Perihippocampal failure after hippocampal-avoidance brain radiotherapy in small cell lung cancer patients: Cases report and literature review.

RATIONALE: Brain metastasis is a major concern, and may occur in roughly 50% of patients during the clinical course of small cell lung cancer (SCLC). Because prophylactic cranial irradiation reduces the incidence of brain metastases and improves overall survival, prophylactic cranial irradiation is recommended for SCLC patients without distant metastases or an extensive stage and have responded well to systemic therapy. Hippocampal-avoidance whole-brain radiotherapy (HA-WBRT) is preferred to preserve hippocampal function while minimizing negative cognitive effects. PATIENT CONCERNS: Reducing the dose delivered to the hippocampus below the therapeutic brain dose may increase the risk of hippocampal progression; thus, HA-WBRT may be associated with a risk of perihippocampal recurrence. DIAGNOSIS: Three patients with SCLC received HA-WBRT and developed intracranial failure during clinical follow-up; 3 relapsed with intracranial failure in the perihippocampal region after 12, 13, and 7 months, respectively. INTERVENTION AND OUTCOMES: Compared to the therapeutic brain dose of cases and the underdose region around the HA region, we matched MRI scans of intracranial failure and previous planning scans of simulation and found a deviation of the underdosed region within the perihippocampal failure of approximately 55% to 63%. LESSONS: Perihippocampal failure is a rare clinical outcome in SCLC patients following HA-WBRT. Perihippocampal failure could be caused by an underdose of radiation or by the aggressiveness of the cancer itself. More research into this topic is encouraged.

PGC-1α drives small cell neuroendocrine cancer progression towards an ASCL1-expressing subtype with increased mitochondrial capacity.

Adenocarcinomas from multiple tissues can converge to treatment-resistant small cell neuroendocrine (SCN) cancers comprised of ASCL1, POU2F3, NEUROD1, and YAP1 subtypes. We investigated how mitochondrial metabolism influences SCN cancer (SCNC) progression. Extensive bioinformatics analyses encompassing thousands of patient tumors and human cancer cell lines uncovered enhanced expression of PGC-1α, a potent regulator of mitochondrial oxidative phosphorylation (OXPHOS), across several SCNC types. PGC-1α correlated tightly with increased expression of the lineage marker ASCL1 through a positive feedback mechanism. Analyses using a human prostate tissue-based SCN transformation system showed that the ASCL1 subtype has heightened PGC-1α expression and OXPHOS activity. PGC-1α inhibition diminished OXPHOS, reduced SCNC cell proliferation, and blocked SCN prostate tumor formation. PGC-1α overexpression enhanced OXPHOS, tripled the SCN prostate tumor formation rate, and promoted commitment to the ASCL1 lineage. These findings reveal the metabolic heterogeneity among SCNC subtypes and identify PGC-1α-induced OXPHOS as a regulator of SCNC lineage plasticity.

Temporal evolution reveals bifurcated lineages in aggressive neuroendocrine small cell prostate cancer trans-differentiation.

Trans-differentiation from an adenocarcinoma to a small cell neuroendocrine state is associated with therapy resistance in multiple cancer types. To gain insight into the underlying molecular events of the trans-differentiation, we perform a multi-omics time course analysis of a pan-small cell neuroendocrine cancer model (termed PARCB), a forward genetic transformation using human prostate basal cells and identify a shared developmental, arc-like, and entropy-high trajectory among all transformation model replicates. Further mapping with single cell resolution reveals two distinct lineages defined by mutually exclusive expression of ASCL1 or ASCL2. Temporal regulation by groups of transcription factors across developmental stages reveals that cellular reprogramming precedes the induction of neuronal programs. TFAP4 and ASCL1/2 feedback are identified as potential regulators of ASCL1 and ASCL2 expression. Our study provides temporal transcriptional patterns and uncovers pan-tissue parallels between prostate and lung cancers, as well as connections to normal neuroendocrine cell states.

