bluuebunny/crossref_metadata_2025 huggingface dataset:
Syringopeptin Contributes to the Virulence of Pseudomonas fuscovaginae, Based on sypA Biosynthesis Mutant Analysis
Authors: Weeraratne Nirodha , Stodart Benjamin J. , Venturi Vittorio , Hofte Monica , Hua Gia Khuong Hoang , Ongena Marc , Savocchia Sandra , Steel Christopher C. , Ash Gavin J.
Published: December 2019

Pseudomonas fuscovaginae, first reported from Japan in 1976, is now present in many agroecological regions around the world; it causes sheath brown rot of rice and is reported as a pathogen of a broad range of hosts. The pathogen can infect rice plants at all stages of growth and is known to cause significant losses due to grain discoloration, poor spike emergence and panicle sterility. Limited information is available on the virulence and mechanisms of pathogenicity for P. fuscovaginae. To address this, an analysis of genomes was conducted, which identified the presence of a gene showing homology to one of the genes contributing to syringopeptin synthetase (sypA) of P. syringae pv. syringae. To study the potential role of this gene in the virulence and pathogenicity of P. fuscovaginae, a site-specific mutation was created. Following inoculation of seeds and plantlets of rice and wheat with P. fuscovaginae wild types and their respective mutants, we demonstrated that the mutation significantly reduced virulence. This was evident on rice and wheat inoculated with mutants causing a significantly higher number of roots, length of roots and seedling height compared with their respective wild types. Characteristic disease symptoms of necrotic lesions were significantly less in rice seedlings infected with bacterial suspensions of mutants indicating a reduction in virulence. Chromatography analysis of bacterial exudates showed suppression of synthesis of metabolites analogous to syringopeptin in the mutants. These data demonstrate that the protein encoded by this sypA homolog gene is a major virulence determinant of P. fuscovaginae.
Right Heart Catheterization-Related Complications
Authors: Chen Yuefeng , Shlofmitz Evan , Khalid Nauman , Bernardo Nelson L. , Ben-Dor Itsik , Weintraub William S. , Waksman Ron
Published: December 2019

Right heart catheterization (RHC) is considered to be the gold standard for the measurement of pulmonary artery pressure and has a class 1 indication to confirm the diagnosis of pulmonary arterial hypertension and to guide treatment decisions. Associated complications with RHC in contemporary practice are uncommon. In this review, we aim to summarize the complications that have been published in case reports or case series with updated management and techniques to prevent and mitigate complications. We searched the PubMed database for the following reports: “right heart catheterization,” “Swan-Ganz catheter,” “pulmonary artery catheter,” “balloon-tip catheter,” and “complication” or “adverse event.” Complications reported in 46 manuscripts were included in the final analysis. After evaluation of all reports, complications were grouped categorically. We found that the most commonly reported access site-related issues were either carotid artery injury or arteriovenous fistula formation, and injury to the tricuspid valve was the most commonly reported catheter-related complication. Our findings suggest that infrequent complications can occur with RHC and can be fatal. The optimal technique should be used to minimize complications. Operators should always be cautious during the procedure and monitor the patient closely.
The effect of Chinese herbal medicine combined with western medicine on vascular endothelial function for patients with hypertension
Authors: Ren Weiquan , Liao Jiangquan , Chen Jialiang , Li Zhonghao , Huang Li
Published: December 2019

Background:

Essential hypertension is one of the most common chronic diseases in the world and a major risk factor for cardiovascular and cerebrovascular diseases. Hypertension often leads to a variety of complications, of which vascular endothelial dysfunction is an important part. Traditional Chinese medicine (TCM) combined with western medicine can significantly improve vascular endothelial function in patients with hypertension, but it has not been systematically evaluated for efficacy and safety of essential hypertension. Therefore, we aim to conduct a systematic review and meta-analysis to evaluate the efficacy and safety of TCM combined with western medicine in improving vascular endothelial function in patients with essential hypertension.

Methods:

We will search PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), Excerpta Medica Database (EMBASE), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, China Science Journal Database (VIP Database) and China Biomedical Literature Database (CBM). Clinical trial registrations, potential grey literature, related conference abstracts, and reference lists of identified studies will also be retrieved. The electronic database will be searched for literatures published from the beginning to October 2018. Based on the heterogeneity test, data integration is performed using a fixed effect model or a random effects model. Changes in blood pressure and endothelial function will be assessed as primary outcomes. Drug use, disease progression and adverse events will be assessed as secondary outcomes. RevMan V.5.3.5 will be used for meta-analysis.

Results:

This systematic review and meta-analysis will provide high-quality evidence from a variety of aspects, including efficacy, blood pressure, vascular endothelial function and adverse reactions, to assess the efficacy and safety of TCM combined with western medicine in patients with hypertension.

Conclusion:

This systematic review will determine whether TCM combined with western medicine provides evidence for effective intervention of vascular endothelial function in patients with essential hypertension.

Ethics and dissemination:

This systematic review and meta-analysis of randomized controlled trials does not require ethical recognition, and the results of this paper will be published in an open access, internationally influential academic journal.

