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Abstract The characterization of cells with tumour initiating potential is significant for advancing our understanding of cancer and improving therapy. Aggressive, triple‐negative breast cancers (TNBCs) are enriched for tumour‐initiating cells (TICs). We investigated that hypothesis that VEGF receptors expressed on TNBC cells mediate autocrine signalling that contributes to tumour initiation. We discovered the VEGF receptor neuropilin‐2 (NRP2) is expressed preferentially on TICs, involved in the genesis of TNBCs and necessary for tumour initiation. The mechanism by which NRP2 signalling promotes tumour initiation involves stimulation of the α6β1 integrin, focal adhesion kinase‐mediated activation of Ras/MEK signalling and consequent expression of the Hedgehog effector GLI1. GLI1 also induces BMI‐1, a key stem cell factor, and it enhances NRP2 expression and the function of α6β1, establishing an autocrine loop. NRP2 can be targeted in vivo to retard tumour initiation. These findings reveal a novel autocrine pathway involving VEGF/NRP2, α6β1 and GLI1 that contributes to the initiation of TNBC. They also support the feasibility of NRP2‐based therapy for the treatment of TNBC that targets and impedes the function of TICs. → See accompanying article http://dx.doi.org/10.1002/emmm.201302505

The quality and uniformity of green coffee beans significantly influence the overall flavor and value of the product. In the coffee industry, automated flaws and bean-type identification offer numerous advantages. This study examines the effectiveness of multiple YOLO (You Only Look Once) models for identifying and classifying green coffee beans. Various YOLO variants, including YOLOv3, YOLOv4, YOLOv5, YOLOv7, YOLOv8, and custom models, are compared with a focus on computational efficiency, accuracy, and speed. Utilizing a dataset of 4,032 training and 506 testing images encompassing diverse bean types, defects, and lighting conditions, we assessed the performance. The bounding boxes generated by our models accurately encompass coffee beans, with the background typically uniform and set to black. Our analysis reveals the superior performance of the custom-YOLOv8n model, which we meticulously customized for green coffee bean detection. This model achieved high precision, recall, f1-score, and mAP, demonstrating its potential for real-world implementation in coffee bean quality control systems. The customization process involved fine-tuning the model to focus on significant features relevant to green coffee bean detection and employing specific labeling strategies. Customization allows you to fine-tune the model to focus on important features relevant to green coffee bean detection. This sensitivity ensures that the model can effectively distinguish between different bean types and detect even subtle defects. This paper clarifies our primary objective of evaluating YOLO models' performance in identifying and categorizing green coffee beans, with potential implications for enhancing efficiency and consistency in the coffee industry. A succinct key sentence underscores the benefits of our research for readers seeking efficient YOLO model selection and implementation in agricultural systems. [ABSTRACT FROM AUTHOR]

This work offers a quite sensitive SPR-based sensor with a new heterostructure based on platinum and ITO using silver as the plasmonic metal to examine the detection of sulfolane, ethylene glycol, diethylene glycol, and polyethylene glycol (PEG-200 and PEG-600) in water. The widely utilized transfer matrix technique (TMM) was employed to evaluate the performance of the suggested sensor. The noble plasmonic material silver (Ag) with a thickness of 40 nm is utilized to induce surface plasmons. As an adhesive layer, Cytop is used between the ITO and sensing layer; the thickness of 0.5 nm has been taken. The sensor's performance was evaluated in terms of reflectance, full width at half maximum (FWHM), detection accuracy, sensitivity, and figure of merit. These parameters are also evaluated by varying the platinum (P) and ITO (I) layers. The suggested sensor has a maximum sensitivity of 144.1988 degree/RIU (for P = 1 , I = 9 ), DA of 1.8867 degree−1, and FoM of 98.66 RIU−1 (for P = 3 , I = 1 ). The operating wavelength of 633 nm is used here for this numerical analysis. [ABSTRACT FROM AUTHOR]

