bluuebunny/crossref_metadata_2025 huggingface dataset:
C-Reactive Protein Predicts Risk of Venous Thromboembolism in Pediatric Musculoskeletal Infection
Authors: Amaro Emilie , Marvi Tanya K. , Posey Samuel L. , Benvenuti Michael A. , An Thomas J. , Dale Kevin M. , Lovejoy Steven A. , Martus Jeffrey E. , Johnson Megan E. , Mencio Gregory A. , Moore-Lotridge Stephanie N. , Thomsen Isaac P. , Schoenecker Jonathan G.
Published: October 2018

Background:

The rate of venous thromboembolism in children with musculoskeletal infections (MSKIs) is markedly elevated compared with hospitalized children in general. Predictive biomarkers to identify high-risk patients are needed to prevent the significant morbidity and rare mortality associated with thrombotic complications. We hypothesize that overactivation of the acute phase response is associated with the development of pathologic thrombi and we aim to determine whether elevations in C-reactive protein (CRP) are associated with increased rates of thrombosis in pediatric patients with MSKI.

Methods:

A retrospective cohort study measuring CRP in pediatric MSKI patients with or without thrombotic complications.

Results:

The magnitude and duration of elevation in CRP values correlated with the severity of infection and the development of pathologic thrombosis. In multivariable logistic regression, every 20 mg/L increase in peak CRP was associated with a 29% increased risk of thrombosis (P<0.001). Peak and total CRP were strong predictors of thrombosis with area under the receiver-operator curves of 0.90 and 0.92, respectively.

Conclusions:

Future prospective studies are warranted to further define the discriminatory power of CRP in predicting infection-provoked thrombosis. Pharmacologic prophylaxis and increased surveillance should be strongly considered in patients with MSKI, particularly those with disseminated disease and marked elevation of CRP.

Level of Evidence:

Level III.
Persistence and Progression of Airway Obstruction in Children With Early Onset Scoliosis
Authors: Redding Gregory J. , Hurn Heidi , White Klane K. , Bompadre Viviana , Emerson Julia , Garza R. Zachary , Anigian Kendall , Waldhausen John , Krengel Walter , Joshi Ajeya
Published: October 2018

Background:

Obstructive lung disease occurs in 30% of children with early onset scoliosis (EOS); changes in degree of airway obstruction over time have not been reported.

Methods:

Longitudinal patterns of incidental, persistent, and progressive airway obstruction were retrospectively analyzed in a cohort of children with EOS with at least 1 forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) value <85% on serial spirometric assessments over a ≥3-year observation period. The prevalence of clinical features and the severity of coronal and sagittal spine deformities for each group at the beginning and end of the study period were compared.

Results:

Airway obstruction was incidental in 12 (24%) and persistent in 37 (76%) of 49 children with EOS. Twenty of 37 (54%) of those with persistent obstruction developed progressive airway obstruction. The decline in FEV1/FVC over 6±2 years was insignificant in the incidental group (4%±2%) and the persistent nonprogressive group (7%±4%) but significant in the progressive group (13%±4%, t test; P=0.002). In total, 29% of the 49 children at the onset and 57% at the end of the study had airway obstruction. The incidental, persistent nonprogressive, and progressive groups did not differ with regard to age, diagnosis distribution, or sex. The initial coronal curve size, apex, direction of the curve, and degree of kyphosis were statistically similar among the 3 groups. Coronal curve magnitude inversely correlated with FEV1/FVC at the end but not the beginning of the study (r=−0.19, P=0.002). Six of 19 responded to bronchodilator treatment, suggesting concurrent asthma. Airway obstruction did not relate to restrictive pulmonary abnormalities measured by FVC at first or last timepoints [slope=−0.076 (95% confidence interval, −0.99 to 0.038; P=0.19)]. Changes in degrees of airway obstruction and restrictive lung disease over time did not correlate [slope=−0.125 (95% confidence interval, −0.294 to 0.044; P=0.14)].

Conclusions:

Children with EOS and progressive airway obstruction represent an important subgroup which may require new surgical and nonsurgical treatment strategies to prevent loss of lung function over time.
Factors Associated With Head and Neck Cancer Hospitalization Cost and Length of Stay—A National Study
Authors: Adjei Boakye Eric , Johnston Kenton J. , Moulin Thiago A. , Buchanan Paula M. , Hinyard Leslie , Tobo Betelihem B. , Massa Sean T. , Osazuwa-Peters Nosayaba
Published: October 2018

Objectives:

The aim of the study was to estimate hospitalization cost, and factors associated with hospitalization costs and length of stay (LOS) of patients treated for head and neck cancer in the United States.

Methods:

Data on 71,440 weighted hospital admissions from the 2014 National Inpatient Sample with a diagnosis of head and neck cancer were examined. Multivariable linear regression models estimated factors associated with hospitalization costs, and negative binomial regression models were used to identify factors associated with hospital LOS. Factor variables included characteristics of the patient, clinical, and hospital characteristics.

Results:

The average hospitalization cost was US $18,371 and the average LOS was 6.6 days. LOS was significantly associated with admissions involving bacterial infection, major operating procedures, chemo procedure, and radiation procedure as well as admissions at medium or small bed size hospitals, and rural hospitals. Admissions among black patients, elective admissions, admissions involving bacterial infection, major operating procedures, chemo procedure, radiation procedure, and advance comorbidities were associated with increased hospitalization costs. In contrast, admissions at urban nonteaching or rural had increased hospitalization costs.

