bluuebunny/crossref_metadata_2025 huggingface dataset:
A risk scoring model to predict renal progression associated with postcontrast acute kidney injury in chronic kidney disease patients
Authors: Baek Seung Don , Kim So Mi , Kang Jae-Young , Han Minkyu , Lee Eun Kyoung , Chang Jai Won
Published: January 2019

Postcontrast acute kidney injury (AKI) occurs more frequently in patients with lower estimated glomerular filtration rate. We hypothesized that postcontrast AKI in chronic kidney disease (CKD) patients with distinct risk factors might be associated with accelerated renal progression.

We undertook this retrospective cohort study to develop and validate a risk scoring model for predicting renal progression. In a development dataset, 18,278 contrast-enhanced CT scans were performed in 9097 patients with CKD (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) who were not undergoing dialysis. Postcontrast AKI was observed in 5.8% (1051/18,278) of all contrast-enhanced CTs with 7.6% (689/9097) of the total CKD patients. We investigated the 1-year renal outcome in 224 eligible patients. A risk scoring model was developed with multivariate regression analysis and was assessed in external validation (independent 154 patients).

Among 224 patients, 70 (31.3%) patients had progression of renal dysfunction at 1 year (defined as reduction in estimated GFR ≥25% at 1 year). A risk score of 4, 4, 6, 6, 7, or 6 was assigned to diabetes, baseline estimated GFR < 45 mL/min/1.73 m2, hypertension, repeated contrast exposure, congestive heart failure, and persistent renal injury (defined as an elevation of serum creatinine ≥25% at 3 months), respectively. An increasing risk score was associated with renal progression. Of note, persistent renal injury was more prevalent in the progression group than in the non-progression group. The AUROC of the model in the development population was 0.765. In the validation dataset, however, the discriminative power decreased (AUROC = 0.653).

Our suggested model provided the risk of renal progression, aiding in predicting prognosis, counseling, and improving outcomes in CKD patients complicated by postcontrast AKI.
Another Useful Application of Point-of-Care Ultrasound
Authors: Mori Takaaki , Nomura Osamu , Hagiwara Yusuke
Published: January 2019

Foreign body ingestion is a common pediatric complaint. Esophageal foreign body (EFB) requires early diagnosis and emergency removal of the object. We report 3 cases of EFB detected by point-of-care ultrasound demonstrating characteristic sonographic findings. Point-of-care ultrasound can be a potentially useful modality for identifying EFB.
Shock Index as a Predictor of Morbidity and Mortality in Pediatric Trauma Patients
Authors: Strutt Jonathan , Flood Andrew , Kharbanda Anupam B.
Published: January 2019

Objectives

Compared with unadjusted shock index (SI) (heart rate/systolic blood pressure), age-adjusted SI improves identification of negative outcomes after injury in pediatric patients. We aimed to further evaluate the utility of age-adjusted SI to predict negative outcomes in pediatric trauma.

Methods

We performed an analysis of patients younger than 15 years using the National Trauma Data Bank. Elevated SI was defined as high normal heart rate divided by low-normal blood pressure for age. Our primary outcome measure was mortality. Secondary outcomes included need for a blood transfusion, ventilation, any operating room/interventional radiology procedures, and intensive care unit stay. Multiple logistic regressions were performed.

Results

Twenty-eight thousand seven hundred forty-one cases met the study criteria. The overall mortality rate was 0.7%, and 1.7% had an elevated SI. Patients with an elevated SI were more likely (P < 0.001) to require blood transfusion, ventilation, an operating room/interventional radiology procedure, or an intensive care unit stay. An elevated SI was the strongest predictor for mortality (odds ratio [OR] 22.0) in pediatric trauma patients compared with hypotension (OR, 12.6) and tachycardia (OR, 2.6).

Conclusions

Elevated SI is an accurate and specific predictor of morbidity and mortality in pediatric trauma patients and is superior to tachycardia or hypotension alone for predicting mortality.
Bilateral Signet-ring Stromal Tumor of the Ovary: A Case Report With Next-generation Sequencing Analysis and FOXL2 Mutation Testing
Authors: Chen Po-Han , Hui Pei , Buza Natalia
Published: January 2019

Signet-ring stromal tumor (SRST) is a rare benign stromal neoplasm of the ovary with only a handful of cases reported in the literature. To date, all but one reported cases have been unilateral, and the pathogenesis and underlying genetic abnormalities of this entity are not well characterized. Here we report a case of a 70-yr-old woman with bilateral ovarian SRST, clinically presenting with abdominal distention and rectal bleeding, and bilateral ovarian masses on imaging studies. Total hysterectomy and bilateral salpingo-oophorectomy were performed, revealing bilateral solid ovarian tumors with characteristic signet-ring cell morphology. The immunohistochemical profile—positive steroidogenic factor 1, calretinin, and smooth muscle actin, and negative epithelial membrane antigen—supported the diagnosis of SRST. CTNNB1 mutation and abnormal nuclear beta-catenin expression have recently been reported in 2 SRSTs. However, we did not identify any mutations in 54 oncogenes and tumor suppressor genes (including CTNNB1) by next-generation sequencing analysis, and PCR Sanger sequencing did not reveal FOXL2 C134W mutation, suggesting the possibility of heterogenous pathogenesis of these tumors.
Perinatal Mental Health Treatment Needs, Preferences, and Barriers in Parents of Multiples
Authors: WENZE SUSAN J. , BATTLE CYNTHIA L.
Published: January 2019

Purpose:

Many parents of multiples experience elevated mental health symptoms in the perinatal period. This population often presents with unique treatment needs and barriers to care; however, no tailored interventions have been developed for pregnant or postpartum mothers of multiples and/or their partners. This study involved an initial exploration of the perceived mental health treatment needs, preferences, and barriers to care in this population, as a first step toward developing such an intervention.

