bluuebunny/crossref_metadata_2025 huggingface dataset:
Application of transvaginal three-dimensional power Doppler ultrasound in benign and malignant endometrial diseases
Authors: Liu Mei-juan , Liu Zhong-feng , Yin Wei-hong , Chen Xiao-ran , Gao Ling-Yun , Sun Hong-jun
Published: November 2019

To investigate the value of transvaginal three-dimensional (3D) power Doppler ultrasound in the diagnosis of benign and malignant endometrial diseases.

A total of 144 patients with endometrial thickness ≥4 mm were enrolled. Endometrial thickness was measured by transvaginal 3D B-mode ultrasound, while blood signals were detected by 3D power Doppler ultrasound. Endometrial volume (EV), vascularization index (VI), blood flow index (FI), and vascularization flow index (VFI) were calculated. All histopathological diagnoses of endometrium were obtained.

There were 86 benign and 58 malignant cases. There were statistically significant differences between two groups in endometrial thickness [1.50 (1.30, 1.80) vs 2.30 (1.80, 3.20),P < .001], EV [10.62 (7.14, 17.36) vs 28.94 (9.59, 67.96),P < .001], VI [6.07 (3.61, 10.33) vs 12.01 (7.50, 19.87),P = .001], FI [27.42 (24.45, 31.33) vs 32.98 (30.22, 35.40),P < .001], and VFI [1.58 (0.92, 3.32) vs 4.28 (2.24, 6.41),P < 0.001]. Sensitivity and specificity of endometrial thickness were relatively high [endometrial thickness (86.2%, 76.1%), EV (48.3%, 97.7%), VI (72.4%, 69.8%), FI (72.4%, 74.4%), and VFI (72.4%, 74.4%)]. There was no significant difference in any parameters of the endometrium between different stages (Ia, Ib, II, and above) or phases (G1, G2, and G3) of Ia phase of endometrial cancer (allP > .05).

Transvaginal 3D power Doppler ultrasound is valuable in the differentiating benign and malignant endometrial lesions.
Abnormal IL-10 levels were related to alanine aminotransferase abnormalities during postpartum in HBeAg positive women with chronic hepatitis B
Authors: Wang Ming , Hou Ying , Meng Shi-Hui , Yang Bo , Yang Ping , Zhang Hua , Zhu Yunxia
Published: November 2019

Alanine transaminase (ALT) abnormalities are common in chronic hepatitis B (CHB) carriers during postpartum period. Disturbances in cytokines are considered to be associated with hepatitis Flares. There are limited data on cytokines changes in HBeAg positive patients with ALT abnormalities.

This is an observational study. Pregnant patients with hepatitis B e-antigen (HBeAg) positive were enrolled from January 2014 to September 2018. Patients were assigned into three groups based on ALT levels in postpartum 6 to 8 weeks: ALT in normal range, ALT in 1 to 2-fold upper limits of normal (ULN) and ALT >2-fold ULN. Serum cytokines, ratios of regulatory T cells, and the concentration of cortisol were collected and compared among the three groups.

Of the 135 mothers enrolled, 80.7% (109/135) completed the postpartum 6-week study. 13.8% (15/109) patients had postpartum ALT higher than 2∗ULN, 27.5% (30/109) patients had ALT in 1 to 2∗ULN and 58.7% (64/109) patients had ALT in normal range. Compared to control group, patients with ALT >2∗ULN had a higher IL-10 level (P < .05). No differences of IL-10 levels were found in the comparison of other inter comparison among three groups. No differences were found in the levels of other collected serum cytokines, cortisol, and regulatory T cells among three groups. On multivariate analysis, abnormal IL-10 level was independent risk factor for postpartum ALT elevating >2∗ULN. At the same time, the incidence of postpartum ALT elevated >2∗ULN were higher in patients with abnormal elevation IL-10 level than in patients with normal IL-10 level (14/68 vs 1/41,P = .008).

CHB patients with postpartum ALT abnormalities show higher IL-10 level and postpartum ALT abnormalities were mainly occurred in patients with abnormal IL-10 level. IL-10 may be an underlying predictor and treatment target of hepatitis B, and further studies are needed.
Outcomes of nonsurgical treatment for transcondylar humeral fractures in adults
Authors: Tomori Yuji , Nanno Mitsuhiko , Takai Shinro
Published: November 2019

To elucidate the clinical outcomes of nonsurgical treatment for transcondylar fractures of the humerus.

From April 2010 to March 2018, 32 elbows with AO classification 13A-2.3 transcondylar fractures of the humerus (extra-articular fracture, metaphyseal simple, transverse, transmetaphyseal) in adult patients were treated in our hospital and related facilities. Fifteen of 32 elbows were treated nonsurgically by immobilization with a long-arm cast or splint. Of these, 14 elbows that were followed up for >3 months were investigated. The patients comprised 6 men and 8 women with a mean age at the time of injury of 78 years. We investigated the follow-up period, duration until bone union, complications at final follow-up, radiological evaluation, elbow range of motion (ROM), total elbow joint range (Arc), and clinical outcome (Mayo Elbow Performance Score [MEPS]).

The mean follow-up period was 8 months. The mean duration until bone union was 7 weeks. No significant complications were observed at the final examination. The ROM of the injured elbow joint was obtained in 13 patients. At the final follow-up, the mean extension and flexion of the injured elbow was −19.2° and 121.2°, respectively. The mean Arc of the injured elbow joint was 102.3°. Joint contracture (<120° flexion) was observed in 6 of the 13 elbows for which ROM was obtained. No patients complained of residual pain of the elbow joint. The mean MEPS was 93.1 points.