Conclusions:

Admissions that involve higher number of comorbidities, metastasis, bacterial infection, radiation, and chemo procedures had longer hospital stay and higher cost whereas admissions are rural hospitals had shorter hospital stay and lower cost. Understanding these factors associated with increased LOS and hospitalization cost will help efforts to decrease health care cost and improve quality of care.
COMPARISON BETWEEN RELEASABLE SCLERAL BUCKLING AND VITRECTOMY IN PATIENTS WITH PHAKIC PRIMARY RHEGMATOGENOUS RETINAL DETACHMENT
Authors: Zhao Xiujuan , Huang Li , Lyu Cancan , Liu Bingqian , Ma Wei , Deng Xiaoyan , Jiang Huaiyan , Wang Yan , Yu Xiling , Ding Xiaoyan , Luo Yan , Ma Jin , Stewart Jay M. , Liang Xiaoling , Jin Chenjin , Lu Lin
Published: October 2018

Purpose:

To compare the efficiency of releasable scleral buckling (RSB) and pars plana vitrectomy (PPV) in the treatment of phakic patients with primary rhegmatogenous retinal detachment.

Methods:

The current study was a prospective randomized clinical trial. One hundred and ten eyes from 110 patients with primary rhegmatogenous retinal detachment and proliferative vitreoretinopathy of Grade B or less were included in this study. The patients were randomly allocated into an RSB group and a PPV group. The functional and anatomical success was compared between groups.

Results:

The primary anatomical success rate (PPV 41/43 [95.35%] and RSB 38/41 [92.68%]) and final anatomical success rate (PPV and RSB 100%) showed a nonsignificant difference. The best-corrected visual acuity, intraocular pressure, and complications were not different between the groups. However, the incidence of cataract progression was higher in the PPV group (26 of 43 [60.47%]) than in the RSB group (4 of 41 [9.76%]) at the 12-month follow-up. The subfoveal choroidal thickness increased significantly in the RSB group 3 months after surgery, but no longer differed at the postoperative 6-month and 12-month follow-ups. The axial length had increased significantly 1 month after surgery, but the difference was no longer significant at 3 months, 6 months, and 12 months.

Conclusion:

The RSB and PPV procedures have the same effects on the functional and anatomical success for patients with phakic primary rhegmatogenous retinal detachment. Nevertheless, based on the few cases of intraocular complications and cataract progression, we believe that the RSB technique should be preferentially recommended.
Impact of Head Tilt on Optical Coherence Tomography Image Orientation
Authors: Mohammad Syed , Jarrar Faisal S. , Torres Lucas A. , Sharpe Glen P. , Vianna Jayme R. , Chauhan Balwantray C.
Published: October 2018

Purpose:

Head tilt can have an impact on the orientation of posterior pole images. We conducted this study to determine the effect of head tilt on image orientation measured by the fovea-Bruch’s membrane opening (FoBMO) angle with optical coherence tomography (OCT) imaging.

Methods:

The study included 56 healthy subjects with mean (range) age of 33 (18 to 61) years. The dominant eye was first determined. To measure head tilt, a smartphone with a built-in gyroscope was affixed to the subject’s head with adjustable straps. OCT imaging was performed in both eyes (in randomized order) at 0, 5, and 10 degrees of head tilt in the direction of the imaged eye (ipsilateral head tilt), and then in the opposite direction (contralateral head tilt). For each image, the device software determined Bruch’s membrane opening center and the foveal pit from which the FoBMO angle was derived.

Results:

Thirty-eight (68%) subjects were right eye dominant and 18 (32%) were left eye dominant. Each 1 degree head tilt resulted in a mean change of 0.76 degree in the FoBMO angle (P<0.01), with no significant difference in effect between the 2 eyes (P=0.72). The magnitude of the effect increased from 5 to 10 degrees, and was similar for both ipsilateral and contralateral head tilt. Ocular dominance did not modulate the effect of head tilt (P=0.42).

Conclusions:

Head tilt significantly affects OCT image orientation as measured by the FoBMO angle, presumably because cyclotorsion is not fully compensatory. The magnitude and direction of the effect does not depend on the dominant eye.
Fecal calprotectin is not superior to serum C-reactive protein or the Harvey–Bradshaw index in predicting postoperative endoscopic recurrence in Crohn’s disease
Authors: Verdejo Cristina , Hervías Daniel , Roncero Óscar , Arias Ángel , Bouhmidi Abdelmouneim , Lorente Rufo , Salueña Irina , Lucendo Alfredo J.
Published: October 2018

Background

Fecal calprotectin (FC) is a widely used noninvasive marker of gut inflammation that is associated with endoscopic severity in Crohn’s disease (CD). However, FC has been inconsistent in predicting postoperative recurrence of CD, and its utility in the postoperative setting remains unclear.

Materials and methods

Blood and fecal samples were collected in consecutively recruited patients with CD who had undergone ileocolonic resection and required a colonoscopy to assess postoperative recurrence, as defined by the Rutgeerts score (RS).