Methods:

Participants were 241 parents of multiples who were recruited in-person and online. They completed self-report measures assessing treatment history/preferences, barriers to care, and symptoms during the perinatal period.

Results:

Participants identified postpartum months 0 to 3 as the most difficult time. Few participants received any form of mental health treatment, although a significant percentage (approximately half) expressed interest in such treatment. Treatment interest was high for a range of clinical concerns. Participants were interested in both traditional treatment paradigms and eHealth approaches. Barriers to care were common, with the most common barrier being lack of time.

Conclusions:

There is a large, unmet need for mental health treatment in parents of multiples in the perinatal period, especially the early postpartum months. eHealth strategies seem particularly feasible and acceptable in this population and may help circumvent common barriers to care. Clinical recommendations and considerations in treatment development are discussed.
Brain and Behavior: Commentary on Two Cases Involving the Effect of Structural Brain Lesions on Psychiatric Disorders
Authors: KAHN DAVID A.
Published: January 2019

In this issue of the journal, 2 case reports are presented that illustrate explicit influences of structural brain lesions on psychiatric symptoms. In both cases, the patients had preexisting, classically diagnosed psychiatric disorders—schizophrenia in the first case and bipolar I disorder in the second case. In the first case, a 61-year-old woman with chronic paranoid schizophrenia experienced a marked reduction in psychotic symptoms after bilateral frontal strokes. In the second case, a 60-year-old man who had experienced manic and depressive episodes since his 20s developed partial complex seizures after having repeated head trauma in his 40s, with subsequent onset of chronic personality changes associated with temporal lobe epilepsy that made his psychiatric treatment a greater challenge. The presentations in these 2 cases raise intriguing neuropsychiatric questions concerning the effects on regional brain activity of a variety of nonpharmacological psychiatric interventions (eg, stereotactic neurosurgical techniques, deep brain stimulation, electroconvulsive therapy, certain types of psychotherapy), and concerning possible physiological pathways shared by seizure kindling in epilepsy and recurrent episodes of bipolar disorder.
Poststroke Psychosis Reduction: A Case Report
Authors: CENTORINO MICHAEL B. , CATALANO GLENN , GRIMSICH LAURA C. , ANTOUN ROULA M.
Published: January 2019

Strokes have been shown to result in psychiatric phenomena that can range from mood disorders to psychosis. Ablative neurosurgeries have been performed with the goal of reducing the burden of psychiatric symptoms following such cerebrovascular accidents. In this report, we review poststroke psychiatric manifestations, and then present the case of a woman with schizophrenia whose thought disorder improved following a hemorrhagic stroke. Not only did she require less medication, but her remaining symptoms were significantly less impairing than they had previously been. We then compare and contrast the effects of this stroke with ablative neurosurgery.
Differentiating Symptoms of Bipolar Disorder From Those of Temporal Lobe Epilepsy: A Case Report
Authors: YEHL JENNIFER L. , KLIPPEL CORY M. , FRONTERA ALFRED T. , KOZEL F. ANDREW
Published: January 2019

Bipolar I disorder and interictal personality syndrome have many overlapping characteristics that are difficult to distinguish. There is scant literature focused on interictal personality syndrome and no case reports to date detailing patients with comorbid bipolar pathology. We describe an individual with a history of bipolar I disorder who developed right temporal lobe epilepsy after several head injuries. He subsequently exhibited symptoms consistent with interictal personality syndrome that were independent of his bipolar symptomatology. Better understanding of these disorders can lead to improved diagnosis and symptom management. The similarities may also point to a partially shared neuropathology.
Symptom Dimensions and Trajectories of Functioning Among Bipolar Youth: A Cluster Analysis
Authors: PETERS AMY T. , WEINSTEIN SALLY M. , ISAIA ASHLEY , VAN METER ANNA , ZULAUF COURTNEY A. , WEST AMY E.
Published: January 2019

Background:

Accurate assessment of pediatric bipolar disorder (BD) is important for allocating appropriate treatment, but it is complicated by significant heterogeneity in symptom presentation and high rates of comorbidity. Investigating clinical subtypes of the disorder may help to clarify diagnostic boundaries and inform targeted treatment. This study used a full diagnostic instrument to examine symptom patterns among youth with BD.

Method:

Trained interviewers completed the Washington University Kiddie Schedule for Affective Disorders and Schizophrenia (WASH-U-KSADS) with 71 children (7 to 13 y of age) and families as part of the baseline assessment for a randomized clinical trial of Child- and Family-focused Cognitive-Behavioral Therapy (CFF-CBT) compared with treatment as usual (TAU) for pediatric BD. All participants met DSM-IV-TR criteria for a bipolar spectrum disorder. Hierarchical and K-means cluster analyses were performed. Resultant clusters were compared on symptom severity and psychosocial functioning at baseline and across treatment.

