A diffusion approach to labeling rows and columns in an irregular array

A robust algorithm is presented for labeling rows and columns in an irregular array. The algorithm is based on hierarchical pattern matching to a local lattice, which is used as a template. Starting from the best local match, the pattern is expanded hierarchically to encompass the entire array. An application to labeling digitized images of an array of tissue sections mounted on a microscope slide is discussed.     

Functional mapping of the porcine reproductive and respiratory syndrome virus capsid protein nuclear localization signal and its pathogenic association

PRRSV (porcine reproductive and respiratory syndrome virus) nucleocapsid (N) protein is the most abundant structural protein of the virus. During infection, the N protein is specifically localized to the nucleus and nucleolus in addition to its normal cytoplasmic distribution. Previously, a nuclear localization signal (NLS, 41-PGKK(N/S)KKKN)-null mutant virus (41-PGGGNKKKN) showed reduced viremia and increased production of neutralizing antibodies in infected pigs. However, the mutagenized NLS underwent strong selection pressure in the pig that resulted in partial or complete reversion and reacquisition of NLS function, and thus the biological effect of the NLS-null mutation needed further investigation. In the present study, a total of 9 "reversion resistant" mutants were generated by amino acid deletions and substitutions using an infectious cDNA clone. Two mutant clones (PG--SKKKS and PG--S-KKS) that produced progeny viruses were genetically stable for at least 20 passages in cell culture. Infection of pigs with those mutants induced neutralizing antibodies to higher titers than with wild-type virus. Both mutant viruses induced viremia of lower titer and of shorter duration than wild-type virus. RT-PCR from tonsils showed that both mutants persisted at a reduced level. Virus transmission to contact pigs was also lower in the mutant virus infected groups. No reversion to functional NLS was detected in either mutant from any pig. These data demonstrate that N protein nuclear localization is indeed associated with viral pathogenesis and host response to PRRS.     

Tumor Response and Symptom Palliation from RAINBOW,a Phase III Trial of Ramucirumab Plus Paclitaxel in Previously Treated Advanced Gastric Cancer

BackgroundIn the intent‐to‐treat (ITT) population of the RAINBOW study, objective response rate (ORR) was 28% and 16% in the ramucirumab and control arms, respectively. To further characterize tumor response, we present details on timing and extent of tumor shrinkage, as well as associations with symptom palliation.Materials and MethodsTumor response was assessed with RECIST v1.1, and quality of life (QoL) was assessed with the European Organization for Research and Treatment of Cancer Quality‐of‐Life Questionnaire‐Core 30 (EORTC QLQ‐C30) v3.0. Prespecified and post hoc analyses were conducted in the ITT population, patients with measurable disease, or responders, and included best overall response (BOR), ORR, disease control rate (DCR), duration of response, time to response (TtR), change in tumor size, and associations of QoL with tumor shrinkage and BOR.ResultsIn both treatment arms, median TtR was 1.5 months. Responses were more durable in the ramucirumab versus control arm (median 4.4 vs. 2.8 months). In patients with measurable disease (78% of ITT), ORR was 36% versus 20%; DCR was 81% versus 61% in the ramucirumab versus control arms. Waterfall plots demonstrated more tumor shrinkage in the ramucirumab versus control arm. Regardless of treatment, tumor response and stable disease were associated with improved or stable QoL, with more tumor shrinkage associated with greater symptom palliation.ConclusionTreatment with ramucirumab plus paclitaxel yielded the highest ORR reported to date for patients with previously treated advanced gastric or gastroesophageal junction adenocarcinoma. Additional details demonstrate robustness of tumor response results. The extent of tumor shrinkage is directly associated with symptom palliation and should be considered when evaluating patient needs and treatment selection. Clinical trial identification number. {"type":"clinical-trial","attrs":{"text":"NCT01170663","term_id":"NCT01170663"}}NCT01170663.Implications for PracticeRamucirumab plus paclitaxel is a recognized standard of care as it improves survival for patients with advanced gastric or gastroesophageal junction adenocarcinoma who have been previously treated with recommended first‐line therapy. These additional data on tumor response demonstrate a positive association between tumor shrinkage and symptom palliation in a patient population that is often symptomatic. These observations included patients with nonmeasurable disease, a group of patients often underrepresented in clinical trials. This knowledge can inform treatment decisions, which align individual patient characteristics and needs with demonstrated benefits.     