PROSPERO registration number:

CRD42019140743
Retrospective analysis of cervical cancer and precancerous lesions in patients with atypical squamous cells of undetermined significance in China
Authors: Wang Yan-Ying , Kong Ling-Hua , Liu Yang , Wang Shu , Fan Qing-Bo , Zhu Lan , Lang Jing-He
Published: December 2019

Atypical squamous cells of undetermined significance (ASCUS) are the most common cytological abnormality of all smear test. No study has demonstrated the prevalence of cervical cancer or its precursor in Chinese patients with ASCUS. This study aims to investigate the prevalence of cervical intraepithelial neoplasia 1 or worse (CIN1+) and CIN3 or worse (CIN3+) in patients with ASCUS in China to provide insight into appropriate management for Chinese health care.

In a retrospective cross-sectional study, patients who underwent liquid-based thin layer cytology and human papillomavirus (HPV) co-testing at the Peking Union Medical College Hospital between January 2014 and January 2017, and had ASCUS results on liquid-based thin layer cytology test and underwent follow-up and colposcopic biopsy were included. Age, HPV DNA test, and pathological outcomes were assessed.

One hundred forty-four patients with ASCUS and positive HPV test results were included. In the 3-year follow-up, 23 (16.0%) patients had CIN1, 28 (19.4%) had CIN2, and 17 (11.8%) had CIN3 or carcinoma in situ. The risk of CIN3+ was significantly higher in those older than 60 years (42.8%, P = .005), whereas the CIN1+ prevalence displayed no significant difference between age groups. Both hybrid Capture II (HC II) value and cytopathological description of HPV infection showed no statistically significant correlation with CIN1+ or CIN3+.

Patients with HPV-positive ASCUS who were older than 60 years had a significantly higher risk of CIN3+, and clinicians should pay more attention to them. Both HC II value and cytopathological description of HPV infection showed no significant correlation with CIN1+ or CIN3+.
Successful treatment of metastatic adrenocortical carcinoma in the spine
Authors: Liu Shuzhong , Zhou Xi , Song An , Huo Zhen , Wang Yipeng , Liu Yong
Published: December 2019

Rationale:

Adrenocortical carcinoma is a rare aggressive type of cancer whose prognosis is poor, particularly for metastatic entities. Metastatic adrenocortical carcinoma in the spine is a rare disease with no standard curative managements yet. The objective of this study is to report a very rare case of spinal metastases of adrenocortical carcinoma successfully managed by combination of cement augmentation, radiotherapy together with adjuvant programmed cell death 1 (PD-1) therapy. The management of these unique cases has yet to be well-documented.

Patient concerns:

A 42-year-old woman presented with a 3-month history of continuous and progressive back pain. The patient, who had been diagnosed of right pheochromocytoma, received surgical treatment of right adrenalectomy 14 months ago in another hospital, followed by no further treatment.

Diagnosis:

Magnetic resonance imaging of spine showed vertebral pathological fracture of L1, spinal cord compression secondary to the epidural component of the L1 mass, with increased metastatic marrow infiltration of the right L1 vertebral body, which presented as a solid tumor. Postoperative pathology confirmed the diagnosis of spinal metastases of adrenocortical carcinoma.

Interventions:

The patient underwent cement augmentation via a posterior approach, radiotherapy, radiofrequency ablation of psoas major muscle occupying lesions, right chest wall, liver and kidney recess together with adjuvant PD-1 therapy.

Outcomes:

The patient's neurological deficits improved significantly after the surgery, and the postoperative period was uneventful at the 6-month and 1-year follow-up visit. There were no complications associated with the operation during the follow-up period.

Lessons:

Combined efforts of specialists from orthopedics, urology, interventional radiology, radiotherapy, pathology, endocrinology, and medical oncology led to the successful diagnosis and management of this patient. Metastatic adrenocortical carcinoma of the spine, although rare, should be part of the differential diagnosis when the patient has a history of adrenal carcinoma and presents with back pain, myelopathy, or radiculopathy. We recommend the posterior approach for total excision of the spinal metastatic adrenocortical carcinoma when the tumor has caused neurological deficits. Osteoplasty by cement augmentation, radiotherapy, and targeted PD-1 therapy may also be good choices for treatment.
A metastatic skull tumor from intrahepatic cholangiocarcinoma
Authors: Wang Dawei , He Shiwei , Chu Liang , Chao Qing , Zhang Qiujian , Shu Hansheng
Published: December 2019

Rationale:

Intrahepatic cholangiocarcinoma (ICC) originates from the epithelial cells of the secondary branches that are distant from the intrahepatic bile duct. ICC is a rare pathological type of primary liver cancer, with a high malignancy rate and poor prognosis. However, patients with ICC metastasis to the skull are extremely rarely encountered. Herein, we present a case of a metastatic skull tumor from ICC, along with a literature review.

Patient concerns:

A 50-year-old right-handed man who did not smoke was diagnosed with a poorly differentiated ICC (T2aN0M0) in segment VI of the liver in February 2017. Hepatectomy was performed. The patient then presented with a painful mass in the posterior occipital region with dizziness experienced since 1 month, for which he underwent posterior occipital craniotomy. Postoperative specimens were sent for pathological examination.

Diagnoses:

We diagnosed the patient with a metastatic skull tumor from ICC.

Interventions:

The patient underwent posterior occipital craniotomy and total resection of the tumor.

Outcomes:

The patient received chemotherapy 1 month after surgery, and after 6 months of follow-up, the patient was alive.

