Translation process of the tested Rome IV diagnostic questionnaire for functional gastrointestinal disorders into Saudi-Arabian Arabic: A mixed-methods approach.

Objective: A report on the cross-cultural adaptation and validation process of the Rome IV Diagnostic Questionnaire for children aged four years and over into Saudi-Arabian Arabic for use in assessing the prevalence of functional gastrointestinal disorders in children in Saudi Arabia. Method: A mixed-methods approach was used in translating the 60-item original English version of the questionnaire. The process included four steps followed by a cognitive debriefing and was guided by the Rome Foundation. The questionnaire was tested for practicability with 10 participants of children aged four years and older. The whole study took place between October 2020 and April 2021. Results: The original questionnaire repeated information on areas of pain experienced by children, which did not show up in the backward, English, translation. The back-translated version occasionally provided medical expressions that were then explained between parentheses in plain English, for example, dyspepsia (burning feeling). The expert panel indicated that all questionnaire items reached the set 90% agreement level, confirming that the questionnaire is fully understandable and valid for use. Preliminary testing with 10 participants (four years and older) revealed functional constipation to have the highest prevalence among the participants (40%, n=4), followed by irritable bowel syndrome (20%) and abdominal migraine (20%). Conclusion: This study provides a detailed report on the translation process of the tested ROME- IV Diagnostic Questionnaire for children aged four years and over into Saudi Arabic following Rome Foundation guidelines. The results of the preliminary test should encourage researchers and clinicians in Saudi Arabia to utilize the tool for non-invasive diagnosis of functional gastrointestinal disorders in children.

HYDIN variants cause primary ciliary dyskinesia in the Finnish population.

INTRODUCTION: Primary ciliary dyskinesia (PCD) is a rare genetic disorder characterized by chronic respiratory tract infections and in some cases laterality defects and infertility. The symptoms of PCD are caused by malfunction of motile cilia, hair-like organelles protruding out of the cell. Thus far, disease causing variants in over 50 genes have been identified and these variants explain around 70% of all known cases. Population specific genetics underlying PCD has been reported highlighting the importance of characterizing gene variants in different populations for development of gene-based diagnostics and management. METHODS: Whole exome sequencing was used to identify disease causing variants in Finnish PCD cohort. The effect of the identified HYDIN variants on cilia structure and function was confirmed by high-speed video analysis, immunofluorescence and electron tomography. RESULTS: In this study, we identified three Finnish PCD patients carrying homozygous loss-of-function variants and one patient with compound heterozygous variants within HYDIN. The functional studies showed defects in the axonemal central pair complex. All patients had clinical PCD symptoms including chronic wet cough and recurrent airway infections, associated with mostly static airway cilia. CONCLUSION: Our results are consistent with the previously identified important role of HYDIN in the axonemal central pair complex and improve specific diagnostics of PCD in different national populations.

Empagliflozin-activated AMPK elicits neuroprotective properties in reserpine-induced depression via regulating dynamics of hippocampal autophagy/inflammation and PKCζ-mediated neurogenesis.

RATIONALE: Major depression has been an area of extensive research during the last decades, for it represents a leading cause of disability and suicide. The stark rise of depression rates influenced by life stressors, economic threats, pandemic era, and resistance to classical treatments, has made the disorder rather challenging. Adult hippocampal neurogenesis and plasticity are particularly sensitive to the dynamic interplay between autophagy and inflammation. In fact, the intricate balance between the two processes contributes to neuronal homeostasis and survival. OBJECTIVES: Having demonstrated promising potentials in AMPK activation, a major metabolic sensor and autophagy regulator, empagliflozin (Empa) was investigated for possible antidepressant properties in the reserpine rat model of depression. RESULTS: While the reserpine protocol elicited behavioral, biochemical, and histopathological changes relevant to depression, Empa outstandingly hindered these pathological perturbations. Importantly, hippocampal autophagic response markedly declined with reserpine which disrupted the AMPK/mTOR/Beclin1/LC3B machinery and, conversely, neuro-inflammation prevailed under the influence of the NLRP3 inflammasome together with oxidative/nitrative stress. Consequently, AMPK-mediated neurotrophins secretion obviously deteriorated through PKCζ/NF-κB/BDNF/CREB signal restriction. Empa restored hippocampal monoamines and autophagy/inflammation balance, driven by AMPK activation. By promoting the atypical PKCζ phosphorylation (Thr403) which subsequently phosphorylates NF-κB at Ser311, AMPK successfully reinforced BDNF/CREB signal and hippocampal neuroplasticity. The latter finding was supported by hippocampal CA3 toluidine blue staining to reveal intact neurons. CONCLUSION: The current study highlights an interesting role for Empa as a regulator of autophagic and inflammatory responses in the pathology of depression. The study also pinpoints an unusual contribution for NF-κB in neurotrophins secretion via AMPK/PKCζ/NF-κB/BDNF/CREB signal transduction. Accordingly, Empa can have special benefits in diabetic patients with depressive symptoms. LIMITATIONS: The influence of p-NF-κB (Ser311) on NLRP3 inflammasome assembly and activation has not been investigated, which can represent an interesting point for further research.

