bluuebunny/crossref_metadata_2025 huggingface dataset:
The relationship between serum 25-hydroxyvitamin D concentration and type 2 diabetic peripheral neuropathy
Authors: Zhang Binjie , Zhao Wenli , Tu Jinli , Wang Xueying , Hao Yu , Wang Hongwu , Zhao Ye , Mizuno Kaito , Tseng Yiider , Bu Huaien
Published: November 2019

Background:

Vitamin D is a fat-soluble vitamin that is related to the health of the human body and is an indispensable nutrient for human beings. Some studies indicated that type 2 diabetes mellitus (T2DM) with diabetic peripheral neuropathy (DPN) may be associated with vitamin D deficiency, but the current understanding of this point of view remains controversial. This study aimed to evaluate the correlation between serum 25-hydroxyl vitamin D (25 [OH] D) concentration and DPN in patients with T2DM by a meta-analysis, and to provide a reference for doctors.

Methods:

Relevant studies were selected from the PubMed, Cochrane Library, China National Knowledge Infrastructure, VIP databases, and Wanfang Data Knowledge Service Platform databases dating from 2000 to December 2017. A total of 75 articles related to serum 25 (OH) D and DPN were selected from 2000 to December 2017. Based on the inclusion and exclusion criteria of the literature, a quality assessment was conducted using the Newcastle–Ottawa scale, and a meta-analysis was performed by RevMan5.3 statistical software.

Results:

Thirteen studies that involved a total of 2814 type 2 diabetic patients were finally included into the meta-analysis. Meta-analysis results, heterogeneity test showed that, P < .000 01, I
2 = 92%, calculation by random effect model revealed that, the serum concentration of 25 (OH) D in T2DM combined with DPN group was lower than that in the group without DPN (weighted mean difference = −0.74, 95% confidence interval: −1.03 to −0.46)

Conclusions:

Vitamin D is associated with type 2 DPN (DPN), and vitamin D deficiency can lead to an increased risk of type 2 DPN. However, more high-quality research is needed.
The characteristics of Posner-Schlossman syndrome
Authors: Murata Kazuhiro , Ishida Kyoko , Ozawa Kenji , Sawada Akira , Mochizuki Kiyofumi , Yamamoto Tetsuya
Published: November 2019

This retrospective observational study aims to report the clinical characteristics and surgical results in eyes with Posner-Schlossman syndrome (PSS), and compare these outcomes between cytomegalovirus (CMV)-positive and -negative eyes.

We reviewed the medical records of 21 consecutive immunocompetent patients clinically diagnosed with PSS between the years 2010 and 2018. Aqueous humor was collected from all the affected eyes to detect if CMV was present, and polymerase chain reaction (PCR) was performed using the herpesvirus family primers.

The average period between the initial PSS attack and aqueous humor sampling at our institute was 9.3 years. Out of the 21 patients, 62% were CMV-positive. Regardless of CMV status, the mean intraocular pressure (IOP), mean deviation (MD), and central corneal endothelium cell (CEC) density, at the initial examination at our institute were already significantly worse in the affected eyes than in the unaffected eyes (all P values < .05). The average visual acuity (VA) was only significantly worse in the CMV-positive group (P = .02). Out of all the patients, those that were CMV-positive had undergone more glaucoma surgeries (P = .056). Fourteen patients underwent either a trabeculectomy (TRAB) or a trabeculotomy (LOT), and their IOP significantly reduced following surgery (P < .001). In 85.7% of those that had surgery, their IOP was successfully lowered to less than 20 mm Hg.

Long-lasting PSS causes a decrease in VA, MD, and the CEC density. A prompt diagnosis is required, and an appropriate treatment plan should be formulated. In those patients with PSS that develop uncontrolled glaucoma, both TRAB and LOT may be effective in controlling IOP.
The efficacy and safety of moxibustion for primary dysmenorrhea
Authors: Wang Hao , Hui Xin , Ha Lue , Zhao Baixiao , Yao Qin
Published: November 2019

Background:

Primary dysmenorrhea (PDM) is one of the most prevalent gynecological diseases in women of childbearing age. The major medications treating PDM usually make sense and side effects, while moxibustion is known as a safe and effective treatment for PDM. This review aims to systematically evaluate the effect and safety of moxibustion for treating PDM.

Methods:

We will search all randomized controlled trials for moxibustion therapy on PDM, electronically and manually, regardless of publication status, till October 31, 2019. Online databases include the Cochrane Central Register of Controlled Trials; PubMed; EMBASE; China National Knowledge Infrastructure; Chinese Biomedical Literature Database; Chinese Scientific Journal Database (VIP database); and Wan-Fang Database. Two reviewers will search these databases, select data and measure the quality of studies independently. The methodological quality will be assessed by the Cochrane Reviewer's Handbook 6.0. The primary outcomes include clinical efficacy and visual analog scale, and the secondary outcomes include adverse events and quality of life. Four reviewers will independently extract the data and assess the qualities of the studies. Statistical analysis will be conducted with R package for each outcome. Study selection, data extraction, and assessment of risk of bias will be performed independently by 2 reviewers.

Results:

This study will provide a comprehensive review of the available evidence for the treatment of moxibustion with PDM.

Conclusion:

The conclusion of our study will provide updated evidence to judge whether moxibustion is an effective and safe intervention for patients with PDM.