Lessons:

ICC often shows metastases to the vertebrae. Therefore, physicians should consider the possibility of metastasis in patients with ICC, especially in those who show a painful skull mass of unknown origin; moreover, among patients with vertebral metastasis, physicians should be very vigilant about an occipital mass. We believe that the craniospinal venous system may be the pathway for occipital metastasis in patients with ICC.
Complications of Cesarean Birth
Authors: Burke Carol , Allen Roma
Published: December 2019

The increase in severe maternal morbidity and mortality in the United States correlates with a significant rise in U.S. cesarean birth rates from 5.5% in 1970 to a rate of 31.9% of all births in 2018, far beyond the World Health Organization goal of 10% to 15%. Three key contributors to maternal morbidity and mortality related to cesarean birth include complications of hemorrhage, surgical site infection, and venous thromboembolism. All women should be screened for risk factors associated with these major complications during the antepartum, intrapartum, and postpartum period to assure the availability of immediate resources based on the assessment. Implementing evidence-based maternity care safety bundles, toolkits, and protocols to manage these complications can reduce adverse outcomes.
A Novel Method to Improve Perfusion of Ex Vivo Pumped Human Kidneys
Authors: Zhu Lin , Qureshi Arshna , Awad Mohamed , Hausladen Alfred , Perez-Protto Silvia , Latifi Samir Q. , Lebovitz Daniel J. , Chavin Kenneth , Stamler Jonathan S. , Reynolds James D.
Published: December 2019

Objective:

To determine if addition of the S-nitrosylating agent ethyl nitrite (ENO) to the preservation solution can improve perfusion parameters in pumped human kidneys.

Background:

A significant percentage of actively stored kidneys experience elevations in resistance and decreases in flow rate during the ex vivo storage period. Preclinical work indicates that renal status after brain death is negatively impacted by inflammation and reduced perfusion—processes regulated by protein S-nitrosylation. To translate these findings, we added ENO to the preservation solution in an attempt to reverse the perfusion deficits observed in nontransplanted pumped human kidneys.

Methods:

After obtaining positive proof-of-concept results with swine kidneys, we studied donated human kidneys undergoing hypothermic pulsatile perfusion deemed unsuitable for transplantation. Control kidneys continued to be pumped a 4°C (ie, standard of care). In the experimental group, the preservation solution was aerated with 50 ppm ENO in nitrogen. Flow rate and perfusion were recorded for 10 hours followed by biochemical analysis of the kidney tissue.

Results:

In controls, perfusion was constant during the monitoring period (ie, flow rate remained low and resistance stayed high). In contrast, the addition of ENO produced significant and sustained reductions in resistance and increases in flow rate. ENO-treated kidneys had higher levels of cyclic guanosine monophosphate, potentially explaining the perfusion benefits, and increased levels of interleukin-10, suggestive of an anti-inflammatory effect.

Conclusions:

S-Nitrosylation therapy restored the microcirculation and thus improved overall organ perfusion. Inclusion of ENO in the renal preservation solution holds promise to increase the number and quality of kidneys available for transplant.
Severe Hypocalcemia After Thyroidectomy
Authors: Kazaure Hadiza S. , Zambeli-Ljepovic Alan , Oyekunle Taofik , Roman Sanziana A. , Sosa Julie A. , Stang Michael T. , Scheri Randall P.
Published: December 2019

Objective:

The aim of the study was to determine severe hypocalcemia rate following thyroidectomy and factors associated with its occurrence.

Background:

Hypocalcemia is the most common complication after thyroidectomy. Severe post-thyroidectomy hypocalcemia can be life-threatening; data on this specific complication are scarce.

Methods:

Patients who underwent thyroidectomy in the American College of Surgeons-National Surgical Quality Improvement Program thyroidectomy-targeted database (2016–2017) were abstracted. A severe hypocalcemic event was defined as hypocalcemia requiring intravenous calcium, emergent clinic/hospital visit, or a readmission for hypocalcemia. Multivariable regression was used to identify factors independently associated with occurrence of severe hypocalcemia.

Results:

Severe hypocalcemia occurred in 5.8% (n = 428) of 7366 thyroidectomy patients, with 83.2% necessitating intravenous calcium treatment. Rate of severe hypocalcemia varied by diagnosis and procedure (0.5% for subtotal thyroidectomy to 12.5% for thyroidectomy involving neck dissections). Overall, 38.3% of severe hypocalcemic events occurred after discharge; in this subset, 59.1% experienced severe hypocalcemia despite being discharged with calcium and vitamin D. Severe hypocalcemia patients had higher rates of recurrent laryngeal nerve injury (13.4% vs 6.6%), unplanned reoperations (4.4% vs 1.3%), and longer hospital stay (30.4% vs 6.2% ≥3 days (all P < 0.01). After multivariate adjustment, severe hypocalcemia was associated with multiple factors including Graves disease [odds ratio (OR) = 2.06], lateral neck dissections (OR: 3.10), and unexpected reoperations (OR = 3.55); all P values less than 0.01.

Conclusions:

Severe hypocalcemia and suboptimal hypocalcemia management after thyroidectomy are common. Patients who experienced severe hypocalcemia had higher rates of nerve injury and unexpected reoperations, indicating surgical complexity and provider inexperience. More biochemical surveillance particularly a parathyroid hormone–based protocol, fine-tuned supplementation, and selective referral could reduce occurrence of this morbid complication.
Tradition Versus Value: Is There Utility in Protocolized Postoperative Laboratory Testing After Elective Colorectal Surgery?
Authors: McKenna Nicholas P. , Habermann Elizabeth B. , Glasgow Amy E. , Cima Robert R.
Published: December 2019

Objective:

Determine if routine ordering of postoperative day 1 (POD 1) serum laboratory tests after elective colorectal surgery are clinically warranted and valuable given the associated costs of these lab tests.