Unraveling the ncRNA landscape that governs colorectal cancer: A roadmap to personalized therapeutics.

Colorectal cancer (CRC) being one of the most common malignancies, has a significant death rate, especially when detected at an advanced stage. In most cases, the fundamental aetiology of CRC remains unclear despite the identification of several environmental and intrinsic risk factors. Numerous investigations, particularly in the last ten years, have indicated the involvement of epigenetic variables in this type of cancer. The development, progression, and metastasis of CRC are influenced by long non-coding RNAs (lncRNAs), which are significant players in the epigenetic pathways. LncRNAs are implicated in diverse pathological processes in CRC, such as liver metastasis, epithelial to mesenchymal transition (EMT), inflammation, and chemo-/radioresistance. It has recently been determined that CRC cells and tissues exhibit dysregulation of tens of oncogenic and tumor suppressor lncRNAs. Serum samples from CRC patients exhibit dysregulated expressions of several of these transcripts, offering a non-invasive method of detecting this kind of cancer. In this review, we outlined the typical paradigms of the deregulated lncRNA which exert significant role in the underlying molecular mechanisms of CRC initiation and progression. We comprehensively discuss the role of lncRNAs as innovative targets for CRC prognosis and treatment.

Exploring the Prevalence of Functional Gastrointestinal Diseases and the Accompanied Differences in Dietary and Lifestyle Patterns: A Two-Generational Study.

BACKGROUND AND OBJECTIVES: Generation Z and millennials in Saudi Arabia both experienced the stress of the COVID-19 pandemic and the accompanying factors that may have had an impact on the incidence of functional gastrointestinal diseases (FGIDs) in both generations. This study aims to explore how prevalent FGIDs are among adolescents and their parents. METHODS AND STUDY DESIGN: A cross-sectional, school-based study conducted in public high schools for boys and girls in Jeddah, Saudi Arabia. We adapted 37 items from the ROME IV Diagnostic Questionnaires for children and adults, as well as other questionnaires. IBM SPSS Statistics (Version 28.0) was used. RESULTS: Generation Z showed a higher prevalence of FGIDs (33.5%, n = 126) in comparison with millennials (20.0%, n = 28). In both generations, the most prevalent FGID was functional constipation; the least prevalent were irritable bowel syndrome and abdominal migraine, with no significant change in the severity or frequency of symptoms during the pandemic. The type of commonly consumed beverages was a risk factor for FGIDs. Participants in generation Z were less likely to use complementary and alternative medicine (67.4%) to prevent diseases and enhance immunity compared with millennials (82.9%). CONCLUSIONS: The study results confirmed disparities in the prevalence of FGIDs between the two generations before and during the COVID-19 pandemic, which requires further research in other areas of Saudi Arabia. Recognizing the differences between the millennial parents and the generation Z high schoolers could assist health professionals in planning individualized, generation-based interventions and educators in designing and tailoring programs based on generational differences.

Unraveling the influence of LncRNA in gastric cancer pathogenesis: a comprehensive review focus on signaling pathways interplay.

