Search Results (75)

Post-operative pancreatic fistula (POPF) is a serious yet far too common complication following distal pancreatectomy (DP), as it affects 20–30% of patients after DP. POPF raises the risk of other complications and causes delays to a patient’s oncologic care. In this review, we present the latest data on patient risk factors for developing POPF, such as obesity, smoking, young age, thick pancreas, lack of epidural anesthesia, hypoalbuminemia, and elevated drain amylase levels. Other risk factors that have been identified with irregular consistency include open surgical approach, non-malignant or neuroendocrine tumor pathology, simultaneous splenectomy, simultaneous vascular resection, and long operative time. We also review the consequences of POPF, which include hemorrhage, infection, delayed gastric emptying, re-operation, re-admission, delays in adjuvant chemotherapy initiation, reduced progression-free survival, and reduced overall survival. Finally, we present strategies that have been studied for avoiding POPF after DP, including reducing pressure at the sphincter of Oddi, the use of sealants and patches, optimizing pancreatic transection, strategies for post-operative drain placement, the use of post-operative somatostatin analogues, and pre-clinical studies of experimental devices and techniques that may inform future trials. This review informs readers on the current state of the art with regard to POPF after DP and sets the stage for future studies to improve patient outcomes. Full article

Gastrointestinal (GI) cancers, including esophageal, gastric, pancreatic, liver, and colorectal malignancies, represent a major global health burden due to their high incidence, aggressive nature, and limited treatment outcomes. This review explores the therapeutic potential of carvacrol, a naturally occurring monoterpenoid phenol predominantly found in oregano and other aromatic plants. Carvacrol has demonstrated strong anticancer properties by modulating multiple molecular pathways governing apoptosis, inflammation, angiogenesis, and metastasis. Preclinical studies have revealed its ability to selectively target cancer cells while sparing healthy tissue. Advances in nanotechnology have further enhanced its pharmacological profile by improving solubility, stability, and tumor-targeted delivery. Additionally, carvacrol shows synergistic effects when used in combination with conventional chemotherapeutics. While the evidence is promising, clinical studies are needed to validate its translational potential. This review aims to consolidate current findings and encourage further investigation into carvacrol’s application as an adjunct or alternative therapeutic agent in GI cancer management. Full article

Neonatal encephalopathy suspected to be due to hypoxic ischaemic encephalopathy (NESHIE) carries the risk of death or severe disability (cognitive defects and cerebral palsy). Previous genetic studies on NESHIE have predominantly focused on exomes or targeted genes. The objective of this study was to identify genetic variants associated with moderate–severe NESHIE through whole-genome, unbiased analysis. Variant filtering and prioritization were performed, followed by association testing both on a case–control basis and to compare the grades of severity and/or progression. Association testing on neonates with NESHIE (N = 172) and ancestry-matched controls (N = 288) produced 71 significant genetic variants (false discovery rate corrected p-value < 6.2 × 10⁻⁴), all located in non-coding regions and not previously implicated in NESHIE. Disease-associated variants in non-coding regions are considered to affect regulatory functions, possibly by modifying gene expression, promoters, enhancers, or DNA structure. The most significant variant was at position 6:162010973 in the Parkin RBR E3 ubiquitin protein ligase (PRKN) intron. Intronic variants were also identified in genes involved in inflammatory processes (SLCO3A1), DNA repair (ZGRF1), synaptogenesis (CNTN5), haematopoiesis (ASXL2), and the transcriptional response to hypoxia (PADI4). Ten variants were associated with a higher severity or lack of improvement in NESHIE, including one in ADAMTS3, which encodes a procollagen amino protease with a role in angiogenesis and lymphangiogenesis. This analysis represents one of the first efforts to analyze whole-genome data to investigate the genetic complexity of NESHIE in diverse ethnolinguistic groups of African origin and provides direction for further study. Full article