There is no objection to the fact that displaced transcondylar fractures of the humerus should be treated surgically. However, significant numbers of intraoperative and postoperative complications of plate osteosynthesis have been reported. Until recently, although few clinical reports regarding nonsurgical treatment for these fractures have been published, several studies have indicated that nonsurgical treatment might be an alternative option for these fractures caused by low-energy trauma. In this study, we presented the radiographic and clinical outcomes of nonsurgical treatment for transcondylar fractures of the humerus. Our study suggests that nonsurgical treatment can be a good option for transcondylar fractures of the humerus.
Case report: A patient coinfected by Borrelia burgdorferi sensu lato and spotted fever group Rickettsiae in Urumqi, China
Authors: Jiang Yi , Hou Xuexia , Zhang Lin , Tan Yuhui , Lu Chen , Xiao Dong , Li Hongyan , Hao Qin , Wan Kanglin
Published: November 2019

Rationale:

Both Borrelia burgdorferi sensu lato and spotted fever group Rickettsiae (SFGR) are pathogens carried by ticks. There is a possibility of co-infection with these tick-borne diseases.

Patient concerns:

Male patient, 63 years-of-age, admitted to hospital with skin rash presenting for 1 week and fever with cough and expectoration for 3 days before admission.

Diagnoses:

We diagnosed that the patient was co-infected by B burgdorferi sl and SFGR using laboratory test results and the patient's clinical manifestations.

Interventions:

The patient started therapy with oral minocycline, then levofloxacin by intravenous injection for SFGR. Meanwhile, he was treated with penicillin G sodium, cefoperazone sulbactam sodium and ceftriaxone by intravenous injection for B burgdorferi sl.

Outcomes:

After the patient was in stable condition, he was discharged from hospital.

Lessons:

This case report highlights the possibility of co-infection by 2 tick-borne diseases in Urumqi, Xinjiang Uygur Autonomous Region, China. The antibiotic therapy should be based on the detection of pathogenic bacteria, and the different susceptibilities of co-infecting bacteria should be considered.
The characteristics of the frequent exacerbators with chronic bronchitis phenotype and the asthma-chronic obstructive pulmonary disease overlap syndrome phenotype in chronic obstructive pulmonary disease patients
Authors: Wu Jian-Jun , Xu Hong-Ri , Zhang Ying-Xue , Li Yi-Xuan , Yu Hui-Yong , Jiang Liang-Duo , Wang Cheng-Xiang , Han Mei
Published: November 2019

To investigate the difference of clinical characteristics between chronic obstructive pulmonary disease (COPD) patients with the frequent exacerbators with chronic bronchitis (FE-CB) phenotype and those with the asthma-COPD overlap syndrome (ACO) phenotype.

We searched CNKI, Wan Fang, Chongqing VIP, China Biology Medicine disc, PubMed, Cochrane Library, and EMBASE databases for studies published as of April 30, 2019. All studies that investigated COPD patients with the FE-CB and ACO phenotypes and which qualified the inclusion criteria were included. Cross-sectional/prevalence study quality recommendations were used to measure methodological quality. RevMan5.3 software was used for meta-analysis.

Ten studies (combined n = 4568) qualified the inclusion criteria. The FE-CB phenotype of COPD was associated with significantly lower forced vital capacity percent predicted (mean difference [MD] −9.05, 95% confidence interval [CI] [−12.00, −6.10], P < .001, I

2
= 66%), forced expiratory volume in 1 second (FEV1) (MD −407.18, 95% CI [−438.63, −375.72], P < .001, I

2
= 33%), forced expiratory volume in 1 second percent predicted (MD −9.71, 95% CI [−12.79, −6.63], P < .001, I

2
 = 87%), FEV1/forced vital capacity (MD −5.4, 95% CI [−6.49, −4.30], P < .001, I

2
 = 0%), and body mass index (BMI) (MD −0.81, 95% CI [−1.18, −0.45], P < .001, I

2
 = 44%) as compared to the ACO phenotype. However, FE-CB phenotype was associated with higher quantity of cigarettes smoked (pack-years) (MD 6.45, 95% CI [1.82, 11.09], P < .001, I

2
 = 73%), COPD assessment test score (CAT) (MD 4.04, 95% CI [3.46, 4.61], P < .001, I

2
 = 0%), mMRC score (MD 0.54, 95% CI [0.46, 0.62], P < .001, I

2
 = 34%), exacerbations in previous year (1.34, 95% CI [0.98, 1.71], P < .001, I
2 = 68%), and BMI, obstruction, dyspnea, exacerbations (BODEx) (MD 1.59, 95% CI [1.00, 2.18], P < .001, I

2
 = 86%) as compared to the ACO phenotype.

Compared with the ACO phenotype, COPD patients with the FE-CB phenotype had poorer pulmonary function, lower BMI, and higher CAT score, quantity of cigarettes smoked (pack-years), exacerbations in previous year, mMRC score, and BODEx.

This study is an analysis of published literature, which belongs to the second study. Therefore, this study does not require the approval of the ethics committee. The findings will be disseminated through a peer-reviewed journal publication or conference presentation.
Cephalic vein approach for the implantable central venous access
Authors: Rhu Jiyoung , Jun Kang Woong , Song Byung Joo , Sung Kiyoung , Cho Jinbeom
Published: November 2019

Long-term venous access is usually required in patients receiving chemotherapy. We hypothesized that, out of the various central line approach techniques, the cephalic vein cut-down technique can be a safe and simple alternative in terms of surgical safety, feasibility, cost-effectiveness, and functional outcomes.