Results:

Two distinct symptom profiles emerged: “dysregulated/defiant” and “classic presentation.” The dysregulated/defiant cluster was characterized by more externalizing and disruptive behaviors, whereas the classic cluster presented with more severe depression, hallmark manic symptoms, anxiety, and inattention. CFF-CBT consistently promoted psychosocial coping skills, such as problem solving and self-control, for the dysregulated/defiant cluster. TAU also promoted these skills among the individuals in the classic presentation group but not those with symptoms in the dysregulated/defiant cluster.

Discussion:

Pediatric BD may be characterized by distinct phenotypes with unique etiologies and pathways to impairment. The use of a parametric approach to classify the diverse symptom presentations helped yield valuable insights into how to promote the best prognosis for improved functional outcomes in CFF-CBT versus TAU for youth with pediatric BD.
Religious Activity, Psychotic Features, and Suicidality in 688 Acute Psychiatric Inpatients
Authors: ABDEL GAWAD NOHA , DESAI PRATIKKUMAR , ALI TAHA , LEWIS KIMBERLY K. , POLO ROBERT , ENGSTROM ALLISON , ALLEN MELISSA , PIGOTT TERESA
Published: January 2019

Background:

Religiosity has been linked to mental health outcomes for decades. This study examined the potential relationship between religiosity and demographic and clinical variables in a sample of psychiatric inpatients.

Methods:

In total, 688 adults admitted to an acute psychiatric facility with a primary mood or psychotic disorder completed the Duke University Religion Index (DUREL). The DUREL measures religious activity in 3 domains: organizational religious activity (ORA), nonorganizational religious activity (NORA), and intrinsic (or subjective) religiosity (IR). We categorized scores into high and low religiosity. Bivariate analyses with χ2 and independent sample t tests were used to examine the association between the DUREL subscales and demographic, clinical, and outcome measures. A generalized linear model was used to identify predictors of suicidality, psychosis, and 30-day rehospitalization.

Results:

Elevated religious activity was common in the inpatient sample, with 58% categorized as high IR, 43% as high NORA, and 36% as high ORA. For all 3 DUREL subscales, high religiosity scores were associated with significantly more psychosis (P<0.05) and significantly less suicidal ideation (P<0.001). High ORA (P=0.001) and high IR (P=0.01) were associated with significantly fewer suicide attempts. High ORA scores were also associated with an increased length of stay (P<0.05) and more frequent 30-day readmission rates (P=0.01). In the generalized linear model, predictors of lower levels of suicidality were high ORA, high IR, and a diagnosis of schizophrenia, schizoaffective disorder, or other psychotic disorder, whereas a diagnosis of depressive disorder was associated with greater suicidality. Predictors of psychosis were high IR and Hispanic ethnicity, whereas a diagnosis of depressive disorder was associated with lower rates of psychosis. Female inpatients were more likely than male inpatients to score high on the ORA (P<0.05), NORA (P<0.05), and IR (P<0.0001) subscales. In addition, a significant relationship was detected between age and high IR scores (P<0.005), with increasing age associated with higher IR scores.

Conclusions:

Although preliminary, these results suggest that a brief measure of religiosity may provide important information concerning clinical features and acute outcomes in patients hospitalized with serious mental illness.
Whether Called Acute Suicidal Affective Disturbance or Suicide Crisis Syndrome, a Suicide-specific Diagnosis Would Enhance Clinical Care, Increase Patient Safety, and Mitigate Clinician Liability
Authors: JOINER THOMAS E. , SIMPSON SKIP , ROGERS MEGAN L. , STANLEY IAN H. , GALYNKER IGOR I.
Published: January 2019

Separate research groups have independently argued the need for a suicide-specific diagnosis within the psychiatric diagnostic nomenclature. Although a suicide-specific diagnosis could possibly enhance clinical care and improve patient safety, some clinicians have expressed concerns regarding the legal risk of utilizing a suicide-specific diagnosis. In this column, the first of a 2-part series exploring the potential risks and benefits of a suicide-specific diagnosis, the authors draw from their decades of experience in clinical work, legal consulting, as well as the litigation of suicide and wrongful death lawsuits and contend that the bona fide use of a suicide-specific diagnosis would mitigate legal liability to clinicians.
Visual Attention Affects the Amplitude of the Transcranial Magnetic Stimulation-associated Motor-evoked Potential: A Preliminary Study With Clinical Utility
Authors: BELL SPENCER J. , LAUER ABIGAIL , LENCH DANIEL H. , HANLON COLLEEN A.
Published: January 2019

Background:

The transcranial magnetic stimulation (TMS)-elicited motor-evoked potential (MEP) is a valuable measure for clinical evaluations of various neurological disorders and is used to determine resting motor threshold for repetitive TMS dosing. Although MEP amplitude is primarily associated with motor system function, there is evidence that nonmotor factors may also influence amplitude. This experiment tested the hypotheses that manipulation of 2 factors (visual attention, cognitive regulation) in human participants would significantly affect MEP amplitude.

