bluuebunny/crossref_metadata_2025 huggingface dataset:
Seizure-like activities in patients with head-up tilt test-induced syncope
Authors: Joo Byung-Euk , Koo Dae Lim , Yim Hye Ran , Park Jungwae , Seo Dae-Won , Kim June Soo
Published: December 2018

The purpose of this study was to assess the prevalence and the characteristics of seizure-like activities during head-up tilt test (HUT)-induced syncope, in patients with suspected vasovagal syncope (VVS). We also evaluated the differences in hemodynamic parameters between patients with and without seizure-like activities.

A total of 71 patients with suspected VVS, who showed syncope during HUT between October 2010 and May 2013, were analyzed. Electrocardiogram and hemodynamic parameters were continuously monitored during HUT. We also performed video recording of patients during HUT to identify eyeball deviation or seizure-like limb movements.

In all, 47 patients (66.2%) showed seizure-like activities at the time of syncope during HUT, 14 patients presented eyeball deviation, without abnormal limb movements, and 33 patients showed abnormal limb movements, such as myoclonic or tonic-clonic activities, as well as eyeball deviation. Upon comparison of the 2 groups with or without seizure-like activities, patients showing seizure-like activities presented a significantly lower heart rate at the time of syncope in HUT (38.51 ± 16.81 vs 49.67 ± 20.12, P < .05). Also, upon comparison within patients showing seizure-like activities, the patients who showed abnormal limb movements with eyeball deviation demonstrated a significantly lower systolic blood pressure and cardiac output at the time of syncope (34.30 ± 12.24 vs 49.00 ± 14.14, P < .05; 0.58 ± 0.40 vs 1.32 ± 0.97, P < .05).

Seizure-like activities were observed in high percentage in about 66% of patients during HUT-induced syncope. The occurrence of seizure-like activities was associated with more severe transient hemodynamic changes, such as lower heart rate, systolic blood pressure, and cardiac output at the time of the HUT-induced syncope.
Promoter hypermethylation of RARβ2, DAPK, hMLH1, p14, and p15 is associated with progression of breast cancer
Authors: Qi Ming , Xiong Xiang
Published: December 2018

Background:

Numerous studies have investigated the associations between RARβ2, DAPK, hMLH1, p14, and p15 promoter hypermethylation and clinical progression of patients with breast cancer, however the results remained uncertain due to the small sample size. Therefore, we performed a meta-analysis to explore the role of RARβ2, DAPK, hMLH1, p14, and p15 promoter hypermethylation in the susceptibility and clinical progression of breast cancer.

Methods:

Eligible studies were obtained by searching Medicine, Embase, Web of knowledge, and Chinese National Knowledge Infrastructure (CNKI) databases. The odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate the associations of RARβ2, DAPK, hMLH1, p14, and p15 promoter hypermethylation with breast cancer pathogenesis. Trial sequential analysis (TSA) was applied to observe the reliability of pooled results of RARβ2 gene, and obtain a conservative required information size (RIS).

Results:

In primary screened 445 articles, 39 literatures with 4492 breast cancer patients were finally enrolled in the final meta-analysis. The results indicated that the frequency of RARβ2 promoter hypermethylation in case group was significantly higher than the frequency of control group (OR = 7.21, 95% CI = 1.54–33.80, P < .05). The RARβ2 promoter hypermethylation had a significant association with lymph node metastasis of breast cancer (OR = 2.13, 95% CI = 1.04–4.47, P < .05). And, the RARβ2 promoter hypermethylation was more common in the breast cancer patients of TNM III–IV stage than those patients of TNM I–II stage (OR = 1.85, 95% CI = 1.33–2.57, P < .05). In addition, the promoter hypermethylation of DAPK, hMLH1, and p14 genes were significantly associated with the susceptibility of breast cancer (for DAPK, OR = 4.93, 95% CI = 3.17–7.65; for hMLH1, OR = 1.84, 95% CI = 1.26–1.29; for p14, OR = 22.52, 95% CI = 7.00–72.41; for p15, OR = 2.13, 95% CI = 0.30–15.07).

Conclusions:

Our findings revealed that the RARβ2 promoter hypermethylation significantly increased the risk of breast cancer. In the meantime, the meta-analysis demonstrated that there were significant associations of RARβ2 promoter hypermethylation with lymph node metastasis and TNM-stage of breast cancer patients. In addition, DAPK, hMLH1, and p14 genes promoter hypermethylation were significantly associated with the susceptibility of breast cancer.
Sirenomelia in twin pregnancy
Authors: Xu Tingting , Wang Xiaodong , Luo Hong , Yu Haiyan
Published: December 2018

Rationale:

Sirenomelia is a very rare congenital malformation and characterized by fused lower extremities, oligohydramnios, renal agenesis, absent urinary tract and external genitalia, single umbilical artery, and imperforate anus. Ultrasonography is an optimal method for prenatal screening and diagnosis of sirenomelia. The incidence of sirenomelia in the twin pregnancy is extremely low.

Patient concerns:

We reported a case of 1 twin with sirenomelia in dichorionic-diamniotic twin pregnancy after in vitro fertilization and embryo transfer.

Diagnoses:

The sirenomelia twin was diagnosed at the 2nd trimester by ultrasonic examination and complicated with oligohydramnios and a single umbilical artery, another twin was normal.

