Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.

OBJECTIVES: Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions. DESIGN: Ambidirectional multisite cohort study. SETTING: Four tertiary children's hospitals. PATIENTS: Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication (p < 0.0001) and contributed to a decision to consult palliative care (p < 0.02). CONCLUSIONS: In this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.

Towards sustainable management of polyacrylamide in soil-water environment: Occurrence, degradation, and risk.

Polyacrylamide (PAM) possesses unique characteristics, including high water solubility, elevated viscosity and effective flocculation capabilities. These properties make it valuable in various sectors like agriculture, wastewater treatment, enhanced oil recovery, and mineral processing industries, contributing to a continually expanding market. Despite its widespread use globally, understanding its environmental fate at the soil-water interface remains limited. This article aims to provide an overview of the occurrence, degradation pathways, toxicity, and risks associated with PAM in the bioenvironment. The findings indicate that various degradation pathways of PAM may occur in the bioenvironment through mechanical, thermal, chemical, photocatalytic degradation, and/or biodegradation. Through a series of degradation processes, PAM initially transforms into oligomers and acrylamide (AM). Subsequently, AM may undergo biodegradation, converting into acrylic acid (AA) and other compounds such as ammonia. Notably, among these degradation intermediates, AM demonstrates high biodegradability, and the bioaccumulations of both AM and AA are not considered significant. Ensuring the sustainable use of PAM necessitates a comprehensive understanding among policymakers, scholars, and industry professionals regarding PAM, encompassing its properties, applications, degradation pathways, toxic effect on humans and the environment, and relevant regulations. Additionally, this study offers insights into future priority research directions, such as establishing of a reliable source-to-destination supply chain system, determining the maximum allowable amount for PAM in farmlands, and conducting long-term trials for the PAM-containing demolition residues.

An unusual uterine papillary serous carcinoma with post therapy disseminating metastasis presenting as primary renal malignancy: a case report.

Introduction: Uterine papillary serous carcinoma (UPSC) is a highly aggressive endometrial carcinoma that often presents as a high-stage disease. UPSC has a high propensity for metastasis and recurrence, even with little or no myometrial invasion. It usually metastasizes to the pelvis, retroperitoneal lymph nodes, upper abdomen, or peritoneum. However, renal metastasis of UPSC is extremely rare. Case presentation: The authors reported a unique UPSC case in a 75-year-old unmarried woman. Twenty years ago, she had a history of right breast cancer and underwent a modified radical mastectomy. Three years ago, she was diagnosed with endometrial carcinoma, and six courses of chemotherapy and radiotherapy were administered. Computed tomography and retrograde pyelography revealed a right renal pelvic tumor, and a right nephroureterectomy was performed. Renal metastatic UPSC was diagnosed. The patient was administered adjuvant chemotherapy. Clinical discussion: Metastatic UPSCs initially presenting at distant sites are uncommon manifestations. This tumor should be differentially diagnosed in patients presenting with metastatic high-grade serous papillary carcinoma of unknown primary origin. Conclusion: Diagnosing metastatic renal UPSC, based on preoperative and imaging examinations, is often challenging. Thus, a review of the past history, histopathology, and immunohistochemical evaluation plays a crucial and valuable role in the definite and differential diagnosis of this tumor type.

Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway.

BACKGROUND: Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity. OBJECTIVE: To explore whether IMQ could induce melanogenesis in melanoma cells. METHODS: The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not. RESULTS: We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity. CONCLUSIONS: Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

Unusually aggressive primary testicular diffuse large B-cell lymphoma initially presenting as systemic disseminating metastases in older adult men: a case report.