Methods:

Blocks of MEPs were recorded from the dominant right hand as participants (N=20) were instructed to shift their visual attention (toward and away from the hand) and cognitively regulate the MEPs (rest, attenuate MEP amplitude, potentiate MEP amplitude) using their thoughts (6 blocks, 20 pulses/block, randomized, 110% resting motor threshold).

Results:

MEP amplitude was significantly affected by the direction of visual attention; looking away from the hand led to higher amplitudes (P=0.003). The relationship with cognitive regulation was nonsignificant.

Conclusions:

The significant effect of visual attention on MEP suggests that this should be a standardized parameter in clinical and research studies. These data underscore the importance of rigorous reporting of methods and use of standardized practices for MEP acquisition and TMS dosing to ensure consistent clinical measurement and treatment.
Association Between Delusions of Infestation and Prescribed Narcotic and Stimulant Use
Authors: ZHU TIAN HAO , WERCHAN ISELA A. , ESCAMILLA KRISTIN V. , SEBASTIAN KATHERINE , HOVINGA COLLIN A. , REICHENBERG JASON S.
Published: January 2019

Objective:

Patients diagnosed with delusions of infestation (DOI) at a psychodermatology clinic appeared to have a higher incidence of being prescribed narcotic or stimulant medications compared with the general dermatologic clinic population with chronic pruritic conditions. A retrospective study was conducted examining the correlation between patients with DOI and prescribed psychoactive medications.

Methods:

Ninety-two patients with a diagnosis of DOI, seen at our University Psychodermatology Clinic, served as the study population. The comparison group (N=354) included dermatology patients seen at a dermatology clinic by the same dermatologist for itching, including adults seen for chronic pruritic conditions and contact dermatitis. For both groups, the reported use of any psychoactive prescription medications was noted.

Results:

Patients with DOI were significantly more likely than other dermatology patients to receive prescriptions for narcotics [adjusted odds ratio (OR)=2.19; confidence interval (CI)=1.21-3.99) and stimulants (OR=5.44; CI=2.37-12.52). Patients with DOI were also more likely to be female (OR=2.49; CI=1.47-4.22) than patients who did not have such delusions.

Discussion:

Few data are available concerning the etiology and management of DOI. Findings from this study indicated an association between the diagnosis of DOI and the prescribing of narcotics and stimulants, even when sex and age were taken into account. This information may be used to assist with the diagnosis of patients presenting with DOI and possible treatment options. It will be important to determine if these medications are a cause of the condition, or are merely correlated with other medical conditions.
Heroin Addiction in Serbian Patients With Tourette Syndrome
Authors: SARAJLIJA MARIJA , RAKETIC DIANA , NESIC NADA
Published: January 2019

Introduction:

Tourette syndrome (TS) is a neurodevelopmental disorder with a high prevalence of psychiatric comorbidity. The most common comorbid disorder in patients with TS is attention-deficit/hyperactivity disorder (ADHD). To date, there have been few reports concerning the association of TS with addiction.

Methods:

We report on 4 patients with TS, ADHD, and heroin addiction.

Results:

All 4 patients were male and initially presented with TS when they were between 5 and 12 years of age, although 2 of the patients were not diagnosed with TS until they were adults. The patients currently range in age from 21 to 52 years, all having experienced the onset of heroin addiction in adolescence. A reduction in tics during periods of heroin abuse was noted in all patients.

Discussion:

The lifetime prevalence of psychiatric comorbidity in patients with TS is 85.7%, with 57.7% of patients having ≥2 psychiatric conditions in addition to TS. All of the 4 patients in our case series demonstrated a pattern of severe tics, ADHD, impulsive behavior, and heroin addiction. Our observation that these 4 patients with TS showed reduced tics during periods of heroin dependence could be related to the previously described effects of opiates on dopaminergic transmission.

Conclusions:

The observed reduction of tics during heroin dependence warrants further clinical research.
Sever's Disease (Calcaneal Apophysitis)
Authors: Ramponi Denise R. , Baker Caron
Published: January 2019

Sever's disease, or calcaneal apophysitis, is the primary cause of heel pain in pediatric patients between the ages of 8 and 15 years. Primary risk factors in pediatric athletes are obesity and high levels of physical activity. Sever's injury primarily results from high-impact sports such as soccer, track, cross-country, gymnastics, tennis, and ballet. This injury mainly occurs during puberty with an open growth plate in the immature calcaneus. Clinical diagnosis can be confirmed by performing a “squeeze test” of the heel on physical examination. Diagnostic imaging findings include increased sclerosis and fragmentation of the calcaneal apophysis on plain radiograph x-rays. Ice, activity restriction, stretching, nonsteroidal anti-inflammatory drugs, immobilization, and heel cups are all methods that can be utilized in treating the pain caused by Sever's. No long-term effects have been associated with Sever's disease.
Vehicles of intercellular communication: exosomes and HIV-1
Authors: Welch Jennifer L. , Stapleton Jack T. , Okeoma Chioma M.
Published: January 2019