Interventions:

A regular and careful antenatal care was conducted. The parents refused to examine the chromosome of sirenomelia twin, and the chromosomal microarray analysis of the amniotic fluid sample was only achieved in the normal anatomy twin after extensively counseled by the multi-disciplinary team.

Outcomes:

At 34+2 gestational weeks, the demise of the malformed twin occurred, while fetal heart rate monitoring of the normal twin was abnormal, and an emergency cesarean section was performed. A healthy male baby was delivered with Apgar scores of 10 and 10 at 1 and 5 minutes, respectively. The mother and the baby were followed up and are in good health until now.

Conclusion:

Sirenomelia is a lethal condition in the perinatal period. Early antenatal diagnosis is very important. Voluntary selective termination of sirenomelia 1 in twin pregnancy may be advised. Expecting parents should be counseled by the multidisciplinary team about the management and prognosis of the sirenomelia.
Cardiac tamponade as the initial symptom due to systemic lupus erythematosus in a young man
Authors: Zhang Xuan , Wu Wenbin
Published: December 2018

Rationale:

Systemic lupus erythematosus (SLE) is a connective tissue disease that has many clinical manifestations. However, cardiac tamponade has been rarely reported especially as an initial presenting feature of systemic lupus erythematosus. Herein, we describe a case of cardiac tamponade as the first presentation of systemic lupus erythematosus in a male and presented the course of diagnosis and treatment of this patient.

Patient concerns:

A 32-year-old male patient developed a rapid progression of pericardial effusion and he was almost healthy in the past. Vital signs were significantly marked by high fever, tachycardia, and accelerated breathing rate of 37 times per minute. The ANA titer was 1:320 and anti-dsDNA was positive during his hospitalization. The complement levels were decreased but the ESR and the CRP level were increased obviously. Soon after, he appeared anemic and thrombocytopenic.

Diagnoses:

The diagnosis of SLE was made based on the clinical and biochemical findings according to 2012 SLICC SLE Criteria.

Interventions:

The interventions included use CT-guided pericardial puncture to relieve symptoms in time; utilize high-dose glucocorticoids and immunosuppressants to therapy SLE; closely monitor the vital signs, blood routine, blood biochemical indicators, and volume of pericardial effusion.

Outcomes:

After 2 months, the symptoms were disappeared almost completely and TTE showed his pericardial effusion had decreased significantly.

Lessons:

We should also keep SLE in mind when assessing male patients with pericardial effusions. Early examinations of sero-immunological markers and closely monitoring the performances are important for the diagnosis of the disease. Early pericardial puncture can quickly relieve symptoms and improve prognosis.
Aggressive angiomyxoma of the prostate
Authors: Zhu Zhirong , Yan Jiajun , Tang Guiliang
Published: December 2018

Rationale

Aggressive angiomyxoma (AAM) of the prostate should be considered as a differential diagnosis for prostatic tumor presenting with classical symptoms of benign prostatic hypertrophy.

Patient concerns

A 55-year-old man experienced persisting symptoms of prostatic enlargement associated with urinary frequency and urgency and nocturia. Computed tomography images showed low density in the enlarged prostate.

Diagnoses

The diagnosis of AAM of the prostate was confirmed based on histopathological findings.

Interventions

The patient underwent transurethral resection of the prostate.

Outcomes

The patient was enrolled into a watchful waiting protocol. His condition was fine without signs of recurrence on magnetic resonance imaging at the 8-month follow-up.

Lessons

AAM of the prostate should be considered a possible cause of urinary difficulty, including retention, although this may be extremely rare. A reliable diagnosis and complete tumor removal enabled optimal treatment and prevention of tumor recurrence.
White blood cell count: an independent predictor of coronary heart disease risk in middle-aged and elderly population with hyperuricemia
Authors: Chen Hu , Ding Xiang , Li Jiatian , Wu Ziying , Wang Yuqing , He Hongyi , Yang Zidan , Wu Jing , Wang Yilun , Xie Dongxing
Published: December 2018

Previous studies have shown that hyperuricemia is an independent risk factor for cardiovascular disease. The aim of the study was to examine the association between white blood cell (WBC) count and coronary heart disease (CHD) risk in middle-aged and elderly population with hyperuricemia.

Data included in this analysis were from a population-based cross-sectional study, that is, the Xiangya Hospital Health Management Center Study. Hyperuricemia was defined as uric acid ≥416 μmol/L in male population and ≥360 μmol/L in female population. The WBC count was classified into 3 categories based on the tertile distribution of the study population. Framingham risk scores calculated by the Adult Treatment Panel III charts were used to estimate 10-year CHD risk for each participant. The relationship between WBC count and CHD risk in patients with hyperuricemia was examined using the multivariable logistic analysis.

A total of 1148 hyperuricemia patients (855 males and 293 females) aged from 40 to 85 years were included and 418 (36.4%) of them were defined with relatively high 10-year CHD risk. Compared with the lowest tertile, the crude odds ratios (ORs) of high 10-year CHD risk were 1.43 (95% confidence interval [CI] 1.06–1.92) and 1.56 (95% CI 1.16–2.11) in the 2nd and 3rd tertiles of WBC count (Pfor trend = .004), and the multivariable adjusted ORs of high 10-year CHD risk were 1.39 (95% CI 1.03–1.89) and 1.47 (95% CI 1.08–2.00) in the 2nd and 3rd tertiles of WBC count (Pfor trend = .015).