We retrospectively reviewed the medical records of 569 patients who underwent implantable central venous access between January 2012 and December 2014 at our hospital.

We classified our cohort according to access routes, as follows: 230 patients underwent subclavian vein access, 134 patients underwent internal jugular vein access, 25 patients underwent external jugular vein access, and 119 patients underwent cephalic vein access. The cephalic vein group had a significantly longer operation time than the subclavian group (P < .01); however, there was no difference in operation time between the internal jugular vein and cephalic vein groups (P = .59). The procedure-related complications and functional outcomes of the implanted venous port during chemotherapy were comparable between the cephalic group and other groups. Additionally, body mass index, operation time, and age did not correlate with catheter dysfunction in the multivariate logistic regression analysis (P = .53; P = .66; P = .19, respectively).

We suggest that a cut-down central venous catheter insertion through the cephalic vein can be performed easily and safely with no differences in surgical and clinical outcomes compared to those of conventional percutaneous approaches. Moreover, the cephalic vein approach requires no specialized equipment, including percutaneous vascular kits, tunneling instruments, and intraoperative ultrasonography. Therefore, this technique might incur less medical expenses than conventional approaches and would be helpful for both patients and surgeons.
Association between insulin-like growth factor 1 gene rs35767 polymorphisms and cancer risk
Authors: Qin Lei , Zhao Jiawen , Wu Yongxian , Zhao Yutong , Chen Cankun , Xu Mingbin , Cheng Jiwen , Li Chengyang
Published: November 2019

Background:

Several studies have been conducted on the relationship between insulin-like growth factor 1 gene (IGF-1) rs35767 polymorphisms and cancer risk, but the results are conflicting. We performed a meta-analysis to investigate the relationship between IGF-1 rs35767 polymorphisms and cancer risk.

Methods:

Eight studies (5 for IGF-1 rs35767 C>T and 3 for IGF-1 rs35767 A>G) with a total of 11,257 cases and 16,213 controls were included. The studies were about the association between IGF-1 rs35767 polymorphisms and cancer risk and acquired by searching PubMed, Embase, and Web of Science databases for articles published before January 20, 2019. STATA software was used to analyze the data and identify the strength of the association by using pooled-odds ratios (ORs) with corresponding 95% confidence intervals (CIs).

Results:

No significant associations were observed between the IGF-1 rs35767 C>T polymorphism and cancer risk in all genetic models. However, the IGF-1 rs35767 A>G polymorphism was significantly associated with increased cancer risk for all genetic models (G vs A: OR = 1.087, 95% CI: 1.036–1.141, P
h = .338; GG vs AA: OR = 1.272, 95% CI: 1.121–1.442, P
h = .359; AG vs AA: OR = 1.187, 95% CI: 1.043–1.351, P
h = .695; AG+GG vs AA: OR = 1.187, 95% CI: 1.043–1.351, P
h = .695; GG vs AA+AG: OR = 1.086, 95% CI: 1.025–1.151, P
h = .275). Begg and Egger tests showed that no publication bias existed.

Conclusion:

Our findings indicated that the IGF-1 rs35767 A>G polymorphism might be a risk factor for cancer development. However, additional well-designed studies with sample sizes larger than ours need to be conducted in the future to verify our findings.
Hemophagocytic Lymphohistiocytosis in Langerhans Cell Histiocytosis: A Case Report and Review of the Literature
Authors: Hinson Ashley R.P. , Patel Niraj , Kaplan Joel
Published: November 2019

A toddler undergoing treatment for refractory Langerhans cell histiocytosis (LCH) developed concurrent hemophagocytic lymphohistiocytosis (HLH). These are thought to be distinct histiocytic disorders, with different pathophysiologies, diagnostic criteria, and treatments. HLH in a patient with LCH is thought to be quite rare. In this report, we review the presentation of our patient, as well as review the existing literature of other pediatric patients who have been diagnosed with both LCH and HLH.
Assessment of Self-Image With the Offer Self-Image Questionnaire in Adolescents With Hemophilia: A Single-Center Experience
Authors: Aydin Köker Sultan , Kaygusuz Arife , Oymak Yeşim , Karapϊnar Tuba H. , Çubukçu Duygu , Gözmen Salih , Ay Yilmaz , Vergϊn Raziye C.
Published: November 2019

Background:

Hemophilia, which is a chronic illness associated with recurrent bleeding, may occur with psychosocial and behavioral problems.

Aim:

The aim of this study was to evaluate the clinical characteristics and demographic features and changes in the self-image of adolescents with hemophilia.

Materials and Methods:

Data about hemophilia type, the severity of hemophilia, secondary prophylaxis received, and annual bleeding rate (ABR) were recorded from patient files. Hemophilia Joint Health Score (HJHS) and the Offer Self-Image Questionnaire (OSIQ) (as a measure of self-esteem) were applied to hemophilia patients and a healthy control group.

Results:

Thirty-two hemophilia patients (mean age=16.2±3.06 y) and 35 healthy male individuals (mean age=16.02±1.4 y) were enrolled in the study. Hemophilia patients had lower total OSIQ score than their peers (P=0.007). There was no difference between patients who received and who did not receive secondary prophylaxis (P=0.408) in terms of total OSIQ score. The median total OSIQ score of patients with pathologic HJHS (>0 points) was lower than that of patients with normal HJHS (0 points) (P=0.010). The median of ABR was 6 (range: 0 to 20) in the whole hemophilia group. There were no differences between hemophilia patients with ABR≤4 and >4 (P=0.084). All of the subscale parameters of the OSIQ were lower for hemophilia patients compared with their peers, besides one. The subscale of sexuality attitudes was better for hemophilia patients than for the healthy control group (P=0.028).

