Effectiveness-implementation hybrid trial of Spanish language, digital cognitive-behavioral therapy (dCBT) intervention for depression and anxiety - protocol for the SUPERA (SUpport from PEeRs to expand Access) study.

BACKGROUND: Limited English Proficiency (LEP) Latinxs experience a longer duration of untreated depression and anxiety. LEP Latinxs have difficulty accessing mental healthcare due to insufficient Spanish-speaking behavioral/mental health clinicians to meet demand. These under-resourced healthcare systems are less likely to be the site for the implementation of innovations. Digital interventions can provide an effective option for overcoming these barriers; yet, when digital evidence-based treatments are available, uptake and engagement is often low. This manuscript presents the protocol for the SUPERA (SUpport from PEeRs to expand Access) study which will evaluate the implementation of an evidence-based, Spanish language, digital cognitive-behavioral therapy (dCBT) intervention (i.e., SilverCloud) in safety-net primary care clinics for LEP Latinx patients with depression or anxiety. METHODS: We will conduct an effectiveness-implementation hybrid trial (Type 2) design comparing engagement and clinical outcomes in two modalities of dCBT delivery (peer-supported vs. unsupported). We will also compare provider-level outreach (using a clinic patient registry) versus inreach (traditional provider referral) to compare rates of initiation, completion, and cost. Participants will be 426 LEP Latinx adults ≥18 years of age, PHQ-9 ≥ 10 or GAD-7 ≥ 8, with access to the internet via smartphone, and not currently receiving individual psychotherapy. We will collect baseline, post-intervention (8 weeks), and follow up (3 months) data. CONCLUSION: The long-term goal of this research is to aid in the implementation of digital mental health interventions that can be sustainably implemented in low-resourced settings, while reducing the reliance on professionals, overcoming workforce deficits, and increasing relevance for diverse populations.

Inhibition of extracellular vesicle-derived miR-146a-5p decreases progression of melanoma brain metastasis via Notch pathway dysregulation in astrocytes.

Melanoma has the highest propensity of all cancers to metastasize to the brain with a large percentage of late-stage patients developing metastases in the central nervous system (CNS). It is well known that metastasis establishment, cell survival, and progression are affected by tumour-host cell interactions where changes in the host cellular compartments likely play an important role. In this context, miRNAs transferred by tumour derived extracellular vesicles (EVs) have previously been shown to create a favourable tumour microenvironment. Here, we show that miR-146a-5p is highly expressed in human melanoma brain metastasis (MBM) EVs, both in MBM cell lines as well as in biopsies, thereby modulating the brain metastatic niche. Mechanistically, miR-146a-5p was transferred to astrocytes via EV delivery and inhibited NUMB in the Notch signalling pathway. This resulted in activation of tumour-promoting cytokines (IL-6, IL-8, MCP-1 and CXCL1). Brain metastases were significantly reduced following miR-146a-5p knockdown. Corroborating these findings, miR-146a-5p inhibition led to a reduction of IL-6, IL-8, MCP-1 and CXCL1 in astrocytes. Following molecular docking analysis, deserpidine was identified as a functional miR-146a-5p inhibitor, both in vitro and in vivo. Our results highlight the pro-metastatic function of miR-146a-5p in EVs and identifies deserpidine for targeted adjuvant treatment.

Case of Esophageal Actinomycosis Occurred after Endoscopic Mucosal Resection for Subepithelial Tumor.

Esophageal actinomycosis is a rare, chronic granulomatous disease caused by Actinomyces species. Endoscopy and biopsy are essential for making a diagnosis. This paper reports a case of esophageal actinomycosis that developed after an endoscopic mucosal resection (EMR) for a subepithelial tumor (SET). A 74-year-old male patient had a 3 cm flat, smooth elevation in the esophagus without symptoms. The SET was partially resected, and histology revealed "nonspecific degenerated mesenchymal tissue". Three months later, the patient exhibited a persistently large ulceration at the EMR site, and a biopsy revealed actinomycosis. CT of the chest and abdomen revealed no abnormal findings. Ampicillin treatment was administered for six months, and the ulceration on the esophageal SET improved.

