bluuebunny/crossref_metadata_2025 huggingface dataset:
Validation of the English version of the difficulty of life scale for patients with ulcerative colitis
Authors: Kawakami Aki , Choong Lee Meng , Tanaka Makoto , Kunisaki Reiko , Maeda Shin , Bjarnason Ingvar , Hayee Bu’Hussain
Published: November 2019

Objective

Patients with ulcerative colitis have abdominal symptoms that affect their quality of life in multiple ways. The difficulty of life scale was developed in Japan to measure these patients’ degree of daily difficulties. We aimed to assess this scale for English-speaking patients and to evaluate its validity and reliability.

Methods

The original Japanese version of the difficulty of life scale was translated into English and administered to 100 consecutive outpatients with ulcerative colitis at a university hospital in London. Medical information was obtained from participants’ medical records. Factor validity, construct validity using the Short Inflammatory Bowel Disease Questionnaire, known group validity with clinically different groups, internal consistency and test-retest reliability were analyzed statistically.

Results

Three factors were extracted by exploratory factor analysis, as in the original scale. The construct validity was supported by the association between the Difficulty of Life Scale and Short Inflammatory Bowel Disease Questionnaire scores (Pearson’s correlation coefficient: 0.73–0.83). Patients with visible bleeding or who were prescribed corticosteroids reported significantly greater difficulty than did those without them, demonstrating a significant effect size. The scaling success rate was acceptable. Internal consistency was confirmed (Cronbach’s alpha: 0.68–0.89). The intraclass correlation coefficients were >0.75, thus confirming the test–retest reliability.

Conclusion

The English version of the difficulty of life scale is a reliable and valid disease-specific scale for ulcerative colitis. It can be used to communicate the challenge of daily living between patients with this long-term condition and health care providers.
Elevated mean platelet volume to platelet ratio predicts advanced fibrosis in chronic hepatitis C
Authors: Gozdas Hasan Tahsin , Ince Nevin
Published: November 2019

Objective

Chronic hepatitis C virus (HCV) infection is an important health problem that can cause liver cirrhosis and hepatocellular carcinoma. Recently, novel inflammatory markers from complete blood count have been used as a precursor of many clinical conditions. In this study, we investigated the role of hemogram parameters in predicting advanced liver fibrosis in chronic HCV patients.

Methods

Patients who underwent percutaneous liver biopsy due to chronic HCV infection between 01.01.2011 and 01.08.2019 were included in this study. Liver biopsies were evaluated according to Ishak method. Patients were classified into those with mild fibrosis (F ≤ 2) and advanced fibrosis (F ≥ 3). Hemogram parameters of these groups were compared and their efficacy in predicting severe fibrosis was investigated.

Results

Of the 81 chronic HCV patients, 38 cases were in the mild fibrosis group and 43 cases were in the severe fibrosis group. Mean platelet volume, mean platelet volume to lymphocyte ratio, mean platelet volume to platelet ratio, and red cell distribution width to platelet ratio of the severe fibrosis group were significantly higher than those of the mild fibrosis group (P < 0.05 for all). In the ROC curve analysis, mean platelet volume to platelet ratio showed the biggest area under the curve in the prediction of advanced fibrosis.

Conclusion

Mean platelet volume to platelet ratio may be an easy and practical biomarker to gain a preliminary insight into advanced fibrosis in chronic HCV patients.
Comparing thoracoabdominal injuries of manual versus load-distributing band cardiopulmonary resuscitation
Authors: Sonnemans Lianne J.P. , Bayat Alireza R. , Bruinen Aniek R.C. , van Wely Marleen H. , Brouwer Marc A. , Bosboom Dennis , van der Hoeven Johannes G. , Prokop Mathias , Klein Willemijn M.
Published: November 2019

Objective

To identify and compare manual and load-distributing band (LDB) cardiopulmonary resuscitation (CPR)-related injuries.

Methods

Retrospective observational cohort study. Adult, nontraumatic deaths with a postmortem computed tomography scan (PMCT) performed were classified into two groups: deceased after LDB CPR or after manual CPR. PMCT scans were reviewed for thoracoabdominal injuries such as fractures, pneumothorax and hemorrhage. The injuries between groups were compared.

Results

LDB CPR (n = 43) showed increased incidences of posterior rib fractures (53 vs 18%, P = 0.006), pneumothorax (23 vs 4%, P = 0.04) and more pericardial fluid (median 12  vs 6 mm, P = 0.002) compared with manual CPR (n = 29). Multivariable regression analysis revealed that LDB CPR was significantly associated with posterior rib fractures [odds ratio (OR) 5.37, 95% confidence interval (CI): 1.44–20.09, P = 0.01). Pneumothorax (OR 6.80, 95% CI: 0.73–62.99, P = 0.09) and the amount of pericardial fluid (OR 3.40, 95% CI: 0.20–56.32) were not significantly associated with LDB CPR. No significant difference was found for anterolateral rib fractures, sternal fractures, vertebral fractures, pleural fluid, hemothorax, hemopericardium, pneumoperitoneum, perihepatic, perisplenic and perirenal hemorrhage.

