Search

Regulatory T cells (Treg) are important players in the tumor microenvironment. However, the mechanisms behind their immunosuppressive effects are poorly understood. We found that CCR6-CCL20 activity in tumor-infiltrating Tregs is associated with greater glycolytic activity and ablation of Ccr6 reduced glycolysis and lactic acid production while increasing compensatory glutamine metabolism. Immunosuppressive activity toward CD8+ T cells was abrogated in Ccr6-/- Tregs due to reduction in activation-induced glycolysis. Furthermore, Ccr6-/- mice exhibited improved survival across multiple tumor models compared to wild-type mice and Treg and CD8+ T-cell depletion abrogated the improvement. In addition, Ccr6 ablation further promoted the efficacy of anti-PD-1 therapy in a preclinical glioma model. Follow-up knockdown of Ccl20 with siRNA also demonstrated improvement in antitumor efficacy. Our results unveil CCR6 as a marker and regulator of Treg-induced immunosuppression and identify approaches to target the metabolic determinants of Treg immunosuppressive activity., (©2024 American Association for Cancer Research.)

Research Question: What are the specific genetic alterations and associated network in endometriotic cells responsible for the disease pathogenesis?, Design: Case control experimental study involving 45 women with endometriosis who underwent laparoscopic surgery (case) and 45 normal samples from women undergoing total abdominal hysterectomy (control). The endometrial samples were subjected to whole exome sequencing (WES) of endometriotic tissue and copy number variation analysis. Validation of gene hits were obtained from WES using polymerase chain reaction techniques, immunological techniques, in-silico tools and transgenic cell line models., Results: Germline heterozygous deletion of mRNA editing enzyme subunit APOBEC3B was identified in about 96% of endometriosis samples. The presence of germline deletion was confirmed with blood, endometrium and normal ovary samples obtained from the same patient. APOBEC3B deletions resulted in a hybrid protein that activates A1CF. APOBEC3B deletion can be a major cause of changes in the endometriotic microenvironment, and contributes to the pathogenesis and manifestation of the disease. The effect of APOBEC3B deletion was proved by in-vitro experiments in a cell line model, which displayed endometriosis-like characteristics. APOBEC3B germline deletion plays a major role in the pathogenesis of endometriosis, which is evident by the activation of A1CF, an increase in epithelial to mesenchymal transition, cellular proliferation, inflammation markers and a decrease in apoptosis markers., Conclusion: The deleterious effects caused by APOBEC3B deletion in endometriosis were identified and confirmed. These results might provide a base for identifying the complete pathogenetic mechanism of endometriosis, thereby moving a step closer to better diagnosis and treatment options., (Copyright © 2024 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

An effective approach to producing sophisticated miniaturized and nanoscale materials involves arranging nanomaterials into layered hierarchical frameworks. Nanostructured layered materials are constructed to possess isolated propagation assets, massive surface areas, and envisioned amenities, making them suitable for a variety of established and novel applications. The utilization of various techniques to create nanostructures adorned with metal nanoparticles provides a secure alternative or reinforcement for the existing physicochemical methods. Supported metal nanoparticles are preferred due to their ease of recovery and usage. Researchers have extensively studied the catalytic properties of noble metal nanoparticles using various selective oxidation and hydrogenation procedures. Despite the numerous advantages of metal-based nanoparticles (NPs), their catalytic potential remains incompletely explored. This article examines metal-based nanomaterials that are supported by layers, and provides an analysis of their manufacturing, procedures, and synthesis. This study incorporates both 2D and 3D layered nanomaterials because of their distinctive layered architectures. This review focuses on the most common metal-supported nanocomposites and methodologies used for photocatalytic degradation of organic dyes employing layered nanomaterials. The comprehensive examination of biological and ecological cleaning and treatment techniques discussed in this article has paved the way for the exploration of cutting-edge technologies that can contribute to the establishment of a sustainable future., 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., (Copyright © 2024. Published by Elsevier Inc.)

Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these interactions with tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow to identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed to recapitulate genes and proteins, some borrowed and others tumor-intrinsic, induced in cancer cells by direct contact. Protein-protein interaction networks revealed the rich connectome between 'borrowed' and 'intrinsic' components. Bioinformatics prioritized one of the 'borrowed' components, CCDC88A/GIV, a multi-modular metastasis-related protein that has recently been implicated in driving a hallmark of cancer, growth signaling autonomy. MSCs transferred GIV protein to ER+ breast cancer cells (that lack GIV) through tunnelling nanotubes via connexin (Cx)43-facilitated intercellular transport. Reinstating GIV alone in GIV-negative breast cancer cells reproduced approximately 20% of both the 'borrowed' and the 'intrinsic' gene induction patterns from contact co-cultures; conferred resistance to anti-estrogen drugs; and enhanced tumor dissemination. Findings provide a multiomic insight into MSC→tumor cell intercellular transport and validate how transport of one such candidate, GIV, from the haves (MSCs) to have-nots (ER+ breast cancer) orchestrates aggressive disease states.

DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors (DNMTis, PARPis) induce a stimulator of interferon (IFN) genes (STING)-dependent pathogen mimicry response (PMR) in ovarian (OC) and other cancers. We now show that combining DNMTis and PARPis upregulates expression of a little-studied nucleic-acid sensor, NFX1-type zinc finger-containing 1 protein (ZNFX1). We demonstrate that ZNFX1 is a novel master regulator for PMR induction in mitochondria, serving as a gateway for STING-dependent PMR. In patient OC databases, high ZNFX1 expression levels correlate with advanced stage disease. ZNFX1 expression alone significantly correlates with an increase in overall survival in a phase 3 trial for therapy-resistant OC patients receiving bevacizumab in combination with chemotherapy. In correlative RNA-seq data, inflammasome signaling through ZNFX1 correlates with abnormal vasculogenesis. ZNFX1 controls PMR signaling through the mitochondria and may serve as a biomarker to facilitate offering personalized therapy in OC patients, highlighting the strong translational significance of our findings., Significance Statement: DNA methyltransferase and poly(ADP-ribose) polymerase inhibitors upregulate expression of a novel nucleic-acid sensor, ZNFX1 that serves as a mitochondrial gateway to STING-dependent interferon/inflammasome signaling with tumor suppressor properties in ovarian cancer.

Skin is an important vital organ that must be given proper care and protection from external damage and harmful microbes. If injured, it must be treated with an ideal wound dressing material with potent hemostatic and non-toxic properties. In the present study, fish collagen (FC) was extracted from the fins and tails of Black pomfret (Parastromateus niger). The isolated fish collagen was homogenized with pectin (P) and freeze dried to obtain fish collagen/pectin (FC/P) scaffolds. Scanning electron microscopic analysis showed the porous nature of scaffolds with intermittent holes. UV-Visible and Fourier infrared spectroscopic analyses demonstrated the physicochemical properties of FC/P scaffolds. Hemolytic assay performed using human blood demonstrated the percentage of hemolysis as 0.5 %. In vitro blood clotting assay carried out to determine the hemostatic behaviour displayed the formation of blood clot within 60 s in the presence of FC/P scaffolds. 95 % of cells were viable with the highest concentration of FC/P scaffold used for MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. Scratch wound assay demonstrated complete closure of wound in FC/P scaffold treated cells after 48 h of treatment. Chick embryo chorioallantoic membrane (CAM) assay showed the development of new blood vessels within 6 h of incubation with the FC/P scaffolds, thereby proving their angiogenic potency. These results indicate the potential use of FC/P scaffolds as effective biomaterials for tissue regenerative applications., 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., (Copyright © 2024 Elsevier B.V. All rights reserved.)

