bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hemodynamic Tolerance to IV Clonidine Infusion in the PICU*
Authors: Kleiber Niina , van Rosmalen Joost , Tibboel Dick , de Wildt Saskia N. 
Published: June 2018

Objectives:
Clonidine is an antihypertensive drug used for analgosedation in the PICU. Lack of reliable data on its hemodynamic tolerance limits its use. This study explores the hemodynamic tolerance of IV clonidine infusion in a broad population of children with high severity of disease.

Design:
Retrospective analysis of prospectively collected data.

Setting:
A tertiary and quaternary referral PICU.

Patients:
Critically ill children age 0–18 years old who received an IV clonidine infusion for analgosedation of at least 1 hour.

Interventions:
None.

Measurements and Main Results:
The primary endpoints were the prevalences of bradycardia and hypotension. Secondary endpoints were changes in heart rate, blood pressure, Vasoactive-Inotropic Score, COMFORT Behavior score (a sedation scoring scale), and body temperature during the infusion. The association of bradycardia with other hemodynamic variables was explored, as well as potential risk factors for severe bradycardia. One-hundred eighty-six children (median age, 12.9 mo [interquartile range, 3.5–60.6 mo]) receiving a maximum median clonidine infusion of 0.7 µg/kg/hr (interquartile range, 0.3–1.5) were included. Severe bradycardia and systolic hypotension occurred in 72 patients (40.2%) and 105 patients (58%), respectively. Clonidine-associated bradycardia was hemodynamically well tolerated, as it was not related with hypotension and the need for vasoactive drugs decreased in parallel with a sedation score guided clonidine infusion rate increase. Younger age was the only identified risk factor for clonidine-associated bradycardia.

Conclusions:
Although administration of clonidine is often associated with bradycardia and hypotension, these complications do not seem clinically significant in a mixed PICU population with a high degree of disease severity. Clonidine may have a vasoactive-inotropic sparing effect.
Ruptured Thoracic and Abdominal Gastrointestinal Duplication Cysts Presenting With Failure to Thrive
Authors: Shinnick Julia K. , Jain Shabnam , Alazraki Adina L. , Durham Megan M. 
Published: June 2018

Abstract
Gastrointestinal duplication cysts are rare congenital malformations, with esophageal and gastric duplication cysts being among the rarest. We report an 8-week-old female who presented to the emergency department with failure to thrive and was subsequently found to have multiple gastric and esophageal duplication cysts that had ruptured intrathoracically and intra-abdominally. We describe the diagnosis and management of this patient who underwent successful resection of 4 gastrointestinal duplication cysts. This report emphasizes the unexpected, and sometimes relatively benign, presentations of gastrointestinal duplication cysts. To our knowledge, this is the first reported occurrence of multiple duplication cysts that independently ruptured thoracically and abdominally.
Perceived Partner Responsiveness, Daily Negative Affect Reactivity, and All-Cause Mortality: A 20-Year Longitudinal Study
Authors: Stanton Sarah C.E. , Selcuk Emre , Farrell Allison K. , Slatcher Richard B. , Ong Anthony D. 
Published: June 2018

ABSTRACT

Objective
This study tested longitudinal associations between absolute levels of perceived partner responsiveness (PPR; how much people perceive that their romantic partners understand, care for, and appreciate them), daily negative affect reactivity and positive affect reactivity, and all-cause mortality in a sample of 1,208 adults for three waves of data collection spanning 20 years. We also tested whether longitudinal changes in PPR predicted mortality via affect reactivity.

Methods
Data were taken from the National Survey of Midlife Development in the United States. PPR was assessed at waves 1 and 2, affect reactivity to stressors was assessed by daily diary reports at wave 2, and mortality status was obtained at wave 3.

Results
Mediation analyses revealed absolute levels of PPR at wave 1 predicted wave 3 mortality via wave 2 affective reactivity in the predicted direction, but this did not remain robust when statistically accounting for covariates (e.g., marital risk, neuroticism), β = .004, 95% confidence interval = −.03 to .04. However, wave 1–2 PPR change predicted negative affect (but not positive affect) reactivity to daily stressors at wave 2, which then predicted mortality risk a decade later (wave 3); these results held when adjusting for relevant demographic, health, and psychosocial covariates, β = −.04, 95% confidence interval = −.09 to −.002.