Conclusion

Rib fractures, sternal fractures, hemothorax and hemopericardium are common CPR-related injuries. LDB CPR is significantly associated with more posterior rib fractures and a trend toward more pneumothoraces is observed when compared with manual CPR. This knowledge is important for caretakers in the case of ongoing CPR, as a pneumothorax may attribute to not achieving persistent return of spontaneous circulation, and to improve postresuscitation care of survivors.
Monogenic, polygenic, and oligogenic familial hypercholesterolemia
Authors: Tada Hayato , Nohara Atsushi , Kawashiri Masa-aki
Published: November 2019

Purpose of review

Familial hypercholesterolemia has long been considered a monogenic disorder. However, recent advances in genetic analyses have revealed various forms of this disorder, including polygenic and oligogenic familial hypercholesterolemia. We review the current understanding of the genetic background of this disease.

Recent findings

Mutations in multiple alleles responsible for low-density lipoprotein regulation could contribute to the development of familial hypercholesterolemia, especially among patients with mutation-negative familial hypercholesterolemia. In oligogenic familial hypercholesterolemia, multiple rare genetic variations contributed to more severe familial hypercholesterolemia.

Familial hypercholesterolemia is a relatively common ‘genetic’ disorder associated with an extremely high risk of developing coronary artery disease. In addition to monogenic familial hypercholesterolemia, different types of familial hypercholesterolemia, including polygenic and oligogenic familial hypercholesterolemia, exist and have varying degrees of severity. Clinical and genetic assessments for familial hypercholesterolemia and clinical risk stratifications should be performed for accurate diagnosis, as should cascade screening and risk stratification for the offspring of affected patients.
The Relationship Between Prematurity, Method of Delivery, and Functional Gastrointestinal Disorders in Children
Authors: Velasco‐Benitez Carlos A. , Axelrod Cara H. , Gutierrez Susan , Saps Miguel
Published: November 2019

Objective:

The pathogenesis of functional gastrointestinal disorders (FGIDs) remains unknown. Early life events including method of delivery and length of gestation may be risk factors for FGIDs. Data from studies on early life events and the development of FGIDs are scarce and contradictory.

Objective:

The aim of the study was to assess the association between mode of delivery, length of gestation, and FGIDs in children. We hypothesized that delivery via Cesarean section and prematurity would be associated with an increased prevalence of FGIDs.

Methods:

Questionnaires were mailed to families from 3 cities in Colombia. Parents provided information on mode of delivery, demographics, and medical history. School children completed the Spanish version of the Questionnaire of Pediatric Gastrointestinal Symptoms Rome IV. Categorical data were analyzed using Fisher exact tests. Calculation of odds ratio with 95% confidence interval was performed.

Results:

A total of 1497 children (535 preadolescents 10–12 years, 962 adolescents 13–18 years) participated. For participants born via Cesarean delivery, there was no significant increase in prevalence of any of the Rome IV FGIDs compared with vaginal delivery. There was a significant association between prematurity and FGIDs for those born between 28 and 32 weeks (confidence interval 0.99–3.37; P = 0.03). In this group, functional nausea was the only category of FGID to reach significance (0.16–112.23) (P = 0.02). However, statistical significance was lost when gestational ages were grouped together with multivariate analysis.

Conclusions:

Our findings provide evidence that Cesarean delivery and prematurity are not risk factors for the development of FGIDs. Future studies are indicated to further evaluate the relationship between early life events and FGIDs.
Liver Failure Among Young Saudi Infants
Authors: Lone Khurram Sadiq , AlSaleem Badr , Asery Ali , Bashir Muhammed Salman , Al‐Hussaini Abdulrahman
Published: November 2019

Objectives:

The published data on early infantile liver failure (EILF) are scarce and limited to Caucasians. We conducted this study to describe the etiology and outcome of EILF among Arabs and identify prognostic factors.

Methods:

We retrospectively reviewed our database of 524 infants presenting with liver impairment from 2008 to 2018, and identified cases of EILF defined as presence of biochemical pattern of liver disease and INR ≥2 (unresponsive to vitamin K) with onset before 3 months of life. Primary outcomes included death or liver transplantation (LT) (poor outcome group) and survival with native liver (good outcome group).

Results:

Forty‐two cases of EILF (22 girls) were identified (8%). The etiology was indeterminate in 14 (33.3%) and established in 27 (64.3%): galactosemia (7 cases, 16.6%), tyrosinemia (5, 12%), neonatal hemochromatosis (NH), and hemophagocytic lymphohistiocytosis (HLH) (4 each, 9.5%]) mitochondrial hepatopathy (3, 7%), and miscellaneous (5, 12%). LF resolved in 15 cases (35.7%), either spontaneously or in response to specific therapy, 23 (54.7%) died, and 4 underwent LT (9.5%). ROC analysis for the best cut‐off value of serum total bilirubin for prediction of study outcomes was 120 μmol/L (sensitivity 81.5%, specificity 80%). Among the diagnostic groups, galactosemia and tyrosinemia predicted good outcome, whereas the idiopathic diagnosis predicted poor outcome (OR = 13).