This research investigates the manufacturing and characterisation of polyester-based composites reinforced with jute fibres and red mud particulates. The motivation stems from the need for sustainable, high-performance materials for applications in industries, like aerospace and automotive, where resistance to erosion is critical. Jute, a renewable fibre, combined with red mud, an industrial byproduct, offers an eco-friendly alternative to conventional composites. The composites were fabricated using compression moulding with varying red mud contents (10, 20, and 30 wt.%) and a fixed 40 wt.% of jute fibre. Fibre treatments included sodium hydroxide (NaOH) and silane treatments to improve bonding and performance. Erosion tests were performed using an air-jet erosion tester, examining the effects of the red mud content, fibre treatment, and impact angles. Scanning Electron Microscope (SEM) analysis provided insights into the erosion mechanisms. A distinctive reduction in erosion rates at higher impact angles (30°-60°) was observed, attributed to the semi-ductile nature of the composites. The addition of red mud enhanced erosion resistance, although an excess of 30 wt.% reduced resistance due to poor surface bonding. Silane-treated composites showed the lowest erosion rates. This study provides new insights into the interplay among material composition, fibre treatment, and erosion dynamics, contributing to the development of optimised, eco-friendly composite materials.

Objective: There is significant practice variation in the use of antithrombotic therapy after endovascular intervention for lower limb peripheral arterial disease, with differences in medication choice and duration. Prescriber decision making is complex, and patient factors have been shown to substantially contribute to prescribing variation. To determine the influence of patient factors on antithrombotic prescribing, a discrete choice experiment was distributed to vascular surgeons and trainees across Australia and Aotearoa New Zealand., Methods: After pilot testing, the discrete choice experiment questionnaire was distributed to 300 vascular surgeons and trainee members of the Australian and New Zealand Society for Vascular Surgery. Multinomial logistic regression models were used to analyse patient factors that had the most influence on decisions to prescribe a second antithrombotic agent, and the preferred choice of antithrombotic (clopidogrel 75 mg daily or rivaroxaban 2.5 mg twice daily) in addition to aspirin 100 mg daily. The odds ratio (OR) with 95% confidence interval (CI) reported preference strength., Results: A total of 44 questionnaires were completed between September and October 2023, reaching the 15% targeted response rate. Prescribing a second antithrombotic was more likely after femoropopliteal stenting compared with angioplasty (OR 1.89, 95% CI 1.20 - 2.13), and in chronic limb threatening ischaemia compared with intermittent claudication (OR 1.58, 95% CI 1.20 - 2.13). Most respondents preferred clopidogrel over rivaroxaban (62%), with over a third of respondents exclusively prescribing clopidogrel. Patients with stents (OR 1.77, 95% CI 1.32 - 2.37) or moderate bleeding risk (OR 1.38, 95% CI 0.97 - 1.84) were more likely to receive clopidogrel than rivaroxaban., Conclusion: This study demonstrates that vascular surgeons primarily prioritise antithrombotic prescribing decisions by procedure type. Clopidogrel is more likely to be prescribed than rivaroxaban as a second agent in combination with aspirin, especially after stenting. Knowing these clinician preferences can target implementation strategies towards supporting decision making in subgroups of patients according to individual risk profiles., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

For several decades, products derived from marine natural sources (PMN) have been widely identified for several therapeutic applications due to their rich sources of bioactive sub-stances, unique chemical diversity, biocompatibility and excellent biological activity. For the past 15 years, our research team explored several PMNs, especially fungi fibrinolytic compounds (FGFCs). FGFC is an isoindolone alkaloid derived from marine fungi, also known as staplabin analogs or Stachybotrys microspora triprenyl phenol (SMTP). For instance, our previous studies explored different types of FGFCs such as FGFC 1, 2, 3 and 4 from the marine fungi Stachybotrys longispora FG216 derived metabolites. The derivatives of FGFC are potentially employed in several disease treatments, mainly for stroke, cancer, ischemia, acute kidney injury, inflammation, cerebral infarction, thrombolysis and hemorrhagic activities, etc. Due to the increasing use of FGFCs in pharmaceutical and biomedical applications, it is important to understand the fundamental signaling concept of FGFCs. Hence, for the first time, this review collectively summarizes the background, types, mode of action and biological applications of FGFCs and their current endeavors for future therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Jeevithan, Diao, Hu, Elango, Wu, Mate Sanchez de Val, Rajendran, Sundaram and Rajamani Sekar.)

Obtaining informed consent before performing any dentoalveolar procedure is a professional, ethical, and legal obligation. Prior to this work, in this oral and maxillofacial department, no standardised consent process existed for dentoalveolar procedures. A targeted literature review established localised gold standards for dentoalveolar procedures, and retrospective data from 56 dentoalveolar consent forms over a four-week period assessed baseline compliance with these standards. Data analysis identified that risks of dry socket and trismus were documented in only 7% of cases, and maxillary tuberosity fracture was never documented. Thirty-three per cent of lower third molar cases did not include consent for inferior alveolar nerve injury. Findings were discussed in a departmental audit meeting, and a root cause analysis identified memory failure, repetition fatigue, and varying clinician knowledge and experience, as key drivers. The evidence base and localised gold standards were discussed. A standardised, bilingual, triple-copy dentoalveolar consent form was developed, including predefined indications, additional procedures, and risks, in a tick-box format. This form was presented to the Department of Patient Safety and Quality and gained local approval. Cases completed with the new form will now be evaluated against the localised gold standards, with a mixed-methods feedback survey investigating staff and patient opinions. Local processes for obtaining and documenting valid consent for dentoalveolar treatment were found to be inconsistent and frequently inadequate. Fifteen localised gold standards were set, and a new standardised consent form developed, which will be evaluated for effectiveness and acceptability., (Copyright © 2024. Published by Elsevier Ltd.)

Background  The normal ability to distinguish two points from one is known as the two-point discriminative (2PD) sense. This forms an extremely important assessment in patient with injuries to the nerves distributed to the upper extremity. Objective  The aim of this study was to estimate the normal reference values of static 2PD in healthy adults and children. Materials and Methods  A total of 624 normal adults comprising 380 men and 244 women were recruited randomly for the study at three different centers. Additionally, 172 healthy children, comprising 110 boys and 62 girls, were studied. Eight sensory areas in the palmar surface of the hand were delineated. The ability to distinguish the static 2PD was estimated in millimeters by using disk discriminator. The results were tabulated and statistically analyzed. Results  The mean static 2PD in the adult population ranged from 2.78 to 3.5 mm in the fingertips and 5.39 to 7.13 mm in the mid-palm. There was a statistically significant difference between men and women in zones 6, 7, and 8. In children, the observed 2PD values were 2.15 to 3.63 mm in the fingertips and 4.10 to 5.77 mm in the palm. Children have a significantly better 2PD sense when compared with adults. Conclusion  The normal value of static 2PD in the palmar surface of the hand among the Indian pediatric and adult populations was established in the study., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Assessing fertilized human embryos is crucial for in vitro fertilization, a task being revolutionized by artificial intelligence. Existing models used for embryo quality assessment and ploidy detection could be significantly improved by effectively utilizing time-lapse imaging to identify critical developmental time points for maximizing prediction accuracy. Addressing this, we develop and compare various embryo ploidy status prediction models across distinct embryo development stages. We present BELA, a state-of-the-art ploidy prediction model that surpasses previous image- and video-based models without necessitating input from embryologists. BELA uses multitask learning to predict quality scores that are thereafter used to predict ploidy status. By achieving an area under the receiver operating characteristic curve of 0.76 for discriminating between euploidy and aneuploidy embryos on the Weill Cornell dataset, BELA matches the performance of models trained on embryologists' manual scores. While not a replacement for preimplantation genetic testing for aneuploidy, BELA exemplifies how such models can streamline the embryo evaluation process., (© 2024. The Author(s).)

