To evaluate in how many cancer-related Cochrane reviews hazard ratio (HR)-based absolute effects in summary of findings (SoF) tables have been correctly calculated and reported.

Owing to the complexity of naphthenic acids (NAs) in oil sands process water (OSPW), previous ozone-treatment studies mainly investigated the removal of classical NAs (aliphatic O2-NAs) and the understanding of ozonation reactivity of other NA species has been limited. This work utilized a silver-ion solid phase extraction (SPE) approach to separate individual NA species into 20 fractions before subsequent ozone treatment. The ozonation reactivity of aromatic and oxidized NA species in isolated fractions was studied for the first time. Untreated and ozone-treated SPE fractions were characterized using ultra performance liquid chromatography ion mobility time-of-flight mass spectrometry. The removals of aliphatic O2-NAs (Fraction 3), aromatic O2-NAs (Fraction 8), O3-NAs (Fraction 11), and O4-NAs (Fraction 17) with an applied ozone dosage of 16.8 mg L-1 were 97.2%, 94.7%, 59.4% and 44.7%, respectively. The results showed that aromatic and oxidized NAs with larger carbon number were favorably removed during ozonation treatment. Comparison of the ozone utilization efficiency for different NA species indicated that the degradation of oxidized NAs consumed more ozone in molar ratio than the degradation of classical and aromatic NAs. The reactivity of oxidized NAs was lower than that of classical NAs because the former consumed more ozone in molar ratio during reactions. Knowing the reactivity of different NA species is crucial for the design of ozonation systems targeting species with high toxicity. Moreover, the utilization of silver-ion SPE pre-separation approach has been demonstrated for future studies investigating the degradation mechanism of distinct NA species under other treatment conditions.

Maternal environmental factors such as diet have profound effects on offspring development and later health. The hypothalamic-pituitary-adrenal (HPA) axis is an important stress neuroendocrine system that is subject to programming by early life challenges. The present study was further to investigate whether maternal high fat diet (HFD) exposure during rat pregnancy and lactation can alter the HPA axis activity in adult male offspring. We observed that maternal HFD consumption exerted long-term effects on the basal activity of the HPA axis in adult offspring, with increased mean plasma corticosterone levels that result from elevated steroid pulse frequence and pulse amplitude. More importantly, maternal HFD offspring displayed enhanced corticosterone responses to restraint (1 h) and lipopolysaccharide (25 μg/kg, iv) but not insulin-induced hypoglycemia (0.3U/kg, iv) stress, suggesting a stressor-specific effect of maternal diet on the hyperresponsiveness of the HPA axis to stress. Additionally, maternal HFD exposure markedly attenuated the habituation of HPA responses to repeated restraint stress. These findings demonstrate that perinatal HFD exposure has a potent and long-lasting influence on development of neuroendocrine regulatory mechanisms. Maternal HFD consumption significantly increased basal corticotropin-releasing factor (CRF) mRNA expression in the paraventricular nucleus; nevertheless, similar increments in CRF mRNA levels following restraint were observed between maternal HFD offspring and control rats. Furthermore, the medial and central nuclei of amygdala played a pivotal role in maternal HFD-induced sensitization of the HPA response to psychological and systemic stress, respectively, suggesting that different neural pathways may mediate maternal HFD-induced HPA hyperresponsivity to different types of stressors. Take together, the long-term effects of maternal HFD challenge on the central regulation of the HPA axis, therefore, expose the adult offspring to greater HPA function throughout lifespan, in stressor-specific and region-specific manner.

Kinetoplastid RNA (kRNA) editing takes place in the mitochondria of kinetoplastid protists and creates translatable mRNAs by uridine insertion/deletion. Extensively edited (pan-edited) transcripts contain quadruplex forming guanine stretches, which must be remodeled to promote uridine insertion/deletion. Here we show that the RRM domain of the essential kRNA-editing factor TbRGG2 binds poly(G) and poly(U) RNA and can unfold both. A region C-terminal to the RRM mediates TbRGG2 dimerization, enhancing RNA binding. A RRM-U4 RNA structure reveals a unique RNA-binding mechanism in which the two RRMs of the dimer employ aromatic residues outside the canonical RRM RNA-binding motifs to encase and wrench open the RNA, while backbone atoms specify the uridine bases. Notably, poly(G) RNA is bound via a different binding surface. Thus, these data indicate that TbRGG2 RRM can bind and remodel several RNA substrates suggesting how it might play multiple roles in the kRNA editing process.