Association between children's home-schooling and parental psychological distress during the COVID-19 pandemic in Taiwan: Risk and protective factors in a multilevel approach.

BACKGROUND: The role home-schooling of children in parental mental health during the COVID-19 pandemic in Taiwan remains unknown. This study aimed to assess the association between parental psychological distress and home-schooling in a socio-ecological context during the peak of the first wave of the COVID-19 pandemic in Taiwan. METHODS: This was a prospective cohort study. In total, 902 parents (father: n = 206, mother: n = 696) who home-schooled children under 18 years of age were recruited by purposive sampling from 17 cities in Taiwan. Data were collected between 19 July and 30 September 2021 through a survey. Multilevel regression models were used to examine the association between parents' psychological distress and home-schooling considering the characteristics at the person and city levels. RESULTS: Parental psychological distress was positively associated with difficulty in setting up electronic devices and increased disputes between parents and children, and it was negatively associated with time management and increased time spent bonding with their children during home-schooling (Ps < 0.05). Parents who had a child with health conditions, lived in an extended family, worked from home, lived during the Level 3 alert level, and lived with a median/sporadic level of the COVID-19 community spread by city also reported greater psychological distress (Ps < 0.05). However, parents who had greater household family support reported less psychological distress (P < .05). CONCLUSIONS: Clinicians and policy makers must carefully consider parental mental health while home-schooling during the COVID-19 pandemic in a broader socio-ecological context. A focus is advised on the home-schooling experiences of parents and other risk and protective factors for parental psychological distress at the person and city levels, especially for those with children who require medical interventions and have a medical condition.

Urinary microRNA in Diabetic Kidney Disease: A Literature Review.

Diabetic kidney disease is the most common primary disease of end-stage kidney disease globally; however, a sensitive and accurate biomarker to predict this disease remains awaited. microRNAs are endogenous single-stranded noncoding RNAs that have intervened in different post-transcriptional regulations of various cellular biological functions. Previous literatures have reported its potential role in the pathophysiology of diabetic kidney disease, including regulation of Transforming Growth Factor-ß1-mediated fibrosis, extracellular matrix and cell adhesion proteins, cellular hypertrophy, growth factor, cytokine production, and redox system activation. Urinary microRNAs have emerged as a novel, non-invasive liquid biopsy for disease diagnosis. In this review, we describe the available experimental and clinical evidence of urinary microRNA in the context of diabetic kidney disease and discuss the future application of microRNA in routine practice.

MicroRNA-based signature for diagnosis and prognosis of colorectal cancer using residuum of fecal immunochemical test.

BACKGROUND: Colorectal cancer (CRC) is still among the most lethal and prevalent malignancies in the world. Despite continuous efforts, the diagnosis and prognosis of CRC have never been satisfying, especially the non-invasive assays. METHODS: Our study comprised three independent cohorts of 835 qualified stool samples. From 46 literature-identified miRNA candidates, four miRNA ratios were selected and developed into a miRNA-based signature after applied to the training and test sets. The clinical performances of this signature were further evaluated in the prospective cohorts. RESULTS: Four miRNA ratios with significant alterations and the highest discriminating power between the CRC and control groups in the training set were successfully validated in the test set. In the training dataset, combining these four miRNA ratios using a logistic regression model improved the area under the curve value to 0.821 and obtained a sensitivity of 73.6% and specificity of 78.9%. This miRNA signature showed consistent performances in the other two sample cohorts, with the highest sensitivity of 85.7% in the prospective cohort. Additionally, the higher miRNA signature was associated with worse disease-free survival (hazard ratio = 2.27) and overall survival (hazard ratio = 1.83) of CRC patients. For fecal immunochemical test (FIT)-positive populations, the positive predictive value for CRC detection in miRNA-positive subjects was 3.43-fold higher in the prospective cohort, compared to FIT alone. CONCLUSION: This stool miRNA signature is highly associated with poor outcome of CRC and can be added to FIT tests to help identify the most at-risk group to receive prompt colonoscopy examination.