Conclusions:

Low self-esteem in hemophilia patients indicates the importance of lifelong psychosocial support. Patients with pathologic HJHS are at risk of low-esteem. Using OSIQ with HJHS during follow-up of hemophilia patients may be useful for management.
The Development and Implementation of Nursing Professional Practice Model in a Tertiary Hospital in China
Authors: Qu Yuedan , Zhuang Yiyu , Yang Lili , Zou Zhaojun , Hu Xiaoyun , Qian Ying
Published: November 2019

Developing a professional practice model (PPM) is essential for hospitals seeking Magnet® designation. The article describes the development and implementation of a PPM in a tertiary hospital that was the 1st hospital in mainland China applying for Magnet recognition. This article provides a framework for hospital administrators who wish to reference a successful process when creating their own Magnet PPMs.
A Professional Nursing Acute Care Practice Curriculum
Authors: Halfer Diana , Brewer Barbara , Ulrich Beth , Kramer Marlene
Published: November 2019

Caring for multiple complex patients simultaneously is 1 of the biggest challenges for clinical nurses (CNs) in acute care. We utilized the results of research to develop a 6-hour Professional Nursing Practice Curriculum (PNPC) specifically for CNs who are professionally and legally responsible for providing holistic care to an assigned group of patients on inpatient clinical units in acute care hospitals. The curriculum can be used by faculty to prepare senior nursing students for their 1st professional practice role in an acute care setting. Components of the PNPC will be beneficial for nurse leaders in an assessment of their educational practices for transitioning newly licensed RNs to practice and addressing professional development needs of CNs.
Increasing Nursing Research Program Visibility
Authors: Scala Elizabeth , Whalen Madeleine , Parks Joyce , Ascenzi Judy , Pandian Vinciya
Published: November 2019

In healthcare, timely communication of critical information is imperative among workforce members. Nurse leaders struggle with how to reach clinical staff effectively when informing them of program updates, practice changes, or available resources. This article provides a review of the marketing and communication literature sharing best practices for improving visibility and program uptake for infrastructure supporting the conduct of inquiry projects among hospital employees using an evidence-based practice approach.
Anthropometric Research of Metric Characters in Zygomatic Complex Region
Authors: Zhang Zhaoqiang , Wu Jiaqi , Mao Qin , Cao Wei , Li Xiaolei , Zhang Yingjie , Zhang Qingbin
Published: November 2019

Objectives:

To get and analyze the metric data of zygomatic region for the plasty of zygoma.

Materials and Methods:

A total of 108 dry skulls in Chinese Han population were randomly collected and measured. The metrical data were divided into 4 parts, including the relative position of contour height of zygomatic bone, the relative prominence of zygomatic bone, the relative prominence of zygomatic arch, and the angle of the zygomatic bone and arch.

Results:

The measurements in the 4 parts showed significantly difference between male and female (P < 0.05). For relative position of contour height of zygomatic bone group, the data of male is significantly bigger than female (P < 0.05). For relative prominence of zygomatic bone/zygomatic arch group, zygoma/zygomatic arch of male significantly protruded more than female (P < 0.05).

Conclusion:

The location of male zygoma is more protruding than female. The female zygoma is squarer than male and marginal process is helpful in zygomatic plasty.

Clinical Relevance:

These studies show and analyze the metric data of zygomatic region in Chinese Han population for the plasty of zygoma. These different characters between males and females could be helpful in zygomatic plasty of Chinese Han population based on this research.
Rocuronium Continuous Infusion for Profound Neuromuscular Blockade: A Systematic Review and Meta-analysis
Authors: Couto Mafalda , Nunes Catarina , Vide Sérgio , Amorim Pedro , Mendes Joaquim
Published: November 2019

Objectives

Rocuronium is a muscle relaxant with increased use, because of the binding relation with the reversal agent sugammadex. Its continuous infusion benefits the maintenance of deeper levels of neuromuscular blockade (NMB) ensuring an improved and stable solution for daily surgical anesthesia. This is systematic review on current approaches on rocuronium infusion and monitoring parameters when using rocuronium continuous infusion for profound muscle relaxation (0–2 posttetanic count).

Methods

Database search included publications worldwide until February 28, 2019. Main outcomes studied were the amount of rocuronium used, surgical conditions, and time of recovery after standard sugammadex dose. Secondary assessments include methodological features of rocuronium administration and blockade monitoring. Meta-analysis was conducted to assess the effect means difference of surgical conditions, followed by heterogeneity and sensitive analysis.

Results

Eight randomized trials were identified as eligible. Three studies allowed to account that maintenance of profound muscle relaxation a mean difference of 0.251 mg/kg per hour (95% confidence interval = 0.169–0.334) of rocuronium is required, in relation to moderate NMB, significantly improving surgical conditions (mean difference = 0.653, 95% confidence interval = 0.451–0.856, in a 5-point scale, including data from 6 trials). Only 2 studies presented results on reversal after sugammadex; therefore, no significant results were yielded regarding the time required to complete NMB recovery.

Conclusions

Rocuronium continuous infusion for profound neuromuscular blockade presents inherent advantages in terms of maintenance and stability of the paralysis. Further studies should address the methodological approaches and benefits/drawbacks of this approach.