Results

A total of 86 patients were prospectively recruited at five centers. Overall, 49 (57%) had CD recurrence (RS≥i2). FC concentrations trended to increase with RS severity; FC median (interquartile range) was significantly higher in patients with endoscopic recurrence than those in endoscopic remission [172.5 (75–375) vs. 75 (36.5–180.5) μg/g, respectively]. The same occurred for C-reactive protein (CRP) [0.5 (0.1–0.95) vs. 0.1 (0.02–0.27)] mg/dl and the Harvey–Bradshaw index (HBI) [4 (2–7) vs. 1 (0–3.5)]. The three variables significantly correlated. The area under the curve to discriminate between patients in endoscopic remission and recurrence was 0.698 for FC, with 62 μg/g being the optimal cut-off point. This indicated FC would have 85.7% sensitivity and 45.9% specificity in detecting any recurrence, having positive predictive value and negative predictive value of 67.7 and 70.8%, respectively. Area under the curve for CRP and HBI were both 0.710. The combination of CRP and HBI provided a positive predictive value 95.7 and a diagnostic odds ratio of 30.8.

Conclusion

FC is not better than CRP combined with HBI to predict endoscopic postoperative recurrence of CD.
A Stimulus-Response Framework to Investigate the Influence of Continuous Versus Interval Walking Exercise on Select Serum Biomarkers in Knee Osteoarthritis
Authors: Jayabalan Prakash , Gustafson Jonathan , Sowa Gwendolyn A. , Piva Sara R. , Farrokhi Shawn
Published: October 2018

Objective

The aim of the study was to compare changes in the concentration of serum biomarkers in response to continuous versus interval walking exercise in participants with knee osteoarthritis.

Design

This study used a two-phase sequential design. Twenty-seven participants with unilateral knee osteoarthritis completed two separate treadmill walking sessions: (1) continuous 45-min walking exercise and (2) three 15-min bouts of walking exercise separated by 1-hr rest periods for a total of 45 mins in an interval format. Participants reported their knee pain using the numeric pain rating scale and serum levels of biomarkers associated with tissue turnover (cartilage oligomeric matrix protein), inflammation (tumor necrosis factor α), and pain (neuropeptide Y) were evaluated at baseline and every 15 mins for both conditions.

Results

Continuous walking resulted in a cumulative increase in cartilage oligomeric matrix protein concentration up to 45 mins, whereas interval walking was associated with return of cartilage oligomeric matrix protein concentrations back to baseline at 45 mins. There were no significant changes in tumor necrosis factor α and neuropeptide Y concentration during walking. There was a significant increase in pain compared with baseline in the continuous walking regimen only.

Conclusions

Incorporating rest breaks in walking regimens may affect the potential deleterious effects of longer continuous bouts on the knee joint as well as limit pain during exercise.
Endometrioid Intraepithelial Neoplasia
Authors: Chiu Yu-Li , Wang Jyh-Seng , Peng Nan-Jing
Published: October 2018

The report describes a 55-year-old woman with postmenopausal abnormal vaginal spotting. PET/CT revealed focal hot 18F-FDG uptake in the fundus portion of the uterine cavity, and pathology of hysteroscopic dilation and curettage showed endometrioid intraepithelial neoplasia of uterine endometrium, an endometrial precancer. This case points to the significance of 18F-FDG PET/CT in determining the dilation and curettage site for the postmenopausal women with abnormal vaginal spotting. Increased 18F-FDG activity in the region of the uterus must be investigated to determine the possibilities of primary malignancies, metastases, and benign diseases.
Quality and Safety in Healthcare, Part XLVII
Authors: Harolds Jay A.
Published: October 2018

The ability to come back from challenges such as the many factors predisposing to burnout is resilience. Individual strategies to prevent and recover from burnout can be learned and practiced. This includes mindfulness, meditation, yoga, various stress reduction techniques, coaching, counseling, mentoring, discussions in small groups, workshops, and better work life balance. Other approaches include building a support network, taking care of one’s personal health, pursuing narrative medicine, engaging in reflection, emphasizing positive psychology approaches including learned optimism, encouraging a growth mindset, and volunteering. This article will focus on the topic of resilience as it is related to burnout, and subsequent articles will discuss some of the strategies for prevention and recovery in detail.
Hypermetabolism Caused by Seizure Mimicking Tumor Recurrence
Authors: Wang Jingnan , Zhang Yiwei , Sun Heyang , Cui Ruixue
Published: October 2018

A 41-year-old man had a right frontal grade I glioma resection 17 years ago. He was tumor free since. However, 1 month ago, he presented with an uncontrollable seizure, which raised the possibility of recurrent tumor. The 18FDG PET/CT brain scan showed increased tracer uptake at the margin of the previous resected tumor, suggesting the possibility of tumor recurrence. However, on a repeat FDG PET brain scan confirmed by electroencephalography monitory as an interictal study, no elevated FDG uptake was revealed at this site. These results indicate that the elevated 18F-FDG activity on the original study was a result of seizure.
Assessment of Subclinical Atherosclerosis in Vitamin D Deficiency
Authors: Aydin Elçin , Altin Cihan , Özcan Söylev Gözde , Tekindal Mustafa Agah , Ağildere Muhteşem
Published: October 2018

Purpose

Patients with vitamin D deficiency (VDD) have potential to have increased cardiovascular morbidity and mortality. In this study, we aimed to discover the findings of early atherosclerosis in patients with VDD by measuring carotid intima-media thickness (CIMT) and epicardial fat thickness (EFT).

