bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence-based practice
Authors: Li Shu , Cao Meijuan , Zhu Xuejiao
Published: September 2019

Background:

This study is to summarize the status of knowledge, attitudes, implementation, facilitators, and barriers of evidence-based practice (EBP) in community nurses (CNs). EBP has been widely adopted but the knowledge, attitudes, and implementation of EBP among CNs, and the facilitators and barriers they perceived have not been clearly confirmed.

Methods:

A literature search was conducted using combined keywords in 3 English databases and 3 Chinese databases of peer-reviewed publications covering the dates of publication from 1996 to July, 2018. Twenty articles were included. The information of the knowledge, attitudes, implementation, and the perceived facilitators and barriers of EBP in CNs was extracted and summarized.

Results:

CNs had positive attitudes toward EBP, but insufficient knowledge and unprepared implementation. The most cited facilitators were academic training, management functions, and younger age. Inadequate time and resources were recognized as main barriers hindering the transforming from knowledge and attitudes to implementation. Developed interventions mainly focused on knowledge facilitation rather than the elimination of objective barriers.

Conclusions:

Findings demonstrate a compelling need for improvement in knowledge and implementation of EBP in CNs, compared with the better attitudes. Except education, knowledge translating into implementation needs more coordination with authorities to magnify the facilitators and overcome the barriers. Further studies need to concentrate on deficient knowledge and implementation of EBP among CNs. Policy makers can use the facilitators and barriers found by this review to modify nursing education, current scientific resources supplement, practice supports for care improving.
Prognostic impact of the Fusobacterium nucleatum status in colorectal cancers
Authors: Chen Yanglong , Lu Ying , Ke Yuting , Li Yanling
Published: September 2019

To investigate the clinicopathological features and prognostic impact of Fusobacterium nucleatum (F nucleatum) status in patients with colorectal cancer (CRC) and its relationships with microsatellite instability (MSI) status.

Retrospective analysis of consecutive 91 CRC tissues from surgically resected specimens of stage III or high-risk stage II CRC patients who had received curative surgery in Wuhan Union Hospital from January, 2017 to January, 2019 was conducted. F nucleatum DNA was quantitatively measured and classified into 1 of the 2 categories: F nucleatum-high, or F nucleatum-low/negative. The Cox risk ratio model analysis was performed to identify independent risk factors of F nucleatum. F nucleatum-high group was compared with the F nucleatum-low/negative group with respect to clinicopathological features and their relationships with MSI status. Kaplan–Meier method and log-rank test were used for univariate analysis of prognostic factors in patients with CRC.

The number of total lymph node acquisition and positive lymph nodes, neurological invasion, vascular tumor thrombus were higher in F nucleatum-high group (27.44 ± 25.213 vs 20.70 ± 10.141; P = .018; 3.80 ± 7.974 vs 1.74 ± 3.531; P = .001; 68.0% vs 33.3%; P = .003; 60.0% vs 25.8%; P = .002). Moreover, microsatellite mutations were more frequent in patients with F nucleatum-high (84.0% vs 60.6%; P = .034). A higher abundance of F nucleatum in CRC is associated with a shorter survival time. The F nucleatum status, peripheral nerve invasion, vascular tumor thrombus, lymph node metastasis, and TNM staging were related factors affecting the prognosis of patients with CRC. The Cox risk ratio model analysis showed that the F nucleatum (odds ratio [OR] 2.094, 95% confidence interval [CI] 1.178–8.122, P = .032) and MSI status (OR 2.243, 95% CI 1.136–5.865, P = 0.039) were independent prognostic factors.

Intratumoral F nucleatum load has a poor prognostic effect of CRC by increasing nerve invasion, vascular tumor thrombus, and microsatellite mutation.
Bilateral proliferative retinopathy and ischemic optic neuropathy in a patient with atypical hemolytic-uremic syndrome
Authors: Lin I-Hung , Chen Ying-Jen , Chang Ping-Ying , Hsiao Po-Wei , Weng Tzu-Heng , Chang Yun-Hsiang
Published: September 2019

Rationale:

To report a rare case of severe atypical hemolytic-uremic syndrome (HUS) in a patient who presented with vitreous hemorrhage and tractional retinal detachment (TRD) in both eyes. To our knowledge, this is the first reported case of atypical HUS complicated with bilateral TRD in the literature.

Patient concerns:

A 20-year-old man with atypical HUS demonstrated bilateral visual acuity of hand motion at 30 cm.

Diagnoses:

Dilated fundus examination revealed diffuse intraretinal hemorrhage with vascular engorgement, neovascularization of the disc, and neovascularization elsewhere bilaterally. Fluorescein angiography revealed bilateral proliferative retinopathy, retinal hemorrhage, and a large nonperfusion area with extensive neovascularization. Intravitreal antivascular endothelial growth factor (ranibizumab) injection was administered in both eyes, but his ophthalmic condition did not improve, and TRD developed bilaterally. Therefore atypical HUS complicated with bilateral TRD was diagnosed.

Interventions:

Pars plana vitrectomy was performed with panretinal photocoagulation and silicone oil tamponade in the right eye.

Outcomes:

After the pars plana vitrectomy of right eye, the retina was well-attached after surgery, but visual acuity remained poor. Visual evoked potential examination showed poor waveforms bilaterally, which suggested ischemic optic neuropathy.

