bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of hydrokinesitherapy on balance and walking ability in stroke survivors: a systematic review and meta-analysis of randomized controlled studies
Authors: Xie Guanli , Wang Tao , Jiang Bo , Su Yan , Tang Xiaoxia , Guo Ying , Liao Jianglong
Published: November 2019

Background

Balance and walking impairment are common dysfunctions after stroke. Emerging data has demonstrated that hydrokinesitherapy may have a positive influence on improvement of balance and walking ability. However, there is no firm evidence to support these results. Therefore, the aim of this review is to evaluate the effects of hydrokinesitherapy in stroke survivors systematically.

Methods

Medline, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, CINAHL and SPORTDiscus were systemic searched from their inception to Septemter 30, 2018. RevMan 5.3 software was used to perform data synthesis. The fixed-effect model or random-effect model was employed according to the results of heterogeneity test. The mean differences (MD) or standardized mean difference (SMD) was used to evaluate the pooled effect of hydrokinesitherapy on balance function, walking ability and activty of daily life (ADL).

Results

A total of 13 studies were included involving 381 stroke survivors. Meta-analysis results indicated that hydrokinesitherapy could improve balance ability based on three test: Berg balance scale (BBS: MD = 3.84, 95% confidence interval (95% CI) 2.84 to 4.86, P < 0.001), Time Up To Go Test (TUGT: MD = − 1.22, 95% CI − 2.25 to − 0.18, P = 0.02, fixed-effect model), Functional Reach Test (FRT: MD = 2.41, 95% CI 1.49 to 3.33, P < 0.001). Additionally, we found a weakly positive effect on walking speed (SMD = 0.75, 95% CI 0.26 to 1.25, P = 0.003) and walking ability test (SMD = 0.36, 95% CI 0.04 to 0.68, P = 0.03). There was no significant difference between experimental group and control group in terms of ADL.

Short conclusion

Hydrokinesitherapy can improve balance function and had a weakly positive effect on walking ability in stroke survivors. We did not find sufficient evidence to indicate that hydrokinesitherapy could improve the ADL of stroke survivors. However, due to the methodological shortcoming and small number of included studies, caution is needed when interpreting these results. Due to imprecision and publication bias, the quality of the evidence was downgraded to “low-quality” for the primary outcomes of balance and walking ability.

Trial registration

CRD42018110787.
An influential meal: host plant dependent transcriptional variation in the beet armyworm, Spodoptera exigua (Lepidoptera: Noctuidae)
Authors: Breeschoten Thijmen , Ros Vera I. D. , Schranz M. Eric , Simon Sabrina
Published: November 2019

Background

To understand the genetic mechanisms of insect herbivory, the transcriptional response of insects feeding on different host plant species has to be studied. Here, we generated gene expression data of the generalist herbivoreSpodoptera exigua(Hübner) feeding on three selected host plant species and a control (artificial diet). The host plant species used in this study –cabbage (Brassica oleracea), maize (Zea mays) and tobacco (Nicotiana tabacum)- are members of different plant families that each employ specific defence mechanisms and toxins.

Results

Spodoptera exigualarvae had a higher growth rate, indicator for herbivore success, when feeding onZ. mayscompared to larvae feeding onB. oleraceaorN. tabacum. Larvae feeding on the different host plant species showed divergent transcriptional responses. We identified shared and unique gene expression patterns dependent of the host plant species the larvae fed on. Unique gene expression patterns, containing uniquely upregulated transcripts including specific detoxification genes, were found for larvae feeding on eitherB. oleraceaorN. tabacum. No diet-specific gene cluster was identified for larvae feeding on the host for which larvae showed optimal herbivore success,Z. mays,or artificial diet.In contrast, for larvae feeding on hosts for which they showed low herbivore success, specific diet-dependent gene clusters were identified. Functional annotation of these clusters indicates thatS. exigualarvae deploy particular host plant-specific genes for digestion and detoxification.

Conclusions

The lack of a host plant-specific gene activity for larvae feeding onZ. maysand the artificial diet suggest a general and non-specific gene activity for host plants with optimal herbivore success. Whereas the finding of specific gene clusters containing particular digestion and detoxifying genes expressed in larvae feeding onB. oleraceaandN. tabacum, with low herbivore success, imply a host plant-specific gene activity for larvae feeding on host plants with suboptimal herbivore success. This observation leads to the conclusion that a polyphagous herbivore is able to feed on a large variation of host plants due to the flexibility and diversity of genes involved in digestion and detoxification that are deployed in response to particular host plant species.
A gastric cancer LncRNAs model for MSI and survival prediction based on support vector machine
Authors: Chen Tao , Zhang Cangui , Liu Yingqiao , Zhao Yuyun , Lin Dingyi , Hu Yanfeng , Yu Jiang , Li Guoxin
Published: November 2019

Background

Recent studies have shown that long non-coding RNAs (lncRNAs) play a crucial role in the induction of cancer through epigenetic regulation, transcriptional regulation, post-transcriptional regulation and other aspects, thus participating in various biological processes such as cell proliferation, differentiation and apoptosis. As a new nova of anti-tumor therapy, immunotherapy has been shown to be effective in many tumors of which PD-1/PD-L1 monoclonal antibodies has been proofed to increase overall survival rate in advanced gastric cancer (GC). Microsatellite instability (MSI) was known as a biomarker of response to PD-1/PD-L1 monoclonal antibodies therapy. The aim of this study was to identify lncRNAs signatures able to classify MSI status and create a predictive model associated with MSI for GC patients.

