bluuebunny/crossref_metadata_2025 huggingface dataset:
A novel de novo mutation in MYH7 gene in a patient with early onset muscular weakness and severe kyphoscoliosis
Authors: Ko Jin Young , Lee Minyong , Jang Ja-Hyun , Jang Dae-Hyun , Ryu Ju Seok
Published: July 2019

Introduction:

Various phenotypes have been identified for MYH7 gene mutation-related myopathy. Here, we describe a patient with severe muscular weakness and skeletal deformity with de novo heterozygous MYH7 gene mutation.

Patient concerns:

A 33-year-old woman presented with early onset of muscular weakness, with delayed motor development during infancy. At age 8 years, she was unable to walk, with signs of skeletal deformity, including the progression of kyphoscoliosis. At age 31 years, she developed dyspnea.

Diagnosis:

She diagnosed with esophageal hiatal hernia with abdominal CT. In electromyography, short duration, small amplitude motor unit action potential (MUAP), and early recruitment patterns were observed in the involved proximal muscles, suggesting myopathy. Muscle histopathology showed fiber-type disproportion.

Interventions:

Next-generation sequencing study revealed a heterozygous in-frame deletion variation in the exon 14 of the MYH7 gene (c.1498_1500del/p.Glu500del), which is a novel variation confirmed by conventional Sanger sequencing. Compared with the parental test, this variant was concluded as de novo.

Outcomes:

She received laparoscopic hiatal hernia repair and Nissen fundoplication for esophageal hiatal hernia. After surgery, her postural dyspnea improved. As there is no fundamental treatment for MYH7-related myopathies, she continued conservative treatment for her symptoms.

Conclusion:

Here, we presented a rare case of de novo mutation of the myosin head domain in the MYH7 gene. This report broadens both the phenotypic and genotypic spectra of MYH7-related myopathies.
Intravascular papillary endothelial hyperplasia occurring in the foot
Authors: Han Yeeun , Yun Sangchul , Choi In Ho
Published: July 2019

Rationale:

Intravascular papillary endothelial hyperplasia (IPEH; Masson tumor) is a type of vascular lesions composed of reactive proliferation of endothelial cells that occur in organizing thrombus. It commonly occurs on the head, neck, trunk, and upper extremities, but rarely in the foot.

Patient concerns:

A 38-year-old woman visited the hospital with a mass on the dorsum of right foot, which gradually increased in size 3 months ago.

Diagnoses:

Ultrasonographic examination suggested angiomyolipoma or hemangioma.

Interventions:

The patient underwent excision under local anesthesia.

Outcomes:

The lesion was confirmed to be IPEH by histological examination. There were no complications or recurrences after successful surgical excision.

Lessons:

IPEH presenting on the dorsum of the foot is vary uncommon. Radiologic diagnosis may be limited for diagnosis, and histologic confirmation should be made after surgical excision. There are some reports suggesting an association between trauma and IPEH occurrence, but this is not yet conclusive.
Four-year pain relief after coblation combined with active exercise for cervical discogenic pain
Authors: Li Xiuhua , Yang Liqiang , Ni Jiaxiang , Zhang Yuqi
Published: July 2019

Rationale:

Coblation of intervertebral disc is an effective and safe minimally invasive technology for treating discogenic pain. The inactivation of neural ingrowth around annulus and tissue ablation and coagulation are currently considered to be the major causes for success of this treatment. However, it has been found by clinical researchers that its long-term clinical outcome is not optimistic. This report has given us favorable information that this situation can be improved with multimodal therapy.

Patient concerns:

A 61-year-old man presented with right severe neck and shoulder pain in 2014 which could not be relieved by medications.

Diagnoses:

According to his symptoms and signs, this patient was diagnosed with cervical discogenic pain. And discography confirmed the diagnosis.

Interventions:

The patient underwent coblation of cervical intervertebral disc 4–5 (C4–5) and got apparently pain relief after surgery. After 1 month, he began to perform active exercise at least 30 min every day.

Outcomes:

The right neck and shoulder pain completely relieved for 4 years. The cervical lordosis of this patient was restored in 2018 which was confirmed by MRI compared in 2014 and NDI (neck disability index) decreased from 58 to 10%.

Lessons:

This report demonstrated that it was important and essential for clinicians to educate patients with discogenic pain to perform active exercise after minimally invasive surgery.
The relationship among GNB3 rs5443, PNPLA3 rs738409, GCKR rs780094 gene polymorphisms, type of maternal gestational weight gain and neonatal outcomes (STROBE-compliant article)
Authors: Mărginean Claudiu , Mărginean Cristina Oana , Bănescu Claudia , Meliţ Lorena Elena , Tripon Florin , Iancu Mihaela
Published: July 2019

The gestational weight gain is determined by food habits, environmental and genetic factors.

The aims of this paper were to establish relationships between maternal gene polymorphisms (patatin-like phospholipase domain-containing protein 3 rs738409 [PNPLA3 rs738409], glucokinase regulatory protein rs780094 [GCKR rs780094], and guanine nucleotide-binding protein rs5443 [GNB3 rs5443]) and mothers’ gestational weight gain, but also neonatal outcomes (birth weight, length, and ponderal index [PI]).

