HADDOCK

BACKGROUND: Radiographic changes might not fully capture the treatment effects of immune checkpoint inhibitors (ICIs). We aimed to assess correlations of overall response rate and progression-free survival with overall survival in trials of ICIs for metastatic non-small-cell lung cancer (NSCLC). METHODS: To assess trial-level and patient-level correlations of overall response rate and progression-free survival with overall survival, we conducted a pooled analysis of first-line randomised trials (including patients aged ≥18 years with metastatic squamous and non-squamous NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1) submitted to the US Food and Drug Administration from June 24, 2016, to March 16, 2021...

BACKGROUND: The novel coronavirus disease of 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Data from the COVID-19 clinical control case studies showed that this disease could also manifest in patients with underlying microbial infections such as aspergillosis. The current study aimed to determine if the Aspergillus (A.) fumigatus culture media (i.e., supernatant) possessed protease activity that was sufficient to activate the SARS-CoV-2 spike protein...

BACKGROUND & AIMS: The PTEN-AKT pathway is frequently altered in extrahepatic cholangiocarcinoma (eCCA). We aim to evaluate the role of PTEN in the pathogenesis of eCCA and find novel therapies for this disease. METHODS: The Pten gene in the biliary epithelial cells were genetically deleted using the Cre-loxp system. The pathologies were evaluated both macroscopically and histologically. The characteristics were further analyzed by immunohistochemistry (IHC), RT-PCR, cell culture, and RNAseq...

OBJECTIVE: 
An algorithm was developed for automated positioning of lattice points within volumetric modulated arc lattice radiation therapy (VMATLRT) planning. These points are strategically placed within the gross tumor volume(GTV) to receive high doses, adhering to specific separation rules from adjacent organs at risk(OARs). The study goals included enhancing planning safety, consistency, and efficiency while emulating human performance. APPROACH: A Monte Carlo-based algorithm was designed to optimize the number and arrangement of lattice points within the GTV while considering placement constraints and objectives...

No abstract text is available yet for this article.

Elucidating antibody-antigen complexes at the atomic level is of utmost interest for understanding immune responses and designing better therapies. Cross-linking mass spectrometry (XL-MS) has emerged as a powerful tool for mapping protein-protein interactions, suggesting valuable structural insights. However, the use of XL-MS studies to enable epitope/paratope mapping of antibody-antigen complexes is still limited up to now. XL-MS data can be used to drive integrative modeling of antibody-antigen complexes, where cross-links information serves as distance restraints for the precise determination of binding interfaces...

PURPOSE: To examine the role of RhoB expression in relation to chemotherapy response, clinical outcomes and associated signaling pathways in colorectal cancer patients. MATERIALS AND METHODS: The study included 5 colon cancer cell lines, zebrafish embryos and 260 colorectal cancer patients treated with 5-fluorouracil (5-FU) and oxaliplatin (OXL). The methods consisted of CRISPR/Cas9, reactive oxygen species (ROS), caspase-3 activity, autophagy flux, in-silico RNA sequencing and immunohistochemistry...

INTRODUCTION: Urinary tract infection (UTI) is one of the most common infections, usually caused by uropathogenic Escherichia coli (UPEC). However, antibiotics are a usual treatment for UTIs; because of increasing antibiotic-resistant strains, vaccination can be beneficial in controlling UTIs. Using immunoinformatics techniques is an effective and rapid way for vaccine development. METHODS: Three conserved protective antigens (FdeC, Hma, and UpaB) were selected to develop a novel multi-epitope vaccine consisting of subunit B of cholera toxin (CTB) as a mucosal build-in adjuvant to enhance the immune responses...

Starting an academic microsurgery practice is a daunting task for plastic surgery graduates. Despite this, academic practice provides many advantages as a starting point for a career. Microsurgical faculty can make use of several unique benefits within an academic center. These include vast resources of clinical and basic science departments, communications and public affairs divisions, and quality improvement teams. Building a multi-disciplinary microsurgery practice with specific focus will jumpstart research questions and outcome data...

Multiple lines of evidence at whole animal, cellular and molecular levels implicate polycyclic aromatic compounds (PACs) with three rings as drivers of crude oil toxicity to developing fish. Phenanthrene (P0) and its alkylated homologs (C1- through C4-phenanthrenes) comprise the most prominent subfraction of tricyclic PACs in crude oils. Among this family, P0 has been studied intensively, with more limited detail available for the C4-phenanthrene 1-methyl-7-isopropyl-phenanthrene (1-M,7-IP, or retene). While both compounds are cardiotoxic, P0 impacts embryonic cardiac function and development through direct blockade of K+ and Ca2+ currents that regulate cardiomyocyte contractions...

Most of the polycyclic aromatic hydrocarbons (PAHs) in petroleum are alkylated (alkyl PAHs), still the metabolism of these alkyl PAHs to the expected acid products (polycyclic aromatic acids; PAAs) has yet to be demonstrated in oil-exposed fish. Should these compounds be discovered in fish as they have in ragworm, rodents, and humans, they could present an indicative biomarker for assessing oil pollution. In this study, the ability to biotransform alkyl PAHs to PAAs was examined on Atlantic haddock (Melanogrammus aeglefinus)...

