Downregulation of SPTAN1 is related to MLH1 deficiency and metastasis in colorectal cancer.

Introduction: Colorectal cancers (CRCs) deficient in the DNA mismatch repair protein MutL homolog 1 (MLH1) display distinct clinicopathological features and require a different therapeutic approach compared to CRCs with MLH1 proficiency. However, the molecular basis of this fundamental difference remains elusive. Here, we report that MLH1-deficient CRCs exhibit reduced levels of the cytoskeletal scaffolding protein non-erythroid spectrin αII (SPTAN1), and that tumor progression and metastasis of CRCs correlate with SPTAN1 levels.

Enhanced Tumoral MLH1-Expression in MLH1-/PMS2-Deficient Colon Cancer Is Indicative of Sporadic Colon Cancer and Not HNPCC.

Hereditary Non-Polyposis Colorectal Cancer (HNPCC) is caused by germline mutations of mismatch-repair (MMR) genes MLH1, MSH2, MSH6 and PMS2. MLH1-/PMS2-deficient colorectal carcinomas might be HNPCC-associated but also caused by MLH1-promoter methylation in sporadic colon carcinoma. This study analyzed semiquantitatively whether the MLH1 staining pattern might be indicative of sporadic or HNPCC-associated colorectal cancer.

Ror is a nervous system-specific co-receptor for Wnt ligands.

Wnt ligands are secreted glycoproteins that control many developmental processes and are crucial for homeostasis of numerous tissues in the adult organism. Signal transduction of Wnts involves the binding of Wnts to receptor complexes at the surface of target cells. These receptor complexes are commonly formed between a member of the Frizzled family of seven-pass transmembrane proteins and a co-receptor, which is usually a single-pass transmembrane protein.

Tracing scientific reasoning in psychiatry: Reporting of statistical inference in abstracts of top journals 1975-2015.

Objective: To analyze the reporting of statistical inference in psychiatry.

Method: We searched 63,928 abstracts, published in 15 leading psychiatric journals (1975-2015).

Results: Median abstract length increased from 664 (1975) to 1,323 (2015) characters, and median use of numbers from two to 14/abstract.

Myc and the Tip60 chromatin remodeling complex control neuroblast maintenance and polarity in .

Stem cells establish cortical polarity and divide asymmetrically to simultaneously maintain themselves and generate differentiating offspring cells. Several chromatin modifiers have been identified as stemness factors in mammalian pluripotent stem cells, but whether these factors control stem cell polarity and asymmetric division has not been investigated so far. We addressed this question in neural stem cells called neuroblasts.

Baclofen for alcohol use disorder-a systematic meta-analysis.

Objective: To evaluate the efficacy and tolerability of baclofen vs. placebo for long-term treatment of alcohol use disorder.

Method: Systematic review and meta-analysis following methods of the Cochrane Collaboration Handbook (PROSPERO registration: CRD42017073663).

Dose Increase Versus Unchanged Continuation of Antidepressants After Initial Antidepressant Treatment Failure in Patients With Major Depressive Disorder: A Systematic Review and Meta-Analysis of Randomized, Double-Blind Trials.

Objective: To evaluate the efficacy and tolerability of dose increase compared to dose continuation of the initially prescribed antidepressant in antidepressant treatment failure (ATF).

Data Sources: We searched CENTRAL, PubMed, Embase, and PsycINFO using generic terms for depression, dose increase, and randomized controlled trials (RCTs), without date or language restrictions.

Study Selection: Of 1,780 studies screened, 9 studies reporting on 1,273 patients were included for meta-analysis (PROSPERO Registration: CRD42017058389).

Imbalance values for baseline covariates in randomized controlled trials: a last resort for the use of values? A pro and contra debate.

Background: Results of randomized controlled trials (RCTs) are usually accompanied by a table that compares covariates between the study groups at baseline. Sometimes, the investigators report values for imbalanced covariates. The aim of this debate is to illustrate the pro and contra of the use of these values in RCTs.

Trajectories of Acute Antidepressant Efficacy: How Long to Wait for Response? A Systematic Review and Meta-Analysis of Long-Term, Placebo-Controlled Acute Treatment Trials.

Background: In patients who are not responding to antidepressant pharmacotherapy, information regarding the future probability of response with the same treatment is scarce. Specifically, it is unclear at what point in time the probability to respond or remit ceases to increase, because few studies report data on response or remission at repeated time points beyond 4 or 8 weeks of treatment. Consequently, treatment recommendations in clinical practice guidelines differ widely.

The histone acetyltransferase inhibitor Nir regulates epidermis development.

In addition to its function as an inhibitor of histone acetyltransferases, Nir (Noc2l) binds to p53 and TAp63 to regulate their activity. Here, we show that epidermis-specific ablation of Nir impairs epidermal stratification and barrier function, resulting in perinatal lethality. Nir-deficient epidermis lacks appendages and remains single layered during embryogenesis.

Test-retest reliability of the diagnosis of schizoaffective disorder in childhood and adolescence - A systematic review and meta-analysis.

Objectives: Reliability of schizoaffective disorder (SAD) diagnoses is low in adults but unclear in children and adolescents (CAD). We estimate the test-retest reliability of SAD and its key differential diagnoses (schizophrenia, bipolar disorder, and unipolar depression).