Purpose: The cumulative effect of hyper-coagulative COVID-19 disease and using steroids leads to increased avascular necrosis (AVN) hip incidence. This study aims to correlate the various factors of COVID-19 infection with the occurrence of AVN hip. Methods: It is a retrospective cross-sectional study of non-traumatic AVN hip patients with a history of COVID-19 infection. A total number of 50 patients satisfied the inclusion criteria. The following details were obtained: (a) patient's demographics, (b) COVID-19: interval of infection and groin pain, duration of symptoms, severity, steroid intake, (c) AVN hip: involved side, Ficat-Arlet staging. Results: The mean age was 36.3 years (range: 20–60), and body mass index (BMI) was 25.13 kg/m2 (range: 18.50–31.50). There were 45 males and five females. Sixty percent (30) of patients managed at home, 24% (12) required admission into the ward, 2% (1) were in ICU only, and 14% (7) admitted to both ICU and ward. The mean interval of COVID-19 infection and onset of hip pain was 359.02 days (range: 10–822 days). Thirty-eight percent (19) patients required steroids (injection and oral), 46% (23) took steroids (oral only), whereas 16% (8) recovered without steroids. The stage of AVN correlated with the severity of COVID-19 infection (p-value −0.038) and significant improvement in VAS and HHS after treatment in each stage. The mean follow-up was 9.79 months (6–19 months). Conclusion: A low-dose steroid intake with moderate to severe COVID-19 infection produces an additive effect on the development of AVN hip. Most affected individuals were adult males, and stage II AVN was the most common, managed with bisphosphonates and core decompression for short intervals. [ABSTRACT FROM AUTHOR]

Due to waning immunity following primary immunization with COVID-19 vaccines, booster doses may be required. The present study assessed a heterologous booster of SII-NVX-CoV2373 (spike protein vaccine) in adults primed with viral vector and inactivated vaccines. In this Phase 3, observer-blind, randomized, active controlled study, a total of 372 adults primed with two doses of ChAdOx1 nCoV-19 (n = 186) or BBV152 (n = 186) at least six months ago, were randomized to receive a booster of SII-NVX-CoV2373 or control vaccine (homologous booster of ChAdOx1 nCoV-19 or BBV152). Anti-S IgG and neutralizing antibodies (nAbs) were assessed at days 1, 29, and 181. Non-inferiority (NI) of SII-NVX-CoV2373 to the control vaccine was assessed based on the ratio of geometric mean ELISA units (GMEU) of anti-S IgG and geometric mean titers (GMT) of nAbs (NI margin > 0.67) as well as seroresponse (≥ 2 fold-rise in titers) (NI margin −10%) at day 29. Safety was assessed throughout the study period. In both the ChAdOx1 nCoV-19 prime and BBV152 prime cohorts, 186 participants each received the study vaccines. In the ChAdOx1 nCoV-19 prime cohort, the GMEU ratio was 2.05 (95% CI 1.73, 2.43) and the GMT ratio was 1.89 (95% CI 1.55, 2.32) whereas the difference in the proportion of seroresponse was 49.32% (95% CI 36.49, 60.45) for anti-S IgG and 15% (95% CI 5.65, 25.05) for nAbs on day 29. In the BBV152 prime cohort, the GMEU ratio was 5.12 (95% CI 4.20, 6.24) and the GMT ratio was 4.80 (95% CI 3.76, 6.12) whereas the difference in the proportion of seroresponse was 74.08% (95% CI 63.24, 82.17) for anti-S IgG and 24.71% (95% CI 16.26, 34.62) for nAbs on day 29. The non-inferiority of SII-NVX-CoV2373 booster to the control vaccine for each prime cohort was met. SII-NVX-CoV2373 booster showed significantly higher immune responses than BBV152 homologous booster. On day 181, seroresponse rates were ≥ 70% in all the groups for both nAbs and anti-S IgG. Solicited adverse events reported were transient and mostly mild in severity in all the groups. No causally related SAE was reported. SII-NVX-CoV2373 as a heterologous booster induced non-inferior immune responses as compared to homologous boosters in adults primed with ChAdOx1 nCoV-19 and BBV152. SII-NVX-CoV2373 showed a numerically higher boosting effect than homologous boosters. The vaccine was also safe and well tolerated. [ABSTRACT FROM AUTHOR]