Treatment outcomes of primary surgery versus chemoradiotherapy for T4 oropharyngeal cancers.

Concurrent chemoradiotherapy (CCRT) has been the standard of care for locally advanced diseases regardless of human papillomavirus infection status. Other treatment options include surgery followed by adjuvant therapy and induction chemotherapy followed by CCRT or radiotherapy. However, for locally advanced T4 laryngeal or hypopharyngeal diseases, surgery is preferred over CCRT. Given the improvement in the functional outcomes of surgery, examining the oncologic outcomes in OPSCC patients is critical. This study aimed to determine whether differences in overall survival (OS) exist between surgery and CCRT. Oropharyngeal cancer patients included in the cancer registry of our hospital from January 2014 to December 2018 were retrospectively analyzed. Patients with T4 disease who underwent curative treatment were identified. In this study, the primary and secondary outcomes were OS and disease-free survival (DFS), respectively. Potential confounding factors were also evaluated. Details regarding recurrence pattern were listed. From 2014 to 2018, 74 newly diagnosed oropharyngeal cancer patients were identified from our cancer registry database, 60 of whom satisfied our inclusion criteria. Our findings showed an OS of 25.5 months and DFS of 17.5 months. No significant difference in both of OS and DFS were observed between the surgery and CCRT cohorts. Sex, stage, second primary cancer, IC, and primary treatment were not correlated with DFS. Male sex was the only significant factor identified, with an HR of 0.2 for OS (95% confidence interval, 0.06-0.71). No significant difference in both OS and DFS were observed between the CCRT and surgery cohorts. CCRT remains the standard of care for locally advanced disease.

Hydrogel Arrays Enable Increased Throughput for Screening Effects of Matrix Components and Therapeutics in 3D Tumor Models.

Cell-matrix interactions mediate complex physiological processes through biochemical, mechanical, and geometrical cues, influencing pathological changes and therapeutic responses. Accounting for matrix effects earlier in the drug development pipeline is expected to increase the likelihood of clinical success of novel therapeutics. Biomaterial-based strategies recapitulating specific tissue microenvironments in 3D cell culture exist but integrating these with the 2D culture methods primarily used for drug screening has been challenging. Thus, the protocol presented here details the development of methods for 3D culture within miniaturized biomaterial matrices in a multi-well plate format to facilitate integration with existing drug screening pipelines and conventional assays for cell viability. Since the matrix features critical for preserving clinically relevant phenotypes in cultured cells are expected to be highly tissue- and disease-specific, combinatorial screening of matrix parameters will be necessary to identify appropriate conditions for specific applications. The methods described here use a miniaturized culture format to assess cancer cell responses to orthogonal variation of matrix mechanics and ligand presentation. Specifically, this study demonstrates the use of this platform to investigate the effects of matrix parameters on the responses of patient-derived glioblastoma (GBM) cells to chemotherapy.

Physical and in silico immunopeptidomic profiling of a cancer antigen prostatic acid phosphatase reveals targets enabling TCR isolation.

Tissue-specific antigens can serve as targets for adoptive T cell transfer-based cancer immunotherapy. Recognition of tumor by T cells is mediated by interaction between peptide-major histocompatibility complexes (pMHCs) and T cell receptors (TCRs). Revealing the identity of peptides bound to MHC is critical in discovering cognate TCRs and predicting potential toxicity. We performed multimodal immunopeptidomic analyses for human prostatic acid phosphatase (PAP), a well-recognized tissue antigen. Three physical methods, including mild acid elution, coimmunoprecipitation, and secreted MHC precipitation, were used to capture a thorough signature of PAP on HLA-A*02:01. Eleven PAP peptides that are potentially A*02:01-restricted were identified, including five predicted strong binders by NetMHCpan 4.0. Peripheral blood mononuclear cells (PBMCs) from more than 20 healthy donors were screened with the PAP peptides. Seven cognate TCRs were isolated which can recognize three distinct epitopes when expressed in PBMCs. One TCR shows reactivity toward cell lines expressing both full-length PAP and HLA-A*02:01. Our results show that a combined multimodal immunopeptidomic approach is productive in revealing target peptides and defining the cloned TCR sequences reactive with prostatic acid phosphatase epitopes.