Methods: Systematic literature search of Medline, Embase, and PsycInfo for studies on test-retest reliability of SAD, in CAD.

The adherens junction-associated LIM domain protein Smallish regulates epithelial morphogenesis.

In epithelia, cells adhere to each other in a dynamic fashion, allowing the cells to change their shape and move along each other during morphogenesis. The regulation of adhesion occurs at the belt-shaped adherens junction, the zonula adherens (ZA). Formation of the ZA depends on components of the Par-atypical PKC (Par-aPKC) complex of polarity regulators.

PD-L1 expression in HNPCC-associated colorectal cancer.

Background: PD-L1 immunohistochemistry is predictive for molecular inhibitors of PD-1/PD-L1 immune checkpoint. Therefore, this study evaluated the PD-L1 expression in patients with Hereditary Non-Polyposis Colorectal Cancer (HNPCC).

Methods: Immunohistochemical expression of PD-L1 in carcinoma cells, stromal macrophages and lymphocytes of 40 HNPCC-patients with colorectal cancer was scored semi-quantitatively.

Notch Signaling: Where Is the Action?

It has been a long-standing question as to whether the activation of Notch by its ligands occurs in a specific region of the plasma membrane. A study now shows that this is indeed the case in the Drosophila sensory organ precursor cell lineage.

Solar insolation in springtime influences age of onset of bipolar I disorder.

Objective: To confirm prior findings that the larger the maximum monthly increase in solar insolation in springtime, the younger the age of onset of bipolar disorder.

Method: Data were collected from 5536 patients at 50 sites in 32 countries on six continents. Onset occurred at 456 locations in 57 countries.

Focal Breast Lesions in Clinical CT Examinations of the Chest: A Retrospective Analysis.

 Based on radiological reports, the percentage of breast cancers visualized as incidental findings in routine CT examinations is estimated at ≤ 2 %. In view of the rising number of CT examinations and the high prevalence of breast cancer, it was the goal of the present study to verify the frequency and image morphology of false-negative senological CT findings.  All first contrast-enhanced CT examinations of the chest in adult female patients carried out in 2012 were retrospectively included.

Long-Term Acute-Phase Treatment With Antidepressants, 8 Weeks and Beyond: A Systematic Review and Meta-Analysis of Randomized, Placebo-Controlled Trials.

Objective: In clinical practice, acute antidepressant treatment is often applied for several months until remission is achieved. However, data on treatment outcomes beyond 8 weeks are sparse and no systematic review exists to date. This study aims at assessing efficacy and tolerability of antidepressants compared to placebo in acute treatment at and beyond 8 weeks.

Switching the Antidepressant After Nonresponse in Adults With Major Depression: A Systematic Literature Search and Meta-Analysis.

Objective: Nonresponders to antidepressant monotherapy during acute treatment of major depression are often switched to a new antidepressant. The objective of this meta-analysis was to compare the efficacy of switching to a new antidepressant with continuation of the first antidepressant.

Data Sources: PubMed, Embase, PsycINFO, and Cochrane Central Register of Controlled Trials (CENTRAL) databases and additional sources were systematically searched independently by 2 authors up to March 2015 without language limitations.

Combining Antidepressants in Acute Treatment of Depression: A Meta-Analysis of 38 Studies Including 4511 Patients.

Objective: Combining antidepressants (ADs) for therapy of acute depression is frequently employed, but randomized studies have yielded conflicting results. We conducted a systematic review and meta-analysis aimed at determining efficacy and tolerability of combination therapy.

Methods: MEDLINE, Embase, PsycINFO, and CENTRAL databases were systematically searched through March 2014 for controlled studies comparing combinations of ADs with AD monotherapy in adult patients suffering from acute depression.

Interrater reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression - A systematic review and meta-analysis.

Schizoaffective disorder is a common diagnosis in clinical practice but its nosological status has been subject to debate ever since it was conceptualized. Although it is key that diagnostic reliability is sufficient, schizoaffective disorder has been reported to have low interrater reliability. Evidence based on systematic review and meta-analysis methods, however, is lacking.

Non-pegylated liposomal doxorubicin for patients with recurrent ovarian cancer: A multicentric phase II trial.

Patients with non-platinum-sensitive recurrent ovarian cancer have a poor prognosis. Non-pegylated liposomal doxorubicin (Myocet) is a promising drug that may be able to improve treatment for such patients. In the current study, patients with recurrent ovarian cancer relapsing within 12 months after primary treatment received non-pegylated liposomal doxorubicin at 75 mg/m d1q22 and 60 mg/m d1q22 after study dose modification, respectively.

Diagnostic shift in patients diagnosed with schizoaffective disorder: a systematic review and meta-analysis of rediagnosis studies.

Objectives: The diagnosis of schizoaffective disorder (SAD) is well established in clinical practice but is heavily disputed on theoretical grounds. We analyzed the extent and direction of diagnostic shift in SAD patients.

Methods: We searched Medline, Embase, and PsycINFO systematically for all studies documenting two diagnostic assessments at different points in time (rediagnosis studies) and used meta-analytic methods to quantify diagnostic shift.