Identifying metabolic steps that are specifically required for the survival of cancer cells but are dispensable in normal cells remains a challenge1. Here we report a therapeutic vulnerability in a sugar nucleotide biosynthetic pathway that can be exploited in cancer cells with only a limited impact on normal cells. A systematic examination of conditionally essential metabolic enzymes revealed that UXS1, a Golgi enzyme that converts one sugar nucleotide (UDP-glucuronic acid, UDPGA) to another (UDP-xylose), is essential only in cells that express high levels of the enzyme immediately upstream of it, UGDH. This conditional relationship exists because UXS1 is required to prevent excess accumulation of UDPGA, which is produced by UGDH. UXS1 not only clears away UDPGA but also limits its production through negative feedback on UGDH. Excess UDPGA disrupts Golgi morphology and function, which impedes the trafficking of surface receptors such as EGFR to the plasma membrane and diminishes the signalling capacity of cells. UGDH expression is elevated in several cancers, including lung adenocarcinoma, and is further enhanced during chemoresistant selection. As a result, these cancer cells are selectively dependent on UXS1 for UDPGA detoxification, revealing a potential weakness in tumours with high levels of UGDH.An enzyme called UXS1 that converts one sugar nucleotide to another is needed more in some cancer cells than in normal cells, providing a potential weakness that can be exploited therapeutically. [ABSTRACT FROM AUTHOR]

Vaccination with live attenuated Leishmania parasites such as centrin deleted Leishmania donovani (LdCen−/−) against visceral leishmaniasis has been reported extensively. The protection induced by LdCen−/− parasites was mediated by both CD4+ and CD8+ T cells. While the host immune mediators of protection are known, parasite determinants that affect the CD4+ and CD8+ T cell populations remain unknown. Parasite encoded inflammatory cytokine MIF has been shown to modulate the T cell differentiation characteristics by altering the inflammation induced apoptosis during contraction phase in experimental infections with Leishmania or Plasmodium. Neutralization of parasite encoded MIF either by antibodies or gene deletion conferred protection in Plasmodium and Leishmania studies. We investigated if the immunogenicity and protection induced by LdCen−/− parasites is affected by deleting MIF genes from this vaccine strain. Our results showed that LdCen−/−MIF−/− immunized group presented higher percentage of CD4+ and CD8+ central memory T cells, increased CD8+ T cell proliferation after challenge compared to LdCen−/− immunization. LdCen−/−MIF−/− immunized group presented elevated production of IFN-γ+ and TNF-α+ CD4+ T cells concomitant with a reduced parasite load in spleen and liver compared to LdCen−/−group following challenge with L. infantum. Our results demonstrate the role of parasite induced factors involved in protection and long-term immunity of vaccines against VL. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the risk of mortality and length of stay in hospitalised patients who have experienced suspected adverse drug reactions (ADRs) as compared to patients who did not experience suspected ADRs. Methods: A systematic literature search was conducted on databases for observational and randomised controlled studies conducted in any inpatient setting that reported deaths and/or length of hospital stay in patients who had suspected ADRs and did not have suspected ADRs during hospitalisation. PRISMA guidelines were strictly followed during the review. The methodological quality of included studies was assessed using a tool designed by Smyth et al. for the studies of adverse drug reactions. The meta-analytic summary of all-cause mortality was estimated using odds ratio—OR (95% CI) and length of stay using mean difference—MD (95% CI). Both outcomes were pooled using a random effect model (DerSimonian and Laird method). Subgroup and meta-regression were performed based on study variables: study design, age group, study ward, study region, types of suspected ADRs (ADRAd—suspected ADRs that lead to hospitalisation and ADRIn—suspected ADRs that occur following hospitalisation), study duration, sample size and study period. The statistical analysis was conducted through the 'Review manager software version 5.4.1 and JASP (Version 0.14.1)'. Results: After screening 475 relevant articles, 55 studies were included in this meta-analysis. Patients having suspected ADRs had reported significantly higher odds of all-cause mortality [OR: 1.50 (95% CI: 1.21–1.86; I2 = 100%) than those patients who did not have suspected ADRs during hospitalisation. Study wards, types of suspected ADRs and sample size were observed as significant predictors of all-cause mortality (p < 0.05). Patients having suspected ADRs had reported significantly higher mean difference in hospital stay [MD: 3.98 (95% CI: 2.91, 5.05; I2 = 99%) than those patients who did not have suspected ADRs during hospitalisation. Types of suspected ADRs and study periods were observed as significant predictors of length of stay (p < 0.05). Conclusion: Suspected ADRs significantly increase the risk of mortality and length of stay in hospitalised patients. Systematic review registration. CRD42020176320. [ABSTRACT FROM AUTHOR]