Methods

Using the data of Stomach adenocarcinoma from The Cancer Genome Atlas (TCGA), we developed and validated a lncRNAs model for automatic MSI classification using a machine learning technology – support vector machine (SVM). The C-index was adopted to evaluate its accuracy. The prognostic values of overall survival (OS) and disease-free survival (DFS) were also assessed in this model.

Results

Using the SVM, a lncRNAs model was established consisting of 16 lncRNA features. In the training cohort with 94 GC patients, accuracy was confirmed with AUC 0.976 (95% CI, 0.952 to 0.999). Veracity was also confirmed in the validation cohort (40 GC patients) with AUC 0.950 (0.889 to 0.999). High predicted score was correlated with better DFS in the patients with stage I-III and lower OS with stage I-IV.

Conclusion

This study identify 16 LncRNAs signatures able to classify MSI status. The correlation between lncRNAs and MSI status indicates the potential roles of lncRNAs interacting in immunotherapy for GC patients. The pathway of these lncRNAs which might be a target in PD-1/PD-L1 immunotherapy are needed to be further study.
Diagnostic tools used in the evaluation of acute febrile illness in South India: a scoping review
Authors: Bhaskaran Divyalakshmi , Chadha Sarabjit Singh , Sarin Sanjay , Sen Rajashree , Arafah Sonia , Dittrich Sabine
Published: November 2019

Background

Acute febrile illness (AFI) is characterized by malaise, myalgia and a raised temperature that is a nonspecific manifestation of infectious diseases in the tropics. The lack of appropriate diagnostics for the evaluation of AFI leads to increased morbidity and mortality in resource-limited settings, specifically low-income countries like India. The review aimed to identify the number, type and quality of diagnostics used for AFI evaluation during passive case detection at health care centres in South India.

Methods

A scoping review of peer-reviewed English language original research articles published between 1946-July 2018 from four databases was undertaken to assess the type and number of diagnostics used in AFI evaluation in South India. Results were stratified according to types of pathogen-specific tests used in AFI management.

Results

The review included a total of 40 studies, all conducted in tertiary care centres (80% in private settings). The studies demonstrated the use of 5–22 tests per patient for the evaluation of AFI. Among 25 studies evaluating possible causes of AFI, 96% tested for malaria followed by 80% for dengue, 72% for scrub typhus, 68% for typhoid and 60% for leptospirosis identifying these as commonly suspected causes of AFI. 54% studies diagnosed malaria with smear microscopy while others diagnosed dengue, scrub typhus, typhoid and leptospirosis using antibody or antigen detection assays. 39% studies used the Weil-Felix test (WFT) for scrub typhus diagnosis and 82% studies used the Widal test for diagnosing typhoid.

Conclusions

The review demonstrated the use of five or more pathogen-specific tests in evaluating AFI as well as described the widespread use of suboptimal tests like the WFT and Widal in fever evaluation. It identified the need for the development of better-quality tests for aetiological diagnosis and improved standardised testing guidelines for AFI.
A novel training simulator for portable ultrasound identification of incorrect newborn endotracheal tube placement – observational diagnostic accuracy study protocol
Authors: Merali Hasan S. , Tessaro Mark O. , Ali Khushboo Q. , Morris Shaun K. , Soofi Sajid B. , Ariff Shabina
Published: November 2019

Background

Endotracheal tube (ETT) placement is a critical procedure for newborns that are unable to breathe. Inadvertent esophageal intubation can lead to oxygen deprivation and consequent permanent neurological impairment. Current standard-of-care methods to confirm ETT placement in neonates (auscultation, colorimetric capnography, and chest x-ray) are time consuming or unreliable, especially in the stressful resuscitation environment. Point-of-care ultrasound (POCUS) of the neck has recently emerged as a powerful tool for detecting esophageal ETTs. It is accurate and fast, and is also easy to learn and perform, especially on children.

Methods

This will be an observational diagnostic accuracy study consisting of two phases and conducted at the Aga Khan University Hospital in Karachi, Pakistan. In phase 1, neonatal health care providers that currently perform standard-of-care methods for ETT localization, regardless of experience in portable ultrasound, will undergo a two-hour training session. During this session, providers will learn to detect tracheal vs. esophageal ETTs using POCUS. The session will consist of a didactic component, hands-on training with a novel intubation ultrasound simulator, and practice with stable, ventilated newborns. At the end of the session, the providers will undergo an objective structured assessment of technical skills, as well as an evaluation of their ability to differentiate between tracheal and esophageal endotracheal tubes. In phase 2, newborns requiring intubation will be assessed for ETT location via POCUS, at the same time as standard-of-care methods. The initial 2 months of phase 2 will include a quality assurance component to ensure the POCUS accuracy of trained providers. The primary outcome of the study is to determine the accuracy of neck POCUS for ETT location when performed by neonatal providers with focused POCUS training, and the secondary outcome is to determine whether neck POCUS is faster than standard-of-care methods.

Discussion

This study represents the first large investigation of the benefits of POCUS for ETT confirmation in the sickest newborns undergoing intubations for respiratory support.