The terms extracellular vesicles, microvesicles, oncosomes, or exosomes are often used interchangeably as descriptors of particles that are released from cells and comprise a lipid membrane that encapsulates nucleic acids and proteins. Although these entities are defined based on a specific size range and/or mechanism of release, the terminology is often ambiguous. Nevertheless, these vesicles are increasingly recognized as important modulators of intercellular communication. The generic characterization of extracellular vesicles could also be used as a descriptor of enveloped viruses, highlighting the fact that extracellular vesicles and enveloped viruses are similar in both composition and function. Their high degree of similarity makes differentiating between vesicles and enveloped viruses in biological specimens particularly difficult. Because viral particles and extracellular vesicles are produced simultaneously in infected cells, it is necessary to separate these populations to understand their independent functions. We summarize current understanding of the similarities and differences of extracellular vesicles, which henceforth we will refer to as exosomes, and the enveloped retrovirus, HIV-1. Here, we focus on the presence of these particles in semen, as these are of particular importance during HIV-1 sexual transmission. While there is overlap in the terminology and physical qualities between HIV-1 virions and exosomes, these two types of intercellular vehicles may differ depending on the bio-fluid source. Recent data have demonstrated that exosomes from human semen serve as regulators of HIV-1 infection that may contribute to the remarkably low risk of infection per sexual exposure.
Effect of foot-and-mouth disease virus 3C protease B2 β-strand proline mutagenesis on expression and processing of the P1 polypeptide using a plasmid expression vector
Authors: Martel Erica , Forzono Emily , Kurker Richard , Clark Benjamin A. , Neilan John G. , Puckette Michael
Published: January 2019

The production of experimental molecular vaccines against foot-and-mouth disease virus utilizes the viral encoded 3C protease for processing of the P1 polyprotein. Expression of wild type 3C protease is detrimental to host cells. The molecular vaccine constructs containing the 3C protease L127P mutant significantly reduce adverse effects associated with protease expression while retaining the ability to process and assemble virus-like particles. In published 3C protease crystal structures, the L127 residue is contained within the B2 β-strand as part of the A2–B2 β-sheet. To provide insight into the mechanism by which the L127P mutant alters the properties of the 3C protease, we performed scanning proline mutagenesis of residues 123–128 of the B2 β-strand and monitored expression and P1 processing. Simultaneously, we utilized random mutagenesis of the full 3C sequence to identify additional mutations presenting a phenotype similar to the L127P mutation. Six of the tested mutants enhanced expression over wild type, and the I22P, T100P and V124P mutations surpassed the L127P mutation in certain cell lines. These data areinterpreted in conjunction with published 3C protease crystal structures to provide insight into the mechanism by which these mutations enhance expression.
Where the plasmids roam: large-scale sequence analysis reveals plasmids with large host ranges
Authors: Brooks Lauren Elisabeth , Kaze Mo , Sistrom Mark
Published: January 2019

Describing the role of plasmids and their contribution to the exchange of genetic material among bacteria is essential for understanding the fields of plasmid epidemiology, microbial ecology, and commercial and synthetic microbiology. Broad-host-range (BHR) plasmids are those that are found not only in a single bacterial species, but in members of different taxonomic groups and are of significant interest to researchers in many fields. We applied a novel approach to computationally identify new BHR plasmids, in which we searched for highly similar cognate plasmids within a comprehensive plasmid database. After identifying 125 plasmid groups with highly similar cognates found in multiple taxa, we closely examined BHR plasmids found in multiple families. The majority of our identified BHR plasmids are found in members of the

Enterobacteriaceae

and closely related taxa, while three BHR plasmids of potential commercial significance were found in two species of

Cyanobacteria

. One plasmid with an exceptionally broad host range was found in both Gram-positive and Gram-negative bacterial species. This analysis demonstrates the utility of this method in identifying new BHR plasmids while highlighting unknown ranges of previously documented plasmids.
HBEGF+macrophages identified in rheumatoid arthritis promote joint tissue invasiveness and are reshaped differentially by medications
Authors: Kuo David , Ding Jennifer , Cohn Ian , Zhang Fan , Wei Kevin , Rao Deepak , Rozo Cristina , Sokhi Upneet K. ,   Accelerating Medicines Partnership RA/SLE Network, DiCarlo Edward F. , Brenner Michael B. , Bykerk Vivian P. , Goodman Susan M. , Raychaudhuri Soumya , Rätsch Gunnar , Ivashkiv Lionel B. , Donlin Laura T.
Published: January 2019

Macrophages tailor their function to the signals found in tissue microenvironments, taking on a wide spectrum of phenotypes. In human tissues, a detailed understanding of macrophage phenotypes is limited. Using single-cell RNA-sequencing, we define distinct macrophage subsets in the joints of patients with the autoimmune disease rheumatoid arthritis (RA), which affects ~1% of the population. The subset we refer to as HBEGF+inflammatory macrophages is enriched in RA tissues and shaped by resident fibroblasts and the cytokine TNF. These macrophages promote fibroblast invasiveness in an EGF receptor dependent manner, indicating that inflammatory intercellular crosstalk reshapes both cell types and contributes to fibroblast-mediated joint destruction. In anex vivotissue assay, the HBEGF+inflammatory macrophage is targeted by several anti-inflammatory RA medications, however, COX inhibition redirects it towards a different inflammatory phenotype that is also expected to perpetuate pathology. These data highlight advances in understanding the pathophysiology and drug mechanisms in chronic inflammatory disorders can be achieved by focusing on macrophage phenotypes in the context of complex interactions in human tissues.