Context: Head and neck paragangliomas (HNPGLs) are rare, usually benign, slow-growing tumours arising from neural crest-derived tissue. Definitive management pathways for HNPGLs have yet to be clearly defined., Objective: To review our experience of the clinical features and management of these tumours and to analyse outcomes of different treatment modalities., Methods: Demographic and clinical data were obtained from The Northern Ireland Electronic Care Record (NIECR) as well from a prospectively maintained HNPGL database between January 2011 through December 2023., Results: There were 87 patients; 50 females: 37 males with a mean age of 52.3 ± 14.2 years old (range 17-91 years old). 58.6% (n = 51) of patients had carotid body tumours, 25.2% (n = 22) glomus vagal tumours, 6.8% (n = 6) tumours in the middle ear, 2.2% (n = 2) in the parapharyngeal space and 1.1% (n = 1) in the sphenoid sinus. 5.7% (n = 5) of patients had multifocal disease. The mean tumour size at presentation was 3.2 ± 1.4 cm (range 0.5-6.9 cm). Pathogenic SDHD mutations were identified in 41.3% (n = 36), SDHB in 12.6% (n = 11), SDHC in 2.2% (n = 2) and SDHA in 1.1% (n = 1) of the patients. Overall treatment modalities included surgery alone in 51.7% (n = 45) of patients, radiotherapy in 14.9% (n = 13), observation in 28.7% (n = 25), and somatostatin analogue therapy with octreotide in 4.5% (n = 4) of patients. Factors associated with a significantly higher risk of recurrence included age over 60 years (p = .04), tumour size exceeding 2 cm (p = .03), positive SDHx variants (p = .01), and vagal and jugular tumours (p = .04)., Conclusion: The majority of our patients underwent initial surgical intervention and achieved disease stability. Our results suggest that carefully selected asymptomatic or medically unfit patients can be safely observed provided lifelong surveillance is maintained. We advocate for the establishment of a UK and Ireland national HNPGL registry, to delineate optimal management strategies for these rare tumours and improve long term outcomes., (© 2024 John Wiley & Sons Ltd.)

Fabrication of haemostatic materials with excellent antimicrobial, biocompatible and biodegradable properties remains as a major challenge in the field of medicine. Haemostatic agents play vital role in protecting patients and military individuals during emergency situations. Natural polymers serve as promising materials for fabricating haemostatic compounds due to their efficacy in promoting hemostasis and wound healing. In the present work, sodium alginate/aloe vera/sericin (SA/AV/S) scaffold has been fabricated using a simple cost-effective casting method. The prepared SA/AV/S scaffolds were characterised for their physicochemical properties such as scanning electron microscope, UV-visible spectroscopy and Fourier transform infra-red spectroscopy. SA/AV/S scaffold showed good mechanical strength, swelling behaviour and antibacterial activity. In vitro experiments using erythrocytes proved the hemocompatible and biocompatible features of SA/AV/S scaffold. In vitro blood clotting assay performed using human blood demonstrated the haemostatic and blood absorption properties of SA/AV/S scaffold. Scratch wound assay was performed to study the wound healing efficacy of prepared scaffolds. Chick embryo chorioallantoic membrane assay carried out using fertilised embryos proved the angiogenic property of SA/AV/S scaffold. Thus, SA/AV/S scaffold could serve as a potential haemostatic healthcare product due to its outstanding haemostatic, antimicrobial, hemocompatible, biocompatible and angiogenic properties.

Background: Low-dose colchicine reduces the risk of cardiovascular events after myocardial infarction (MI). The purpose of this study was to assess the effect of colchicine post-MI on coronary plaque morphology in non-culprit segments by optical coherence tomography (OCT)., Methods and Results: COCOMO-ACS was a double-blind, placebo-controlled trial that randomized 64 patients (median age 61.5 years; 9.4% female) with acute non-ST-segment elevation MI to colchicine 0.5 mg daily or placebo for a median of 17.8 months in addition to guideline-recommended therapy. Participants underwent serial OCT imaging within a matched segment of non-culprit coronary artery which contained at least one lipid-rich plaque causing ≥20% stenosis. The primary outcome was the change in minimum fibrous cap thickness (FCT) in non-culprit segments from baseline to final visit. Of those randomized, 57 (29 placebo, 28 colchicine) had evaluable imaging at baseline and follow-up. Overall, colchicine had no effect on relative (placebo +48.0±35.1% vs. colchicine +62.4±38.1%, P=0.18) or absolute changes in minimum FCT (+29.2±20.9 µm vs. +37.2±21.3 µm, P=0.18), or change in maximum lipid arc (-38.8±32.2° vs. -54.8±46.9°, P=0.18) throughout the imaged non-culprit segment. However, in patients assigned colchicine, cap rupture was less frequent (placebo 27.6% vs. colchicine 3.6%, P=0.03). In post-hoc analysis of 43 participants who had been followed for at least 16 months, minimum FCT increased to a greater extent in the colchicine group (placebo +38.7±25.4% vs. colchicine +64.7±34.1%, P=0.005)., Conclusion: In this study, OCT failed to detect an effect of colchicine on the minimum FCT or maximum lipid arc of plaques in non-culprit segments post-MI. The post-hoc observation that minimum FCT increased to a greater extent with colchicine after more prolonged treatment suggests longer-term studies may be required to detect the effect of anti-inflammatory therapies on plaque morphology by OCT., Trial Registration: Australian New Zealand Clinical Trials Registry Identifier, ACTRN12618000809235, registered on the 11th of May 2018., (© 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.)

The second most common type of malignant tumor worldwide is colorectal cancer. Histopathology image analysis offers crucial data for the clinical diagnosis of colorectal cancer. Currently, deep learning techniques are applied to enhance cancer classification and tumor localization in histopathological image analysis. Moreover, traditional deep learning techniques might loss integrated information in the image while evaluating thousands of patches recovered from whole slide images (WSIs). This research proposes a novel colorectal cancer detection network (CCDNet) that combines coordinate attention transformer with atrous convolution. CCDNet first denoises the input histopathological image using a Wiener based Midpoint weighted non-local means filter (WMW-NLM) for guaranteeing precise diagnoses and maintain image features. Also, a novel atrous convolution with coordinate attention transformer (AConvCAT) is introduced, which successfully combines the advantages of two networks to classify colorectal tissue at various scales by capturing local and global information. Further, coordinate attention model is integrated with a Cross-shaped window (CrSWin) transformer for capturing tiny changes in colorectal tissue from multiple angles. The proposed CCDNet achieved accuracy rates of 98.61% and 98.96%, on the colorectal histological image and NCT-CRC-HE-100 K datasets correspondingly. The comparison analysis demonstrates that the suggested framework performed better than the most advanced methods already in use. In hospitals, clinicians can use the proposed CCDNet to verify the diagnosis., (© 2024. The Author(s).)

High-grade gliomas (HGGs) and glioblastomas (GBMs) are the most aggressive and lethal brain tumors. The current standard of care (SOC) includes gross safe surgical resection followed by chemoradiotherapy. The main chemotherapeutic agents are the DNA-alkylating agent temozolomide (TMZ) and adjuvants. Due to the outdated therapeutic protocols and lack of specific treatments, there is an urgent and rising need to improve our understanding of tumor biology and design more effective therapeutic strategies. In vitro models are essential for investigating glioma biology and testing novel therapeutic approaches. While using commercially available and patient-derived glioma cell lines for in vitro studies is common practice, they exhibit several limitations, including failing to maintain the genetic and phenotypic diversity of primary tumors, undergo genetic drift over time, and often lacking the invasive and stem-like characteristics of patient tumors. These limitations can lead to inconsistent and non-reproducible results, hampering translational research progress. In this study, we established a novel primary murine HGG cell line, isolated from an immunocompetent HGG-bearing RCAS/T-va mouse. We characterized the transcriptome and phenotype to ensure that this cell line resembles the nature of HGGs and retains the ability to reprogram primary murine T lymphocytes., Competing Interests: P.R. and K.C. are associate editors of Molecular Therapy Oncology., (© 2024 The Author(s).)