Trial registration

ClinicalTrials.gov Identifier: NCT03533218. Registered May 2018.
Maternal and paternal perinatal depressive symptoms associate with 2- and 3-year-old children’s behaviour: findings from the APrON longitudinal study
Authors:   The APrON Team, Letourneau Nicole , Leung Brenda , Ntanda Henry , Dewey Deborah , Deane Andrea J. , Giesbrecht Gerald F.
Published: November 2019

Background

Prenatal and postnatal depressive symptoms are common in expectant and new mothers and fathers. This study examined the association between four patterns of probable perinatal depression (mother depressed, father depressed, both depressed, neither depressed) in co-parenting mothers and fathers and their children’s internalizing and externalizing behaviours at 24 and 36 months of age. The influence of sociodemographic, risk and protective factors was also examined.

Methods

Depressive symptoms were measured during pregnancy and at 3 months postpartum and children’s behaviour was assessed at 24 and 36 months of age. Families (n = 634) provided data on their children’s internalizing (i.e. emotionally reactive, anxious/depressed, somatic complaints, withdrawn and total) and externalizing (i.e. attention problems, aggression and total) behaviour. Marginal models were employed to determine the relationship between children’s behaviour over the two time points and the four patterns of probable parental depression. Sociodemographic variables as well as risk (stress) and protective (social support) factors were included in these models.

Results

In the perinatal period 19.40% (n = 123) of mothers scored as probably depressed and 10.57% (n = 67) of fathers. In 6.31% (n = 40) of the participating families, both parents scored as probably depressed and in 63.72% (n = 404) neither parent scored as depressed. For children’s emotionally reactive, withdrawn and total internalizing behaviours, both mothers’ probable depression and mothers and fathers’ co-occurring probable depression predicted higher scores, while for children’s aggressive behaviour, attention problems, and total externalizing behaviours, only mothers’ probable depression predicted higher scores, controlling for sociodemographic, risk and protective factors.

Conclusions

While probable perinatal depression in mothers predicted 2 and 3 year-old children’s behavioural problems, co-occurrence of depression in mothers and fathers had an increased association with internalizing behavioural problems, after considering sociodemographic, risk and protective factors. Health care providers are encouraged to consider the whole family in preventing and treating perinatal depression.
Association between early childhood caries and malnutrition in a sub-urban population in Nigeria
Authors: Folayan Morenike Oluwatoyin , Arije Olujide , El Tantawi Maha , Kolawole Kikelomo Adebanke , Obiyan Mary , Arowolo Olaniyi , Oziegbe Elizabeth O.
Published: November 2019

Background

To determine the association between malnutrition and early childhood caries (ECC) in children resident in sub-urban, Nigeria.

Methods

This study was a subset of a larger cross-sectional study the data of which was generated through a household survey conducted in Ile-Ife, Nigeria. The study’s explanatory variable was malnutrition (underweight, overweight, wasting and stunting) and the outcome variable was ECC. Poisson regression analysis was used to determine the association between ECC and malnutrition. Variables (sex, frequency of sugar consumption, maternal knowledge of oral hygiene, oral hygiene status) associated with ECC in the primary study were adjusted for to obtain the adjusted prevalence ratio (APR).

Results

Of the 370 children, 20 (5.41%) were underweight, 20 (5.41%) were overweight, 67 (18.11%) were wasting, 120 (32.43%) were stunted and 18 (4.86%) had ECC. Factors associated with ECC were being stunted, underweight, overweight and fair oral hygiene. The prevalence of ECC was lower in children who were stunted (APR: 0.14; 95% CI: 0.03–0.69;p = 0.02), almost seven times higher in children who were overweight (APR: 6.88; 95% CI: 1.83–25.85;p < 0.001), and predictively absent in children who were underweight (APR: 0; 95% CI: 0–0; p < 0.001) when compared with children who had normal weight. Non-significant risk indicators for ECC included consuming sugar between meals three times a day or more, having low socioeconomic status and being female.

Conclusions

For this study population, the indicators of malnutrition – being stunted, underweight, overweight - and fair oral hygiene were risk indicators for ECC. The frequency of sugar consumption was not a significant risk indicator when malnutrition was included as an explanatory variable for ECC in the study population.
Does the treatment of anxiety in children with Attention-Deficit/Hyperactivity Disorder (ADHD) using cognitive behavioral therapy improve child and family outcomes? Protocol for a randomized controlled trial
Authors: Sciberras Emma , Efron Daryl , Patel Pooja , Mulraney Melissa , Lee Katherine J. , Mihalopoulos Cathy , Engel Lidia , Rapee Ronald M. , Anderson Vicki , Nicholson Jan M. , Schembri Rachel , Hiscock Harriet
Published: November 2019

Background

Up to 60% of children with Attention-Deficit/Hyperactivity Disorder (ADHD) meet diagnostic criteria for at least one anxiety disorder, including Social, Generalized and/or Separation Disorder. Anxiety in children with ADHD has been shown to be associated with poorer child and family functioning. Small pilot studies suggest that treating anxiety in children with ADHD using cognitive-behavioral therapy (CBT) has promising benefits. In a fully powered randomized controlled trial (RCT), we aim to investigate the efficacy of an existing CBT intervention adapted for children with ADHD and comorbid anxiety compared with usual care.