Perihippocampal failure after hippocampal-avoidance whole-brain radiotherapy in cancer patients with brain metastases: Results of a retrospective analysis.

ABSTRACT: Perihippocampal failure is a rare clinical scenario in brain metastatic cancer patients following hippocampal-avoidance (HA) whole-brain radiotherapy (HA-WBRT). The clinical features have not been fully identified because clinical data on intracranial failure after HA-WBRT are limited. It is thus necessary to accumulate clinical data.We retrospectively analyzed cancer patients with brain metastases who were diagnosed between January 2014 and September 2020 at a regional referral hospital. The medical records of patients who underwent HA-WBRT were reviewed. The clinical features of intracranial recurrence were described. Dosimetry parameters were compared in terms of deviation from the recommended protocol of the Radiation Therapy Oncology Report 0933.Twenty-four eligible patients with brain metastases who underwent HA-WBRT were identified; 13 (54%) were male. Seventeen patients (71%) had lung cancer, 6 (25%) had breast cancer, and 1 (4%) had liver cancer. The median overall survival was 12 months. Three patients developed intracranial failure during clinical follow-up, and 2 relapsed with intracranial failure in the perihippocampal region at 13 and 22 months, respectively. The perihippocampal failure rate was about 8%. One patient with small cell lung cancer received HA-prophylactic cranial irradiation; the minimum and maximum doses to the hippocampi were 6.8 and 10.7 Gy, respectively. Another patient with brain metastases from lung adenocarcinoma received HA-WBRT; the minimum and maximum doses to the hippocampi were 5.4 and 10.6 Gy, respectively.We reported unusual cases of intracranial failure in the perihippocampal region following HA-WBRT. Perihippocampal failure could be attributed to an under-dose of radiation partially or be resulted from aggressiveness of cancer per se. Further research on this topic is encouraged.

Serum microRNA panels predict bariatric surgery outcomes.

OBJECTIVE: The weight losses after bariatric surgery are modulated by multiple factors in people with obesity. MicroRNAs (miRNAs) have been reported to show significant regulatory roles in adipose tissue. However, a serum miRNA signature to serve as a biomarker of sustained weight losses following bariatric surgery has not yet been established. METHODS: MiRNA microarray was used to identify differentially expressed miRNAs in the serum of patients with an effective response after bariatric surgery compared with those without. Excess weight loss > 55% at 6 months after surgery was defined as an effective response. RESULTS: Three miRNAs were shown to have a significantly differential expression between patients with or without an effective response following bariatric surgery. The miR-31-5p was downregulated, whereas miR-328-3p and miR-181a-5p were upregulated in the patients with effective responses compared with those without effective responses. Panels of the serum ratios of miR-328-3p/miR-31-5p or miR-181a-5p/miR-31-5p and individual BMI value exhibited good performance in preoperative prediction of treatment effectiveness. Bioinformatic analysis depicted that predicted targets of these miRNAs were involved in the regulation of the AMP-activated protein kinase signaling pathway. CONCLUSIONS: A circulating miRNA signature with clinical variables (BMI) can be a clinical biomarker to predict effectiveness following bariatric surgery.

Pathogenic Germline Mutations of DNA Repair Pathway Components in Early-Onset Sporadic Colorectal Polyp and Cancer Patients.