Estrogen receptor-positive (ER+) breast cancer commonly disseminates to bone marrow, where interactions with mesenchymal stromal cells (MSCs) shape disease trajectory. We modeled these interactions with tumor-MSC co-cultures and used an integrated transcriptome-proteome-network-analyses workflow to identify a comprehensive catalog of contact-induced changes. Conditioned media from MSCs failed to recapitulate genes and proteins, some borrowed and others tumor-intrinsic, induced in cancer cells by direct contact. Protein-protein interaction networks revealed the rich connectome between 'borrowed' and 'intrinsic' components. Bioinformatics prioritized one of the 'borrowed' components, CCDC88A /GIV, a multi-modular metastasis-related protein that has recently been implicated in driving a hallmark of cancer, growth signaling autonomy. MSCs transferred GIV protein to ER+ breast cancer cells (that lack GIV) through tunnelling nanotubes via connexin (Cx)43-facilitated intercellular transport. Reinstating GIV alone in GIV-negative breast cancer cells reproduced ∼20% of both the 'borrowed' and the 'intrinsic' gene induction patterns from contact co-cultures; conferred resistance to anti-estrogen drugs; and enhanced tumor dissemination. Findings provide a multiomic insight into MSC→tumor cell intercellular transport and validate how transport of one such candidate, GIV, from the haves (MSCs) to have-nots (ER+ breast cancer) orchestrates aggressive disease states.

Cervical adenocarcinomas are now classified as human papillomavirus (HPV)-associated and HPV-independent types with the former being more common. However, population-based studies regarding the relative incidences of the 2 types are few. This study investigates the incidence of cervical adenocarcinomas in Northern Ireland (a country with a relatively stable population of ~1.8 million) over a recent 9-year period (2015-2023). Overall, there were 146 primary cervical adenocarcinomas, 130 HPV-associated (89%) and 16 HPV-independent (11%). The median age was 43 years (range: 24-82) for HPV-associated and 62.5 years (range: 31-84) for HPV-independent neoplasms; this was statistically significant (P < 0.001). The calculated age-adjusted incidence of the patients with HPV-associated and HPV-independent neoplasms was 1.68 and 0.20 per 100,000 person-years, respectively. The HPV-independent neoplasms were more often advanced stage at diagnosis; 97 of 130 (75.4%) of the HPV-associated cases were diagnosed at Stage I compared with 5 of 16 (31.3%) of the HPV-independent cases. The HPV-independent neoplasms were mostly gastric-type (56.3%) with smaller numbers of clear cells and mesonephric. Despite the relatively short follow-up, the mortality of patients with HPV-independent adenocarcinomas was significantly higher than patients with HPV-associated neoplasms (56.3% vs 5.4%) with a median survival of just over a year (13.2 mo) in the former for those who died., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Bacterial fermentation is considered to be a cost-effective means of generating desired flavour compounds from plant-based substrates. However, the wide range of substrates present in plants makes it challenging to understand how individual components impact on flavour volatile organic compound (VOC) production. To simplify this, a defined medium can be used to better understand VOCs production with regard to individual compounds. In the current study, the VOCs produced by the lactic acid bacterium, Levilactobacillus brevis WLP672, growing in a defined medium containing different carbon sources (either glucose (DM), fructose (DMFr) or citrate (DMCi)) under a range of fermentation conditions (time: 0, 7, and 14 days; and temperature: 25 and 35 °C) were assessed using proton transfer reaction time-of-flight mass spectrometry (PTR-ToF-MS). Among the detected mass peaks ( m / z ), after 7 days of fermentation, the concentrations of m / z 45.033 (t.i. acetaldehyde), m / z 49.011 (t.i. methanethiol), and m / z 89.060 (t.i. ethyl acetate) were significantly ( p < 0.05) higher in DM at 35 °C than all other treatments at either temperature. The knowledge obtained will help to produce desirable LAB fermentation flavour VOCs or VOC mixtures that could be used in developing plant-based analogues with acceptable sensory properties.

Myxobacteria are predatory bacteria with antimicrobial activity, utilizing complex mechanisms to kill their prey and assimilate their macromolecules. Having large genomes encoding hundreds of secondary metabolites, hydrolytic enzymes and antimicrobial peptides, these organisms are widely studied for their antibiotic potential. MyxoPortal is a comprehensive genomic database hosting 262 genomes of myxobacterial strains. Datasets included provide genome annotations with gene locations, functions, amino acids and nucleotide sequences, allowing analysis of evolutionary and taxonomical relationships between strains and genes. Biosynthetic gene clusters are identified by AntiSMASH, and dbAMP-generated antimicrobial peptide sequences are included as a resource for novel antimicrobial discoveries, while curated datasets of CRISPR/Cas genes, regulatory protein sequences, and phage associated genes give useful insights into each strain's biological properties. MyxoPortal is an intuitive open-source database that brings together application-oriented genomic features that can be used in taxonomy, evolution, predation and antimicrobial research. MyxoPortal can be accessed at http://dicsoft1.physics.iisc.ac.in/MyxoPortal/. Database URL:  http://dicsoft1.physics.iisc.ac.in/MyxoPortal/. Graphical Abstract., (© The Author(s) 2024. Published by Oxford University Press.)

Objective: To investigate how the shift of the United States Medical Licensing Examination (USMLE) Step 1 to a Pass/Fail (P/F) scoring system impacts the perceptions of Urology Program Directors (PDs) on evaluating urology residency applicants., Methods and Materials: A cross-sectional survey was sent to 117 PDs, including questions about program characteristics, perceptions of shelf scores and medical school rank post-transition, beliefs about the predictive value of Step 1 and Step 2 Clinical Knowledge (CK) scores for board success and residency performance, and changes in applicant parameter ranking., Results: Forty-five PDs (38% response rate) participated. Notably, 49% favored releasing quantitative clerkship grades, and 71% valued medical school rank more. Opinions on Step 1 scores' correlation with board success were split (49% agreed), and 44% endorsed Step 2 CK scores' connection to board performance. As predictors of good residents, only 9% and 22% considered Step 1 and Step 2 CK scores, respectively, indicative. Clerkship grades and Urology rotation recommendation letters maintained significance, while research experience gained importance. Step 2 CK scores' importance rose but did not match Step 1 scores' previous significance., Conclusion: The transition to P/F for USMLE Step 1 adds intricacies to urology residency selection, exposing PDs' uncertainties regarding clerkship grades and the relevance of medical school rank. This research underscores the dynamic nature of urology residency admissions, emphasizing the increasing importance of research in evaluating applicants and a diminishing emphasis on volunteering and leadership., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

This study aimed to investigate bone char's physicochemical transformations through co-torrefaction and co-pyrolysis processes with biomass. Additionally, it aimed to analyze the carbon sequestration process during co-torrefaction of bone and biomass and optimize the process parameters of co-torrefaction. Finally, the study sought to evaluate the arsenic sorption capacity of both torrefied and co-torrefied bone char. Bone and biomass co-torrefaction was conducted at 175 °C-300 °C. An orthogonal array of Taguchi techniques and artificial neural networks (ANN) were employed to investigate the influence of various torrefaction parameters on carbon dioxide sequestration within torrefied bone char. A co-torrefied bone char, torrefied at a reaction temperature of 300 °C, a heating rate of 15 °C·min -1 , and mixed with 5 g m of biomass (wood dust), was selected for the arsenic (III) sorption experiment due to its elevated carbonate content. The results revealed a higher carbonate fraction (21%) in co-torrefied bone char at 300 °C compared to co-pyrolyzed bone char (500-700 °C). Taguchi and artificial neural network (ANN) analyses indicated that the relative impact of process factors on carbonate substitution in bone char followed the order of co-torrefaction temperature (38.8%) > heating rate (31.06%) > addition of wood biomass (30.1%). Co-torrefied bone chars at 300 °C exhibited a sorption capacity of approximately 3 mg g -1 , surpassing values observed for pyrolyzed bone chars at 900 °C in the literature. The findings suggest that co-torrefied bone char could serve effectively as a sorbent in filters for wastewater treatment and potentially fulfill roles such as a remediation agent, pH stabilizer, or valuable source of biofertilizer in agricultural applications., 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., (Copyright © 2024 Elsevier Inc. All rights reserved.)