Registration number: CRD42018106626
Risperidone Combination Therapy With Propentofylline for Treatment of Irritability in Autism Spectrum Disorders: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial
Authors: Behmanesh Helen , Moghaddam Hossein Sanjari , Mohammadi Mohammad-Reza , Akhondzadeh Shahin
Published: November 2019

Objectives

Propentofylline is a xanthine phosphodiesterase inhibitor and adenosine reuptake blocker with neuroprotective effects linked to anti-inflammatory and antiexcitatory properties. This is a double-blind, placebo-controlled trial investigating the potential beneficial effects of propentofylline, as an adjunctive treatment with risperidone, on the severity and behavioral abnormalities of autism spectrum disorder (ASD).

Methods

A total of 48 children with ASD were randomly allocated into 2 groups of risperidone (initiating at 0.5 mg/d) plus propentofylline (initiating at 300 mg/d) and risperidone plus placebo. The Aberrant Behavior Checklist—Community (ABC-C) and Childhood Autism Rating Scale (CARS) were used for the evaluation of ASD severity and behavioral disruptions at baseline, week 4, and week 10. Primary outcome measure of the study was ABC-C irritability subscale score, whereas CARS score along with other 4 subscales of ABC-C (lethargy/social withdrawal, stereotypic behavior, hyperactivity/noncompliance, and inappropriate speech subscales) were considered as secondary outcome measures.

Results

Results from the general linear model repeated measures analysis demonstrated significant time-treatment interaction on irritability subscale (F
1.55 = 3.45; P = 0.048) and CARS (F
1.41 = 4.08; P = 0.034) scores. Compared with the placebo group, children receiving propentofylline showed greater improvements in the CARS score (P = 0.037) from baseline to the study endpoint. Our results found no significant time-treatment effect on other subscales of ABC-C. Two trial groups were comparable based on the frequency of adverse effects.

Conclusions

Our findings demonstrated that adjunctive treatment with propentofylline is effective in alleviating disease severity and improving irritability in ASD patients. However, larger studies with longer durations are required to confirm these results.
Efficacy and Placebo Response of Multimodal Treatments for Primary Insomnia: A Network Meta-Analysis
Authors: Jiang Binghu , He Dongmei , Gao Zhanhui
Published: November 2019

Background

Pharmacotherapy, psychotherapy, and complementary therapy have been used for primary insomnia. However, the efficacy and placebo response are not exactly clear because of limited clinical data. We therefore conducted a systematic review to examine the efficacy and placebo response of multimodal treatments.

Methods

We performed a comprehensive literature search for randomized placebo-controlled clinical trials evaluating the efficacy of multimodal treatments addressing primary insomnia. To pool effect size estimates (Hedges' g) of active and placebo conditions across studies for outcome measures, a meta-analysis was done according to the Cochrane guideline.

Results

The results of network meta-analysis for sleep efficiency showed that orexin receptor antagonists had the maximum effect size of 1.35 (95% confidence interval [CI], 0.88–1.82), followed by γ-aminobutyric acid agonists of 1.28 (95% CI, 0.85–1.71), cognitive behavioral therapy for insomnia of 1.07 (95% CI, 0.10–2.05), acupuncture of 0.64 (95% CI, −0.17 to 2.36), and repetitive transcranial magnetic stimulation of 0.61 (95% CI, −0.52 to 1.75), respectively. However, the placebo response was also significant and robust to improve insomnia symptoms, and 65.9% (95% CI, 49.3%–82.5%) of the effect size of multimodal treatments was actually produced by placebo conditions.

Conclusions

The pharmacotherapy seems the most effective in improving sleep efficiency. However, the optimal therapeutic regimen is still uncertain. In addition, the placebo response is significant and robust in treatments of primary insomnia.
Identification of suitable reference genes for qPCR expression analysis on the gonads of the invasive mussel Limnoperna fortunei
Authors: Americo Juliana Alves , Guerreiro Luana Tatiana Albuquerque , Gondim Tayssa Santos , da Cunha Yasmin Rodrigues , Wajsenzon Inês Julia Ribas , Afonso Luana Ferreira , Soares-Souza Giordano Bruno , de Freitas Rebelo Mauro
Published: November 2019

Limnoperna fortunei — popularly known as the Golden mussel — is an aggressive invasive species that has been causing environmental damage and adversely affecting economic sectors dependent on freshwater ecosystems in South America. As a non-model species, knowledge about its biology is very limited, especially molecular mechanisms that contribute to its invasiveness, such as its high reproduction rate. Quantitative PCR (qPCR) is considered the gold standard technique to determine gene expression levels and its accuracy relies on the use of stably expressed reference genes for data normalization and to minimize technical variability. Our goal was to identify reliable reference genes to perform gene expression analysis on the gonads of L. fortunei. The stability of five candidate genes (RPS3, EF1a, HS6ST3B, NAPA and UBE2F) in the gonads of male and female mussels was evaluated by using two algorithms, Bestkeeper and Genorm. Results show that NAPA, UBE2F and RPS3 genes are stable enough to compose a reliable normalization factor for gene expression analyses comparing both sexes. HS6ST3B and NAPA were found to be more stable in female gonads; thus, their application as a normalization factor is preferable for studies limited to female processes only.
Neuronal identity is maintained in the adult brain through KAT3-dependent enhancer acetylation
Authors: Lipinski Michal , Muñoz-Viana Rafael , del Blanco Beatriz , Medrano-Relinque Juan , Marquez-Galera Angel , Carames Jose M. , Szczepankiewicz Andrzej A. , Fernandez-Albert Jordi , Navarrón Carmen M. , Olivares Roman , Wilczynski Grzegorz M. , Canals Santiago , Lopez-Atalaya Jose P. , Barco Angel
Published: November 2019