One Sentence Summary

A newly identified human macrophage phenotype from patients with the autoimmune condition RA is found to promote joint tissue invasiveness and demonstrates variable sensitivities to anti-inflammatory medications used to treat the disease.
Network analysis to evaluate the impact of research funding on research community consolidation
Authors: Hicks Daniel J. , Coil David , Stahmer Carl G. , Eisen Jonathan A.
Published: January 2019

In 2004, the Alfred P. Sloan Foundation launched a new program focused on incubating a new field, “Microbiology of the Built Environment” (MoBE). By the end of 2017, the program had supported the publication of hundreds of scholarly works, but it was unclear to what extent it had stimulated the development of a new research community. We identified 307 works funded by the MoBE program, as well as a comparison set of 698 authors who published in the same journals during the same period of time but were not part of the Sloan Foundation-funded collaboration. Our analysis of collaboration networks for both groups of authors suggests that the Sloan Foundation’s program resulted in a more consolidated community of researchers, specifically in terms of number of components, diameter, density, and transitivity of the coauthor networks. In addition to highlighting the success of this particular program, our method could be applied to other fields to examine the impact of funding programs and other large-scale initiatives on the formation of research communities.
Translational landscape in tomato revealed by transcriptome assembly and ribosome profiling
Authors: Wu Hsin-Yen Larry , Song Gaoyuan , Walley Justin W. , Hsu Polly Yingshan
Published: January 2019

mRNA translation is a critical step in gene expression, but our understanding of the landscape and control of translation in diverse crops remains lacking. Here, we combined de novo transcriptome assembly and ribosome profiling to study global mRNA translation in tomato roots. Taking advantage of the 3-nucleotide periodicity displayed by translating ribosomes, we identified 354 novel small ORFs (sORFs) translated from previously unannotated transcripts, as well as 1329 upstream ORFs (uORFs) translated within the 5-prime UTRs of annotated protein-coding genes. Proteomic analysis confirmed that some of these novel uORFs and sORFs generate stable proteins in planta. Compared with the annotated ORFs, the uORFs use more flexible Kozak sequences around translation start sites. Interestingly, uORF-containing genes are enriched for protein phosphorylation/dephosphorylation and signaling transduction pathways, suggesting a regulatory role for uORFs in these processes. We also demonstrated that ribosome profiling is useful to facilitate the annotation of translated ORFs and noncanonical translation initiation sites. In addition to defining the translatome, our results revealed the global control of mRNA translation by uORFs and microRNAs in tomato. In summary, our approach provides a high-throughput method to discover unannotated ORFs, elucidates evolutionarily conserved translational features, and identifies new regulatory mechanisms hidden in a crop genome.
Genome-wide copy number variation-, validation- and screening study implicates a novel copy number polymorphism associated with suicide attempts in major depressive disorder
Authors: Rao Shitao , Shi Mai , Han Xinyu , Lam Marco Ho Bun , Liu Guangming , Wing Yun Kwok , So Hon-Cheong , Waye Mary Miu Yee
Published: January 2019

Background

The genetic basis of suicide attempts (SA) remained unclear, especially for the copy number variations (CNVs) involved. The present study aimed to identify the susceptibility variants associated with SA among major depressive disorder (MDD) patients in Chinese, covering both single-nucleotide polymorphisms and CNVs.

Methods

We conducted GWAS on MDD patients with or without SA and top results were tested in a replication study. A genome-wide CNV study was performed. Subsequently, a validation assay using the qRT-PCR technology was performed to confirm the existence of the associated CNV and then applied to the entire cohort to examine the association.

Results

In CNV analysis, we found that the global rate of CNV was higher in SA compared to non-SA subjects (p=0.023). The genome-wide CNV study revealed a SA-associated CNV region that achieved genome-wide significance (corrected p-value=0.014). The associated CNV was successfully validated and identified to be a common variant in this cohort and its deletion rate was higher in suicide attempters (OR=2.05). Based on the GTEx database, genetic variants that probe this CNV was significantly associated with the expression level of ZNF33B in two brain regions (p-value<4.2e-05). Besides, there was a significant interaction between neuroticism and the CNV in affecting suicidal risk; the CNV showed a significant effect (OR=2.58) in subjects with high neuroticism only.

Conclusions

We identified a new common CNV that may be involved in the etiology of SA. These findings imply an important role of common CNVs in the etiology of SA, which suggests a new promising avenue for investigating the genetic architecture of SA.
Do Brucella Antibody Titers Correlate with Clinical Outcomes and Culture Positivity of Brucellosis?
Authors: Alsubaie Shahad A. , Turkistani Shouq A. , Zeaiter Alanoud A. , Thabit Abrar K.
Published: January 2019