PROSPERO registration number:

CRD42019129993
Left atrial diameter in heart failure with left ventricular preserved, mid-range, and reduced ejection fraction
Authors: Zhu Ning , Chen Hao , Zhao Xuyong , Ye Fanhao , Jiang Wenbing , Wang Yi
Published: November 2019

Left atrial (LA) remodeling has been identified to predict atrial fibrillation (AF) and heart failure. However, the role of LA diameter (LAD) in patients with heart failure (HF) with preserved (HFpEF), mid-range (HFmrEF), and reduced ejection fraction (HFrEF) remains poorly understood.

A total of 142 patients including 71 subjects with AF (21 of HFpEF, 22 of HFmrEF, and 28 of HFrEF) and 71 ejection fraction (EF)-matched subjects with sinus rhythm (SR) were included in the study. Baseline characteristics and echocardiographic parameters including LAD were compared between both groups as well as among HFpEF, HFmrEF, and HFrEF.

In receiver-operating characteristic (ROC) analyses, LAD predicted AF in HFpEF, HFmrEF, and HFrEF [area under the curve (AUC): 0.646; P = .03]. LAD was negatively association with left ventricular ejection fraction while positively with Nt-proNP and left ventricular end-diastolic diameter (regression coefficient: −0.239, P = .004; regression coefficient: 0.191, P = .023; regression coefficient: 0.357, P < .001). In ROC analyses, LAD predicted HFrEF among the 3 categories (AUC: 0.629, P = .01).

In the setting of HF, LAD was higher in AF than in and SR, and predicted AF. Furthermore, LAD was associated with severity of HF in HFpEF, HFmrEF, and HFrEF, and also predicted HFrEF.
Clinical observation on the effect of Wuzhi soft capsule on FK506 concentration in membranous nephropathy patients
Authors: Zhang Zhu , Lu Xiaobei , Dong Leipeng , Ma Jiwei , Fan Xiaoguang
Published: November 2019

The current research aimed to investigate the correlation between the effect of Wuzhi soft capsule (WZC) on FK506 concentration and CYP3A5 gene polymorphism in patients with membranous nephropathy (MN).

Seventy-five patients with idiopathic MN were enrolled and divided according to the expression of CYP3A5 gene metabolic enzyme into group A (CP3A5 metabolic enzyme function expression types CYP3A5∗1/∗1 type and CYP3A5∗1/∗3 type), and group B (non-expression type CYP3A5∗3/∗3 type). All patients were given oral administration of tacrolimus capsule at the initial dose of 1 mg for twice a day 1 hour before breakfast and dinner. Afterwards, the oral administration of WZC was added at the dose of 0.5 g for 3 times a day within half an hour after 3 meals.

The blood concentrations of FK506 in groups A and B were significantly higher than those before administration. Compared with that before administration, the FK506 blood concentration was increased by 3.051 ± 0.774 ng/ml after adding the WZC. Besides, the blood concentrations of FK506 in group A were lower than those in group B before and after administration; meanwhile, the 24 hours total urine protein and the biochemical indexes in both groups displayed no statistically significant difference. Only 1 case of diarrhea was observed, which was relieved after the reduction of tacrolimus.

Wuzhi soft capsule can significantly increase the blood concentration of FK506 in MN patients. Moreover, the CYP3A5 genotyping should be considered when WZC is used to increase the blood concentration of FK506.
Invasive pyogenic infection and infective endocarditis due to Streptococcus anginosus
Authors: Cheng Chiao-Wen , Feng Cheng-Min , Chua Chian Sem
Published: November 2019

Rationale:

Streptococcus anginosus mostly colonizes the digestive and genitourinary system, including the oropharyngeal region. It commonly causes invasive pyogenic infection, but less likely causes infective endocarditis (IE).

Patient concerns:

An 18-year-old woman who had an underlying mitral valve prolapse without mitral regurgitation presented to our hospital with low-grade fever, left leg weakness, and left abdominal pain. She was diagnosed with brain infarction and microabscess as well as IE. The patient totally recovered after the 6-week course of intravenous antibiotics.

Diagnosis:

Brain magnetic resonance imaging revealed brain infarction and microabscess. Abdominal computed tomography revealed splenic and left renal infarction. Three sets of blood culture were positive for S anginosus. Transthoracic echocardiogram identified mitral valve prolapse with moderate eccentric mitral valve regurgitation, and a 0.3 × 0.6-cm vegetation was found on the left mitral valve. All of these results meet the modified Duke criteria.

Interventions:

The abdominal pain and left leg weakness were improving after 2 weeks of intravenous antibiotics treatment. No neurological sequelae were noted after completing the 6-week course of medical treatment.

Outcomes:

The patient was successfully treated and discharged after completing the 6-week intravenous antibiotics treatment.

Lessons:

IE should be considered in young patients with native valve disease who have prolonged fever. Though S anginosus commonly causes invasive pyogenic infection, patients with native valve disease should be checked for IE.
Treating an intramuscular abscess following toothpick injury in a diabetic patient
Authors: Cheng Yu-Cheng , Liu Po-Yu , Hu Sung-Yuan
Published: November 2019

Rationale:

Toothpick puncture (TPP) is a penetrating injury that can result in bringing pathogens to the deep space. Such penetrating wounds are typically of pinpoint size with initial symptoms appearing subtle. Consequently, the injury itself is often neglected by patients, or is not detected during physical examinations by medical doctors. Reported complications from such injuries include osteomyelitis and septic arthritis, mostly due to delayed treatment.