Methods

This RCT is recruiting children aged 8–12 years (N = 228) from pediatrician practices in Victoria, Australia. Eligibility criteria include meeting full diagnostic criteria for ADHD and at least one anxiety disorder (Generalized, Separation or Social). Eligible children are randomized to receive a 10 session CBT intervention (Cool Kids) versus usual clinical care from their pediatrician. The intervention focuses on building child and parent skills and strategies to manage anxiety and associated impairments including cognitive restructuring and graded exposure. Minor adaptations have been made to the delivery of the intervention to meet the needs of children with ADHD including increased use of visual materials and breaks between activities. The primary outcome is change in the proportion of children meeting diagnostic criteria for an anxiety disorder at 5 months randomization. This will be assessed via diagnostic interview with the child’s parent (Anxiety Disorders Interview Schedule for Children V) conducted by a researcher blinded to intervention condition. Secondary outcomes include a range of child (e.g., anxiety symptoms, ADHD severity, behavior, quality of life, sleep, cognitive functioning, school attendance) and parent (e.g., mental health, parenting behaviors, work attendance) domains of functioning assessed at 5 and 12 months post-randomization. Outcomes will be analyzed using logistic and mixed effects regression.

Discussion

The results from this study will provide evidence on whether treating comorbid anxiety in children with ADHD using a CBT approach leads to improvements in anxiety and/or broader functional outcomes.

Trial registration

This trial was prospectively registered: Current Controlled Trials ISRCTN59518816 (10.1186/ISRCTN59518816). The trial was first registered 29/9/15 and last updated 15/1/19.
Impact of a double-layer cementing technique on the homogeneity of cementation and the generation of loose bone cement fragments in tibial unicompartmental knee arthroplasty
Authors: Scheele Christian B. , Pietschmann Matthias F. , Schröder Christian , Suren Christian , Grupp Thomas M. , Müller Peter E.
Published: November 2019

Background

The objective of this study was to evaluate the impact of a single- vs. double-layer cementing technique on morphological cementation and the generation of microscopic cement layers or loose cement fragments in unicompartmental knee arthroplasty (UKA).

Methods

UKAs were implanted in 12 cadaver knees. The specimens were divided into two groups of comparable bone mineral density. Six UKAs were implanted using a single-layer cementing technique (group A) and six UKAs were implanted using a double-layer cementing technique (group B). Morphological cementation was assessed on nine cuts through the implant–cement–bone interface in the frontal plane. Loose bone cement fragments and the microscopically quality of layer formation were evaluated.

Results

Contact between bone and prosthesis was observed in 45.4% of interfaces in group A and 27.8% in group B (p = 0.126). The significant increase of areas without visible cement interlocking in the anteroposterior direction in group A (p = 0.005) was not evident in group B (p = 0.262). Penetration around the peg tended to occur more frequently in group B (67.5% vs. 90.6%p = 0.091). Scanning electron microscopy identified no evidence of fissure formations within the bilaminar cement mantle. Free bone cement fragments were documented in 66.7% in both groups with no difference concerning mass (p = 1.0).

Conclusions

This in-vitro study showed a tendency towards a more homogenous cementation of tibial UKAs using a double-layer cementing technique, although most of the differences did not reach the level of significance. However, theoretical downsides of the double-layer cementing technique such as an increased formation of free bone fragments or a microscopically fissure formation within the cement layer could not be detected either.
A new method to predict the outcome of the volar locked plate treatment for distal radius fracture
Authors: Yao Hui , Zhang Weijia , Xu Wenbin , Liu Kaihua , Xu Yichun
Published: November 2019

Background

Volar locked plate for distal radius fracture is one of the common procedures performed in trauma surgery. There are already some factors which can be used to predict the functional outcome after volar locked plating for distal radius fracture. However their limitations caused that the outcomes couldn’t be satisfactorily predicted. Better factors for predicting the prognosis more precisely are of great interest. The aim of this study is to introduce such a new factor.

Methods

A total of 56 patients suffered from unilateral distal radius fracture were managed operatively with the volar locked plate. Before operation, all CT scans of the distal radius were obtained. The ratios of soft tissue circumference to bone circumference at the watershed line in the distal radius were calculated based on the preoperative CT scans. Outcomes were evaluated after operation. The correlations between the ratio and the outcomes were analyzed using single factor linear regression analysis.

Results

Statistically significant linear relationships between the ratio and flexion degrees, extension degrees also patient-rated wrist evaluation (PRWE) scores were discovered. With the increase of the ratios, the flexion and extension range increased and the PRWE scores declined.

Conclusions

There are obvious linear relationships between the ratio and postoperative wrist flexion-extension degrees also PRWE scores when using volar locked plating for distal radius fracture. So the ratio can be used as a predictor aiding surgeons to predict the outcome.
Composition and diversity of the subgingival microbiome and its relationship with age in postmenopausal women: an epidemiologic investigation
Authors: LaMonte Michael J. , Genco Robert J. , Buck Michael J. , McSkimming Daniel I. , Li Lu , Hovey Kathleen M. , Andrews Christopher A. , Zheng Wei , Sun Yijun , Millen Amy E. , Tsompana Maria , Banack Hailey R. , Wactawski-Wende Jean
Published: November 2019

Background

The extent to which the composition and diversity of the oral microbiome varies with age is not clearly understood.

Methods

The 16S rRNA gene of subgingival plaque in 1219 women, aged 53–81 years, was sequenced and its taxonomy annotated against the Human Oral Microbiome Database (v.14.5). Composition of the subgingival microbiome was described in terms of centered log(2)-ratio (CLR) transformed OTU values, relative abundance, and prevalence. Correlations between microbiota abundance and age were evelauted using Pearson Product Moment correlations. P-values were corrected for multiple testing using the Bonferroni method.