We performed a cross-sectional study in a sample of 158 mothers and their product of conception’ in an Obstetrics-Gynecology Clinic from Romania. We divided the pregnant women according to the Institute of Medicine recommendations into 3 subgroups: (1) insufficient gestational weight gain; (2) normal gestational weight gain; and (3) excessive gestational weight gain.

The gestational weight gain among pregnant women included in this study was classified as insufficient (10.1%), normal (31%), and excessive (58.9%). We found a tendency towards statistical significance for mothers that were overweight or obese before pregnancy to present an excessive gestational weight gain as compared to the normal weight ones. Similarly, we identified a tendency for statistical significance regarding the association between the variant genotype of GNB3 rs5443 and excessive gestational weight gain. We noticed differences that tended to be statistical significant concerning aspartate aminotransferase values between the 3 subgroups, mothers with excessive gestational weight gain having higher values than mothers with normal gestational weight gain (median, IQR: 22.89[17.53; 31.59] for mothers with excessive gestational weight gain versus 22.71[18.58; 27.37] for mothers with normal gestational weight gain). In mothers with excessive gestational weight gain, we found a significant association between the variant genotype of PNPLA3 rs738409 polymorphism and neonatal PI noticing a decrease of this index in case of newborns from mothers carrying the variant genotype.

Excessive gestational weight gain was noticed in pregnant women that were obese and overweight before pregnancy. We found a positive association between the variant genotype of GNB3 rs5443 polymorphism and excessive gestational weight gain. Similarly, the presence of variant genotype of PNPLA3 rs738409 in mothers was associated with a lower PI in their newborns. Our study pointed out the most important factors that influence gestational weight gain and related birth outcomes.
MC4R and HNF4α promoter methylation at birth contribute to triglyceride levels in childhood
Authors: Kwon Eun Jin , Lee Hye Ah , You Young-Ah , Yoo Jae Young , Park Hyesook , Park Eun Ae , Ha Eun Hee , Kim Young Ju
Published: July 2019

Although the changes in DNA methylation are assumed to be due to the association between adverse intrauterine conditions and adult metabolic health, evidence from human studies is rare. Little is known about the changes in DNA methylation present at birth that affect metabolic profiles in childhood. Previous studies have shown that the melanocortin 4 receptor (MC4R) and hepatocyte nuclear factor 4 alpha (HNF4α) genes are associated with obesity and metabolic disorders. Thus, we investigated the associations of the DNA methylation statuses of MC4R and HNF4α in cord blood with metabolic profiles in childhood.

We collected data from 90 children 7 to 9 years of age included in the Ewha Birth & Growth Cohort Study in Korea. DNA methylation was analyzed by pyrosequencing. The children were split into 2 groups according to the cutoff triglyceride (TG) levels (<110 and ≥110 mg/dL).

The methylation statuses of MC4R and HNF4α at birth were significantly associated with the TG level in childhood (P < .05). It was interesting to note that the methylation statuses of MC4R and HNF4α in cord blood were significantly decreased, whereas childhood body mass index was significantly increased, in children with high TG levels compared with children with low TG levels (P < .05).

Our findings show that the methylation statuses of MC4R and HNF4α at birth are associated with metabolic profiles in childhood. These epigenetic modifications occurring in early life may contribute to subsequent metabolic-related disorders. Thus, we suggest that DNA methylation status in cord blood may be predictive of the risk of developing metabolic syndrome.
Circulating alarin concentrations are high in patients with type 2 diabetes and increased by glucagon-like peptide-1 receptor agonist treatment
Authors: Hu Wenjing , Fan Xiaoyun , Zhou Baoyong , Li Ling , Tian Bo , Fang Xia , Xu Xiaohui , Liu Hua , Yang Gangyi , Liu Yongsheng
Published: July 2019

Context:

Alarin has been reported to be relative to food intake and an increase in body weight. However, to date, no report has demonstrated the relationship between circulating alarin and diabetes in humans.

Objective:

The objective of this study is to gain insight into the possible role of alarin in humans.

Design and methods:

164 patients with newly diagnosed type 2 diabetes mellitus (nT2DM), 112 IGT and 134 healthy subjects were recruited for this study. In an interventional study, 29 nT2DM patients were treated by a weekly GLP-1RA for 6 months. Plasma alarin concentrations were measured by ELISA.

Results:

Circulating alarin concentrations were significantly higher in both IGT and nT2DM subjects than in healthy individuals (0.40 ± 0.14 and 0.54 ± 0.24 vs 0.37 ± 0.10 μg/L, P < .05 or P < .01), whereas in T2DM patients, circulating alarin levels were higher than in IGT subjects. Circulating alarin positively correlated with FBG, HbA1c, HOMA-IR, AUCglucose and TNFα (P < .05 or P < .01). Multivariate logistic regression revealed that circulating alarin levels were correlated with IGT and T2DM. GLP-1RA treatment for 6 months increased circulating alarin levels in T2DM patients (from 0.34 ± 0.10 for baseline, to 0.39 ± 0.14 for 12 weeks, and finally to 0.38 ± 0.15 μg/L for 24 weeks; vs. pre-treatment P < .05).

Conclusions:

These data suggest that alarin might be involved in the pathogenesis of T2DM in humans.