This study indicated that WBC count was associated with CHD risk in patients with hyperuricemia, suggesting that WBC count, an easily accessible biomarker, could probably predict CHD risk in middle-aged and elderly population with hyperuricemia.
The clinical application value of MR diffusion-weighted imaging in the diagnosis of rectal cancer
Authors: Li Feng , Zhang Wei , Li Jun , Zhu Xiangming , Chen Hui , Wu Yongjuan , Wang Jingzhong
Published: December 2018

The present study evaluated the clinical potential of magnetic resonance (MR) diffusion-weighted imaging (DWI) in the diagnosis of rectal cancer.

A total of 84 patients confirmed with rectal cancer were used as study subjects in the present study. All patients received conventional sequence MR T1WI, T2WI, and DWI examination as well as operative pathological examination. The differences between the MRI results and operative pathological results were analyzed.

The diagnosis accordance rates of conventional sequence examination in stage T1, T2, T3, and T4 were 60.00%, 82.75%, 62.85%, and 80.00%, respectively. The diagnosis accordance rates of conventional sequence combined with DWI examination in stages T1, T2, T3, and T4 were 100.00%, 100.00%, 82.85%, and 100.00% respectively. The total diagnosis accordance rates in the T staging of rectal cancer with conventional (Routinely or generally applied) sequence examination and conventional sequence combined with DWI examination were 71.42% and 92.85%, respectively.

The analysis on consistency of MR conventional sequence examination suggested that the conventional sequence combined with DWI examination is more consistent with pathological staging when compared with the convention sequence examination alone. MR DWI combined with conventional sequences reveals quite good accuracy in the T staging of rectal cancer.
Impact of adding a cognitive task while performing physical fitness tests in women with fibromyalgia
Authors: Villafaina Santos , Collado-Mateo Daniel , Domínguez-Muñoz Francisco J. , Fuentes-García Juan P. , Gusi Narcis
Published: December 2018

Fibromyalgia symptoms cause a significant reduction in the ability to perform daily life activities. These activities often require the ability to perform more than 1 task at the same time.

The aim was to investigate how the addition of a cognitive task modifies the performance in physical fitness tests in fibromyalgia and healthy controls.

A total of 61 women participated in this study, 31 of them diagnosed with fibromyalgia by a rheumatologist. They performed 3 physical fitness tests (arm curl, handgrip, and 10-steps stair tests) in 2 conditions:

The dual task cost was calculated as the difference between the performances in the regular and dual-task (DT) conditions.

Healthy controls obtained significantly better results than fibromyalgia in both, dual and single-task conditions. Women with fibromyalgia significantly decreased the performance in the 10-steps stair test when a cognitive task was added. Between-group differences in the dual-task costs (DTC) were not found.

Women with fibromyalgia showed lower physical performance than healthy controls in both, single and dual task conditions. In addition, differences between single and dual task conditions were observed in the 10-steps stair test in women with fibromyalgia. This could be related with a reduction in the ability to perform daily life activities. However, results regarding DTC indicate that both groups may be similarly influenced by the addition of a secondary cognitive. Thus, further research with different difficulty levels of DT conditions is needed in fibromyalgia.
Antineutrophil cytoplasmic antibody-positive familial Mediterranean fever and hyperthyroidism
Authors: Segoe Sorato , Sada Ken-ei , Hayashi Keigo , Yamamura Yuriko , Morishita Michiko , Watanabe Haruki , Matsumoto Yoshinori , Wada Jun
Published: December 2018

Rationale:

Familial Mediterranean fever (FMF) is a genetic autoinflammatory disorder characterized by serositis and recurrent fever. Previous reports identified patients with antineutrophil cytoplasmic antibody (ANCA)-positive FMF, but vasculitis symptoms were not reported.

Patient concerns:

We report the case of a 44-year-old man with numbness. He had a history of 3 episodes of pleurisy and was being treated with propylthiouracil for hyperthyroidism. Because he was ANCA-positive, we suspected drug-induced ANCA-associated vasculitis and propylthiouracil was discontinued. However, his numbness was not ameliorated, and he again developed high fever with pleurisy.

Diagnosis:

Diagnosis of FMF was finally made, and genetic analysis revealed compound heterozygous mutations in exon 2 of the familial Mediterranean fever gene (L110P/E148Q).

Interventions:

The patient was treated with 0.5 mg/day of colchicine.

Outcomes:

His numbness improved, and fever has not recurred.

Lessons:

Appearance of ANCA and development of vasculitis should be considered in a clinical course of FMF with hyperthyroidism.
Effect of the soft-tissue techniques in the quality of life in patients with Crohn's disease
Authors: Espí-López Gemma V. , Inglés Marta , Soliva-Cazabán Isabel , Serra-Añó Pilar
Published: December 2018

Background:

Crohn's disease (CD) is a highly prevalent inflammatory bowel disease (IBD), characterized by recurring flares altered by periods of inactive disease and remission, affecting physical and psychological aspects and quality of life (QoL). The aim of this study was to determine the therapeutic benefits of soft non-manipulative osteopathic techniques in patients with CD.

Methods:

A single-blind randomized controlled trial was performed. 30 individuals with CD were divided into 2 groups: 16 in the experimental group (EG) and 14 in the control group (CG). The intervention period lasted 30 days (1 session every 10 days). Pain, global quality of life (GQoL) and QoL specific for CD (QoLCD) were assessed before and after the intervention. Anxiety and depression levels were measured at the beginning of the study.