Brucellosis is a zoonotic disease caused by Brucella spp., namely B. meletinsis and B. abortus in humans. Studies on the correlation between Brucella antibody titers and clinical outcomes are limited. Therefore, this study assessed such correlation and evaluated the correlation between baseline serologic results with culture positivity and clinical picture. Patients tested positive for Brucella antibodies at baseline and diagnosed with brucellosis between January 2008 and December 2018 were included. Collected data included clinical outcomes, baseline culture positivity, arthralgia, baseline and EOT temperature, white blood cell (WBC) count, C-reactive protein level, and erythrocyte sedimentation rate. Of 695 patients tested for Brucella antibodies, only 94 had positive baseline serology and diagnosed with brucellosis, among whom 63 had EOT serology. No significant correlations were found between EOT antibody titers of both Brucella spp. and clinical cure, mortality, length of stay, and duration of therapy. Additionally, no correlations were found between baseline serology and culture positivity, arthralgia, temperature, and other lab values. Brucella serology does not correlate with clinical outcomes at EOT nor with culture positivity at baseline. Therefore, healthcare providers are advised to consider the whole clinical picture of a brucellosis patient without relying solely on serologic results during follow up and not replace culturing with serology testing alone at the time of diagnosis.
A Gradient of Hippocampal Inputs to the Medial Mesocortex
Authors: Ferreira-Fernandes Emanuel , Quintino Carolina , Remondes Miguel
Published: January 2019

Memory-guided decisions depend on complex, finely tuned interactions between hippocampus and medial mesocortical regions anterior cingulate and retrosplenial cortices. The functional circuitry underlying these interactions is unclear. Using viral anatomical tracing,in vitroandin vivoelectrophysiology, and optogenetics, we show that such circuitry is characterized by a functional-anatomical gradient. While CG receives excitatory projections from dorsal-intermediate CA1 originated exclusively instratum pyramidale, retrosplenial cortex also receives inputs originating instratum radiatumandlacunosum-moleculare, including GAD+ neurons providing long-range GABAergic projections. Such hippocampal projections establishbona fidesynapses throughout cortical layers, with retrosplenial cortex densely targeted on its layer 3, around which it receives a combination of inhibitory and excitatory synapses. This gradient is reflected in the pattern of spontaneous oscillatory synchronicity found in the awake-behaving animal, compatible with the known functional similarity of hippocampus with retrosplenial cortex, which contrasts with the encoding of actions and “task-space” by cingulate cortex.

Highlights

Both MMC regions CG and RSC receive monosynaptic connections from the dorsal-intermediate CA1

CG receives layer-sparse excitatory projections exclusively originated fromstratum piramidalewhereas RSC is targeted densely in superficial layers by a mixed excitatory and inhibitory input originating from all CA1strata

CA1 monosynaptic projections correspond to active synapses onto distinct layers of the two MMC regions

Diverse synchrony between MMC and HIPP recordedin vivois consistent with the rostro-caudal diversity of direct HIPP-MMC connections
Saccade countermanding reflects automatic inhibition as well as top-down cognitive control
Authors: Bompas Aline , Campbell Anne Eileen , Sumner Petroc
Published: January 2019

Countermanding behavior has long been seen as a cornerstone of executive control – the human ability to selectively inhibit undesirable responses and change plans. In recent years, however, scattered evidence has emerged that stopping behavior is entangled with simpler automatic stimulus-response mechanisms. Here we give flesh to this idea by merging the latest conceptualization of saccadic countermanding with a versatile neural network model of visuo-oculomotor behavior that integrates bottom-up and top-down drives. This model accounts for all fundamental qualitative and quantitative features of saccadic countermanding, including neuronal activity. Importantly, it does so by using the same architecture and parameters as basic visually guided behavior and automatic stimulus-driven interference. Using simulations and new data, we compare the temporal dynamics of saccade countermanding with that of saccadic inhibition (SI), a hallmark effect thought to reflect automatic competition within saccade planning areas. We demonstrate how SI accounts for a large proportion of the saccade countermanding process when using visual signals. We conclude that top-down inhibition acts later, piggy-backing on the quicker automatic inhibition. This conceptualization fully accounts for the known effects of signal features and response modalities traditionally used across the countermanding literature. Moreover, it casts different light on the concept of top-down inhibition, its timing and neural underpinning, as well as the interpretation of stop-signal reaction time, the main behavioral measure in the countermanding literature.
Stimulation of the vagus nerve reduces learning in a go/no-go reinforcement learning task
Authors: Kühnel Anne , Teckentrup Vanessa , Neuser Monja P. , Huys Quentin J. M. , Burrasch Caroline , Walter Martin , Kroemer Nils B.
Published: January 2019

When facing decisions to approach rewards or to avoid punishments, we often figuratively go with our gut, and the impact of metabolic states such as hunger on motivation are well documented. However, whether and how vagal feedback signals from the gut influence instrumental actions is unknown. Here, we investigated the effect of non-invasive transcutaneous vagus nerve stimulation (tVNS) vs. sham (randomized cross-over design) on approach and avoidance behavior using an established go/no-go reinforcement learning paradigm (Guitart-Masip et al., 2012) in 39 healthy, participants after an overnight fast. First, mixed-effects logistic regression analysis of choice accuracy showed that tVNS acutely impaired decision-making, p = .045. Computational reinforcement learning models identified the cause of this as a reduction in the learning rate through tVNS (Δα = −0.092, pboot= .002), particularly after punishment (ΔαPun= −0.081, pboot= .012 vs. ΔαRew= −0.031, p = .22). However, tVNS had no effect on go biases, Pavlovian response biases or response time. Hence, tVNS appeared to influence learning rather than action execution. These results highlight a novel role of vagal afferent input in modulating reinforcement learning by tuning the learning rate according to homeostatic needs.
Contextual fear learning and memory differ between stress coping styles in zebrafish
Authors: Baker Matthew R , Wong Ryan Y
Published: January 2019