Given recent increases in the proportion of early-onset colorectal cancer (CRC), researchers are urgently working to establish a multi-gene screening test for both inherited and sporadic cancer-susceptible individuals. However, the incidence and spectrum of germline mutations in young sporadic CRC patients in East Asian countries and, especially, in sporadic polyp carriers and normal individuals are unknown. Peripheral blood samples were collected from 43 colonoscopy-proved normal controls and from 50 polyp patients and 49 CRC patients with no self-reported family history of cancer. All participants were under 50 years old. Next-generation sequencing with a panel of 30 CRC-associated susceptibility genes was employed to detect pathogenic germline mutations. The germline mutation carrier rates were 2.3%, 4.0%, and 12.2% in the normal, polyp, and cancer groups, respectively. A total of seven different mutations in six DNA repair pathway-related genes (MLH1, BRCA1, BRCA2, CHEK2, BLM, and NTHL1) were detected in nine participants. One frameshift mutation in BRCA2 and one frameshift mutation in the CHEK2 gene were found in a normal control and two colorectal polyp patients, respectively. One young sporadic CRC patient carried two heterozygous mutations, one in MLH1 and one in BRCA1. Three mutations (MLH1 p.Arg265Cys, MLH1 p.Tyr343Ter and CHEK2 p.Ile158TyrfsTer10) were each found in two independent patients and were considered "founder" mutations. This is the first report to demonstrate high percentage of germline mutations in young sporadic colorectal polyp, CRC, and general populations. A multi-gene screening test is warranted for the proactive identification of cancer-predisposed individuals.

Induction Chemotherapy Improved Long Term Outcomes in Stage IV Locoregional Advanced Nasopharyngeal Carcinoma.

Purpose: We aimed to determine whether adding induction chemotherapy (IC) to concurrent chemoradiation (CCRT) improved outcomes in each stage of locally advanced nasopharyngeal carcinoma (LANPC). Methods: From 2007 to 2013, we retrospectively collected 259 histopathologically identified adult LANPC patients from two campuses in south Taiwan. Among the 238 eligibly treated cases, 156 patients received CCRT (CCRT group) upfront and 82 received IC followed by CCRT (IC group). Of these patients, 130 were stage III (92 patients that received CCRT and 38 that received IC adding CCRT) and 108 were stage IV (76 CCRT and 32 IC adding CCRT). Most chemotherapy regimens for IC are composed of cisplatin (P), 5-fluorouracil (F), and ifosfamide (I), while concurrent chemotherapy (CC) was essentially cisplatin-based. For CCRT as the upfront treatment, a P or PF regimen was usually used in CC. Survival outcomes were accessed with a Kaplan-Meier estimate and a p-value by log-rank test to compare the survival distributions of IC added to CCRT or CCRT as the upfront treatment in all LANPC stage III and LANPC IV patients. The failure free survival (FFS), overall survival (OS), local relapse free survival (LRFS), regional recurrence-free survival (RRFS), distant metastasis-free survival (DMFS), first failure site, and other prognostic factors were analyzed. Results: The median follow-up time of all treated LANPC patients was 59 months. For all LANPC patients, there was a significant difference only in the DMFS favoring IC group (91.5% vs 79.4%, p=0.013). In the subgroup study, for the stage III group, there was no significant difference between the groups for overall OS (IC group 71.3% vs CCRT group 78.7%), FFS (71.5% vs 62.4%) and RRFS (91.9% vs 90.9%). However, inferior LRLS (71.7% vs 91.5%; p = 0.03) was noted for the IC group. In contrast, for stage IV, there were significantly longer OS (75.8% vs 52.6%), FFS (66.8% vs 46.8%), and DMFS (86.0% vs 69.6%; p = 0.02, p = 0.04, and p = 0.03, respectively) rates in the IC group. Conclusion: Adding PIF-based IC to CCRT for the LANPC patients resulted in better outcomes for stage IV patients, but not for stage III patients. A future properly designed study should stratify enough LANPC cases under the structure of the AJCC stage grouping system to determine which subgroups truly benefit from adding IC to CCRT.

A circulating miRNA signature for early diagnosis of acute kidney injury following acute myocardial infarction.