Purpose: To estimate the prevalence of drug-related deaths with regard to total hospital mortality and to explore the heterogeneity in its estimation through subgroup analysis, univariate and multivariate analysis. Methods: Two investigators independently searched the PubMed and Google Scholar databases with appropriate key terms to identify observational and randomised studies assessing drug-related problems. The prevalence of drug-related deaths was estimated using a double arcsine method. The heterogeneity was explored through subgroup and univariate analysis for the following study characteristics: study design, age group, study ward, study region, types of drug-related problems, study duration, sample size and study period. The study variables showing significant effects were further explored through a multivariable regression model. The percentage of preventable drug-related deaths was explored as a secondary objective. Results: Of the 480 full-text articles assessed, 23 studies satisfying the selection criteria were included. The mean percentage of drug-related deaths was 5.6% (95% CI: 3.8–7.6%; I2 = 96%). The univariable analysis showed study design (regression coefficient: 4.31) and study wards (regression coefficient: − 6.37) as heterogeneity modifiers. In the multivariable model, only the study ward was considered a significant predictor of drug-related deaths (regression coefficient: − 5.78; p = 0.04). The mean percentage of preventable drug-related deaths was 45.2% (95% CI: 33.6–57.0%; I2 = 60%). Conclusion: Drug-related problems are an important cause of mortality. The variability in its estimation could be explained by admission wards. [ABSTRACT FROM AUTHOR]

Purpose: We have consistently observed a connective tissue lining over the intercondylar notch's roof (CTLINR) during arthroscopic surgeries of the knee joint. As there is a strong association of the intercondylar fossa with the anterior cruciate ligament (ACL), we believe that this tissue must be having some role in the functioning of the ACL. The purpose of this pilot study was to investigate the anatomic characteristics of the CTLINR. Methods: In this observational anatomical study, we have investigated the gross anatomical and histological features of the CTLINR in four knees of two fresh frozen non-embalmed cadavers. We have also studied its ultrastructural characteristics by obtaining an arthroscopic biopsy of the tissue from a patient undergoing ACL reconstruction. Results: At gross examination, the CTLINR had a typical glistening white surface with transversely oriented fibres. It entirely covered the roof of the intercondylar notch and was soft to touch. Histological examination with haematoxylin–eosin stain revealed fibro-collagenous tissue with intervening blood vessels. Transmission electron microscopy manifested loosely arranged collagen fibres of variable diameter. Conclusion: The histological and electron microscopic characteristics of the tissue differentiate it from the ACL and its femoral enthesis, suggesting that it was a distinct anatomical structure. As it entirely covered the roof of the intercondylar fossa and had a smooth surface and soft consistency, it may protect the reconstructed ACL from graft abrasion. Furthermore, as it had a characteristic arthroscopic appearance, future research can investigate its role in femoral tunnel positioning. [ABSTRACT FROM AUTHOR]