A previously elusive organocatalytic protocol for the esterification of amides is disclosed. DABCO (10 mol%) is identified as an effective catalyst for the esterification of N -pivaloyl amides. Although N -pivaloyl amides are nearly planar (amide bond twist ( τ ) = 4.54° and pyramidalization ( χ N = 6.39°)) and resonance stabilized, esterification is achieved with high efficiency. The developed protocol is generic, phenols, thiophenols, aliphatic alcohols, and thiols were identified as effective substrates. Furthermore, the reaction features a broad substrate scope and excellent functional group tolerance. To exemplify the practical applicability of the developed protocol, the esterification of bioactive natural products, pterostilbene and menthol, is demonstrated. In addition, a series of competitive experiments were conducted to establish the reactivity pattern of alcohols, thiols, and phenols, which could serve as selectivity principles for future synthetic design. Our findings signify a notable advancement in utilizing amides as versatile synthetic building blocks in organic synthesis under metal-free conditions.

Sugarcane (Saccharum officinarum) is an important crop, native to tropical and subtropical regions and it is a major source of sugar and Bioenergy in the world. Abiotic stress is defined as environmental conditions that reduce growth and yield below the optimum level. To tolerate these abiotic stresses, plants initiate several molecular, cellular, and physiological changes. These responses to abiotic stresses are dynamic and complex; they may be reversible or irreversible. Waterlogging is an abiotic stress phenomenon that drastically reduces the growth and survival of sugarcane, which leads to a 15-45% reduction in cane's yield. The extent of damage due to waterlogging depends on genotypes, environmental conditions, stage of development and duration of stress. An improved understanding of the physiological, biochemical, and molecular responses of sugarcane to waterlogging stress could help to develop new breeding strategies to sustain high yields against this situation. The present review offers a summary of recent findings on the adaptation of sugarcane to waterlogging stress in terms of growth and development, yield and quality, as well as biochemical and adaptive-molecular processes that may contribute to flooding tolerance., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Purpose of Review: Update on the most recent clinical evidence on CDK4/6 inhibitors (CDK4/6i) in the treatment of hormone receptor (HR)-positive, human epidermal growth factor receptor (HER)2-negative breast cancer., Recent Findings: Over the past decade, CDK4/6i have become part of the standard of care treatment of patients with both metastatic and high-risk early HR + /HER2- breast cancers. The three available CDK4/6i (palbociclib, ribociclib and abemaciclib) have been extensively studied in combination with endocrine therapy (ET) in metastatic breast cancer (mBC) with consistent prolongation of progression free survival; however, ribociclib has emerged as the preferred first line agent in mBC given overall survival benefit over endocrine monotherapy. In early BC, abemaciclib is the only currently approved agent while ribociclib has early positive clinical trial data. Toxicities and financial burden limit the use of CDK4/6i in all patients and resource-poor settings, and optimal timing of their use in mBC remains unclear. There is considerable evidence for the use of CDK4/6i in metastatic and early HR + /HER2- breast cancer, but knowledge gaps remain, and further research is necessary to better define their optimal use., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The work investigates the implementation of personalized radiotherapy boluses by means of additive manufacturing technologies. Boluses materials that are currently used need an excessive amount of human intervention which leads to reduced repeatability in terms of dosimetry. Additive manufacturing can solve this problem by eliminating the human factor in the process of fabrication. Planar boluses with fixed geometry and personalized boluses printed starting from a computed tomography scan of a radiotherapy phantom were produced. First, a dosimetric characterization study on planar bolus designs to quantify the effects of print parameters such as infill density and geometry on the radiation beam was made. Secondly, a volumetric quantification of air gap between the bolus and the skin of the patient as well as dosimetric analyses were performed. The optimization process according to the obtained dosimetric and airgap results allowed us to find a combination of parameters to have the 3D-printed bolus performing similarly to that in conventional use. These preliminary results confirm those in the relevant literature, with 3D-printed boluses showing a dosimetric performance similar to conventional boluses with the additional advantage of being perfectly conformed to the patient geometry., (© 2024. The Author(s).)

Fluorescence microscopy has undergone rapid advancements, offering unprecedented visualization of biological events and shedding light on the intricate mechanisms governing living organisms. However, the exploration of rapid biological dynamics still poses a significant challenge due to the limitations of current digital camera architectures and the inherent compromise between imaging speed and other capabilities. Here, we introduce sHAPR, a high-speed acquisition technique that leverages the operating principles of sCMOS cameras to capture fast cellular and subcellular processes. sHAPR harnesses custom fiber optics to convert microscopy images into one-dimensional recordings, enabling acquisition at the maximum camera readout rate, typically between 25 and 250 kHz. We have demonstrated the utility of sHAPR with a variety of phantom and dynamic systems, including high-throughput flow cytometry, cardiomyocyte contraction, and neuronal calcium waves, using a standard epi-fluorescence microscope. sHAPR is highly adaptable and can be integrated into existing microscopy systems without requiring extensive platform modifications. This method pushes the boundaries of current fluorescence imaging capabilities, opening up new avenues for investigating high-speed biological phenomena., (© 2024. The Author(s).)

The early stages of ageing are a critical time window in which the ability to detect and identify precocious molecular and cognitive markers can make the difference in determining a healthy vs unhealthy course of ageing. Using the 6-different object task (6-DOT), a highly demanding hippocampal-dependent recognition memory task, we classified a population of middle-aged (12-month-old) CD1 male mice in Impaired and Unimpaired based on their short-term memory. This approach led us to identify a different microRNAs expression profile in the hippocampus of Impaired mice compared to Unimpaired ones. Among the dysregulated microRNAs, miR-153-3p was upregulated in the hippocampus of Impaired mice and appeared of high interest for its putative target genes and their possible implication in memory-related synaptic plasticity. We showed that intra-hippocampal injection of the miR-153-3p mimic in adult (3-month-old) mice is sufficient to induce a short-term memory deficit similar to that observed in middle-aged Impaired mice. Overall, these findings unravel a novel role for hippocampal miR-153-3p in modulating short-term memory that could be exploited to prevent early cognitive deficits in ageing., (© 2023. The Author(s).)

We investigated the angiogenesis-modulating ability of noscapine in vitro using osteosarcoma cell line (MG-63) and in vivo using a zebrafish model. MTT assay and the scratch wound healing assay were performed on the osteosarcoma cell line (MG-63) to analyze the cytotoxic effect and antimigrative ability of noscapine, respectively. We also observed the antiangiogenic ability of noscapine on zebrafish embryos by analyzing the blood vessels namely the dorsal aorta, and intersegmental vessels development at 24, 48, and 72 h postfertilization. Real-time polymerase chain reaction was used to analyze the hypoxia signaling molecules' gene expression in MG-63 cells and zebrafish embryos. The findings from the scratch wound healing demonstrated that noscapine stopped MG-63 cancer cells from migrating under both hypoxia and normoxia. Blood vessel development and the heart rate in zebrafish embryos were significantly reduced by noscapine under both hypoxia and normoxia which showed the hemodynamics impact of noscapine. Noscapine also downregulated the cobalt chloride (CoCl 2 ) induced hypoxic signaling molecules' gene expression in MG-63 cells and zebrafish embryos. Therefore, noscapine may prevent MG-63 cancer cells from proliferating and migrating, as well as decrease the formation of new vessels and the production of growth factors linked to angiogenesis in vivo under both normoxic and hypoxic conditions., (© 2024 Wiley Periodicals LLC.)