BACKGROUND: Acute kidney injury (AKI) is a common complication of acute myocardial infarction (AMI), and is associated with adverse outcomes. The study aimed to identify a miRNA signature for the early diagnosis of post-AMI AKI. METHODS: A total of 108 patients admitted to a coronary care unit (CCU) were divided into four subgroups: AMI-AKI-, AMI+AKI-, AMI+AKI+, and AMI-AKI+. Thirty-six miRNA candidates were selected based on an extensive literature review. Real-time quantitative RT-PCR analysis was used to determine the expression levels of these miRNAs in the serum collected on the day of CCU admittance. TargetScan 7.1 and miRDB databases were used for target prediction and Metacore 6.13 was used for pathway analysis. RESULTS: Through a stepwise selection based on abundance, hemolytic effect and differential expression between four groups, 9 miRNAs were found to have significantly differential expression levels as potential biomarkers for post-AMI AKI specifically. Noticeably, the expression levels of miR-24, miR-23a and miR-145 were significantly down-regulated in AMI+AKI+ patients compared to those in AMI+AKI- patients. Combination of the three miRNAs as a panel showed the best performance in the early detection of AKI following AMI (AUC = 0.853, sensitivity 95.65%), compared to the analysis of serum neutrophil gelatinase-associated lipocalin (AUC = 0.735, sensitivity 63.16%). Furthermore, bioinformatic analysis indicated that these three miRNAs regulate the transforming growth factor beta signaling pathway and involve in apoptosis and fibrosis in AKI. CONCLUSIONS: For the first time, this study identify a unique circulating miRNA signature (miR-24-3p, miR-23a-3p, miR-145-5p) that can potentially early detect AKI following AMI and may be involved in renal injury and fibrosis in post-AMI AKI pathogenesis.

A case of palatine tonsillar metastasis of lung adenocarcinoma: A CARE-compliant article.

RATIONALE: Palatine tonsil is an extremely rare site for metastatic disease, accounting for 0.8% of malignant tonsillar neoplasms. To the best of our knowledge, this is the first report of metastatic adenocarcinoma in the tonsil treated with wide excision and targeted therapy, with no local recurrence 6 months postoperatively. PATIENT CONCERNS: A 75-year-old man presented hemoptysis and mild productive cough for 2 weeks. DIAGNOSES: Palatine tonsil metastasis from lung adenocarcinoma, pT2bN0M1b, stage IVA, was confirmed. INTERVENTIONS: Wide excision of primary lung tumor and metastatic tonsil carcinoma has been performed, and the patient was undergoing targeted therapy with the epidermal growth factor receptor inhibitor afatinib. OUTCOMES: There was no local recurrence in the oropharynx 6 months postoperatively. LESSONS: We aim at highlighting the importance of a thorough evaluation for suspicion of tonsillar enlargement, which might be a sign of a primary malignancy elsewhere.

A Simple and Highly Specific MassARRAY-Based Stool DNA Assay to Prioritize Follow-up Decisions in Fecal Immunochemical Test-Positive Individuals.

BACKGROUND: Seventy-five percent of fecal immunochemical test (FIT)-positive individuals are false positives and undergo unnecessary colonoscopies. Here, we established a stool DNA (sDNA) test that uses the Single Allele Base Extension Reaction (SABER) MassARRAY platform to improve the accuracy of FIT-based CRC detection. METHODS: Twenty-one variants in five CRC-associated genes were selected for the sDNA panel. Cell line DNA and matched mutation-confirmed tissue and stool samples from 34 patients were used for accuracy assessment (cohort 1). The clinical performance of the sDNA assay was further evaluated in 101 independent FIT-positive stool samples (cohort 2). RESULTS: In cohort 1, we obtained a 62% mutation concordance rate in paired tissue and stool samples of the CRC group, regardless of the FIT status. In cohort 2, 100% specificity in normal controls with positive FIT results was observed. By weighting the FIT value and the presence of a given variant type in stool and then summing the two scores, we found that a one-increment increase in the score was associated with a 4.538-fold risk (95% CI = 2.121⁻9.309) for malignancy in the FIT-positive setting. CONCLUSIONS: Our highly specific sDNA assay can help prioritize the most at-risk FIT-positive persons to receive prompt colonoscopic confirmation of CRC.