Patient concerns:

A diabetic patient aged 83-year-old presented a 2-day history of skin redness, swelling, and tenderness over his forearm following a TPP a week earlier. Laboratory investigations showed leukocytosis with neutrophilic predominance and a high level of C-reactive protein. Before his operation, cultures of aspirated fluid from the injured site revealed the presence of Streptococcus anginosus, Streptococci viridans, Prevotella intermedia, and Pavimonas (Peptostreptococcus) micra.

Diagnosis:

Intramuscular abscess associated with toothpick injury.

Interventions:

Surgical irrigation with debridement and adjunctive antibiotics of ceftriaxone and clindamycin were given with a satisfactory response. Cultures of debrided tissue showed the presence of P intermedia and P (Peptostreptococcus) micra.

Outcomes:

A split-thickness skin graft was done. Patient was discharged on the 30th postoperative day.

Lessons:

Toothpick injury, initial symptoms of which are subtle, can in some cases, lead to serious complications especially when managements are delayed. In such situations (including the present case), surgical irrigation and debridement are administrated for the eradication of infections, removal of potentially retained toothpick, and tissue cultures analyzed. Adjunctive antibiotics is recommended to combat both the aerobic and anaerobic microorganisms of the gastrointestinal tract, skin surface, and oral cavity.
Total hip arthroplasty in hereditary multiple exostoses with secondary osteoarthritis
Authors: Kim Woo Jong , Park Jong Seok , Won Sung Hun , Lee Hong Seop , Lee Dhong Won , Jang Byung-Woong , Lee Jae Jun , Hong Yong Cheol , Kang Jin Ku , Wibowo Ricky , Kim Chang Hyun
Published: November 2019

Rationale:

Hereditary multiple exostoses (HME) is an autosomal dominant disease that causes multiple exostoses throughout the body. It usually occurs around the metaphysis of the long bones, and when it involves the hip, symptoms arise due to deformity and the mass effect. If the lesion does not involve the joint or is not associated with arthritis, symptoms can be relieved by surgical excision of the osteochondroma. However, if secondary osteoarthritis (OA) or subluxation of the joint has progressed, joint replacement arthroplasty should be considered.

Patient concerns:

A 57-year-old woman with HME visited our outpatient department with severe right hip pain. She complained of difficulty walking and severe discomfort during activities of daily living. She was short in stature and had a family history of HME.

Diagnosis:

A physical examination revealed limited motion in the hip joint and a limb length discrepancy. Plain radiography and a computed tomography scan revealed huge osteochondromas on bilateral proximal femurs and advanced OA with subluxation of the right hip joint.

Interventions:

Cementless total hip arthroplasty of the right hip joint via the modified posterolateral approach was done.

Outcomes:

The patient showed good clinical scores and functional improvement at the 2-year follow-up.

Lessons:

Total hip arthroplasty for an anatomically deformed joint is technically difficult, and there are many factors to consider that can make surgeons reluctant to use this modality. However, with careful preparation, arthroplasty is a good surgical option for symptomatic and functional recovery in HME patients with hip joint involvement.
Using Cards to Facilitate Conversations About Wishes and Priorities of Patients in Palliative Care
Authors: Möller Ulrika Olsson , Pranter Christa , Hagelin Carina Lundh , Beck Ingela , Malmström Marlene , Fürst Carl Johan , Rasmussen Brigit H.
Published: November 2019

To avoid discomfort, health care professionals may hesitate to pursue conversations about end of life with patients. Certain tools have the potential to facilitate smoother conversations in this matter. The objective was to explore the experiences of patients in palliative care in using statement cards to talk about their wishes and priorities. Forty-six cards with statements of wishes and priorities were developed and tested for feasibility with 40 participants, who chose the 10 most important cards and shared their thoughts about the statements and conversation. Data from individual interviews and field notes were analyzed using content analysis. One category describes practical aspects of using the cards including the relevance of the content and the process of sorting the cards. The second category describes the significance of using the cards including becoming aware of what is important, sharing wishes and priorities, and reflecting on whether wishes and priorities change closer to death. The cards helped raise awareness and verbalize wishes and priorities. All statements were considered relevant. The conversations focused not only on death and dying, but also on challenges in the participants' current life situation. For the most ill and frail participants, the number of cards needs to be reduced.
Guidance on Expedited Partner Therapy: A Content Analysis of Informational Materials for Providers, Pharmacists, Patients, and Partners
Authors: Carman-McClanahan Michelle , McCool-Myers Megan
Published: November 2019

Background

The rates of sexually transmitted infections have steadily increased in the United States over the last 5 years. The Centers for Disease Control and Prevention has endorsed the use of expedited partner therapy (EPT) as an evidence-based practice to prevent chlamydial reinfection in index patients and lower barriers to treatment for partners. State health departments release guidance on EPT for providers, but it is unclear if information is available for other key stakeholders, for example, pharmacists, patients, and partners. The primary objective of this study was to conduct a review of state and territory health department websites to ascertain the availability, readability, utility, and content of EPT informational materials.

Methods

A content analysis of 84 EPT informational materials was conducted using validated tools to measure readability, adherence to design standards, and EPT content inclusion. Results were stratified for each target audience.