Gastric cancers (GCs) are among the most common and fatal malignancies in the world. Despite our increasing understanding of the molecular mechanisms underlying GC, further biomarkers are still needed for more in-depth examination, focused prognosis, and treatment. GC is one among the long non-coding RNAs, or lncRNAs, that have emerged as key regulators of the pathophysiology of cancer. This comprehensive review focuses on the diverse functions of long noncoding RNAs (lncRNAs) in the development of GC and their interactions with important intracellular signaling pathways. LncRNAs affect GC-related carcinogenic signaling cascades including pathways for EGFR, PI3K/AKT/mTOR, p53, Wnt/ß-catenin, JAK/STAT, Hedgehog, NF-κB, and hypoxia-inducible factor. Dysregulated long non-coding RNA (lncRNA) expression has been associated with multiple characteristics of cancer, such as extended growth, apoptosis resistance, enhanced invasion and metastasis, angiogenesis, and therapy resistance. For instance, lncRNAs such as HOTAIR, MALAT1, and H19 promote the development of GC via altering these pathways. Beyond their main roles, GC lncRNAs exhibit potential as diagnostic and prognostic biomarkers. The overview discusses CRISPR/Cas9 genome-modifying methods, antisense oligonucleotides, small molecules, and RNA interference as potential therapeutic approaches to regulate the expression of long noncoding RNAs (lncRNAs). An in-depth discussion of the intricate functions that lncRNAs play in the development of the majority of stomach malignancies is provided in this review. It provides the groundwork for future translational research in lncRNA-based whole processes toward GC by highlighting their carcinogenic effects, regulatory roles in significant signaling cascades, and practical scientific uses as biomarkers and therapeutic targets.

Exploring the role of circ-0091579/miR-1225-5p and circ-HIPK3/miR-338-3p axes in the pathogenesis of postmenopausal osteoporosis.

CircRNAs have been increasingly appreciated as modulators of osteoporosis. This study investigated the expression of circ-0091579 and circ-HIPK3 in PBMCs of postmenopausal women with osteopenia and osteoporosis, aiming to underline their molecular mechanisms involved in pathogenesis of the disease. Seventy patients were stratified into two groups: 35 with osteopenia and 35 with osteoporosis, along with 30 healthy controls. Expressions of circ-0091579 and circ-HIPK3, miR-1225-5p and miR-338-3p, together with NF-κB, were assessed using RT-PCR. Keap1, Nrf2, and MAFB were determined using Western blot, while RANKL, OPG, IL-1ß, and IL-6 were measured by ELISA. GSH and MDA were estimated colorimetrically. Data revealed that circ-0091579 was markedly upregulated, whereas miR-1225-5p was downregulated in patients relative to controls. Additionally, circ-HIPK3 was significantly decreased, while miR-338-3p was increased in the diseased groups. Circ-0091579 was directly correlated with RANKL/OPG, NF-κB, IL-1ß, IL-6 and MDA, while inversely correlated with miR-1225-5p, T-score, BMD and GSH. Meanwhile, circ-HIPK3 and miR-338-3p were interrelated in an opposite manner. Eventually, the interplay among these downstream players induced an imbalance in bone homeostasis, triggering osteoporosis. Notably, these circRNAs differentiated patients from controls and those with osteopenia from osteoporotic ones. Thus, they could serve as biomarkers for early detection and tracking of osteoporosis.

Transcecal endoscopic appendectomy for management of complex appendiceal polyps extending into the appendiceal orifice.

Background and study aims Endoscopic resection of appendiceal orifice (AO) polyps extending inside the appendiceal lumen is challenging given the inability to determine polyp lateral margins and risk of appendicitis. Transcecal endoscopic appendectomy (TEA) ensures en bloc resection of these complex polyps. Patients and methods This case series includes patients who underwent TEA by a single endoscopist in the United States. Technical success was defined as achieving complete removal of the appendix along with AO polyp in an en bloc fashion. Results In total, nine patients were included (mean age 69.7 ± 9.6 years). The average appendix size was 4.07 ± 2.02 cm. Technical success was achieved in 100% of the patients. The average procedure length was 118.1 ± 44.21 minutes. The en bloc resection rate, R0 resection rate, and curative resection rates were 100%. Patients were observed for an average of 3.1 ± 1.6 days. One patient developed loculated fluid collection 9 days post procedure, which resolved on its own with oral antibiotic therapy. No other adverse events were recorded. Conclusions This was an early study of the feasibility of TEA in the United States. This novel technique, in early-stage development, is potentially safe and associated with a minimal risk profile in expert hands. Further prospective studies are needed to standardize the technique.