Quantitative Analysis of Glucose Metabolic Cleavage in Glucose Transporters Overexpressed Cancer Cells by Target-Specific Fluorescent Gold Nanoclusters.

The glucose metabolism rate in cancer cells is a crucial piece of information for the cancer aggressiveness. A feasible method to monitor processes of oncogenic mutations has been demonstrated in this work. The fluorescent gold nanoclusters conjugated with glucose (glucose-AuNCs) were successfully synthesized as a cancer-targeting probe for glucose transporters (Gluts) overexpressed by U-87 MG cancer cells, which can be observed under confocal microscopy. The structural and optical characterizations of fluorescent glucose-AuNCs were confirmed by transmission electron microscope (TEM) and Fourier transform infrared spectroscopy (FTIR). The MTT assay exhibited the high biocompatibility of water-soluble glucose-AuNCs for further biomedical applications. The glucose metabolic cleavage of glucose-AuNCs by glycolytic enzymes from U-87 MG cancer cell was measured by fluorescence change of glucose-AuNCs. The fluorescence change based on the integrated area under fluorescence spectra ( A t) of glucose-AuNCs was plotted as a function of different reaction time ( t) with glycolytic enzymes. The fitted curve of A t versus t showed the first-order kinetics to explain the mechanism of glucose metabolic cleavage rate of glucose-AuNCs by glycolytic enzymes. The rate constant k could be utilized to determine the glucose metabolism rate of glucose-AuNCs for the quantitative analysis of cancer aggressiveness. Our work provides a practical application of target-specific glucose-AuNCs as a fluorescence probe to analyze the glucose metabolism in Gluts overexpressed cancer cells.

Improving Hydrogen Evolution Activity of Earth-Abundant Cobalt-Doped Iron Pyrite Catalysts by Surface Modification with Phosphide.

Hydrogen is considered as sustainable and environmentally friendly energy for global energy demands in the future. Here a Co-FeS2 catalyst with surface phosphide doping (P/Co-FeS2 ) for hydrogen evolution reaction (HER) in acidic solutions is developed. The P/Co-FeS2 exhibits superior HER electrochemical performance with overpotential of -90 mV at 100 mA cm-2 and Tafel slope of 41 mV/decade and excellent durability.

Saliva protein biomarkers to detect oral squamous cell carcinoma in a high-risk population in Taiwan.

Most cases of oral squamous cell carcinoma (OSCC) develop from visible oral potentially malignant disorders (OPMDs). The latter exhibit heterogeneous subtypes with different transformation potentials, complicating the early detection of OSCC during routine visual oral cancer screenings. To develop clinically applicable biomarkers, we collected saliva samples from 96 healthy controls, 103 low-risk OPMDs, 130 high-risk OPMDs, and 131 OSCC subjects. These individuals were enrolled in Taiwan's Oral Cancer Screening Program. We identified 302 protein biomarkers reported in the literature and/or through in-house studies and prioritized 49 proteins for quantification in the saliva samples using multiple reaction monitoring-MS. Twenty-eight proteins were successfully quantified with high confidence. The quantification data from non-OSCC subjects (healthy controls + low-risk OPMDs) and OSCC subjects in the training set were subjected to classification and regression tree analyses, through which we generated a four-protein panel consisting of MMP1, KNG1, ANXA2, and HSPA5. A risk-score scheme was established, and the panel showed high sensitivity (87.5%) and specificity (80.5%) in the test set to distinguish OSCC samples from non-OSCC samples. The risk score >0.4 detected 84% (42/50) of the stage I OSCCs and a significant portion (42%) of the high-risk OPMDs. Moreover, among 88 high-risk OPMD patients with available follow-up results, 18 developed OSCC within 5 y; of them, 77.8% (14/18) had risk scores >0.4. Our four-protein panel may therefore offer a clinically effective tool for detecting OSCC and monitoring high-risk OPMDs through a readily available biofluid.