Immunotherapy-extended survival in patients with recurrent pulmonary pleomorphic carcinoma following surgery.

Objective: Pulmonary pleomorphic carcinoma is a relatively rare and aggressive subtype of non-small cell lung cancer (NSCLC), with a poor prognosis and early recurrence, and is resistant to conventional therapies. This study investigated the efficacy of immune checkpoint inhibitors (ICIs) in improving the survival outcomes of patients with pulmonary pleomorphic carcinoma with postoperative recurrence.

Methods: We conducted a retrospective analysis of 71 patients with pulmonary pleomorphic carcinoma who underwent pulmonary resection at Tokyo Medical University Hospital between 2008 and 2022.

Near-Native Imaging of Metal Ion-Initiated Cell State Transition.

Metal ions are indispensable to life, as they can serve as essential enzyme cofactors to drive fundamental biochemical reactions, yet paradoxically, excess is highly toxic. Higher-order cells have evolved functionally distinct organelles that separate and coordinate sophisticated biochemical processes to maintain cellular homeostasis upon metal ion stimuli. Here, we uncover the remodeling of subcellular architecture and organellar interactome in yeast initiated by several metal ion stimulations, relying on near-native three-dimensional imaging, cryo-soft X-ray tomography.

Thyroid Nodules with Indeterminate Cytology and Negative Molecular Profile: Prevalence of Malignancy and Practice Paradigms for Surveillance.

In the era of molecular testing, thyroid nodules with indeterminate cytology are increasingly being managed nonoperatively. The false-negative rates of these molecular tests, and therefore missed malignancies, are not well defined in real-world clinical practice. This retrospective study of patients undergoing fine needle aspiration (FNA) biopsy at our health system between November 2017 and March 2022 included nodules with The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC) III and IV cytology and negative, currently negative, or negative but limited ThyroSeq version 3 (TSv3) results.

Utility of Computed Tomography Angiography of the Head in the Management of the Blunt Trauma Patient with Intracranial Hemorrhage.

Background: Computed tomography angiography of the head (CTAH) is not routinely obtained during the initial evaluation of patients with traumatic intracranial hemorrhage (ICH); however, it is useful for diagnosing vascular pathologies that may have led to the bleed. The aims of this study were to identify traumatic ICH patient characteristics on presentation that are associated with positive CTAH findings to elucidate which ones should prompt a CTAH and compare outcomes of patients with positive and negative CTAH findings.

Methods: This is a retrospective cohort study of 522 patients who had blunt traumatic ICH and subsequently received CTAH between January 1, 2017, and January 1, 2022.

Immune checkpoint inhibitors plus taxane-based chemotherapy for patients with advanced/metastatic NSCLC: a systematic review and meta-analysis across different PD-L1 expression levels.

Background: Immune checkpoint inhibitors (ICIs) are currently the primary approach for managing NSCLC. However, numerous combination therapies are currently under investigation. Our goal is to investigate the overall efficacy and safety of ICIs and taxane-based chemotherapy.

Prion Protein Endoproteolysis: Cleavage Sites, Mechanisms and Connections to Prion Disease.

Highly abundant in neurons, the cellular prion protein (PrP) is an obligatory precursor to the disease-associated misfolded isoform denoted PrP that accumulates in the rare neurodegenerative disorders referred to either as transmissible spongiform encephalopathies (TSEs) or as prion diseases. The ability of PrP to serve as a substrate for this template-mediated conversion process depends on several criteria but importantly includes the presence or absence of certain endoproteolytic events performed at the cell surface or in acidic endolysosomal compartments. The major endoproteolytic events affecting PrP are referred to as α- and β-cleavages, and in this review we outline the sites within PrP at which the cleavages occur, the mechanisms potentially responsible and their relevance to pathology.

Cell-free assays reveal that the HIV-1 capsid protects reverse transcripts from cGAS immune sensing.

Retroviruses can be detected by the innate immune sensor cyclic GMP-AMP synthase (cGAS), which recognizes reverse-transcribed DNA and activates an antiviral response. However, the extent to which HIV-1 shields its genome from cGAS recognition remains unclear. To study this process in mechanistic detail, we reconstituted reverse transcription, genome release, and innate immune sensing of HIV-1 in a cell-free system.

Lineage tracing studies suggest that the placenta is not a de novo source of hematopoietic stem cells.

Definitive hematopoietic stem and progenitor cells (HSPCs) arise from a small number of hemogenic endothelial cells (HECs) within the developing embryo. Understanding the origin and ontogeny of HSPCs is of considerable interest and potential therapeutic value. It has been proposed that the murine placenta contains HECs that differentiate into HSPCs.

Association between chiropractic spinal manipulation for sciatica and opioid-related adverse events: A retrospective cohort study.

Background: Patients receiving chiropractic spinal manipulation (CSM) for spinal pain are less likely to be prescribed opioids, and some evidence suggests that these patients have a lower risk of any type of adverse drug event. We hypothesize that adults receiving CSM for sciatica will have a reduced risk of opioid-related adverse drug events (ORADEs) over a one-year follow-up compared to matched controls not receiving CSM.