Cross-relationship between COVID-19 infection and anti-obesity products efficacy and incidence of side effects: A cross-sectional study.

BACKGROUND: Obesity and COVID-19 are at the top of nowadays health concerns with significant crosstalk between each other. The COVID-19 pandemic negatively affected healthy lifestyles and increased obesity prevalence. Thus, there was a surge in anti-obesity products (AOPs) intake. Herein, we evaluated how the pandemic has affected slimming products' efficacy and safety in patients seeking weight reduction at an urban, weight management centre in Alexandria, Egypt. In addition, the effect of AOPs on COVID-19 infection severity was also appraised to detect whether AOPs can alter COVID-19 host cell entry and infective mechanisms, and thus, affect infection severity. METHODS: Patients were invited to complete an anonymous survey. The survey assessed self-reported changes in weight, the use of AOPs during the COVID-19 pandemic, COVID-19 infection severity, AOPs efficacy, and incidence of side effects. Inclusion criteria were obese patients above 18 years old who got infected by COVID-19 while receiving a single-ingredient AOP. RESULTS: A total of 462 participants completed our anonymous validated questionnaire. Most of the participants were females (450; 98.4%) with BMI ranging from 24.98-58.46. Eligible participants were only 234 and the top-administered products were orlistat, liraglutide, metformin, green tea, cinnamon, Garcinia cambogia, and Gymnema Sylvestre. In most cases, AOPs intake was beneficial for COVID-19 infection, and most patients experienced mild-to-moderate COVID-19 symptoms. On the other hand, SARS-CoV-2 significantly interferes with AOPs' mechanisms of action which positively or negatively influences their efficacy and side effects incidence due to predictable pharmacological link. CONCLUSION: Concurrent AOPs intake with COVID-19 infection is a two-sided weapon; AOPs attenuate COVID-19 infection, while SARS-CoV-2 interferes with efficacy and side effects incidence of AOPs.

Innovative molecular and immunological approaches of heterophyiasis infecting some Egyptian marketed fishes.

Heterophyiasis is a highly endemic disease in the Nile Delta, Egypt, where people consume raw or undercooked Oreochromis niloticus and Mugil cephalus. Birds and rats play a crucial role in fish-borne zoonotic trematode transmission since they serve as natural and experimental hosts. This study aimed to update the epidemiological information, morphological description, molecular identification and gene expression of two distinct heterophyid metacercariae in Giza, Wadi Al-Rayan, and Lake Manzala, Egypt, whereas various heterophyid infections could be expected. The present Centrocestus formosanus, Heterophyes heterophyes, and Heterophyes nocens with accession numbers OR947651.1, OR947700.1, and OR947719.1, respectively, matched with those recorded in the GenBank. Findings of the current investigation indicated that various cytokines like IL-1ß, MHC-II, and TNF-α rapidly elevated in the infected pigeon's intestines. Additionally, the infection expanded due to the parasite's ejection from the host and the host's clinical affliction, which induced humoral immune responses. Interestingly, investigation of other trematode species is in extreme demand in terms of zoonoses. We suggest controlling snails, managing migratory birds, and examining and frying fishes to the point when the encysted metacercariae is destroyed.

Purification and characterization of the produced hyaluronidase by Brucella Intermedia MEFS for antioxidant and anticancer applications.

