Search Results (2,337)

African swine fever (ASF) is an acute, febrile, and lethal pig disease induced by the African swine fever virus (ASFV). In the absence of an effective vaccine, early diagnosis is essential for the prevention and control of ASF disease. The p54 protein is important for ASFV diagnosis and vaccine design. In this study, ASFV p54 protein was constructed, expressed, purified, and used to generate three mAbs, namely 9A3, 5H2, and 2G6. Epitope mapping was performed using alanine mutants; the minimal linear epitope recognized by 9A3 and 5H2 was ⁵⁶KKKAAAI⁶², and the minimal linear epitope recognized by 2G6 was ¹⁰⁸TNRPATN¹¹⁴. Of these, ⁵⁶KKKAAAI⁶² was identified as a new linear epitope for the first time. The epitopes were highly conserved in at least genotypes I and II. Alanine-scanning mutagenesis further revealed that residues 56K, 57K, 60A, 61A, 62L, 108T, 110R, 111P, 113T, and 114N were the core sites involved in antibody recognition. Overall, the mAbs and epitopes of the p54 protein identified in this study provide theoretical support for the development of ASFV vaccines based on the B cell epitope, the development of ASFV therapeutic antibody drugs, and the development of ASFV diagnostic tools. Full article

Introduction: Ado-trastuzumab emtansine (T-DM1) is a targeted agent for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, which combines the anti-tumor activity of trastuzumab with the cytotoxic effect of DM1, a microtubule inhibitor. Although T-DM1 has improved outcomes in patients with HER2-positive breast cancer, portal hypertension may occur during treatment in the absence of overt cirrhosis on liver biopsy. These clinical and pathological features are consistent with porto-sinusoidal vascular disorder (PSVD). This study aimed to summarize the reported clinical, biochemical, imaging, histological, therapeutic, and prognostic features of T-DM1-associated PSVD. Methods: PubMed and Web of Science were searched for published cases of T-DM1-associated PSVD. Given the evolving terminology of PSVD, related terms, including non-cirrhotic portal hypertension and nodular regenerative hyperplasia, were also included in the search strategy. If the patient has a recorded history of T-DM1 exposure and the liver biopsy results meet PSVD criteria, the case is included regardless of whether there is clinical, endoscopic, or imaging evidence of portal hypertension. Cases without liver biopsy or with features suggestive of overt cirrhosis were excluded. Patient-level data were extracted and descriptively summarized, including demographic characteristics, clinical manifestations, biochemical indicators, imaging examination results, liver biopsy results, treatment methods, and prognosis. Unreported data were considered missing values and were not imputed. Results: Seven eligible articles comprising eight patients were identified. All patients were female, with a mean age of 60.38 years and a median age of 62.50 years. The interval from T-DM1 initiation to PSVD diagnosis ranged from 6 to 30 months. When reported, the mean interval from treatment initiation to symptom onset was 18.3 months. Thrombocytopenia and splenomegaly were observed in 7 of 8 patients. Mild elevations in alanine aminotransferase and aspartate aminotransferase were observed in all patients. Liver biopsy showed thinned and disorganized hepatic plates accompanied by nodular regeneration of hepatocytes in six patients. Clinical improvement was observed after discontinuation or modification of T-DM1 in most cases. Conclusions: T-DM1-associated PSVD is a rare but clinically significant complication that may develop months after treatment initiation. It commonly presents with thrombocytopenia, splenomegaly, gastrointestinal bleeding, or mild liver biochemical abnormalities in the absence of overt cirrhosis. Early recognition of unexplained platelet decline, splenic enlargement, or portal hypertension-related findings during T-DM1 therapy may facilitate timely diagnosis and individualized management. Withdrawal or modification of the suspected drug may contribute to clinical improvement, although further studies are needed to clarify the mechanism and optimal management strategy. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, largely due to late-stage diagnosis, biological heterogeneity, and persistent challenges in staging and treatment selection. This narrative review summarizes current and emerging applications of AI across lung cancer screening and early detection, imaging-based staging and prognostication, tissue and liquid biopsy-based tumor characterization, treatment planning, surgical and intraoperative guidance, and drug discovery. In imaging, deep learning models have demonstrated high performance in pulmonary nodule detection, risk stratification, and prediction of molecular alterations, while also showing promise in improving screening efficiency and reducing interpretive variability. In pathology and liquid biopsy domains, AI enables prediction of driver mutations, immunotherapy response, and survival outcomes directly from histopathology slides, circulating tumor DNA, and other blood-based biomarkers, facilitating minimally invasive precision oncology approaches. In treatment planning and delivery, AI systems are being developed to support clinical decision-making, surgical planning (through advanced image segmentation and delineation of operative anatomy), and intraoperative navigation through robotic and computer vision-enabled platforms. Despite these advances, significant barriers remain, including limited real-world validation, algorithmic biases, workflow integration issues, and unresolved ethical and legal concerns. Future progress will depend on the development of transparent, clinically validated, and generalizable AI systems that augment rather than replace the expertise of clinical providers and healthcare teams. Active engagement from pulmonologists, oncologists, radiologists, and thoracic surgeons will be essential in guiding safe implementation and ensuring that AI-driven innovations translate into meaningful improvements in patient outcomes. Full article

