Search Results (56)

Ensete ventricosum is a morphologically gigantic, monocot, diploid sister to the banana plant species. It is commercially cultivated as a starch source, only in Ethiopia, where it feeds twenty million people. Here, the complete chloroplast (CP) genomes of 15 diverse landraces of E. ventricosum were assembled and annotated, for comparative genomics, genetic diversity analysis, and molecular marker development. The assembled E. ventricosum CP genomes ranged between 168,388 and 168,806 bp. The sampled CP genomes were quadripartite in structure and had two single-copy regions, a large single-copy region (LSC, average length 88,657 bp), and a small single-copy region (SSC, average length 11,098 bp) separated by inverted repeat regions (IR, average length 34,437 bp). The total number of annotated genes varies between 135 and 138, including 89–92 protein-coding genes, 38 tRNA genes, and 4 rRNA genes. All CP genes, including non-functional ones and intergenic regions, were transcribed with the transcriptome, covering almost 92% of the E. ventricosum CP genome. Codon usage, amino acid frequency, GC contents, and repeat nucleotides were similar among the 15 landraces. Mono- and tetranucleotide simple sequence repeats (SSRs) were found more frequently than other SSRs. An average of 71% of these SSRs were located in the LSC region, and the majority of the SSR motifs were composed of A/T nucleotides. A phylogenetic analysis of the 15 Ensete landraces indicated a common evolutionary origin, while the China sample was positioned separately, suggesting notable genetic differences. This study presents a comparative analysis of the chloroplast genomes of 15 E. ventricosum landraces, providing valuable insights into their genetic diversity and evolution. The identified SSR markers and conserved genomic features offer essential resources for future research and an improvement in Ensete conservation and breeding. Full article

The recommended surgery for pancreatic tumors is dependent on the diagnosis. For pancreatic adenocarcinoma, duodenal, and ampullary adenocarcinoma, a Whipple pancreaticoduodenectomy with lymph node dissection is recommended. For small < 2 cm or non-imageable gastrinomas, duodenal transillumination, duodenotomy, duodenal tumor excision and adjacent lymphadenectomy is recommended. For large > 3 cm gastrinomas, a Whipple pancreaticoduodenectomy with adjacent lymph node dissection is recommended. For small 1–2 cm insulinomas, intraoperative ultrasound with enucleation is recommended. If the patient with gastrinoma, insulinoma, or multiple nonfunctional NETs occurs in the setting of MEN-1, a subtotal pancreatectomy with or without splenectomy with enucleation of pancreatic head tumors is recommended, with adjacent lymph node dissection. The detail of each procedure is described with illustrations. Full article

The large portion of the eukaryotic genomes was considered non-functional and called the “dark matter” of the genome, now appearing as regulatory hubs coding for RNAs without the potential for making proteins, known as non-coding RNA. Long non-coding RNA (lncRNA) is defined as functional RNA molecules having lengths larger than 200 nucleotides without the potential for coding for proteins. Thousands of lncRNAs are identified in different plants and animals. LncRNAs are characterized by a low abundance, fewer exons than mRNA, tissue-specific expression, and low sequence conservation compared to protein-coding genes (PCGs). LncRNAs, like PCGs, are regulated by promoters and enhancers with characteristic chromatin signatures, DNA methylation, multiple exons, introns, and alternate splicing. LncRNAs interact with DNA, mRNA, microRNA, and proteins, including chromatin/histone modifiers, transcription factors/repressors, epigenetic regulators, spliceosomal, and RNA-binding proteins. Recent observations indicate that lncRNAs code for small peptides, also called micropeptides (<100 amino acids), and are involved in the development and growth of plants, suggesting the bi-functional activities of lncRNAs. LncRNAs have emerged as the major regulators of diverse functions, principally by altering the transcription of target genes. LncRNAs are involved in plant growth, development, immune responses, and various physiological processes. Abiotic, biotic, nutrient, and other environmental stresses alter the expressions of numerous lncRNAs. Understanding the mechanisms of actions of lncRNAs opens up the possibility of improving agronomic traits by manipulating lncRNAs. However, further studies are required in order to find the interactions among the deregulated lncRNAs and validate the findings from high-throughput studies to harness their potential in crop improvement. Full article