Materials and Methods

The study population includes 52 patients with VDD (n = 30 [57% female], mean ± SD age 54.28 ± 8.77 years, mean ± SD serum 25-hydroxyvitamin D (25 [OH] D) 11 ± 2.4 ng/mL) and 82 participants for control group (n = 52 [63.4% female], mean ± SD age 56.40 ± 7.90 years, mean ± SD serum (25 [OH] D) 53 ± 4.2 ng/mL) who have no cardiovascular disease. Carotid intima-media thickness was assessed by using ultrasonography, and EFT was measured on the free wall of the right ventricle at end diastole from the parasternal long-axis views by standard transthoracic 2-dimensional echocardiography.

Results

Both CIMT and EFT were significantly higher in patients with VDD compared with controls (0.75 ± 0.16 mm vs 0.68 ± 0.21 mm, P < 0.05, and 0.66 ± 0.15 cm vs 0.56 ± 0.15 cm, P < 0.001).

Conclusions

Patients with VDD seem to have increased CIMT and EFT, which are predictors of atherosclerotic process. Further studies are needed to confirm these results.
Cross-sectional Area Just Proximal to the Carpal Tunnel According to the Ulnar Variances
Authors: Cha Soo Min , Shin Hyun Dae , Song Seok Hwan
Published: October 2018

Purpose

We evaluated the relationship between the area around the distal radioulnar joint according to the ulnar variances and the cross-sectional area using magnetic resonance imaging (MRI) scans in this prospective study of patients with carpal tunnel syndrome (CTS).

Methods

From among a total of 243 patients who had been diagnosed with CTS between March 2012 and February 2017 at our hospital, 41 patients with positive ulnar variance were enrolled in group 1. As control groups, 39 healthy volunteers who underwent MRI evaluations were included in group 2 (neutral ulnar variance) and group 3 (negative variance). Basic demographic data, including age, sex, and body mass index, were recorded for all 3 groups. An area encompassing the contents of carpal tunnel (nerves/tendons) was designated as area “A,” and the area just beneath the subcutaneous fat was designated as area “B” at the levels of the lunate (L) and pisiform (P) on axial MRI. Ratios of these areas (“A/B at L” and “A/B at P”) were evaluated in terms of their correlations with ulnar variance.

Results

Mean age, sex, and body mass index were not statistically different among the groups, respectively. Within each group, there was no difference between “A/B at L” and “A/B at P,” respectively. When comparing the 3 groups, “A/B at L” and “A/B at P” were all significantly decreased in group 1 than in other groups. Regardless of the group, ulnar length negatively correlated with both “A/B at L” and “A/B at P” ratios.

Conclusions

We found a positive relationship between decreased cross-sectional area around the distal radioulnar joint and positive ulnar variance on radiologic investigation. These findings show the importance of variance in the positive ulna variance to the development of CTS.
Maternal Tobacco Exposure and Development of Orofacial Clefts in the Child
Authors: Bui Anthony H. , Ayub Ayisha , Ahmed Mairaj K. , Taioli Emanuela , Taub Peter J.
Published: October 2018

Introduction

The purpose of this study was to evaluate the association between maternal tobacco exposure and development of orofacial clefts (OFCs) in the child in a Pakistani population.

Methods

A case-control study was conducted at the Cleft Hospital and Bashir Hospital in Gujrat, Pakistan, from December 2015 to December 2016. All new cases of OFC at the Cleft Hospital were included. Patients at Bashir Hospital younger than 3 years and without congenital malformations were selected as control subjects. Risk factors associated with OFC were identified through bivariate analyses. Multiple logistic regression was then performed to calculate adjusted odds ratios (ORs) of developing OFC according to various risk factors.

Results

The study included 297 patients with OFC and 131 control subjects. Upon univariable analysis, the following were associated with OFC: maternal tobacco exposure (P< 0.001), complications during pregnancy (P< 0.001), maternal hypertension (P= 0.01), mother not on physician-recommended medications (P< 0.001), mother not receiving vaccinations (P< 0.001), consanguineous marriage (P< 0.001), and lower socioeconomic status (P< 0.001). Upon multivariable analysis, having a smoking parent (OR, 1.89; 95% confidence interval [CI], 1.10–3.26), complications during pregnancy (OR, 2.36; 95% CI, 1.43–3.88), and consanguineous marriage (OR, 1.79; 95% CI, 1.13–2.85) were associated with increased odds of development of OFC; receiving vaccinations (OR, 0.31; 95% CI, 0.16–0.63) and higher socioeconomic status (OR, 0.20; 95% CI, 0.05–0.74) were protective.

Conclusions

Patients with OFC were nearly twice as likely to have a parent who smokes as those without. Efforts to reduce tobacco consumption among prospective parents, such as perinatal tobacco cessation counseling programs, should be evaluated in this population.
Complete Jejunal Transection After Blunt Abdominal Trauma: A Case Report
Authors: Kuchen Natalie , Gmuer Christian , Schoeb Othmar
Published: October 2018

Introduction:

Isolated complete transection of the small bowel is extremely rare in blunt abdominal trauma. If it occurs, it is often associated with high-energy impact, as seen in motor vehicle accidents and falls from heights. In this case, a trivial trauma due to a handlebar injury caused a complete transection of the middle jejunum.