Results:

We observed a significant effect of the treatment in both the physical and task subscales of the GQoL (P = .01 andP = .04, respectively) and also in the QoLCD (P ≤.0001) but not in pain score (P = .28). When the intensity of pain was taken into consideration in the analysis of the EG, there was a significantly greater increment in the QoLCD after treatment in people without pain than in those with pain (P = .02) The improvements in GQoL were independent from the disease status (P = .16).

Conclusions:

Soft, non-manipulative osteopathic treatment is effective in improving overall and physical-related QoL in CD patients, regardless of the phase of the disease. Pain is an important factor that inversely correlates with the improvements in QoL.
Comparing the effect between continuous infusion and intermittent bolus of rocuronium for intraoperative neurophysiologic monitoring of neurointervention under general anesthesia
Authors: Ko Myoung Jin , Oh Beomjin , Jung Jae-Wook , Oh Dae Seok , Jin Sung Chul , Kang Eunsu , Kim Yong Han , Kim Se Hun , Kim Hyojoong
Published: December 2018

Background:

Medical researchers have been reluctant to use neuromuscular blocking drugs (NMBD) during the use of intraoperative motor evoked potential (MEP) monitoring despite the possibility of patient movement. In this study, we compared the effects of no NMBD and continuous rocuronium infusion on the incidence of patient involuntary movement and MEP monitoring.

Methods:

In this study, 80 patients who underwent neuro intervention with MEP monitoring were randomly assigned into 2 groups. After an anesthetic induction, bolus of rocuronium 0.1 mg/kg was injected when it was needed (for patient involuntary movement or at the request of the surgeon) in group B, and 5 mcg/kg/min of rocuronium were infused in group I study participants. The incidence of patient involuntary movement and spontaneous respiration, the mean MEP amplitude, coefficient of variation (CV), the incidence of MEP stimulus change and train-of-four (TOF) count were compared.

Results:

The incidence of involuntary movement and spontaneous movement were measured as significantly lower in group I (P < .05). The incidence of undetectable MEP did not differ as measured in both groups. The means and CVs of MEP amplitude in all limbs were significantly lower in group I. The mean TOF counts from 30 to 80 min of operation were significantly higher in group B.

Conclusion:

We conclude that the continuous infusion of rocuronium effectively inhibited the involuntary movement and spontaneous respiration of the patient while enabling MEP monitoring.
Application of graft-derived cell-free DNA in ornithine transcarbamylase deficiency patient after living donor liver transplantation
Authors: Ng Hoi-Ioi , Sun Li-Ying , Zhu Zhi-Jun
Published: December 2018

Rationale:

Graft-derived-cell-free DNA (Gcf-DNA) in plasma was a promising biomarker to monitor graft-rejection after liver transplantation. However, little is known about the application of Gcf-DNA in living-donor-liver-transplantation (LDLT).

Patients concern:

In this study, 2 patients diagnosed with Ornithine Transcarbamylase Deficiency (OTCD) were enrolled and indicated for LDLT.

Diagnoses:

Two patients were genetically diagnosed with OTCD, and they suffered from recurrent and uncontrollable hyper-ammonemia and failed in accepting the normalized OTCD treatments, such as decreasing dietary nitrogen intake and increasing waste-nitrogen excretion.

Interventions:

LDLT was performed in the 2 patients uneventfully, and we collected circulating cell-free DNA from plasma in specific postoperative time points (day 1, day 7, day 14, day 30, day 60). Since both of the recipients were sex-mismatch with the donors, we measured Gcf-DNA through the Y-chromosome method and compared it with the routine liver function.

Outcomes:

The result showed that Gcf-DNA had the similar discrimination of graft injury trend while compared to routine liver function. The follow-up showed these 2 patients’ status is stable.

Lessons:

Applying Gcf-DNA to monitor graft injury in LDLT is promising, but still long term follow-up and more samples are needed for validation.
Intracranial Hemorrhage in Children With Inherited Bleeding Disorders: A Single Center Study in China
Authors: Haque Qareen , Abuduaini Yilifan , Li Huiping , Wen Jianyun , Wu Xuedong , Feng Xiaqin
Published: December 2018

Background:

Intracranial hemorrhage (ICH) is a life-threatening condition in children. Inherited bleeding disorders (IBD) have high risk of ICH.

Aim:

This single center study aims to identify the incidence, risk factors, and neurological outcome of ICH in children who suffer from IBD.

Methods:

From 2005 to 2017, 241 children with IBDs from Nanfang hospital, Department of Pediatrics, were evaluated. The ICH episodes were identified by medical history, general physical examination, detailed neurological examination, and computed tomographic or magnetic resonance imaging examination. The risk factors, location of ICH, management strategies, and outcome were noted.