Clinical Trial Registration Number:

ChiCTR-OCS-13003185 (18/03/2013 ).
Accommodation changes after visian implantable collamer lens with central hole for high myopia
Authors: Chen Minjie , Long Qiurong , Gu Hao , Hong Jiaxu
Published: July 2019

To characterize the accommodative changes in high-myopic patients after the implantation of the Visian implantable collamer lens with a central hole (ICL V4c).

This prospective study enrolled 30 patients (60 eyes) with uneventful surgery of ICL V4c implantation. Parameters including amplitude of accommodation (AA), monocular and binocular facility of accommodation (FA), positive relative accommodation (PRA), negative relative accommodation (NRA), near point convergence (NPC), accommodative response, and accommodation convergence/accommodation (AC/A) ratio were assessed before surgery, at 1 and 3 months postoperatively.

Mean preoperative SE was −10.86 ± 3.87 diopter (D) (range, −6.5D to −22D), which improved to 0.27 ± 0.51D at 1 month and 0.09 ± 0.47D at 3 months after surgery (P <.001). Significant improvements in AA, NRA, PRA, NPC, monocular, and binocular FA were seen at 1 month and 3 months postoperatively compared to the values before surgery (P <.05), but the difference between 1 month and 3 months were not obvious (P >.05) except for binocular FA (P = .002). However, no significant changes were seen in either AC/A ratio or accommodative response at any postoperative follow-ups in contrast to those before surgery (P >.05). Similar changes in accommodative function were found in patients with less myopia (> −10.00D) and those with more myopia (≤10.00D) (P >.05).

The accommodative function of eyes after the implantation of ICL V4c is enhanced and stabilizes at 1 month, except for the AC/A ratio and accommodative response. The clearer vision and increased amount of accommodation for near target account for the majority of the improvement.
Tuina for children with upper respiratory tract infections
Authors: Zhang Jiayuan , Chen Yunhui , Cao Liu , Zhang Renyan , Ren Renyuan , Zhang Qi
Published: July 2019

Background:

Upper respiratory tract infections (URTIs) is a common disease in children, which is also known as the common cold. Pediatric Tuina is a common treatment that Traditional Chinese Medicine (TCM) doctors commonly use for URTIs. However, there has no relevant systematic review studied on its effects and safety been reported. We plan to perform a systematically reviewing of all the clinical evidence on the effectiveness and safety of Tuina for URTIs in children.

Methods:

We will conduct the literature searching in the following electronic databases: Pubmed, Embase, Cochrane Library, Web of science, Chinese National Knowledge Infrastructure (CNKI), VIP, Wanfang, China Biomedical Literature Database (CBM), Chinese Clinical Trial Registry System. The time limit for retrieving studies is from establishment to July 2019 for each database. All published randomized controlled trials (RTCs) related to this review will be included. Review Manager (V.5.3.5) will be implemented for the assessment of bias risk and data analyses. Subgroup analysis and sensitivity analysis will be performed based on the conditions of included data.

Results:

A high-quality synthesis of current evidence of Tuina for children with URTIs will be provided in this study.

Conclusion:

This systematic review will provide evidence of whether Tuina is an effective intervention for children with URTIs.

PROSPERO registration number:

CRD42019126963.
Increased renal cortical stiffness is associated with coronary artery disease severity in patients with acute coronary syndrome
Authors: Demirtaş Abdullah Orhan , Bulut Atilla
Published: July 2019

Atherosclerosis is the primary etiological factor associated with acute coronary syndrome (ACS). Kidneys have a highly arterial vascular structure and are therefore commonly affected by atherosclerosis, including those affecting the coronary arteries. Renal shear wave elastography (SWE) is an ultrasonographic method, which provides reliable information regarding the condition of the renal parenchyma.

We investigated the relationship between SWE findings and the severity of coronary atherosclerosis.

We calculated the following: the renal cortical stiffness (rCS) evaluated via SWE, the renal resistive index, the renal pulsatility index, the acceleration time, and the mean Syntax score (SS). Patients with a mean SS <12 were categorized into a low-risk (LR) and those with a mean SS ≥12 were categorized into the high-risk (HR) group.

Our study included 132 patients—76 in the LR and 56 in the HR group. Creatinine, high-sensitivity C-reactive protein (hs-CRP), and rCS were significantly higher, but the glomerular filtration rate (GFR) was significantly lower in the HR group. The Hs-CRP (odds ratio [OR] 1.220), GFR (OR 0.967), and rCS (OR 1.316) were observed to be independent predictors for the HR group. The cutoff value of rCS using receiver-operating characteristic curve analysis was 4.43 for the prediction of HR patients and showed 60.7% sensitivity and 57.9% specificity (area under the curve 0.642).

SWE which shows renal parenchymal injury and atherosclerosis in renal vessels may give an idea about the severity of coronary atherosclerosis.
Prevalence of actinic keratosis in patients attending the dermatology outpatient clinic
Authors: Yaldiz Mahizer
Published: July 2019

Actinic keratoses (AKs) are precancerous epidermal lesions that develop on sensitive, frequently sun-exposed skin surfaces. There are very little data regarding AK prevalance. The aim of this study was to investigate the prevalence of AK and related conditions among patients in a dermatology outpatient clinic.

Patients attending our dermatology outpatient clinic between January 1, 2015 and December 31, 2017 were evaluated retrospectively usingan automated system. A total of 54,786 patients aged ≥30 years attending the dermatology outpatient clinic were included in the study. We identified 1375 patients diagnosed with AK.