Primary testicular lymphoma (PTL) accounts for 1-2% of all nonHodgkin lymphomas (NHL), 4% of extranodal nonHodgkin lymphomas, and ~9% of testicular malignancies. A rare subtype of PTL is primary testicular diffuse large B-cell lymphoma (PT-DLBCL), which may initially present as disseminating metastasis in older adult males and has a poor prognosis. Case presentation: Herein, the authors describe the case of a 64-year-old man with the chief complaint of a painless unilateral scrotal mass. Computed tomography scans of the abdomen and a pelvic examination demonstrated a left testicular tumor with multiple lymphadenopathies partially aggregated in the para-aortic area and disseminated to multiple soft tissues and organs. Subsequently, the patient underwent a left radical orchiectomy. Pathological and immunohistochemical examinations confirmed the diagnosis of left PT-DLBCL with systemic disseminating metastases. Clinical discussion: PTL often aggressively spreads to other extranodal organs, such as the contralateral testis, central nervous system, lung, pleura, Waldeyer's ring, and soft tissues. In men over 60 years of age, PT-DLBCL is the most common testicular malignancy. However, extensive systemic metastasis as the initial presentation is extremely rare. PT-DLBCL has a dismal prognosis and requires radical orchiectomy followed by multimodal therapy and central nervous system prophylaxis or systemic intervention to improve survival. Conclusion: The diagnosis of PT-DLBCL through preoperative and imaging examinations is often challenging. Thus, histopathology and immunohistochemical markers play a crucial and valuable role in the definite diagnosis and differential diagnosis of PTLs.

Machine learning approaches for the optimization of packing densities in granular matter.

The fundamental question of how densely granular matter can pack and how this density depends on the shape of the constituent particles has been a longstanding scientific problem. Previous work has mainly focused on empirical approaches based on simulations or mean-field theory to investigate the effect of shape variation on the resulting packing densities, focusing on a small set of pre-defined shapes like dimers, ellipsoids, and spherocylinders. Here we discuss how machine learning methods can support the search for optimally dense packing shapes in a high-dimensional shape space. We apply dimensional reduction and regression techniques based on random forests and neural networks to find novel dense packing shapes by numerical optimization. Moreover, an investigation of the regression function in the dimensionally reduced shape representation allows us to identify directions in the packing density landscape that lead to a strongly non-monotonic variation of the packing density. The predictions obtained by machine learning are compared with packing simulations. Our approach can be more widely applied to optimize the properties of granular matter by varying the shape of its constituent particles.

Enhanced Optical Response of SnS/SnS2 Layered Heterostructure.

The SnS/SnS2 heterostructure was fabricated by the chemical vapor deposition method. The crystal structure properties of SnS2 and SnS were characterized by X-ray diffraction (XRD) pattern, Raman spectroscopy, and field emission scanning electron microscopy (FESEM). The frequency dependence photoconductivity explores its carrier kinetic decay process. The SnS/SnS2 heterostructure shows that the ratio of short time constant decay process reaches 0.729 with a time constant of 4.3 × 10-4 s. The power-dependent photoresponsivity investigates the mechanism of electron-hole pair recombination. The results indicate that the photoresponsivity of the SnS/SnS2 heterostructure has been increased to 7.31 × 10-3 A/W, representing a significant enhancement of approximately 7 times that of the individual films. The results show the optical response speed has been improved by using the SnS/SnS2 heterostructure. These results indicate an application potential of the layered SnS/SnS2 heterostructure for photodetection. This research provides valuable insights into the preparation of the heterostructure composed of SnS and SnS2, and presents an approach for designing high-performance photodetection devices.

Metal-free highly chemo-selective bisphosphorylation and deoxyphosphorylation of carboxylic acids.

Carboxylic acids are readily available in both the natural and synthetic world. Their direct utilization for preparing organophosphorus compounds would greatly benefit the development of organophosphorus chemistry. In this manuscript, we describe a novel and practical phosphorylating reaction under transition metal-free reaction conditions that can selectively convert carboxylic acids into the P-C-O-P motif-containing compounds through bisphosphorylation, and the benzyl phosphorus compounds through deoxyphosphorylation. This strategy provides a new route for carboxylic acid conversion as the alkyl source, enabling highly efficient and practical synthesis of the corresponding value-added organophosphorus compounds with high chemo-selectivity and wide substrate scope, including the late modification of complex APIs (active pharmaceutical ingredients). Moreover, this reaction also indicates a new strategy for converting carboxylic acids into alkenes by coupling this work and the subsequent WHE reaction with ketones and aldehydes. We anticipate that this new mode of transforming carboxylic acids will find wide application in chemical synthesis.

Incidental finding of multiple diffuse large B-cell lymphomas masquerading as jejunojejunal intussusception with unexplained pleural effusion: a case report.