Background: As the rehabilitation of the upper anterior maxilla primarily requires high predictability of successful aesthetic outcomes, procedures of immediate implant placement are frequently employed. The aim of this pilot study was to retrospectively evaluate the short-term outcomes of a protocol of immediate implant placement in fresh extraction sockets, followed by immediate non-functional provisional restorations. Methods: Patients were treated for the replacement of maxillary central or lateral incisors, or cuspid teeth with a single-crown locking-taper implant. Clinical and photographic records were retrospectively compared between the teeth prior to extraction (T0) and restorations one year after prosthetic loading (T1). Outcomes were analyzed using the Pink Esthetic Score (PES), according to the patient’s phenotype (thin/thick), with or without the use of connective tissue graft (CTG). Results: The overall mean PES of 25 implants treated was 9.24 ± 2.36 at T0 and 9.60 ± 1.70 at T1. Comparison of groups between T0 and T1 revealed significant PES variations (p = 0.04), with the best and the worst scores, respectively, registered for thin + CTG group (from 7.50 ± 1.91 to 9.75 ± 2.87) and thin group (from 11.33 ± 2.33 to 10 ± 0.89); moderate increases were assessed for thick group (from 8.44 ± 2.40 to 9.44 ± 2.12) and thick + CTG group (from 9.50 ± 1.04 to 9.33 ± 0.81). Conclusions: Within the limits of a short-term analysis of a small number of patients, immediate implant rehabilitation for aesthetic areas of the upper maxilla can be assumed as a safe and predictable protocol. Concomitant use of CTG seems to provide beneficial effects in thin phenotypes, not any additional value in thick phenotypes. Full article

Background: Decathlon is a multimodality sport that requires the combination of endurance, strength, speed, and agility. A polymorphism present in the gene encoding for alpha-actinin-3 (ACTN3) potentially influences sports performance, since this protein is a structural component of skeletal muscle contributing to muscle contraction effectiveness. Aim: To investigate whether the presence of the ACTN3 R577X polymorphism is associated with decathlon athletes’ performance in the different modalities of decathlon. Methods: Thirty-one male athletes from the Brazilian national federation of decathlon aged between 18 and 50 years were genotyped for the ACTN3 R577X polymorphism using real-time polymerase chain reaction (RT-PCR). The athletes’ latest decathlon performances were recorded over ten competitions. The Hardy–Weinberg equilibrium was verified. Pearson’s correlation coefficient was utilized to assess the relationship between the obtained sports performance (score) by event and sets of events (speed events, jumps, and throws) with significance considered at p < 0.05. Results: Strong and significant correlations were identified between the speed events, the jumping, and the launching performances. Among the athletes, the distribution of ACTN3 genotypes was as follows: R577R—51.6%, R577X—48.4%, and X577X—0%, indicating a complete absence of homozygosity for the non-functional X allele in this cohort. No significant differences in sports performance (score) could be observed based on the genotype. Conclusions: Our results may support the importance of the ACTN3 genotype, specifically, the presence of the 577R allele, as one of the contributive factors for athletes’ performance in modalities that involve muscle strength, power, and speed. However, given the small sample size and the retrospective nature of this study, further research is warranted. Full article

The prognosis for Hormonal Receptor positive-HER2-negative (HR+ HER2-negative) metastatic breast cancer (mBC) has significantly improved by advances in hormone therapies, targeted drugs, and antibody–drug conjugates (ADCs). Nevertheless, maintaining quality of life (QoL), managing symptoms, and reducing treatment-related toxicity remain essential. Background: eHealth solutions offer new opportunities to enhance patient engagement and well-being through digital tools. This paper aims to delineate the fundamental functionalities and objectives of TreC_Metha, a technologically advanced instrument to provide effective support during all care process of patients diagnosed with HR+HER2-negative mBC able to proactively change its configuration depending on the treatment line or on the intra-line treatment phase the patient undergoes, as set by the healthcare team. Methods: The TreC_Metha platform was developed through a structured, evidence-based four-phase process aimed at scalability, usability, and clinical relevance. The development began with a formal analysis of the metastatic breast cancer (mBC) care pathway using BPMN modeling to map phases, activities, and stakeholders, highlighting differences from early-stage breast cancer. This analysis informed the identification of key points where digital support could enhance care. Patient needs were assessed through a web-based questionnaire (N = 20) and two focus groups (N = 11), enabling a participatory design approach. Based on these insights, the platform’s functional and non-functional requirements were defined, leading to the design and implementation of a patient-facing mobile app and a clinical dashboard tailored to mBC-specific needs. Results: Preliminary findings from the web survey focus groups revealed significant gaps in communication and information delivery during the mBC care journey, contributing to patient anxiety and reduced confidence. Participants expressed a preference for digital and printed resources to improve understanding and facilitate interactions with healthcare providers. These insights informed the development of the TreC_Metha platform. The clinical dashboard enables real-time monitoring and decision-making, while the mobile app supports bidirectional communication, therapy adherence, and patient-reported data collection. A system prototype is currently under refinement and will undergo usability testing with a small cohort of users. Following this phase, the pilot study will evaluate the platform’s impact on QoL, aiming for a ≥10% improvement in outcome measures and contributing to a more patient-centered care model in the mBC setting. Conclusions: TreC_Metha represents an innovative tool that may enable involvement and active participation in the mBC care process for both a multidisciplinary care team of professionals and the patient, and that can be easily adapted to other cancer types and chronic diseases. Full article