Trichosporon is a type of non-candida yeast-like fungus. At one time, it was commonly reported in immunocompromised patients, but after the introduction of fluconazole as prophylaxis and for the treatment of fungal infections, there was a decrease in the incidence of the disease. With the introduction of echinocandins as the first line of treatment for fungal infections, and the intrinsic resistance of Trichosporon to the drug, there has been a small but increased reported incidence of the disease. Trichosporon usually causes skin infections, but invasive disease can occur in vulnerable patients. Endocarditis due to Trichosporon has been reported rarely, and usually occurs in prosthetic valves. In this paper, we report a patient with dialysis-dependent chronic kidney disease who presented with fever and was found to have native aortic valve endocarditis. In view of the large vegetation, he underwent early aortic valve replacement. Both the blood and tissue cultures grew Trichosporon spp. Post-operatively, he developed fungal septic shock, deteriorated, and died. Invasive Trichosporon disease has been associated with high rates of mortality ranging from 30 to 90%. There is limited literature on endocarditis resulting from Trichosporon. Specific treatment recommendations are unavailable, and a combination of surgery and prolonged antifungal medication will generally be required. Full article

Background: Toxic epidermal necrolysis (TEN) is a rare but life-threatening complication that may occur in patients after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in the context of extensive drug exposure. In this population, TEN can closely resemble severe acute graft-versus-host disease (GVHD), making diagnosis and management challenging. Case presentation: We report the clinical course of an allo-HSCT recipient who developed a rapidly progressive skin rash early after transplantation, and we analyzed the clinical features, histopathology, treatment and outcome. Results: The patient developed rapidly progressive epidermal detachment with severe oral, ocular, and genital mucosal involvement shortly after exposure to trimethoprim/sulfamethoxazole (TMP-SMX). Disease severity was reflected by a SCORTEN score of 5, corresponding to a very high predicted mortality risk. The clinical picture raised concern for both TEN and severe acute GVHD, while histopathological findings favored TEN but were not definitive. Management included systemic corticosteroids, intravenous immunoglobulin, ruxolitinib, and intensive supportive care. The patient gradually re-epithelialized and recovered without long-term sequelae. Conclusions: This case underscores the diagnostic difficulty of distinguishing TEN from severe acute GVHD in the early post-transplant period. Careful assessment of drug exposure, clinical evolution, and multidisciplinary evaluation are essential to guide timely and appropriate management. Full article