Conclusions:

Similar to Western countries, galactosemia, tyrosinemia, NH, HLH, and mitochondrial hepatopathy are the main players in EILF in Saudi Arabia. Galactosemia and tyrosinemia predict good prognosis and idiopathic diagnosis predicts poor prognosis.
Clinical Implications of Fetal Heart Rate Interpretation Based on Underlying Physiology
Authors: O'Brien-Abel Nancy
Published: November 2019

Understanding the physiology of fetal oxygenation and various influences on fetal heart rate control supports nurses, midwives, and physicians in interpreting and managing electronic fetal heart rate tracings during labor and birth. Maternal oxygenation, placental circulation and exchange, umbilical blood flow and fetal circulation affect fetal oxygenation, which is reflected in observed fetal heart rate patterns. Fetal heart control is further influenced by the central and autonomic nervous systems, baroreceptors, chemoreceptors, humoral factors, sleep–wake patterns, breathing movements, medications, painful stimuli, sound and vibrations, and temperature. Knowledge of the physiologic basis for fetal heart rate pattern characteristics guides interventions to improve fetal oxygenation when indicated. A review and update on clinical implications of fetal heart rate pattern interpretation based on underlying physiology is presented.
Associations of B7-H3 and B7-H4 Expression in Ductal Carcinoma In Situ of the Breast With Clinicopathologic Features and T-Cell Infiltration
Authors: Kim Nah Ihm , Park Min Ho , Lee Ji Shin
Published: November 2019

B7-H3 and B7-H4 play an inhibitory role in T-cell function by limiting proliferation and cytokine production. Information about B7-H3 and B7-H4 expression in ductal carcinoma in situ (DCIS) remains uncertain. The objective of this study was to evaluate the expression levels of B7-H3 and B7-H4 in DCIS and their associations with clinicopathologic features and T-cell infiltration. B7-H3 and B7-H4 mRNA and protein expression levels in 8 pairs of DCIS tissues and matched normal adjacent tissues were examined by RNAscope in situ hybridization and immunohistochemistry analysis. Immunohistochemical staining of B7-H3, B7-H4, CD3, and CD8 was performed for 79 DCIS samples using tissue microarray. RNAscope in situ hybridization and immunohistochemistry analysis revealed that expression levels of B7-H3 and B7-H4 in DCIS tissues were higher than those in corresponding normal tissues. B7-H3 and B7-H4 mRNA and protein appeared to be mainly expressed in DCIS carcinoma cells. High B7-H3 and B7-H4 expression was observed in 58 (73.4%) and 62 (78.5%) cases with DCIS, respectively. High B7-H3 expression was significantly associated with high-nuclear grade and presence of comedo-type necrosis (both P<0.05). B7-H3 expression in HR−/HER2+ subtype was higher than that in HR+/HER2− subtype (P<0.05). B7-H3 and B7-H4 expression levels were negatively related to the density of CD3+ and CD8+ T-cell infiltrates. B7-H3 and B7-H4 may play an important role in immune surveillance mechanisms of DCIS. They might be useful targets to develop immune-based therapy to alter or prevent DCIS progression.
Genomic Molecular Classification of CNS Malignancies
Authors: Spino Marissa , Snuderl Matija
Published: November 2019

Molecular studies have identified distinct genomic drivers providing insights in biology of brain tumors. Advances in genetic and epigenetic analysis, as well as development of mutation-specific antibodies enable more accurate classification of histologically indistinguishable tumors. Compared with histopathologic grading, molecular biomarkers are also superior in predicting natural behavior of tumors and therapeutic response. Diffuse gliomas can be separated in astrocytoma and oligodendroglioma based on IDH1/2, ATRX, and TP53 mutational status. Pediatric gliomas are molecularly distinct from adult tumors and molecular drivers include histone H3 genes and fusions involving the MAPK pathway. Using genetic and epigenetic profiling, ependymal tumors, medulloblastomas, and atypical teratoid/rhabdoid tumors can be separated in biologically and clinically distinct entities. Identification of novel gene fusions and matched DNA methylation signatures enable accurate diagnosis of primitive neuroectodermal tumors, which were previously misdiagnosed. Genomic classification of central nervous system tumors is being readily translated into the clinical practice and will enable molecularly based patient management and clinical trials.
Effects of Different Exercise Intensities on Headache
Authors: Machado-Oliveira Luciano , da Silva Gauto Yumie Okuyama , de Santana Neto Fernando José , da Silva Magno Gomes , Germano-Soares Antonio Henrique , Diniz Paula Rejane Beserra
Published: November 2019

The benefits of the regular exercise on quality of life of individuals living with a headache are well known. However, whether the benefits of the exercise training on headache parameters (i.e., intensity, frequency, and pain duration) occur in an intensity-dependent fashion remains unknown.

Objective

The aim of the study was to investigate the effects of different exercise intensities on headache parameters.

Design

A systematic review of clinical trials that analyzed the effect of physical exercise on headache, without time or language restriction. The TESTEX scale was used to evaluate the methodological quality of the articles.

Results

Sixteen (16) articles were included with interventions with aerobic training and resistance training. Primary results are positive effects of exercise on migraine symptoms, tension-type headache among others, and a decrease in the use of headache-related medications. On the other hand, the studies did not provide information on exercise intensity, especially studies with aerobic exercises. The intensities used for aerobic training was mostly controlled subjectively and the resistance training ranged from 10% to 80% of maximum repetition.

Conclusions

Exercise had a positive influence on the frequency and severity of headache crises, although the studies presented inconclusive data regarding the exercise parameters.
Deep Learning Analysis of Cerebral Blood Flow to Identify Cognitive Impairment and Frailty in Persons Living With HIV
Authors: Luckett Patrick , Paul Robert H. , Navid Jaimie , Cooley Sarah A. , Wisch Julie K. , Boerwinkle Anna H. , Tomov Dimitre , Ances Beau M.
Published: November 2019

Background:

Deep learning algorithms of cerebral blood flow were used to classify cognitive impairment and frailty in people living with HIV (PLWH). Feature extraction techniques identified brain regions that were the strongest predictors.