In our study, the AK prevalence was 0.01% for patients between 30 and 39 years of age, 0.45% for patients between 40 and 49 years of age, 1.77% for patients between 50 and 59 years of age, 4.61% for patients between 60 and 69 years of age, 9.38% for patients between 70 and 79 years of age, and 14.57% for patients ≥80 years. AK prevalence was 2.50% among patients of all ages.

The exposure to sunlight is excessive due to the geographical location of our country. Due to the tendency of AKs to convert to malignancies, the identification of patients at high risk for AK development and the identification of high-risk anatomical regions are important to establish the basis of effective screening programs to support public health.
Endoscopic nasogastric tube insertion for treatment of benign afferent loop obstruction after radical gastrectomy for gastric cancer
Authors: Cao Yuning , Kong Xiangheng , Yang Daogui , Li Senlin
Published: July 2019

Afferent loop obstruction is an uncommon complication associated with Billroth-II distal gastrectomy. Inappropriate treatment may result in life-threatening events as perforation and peritonitis. For the benign afferent loop obstruction, Braun or Roux-en-Y reconstruction has been reported as the choice. However, the edematous afferent loop may result in anastomotic fistula. In this study, a less invasive technique was described for treatment of benign afferent loop obstruction. The aim of this study was to investigate the effectiveness and safety of endoscopic nasogastric tube insertion for treatment of benign afferent loop obstruction.

We conducted a retrospective review of the data of 2548 gastric cancer patients who underwent distal gastrectomy from January 2002 to January 2018. Patients who developed benign afferent loop obstruction were treated by this procedure. Outcomes were recorded. Follow-up was scheduled at 3, 6, and 12 months after the treatment.

Twenty-six patients (1.0%) developed afferent loop obstruction. The median age, consisting of 19 men and 7 women, was 60 years (range 36–69 years). Of these 26 patients, 23 underwent the endoscopic treatment. The obstructive symptoms had a rapid relief in all the 23 patients. No one died due to this procedure. However, 2 patients underwent surgical treatment due to intestinal obstruction because of adhesion at >4 and 7 months after the endoscopic drainage, respectively.

Endoscopic nasogastric tube insertion is an effective and safe procedure for treatment of benign afferent loop obstruction. In addition, it could be considered as the first step in treatment, especially in high-surgical-risk patients.
Recurrent Stroke in a Child With Atlantoaxial Instability Following Chiropractic Manipulation
Authors: Ghanim Majd T. , Bergmann Shayla , Turner Raymond D. , Eskandari Ramin , Mahajerin Arash
Published: July 2019

Pediatric stroke presents with a variety of signs and symptoms. Correct modality of imaging is essential in decreasing the time from symptom onset to appropriate management. Evaluation of pediatric stroke should include both blood work as well as imaging in a parallel rather than a sequential matter. We report a case of a child with a bow hunter’s stroke that was challenging to diagnose. This type of stroke happens when the vertebral artery is occluded at the atlantoaxial or subaxial level during neck rotation. This case demonstrates that workup of stroke should be comprehensive to include all mechanical and anatomic possibilities before investigating rarer hypercoagulable disorders.
Parenteral Nutrition Complications in Children Undergoing Bone Marrow Transplantation
Authors: Soussi Mohamed A. , Besbes Habib , Mellouli Fethi , Drira Chema , Lazreg Olfa , Belghith Asma , Zouari Bechir , Zaouali Selima , Bejaoui Mohamed , Razgallah Khrouf Myriam
Published: July 2019

Background:

Parenteral nutrition (PN) seems to be a practical solution to face the negative nutritional effects of bone marrow transplantation.

Objective:

Report and describe all observed PN-related complications in children undergoing allogenic bone marrow transplantation in a tertiary center and determine the possible risk factors.

Materials and Methods:

This was a retrospective and observational study including 51 allografted children 2 to 17 years of age. We collected from medical patient records any noticed PN-related complications using an assessment causality method. The independent risk factors for complications were investigated by multivariate analysis.

Results:

A total of 92% of patients (n=47) developed a total of 136 complications attributable to PN. The incidence rate of complications was 5 for 100 patient days of PN. Infectious complications (32.3%) and electrolytic disorders (27.9%) were the most common conditions identified during our study. Multivariate analysis showed that the duration of PN exposure, age, and hyperglycemia were the risk factors for the onset of these complications.

Conclusions:

Although we have noticed multiple complications attributable to PN, a certain causal link is difficult to establish in this particular context. Emphasizing enteral nutrition in bone marrow graft protocols would be the best way to avoid these complications.
Do Errorless Methods Improve Discharge Medication Instruction and Adherence?
Authors: Patiag Maricel Carlos , Deveux Sharon , Farrar Highfield Martha E.
Published: July 2019

Purpose and Design

Postdischarge adverse drug events are a national issue, and effective inpatient instruction may help. Therefore, this intervention study examined whether using errorless teaching/learning methods including pictorial medication cards (ETL + card) improved RN teaching and patient medication adherence among persons with cognitive challenges (PWCCs).

Methods

Convenience samples of RNs and PWCCs from a 24-bed rehabilitation unit provided baseline data. RNs implemented ETL + card, and postintervention data were collected. Adapted and investigator-designed instruments had preliminary reliability/validity.