Lessons:

Atypical HUS can cause systemic thrombotic microangiopathy, resulting in ischemic retinal changes. These ischemic retinal changes can then cause hypoxia, which triggers production of angiogenic factors and subsequently causes retinal vascular hyperpermeability, retinal and vitreous neovascularization, fibrovascular proliferation, vitreous hemorrhage, and TRD, in a manner similar to that of other ischemia-induced proliferative retinopathies. Despite successful surgery in the right eye, our patient's visual acuity did not improve, possibly because of severe and generalized ischemia of intraocular tissue, which resulted in ischemic optic neuropathy.
Effectiveness of neuromuscular electrical stimulation combined with rehabilitation training for treatment of post-stroke limb spasticity
Authors: He Ya-long , Gao Yan , Fan Bai-ya
Published: September 2019

Background:

This study aims to systematically explore the effectiveness of neuromuscular electrical stimulation (NMES) combined with rehabilitation training (RT) for the treatment of post-stroke limb spasticity (PSLS).

Methods:

We will search Cochrane Library, MEDILINE, EMBASE, CINAHL, AMED, PsycINFO, WOS, Scopus, OpenGrey, and 4 Chinese databases from inception to the present without language restrictions. We will only consider randomized controlled trial on assessing the effectiveness and safety of NMES combined with RT for the treatment of PSLS. All included randomized controlled trials will be assessed using Cochrane risk of bias tool. Two researchers will independently perform study selection, risk of bias assessment, and data extraction, respectively. Any disagreements will be solved by a third researcher through discussion.

Results:

Primary outcome is limb spasticity status. Secondary outcomes comprise of limb function, quality of life, and adverse events.

Conclusion:

This study will summarize the latest evidence of NMES combined with RT for the treatment of patients with PSLS.

Systematic review registration:

PROSPERO CRD42019138900.
Effectiveness of acupuncture for treatment of diabetic peripheral neuropathy
Authors: Zhang You-jie , Liu Fan-rong
Published: September 2019

Background:

This study will assess the effectiveness and safety of acupuncture for the treatment of patients with diabetic peripheral neuropathy (DPN).

Methods:

We will comprehensively search electronic databases of MEDLINE, EMBASE, Cochrane Library, Web of Science, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, and China National Knowledge Infrastructure from their inception to July 1, 2019. We will also search grey literature to avoid missing any potential studies. Randomized controlled trials related to acupuncture for the treatment of DPN will be included. All record literatures are searched without language limitation. Two researchers will independently carry out research selection, data extraction, and research quality evaluation. We will perform RevMan 5.3 software for statistical analysis.

Results:

Primary outcomes consist of severity of neuropathy and pain intensity. Secondary outcomes include diabetes mellitus duration, body mass index, HbA1c level, blood glucose levels, and adverse events.

Conclusion:

The findings of this study will summarize recent evidence for the effectiveness and safety of acupuncture for the treatment of patients with DPN.

Ethics and dissemination:

We will not analyze individual data, thus no ethic approval is needed. The results of this study are expected to be published at a peer-reviewed journal.

PROSPERO registration number:

PROSPERO CRD42019139635.
The prevalence and genotype distribution of human papillomaviruses among women in Taizhou, China
Authors: Jin Rongrong , Qian Hua , Zhang Yongsheng , Yuan Donglan , Bao Jingjing , Zhou Huilin , Chen Min , Huang Junxing , Yu Hong
Published: September 2019

Human papillomavirus (HPV) infection is the leading cause of cervical cancer and precancerous lesions. Knowledge regarding the prevalence and genotype distribution of HPV in women is important to establish strategies for cervical cancer screening and HPV vaccination. This study aimed to evaluate the characteristics of HPV infection in Taizhou, China. HPV genotype of 10,733 women who visited Taizhou People's Hospital from November 2016 to October 2018 was determined using a PCR and hybridization-based detection test. The prevalence of overall, high risk (HR), and low risk (LR) HPV infections was 34.58%, 29.92%, and 10.12%, respectively. Of HPV-positive cases, 2417 (65.13%) were infected with a single HPV genotype and 1294 (34.87%) were infected with multiple HPV genotypes. HPV-52 was the most prevalent genotype (6.21%), followed by HPV-16 (5.33%), HPV-53 (4.03%), HPV-58 (3.89%), and HPV-81 (3.75%). The highest prevalence of HPV infection was found in women aged ≥60 years (40.72%). Furthermore, the prevalence of HPV increased with the severity of cervical lesions. In conclusions, the prevalence and genotype distribution of HPV varied with age and cervical lesions. The findings might serve as a potential reference for guiding cervical cancer screening and vaccine-based HPV prevention in Taizhou.
Association of rs2000999 in the haptoglobin gene with total cholesterol, HDL-C, and LDL-C levels in Mexican type 2 diabetes patients
Authors: Suarez-Sanchez Fernando , Vazquez-Moreno Miguel , Herrera-Lopez Ema , Gomez-Zamudio Jaime H. , Peralta-Romero José J. , Castelan-Martinez Osvaldo D. , Cruz Miguel , Parra Esteban J. , Valladares-Salgado Adan
Published: September 2019