Bacterial recombinational repair of double-strand breaks often begins with creation of initiating 3' single-stranded DNA (ssDNA) tails on each side of a double-strand break (DSB). Importantly, if the RecBCD pathway is followed, RecBCD creates a gap between the sequences at 3' ends of the initiating strands. The gap flanks the DSB and extends at least to the nearest Chi site on each strand. Once the initiating strands form ssDNA-RecA filaments, each ssDNA-RecA filament searches for homologous double-stranded DNA (dsDNA) to use as a template for the DNA synthesis needed to fill the gap created by RecBCD. Our experimental results show that the DNA synthesis requires formation of a heteroduplex dsDNA that pairs >20 contiguous bases in the initiating strand with sequence matched bases in a strand from the original dsDNA. To trigger synthesis, the heteroduplex must be near the 3' end of the initiating strand. Those experimentally determined requirements for synthesis combined with the Chi site dependence of the function of RecBCD and the distribution of Chi sites in bacterial genomes could allow the RecBCD pathway to avoid some genomic rearrangements arising from directly induced DSBs; however, the same three factors could promote other rearrangements.

Small interfering RNA (siRNA)-based therapies are proving to be efficient for treating liver-associated disorders. However, extra-hepatic delivery remains challenging, limiting therapeutic siRNA utility. We synthesized a panel of fifteen lipid-conjugated siRNAs and systematically evaluated the impact of conjugate on siRNA tissue distribution and efficacy. Generally, conjugate hydrophobicity defines the degree of clearance and the liver-to-kidney distribution profile. In addition to primary clearance tissues, several conjugates achieve significant siRNA accumulation in muscle, lung, heart, adrenal glands and fat. Oligonucleotide distribution to extra-hepatic tissues with some conjugates was significantly higher than with cholesterol, a well studied conjugate, suggesting that altering conjugate structure can enhance extra-hepatic delivery. These conjugated siRNAs enable functional gene silencing in lung, muscle, fat, heart and adrenal gland. Required levels for productive silencing vary (5-200 μg/g) per tissue, suggesting that the chemical nature of conjugates impacts tissue-dependent cellular/intracellular trafficking mechanisms. The collection of conjugated siRNA described here enables functional gene modulation in vivo in several extra-hepatic tissues opening these tissues for gene expression modulation. A systemic evaluation of a panel of conjugated siRNA, as reported here, has not previously been investigated and shows that chemical engineering of lipid siRNAs is essential to advance the RNA therapeutic field.

Temporal data on gene expression and context-specific open chromatin states can improve identification of key transcription factors (TFs) and the gene regulatory networks (GRNs) controlling cellular differentiation. However, their integration remains challenging. Here, we delineate a general approach for data-driven and unbiased identification of key TFs and dynamic GRNs, called EPIC-DREM. We generated time-series transcriptomic and epigenomic profiles during differentiation of mouse multipotent bone marrow stromal cell line (ST2) toward adipocytes and osteoblasts. Using our novel approach we constructed time-resolved GRNs for both lineages and identifed the shared TFs involved in both differentiation processes. To take an alternative approach to prioritize the identified shared regulators, we mapped dynamic super-enhancers in both lineages and associated them to target genes with correlated expression profiles. The combination of the two approaches identified aryl hydrocarbon receptor (AHR) and Glis family zinc finger 1 (GLIS1) as mesenchymal key TFs controlled by dynamic cell type-specific super-enhancers that become repressed in both lineages. AHR and GLIS1 control differentiation-induced genes and their overexpression can inhibit the lineage commitment of the multipotent bone marrow-derived ST2 cells.

Epidermolysis bullosa (EB) refers to a group of rare inherited mechanobullous disorders that present with great clinical and genetic heterogeneity. Its severity ranges from mild blistering to life-threatening. However, the clinical symptoms of different types of EB overlap significantly, especially at an early stage. Thus it is important to clarify the diagnosis for prognostic implications, patient management, and genetic counseling.

A thyroid nodule discovered during imaging study performed due to unrelated thyroid disease is known as a thyroid incidentaloma, while positron emission tomography (PET) associated incidental neoplasm of thyroid is known as a "PAIN" phenomenon.To evaluate which patients with "PAIN" phenomenon should undergo surgery in regards to cytology results.Retrospective review of 4716 patients consecutively admitted and surgically treated in tertiary surgical center. 49 (1.04%) patients with "PAIN" phenomenon were identified. All of them had ultrasound-guided fine needle aspiration biopsy (UG-FNAB) performed and cytological results were evaluated according to The Bethesda System for Reporting Thyroid Cytopathology (TBSRTC). Patients were divided into 2 subgroups according to histopathological diagnosis: group 1 (n = 25) with benign tumor and group 2 (n = 24) with thyroid cancer.Cytology results were the significant predictors of cancer occurrence in patients with "PAIN" phenomenon (P < .0001). Logistic regression analysis confirmed that category III or higher of TBSRTC in patients with "PAIN" phenomenon significantly increased the risk of cancer (OR = 168.7, P < .0001).Patients with "PAIN" phenomenon and cytology assigned to category III or higher of the Bethesda system should undergo surgery due to significant risk of thyroid malignancy.