Findings

Postintervention RNs demonstrated more teaching strategies (p = .003), and teaching satisfaction rose from 0% to 50%. Minutes per teaching interaction were unchanged (p > .05). Baseline patients filled a higher number (p = .02) but a lower percentage (67%) of their prescriptions than did postintervention patients (85%). Medication dose adherence scores were unchanged (p > .05).

Conclusions

ETL + card improved RN teaching and possibly patient adherence. Further study is warranted.

Clinical Relevance

ETL + card may help PWCCs achieve safe medication self-management.
VGF in Cerebrospinal Fluid Combined With Conventional Biomarkers Enhances Prediction of Conversion From MCI to AD
Authors: Llano Daniel A. , Devanarayan Priya , Devanarayan Viswanath
Published: July 2019

Background:

Previous work has suggested that the brain and cerebrospinal fluid (CSF) levels of a neural protein involved in synaptic transmission, VGF (a noninitialism), may be altered in mild cognitive impairment (MCI) and Alzheimer Disease (AD). The objective of the current work is to examine the potential of CSF levels of a peptide derived from VGF to predict conversion from MCI to AD.

Materials and Methods:

Using multivariate analytical approaches, the performance of the conventional biomarkers (CSF Aβ1-42 and phosphorylated tau +/− hippocampal volume) was compared with the same biomarkers combined with CSF VGF peptide levels in a large publicly available data set from human subjects.

Results:

It was observed that VGF peptides are lowered in CSF of patients with AD compared with controls and that combinations of CSF Aβ1-42 and phosphorylated tau, hippocampal volume, and VGF peptide levels outperformed conventional biomarkers alone (hazard ratio=2.2 vs. 3.9), for predicting MCI to AD conversion.

Conclusions:

CSF VGF enhances the ability of conventional biomarkers to predict MCI to AD conversion. Future work will be needed to determine the specificity of VGF for AD versus other neurodegenerative diseases.
The fecal microbiome in diverticulitis and asymptomatic diverticulosis: A case-control study in the US
Authors: Hullar Meredith A. J. , Sandstrom Richard S. , Stamatoyannopoulos John A. , Lampe Johanna W. , Strate Lisa L.
Published: July 2019

Objective

The intestinal microbiota are hypothesized to play a role in the pathogenesis of diverticulitis. We compared fecal microbial communities in individuals with diverticulitis to those with uncomplicated diverticulosis.

Methods

We used 16S ribosomal RNA gene sequencing to assess and compare the microbiota composition of fecal samples from 10 patients presenting with acute diverticulitis (cases) and 10 controls with asymptomatic diverticulosis matched on age and sex.

Results

We found differences in the distribution of relative abundances of bacterial phyla and genera in diverticulitis cases versus diverticulosis controls. At the phyla level, Verrucomicrobia was more abundant on average in diverticulitis cases at the time of diagnosis than in diverticulosis controls (p=0.07). Univariate analysis identified a significant increase in the genera Coriobacteria (p=0.050), Anaerotruncus (0.046), Subdoliganulum (p=0.034), Marvinabryantia (p=0.006), and Akkermansia (p=0.04), and a decrease in Barnesiella (p=0.035) and Coprococcus (p=0.035) in diverticulitis cases at the time of diagnosis compared to diverticulosis controls. However, after correction for multiple comparisons, these differences were no longer significant. Partial least squares discriminant analysis on all microbial genera showed partial separation of diverticulitis cases at diagnosis and diverticulosis controls. The microbial alpha diversity was higher in diverticulitis cases at time of diagnosis vs controls but this was not significant (Shannon diversity index 7.4±0.6 vs 6.8±0.7, p=0.08).

Conclusions

Individuals with diverticulitis differ from those with asymptomatic diverticulosis based on components of the fecal microbiome.
Punchline: Identifying and comparing significant Pfam protein domain differences across draft whole genome sequences
Authors: Crossman Lisa C
Published: July 2019

Motivation: Short-read draft paired-end Illumina assemblies can be fragmented, contain many contigs and be impacted on by repeat regions, caused by mobile element activity within the genome or inherently repetitive gene structure. Annotating such assemblies for function and analysing gene content can be challenging if predicted genes are fragmented across contigs. Such a case can often occur within specific families of genes such as longer genes with repeating domains, genes specifying several transmembrane domains and of unusual nucleotide content. These genes can often be virulence determinants, therefore losing these specific types of data can seriously impact downstream studies.
Results: Rather than studying the predicted gene content of draft genomes, we examined predicted protein content using the Pfam domain complements of predicted proteins. We produced a workflow, Punchline, to study the genetic content of draft contig assemblies by looking at the complement of short domains that are unlikely to be affected. We investigated a dataset of Bacteroides ovatus in terms of a grouping involving the vertebrate host from which the organism was isolated and identified potential host restricted functions and host restricted phylogenetic clustering.
Availability: https://github.com/LCrossman
SICM6A: Identifying m6A Site across Species by Transposed GRU Network
Authors: Liu Wenzhong
Published: July 2019