Setting:

Virologically suppressed (<50 copies/mL) PLWH (n = 125) on combination antiretroviral therapy were enrolled. Participants averaged 51.4 (11.4) years of age and 13.7 (2.8) years of education. Participants were administered a neuropsychological battery, assessed for frailty, and completed structural neuroimaging.

Methods:

Deep neural network (DNN) models were trained to classify PLWH as cognitively unimpaired or impaired based on neuropsychological tests (Hopkins Verbal Learning Test-Revised and Brief Visuospatial Memory Test-Revised, Trail making, Letter-Number Sequencing, Verbal Fluency, and Color Word Interference), as well as frail, prefrail, or nonfrail based on the Fried phenotype criteria (at least 3 of the following 5: weight loss, physical inactivity, exhaustion, grip strength, walking time).

Results:

DNNs classified individuals with cognitive impairment in the learning, memory, and executive domains with 82%–86% accuracy (0.81–0.87 AUC). Our model classified nonfrail, prefrail, and frail PLWH with 75% accuracy. The strongest predictors of cognitive impairment were cortical (parietal, occipital, and temporal) and subcortical (amygdala, caudate, and hippocampus) regions, whereas the strongest predictors of frailty were subcortical (amygdala, caudate, hippocampus, thalamus, pallidum, and cerebellum).

Conclusions:

DNN models achieved high accuracy in classifying cognitive impairment and frailty status in PLWH. Feature selection algorithms identified predictive regions in each domain and identified overlapping regions between cognitive impairment and frailty. Our results suggest frailty in HIV is primarily subcortical, whereas cognitive impairment in HIV involves subcortical and cortical brain regions.
Dual Analysis of Loss to Follow-up for Perinatally HIV-Infected Adolescents Receiving Combination Antiretroviral Therapy in Asia
Authors: Bartlett Adam W. , Lumbiganon Pagakrong , Jamal Mohamed Thahira A. , Lapphra Keswadee , Muktiarti Dina , Du Quy Tuan , Hansudewechakul Rawiwan , Ly Penh Sun , Truong Khanh Huu , Van Nguyen Lam , Puthanakit Thanyawee , Sudjaritruk Tavitiya , Chokephaibulkit Kulkanya , Do Viet Chau , Kumarasamy Nagalingeswaran , Nik Yusoff Nik Khairulddin , Kurniati Nia , Fong Moy Siew , Wati Dewi Kumara , Nallusamy Revathy , Sohn Annette H. , Kariminia Azar ,   for the TREAT Asia Pediatric HIV Observational Database of IeDEA Asia-Pacific
Published: November 2019

Background:

Perinatally HIV-infected adolescents (PHIVA) are an expanding population vulnerable to loss to follow-up (LTFU). Understanding the epidemiology and factors for LTFU is complicated by varying LTFU definitions.

Setting:

Asian regional cohort incorporating 16 pediatric HIV services across 6 countries.

Methods:

Data from PHIVA (aged 10–19 years) who received combination antiretroviral therapy 2007–2016 were used to analyze LTFU through (1) an International epidemiology Databases to Evaluate AIDS (IeDEA) method that determined LTFU as >90 days late for an estimated next scheduled appointment without returning to care and (2) the absence of patient-level data for >365 days before the last data transfer from clinic sites. Descriptive analyses and competing-risk survival and regression analyses were used to evaluate LTFU epidemiology and associated factors when analyzed using each method.

Results:

Of 3509 included PHIVA, 275 (7.8%) met IeDEA and 149 (4.3%) met 365-day absence LTFU criteria. Cumulative incidence of LTFU was 19.9% and 11.8% using IeDEA and 365-day absence criteria, respectively. Risk factors for LTFU across both criteria included the following: age at combination antiretroviral therapy initiation <5 years compared with age ≥5 years, rural clinic settings compared with urban clinic settings, and high viral loads compared with undetectable viral loads. Age 10–14 years compared with age 15–19 years was another risk factor identified using 365-day absence criteria but not IeDEA LTFU criteria.

Conclusions:

Between 12% and 20% of PHIVA were determined LTFU with treatment fatigue and rural treatment settings consistent risk factors. Better tracking of adolescents is required to provide a definitive understanding of LTFU and optimize evidence-based models of care.
Ectopic Corticotropin-Releasing Hormone–Secreting Pancreatic Neuroendocrine Tumor
Authors: Zhang Jingjing , Kulkarni Harshad R. , Baum Richard P.
Published: November 2019

Ectopic Cushing syndrome secondary to corticotropin releasing hormone (CRH)–secreting tumors or CRH and adrenocorticotropin hormone cosecreting tumors is extremely rare. We report here the case of a 54-year-old man who experienced CRH-secreting pancreatic neuroendocrine tumor causing Cushing syndrome, initially detected by SSTR (somatostatin receptor) scintigraphy, then significantly progressed with multiple liver metastases, demonstrating significantly increased SSTR expression on 68Ga-DOTATOC PET/CT and a “mismatch” imaging pattern on 18F-FDG PET/CT. The patient underwent peptide receptor radionuclide therapy with 177Lu/90Y-DOTATOC and demonstrated excellent response to the treatment.
Compartment Syndrome of the Temporal Muscle
Authors: Bottini Gian Battista , Tükel Hüseyin Can , Brandtner Christian , Wittig Jörn , Gaggl Alexander
Published: November 2019

The authors report a patient with masticator space abscess due to an ascending infection following a wisdom tooth extraction. They administered antibiotics and did an incision and drainage; however, osteomyelitis of the mandible and compartment syndrome of the temporal muscle complicated the course. The authors suggest a physiopathology and discuss the management of this study.
New Ileostomy Formation and Subsequent Community-onset Acute and Chronic Kidney Disease
Authors: Smith Stephen A. , Ronksley Paul E. , Tan Zhi , Dixon Elijah , Hemmelgarn Brenda R. , Buie W. Donald , Pannu Neesh , James Matthew T.
Published: November 2019

Objective:

The aim of this study was to examine relationships between ileostomy formation and subsequent kidney disease.