Introduction: There is no consensus on managing non-functioning pancreatic neuroendocrine tumors smaller than 2 cm (NF-PANNETs < 2 cm). Therefore, their treatment remains controversial. The aim of this study, by literature review and meta-analysis, is to establish the best management of NF-PANNETs < 2 cm based on overall survival (OS) and cancer-specific survival (CSS). Materials and Methods: An extensive online search was conducted using the MEDLINE, EMBASE, Google Scholar, Scopus, Web of Science, and Cochrane Central databases. All retrospective and prospective studies were included in this study, comparing the outcomes of surgical management vs. conservative management in patients with NF-PANNETs < 2 cm. The pooled odds ratio and 95% CI for survival were calculated. Results: Six studies were included in the quantitative analysis, with 2708 patients managed operatively and 985 managed conservatively. A pooled analysis of all the data demonstrated increased OS in patients managed operatively compared with those managed conservatively at five years (OR = 1.77, 95% CI: 0.96 to 2.58; p = 0.002). In contrast, the meta-analysis did not demonstrate increased CSS in patients undergoing surgical resection compared with conservative management (OR = 1.01, 95% CI: −5.25 to 7.27; p = 0.56). Furthermore, analysis demonstrated a high heterogeneity for OS (Q = 43.98, p < 0.001, tau² = 0.46, I² = 88.63%) and for CSS (Q = 22.81, p < 0.0001, tau² = 1.72, I² = 91.23%). Conclusion: This systematic review and meta-analysis indicated that surgical management of NF-PANNETs < 2 cm improves overall survival (OS) but does not significantly enhance cancer-specific survival (CSS). There is variability in outcomes among studies, and while surgery may help some patients, the lack of clear CSS benefits and associated risks call for individualized decision-making. Therefore, a conservative approach with active surveillance may be more suitable for low-risk patients. Full article

Pancreatic neuroendocrine neoplasms (pNENs) represent approximately 2% of all solid pancreatic tumors. The incidence of pNENs has been increasing in the last decade. The clinical manifestations of pNENs range from hormone secretion syndromes in functioning neoplasms (F-pNENs) to local infiltration or distant metastases in late-stage diagnoses or incidental findings in small non-functioning neoplasms (NF-pNENs). While surgery is the gold-standard treatment for larger and more aggressive tumors, small and low-grade tumors (G1) may be followed-up due to the indolent course of disease. Recently, endoscopic ultrasound (EUS)-guided ablative techniques, such as ethanol injection (EUS-EI) and radiofrequency ablation (EUS-RFA), have emerged as promising options for loco-regional ablations in selected cases. Despite promising safety profile and efficacy, high-quality evidence is needed to support their widespread adoption. This article reviews the current state of EUS-guided locoregional therapies, patient selection criteria, procedural details, and associated risks. Full article