Selective detection of HBV pre-genomic RNA in chronic hepatitis B patients using a novel RT-PCR assay.

In chronic hepatitis B (CHB) patients, quantification of HBV pgRNA in plasma has the potential to provide information on disease prognosis and liver injury or histopathology. However, current methods for detecting HBV pgRNA present technical difficulties due to the co-existence of HBV DNA in plasma samples. We have successfully established a novel one-step RT-PCR assay that allows selective quantification of HBV pgRNA. Two cohorts of participants were recruited for assay validation, including treatment-naïve patients with CHB and HBeAg-positive CHB patients who were treated with Tenofovir and monitored for 6 months to assess the predictive value of baseline HBV RNA for HBeAg seroclearance. Statistical analysis was performed using MedCalc version 20.019 software. The novel selective one-step RT-PCR assay for detecting HBV pgRNA was validated with a limit of detection of 100 copies/mL. The assay was able to selectively measure HBV pgRNA even in the presence of excess HBV rcDNA. In treatment-naïve CHB patients, HBV pgRNA levels were significantly lower than HBV DNA concentration. Serum HBV DNA levels and HBeAg status were positively associated with HBV pgRNA. Baseline serum HBV pgRNA levels were found to be strong predictors of HBeAg seroclearance after 6 months of Tenofovir treatment. The study presents a novel RT-PCR assay that allows accurate measurement of plasma HBV pgRNA in chronic hepatitis B patients, even in the presence of excess HBV DNA. The assay is highly selective and represents a significant advancement with potential for further breakthroughs in understanding the clinical significance of HBV pgRNA.

Typhoid fever, complicated by syncope due to relative bradycardia: A case report.

In a United Nations (UN) staff member headquarters in South Sudan, we present a rare typhoid fever complicated by syncope due to relative bradycardia. A 25-year-old male presented to our hospital with a high fever, diarrhea, and no vomiting. He had no substantial medical background. He was diagnosed with an unspecified digestive disorder and received initial treatment. Two syncope episodes were recorded in the Level 1 hospital. He was referred to our hospital at the 30th hour and the third fainting occurred. Electrocardiogram showed bradycardia with a heart rate of 40 beats/min. The atropine test was negative; the initial diagnosis was sinus sickness syndrome. Microbiology tests later suggested typhoid infection. Then, the diagnosis changed to relative bradycardia caused by Salmonella typhi; and he was orally treated with the third-generation Quinolone antibiotic. He significantly improved and got discharged on the seventh day. In conclusion, typhoid remains a real and present threat to UN staff and civilians in South Sudan.

CCT196969 effectively inhibits growth and survival of melanoma brain metastasis cells.

Melanomas frequently metastasize to the brain. Despite recent progress in the treatment of melanoma brain metastasis, therapy resistance and relapse of disease remain unsolved challenges. CCT196969 is a SRC family kinase (SFK) and Raf proto-oncogene, serine/threonine kinase (RAF) inhibitor with documented effects in primary melanoma cell lines in vitro and in vivo. Using in vitro cell line assays, we studied the effects of CCT196969 in multiple melanoma brain metastasis cell lines. The drug effectively inhibited proliferation, migration, and survival in all examined cell lines, with viability IC50 doses in the range of 0.18-2.6 µM. Western blot analysis showed decreased expression of p-ERK, p-MEK, p-STAT3 and STAT3 upon CCT196969 treatment. Furthermore, CCT196969 inhibited viability in two B-Raf Proto-Oncogene (BRAF) inhibitor resistant metastatic melanoma cell lines. Further in vivo studies should be performed to determine the treatment potential of CCT196969 in patients with treatment-naïve and resistant melanoma brain metastasis.

Community-based Interventions to Prevent Dental Caries among Kindergarten Children in Vietnam: A 12-month Study of Field Trial.