Primary non-Hodgkin's lymphoma of the gastrointestinal (GI) tract is rare. It is aggressive and necessitates early diagnosis and management. Simultaneous primary GI lymphomas are unusual with rarely reported cases. Case presentation: This novel case report describes an 84-year-old man with multiple primary diffuse large B-cell lymphomas (DLBCLs) of the jejunum with disseminating pleural and multiple regional lymph nodes involvement presenting as intestinal obstruction and segments of jejunojejunal intussusception. The patient underwent surgical intervention and adjuvant chemotherapy. Unfortunately, the patient suffered from multiple organ failure and died 4 months after surgery. Clinical discussion: Obstruction and perforation are rare and life-threatening complications of GI lymphoma. Multiple DLBCLs of the jejunum are rare. Moreover, primary GI-DLBCL that initially presents with pleural effusion or with intestinal perforation is uncommon. This report aims to remind clinicians that lymphoma should be considered when assessing the cause of unexplained pleural effusion, especially when the available examination data cannot be confirmed by clinical manifestations. Conclusion: Through this case report, the authors learn that clinical manifestations, morphological characteristics, immunophenotypes, and molecular biological characteristics are vastly different and important. This poses the biggest challenge before surgery and should not be ignored.

Investigation of the Mechanical Properties of Quick-Strength Geopolymer Material Considering Preheated-to-Room Temperature Ratio of Sand, Na2SiO3-to-NaOH Ratio, and Fly Ash-to-GGBS Ratio.

Geopolymer concrete is a useful alternative construction material for bridge deck systems, as it is characterized by a low carbon footprint, rapid setting, quick strength development, low cost, freeze-thaw resistance, low shrinkage, and sulphate and corrosion resistance. Heat curing enhances the mechanical properties of geopolymer materials (GPM), but it is not suitable for large structures, as it affects construction activities and increases energy consumption. Therefore, this study investigated the effect of preheated sand at varying temperatures on GPM compressive strength (Cs), the influence of Na2SiO3 (sodium silicate)-to-NaOH (sodium hydroxide-10 molar concentration), and fly ash-to-granulated blast furnace slag (GGBS) ratios on the workability, setting time, and mechanical strength properties of high-performance GPM. The results indicate that a mix design with preheated sand improved the Cs of the GPM compared to sand at room temperature (25 ± 2 °C). This was caused by the heat energy increasing the kinetics of the polymerization reaction under similar curing conditions and with a similar curing period and fly ash-to-GGBS quantity. Additionally, 110 °C was shown to be the optimal preheated sand temperature in terms of enhancing the Cs of the GPM. A Cs of 52.56 MPa was achieved after three hours of hot oven curing at a constant temperature of 50 °C. GGBS in the geopolymer paste increased the mechanical and microstructure properties of the GPM as a result of different formations of crystalline calcium silicate (C-S-H) gel. The synthesis of C-S-H and amorphous gel in the Na2SiO3 (SS) and NaOH (SH) solution increased the Cs of the GPM. We conclude that a Na2SiO3-to-NaOH ratio (SS-to-SH) of 5% was optimal in terms of enhancing the Cs of the GPM for sand preheated at 110 °C. Additionally, as the quantity of ground GGBS in the geopolymer paste increased, the thermal resistance of the GPM was significantly reduced.

Whole-genome sequencing-based analyses of drug-resistant Mycobacterium tuberculosis from Taiwan.

Drug-resistant tuberculosis (DR-TB) posed challenges to global TB control. Whole-genome sequencing (WGS) is recommended for predicting drug resistance to guide DR-TB treatment and management. Nevertheless, data are lacking in Taiwan. Phenotypic drug susceptibility testing (DST) of 12 anti-TB drugs was performed for 200 Mycobacterium tuberculosis isolates. WGS was performed using the Illumina platform. Drug resistance profiles and lineages were predicted in silico using the Total Genotyping Solution for TB (TGS-TB). Using the phenotypic DST results as a reference, WGS-based prediction demonstrated high concordance rates of isoniazid (95.0%), rifampicin (RIF) (98.0%), pyrazinamide (98.5%) and fluoroquinolones (FQs) (99.5%) and 96.0% to 99.5% for second-line injectable drugs (SLIDs); whereas, lower concordance rates of ethambutol (87.5%), streptomycin (88.0%) and ethionamide (84.0%). Furthermore, minimum inhibitory concentrations confirmed that RIF rpoB S450L, FQs gyrA D94G and SLIDs rrs a1401g conferred high resistance levels. Besides, we identified lineage-associated mutations in lineage 1 (rpoB H445Y and fabG1 c-15t) and predominant lineage 2 (rpoB S450L and rpsL K43R). The WGS-based prediction of drug resistance is highly concordant with phenotypic DST results and can provide comprehensive genetic information to guide DR-TB precision therapies in Taiwan.