N6-methyladenosine (m6A) is the most prevalent cross-species RNA methylation modification and plays a pivotal role in various biological processes. The biochemical methods to find m6A sites are expensive and time-consuming, and the false positive rate of identified sites is high relatively. Meanwhile, the current computations are complex, and the prediction performance is relatively low both on little data sets and large data sets. This paper, at this point, presents a deep learning model with a transposed operation in the middle of GRU layers, SICM6A, for identifying m6A sites across-species. It adopts the mixed precision training manner to improve the speed and performance, and predicts m6A sites only by directly reading the 3-mer encoding of the m6A short sequence. The cross-validation and independent test verification show SICM6A is more accurate than the state-of-the-art methods. This, therefore, makes SICM6A provide new idea for predicting other modification sites of RNA sequences. The prediction software SICM6A is on github (https://github.com/lwzyb/SICM6A).
Mutational impact of chronic alcohol use on stem cells in cirrhotic liver
Authors: Jager Myrthe , Kuijk Ewart , Lieshout Ruby , Locati Mauro D. , Besselink Nicolle , van der Roest Bastiaan , Janssen Roel , Boymans Sander , de Jonge Jeroen , IJzermans Jan N.M. , Doukas Michael , Verstegen Monique M.A. , van Boxtel Ruben , van der Laan Luc J.W. , Cuppen Edwin
Published: July 2019

Excessive alcohol consumption increases the risk of developing liver cancer, but the mechanism through which alcohol drives carcinogenesis is as yet unknown. Here, we determined the mutational consequences of chronic alcohol use on the genome of human liver stem cells prior to cancer development. No change in base substitution rate or spectrum could be detected. Analysis of the trunk mutations in an alcohol-related liver tumor by multi-site whole-genome sequencing confirms the absence of specific alcohol-induced mutational signatures driving the development of liver cancer. However, we did identify an enrichment of nonsynonymous base substitutions in cancer genes in stem cells of the cirrhotic livers, such as recurrent nonsense mutations in PTPRK that disturb Epidermal Growth Factor (EGF)-signaling. Our results thus suggest that chronic alcohol use does not contribute to carcinogenesis through altered mutagenicity, but instead induces microenvironment changes which provide a ‘fertile ground’ for selection of cells with oncogenic mutations.
A reference map of the human proinsulin biosynthetic interaction network
Authors: Tran Duc T. , Pottekat Anita , Mir Saiful A. , Jang Insook , Loguercio Salvatore , Campos Alexandre Rosa , Lahmy Reyhaneh , Liu Ming , Arvan Peter , Balch William E. , Kaufman Randal J. , Itkin-Ansari Pamela
Published: July 2019

The beta-cell protein synthetic machinery is dedicated to the production of insulin, which plays a critical role in organismal homeostasis. Insulin synthesis requires the proper folding and trafficking of its precursor, proinsulin, yet the precise network of proinsulin protein interactions in the secretory pathway remains poorly defined. In the present study we conducted unbiased profiling of the proinsulin interactome in human islets, utilizing a human proinsulin-specific monoclonal antibody for affinity purification and mass spectrometry. Stringent analysis identified a central node of interactions between human proinsulin and sequential secretory pathway proteins that is remarkably conserved across 3 ethnicities and both genders. Among the most prominent proinsulin interactions was with ER-localized peroxiredoxin-4 (PRDX4). A functional role for PRDX4 in beta-cells was demonstrated by gene silencing that rendered proinsulin susceptible to misfolding, particularly in response to oxidative stress. Conversely, exogenous PRDX4 improved proinsulin folding. Notably, oxidative stress and even high glucose treatment alone induced proinsulin misfolding in human islets and MIN6 cells, and this was accompanied by sulfonylation of PRDX4, a modification known to inactivate peroxiredoxins. This finding prompted PRDX4 analysis in a panel of human islet samples that revealed significantly higher levels of sulfonylated (inactive) PRDX4 in islets from patients with T2D compared to that of healthy individuals. Taken together, these data highlight the importance of elucidating the complete proinsulin interactome in human islets in order to understand critical steps controlling insulin biosynthesis, beta cell function, and T2D.
Synthetic mycobacterial molecular patterns partially complete Freund’s adjuvant
Authors: Dubé Jean-Yves , McIntosh Fiona , Zarruk Juan G. , David Samuel , Nigou Jérôme , Behr Marcel A.
Published: July 2019

Complete Freund’s adjuvant (CFA) has historically been one of the most useful tools of immunologists. Essentially comprised of dead mycobacteria and mineral oil, we asked ourselves what is special about the mycobacterial part of this adjuvant, and could it be recapitulated synthetically? Here, we demonstrate the essentiality of N-glycolylated peptidoglycan plus trehalose dimycolate (both unique in mycobacteria) for the complete adjuvant effect using knockouts and chemical complementation. A combination of synthetic N-glycolyl muramyl dipeptide and minimal trehalose dimycolate motif GlcC14C18 was able to upregulate dendritic cell effectors, plus induce experimental autoimmunity qualitatively similar but quantitatively milder compared to CFA. This research outlines how to substitute CFA with a consistent, molecularly-defined adjuvant which may inform the design of immunotherapeutic agents and vaccines benefitting from cell-mediated immunity. We also anticipate using synthetic microbe-associated molecular patterns (MAMPs) to study mycobacterial immunity and immunopathogenesis.
Mathematical model of molecular evolution through a stochastic analysis
Authors: Ortega Joel Valdivia
Published: July 2019

1

Today we are able to describe genome evolution but, there are still several open questions on this area such as: Which is the probability that a mutation occurs at a nucleotide level? Is it possible to predict the evolution of a particular genome?, or talking about preservation, is there a way to simulate the genetic diversity for endangered species? In this paper it is shown that it is possible to make a mathematical model not only of mutations on the genome of species, but of evolution itself, including factors such as artificial and natural selection. It is also presented the algorithm to obtain the probabilities of mutation for each specific part of the genome and for each specie.