Recently, studies have shown significant association between the rs2000999 polymorphism in the haptoglobin-encoding gene (HP) and low-density lipoprotein cholesterol (LDL-C) and total cholesterol (TC) levels, which are important risk factors for cardiovascular diseases. However, the association of rs2000999 with serum lipids in Latin American diabetic populations is still uncharacterized. Here, we analyzed the association of rs2000999 with TC, high-density lipoprotein cholesterol (HDL-C), and LDL-C levels in 546 Mexican adults with type 2 diabetes (T2D) and in 654 controls without T2D. In this observational case-control study we included adults from 4 centers of the Mexican Social Security Institute in Mexico City recruited from 2012 to 2015. TC, HDL-C, LDL-C, triglycerides (TG), and glucose levels were measured by an enzymatic colorimetric method. The variant rs2000999 was genotyped using TaqMan real time polymerase chain reaction. The percentage of Native-American ancestry showed a negative association with the rs2000999 A allele. In contrast, the rs2000999 A allele had a strong positive association with European ancestry, and to a lesser extent, with African ancestry. Linear regression was used to estimate the association between the variant rs2000999 and lipid concentrations, using different genetic models. Under codominant and recessive models, rs2000999 was significantly associated with TC and LDL-C levels in the T2D group and in controls without T2D. In addition, the group with T2D showed a significant association between the variant and HDL-C levels. In summary, the rs2000999 A allele in Mexican population is positively associated with the percentage of European and negatively associated with Native American ancestry. Carriers of the A allele have increased levels of TC and LDL-C, independently of T2D diagnosis, and also increased concentrations of HDL-C in the T2D sample.
Clinical and histopathologic features of sodium taurocholate cotransporting polypeptide deficiency in pediatric patients
Authors: Dong Chen , Zhang Ben-ping , Wang Hong , Xu Hui , Zhang Chao , Cai Zai-sheng , Wang Dao-wen , Shu Sai-nan , Huang Zhi-hua , Luo Xiao-ping
Published: September 2019

Until now, the recognition of sodium taurocholate cotransporting polypeptide (NTCP) deficiency has been mainly based on sporadic case reports. It was previously believed to be mildly symptomatic and resulting in mild liver dysfunction. However, to our knowledge, there have been no reports about the histopathologic and ultrastructural pathologic characteristics of the disease. The aim of the study was to analyze the clinical, histopathologic and ultrastructural pathologic characteristics of NTCP deficiency in 13 pediatric patients.

From August 2012 to October 2018, this retrospective study conducted in the Department of Pediatrics of Tongji Hospital, China analyzed the data of 13 NTCP deficient patients with an SLC10A1 gene mutation. Except for NTCP deficiency, no other liver diseases were present in the patients, which was determined by both a genetic testing panel for jaundice and by reviewing medical records. The laboratory results, imaging, histopathologic, and ultrastructural pathologic information were recorded for analysis.

The serum level of total bile acid was high in all 13 patients. All patients had adequate growth and development. Eight of the patients (8/13) presented with visible jaundice and 12 (12/13) were found to have hyperbilirubinemia. A needle liver biopsy was performed in 11 cases, which revealed slightly chronic inflammation in all 11 patients. One of the patients (1/13) was found to be suffering from gallstones.

The data showed that although NTCP deficiency was often asymptomatic, some of the patients showed obvious clinical expressions, such as jaundice. Among the 13 pediatric patients with NTCP deficiency, both the biochemical and histopathologic features were similar to those of mild hepatocellular jaundice. In addition, it was determined that the clinical features in the patient with gallstones may have been caused by NTCP deficiency.
Cangfu daotan decoction for polycystic ovary syndrome
Authors: Park Hye-Rin , Kim Jong-Hwan , Lee Donghun , Jo Hee-Geun
Published: September 2019

Backgrounds:

Polycystic ovary syndrome (PCOS) is common endocrine disorder in women and can lead to serious social burdens associated with various reproductive and metabolic abnormalities. Existing therapy is controversial in its effectiveness including side effects. In traditional Korean Medicine, Cangfu Daotan Decoction (CDD), also known as Changbudodam-tang, is used for PCOS patients who are in the type of stagnation of phlegm and dampness. In this study, we aimed to evaluate the efficacy and safety of CDD for PCOS as alternative treatment.

Methods:

Two researchers will search the following databases from their inception to February 2019 for relevant randomized controlled trials (RCTs): The Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure Database (CNKI), and 5 Korean medical databases (Korean Studies Information Service System, KoreaMed, DBPIA, Oriental Medicine Advanced Searching Integrated System, and Research Information Service System). The primary outcome will be the scales that assessed drug efficacy including total response rate, sex hormone level (LH, FSH, Testosterone, LH/FSH ratio), BMI, ovulation rate, and pregnancy rate. Adverse events will be assessed as the secondary outcome. Study selection, data extraction, and assessment of risk of bias will be conducted by 2 researchers independently. Statistical analysis will be performed by using the Cochrane Review Manager (RevMan 5.3) software.

Results and Conclusion:

This review will provide the latest knowledge and evidence on the efficacy and safety of CDD for PCOS women through the analysis of various evaluation scales.

Ethics and dissemination:

This systematic review does not require ethical approval and will be published in a peer-reviewed journal.

PROSPERO registration number:

CRD42019134270.
Efficacy of orthodontic and orthognathic treatment for oral and maxillofacial deformities
Authors: Gao Jin-Yu , Yu Xiao-Qin
Published: September 2019

Background:

This study aims to assess the efficacy and safety of orthodontic and orthognathic treatment (OOT) for patients with oral and maxillofacial deformities (OMDF) systematically.

Methods:

This study will comprehensively search Cochrane Library, PubMed, EMBASE, Scopus, Web of Science, PsycINFO, Index to Nursing and Allied Health Literature, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their inceptions to the July 1, 2019. Grey literature will be explored via searching dissertations, Google scholar and conference abstracts. Two team members will independently perform all citations, data extraction, and methodological quality. We will also utilize RevMan 5.3 Software for statistical analysis.