Results:

ICH was confirmed in 54/241 (22.4%) children with IBD among them 52/54 (96.2%) (95% confidence interval [CI], 91.1%-99.9%) were hemophilia A and hemophilia B patients. The overall risk of ICH among children with IBD was 22.4% (95% CI, 17.2%-27.8%). The median age of ICH was 30 months (0 to 204) and 18/54 (33.3%) (95% CI, 20.3%-46.3%) children had an ICH in the first year of life. Twenty-eight of 52 (53.8%) hemophilic children with ICH were assessed for inhibitor of FVIII and FIX. Nine of 28 (32%) hemophilic children with inhibitor developed the ICH. Six of 52 (11.5%) (95% CI, 2.6%-20.5%) hemophilic children had multiple episodes of ICH in which 4 were inhibitor positive. Thirteen of 54 (24%) (95% CI, 12.3%-35.9%) had positive family history of IBD. Twenty-two (36%) (95% CI, 23.7%-48.5%) of 61 ICH episodes were caused by trauma and 39 (63.9%) (95% CI, 51.5%-76.3%) were nontrauma related. Subdural hematoma was most frequently observed. Mortality risk from ICH in children with IBD was 5/54 (9.2%) (95% CI, 1.3%-17.2%). Eleven (22.4%) (95% CI, 10.3%-34.6%) of 49 survivors had known neurological squeal, whereas 38 (77.5%) (95% CI, 65.4%-89.7%) had no documented evidence of neurological impairment.

Conclusions:

Hemophilia is the most common IBD and most frequently associated with ICH. Risk and consequences of ICH in IBD were high during the first year of life while in older children better outcome may be expected. The optimal management of ICH depends on immediate recognition and prompt replacement therapy.
Causes of Hypochromic Microcytic Anemia in Children and Evaluation of Laboratory Parameters in the Differentiation
Authors: Aydogan Gonul , Keskin Salim , Akici Ferhan , Salcioglu Zafer , Bayram Cengiz , Uysalol Ezgi P. , Gucer Tuba N.T. , Ersoy Gizem , Ozdemir Nihal
Published: December 2018

Most common causes of microcytic anemia in children are iron deficiency anemia (IDA) and thalassemia. Differentiation of these and detection of coexistence is essential for genetic counseling and to set a treatment plan. Aim is to characterize the frequency of IDA and thalassemia trait (TT) in children presenting with hypochromic, microcytic anemia and to define the significance of blood count parameters in differential diagnosis. Of the 200 enrolled, 107 were male (53.5%). In total 154 had IDA (77%), 27 had β-TT (13.5%), and in 11 (5.5%) both conditions coexisted. Eight patients had α-thalassemia gene mutations, 3 of these also had IDA. RBC, MCV, Mentzer index, serum iron, TIBC, ferritin were significantly different between IDA and β-TT patients (P<0.001); however, RDW was not different between the 2 groups (P>0.05). Sensitivity and specificity of Mentzer index for the detection of β-TT were 100% and 69.4%, respectively. The positive and negative predictive values of Mentzer index in diagnosing β-TT were 36.6% and 100%, respectively. Differential diagnosis of microcytic anemia is important in children, especially in regions where IDA and thalassemia are both prevalent. We found that 7% of children referred to our clinic for hypochromic, microcytic anemia had both TT and IDA. Our data showed that serum iron, ferritin, TIBC, MCV, and Mentzer index were all valuable markers in diagnosing IDA and were significantly different compared with β-TT patients; RDW was not different between the 2 groups.
Characterization of Brain Signatures to Add Precision to Self-Management Health Information Interventions
Authors: Moore Shirley M. , Musil Carol M. , Jack Anthony I. , Alder Megan L. , Fresco David M. , Webel Allison , Wright Kathy D. , Sattar Abdus , Higgins Patricia
Published: December 2018

Background

Although many of the proposed mediating processes of self-management interventions are operationally defined as cognitive processes (e.g., acquiring and using information, self-efficacy, motivation, and decision-making), little is known about their underlying brain mechanisms. Brain biomarkers of how people process health information may be an important characteristic on which to individualize health information to optimize self-management of chronic conditions.

Objectives

We describe a program of research addressing the identification of brain biomarkers that differentially predict responses to two types of health information (analytic focused and emotion focused) designed to support optimal self-management of chronic conditions.

Methods

We pooled data from two pilot studies (N = 52) that included functional magnetic resonance imaging during a specially designed, ecologically valid protocol to examine brain activation (task differentiation) associated with two large-scale neural networks—the Analytic Network and the Empathy Network—and the ventral medial prefrontal cortex while individuals responded to different types of health information (analytic and emotional).

Results

Findings indicate that analytic information and emotional information are processed differently in the brain, and the magnitude of this differentiation in response to type of information varies from person to person. Activation in the a priori regions identified in response to both analytic and emotion information was confirmed. The feasibility of obtaining brain imaging data from persons with chronic conditions also is demonstrated.

Discussion

An understanding of brain signatures related to information processing has potential to assist in the design of more individualized, effective self-management interventions.
A Comprehensive Analysis of the Association Between Gleason Score at a Positive Surgical Margin and the Risk of Biochemical Recurrence After Radical Prostatectomy
Authors: Iremashvili Viacheslav , Pelaez Liset , Jorda Merce , Parekh Dipen J. , Punnen Sanoj
Published: December 2018