Case Presentation:

A 47-year-old man walked into the emergency department with moderate abdominal pain ∼10 hours after a fall on to a bicycle’s handlebar from a standing position. A bedside ultrasound showed minimal amount of free fluid and a following performed computed tomographic scan indicated an edematous loop of small bowel with diminutive amount of extraluminal air, suggesting small bowel perforation. Because of the absence of abdominal peritonism in a hemodynamically stable patient, a conservative treatment and surveillance was established. In the follow-up, the patient suddenly developed severe abdominal pain with now clear signs of peritonism. An emergency laparoscopy showed a complete transection of the middle jejunum. A primary anastomosis was performed. The patient had an uneventful recovery and was discharged after 7 days.

Conclusions:

Even seemingly trivial blunt abdominal traumas can cause complete transection of the small bowel, as shown in this case. Patients with blunt abdominal trauma need to be reviewed frequently by an experienced clinician. Diagnostic laparoscopy attaches a great importance to early detection and treatment of small bowel injuries. The mechanical pattern of the injury seems to be more important than the energy of the impact itself.
Is Prophylactic Steroid Treatment Mandatory for Subclinical Cushing Syndrome After Unilateral Laparoscopic Adrenalectomy?
Authors: Wang Dong , Li Han-zhong , Zhang Yu-shi , Wang Liang , Ji Zhi-gang
Published: October 2018

Objective:

This study aimed to provide rational guidelines for patients with subclinical Cushing syndrome (SCS), who are undergoing laparoscopic adrenalectomy, in order to avoid the risk of overtreatment.

Methods:

A total of 59 patients diagnosed with SCS caused by unilateral adrenal adenoma, who underwent laparoscopic adrenalectomy from 2010 to 2017, were included into the study. These patients did not receive prophylactic steroid treatment. After discharge, patients with adrenal insufficiency (AI) were treated with glucocorticoid. Then, cortisol levels were reevaluated at three months after surgery by morning serum cortisol.

Results:

No severe perioperative complications occurred. After unilateral laparoscopic adrenalectomy, no patient developed AI and was readmitted. In the first week after surgery, 10 patients (16.9%) received steroid therapy at the clinic because of mild symptoms of AI. The probability of developing AI was greater in patients with 1-mg dexamethasone midnight suppression test (1 mg-DST) >5 μg/dL than patients with mg-DST ranging within 1.8 to 5.0 μg/dL (P=0.042). The initial dose of hydrocortisone was 20.00±6.67 mg/d (range, 10 to 30), and the duration of treatment was 6.90±3.51 weeks (range, 3 to 12 wk). At three months after surgery, morning cortisol was >5 μg/dL in all patients.

Conclusions:

After laparoscopic adrenalectomy, the probability of AI is small in patients with adrenal SCS, and the symptoms of AI were mild. Meanwhile, the HPA axis rapidly recovered. Therefore, prophylactic steroid treatment is not mandatory. Given that AI is more frequent in patients with higher cut-offs of 1 mg-DST, a more precise definition of SCS is necessary to better manage these patients.
Importance of Hematopoietic Mixed Chimerism for Induction of Renal Allograft Tolerance in Nonhuman Primates
Authors: Thaiss Cornelius C. , Oura Tetsu , Sasaki Hajime , Dehnadi Abbas , Matsunami Masatoshi , Rosales Ivy A. , Cosimi A. Benedict , Kawai Tatsuo
Published: October 2018

Background.

Although induction of durable mixed chimerism is required for murine skin allograft tolerance (TOL), renal allograft TOL has been achieved after induction of only transient mixed chimerism in nonhuman primates (NHPs) and humans. To better define the level/duration of chimerism required for stable renal allograft TOL, we retrospectively analyzed these parameters and compared them with transplant outcomes in NHP combined kidney and bone marrow transplant recipients.

Methods.

Peripheral blood levels and duration of myeloid or lymphoid chimerism were retrospectively analyzed in 34 NHP combined kidney and bone marrow transplantation recipients which were divided into 3 groups: TOL, n = 10; chronic antibody-mediated rejection (CAMR), n = 12; and T cell-mediated rejection (TCMR), n = 12.

Results.

All 4 of the recipients that failed to develop any chimerism lost their allografts due to TCMR after discontinuation of immunosuppression (56 ± 3 d). Among 30 recipients who successfully developed multilineage chimerism, 10 achieved long-term immunosuppression-free survival without rejection (1258 ± 388 d), 12 eventually developed CAMR (932 ± 155 d), and 8 developed TCMR (82 ± 10 d). The maximum level but not duration of lymphoid chimerism was significantly higher in TOL recipients compared with both CAMR (P = 0.0159) and TCMR (P = 0.0074). On the other hand, the maximum myeloid chimerism was significantly higher in TOL than in TCMR (P = 0.0469), but not in CAMR. Receiver operating characteristic analyses revealed that lymphoid chimerism levels of 3.1% or greater could reliably predict long-term immunosuppression-free renal allograft survival (P < 0.0001).

Conclusions.

This retrospective study confirmed that induction of chimerism is essential for long-term immunosuppression-free survival, which best correlates with lymphoid chimerism levels higher than 3.1%.
Urinary TIMP-2 Predicts the Presence and Duration of Delayed Graft Function in Donation After Circulatory Death Kidney Transplant Recipients
Authors: Bank Jonna R. , Ruhaak Renée , Soonawala Darius , Mayboroda Oleg , Romijn Fred P. , van Kooten Cees , Cobbaert Christa M. , de Fijter Johan W.
Published: October 2018

Background.

Urinary tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor binding protein-7 (IGFBP7) have been validated as biomarkers for acute kidney injury. We investigated the performance of both markers in predicting the occurrence and duration of functionally defined delayed graft function (fDGF) in donation after circulatory death (DCD) kidney transplant recipients.