Summary and Background Data:

Colonic absorptive capacity loss from ileostomy formation can cause volume depletion and could result in kidney disease

Methods:

We conducted a population-based cohort study comparing patients who underwent ileostomy formation with or without bowel resection (ileostomy group) to patients who underwent bowel resection without ileostomy formation (reference group). Adjusted odds ratios (aORs) for community-onset acute kidney injury (AKI) within 3 months and new-onset chronic kidney disease (CKD) within 1 year following hospital discharge were determined.

Results:

Among 19,889 patients, 4136 comprised the ileostomy group and 15,753 comprised the reference group; 1350 patients experienced community-onset AKI and 464 developed new-onset CKD. The aOR for community-onset AKI with ileostomy formation was 4.08 [95% confidence interval (CI) = 3.62–4.61] for any stage AKI, 7.08 (95% CI = 5.66–8.85) for stage ≥2 injury, and 7.67 (95% CI = 5.06–11.63) for stage 3 injuries. Community-onset AKI modified associations between ileostomy formation and new-onset CKD (P = 0.002). Odds of new-onset CKD were increased in the ileostomy group relative to the reference group for patients both with (aOR = 4.99; 95% CI = 3.42–7.28) and without (aOR = 2.45; 95% CI = 1.85–2.23) previous community-onset AKI episodes. In analyses comparing patients that underwent ileostomy formation and subsequent reversal within 1 year to the reference group without ileostomy, the relationship with new-onset CKD was attenuated for patients both with (aOR = 2.49; 95% CI = 1.50–4.12) and without (aOR = 0.97; 95% CI = 0.67–1.40) previous community-onset AKI episodes.

Conclusions:

Ileostomy formation is strongly associated with subsequent kidney disease. Vigilance for this complication and new strategies for prevention and treatment are necessary.
Survival Advantage of Laparoscopic Versus Open Resection For Colorectal Liver Metastases
Authors: Syn Nicholas L. , Kabir Tousif , Koh Ye Xin , Tan Hwee Leong , Wang Louis Z. , Chin Brian Zhaojie , Wee Ian , Teo Jin Yao , Tai Bee Choo , Goh Brian K. P.
Published: November 2019

Objective:

To perform an individual participant data meta-analysis using randomized trials and propensity-score matched (PSM) studies which compared laparoscopic versus open hepatectomy for patients with colorectal liver metastases (CLM).

Background:

Randomized trials and PSM studies constitute the highest level of evidence in addressing the long-term oncologic efficacy of laparoscopic versus open resection for CLM. However, individual studies are limited by the reporting of overall survival in ways not amenable to traditional methods of meta-analysis, and violation of the proportional hazards assumption.

Methods:

Survival information of individual patients was reconstructed from the published Kaplan-Meier curves with the aid of a computer vision program. Frequentist and Bayesian survival models (taking into account random-effects and nonproportional hazards) were fitted to compare overall survival of patients who underwent laparoscopic versus open surgery. To handle long plateaus in the tails of survival curves, we also exploited “cure models” to estimate the fraction of patients effectively “cured” of disease.

Results:

Individual patient data from 2 randomized trials and 13 PSM studies involving 3148 participants were reconstructed. Laparoscopic resection was associated with a lower hazard rate of death (stratified hazard ratio = 0.853, 95% confidence interval: 0.754–0.965, P = 0.0114), and there was evidence of time-varying effects (P = 0.0324) in which the magnitude of hazard ratios increased over time. The fractions of long-term cancer survivors were estimated to be 47.4% and 18.0% in the laparoscopy and open surgery groups, respectively. At 10-year follow-up, the restricted mean survival time was 8.6 months (or 12.1%) longer in the laparoscopy arm (P < 0.0001). In a subgroup analysis, elderly patients (≥65 years old) treated with laparoscopy experienced longer 3-year average life expectancy (+6.2%, P = 0.018), and those who live past the 5-year milestone (46.1%) seem to be cured of disease.

Conclusions:

This patient-level meta-analysis of high-quality studies demonstrated an unexpected survival benefit in favor of laparoscopic over open resection for CLM in the long-term. From a conservative viewpoint, these results can be interpreted to indicate that laparoscopy is at least not inferior to the standard open approach.
Biochemical Modulation and Pathophysiology of Migraine
Authors: Chan Calvin , Wei Diana Y. , Goadsby Peter J.
Published: November 2019

Background:

Migraine is a common disabling neurological disorder where attacks have been recognized to consist of more than headache. The premonitory, headache, and postdromal phases are the various phases of the migraine cycle, where aura can occur before, during, or after the onset of pain. Migraine is also associated with photosensitivity and cranial autonomic symptoms, which includes lacrimation, conjunctival injection, periorbital edema, ptosis, nasal congestion, and rhinorrhoea. This review will present the current understanding of migraine pathophysiology and the relationship to the observed symptoms.