Results:

This study will provide high quality evidence of OOT for OMDF. The primary outcomes consist of number of patients cured; proportion of patients healed; and time to complete healing within trial period. Secondary outcomes include quality of life (often assessed as any relevant scales, such as 36-Item Short Form Survey), costs, and complications.

Conclusion:

This study will provide evidence for judging whether OOT is effective treatment for OMDF.

Systematic review registration:

CRD42019144610.
Efficacy and safety of Shenqi Fuzheng injection combined with platinum-based chemotherapy for stage III/IV non-small cell lung cancer
Authors: Chen Hongwei , Yao Xiaojun , Liu Zhengtang , Li Ting , Xu Cong , Wang Jue , Sui Xinbing , Leung Elaine Lai-Han , Wu Qibiao
Published: September 2019

Background:

Shenqi Fuzheng injection (SFI) is a commonly used anti-cancer Chinese patent medicine and has long been prescribed as adjunctive treatment to platinum-based chemotherapy (PBC) in patients with stage III/IV non-small cell lung cancer (NSCLC). However, the efficacy and safety of this combination therapy remain unclear.

Methods:

A systematic review and meta-analysis will be conducted following the Preferred Reported Items for Systematic Review and Meta-analysis (PRISMA) guidelines. Seven databases will be searched for relevant studies from their inception to the present date: PubMed, Web of Science, Cochrane Library, EMBASE, ClinicalTrials.gov, China National Knowledge Infrastructure (CNKI), and Wanfang Databases. All randomized clinical trials comparing SFI in combination with PBC versus PBC alone will be retrieved and assessed for inclusion. Two researchers will independently perform the selection of the studies, data extraction, and synthesis. The Cochrane Risk of Bias Tool will be used to evaluate the risk of bias of the RCTs. The primary endpoint is the disease control rate (DCR), the secondary outcomes are the objective response rate (ORR), survival rate, quality of life (QOL), cellular immune function, and toxicities. Review Manager 5.3 (Nordic Cochrane Centre, Cochrane Collaboration, 2014 Copenhagen, Denmark) will be used to analyze the outcomes.

Results:

This study will systematically evaluate the efficacy and safety of SFI combined with platinum-based chemotherapy in the treatment of stage III/IV NSCLC. The results will be published in a peer-reviewed journal.

Conclusion:

This systematic review will evaluate the effects of SFI as adjunctive treatment to platinum-based chemotherapy in the patients with stage III/IV non-small cell lung cancer, thus providing evidence to the clinical application of this combination therapy.

PROSPERO registration number:

CRD42019137196
Antimicrobial photodynamic therapy on teeth with molar incisor hypomineralization—controlled clinical trial
Authors: Vieira Letícia Diniz Santos , Paschoal Marco Aurelio Benini , de Barros Motta Pamella , Ferri Elza Padilha , Ribeiro Caroline Diniz Pagani Vieira , dos Santos-Pinto Lourdes Aparecida Martins , Motta Lara Jansiski , Gonçalves Marcela Letícia Leal , Horliana Anna Carolina Ratto Tempestini , Fernandes Kristianne Porta Santos , Ferrari Raquel Agnelli Mesquita , Deana Alexandre Melo , Bussadori Sandra Kalil
Published: September 2019

Background:

Molar incisor hypomineralization (MIH) is a change in the formation of dental enamel of systemic origin that affects at least one of the first 4 permanent molars and usually affects incisors. During the eruption, the affected surfaces tend to fracture, exposing the dentin, which causes excessive sensitivity in addition to making the region very susceptible to the appearance of carious lesions. The objective of this research will be to evaluate the clinical effect of antimicrobial photodynamic therapy (aPDT) in permanent teeth with severe and sensitive MIH.

Methods:

The methodology will be based on the selection of patients from 6 to 12 years of age with permanent molar teeth, randomly divided in 2 groups. The selected teeth should have MIH on the occlusal surface, indicated for clinical restorative treatment. In Group 1, aPDT will be applied for the treatment of infected dentin. Afterward, the teeth will be restored with high viscosity glass ionomer cement. In Group 2, the removal of the softened dentin around the side walls of the cavity with sharp dentine curettes and posterior restoration with high viscosity glass ionomer cement will be performed. All patients will have clinical and radiographic follow-up with a time interval of 6 and 12 months. The data obtained will be submitted to descriptive statistical analysis to evaluate the association of categorical variables. Chi-square test and Fisher exact test will be applied, to analyze the correlation between the continuous variables, Pearson correlation test will be applied. For the analysis of dentin density in the scanned radiographic images and the microbiological results for colony-forming units, ANOVA and Kruskal–Wallis will be applied.

Discussion:

Often in the presence of severe MIH, the presence of dentin sensitivity is also associated with caries lesion, making it even more necessary to respect the principles of minimal intervention.

Trial registration:

NCT03904641.
The efficacy and safety of irinotecan ± bevacizumab compared with oxaliplatin ± bevacizumab for metastatic colorectal cancer
Authors: Dai Jiali , Chen Yuetong , Gong Yang , Wei Jingsun , Cui Xiaowen , Yu Hualin , Zhao Wenjing , Gu Dongying , Chen Jinfei
Published: September 2019

Background:

Irinotecan (IRI)-based and oxaliplatin (OXA)-based regimens are available for the treatment of metastatic colorectal cancer (mCRC). Several studies have published inconsistent results in their comparisons of the efficacy and toxicity of IRI ± bevacizumab and OXA ± bevacizumab. This meta-analysis was performed to evaluate the efficacy and safety of these 2 regimens in patients with mCRC.