Methods.

Urine samples of 74 DCD recipients were analyzed. TIMP-2 and IGFBP7 were measured with ELISA on postoperative days 1 to 7, day 10, week 6, and month 6, and values were corrected for osmolality (mOsm). Immunosuppression consisted of anti-CD25 antibody induction and triple maintenance therapy (steroids, mycophenolate mofetil, and calcineurin inhibitor). Statistical analysis included receiver operating characteristic curves and multivariate logistic regression.

Results.

Fifty-one (69%) renal transplant recipients had fDGF, of which 14 experienced prolonged fDGF (≥21 days). TIMP-2/mOsm on day-1 and day-10 adequately identified patients with fDGF (area under the curve [AUC], 0.91) and prolonged fDGF (AUC, 0.80), respectively, whereas IGFBP7/mOsm did not (AUC, 0.63 and 0.60). Multivariate analysis on day 1 identified 24-hour urinary creatinine excretion and TIMP-2/mOsm as significant predictors of fDGF (AUC, 0.90, 95% confidence interval, 0.80-0.98). The best predictors of prolonged fDGF on day 10 were 24-hour urinary creatinine excretion, TIMP-2/mOsm, and total warm ischemia time with an AUC of 0.85 (95% confidence interval, 0.72-0.95). Consecutive TIMP-2/mOsm values showed a decrease in TIMP-2/mOsm before an increase in estimated glomerular filtration rate, enabling us to monitor fDGF and predict resolution of fDGF.

Conclusions.

Urinary TIMP-2, but not IGFBP7, is a promising biomarker to predict the occurrence and duration of fDGF in DCD kidney transplant recipients.
Genetic and Epigenetic Fine Mapping of Complex Trait Associated Loci in the Human Liver
Authors: Çalışkan Minal , Manduchi Elisabetta , Rao H. Shanker , Segert Julian A , Beltrame Marcia Holsbach , Trizzino Marco , Park YoSon , Baker Samuel W , Chesi Alessandra , Johnson Matthew E , Hodge Kenyaita M , Leonard Michelle E , Loza Baoli , Xin Dong , Berrido Andrea M , Hand Nicholas J , Bauer Robert C , Wells Andrew D , Olthoff Kim M , Shaked Abraham , Rader Daniel J , Grant Struan FA , Brown Christopher D
Published: October 2018

Deciphering the impact of genetic variation on gene regulation is fundamental to understanding common, complex human diseases. Although histone modifications are important markers of gene regulatory regions of the genome, any specific histone modification has not been assayed in more than a few individuals in the human liver. As a result, the impacts of genetic variation that direct histone modification states in the liver are poorly understood. Here, we generate the most comprehensive genome-wide dataset of two epigenetic marks, H3K4me3 and H3K27ac, and annotate thousands of putative regulatory elements in the human liver. We integrate these findings with genome-wide gene expression data collected from the same human liver tissues and high-resolution promoter-focused chromatin interaction maps collected from human liver-derived HepG2 cells. We demonstrate widespread functional consequences of natural genetic variation on putative regulatory element activity and gene expression levels. Leveraging these extensive datasets, we fine-map a total of 77 GWAS loci that have been associated with at least one complex phenotype. Our results contribute to the repertoire of genes and regulatory mechanisms governing complex disease development and further the basic understanding of genetic and epigenetic regulation of gene expression in the human liver tissue.
Managing the Spatial Covariance of Genetic Diversity in Niemann-Pick C1 Through Modulation of the Hsp70 Chaperone System
Authors: Wang Chao , Scott Samantha M , Hutt Darren M , Zhao Pei , Shao Hao , Gestwicki Jason E , William E Balch
Published: October 2018

Genetic diversity provides a rich repository for understanding the role of proteostasis in the management of the protein fold to allow biology to evolve through variation in the population and in response to the environment. Failure in proteostasis can trigger multiple disease states affecting both human health and lifespan. Niemann-Pick C (NPC) disease is a genetic disorder mainly caused by mutations in NPC1, a multi-spanning transmembrane protein that is trafficked through the exocytic pathway to late endosomes and lysosomes (LE/Ly) to manage cholesterol homeostasis. Proteostatic defects triggered by >600 NPC1 variants found in the human population inhibit export of NPC1 protein from ER or function in downstream LE/Ly, leading to accumulation of cholesterol and rapid onset neurodegeneration in childhood for most patients. We now show that chemical allosteric inhibitors, such as JG98, targeting the cytosolic Hsp70 chaperone/co-chaperone complex improves the trafficking and stability of NPC1 variants with diverse NPC1 genotypes. By exploiting the knowledge-base of NPC1 variants found in the world-wide patient population using Variation Spatial Profiling (VSP), a Gaussian-process based machine learning (ML) approach, we show how the Hsp70 chaperone system alters the spatial covariance (SCV) tolerance of the ER and the SCV set-points for each residue of the NPC1 polypeptide chain differentially to improve trafficking efficiency and post-ER stability for variants distributed across the entire NPC1 polypeptide. The impact of JG98 is supported by the observation that silencing of Hsp70 specific nucleotide exchange factors (NEF) (BCL-anthogene (BAG) family) co-chaperones significantly improve the folding status of NPC1 variants. Together, these studies suggest that targeting the cytosolic Hsp70 system to adjust the SCV tolerance of the proteostasis network can improve recognition of the plasticity of the NPC1 fold found in the disease population for trafficking to the LE/Ly compartments.
Transcriptomic metaanalyses of autistic brains reveals shared gene expression and biological pathway abnormalities with cancer
Authors: Forés-Martos Jaume , Catalá-López Ferrán , Sánchez-Valle Jon , Ibáñez Kristina , Tejero Héctor , Palma-Gudiel Helena , Climent Joan , Pancaldi Vera , Fañanás Lourdes , Arango Celso , Parellada Mara , Baudot Anaïs , Vogt Daniel , Rubenstein John L. , Valencia Alfonso , Tabarés-Seisdedos Rafael
Published: October 2018