Sterubin (7-O-Methyleriodicytol), a flavanone compound isolated from the leaves of Eriodicyton californicum and Eriodicyton angustifolium, has neuroprotective, anti-inflammatory, and antioxidant properties. Therefore, it is of interest to identify the potential targets for Alzheimer disease using network pharmacology. We report 25 overlapping targets among 100 potential targets of sterubin and 673 known targets of Alzheimer. APP, BACE-1, and AChE were among the ten hub targets enriched in biological processes and pathways relevant to Alzheimer's disease. Subsequent, molecular docking analysis shows that sterubin have optimal binding features with these hub gene targets for further consideration., (© 2024 Biomedical Informatics.)

Protein dynamics linked to numerous biomolecular functions, such as ligand binding, allosteric regulation, and catalysis, must be better understood at the atomic level. Reactive atoms of key residues drive a repertoire of biomolecular functions by flipping between alternate conformations or conformational substates, seldom found in protein structures. Probing such sparsely sampled alternate conformations would provide mechanistic insight into many biological functions. We are therefore interested in evaluating the instance of amino acids adopted alternate conformations, either in backbone or side-chain atoms or in both. Accordingly, over 70000 protein structures appear to contain alternate conformations only 'A' and 'B' for any atom, particularly the instance of amino acids that adopted alternate conformations are more for Arg, Cys, Met, and Ser than others. The resulting protein structure analysis depicts that amino acids with alternate conformations are mainly found in the helical and β-regions and are often seen in high-resolution X-ray crystal structures. Furthermore, a case study on human cyclophilin A (CypA) was performed to explain the pre-existing intrinsic dynamics of catalytically critical residues from the CypA and how such intrinsic dynamics perturbed upon Ser99Thr mutation using molecular dynamics simulations on the ns-μs timescale. Simulation results demonstrated that the Ser99Thr mutation had impaired the alternate conformations or the catalytically productive micro-environment of Phe113, mimicking the experimentally observed perturbation captured by X-ray crystallography. In brief, a deeper comprehension of alternate conformations adopted by the amino acids may shed light on the interplay between protein structure, dynamics, and function., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors.)

Natural products are small molecules synthesized by fungi, bacteria and plants, which historically have had a profound effect on human health and quality of life. These natural products have evolved over millions of years resulting in specific biological functions that may be of interest for pharmaceutical, agricultural, or nutraceutical use. Often natural products need to be structurally modified to make them suitable for specific applications. Combinatorial biosynthesis is a method to alter the composition of enzymes needed to synthesize a specific natural product resulting in structurally diversified molecules. In this review we discuss different approaches for combinatorial biosynthesis of natural products via engineering fungal enzymes and biosynthetic pathways. We highlight the biosynthetic knowledge gained from these studies and provide examples of new-to-nature bioactive molecules, including molecules synthesized using combinations of fungal and non-fungal enzymes., (© 2024. The Author(s).)

Plant-specific transcription factors (TFs) are responsible for regulating the genes involved in the development of plant-specific organs and response systems for adaptation to terrestrial environments. This includes the development of efficient water transport systems, efficient reproductive organs, and the ability to withstand the effects of terrestrial factors, such as UV radiation, temperature fluctuations, and soil-related stress factors, and evolutionary advantages over land predators. In rice and Arabidopsis, INDETERMINATE DOMAIN (IDD) TFs are plant-specific TFs with crucial functions, such as development, reproduction, and stress response. However, in tomatoes, IDD TFs remain uncharacterized. Here, we examined the presence, distribution, structure, characteristics, and expression patterns of SlIDDs. Database searches, multiple alignments, and motif alignments suggested that 24 TFs were related to Arabidopsis IDDs. 18 IDDs had two characteristic C2H2 domains and two C2HC domains in their coding regions. Expression analyses suggest that some IDDs exhibit multi-stress responsive properties and can respond to specific stress conditions, while others can respond to multiple stress conditions in shoots and roots, either in a tissue-specific or universal manner. Moreover, co-expression database analyses suggested potential interaction partners within IDD family and other proteins. This study functionally characterized SlIDDs, which can be studied using molecular and bioinformatics methods for crop improvement., (© 2024. The Author(s).)

Introduction: Peripheral artery disease (PAD) is a major risk factor for cardiovascular morbidity and mortality, despite surgical and endovascular treatments. Emerging evidence supports the use of immediate antithrombotic medications after endovascular intervention for PAD, however, there is a lack of consensus regarding choice and duration of antithrombotic therapy. Prescriber decision-making is a complex process, with prior studies demonstrating patient factors can influence variability in antithrombotic therapy for PAD. However, it remains unclear the relative contribution of these factors. This paper describes a planned study that aims to (1) determine the influence of patient factors on clinician preference for antithrombotic therapy following endovascular intervention and (2) compare differences in prescribing preferences between consultant vascular surgeons and trainees., Methods and Analysis: This cross-sectional survey will evaluate antithrombotic prescribing choices using a discrete choice experiment (DCE) that has been developed and piloted for this study. A list of attributes and levels was generated using a mixed-methods approach. This included an extensive literature review and semistructured interviews with prescribing clinicians. Following final selection of included attributes, specialised software was used to construct a D-efficient design for the DCE questionnaire. The electronic questionnaire will be administered to vascular trainees and consultant surgeons across Australia. These data will be analysed using multinomial logistic regression, treating the decision to prescribe antithrombotic therapy as a function of both the attributes of the two alternatives, as well as characteristics of the respondent. Latent class analysis will be used to explore heterogeneity of responses., Ethics and Dissemination: Ethics approval was obtained from the University of Sydney Human Ethics committee (2023/474). The results of this study will be published in peer-reviewed journals and presented at national vascular surgical conferences. These results will be used to improve understanding how clinicians make prescribing decisions and to inform future strategy to enhance guideline-directed prescribing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Soil health is essential for whirling stale soil into rich coffee-growing land. By keeping healthy soil, coffee producers may improve plant growth, leaf health, buds, cherry and bean quality, and yield. Traditional soil monitoring is tedious, time-consuming, and error-prone. Enhancing the monitoring system using AI-based IoT technologies for quick and precise changes. Integrated soil fertility control system to optimize soil health, maximize efficiency, promote sustainability, and prevent crop threads using real-time data analysis to turn infertile land into fertile land. The RNN-IoT approach uses IoT sensors in the coffee plantation to collect real-time data on soil temperature, moisture, pH, nutrient levels, weather, CO2 levels, EC, TDS, and historical data. Data transmission using a wireless cloud platform. Testing and training using recurrent neural networks (RNNs) and gated recurrent units gathered data for predicting soil conditions and crop hazards. Researchers are carrying out detailed qualitative testing to evaluate the proposed RNN-IoT approach. Utilize counterfactual recommendations for developing alternative strategies for irrigation, fertilization, fertilizer regulation, and crop management, taking into account the existing soil conditions, forecasts, and historical data. The accuracy is evaluated by comparing it to other deep learning algorithms. The utilization of the RNN-IoT methodology for soil health monitoring enhances both efficiency and accuracy in comparison to conventional soil monitoring methods. Minimized the ecological impact by minimizing water and fertilizer utilization. Enhanced farmer decision-making and data accessibility with a mobile application that provides real-time data, AI-generated suggestions, and the ability to detect possible crop hazards for swift action., (© 2024. The Author(s).)