Our objective was to identify the best of the existing definitions of Gleason score (GS) at a positive surgical margin (PSM) by validating them in our radical prostatectomy cohort. We analyzed 251 patients who had mixed (3+4, 3+5, 4+3 or 5+3) pathologic GS and PSM. We used 5 definitions to record GS at a PSM. Univariate and multivariate analyses were used to study the association between each definition and the risk of biochemical recurrence (BCR). We also tested the prognostic value of multivariate models including established predictors and each of the studied definitions of GS at a PSM. GS 3+3 was seen at a PSM in 57.4% of the cases and was more common in patients with lower overall GS. Over a median follow-up of 4.0 years 89 patients (35.5%) developed BCR. All of the definitions of GS at a PSM were independent predictors of the BCR-free survival. Most of them also improved the prognostic value of the multivariate models when added to the established parameters. The degree of improvement was similar for the most complex definition (full GS at a PSM) and the easiest to record binary definition (presence of Gleason 4/5 pattern at a PSM). We conclude that compared with the other possible options of reporting GS at a PSM, the presence of Gleason 4/5 pattern may be the most practical definition. It is at least as predictive as other definitions, may be the easiest to record and is the best studied of the existing alternatives.
From A to D
Authors: Jackson Steven D. , Wiering Bethany A. , Bentley Ingrid A. , Herrmann Amanda A. , Hanson Leah R.
Published: December 2018

Longitudinal myelitis secondary to an acute flare of systemic lupus erythematosus has been reported in the literature. There have been few published cases of complete functional recovery in patients with systemic lupus erythematosus–related longitudinal myelitis (systemic lupus erythematosus–related longitudinal myelitis). Of those cases, none have described in detail the rehabilitation course of treatment. In the current case, intensive rehabilitation was coupled with aggressive pharmaceutical treatment resulting in almost full functional recovery. A 23-yr-old African American woman with a history of systemic lupus erythematosus was originally admitted as an inpatient for flank pain. Overnight, she progressed rapidly to complete flaccid paraplegia classified as T3 American Spinal Injury Association Impairment Scale A based on the International Standards for Neurological Classification of Spinal Cord Injury. Throughout the next year, she participated in acute inpatient rehabilitation, followed by outpatient rehabilitation (physical, occupational, and aquatic therapies). A year after her initial hospital admission, she progressed to full community ambulation T3 American Spinal Injury Association Impairment Scale D. This case illustrates the importance of proper medical treatment and a comprehensive rehabilitation program, which improved functional outcomes for a patient with a complete spinal cord injury due to systemic lupus erythematosus–related longitudinal myelitis.
Minor environmental concentrations of antibiotics can modify bacterial virulence in co-infection with a non-targeted parasite
Authors: Sundberg Lotta-Riina , Karvonen Anssi
Published: December 2018

Leakage of medical residues into the environment can significantly impact natural communities. For example, antibiotic contamination from agriculture and aquaculture can directly influence targeted pathogens, but also other non-targeted taxa of commensals and parasites that regularly co-occur and co-infect the same host. Consequently, antibiotics could significantly alter interspecific interactions and epidemiology of the co-infecting parasite community. We studied how minor environmental concentrations of antibiotic affects the co-infection of two parasites, the bacterium
Flavobacterium columnare
and the fluke
Diplostomum pseudospathaceum
, in their fish host. We found that antibiotic in feed, and particularly the minute concentration in water, significantly decreased bacterial virulence and changed the infection success of the flukes. These effects depended on the level of antibiotic resistance of the bacterial strains. Antibiotic, however, did not compensate for the higher virulence of co-infections. Our results demonstrate that even very low environmental concentrations of antibiotic can influence ecology and epidemiology of diseases in co-infection with non-targeted parasites. Leakage of antibiotics into the environment may thus have more complex effects on disease ecology than previously anticipated.
Migrating ospreys use thermal uplift over the open sea
Authors: Duriez Olivier , Peron Guillaume , Gremillet David , Sforzi Andrea , Monti Flavio
Published: December 2018

Most large raptors on migration avoid crossing the sea because of the lack of atmospheric convection over temperate seas. The osprey
Pandion haliaetus
is an exception among raptors, since it can fly over several hundred kilometres of open water. We equipped five juvenile ospreys with GPS-Accelerometer–Magnetometer loggers. All birds were able to find and use thermal uplift while crossing the Mediterranean Sea, on average 7.5 times per 100 km, and could reach altitudes of 900 m above the sea surface. Their climb rate was 1.6 times slower than over land, and birds kept flapping most of the time while circling in the thermals, indicating that convections cells were weaker than over land. The frequency of thermal soaring was correlated with the difference between the sea surface and air temperature, indicating that atmospheric convection occurred when surface waters were warmer than the overlaying air. These observations help explain the transoceanic cosmopolitan distribution of osprey, and question the widely held assumption that water bodies represent strict barriers for large raptors.
Deciphering noise amplification and reduction in open chemical reaction networks
Authors: Pucci Fabrizio , Rooman Marianne
Published: December 2018

The impact of fluctuations on the dynamical behaviour of complex biological systems is a longstanding issue, whose understanding would elucidate how evolutionary pressure tends to modulate intrinsic noise. Using the Itō stochastic differential equation formalism, we performed analytic and numerical analyses of model systems containing different molecular species in contact with the environment and interacting with each other through mass-action kinetics. For networks of zero deficiency, which admit a detailed- or complex-balanced steady state, all molecular species are uncorrelated and their Fano factors are Poissonian. Systems of higher deficiency have non-equilibrium steady states and non-zero reaction fluxes flowing between the complexes. When they model homo-oligomerization, the noise on each species is reduced when the flux flows from the oligomers of lowest to highest degree, and amplified otherwise. In the case of hetero-oligomerization systems, only the noise on the highest-degree species shows this behaviour.
Macropinosome formation, maturation and membrane recycling: lessons from clathrin-independent endosomal membrane systems
Authors: Donaldson Julie G.
Published: December 2018

Macropinocytosis is a form of endocytosis that brings large fluid-filled endosomes into the cell interior. Macrophages and dendritic cells are especially active in this process, but all cells can be stimulated to initiate this remarkable form of endocytosis. Although much is known about the membrane lipid and actin requirements for initiating macropinocytosis, less is known about the membrane that forms the macropinosome and the fate of that membrane once the macropinosome enters the cell interior. Since macropinocytosis is a specialized form of clathrin-independent endocytosis (CIE), studies of the constitutive internalization and trafficking of cargo proteins and membrane that enter cells independently of clathrin could reveal the types of membrane that form the macropinosome and the machinery that handles cargo sorting and recycling during the maturation of the macropinosome.