Evidence Acquisition:

The literature was reviewed with specific focus on clinical, neurophysiological, functional imaging, and preclinical studies in migraine including the studies on the role of calcitonin gene-related peptide (CGRP) and pituitary adenylate cyclase activating polypeptide (PACAP).

Results:

The phases of the migraine cycle have been delineated by several studies. The observations of clinical symptoms help develop hypotheses of the key structures involved and the biochemical and neuronal pathways through which the effects are mediated. Preclinical studies and functional imaging studies have provided evidence for the role of multiple cortical areas, the diencephalon, especially the hypothalamus, and certain brainstem nuclei in the modulation of nociceptive processing, symptoms of the premonitory phase, aura, and photophobia. CGRP and PACAP have been found to be involved in nociceptive modulation and through exploration of CGRP mechanisms, new successful treatments have been developed.

Conclusions:

Migraine is a complex neural disorder and is important to understand when seeing patients who present to neuro-ophthalmology, especially with the successful translation from preclinical and clinical research leading to successful advances in migraine management.
Analysis of phylogenetic diversity and in vitro adherence characteristics of respiratory syncytial virus and Streptococcus pneumoniae clinical isolates obtained during pediatric respiratory co-infections
Authors: Brealey Jaelle C. , Sly Peter D. , Young Paul R. , Chappell Keith J.
Published: November 2019

Respiratory syncytial virus (RSV) andStreptococcus pneumoniaeare frequently co-associated during acute respiratory infections, particularly amongst infants and young children. In this study, we aimed to identify strains of RSV and serotypes/sequence types ofS. pneumoniaeassociated with co-infections within a cohort of paediatric patients, and to assess RSV-mediated adhesion of pneumococcal isolates. The RSV glycoprotein sequence was determined for 58 RSV-positive samples and molecular serotyping and MLST was used to analyse 26 pneumococcal isolates. We also compared 23 pneumococcal isolates for their adherence to RSV-infected or mock-infected airway epithelia cells using immunofluorescence microscopy and automated particle counting. The tight association between RSV andS. pneumoniaewas also visualized using scanning electron microscopy. This study did not identify any statistically significant trend in the strains of RSV andS. pneumoniaeassociated with co-infections. Furthermore, almost all isolates (22 of 23) showed significantly increased adherence to RSV-infected cells. The level of adherence did not appear to correlate with pneumococcal strain or sequence type, and isolates obtained from RSV-infected patients displayed a similar level of adherence as those from RSV-negative patients. The absence of particularS. pneumoniaeor RSV strains associated with co-infection, together with the near ubiquitous presence of RSV-mediated adhesion throughout the pneumococcal clinical isolates, may indicate that the mechanisms governing the association with RSV are of sufficient importance to be maintained across much of the species.
Classification of clear cell renal cell carcinoma based onPKMalternative splicing
Authors: Li Xiangyu , Turanli Beste , Juszczak Kajetan , Kim Woonghee , Arif Muhammad , Sato Yusuke , Ogawa Seishi , Turkez Hasan , Nielsen Jens , Boren Jan , Uhlen Mathias , Zhang Cheng , Mardinoglu Adil
Published: November 2019

Clear cell renal cell carcinoma (ccRCC) accounts for 70–80% of kidney cancer diagnoses and displays high molecular and histologic heterogeneity. Hence, it is necessary to reveal the underlying molecular mechanisms involved in progression of ccRCC to better stratify the patients and design effective treatment strategies. Here, we analyzed the survival outcome of ccRCC patients as a consequence of the differential expression of four transcript isoforms of the pyruvate kinase muscle type (PKM). We first extracted a classification biomarker consisting of eight gene pairs whose within-sample relative expression orderings (REOs) could be used to robustly classify the patients into two groups with distinct molecular characteristics and survival outcomes. Next, we validated our findings in a validation cohort and an independent Japanese ccRCC cohort. We finally performed drug repositioning analysis based on transcriptomic expression profiles of drug-perturbed cancer cell lines and proposed that paracetamol, nizatidine, dimethadione and conessine can be repurposed to treat the patients in one of the subtype of ccRCC whereas chenodeoxycholic acid, fenoterol and hexylcaine can be repurposed to treat the patients in the other subtype.
scGAIN: Single Cell RNA-seq Data Imputation using Generative Adversarial Networks
Authors: Gunady Mohamed K. , Kancherla Jayaram , Bravo Héctor Corrada , Feizi Soheil
Published: November 2019

Single cell RNA sequencing (scRNA-seq) provides a rich view into the heterogeneity underlying a cell population. However single-cell data are usually noisy and very sparse due to the presence of dropout genes. In this work we propose an approach to impute missing gene expressions in single cell data using generative adversarial networks (GANs). By learning an approximate distribution of the data, our approach, scGAIN, can impute dropouts in simulated and real single cell data. The work in this paper discusses how to adopt GAIN training model into the domain of imputing single cell data. Experiments show that scGAIN gives competitive results compared to the state-of-the-art approaches while showing superiority in various aspects in simulation and real data. Imputation by scGAIN successfully recovers the underlying clustering of different subpopulations, provides sharp estimates around true mean expressions and increase the correspondence with matched bulk RNAseq experiments.
Different α2δ Accessory Subunits Regulate Distinctly Different Aspects of Calcium Channel Function in the Same Drosophila Neurons
Authors: Heinrich Laurin , Ryglewski Stefanie
Published: November 2019