Epidemiological and clinical evidence points to cancer as a comorbidity in people with autism spectrum disorders (ASD). A significant overlap of genes and biological processes between both diseases has also been reported. Here, for the first time, we compared the gene expression profiles of ASD frontal cortex tissues and 22 cancer types obtained by differential expression meta-analysis. Four cancer types (brain, thyroid, kidney, and pancreatic cancers) presented a significant overlap in gene expression deregulations in the same direction as ASD whereas two cancer types (lung and prostate cancers) showed differential expression profiles significantly deregulated in the opposite direction from ASD. Functional enrichment and LINCS L1000 based drug set enrichment analyses revealed the implication of several biological processes and pathways that were affected jointly in both diseases, including impairments of the immune system, and impairments in oxidative phosphorylation and ATP synthesis among others. Our data also suggest that brain and kidney cancer have patterns of transcriptomic dysregulation in the PI3K/AKT/MTOR axis that are similar to those found in ASD. These shared transcriptomic alterations could help explain epidemiological observations suggesting direct and inverse comorbid associations between ASD and particular cancer types.
RegKnock: identifying gene knockout strategies for microbial strain optimization based on regulatory and metabolic integrated network
Authors: Xu Zixiang
Published: October 2018

Background

Gene knockout has been used to improve the conversion ratio of strains for some chemical products. Based on mixed integer bi-level linear programming (MIBLP) and cell network models, there have been several algorithms to predict the target for deletion to improve the productivity of chemicals. At present, the cell models on which these algorithms based have changed from metabolic network to metabolic-regulatory integrated network, for integrated network is more comprehensive in describing the behavior of cells. Metabolic-regulatory integrated network is better than metabolic network in flux prediction, but will introduce integer variables in the inner of MIBLP. How to solve the intractable MIBLP, however, is not explicated clearly as in mathematical literatures, especially for MIBLP with integer variables in the inner problem (named as MIBLP-2) where integer variables are introduced by the flux balance analysis (FBA) for integrated network. Dual theory was still be used to transform MIBLP-2 to a single level with ignoring integer variables in the inner problem. Intelligent computation is another choice for solving MIBLP, but it usually was used to solve the single level nonlinear programming (NLP) which was the transformation from MIBLP by using joint objective of upper/lower level, while the equivalence between this MIBLP and this NLP was not be proved in mathematics.

Methods

In this study, we develop a new target predicting algorithm for gene knockouts, named RegKnock. The cell model on which we base is metabolic-regulatory integrated network as well. When solving the MIBLP-2, RegKnock uses Parallel Genetic Algorithm (PGA), but not use joint objective. GA was used to generate control variables of the upper, indicating which genes should be deleted, while the fitness function is to maximize the objective product calculated from the inner FBA of the integrated network. FBA of the inner problem, a mixed integer programming, could be solved by existing optimization softwares. Parallel computation aims to accelerate finding the optimal solution and thus decreases the time of computation.

Results and Conclusions

With comparing with OptORF and OptFlux, two published target predicting algorithm for gene knockouts which also aiming at integrated network, two merits have been shown for RegKnock, i.e. absolutely accuracy and not a long time of computation. So RegKnock is a nice algorithm for predicting algorithm for gene deletions as for integrated network.
Using QC-Blind for quality control and contamination screening of bacteria DNA sequencing data without reference genome
Authors: Xi Wang , Gao Yan , Cheng Zhangyu , Chen Chaoyun , Han Maozhen , Ning Kang
Published: October 2018

Quality control in next generation sequencing has become increasingly important as the technique becomes widely used. Tools have been developed for filtering possible contaminants in the sequencing data of species with known reference genome. Unfortunately, reference genomes for all the species involved, including the contaminants, are required for these tools to work. This precludes many real-life samples that have no information about the complete genome of the target species, and are contaminated with unknown microbial species.

In this work we propose QC-Blind, a novel quality control pipeline for removing contaminants without any use of reference genomes. The pipeline requires only very little information from the marker genes of the target species. The entire pipeline consists of unsupervised read assembly, contig binning, read clustering and marker gene assignment.

When evaluated onin silico,ab initioandin vivodatasets, QC-Blind proved effective in removing unknown contaminants with high specificity and accuracy, while preserving most of the genomic information of the target bacterial species. Therefore, QC-Blind could serve well in situations where limited information is available for both target and contamination species.