The impact of metabolic syndrome on mental health-related quality of life and depressive symptoms

Quality of Life Research - Results examining associations between metabolic syndrome (MetS) and depression, as well as on quality of life (QoL), are inconsistent. We aimed to determine whether...     

Biomarker-Driven Therapy in Metastatic Gastric and Esophageal Cancer: Real-Life Clinical Experience

Background

Precision treatment of cancer uses biomarker-driven therapy to individualize and optimize patient care.

Objective

To evaluate real-life clinical experience with biomarker-driven therapy in metastatic gastric and esophageal cancer in Israel.

Patients and Methods

This multicenter retrospective cohort study included patients with metastatic gastric or esophageal cancer who were treated in the participating institutions and underwent biomarker-driven therapy. Treatment was considered to have a benefit if the ratio between the longest progression-free survival (PFS) post biomarker-driven therapy and the last PFS before the biomarker-driven therapy was ≥1.3. The null hypothesis was that ≤15% of patients gain such benefit.

Results

The analysis included 46 patients (61% men; median age, 58 years; 57% with poorly-differentiated tumors). At least one actionable (i.e., predictive of response to a specific therapy) biomarker was identified for each patient. Immunohistochemistry was performed on all samples and identified 1–8 (median: 3) biomarkers per patient (most commonly: low TS, high TOPO1, high TOP2A). Twenty-eight patients received therapy after the biomarker analysis (1–4 lines). In the 1st line after biomarker analysis, five patients (18%) achieved a partial response and five (18%) stable disease; the median (range) PFS was 129 (12–1155) days. Twenty-four patients were evaluable for PFS ratio analysis; in seven (29.2%), the ratio was ≥1.3. In a one-sided exact binomial test vs. the null hypothesis, p?=?0.019; therefore, the null hypothesis was rejected.

Conclusions

Our findings demonstrated that implementing biomarker-driven analysis is feasible and could provide clinical benefit for a considerable proportion (~30%) of patients with metastatic gastric or esophageal cancer.

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Informational Needs of Head and Neck Cancer Patients

The patient journey with head and neck cancer (HNC) is particularly challenging given the physical and functional impact of the cancer and treatment. The ability to perform activities of daily living can be severely compromised and have a profound impact on psychosocial well-being. These complex and long-lasting effects can affect patient quality of life for months to years and the literature shows that information for HNC patients is often insufficient. This observational cross-sectional study utilized survey methodology to investigate the informational needs of HNC patients and the preferred modalities for delivery. This was done to inform the development of resources for HNC patients. Four hundred fifty surveys were analyzed. The median age was 61 years and 58% of the cohort was born in Canada. Most were Caucasian (72%), Chinese being the next largest ethnicity (12%). A third had less than high school education and most had cancer of the oral cavity (28%) and were in long-term follow-up (41%). Comparison of the percentage of items to which a patient responded “very important” across the six domains shows variation of importance by domain (overall mixed effects regression model p < 0.0001). Additionally, each domain was compared to the medical domain and all had significantly lower mean scores (all p < 0.0001) with the medical domain scoring highest (mean score 64.6). The top preferred education modalities were teaching with a healthcare professional and pamphlets. This study highlights the type of information that HNC patients want and the format they wish to receive it in. The design provides a comprehensive way to consult with patients toward building education that responds to their specific needs.     

Unusual SCD in cancer cells: A phenomenon related to decreased BrdU incorporation?

The simultaneous presence of chromosome segments with and without sister chromatid differentiation (SCD) in the same metaphase was observed in a human melanoma cell line after BrdU incorporation for 48-72 hr. This phenomenon was related to the time of BrdU incorporation by the cells: i.e., it was not observed after exposure to BrdU for only 17-20 hr. It is proposed, therefore, that the unusual staining pattern is caused through reduced BrdU incorporation by the cells after completing the first division.     

Comparison of clinical outcomes in diabetic and non-diabetic burns patients in a national burns referral centre in southeast Asia: A 3-year retrospective review

Objective

Diabetic burns patients may be at risk of worse clinical outcomes. This study aims to further investigate the impact of diabetes mellitus on clinical outcomes in burns patients in Singapore.