Methods:

We searched several databases to identify relevant studies, including PubMed, EMBASE, and the Cochrane Controlled Trials Register. The primary endpoints were overall survival (OS) and time to progression (TTP). The secondary comparisons were overall response rate (ORR) and toxicity. In addition, the hazard ratio (HR) or risk ratio (RR) values with their corresponding 95% confidence intervals (CIs) were extracted from these studies.

Results:

Pooled data of 13 studies demonstrated no significant differences in OS (HR = 0.96, 95% CI: 0.86–1.08, P = .53) and TTP (HR = 0.88, 95% CI: 0.72–1.08, P = .24) between the 2 groups. However, the ORR (RR = 0.87, 95% CI: 0.78–0.97, P = .02) was clearly improved in the OXA ± bevacizumab arm. Higher incidences of grade 3/4 nausea (RR = 1.63, 95% CI: 1.28–2.07, P < .001), vomiting (RR = 1.40, 95% CI: 1.09–1.81, P = .01), diarrhea (RR = 1.44, 95% CI: 1.23–1.70, P < .001), and anemia (RR = 4.13, 95% CI: 2.75–6.22, P < .001) were observed in the IRI group. However, the incidences of grade 3/4 neutropenia (RR = 0.75, 95% CI: 0.68–0.83, P < .001), thrombocytopenia (RR = 0.43, 95% CI: 0.26–0.73, P = .002), and paresthesia/neurological disturbances (RR = 0.04, 95% CI: 0.02–0.07, P < .001) were higher in the OXA group.

Conclusion:

This meta-analysis confirmed that the OXA ± bevacizumab regimen as a maintenance therapy significantly improved the ORR in patients with mCRC. Exhibiting strong efficacy and safety, the OXA and OXA plus bevacizumab regimens are preferred as first-line treatments for mCRC.
Delirium in a Tertiary PICU: Risk Factors and Outcomes*
Authors: Dervan Leslie A. , Di Gennaro Jane L. , Farris Reid W. D. , Watson R. Scott
Published: September 2019

Objectives:

To determine risk factors and outcomes associated with delirium in PICU patients.

Design:

Retrospective cohort study.

Setting:

Thirty-two–bed PICU within a tertiary care academic children’s hospital.

Patients:

All children admitted to the PICU March 1, 2014, to October 1, 2016, with at least one Cornell Assessment of Pediatric Delirium score (n = 2,446).

Interventions:

None.

Measurements and Main Results:

Cornell Assessment of Pediatric Delirium score was performed twice daily as standard of care. We characterized delirium as: 1) presence of greater than or equal to 1 positive score (Cornell Assessment of Pediatric Delirium ≥ 9) and 2) number of days with a positive score. We built multivariable logistic and linear regression models using electronic medical records data. Many patients (n = 1,538; 63%) had a short length of stay (< 48 hr). Compared with patients with length of stay greater than or equal to 48 hours, fewer experienced delirium (30% vs 69%; p < 0.0001). Among 908 patients with length of stay greater than or equal to 48 hours, presence of delirium was independently associated with age less than 2 years old, baseline cognitive dysfunction, primary diagnosis, and duration of mechanical ventilation. Benzodiazepines demonstrated a dose-response effect (odds ratio for presence of delirium, 1.8 [p = 0.03], 3.4 [p < 0.001], and 9.7 [p = 0.005] for < 25th percentile, 25–75th percentile, and > 75th percentile of total dose, vs no exposure). In terms of outcomes, presence of delirium was independently associated with increased ICU length of stay (p < 0.001), whereas days of delirium were independently associated with decline in cognitive function from ICU admission to discharge (odds ratio, 1.06; p < 0.001), increased ICU (p < 0.001), and hospital length of stay (p < 0.001). Neither delirium presence nor total days were independently associated with mortality.

Conclusions:

Delirium is common in the PICU, particularly among patients with length of stay greater than or equal to 48 hours. It is independently associated with patient characteristics and PICU exposures, including benzodiazepines. The role of delirium as an independent causal factor in patient outcome requires further investigation.
Quality Improvement Interventions to Improve Critical Congenital Heart Disease Screening
Authors: Hom Lisa A. , Chan Salcedo Clarissa , Revenis Mary , Martin Gerard R.
Published: September 2019

Introduction:

Newborn screening for critical congenital heart disease (CCHD) using pulse oximetry improves detection and is associated with decreased related infant mortality. In 2015, the Healthy Hearts of Babies Act required hospitals to screen all newborns in the District of Columbia for CCHD using pulse oximetry and to provide documentation of individual screening results to the Department of Health. A regulatory report from the electronic health record revealed an opportunity to improve both documentation and protocol adherence within our hospital. We aimed to reduce documentation errors and protocol violations by 75% and sustain this improvement for 6 months.

Methods:

In February of 2014, our center, a large free-standing children’s hospital, implemented CCHD screening in the neonatal intensive care unit on all infants without known congenital heart disease or receiving supplemental oxygen. During the intervention period (January 2016 to December 2018), an interdisciplinary team engaged in regular review and analysis of reports, monthly closed-loop feedback, and iterative refinements to the electronic health record. Statistical process control charts were used to compare a baseline period to the intervention period and track monthly progress.

Results:

Between February 2014 and December 2018, we screened 2,214 infants for CCHD. The average percentage of documentation errors decreased from 23.5% during the baseline period to 1.2% during the intervention period, a sustained reduction for over 2 years. Protocol violations occurred at an average of 2.1% in the baseline period, with a sustained decrease to 0.6% during the intervention period.