Background/Objectives: Neuroendocrine tumors (NETs) are heterogeneous malignancies arising from enterochromaffin cells that can arise from the gastrointestinal (GI) tract and pancreas. Surgical management is the cornerstone of treatment, with the optimal approach tailored by tumor grade, size, location, and presence of metastasis. This review discusses the current strategies for the surgical management of NETs of the gastroenteropancreatic tract. Methods: A review of the available literature was conducted to evaluate surgical approaches to NETs. Consensus guidelines were incorporated to synthesize evidence-based recommendations. Results: For gastric NETs, surgical approach depends on Rindi Classification, WHO grade, and tumor size, with endoscopic approaches favored for smaller and low-grade lesions. Small bowel NETs can be multifocal and thus often require a surgical approach with careful evaluation of the entire intestine. Pancreatic NETs are categorized as functional or non-functional, with enucleation or formal resection strategies based on size, location, functional status, and risk of malignancy. Colorectal NETs are primarily treated with transanal localized or formal surgical resection, depending on lesion size and depth of invasion or presence of lymph node involvement. Appendiceal NETs are either treated with appendectomy or right hemicolectomy, depending on the size, location, and invasiveness of the lesions. For metastatic NETs, cytoreduction, liver transplantation, and targeted therapies offer symptom relief and possible survival benefits. Conclusions: Surgical resection provides curative potential for localized NETs and symptom control in metastatic cases. Future research is essential to refine guidelines for intermediate-risk lesions and multifocal tumors, ensuring optimal outcomes for patients with gastroenteropancreatic NETs. Full article

Anderson–Fabry (or Fabry) disease is a rare lysosomal storage disorder caused by a functional deficiency of the enzyme alpha-galactosidase A. The partial or total defect of this lysosomal enzyme, which is caused by variants in the GLA gene, leads to the accumulation of glycosphingolipids, mainly globotriaosylceramide in the lysosomes of different cell types. The clinical presentation of Fabry disease is multisystemic and can vary depending on the specific genetic variants associated with the disease. To date, more than 1000 different variants have been identified in the human GLA gene, including missense and nonsense variants, as well as small and large insertions or deletions. The identification of novel variants in individuals exhibiting symptoms indicative of Fabry disease, expands the molecular comprehension of the GLA gene, providing invaluable insights to physicians in the diagnosis of the disease. In this article, we present the case of two members of the same family, mother and son, in whom a new pathogenic variant was identified. This variant has not been previously described in the literature and is not present in databases. The two family members presented with a number of typical clinical manifestations of the disease, including cornea verticillata, neuropathic pain, left ventricular hypertrophy, angiokeratomas and abdominal pain. The son, but not his mother, showed reduced alpha-galactosidase A activity, while high levels of Lyso-Gb3 in the blood, a specific substrate accumulation biomarker, were found in both. Sequencing of the GLA gene revealed the presence of a variant, c.484delT, which is characterised by the deletion of a single nucleotide, a thymine, in exon 3 of the gene. This results in a frameshift variant, which introduces a premature stop codon, thereby generating a truncated and consequently non-functional protein. Therefore, the clinical and laboratory data indicate that the novel p.W162Gfs*3 variant described herein is associated with the classical form of Fabry disease. Full article

Background: Neuroendocrine neoplasms are a rare and heterogeneous group of neoplasms. Small-sized (≤2 cm) pancreatic neuroendocrine tumors (PanNETs) are of particular interest as they are often associated with aggressive behavior, with no specific prognostic or progression markers. Methods: This article describes a clinical case characterized by a progressive growth of nonfunctional PanNET requiring surgical treatment in a patient with a germline FANCD2 mutation, previously not reported in PanNETs. The patient underwent whole exome sequencing and single-cell RNA sequencing. Results: The patient underwent surgical treatment. We confirmed the presence of the germline mutation FANCD2 and also detected the germline mutation WNT10A. The cellular composition of the PanNET was analyzed using single-cell sequencing, and the main cell clusters were identified. We analyzed the tumor genomics, and used the data to define the effect the germline FANCD2 mutation had. Conclusions: Analysis of the mutational status of patients with PanNET may provide additional data that may influence treatment tactics, refine the plan for monitoring such patients, and provide more information about the pathogenesis of PanNET. PanNET research using scRNA-seq data may help in predicting the effect of therapy on neuroendocrine cells with FANCD2 mutations. Full article