Acne scars are one of the most common complications of acne. They can significantly affect the patient's quality of life. Often, several types of atrophic acne scars are observed simultaneously; therefore, consideration must be given to the type of scar while choosing the treatment modality. Effective treatment is not only important to prevent and improve acne scars but also crucial in preventing psychosocial effects. Treatment of acne scars requires an algorithmic approach that targets each component of the scars, and combination therapy on a patient-specific basis may offer the best chance for significant improvement. The goal of the current article is to discuss the practical aspects of management of atrophic acne scars using the vast modalities of treatment available. The panel of dermatologists and plastic surgeons, each one with at least 20 years of experience in acne scar treatment, participated in a series of 'Practical Aspects of Acne Scar Management' (ASAP) meetings: ASAP 2024. ASAP meetings were organized by "Scar Forum India" from March 2023 to July 2023 in four Indian cities (Mumbai, Delhi, Bengaluru, and Kolkata), each one for a duration of at least three hours. During these meetings and discussions, panelists reviewed and discussed the acne scar-related literature, their clinical experience in its management, available treatment options, along with recent advances. Consequently, a summary of the discussion and practical approach for the management of acne scars is developed. It was concluded that, though there is no specific guideline available to optimize acne scar management despite the multitude of treatment options, the best results can be achieved through the synergy of multiple treatment modalities and using the algorithmic approach., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Tahiliani et al.)

We propose a novel experimental method for probing light dark matter candidates. We show that an electro-optical material's refractive index is modified in the presence of a coherently oscillating dark matter background. A high-precision resonant Michelson interferometer can be used to read out this signal. The proposed detection scheme allows for the exploration of an uncharted parameter space of dark matter candidates over a wide range of masses-including masses exceeding a few tens of microelectronvolts, which is a challenging parameter space for microwave cavity haloscopes.

Background and Objectives: Intrathecal drug therapy is a common treatment for dystonia, pain, and spasticity using implanted pump and catheter systems. Standardized management of intrathecal drug pump (ITDP) migration and flipping has not been well established in the literature. This study reports the use of soft tissue to address less common pump complications such as pump flipping, migration, and difficulty in medication refill., Methods: A retrospective chart review of intrathecal pump cases performed by two surgeons between February 2020 and August 2022 was conducted. Patients with complications such as pump flipping, migration, or challenges in medication refill treated with soft tissue flaps were included. Patient demographics, comorbidities, and perioperative data were collected., Results: A total of five patients with ITDP complicated by pump flipping, migration, malposition, or difficulty in medication refill that were treated using fascial flaps were included in the study. Three technical considerations when revising ITDP complications are secure pump anchoring, reliable wound closure, and ease of pump medication refill. Cases 1 and 2 demonstrate the technique of secure pump anchoring with a rectus fascial flap. Cases 3 and 4 show a technique to achieve reliable vascularized wound closure, and case 5 describes a technique to solve an uncommon problem of a thick subcutaneous abdominal tissue preventing the refill of the ITDP medication., Conclusion: Soft tissue flaps may serve as a treatment option for patients with uncommon ITDP complications. De-epithelialized dermal fasciocutaneous or fascial flaps may be developed to anchor the pump more securely. Cross-discipline collaboration may further delineate the technique, benefits, and outcomes of this approach., (Copyright © Congress of Neurological Surgeons 2023. All rights reserved.)

This study extensively explored the impact of integrating waste tire rubber into high-performance concrete (HPC) by substituting natural sand. Different fractions of rubber particles-5%, 10%, and 15% replacements of the fine aggregate-were rigorously investigated. Properties from fresh to hardened concrete were assessed, including compressive and tensile strength, modulus of elasticity, workability, and damping coefficient. Replacing up to 10% of sand with 0.6 mm rubber particles showed minimal strength compromise compared to standard HPC. However, at a 15% replacement rate, a noticeable decline in strength became evident, highlighting an optimal threshold for inclusion. Additionally, rubber incorporation notably enhanced concrete ductility and damping, marking a substantial improvement in dynamic properties. Efforts to offset strength reduction through increased fines content and mineral admixture could not counteract the decline at the 15% replacement level, suggesting limitations in compensatory measures. Methodological refinements enhanced data accuracy, including capping and surface treatments during compression testing. The study underlined the viability of controlled rubber substitution for bolstering HPC's dynamic attributes. Despite strength reductions at higher replacement rates, controlled waste tire rubber integration proves promising for enhancing HPC's dynamics without compromising structural integrity, advocating its suitability across diverse construction applications., (© 2024. The Author(s).)

There is an urgent need to explore climate-resilient alternative agriculture production systems that focus on resilience, resource efficiency, and disease management. Hydroponics, a soilless cultivation system, gaining interest as it reduces the dependency on agricultural land, and pesticides, and can be implemented in areas with poor soil quality, thus mitigating the negative effects of extreme weather events. Potato is an essential dietary staple crop grown throughout the world and is a major source of food security in underdeveloped countries. However, due to the climatic changes, it is predicted that a significant loss in the suitability of land for potato production would occur, thus leading to potato yield loss. Recently, many case studies have emerged to highlight the advancement of agricultural hydroponic systems that provide a promising solution to the massive production of potato mini tuber at high efficiency. This review paper evaluates popular hydroponic methods and demonstrates how hydroponic has emerged as the go-to, long-term, sustainable answer to the perennial problem of insufficient access to high-quality potato seed stock. The paper discusses the research and innovation possibilities (such as artificial intelligence, nanoparticles, and plant growth-promoting rhizobacteria) that potentially increase tuber production per plant under optimal hydroponic growth circumstances. These approaches are examined considering new scientific discoveries and practical applications. Furthermore, it emphasizes that by enduring significant reforms in soilless food production systems (particularly for potatoes), the food supply of a rapidly growing population can be addressed. Since hydroponics systems are productive and easily automated without soil and optimal environmental conditions, future hydroponics farming is promising. In conclusion, the hydroponics system provides better yield and crop productivity by saving water, energy, and space. Henceforth, it can be the alternate choice for modern sustainable agriculture., Competing Interests: 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., (© 2024 Published by Elsevier Ltd.)

Roads are closely intertwined with human existence, and the process of extracting road networks has emerged as the most prominent task in remote sensing (RS). The automated road interpretation process of remote sensing images (RSI) efficiently acquires road network data at a reduced expense in comparison to the traditional visual interpretation of RSI. However the manifestation of RSI is completely distinct because of the great difference in length, width, material, and shape of road networks in dissimilar areas. Thus, the extraction of road network data in RSI is still a complex issue. In recent times, DL-based approaches have projected a famous development in image segmentation outcomes, but a lot of them still could not retain boundary data and attain high-resolution road segmentation maps while processing the RSI. Traditional convolutional neural networks (CNNs) demonstrate impressive performance in road extract tasks; however, they frequently encounter difficulties in capturing intricate details and contextual information. The study introduces a novel method, named Archimedes Optimisation Algorithm, Quantum Dilated Convolutional Neural Network for Road Extraction (AOA-QDCNNRE), to tackle the challenges encountered in remote sensing images. The AOA-QDCNNRE technique aims to generate a high-resolution road segmentation map using DL with a hyperparameter tuning process. The AOA-QDCNNRE technique primarily relies on the QDCNN model, which integrates quantum technology (QC) with dilated convolutions to augment the network's capacity to capture local as well as global contextual information. In addition, the incorporation of the dilated convolutional technique effectively enhances the receptive field without sacrificing spatial resolution, enabling the extraction of precise road features. To develop the road extraction outcomes of the QDCNN approach, the AOA-based hyperparameter tuning process can be exploited. The AOA-QDCNNRE system's simulation results can be tested on benchmark databases, and the results indicate that the AOA-QDCNNRE method surpasses recent algorithms., Competing Interests: 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., (© 2024 The Authors.)

