferroptosis have been explored to mitigate PAC-induced ferroptotic toxicity., Conclusion: While ferroptosis in cisplatin- and oxaliplatin-induced toxicities has been investigated, there remains a notable dearth of studies examining its involvement in carboplatin-induced toxicities. Hence, further exploration is warranted to define the role of ferroptosis in carboplatin-induced toxicities, and its further mitigation. Moreover, in-depth mechanistic evaluation is necessary to establish natural products evaluated against PAC-induced ferroptosis, as PAC adjuvants., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Multiproduct manufacturing of biotherapeutic proteins generate cleaning-induced protein degradants because of extreme pH and temperature conditions during the cleaning process. Cleaning Acceptance limits are calculated based on the maximum allowable carryover (MAC) assessment of the previously manufactured active pharmaceutical ingredient (API) - or drug product - based on the permitted daily exposure (PDE) of the previously manufactured API into the dose of subsequent product. In this study, we tested a previously determined PDE value for cleaning-induced protein degradants of 650 µg/dose. A bench-scale cleaning method was used to generate cleaning induced degradants from both a half-life extension (HLE) BiTE® molecule and a mAb product. For this investigation degradants of HLE BiTE®-A and mAb-1 were characterized either alone or degradants of HLE BiTE®-A and mAb-1 spiked into mAb-1 at 650 µg. These samples were characterized by endotoxin testing, size exclusion chromatography (SEC), light obscuration by HIAC, and micro-fluidic imaging (MFI). These results suggest that significant degradation of the molecule occurs because of the cleaning procedure, and it is no longer in the intact form or active state. The biological impact was assessed using a cell line assay to assess immune activation, and a human Peripheral Blood Mononuclear Cell (PBMC) assay to assess T cell activation, T cell proliferation, and cytokine release after 20 hours and 7 days. Findings from the various in vitro cell-based assays suggest that the presence of 650 µg of carryover of degradants either alone or spiked into the same or a cross-product do not increase immunogenicity risk in cell-based assays - suggesting that the current PDE of 650 µg/dose for cleaning-induced degradant carryover does not have a risk of immunogenicity in patients., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: All authors are currently, or were previously, employees, shareholders, or both employees and shareholders, of Amgen where the work was conducted., (Copyright © 2024. Published by Elsevier Inc.)

Long bone injuries heal through either endochondral or intramembranous bone formation pathways. Unlike the endochondral pathway that requires a cartilage template, the process of intramembranous ossification involves the direct conversion of skeletal stem and progenitor cells (SSPCs) into bone-forming osteoblasts. There are limited surgical methods to model this process in experimental mice. Here, we have improved upon a bone marrow injury model in mice to facilitate the study of bone repair via intramembranous ossification and to assess postnatal regulators of osteogenesis. This method is highly reproducible and user-friendly, and it allows temporal assessment of new bone formation in a short period (3-7 days post-injury) using μCT and frozen section histology. Furthermore, the contributions of SSPCs and mature osteoblasts can be readily assessed using a combination of fluorescent reporter mice and this intramembranous bone marrow injury model. In clinical contexts, intramembranous bone formation is relevant for healing critical size defects, stress fractures, cortical defects, trauma from tumor resections, and joint replacements.

Appendicitis, an infection and inflammation of the appendix is a prevalent condition in children that requires immediate treatment. Rupture of the appendix may lead to several complications, such as peritonitis and sepsis. Appendicitis is medically diagnosed using urine, blood, and imaging tests. In recent times, Artificial Intelligence and machine learning have been a boon for medicine. Hence, several supervised learning techniques have been utilized in this research to diagnose appendicitis in pediatric patients. Six heterogeneous searching techniques have been used to perform hyperparameter tuning and optimize predictions. These are Bayesian Optimization, Hybrid Bat Algorithm, Hybrid Self-adaptive Bat Algorithm, Firefly Algorithm, Grid Search, and Randomized Search. Further, nine classification metrics were utilized in this study. The Hybrid Bat Algorithm technique performed the best among the above algorithms, with an accuracy of 94% for the customized APPSTACK model. Five explainable artificial intelligence techniques have been tested to interpret the results made by the classifiers. According to the explainers, length of stay, means vermiform appendix detected on ultrasonography, white blood cells, and appendix diameter were the most crucial markers in detecting appendicitis. The proposed system can be used in hospitals for an early/quick diagnosis and to validate the results obtained by other diagnostic modalities., (© 2024. The Author(s).)