Summary of Background Data:

Routine postoperative serum laboratory tests are a part of many colorectal surgery order sets. Whether these protocolized lab tests represent cost-effective care is unknown.

Methods:

Patients undergoing elective colorectal surgery between January 1, 2015 and December 31, 2017 at our institution were identified. The protocolized POD 1 lab tests obtained as part of the postoperative order set were reviewed to determine the rate of abnormal values and any intervention in response. Costs associated with protocolized laboratory testing were calculated using dollar amounts representing 2017 outpatient Medicare reimbursement.

Results:

A total of 2252 patients were identified with 8205 total lab test values. Of these, only 4% were abnormal (3% of hemoglobin values, 6% of creatinine values, 3% of potassium of values, and 3% of glucose values), and only 1% were actively intervened upon. The total aggregate cost of the protocolized POD 1 laboratory tests in these years was $64,000 based on Medicare outpatient reimbursement dollars.

Conclusions:

Routine POD 1 lab tests after elective colorectal surgery are rarely abnormal, and they even less frequently require active intervention beyond rechecking. This results in increased resource utilization and cost of care without appreciable impact on clinical care, and is not cost-effective. Protocolized POD 1 laboratory testing should be replaced with clinically-based criteria to trigger serum laboratory investigations.
Hexamaps for Visualizing Age-Period-Cohort Data Trends
Authors: Jalal Hawre , Burke Donald S.
Published: November 2019

Age-period-cohort (APC) analyses often reveal important insights into patterns of disease incidence and mortality such as cancer. Both visual and analytical APC tools are available to reveal patterns by age, period and cohort. While developing new analytical methods of APC data is an active area of research, the choices of visual tools specific to APC data has been limited. In this study, we propose a “hexamap” as a new APC specific data visualization tool. This tool uses hexagons to address the unique challenge of APC data visualization, that is cohort= period - age. The approach is further illustrated using alcohol related mortality. Flexible Open-Source functions for implementation in R is also provided.
Compromised intestinal barrier underlies gut microbiota dysbiosis of intestinal diseases
Authors: Jiang Puzi , Lai Senying , Wu Sicheng , Yin Xiushan , Zhang Jingjing , Zhao Xing-Ming , Xu Shun-Qing , Chen Wei-Hua
Published: November 2019

Background

Despite recent efforts, a single factor underlying the gut microbiota dysbiosis in intestinal diseases is not identified. We hypothesized that compromised intestinal barrier (CIB) could lead to increased host-derived contents including human cells in the gut, change its physio-metabolic properties, and globally alter gut microbiota and their metabolic capacities.

Results

Consistently, we found human DNA contents (HDCs), calculated as the percentage of metagenomic sequencing reads mapped to the human genome, were significantly elevated in colorectal cancer (CRC) patients; HDC correlated with microbial- and metabolic-pathway-biomarkers of CRC, and was the most important contributor to patient stratification. We found similar results in Crohn’s disease (CD); additionally, patients treated with diet and drug intervention showed reduced HDC levels over time, and were accompanied by reversing changes of many CD-signature species.

Conclusions

Our results suggested that host-derived contents may have greater impact on gut microbiota than previously anticipated, and CIB could be an ideal treatment target that could reverse dysbiosis globally and precisely.
Population based targeted sequencing of 54 candidate genes identifies PALB2 as a susceptibility gene for high grade serous ovarian cancer
Authors: Song Honglin , Dicks Ed , Tyrer Jonathan P. , Intermaggio Maria , Chenevix-Trench Georgia , Bowtell David D , Traficante Nadia ,   AOCS Group, Brenton James D. , Goranova Teodora , Hosking Karen , Piskorz Anna , Van Oudenhove Elke , Doherty Jennifer Anne , Harris Holly R. , Rossing Mary Anne , Dürst Matthias , Dörk Thilo , Bogdanova Natalia V. , Modugno Francesmary , Moysich Kirsten B. , Odunsi Kunle , Ness Roberta B. , Karlan Beth Y. , Lester Jenny , Jensen Allan , Kjaer Susanne K. , Høgdall Estrid , Campbell Ian , Lazaro Conxi , Pujana Miquel Angel , Cunningham Julie M. , Vierkant Robert A. , Winham Stacey J. , Hildebrandt Michelle A.T. , Huff Chad , Li Donghui , Wu Xifeng , Yu Yao , Permuth Jennifer B. , Levine Douglas A. , Schildkraut Joellen M. , Riggan Marjorie J. , Berchuck Andrew , Webb Penelope M. ,   OPAL Study Group, Cybulski Cezary , Gronwald Jacek , Jakubowska Anna , Lubiński Jan , Alsop Jennifer , Harrington Patricia A. , Chan Isaac , Menon Usha , Pearce Celeste L. , Wu Anna H. , de Fazio Anna , Kennedy Catherine J. , Goode Ellen L. , Ramus Susan J. , Gayther Simon A. , Pharoah Paul D.P.
Published: November 2019

Purpose

The known EOC susceptibility genes account for less than 50% of the heritable risk of ovarian cancer suggesting other susceptibility genes exist. The aim of this study was to evaluate the contribution to ovarian cancer susceptibility of rare deleterious germline variants in a set of candidate genes.