AIM: To investigate the status of dental caries and assess the effectiveness of dental caries prevention interventions in children from 3 to 5-year-old in Hue City, Vietnam. MATERIALS AND METHODS: The subjects were 464 children and their direct caregivers at some kindergartens in Hue City from June 2020 to October 2021. The study included two consecutive phases: the first one was a cross-sectional study to identify the rate of dental caries and related factors in the studied kindergartens, and phase 2 was a controlled comparative interventional study for a period of 12 months. RESULTS: The mean of decayed, missing, filled, and DMFT index was 8.25, 0.09, 0.48, and 8.82, respectively, with no statistically significant difference in these figures between the living areas. The multivariable logistic regression model revealed some factors related to dental caries, including age, frequency of toothbrushing per day, parent-assisted toothbrushing, and eating and drinking sweets. Results showed the effectiveness of a community-based intervention for preventing dental caries, gingivitis, and plaque in the intervention group, compared to the control group. CONCLUSION: The rate of dental caries among Vietnamese children was remarkably high. A comprehensive intervention to prevent early childhood dental caries was effective and might be considered a necessary program in healthcare prophylaxis. CLINICAL SIGNIFICANCE: This intervention was consistent with the guidelines of WHO and based on evidences of related factors of dental caries identified in a previous cross-sectional study.

Effect of intimate partner violence during pregnancy on maternal mental health: a cohort study in central Vietnam.

This study aims to explore the effects of intimate partner violence during pregnancy (p-IPV) on postpartum depression among women in central Vietnam. p-IPV was defined among 150 women aged 18 years and older in the third trimester of their pregnancy. Baseline data was collected between February and May 2019, and then those women were followed up to 3-5 months after childbirth to assess depression using the Patient Health Questionnaire-9 (PHQ-9). Data collection was completed in September 2019. Relative risk was estimated to identify the effect of p-IPV on maternal postpartum depression. Twenty-one women reported IPV during pregnancy. In the follow-up assessment, 8 of 21 mothers exposed to p-IPV and 23 of 127 mothers not exposed to p-IPV developed postpartum depression. p-IPV including emotional and physical violence were increased the risk of postpartum depression. The findings support evidence that p-IPV increases the risk of postpartum depression among women in central Vietnam.

Adherence to COVID-19 Preventive Measures among Dental Care Workers in Vietnam: An Online Cross-Sectional Survey.

An online cross-sectional survey using a "snowball" sampling method was carried out to assess the adherence to COVID-19 preventive measures among dental care workers (DCWs) during the pandemic. Six questions concerning the COVID-19 preventive guidelines issued by the Vietnam Ministry of Health were used to evaluate DCWs' adherence to preventive measures at dental care clinics. The quality of life of DCWs was assessed using the WHO-5 questionnaire and was defined as low if the total score was less than 13 points. Factors relating to adherence to COVID-19 prevention measures of DCWs were determined by multivariate linear regression analysis. In total, 514 DCWs completed the questionnaire. A total of 37% DCWs rated their quality of life as low. Regression analysis suggested that older age, a better quality of life, living in an urban area, and training on COVID-19 prevention were associated with better adherence to COVID-19 preventive measures, while being a dentist and lack of personal protective equipment was associated with less adherence to COVID-19 preventive measures. The pandemic had a significant negative impact on the physical and mental health of DCWs. Therefore, specific national guidelines for the prevention and control of the spread of COVID-19 in dental facilities should be issued.

Cabozantinib Is Effective in Melanoma Brain Metastasis Cell Lines and Affects Key Signaling Pathways.