Rivers play a crucial role in nutrient cycling, yet are increasingly affected by eutrophication due to anthropogenic activities. This study focuses on the Barato River in Hokkaido, Japan, employing an integrated approach of field measurements and Sentinel-2 satellite remote sensing to monitor eutrophication as the river experiencing huge sewage effluents. Key parameters such as chlorophyll-a (Chla), dissolved inorganic nitrogen (DIN), dissolved inorganic phosphorus (DIP), and Secchi Disk Depth (SDD) were analyzed. The developed empirical models showed a strong predictive capability for water quality, particularly for Chla (R² = 0.87), DIP (R² = 0.61), and SDD (R² = 0.82). Seasonal analysis indicated peak Chla concentrations in October, reaching up to 92.4 μg/L, alongside significant decreases in DIN and DIP, suggesting high phytoplankton activity. Advanced machine learning models, specifically back propagation neural networks, improved the prediction accuracy with R² values up to 0.90 for Chla and 0.83 for DIN. Temporal analyses from 2018 to 2022 consistently revealed the Barato River’s eutrophic state, with severe eutrophication occurring for 33% of the year and moderate for over 50%, emphasizing the ongoing nutrient imbalance. The strong correlation between DIP and Chla highlights phosphorus as the main driver of eutrophication. These findings demonstrate the efficacy of integrating remote sensing and machine learning for dynamic monitoring of river eutrophication, providing critical insights for nutrient management and water quality improvement. Full article

Uptake of excess iron by lowland rice plants causes iron toxicity, which is a major problem in the affected areas. This study investigated molecular diversity, genetic structure, and marker–trait associations for tolerance to iron toxicity in a panel of germplasm lines using microsatellite markers. The studied population showed a moderate to high degree of genetic diversity, as revealed by the estimated molecular diversity parameters and principal component, cluster and box plot analyses. The landraces Mahipal, Dhusura, Dhabalabhuta, Champa, Sunapani and Kusuma were identified as suitable for cultivation in the areas affected by high iron levels. The landraces Dhusura, Kusuma, Kendrajhali, Ranisaheba, Panjabaniswarna, Mahipal, Dhinkisiali, Champa, Kalamara and Ratanmali, which showed low scores for tolerance, were considered good donors for iron toxicity tolerance improvement programs. Utilizing STRUCTURE software, a total of four genetic structure groups were detected in the panel germplasm of lines. These structural subgroups exhibited good correlations among their members for iron toxicity tolerance and other yield-related traits. Marker–trait association analysis validated the reported iron toxicity tolerance QTLs qFeTox 4.2 and qFeTox 4.3, which are useful for marker-assisted improvement. A new QTL, qFeTox 7.1, located on chromosome 7, was detected as controlling iron toxicity tolerance in rice. Full article

Background: Breast cancer influences more than 2 million women worldwide annually. Since apoptotic dysregulation is a cancer hallmark, targeting apoptotic regulators encompasses strategic drug development for cancer therapy. One such class of apoptotic regulators is inhibitors of apoptosis proteins (IAP) which are a class of E3 ubiquitin ligases that actively function to support cancer growth and survival. Methods: The current study reports design, synthesis, docking analysis (based on binding to IAP-BIR3 domains), anti-proliferative and anti-tumor potential of the azomethine derivative, 1-(4-chlorophenyl)-N-(4-ethoxyphenyl)methanimine (BCS3) on breast cancer (in vitro and in vivo) and its possible mechanisms of action. Results: Strong selective cytotoxic activity was observed in MDA-MB-231, MCF-7, and MDA-MB-468 breast cancer cell lines that exhibited IC50 values, 1.554 µM, 5.979 µM, and 6.462 µM, respectively, without affecting normal breast cells, MCF-10A. For the evaluation of the cytotoxic potential of BCS3, immunofluorescence, immunoblotting, and FACS (apoptosis and cell cycle) analyses were conducted. BCS3 antagonized IAPs, thereby causing MDM2-p53 and Bcl-2-Caspase-mediated intrinsic and extrinsic apoptosis. It also modulated p53 expression causing p21-CDK1/cyclin B1-mediated cell cycle arrest at S and G2/M phases. The in vitro findings were consistent with in vivo findings as observed by reduced tumor volume and apoptosis initiation (TUNEL assay) by IAP downregulation. BCS3 also produced potent synergistic effects with doxorubicin on tumor inhibition. Conclusions: Having witnessed the profound anti-proliferative potential of BCS3, the possible adverse effects related to anti-cancer therapy were examined following OECD 407 guidelines which confirmed its systemic safety profile and well tolerability. The results indicate the promising effect of BCS3 as an IAP antagonist for breast cancer therapy with fewer adverse effects. Full article

