Surgical management for hepatocellular carcinoma with concurrent portal vein tumour thrombus and bile duct tumour thrombus: a case report.

Introduction: Hepatocellular carcinoma (HCC) associated with concurrent portal vein tumour thrombus (PVTT) and bile duct tumour thrombus (BDTT) is sporadic and presents a puzzle to management with miserable prognostic. Case presentation: The authors reported a case of HCC in the right liver with PVTT involving the right portal vein and BDTT developing in the common bile duct, detected in a 43-year-old man. The patient was admitted to our hospital with abdominal pain in the right hypochondrium and obstructive jaundice. Imaging studies showed a large mass in the right liver with invasion of the first branch of the portal vein and dilated intrahepatic bilateral bile ducts. A liver biopsy confirmed the diagnosis of hepatocellular carcinoma. Right hepatectomy plus thrombectomy en bloc with extrahepatic bile duct resection was performed. Subsequently, the patient received a postoperative adjuvant transarterial chemoembolization (PA-TACE) 1 month after surgery. Discussion: In the present case, the authors were not aiming for curative treatment by aggressive management but for palliative treatment. At the time of diagnosis, the tumour had already invaded the portal bifurcation. Hepatectomy plus thrombectomy en bloc with resection of common bile duct can remove biliary obstruction caused by BDTT, optimize portal flow by eliminating PVTT, and reduce the tumour burden, consequently improving the quality of life and liver function. Then, PA-TACE takes care of microfoci left behind by the surgery, which may prolong survival time. Conclusion: An aggressive therapeutic strategy should be considered in exceptional cases for resectable HCC with PVTT and obstructive BDTT. However, the follow-up period remains limited. A longer duration of observation is necessary to definitively assess the surgery's impact on patient's recurrence and survival time.

AI in Colorectal Cancer: From Patient Screening over Tailoring Treatment Decisions to Identification of Novel Biomarkers.

BACKGROUND: Artificial intelligence (AI) is increasingly entering and transforming not only medical research but also clinical practice. In the last ten years, new AI methods have enabled computers to perform visual tasks, reaching high performance, and thereby potentially supporting and even outperforming human experts. This is in particular relevant for colorectal cancer (CRC), which is the 3rd most common cancer type in general, as along the CRC patient journey many complex visual tasks need to be performed: from endoscopy over imaging to histopathology, the screening, diagnosis and treatment of CRC involve visual image analysis tasks. SUMMARY: In all these clinical areas, AI models have shown promising results by supporting physicians, improving accuracy, and providing new biological insights and biomarkers. By predicting prognostic and predictive biomarkers from routine images/slides, AI models could lead to an improved patient stratification for precision oncology approaches in the near future. Moreover, it is conceivable that AI models, in particular together with innovative techniques such as single-cell or spatial profiling, could help to identify novel clinically as well as biologically meaningful biomarkers that could pave the way to new therapeutic approaches. KEY MESSAGES: Here, we give a comprehensive overview of AI in colorectal cancer, describing and discussing these developments as well as the next steps which need to be taken to incorporate AI methods more broadly into the clinical care of CRC.

Technique for Harvest of Superficial Quadriceps Tendon Autograft.

The idea of using quadriceps tendon autograft (QT) anterior cruciate ligament reconstruction first came into being in the 1990s; it was, however, not widely recognized and has resurfaced only in recent times. Because sufficient technological supports have not been developed to enable an optimal artificial graft, autologous grafts are still the most dependable option. The major reason for choosing QT instead of hamstring or patellar tendon to get autologous grafts is that it seems to cause the fewest donor site problems. Two commonly applied ways of using the quadriceps are partial and full thickness; another option is superficial. Our technique for harvesting the superficial part of the QT, which starts proximal to the fused point of the 3 layers, is aimed at circumventing premature cutting of the graft.

Exploring the Progress of Hyaluronic Acid Hydrogels: Synthesis, Characteristics, and Wide-Ranging Applications.