Methods

We sequenced the coding region of 54 candidate genes in 6385 invasive EOC cases and 6115 controls of broad European ancestry. Genes with an increased frequency of putative deleterious variants in cases verses controls were further examined in an independent set of 14,146 EOC cases and 28,661 controls from the ovarian cancer association consortium and the UK Biobank. For each gene, we estimated the EOC risks and evaluated associations between germline variant status and clinical characteristics.

Results

The odds ratios (OR) associated for high-grade serous ovarian cancer were 3.01 for PALB2 (95% CI 1.59 – 5.68; P = 0.00068), 1.99 for POLK (95% CI 1.15 – 3.43; P = 0.014), and 4.07 for SLX4 (95% CI 1.34-12.4; P = 0.013). Deleterious mutations in FBXO10 were associated with a reduced risk of disease (OR 0.27, 95% CI 0.07 −1.00, P=0.049). However, based on the Bayes false discovery probability, only the association for PALB2 in high-grade serous ovarian cancer is likely to represent a true positive.

Conclusions

We have found strong evidence that carriers of PALB2 deleterious mutations are at increased risk of high-grade serous ovarian cancer. Whether the magnitude of risk is sufficiently high to warrant the inclusion of PALB2 in cancer gene panels for ovarian cancer risk testing is unclear; much larger sample sizes will be needed to provide sufficiently precise estimates for clinical counselling.
Obstetrical safety indicators for preventing hospital harms: a scoping review protocol
Authors: Conway Aislinn , Reszel Jessica , Walker Mark C , Grimshaw Jeremy M , Dunn Sandra I
Published: November 2019

Introduction: Optimizing the safety of obstetric patient care is a primary concern for many hospitals. Identifying performance indicators that measure aspects of patient care processes related to preventable harms can present opportunities to improve health systems.
In this paper, we present our protocol for a scoping review to identify performance indicators for obstetric safety. We aim to identify a comprehensive list of obstetric safety indicators which may help reduce the number of preventable patient harms, to summarize the data and to synthesize the results.

Methods and analysis: We will use the methodological framework described by Arksey and O Malley and further expanded by Levac. We will search multiple electronic databases such as Medline, Embase, CINAHL and the Cochrane Library as well as websites from professional bodies and other organisations, using an iterative search strategy. We will include indicators that relate to preventable harms in the process of obstetric care.
Two reviewers will independently screen titles and abstracts of search results to determine eligibility for inclusion. For records where eligibility is not clear, the reviewers will screen the full text version. If reviewers decisions regarding eligibility differ, a third reviewer will review the full text record. Two reviewers will independently extract data from records that meet our inclusion criteria using a standardized data collection form. We will narratively describe quantitative data, such as the frequency with which indicators are identified, and conduct a thematic analysis of the qualitative data. We will compile a comprehensive list of patient safety indicators identified during our scoping review and organise them according to concepts that best suit the data such as the Donabedian model or the Hospital Harm Framework. We will discuss the implications of the indicators for future research, clinical practice and policy making.
We will report the conduct of the review using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for scoping reviews (PRISMA ScR) Checklist.

Ethics and Dissemination: The sources of information included in this scoping review will be available to the public. Therefore, ethical review for this research is not warranted. We will disseminate our research results using multiple modes of delivery such as a peer-reviewed publication, conference presentations and stakeholder communications.

Keywords: Obstetrics, patient safety, performance indicators, prevention, hospital harms, scoping review, protocol.
Asthma Exacerbation Prediction and Interpretation based on Time-sensitive Attentive Neural Network: A Retrospective Cohort Study
Authors: Xiang Yang , Ji Hangyu , Zhou Yujia , Li Fang , Du Jingcheng , Rasmy Laila , Wu Stephen , Zheng Wenjin.Jim , Xu Hua , Zhi Degui , Zhang Yaoyun , Tao Cui
Published: November 2019

Background

Asthma exacerbation is an acute or sub-acute episode of progressive worsening of asthma symptoms and can have significant impacts on patients’ daily life. In 2016, 12.4 million current asthmatics (46.9%) in the U.S. had at least one asthma exacerbation in the previous year.

Objective

The objectives of this study were to predict the risk of asthma exacerbations and to explore potential risk factors involved in progressive asthma.

Methods

We proposed a time-sensitive attentive neural network to predict asthma exacerbation using clinical variables from electronic health records (EHRs). The clinical variables were collected from the Cerner Health Facts® database between 1992 and 2015 including 31,433 asthmatic adult patients. Interpretations on both the patient level and the cohort level were investigated based on the model parameters.

Results

The proposed model obtains an AUC value of 0.7003 through 5-fold cross-validation, which outperforms the baseline methods. The results also demonstrate that the addition of elapsed time embeddings considerably improves the performance on this dataset. Through further analysis, it was witnessed that risk factors behaved distinctly along the timeline and across patients. We also found supporting evidence from peer-reviewed literature for some possible cohort-level risk factors such as respiratory syndromes and esophageal reflux.