Results

Of the 267 species identified overall, Veillonella dispar was the most abundant bacteria when described by CLR OTU (mean 8.3) or relative abundance (mean 8.9%); whereas Streptococcus oralis, Veillonella dispar and Veillonella parvula were most prevalent (100%, all) when described as being present at any amount. Linear correlations between age and several CLR OTUs (Pearson r = − 0.18 to 0.18), of which 82 (31%) achieved statistical significance (P < 0.05). The correlations lost significance following Bonferroni correction. Twelve species that differed across age groups (each corrected P < 0.05); 5 (42%) were higher in women ages 50–59 compared to ≥70 (corrected P < 0.05), and 7 (48%) were higher in women 70 years and older.

Conclusions

We identified associations between several bacterial species and age across the age range of postmenopausal women studied. Understanding the functions of these bacteria could identify intervention targets to enhance oral health in later life.
Parents and nurses telling their stories: the perceived needs of parents caring for critically ill children at the Kilimanjaro Christian Medical Centre in Tanzania
Authors: Saria Vivian Frank , Mselle Lilian Teddy , Siceloff Birgit Anne
Published: November 2019

Background

Parents have significant responsibility in the care of their critically ill children who have been admitted to the intensive care unit (ICU). When staying with their children in the hospital, they also have particular needs that should be adequately acknowledged and responded to by healthcare providers. Moreover, when their needs are not identified and addressed, parents may experience stress and anxiety as a result. This study describes the needs of parents caring for hospitalized critically ill children, as perceived by parents and nurses.

Methods

This study used a descriptive qualitative research design. Five focus group discussions with nurses and parents of critically ill children, who were purposefully recruited, were conducted at the Kilimanjaro Christian Medical Centre Hospital. A qualitative content analysis guided the analysis of the data.

Results

Two themes emerged from the perceptions of parents and nurses about the needs of parents caring for hospitalized critically ill children. These were: “engaging parents in the care of their children” and “receiving psychosocial support”. Both parents and nurses identified the importance of providing adequate information about their children’s progress, encouraging and involving parents in the care of their children and having flexible visiting time for parents was vital when caring for critically ill children.

Conclusions

This study provides an in-depth understanding of parents’ needs when caring for critically ill children in the hospital setting. Nurses caring for these children should understand the needs of parents and integrate the parents into the daily care of their children. Nurses should also continuously support, inform and engage parents during child-caring procedures. Finally, visiting times for intensive care units should be flexible and allow more time for parents to connect with their hospitalized children.
Single-cell reconstruction of differentiation trajectory reveals a critical role of ETS1 in human cardiac lineage commitment
Authors: Ruan Hang , Liao Yingnan , Ren Zongna , Mao Lin , Yao Fang , Yu Peng , Ye Youqiong , Zhang Zhao , Li Shengli , Xu Hanshi , Liu Jiewei , Diao Lixia , Zhou Bingying , Han Leng , Wang Li
Published: November 2019

Background

Cardiac differentiation from human pluripotent stem cells provides a unique opportunity to study human heart development in vitro and offers a potential cell source for cardiac regeneration. Compared to the large body of studies investigating cardiac maturation and cardiomyocyte subtype-specific induction, molecular events underlying cardiac lineage commitment from pluripotent stem cells at early stage remain poorly characterized.

Results

In order to uncover key molecular events and regulators controlling cardiac lineage commitment from a pluripotent state during differentiation, we performed single-cell RNA-Seq sequencing and obtained high-quality data for 6879 cells collected from 6 stages during cardiac differentiation from human embryonic stem cells and identified multiple cell subpopulations with distinct molecular features. Through constructing developmental trajectory of cardiac differentiation and putative ligand-receptor interactions, we revealed crosstalk between cardiac progenitor cells and endoderm cells, which could potentially provide a cellular microenvironment supporting cardiac lineage commitment at day 5. In addition, computational analyses of single-cell RNA-Seq data unveiled ETS1 (ETS Proto-Oncogene 1) activation as an important downstream event induced by crosstalk between cardiac progenitor cells and endoderm cells. Consistent with the findings from single-cell analysis, chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-Seq) against ETS1 revealed genomic occupancy of ETS1 at cardiac structural genes at day 9 and day 14, whereas ETS1 depletion dramatically compromised cardiac differentiation.

Conclusion

Together, our study not only characterized the molecular features of different cell types and identified ETS1 as a crucial factor induced by cell-cell crosstalk contributing to cardiac lineage commitment from a pluripotent state, but may also have important implications for understanding human heart development at early embryonic stage, as well as directed manipulation of cardiac differentiation in regenerative medicine.
Live birth rates and perinatal outcomes when all embryos are frozen compared with conventional fresh and frozen embryo transfer: a cohort study of 337,148 in vitro fertilisation cycles
Authors: Smith Andrew D. A. C. , Tilling Kate , Lawlor Deborah A. , Nelson Scott M.
Published: November 2019

Background

It is not known whether segmentation of an in vitro fertilisation (IVF) cycle, with freezing of all embryos prior to transfer, increases the chance of a live birth after all embryos are transferred.

Methods

In a prospective study of UK Human Fertilisation and Embryology Authority data, we investigated the impact of segmentation, compared with initial fresh embryo followed by frozen embryo transfers, on live birth rate and perinatal outcomes. We used generalised linear models to assess the effect of segmentation in the whole cohort, with additional analyses within women who had experienced both segmentation and non-segmentation. We compared rates of live birth, low birthweight (LBW < 2.5 kg), preterm birth (< 37 weeks), macrosomia (> 4 kg), small for gestational age (SGA < 10th centile), and large for gestational age (LGA > 90th centile) for a given ovarian stimulation cycle accounting for all embryo transfers.