This comprehensive review delves into the world of hyaluronic acid (HA) hydrogels, exploring their creation, characteristics, research methodologies, and uses. HA hydrogels stand out among natural polysaccharides due to their distinct features. Their exceptional biocompatibility makes them a top choice for diverse biomedical purposes, with a great ability to coexist harmoniously with living cells and tissues. Furthermore, their biodegradability permits their gradual breakdown by bodily enzymes, enabling the creation of temporary frameworks for tissue engineering endeavors. Additionally, since HA is a vital component of the extracellular matrix (ECM) in numerous tissues, HA hydrogels can replicate the ECM's structure and functions. This mimicry is pivotal in tissue engineering applications by providing an ideal setting for cellular growth and maturation. Various cross-linking techniques like chemical, physical, enzymatic, and hybrid methods impact the mechanical strength, swelling capacity, and degradation speed of the hydrogels. Assessment tools such as rheological analysis, electron microscopy, spectroscopy, swelling tests, and degradation studies are employed to examine their attributes. HA-based hydrogels feature prominently in tissue engineering, drug distribution, wound recovery, ophthalmology, and cartilage mending. Crafting HA hydrogels enables the production of biomaterials with sought-after qualities, offering avenues for advancements in the realm of biomedicine.

Redox-Responsive Gold Nanoparticles Coated with Hyaluronic Acid and Folic Acid for Application in Targeting Anticancer Therapy.

Methotrexate (MTX) has poor water solubility and low bioavailability, and cancer cells can become resistant to it, which limits its safe delivery to tumor sites and reduces its clinical efficacy. Herein, we developed novel redox-responsive hybrid nanoparticles (NPs) from hyaluronic acid (HA) and 3-mercaptopropionic acid (MPA)-coated gold NPs (gold@MPA NPs), which were further conjugated with folic acid (FA). The design of FA-HA-ss-gold NPs aimed at enhancing cellular uptake specifically in cancer cells using an active FA/HA dual targeting strategy for enhanced tumor eradication. MTX was successfully encapsulated into FA-HA-ss-gold NPs, with drug encapsulation efficiency (EE) as high as >98.7%. The physicochemical properties of the NPs were investigated in terms of size, surface charges, wavelength reflectance, and chemical bonds. MTX was released in a sustained manner in glutathione (GSH). The cellular uptake experiments showed effective uptake of FA-HA-ss-gold over HA-ss-gold NPs in the deep tumor. Moreover, the release studies provided strong evidence that FA-HA-ss-gold NPs serve as GSH-responsive carriers. In vitro, anti-tumor activity tests showed that FA-HA-ss-gold/MTX NPs exhibited significantly higher cytotoxic activity against both human cervical cancer (HeLa) cells and breast cancer (BT-20) cells compared to gold only and HA-ss-gold/MTX NPs while being safe for human embryonic kidney (HEK-293) cells. Therefore, this present study suggests that FA-HA-ss-gold NPs are promising active targeting hybrid nanocarriers that are stable, controllable, biocompatible, biodegradable, and with enhanced cancer cell targetability for the safe delivery of hydrophobic anticancer drugs.

WITHDRAWN: TRIM44 promotes autophagy through SQSTM1 oligomerization in the response to oxidative stress induced by Arsenic Trioxide in cancer cells.

The authors have requested that this preprint be removed from Research Square.

Pisachini planthoppers of Vietnam: new records of Pisacha and a new Goniopsarites species from Central Vietnam (Hemiptera, Fulgoromorpha, Nogodinidae).

Two planthopper species of the family Nogodinidae are added to the fauna of Vietnam, both from two localities in Thua Thien-Hue Province: Bach Ma National Park and Phong Dien District. The first species belongs to Goniopsarites Meng, Wang & Wang, 2014, G.mientrunganus Constant & Pham, sp. nov., and the second belongs to Pisacha Distant, 1906, P.yinggensis Meng, Wang & Wang, 2014. Pisachayinggensis was previously recorded from Hainan Island, China. These new records greatly extend the distribution of both genera, which were known from southern China, Hainan and North Vietnam, to the south, reaching the mid area of Central Vietnam. Sexual dimorphism is reported in P.yinggensis for the first time. Illustrations of habitus and male terminalia of the new species are given as well as distribution maps and photographs of live specimens and their habitat. The family Nogodinidae now comprises nine species in Vietnam, with three of them present in Bach Ma National Park.

Injectable and Multifunctional Hydrogels Based on Poly(N-acryloyl glycinamide) and Alginate Derivatives for Antitumor Drug Delivery.