Thumb tip injuries constitute one of the most common hand injuries. There are various reconstructive options for thumb tip injuries. We present our series of thumb tip injuries reconstructed using Elliot's modification of the Moberg flap, which provides like-for-like tissue. We also present our flap improvisation, which can be useful in the armamentarium of plastic surgeons. Background  Moberg described the advancement flap for thumb defects in 1964, which was modified by O'Brien in which the proximal part of the flap is incised and advanced. Although it is a popular flap, it has the disadvantage of interphalangeal (IP) joint flexion deformity. Among the various modifications of the Moberg flap, Elliot's flap provided more tissue with minimal donor site morbidity and no usage of skin grafts or first web skin. Methods  We retrospectively analyzed the patients who underwent reconstruction of thumb defects by Elliot's modified Moberg's flap. The size of the defect, etiology, and IP joint movement were analyzed. Two patients underwent our improvised flap where a daughter flap was elevated within Elliot's flap. Results  Between January 2021 and September 2023, 12 patients underwent reconstruction by Elliot's flap. All flaps settled well. There was no IP joint deformity. Two patients had scar hypertrophy that was managed conservatively. Conclusion  Elliot's modification of the Moberg flap is a very useful but underutilized flap for thumb tip injuries that provides like tissue with sensation and with little donor site morbidity. It can be used for thumb tip defects of up to 3 cm . It is possible to incorporate a second V-Y flap in patients for whom additional movement is required for tension-free closure., Competing Interests: Conflict of Interest None declared., (Association of Plastic Surgeons of India. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. ( https://creativecommons.org/licenses/by-nc-nd/4.0/ ).)

Fermentation by lactic acid bacteria (LAB) is a promising approach to meet the increasing demand for meat or dairy plant-based analogues with realistic flavours. However, a detailed understanding of the impact of the substrate, fermentation conditions, and bacterial strains on the volatile organic compounds (VOCs) produced during fermentation is lacking. As a first step, the current study used a defined medium (DM) supplemented with the amino acids L-leucine (Leu), L-isoleucine (Ile), L-phenylalanine (Phe), L-threonine (Thr), L-methionine (Met), or L-glutamic acid (Glu) separately or combined to determine their impact on the VOCs produced by Levilactobacillus brevis WLP672 (LB672). VOCs were measured using headspace solid-phase microextraction (HS-SPME) gas chromatography-mass spectrometry (GC-MS). VOCs associated with the specific amino acids added included: benzaldehyde, phenylethyl alcohol, and benzyl alcohol with added Phe; methanethiol, methional, and dimethyl disulphide with added Met; 3-methyl butanol with added Leu; and 2-methyl butanol with added Ile. This research demonstrated that fermentation by LB672 of a DM supplemented with different amino acids separately or combined resulted in the formation of a range of dairy- and meat-related VOCs and provides information on how plant-based fermentations could be manipulated to generate desirable flavours.

Concrete block production significantly contributes to environmental degradation. A thorough understanding of its ecological implications is critical for sustainable development. This study investigates concrete block manufacturing's environmental impact by quantifying embodied energy, CO 2 emissions, and water consumption via a comprehensive life cycle assessment. An extended life cycle assessment methodology is utilized to quantify the environmental indicators throughout the concrete block production lifecycle. Primary industry data and secondary research data ensure accuracy and reliability. Findings showed that concrete block manufacturing requires 2.5-4.1 times more embodied energy than equal clinker mass. Cement and aggregate production and transportation account for substantial energy needs. Limestone calcination during cement production causes significant CO 2 emissions, 2.3-3.3 times higher than the minimum. Water consumption is concerning during curing and washing. Exploring alternative cementitious materials, optimized processes, and water recycling can reduce embodied energy by up to 75%, CO 2 emissions by up to 67%, and water consumption by up to 80%. Concrete block manufacturing necessitates considerable energy and generates significant emissions. Implementing sustainable measures can minimize embodied energy, CO 2 emissions, and water consumption, enabling environmentally responsible manufacturing. This research emphasizes adopting sustainability practices to mitigate environmental impact. Policymakers, industry professionals, and researchers can employ these insights to develop effective strategies promoting green manufacturing. The concrete block industry can contribute to a sustainable future through sustainable practices., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Problem: With the rapid advancement of remote sensing technology is that the need for efficient and accurate crop classification methods has become increasingly important. This is due to the ever-growing demand for food security and environmental monitoring. Traditional crop classification methods have limitations in terms of accuracy and scalability, especially when dealing with large datasets of high-resolution remote sensing images. This study aims to develop a novel crop classification technique, named Dipper Throated Optimization with Deep Convolutional Neural Networks based Crop Classification (DTODCNN-CC) for analyzing remote sensing images. The objective is to achieve high classification accuracy for various food crops., Methods: The proposed DTODCNN-CC approach consists of the following key components. Deep convolutional neural network (DCNN) a GoogleNet architecture is employed to extract robust feature vectors from the remote sensing images. The Dipper throated optimization (DTO) optimizer is used for hyper parameter tuning of the GoogleNet model to achieve optimal feature extraction performance. Extreme Learning Machine (ELM): This machine learning algorithm is utilized for the classification of different food crops based on the extracted features. The modified sine cosine algorithm (MSCA) optimization technique is used to fine-tune the parameters of ELM for improved classification accuracy., Results: Extensive experimental analyses are conducted to evaluate the performance of the proposed DTODCNN-CC approach. The results demonstrate that DTODCNN-CC can achieve significantly higher crop classification accuracy compared to other state-of-the-art deep learning methods., Conclusion: The proposed DTODCNN-CC technique provides a promising solution for efficient and accurate crop classification using remote sensing images. This approach has the potential to be a valuable tool for various applications in agriculture, food security, and environmental monitoring., Competing Interests: The authors declare that they have no competing interests., (© 2024 Alotaibi et al.)

A suitable drug delivery strategy for metallodrugs is as significant as the strategies adopted for an efficient metallodrug design. In this study, piperlongumine, which is isolated from long pepper, is coordinated with a Ru(II)- p -cymene moiety to obtain an organoruthenated complex containing the natural product ( Ru(pip) ). The isolated complex shows higher cytotoxicity in MCF-7 breast cancer cells than in THP-1 leukemia and HepG2 liver cancer cells. The IC 50 value of the complex in non-cancerous HEK-239 cells is also almost equal to that in MCF-7 cells. Next, with an aim to modulate the antiproliferative activity of Ru(pip) using a drug delivery strategy, the complex is loaded into mesoporous silica nanorods ( MSNRs ), which have a higher surface area than spherical silica nanoparticles. Furthermore, the outer surface of the loaded nanorods is covered with a polydiacetylene-lipid ( PL ) hybrid bilayer. Given the unique optical properties of polydiacetylene, the PL coating modifies non-fluorescent MSNRs into red-emissive particles ( PL-Ru(pip)@MSNRs ), which can be useful for diagnostic applications. The release profile studies reveal that the ene-yne conjugation in the PL coating ensures the sustained release of the complex from nanoparticles in both physiological and simulated cancer cell media. While Ru(pip) exhibits both necrotic and apoptotic modes of cell death, PL-Ru(pip)@MSNRs preferably induce the apoptotic mode of cell death in MCF-7 and THP-1 cells. Also, the nanoformulation exhibits a higher percentage of cell cycle arrest in the G0/G1 phase than Ru(pip), as measured by flow cytometry analysis. In contrast, the in vitro antioxidant potency of the complex is decreased after being loaded into PL-coated silica nanoparticles.