Results

We assessed 202,968 women undergoing 337,148 ovarian stimulation cycles and 399,896 embryo transfer procedures. Live birth rates were similar in unadjusted analyses for segmented and non-segmented cycles (rate ratio 1.05, 95% CI 1.02–1.08) but lower in segmented cycles when adjusted for age, cycle number, cause of infertility, and ovarian response (rate ratio 0.80, 95% CI 0.78–0.83). Segmented cycles were associated with increased risk of macrosomia (adjusted risk ratio 1.72, 95% CI 1.55–1.92) and LGA (1.51, 1.38–1.66) but lower risk of LBW (0.71, 0.65–0.78) and SGA (0.64, 0.56–0.72). With adjustment for blastocyst/cleavage-stage embryo transfer in those with data on this (329,621 cycles), results were not notably changed. Similar results were observed comparing segmented to non-segmented within 3261 women who had both and when analyses were repeated excluding multiple embryo cycles and multiple pregnancies. When analyses were restricted to women with a single embryo transfer, the transfer of a frozen-thawed embryo in a segmented cycles was no longer associated with a lower risk of LBW (0.97, 0.71–1.33) or SGA (0.84, 0.61–1.15), but the risk of macrosomia (1.74, 1.39–2.20) and LGA (1.49, 1.20–1.86) persisted. When the analyses for perinatal outcomes were further restricted to solely frozen embryo transfers, there was no strong statistical evidence for associations.

Conclusions

Widespread application of segmentation and freezing of all embryos to unselected patient populations may be associated with lower cumulative live birth rates and should be restricted to those with a clinical indication.
Human bone marrow mesenchymal stem cell-derived extracellular vesicles attenuate neuroinflammation evoked by focal brain injury in rats
Authors: Dabrowska Sylwia , Andrzejewska Anna , Strzemecki Damian , Muraca Maurizio , Janowski Miroslaw , Lukomska Barbara
Published: November 2019

Background

Ischemic stroke is the major cause of long-term severe disability and death in aged population. Cell death in the infarcted region of the brain induces immune reaction leading to further progression of tissue damage. Immunomodulatory function of mesenchymal stem cells (MSCs) has been shown in multiple preclinical studies; however, it has not been successfully translated to a routine clinical practice due to logistical, economical, regulatory, and intellectual property obstacles. It has been recently demonstrated that therapeutic effect of intravenously administered MSCs can be recapitulated by extracellular vesicles (EVs) derived from them. However, in contrast to MSCs, EVs were not capable to decrease stroke-induced neuroinflammation. Therefore, the aim of the study was to investigate if intra-arterial delivery of MSC-derived EVs will have stronger impact on focal brain injury-induced neuroinflammation, which mimics ischemic stroke, and how it compares to MSCs.

Methods

The studies were performed in adult male Wistar rats with focal brain injury induced by injection of 1 μl of 50 nmol ouabain into the right hemisphere. Two days after brain insult, 5 × 105 human bone marrow MSCs (hBM-MSCs) labeled with Molday ION or 1.3 × 109 EVs stained with PKH26 were intra-arterially injected into the right hemisphere under real-time MRI guidance. At days 1, 3, and 7 post-transplantation, the rats were decapitated, the brains were removed, and the presence of donor cells or EVs was analyzed. The cellular immune response in host brain was evaluated immunohistochemically, and humoral factors were measured by multiplex immunoassay.

Results

hBM-MSCs and EVs transplanted intra-arterially were observed in the rat ipsilateral hemisphere, near the ischemic region. Immunohistochemical analysis of brain tissue showed that injection of hBM-MSCs or EVs leads to the decrease of cell activation by ischemic injury, i.e., astrocytes, microglia, and infiltrating leucocytes, including T cytotoxic cells. Furthermore, we observed significant decrease of pro-inflammatory cytokines and chemokines after hBM-MSC or EV infusion comparing with non-treated rats with focal brain injury.

Conclusions

Intra-arterially injected EVs attenuated neuroinflammation evoked by focal brain injury, which mimics ischemic stroke, and this effect was comparable to intra-arterial hBM-MSC transplantation. Thus, intra-arterial injection of EVs might be an attractive therapeutic approach, which obviates MSC-related obstacles.
TRPV1 translocated to astrocytic membrane to promote migration and inflammatory infiltration thus promotes epilepsy after hypoxic ischemia in immature brain
Authors: Wang Xin , Yang Xing-Liang , Kong Wei-Lin , Zeng Meng-Liu , Shao Lin , Jiang Guang-Tong , Cheng Jing-Jing , Kong Shuo , He Xiao-Hua , Liu Wan-Hong , Chen Tao-Xiang , Peng Bi-Wen
Published: November 2019

Background

Neonatal hypoxic-ischemic brain damage (HIBD), a leading cause of neonatal mortality, has intractable sequela such as epilepsy that seriously affected the life quality of HIBD survivors. We have previously shown that ion channel dysfunction in the central nervous system played an important role in the process of HIBD-induced epilepsy. Therefore, we continued to validate the underlying mechanisms of TRPV1 as a potential target for epilepsy.