Chemotherapy is a conventional treatment that uses drugs to kill cancer cells; however, it may induce side effects and may be incompletely effective, leading to the risk of tumor recurrence. To address this issue, we developed novel injectable thermal/near-infrared (NIR)-responsive hydrogels to control drug release. The injectable hydrogel formulation was composed of biocompatible alginates, poly(N-acryloyl glycinamide) (PNAGA) copolymers with an upper critical solution temperature, and NIR-responsive cross-linkers containing coumarin groups, which were gelated through bioorthogonal inverse electron demand Diels-Alder reactions. The hydrogels exhibited quick gelation times (120-800 s) and high drug loading efficiencies (>90%). The hydrogels demonstrated a higher percentage of drug release at 37 °C than that at 25 °C due to the enhanced swelling behavior of temperature-responsive PNAGA moieties. Upon NIR irradiation, the hydrogels released most of the entrapped doxorubicin (DOX) (97%) owing to the cleavage of NIR-sensitive coumarin ester groups. The hydrogels displayed biocompatibility with normal cells, while induced antitumor activity toward cancer cells. DOX/hydrogels treated with NIR light inhibited tumor growth in nude mice bearing tumors. In addition, the injected hydrogels emitted red fluorescence upon excitation at a green wavelength, so that the drug delivery and hydrogel degradation in vivo could be tracked in the xenograft model.

CircNetVis: an interactive web application for visualizing interaction networks of circular RNAs.

Analyzing the interactions of circular RNAs (circRNAs) is a crucial step in understanding their functional impacts. While there are numerous visualization tools available for investigating circRNA interaction networks, these tools are typically limited to known circRNAs from specific databases. Moreover, these existing tools usually require complex installation procedures which can be time-consuming and challenging for users. There is a lack of a user-friendly web application that facilitates interactive exploration and visualization of circRNA interaction networks. CircNetVis is an interactive online web application to enhance the analysis of human/mouse circRNA interactions. The tool allows three different input formats of circRNAs including circRNA IDs from CircBase, circRNA coordinates (chromosome, start position, end position), and circRNA sequences in the FASTA format. It integrates multiple interaction networks for visualization and investigation of the interplay between circRNA, microRNAs, mRNAs and RNA binding proteins. CircNetVis also enables users to interactively explore the interactions of unknown circRNAs which are not reported from previous databases. The tool can generate interactive plots and allows users to save results as output files for offline usage. CircNetVis is implemented as a web application using R-shiny and freely available for academic use at https://www.meb.ki.se/shiny/truvu/CircNetVis/ .

NIR-responsive carboxymethyl-cellulose hydrogels containing thioketal-linkages for on-demand drug delivery system.

Near-infrared (NIR) light-responsive hydrogels have emerged as a highly promising strategy for effective anticancer therapy owing to the remotely controlled release of chemotherapeutic molecules with minimal invasive manner. In this study, novel NIR-responsive hydrogels were developed from reactive oxygen species (ROS)-cleavable thioketal cross-linkers which possessed terminal tetrazine groups to undergo a bio-orthogonal inverse electron demand Diels Alder click reaction with norbornene modified carboxymethyl cellulose. The hydrogels were rapidly formed under physiological conditions and generated N2 gas as a by-product, which led to the formation of porous structures within the hydrogel networks. A NIR dye, indocyanine green (ICG) and chemotherapeutic doxorubicin (DOX) were co-encapsulated in the porous network of the hydrogels. Upon NIR-irradiation, the hydrogels showed spatiotemporal release of encapsulated DOX (>96 %) owing to the cleavage of thioketal bonds by interacting with ROS generated from ICG, whereas minimal release of encapsulated DOX (<25 %) was observed in the absence of NIR-light. The in vitro cytotoxicity results revealed that the hydrogels were highly cytocompatible and did not induce any toxic effect on the HEK-293 cells. In contrast, the DOX + ICG-encapsulated hydrogels enhanced the chemotherapeutic effect and effectively inhibited the proliferation of Hela cancer cells when irradiated with NIR-light.

Antibiotic resistance determination using Enterococcus faecium whole-genome sequences: a diagnostic accuracy study using genotypic and phenotypic data.