Melanoma has long represented a unique challenge in oncology. In its early stages, it can often be cured with surgery alone, resulting in excellent survival outcomes. Its biology is complex and heterogeneous, often including mutations such as BRAF and NRAS, which partly explain its high immunogenicity but also its capacity to relapse. For many decades, the standard approach in resectable stage III melanoma was surgery first, followed by adjuvant therapy. In the last decade, the development of immune checkpoint inhibitors created the opportunity to treat patients before surgery. The neoadjuvant approach is based on the hypothesis that treatment of the intact tumor may enhance antitumor immune priming and activation. The first prospective neoadjuvant studies, including OpACIN and OpACIN-neo, showed high pathological response rates with ipilimumab plus nivolumab and introduced pathological response as an early marker of long-term benefit. The PRADO study showed that treatment response could guide the extent of surgery required. The SWOG S1801 trial demonstrated better event-free survival with perioperative pembrolizumab compared to adjuvant therapy alone. Lastly, the phase III NADINA trial showed that neoadjuvant ipilimumab plus nivolumab followed by response-adapted adjuvant therapy significantly improves outcomes. Biomarkers such as PD-L1, IFN-γ signature, tumor mutational burden and imaging (PET scan) appear promising to predict response, but none have been sufficiently validated for routine clinical practice. Full article

The vitreous body is not only a transparent filling material of the posterior segment; it is a soft, hydrated, and biologically active matrix that supports structural, optical, and biochemical homeostasis. Vitrectomy therefore leaves a functional deficit that current substitutes only partly address. Intraocular gases, silicone oils, and perfluorocarbon liquids remain essential surgical tools, but they mainly provide mechanical tamponade and do not reproduce native viscoelasticity, diffusion control, or protection against oxidative and inflammatory stress. This review considers vitreous replacement as a functional biomaterials challenge. We discuss native vitreous physiology, the limitations of present tamponade agents, and emerging bioengineered substitutes designed to create a more physiological intravitreal environment. Particular attention is given to hydrogel and polymer-based systems, especially hyaluronic acid-based and in situ crosslinked platforms, which are being developed to combine optical clarity, injectability, soft mechanical support, controlled degradation, and favorable tissue interaction. We also emphasize the need for standardized preclinical testing of swelling, enzymatic stability, drug diffusion, rheology, and long-term biocompatibility. Although next-generation materials may move the field beyond passive space filling, manufacturing reproducibility, regulatory validation, chronic safety, and cautious early-phase trials remain major translational barriers. Full article

Gallbladder cancer (GBC) is an aggressive tumor that, together with the cholangiocarcinomas, constitutes the spectrum of biliary tract cancer (BTC). These tumors are characterized by a frequently late diagnosis, marked genomic heterogeneity, variable response to cytotoxic therapies, and poor overall survival in advanced stages. Nevertheless, the characterization of the tumor microenvironment (TME) and the identification of actionable molecular targets have driven the development of biological therapies. This review summarizes current and emerging evidence on monoclonal antibodies, bispecific antibodies, and antibody–drug conjugates (ADCs) in the management of GBC. The analysis addresses the early exploration of autoantibodies as potential diagnostic biomarkers, mechanistic hypotheses of immune evasion, and the clinical translation of targeted agents in the metastatic setting. Additionally, we critically discuss the extrapolation of data from global BTC trials to the specific GBC setting, the integration of population genetics into epidemiological studies such as the EULAT Eradicate GBC initiative, and the preliminary status of immunotherapy in perioperative scenarios. Full article

Fibroblast growth factor receptor 2 (FGFR2) inhibitors such as pemigatinib are targeted therapies for cholangiocarcinoma with FGFR2 alterations. While generally well tolerated, they are associated with unique adverse events. Calciphylaxis, a potentially fatal vascular calcification disorder, is a rare complication. We present a 43-year-old woman with metastatic intrahepatic cholangiocarcinoma harboring an FGFR2 fusion who developed calciphylaxis after seven months of pemigatinib therapy. Despite drug discontinuation, antibiotics, and multidisciplinary supportive care, she deteriorated rapidly and died from sepsis and advanced disease. Histopathological analysis confirmed dermal and vascular calcifications consistent with calciphylaxis. This case highlights the importance of early recognition of cutaneous lesions in patients on FGFR inhibitors. Prompt cessation of therapy, management of metabolic derangements, and consideration of sodium thiosulfate may be lifesaving. Full article