Voltage gated calcium channels (VGCCs) regulate neuronal excitability and translate activity into calcium dependent intracellular signaling. The pore forming α1subunit of high voltage activated (HVA) VGCCs operates not in isolation but associates with α2δ accessory subunits. α2δ subunits can affect calcium channel biophysical properties, surfacing, localization and transport, but theirin vivofunctions are incompletely understood. In vertebrates, it is largely unknown whether different combinations of the four α2δ and the 7 α1subunits mediate different or partially redundant functions or whether different α1/α2δ combinations regulate different aspects of VGCC function. This study capitalizes on the relatively simpler situation in the Drosophila genetic model that contains only two genes for HVA calcium channels, one Cav1 homolog and one Cav2 homolog, both with well-described functions in different compartments of identified motoneurons. We find that both dα2δ1and dα2δ3(stj) are broadly but differently expressed in the nervous system. Both are expressed in motoneurons, but with differential subcellular localization. Functional analysis reveals that dα2δ3is required for normal Cav1 and Cav2 current amplitudes and for correct Cav2 channel function in all neuronal compartments, axon terminal, axon, and somatodendritic domain. By contrast, dα2δ1does not affect Cav1 or Cav2 current amplitudes or presynaptic function, but it is required for correct Cav2 channel allocation to the axonal versus the dendritic domain. Therefore, different α2δ subunits are required in the same neurons to precisely regulate distinctly different functions of HVA calcium channels, which is in accord with specific α2δ mutations causing different brain diseases.

Significance Statement

Calcium influx through the pore forming α1-subunit of voltage gated calcium channels serves essential neuronal functions, such as synaptic vesicle release, control of action potential shape and frequencies, synaptic input computations, and transcriptional control. Localization and function of α1-calcium channel subunits depend on interactions with α2δ accessory subunits. Here we presentin vivoanalysis of Drosophila motoneurons revealing that different α2δ subunits independently regulate distinctly different aspects of calcium channel function in the same neuron, such as current amplitude and dendritic versus axonal channel localization. Our findings start unraveling how different α1/α2δ combinations regulate functional calcium channel diversity in different sub-neuronal compartments, and may provide an entry point toward understanding how mutations of different α2δ genes underlie brain diseases.
Promotion of hyperthermic-induced rDNA hypercondensation inSaccharomyces cerevisiae
Authors: Shen Donglai , Skibbens Robert V.
Published: November 2019

Ribosome biogenesis is tightly regulated through stress-sensing pathways that impact genome stability, aging and senescence. InSaccharomyces cerevisiae, ribosomal RNAs are transcribed from rDNA located on the right arm of chromosome XII. Numerous studies reveal that rDNA decondenses into a puff-like structure during interphase and condenses into a tight loop-like structure during mitosis. Intriguingly, a novel and additional mechanism of increased mitotic rDNA compaction (termed hypercondensation) was recently discovered that occurs in response to temperature stress (hyperthermic-induced) and is rapidly reversible. Here, we report that neither changes in condensin nor cohesin binding dynamics appear to play a critical role in hyperthermic-induced rDNA hypercondensation – differentiating this architectural state from normal mitotic condensation (requiring cohesins and condensins) and the premature condensation (requiring condensins) that occurs during interphase in response to nutrient starvation. A candidate genetic approach revealed that deletion of either Hsp82 or Hsc82 (Hsp90 heat shock paralogs) result in significantly reduced hyperthermic-induced rDNA hypercondensation. Intriguingly, Hsp inhibitors do not impact rDNA hypercondensation. In combination, these findings suggest that Hsp90 either stabilizes client proteins, which are sensitive to very transient thermic challenges, or directly promotes rDNA hypercondensation during preanaphase. Our findings further reveal that the high mobility group protein Hmo1 is a negative regulator of mitotic rDNA condensation, distinct from its role in promoting premature-condensation of rDNA during interphase upon nutrient starvation.
An automatic approach to constrained quadrilateral mesh generation
Authors: Ma Xinwu , Sun Lu
Published: November 2019

Purpose

Arbitrary constraints might be included into the problem domain in many engineering applications, which represent specific features such as multi-domain interfaces, cracks with small yield stresses, stiffeners attached on the plate for reinforcement and so on. To imprint these constraints into the final mesh, additional techniques need to be developed to treat these constraints properly.

Design/methodology/approach

This paper proposes an automatic approach to generate quadrilateral meshes for the geometric models with complex feature constraints. Firstly, the region is decomposed into sub-regions by the constraints, and then the quadrilateral mesh is generated in each sub-region that satisfies the constraints. A method that deals with constraint lines and points is presented. A distribution function is proposed to represent the distribution of mesh size over the region by using the Laplace equation. The density lines and points can be specified inside the region and reasonable mesh size distribution can be obtained by solving the Laplace equation.

Findings

An automatic method to define sub-regions is presented, and the user interaction can be avoided. An algorithm for constructing loops from constraint lines is proposed, which can deal with the randomly distributed constraint lines in a general way. A method is developed to deal with constraint points and quality elements can be generated around constraint points. A function defining the distribution of mesh size is put forward. The examples of constrained quadrilateral mesh generation in actual engineering analysis are presented to show the performance of the approach.