Osimertinib Induces the Opposite Effect of Proliferation and Migration in the Drug Resistance of EGFR-T790M Non-small Cell Lung Cancer Cells.

BACKGROUND: Lung cancer has become one of the leading causes of cancer incidence and mortality worldwide. Non-small cell lung carcinoma (NSCLC) is the most common type among all lung cancer cases. NSCLC patients contained high levels of activating epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletion, L858R and T790M. Osimertinib, a third-generation of EGFR tyrosine kinase inhibitor (EGFR-TKI), has therapeutic efficacy on the EGFR-T790M mutation of NSCLC patients; however, treatment of osimertinib still can induce drug resistance in lung cancer patients. Therefore, investigation of the drug resistance mechanisms of osimertinib will provide novel strategies for lung cancer therapy. METHODS: The H1975OR osimertinib-resistant cell line was established by prolonged exposure with osimertinib derived from the H1975 cells. The cell proliferation ability was evaluated by the cell viability and cell growth assays. The cell migration ability was determined by the Boyden chamber assays. The differential gene expression profile was analyzed by genome-wide RNA sequencing. The protein expression and location were analyzed by western blot and confocal microscopy. RESULTS: In this study, we established the osimertinib-resistant H1975 (T790M/L858R) cancer cells, named the H1975OR cell line. The cell growth ability was decreased in the H1975OR cells by comparison with the H1975 parental cells. Conversely, the cell migration ability was elevated in the H1975OR cells. We found the differential gene expression profile of cell proliferation and migration pathways between the H1975OR and H1975 parental cells. Interestingly, the protein levels of phospho-EGFR, PD-L1, E-cadherin and ß-catenin were decreased, but the survivin and N-cadherin proteins were increased in the H1975OR drug-resistant cells. CONCLUSION: Osimertinib induces the opposite effect of proliferation and migration in the drug resistance of EGFRT790M lung cancer cells. We suggest that differential gene and protein expressions in the cell proliferation and migration pathways may mediate the drug resistance of osimertinib in lung cancer cells. Understanding the molecular drugresistant mechanisms of proliferation and migration pathways of osimertinib may provide novel targets and strategies for the clinical treatment of EGFR-TKIs in lung cancer patients.

Epidemiological characteristics of elderly pulmonary tuberculosis in Xianning, Hubei Province, 2011-2021 / 中国热带医学

@#Abstract: Objective　To analyze the incidence of pulmonary tuberculosis infection in the elderly(≥ 65 years old) in Xianning City from 2011 to 2021, and to provide scientific basis for formulating strategies and measures for tuberculosis prevention and treatment in the elderly. Methods　Descriptive epidemiological analysis was used to analyze the epidemic characteristics and influencing factors of elderly (this article studies elderly people aged 65 and above) pulmonary tuberculosis in Xianning City, Hubei Province from 2011 to 2021. Results　From 2011 to 2021, the average annual registration rate of elderly patients with pulmonary tuberculosis in Xianning City, Hubei Province was 211.52/100 000 (5 289/2 500 496), which showed a downward trend （χ2 trend=58.06, P<0.05), and significantly higher than the average registration rate of 96.04/100 000 patients with pulmonary tuberculosis (26 463/27 554 195)(χ2=2 896.69, P<0.05). The average proportion of the registered number of elderly patients with pulmonary tuberculosis in the whole population was 19.99% (5 289/26 463), which showed an upward trend (χ2trend=272.05, P<0.05). The average positive rate of etiology in elderly patients with pulmonary tuberculosis was 51.86% (2 743/5 289), which was significantly higher than that in the whole population 46.41% (12 282/26 463) (χ2=52.53, P<0.05). The average proportion of retreated patients in elderly patients with pulmonary tuberculosis was 8.92% (472/5 289), which was significantly higher than that of retreated patients in the whole population 6.33% (1 674/26 463) (χ2=47.23, P<0.05). The sex ratio of male to female in elderly patients with pulmonary tuberculosis was 2.92∶1. Among the six counties (districts) under the jurisdiction of Xianning City, Hubei Province the registration rate of elderly tuberculosis patients in Xian'an district was the highest 262.20/100 000 (1 267/483 220), and that in Tongcheng County was the lowest 123.83/100 000 (575/464 338), with significant differences (χ2=233.67, P<0.05). Conclusion　The overall incidence of tuberculosis in the elderly in Xianning City , Hubei Province showed a downward trend, but the proportion of the incidence of tuberculosis in the elderly in the whole population has increased year by year, suggesting that the elderly are the key population of tuberculosis prevention and control in Xianning City in the future, and comprehensive prevention and control measures should be taken to reduce the incidence of tuberculosis in the elderly population.