Conclusions

The proposed time-sensitive attentive neural network is superior to traditional machine learning methods and performs better than state-of-the-art deep learning methods in realizing effective predictive models for the prediction of asthma exacerbation. We believe that the interpretation and visualization of risk factors can help the clinical community to better understand the underlying mechanisms of the disease progression.
Does the metabolic syndrome exist? The identification of cardio-metabolic profiles in a South Asian population study
Authors: Harber-Aschan Lisa , Bakolis Ioannis , Glozier Nicholas , Ismail Khalida , Jayaweera Kaushalya , Pannala Gayani , Pariante Carmine , Rijsdijk Fruhling , Siribaddana Sisira , Sumathipala Athula , Zavos Helena M.S. , Zunszain Patricia , Hotopf Matthew
Published: November 2019

OBJECTIVE

Research testing the validity of the metabolic syndrome (MetS) as a clinical construct associated with cardiovascular disease risk has produced inconsistent results. This study tested the existence of the MetS, explored alternative cardiometabolic risk characterisations, and examined the relative influence of genetic and environmental factors in a South Asian sample.

RESEARCH DESIGN AND METHODS

Data came from the Colombo Twin and Singleton follow-up Study, CoTaSS-2 (N=3969). Latent class analysis tested the clustering of MetS indicators (waist circumference, high-density-lipoprotein cholesterol (HDL-C), triglycerides (TG), blood pressure, fasting plasma glucose (FPG), medications and diabetes). Regression analyses tested cross-sectional associations between identified latent classes and covariates. Structural equation modelling estimated genetic and environmental influences on these classes. Analyses were stratified by gender (n=1681 men, n=2288 women).

RESULTS

Three classes were identified in men: 1) “Healthy” (52.3%), 2) “Central obesity, high TG, high FPG” (40.2%), and 3) “Central obesity, high TG, diabetes” (7.6%). Four classes were identified in women: 1) “Healthy” (53.2%), 2) “Very high central obesity, low HDL-C, raised FPG” (32.8%), 3) “Very high central obesity, diabetes” (7.2%) and 4) “Central obesity, hypertension, raised FPG” (6.8%). Older age in men and women, and high socioeconomic status in men, was associated with cardiometabolic risk categories, compared to the “Healthy” classes. In men, individual differences in cardiometabolic class membership were due to environmental effects. In females, genetic differences significantly predicted class membership.

CONCLUSIONS

The findings did not support the MetS construct. Instead, distinct clinical profiles were identified in men and women, suggesting different aetiological pathways.
CAPICE: a computational method for Consequence-Agnostic Pathogenicity Interpretation of Clinical Exome variations
Authors: Li Shuang , van der Velde K. Joeri , de Ridder Dick , van Dijk Aalt D.J. , Soudis Dimitrios , Zwerwer Leslie R. , Deelen Patrick , Hendriksen Dennis , Charbon Bart , van Gijn Marielle , Abbott Kristin M. , Sikkema-Raddatz B. , van Diemen Cleo C. , Kerstjens-Frederikse Wilhelmina S. , Sinke Richard J. , Swertz Morris A.
Published: November 2019

Exome sequencing is now mainstream in clinical practice, however, identification of pathogenic Mendelian variants remains time consuming, partly because limited accuracy of current computational prediction methods leaves much manual classification. Here we introduce CAPICE, a new machine-learning based method for prioritizing pathogenic variants, including SNVs and short InDels, that outperforms best general (CADD, GAVIN) and consequence-type-specific (REVEL, ClinPred) computational prediction methods, for both rare and ultra-rare variants. CAPICE is easily integrated into diagnostic pipelines and is available as free and open source command-line software, file of pre-computed scores, and as a web application with web service API.
The Project for Objective Measures Using Computational Psychiatry Technology (PROMPT): Rationale, Design, and Methodology
Authors: Kishimoto Taishiro , Takamiya Akihiro , Liang Kuo-ching , Funaki Kei , Fujita Takanori , Kitazawa Momoko , Yoshimura Michitaka , Tazawa Yuki , Horigome Toshiro , Eguchi Yoko , Kikuchi Toshiaki , Tomita Masayuki , Bun Shogyoku , Murakami Junichi , Sumali Brian , Warnita Tifani , Kishi Aiko , Yotsui Mizuki , Toyoshiba Hiroyoshi , Mitsukura Yasue , Shinoda Koichi , Sakakibara Yasubumi , Mimura Masaru
Published: November 2019

Background

Depressive and neurocognitive disorders are debilitating conditions that account for the leading causes of years lived with disability worldwide. Overcoming these disorders is an extremely important public health problem today. However, there are no biomarkers that are objective or easy-to-obtain in daily clinical practice, which leads to difficulties in assessing treatment response and developing new drugs. Due to advances in technology, it has become possible to quantify important features that clinicians perceive as reflective of disorder severity. Such features include facial expressions, phonic/speech information, body motion, daily activity, and sleep. The overall goal of this proposed study, the Project for Objective Measures Using Computational Psychiatry Technology (PROMPT), is to develop objective, noninvasive, and easy-to-use biomarkers for assessing the severity of depressive and neurocognitive disorders.

Methods

This is a multi-center prospective study. DSM-5 criteria for major depressive disorder, bipolar disorder, and major and minor neurocognitive disorders are inclusion criteria for the depressive and neurocognitive disorder samples. Healthy samples are confirmed to have no history of psychiatric disorders by Mini-International Neuropsychiatric Interview, and have no current cognitive decline based on the Mini Mental State Examination. Participants go through approximately 10-minute interviews with a psychiatrist/psychologist, where participants talk about non-specific topics such as everyday living, symptoms of disease, hobbies, etc. Interviews are recorded using RGB and infrared cameras, and an array microphone. As an option, participants are asked to wear wrist-band type devices during the observational period. The interviews take place ≤10 times within up to five years of follow-up. Various software is used to process the raw video, voice, infrared, and wearable device data. A machine learning approach is used to predict the presence of symptoms, severity, and the improvement/deterioration of symptoms.