Background: Cluster epilepsy related to PCDH19 is a rare X-linked disorder that mainly affects females. Atypical presentations, such as infantile spasms, are exceptionally rare, leading to diagnostic and therapeutic challenges. Case Summary: An 8-month-old girl presented with early-onset, drug-resistant epilepsy from 4 months of age, displaying tonic and focal seizures, infantile spasms with hypsarrhythmia, and neurodevelopmental regression. Whole exome sequencing identified a novel heterozygous mutation, c.1072del (p.Val358SerfsTer10), in the PCDH19 gene. Following vigabatrin therapy for infantile spasms, the patient subacutely developed a movement disorders: dystonic movements and action tremor in forearm and hands. Brain Magnetic Resonance Imaging (MRI) revealed symmetrical restricted diffusion and cytotoxic edema in both the thalami and the internal capsules, confirming Vigabatrin-Associated Brain Abnormalities on MRI (VABAMR). Concurrently, a systemic carnitine deficiency was identified, which could additionally have compromised mitochondrial bioenergetics and intensified the tendency to cytotoxic cerebral edema. A strategic reduction in vigabatrin led to complete resolution of movement disorder and neuroimaging abnormalities. Conclusions: This case underscores the high phenotypic variability of PCDH19 mutations, and also the importance of early advanced genetic testing and the consideration of even rare side effects of drugs in differential diagnosis. It is unclear whether that baseline carnitine deficiency could potentially increase the risk of VABAMR. Full article

Designing an optimal digital pathology workspace is essential to ensure diagnostic accuracy and safeguard the long-term well-being of pathologists. While digital pathology improves reproducibility, facilitates multidisciplinary collaboration, and supports data-driven precision medicine, its clinical effectiveness depends not only on computational performance but also on the physical and ergonomic environment in which pathologists operate. Inadequate workstation design may impair visual perception, increase cognitive and musculoskeletal strain, and potentially affect diagnostic consistency. Moreover, the progressive integration of artificial intelligence (AI) into routine diagnostics introduces additional requirements related to display performance, visualization interfaces, and human–machine interaction. Despite the rapid global adoption of digital pathology systems, standardized recommendations addressing ergonomic, environmental, and technological aspects of the digital workspace remain limited. In this work, we propose a clinically oriented framework for the design of digital pathology workspaces suitable for AI-assisted diagnostics. Key elements include the selection and calibration of medical-grade displays, ergonomic furniture and input devices, optimized ambient lighting conditions, and institutional quality assurance procedures. Emerging developments, such as intelligent ergonomic monitoring, advanced visualization interfaces, and adaptive AI-assisted workflows, may further support safe, sustainable, and high-performance digital diagnostic environments. Full article

Background: Polymeric drug-eluting films are promising platforms for local antibacterial delivery, but their release profiles depend strongly on the permeability and morphology of the barrier layer. Here, the previously proposed concept of additively manufactured PLACE (Printed Layered Adjustable Cargo Encapsulation) coatings was extended from "single orifice"-defined release toward porosity-assisted barrier control. Two conventional water-soluble porogens, polyethylene glycol (PEG) and polyvinylpyrrolidone (PVP), were compared with poly(2-ethyl-2-oxazoline) (PEOx), a hydrophilic polymer proposed as an alternative to PEG in biomedical formulations, but whose use as a leachable porogen has received little attention. Methods: Each porogen was introduced into the upper PLGA barrier of multilayer PLACE films. The resulting films were characterized for film formation, post-hydration morphology by SEM, release of methylene blue and vancomycin, and antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA). Results/Conclusions: PEG was poorly compatible with PLGA and mainly produced surface-localized defects rather than a barrier with controlled permeability suitable for prolonged delivery. PVP K17 provided sustained release at 10 wt.%, whereas 20 wt.% PVP caused burst-dominated release and stronger morphological disruption. PEOx formed developed porosity at lower loading and produced release regimes ranging from several days to approximately two weeks. Vancomycin-loaded films containing 5 wt.% PEOx enabled near-complete release over two weeks while preserving film integrity and showed pronounced early anti-MRSA activity. These results identify porogen selection as a key formulation step and support PEOx as a useful porogen for early high-output antibacterial PLACE coatings. Full article