Gefitinib is a selective inhibitor of the epidermal growth factor receptor that is used to treat advanced and metastatic non-small cell lung cancer (NSCLC). Dermatological adverse reactions are most commonly associated with gefitinib treatment. The cause of adverse reactions in individuals is multifactorial. Pharmacogenetics is an effective tool to detect such adverse reactions. This case report describes a female patient with NSCLC who was administered gefitinib at a dose of 250 mg/day. However, due to severe adverse dermatological reactions, the treatment was interrupted for 15 d and antibiotic therapy was administered to manage the skin rashes, maculopapular rashes, and hyperpigmentation. Treatment adherence was adequate, and no drug interactions were detected. A pharmacogenetic analysis revealed homozygosity in the ATP-binding cassette (ABC)-B1 rs1128503 (c.1236A>G), heterozygosity in ABCG2 rs2231142 (c.421G>T) and rs2622604 (c.-20+614T>C), and a non-functional variant of the cytochrome P450 family 3, subfamily A, member 5 (CYP3A5). The relationship between altered genetic variants and the presence of adverse reactions induced by gefitinib is still controversial. Overall, this case report highlights the importance of continuing to study pharmacogenetics as predictors of adverse drug reactions. Full article

Model-driven architecture (MDA) has demonstrated significant potential in automating code generation processes, yet its application often falls short in addressing the complexities of modern architectural styles, notably microservices. Microservice architecture, characterized by its decomposition of applications into small, independently deployable services, presents unique challenges and opportunities that traditional MDA approaches struggle to accommodate. In this paper, Zynerator, a novel framework that bridges the gap between model-driven architecture and microservice development, is presented. By integrating semantic decorators into the PIM, Zynerator empowers end-users to express intricate functional and non-functional requirements, laying the foundation for the generation of contextually appropriate code. Moreover, Zynerator goes beyond traditional MDA capabilities by offering a solution for microservice architecture integration, enabling the generation of service gateways, service discovery mechanisms, and other essential components inherent to microservice ecosystems. This integration not only streamlines the development process but also ensures the scalability, resilience, and maintainability of microservice-based applications. Through Zynerator, a flexible and comprehensive solution is presented that leverages the strengths of model-driven architecture (MDA), while addressing the evolving needs of modern software architecture, particularly in the realm of microservice development. Empirical results showed that Zynerator enhances code generation alignment to functional requirements by 55%, reduces microservice adoption in terms of communication and deployment times by 30%, and increases system scalability by supporting up to 10,000 concurrent users, without performance degradation. Full article

Organophosphoate (OP) chemicals are known to inhibit the enzyme acetylcholinesterase (AChE). Studying OP poisoning is difficult because common small animal research models have serum carboxylesterase, which contributes to animals’ resistance to OP poisoning. Historically, guinea pigs have been used for this research; however, a novel genetically modified mouse strain (KIKO) was developed with nonfunctional serum carboxylase (Es1 KO) and an altered acetylcholinesterase (AChE) gene, which expresses the amino acid sequence of the human form of the same protein (AChE KI). KIKO mice were injected with 1xLD₅₀ of an OP nerve agent or vehicle control with or without atropine. After one to three minutes, animals were injected with 35 mg/kg of the currently fielded Reactivator countermeasure for OP poisoning. Postmortem brains were imaged on a Bruker RapifleX ToF/ToF instrument. Data confirmed the presence of increased acetylcholine in OP-exposed animals, regardless of treatment or atropine status. More interestingly, we detected a small amount of Reactivator within the brain of both exposed and unexposed animals; it is currently debated if reactivators can cross the blood–brain barrier. Further, we were able to simultaneously image acetylcholine, the primary affected neurotransmitter, as well as determine the location of both Reactivator and acetylcholine in the brain. This study, which utilized sensitive MALDI-MSI methods, characterized KIKO mice as a functional model for OP countermeasure development. Full article

The incidence of pancreatic neuroendocrine tumors (PNETs) is on the rise primarily due to the increasing use of cross-sectional imaging. Most of these incidentally detected lesions are non-functional PNETs with a small proportion of lesions being hormone-secreting, functional neoplasms. With recent advances in surgical approaches and systemic therapies, the management of PNETs have undergone a paradigm shift towards a more individualized approach. In this manuscript, we review the histologic classification and diagnostic approaches to both functional and non-functional PNETs. Additionally, we detail multidisciplinary approaches and surgical considerations tailored to the tumor’s biology, location, and functionality based on recent evidence. We also discuss the complexities of metastatic disease, exploring liver-directed therapies and the evolving landscape of minimally invasive surgical techniques. Full article