Conclusions
These findings are among the first to provide direct evidence of psychological mechanisms underlying the links between intimate relationships and mortality and have implications for research aiming to develop interventions that increase or maintain responsiveness in relationships over time.
Attrition Across the HIV Cascade of Care Among a Diverse Cohort of Women Living With HIV in Canada
Authors: Kerkerian Geneviève , Kestler Mary , Carter Allison , Wang Lu , Kronfli Nadine , Sereda Paul , Roth Eric , Milloy M-J , Pick Neora , Money Deborah , Webster Kath , Hogg Robert S. , de Pokomandy Alexandra , Loutfy Mona , Kaida Angela ,   on behalf of the CHIWOS Research Team
Published: June 2018

Background:
In North America, women have lower engagement across the HIV cascade of care compared with men. Among women living with HIV (WLWH) in Canada, we measured the prevalence and correlates of attrition across cascade stages overall, and by key subpopulations.

Methods:
We analyzed baseline survey data regarding 6 nested stages of the HIV cascade among 1424 WLWH enrolled in the Canadian HIV Sexual and Reproductive Health Cohort Study (CHIWOS), including: linked to care, retained in care, initiated antiretroviral therapy (ART), current ART use, ART adherence (≥90%), and viral suppression (<50 copies/mL). Logistic regression identified factors associated with attrition at each stage.

Results:
Overall, 98% of WLWH were linked to care; 96% retained; 88% initiated ART; 83% were currently on ART; and, among those on ART, 68% were adherent and 72% were virally suppressed, with substantial variability by subpopulation (49%–84%).
The largest attrition occurred between current ART use and adherence (−17%), with the greatest losses among indigenous women (−25%), women who use illicit drugs (−32%), and women incarcerated in the past year (−45%). Substantial attrition also occurred between linkage to care and ART initiation (−11%), with the greatest losses among women 16–29 years (−20%) and with unstable housing (−27%). Factors independently associated with attrition at viral suppression included household annual income, racial discrimination, incarceration history, age, and resilience.

Conclusions:
Overall, 28% of WLWH were lost across the HIV care cascade, with significant differences by stage, subpopulation, and social inequities. Targeted interventions are needed to improve women's retention across the cascade.
Somatostatin Receptor PET/CT Features of Carcinoid Heart Disease
Authors: Arora Saurabh , Passah Averilicia , Damle Nishikant A. , Narang Rajiv , Sharma Atul , Yadav Madhav P. , Ballal Sanjana , Bhasin Dinkar , Bal Chandrasekhar 
Published: June 2018

Abstract
We present the case of a 35-year-old woman with metastatic neuroendocrine tumor undergoing treatment with long-acting octreotide and 177Lu-DOTATATE therapy. We present features of carcinoid heart disease on 68Ga-DOTANOC PET/CT, which revealed dilated right atrium, pericardial effusion, ascites, and congestive hepatopathy apart from the metastatic lesions in the liver. The scan cardiac findings were confirmed by echocardiography. This highlights the significance of identifying such patients early because additional management is required for carcinoid heart disease per se and a cautious approach is needed in administering amino acid infusion during PRRT that can result in fluid overload.
Imaging of Chemokine Receptor CXCR4 in Mycosis Fungoides Using 68Ga-Pentixafor PET/CT
Authors: Kuyumcu Serkan , Yilmaz Ebru , Büyükkaya Fikret , Özkan Zeynep Gözde , Ünal Seher Nilgün 
Published: June 2018