This article is part of the Theo Murphy meeting issue ‘Macropinocytosis’.
Unusual physiological properties of two ganglion cell types in primate retina
Authors: Rhoades Colleen E. , Shah Nishal P. , Manookin Michael B. , Brackbill Nora , Kling Alexandra , Goetz Georges , Sher Alexander , Litke Alan M. , Chichilnisky E. J.
Published: December 2018

The visual functions of the diverse retinal ganglion cell types in the primate retina, and the parallel visual pathways they initiate, remain poorly understood. Here, the unusual physiological and computational properties of the ON and OFF smooth monostratified (SM) ganglion cells are explored. Large-scale multi-electrode recordings from 48 macaque retinas revealed that these cells exhibited strikingly irregular receptive field structure composed of spatially segregated hotspots, quite different from the receptive fields of previously described retinal ganglion cell types. The ON and OFF SM cells are paired cell types, but OFF SM cells exhibited stronger hotspot structure than ON cells. Targeted visual stimulation and computational inference demonstrate strong nonlinear subunit properties of each hotspot that contributed to the signaling properties of SM cells. Analysis of shared inputs to neighboring SM cells indicated that each hotspot could not be explained by an individual presynaptic input. Surprisingly, visual stimulation of different hotspots produced subtly different spatiotemporal spike waveforms in the same SM cell, consistent with a dendritic contribution to hotspot structure. These findings point to a previously unreported nonlinear mechanism in the output of the primate retina that contributes to signaling spatial information.
Rapid single-cell cytometry data visualization with EmbedSOM
Authors: Kratochvíl Miroslav , Koladiya Abhishek , Balounova Jana , Novosadova Vendula , Fišer Karel , Sedlacek Radislav , Vondrášek Jiří , Drbal Karel
Published: December 2018

Efficient unbiased data analysis is a major challenge for laboratories handling large cytometry datasets. We present EmbedSOM, a non-linear embedding algorithm based on FlowSOM that improves the analyses by providing high-performance visualization of complex single cell distributions within cellular populations and their transition states. The algorithm is designed for linear scaling and speed suitable for interactive analyses of millions of cells without downsampling. At the same time, the visualization quality is competitive with current state-of-art algorithms. We demonstrate the properties of EmbedSOM on workflows that improve two essential types of analyses: The native ability of EmbedSOM to align population positions in embedding is used for comparative analysis of multi-sample data, and the connection to FlowSOM is exploited for simplifying the supervised hierarchical dissection of cell populations. Additionally, we discuss the visualization of the trajectories between cellular states facilitated by the local linearity of the embedding.
Genome-wide association study of alcohol consumption in Russian population
Authors: Nizamutdinov Igor , Popov Yaroslav , Romanov Dmitriy , Surkova Ekaterina , Ilinsky Valery , Rakitko Alexander
Published: December 2018

Liability to alcohol dependence is heritable, but little is known about its complex polygenic architecture. We performed a genome-wide association study (GWAS) of self-reported alcohol consumption in 1798 of Russian individuals. No SNP reached genome-wide significance for any alcohol drinking patterns: never drinking, everyday drinking, once per week drinking and once per month drinking. Polymorphisms in previously reported genes of KLB and AUTS2 were significant associated with everyday drinking and once per week drinking patterns, respectively. We also found associations of genes involved in nervous system function and mental disorders with some alcohol drinking patterns. This study identifies novel gene associations that should be the focus of future studies investigating the neurobiology of alcohol consumption.
Incomplete annotation of disease-associated genes is limiting our understanding of Mendelian and complex neurogenetic disorders
Authors: Zhang David , Guelfi Sebastian , Ruiz Sonia Garcia , Costa Beatrice , Reynolds Regina H. , D’Sa Karishma , Liu Wenfei , Courtin Thomas , Peterson Amy , Jaffe Andrew E. , Hardy John , Botia Juan , Collado-Torres Leonardo , Ryten Mina
Published: December 2018

There is growing evidence to suggest that human gene annotation remains incomplete, with a disproportionate impact on the brain transcriptome. We used RNA-sequencing data from GTEx to detect novel transcription in an annotation-agnostic manner across 13 human brain regions and 28 human tissues. We found that genes highly expressed in brain are significantly more likely to be re-annotated, as are genes associated with Mendelian and complex neurodegenerative disorders. We improved the annotation of 63% of known OMIM-morbid genes and 65% of those with a neurological phenotype. We determined that novel transcribed regions, particularly those identified in brain, tend to be poorly conserved across mammals but are significantly depleted for genetic variation within humans. As exemplified by SNCA, we explored the implications of re-annotation for Mendelian and complex Parkinson’s disease. We validated in silico and experimentally a novel, brain-specific, potentially protein-coding exon of SNCA. We release our findings as tissue-specific transcriptomes in BED format and via vizER: http://rytenlab.com/browser/app/vizER. Together these resources will facilitate basic genomics research with the greatest impact on neurogenetics.
Hepatic JARID1a ablation disrupts the transcription adaptation to feeding and alters systemic metabolism
Authors: DiTacchio Kacee A. , Kalinowska Diana , Saran Anand , Byrne Ashley , Vollmers Christopher , DiTacchio Luciano
Published: December 2018