Colorectal cancer (CRC) remains a significant global health burden with high incidence and mortality. MicroRNAs (miRNAs) are small non-protein coding transcripts, conserved throughout evolution, with an important role in CRC tumorigenesis, and are either upregulated or downregulated in various cancers. RNA-binding proteins (RBPs) are known as essential regulators of miRNA activity. Human antigen R (HuR) is a prominent RBP known to drive tumorigenesis with a pivotal role in CRC. In this review, we discuss the regulatory role of the HuR/miRNA axis in CRC. Interestingly, miRNAs can directly target HuR, altering its expression and activity. However, HuR can also stabilize or degrade miRNAs, forming complex feedback loops that either activate or block CRC-associated signaling pathways. Dysregulation of the HuR/miRNA axis contributes to CRC initiation and progression. Additionally, HuR-miRNA regulation by other small non-coding RNAs, circular RNA (circRNAs), or long-non-coding RNAs (lncRNAs) is also explored here. Understanding this HuR-miRNA interplay could reveal novel biomarkers with better diagnostic or prognostic accuracy. Full article

Acetamiprid (ACMP) is a neonicotinoid insecticide that poses a significant threat to the environment and mankind. Oxidative stress and mitochondrial dysfunction are considered prime contributors to ACMP-induced toxic effects. Meanwhile, berberine (BBR) a natural plant alkaloid, is a topic of interest because of its therapeutic and prophylactic actions. Therefore, this study evaluated the effects of BBR on ACMP-mediated alterations in mitochondrial functions and apoptosis in rat liver tissue. Male Wistar rats were divided into four groups: (I) control, (II) BBR-treated, (III) ACMP-exposed, and (IV) BBR+ACMP co-treated groups. The doses of BBR (150 mg/kg b.wt) and ACMP (1/10 of LD_50, i.e., 21.7 mg/kg b.wt) were given intragastrically for 21 consecutive days. The results showed that the administration of ACMP diminished mitochondrial complex activity, downregulated complex I (ND1 and ND2) and complex IV (COX1 and COX4) subunit mRNA expression, depleted the antioxidant defense system, and induced apoptosis in rat liver. BBR pre-treatment significantly attenuated ACMP-induced mitochondrial dysfunction by maintaining mitochondrial complex activity and upregulating ND1, ND2, COX1, and COX4 mRNA expression. BBR reversed ACMP-mediated apoptosis by diminishing Bax and caspase-3 and increasing the Bcl-2 protein level. BBR also improved the mitochondrial antioxidant defense system by upregulating mRNA expression of PGC-1α, MnSOD, and UCP-2 in rat liver tissue. This study is the first to evaluate the protective potential of BBR against pesticide-induced mitochondrial dysfunction in liver tissue. In conclusion, BBR offers protection against ACMP-induced impairment in mitochondrial functions by maintaining the antioxidant level and modulating the apoptotic cascade. Full article