Hyaluronidase (hyase) is an endoglycosidase enzyme that degrades hyaluronic acid (HA) and is mostly known to be found in the extracellular matrix of connective tissues. In the current study, eleven bacteria isolates and one actinomycete were isolated from a roaster comb and screened for hyase production. Seven isolates were positive for hyase, and the most potent isolate was selected based on the diameter of the transparent zone. Based on the morphological, physiological, and 16 S rRNA characteristics, the most potent isolate was identified as Brucella intermedia MEFS with accession number OR794010. The environmental conditions supporting the maximum production of hyase were optimized to be incubation at 30 ºC for 48 h and pH 7, which caused a 1.17-fold increase in hyase production with an activity of 84 U/mL. Hyase was purified using a standard protocol, including precipitation with ammonium sulphate, DEAE as ion exchange chromatography, and size exclusion chromatography using Sephacryle S100, with a specific activity of 9.3-fold compared with the crude enzyme. The results revealed that the molecular weight of hyase was 65 KDa, and the optimum conditions for hyase activity were at pH 7.0 and 37 °C for 30 min. The purified hyase showed potent anticancer activities against colon, lung, skin, and breast cancer cell lines with low toxicity against normal somatic cells. The cell viability of hyase-treated cancer cells was found to be in a dose dependent manner. Hyase also controlled the growth factor-induced cell cycle progression of breast cancer cells and caused relative changes in angiogenesis-related genes as well as suppressed many pro-inflammatory proteins in MDA cells compared with 5-fluorouracil, indicating the significant role of hyase as an anticancer agent. In addition, hyase recorded the highest DPPH scavenging activity of 65.49% and total antioxidant activity of 71.84% at a concentration of 200 µg/mL.

Impact of adding zeolite to broilers' diet and litter on growth, blood parameters, immunity, and ammonia emission.

This work was designed to assess the impact of varying zeolite concentrations in diet and litter to enhance broiler's growth performance, immunity, and litter quality. A complete random arrangement was used for distributing 525 unsexed "Cobb 500" broiler chicks into seven treatments (75 chick / treatment), each treatment divided into 3 replicates (25 chicks / replicate). The 1st group (control one) received the recommended basal diet. Zeolite has been introduced to the basal diet (ZD) of the second, third, and fourth groups at concentrations of 5, 10, and 15 g/kg, respectively. The 5th, 6th and 7th groups used zeolite mixed with litter (ZL) at 0.5, 1, and 1.5 kg/m2 of litter, respectively. Due to the obtained results, adding zeolite with levels 15 g/kg of diet and 1.5 kg/1 m2 of litter, a significant improvement occurred in live body weight (LBW), body weight gain (BWG), feed intake (FI), feed conversion ratio (FCR) and European production efficiency factor (EPEF). Also, transaminase enzymes (ALT and AST), creatinine, white blood cells (WBCs) and different Immunoglobulins were significantly increased with different zeolite levels, except urea concentrations which showed reduced due to different zeolite treatments. In addition, spleen relative weight hasn't been affected by zeolite treatments, even though thymus and bursa relative weights had been affected significantly. Moreover, the antibodies' production to Newcastle disease virus (NDV) and Avian influenza virus (AIV) had increased significantly with adding zeolite with levels 10 g/kg of diet and 1.5 kg/1m2 of litter. Litter quality traits (NH3 concentration, pH values, and Moisture content) were improved with zeolite addition. So, zeolite could be employed in both feed and litter of broilers to maximize their production, immunity and improve farm's climate.

Molecular and immunological studies on Theileria equi and its vector in Egypt.

Equine piroplasmosis is not fully understood regarding pathogenicity, prophylaxis, host immune response expression, and specific vectors. Accurately identifying the parasite vector is crucial for developing an effective control plan for a particular infection. This study focused on morphologically identifying two Hyalomma species (H. anatolicum and H. marginatum) and one Rhipicephalus annulatus (R. annulatus) at the species level. The identification process was followed by phylogenetic analysis using the neighbor-joining method based on the cytochrome oxidase subunit 1 (COXI) gene as a specific vector for Theileria equi (T. equi) in horses. T. equi was diagnosed morphologically and molecularly from infected blood samples and crushed tick species using conventional PCR. Subsequently, phylogenetic analysis based on the amplification of the 18 S rRNA gene was conducted. The obtained sequence data were evaluated and registered in GenBank under accession numbers OR064161, OR067911, OR187727, and OR068139, representing the three tick species and the isolated T. equi, respectively. The study demonstrated that T. equi infection leads to immune system suppression by significantly increasing the levels of oxidative stress markers (CAT, GPx, MDA, and SOD) (P ≤ 0.0001), with this elevation being directly proportional to parasitemia levels in infected blood cells. Furthermore, a correlation was observed between parasitemia levels and the expression of immune response infection genes (IFN-gamma, TGF-ß1, and IL-1ß cytokines) in infected horses compared to non-infected equine. Common macroscopic symptoms indicating T. equi infection in horses include intermittent fever, enlarged lymph nodes (LN), and tick infestation.