Results

Only 64% of states where EPT is allowable had informational materials available. The materials targeted providers (51.2%) and partners (35.7%). Little information targeted pharmacists (7.1%) or index patients (4.8%). The average reading level was 11th grade. Mean design score was 9.57 points of a possible 13 points. Most provider and pharmacist materials did not meet the content criteria; index and partner materials did not thoroughly describe cost of EPT, how to communicate with sex partners about EPT/chlamydia, or how to fill an EPT prescription.

Conclusions

To better support the uptake of EPT, existing resources for EPT should be improved in their design, readability, content, and availability for all target audiences.
Guidelines for Diuretic Utilization Reduce High Charge Medications
Authors: Simsic Janet M. , Dolan Kevin , Miller Julie , Yates Andrew R. , Fernandez Richard , Phelps Christina , Fitch Jill , Lee Anthony , Lloyd Eric , Gauntt Jennifer , Gajarski Robert
Published: November 2019

Background:

Decreasing practice variation and following evidence-based clinical guidelines improve patient outcomes and often reduce cost. Essentially all postsurgical cardiac patients require diuretics. The approach to diuresis in the pediatric cardiothoracic intensive care unit (CTICU) is not standardized. Our objective was to develop and implement guidelines for diuretic utilization in the CTICU to reduce high charge medication utilization while maintaining the delivery of high-quality care.

Methods:

Two of the top 10 medications by charge in the CTICU during 2016 were diuretics [fenoldopam and intravenous (IV) chlorothiazide]. Standardized diuretic utilization guidelines were developed to reduce the utilization of fenoldopam and IV chlorothiazide. We implemented guidelines in April 2017. The utilization of fenoldopam and IV chlorothiazide, as well as overall diuretic charges, before and after guideline implementation were compared.

Results:

We normalized all comparisons to 100 CTICU patient-days. Fenoldopam starts were reduced from 1.1 in 2016 to 0.03 in 2019 (through February); days of fenoldopam use were reduced from 4 in 2016 to 0.15 days in 2019 (through February); IV chlorothiazide doses decreased from 20 in 2016 to 8 in 2019 (through February). These changes reduced the mean charges for diuretics from $25,762 in 2016 to $8,855 in 2019 (through February). CTICU average daily census did not change significantly during the study period (12.8 in 2016 vs 11.8 in 2018).

Conclusion:

Value-added implementation of standardized diuretic utilization guidelines in the CTICU successfully reduced the use of high-charge diuretics without unfavorably impacting the quality of care delivery.
Patient-defined outcomes for pain, fatigue, emotional distress, and interference with activities did not differ by age for individuals with musculoskeletal pain
Authors: Wilson Abigail T. , George Steven Z. , Bialosky Joel E.
Published: November 2019

Introduction:

Age impacts the prevalence and experience of musculoskeletal pain; however, it is unknown whether this factor impacts patient's anticipated outcomes after treatment.

Objective:

Using the Patient-Centered Outcomes Questionnaire (PCOQ), the primary purpose was to determine whether there are age-related differences in desired, successful, expected levels, and importance of improvement in pain, fatigue, emotional distress, and interference with daily activities. As a secondary purpose, anatomical location and sex were then included in the model to examine for interaction effects.

Methods:

A secondary analysis of the Optimal Screening for Prediction of Referral and Outcome cross-sectional and longitudinal cohorts was conducted. Included in this analysis were 572 individuals seeking physical therapy for nonsurgical neck, low back, shoulder, and knee pain who completed the PCOQ at the initial evaluation. A three-way analysis of variance examined PCOQ domains by age categories, sex, and anatomical location.

Results:

Interaction effects were not observed for any of the domains of interest (P > 0.01). Significant main effects were also not observed for age, sex, and anatomical location (P > 0.01).

Conclusion:

Musculoskeletal pain prevalence may differ across age categories but, in this cohort, neither age, nor sex, nor anatomical location impacted patient-defined outcomes for intensity, fatigue, emotional distress, and interference with daily activities.
Maturation and interhemispheric asymmetry in neurite density and orientation dispersion in early childhood
Authors: Dimond Dennis , Heo Stella , Ip Amanda , Rohr Christiane S. , Tansey Ryann , Graff Kirk , Dhollander Thijs , Smith Robert E. , Lebel Catherine , Dewey Deborah , Connelly Alan , Bray Signe
Published: November 2019

Background

The brain’s white matter undergoes profound changes during early childhood, which are believed to underlie the rapid development of cognitive and behavioral skills during this period. Neurite density, and complexity of axonal projections, have been shown to change across the life span, though changes during early childhood are poorly characterized. Here, we utilize neurite orientation dispersion and density imaging (NODDI) to investigate maturational changes in tract-wise neurite density index (NDI) and orientation dispersion index (ODI) during early childhood. Additionally, we assess hemispheric asymmetry of tract-wise NDI and ODI values, and longitudinal changes.

Methods

Two sets of diffusion weighted images (DWI) with different diffusion-weighting were collected from 125 typically developing children scanned at baseline (N=125; age range=4.14-7.29; F/M=73/52), 6-month (N=8; F/M=8/0), and 12-month (N=52; F/M=39/13) timepoints. NODDI and template-based tractography using constrained spherical deconvolution were utilized to calculate NDI and ODI values for major white matter tracts. Mixed-effects models controlling for sex, handedness, and in-scanner head motion were utilized to assess developmental changes in tract-wise NDI and ODI. Paired t-tests were used to assess interhemispheric differences in tract-wise NDI and ODI values and longitudinal changes in cross-sectional and 12-month longitudinal analyses, respectively.

