Notes

PHF6 Mutations throughout Hematologic Malignancies.
To investigate the impact of reminder-focused positive psychiatry (RFPP) on attention-deficit/hyperactive disorder (ADHD) and posttraumatic stress disorder (PTSD) symptoms, vascular-function, inflammation and well-being of adolescents with comorbid ADHD and PTSD.

After obtaining informed-consent, 11 adolescents were randomized to RFPP (n = 5) or trauma-focused cognitive-behavioral therapy (TF-CBT) (n = 6). Eight participants (RFPP n = 4, TF-CBT n = 4) completed the twice-weekly intervention for a 6-week trial. The RFPP intervention was inclusive of positive psychiatry interventions on (1) traumatic reminders and (2) avoidance and negative cognition. Vascular function measured as temperature rebound, C-reactive protein, homocysteine, ADHD Swanson, Nolan, and Pelham (SNAP) Questionnaire, Clinician-Administered PTSD Scale for DSM-5-Child/Adolescent Version (CAPS-CA), and neuropsychiatric-measures were measured at baseline and 6 weeks. Subjects were followed for 12 months. The study was conducted from Septemb well-being, vascular function, and posttraumatic growth, as well as a favorable long-term clinical outcome. This finding highlights the importance of the dual role of RFPP in addressing vulnerability symptoms as well as enhancing well-being in youth with comorbid ADHD and PTSD.

ClinicalTrials.gov identifier NCT04336072.
ClinicalTrials.gov identifier NCT04336072.
Several randomized controlled trials (RCTs) investigated omega-3 polyunsaturated fatty acids (PUFAs) (ie, fish oil) in perinatal depression, but their efficacy remains unclear. Adenosine Receptor antagonist We performed a meta-analysis of RCTs on omega-3 PUFAs for perinatal depression, comparing a priori defined subgroups pregnant women vs postpartum women and prevention vs treatment of perinatal depression.

We searched Web of Science, Embase, PsycINFO, and the Cochrane Library, combining omega-3 PUFAs and perinatal depression terms and including publications up to February 18, 2019, for RCTs on omega-3 PUFAs compared to placebo or any active comparator.

Data from 18 RCTs on 4,052 participants showed an overall significant small beneficial effect of omega-3 PUFAs on depressive symptoms compared to placebo (-0.236 standardized difference in means [SDM]; 95% CI = -0.463 to -0.009; P = .042). Heterogeneity was considerable (I² = 88.58; P < .001), with significant subgroup differences explaining 55% of between-study variance (P = .00g omega-3 PUFAs for the treatment or prevention of depressive symptoms during pregnancy, given a lack of effect with low heterogeneity. In contrast, omega-3 PUFA supplementation may be a promising (add-on) treatment for postpartum depression.
The coronavirus disease 2019 (COVID-19) has spread rapidly around the globe, causing significant morbidity and mortality. This study aims to describe electrocardiographic (ECG) characteristics of COVID-19 patients and to identify ECG parameters that are associated with cardiac involvement.

The study included patients who were hospitalized with COVID-19 diagnosis and had cardiac biomarker assessments and simultaneous 12-lead surface ECGs. Sixty-three hospitalized patients (median 53 [inter-quartile range, 43-65] years, 76.2% male) were enrolled, including patients with (n=23) and without (n=40) cardiac injury. Patients with cardiac injury were older, had more pre-existing co-morbidities, and had higher mortality than those without cardiac injury. They also had prolonged QTc intervals and more T wave changes. Logistic regression model identified that the number of abnormal T waves (odds ratio (OR), 2.36 [95% confidence interval (CI), 1.38-4.04], P=0.002) and QTc interval (OR, 1.31 [95% CI, 1.03-1.66], P=0.027) were independent indicators for cardiac injury. The combination model of these two parameters along with age could well discriminate cardiac injury (area the under curve 0.881, P<0.001) by receiver operating characteristic analysis. Cox regression model identified that the presence of T wave changes was an independent predictor of mortality (hazard ratio, 3.57 [1.40, 9.11], P=0.008) after adjustment for age.

In COVID-19 patients, presence of cardiac injury at admission is associated with poor clinical outcomes. Repolarization abnormalities on surface ECG such as abnormal T waves and prolonged QTc intervals are more common in patients with cardiac involvement and can help in further risk stratification.
In COVID-19 patients, presence of cardiac injury at admission is associated with poor clinical outcomes. link2 Repolarization abnormalities on surface ECG such as abnormal T waves and prolonged QTc intervals are more common in patients with cardiac involvement and can help in further risk stratification.The corona virus disease 2019 (COVID-19) is a highly contagious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). More than 18 million people were infected with a total of 0.7 million deaths in ∼188 countries. Controlling the spread of SARS-CoV-2 is therefore inherently dependent on identifying and isolating infected individuals, especially since COVID-19 can result in little to no symptoms. Here, we provide a comprehensive review of the different primary technologies used to test for COVID-19 infection, discuss the advantages and disadvantages of each technology, and highlight the studies that have employed them. We also describe technologies that have the potential to accelerate SARS-CoV-2 detection in the future, including digital PCR, CRISPR, and microarray. Finally, remaining challenges in COVID-19 diagnostic testing are discussed, including (a) the lack of universal standards for diagnostic testing; (b) the identification of appropriate sample collection site(s); (c) the difficulty in performing large population screening; and (d) the limited understanding of SARS-COV-2 viral invasion, replication, and transmission.
While there have been encouraging preliminary clinical results for immune checkpoint inhibitors (ICIs) in BTCs, it remains a challenge to identify the subset of patients who may benefit. In this study, we evaluated the efficacy of ICI treatment in patients with advanced BTCs, and explored potential biomarkers that are predictive of response.