BACKGROUND: DNA sequencing could become an alternative to in vitro antibiotic susceptibility testing (AST) methods for determining antibiotic resistance by detecting genetic determinants associated with decreased antibiotic susceptibility. Here, we aimed to assess and improve the accuracy of antibiotic resistance determination from Enterococcus faecium genomes for diagnosis and surveillance purposes. METHODS: In this retrospective diagnostic accuracy study, we first conducted a literature search in PubMed on Jan 14, 2021, to compile a catalogue of genes and mutations predictive of antibiotic resistance in E faecium. We then evaluated the diagnostic accuracy of this database to determine susceptibility to 12 different, clinically relevant antibiotics using a diverse population of 4382 E faecium isolates with available whole-genome sequences and in vitro culture-based AST phenotypes. Isolates were obtained from various sources in 11 countries worldwide between 2000 and 2018. We included isolates tested with broth microdilution, Vitek 2, and disc diffusion, and antibiotics with at least 50 susceptible and 50 resistant isolates. Phenotypic resistance was derived from raw minimum inhibitory concentrations and measured inhibition diameters, and harmonised primarily using the breakpoints set by the European Committee on Antimicrobial Susceptibility Testing. A bioinformatics pipeline was developed to process raw sequencing reads, identify antibiotic resistance genetic determinants, and report genotypic resistance. We used our curated database, as well as ResFinder, AMRFinderPlus, and LRE-Finder, to assess the accuracy of genotypic predictions against phenotypic resistance. FINDINGS: We curated a catalogue of 228 genetic markers involved in resistance to 12 antibiotics in E faecium. Very accurate genotypic predictions were obtained for ampicillin (sensitivity 99·7% [95% CI 99·5-99·9] and specificity 97·9% [95·8-99·0]), ciprofloxacin (98·0% [96·4-98·9] and 98·8% [95·9-99·7]), vancomycin (98·8% [98·3-99·2] and 98·8% [98·0-99·3]), and linezolid resistance (after re-testing false negatives: 100·0% [90·8-100·0] and 98·3% [97·8-98·7]). High sensitivity was obtained for tetracycline (99·5% [99·1-99·7]), teicoplanin (98·9% [98·4-99·3]), and high-level resistance to aminoglycosides (97·7% [96·6-98·4] for streptomycin and 96·8% [95·8-97·5] for gentamicin), although at lower specificity (60-90%). Sensitivity was expectedly low for daptomycin (73·6% [65·1-80·6]) and tigecycline (38·3% [27·1-51·0]), for which the genetic basis of resistance is not fully characterised. Compared with other antibiotic resistance databases and bioinformatic tools, our curated database was similarly accurate at detecting resistance to ciprofloxacin and linezolid and high-level resistance to streptomycin and gentamicin, but had better sensitivity for detecting resistance to ampicillin, tigecycline, daptomycin, and quinupristin-dalfopristin, and better specificity for ampicillin, vancomycin, teicoplanin, and tetracycline resistance. In a validation dataset of 382 isolates, similar or improved diagnostic accuracies were also achieved. INTERPRETATION: To our knowledge, this work represents the largest published evaluation to date of the accuracy of antibiotic susceptibility predictions from E faecium genomes. The results and resources will facilitate the adoption of whole-genome sequencing as a tool for the diagnosis and surveillance of antimicrobial resistance in E faecium. A complete characterisation of the genetic basis of resistance to last-line antibiotics, and the mechanisms mediating antibiotic resistance silencing, are needed to close the remaining sensitivity and specificity gaps in genotypic predictions. FUNDING: Wellcome Trust, UK Department of Health, British Society for Antimicrobial Chemotherapy, Academy of Medical Sciences and the Health Foundation, Medical Research Council Newton Fund, Vietnamese Ministry of Science and Technology, and European Society of Clinical Microbiology and Infectious Disease.

Active site engineering of Zn-doped mesoporous ceria toward highly efficient organophosphorus hydrolase-mimicking nanozyme.