Atrial fibrillation (AF) is the most common type of heart arrhythmia, but the impact of long-term, high-intensity endurance exercise on the risk of AF remains uncertain.

We aimed to evaluate the prognostic significance of the preoperative Controlling Nutritional Status (CONUT) score in patients with renal cell carcinoma (RCC), and then compared its accuracy of the prognostic nutritional index (PNI), neutrophil-to-lymphocyte ratio (NLR), and platelet-to-lymphocyte ratio (PLR) as predictors of survival.We included 635 patients who underwent nephrectomy for RCC from January 2004 to July 2014. The X-tile program was used to determine the optimal cut-off values for CONUT score, PNI, NLR, and PLR.The median follow-up duration after surgery was 48.40 (29.30-80.10) months. The optimal cutoff values were 2 for CONUT score, 48 for PNI, 3.5 for NLR and 204.7 for PLR by X-tile program with cancer-specific survival (CSS) as end-point. Higher CONUT score, NLR and PLR, and lower PNI were statistically associated with worse OS and CSS in the univariate analysis. Multivariate analysis showed that higher CONUT score was an independent predictor for OS (HR = 3.012; 95% CI, 1.525-5.948; P = .001) and CSS (HR = 3.001; 95% CI, 1.290-6.984; P = .011), and CONUT score was superior to PNI, NLR, and PLR according to the HR.Therefore, preoperative CONUT score can be a strong independent predictor in RCC patients after nephrectomy.

Prediction of pain using machine learning algorithms is an emerging field in both computer science and clinical medicine. Several machine algorithms were developed and validated in recent years. However, the majority of studies in this topic was published on bioinformatics or computer science journals instead of medical journals. This tendency and preference led to a gap of knowledge and acknowledgment between computer scientists who invent the algorithm and medical researchers who may use the algorithms in practice. As a consequence, some of these prediction papers did not discuss the clinical utility aspects and were causally reported without following related professional guidelines (e.g., TRIPOD statement). The aim of this protocol is to systematically summarize the current evidences about performance and utility of different machine learning methods used for automatic pain assessments based on human facial expression. In addition, this study is aimed to demonstrate and fill the knowledge gap to promote interdisciplinary collaboration.

Drug-induced liver injury (DILI) is a potentially severe adverse drug reaction especially in susceptible patients. But there are no sensitive or specific parameters to detecting DILI. The specific expression of miR-122 in the liver has been a hotspot in the evaluation of hepatic toxicity due to its high stability and sensitivity.

To analyze the clinical outcome and prognostic factors of N3 nasopharyngeal carcinomas (NPCs), provide a basis for rational treatment and improve the cure rate.

Vitamin K antagonists (VKAs) may have potential antitumor effects in prostate cancer. However, the findings of observational studies are inconsistent. The purpose of the present study was to estimate the quantitative association between VKAs use and prostate cancer risk by combining the results of all eligible observational studies.

Phosphatase and tension homolog deleted on chromosome 10 (PTEN) was considered as a promising target in type 2 diabetes mellitus (T2DM) because of its negative effects on insulin resistance. Alteration in DNA methylation is thought to play a role in the pathogenesis of T2DM. The aim of the present study was to quantitatively evaluate the promoter methylation of PTEN in Uyghur patients with mild T2DM. We evaluated methylation levels in 21 CpG sites from -2515 bp to -2186 bp relative to the translation initiation site in 55 cases of T2DM and 50 cases of normal glucose tolerance (NGT) using the MassARRAY spectrometry. In addition, PTEN mRNA and protein levels were measured by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) and western blotting to determine whether DNA methylation alterations were responsible for PTEN expression. Compared with NGT groups, the PTEN mRNA expression was significantly higher in Uyghur patients with mild T2DM groups. We also showed that PTEN protein expression was upregulated in Uyghur patients with mild T2DM groups, but the level of protein kinase B (AKT) was downregulated. PTEN methylation in T2DM patients was significantly lower than that in NGT groups. In addition, 2 CpG units demonstrated a significant difference between the NGT and Uyghur patients with mild T2DM groups. Furthermore, there was a negative association between promoter methylation and PTEN expression. Together, these findings suggest that epigenetic inactivation of PTEN plays an important role in Uyghur patients with mild T2DM. The aberrant methylation of CpG sites within the PTEN promoter may serve as a potential candidate biomarker for T2DM in the Uyghur population.