Results

Maturational increases in NDI were seen in all major white matter tracts, though we did not observe the expected tract-wise pattern of maturational rates (e.g. fast commissural/projection and slow frontal/temporal tract change). ODI did not change significantly with age in any tract. We observed higher cross-sectional NDI and ODI values in the right as compared to the left hemisphere for most tracts, but no hemispheric asymmetry for longitudinal changes.

Conclusions

These findings suggest that neurite density, but not orientation dispersion, increases with age during early childhood. In relation to NDI growth trends reported in infancy and late-childhood, our results suggest that early childhood may be a transitional period for neurite density maturation wherein commissural/projection fibers are approaching maturity, maturation in long range association fibers is increasing, and changes in limbic/frontal fibers remain modest. Rightward asymmetry in NDI and ODI values, but not longitudinal changes, suggests that rightward asymmetry of neurite density and orientation dispersion is established prior to age 4.
Evolution of gastrointestinal tract morphology and plasticity in cave-adapted Mexican tetra, Astyanax mexicanus
Authors: Riddle Misty R. , Damen Fleur , Aspiras Ariel , Tabin Julius A. , McGaugh Suzanne , Tabin Clifford J.
Published: November 2019

The gastrointestinal tract has evolved in numerous ways to allow animals to optimally assimilate energy from different foods. The morphology and physiology of the gut is plastic and can be greatly altered by diet in some animals. In this study, we investigated the evolution and plasticity of gastrointestinal tract morphology by comparing laboratory-raised cave- and river-adapted forms of the Mexican tetra, Astyanax mexicanus, reared under different dietary conditions. In the wild, river-dwelling populations (surface fish) consume plants and insects throughout the year, while cave-dwelling populations (cavefish) live in a perpetually dark environment and depend on nutrient-poor food brought in by bats or seasonal floods. We found that multiple cave populations converged on a reduced number of digestive appendages called pyloric caeca and that some cave populations have a lengthened gut while others have a shortened gut. Moreover, we identified differences in how gut morphology and proliferation respond to diet between surface fish and cavefish. Using a combination of quantitative genetic mapping, population genetics, and RNA sequencing, we found that changes to the molecular and genetic pathways that influence cell proliferation, differentiation, and immune system function may underlie evolution of the cavefish gut.
High-resolution transcriptomic profiling of the heart during chronic stress reveals cellular drivers of cardiac fibrosis and hypertrophy
Authors: McLellan Micheal A. , Skelly Daniel A. , Dona Malathi S.I. , Squiers Galen T. , Farrugia Gabriella E. , Gaynor Taylah L. , Cohen Charles D. , Pandey Raghav , Diep Henry , Vinh Antony , Rosenthal Nadia A. , Pinto Alexander R.
Published: November 2019

Background

Cardiac fibrosis is a key antecedent to many types of cardiac dysfunction including heart failure. Physiological factors leading to cardiac fibrosis have been recognized for decades. However, the specific cellular and molecular mediators that drive cardiac fibrosis, and the relative impact of disparate cell populations on cardiac fibrosis, remain unclear.

Methods

We developed a novel cardiac single-cell transcriptomics strategy to characterize the cardiac cellulome—the network of cells that forms the heart. This method was utilized to profile the cardiac cellular ecosystem in response to two weeks of continuous administration of Angiotensin II, a pro-fibrotic stimulus which drives pathological cardiac remodeling.

Results

This analysis uncovered multiple cell populations contributing to pathological remodeling of the extracellular matrix of the heart. Two phenotypically distinct fibroblast populations emerged after induction of tissue stress to promote fibrosis in the absence of smooth muscle actin-expressing myofibroblasts, a key pro-fibrotic cell population. Further, the cellular responses to Angiotensin II and the relative abundance of fibrogenic cells were sexually dimorphic.

Conclusions

These results offer a valuable resource for exploring the cardiac cellular landscape in health and after chronic cardiovascular stress. These data provide insights into the cellular and molecular mechanisms that promote pathological remodeling of the mammalian heart, highlighting early transcriptional changes which precede chronic cardiac fibrosis.
Integrative Genomic Analysis and Functional Studies Reveal GP5, GRN, MPO and MCAM as Causal Protein Biomarkers for Platelet Traits
Authors: Lee Dong Heon , Yao Chen , Bhan Arunoday , Schlaeger Thorsten , Keefe Joshua , Rodriguez Benjamin AT , Hwang Shih-Jen , Chen Ming-Huei , Levy Daniel , Johnson Andrew D
Published: November 2019

Rationale

Mean platelet volume (MPV) and platelet count (PLT) are platelet measures that have been linked to cardiovascular disease (CVD) and mortality risk. Identifying protein biomarkers for these measures may yield insights into CVD mechanisms.

Objective

We aimed to identify causal protein biomarkers for MPV and PLT among 71 CVD-related plasma proteins measured in Framingham Heart Study (FHS) participants.