IMPORTANCE

At present, many sequencing projects are still performed on potentially contaminated samples, which bring into question their accuracies. However, current reference-based quality control method are limited as they need either the genome of target species or contaminations. In this work we propose QC-Blind, a novel quality control pipeline for removing contaminants without any use of reference genomes. When evaluated onin silico,ab initioandin vivodatasets, QC-Blind proved effective in removing unknown contaminants with high specificity and accuracy, while preserving most of the genomic information of the target bacterial species. Therefore, QC-Blind is suitable for real-life samples where limited information is available for both target and contamination species.
Protein complex stoichiometry and expression dynamics of transcription factors modulate stem cell division
Authors: Clark Natalie M. , Fisher Adam P. , Berckmans Barbara , Van den Broeck Lisa , Nelson Emily C. , Nguyen Thomas T. , Bustillo-Avendaño Estefano , Zebell Sophia G. , Moreno-Risueno Miguel , Simon Rüdiger , Gallagher Kimberly L. , Sozzani Rosangela
Published: October 2018

Stem cells divide and differentiate to form all the specialized cell types in a multicellular organism. In the Arabidopsis root, stem cells are maintained in an undifferentiated state by a less mitotically active population of cells called the Quiescent Center (QC). Determining how the QC regulates the surrounding stem cell initials, or what makes the QC fundamentally different from the actively dividing initials, is important for understanding how stem cell divisions are maintained. Here, we gained insight into the differences between the QC and the Cortex Endodermis Initials (CEI) by studying the mobile transcription factor SHORTROOT (SHR) and its binding partner SCARECROW (SCR). We constructed an Ordinary Differential Equation (ODE) model of SHR and SCR in the QC and CEI which incorporated the stoichiometry of the SHR-SCR complex as well as upstream transcriptional regulation of SHR and SCR. Our model prediction coupled with experimental validation showed that high levels of the SHR-SCR complex is associated with more CEI division but less QC division. Further, our model prediction allowed us to establish the timing of QC and CEI division and propose that SHR repression of QC division depends on the formation of SHR homodimer. Thus, our results support that SHR-SCR protein complex stoichiometry and regulation of SHR transcription modulate the division timing of two different specialized cell types in the root stem cell niche.
A pose/force symmetric coordination method for a redundant dual-arm robot
Authors: Zhang Fuhai , Qu Jiadi , Liu He , Fu Yili
Published: October 2018

Purpose

This paper aims to develop a pose/force coordination method for a redundant dual-arm robot to achieve a symmetric coordination task.

Design/methodology/approach

A novel control strategy of dual-arm coordination is proposed that associates pose coordination with force coordination. The spatial in-parallel spring and damping model is built to regulate the relative pose error of two end-effectors in real time, and force coordination factor is introduced to realize the dynamic distribution of loadings to limit the object’s internal force in real time.

Findings

The proposed method was verified on a real dual-arm robot platform. The symmetric coordination task is performed and the experiment results show that a good behavior on the regulation of the relative pose errors between two arms to achieve the object’s trajectory tracking, and the distribution of the two end-effectors’ loadings to limit the object’s internal force.

Originality/value

The benefits of the proposed method are to improve the object’s tracking performance and avoid the object damage during the symmetric coordination task.
Method of electrical connector intermittent fault reproduction
Authors: Huakang Li , Lv Kehong , Qinmu Shen , Qiu Jing , Liu Guanjun
Published: October 2018

Purpose

This paper aims to reproduce the electrical connector intermittent fault behaviours with step-up vibration stress while maintaining the integrity of the product.

Design/methodology/approach

A dynamic model of an electrical connector under vibration is established for contact resistance analysis. Next, the dynamic characteristics of contact resistance are analysed, and cumulative damage theory is used to calculate the damage under different stresses during the intermittent fault reproduction test. To reduce damage and improve efficiency, the step-up stress is used for the reproduction test.

Findings

The proposed method can reproduce the intermittent fault behaviour, and the step-up stress test is more efficient than the constant stress test.

Research limitations/implications

Step-up stress is used for intermittent fault reproduction, and the quantitative relationships between intermittent fault and product damage can be further studied.

Practical implications

It is expected that the proposed methodology can help engineers to reproduce the intermittent fault behaviours to facilitate the detection and diagnosis of intermittent fault and to improve equipment safety.

Originality/value

The mechanism of electrical connector reproduction is analysed and the step-up stress test is used for intermittent fault reproduction.
Collaborative authenticity
Authors: Orazi Davide Christian , Newton Fiona Joy
Published: October 2018

Purpose

Effective communication of information is central to integrated care systems (ICS), particularly between providers and care-consumers. Drawing on communication theory, this paper aims to investigate whether and why source effects increase positive evaluations of health-related messages among care-consumers.

Design/methodology/approach

A preliminary online survey (N = 525) establishes the discriminant validity of the measures used in the main experimental study. The main study (N = 116) examines whether identical messages disclosed to be created by different sources (i.e. institutional, care-consumer, collaborative) lead to different message evaluations, and whether source credibility and similarity, and message authenticity, explain this process.

Findings

In comparison to any other source, messages disclosed to be co-created are evaluated more positively by care-consumers. This effect occurs through a parallel serial mediation carried over by perceptions of source credibility and source similarity (parallel, first serial-level mediators) and message authenticity (second serial-level mediator).

Practical implications

The findings offer guidelines for leveraging source effects in ICS communication strategies, signaling how collaborative message sources increase the favorableness of health message evaluations.

Originality/value

This research demonstrates the efficacy of drawing on marketing communication theory to build ICS communication capacity by showing how re-configuring the declared source of informational content can increase positive evaluations of health-related messages. In so doing, this research extends existing literature on message authenticity by demonstrating its key underlying role in affecting message evaluations.