The liver is a key regulator of systemic energy homeostasis whose proper function is dependent on the circadian clock. Here, we show that livers deficient in the oscillator component JARID1a exhibit a dysregulation of genes involved in energy metabolism. Importantly, we find that mice that lack hepatic JARID1a have decreased lean body mass, decreased respiratory exchange ratios, faster production of ketones and increased glucose production in response to fasting. Finally, we find that JARID1a loss compromises the response of the hepatic transcriptome to nutrient availability. In all, ablation of hepatic JARID1a disrupts the coordination of hepatic metabolic programs with whole-body consequences.
Bacterial analogs of plant piperidine alkaloids mediate microbial interactions in a rhizosphere model system
Authors: Lozano Gabriel L. , Park Hyun Bong , Bravo Juan I. , Armstrong Eric A. , Denu John M. , Stabb Eric V. , Broderick Nichole A. , Crawford Jason M. , Handelsman Jo
Published: December 2018

Plants expend significant resources to select and maintain rhizosphere communities that benefit their growth and protect them from pathogens. A better understanding of assembly and function of rhizosphere microbial communities will provide new avenues for improving crop production. Secretion of antibiotics is one means by which bacteria interact with neighboring microbes and sometimes change community composition. In our analysis of a taxonomically diverse consortium from the soybean rhizosphere, we found that Pseudomonas koreensis selectively inhibits growth of Flavobacterium johnsoniae and other members of the Bacteroidetes grown in soybean root exudate. A genetic screen in P. koreensis identified a previously uncharacterized biosynthetic gene cluster responsible for the inhibitory activity. The metabolites were isolated based on biological activity and were characterized using tandem-mass spectrometry, multidimensional NMR, and Mosher ester analysis, leading to the discovery of a new family of bacterial piperidine alkaloids, koreenceine A-D (1–4). Three of these metabolites are analogs of the plant alkaloid γ-coniceine. Comparative analysis of the koreenceine cluster with the γ-coniceine pathway revealed distinct polyketide synthase (PKS) routes to the defining piperidine scaffold, suggesting convergent evolution. Koreenceine-type pathways are widely distributed among Pseudomonas species, and koreenceine C was detected in another Pseudomonas sp. from a distantly related cluster. This work suggests that Pseudomonas and plants convergently evolved the ability to produce similar alkaloid metabolites that can mediate inter-bacterial competition in the rhizosphere.

IMPORTANCE

The microbiomes of plants are critical to host physiology and development. Microbes are attracted to the rhizosphere due to massive secretion of plant photosynthates from roots. Microorganisms that successfully join the rhizosphere community from bulk soil have access to more abundant and diverse molecules, producing a highly competitive and selective environment. In the rhizosphere, as in other microbiomes, there is little known about the genetic basis for individual species’ behaviors within the community. In this study, we characterized competition between Pseudomonas koreensis and Flavobacterium johnsoniae, two common rhizosphere inhabitants. We identified a widespread gene cluster in several Pseudomonas spp., which is necessary for the production of a novel family of piperidine alkaloids that are structural analogs of plant alkaloids. We expand the known repertoire of antibiotics produced from Pseudomonas in the rhizosphere and demonstrate the role of the metabolites in interactions with other bacteria of the rhizosphere.
Structural basis of envelope and phase intrinsic coupling modes of the cerebral cortex
Authors: Messé Arnaud , Hollensteiner Karl J. , Delettre Céline , Dell Leigh-Anne , Pieper Florian , Nentwig Lena J. , Galindo-Leon Edgar E. , Larrat Benoît , Mériaux Sébastien , Mangin Jean-François , Reillo Isabel , de Juan Romero Camino , Borrell Víctor , Engler Gerhard , Toro Roberto , Engel Andreas K. , Hilgetag Claus C.
Published: December 2018

Intrinsic coupling modes (ICMs) provide a framework for describing the interactions of ongoing brain activity at multiple spatial and temporal scales. Two families of ICMs can be distinguished: phase and envelope ICMs. The principles that shape these ICMs remain partly elusive, in particular their relation to the underlying brain structure. Here we explored structure-function relationships in the ferret brain between ICMs quantified from ongoing brain activity recorded with chronically implanted ECoG arrays and structural connectivity (SC) obtained from high-resolution diffusion MRI tractography. Large-scale computational models as well as simple topological ingredients of SC were used to explore the ability to predict both types of ICMs. Importantly, all investigations were conducted with ICM measures that are sensitive or insensitive to volume conduction effects. The results show that both types of ICMs are strongly related to SC, except when using ICM measures removing zero-lag synchronizations. Computational models are challenged to predict these ICM patterns consistently, and simple predictions from SC topological features can sometimes outperform them. Overall, the results demonstrate that patterns of cortical functional coupling as reflected in both phase and envelope ICMs bear a substantial relation to the underlying structural connectivity of the cerebral cortex.