Methods and Results

We conducted integrative analyses of genetic variants associated with PLT and MPV with protein quantitative trait locus (pQTL) variants associated with plasma proteins followed by Mendelian randomization (MR) to infer causal relations of proteins for PLT/MPV, and tested protein-PLT/MPV association in FHS participants. Utilizing induced pluripotent stem cell (iPSC)-derived megakaryocyte (MK) clones that produce functional platelets, we conducted RNA-sequencing and analyzed transcriptome-wide differences between low- and high-platelet producing clones. We then performed small interfering RNA (siRNA) gene knockdown experiments targeting genes encoding proteins with putatively causal platelet effects in MK clones to examine effects on platelet production. Protein-trait association analyses were conducted for MPV (n = 4,348) and PLT (n = 4,272). Eleven proteins were associated with MPV and 31 with PLT. MR identified four putatively causal proteins for MPV and four for PLT. Glycoprotein V (GP5), granulin (GRN), and melanoma cell adhesion molecule (MCAM) were associated with PLT in both protein-trait and MR analyses. Myeloperoxidase (MPO) showed significant association with MPV in both analyses. MK RNA-sequencing analysis results were directionally concordant with observed and MR-inferred associations for GP5, GRN, and MCAM. In siRNA gene knockdown experiments, silencing GP5, GRN, and MPO decreased platelet counts.

Conclusions

By integrating population genomics data, epidemiological data, and iPSC-derived MK experiments, we identified four proteins that are causally linked to platelet counts. These proteins and genes may be further explored for their utility in increasing platelet production in bioreactors for transfusion medicine purposes as well as their roles in the pathogenesis of CVD via a platelet/blood coagulation-based mechanism.
Fully Bayesian longitudinal unsupervised learning for the assessment and visualization of AD heterogeneity and progression
Authors: Poulakis Konstantinos , Ferreira Daniel , Pereira Joana B. , Smedby Örjan , Vemuri Prashanthi , Westman Eric ,   for the Alzheimer’s Disease Neuroimaging Initiative
Published: November 2019

Tau pathology and regional brain atrophy are the closest correlate of cognitive decline in Alzheimer’s disease (AD). Understanding heterogeneity and longitudinal progression of brain atrophy during the disease course will play a key role in understanding AD pathogenesis. We propose a framework for longitudinal clustering that: 1) incorporates whole brain data, 2) leverages unequal visits per individual, 3) compares clusters with a control group, 4) allows to study confounding effects, 5) provides clusters visualization, 6) measures clustering uncertainty, all these simultaneously. We used amyloid-β positive AD and negative healthy subjects, three longitudinal sMRI scans (cortical thickness and subcortical volume) over two years. We found 3 distinct longitudinal AD brain atrophy patterns: a typical diffuse pattern (n=34, 47.2%), and 2 atypical patterns: Minimal atrophy (n=23 31.9%) and Hippocampal sparing (n=9, 12.5%). We also identified outliers (n=3, 4.2%) and observations with uncertain classification (n=3, 4.2%). The clusters differed not only in regional distributions of atrophy at baseline, but also longitudinal atrophy progression, age at AD onset, and cognitive decline. A framework for the longitudinal assessment of variability in cohorts with several neuroimaging measures was successfully developed. We believe this framework may aid in disentangling distinct subtypes of AD from disease staging.
Loss of Nuclear Deformability of Breast Cancer Cells by the Disruption of Actin Filaments
Authors: Antmen Ezgi , Demirci Utkan , Hasirci Vasif
Published: November 2019

It is well known that chemical and biomechanical interactions between the nucleus and cytoskeleton are involved in and critical for movement, migration and nuclear positioning of cancer cells. Through nucleo-cytoskeletal coupling, proteins of the LINC complex and the nuclear envelope are capable of transducing cytoplasmic mechanical input across the nuclear membrane; however, their functional importance in the behavior of cancer cells and their nuclei has never been directly tested. In this study, our assumption was that the differences in the malignancies of breast cancer cells are the result of the differences in their nuclear deformation and its expression can be amplified on micropatterned surfaces. Based on this, our hypothesis was that the level of completeness of polymerization of actin filaments can affect nuclear deformability, and as a result, the metastatic capability of the cancer cells. In order to prove this we disrupted the polymerization of the actin filaments by using two drugs, Cytochalasin D and Jasplakinolide, which caused impaired propagation of intracellular forces, prevented nuclear deformation and increased in the expression levels of Lamin A/C and Nesprin-2 in malignant breast cancer cells. Our findings suggest that activity of these two proteins is critical for nucleo-cytoskeletal force transmission. More importantly, actin filament disruption can prevent the distortions in nuclear morphology and as a result avoid the development of cancer metastasis.
TORC1 regulates vacuole membrane composition through ubiquitin- and ESCRT-dependent microautophagy
Authors: Yang Xi , Zhang Weichao , Wen Xin , Bulinski Patrick J. , Chomchai Dominic A. , Arines Felichi Mae , Liu Yun-Yu , Sprenger Simon , Teis David , Klionsky Daniel J. , Li Ming
Published: November 2019