Discussion

The PROMPT goal is to develop objective digital biomarkers for assessing the severity of depressive and neurocognitive disorders in the hopes of guiding decision-making in clinical settings as well as reducing the risk of clinical trial failure. Challenges may include the large variability of samples, which makes it difficult to extract the features that commonly reflect disorder severity.

Trial Registration

UMIN000021396, University Hospital Medical Information Network (UMIN)
Polygenic background modifies penetrance of monogenic variants conferring risk for coronary artery disease, breast cancer, or colorectal cancer
Authors: Fahed Akl C. , Wang Minxian , Homburger Julian R. , Patel Aniruddh P. , Bick Alexander G. , Neben Cynthia L. , Lai Carmen , Brockman Deanna , Philippakis Anthony , Ellinor Patrick T. , Cassa Christopher A. , Lebo Matthew , Ng Kenney , Lander Eric S. , Zhou Alicia Y. , Kathiresan Sekar , Khera Amit V.
Published: November 2019

Background

Genetic variation can predispose to disease both through (i) monogenic risk variants in specific genes that disrupt a specific physiologic pathway and have a large effect on disease risk and (ii) polygenic risk that involves large numbers of variants of small effect that affect many different pathways. Few studies have explored the interaction between monogenic risk variants and polygenic risk.

Methods

We identified monogenic risk variants and calculated polygenic scores for three diseases, coronary artery disease, breast cancer, and colorectal cancer, in three study populations — case-control cohorts for coronary artery disease (UK Biobank; N=12,879) and breast cancer (Color Genomics; N=19,264), and an independent cohort of 49,738 additional UK Biobank participants.

Results

In the coronary artery disease case-control cohort, increased risk for carriers of a monogenic variant ranged from 1.3-fold for those in the lowest polygenic score quintile to 12.6-fold for those in the highest. For breast cancer, increased risk ranged from 2.4 to 6.9-fold across polygenic score quintiles. Among the 49,738 UK Biobank participants who carried a monogenic risk variant, the probability of disease at age 75 years was strongly modified by polygenic risk. Across individuals in the lowest to highest percentiles of polygenic risk, the probability of disease ranged from 17% to 78% for coronary artery disease; 13% to 76% for breast cancer; and 11% to 80% for colon cancer.

Conclusions

For three important genomic conditions, polygenic risk powerfully modifies the risk conferred by monogenic risk variants.
Metagenomic analysis of common intestinal diseases reveals relationships among microbial signatures and powers multi-disease diagnostic models
Authors: Jiang Puzi , Wu Sicheng , Luo Qibin , Zhao Xing-ming , Chen Wei-Hua
Published: November 2019

Common intestinal diseases such as Crohn’s disease (CD), ulcerative colitis (UC) and colorectal cancer (CRC), share clinical symptoms and altered gut microbes, necessitating cross-disease comparisons and the use of multi-disease models. Here, we performed meta-analyses on thirteen fecal metagenome datasets of the three diseases. We identified 87 species and 65 pathway markers that were consistently changed in multiple datasets of the same diseases. According to their overall trends, we grouped the disease-enriched marker species into disease-specific and -common clusters, and revealed their distinct phylogenetic relationships: species in CD-specific cluster are phylogenetically related, while those in CRC-specific cluster are more distant; strikingly, UC-specific species are phylogenetically closer to CRC, likely because UC-patients have higher risk of CRC. Consistent to their phylogenetic relationships, marker species had similar within-cluster and different between-cluster metabolic preferences. There were part of marker species and pathways correlated with an indicator of leaky gut, suggesting a link between gut dysbiosis and human derived contents. Marker species showed more coordinated changes and tighter inner-connections in cases than the controls, suggesting that the diseased gut may represent a stressed environment and pose stronger selection to gut microbes. With the marker species and pathways, we constructed four high-performance (including multi-disease) models with AUROC of 0.87 and true positive rates up to 90%, and explained their putative clinical applications. We identified consistent microbial alterations in common intestinal diseases, revealed metabolic capacities and the relationships among marker bacteria in distinct states, and supported the feasibility of metagenome-derived multi-disease diagnosis.

Importance

Gut microbes have been identified as potential markers in distinguishing patients from controls in colorectal cancer, ulcerative colitis and Crohn’s disease individually, whereas there lacks a systematic analysis to investigate the exclusive microbial shifts of these enteropathies with similar clinical symptoms. Our meta-analysis and cross-disease comparisons identified consistent microbial alterations in each enteropathy, revealed microbial ecosystems among marker bacteria in distinct states, and demonstrated the necessity and feasibility of metagenome-based multi-disease classifications. To the best of our knowledge, this is the first study that constructed multi-class models in these common intestinal diseases.
Quality of life in cancer patients treated with mistletoe: a systematic review and meta-analysis
Authors: Loef Martin , Walach Harald
Published: November 2019

Background

Mistletoe extracts are used as an adjunct therapy for cancer patients, but there is dissent as to whether this therapy has a positive impact on quality of life (QoL).

Methods

We conducted a systematic review searching in several databases (Medline, Embase, CENTRAL, CINAHL, PsycInfo, Science Citation Index, clinicaltrials.gov, opengrey.org) by combining terms that cover the fields of “neoplasm”, “quality of life” and “mistletoe”. We included prospective controlled trials that compared mistletoe extracts with a control in cancer patients and reported QoL or related dimensions. The quality of the studies was assessed with the Cochrane Risk of Bias tool version 2.We conducted a quantitative meta-analysis.