Methods: We searched a United States (US) claims-based data resource (Diamond Network, TriNetX, Inc.

Fipronil in sub-lethal doses leads to immuno-toxicological effects in broiler birds.

Pesticides, including fipronil, are used mainly in agriculture; however, in veterinary and animal husbandry, their potential use is to control the pests responsible for vector-borne diseases. Their residues in agriculture products and direct use on farms are responsible for potentially harming livestock and poultry. So, this study was designed to evaluate the toxico-pathological effects of fipronil on the immune system of poultry birds.

Characterizing temporal and global host innate immune responses against SARS-CoV-1 and -2 infection in pathologically relevant human lung epithelial cells.

Severe acute respiratory syndrome coronavirus-1 (SARS-CoV-1) and -2 (SARS-CoV-2) are beta-coronaviruses (β-CoVs) that have caused significant morbidity and mortality worldwide. Therefore, a better understanding of host responses to β-CoVs would provide insights into the pathogenesis of these viruses to identify potential targets for medical countermeasures. In this study, our objective is to use a systems biology approach to explore the magnitude and scope of innate immune responses triggered by SARS-CoV-1 and -2 infection over time in pathologically relevant human lung epithelial cells (Calu-3/2B4 cells).

Toll-like receptor 1/2 activation reduces immunoglobulin free light chain production by multiple myeloma cells in the context of bone marrow stromal cells and fibronectin.

Toll-like receptor (TLRs) activation in multiple myeloma (MM) cells induces heterogeneous functional responses including cell growth and proliferation, survival or apoptosis. These effects have been suggested to be partly due to increase in secretion of cytokines such as IL-6 or IFNα among others from MM cells following TLR activation. However, whether triggering of these receptors also modulates production of immunoglobulin free light chains (FLCs), which largely contribute to MM pathology, has not been investigated in MM cells before.

A clinical study exploring the prediction of microvascular invasion in hepatocellular carcinoma through the use of combined enhanced CT and MRI radiomics.

Objective: To develop a predictive model for microvascular invasion (MVI) in hepatocellular carcinoma (HCC) through radiomics analysis, integrating data from both enhanced computed tomography (CT) and magnetic resonance imaging (MRI).

Methods: A retrospective analysis was conducted on 93 HCC patients who underwent partial hepatectomy. The gold standard for MVI was based on the histopathological diagnosis of the tissue.

Fertility before and after treatment of the patient with Leydig cell tumor - case report.

Even though Leydig cell tumor (LCT) represents the most common neoplasia among testicular sex cord-stromal tumors (SCSTs), it is a rare condition, comprising 1-2% of all testicular tumors, with a 10% risk of malignancy most commonly located in retroperitoneal lymph nodes. LCTs may demonstrate various clinical manifestations - from asymptomatic intratesticular swelling through nonspecific symptoms such as loss of libido, impotence or infertility, up to feminizing or virilizing syndromes due to hormonal activity of the tumor. This article presents a case of Leydig cell tumor that was associated with azoospermia what have rarely been reported worldwide.

Immunohistochemical evaluation of SOX-10 in patients with urinary bladder cancer.

Objective: Aim: To evaluate the expression levels of SOX-10 in tissues of bladder tumor and to prove the correlation between SOX-10 expression and clinicopathological characteristics of bladder tumors, including patient age, sex, tumor grade, and muscle invasion.

Patients And Methods: Materials and Methods: Forty formalin fixed paraffin embedded FFPE tissue blocks gathered by transurethral resection of bladder tumor are collected from teaching hospitals at Al-Najaf governorate. Those blocks were stained by hematoxylin and eosin.

Phytochemical analysis of ethanolic leaf extract of Cordia myxa and its anti-Inflammatory and cytotoxic activities.

Objective: Aim: Testing Cordia myxa extract on colon cancer cell line and caspase-3 gene and COX-2 protein expression.

Patients And Methods: Materials and Methods: This study used Cordia myxa ethanolic extract at various dosages on SW480 cells. Cell proliferation was measured using MTT, also examined effect of Cordia myxa extract on caspase-3 gene expression using quantitative real-time polymerase chain reaction.

Immunohistochemical evaluation of GATA-3 in patients with urinary bladder cancer.

Objective: Aim: To analyze expression levels of GATA-3 in bladder tumor tissues and to prove a relation between expression of GATA-3 and clinicopathological characteristics of bladder tumors, including patient age, sex, tumor grade, and muscle invasion.

Patients And Methods: Materials and Methods: Forty formalin fixed paraffin embedded (FFPE) tissue blocks obtained from bladder tumor by transurethral resection are collected from teaching hospitals at Al-Najaf governorate. Those blocks are stained by using hematoxylin and eosin stain.

Deciphering the dose-dependent effects of thymoquinone on cellular proliferation and transcriptomic changes in A172 glioblastoma cells.