Originality/value

An automatic approach to constrained quadrilateral mesh generation is presented in this paper. It can generate required quality meshes for special applications with complex internal feature constraints.
Selecting project delivery methods for water treatment plants
Authors: Feghaly Jeffrey , El Asmar Mounir , Ariaratnam Samuel , Bearup Wylie
Published: November 2019

Purpose

The purpose of this paper is to identify key project delivery method selection factors to assist water industry decision-makers in selecting the most appropriate delivery method for their water treatment plant projects.

Design/methodology/approach

The selection factors were identified by compiling and validating key project delivery selection factors across various industries through an extensive literature review and two industry expert workshops. This resulted in the development of a web-based decision-support tool to facilitate project delivery method selection within the water industry.

Findings

The research effort led to the identification of 13 key project delivery method selection factors (seven primary factors and six secondary factors) for water treatment plant projects. These factors were utilized to develop EXPRSS-TP, a pioneering web-based project delivery method decision-support tool for the water industry.

Practical implications

A project delivery method selection process is typically an informal process that may range from days to weeks at a time. Based on this work, the assessment can now be completed in about one hour and provides decision-makers with the most favorable delivery method for their project. And with the new tool that encompasses the new knowledge, not only is the decision reached at an accelerated pace, EXPRSS-TP also documents the entire selection process, allowing for a written and retained record of this key decision and its procedure.

Originality/value

This paper contributes to the exisiting body of knowledge by identifying key project delivery selection factors across numerous industries, assessing and combining them, and finally incorporating them into one comprehensive process. EXPRSS-TP improves the traditional project delivery method selection process and provides evidence-based project delivery method selection recommendations.
Time-dependent reliability analysis of the motor hanger for EMU based on stochastic process
Authors: Zhi Pengpeng , Xu Yue , Chen Bingzhi
Published: November 2019

Purpose

Most of the previous work on reliability analysis was based on the traditional reliability theory. The calculated results can only reflect the reliability of components at a specific time, which neglects the uncertainty of load and resistance over time. The purpose of this paper is to develop a time-dependent reliability analysis approach based on stochastic process to deal with the problem and apply it to the structural design of railway vehicle components.

Design/methodology/approach

First, the parametric model of motor hanger for electric multiple unit (EMU) is established by ANSYS parametric design language, and its structural stress is analyzed according to relevant standards. The Latin hypercube method is used to analyze the sensitivity of the structure, and the uncertainty parameters (sizes and loads) which have great influence on the structural strength are determined. The D-optimal experimental design is carried out to establish the polynomial response surface function, which characterizes the relationship between uncertainty parameters and structural stress. Second, the Poisson stochastic process is adopted to describe the number of loads acting, and the Monte Carlo method is used to obtain the load acting history according to its probability distribution characteristics. The load history is introduced into the response surface function and the uncertainty of other parameters is considered at the same time, and the stress history of the motor hanger is obtained. Finally, the degradation process of structural resistance is described by a Gamma stochastic process, and the time-dependent reliability of the motor hanger is calculated based on the reliability theory.

Findings

Time and the uncertainties of parameters have great impact on reliability. The results of reliability decrease with time fluctuation are more reasonable, stable and credible than traditional methods.

Practical implications

In this paper, the proposed method is applied to the structural design of the motor hanger for EMU, which has a good guiding significance for accurately evaluating whether if the design meets the reliability requirements.

Originality/value

The value of this paper is that the method takes both the randomness of load over time and the uncertainty of structural parameters in the design and manufactures process into consideration, and describes the monotonous degradation characteristics of structural resistance. At the same time, the time-dependent reliability of mechanical components is calculated by a response surface method. It not only improves the accuracy of reliability analysis, but also improves the analysis efficiency and solves the problem that the traditional reliability analysis method can only reflect the static reliability of components.
Why ostracized full-time faculty should not be labeled as “low performer”? A qualitative insight from higher education in Pakistan
Authors: Bilal Ahmad Raza , Fatima Tehreem , Imran Muhammad Kashif
Published: November 2019

Purpose

The purpose of this paper is to explore how the exclusionary work environment characterized by ostracism impacts full-time faculty experiences and responses in higher educational institutions working in eastern and collectivist culture of Pakistan.

Design/methodology/approach

Using a qualitative phenomenological approach, the data were gathered form 25 ostracized full-time faculty working in the public and private universities in Lahore, Pakistan via in-depth semi-structured interviews. The interviews are subsequently recorded, transcribed and analyzed by thematic analysis using NVivo 11 Plus software.

Findings

Prosocial work outcomes coupled with high intensity of negative psychological impacts were traced based on the re-inclusion expectations, long-term relational contract, the socially interdependent, collaborative and collectivist culture of academic settings. However, the faculty indicated, in case of chronic exposure to ostracism they will engage in negative outcomes such as withdrawal, decrease in performance and resignation.

Research limitations/implications

The results of this study can be used by the university administration to develop an inclusive and non-discriminatory culture. This can be done by devising policies for information sharing, better formal and informal relationships in full-time teaching faculty along with grievance mechanism to minimize the occurrence of workplace ostracism.

Originality/value

The study promotes the understating of exclusionary work environments in academic settings. It has shown that the full-time faculty from all levels, specifically lecturers, experience workplace ostracism. This study has highlighted the specific contextual factors and temporal trends that shape the unique nature and responses (i.e. more social exclusion, prosocial responses and higher psychological distress) to ostracism in scantly researched academic settings in Pakistan.