LINEs

BACKGROUND: Paclitaxel is commonly used as a second-line therapy for advanced gastric cancer (AGC). The decision to proceed with second-line chemotherapy and select an appropriate regimen is critical for vulnerable patients with AGC progressing after first-line chemotherapy. However, no predictive biomarkers exist to identify patients with AGC who would benefit from paclitaxel-based chemotherapy. METHODS: This study included 288 patients with AGC receiving second-line paclitaxel-based chemotherapy between 2017 and 2022 as part of the K-MASTER project, a nationwide government-funded precision medicine initiative...

Chimeric antigen receptor T-cell (CAR-T) therapy has significantly impacted treatment algorithms and clinical outcomes for a variety of patients with hematologic malignancies over the past decade. The field of cellular immunotherapy is currently experiencing a rapid expansion of the number of patients eligible for CAR-T therapies as approvals are being seen in earlier lines of therapy. With the expanded patients eligible for these therapies, more treatment centers will be necessary to keep up with demand. Building a cellular therapy program can be a daunting task, and therefore, we present our experience with building a clinical cellular therapy program...

OBJECTIVE: To describe persistent pulmonary abnormalities detected on HRCT after 18 months of SARS-CoV-2 pneumonia, and to determine their extension and correlation with pulmonary function. PATIENTS AND METHODS: A prospective cross-sectional study with an initial cohort of 90 patients in follow-up due to persisting lung abnormalities on imaging, functional respiratory impairment and/or respiratory symptoms. Of these, 31 (34%) were selected for analysis due to the persistence of their lung abnormalities on HRCT at 18 months after infection...

BACKGROUND: Smoking households in Indonesia diverted a significant share of their budget to tobacco. Tobacco expenditure is deemed unproductive, as it crowds out resources from essential commodities and increases health care expenditure driven by tobacco-induced diseases. Therefore, despite having adequate resources, some smoking families in Indonesia may spend less on basic needs, which inadvertently puts their standard of living below the poverty line. METHODS: Employing data from 2021 (March) Indonesia's Socioeconomic Survey (SUSENAS), this research aims to quantify the impoverishing effect of tobacco consumption in Indonesia, considering spending on tobacco and tobacco-attributable health care costs as unproductive expenditure...

Catuneragam nilotica has been used in ethnomedicine to treat snakebite, inflammation, and diarrhea among others. The aim of this research is to isolate, and characterize potential potential phospholipase A2 (PLA2 ) inhibitors from the roots of C. nilotica. The plant material was collected, authenticated, and sequentially extracted using solvents of increasing polarity starting from n-hexane, ethyl acetate, and methanol. The extracts as reported in our previous work, were screened in vitro for their inhibitory activity against PLA2 enzyme from N...

BACKGROUND AND OBJECTIVE: Painful trigeminal neuropathy is a complex clinical entity due to its severity and refractoriness to pharmacological and interventional management. We describe our experience in treating refractory painful trigeminal neuropathy (RPTN) with gasserian ganglion stimulation (GGS). MATERIALS AND METHODS: Six patients with RPTN were treated with GGS in our Unit between 2019 and 2022. The following data were collected: socio-demographic characteristics, triggering event, duration of the disease and treatment received prior to surgery, pre- and post-intervention visual analogue scale (VAS) score, follow-up time, and pre- and post-intervention functionality and quality of life...

BACKGROUND: Short- or mid-term fasting, full or partial, triggers metabolic response known to have in turn health effects in an organism. At central level, the metabolic stimulus triggered by fasting is known to be perceived firstly by hypothalamic neurons. In the field of neuroscience, ribosomal protein S6 (S6) phosphorylation is commonly used as a readout of the mammalian target of rapamycin complex 1 signalling activation or as a marker for neuronal activity. The aim of this study is addressed to evaluate whether the phosphorylation of S6 occurs in the central neurons of zebrafish exposed to four (short-term) and seven (mid-term) days of complete fasting...

OBJECTIVE: Determine if herniation morphology based on the Michigan State University (MSU) Classification is associated with differences in (1) patient-reported outcome measures (PROMs) or (2) surgical outcomes after a microdiscectomy. METHODS: Adult patients undergoing single-level microdiscectomy between 2014 - 2021 were identified. Demographics and surgical characteristics were collected through a query search and manual chart review. The MSU classification, which assesses disc herniation laterality (zone A was central, zone B/C was lateral) and degree of extrusion into the central canal (grade 1 was up to 50% of the distance to the intra-facet line, grade >1 was beyond this line), was identified on preoperative MRIs...

Mitomycin C (MC) is an anti-cancer drug which functions by forming interstrand crosslinks (ICLs) between opposing DNA strands. MC analog, 10-decarbamoyl mitomycin C (DMC), unlike MC, has stronger cytotoxic effects on cancer cells with TP53 mutation. We previously demonstrated that MC/DMC could activate p21WAF1/CIP1 in MCF-7 (TP53-proficient) and K562 (TP53 deficient) cells in a TP53-independent mode. We also found that MC/DMC regulate AKT activation in a TP53-dependent manner and that AKT deactivation is not associated with the activation of p21WAF1/CIP1 in response to MC/DMC treatment...

Signalling networks are critical for virtually all cell functions. Our current knowledge of cell signalling has been summarised in signalling pathway databases, which, while useful, are highly biassed towards well-studied processes, and do not capture context specific network wiring or pathway cross-talk. Mass spectrometry-based phosphoproteomics data can provide a more unbiased view of active cell signalling processes in a given context, however, it suffers from low signal-to-noise ratio and poor reproducibility across experiments...