Methods

Neonatal hypoxic ischemia and oxygen-glucose deprivation (OGD) were used to simulate HIBD in vivo and in vitro. Primarily cultured astrocytes were used to assess the expression of TRPV1, glial fibrillary acidic protein (GFAP), cytoskeletal rearrangement, and inflammatory cytokines by using Western blot, q-PCR, and immunofluorescence. Furthermore, brain electrical activity in freely moving mice was recorded by electroencephalography (EEG). TRPV1 current and neuronal excitability were detected by whole-cell patch clamp.

Results

Astrocytic TRPV1 translocated to the membrane after OGD. Mechanistically, astrocytic TRPV1 activation increased the inflow of Ca2+, which promoted G-actin polymerized to F-actin, thus promoted astrocyte migration after OGD. Moreover, astrocytic TRPV1 deficiency decreased the production and release of pro-inflammatory cytokines (TNF, IL-6, IL-1β, and iNOS) after OGD. It could also dramatically attenuate neuronal excitability after OGD and brain electrical activity in HIBD mice. Behavioral testing for seizures after HIBD revealed that TRPV1 knockout mice demonstrated prolonged onset latency, shortened duration, and decreased seizure severity when compared with wild-type mice.

Conclusions

Collectively, TRPV1 promoted astrocyte migration thus helped the infiltration of pro-inflammatory cytokines (TNF, IL-1β, IL-6, and iNOS) from astrocytes into the vicinity of neurons to promote epilepsy. Our study provides a strong rationale for astrocytic TRPV1 to be a therapeutic target for anti-epileptogenesis after HIBD.
Associations of dairy and fiber intake with circulating odd-chain fatty acids in post-myocardial infarction patients
Authors: Pertiwi Kamalita , Küpers Leanne K. , Wanders Anne J. , de Goede Janette , Zock Peter L. , Geleijnse Johanna M.
Published: November 2019

Background

Circulating odd-chain fatty acids pentadecanoic (15:0) and heptadecanoic acid (17:0) are considered to reflect dairy intake. In cohort studies, higher circulating 15:0 and 17:0 were associated with lower type 2 diabetes risk. A recent randomized controlled trial in humans suggested that fiber intake also increased circulating 15:0 and 17:0, potentially resulting from fermentation by gut microbes. We examined the associations of dairy and fiber intake with circulating 15:0 and 17:0 in patients with a history of myocardial infarction (MI).

Methods

We performed cross-sectional analyses in a subsample of 869 Dutch post-MI patients of the Alpha Omega Cohort who had data on dietary intake and circulating fatty acids. Dietary intakes (g/d) were assessed using a 203-item food frequency questionnaire. Circulating 15:0 and 17:0 (as % of total fatty acids) were measured in plasma phospholipids (PL) and cholesteryl esters (CE). Spearman correlations (rs) were computed between intakes of total dairy, dairy fat, fiber, and circulating 15:0 and 17:0.

Results

Patients were on average 69 years old, 78% was male and 21% had diabetes. Total dairy intake comprised predominantly milk and yogurt (69%). Dairy fat was mainly derived from cheese (47%) and milk (15%), and fiber was mainly from grains (43%). Circulating 15:0 in PL was significantly correlated with total dairy and dairy fat intake (bothrs = 0.19,p < 0.001), but not with dietary fiber intake (rs = 0.05,p = 0.11). Circulating 17:0 in PL was correlated both with dairy intake (rs = 0.14 for total dairy and 0.11 for dairy fat,p < 0.001), and fiber intake (rs = 0.19,p < 0.001). Results in CE were roughly similar, except for a weaker correlation of CE 17:0 with fiber (rs = 0.11,p = 0.001). Circulating 15:0 was highest in those with high dairy intake irrespective of fiber intake, while circulating 17:0 was highest in those with high dairy and fiber intake.

Conclusions

In our cohort of post-MI patients, circulating 15:0 was associated with dairy intake but not fiber intake, whereas circulating 17:0 was associated with both dairy and fiber intake. These data suggest that cardiometabolic health benefits previously attributed to 17:0 as a biomarker of dairy intake may partly be explained by fiber intake.
The role of the outer setting in implementation: associations between state demographic, fiscal, and policy factors and use of evidence-based treatments in mental healthcare
Authors: Bruns Eric J. , Parker Elizabeth M. , Hensley Spencer , Pullmann Michael D. , Benjamin Philip H. , Lyon Aaron R. , Hoagwood Kimberly E.
Published: November 2019

Background

Despite consistent recognition of their influence, empirical study of how outer setting factors (e.g., policies, financing, stakeholder relationships) influence public systems’ investment in and adoption of evidence-based treatment (EBT) is limited. This study examined associations among unmodifiable (e.g., demographic, economic, political, structural factors) and modifiable (e.g., allocation of resources, social processes, policies, and regulations) outer setting factors and adoption of behavioral health EBT by US states.

Methods

Multilevel models examined relationships between state characteristics, an array of funding and policy variables, and state adoption of behavioral health EBTs for adults and children across years 2002–2012, using data from the National Association for State Mental Health Program Directors Research Institute and other sources.

Results

Several unmodifiable state factors, including per capita income, controlling political party, and Medicaid expansion, predicted level of state fiscal investments in EBT. By contrast, modifiable factors, such as interagency collaboration and investment in research centers, were more predictive of state policies supportive of EBT. Interestingly, level of adult EBT adoption was associated with state fiscal supports for EBT, while child EBT adoption was predicted more by supportive policies. State per capita debt and direct state operation of services (versus contracting for services) predicted both child and adult EBT adoption.