Cellular adaptation in response to nutrient limitation requires the induction of autophagy and lysosome biogenesis for the efficient recycling of macromolecules. Here, we discovered that starvation and TORC1 inactivation not only lead to the upregulation of autophagy and vacuole proteins involved in recycling, but also result in the downregulation of many vacuole membrane proteins to supply amino acids as part of a vacuole remodeling process. Downregulation of vacuole membrane proteins is initiated by ubiquitination, which is accomplished by the coordination of multiple E3 ubiquitin ligases, including Rsp5, the Dsc complex, and a newly characterized E3 ligase, Pib1. The Dsc complex is negatively regulated by TORC1 through the Rim15-Ume6 signaling cascade. After ubiquitination, vacuole membrane proteins are sorted into the lumen for degradation by ESCRT-dependent microautophagy. Thus, our study uncovered a complex relationship between TORC1 inactivation and vacuole biogenesis.
Binary integer programming for Multiple Sequence Alignment
Authors: Ali Lajevardy S. , Kargari Mehrdad
Published: November 2019

Molecular biology advances in the past few decades have contributed to the rapid increase in genome sequencing of various organisms; sequence alignment is usually considered as the first step in understanding the molecular function of a sequence. An optimal alignment adjusts two or more sequences in a way that it could compare the maximum number of identical or similar residues. The two sequence alignments types are: Pairwise Sequence Alignment (PSA) and Multiple Sequence Alignment (MSA). While dynamic programming (DP) technique is used in PSA to provide the optimal method, it will lead to more complexity if used in MSA. So, the MSA mainly uses heuristic and approximation methods. This paper presents a mathematical model for MSA that can be used as a basis for optimal solution in different ways. In order to obtain the results, the model is implemented using Genetic Algorithm method on the web.
Transitional evolutionary forms and stratigraphic trends in chasmosaurine ceratopsid dinosaurs : evidence from the Campanian of New Mexico
Authors: Fowler Denver Warwick , Freedman Fowler Elizabeth Anne
Published: November 2019

Three new chasmosaurines from the Kirtland Formation (∼75.0 - 73.4 Ma), New Mexico, form morphological and stratigraphic intermediates betweenPentaceratops(∼74.7 - 75Ma, Fruitland Formation, New Mexico) andAnchiceratops(∼72 - 71Ma, Horseshoe Canyon Formation, Alberta). The new specimens exhibit gradual enclosure of the parietal embayment that characterizesPentaceratops, providing support for the phylogenetic hypothesis thatPentaceratopsandAnchiceratopsare closely related. This stepwise change of morphologic characters observed in chasmosaurine taxa that do not overlap stratigraphically is supportive of evolution by anagenesis. Recently published hypotheses that placePentaceratopsandAnchiceratopsinto separate clades are not supported. This phylogenetic relationship demonstrates unrestricted movement of large-bodied taxa between hitherto purported northern and southern provinces in the Late Campanian, weakening support for the hypothesis of extreme faunal provincialism in the Late Cretaceous Western Interior.
Apparent increase in lip size is linked to tactile discrimination improvement
Authors: Ambron Elisabetta , Coslett H. Branch
Published: November 2019

Magnified vision of one’s body part has been shown to improve tactile acuity. We used an anesthetic cream (AC) to explore this effect. In Experiment 1, application of AC caused an increase in perceived lip size. As perceived lip size increased, tactile discrimination (as assessed by two-point discrimination) improved. In Experiment 2, we replicated these results in a larger sample and showed that these effects are not observed without AC. Tactile discrimination was better and improved as a function of lip size with AC, while performance remained consistent without AC. In Experiment 3, we showed that the increase in perceived lip size occurred only with the application of AC, but not with moisturizing cream. The application of either cream induced an improvement in two-point discrimination, but this improvement was modulated by perceived lip size only for AC. Magnification effects are mediated by malleable, experience-dependent representations of the human body.
Effect of sinusoidal electrical cortical stimulation on brain cells
Authors: Ryu Seungjun , Kim Kyung-Tai , Seo Hyeon , Cho Jongwook , Park Jiyoung , Jun Sung Chan , Kim Hyoung-Ihl
Published: November 2019

Background

Electrical cortical stimulation is often used in patients with neurological disorders but it is unclear how it modulates different types of brain cells.

Objective

The aim of this study was to determine the effect of sinusoidal electrical brain stimulation (SEBS) on different types of brain cells and to identify the exact types of brain cells that are stimulated.

Methods

The study subjects were 40 male Sprague Dawley rats (weight 300–350 g; age 9 weeks). SEBS was delivered continuously at frequencies of 20, 40, 60, or 100 Hz to the sensory parietal cortex using epidurally placed electrodes for 1 week. Transverse rat brain tissue sections were immunolabeled with calmodulin-dependent protein kinase II and parvalbumin (PV) antibodies and with c-Fos for counting of activated excitatory and inhibitory neurons. Computer simulation was performed to cross-validate the frequency-specific cell stimulation results.

Results

Inhibitory neurons were more excited than excitatory neurons after epidural EBS. Most excitatory neural activity was evoked at 40 Hz (p<0.05) and most inhibitory neuronal activity was evoked at 20 Hz (p<0.01). The contralateral sensory cortex was activated significantly more at 40 Hz (p<0.05) and the corticothalamic circuit at 20 Hz (p<0.001). Stimulation-induced excitatory and inhibitory neuronal activation was widest at 20 Hz.

Conclusions

Epidural electrical stimulation targets both excitatory and inhibitory neurons and the related neural circuits. Further exploration is needed to identify circuits that promote the plasticity needed for recovery in patients with specific neurological diseases.

Graphical Abstract
Concepts of quality in independent accreditation in Kyrgyzstan
Authors: Ryskulova Chynarkul
Published: November 2019

Purpose

The purpose of this paper is to explore the concept, criteria and definitions of quality of higher education from the perspectives of the leadership of three new independent accreditation agencies in Kyrgyzstan.