The study enrolled 26 patients with advanced microsatellite stable BTCs (15 with gallbladder cancers [GCs] and 11 with intrahepatic cholangiocarcinoma [ICCs]) who received ICI treatment. Targeted next-generation sequencing (NGS) was performed on tumor tissue samples collected from 17 patients. Clinical and genomic characteristics were assessed for the correlation with clinical outcome.

Analysis of the baseline clinical characteristics showed that performance score (PS) of 0 was associated with a better prognosis than PS of 1 (HR=1.08×10
; 95% CI, 0∼Inf; P=.002). No significant correlations were found between clinical outcome and inflammation-related indicators. NGnical response to ICIs in advanced BTCs patients. A larger sample size is required for further verification.
Our study identified several potential clinical and genomic features that may serve as biomarkers of clinical response to ICIs in advanced BTCs patients. A larger sample size is required for further verification.
Although targeting histone deacetylases (HDACs) may be an effective strategy for core binding factor-acute myeloid leukemia (CBF-AML) harboring t(8;21) or inv(16), HDAC inhibitors are reported to be limited by drug-resistant characteristic. Our purpose is to evaluate the anti-leukemia effects of Baicalein on CBF-AML and clarify its underlying mechanism.

Enzyme activity assay was used to measure the activity inhibition of HDACs. Rhodamine123 and RT-qPCR were employed to evaluate the distribution of drugs and the change of ATP-binding cassette (ABC) transporter genes. CCK8, Annexin V/PI, and FACS staining certified the effects of Baicalein on cell growth, apoptosis, and differentiation. Duolink and IP assay assessed the interaction between HDAC-1 and ubiquitin, HSP90 and AML1-ETO, and Ac-p53 and CBFβ-MYH11. AML cell lines and primary AML cells-bearing NOD/SCID mice models were used to evaluate the anti-leukemic efficiency and potential mechanism of Baicalein in vivo.

Baicalein showed HDAC-1/8 inhibition tregulation of Baicalein, and warrant therapeutic potential of Baicalein for CBF-AML.
Gut microbiome plays a crucial role in modulating human and animal immune responses. Rabies is a fatal zoonosis causing encephalitis in mammals and vaccination is the most effective method to control and eliminate rabies. The relationship between the gut microbiome and humoral immunity post rabies vaccination has not been investigated yet.

Mice orally administrated with a cocktail of broad-spectrum antibiotics were inoculated with rabies vaccines, and humoral immune response was analyzed at indicated time points. The 16S ribosomal RNA (16S rRNA) gene sequencing was performed on fecal samples from groups in vancomycin-treated and untreated mice. Mice were immunized with rabies vaccines and virus-neutralizing antibody (VNA) levels were measured, resulting in VNA high (H) and low (L) groups. Then 16S rRNA gene sequencing was performed on fecal samples from H and L group mice.

After antibiotic (Abx) treatment, mice had decreased levels of rabies virus (RABV)-specific IgM, IgG, and virus-neutralizing antibods and vaccines.
Pyrotinib was well tolerated but its efficacy was unsatisfactory in patients with HER2-positive gastric cancer (GC) (NCT02378389). This study was to optimize the efficacy of pyrotinib.

Human GC cell lines and AVATAR mice were used to explore the refractory mechanisms of pyrotinib. A pyrotinib-combined strategy was proposed, which was validated in preclinical AVATAR mouse and in clinical patients enrolled in a phase I clinical trial (NCT03480256).

Dysregulation of CCND1-CDK4/6-Rb axis might be the key to pyrotinib refractory. The strategy of pyrotinib combined with a CDK4/6 inhibitor SHR6390 was proposed and validated in preclinical AVATAR mouse, which was successfully verified in clinical patients. For five patients treated with pyrotinib plus SHR6390 who had available response evaluation, the best response was partial response in three patients, stable disease in one patient, and progressive disease in one patient. The progression-free survival times were 120, 200, 532, 109, and 57 days, respectively.

This translational study suggests that pyrotinib combined with SHR6390 may serve as a promising strategy for patients with HER2-positive GC.

The ClinicalTrials.gov identifiers are NCT02378389 (https//clinicaltrials.gov/ct2/show/study/NCT02378389, registered in 11 February 2015) and NCT03480256 (https//clinicaltrials.gov/ct2/show/study/NCT03480256, registered in 8 March 2018).
The ClinicalTrials.gov identifiers are NCT02378389 (https//clinicaltrials.gov/ct2/show/study/NCT02378389, registered in 11 February 2015) and NCT03480256 (https//clinicaltrials.gov/ct2/show/study/NCT03480256, registered in 8 March 2018).Lung cancer has high mortality, often accompanied with systemic metabolic disorders. The present study aimed at defining values of trans-nodules cross-clinical phenomic and lipidomic network layers in patients with adenocarcinoma (ADC), squamous cell carcinomas, or small cell lung cancer (SCLC). link3 We measured plasma lipidomic profiles of lung cancer patients and found that altered lipid panels and concentrations varied among lung cancer subtypes, genders, ages, stages, metastatic status, nutritional status, and clinical phenome severity. It was shown that phosphatidylethanolamine elements (362, 180/182, and 181/181) were SCLC specific, whereas lysophosphatidylcholine (201 and 220 sn-position-1) and phosphatidylcholine (190/190 and 190/212) were ADC specific. There were statistically more lipids declined in male, less then 60 ages, late stage, metastasis, or body mass index less then 22 . Clinical trans-omics analyses demonstrated that one phenome in lung cancer subtypes might be generated from multiple metabolic pathways and metabolites, whereas a metabolic pathway and metabolite could contribute to different phenomes among subtypes, although those needed to be furthermore confirmed by bigger studies including larger population of patients in multicenters.
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