Conclusions:

This multimodal quality improvement project demonstrated a sustained reduction of CCHD screening documentation errors and protocol violations.
Postoperative Management of Zygomatic Arch Fractures: In-House Rapid Prototyping System for the Manufacture of Protective Facial Shields
Authors: Orabona Giovanni Dell’Aversana , Abbate Vincenzo , Maglitto Fabio , Committeri Umberto , Improta Giovanni , Bonavolontà Paola , Reccia Alfonso , Somma Teresa , Iaconetta Giorgio , Califano Luigi
Published: September 2019

Zygomatic fractures account for 10% to 15% of all facial fractures. The surgical management of isolated zygomatic arch fractures usually requires open reduction treatment without fixation through an intraoral access. Therefore, the main problem in the non-fixed treatment of zygomatic arch fractures is related to the difficulty in obtaining a stable reduction for a period long enough to guarantee the physiological bone healing process. We propose an innovative “in-house” rapid prototyping (RP) protocol for the 3D-zygoma mask manufacture of a patient-specific protective device to apply after zygomatic arch fracture reduction. Our study includes 16 consecutive patients who underwent surgical open reduction for an isolated zygoma fracture without fixation between January 2017 and February 2018. The patients received regular postoperative checks at weeks 1 and 2. Before the device was removed, a multiple choice questionnaire was administered to measure the degree of wearability of the mask. The estimated cost of the production is around €5 per case and the construction time is around 90 minutes. Based on the encouraging results, obtained in our experience, we hope that other studies can be conducted to confirm our procedure and improve its functionality in the field of facial trauma.
Histologic Evaluation of Healing Lip Defects Treated With Injected Onabotulinum Toxin A and Topical Mitomycin C
Authors: Jahanbin Arezoo , Namdar Parastoo , Ghazi Narges , Kazemian Mozhgan
Published: September 2019

Objective:

Using an experimental rat model, the efficacy of injected Onabotulinum Toxin A (BoNT-A) versus topical Mitomycin C in surgical wound healing of rat lip defects was evaluated.

Methods and Materials:

Sixty-seven male Wister rats received a triangular cut (7 × 7 × 4 mm) on their upper lip. Then they were divided randomly into 4 equal groups: group A (topical Mitomycin C plus injected BoNT-A); group B (topical Mitomycin C); group C or control group (saline solution) and group D (injected (BoNT-A). After 3 months, the animals were euthanized and scars were evaluated using hematoxylin and eosin and Masson's trichrome.

For qualitative analysis, inflammatory cell density, new capillary formation, fibroblast proliferation, and collagen deposition were reported using relative ranks from 0 to 3 (absence, mild, moderate, marked). Data were analyzed by post hoc and Kruskal–Wallis tests. The significance level was P < 0.05.

Result:

Mean collagen deposition values and fibroblast proliferation in the 4 groups showed statistically significant differences with each other (P value < 0.001). A significant difference between group A and controls existed for fibroblast proliferation (median 1 versus 2, P value < 0.001); also, collagen deposition (median 1 versus 2, P value < 0.001). A significant difference existed between the control and group D (median 2 versus 1, P value = 0.004); also, group A and B (median 1 versus 2, P value = 0.002) for collagen deposition. However, no significant differences existed between the 4 groups regarding inflammatory cells and angiogenesis (P value > 0.05).

Conclusion:

Local injection of BoNT-A plus Mitomycin C followed by BoNT-A alone provided less collagen formation and fibroblastic proliferation in the healing lip defect in a rat model.
A Small Dose of Butorphanol Prevents Sufentanil-induced Cough During General Anesthesia Induction
Authors: Yin Fang , Zhang Tiejun
Published: September 2019

Purpose:

This study aimed to evaluate the suppressive effects of a small dose of butorphanol on sufentanil-induced cough during general anesthesia induction.

Methods:

120 patients who were scheduled for elective maxillofacial surgery of American Society of Anesthesiologists I∼II, aged 18∼65 years were randomly divided into 3 groups (n = 40). Patients received butorphanol 0.1 mg (group I), 1 mg (group II) or an equal volume of 0.9% normal saline (group III) 5 seconds right before sufentanil bolus (0.5ug/kg). Sufentanil was diluted into 5ug/mL and administrated within 5 seconds. The incidence and reflex degree of cough in all groups were evaluated within 2 minutes after the injection of sufentanil during anesthesia induction. Mean arterial pressure (MAP) and heart rate (HR) were recorded at T0 (before the injection of butorphanol or normal saline), T1 (before the injection of sufentanil) and T2 (2 minutes after sufentanil injection).

Results:

The HR and MAP values were no significant difference among the 3 groups at the same observation point. In group II, the HR decreased significantly at T2 compared with T0 and T1 (P <0.05, T2 VS T0, T1). None of the patients in group I and group II had cough, and 33 patients in group III developed cough, of which 12.5% were mild, 40% were moderate, and 30% were severe.

Conclusions:

The results of present study suggest that a small dose of butorphanol 0.1 mg can prevent sufentanil-induced cough and ensure a relatively stable hemodynamic state during general anesthesia induction.
Identification and Recent Approaches for Evaluation, Operative Counseling, and Management in Patients With Freeman-Burian Syndrome: Principles for Global Treatment
Authors: Poling Mikaela I. , Dufresne Craig R. , Portillo Augusto L.
Published: September 2019

For many, the experience of a complex craniofacial malformation condition, such as Freeman-Burian syndrome (FBS), formerly Freeman-Sheldon syndrome, is deeply distressing. There are few references in the literature addressing initial evaluation and operative counseling for FBS, and guidance is absent. Two major outcomes of FBS are explored, namely diagnostic accuracy and therapeutic result, to identify factors influencing optimal clinical care in (1) diagnosis, (2) evaluation, (3) general and craniofacial operative counseling, and (4) craniofacial management.