Even more, it is presented a mathematical method to estimate the amount of generations between two related genomes and a function capable of predict the amount of mutations through time a genome will suffer.

The potential of having this tool is giantic going from genetic engineering applied to medicine to filling up blank spaces in phylogenetic studies or preservation of endangered species due to genetic diversity.
Quantifying the surveillance required to sustain genetic marker-based antibiotic resistance diagnostics
Authors: Hicks Allison L. , Kissler Stephen M. , Lipsitch Marc , Grad Yonatan H.
Published: July 2019

Diagnostics that minimize the time to selection of an appropriate antibiotic treatment represent an important strategy in addressing the challenge of antimicrobial resistance (AMR). Among this class of diagnostics, the use of pathogen genotype to predict AMR phenotype has been facilitated by advances in rapid sequencing platforms. A longstanding objection to this approach, however, is that the emergence of novel resistance mechanisms will inevitably lead to a decline in the sensitivity of these diagnostics. Here, we show that while the sensitivities of some genetic markers of resistance remain stably high, sensitivities of other markers rapidly decline, as expected, due to the emergence of novel resistance variants. We then present a simple mathematical framework that defines the sampling and phenotypic testing rates needed for early detection of novel resistance variants and thus demonstrate how surveillance can help maintain the sensitivity and utility of sequence-based AMR diagnostics.

One sentence summary

Targeted sampling strategies are necessary for early detection of novel resistance mechanisms and sustainability of genotype-based detection of novel resistance mechanisms and sustainability of genotype-based diagnostics.
Crystal structure of catena-poly[[gold(I)-μ-cyanido-[diaquabis(2-phenylpyrazine)iron(II)]-μ-cyanido] dicyanidogold(I)]
Authors: Kucheriv Olesia I. , Barakhtii Diana D. , Malinkin Sergey O. , Shova Sergiu , Gural'skiy Il'ya A.
Published: July 2019

In the title polymeric complex, {[Fe(CN)2(C10H8N2)2(H2O)2][Au(CN)2]}
n
, the FeII ion, which is located on a twofold rotation axis, has a slightly distorted FeN4O2 octahedral geometry. It is coordinated by two phenylpyrazine molecules, two water molecules and two dicyanoaurate anions, the Au atom also being located on a second twofold rotation axis. In the crystal, the coordinated dicyanoaurate anions bridge the FeII ions to form polymeric chains propagating along the b-axis direction. In the crystal, the chains are linked by Owater—H...Ndicyanoaurate anions hydrogen bonds and aurophillic interactions [Au...Au = 3.5661 (3) Å], forming layers parallel to the bc plane. The layers are linked by offset π–π stacking interactions [intercentroid distance = 3.643 (3) Å], forming a supramolecular metal–organic framework.
Slums and prosperity: a complex, dynamic pathway of intervention
Authors: Abubakar Aisha , Romice Ombretta , Salama Ashraf M.
Published: July 2019

Purpose

Slums have existed as long as cities have and are a growing context in the developing world. The challenge is in their efficient, effective and inclusive management. The purpose of this paper is to frame slums in the broad aim of urban development and the pursuit of prosperity, as active players and positive contributors in every right – a slum-prosperity framework. First, however, they need to be comprehensively defined in a non-exclusive, structured, dynamic and heuristic way; a previous publication was set to resolve this challenge.

Design/methodology/approach

Guided by a synthesized operative model for prosperity, such a definition for slums is used to precisely relate their characters to the pursuit of prosperity through a mapping process, whereby these characters are linked to potentials for prosperity, improvement goals, resources and intervention plans.

Findings

Both slums and prosperity are fuzzy, complex and variable terms; the only possibility to deal with them both is to break them down into simple and manageable yet operative units and establish the most influential and effective links between them to organize intervention according to patterns of change in both slums and city.

Research limitations/implications

An intervention agenda like the one proposed here, that gives room for contextual and temporal urban complexities, has the potential to augment urban practice and help curb the slum phenomenon. A final paper (forthcoming) will illustrate the application of both the comprehensive definition of slum and the implementation of a pathway toward prosperity.

Originality/value

The proposal in this paper is derived as part of research conducted for the award of a PhD at the University of Strathclyde Glasgow. This was in general set to contribute to the proactive and inclusive improvement of slums and cities. The proposal is further derived from the authors’ involvement and personal interest in developing regions and is designed on local experience and on wider expertise in urban renewal.
Rights, duties and spaces of agency amidst high-stakes testing
Authors: Taylor Laura A.
Published: July 2019

Purpose

By recognizing high-stakes testing as a key constraint to teacher agency, this paper aims to provide a close analysis of one teacher’s testing narrative to illustrate how emerging positioning is relative to high-stakes testing shapes perception of pedagogical agency.

Design/methodology/approach

Data were generated through a series of semi-structured interviews with an early career fourth-grade teacher, Ms Moore, in a school facing pressure to raise test scores. Using theoretical lenses of narrative positioning and a linguistic anthropological centering of constraint and emergence, 67 narratives of accountability were analyzed, with particular focus on how Ms Moore positioned herself relative to other actors involved in high-stakes testing and the consequent rights and duties these positions afforded.