Very little is known about the mechanisms responsible for maintaining cell identity in mature tissues. The paralogous type 3 lysine acetyltransferases (KAT3) CBP and p300 are both essential during development, but their specific functions in nondividing differentiated cells remains unclear. Here, we show that when both proteins are simultaneously knocked-out in excitatory neurons of the adult brain, the mice express a rapidly progressing neurological phenotype associated with reduced dendritic complexity and electrical activity, the transcriptional shutdown of neuronal genes, and a dramatic loss of H3K27 acetylation and pro-neural transcription factor binding at neuronal enhancers. The neurons lacking both KAT3 rapidly acquire a molecularly undefined fate with no sign of dedifferentiation, transdifferentiation or death. Restoring CBP expression or lysine acetylation reestablished neuronal-specific transcription. Our experiments demonstrate that KAT3 proteins act as fate-keepers in excitatory neurons and other cell types by jointly safeguarding chromatin acetylation levels at cell type-specific enhancers throughout life.
Antithetic integral feedback for the robust control of monostable and oscillatory biomolecular circuits
Authors: Olsman Noah , Forni Fulvio
Published: November 2019

Biomolecular feedback systems are now a central application area of interest within control theory. While classical control techniques provide valuable insight into the function and design of both natural and synthetic biomolecular systems, there are certain aspects of biological control that have proven difficult to analyze with traditional methods. To this end, we describe here how the recently developed tools of dominance analysis can be used to gain insight into the nonlinear behavior of the antithetic integral feedback circuit, a recently discovered control architecture which implements integral control of arbitrary biomolecular processes using a simple feedback mechanism. We show that dominance theory can predict both monostability and periodic oscillations in the circuit, depending on the corresponding parameters and architecture. We then use the theory to characterize the robustness of the asymptotic behavior of this circuit in a nonlinear setting.
Hippocampal ensembles represent sequential relationships among discrete nonspatial events
Authors: Shahbaba Babak , Li Lingge , Agostinelli Forest , Saraf Mansi , Elias Gabriel A. , Baldi Pierre , Fortin Norbert J.
Published: November 2019

The hippocampus is critical to the temporal organization of our experiences, including the ability to remember past event sequences and predict future ones. Although this fundamental capacity is conserved across modalities and species, its underlying neuronal mechanisms remain poorly understood. Here we recorded hippocampal ensemble activity as rats remembered a sequence of nonspatial events (5 odor presentations unfolding over several seconds), using a task with established parallels in humans. Using novel statistical methods and deep learning techniques, we then identified new forms of sequential organization in hippocampal activity linked with task performance. We discovered that sequential firing fields (“time cells”) provided temporal information within and across events in the sequence, and that distinct types of task-critical information (stimulus identity, temporal order, and trial outcome) were also sequentially differentiated within event presentations. Finally, as previously only observed with spatial information, we report that the representations of past, present and future events were sequentially activated within individual event presentations, and that these sequential representations could be compressed within an individual theta cycle. These findings strongly suggest that a fundamental function of the hippocampal network is to encode and preserve the sequential order of experiences, and use these representations to generate predictions to inform decision-making.
Whole Genome Sequencing and Assembly of the Asian Honey BeeApis dorsata
Authors: Oppenheim Sara , Cao Xiaolong , Rueppel Olav , Chantawannakul Panuwan , Krongdang Sasiprapa , Phokasem Patcharin , DeSalle Rob , Goodwin Sara , Xing Jinchuan , Rosenfeld Jeffrey
Published: November 2019

The Asian honey bee (Apis dorsata)is distinct from its more widely distributed cousinA. melliferaby a few key characteristics. Most prominently,A. dorsata, nest in the open by forming a colony clustered around the honeycomb, whileA. melliferanest in concealed cavities. Additionally, the worker and reproductive castes are all of the same size inA. dorsata. In order to investigate these differences, we performed whole genome sequencing ofA. dorsatausing a hybrid Oxford Nanopore and Illumina approach. The 223MB genome has an N50 of 35kb with the largest scaffold of 302kb. We have found that there are many genes in thedorsatagenome that are distinct from other hymenoptera and also large amounts of transposable elements, and we suggest some candidate genes forA. dorsata’s exceptional level of defensive aggression.
SOLQC : Synthetic Oligo Library Quality Control Tool
Authors: Sabary Omer , Orlev Yoav , Shafir Roy , Anavy Leon , Yaakobi Eitan , Yakhini Zohar
Published: November 2019

Motivation

Recent years have seen a growing number and a broadening scope of studies using synthetic oligo libraries for a range of applications in synthetic biology. As experiments are growing by numbers and complexity, analysis tools can facilitate quality control and help in assessment and inference.

Results

We present a novel analysis tool, called SOLQC, which enables fast and comprehensive analysis of synthetic oligo libraries, based on NGS analysis performed by the user. SOLQC provides statistical information such as the distribution of variant representation, different error rates and their dependence on sequence or library properties. SOLQC produces graphical descriptions of the analysis results. The results are reported in a flexible report format. We demonstrate SOLQC by analyzing literature libraries. We also discuss the potential benefits and relevance of the different components of the analysis.