BACKGROUND: Infantile-onset inflammatory bowel disease (IOIBD) is a gastrointestinal inflammatory condition often associated with monogenic disorders and is frequently caused by Interleukin-10 deficiencies. This study aimed to identify the mutation responsible for IBD in an 8-year-old patient from an Iranian family with consanguineous parents. METHODS: Whole-exome sequencing (WES) was employed to identify disease-causing variations. Furthermore, we utilized integrated experimental data of HADDOCK molecular docking platform, including NMR spectroscopy, to characterize the mutant protein and elucidate the underlying functional mechanism of the identified mutation's pathogenicity...

BACKGROUND: The inovirus Pf4 is a lysogenic bacteriophage of Pseudomonas aeruginosa ( Pa ). People with Cystic Fibrosis (pwCF) experience chronic airway infection with Pa and a significant proportion have high numbers of Pf4 in their airway secretions. Given the known severe damage in the airways of Pa -infected pwCF, we hypothesized a high Pf4 burden can affect airway healing and inflammatory responses. In the airway, basal epithelial cells (BCs) are a multipotent stem cell population critical to epithelium homeostasis and repair...

Zika virus is a re-merging flavivirus allied to serious mental health conditions in the fetuses. There is currently no preventives or treatment available for Zika infection. In this work, we have extended the in silico analysis by performing the molecular docking of previous reported three conserved Zika virus precursor membrane (prM) peptides (MP1, MP2 and MP3) with HLA complex (pHLA) and T cell receptors (TCR) and also evaluated the peptide specific immune response in human peripheral blood mononuclear cells (PBMC)...

Thirty percent of all mutations causing human disease generate mRNAs with premature termination codons (PTCs). Recognition and degradation of these PTC-containing mRNAs is carried out by the mechanism known as nonsense-mediated mRNA decay (NMD). Upf2 is a scaffold protein known to be a central component of the NMD surveillance pathway. It harbors three middle domains of eukaryotic initiation factor 4G (mIF4G-1, mIF4G-2, mIF4G-3) in its N-terminal region that are potentially important in regulating the surveillance pathway...

The water column of the deep ocean is dark, cold, low in food, and under crushing pressures, yet it is full of diverse life. Due to its enormous volume, this mesopelagic zone is home to some of the most abundant animals on the planet. Rather than struggling to survive, they thrive-owing to a broad set of adaptations for feeding, behavior, and physiology. Our understanding of these adaptations is constrained by the tools available for exploring the deep sea, but this tool kit is expanding along with technological advances...

IMPORTANCE: Robotic-assisted nipple-sparing mastectomies with multiport robots have been described in the US since 2015; however, significant hurdles to multiport robotic surgery exist in breast surgery. OBJECTIVE: To demonstrate that the single-port da Vinci SP (Intuitive Surgical) robotic system is feasible in patients undergoing robotic nipple-sparing mastectomy (rNSM). DESIGN, SETTING, AND PARTICIPANTS: An initial case series of 20 patients at a large university hospital underwent bilateral single-port robotic nipple-sparing mastectomies (SPrNSM) with tissue expander reconstruction from February 1, 2020, through January 4, 2023...

Ebola viral disease (EVD) is a highly infectious and potentially fatal illness with a case fatality rate ranging from 25% to 90%. To effectively control its spread, there is a need for rapid, reliable and lowcost point-of-care (P OC) diagnostic tests. While various EVD diagnostic tests exist, few are P OC tests, and many are not cost-effective. The use of antibodies in these tests has limitations, prompting the exploration of aptamers as potential alternatives. Various proteins from the Ebola virus (EBOV) proteome, including EBOV nucleoprotein (NP), are considered viable targets for diagnostic assays...

In order to support or refute the clinical suspicion of cranial giant cell arteritis (GCA), a supplemental imaging modality is often required. High-resolution black blood Magnetic Resonance Imaging (BB MRI) techniques with contrast enhancement can visualize artery wall inflammation in GCA. We compared findings on BB MRI without contrast enhancement with findings on 2-deoxy-2-[18 F]fluoro-D-glucose positron emission tomography/low-dose computed tomography (2-[18 F]FDG PET/CT) in ten patients suspected of having GCA and in five control subjects who had a 2-[18 F]FDG PET/CT performed as a routine control for malignant melanoma...

Human β defensin type 2 (hBD-2), a cationic cysteine-rich peptide secreted from the human innate immune system, can bind Spike-RBD at the same site as receptor ACE2, thus blocking viral entry into ACE2-expressing cells. In order to find out the impact of CoV-2 mutations on hBD-2's antiviral activity, it is important to investigate the binding and interaction of hBD-2 with RBD mutants. All-atom molecular dynamics simulations were conducted on typical RBD mutants, including N501Y, E484K, P479S, T478I, S477N, N439K, K417N, and N501Y-E484K-K417N, binding with hBD-2...