Nanostructures are tiny objects at the molecular and microscopic scale, with carbon nanotubes being the most notable among them. The elements possess exceptional microelectronic properties and other unique characteristics. Researchers have recently focused on the mathematical features of these materials. Molecular descriptors are crucial in mathematical chemistry, particularly in QSAR and QSPR modeling. Topological indices hold a significant position among them. This study presents the precise formulation of the ten most crucial topological indices for a benzene ring positioned on a P-type surface within the highly symmetric 2D lattice BCZ 48 . We have incorporated the computed indices to develop a predictive model for the graph energy of the 2D lattice and, in addition, provided the NMR patterns and the HOMO-LUMO gap., (© 2024. The Author(s).)

Objective: This study aimed to evaluate the effect of a psychosocial education program on postnatal depression (PND), perceived stress, (PSS), and perceived maternal parenting self-efficacy (PMPSE)., Methods: A randomized controlled trial design was used with stratified block randomization. The sample size consisted of 128 pregnant women. The women in the experimental group were provided with a psychosocial education program along with standard care, and the control group received standard care with an information pamphlet. Post-test assessments (PND, PSS, and PMPSE) were performed at 1 week, 6 weeks, and 12 weeks after delivery in both groups., Results: The result of the effect of the intervention on outcome variables on repeated measures ANOVA revealed that there was a positive statistically significant reduction in scores of postnatal depression [F (1, 119) = 18.832, p = 0 < 0.001] and perceived stress [F (1,119) = 22.488, p = < 0.001] and no statistically significant change in perceived maternal parenting self-efficacy in the experimental group [F (1,119) = 0.036, p = 0.850]., Conclusion: The psychosocial education program was found to be effective in reducing postnatal depression and stress related to pregnancy and childbirth to enable a smooth transition to motherhood., Practice Implications: Given the benefits the program provides to women, this psychosocial education program could be incorporated into routine antenatal care for pregnant women., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Declaration of Competing Interest The authors declare that they have no potential conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objectives: To describe the participants of a university-based COVID-19 contact tracing course and determine whether the course changed knowledge, attitudes, and intention to participate in contact tracing., Participants: Faculty, staff, and students were eligible., Methods: Surveys evaluated the impact of the course on participant intentions to engage in contact tracing. Logistic regression identified characteristics associated with increased likelihood of participating in contact tracing., Results: Nearly 800 individuals participated, of whom 26.2% identified as Hispanic/Latino and 14.0% as Black. Nearly half (48.8%) planned to conduct contact tracing. While attitudes did not change, knowledge improved (67.9% vs. 93.8% scores on assessments; p  < 0.001). Younger participants and Black individuals were more more likely to be confident that they would participate in contact tracing., Conclusions: Course completion was associated with increased knowledge. Participants were racially and ethnically diverse, highlighting how universities can partner with health departments to develop workforces that reflect local communities.

Background: The prevalence and impact of obesity on outcomes of atrial fibrillation (AF) ablation randomized controlled trials (RCTs) have not been well studied., Objective: To examine the proportion of participants with obesity enrolled in RCTs of AF ablation and outcomes of ablation when subgroup analysis of participants with obesity were available., Methods: We systematically searched PubMed and EMBASE for AF ablation RCTs published between January 1, 2015 to May 31, 2022. When body mass index (BMI) data were available, normal distribution was assumed and a z score was used to estimate the proportion of obesity. Results categorized by BMI or body weight status were reviewed. Authors were contacted for additional information., Results: Of 148 eligible RCTs with 30174 participants, 144 (97.30%) RCTs did not report the proportion of participants with obesity, while published information regarding BMI was available in 63.51%. Three trials excluded patients based on BMI. Using reported BMI, we estimated the proportion of participants with obesity varied greatly across these trials, ranging from 5.82%-71.9% (median 38.02%, interquartile 29.64%, 49.10%). Patients with obesity were represented in a greater proportion among trials conducted in North America (50.23%) and Asia (44.72%), compared to others (32.16%), p < .001. Subgroup analysis or analysis adjusting for BMI was reported in only 13 (8.78%) RCTs; four (30.77%) of these suggested that BMI or body weight might negatively affect primary outcomes., Conclusion: Obesity is a common comorbidity among AF patients. However, most AF ablation RCTs underreported the proportion of participants with obesity and its impact on the primary outcomes., (© 2024 The Author(s). Journal of Cardiovascular Electrophysiology published by Wiley Periodicals LLC.)