The transcriptional activity of Bradyrhizobium diazoefficens isolated from soybean nodules was monitored over the period from symbiosis to late plant nodule senescence. The bacteria retained a near constant level of RNA throughout this period, and the variation in genes demonstrating increased, decreased, and/or patterned transcriptional activity indicates that the bacteria are responding to the changing environment within the nodule as the plant cells progress from an organized cellular structure to an unorganized state of internal decay. The transcriptional variation and persistence of the bacteria suggest that the bacteria are adapting to their environment and acting similar to hemibiotrophs, which survive both as saprophytes on live plant tissues and then as necrophytes on decaying plant tissues. The host plant restrictions of symbiosis make B. diazoefficiens a highly specialized, restricted hemibiotroph.

Omnidirectional sound sources are needed to perform a large variety of tests in acoustics. Typically, they consist of conventional speaker drivers arranged in a dodecahedron. However, the directivity of the speaker drivers sharpens with frequency, which induces an intense decrease of the sound pressure levels at the edges of the dodechaedron. In this work, the problem is mitigated by building an Omnidirectional Parametric Loudspeaker (OPL), which contains hundreds of small ultrasound transducers set on a sphere. Each transducer emits an ultrasonic carrier wave modulated by an audible signal. Thanks to nonlinear propagation, the air itself demodulates the signal bringing it back to the audible range. The construction of an OPL prototype is challenging. The structure has been built by 3D-printing a set of pieces that conform to the sphere. Each piece contains the exact location of the transducers, which are aligned in parallels to facilitate the structural assembly and the wiring. The performance of the OPL has been tested in an anechoic chamber. Measurements show that the OPL has a good omnidirectional behavior for most frequencies. It clearly improves the directivity of dodechaedral sources in the high frequency range, but performs worse at low frequencies.

Polymorphisms of the estrogen receptor ESR1 and ESR2 genes have been linked with cognitive deficits and affective disorders. The effects of these genetic variants on emotional processing in females with low estrogen levels are not well known. The aim was to explore the impact of the ESR1 and ESR2 genes on the responses to the facial emotion recognition task in females. Postmenopausal healthy female volunteers were genotyped for the polymorphisms Xbal and PvuII of ESR1 and the polymorphism rs1256030 of ESR2. The effect of these polymorphisms on the response to the facial emotion recognition of the emotions happiness, sadness, disgust, anger, surprise, and fear was analyzed. Females carrying the P allele of the PvuII polymorphism or the X allele of the Xbal polymorphism of ESR1 easily recognized facial expressions of sadness that were more difficult for the women carrying the p allele or the x allele. They displayed higher accuracy, fast response time, more correct responses, and fewer omissions to complete the task, with a large effect size. Women carrying the ESR2 C allele of ESR2 showed a faster response time for recognizing facial expressions of anger. These findings link ESR1 and ESR2 polymorphisms in facial emotion recognition of negative emotions.

Atractylodis Rhizoma is the dried rhizome of Atractylodes lancea (Thunb.) DC. or Atractylodes chinensis (DC.) Koidz and is often processed by stir-frying with wheat bran to reduce its dryness and increase its spleen tonifying activity. However, the mechanism by which the processing has this effect remains unknown. To explain the mechanism based on the pharmacokinetics of the active compounds, a rapid, sensitive ultra-performance liquid chromatography-tandem mass spectrometry method was developed to analyze atractylenolides I, II, and III, and atractyloside A simultaneously in rat plasma after oral administration of raw and processed Atractylodis Rhizoma. Acetaminophen was used as the internal standard and the plasma samples were pretreated with methanol. Positive ionization mode coupled with multiple reaction monitoring mode was used to analyze the four compounds. The method validation revealed that all the calibration curves displayed good linear regression over the concentration ranges of 3.2⁻350, 4⁻500, 4⁻500, and 3.44⁻430 ng/mL for atractylenolides I, II, and III, and atractyloside A, respectively. The relative standard deviations of the intra- and inter-day precisions of the four compounds were less than 6% with accuracies (relative error) below 2.38%, and the extraction recoveries were more than 71.90 ± 4.97%. The main pharmacokinetic parameters of the four compounds were estimated with Drug and Statistics 3.0 and the integral pharmacokinetics were determined based on an area under the curve weighting method. The results showed that the integral maximum plasma concentration and area under the curve increased after oral administration of processed Atractylodis Rhizoma.