Melanomas have a high potential to metastasize to the brain. Recent advances in targeted therapies and immunotherapies have changed the therapeutical landscape of extracranial melanomas. However, few patients with melanoma brain metastasis (MBM) respond effectively to these treatments and new therapeutic strategies are needed. Cabozantinib is a receptor tyrosine kinase (RTK) inhibitor, already approved for the treatment of non-skin-related cancers. The drug targets several of the proteins that are known to be dysregulated in melanomas. The anti-tumor activity of cabozantinib was investigated using three human MBM cell lines. Cabozantinib treatment decreased the viability of all cell lines both when grown in monolayer cultures and as tumor spheroids. The in vitro cell migration was also inhibited and apoptosis was induced by cabozantinib. The phosphorylated RTKs p-PDGF-Rα, p-IGF-1R, p-MERTK and p-DDR1 were found to be downregulated in the p-RTK array of the MBM cells after cabozantinib treatment. Western blot validated these results and showed that cabozantinib treatment inhibited p-Akt and p-MEK 1/2. Further investigations are warranted to elucidate the therapeutic potential of cabozantinib for patients with MBM.

Well-Being of Healthcare Workers and the General Public during the COVID-19 Pandemic in Vietnam: An Online Survey.

The COVID-19 pandemic and associated restrictive measures implemented may considerably affect people's lives. This study aimed to assess the well-being of Vietnamese people after COVID-19 lockdown measures were lifted and life gradually returned to normal. An online survey was organized from 21 to 25 April 2020 among Vietnamese residents aged 18 and over. The survey was launched by the Hue University of Medicine and Pharmacy. The WHO-5 Well-Being Index (scored 0-25) was used to score participants' well-being. A multivariate logistic regression model was used to determine the predictors of well-being. A total of 1922 responses were analyzed (mean age: 31 years; 30.5% male; 88.2% health professionals or students in the health sector). The mean well-being score was 17.35 ± 4.97. Determinants of a high well-being score (≥13) included older age, eating healthy food, practicing physical exercise, working from home, and adhering to the COVID-19 preventive measures. Female participants, persons worried about their relatives' health, and smokers were more likely to have a low well-being score. In conclusion, after the lockdown measures were lifted, the Vietnamese have people continued to follow COVID-19 preventive measures, and most of them scored high on the well-being scale. Waiting to achieve large-scale COVID-19 vaccine coverage, promoting preventive COVID-19 measures remains important, together with strategies to guarantee the well-being of the Vietnamese people.

Depression and its associated factors among pregnant women in central Vietnam.

To date, little attention has been given to prenatal depression, especially in low and middle-income countries. The aim of this research was to assess the prevalence of depression and its associated factors amongst pregnant women in a central Vietnamese city. This cross-sectional study included 150 pregnant women from 29 to 40 weeks of gestation, from eight wards of Hue city, via quota sampling from February to May 2019. We employed the Patient Health Questionnaire (PHQ-9) to assess depression. Findings suggest the need to provide routine screening of pregnant women in primary care for depressive symptoms and other mental health problems.

An in vitro vascularized micro-tumor model of human colorectal cancer recapitulates in vivo responses to standard-of-care therapy.

Around 95% of anti-cancer drugs that show promise during preclinical study fail to gain FDA-approval for clinical use. This failure of the preclinical pipeline highlights the need for improved, physiologically-relevant in vitro models that can better serve as reliable drug-screening and disease modeling tools. The vascularized micro-tumor (VMT) is a novel three-dimensional model system (tumor-on-a-chip) that recapitulates the complex human tumor microenvironment, including perfused vasculature, within a transparent microfluidic device, allowing real-time study of drug responses and tumor-stromal interactions. Here we have validated this microphysiological system (MPS) platform for the study of colorectal cancer (CRC), the second leading cause of cancer-related deaths, by showing that gene expression, tumor heterogeneity, and treatment responses in the VMT more closely model CRC tumor clinicopathology than current standard drug screening modalities, including 2-dimensional monolayer culture and 3-dimensional spheroids.

Variability in multimodality treatment influences survival in non-metastatic gastric cancer patients.