Background: Many patients with persistent atrial fibrillation (PsAF) have progressed from an initial paroxysmal phenotype; however, there are patients in whom atrial fibrillation (AF) is persistent at diagnosis. Relatively little is known about this subgroup, but prior observational studies have suggested these patients have worse outcomes with ablation., Objectives: This study sought to: 1) assess demographic and electrophysiologic characteristics of patients with PsAF at first diagnosis compared with those with who have progressed from paroxysmal atrial fibrillation (PAF); and 2) assess the impact of pattern of AF at diagnosis on recurrence post ablation., Methods: CAPLA (Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein isolation [PVI] vs PVI with posterior Left Atrial wall isolation [PWI]) was a multicenter trial that randomized patients with PsAF to PVI plus PWI or PVI alone. Follow-up was 12 months. Outcomes were assessed after a 3-month blanking period., Results: A total of 334 patients were included (median age 65.6 years, 23.1% female), 194 (58.1%) had PsAF at first AF diagnosis and 140 (41.9%) had PAF. Patients with PsAF at diagnosis were younger (age 64.0 vs 67.7 years, P = 0.005), had higher rates of heart failure (P < 0.001), and lower left ventricular ejection fraction (54.5% IQR: 40-60 vs 60% IQR: 50-61, P = 0.007). AF recurrence occurred in 85 (43.8%) with PsAF at diagnosis and 70 (50%) with PAF at diagnosis. PsAF at diagnosis was not associated with risk of recurrence on univariable (HR: 0.802; 95% CI: 0.585-1.101; P = 0.173) or multivariable analysis (HR: 0.922; 95% CI: 0.647-1.312; P = 0.650). Median AF burden was 0% in both groups (P = 0.125). There was no difference in left atrial size (P = 0.337) or bipolar voltage (P = 0.579) between the groups., Conclusions: In the CAPLA cohort of patients, pattern of AF at first diagnosis did not influence post-ablation rate of AF recurrence or AF burden. (Catheter Ablation for persistent atrial fibrillation: A Multicentre randomised trial of Pulmonary vein isolation [PVI] vs PVI with posterior Left Atrial wall isolation [PWI]; ACTRN12616001436460)., Competing Interests: Funding Support and Author Disclosures Dr Kalman is a recipient of a National Health and Medical Research Council (NHMRC) Clinical Investigator Grant; and has received research and fellowship support from Medtronic, Abbott, Zoll, and Biosense Webster. Dr Kistler is a recipient of a Clinical Investigator grant from the NHMRC; has received funding from Abbott Medical for consultancy and speaking engagements; and has served on the advisory board with fellowship support from Biosense Webster. Dr Sanders has served on advisory boards for Medtronic, Abbott Medical, CathRx, Pacemate, and Boston Scientific; and has been supported by a practitioner fellowship from NHMRC and the National Heart Foundation of Australia (NHF). Dr Lee has received consulting fees from Biosense Webster. Dr Prabhu is supported by an NHMRC Post-Doctoral Research Fellowship; and has received consulting fees, fellowship support, and educational grants from Biosense Webster, Abbott Medical, and Boston Scientific. Dr Ling has received grants from Abbott Australia. Dr Chieng is supported by an NHF Post-Doctoral Fellowship. Dr Crowley is supported by a Baker institute PhD scholarship. Dr William is supported by an NHF postgraduate PhD scholarship. Dr Segan is support by a co-funded NHMRC/NHF postgraduate PhD scholarship. Dr Sterns has received personal fees from Biosense Webster. Dr Ginks has served on Speakers Bureau for Biosense Webster Speaker and Abbott. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: The optimal timing of catheter ablation in individuals with atrial fibrillation (AF) and left ventricular systolic dysfunction (LVSD) remains uncertain., Objective: We examined whether AF diagnosis to ablation time (DAT) influences outcomes following catheter ablation (CA) in patients with persistent AF (PsAF) and LVSD from the CAMERA-MRI and CAPLA randomized studies., Methods: We evaluated clinical outcomes according to DAT < 1 year ("shorter DAT") and ≥1 year ("longer DAT"), comparing AF recurrence, AF burden, left ventricular ejection fraction (LVEF), and LV recovery (LVEF ≥ 50%) at 12 months. DAT was also compared according to the median (24 months)., Results: Two hundred and ten individuals with AF and LVSD were identified, with a median DAT of 24 months. Shorter DAT was associated with lower LA global and posterior wall scar (<0.05 mV; both P < .05). At 12 months, 69.4% with shorter DAT (<1year) were free from recurrent atrial arrhythmias vs 53.6% in longer DAT (hazard ratio [HR] 1.63, 95% confidence interval [CI] 1.01-2.65, P = .040). Median AF burden was 0% in both groups (shorter DAT: interquartile range [IQR] 0.0-2.0% vs longer DAT: IQR 0.0-7.3%, P = .017). At 12 months, shorter DAT was associated with higher LVEF (55.3% vs 51.0%, P = .009), greater LVEF improvement (+20.8 ± 13.0% vs +13.9 ± 13.2% longer DAT, P < .001) and LV recovery (75.0% vs longer DAT: 57.2%, P = .011). Shorter DAT was associated with fewer hospitalizations and electrical cardioversions at 12 months., Conclusion: In individuals with AF and LVSD, shorter DAT was associated with greater LVEF improvement and arrhythmia-free survival with lower AF burden and rehospitalization at 12 months, highlighting the prognostic benefit of early CA in AF and LVSD., Competing Interests: Disclosures The following industry funding sources regarding activities outside the submitted work have been declared in accordance with ICMJE guidelines. Dr Segan is a recipient of a cofunded NHMRC and National Heart Foundation PhD stipend. Dr Kistler is a recipient of the Investigator grant from the NHMRC and has received funding from Abbott Medical for consultancy and speaking engagements and has served on the advisory board with fellowship support from Biosense Webster. Dr Kalman has received fellowship support from Medtronic and Biosense Webster. Dr Lee has received consulting fees from Biosense Webster. Dr Prabhu is supported by a NHMRC Post-Doctoral Research Fellowship and has received consulting fees, fellowship support, and educational grants from Biosense Webster, Abbott Medical, and Boston Scientific. The remaining authors have no conflicts of interest to disclose., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures P.M.K. is a recipient of the Investigator Grant from the NHMRC; has received funding from Abbott Medical for consultancy and speaking engagements; and has served on the advisory board with fellowship support from Biosense Webster. J.M.K. has received research and fellowship support from Medtronic, Abbott, Zoll, and Biosense Webster. S.P. is supported by an NHMRC Post-Doctoral Research Fellowship and has received consulting fees, fellowship support, and educational grants from Biosense Webster, Abbott Medical, and Boston Scientific. L.L. received grants from Abbott Australia. D.C. is supported by an NHF Post-Doctoral Fellowship. R.C. is supported by a Baker Institute PhD scholarship. J.W. is supported by an NHF postgraduate PhD scholarship. L.S. is supported by a co-funded NHMRC/NHF postgraduate PhD scholarship.

Systemic lupus erythematosus (SLE) is a chronic, heterogeneous, systemic autoimmune disease characterized by autoantibody production, complement activation, and immune complex deposition. SLE predominantly affects young, middle-aged, and child-bearing women with episodes of flare-up and remission, although it affects males at a much lower frequency (female: male; 7:1 to 15:1). Technological and molecular advancements have helped in patient stratification and improved patient prognosis, morbidity, and treatment regimens overall, impacting quality of life. Despite several attempts to comprehend the pathogenesis of SLE, knowledge about the precise molecular mechanisms underlying this disease is still lacking. The current treatment options for SLE are pragmatic and aim to develop composite biomarkers for daily practice, which necessitates the robust development of novel treatment strategies and drugs targeting specific responsive pathways. In this communication, we review and aim to explore emerging therapeutic modalities, including multiomics-based approaches, rational drug design, and CAR-T-cell-based immunotherapy, for the management of SLE., (© 2024. The Author(s).)