Conclusions

State-level EBT adoption and associated implementation support is associated with an interpretable array of policy, financing, and oversight factors. Such information expands our knowledge base of the role of the outer setting in implementation and may provide insight into how best to focus efforts to promote EBT for behavioral health disorders.
Meta-analysis of segmentectomy versus lobectomy for radiologically pure solid or solid-dominant stage IA non-small cell lung cancer
Authors: Rao Sunyin , Ye Lianhua , Min Li , Zhao Guangqiang , Chen Ya , Huang Yunchao , Yang Jichen , Xiao Shouyong , Cao Run
Published: November 2019

Objective

Whether segmentectomy can be used to treat radiologically determined pure solid or solid-dominant lung cancer remains controversial owing to the invasive pathologic characteristics of these tumors despite their small size. This meta-analysis compared the oncologic outcomes after lobectomy and segmentectomy regarding relapse-free survival (RFS) and overall survival (OS) in patients with radiologically determined pure solid or solid-dominant clinical stage IA non-small cell lung cancer (NSCLC).

Methods

A literature search was performed in the MEDLINE, EMBASE, and Cochrane Central databases for information from the date of database inception to March 2019. Studies were selected according to predefined eligibility criteria. The hazard ratio (HR) and associated 95% confidence interval (CI) were extracted or calculated as the outcome measure for data combining.

Results

Seven eligible studies published between 2014 and 2018 enrolling 1428 patients were included in the current meta-analysis. Compared with lobectomy, segmentectomy had a significant benefit on the RFS of radiologically determined pure solid or solid-dominant clinical stage IA NSCLC patients (combined HR: 1.46; 95% CI, 1.05–2.03; P = 0.024) and there were no significant differences on the OS of these patients (HR: 1.52; 95% CI, 0.95–2.43; P = 0.08).

Conclusions

Segmentectomy leads to lower survival than lobectomy for clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors. Moreover, applying lobectomy to clinical stage IA NSCLC patients with radiologically determined pure solid or solid-dominant tumors (≤2 cm) could lead to an even bigger survival advantage. However, there are some limitations in the present study, and more evidence is needed to support the conclusion.
mTOR pathway in human cardiac hypertrophy caused by LEOPARD syndrome: a different role compared with animal models?
Authors: Cui Hao , Song Lei , Zhu Changsheng , Zhang Ce , Tang Bing , Wang Shengwei , Wu Guixin , Zou Yubao , Huang Xiaohong , Hui Rutai , Wang Shuiyun , Wang Jizheng
Published: November 2019

Background

Animal studies suggested that blocking the activation of the mammalian target of rapamycin (mTOR) pathway might be effective to treat cardiac hypertrophy in LEOPARD syndrome (LS) caused by PTPN11 mutations.

Results

In the present study, mTOR pathway activity was examined in human myocardial samples from two patients with LS, four patients with hypertrophic cardiomyopathy (HCM), and four normal controls. The two patients with LS had p.Y279C and p.T468 M mutations of the PTPN11 gene, respectively. Although PTPN11 mutation showed initially positive regulation on phosphoinositide 3-kinase, overall the mTOR complex 1 pathway showed widely attenuated activity in LS. This included mildly hypophosphorylated mTOR and ribosomal protein S6 kinase and significantly hypophosphorylated Akt308 and ribosomal protein S6, which is similar to HCM. Akt473 is a basal molecule of the mTOR complex 2 pathway. Akt473 was less affected and showed hyperactivity in LS compared with HCM and normal controls. Additionally, MAPK/ERK kinase and ERK1/2 were significantly more phosphorylated in both HCM and LS than normal controls.

Conclusions

In LS, the mTOR signaling pathway shows similar activity to HCM and is attenuated compared with normal controls. Thus, caution should be applied when using rapamycin to treat heart hypertrophy in LS.
Developing the universal unified prevention program for diverse disorders for school-aged children
Authors: Ishikawa Shin-ichi , Kishida Kohei , Oka Takuya , Saito Aya , Shimotsu Sakie , Watanabe Norio , Sasamori Hiroki , Kamio Yoko
Published: November 2019

Background

Psychological problems during childhood and adolescence are highly prevalent, frequently comorbid, and incur severe social burden. A school-based universal prevention approach is one avenue to address these issues.

Objective

The first aim of this study was the development of a novel, transdiagnostic cognitive-behavioral universal prevention program: The Universal Unified Prevention Program for Diverse Disorders (Up2-D2). The second aim of this study was to examine the acceptability and fidelity of the Up2-D2.

Methods

Classroom teachers who attended a 1-day workshop implemented the Up2-D2 independently as a part of their regular curricula. To assess the acceptability of the Up2-D2, 213 children (111 boys and 102 girls) aged 9–12 years completed questionnaires about their enjoyment, comprehension, attainment, applicability, and self-efficacy after completing Lessons 1–12. For fidelity, research assistants independently evaluated audio files that were randomly selected and assigned (27.3%).

Results

Our preliminary evaluation revealed the program was highly enjoyable, clear, and applicable for students. In addition, self-efficacy demonstrated a trend of gradually increasing over the 12 sessions. The total fidelity observed in the two schools was sufficient (76.2%), given the length of the teacher training.

Conclusions

The results of this study supported the theory that the Up2-D2 could be feasible in real-world school settings when classroom teachers implement the program. We discussed current research and practical issues of using universal prevention to address mental health problems in school, based on implementation science for user-centered design.