Additive manufacturing has witnessed significant growth in recent years, revolutionizing the automotive and aerospace industries amongst others. Despite the use of additive manufacturing for creating complex geometries and reducing material consumption, there is a critical need to enhance the mechanical properties of manufactured parts to broaden their industrial applications. In this work, AISI 316L stainless steel is used to fabricate parts using three different strategies of the additively manufactured Laser Powder Bed Fusion (LPBF) technique, i.e., continuous, alternate, and island. This study aims to identify methods to optimize grain orientation and compaction support provided to the material under load, which influence the frictional and wear properties of the manufactured parts. The load-bearing capacity is evaluated by measuring the frictional and wear properties. The wear patch track is also examined to establish the physical mechanisms at the surface interface that lead to the smooth transition in response to the load. Grain orientation is compared across different strategies using Electron Backscatter Diffraction (EBSD) maps, and the influence of surface roughness on sliding behavior is also evaluated. The results demonstrate that the island scanning strategy yields the best performance for load-bearing applications, exhibiting superior grain orientation and hardness in the additively manufactured parts. Full article

Background: KEYNOTE-522 resulted in FDA approval of the immune checkpoint inhibitor pembrolizumab in combination with neoadjuvant chemotherapy for patients with early-stage, high-risk, triple-negative breast cancer (TNBC). Unfortunately, pembrolizumab is associated with several immune-related adverse events (irAEs). We aimed to identify potential tumor microenvironment (TME) biomarkers which could predict patients who may attain pathological complete response (pCR) with chemotherapy alone and be spared the use of anti-PD-1 immunotherapy. Methods: Comprehensive immune profiling, including RNA-seq gene expression assessment of 395 immune genes, was performed on matched FFPE tumor samples from 22 stage I-III TNBC patients (14 patients treated with neoadjuvant chemotherapy alone (NAC) and 8 treated with neoadjuvant chemotherapy combined with pembrolizumab (NAC+I)). Results: Differential gene expression analysis revealed that in the NAC group, IL12B and IL13 were both significantly associated with pCR. In the NAC+I group, LCK and TP63 were significantly associated with pCR. Patients in both treatment groups exhibiting pCR tended to have greater tumor inflammation than non-pCR patients. In the NAC+I group, patients with pCR tended to have greater cell proliferation and higher PD-L1 expression, while in the NAC group, patients with pCR tended to have lower cancer testis antigen expression. Additionally, the NAC+I group trended toward a lower relative dose intensity averaged across all chemotherapy drugs, suggesting that more dose reductions or treatment delays occurred in the NAC+I group than the NAC group. Conclusions: A comprehensive understanding of immunologic factors could potentially predict pCR to chemotherapy alone, enabling the avoidance of the unnecessary treatment of these patients with checkpoint inhibitors. Full article

This article explores the life and influence of Indira Devi Niloy (1920–1997) who in 1949 began to encounter the sixteenth-century saint–poet Mirabai during her meditative trance states. She would recount songs, stories, and teachings that the saint gave to her as well as scenes from Mirabai’s life that she witnessed as an observer and at other times experienced directly as a participant. Their ongoing relationship would have a tremendous influence on Indira Devi as well as her guru Dilip Kumar Roy (1897–1980) and the increasingly international community that grew up around them. Their interactions and Indira Devi’s reports in turn would also significantly influence the reception and perceived continuing relevance of Mirabai as both inspiration and authorization for women’s self-realization. Additionally, Indira Devi’s own story reveals a mode of female guruhood, with a distinct absence of identification with shakti or divine incarnation, a more egalitarian model for the guru–disciple relationship, and an alternate bhakti mode of male–female collaborative leadership with Roy. Further their experiences with Mirabai offer insight into the ongoing engagement of women and men with such influential women of the past, the intersubjective nature of the traditions that surround them, and what Mirabai’s message might be for women (and men) today. Full article