Glioblastoma multiforme (GBM), the most prevalent primary malignant brain tumor in adults, exhibits a dismal 6.9% five-year survival rate post-diagnosis. Thymoquinone (TQ), the most abundant bioactive compound in Nigella sativa, has been extensively researched for its anticancer properties across various human cancers.

Endogenous LRRK2 and PINK1 function in a convergent neuroprotective ciliogenesis pathway in the brain.

Mutations in Leucine-rich repeat kinase 2 (LRRK2) and PTEN-induced kinase 1 (PINK1) are associated with familial Parkinson's disease (PD). LRRK2 phosphorylates Rab guanosine triphosphatase (GTPases) within the Switch II domain while PINK1 directly phosphorylates Parkin and ubiquitin (Ub) and indirectly induces phosphorylation of a subset of Rab GTPases. Herein we have crossed LRRK2 [R1441C] mutant knock-in mice with PINK1 knock-out (KO) mice and report that loss of PINK1 does not impact endogenous LRRK2-mediated Rab phosphorylation nor do we see significant effect of mutant LRRK2 on PINK1-mediated Rab and Ub phosphorylation.

Triethylamine-mediated protonation-deprotonation unlocks dual-drug self assembly to suppress breast cancer progression and metastasis.

Carrier-free nanomedicines exhibited significant potential in elevating drug efficacy and safety for tumor management, yet their self assembly typically relied on chemical modifications of drugs or the incorporation of surfactants, thereby compromising the drug's inherent pharmacological activity. To address this challenge, we proposed a triethylamine (TEA)-mediated protonation-deprotonation strategy that enabled the adjustable-proportion self assembly of dual drugs without chemical modification, achieving nearly 100% drug loading capacity. Molecular dynamic simulations, supported by experiment evidence, elucidated the underlying self-assembly mechanism.

Suppressing APOE4-induced neural pathologies by targeting the VHL-HIF axis.

The ε4 variant of human apolipoprotein E () is a key genetic risk factor for neurodegeneration in Alzheimer's disease and elevated all-cause mortality in humans. Understanding the factors and mechanisms that can mitigate the harmful effects of has significant implications. In this study, we find that inactivating the VHL-1 (Von Hippel-Lindau) protein can suppress mortality, neural and behavioral pathologies caused by transgenic human in .

Neomorphic leukemia-derived mutations in the TET2 enzyme induce genome instability via a substrate shift from 5-methylcytosine to thymine.

Ten-eleven translocation (TET) enzymes oxidize 5-methylcytosine (mC) in DNA, contributing to the regulation of gene transcription. Diverse mutations of TET2 are frequently found in various blood cancers, yet the full scope of their functional consequences has been unexplored. Here, we report that a subset of TET2 mutations identified in leukemia patients alter the substrate specificity of TET2 from acting on mC to thymine.

Transthyretin variants impact blood-nerve barrier and neuroinflammation in amyloidotic neuropathy.

Hereditary transthyretin amyloidosis with polyneuropathy (ATTRv-PN) is a neurodegenerative disease caused by mutations in the gene encoding transthyretin (TTR). Despite amyloid deposition being pathognomonic for diagnosis, this pathology in nervous tissues cannot fully account for nerve degeneration, implying additional pathophysiology for neurodegeneration, which, however, has not yet been fully elucidated. In this study, neuroinflammation in ATTRv-PN was investigated by examining nerve morphometry, the blood-nerve barrier, and macrophage infiltration in the sural nerves of ATTRv-PN patients and the sciatic nerves of a complementary mouse system, i.

Performance analysis of a deep-learning algorithm to detect the presence of inflammation in MRI of sacroiliac joints in patients with axial spondyloarthritis.

Objectives: To assess the ability of a previously trained deep-learning algorithm to identify the presence of inflammation on MRI of sacroiliac joints (SIJ) in a large external validation set of patients with axial spondyloarthritis (axSpA).

Methods: Baseline SIJ MRI scans were collected from two prospective randomised controlled trials in patients with non-radiographic (nr-) and radiographic (r-) axSpA (RAPID-axSpA: NCT01087762 and C-OPTIMISE: NCT02505542) and were centrally evaluated by two expert readers (and adjudicator in case of disagreement) for the presence of inflammation by the 2009 Assessment of SpondyloArthritis International Society (ASAS) definition. Scans were processed by the deep-learning algorithm, blinded to clinical information and central expert readings.

Comparison of definitions of early knee osteoarthritis for likelihood of progression at 2-year and 5-year follow-up: the Multicenter Osteoarthritis Study.

Background: Preventing worsening osteoarthritis (OA) in persons with early OA is a major treatment goal. We evaluated if different early OA definitions yielded enough cases of worsening OA within 2-5 years to make trial testing treatments feasible.

Methods: We assessed different definitions of early OA using data from Multicenter Osteoarthritis (MOST) Study participants who were followed up longitudinally.