Pemphigus is a severe blistering disease caused by autoantibodies primarily against the desmosomal cadherins desmoglein (DSG)1 and DSG3 which impair desmosome integrity. Especially for the acute phase, additional treatment options allowing to reduce corticosteroids would fulfill an unmet medical need. Here, we provide evidence that epidermal growth factor receptor (EGFR) inhibition by erlotinib ameliorates pemphigus vulgaris immunoglobulin G (PV-IgG) -induced acantholysis in intact human epidermis. PV-IgG caused phosphorylation of EGFR (Y845) and SRC in human epidermis...

OBJECTIVE: De Quervain's tenosynovitis causes pain and impairment of thumb function. Conservative treatments comprise corticosteroid injection and immobilization, and it is unclear which offers greater efficacy. Previous reviews were limited by the small number of included studies; thus an updated review and meta-analysis is warranted. METHODS: A systematic review of the PubMed, Embase, and Web of Science databases was conducted. Randomized control trials comparing corticosteroid injection to immobilization were included...

Copper (Cu) dyshomeostasis has been linked to obesity and related morbidities and also to aging. Cu levels are higher in older or obese individuals, and adipose tissue (AT) Cu levels correlate with body mass index. Aging and obesity induce similar AT functional and structural changes, including an accumulation of senescent cells. To study the effect of Cu-mediated stress-induced premature senescent (Cu-SIPS) on preadipocytes, 3T3-L1 cell line was exposed to a subcytotoxic concentration of copper sulfate. After Cu treatment, preadipocytes acquired typical senescence characteristics including diminished cell proliferation, cell and nuclei enlargement and increased lysosomal mass (higher Lamp2 expression and a slight increased number of cells positive for β-galactosidase associated with senescence (SA-β-Gal))...

Head and neck cancer (HNC) is the sixth most common malignancy worldwide. Although current modalities offer a wide variety of therapy choices, head and neck carcinoma has poor prognosis due to its diagnosis at later stages and development of resistance to current therapeutic tools. In the current study, we aimed at exploring the roles of miR-200c-3p during head and neck carcinogenesis and acquisition of taxol resistance. We analyzed miR-200c-3p levels in HNC clinical samples and cell lines using quantitative real-time polymerase chain reaction and evaluated the effects of differential miR-200c-3p expression on cancer-related cellular phenotypes using in-vitro tools...

BACKGROUND: histone deacetylase 6 (HDAC6) inhibitor CAY10603 has been identified as a potential therapeutic agent for the treatment of diabetic kidney disease (DKD). The objective of this study was to investigate the therapeutic effects of CAY10603 in mice with acute kidney injury (AKI) and chronic kidney diseases (CKD). METHODS: Renal immunohistology was performed to assess expression level of HDAC6 in both human and mouse kidney samples. C57BL/6J mice were intraperitoneal injected with lipopolysaccharide (LPS) to induce AKI; CD-1 mice were fed with adenine diet to induce adenine-nephropathy as CKD model...

Residence time distribution (RTD) method has been widely used in the pharmaceutical manufacturing for understanding powder dynamics within unit operations and continuous integrated manufacturing lines. The dynamics thus captured is then used to develop predictive models for unit operations and important RTD-based applications ensuring product quality assurance. Despite thorough efforts in tracer selection, data acquisition, and calibration model development to obtain tracer concentration profiles for RTD studies, there can exist significant noise in these profiles...

INTRODUCTION AND OBJECTIVES: The aim of this study is to assess the results and outcome of a series of patients with trigeminal neuralgia (TGN) and underwent gamma knife radiosurgery (GKRS). MATERIALS AND METHODS: Fifty-three patients with symptoms of typical TGN were operated from May 2012 until December 2022. Among these patients, 45 patients were included to the study, who have at least 12 months of follow-up. A mean dose of 87.5 Gy (range 80-90) was delivered to the trigeminal nerve...

KRAS plays a crucial role in regulating cell survival and proliferation and is one of the most commonly mutated oncogenes in human cancers. The novel KRASG12D inhibitor, MRTX1133, demonstrates promising antitumor efficacy in vitro and in vivo. However, the development of acquired resistance in treated patients presents a considerable challenge to sustained therapeutic effectiveness. In response to this challenge, we conducted site-specific mutagenesis screening to identify potential secondary mutations that could induce resistance to MRTX1133...

UNLABELLED: objective：The management of thyroid eye disease (TED) has undergone significant changes for decades. The study sought to investigate current clinical practice on the management of TED in China. METHODS: An online questionnaire survey was conducted from April to May 2023. The questionnaire involved diagnostic criteria for TED, multidisciplinary treatment (MDT) collaboration, and treatment preference for mild, moderate, and severe TED. RESULTS: A total of 289 questionnaires were collected, with 165 from endocrinologists and 124 from ophthalmologists...

Alveolar epithelial type I cells (AT1s) line the gas exchange barrier of the distal lung and have been historically challenging to isolate or maintain in cell culture. Here, we engineer a human in vitro AT1 model system via directed differentiation of induced pluripotent stem cells (iPSCs). We use primary adult AT1 global transcriptomes to suggest benchmarks and pathways, such as Hippo-LATS-YAP/TAZ signaling, enriched in these cells. Next, we generate iPSC-derived alveolar epithelial type II cells (AT2s) and find that nuclear YAP signaling is sufficient to promote a broad transcriptomic shift from AT2 to AT1 gene programs...