PubMed searches have yielded 15 results describing craniofacial surgery in FBS and 29 manuscripts describing psychosocial aspects of surgery and patient and family counseling and education in other non-intellectually impairing craniofacial malformation conditions. Research in this area of scholarship is plagued by problems, especially considerable knowledge gaps and an absence of study data for operative outcomes. As a result, the literature remains unsettled, though our experience presents a much more clear picture of the clinical reality for this challenging patient population. While many challenges and limitations to treatment are present, much can be done to afford these patients a good and productive quality of life through operative intervention and longitudinal psychosocial support.
Restricting Saturated Fat May Not Be Required to Reduce Risk of Cardiovascular Disease
Authors: Colin Casey R. , Kattelmann Kendra K.
Published: September 2019

The purpose of this review was to determine whether the recommendation to reduce saturated fatty acid (SFA) consumption to treat or prevent cardiovascular disease (CVD) is relevant in the context of current peer-reviewed, evidence-based literature. A literature review regarding SFA and CVD was conducted using articles from 2011 to 2018 through PubMed. Three hundred seventy-four articles were found, of which 211 were excluded. The remainder included 37 primary research articles and 21 reviews. All of the publications were examined using the Evidence Analysis Library Quality Criteria. Existing evidence supporting a reduction in SFA to treat/prevent CVD is limited and conflicting.
Ancient genomic regulatory blocks are a major source for gene deserts in vertebrates after whole genome duplications
Authors: Touceda-Suárez María , Kita Elizabeth M. , Acemel Rafael D. , Firbas Panos N. , Magri Marta S. , Naranjo Silvia , Tena Juan J. , Gómez-Skarmeta Jose Luis , Maeso Ignacio , Irimia Manuel
Published: September 2019

We investigated how the two rounds of whole genome duplication that occurred at the base of the vertebrate lineage have impacted ancient microsyntenic associations involving developmental regulators (known as genomic regulatory blocks, GRBs). We showed that the majority of GRBs present in the last common ancestor of chordates have been maintained as a single copy in humans. We found evidence that dismantling of the additional GRB copies occurred early in vertebrate evolution often through the differential retention of the regulatory gene but loss of the bystander gene’s exonic sequences. Despite the large evolutionary scale, the presence of duplicated highly conserved non-coding regions provided unambiguous proof for this scenario for dozens of ancient GRBs. Remarkably, the dismantling of ancient GRB duplicates has contributed to the creation of large gene deserts associated with regulatory genes in vertebrates, providing a widespread mechanism for the origin of these enigmatic genomic traits.
Understanding artificial mouse-microbiome heterogeneity and six actionable themes to increase study power
Authors: Basson Abigail R , LaSalla Alexandria , Lam Gretchen , Kulpins Danielle , Moen Erika L , Sundrud Mark , Miyoshi Jun , Ilic Sanja , Theriault Betty R , Cominelli Fabio , Rodriguez-Palacios Alexander
Published: September 2019

The negative effects of data clustering due to (intra-class/spatial) correlations are well-known in statistics to interfere with interpretation and study power. Therefore, it is unclear why housing many laboratory mice (≥4), instead of one-or-two per cage, with the improper use/reporting of clustered-data statistics, abound in the literature. Among other sources of ‘artificial’ confounding, including cyclical oscillations of the ‘cage microbiome’, we quantified the heterogeneity of modern husbandry practices/perceptions. The objective was to identify actionable themes to re-launch emerging protocols and intuitive statistical strategies to increase study power. Amenable for interventions, ‘cost-vs-science’ discordance was a major aspect explaining heterogeneity and the reluctance to change. Combined, four sources of information (scoping-reviews, professional-surveys, expert-opinion, and ‘implementability-score-statistics’) indicate that a six-actionable-theme framework could minimize ‘artificial’ heterogeneity. With a ‘Housing Density Cost Simulator’ in Excel and fully annotated statistical examples, this framework could reignite the use of ‘study power’ to monitor the success/reproducibility of mouse-microbiome studies.
Shadow enhancers suppress input transcription factor noise through distinct regulatory logic
Authors: Waymack Rachel , Fletcher Alvaro , Enciso German , Wunderlich Zeba
Published: September 2019

Shadow enhancers, groups of seemingly redundant enhancers, are found in a wide range of organisms and are critical for robust developmental patterning. However, their mechanism of action is unknown. We hypothesized that shadow enhancers drive consistent expression levels by buffering upstream noise through a separation of transcription factor (TF) inputs at the individual enhancers. By measuring transcriptional dynamics of several Kruppel shadow enhancer configurations in live Drosophila embryos, we showed individual member enhancers act largely independently. We found that TF fluctuations are an appreciable source of noise that the shadow enhancer pair can better buffer than duplicated enhancers. The shadow enhancer pair is uniquely able to maintain low levels of expression noise across a wide range of temperatures. A stochastic model demonstrated the separation of TF inputs is sufficient to explain these findings. Our results suggest the widespread use of shadow enhancers is partially due to their noise suppressing ability.
The HLA Ligand Atlas - A resource of natural HLA ligands presented on benign tissues
Authors: Marcu Ana , Bichmann Leon , Kuchenbecker Leon , Kowalewski Daniel Johannes , Freudenmann Lena Katharina , Backert Linus , Mühlenbruch Lena , Szolek András , Lübke Maren , Wagner Philipp , Engler Tobias , Matovina Sabine , Wang Jian , Hauri-Hohl Mathias , Martin Roland , Kapolou Konstantina , Walz Juliane Sarah , Velz Julia , Moch Holger , Regli Luca , Silginer Manuela , Weller Michael , Löffler Markus W. , Erhard Florian , Schlosser Andreas , Kohlbacher Oliver , Stevanović Stefan , Rammensee Hans-Georg , Neidert Marian Christoph
Published: September 2019