BACKGROUND: While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the USA. Recommendations regarding optimal treatment of non-metastatic gastric cancer (nmGC) with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary across geographic locations. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study to evaluate clinical outcomes in nmGC patients treated at four high-volume academic institutions. METHODS: California Cancer Registry data were collected for nmGC patients who underwent gastrectomy with curative intent from 2010 to 2018. We conducted chart reviews of the patients' electronic health records to validate clinical factors and outcomes. We performed multivariable Cox regressions to determine prognostic factors for outcomes. RESULTS: Demographics of study cohort (n=326): mean age 66 years; 64% male; 44% Caucasian, 35% Asian, 16% Latino. Tumor stage: 48% loco-regional (pT4 or pN1+) vs. 52% localized (pT1-3, pN0). Histology: 47% intestinal, 30% diffuse, 8% mixed, 15% unknown. Surgery: 34% open gastrectomy, 48% laparoscopic, 18% unknown; number of recovered lymph nodes varied from 0 to 60 in any tumor stage. Chemotherapy: 20% neoadjuvant alone, 25% adjuvant alone, 16% perioperative, 39% none. Multimodality therapy: 44% surgery only, 31% chemotherapy, 25% chemotherapy and radiation. With a median post-surgical follow-up of 6 years, 24% of patients developed recurrence and 40% had died. Compared to open surgery, laparoscopic surgeries were associated with fewer recovered lymph nodes (mean =18 vs. 25, P=0.0042). Fewer recovered lymph nodes were associated with a significant decrease in 5-year overall survival [hazard ratio (HR) =1.9, 95% confidence interval (CI): 1.3-2.8]. Timing of chemotherapy and addition of radiation therapy to chemotherapy did not confer further improvements in survival; in contrast, greater lymph node recovery plus chemotherapy were associated with a significant increase in survival (HR =0.3, 95% CI: 0.1-0.6). CONCLUSIONS: This study highlights major practice differences in the management of nmGC patients across providers and institutions. Further efforts should be made to standardize the use of chemotherapy and adequate recovery and assessment of lymph nodes in this patient population.

Preventive behavior of Vietnamese people in response to the COVID-19 pandemic.

We sought to evaluate the adherence of Vietnamese adults to Coronavirus Disease 2019 (COVID-19) preventive measures, and gain insight into the effects of the epidemic on the daily lives of Vietnamese people. An online questionnaire was administered from March 31 to April 6, 2020. The questionnaire assessed personal preventive behavior (such as physical distancing, wearing a face mask, cough etiquette, regular handwashing and using an alcohol hand sanitizer, body temperature check, and disinfecting mobile phones) and community preventive behavior (such as avoiding meetings, large gatherings, going to the market, avoiding travel in a vehicle/bus with more than 10 persons, and not traveling outside of the local area during the lockdown). A total adherence score was calculated by summing the scores of the 9 personal and the 11 community prevention questions. In total, 2175 respondents completed the questionnaire; mean age: 31.4 ± 10.7; (range: 18-69); 66.9% were women; 54.2% were health professionals and 22.8% were medical students. The mean adherence scores for personal and community preventive measures were 7.23 ± 1.63 (range 1-9) and 9.57 ± 1.12 (range 1-11), respectively. Perceived adaptation of the community to lockdown (Beta (ß) = 2.64, 95% Confidence Interval (CI) 1.25-4.03), fears/worries concerning one's health (ß = 2.87, 95% CI 0.04-5.70), residing in large cities (ß = 19.40, 95% CI 13.78-25.03), access to official COVID-19 information sources (ß = 16.45, 95% CI 6.82-26.08), and working in healthcare/medical students (ß = 22.53, 95% CI 16.00-29.07) were associated with a higher adherence score to anti-COVID instructions. In conclusion, this study confirmed a high degree of adherence to personal and community preventive behavior among Vietnamese people. Our findings are consistent with the epidemiology of COVID-19 in Vietnam, where there have been few infections and no recorded deaths up to the first week of July 2020.

Predictors of outcomes in patients with gastric cancer treated with contemporary multimodality strategies-a single institution experience.