Availability

https://app.gitbook.com/@yoav-orlev/s/solqc/
Optimal reproductive phenology under size-dependent cannibalism
Authors: Takashina Nao , Fiksen Øyvind
Published: November 2019

Intra-cohort cannibalism is an example of a size-mediated priority effect. If early life stages cannibalize slightly smaller individuals, then parents face a trade-off between breeding at the best time for larval growth or development and predation risk from offspring born earlier. This game-theoretic situation among parents may drive adaptive reproductive phenology towards earlier breeding. However, it is not straightforward to quantify how cannibalism affects seasonal egg fitness or to distinguish emergent breeding phenology from alternative adaptive drivers. Here, we devise an age-structured game-theoretic mathematical model to find evolutionary stable breeding phenologies. We predict how size-dependent cannibalism acting on eggs, larvae, or both change emergent breeding phenology, and find that breeding under inter-cohort cannibalism occurs earlier than the optimal match to environmental conditions. We show that emergent breeding phenology patterns at the level of the population are sensitive to the ontogeny of cannibalism, i.e. which life stage is subject to cannibalism. This suggests that the nature of cannibalism among early life stages is a potential driver of the diversity of reproductive phenologies seen across taxa, and may be a contributing factor in situations where breeding occurs earlier than expected from environmental conditions.
Mediator subunit Med15 dictates the conserved “fuzzy” binding mechanism of yeast transcription activators Gal4 and Gcn4
Authors: Tuttle Lisa M. , Pacheco Derek , Warfield Linda , Hahn Steven , Klevit Rachel E.
Published: November 2019

The acidic activation domain (AD) of yeast transcription factor Gal4 plays a dual role in both transcription repression and activation through sequence-dependent binding to Gal80 repressor and sequence-independent binding to Mediator subunit Med15. The activation function of Gal4 arises from two hydrophobic regions within the 40-residue AD. We show by NMR that each AD region binds the Mediator subunit Med15 using a “fuzzy” protein interface. Remarkably, comparison of chemical shift perturbations shows that Gal4 and Gcn4, two ADs of different sequence, interact nearly identically with Med15. The findings that two ADs of different sequence use an identical fuzzy binding mechanism shows a common sequence-independent mechanism for AD-Mediator binding, similar to interactions within a hydrophobic cloud. In contrast, the same region of Gal4 AD interacts with Gal80 via a tight structured complex, implying that the structured binding partner of an intrinsically disordered protein dictates the type of protein interaction.
BDKANN - Biological Domain Knowledge-based Artificial Neural Network for drug response prediction
Authors: Snow Oliver , Sharifi-Noghabi Hossein , Lu Jialin , Zolotareva Olga , Lee Mark , Ester Martin
Published: November 2019

Motivation

One of the main goals of precision oncology is to predict the response of a patient to a given cancer treatment based on their genomic profile. Although current models for drug response prediction are becoming more accurate, they are also ‘black boxes’ and cannot explain their predictions, which is of particular importance in cancer treatment. Many models also do not leverage prior biological knowledge, such as the hierarchical information on how proteins form complexes and act together in pathways.

Results

In this work, we use this prior biological knowledge to form the architecture of a deep neural network to predict cancer drug response from cell line gene expression data. We find that our approach not only has a low prediction error compared to baseline models but also allows meaningful interpretation of the network. These interpretations can both explain predictions made and discover novel connections in the biological knowledge that may lead to new hypotheses about mechanisms of drug action.

Availability

Code at https://github.com/osnow/BDKANN

Supplementary information

Included with submission
SpecificgyrAgene mutations correlate with high prevalence of discordant levofloxacin resistance inMycobacterium tuberculosisisolates from Beijing, China
Authors: Huo Fengmin , Ma Yifeng , Li Shanshan , Xue Yi , Shang Yuanyuan , Dong Lingling , Li Yunxu , Pang Yu
Published: November 2019

Although molecular diagnostics are highly sensitive in the diagnosis of fluroquinolone (FQ)-resistant tuberculosis (TB), the discordant results with the sequential phenotypic drug susceptibility testing (DST) invariably occur. To investigate the prevalence and the cause of discordant results between molecular and phenotypic DST for levofloxacin (LFX), the cases who were determined to be LFX-susceptible using the phenotypic DST but LFX-resistant using the MeltPro assay were retrospectively reviewed in Beijing, China. We measured LFX minimal inhibitory concentrations (MICs) using Middlebrook 7H9 broth. Sanger sequencing was used to determine genotypic characteristics of discordant isolates. Between January and December 2018, 126 (22.1%) out of 571 smear-positive TB patients were identified as LFX-resistant TB by MeltPro assay. Among the 126 LFX-resistant TB, there were 34 isolates identified as LFX-susceptible TB by phenotypical DST. This result demonstrated a discordance prevalence of 27.0%. LFX MICs were majorly centered around the critical concentration, and 7 (21.2%) and 13 (39.4%) had MICs of 2.0 mg/l and 4.0 mg/l, respectively. The most prevalent mutations conferring discordant LFX resistance were the amino acid substitutions of Ser to Leu in 90 codon (13, 39.4%) and Asp to Ala in 94 codon ofgyrA(11, 33.3mg/l belonged to Ala90Val and Asp94Ala group. In conclusion, our data demonstrate that more than one quarter of LFX-resistant isolates by molecular method are susceptible to LFX using the phenotypic DST. The high prevalence of discordant LFX resistance is majorly due to the isolates with specific mutations withingyrAgene conferring proximity of MICs to the critical concentration.
Integrating genome-wide association mapping of additive and dominance genetic effects to improve genomic prediction accuracy inEucalyptus
Authors: Tan Biyue , Ingvarsson Pär K.
Published: November 2019