Introduction: Biliary hamartomas are rare congenital development anomaly of bile ducts, which are detected incidentally. They often present as multiple lesions on liver surface which resembles metastatic lesions. We report a case of acute calculous cholecystitis ultimately diagnosed to have asymptomatic multiple biliary hamartomas., Case Description: A 42-year-old male with no co-morbidities presented with pain in upper abdomen associated with fever and vomiting. Contrast enhanced computed tomography (CECT) of abdomen showed acute calculous cholecystitis, hepatomegaly with fatty changes in liver. On laparoscopy the liver was found to have grey-white nodular lesions of about 0.5 cm in diameter scattered on the surface of both the lobes. One of the lesion was biopsied along with cholecystectomy., Discussion: Biliary hamartoma commonly referred to as "von Meyenburg complexes" are uncommon lesions found in the liver which are usually asymptomatic. In this case the patient presented with symptoms of acute cholecystitis but the biopsy report from liver lesions proved to be benign biliary hamartoma which on initial impression looked like multiple liver secondaries., Conclusion: We have described a case of an adult with multiple biliary hamartoma which was an incidental finding. Biliary hamartoma is a rare entity which can sometime mimic metastasis in the liver. Thus, histopathological confirmation is essential before planning any further treatment., Competing Interests: Declaration of competing interest Dr. Deepika C.A declares no conflict of interest in this study. Dr. Poornachandra Thejeswi declares no conflict of interest in this study. Dr. Shivananda Prabhu declares no conflict of interest in this study. Dr. Jyothi Kini declares no conflict of interest in this study. No external funding was obtained for this study., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Implantable loop recorders (ILRs) are increasingly used to evaluate patients with unexplained syncope. Identification of all predictors of bradycardic syncope and consequent permanent pacemaker (PPM) insertion is of substantial clinical interest as patients in the highest risk category may benefit from upfront pacemaker insertion., Objective: We performed a systematic review and meta-analysis to identify risk predictors for PPM insertion in ILR recipients with unexplained syncope., Methods: An electronic database search (MEDLINE, Embase, Scopus, Cochrane) was performed in June 2023. Studies evaluating ILR recipients with unexplained syncope and recording risk factors for eventual PPM insertion were included. A random effects model was used to calculate the pooled odds ratio (OR) for clinical and electrocardiographic characteristics with respect to future PPM requirement., Results: Eight studies evaluating 1007 ILR recipients were included; 268 patients (26.6%) underwent PPM insertion during study follow-up. PPM recipients were older (mean age, 70.2 ± 15.4 years vs 61.6 ± 19.7 years; P < .001). PR prolongation on baseline electrocardiography was a significant predictor of PPM requirement (pooled OR, 2.91; 95% confidence interval, 1.63-5.20). The presence of distal conduction system disease, encompassing any bundle branch or fascicular block, yielded a pooled OR of 2.88 for PPM insertion (95% confidence interval, 1.53-5.41). Injurious syncope and lack of syncopal prodrome were not significant predictors of PPM insertion. Sinus node dysfunction accounted for 62% of PPM insertions, whereas atrioventricular block accounted for 26%., Conclusion: Approximately one-quarter of ILR recipients for unexplained syncope require eventual PPM insertion. Advancing age, PR prolongation, and distal conduction disease are the strongest predictors for PPM requirement., Competing Interests: Disclosures Jeremy William is supported by PhD scholarships from the Monash University (Graduate Excellence Scholarship), the Australian Government (Research Training Program stipend), and Heart Foundation of Australia., (Crown Copyright © 2024. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Posterior wall isolation (PWI) is commonly incorporated into catheter ablation (CA) strategies for persistent atrial fibrillation (AF) in an attempt to improve outcomes. In the CAPLA randomized study, adjunctive PWI did not improve freedom from atrial arrhythmia at 12 months compared with pulmonary vein isolation (PVI) alone. Whether additional PWI reduces arrhythmia recurrence over the longer term remains unknown., Methods: In this multicenter, international, randomized study patients with persistent AF undergoing index CA using radiofrequency (RF) were randomized to PVI+PWI versus PVI alone. Patients underwent regular follow-up including rhythm monitoring for a minimum of 3 years post CA. AF burden at 3 years post-ablation was evaluated with either 28-day continuous ambulatory ECG monitoring, twice daily single-lead ECG or from cardiac implanted device. Evaluated endpoints included freedom from any documented atrial arrhythmia recurrence after a single procedure, AF burden, need for redo catheter ablation, rhythm at last clinical follow-up, healthcare utilisation metrics and AF-related quality of life., Results: 333 of 338 (98.5%) patients (mean age 64.3±9.4 years, 23% female) completed 3-year follow-up, with 169 patients randomized to PVI+PWI and 164 patients to PVI alone. At a median of 3.62 years post-index ablation, freedom from recurrent atrial arrhythmia occurred in 59 patients (35.5%) randomized to PVI+PWI vs 68 patients (42.1%) randomized to PVI alone (HR 1.15, 95% CI 0.88-1.51, p=0.55). Median time to recurrent atrial arrhythmia was 0.53 years (IQR 0.34-1.01 years). Redo ablation was performed in 54 patients (32.0%) in the PVI+PWI group vs 49 patients (29.9%, p=0.68) in the PVI alone group. Pulmonary vein reconnection was present in 54.5% (mean number of reconnected PVs 2.2±0.9) and posterior wall reconnection in 75%. Median AF burden at 3 years was 0% in both groups (IQR 0-0.85% PVI+PWI vs 0-1.43% PVI alone, p=0.49). Sinus rhythm at final clinical follow-up was present in 85.1% with PVI+PWI vs 87.1% with PVI alone (p=0.60). Mean AF Effect On Quality-Of-Life (AFEQT) score at 3 years post-ablation was 88.0±14.8 with PVI+PWI vs 88.9±15.4 with PVI alone (p=0.63)., Conclusions: In patients with persistent AF, the addition of PWI to PVI alone at index RF catheter ablation did not significantly improve freedom from atrial arrhythmia recurrence at long-term follow-up. Median AF burden remains low and AF quality of life high at 3 years with either ablation strategy., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Quantum reservoir computing (QRC) has been proposed as a paradigm for performing machine learning with quantum processors where the training takes place in the classical domain, avoiding the issue of barren plateaus in parameterized-circuit quantum neural networks. It is natural to consider using a quantum processor based on microwave superconducting circuits to classify microwave signals that are analog-continuous in time. However, while there have been theoretical proposals of analog QRC, to date QRC has been implemented using the circuit model-imposing a discretization of the incoming signal in time. In this paper we show how a quantum superconducting circuit comprising an oscillator coupled to a qubit can be used as an analog quantum reservoir for a variety of classification tasks, achieving high accuracy on all of them. Our work demonstrates processing of ultra-low-power microwave signals within our superconducting circuit, a step towards achieving a quantum sensing-computational advantage on impinging microwave signals., (© 2024. The Author(s).)