Hydroxychloroquine has been promoted for its use in treatment of COVID-19 patients based on in-vitro evidences. We searched the databases to include randomized and observational studies evaluating the effect of Hydroxychloroquine on mortality in COVID-19 patients. The outcome was summarized as odds ratios (OR) with a 95% confidence interval (CI).We used the inverse-variance method with a random effect model and assessed the heterogeneity using I2 test. We used ROBINS-I tool to assess methodological quality of the included studies. We performed the meta-analysis using 'Review manager software version 5.3'. We identified 6 observationalstudies satisfying the selection criteria. In all studies, Hydroxychloroquine was given as add on to the standard care and effect was compared with the standard care alone. A pooled analysis observed 251 deaths in 1331 participants of the Hydroxychloroquine arm and 363 deaths in 1577 participants of the control arm. There was no difference in odds of mortality events amongst Hydroxychloroquine and supportive care arm [1.25 (95% CI: 0.65, 2.38); I2 = 80%]. A similar trend was observed with moderate risk of bias studies [0.95 (95% CI: 0.44, 2.06); I2 = 85%]. The odds of mortality were significantly higher in patients treated with Hydroxychloroquine + Azithromycin than supportive care alone [2.34 (95% CI: 1.63, 3.34); I2 = 0%]. A pooled analysis of recently published studies suggests no additional benefit for reducing mortality in COVID-19 patients when Hydroxychloroquine is given as add-on to the standard care. [ABSTRACT FROM AUTHOR]

Fibroblasts and myofibroblasts have been known to be present in both ruptured and intact human anterior cruciate ligament (ACL), and although their relevant histology and immunochemistry have been studied in the past, ultrastructural features of these cells are largely lacking. Therefore, we aim to characterise the ultrastructural details of these cells with the help of transmission electron microscopy (TEM) and to study the changes and their significance with duration of injury. Samples from 60 ruptured human ACL undergoing surgery were obtained and categorised according to duration of injury and observed under TEM with main focus on the following ultrastructural features: cellular morphology, presence of rough endoplasmic reticulum, Golgi apparatus, lamina, myofilaments, and presence of myofibroblasts. These features were further correlated with the duration of injury and association, if any, determined using appropriate statistical analysis. A total of 54 male and 6 female patients with mean duration of the injury of 23.01 ± 26.09 weeks (2–108 weeks) were included in the study and categorised into five groups based on duration of injury as follows: I (< 6 weeks), II (7–12 weeks), III (13–20 weeks), IV (21–50 weeks) and V (> 50 weeks). There was a significant association between the above-mentioned ultrastructural features and the duration of injury (p < 0.05) except for the presence of ovoid fibroblast cells (p = 0.53). Furthermore, number of myofibroblasts and cells with Golgi apparatus and rough endoplasmic reticulum was seen to peak at 13–20 weeks following injury. We describe ultrastructural features of fibroblast of different morphology along with myofibroblasts in the ligaments following injury, the changes in which might have a potential bearing on ligament healing. [ABSTRACT FROM AUTHOR]

The function of vascular endothelial growth factor (VEGF) in cancer is not limited to angiogenesis and vascular permeability. VEGF-mediated signalling occurs in tumour cells, and this signalling contributes to key aspects of tumorigenesis, including the function of cancer stem cells and tumour initiation. In addition to VEGF receptor tyrosine kinases, the neuropilins are crucial for mediating the effects of VEGF on tumour cells, primarily because of their ability to regulate the function and the trafficking of growth factor receptors and integrins. This has important implications for our understanding of tumour biology and for the development of more effective therapeutic approaches. [ABSTRACT FROM AUTHOR]