High Expression of Folate Receptor Alpha (FOLR1) is Associated With Aggressive Tumor Behavior, Poor Response to Chemoradiotherapy, and Worse Survival in Rectal Cancer.

Objectives: Recently, molecular medicine targeting Folate Receptor Alpha (FOLR1), which mediates intracellular folate uptake and tumor cell proliferation, has been identified in several malignancies. However, the association between FOLR1 expression and rectal cancer remains unclear. Methods: Immunostaining of FOLR1 was performed on biopsy specimens from 172 rectal cancer patients undergoing preoperative chemoradiotherapy (CRT). FOLR1 expression was measured and divided into low (0+-2+) or high (3+-4+) level. Correlations between FOLR1 status and clinicopathologic features, tumor regression grade, disease-specific survival (DSS), local recurrence-free survival, and metastasis-free survival (MeFS) were analyzed, retrospectively. Results: High FOLR1 expression was significantly associated with advanced post-treatment tumor and nodal status (T3-4; N1-2, P = .001), vascular invasion (P = .042), perineural invasion (P = .012), and poor regression change after CRT (P = .001). In uni- and multi-variable survival analysis, FOLR1 overexpression remained a significant predictor of lower DSS (hazard ratio [HR], 2.328; 95% confidence interval [CI], 1.014-5.344; P = .046) and MeFS (HR, 2.177; 95% CI, 1.000-1.1286; P = .050). Conclusion: These results indicate that high FOLR1 status is associated with aggressive tumor behavior, poor response to CRT, and worse survival. Therefore, FOLR1 expression at initial biopsy may be useful in predicting outcomes and also be a target for the exploration of FOLR1-based therapeutic agents.

High SLC28A2 expression endows an inferior survival for rectal cancer patients managed by neoadjuvant CCRT.

For rectal cancer patients with stage T3-4 disease or positive lymph node, neoadjuvant concurrent chemoradiotherapy (CCRT) has become the standard treatment, but the clinical outcomes are still far from satisfactory. Accordingly, a more precise predictive tool such as genetic biomarkers is urgently required to optimize therapy decisions. Colorectal cancer (CRC) development has been considerably correlated with cellular metabolic process involving nucleotides, but the underlying molecular mechanisms remain unclear. In this study, we employed a transcriptome dataset comprising 46 rectal adenocarcinoma patients undergoing preoperative CCRT and focused on nucleobase-containing compound metabolic process (GO: 0055134) for data mining. We identified solute carrier family 28 member 2 (SLC28A2) as the most considerably upregulated gene among rectal cancer patients with CCRT resistance. Afterwards, there were a total of 172 rectal cancer tissue blocks procuring from our biobank, and the immunointensity of SLC28A2 was appraised utilizing immunohistochemical staining. Strong SLC28A2 immunointensity was significantly linked to female patients (p = 0.032), vascular invasion (p = 0.021), and post-CCRT tumor invasion and regional lymph node involvement (p < 0.001 and p = 0.005). Notably, patients with strong SLC28A2 immunointensity had no tumor downstaging (p < 0.001). Univariate analysis revealed that high SLC28A2 immunoexpression was considerably unfavorably linked to all three endpoints: local recurrence-free survival (LRFS), metastasis-free survival (MeFS), and disease-specific survival (DSS) (all p ≤ 0.0333). Moreover, both high SLC28A2 immunoexpression and low tumor regression grade were independently unfavorable prognostic factors for all three endpoints (all p ≤ 0.013) in the multivariate analysis. Utilizing function prediction analysis, SLC28A2 upregulation was more likely to be linked with stem cell homeostasis in rectal cancer. In brief, we demonstrated that high SLC28A2 immunoexpression is substantially linked to an advanced stage, poor response to CCRT, and worse patient survival. Consequently, SLC28A2 expression can be a valuable predictive and prognostic marker for rectal cancer patients and be an encouraging therapeutic target for those with CCRT resistance.