The human leukocyte antigen (HLA) complex controls adaptive immunity by presenting defined fractions of the intracellular and extracellular protein content to immune cells. Here, we describe the HLA Ligand Atlas, an extensive collection of mostly matched HLA-I and -II ligandomes from 225 benign samples (29 tissues, 21 subjects). The initial release covers 51 HLA-I and 86 HLA-II allotypes presenting 89,853 HLA-I- and 140,861 HLA-II ligands. We observe that the immunopeptidomes differ considerably between tissues and individuals on both source protein and HLA-ligand level. 1,407 HLA-I ligands stem from non-canonical genomic regions. We highlight the importance of comparatively analyzing both benign and malignant tissues to inform tumor association, based on a case study in three glioblastoma patients. The resource provides insights into applied and basic immune-associated questions in the context of cancer immunotherapy, infection, transplantation, allergy, and autoimmunity. It is publicly available atwww.hla-ligand-atlas.org.
The mood stabilizer lithium slows down synaptic vesicle cycling at glutamatergic synapses
Authors: Tang Willcyn , Cory Bradley , Lim Kah Leong , Fivaz Marc
Published: September 2019

Lithium is a mood stabilizer broadly used to prevent and treat symptoms of mania and depression in people with bipolar disorder (BD). Little is known, however, about its mode of action. Here, we analyzed the impact of lithium on synaptic vesicle (SV) cycling at presynaptic terminals releasing glutamate, a neurotransmitter previously implicated in BD and other neuropsychiatric conditions. We used the pHluorin-based synaptic tracer vGpH and a fully automated image processing pipeline to quantify the effect of lithium on both SV exocytosis and endocytosis in hippocampal neurons. We found that lithium selectively reduces SV exocytic rates during electrical stimulation, and markedly slows down SV recycling post-stimulation. Analysis of single bouton responses revealed the existence of functionally distinct excitatory synapses with varying sensitivity to lithium ― some terminals show responses similar to untreated cells, while others are markedly impaired in their ability to recycle SVs. While the cause of this heterogeneity is unclear, these data indicate that lithium interacts with the SV machinery and influences glutamate release in a large fraction of excitatory synapses. Together, our findings show that lithium down modulates SV cycling, an effect consistent with clinical reports indicating hyperactivation of glutamate neurotransmission in BD.
dotdotdot: an automated approach to quantify multiplex single molecule fluorescent in situ hybridization (smFISH) images in complex tissues
Authors: Maynard Kristen R. , Tippani Madhavi , Takahashi Yoichiro , Phan BaDoi N. , Hyde Thomas M. , Jaffe Andrew E. , Martinowich Keri
Published: September 2019

Multiplex single-molecule fluorescent in situ hybridization (smFISH) is a powerful method for validating RNA sequencing and emerging spatial transcriptomic data, but quantification remains a computational challenge. We present a framework for generating and analyzing smFISH data in complex tissues while overcoming autofluorescence and increasing multiplexing capacity. We developed dotdotdot (https://github.com/LieberInstitute/dotdotdot) as a corresponding software package to quantify RNA transcripts in single nuclei and perform differential expression analysis. We first demonstrate robustness of our platform in single mouse neurons by quantifying differential expression of activity-regulated genes. We then quantify spatial gene expression in human dorsolateral prefrontal cortex (DLPFC) using spectral imaging and dotdotdot to mask lipofuscin autofluorescence. We lastly apply machine learning to predict cell types and perform downstream cell type-specific expression analysis. In summary, we provide experimental workflows, imaging acquisition and analytic strategies for quantification and biological interpretation of smFISH data in complex tissues.
Improved genome assembly and annotation of the soybean aphid (Aphis glycinesMatsumura)
Authors: Mathers Thomas C.
Published: September 2019

Aphids are an economically important insect group due to their role as plant disease vectors. Despite this economic impact, genomic resources have only been generated for a small number of aphid species. The soybean aphid (Aphis glycinesMatsumura) was the third aphid species to have its genome sequenced and the first to use long-read sequence data. However, version 1 of the soybean aphid genome assembly has low contiguity (contig N50 = 57 KB, scaffold N50 = 174 KB), poor representation of conserved genes and the presence of genomic scaffolds likely derived from parasitoid wasp contamination. Here, I use recently developed methods to reassemble the soybean aphid genome. The version 2 genome assembly is highly contiguous, containing half of the genome in only 40 scaffolds (contig N50 = 2.00 Mb, scaffold N50 = 2.51 Mb) and contains 11% more conserved single copy arthropod genes than version 1. To demonstrate the utility this improved assembly, I identify a region of conserved synteny between aphids andDrosophilacontaining members of theOsirisgene family that was split over multiple scaffolds in the original assembly. The improved genome assembly and annotation ofA. glycinesdemonstrates the benefit of applying new methods to old data sets and will provide a useful resource for future comparative genome analysis of aphids.