Results

We included 26 publications with 30 data sets. The studies were heterogeneous. The pooled standardized mean difference (random effects model) for global QoL after treatment with mistletoe extracts vs. control was d = 0.61 (95% CI 0.41-0.81; p<0,00001). The effect was stronger for younger patients, with longer treatment, in studies with lower risk of bias, in randomized and blinded studies. Sensitivity analyses support the validity of the finding. 50% of the QoL subdomains (e.g. pain, nausea) show a significant improvement after mistletoe treatment. Most studies have a high risk of bias or at least raise some concern.

Conclusion

Mistletoe extracts produce a significant, medium-sized effect on QoL in cancer. Risk of bias in the analyzed studies is likely due to the specific type of treatment, which is difficult to blind; yet this risk is unlikely to affect the outcome.

PROSPERO registration number

CRD42019137704
Multimodal neuroimaging and suicidality in a US population-based sample of school-aged children
Authors: Vidal-Ribas Pablo , Janiri Delfina , Doucet Gaelle E. , Pornpattananangkul Narun , Nielson Dylan M. , Frangou Sophia , Stringaris Argyris
Published: November 2019

Importance

Suicide deaths and suicidality are considered a public health emergency, yet their brain underpinnings remain elusive.

Objective

To examine individual, environmental, and clinical characteristics, as well as multimodal brain imaging correlates of suicidality in a US population-based sample of school-aged children.

Design

Cross-sectional analysis of the first wave of data from the Adolescent Brain Cognitive Development study

Setting

Multicenter population-based study

Participants

Children aged 9-10 years from unreferred, community samples with suicidality data available (n=7,994). Following quality control, we examined structural magnetic resonance imaging (sMRI) (n=6,238), resting state functional MRI (rs-fMRI) (n=4,134), and task-based fMRI (range n=4,075 to 4,608).

Exposure

Lifetime suicidality, defined as suicidal ideation, plans and attempts reported by children or/and caregivers.

Main Outcomes and Measures

Multimodal neuroimaging analyses examined differences with Welch’s t-test and Equivalence Tests, with observed effect sizes (ES, Cohen’s d) and their 90% confidence interval (CI) < |0.15|. Predictive values were examined using the area under precision-recall curves (AUPRC). Measures included, cortical volume and thickness, large-scale network connectivity and task-based MRI of reward processing, inhibitory control and working memory.

Results

Among the 7,994 unrelated children (3,757 females [47.0%]), those will lifetime suicidality based on children (n=684 [8.6%]; 276 females [40.4%]), caregiver (n=654 [8.2%]; 233 females [35.6%]) or concordant reports (n=198 [2.5%]; 67 females [33.8%]), presented higher levels of social adversity and psychopathology on themselves and their caregivers compared to never-suicidal children (n=6,854 [85.7%]; 3,315 females [48.3%]). A wide range of brain areas was associated with suicidality, but only one test (0.06%) survived statistical correction: children with caregiver-reported suicidality had a thinner left bank of the superior temporal sulcus compared to never-suicidal children (ES=-0.17, 95%CI -0.26, -0.08, pFDR=0.019). Based on the prespecified bounds of |0.15|, ∼48% of the group mean differences for child-reported suicidality comparisons and a ∼22% for parent-reported suicidality comparisons were considered equivalent. All observed ES were relatively small (d≤|0.20|) and with low predictive value (AUPRC≤0.10).

Conclusion and Relevance

Using commonly-applied neuroimaging measures, we were unable to find a discrete brain signature related to suicidality in youth. There is a great need for improved approaches to the neurobiology of suicide.
Current practice and challenges in screening for visual perception deficits after stroke: a qualitative study
Authors: Vancleef Kathleen , Colwell Michael J , Hewitt Olivia , Demeyere Nele
Published: November 2019

AIM

We aimed to document current clinical practice and needs in screening for visual perception problems after stroke to inform development of new screening tools.

METHODS

We interviewed 25 health care professionals (12 occupational therapists, 13 orthoptists) from 16 organisations in England. Interviews were transcribed and coded in NVivo Software. Data were thematically analysed using the Value Proposition Canvas, a model which establishes what people want to achieve, the challenges they face and what facilitates their jobs.

RESULTS

Participants’ understanding of visual perception varied and often included sensory and cognitive deficits. Occupational therapists commonly screened for visual field deficits and hemispatial neglect, while other aspects of visual cognition were rarely assessed. They decided on referrals to orthoptists for further assessment. Screening generally occurred during functional assessments and/or with in-house developed tools. Challenges to practice were: lack of time, lack of training, environmental and stroke survivor factors (e.g. aphasia), insufficient continuation of care, and test characteristics (e.g. not evidence-based). Facilitators to practice were: quick and practical tools, experienced staff or tools with minimal training requirements, a streamlined care pathway between a stroke unit and eye hospital supported by occupational therapists and orthoptists.

CONCLUSION

Screening employs non-standardised assessments and rarely covers visual perceptual deficits in higher order perception. Our service evaluation demonstrates the need for a standardised visual perception screen, which should ideally be 15 minutes or less, be portable, and require minimal equipment. The screen should be suitable for bedside testing in noisy environments, inclusive for participants with aphasia and evidence-based.