A rare primary pericardial DLBCL masquerading as an unexplained malignant pleural effusion in an elderly woman: A case report.

Introduction: Primary cardiac lymphoma (PCL) is an extremely rare and fatal heart neoplasm. Primary cardiac non-Hodgkin lymphoma (NHL) is uncommon, considering the rarity of pericardial diffuse large B-cell lymphoma (DLBCL) with advanced pleural metastasis. Case presentation: We reported an 86-year-old female with primary pericardial DLBCL diagnosed initially by pleural effusion cytology. The chest imaging study revealed multiple pericardial lobulated infiltrative masses and epicardial invasion. Subsequently, she underwent an emergent pericardial window with a pericardial mass biopsy. The final histopathological and immunohistochemical (IHC) stain confirmed primary pericardial DLBCL, initially showing unexplained malignant pleural effusion. Clinical discussion: The presence and extent of tumour invasion in the heart can be confirmed by echocardiography, computerised tomography (CT), or magnetic resonance imaging (MRI). However, the final histopathological diagnosis requires an examination of the endocardial, myocardial, pericardial window and biopsy or pericardial and pleural effusion cytology. This is the first case report of primary pericardial DLBCL diagnosed by metastatic malignant pleural effusion cytology per the literature review. Conclusion: The definitive diagnosis for primary pericardial DLBCL is based on effusion cytology, histopathological and IHC evaluation, and clinical characteristics and image feature correlation.

Imiquimod-induced ROS production causes lysosomal membrane permeabilization and activates caspase-8-mediated apoptosis in skin cancer cells.

BACKGROUND: Lysosomal cell death is induced by lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteolytic enzymes, including cathepsins (CTSs), which results in mitochondrial dysfunction and apoptosis. Imiquimod (IMQ), a synthetic TLR7 ligand, has both antiviral and antitumor activity against various skin malignancies in clinical treatment. Previously, we demonstrated IMQ not only caused lysosomal dysfunction but also triggered lysosome biogenesis to achieve lysosomal adaptation in cancer cells. OBJECTIVE: To determine whether lysosomes are involved in IMQ-induced apoptosis. METHODS: The human skin cancer cell lines BCC, A375 and mouse melanoma cell line B16F10 were used in all experiments. Cell death was determined by the Cell Counting Kit-8 (CCK-8) assay and DNA content assay. Protein expression was determined by immunoblotting. Caspase-8 activity was assessed using a fluorescence caspase-8 kit and determined by flow cytometry and confocal microscopy. RESULTS: IMQ not only induced lysosome damage but also abrogated lysosome function in skin cancer cells. IMQ-induced caspase-8 activation contributed to the processes of lysosomal cell death. Moreover, the use of ROS scavengers significantly abolished caspase-8 activation and inhibited IMQ-induced LMP. Additionally, pharmacological inhibition of CTSD not only abrogated caspase-8 activation but also rescued IMQ-induced cell death. Finally, lysosome-alkalizing agents enhanced the cytotoxicity of IMQ in vitro and in vivo. CONCLUSIONS: IMQ-induced ROS accumulation promotes LMP, releases CTSs into the cytosol, stimulates caspase-8 activation and finally causes lysosomal cell death. Lysosomal cell death and the CTSD/caspase-8 axis may play a crucial role in IMQ-induced cell death.

The impact of a multispecialty operative team on colorectal cancer surgery: A retrospective study from a would-be medical center in Taiwan.