BACKGROUND: While gastric cancer is a leading cause of cancer-related mortality in Eastern Europe and Asia, it is less common in the United States. Recommendations regarding optimal treatment of non-metastatic gastric cancer with regard to type and extent of surgery, choice and sequence of chemotherapeutic agents, and use of radiation therapy vary somewhat depending on geographic location. There is paucity in the literature for direct comparison of various practices. To determine how variability in treatment practices affects patient outcomes, we conducted a retrospective study in patients with gastric cancer who had multimodality treatment for non-metastatic gastric cancer. METHODS: We gathered clinical data (patient demographics, pathology reports, type of surgical intervention, chemotherapy, and radiation therapy) for patients diagnosed with gastric adenocarcinoma who underwent gastrectomy at five sites from 2010-2017 using Electronic Health Records and California Cancer Registry databases. Medical chart reviews were conducted to validate patient outcomes. We performed multivariate Cox regression analyses to determine predictors for cancer recurrence and survival. We also performed logistic regression analyses to determine predictors of positive resection margins and hospitalization. RESULTS: One hundred and sixteen patients met eligibility criteria to be included. Mean age was 65.7±11.6 years. About 65.5% were male. The most common ethnicities were Asian (44.0%) and Caucasian (37.9%). About 58.6% of the patients had localized disease (defined as pT1-3, pN0) and the remaining 41.4% had loco-regional disease (i.e., pT4 or pN+). About 41.4% of the tumors were diffuse, 27.6% intestinal, 12.0% mixed, and 19.0% unknown histology. Surgery included laparoscopic (94.8%) and open gastrectomy (5.2%). Chemotherapy and radiation therapy were given in 51.7% and 19.0% of the patients, respectively. After a median follow-up time of 19 months after gastrectomy, 16.4% of patients had recurrence and 19.8% had died. Patients who had loco-regional tumors were more likely to have recurrence and death than those who had localized tumors (hazard ratios =7.0, P=0.0228 for recurrence and hazard ratios =3.3, P=0.0160 for death). Positive resection margins were seen in 9% of the patients and were associated with diffuse histology (odds ratio =6.6, P=0.0207). Hospitalization within six months of gastrectomy was seen in 22% of the patients. Peri-operative chemotherapy was the only significant predictor for re-hospitalization (odds ratio =3.5, P=0.0415). CONCLUSIONS: In this contemporary cohort of patients with localized gastric cancer, only the pathological stage was significantly associated with survival while positive resection margins were associated with diffuse histology. Closer monitoring of patients undergoing perioperative chemotherapy within 6 months of surgery is warranted based on our observation of higher rate of re-hospitalization.

Surface-Treated Pellethanes: Comparative Quantification of Encrustation in Artificial Urine Solution.

Introduction: Encrustation of implanted urinary tract devices is associated with significant morbidity. Pellethane® is a polyether-based compound noted for its strength, porosity, and resistance to solvents. We assessed Pellethane thermoplastic polyurethane (TPU) with and without surface coatings 2-hydroxyethyl methacrylate (HEMA) and tetraethylene glycol dimethyl ether (TETRA) for the potential to resist encrustation in an artificial urine environment. Materials and Methods: Samples of Pellethane TPU, HEMA Pellethane TPU, TETRA Pellethane TPU, and hydrogel-coated ureteral stent (Cook®) were suspended in a batch-flow model with an artificial urine solution (AUS). Every 48 hours for 90 days, 40% of the solution was replaced with fresh AUS. All samples were stored in a 37°C incubator. Subsequently, the samples were thoroughly dried for 48 hours before weighing. Scanning electron microscopy was used to assess the degree of encrustation. Nu-Attom Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to determine the precise compositions of the encrustation specifically with regard to calcium, magnesium, and phosphate. Results: At the conclusion of the 90-day trial, the samples were analyzed, and the average mass changes were as follows: stent 63.78%, uncoated Pellethane TPU 11.50%, HEMA-coated Pellethane TPU 2.90%, and TETRA-coated Pellethane TPU 0.60%. Pellethane TPU products, and specifically those coated with HEMA and TETRA, exhibited less average mass increase and a lesser propensity to form encrustation than the traditional urinary tract stent. The mass increases noted on coated Pellethane devices were primarily ionic, whereas that of the stent was not. Conclusion: Pellethane, particularly with an HEMA-based preventative coating, may serve as a favorable alternative to traditional urinary stent material, providing its improved resistance to encrustation.