Marburg virus (MARV), a highly pathogenic member of the Filoviridae family, causes severe hemorrhagic fever with a high case fatality rate and currently lacks effective therapeutics. The viral entry process, mediated by the interaction between the MARV glycoprotein (GP) and host receptor C-type lectin domain family 4 member M (CLEC4M) (L-SIGN), represents a critical target for early-stage intervention. The active compounds from BindingDB and the decoy from DUDE were used. The RDKit was used for feature engineering. Machine learning models were trained on an initial dataset consisting of 56 active chemicals and 1232 decoys. Among the tested algorithms, the Random Forest model demonstrated superior performance, achieving the highest discriminative ability (AUC = 0.93, MCC = 0.88) on the test set. Virtual screening of 11,032 phytochemicals resulted in 120 predicted actives, of which 42 compounds satisfied drug-likeness criteria. Subsequent molecular docking identified three lead compounds (PubChem IDs: 42608095, 5281601, and 11243993) with moderate-to-promising binding affinities (−6.3 to −6.5 kcal/mol) toward the CLEC4M binding site. ADMET analysis revealed favorable pharmacokinetic and toxicity profiles for the selected lead compounds. DFT calculations of the three compounds highlighted their electronic stability and reactive nature, indicating that PubChem IDs 42608095 and 5281601 possess particularly stable electronic properties conducive to favorable target interactions. Combining machine learning models with molecular docking and Molecular Dynamics (MD) simulations worked well in finding promising phytochemical inhibitors. The MM/GBSA binding free energy calculations further confirmed binding affinities, with values of −10.83 and −11.08 kcal/mol, respectively, suggesting favorable complex stability. These findings provide a pathway for developing new antiviral agents against MARV, pending further experimental validation and optimization. Full article

Newborns may suffer from dangerous bacterial infections caused by life-threatening multi-drug resistant pathogens. Thus, despite bactericidal capabilities of antibiotics, microorganisms are known to circumvent this therapy, and a new, more effective type of remedy is needed. An increasingly recognized strategy for addressing these challenges is the use of bacteriophages—viruses infecting bacteria—collectively referred to as phage therapy. Nonetheless, the research considering phage therapy amongst newborns is still at a pioneering stage, owing to the scarcity of systematic investigations and the prevalence of case-study data, leaving room for further discovery and analysis. This review summarizes the information needed to understand this complex issue, considering the description of pathogens causing infections affecting newborns, the formation of the early microbiota and phageome (defining its composition followed by an influence on immune system development), and the possible use of bacteriophages in the treatment, which may be complicated by ethical concerns. Full article

Cervical cancer continues to require more precise and clinically adaptable local treatment strategies, particularly in the face of insufficient drug accumulation at the lesion site, systemic toxicity of conventional chemotherapy, limited development of postoperative tissue-interfacing platforms, and the anatomical constraints of standard radiotherapy devices. In this mini-review, we summarize the current landscape of polymer-based biomaterials for local therapy in cervical cancer from both materials and clinical perspectives. Specifically, we discuss three interconnected application domains: local drug delivery systems, polymeric scaffolds and tissue-interfacing platforms, and 3D-printed radiotherapy devices. Recent studies indicate that polymer-based local delivery systems, including nanofiber- and hydrogel-based formulations, can improve cervicovaginal retention, controlled release, and local therapeutic exposure. Scaffold-based systems further extend the role of biomaterials by combining sustained local delivery with defect-specific support and tissue interaction, whereas 3D-printed radiotherapy devices contribute primarily through precision enablement, individualized implantation guidance, and improved conformity in anatomically challenging cases. Despite these advances, most available studies remain preclinical or early translational, and important barriers persist in long-term safety, standardization, clinically relevant validation, and workflow integration. Future progress will depend on application-specific design, stronger translational rigor, and closer integration of biomaterials, imaging, and personalized clinical practice. Full article