Hydrolase-mimicking nanozymes have received increasing attention in recent years, but the effective rational design and development of these materials has not been realized, as they are not at present considered a critical research target. Herein, we report that Zn-doped mesoporous ceria (Zn-m-ceria) engineered to have an abundance of two different active sites with different functions-one that allows both co-adsorption binding of organophosphate (OP) and water and another that serves as a general base-has significant organophosphorus hydrolase (OPH)-like catalytic activity. Specifically, Zn-m-ceria exhibits a catalytic efficiency over 75- and 25-fold higher than those of m-ceria and natural OPH, respectively. First-principles calculations reveal the importance of Zn for the OPH-mimicking activity of the material, promoting substrate adsorption and proton-binding. The OPH-like Zn-m-ceria catalyst is successfully applied to detect a model OP, methyl paraoxon, in spiked tap water samples with excellent sensitivity, stability, and detection precision. We expect that these findings will promote research based on the rational engineering of the active site of nanozymes and efficient strategies for obtaining a diverse range of catalysts that mimic natural enzymes, and hence the utilization in real-world applications of enzyme-mimicking catalysts with properties superior to their natural analogs should follow.

Endoscopic papillectomy for ampullary lesions of minor papilla.

BACKGROUND AND AIMS: Ampullary lesions (ALs) of the minor duodenal papilla are extremely rare. Endoscopic papillectomy (EP) is a routinely used treatment for AL of the major duodenal papilla, but the role of EP for minor AL has not been accurately studied. METHODS: We identified 20 patients with ALs of minor duodenal papilla in the multicentric database from the Endoscopic Papillectomy vs Surgical Ampullectomy vs Pancreatitcoduodenectomy for Ampullary Neoplasm study, which included 1422 EPs. We used propensity score matching (nearest-neighbor method) to match these cases with ALs of the major duodenal papilla based on age, sex, histologic subtype, and size of the lesion in a 1:2 ratio. Cohorts were compared by means of chi-square or Fisher exact test as well as Mann-Whitney U test. RESULTS: Propensity score-based matching identified a cohort of 60 (minor papilla 20, major papilla 40) patients with similar baseline characteristics. The most common histologic subtype of lesions of minor papilla was an ampullary adenoma in 12 patients (3 low-grade dysplasia and 9 high-grade dysplasia). Five patients revealed nonneoplastic lesions. Invasive cancer (T1a), adenomyoma, and neuroendocrine neoplasia were each found in 1 case. The rate of complete resection, en-bloc resection, and recurrences were similar between the groups. There were no severe adverse events after EP of lesions of minor papilla. One patient had delayed bleeding that could be treated by endoscopic hemostasis, and 2 patients showed a recurrence in surveillance endoscopy after a median follow-up of 21 months (interquartile range, 12-50 months). CONCLUSIONS: EP is safe and effective in ALs of the minor duodenal papilla. Such lesions could be managed according to guidelines for EP of major duodenal papilla.

Flexible Iron-On Sensor Embedded in Smart Sock for Gait Event Detection.

Portable and wearable electronics for biomechanical data collection have become a growing part of everyday life. As smart technology improves and integrates into our lives, some devices remain ineffective, expensive, or difficult to access. We propose a washable iron-on textile pressure sensor for biometric data acquisition. Biometric data, such as human gait, are a powerful tool for the monitoring and diagnosis of ambulance and physical activity. To demonstrate this, our washable iron-on device is embedded into a sock and compared to gold standard force plate data. Biomechanical testing showed that our embedded sensor displayed a high aptitude for gait event detection, successfully identifying over 96% of heel strike and toe-off gait events. Our device demonstrates excellent attributes for further investigations into low-cost, washable, and highly versatile iron-on textiles for specialized biometric analysis.

Facile Fabrication of NIR-Responsive Alginate/CMC Hydrogels Derived through IEDDA Click Chemistry for Photothermal-Photodynamic Anti-Tumor Therapy.

Novel chemically cross-linked hydrogels derived from carboxymethyl cellulose (CMC) and alginate (Alg) were prepared through the utilization of the norbornene (Nb)-methyl tetrazine (mTz) click reaction. The hydrogels were designed to generate reactive oxygen species (ROS) from an NIR dye, indocyanine green (ICG), for combined photothermal and photodynamic therapy (PTT/PDT). The cross-linking reaction between Nb and mTz moieties occurred via an inverse electron-demand Diels-Alder chemistry under physiological conditions avoiding the need for a catalyst. The resulting hydrogels exhibited viscoelastic properties (G' ~ 492-270 Pa) and high porosity. The hydrogels were found to be injectable with tunable mechanical characteristics. The ROS production from the ICG-encapsulated hydrogels was confirmed by DPBF assays, indicating a photodynamic effect (with NIR irradiation at 1-2 W for 5-15 min). The temperature of the ICG-loaded hydrogels also increased upon the NIR irradiation to eradicate tumor cells photothermally. In vitro cytocompatibility assessments revealed the non-toxic nature of CMC-Nb and Alg-mTz towards HEK-293 cells. Furthermore, the ICG-loaded hydrogels effectively inhibited the metabolic activity of Hela cells after NIR exposure.