Agriculture is essential to the existence of the human race, as well as the foundation of our civilization, because it provides food, fuel, fiber, and other resources necessary for survival; however, it is facing critical challenges due to anthropogenic climate change, which hampers food and nutritional security. Consequently, the agriculture industry must adjust to farming issues, such as the shift in global temperatures and environmental degradation, the scarcity of farm workers, population growth, and dietary changes. Several measures have been implemented to enhance agricultural productivity, including plant breeding, genetic engineering, and precision agriculture. In recent years, the world has witnessed the burgeoning development of novel scientific innovations and technological advancements enabled by drones, smart sensors, robotics, and remote sensing, resulting in a plethora of revolutionary methods that can be applied to real-time crop modeling, high-throughput phenotyping, weather forecasting, yield prediction, fertilizer application, disease detection, market trading, farming practices, and other environmental practices vital to crop growth, yield, and quality. Furthermore, the rise in big data, advanced analytics, falling technology costs, faster internet connections, increased connectivity, and increases in computational power are all part of the current digitalization wave that has the potential to support commercial agriculture in achieving its goals of smart farming, resilience, productivity, and sustainability. These technologies enable efficient monitoring of crops, soil, and environmental conditions over large areas, providing farmers with data to support precise management that optimizes productivity and minimizes environmental impacts. Though smart farming has significant potential, challenges like high implementation costs, data security concerns, and inadequate digital literacy among farmers remain. In summary, agriculture is rapidly transforming from conventional to digital farming, offering global solutions, efficient resource utilization, and minimized input costs while fostering farmer livelihoods and economic growth. Delivering a comprehensive view of how technology could help in tackling critical issues like environmental degradation and threatened world biodiversity, this perspective emphasizes the perks of digitalization. Future advancements may involve data encryption, digital literacy, and particular economic policies. Full article

Programmed cell death ligand (PD-L1) expression by immunohistochemistry (IHC) lacks sensitivity for pembrolizumab immunotherapy selection in non-small cell lung cancer (NSCLC), particularly for tumors with low expression. We retrospectively evaluated transcriptomic PD-L1 by mRNA next-generation sequencing (RNA-seq). In an unselected NSCLC patient cohort (n = 3168) tested during standard care (2017–2021), PD-L1 IHC and RNA-seq demonstrated moderate concordance, with 80% agreement overall. Most discordant cases were either low or negative for PD-L1 expression by IHC but high by RNA-seq. RNA-seq accurately discriminated PD-L1 IHC high from low tumors by receiver operator curve (ROC) analysis but could not distinguish PD-L1 IHC low from negative tumors. In a separate pembrolizumab monotherapy cohort (n = 102), NSCLC tumors classified as PD-L1 high versus not high by RNA-seq had significantly improved response, progression-free survival, and overall survival as an individual measure and in combination with IHC high or low status. PD-L1 IHC status (high or low) trended toward but had no significant associations with improved outcomes. Conventional PD-L1 IHC testing has inherent limitations, making it an imperfect reference standard for evaluating novel testing technologies. RNA-seq offers an objective PD-L1 measure that could represent a complementary method to IHC to improve NSCLC patient selection for immunotherapy. Full article

Virtual reality (VR) technology has recently been adopted by educators for use in the classroom. Currently, this educational model includes not only lectures with teachers in the online classroom but also practical sessions using online platforms. Few studies have explored the potential of pedagogical approaches to implementing VR in the classroom for the purpose of design education. The focus of this paper was to study the learning experiences of the 3D visualisation of products among industrial design students through the strategic implementation of virtual reality technology. A within-subjects comparative study was conducted to measure cognitive workload and engagement and enjoyment, while a 3D modelling task was given using two different set-ups (conventional 3D software versus VR-based software). The statistical results show that the NASA-TLX score was lower in the case of the VR-based 3D modelling exercise compared to the conventional 3D software-based exercise. On the other hand, the mean values were higher for the engagement and enjoyment and usability scores, which means that the VR-based experience for 3D modelling was better than the traditional modelling experience using conventional software. Hence, there are possibilities to implement VR-based 3D modelling tools for online industrial design education for 3D visualisation in the near future. Full article