Animals frequently overcome stressors and the ability to learn and recall these salient experiences is essential to an individual’s survival. As part of an animal’s stress coping style, behavioral and physiological responses to stressors are often consistent across contexts and time. However, we are only beginning to understand how cognitive traits can be biased by different coping styles. Here we investigate learning and memory differences in zebrafish (Danio rerio) displaying proactive and reactive stress coping styles. We assessed learning rate and memory duration using an associative fear conditioning paradigm that trained zebrafish to associate a context with exposure to a natural olfactory alarm cue. Our results show that both proactive and reactive zebrafish learn and remember this fearful association. However, we note significant interaction effects between stress coping style and cognition. Zebrafish with the reactive stress coping style acquired the fear memory at a significantly faster rate than proactive fish. While both stress coping styles showed equal memory recall one day post-training, reactive zebrafish showed significantly stronger recall of the conditioned context relative to proactive fish four days post-training. Through understanding how stress coping strategies promote biases in processing salient information, we gain insight into mechanisms that can constrain adaptive behavioral responses.
Long-term Brillouin imaging of live cells with reduced absorption-mediated damage at 660nm wavelength
Authors: Nikoliš Miloć , Scarcelli Giuliano
Published: January 2019

In Brillouin microscopy, absorption-induced photodamage of incident light is the primary limitation on signal-to-noise ratio in many practical scenarios. Here we show that 660 nm may represent an optimal wavelength for Brillouin microscopy as it offers minimal absorption-mediated photodamage at high Brillouin scattering efficiency and the possibility to use a pure and narrow laser line from solid-state lasing medium. We demonstrate that live cells are ~80 times less susceptible to the 660 nm incident light compared to 532 nm light, which overall allows Brillouin imaging of up to more than 30 times higher SNR. We show that this improvement enables Brillouin imaging of live biological samples with improved accuracy, higher speed and/or larger fields of views with denser sampling.
FOURIER RING CORRELATION SIMPLIFIES IMAGE RESTORATION IN FLUORESCENCE MICROSCOPY
Authors: Koho Sami , Tortarolo Giorgio , Castello Marco , Deguchi Takahiro , Diaspro Alberto , Vicidomini Giuseppe
Published: January 2019

Fourier ring correlation (FRC) has recently gained some popularity among (super-resolution) fluorescence microscopists as a straightforward and objective method to measure the effective resolution of a microscopy image. While the knowledge of the numeric resolution value is helpful in e.g. interpreting imaging results, much more practical use can be made of FRC analysis – in this article we propose novel blind image restoration methods enabled by it. We apply FRC to perform image de-noising by frequency domain filtering. We propose novel blind linear and non-linear image deconvolution methods that use FRC to estimate the effective point-spread-function, directly from the images, with no need for prior knowledge of the instrument or sample characteristics. The deconvolution is shown to work exquisitely with both two- and three-dimensional images. We also show how FRC can be used as a powerful metric to observe the progress of iterative deconvolution. While developing the image restoration methods, we also addressed two important limitations in FRC that are of more general interest: how to make FRC work with single images and with three-dimensional images with anisotropic resolution.
The genetic structure of the European black pine (Pinus nigraArnold) is shaped by its recent Holocene demographic history
Authors: Giovannelli Guia , Scotti-Saintagne Caroline , Scotti Ivan , Roig Anne , Spanu Ilaria , Vendramin Giovanni Giuseppe , Guibal Frédéric , Fady Bruno
Published: January 2019

Fragmentation acting over geological times confers wide, biogeographical scale, genetic diversity patterns to species, through demographic and natural selection processes. To test the effects of historical fragmentation on the genetic diversity and differentiation of a major European forest tree and to resolve its demographic history, we describe and model its spatial genetic structure and gene genealogy. We then test which Pleistocene event, whether recent or ancient, could explain its widespread but patchy geographic distribution using population genetic data, environmental data and realistic demographic timed scenarios.

The taxon of interest is a conifer forest tree,Pinus nigra(Arnold), the European black pine, whose populations are located in the mountains of southern Europe and North Africa, most frequently at mid-elevation. We used a set of different genetic markers, both neutral and potentially adaptive, and either bi-parentally or paternally inherited, and we sampled natural populations across the entire range of the species. We analysed the data using frequentist population genetic methods as well as Bayesian inference methods to calibrate realistic, demographic timed scenarios.

Species with geographically fragmented distribution areas are expected to display strong among-population genetic differentiation and low within-population genetic diversity. Contrary to these expectations, we show that the current diversity ofPinus nigraand its weak genetic spatial structure are best explained as resulting from late Pleistocene or early Holocene fragmentation of one ancestral population into seven genetic lineages, which we found to be the main biogeographical contributors of the natural black pine forests of today. Gene flow among the different lineages is strong across forests and many current populations are admixed between lineages. We propose to modify the currently accepted international nomenclature made of five subspecies and name these seven lineages using regionally accepted subspecies-level names.

Highlights

The European black pine,Pinus nigra(Arnold), has a weak spatial genetic structure.

Gene flow among populations is frequent and populations are often of admixed origin.

Current genealogies result from recent, late Pleistocene or Holocene events.

Seven modern genetic lineages emerged from divergence and demographic contractions.

These seven lineages warrant a revision of subspecies taxonomic nomenclature.