Genome-wide association studies (GWAS) is a powerful and widely used approach to decipher the genetic control of complex traits. A major challenge for dissecting quantitative traits in forest trees is statistical power. In this study, we use a population consisting of 1123 samples from two successive generations that have been phenotyped for growth and wood property traits and genotyped using the EuChip60K chip, yielding 37,832 informative SNPs. We use multi-locus GWAS models to assess both additive and dominance effects to identify markers associated with growth and wood property traits in the eucalypt hybrids. Additive and dominance association models identified 78 and 82 significant SNPs across all traits, respectively, which captured between 39 and 86% of the genomic-based heritability. We also used SNPs identified from the GWAS and SNPs using less stringent significance thresholds to evaluate predictive abilities in a genomic selection framework. Genomic selection models based on the top 1% SNPs captured a substantially greater proportion of the genetic variance of traits compared to when all SNPs were used for model training. The prediction ability of estimated breeding values was significantly improved for all traits using either the top 1% SNPs or SNPs identified using a relaxedp-value threshold (p<10-3). This study highlights the added value of also considering dominance effects for identifying genomic regions controlling growth traits in trees. Moreover, integrating GWAS results into genomic selection method provides enhanced power relative to discrete associations for identifying genomic variation potentially useful in tree breeding.
Motor circuit function is stabilized during postembryonic growth by anterograde trans-synaptic Jelly Belly - Anaplastic Lymphoma Kinase signaling
Authors: Gärtig Phil-Alan , Ostrovsky Aaron , Manhart Linda , Giachello Carlo N. G. , Kovacevic Tatjana , Lustig Heidi , Chwalla Barbara , Cachero Sebastian , Baines Richard A. , Landgraf Matthias , Evers Jan Felix
Published: November 2019

The brain adapts to a changing environment or growing body size by structural growth and synaptic plasticity. Mechanisms studied to date promote synaptic growth between partner neurons, while negative counterparts that inhibit such interactions have so far remained elusive. Here, we investigate the role of Jeb-Alk signaling in coordinating motor circuit growth during larval stages of Drosophila. We quantify neuronal growth dynamics by intra-vital imaging, and synaptogenesis at nanometer resolution using endogenously labeled synaptic proteins, conditionally tagged with a fluorophore, and link changes in circuit anatomy with altered synaptic physiology and behavior. We find that loss of Jeb-Alk signaling leads to increased strengthening of synaptic excitation by developmental addition of additional postsynaptic but not pre-synaptic specializations. These changes ultimately lead to an epilepsy-like seizure behavior. We thus demonstrate that trans-synaptic anterograde Jeb-Alk signaling acts to stabilize developmental plasticity and circuit function, and that it does so specifically during postembryonic growth.
Sequencing-based quantitative mapping of the cellular small RNA landscape
Authors: Hu Jennifer F. , Yim Daniel , Huber Sabrina M. , Bacusmo Jo Marie , Ma Duanduan , DeMott Michael S. , Levine Stuart S. , de Crécy-Lagard Valerie , Dedon Peter C. , Cao Bo
Published: November 2019

Current next-generation RNA sequencing methods cannot provide accurate quantification of the population of small RNAs within a sample due to strong sequence-dependent biases in capture, ligation, and amplification during library preparation. We report the development of an RNA sequencing method – AQRNA-seq – that minimizes biases and enables absolute quantification of all small RNA species in a sample mixture. Validation of AQRNA-seq library preparation and data mining algorithms using a 963-member microRNA reference library, RNA oligonucleotide standards of varying lengths, and northern blots demonstrated a direct, linear correlation between sequencing read count and RNA abundance. Application of AQRNA-seq to bacterial tRNA pools, a traditionally hard-to-sequence class of RNAs, revealed 80-fold variation in tRNA isoacceptor copy numbers, patterns of site-specific tRNA fragmentation caused by stress, and quantitative maps of ribonucleoside modifications, all in a single AQRNA-seq experiment. AQRNA-seq thus provides a means to quantitatively map the small RNA landscape in cells and tissues.
Characterising sensorimotor adaptation in Complex Regional Pain Syndrome
Authors: Vittersø Axel D. , Buckingham Gavin , Ten Brink Antonia F. , Halicka Monika , Proulx Michael J. , Bultitude Janet H.
Published: November 2019

It has been suggested that sensorimotor conflict contributes to the maintenance of some pathological pain conditions, implying that there are problems with the adaptation processes that normally resolve such conflict. We tested whether sensorimotor adaptation is impaired in people with Complex Regional Pain Syndrome (CRPS) by characterising their adaption to lateral prismatic shifts in vision. People with unilateral upper-limb CRPS Type I (n = 17), and pain-free individuals (n = 18; matched for age, sex, and handedness) completed prism adaptation with their affected/non-dominant and non-affected/dominant arms. We examined 1) the rate at which participants compensated for the optical shift during prism exposure (i.e. strategic recalibration), 2) endpoint errors made directly after prism adaptation (sensorimotor realignment) and the retention of these errors, and 3) kinematic markers associated with strategic control. Direct comparisons between people with CRPS and controls revealed no evidence of any differences in strategic recalibration, including no evidence for differences in a kinematic marker associated with trial-by-trial changes in movement plans during prism exposure. All participants made significant endpoint errors after prism adaptation exposure, indicative of sensorimotor realignment. Overall, the magnitude of this realignment did not differ between people with CRPS and pain-free controls. However, when endpoint errors were considered separately for each hand, people with CRPS madegreatererrors (indicating more rather than less realignment) when using their affected hand than their non-affected hand. No such difference was seen in controls. Taken together, these findings provide no evidence of impaired strategic control or sensorimotor realignment in people with CRPS. In contrast, they provide some indication that there could be a greater propensity for sensorimotor realignment in the CRPS-affected arm, consistent with more flexible representations of the body and peripersonal space. Our study challenges an implicit assumption of the theory that sensorimotor conflict might underlie some pathological pain conditions.