Design/methodology/approach

The author employed interpretative qualitative research design. The data for this study were collected through semi-structured interviews with the leadership of three independent accreditation agencies and through review and the qualitative analyses of new policies on accreditation of higher education institutions, new accreditation standards and criteria. A priori codes by using categories were defined in advance and emergent codes based on data driven were used for data analyses.

Findings

The research findings support the author’s argument that the new independent accreditation processes will not assure quality because first, the agencies are not independent of the Ministry of Education and Science; second, the current standards do not provide evidence of quality; and third, the institutions do not have what in Europe is called a “quality culture” – ongoing, continuous efforts toward quality.

Originality/value

This is first scholarly work looking at independent accreditation process at its beginning stage. The results of an article can have influence on further development of accreditation system and improvement of accreditation standards.
Self-reported experiences of intimate partner violence in a female forensic intellectual disability population
Authors: Morris Deborah , Camden-Smith Claudia , Batten Robert
Published: November 2019

Purpose

Intimate partner violence (IPV) is a complex public health and social issue. Women with an intellectual disability (ID) are at greater risk of experiencing IPV. However, little is known about the IPV experiences of women with an ID and forensic care needs. The purpose of this paper is to explore the history of experienced and perpetrated IPV in women detained to secure specialist ID forensic service.

Design/methodology/approach

Participants completed the Conflict Tactics Scale-2 (CTS-2, Straus et al., 1996). The CTS-2 measures experienced and perpetrated relationship tactics of common forms of IPV.

Findings

Participants reported high levels of experiencing and perpetrating IPV across all relationship tactics measured by the CTS-2. Participants reported they engaged in similar levels of experiencing and perpetrating positive and negative relationship tactics. The only significant difference was “minor sexual coercive behavior” where participants were significantly more likely to experience than perpetrate this behaviour.

Research limitations/implications

Further research exploring the risk factors that contribute to IPV is needed. Shortcomings in the current study are acknowledged.

Practical implications

Women with an ID and forensic profiles may present with treatment needs as victims and perpetrators of IPV. Clinical activities of women in Forensic ID services should include possible IPV care needs. The importance of developing national guidance and interventions to prevent and manage IPV are discussed.

Originality/value

This is the first paper, to the authors’ knowledge, to explore experiences of IPV in women with an ID and forensic care needs.
Active vibration control of flexible-joint manipulators using accelerometers
Authors: Zhao Pu , Zhou Yunfei
Published: November 2019

Purpose

Manipulators are often subjected to joint flexibility caused by various causes in industrial applications, such as shaft windup, harmonic drives and bearing deformation. However, many industrial robots are only equipped with motor-side encoders because link-side encoders and torque transducers are expensive. Because of joint flexibility and resulted slow response rate, control performance of these manipulators is very limited. Based on this, the purpose of this paper is to use easy-to-install and cheap accelerometers to improve control performance of such manipulators.

Design/methodology/approach

First, a novel tip-acceleration feedback method is proposed to avoid amplifications of approximation errors caused by inversion of the Jacobian matrix. Then, a new control scheme, consisting an artificial neural network, a proportional-derivative (PD) controller and a reference model, is proposed to track motor-side position and suppress link-side vibration.

Findings

By using the proposed tip-acceleration feedback method, each link’s vibration can be suppressed correlatively. Through the networks, smaller motor-side tracking errors can be obtained and unknown dynamics can be compensated. Tracking and convergence performance of the network-based system can be improved by using the additional PD controller.

Originality/value

The originality is based on using accelerometers to improve link-side vibration suppression and control performance of flexible-joint manipulators. The previously used methods need expensive link-side sensors or accurate robot model, which is unavailable for many industrial robots only equipped with motor-side encoders. The report proposed a novel acceleration feedback method and used networks to solve such problems.
A proposed model for sustainable business excellence
Authors: Jabnoun Naceur
Published: November 2019

Purpose

The purpose of this paper is to develop an excellence model that combines noble ends and noble means to achieve sustainable business excellence (SBE).

Design/methodology/approach

The general framework of existing excellence models is used to develop the new model. Relevant literature on business excellence and current business and economic trends such as constructive capitalism, conscious capitalism, shared value, values-driven organizations and corporate governance are used to develop the basic concepts of the model. The criteria and the assessment method of the model are then developed based on the basic concepts.

Findings

This paper proposes a model for SBE. This model is aligned with conscious capitalism, constructive capitalism, shared value, values-driven organizations and corporate governance. The paper includes a comparison between this model and the most popular excellence models.

Research limitations/implications

This paper paves the way for more empirical and theoretical research on stakeholders’ business excellence models.

Practical implications

This model can be adopted by different national and international excellence awards. The adoption of this model can improve the benefits of shareholders, partners, customers, employees and the society at large. Implementing this model may be effective in transferring knowledge about conscious capitalism, values-driven organization and corporate governance to corporations worldwide.

Social implications

This may contribute to protecting the environment and reducing economic inequalities that have caused political and social instability.

Originality/value

Excellence models have been widely used with significant success all over the world. Although these models paid attention to customers and employees, they still reflect traditional capitalism that focuses on shareholders’ value. This model is aligned to new economic trends that foster sustainability and improve benefits of all stakeholders.