Findings

In narrating the constraints of high-stakes testing, Ms Moore positioned herself relative to three groups involved in high-stakes testing: “purposefully tricky” test creators, “disjointed” administrators and “worried” students. The rights and duties associated with three positions varied with respect to two dimensions – proximity and hierarchy – in turn providing her distinct resources for responding to the pedagogical constraints of high-stakes testing.

Practical implications

Teachers might use positioning analysis as a tool to locate possibilities for agency amidst high-stakes testing, both by exploring the resources afforded by their positioning and by considering how alternative positions might afford different resources.

Originality/value

These findings suggest that high-stakes testing serves as a dynamic and perhaps malleable constraint to teacher agency. Teacher positioning, particularly relative to hierarchy and proximity, provides possible resource for responding to such constraints.
Local government and coastal damage: confusion, potential and dreams
Authors: Kelly Andrew H. , Brown Jasper , Strickland Aaron
Published: July 2019

Purpose

This paper aims to not only disentangle the recently altered law and policy on coastal management in New South Wales (NSW), Australia, but also raise opportunities for fresh ideas to develop when dealing with both existing and future coastal damage. The focus is on the role of local government which is not only closer to concerned citizens but also faces costal damage on its own doorstep.

Design/methodology/approach

The paper explores the topic from the beginnings of relevant statutory law to the current situation, supported by a case study. It is transdisciplinary in nature, encompassing land use and coastal legislation.

Findings

The narrative encourages further attention to the key issues at the local level. This is underpinned by the need for planners to move beyond zoning and other restrictive mechanisms to more strategic approaches. All levels of government must recognise that regulatory planning on its own is insufficient. This leads to the need for champions to consider opportunities beyond the ordinary.

Originality/value

While this paper will add to a growing literature on coastal damage and action at the local level, its emphasis on the benefits and limitations of the changing statutory system will assist not only policy makers but professional officers at the local forefront.
Developing substantive theories into formal theories via disruption
Authors: Rosenbaum Mark Scott , Russell-Bennett Rebekah
Published: July 2019

Purpose

The purpose of this paper is to encourage service researchers to engage in “theoretical disruption” by purposefully adding variance to existing substantive theories, and conceptual frameworks, to construct formal theories of buyer–seller marketplace behaviors. The authors put forth an original four-stage process that illustrates the way substantive theories may be developed into formal theories.

Design/methodology/approach

The authors provide their opinions regarding theoretical creation and their interpretations of Grounded Theory methodological techniques that support the development of general theories within the social sciences.

Findings

In general, the services marketing discipline is based on a foundation of substantive theories, and proposed conceptual frameworks, which emerged from samples, contexts and conditions that ensue within industrialized, upper-income locales. Rather than seek to expand substantive theories by generating new categories and relationships between categories, most researchers limit their verification studies within the scope of original theoretical frameworks. Resultantly, the services marketing domain has not developed a set of formal theories.

Research limitations/implications

The editors encourage researchers to reconsider the discipline’s substantive theories and to transform them into formal theories. Substantive theories expand into formal theories when researchers question original theoretical frameworks and show situations in which they require modification. Theoretical verification does not transform substantive theories into formal theories; rather, the discovery of negative cases suggests the need for theoretical modification.

Originality/value

This work suggests that researchers may be over-emphasizing the generalizability of their proposed theories in papers because of a lack of sample variance in empirical studies.
Multiple case study analysis and development of an interpretive structural model for greening of supply chains in Indian ceramic enterprises
Authors: Choudhary Kailash , Sangwan Kuldip Singh
Published: July 2019

Purpose

The purpose of this paper is to aim at prioritizing and identifying the interrelations among the green supply chain management pressures, practices and performance measures. The study also compares the reasons of green supply chain management implementation, levels of implementation and improvement in performance for medium and large Indian ceramic enterprises because of green supply chain management implementation.

Design/methodology/approach

The most frequent constructs and measures of green supply chain management pressure, practice and performance are identified from the literature. The identified measures are corrected/added/removed, as per the suggestions of industry professionals, to develop a survey instrument. An interpretive structural model is developed to prioritize the constructs. Matriced “impacts croises-multiplication applique” and “classment” (MICMAC) analysis is done to identify the driving and dependence powers of the constructs. The identified results are validated through the descriptive analysis of responses obtained from multiple case studies.

Findings

It is observed that the informative pressures followed by coercive and mimetic pressures are the main drivers for the implementation of green supply chain management practices. Internal environmental management in enterprises is found to be the driving power behind the implementation of other green supply chain management practices. The implementation of these practices drives the environmental and operational performance. It is observed, through the multiple case study analysis that the impact of the pressures to adopt green supply chain management practices is high on Indian ceramic enterprises but the implementation of practices is in the early stage. The improvement in performance is also not found to be significant at this stage. This study also found that large ceramic enterprises are doing better than the medium enterprises in terms of green supply chain management implementation, largely because of higher pressures and availability of resources.

Originality/value

This study prioritizes the constructs of green supply chain management pressure, practice and performance for Indian ceramic enterprises and compares the large and medium enterprises on the basis of these constructs.