Background and Aims: Patterns of atrial fibrillation (AF) recurrence post-catheter ablation for persistent AF (PsAF) are not well described. This study aimed to describe the pattern of AF recurrence seen following catheter ablation for PsAF and the implications for healthcare utilization and quality of life (QoL)., Methods: This was a post-hoc analysis of the CAPLA study, an international, multicentre study that randomized patients with symptomatic PsAF to pulmonary vein isolation plus posterior wall isolation or pulmonary vein isolation alone. Patients underwent twice daily single lead ECG, implantable device monitoring or three monthly Holter monitoring., Results: 154 of 333 (46.2%) patients (median age 67.3 years, 28% female) experienced AF recurrence at 12-month follow-up. Recurrence was paroxysmal in 97 (63%) patients and persistent in 57 (37%). Recurrence type did not differ between randomization groups (P = .508). Median AF burden was 27.4% in PsAF recurrence and .9% in paroxysmal AF (PAF) recurrence (P < .001). Patients with PsAF recurrence had lower baseline left ventricular ejection fraction (PsAF 50% vs. PAF 60%, P < .001) and larger left atrial volume (PsAF 54.2 ± 19.3 mL/m² vs. PAF 44.8 ± 11.6 mL/m², P = .008). Healthcare utilization was significantly higher in PsAF (45 patients [78.9%]) vs. PAF recurrence (45 patients [46.4%], P < .001) and lowest in those without recurrence (17 patients [9.5%], P < .001). Patients without AF recurrence had greater improvements in QoL as assessed by the Atrial Fibrillation Effect on Quality-of-Life (AFEQT) questionnaire (Δ33.3 ± 25.2 points) compared to those with PAF (Δ24.0 ± 25.0 points, P = .012) or PsAF (Δ13.4 ± 22.9 points, P < .001) recurrence., Conclusions: AF recurrence is more often paroxysmal after catheter ablation for PsAF irrespective of ablation strategy. Recurrent PsAF was associated with higher AF burden, increased healthcare utilization and antiarrhythmic drug use. The type of AF recurrence and AF burden may be considered important endpoints in clinical trials investigating ablation of PsAF., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Alzheimer's disease (AD) is an extremely complex, heterogeneous, and multifactorial neurodegenerative disease clinically characterized by progressive memory loss and progressive decline in cognitive function. There is currently no effective treatment for the onset and/or progression of the pathophysiological diseases of AD. The global prevalence of this disease has increased in recent years due to modern lifestyle. Therefore, there is an urgent need to develop a drug with significant neuroprotective potential. Since plant metabolites, especially polyphenols, have important pharmacological properties acting against β-amyloid (Aβ), Tau, neuroinflammation, and oxidative stress, such phytochemicals were selected in the present research. Using the Schrödinger tool (Maestro V.13.6), the drug potency of these metabolites was studied after installation in the highly configured workstation. Among the 120 polyphenols docked, amygdalin showed notable docking values of - 11.2638, followed by eriocitrin (- 10.9569), keracyanin (- 10.7086), and amaroswerin (- 9.48126). The prominent MM-GBSA values of these molecules were - 62.8829, - 52.1914, - 68.6307, and - 63.1074, respectively. The MM-GBSA energy values demonstrated the drug stability of these molecules for β-site amyloid precursor protein-cleaving enzyme 1 (BACE1)-causing AD. In the absorption and distribution assessment, these phytochemicals showed significantly better values than the inhibitors CNP520. The chosen phytochemicals have been demonstrated as non-hepatotoxic; however, the BACE1 inhibitor CNP520 is hepatotoxic. In both the molecular docking and ADMET assessments, these natural chemicals have shown optimism as potential drug candidates for Alzheimer's disease. However, in order to understand the detailed biological metabolism of these compounds in AD, they need to be evaluated in in vivo studies to validate its efficacy., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Blastoid mantle cell lymphoma (B-MCL) is a rare aggressive lymphoma. It is characterized by blastoid morphology with high proliferation and inconsistent immunohistochemistry (IHC), making it a diagnostic challenge for the pathologist., Methods: This is a retrospective analytical cohort study. We reviewed biopsy confirmed cases of B-MCL diagnosed over a period of 10 years (January 2012 to December 2022). The clinical presentation, histopathological and IHC findings, treatment received, and survival outcomes were studied. Randomly selected cases of classic MCL (n=12), diagnosed during the same period served as controls., Results: A total of 12 cases were studied. Four cases were transformed from previously diagnosed MCL; 8 cases arose de novo. Mean age was 61.17 years and the male: female ratio was 5:1. Half of the cases showed extra nodal extension and 81.8% had bone marrow involvement. Gastrointestinal tract was the most common site of extra nodal involvement. Histopathological examination showed diffuse involvement of the lymph node with medium sized cells. On immunohistochemistry, one of the cases showed loss of CD5 expression while the other had aberrant CD10 expression. Mean Ki-67 index was 58.09% in the cases and 16.33% in controls and was statistically significant ( p =0.005). The median overall survival (OS) for cases was 2 years vs 8 years in controls. The p53 over expression (>30% nuclear positivity) was seen in 66.6% cases (4/6)., Conclusion: There are several factors that contribute to the aggressiveness of B-MCL, and new treatment approaches might be required to improve patient outcomes., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Monappa V et al.)