The impact of tetrodotoxin (TTX) on the gut microbiome in juvenile tiger pufferfish, Takifugu rubripes.

Tetrodotoxin (TTX) is a potent neurotoxin that accumulates in Takifugu rubripes, commonly known as pufferfish, through the ingestion of TTX-bearing organisms as part of their food chain. Although researchers believe that pufferfish use TTX to relieve stress, data are not currently available on how TTX affects the gut microbiota of pufferfish. To address this gap, our study aimed to investigate whether administering TTX to fish could alter their gut microbiota and overall health under various salinity conditions, including 30.0 ppt, 8.5 ppt, and 1.7 ppt salinity, which represent full-strength, isosmotic, and low-salinity stress, respectively. We analyzed the effect of TTX ingestion on the community structure, core microbiome, and metabolic capabilities of the gut microbiome using high-throughput sequencing technologies. The predominant bacterial taxa within the gut microbiome were Firmicutes (21-85%), Campilobacterota (2.8-67%), Spirochaetota (0.5-14%), and Proteobacteria (0.7-9.8%), with Mycoplasma, uncultured Arcobacteraceae, Brevinema, Vibrio, Rubritalea, and uncultured Pirellulaceae as core genera. Our findings indicated that the impact of TTX on high-abundance genera at 30.0 ppt and 8.5 ppt salinity levels was negligible, indicating their stability and resilience to TTX ingestion. However, at 1.7 ppt, TTX-fed fish showed a significant increase in uncultured Arcobacteraceae. Furthermore, our analysis of TTX-fed fish revealed taxonomic alterations in low-abundance taxa, which altered the predicted functions of the gut microbiota at all salinity levels. These results suggest that TTX administration could cause subtle effects on the metabolic functions of gut microbial communities. Overall, our study provides insights into the complex relationship between a TTX-accumulating animal, T. rubripes, and its gut microbiota.

Development of a 3D printed perfusable in vitro blood-brain barrier model for use as a scalable screening tool.

Despite recent technological advances in drug discovery, the success rate for neurotherapeutics remains alarmingly low compared to treatments for other areas of the body. One of the biggest challenges for delivering therapeutics to the central nervous system (CNS) is the presence of the blood-brain barrier (BBB). In vitro blood-brain barrier models with high predictability are essential to aid in designing parameters for new therapeutics, assess their ability to cross the BBB, and investigate therapeutic strategies that can be employed to enhance transport. Here, we demonstrate the development of a 3D printable hydrogel blood-brain barrier model that mimics the cellular composition and structure of the blood-brain barrier with human brain endothelial cells lining the surface, pericytes in direct contact with the endothelial cells on the abluminal side of the endothelium, and astrocytes in the surrounding printed bulk matrix. We introduce a simple, static printed hemi-cylinder model to determine design parameters such as media selection, co-culture ratios, and cell incorporation timing in a resource-conservative and high-throughput manner. Presence of cellular adhesion junction, VE-Cadherin, efflux transporters, P-glycoprotein (P-gp) and Breast cancer resistance protein (BCRP), and receptor-mediated transporters, Transferrin receptor (TfR) and low-density lipoprotein receptor-related protein 1 (LRP1) were confirmed via immunostaining demonstrating the ability of this model for screening in therapeutic strategies that rely on these transport systems. Design parameters determined in the hemi-cylinder model were translated to a more complex, perfusable vessel model to demonstrate its utility for determining barrier function and assessing permeability to model therapeutic compounds. This 3D-printed blood-brain barrier model represents one of the first uses of projection stereolithography to fabricate a perfusable blood-brain barrier model, enabling the patterning of complex vessel geometries and precise arrangement of cell populations. This model demonstrates potential as a new platform to investigate the delivery of neurotherapeutic compounds and drug delivery strategies through the blood-brain barrier, providing a useful in vitro screening tool in central nervous system drug discovery and development.