Gene mutations distinguishing gastric from colorectal and esophageal adenocarcinomas.

BACKGROUND: Genetic analysis of gastrointestinal malignancies shows a great number of mutations. Most mutations found in gastric tumors are also found in colorectal and esophageal tumors. The challenge remains to identify mutations that distinguish gastric from colorectal and esophageal cancers. Using open-access cancer genomics data, we sought to identify mutations that accounted for the unique phenotypic features of gastric tumors. METHODS: Thirteen cancer genomics datasets with demographic, clinical, and genetic variables were analyzed. Pathologic stage and histology were compared between subjects with and without a specific mutated gene using two-sample t-tests, adjusted for multiple gene testing. Sequence convergence and functional impact of genetic mutations were analyzed using permutation test and PolyPhen-2 score. RESULTS: Analysis included 1,915 subjects with valid pathologic stage and histology. Mean age was 68 years (SD =10). About 54% were female. The most common race was Caucasian (37%) while minorities were rare with high rates of missing data (44%). Pathologic stage: 20% stage I, 35% stage II, 31% stage III, and 14% stage IV. Anatomical location: 30% gastric, 59% colorectal, and 11% esophageal. Histology of gastric cancer: 61% intestinal, 23% diffuse, 15% mixed, and 1% missing. Two mutated genes-CDH1, RHOA-distinguished gastric from colorectal and esophageal tumors. These mutations were highly specific to diffuse histology and advanced stages of gastric tumors and recurrent in transcribed regions known to impact protein functions. CONCLUSIONS: CDH1 and RHOA regulate cell-cell adhesion which is vital to cell growth and proliferation. Identification of these potential driver mutations is critical to better define therapeutic vulnerabilities for the rational design of gastric cancer therapies.

Effective Treatment of Metastatic Melanoma by Combining MAPK and PI3K Signaling Pathway Inhibitors.

Malignant melanoma is the most aggressive type of skin cancer and is closely associated with the development of brain metastases. Despite aggressive treatment, the prognosis has traditionally been poor, necessitating improved therapies. In melanoma, the mitogen activated protein kinase and the phosphoinositide 3-kinase signaling pathways are commonly altered, and therapeutically inhibiting one of the pathways often upregulates the other, leading to resistance. Thus, combined treatment targeting both pathways is a promising strategy to overcome this. Here, we studied the in vitro and in vivo effects of the PI3K inhibitor buparlisib and the MEK1/2 inhibitor trametinib, used either as targeted monotherapies or in combination, on patient-derived melanoma brain metastasis cell lines. Scratch wound and trans-well assays were carried out to assess the migratory capacity of the cells upon drug treatment, whereas flow cytometry, apoptosis array and Western blots were used to study apoptosis. Finally, an in vivo treatment experiment was carried out on NOD/SCID mice. We show that combined therapy was more effective than monotherapy. Combined treatment also more effectively increased apoptosis, and inhibited tumor growth in vivo. This suggests a clinical potential of combined treatment to overcome ceased treatment activity which is often seen after monotherapies, and strongly encourages the evaluation of the treatment strategy on melanoma patients with brain metastases.

Investigation of long wavelength mid-infrared generation in the tight focusing limit.

An ultrafast coherent long wavelength MIR source based on difference frequency generation was demonstrated. An average power of 2.5 mW at ∼18 µm was achieved. The angular distribution of the generated MIR source under the condition of tight-focusing limit shows the onset of conical emission of the MIR beam due to on-axis phase mismatching.