Highly Efficient Fluorescent Detection of Vitamin B12 Based on the Inner Filter Effect of Dithiol-Functionalized Silver Nanoparticles.

We report a fluorescent assay for the determination of vitamin B12 (VB12) based on the inner filter effect (IFE) of 1,3-propanedithiol-functionalized silver nanoparticles (PDT-AgNPs). PDT was simply functionalized on the surface of AgNPs through Ag-thiol interaction, which leads to significantly enhanced fluorescence, with excitation and emission at 360 and 410 nm, respectively, via their thiol-mediated aggregation. Since target VB12 has strong absorption centered at 360 nm, which is almost completely overlapping with the excitation spectra of PDT-AgNPs, the VB12 induced strong quenching of the fluorescence of PDT-AgNPs via IFE. The IFE-based mechanism for the fluorescence quenching of PDT-AgNPs in the presence of VB12 was confirmed by the analyses of Stern-Volmer plots at different temperatures and fluorescence decay curves. The fluorescence-quenching efficiency of PDT-AgNPs was linearly proportional to the concentration of VB12 in a wide range of 1 to 50 µM, with a lower detection limit of 0.5 µM, while preserving excellent selectivity toward target VB12 among possible interfering molecules. Furthermore, the PDT-AgNPs-mediated assay succeeded in quantitatively detecting VB12 in drug tablets, indicating that PDT-AgNPs can serve as an IFE-based fluorescent probe in pharmaceutical preparations by taking advantages of its ease of use, rapidity, and affordability.

Comprehensive Analysis of the Prognostic Significance of the TRIM Family in the Context of TP53 Mutations in Cancers.

The p53 protein is an important tumor suppressor, and TP53 mutations are frequently associated with poor prognosis in various cancers. Mutations in TP53 result in a loss of p53 function and enhanced expression of cell cycle genes, contributing to the development and progression of cancer. Meanwhile, several tripartite motif (TRIM) proteins are known to regulate cell growth and cell cycle transition. However, the prognostic values between TP53 and TRIM family genes in cancer are unknown. In this study, we analyzed the relationship between the TP53 mutations and TRIM family proteins and evaluated the prognostic significance of TRIM family proteins in cancer patients with P53 mutations. Our findings identified specific TRIM family members that are upregulated in TP53 mutant tumors and are associated with the activation of genes related to a cell-cycle progression in the context of TP53 mutations.

Spinal cysticercosis: A case report.

Spinal cysticercosis is a rare and severe cysticercosis complication. The pathology is from the inflammatory reaction and granuloma formation around the eggs, which cause focal neurological deficits. Because of the rarity of this condition, diagnosis may be delayed and confused with other myelopathies such as neoplasms or myelitis. We report a 42-year-old woman with low back pain and paraplegia. Magnetic resonance imaging showed a lesion in the spinal canal at the level of L4/L5 that was toward the diagnosis of myelitis. The patient underwent an open biopsy, and the result was granulomatosis caused by cysticercosis. The patient was then given an anticysticercosis medication and gradually recovered.

Pygmy grasshoppers (Orthoptera: Tetrigidae) from Bach Mã National Park, central Vietnam.

A list of 10 species from three subfamilies of Tetrigidae from Bach Mã National Park in the province of Thua Thiên-Hue, Vietnam is presented here. Eight of which are new for the national park. Among these, two new species are described: Miriatroides luna Tan & Storozhenko, sp. nov. and Rhopalina bachma Tan & Storozhenko, sp. nov. New synonymy is proposed: Systolederus cinereus Brunner von Wattenwyl, 1893 = Systolederus ridleyi Hancock, 1909, syn. nov. Three species are also recorded in Vietnam for the first time: Tegotettix bufocrocodil (Storozhenko & Dawwrueng, 2015) previously known from Thailand and Cambodia, Zhengitettix albitarsus Storozhenko, 2013 so far considered as endemic to Thailand, and Systolederus cinereus widely distributed in Southeast Asia.