Natural products and long noncoding RNA signatures in gallbladder cancer: a review focuses on pathogenesis, diagnosis, and drug resistance.

Gallbladder cancer (GBC) is an aggressive and lethal malignancy with a poor prognosis. Long noncoding RNAs (lncRNAs) and natural products have emerged as key orchestrators of cancer pathogenesis through widespread dysregulation across GBC transcriptomes. Functional studies have revealed that lncRNAs interact with oncoproteins and tumor suppressors to control proliferation, invasion, metastasis, angiogenesis, stemness, and drug resistance. Curcumin, baicalein, oleanolic acid, shikonin, oxymatrine, arctigenin, liensinine, fangchinoline, and dioscin are a few examples of natural compounds that have demonstrated promising anticancer activities against GBC through the regulation of important signaling pathways. The lncRNAs, i.e., SNHG6, Linc00261, GALM, OIP5-AS1, FOXD2-AS1, MINCR, DGCR5, MEG3, GATA6-AS, TUG1, and DILC, are key players in regulating the aforementioned processes. For example, the lncRNAs FOXD2-AS1, DILC, and HOTAIR activate oncogenes such as DNMT1, Wnt/ß-catenin, BMI1, and c-Myc, whereas MEG3 and GATA6-AS suppress the tumor proteins NF-κB, EZH2, and miR-421. Clinically, specific lncRNAs can serve as diagnostic or prognostic biomarkers based on overexpression correlating with advanced TNM stage, metastasis, chemoresistance, and poor survival. Therapeutically, targeting aberrant lncRNAs with siRNA or antisense oligos disrupts their oncogenic signaling and inhibits GBC progression. Overall, dysfunctional lncRNA regulatory circuits offer multiple avenues for precision medicine approaches to improve early GBC detection and overcome this deadly cancer. They have the potential to serve as novel biomarkers as they are detectable in bodily fluids and tissues. These findings enhance gallbladder treatments, mitigating resistance to chemo- and radiotherapy.

Affordable and real-time antimicrobial resistance prediction from multimodal electronic health records.

The spread of antimicrobial resistance (AMR) leads to challenging complications and losses of human lives plus medical resources, with a high expectancy of deterioration in the future if the problem is not controlled. From a machine learning perspective, data-driven models could aid clinicians and microbiologists by anticipating the resistance beforehand. Our study serves as the first attempt to harness deep learning (DL) techniques and the multimodal data available in electronic health records (EHR) for predicting AMR. In this work, we utilize and preprocess the MIMIC-IV database extensively to produce separate structured input sources for time-invariant and time-series data customized to the AMR task. Then, a multimodality fusion approach merges the two modalities with clinical notes to determine resistance based on an antibiotic or a pathogen. To efficiently predict AMR, our approach builds the foundation for deploying multimodal DL techniques in clinical practice, leveraging the existing patient data.

Learning curve for endoscopic submucosal dissection (ESD) in the United States: Large, untutored, single-operator experience.

Background and study aims Endoscopic submucosal dissection (ESD) allows removal of tumors en-bloc. Western adoption of ESD has been hindered by its steep learning curve. Western data regarding ESD learning curve are limited. We analyzed the learning curve of a single endoscopist at a tertiary referral center in the United States. Patients and methods All consecutive ESDs performed by a single endoscopist at a tertiary referral center in the United States from 2015 through 2022 were identified. Descriptive statistics and CUSUM analysis were used to describe the learning curve for en-bloc, R0 resection, and resection speed. Results In our study, 503 patients with 515 lesions were included. Severe submucosal fibrosis was found in 17% of the lesions. The rates of en-bloc, R0, and curative resections were 81.9%, 71.1%, and 68.4%, respectively. CUSUM analysis showed that the learning curve plateaued at 268, 347, and 170 cases for en-bloc resection, R0 resection, and achieving a resection speed > 9 cm 2 /hr. Fibrosis significantly affected the R0 resection rate in the regression analysis (95% confidence interval 0.21-0.55). In colonic ESD curve analysis, the learning plateau was reached after 185 cases for both en-bloc and R0 resection. Conclusions Following ex-vivo training in an animal model, an untutored expert operator achieved competency in ESD between 250 and 350 procedures. Our data can inform development of future training programs in the West.