Some studies showed that when distant metastasis or locally advanced tumors were observed, the participation of 2 or more operating surgeons (combined surgery) in the operation could improve the prognosis of patients. The multispecialty operative team would perform combined surgery in colon cancer patients with some complications since 2015. The goal of this study is to confirm performing combined surgery would improve the outcomes of colon cancer patients. A retrospective observational study was conducted, which involved all colon cancer patients between November 2015 and December 2019 at one would-be medical center. Patients were divided into 3 cohorts: those with complicated cases and had combined surgery (C_2S), those with complicated cases and had surgery performed by a single surgeon (C_1S), and those with uncomplicated cases and had surgery performed by a single surgeon (NC_1S). Overall survival and disease-free survival were compared among the 3 groups. A total of 296 colon cancer patients during the study period. Among them, 35 were C_2S, 87 were C_1S, and 174 were NC_1S. Patients in the NC_1S group had significantly higher 12-, 24-, and 36-month OS rates compared to those in the C_1S group (P < .01). In contrast, there was no significant difference in overall survival among patients in the NC_1S and C_2S group (P =.15). The quality of surgery must be impact the prognosis, especially in the individual who was complicated case, the survival in patients who had surgery performed by multispecialty operative team would be improved.

Experimental Prognostication of Ultra-High-Performance Lightweight Hybrid Fiber-Reinforced Concrete by Using Sintered Fly Ash Aggregate, Palm Oil Shell Aggregate, and Supplementary Cementitious Materials.

To create cost-effective structures, the modern construction industry has sought to reduce the dead load of buildings. Lightweight concrete is a quick way to reduce dead load. The current study is primarily concerned with identifying modern substitutes for coarse aggregate likely to aid in waste management and offer potential alternatives to the most exploited natural resources. According to ACI C 39-M, this study developed a novel lightweight hybrid fiber-reinforced concrete (LWHFRC) with a density of less than 1825 kg/m3 and compressive strength of 50 to 75 MPa. Ordinary Portland cement (53 Grade) was mixed with fly ash, silica fume, and GGBS. Sintered fly ash aggregate (SFA) and palm oil shell aggregate (POS) were used as coarse aggregates. Hooked steel fibers and polyvinyl alcohol fibers were combined in a hybrid form to improve crack propagation properties at the initial and subsequent stages. The water-to-binder ratio was kept constant at 0.30 to 0.35 with a 1% superplasticizer. Four volume fractions of hybrid fibers (both steel and PVA with Vf = 0%, 1%, 1.5%, and 2%) were added. In addition, XRD, SEM, EDS, and EDS mapping tests were performed to finalize the material's chemical composition and crystalline structure. Furthermore, beams and cylinders were tested to determine the modulus of rupture, which was determined to be between 9.5 and 14 MPa by ACI code C 1609-M, and indirect tensile strength, achieved as 10 to 14 MPa by ACI code C 496-M. The researcher altered the modulus of elasticity (Ec) formula for lightweight concrete and discovered a relationship between fc' and fcb, fc' and fspt, and fcb and fspt. Finally, ANOVA and regression tests were run to check the significance of the experiment. The cost analysis revealed that the cost of LWHFRC increased by approximately 16.46%, while the strength increased by 55.98% compared to regular concrete.

HwMR is a novel magnesium-associated protein.

Microbial rhodopsins (MRho) are vital proteins in Haloarchaea for solar light sensing in extreme living environments. Among them, Haloquadratum walsbyi (Hw) is a species known to survive high MgCl2 concentrations, with a total of three MRhos identified, including a high-acid-tolerance light-driven proton outward pump, HwBR, a chloride-insensitive chloride pump, HwHR, and a functionally unknown HwMR. Here, we showed that HwMR is the sole magnesium-sensitive MRho among all tested MRho proteins from Haloarchaea. We identified at least D84 as one of the key residues mediating such magnesium ion association in HwMR. Sequence analysis and molecular modeling suggested HwMR to have an extra H8 helix in the cytosolic region like those in signal-transduction-type MRho of deltarhodopsin-3 (dR-3) and Anabaena sensory rhodopsin (ASR). Further, HwMR showed a distinctly prolonged M-state formation under a high concentration of Mg2+. On the other hand, an H8 helix truncated mutant preserved photocycle kinetics like the wild type, but it led to missing M-state structure. Our findings clearly suggested not only that HwMR is a novel Mg2+-associated protein but that the association with both Mg2+ and the H8 domain stabilizes M-state formation in HwMR. We conclude that Mg2+ association and H8 are crucial in stabilizing HwMR M state, which is a well-known photoreceptor signaling state.