Abstract
A 52-year-old woman diagnosed with mycosis fungoides was referred for 18F-FDG PET/CT before treatment for the evaluation of disease severity. The patient also underwent 68Ga-pentixafor PET/CT for further evaluation. FDG uptake was observed in cervical, axillary, and pelvic lymph nodes and multiple widespread skin lesions throughout the body, suggestive of extensive involvement of mycosis fungoides. All lesions were visually identifiable with high target-to-background ratio on 68Ga-pentixafor PET/CT which demonstrated marked CXCR4 expression in all lesions that were detected using 18F-FDG PET/CT.
Modified Lefort Distraction Osteogenesis for the Treatment of Nager Syndrome-Associated Midface Hypoplasia: Technique and Review
Authors: Simpson Andrew M. , Mehta Sagar T. , Siddiqi Faizi , Yamashiro Duane , Gociman Barbu 
Published: June 2018

Abstract
The surgical management of midface hypoplasia in the setting of Nager syndrome remains a significant challenge for craniofacial surgeons. This study describes a novel technique using distraction osteogenesis and modified osteotomies for the treatment of midface bony defects in an 11-year-old child with Nager syndrome.
Presurgical 3-dimensional planning was performed to design the osteotomies and placement of distractors. The surgical approach required upper buccal sulcus and extended transconjunctival incisions only. Osteotomies were performed from the pyriform aperture through the orbit to include the lateral orbital wall, with bilateral osteotomy of the zygomas through the anterior arch via the transconjunctival incision. Distraction of the en bloc midface segment was successfully performed using external distractors. Bone grafting was not required. There were no complications.
External distraction was well tolerated and there were no intraoperative or postoperative complications. The distractors were removed uneventfully after consolidation. The midface was successfully advanced without the need for bone grafting or bicoronal incision. The occlusal plane was leveled and the aesthetic appearance of the child was improved.
Symmetrical midface hypoplasia in the context of Nager syndrome can be successfully corrected with en bloc distraction osteogenesis of the maxilla and bilateral zygomas through modified osteotomies that exclude the upper nasal pyramid. The approach is simplified and the need for bicoronal incision and bone grafting is mitigated in this technique, which the authors have named Lefort 2.5.
Positive airway pressure devices for the management of breathlessness
Authors: D’Cruz Rebecca F. , Kaltsakas Georgios , Suh Eui-Sik , Murphy Patrick B. , Hart Nicholas 
Published: June 2018

Purpose of review
Breathlessness is a common symptom in many chronic diseases and may be refractory to pharmacotherapy. In this review, we discuss the pathophysiology of breathlessness and the role of positive airway pressure (PAP) devices to ameliorate it.

Recent findings
Breathlessness is directly related to neural respiratory drive, which can be modified by addressing the imbalance between respiratory muscle load and capacity. Noninvasive PAP devices have been applied to patients limited by exertional breathless and, as the disease progresses, breathlessness at rest. The application of PAP is focussed on addressing the imbalance in load and capacity, aiming to reduce neural respiratory drive and breathlessness. Indeed, noninvasive bi-level PAP devices have been employed to enhance exercise capacity by enhancing pulmonary mechanics and reduce neural drive in chronic obstructive pulmonary disease (COPD) patients, and reduce breathlessness for patients with progressive neuromuscular disease (NMD) by enhancing respiratory muscle capacity. Novel continuous PAP devices have been used to maintain central airways patency in patients with excessive dynamic airway collapse (EDAC) and target expiratory flow limitation in severe COPD.

Summary
PAP devices can reduce exertional and resting breathlessness by reducing the load on the system and enhancing capacity to reduce neural respiratory drive.
Size control of the inner ear via hydraulic feedback
Authors: Mosaliganti Kishore R. , Swinburne Ian A. , Chan Chon U , Obholzer Nikolaus D. , Green Amelia A. , Tanksale Shreyas , Mahadevan L. , Megason Sean G. 
Published: June 2018

SUMMARYAnimals make organs of precise size, shape, and symmetry despite noise in underlying molecular and cellular processes. How developing organs manage this noise is largely unknown. Here, we combine quantitative imaging, physical theory, and physiological measurement of hydrostatic pressure and fluid transport in zebrafish to study size control of the developing inner ear. We find that fluid accumulation creates hydrostatic pressure in the lumen leading to stress in the epithelium and expansion of the otic vesicle. Pressure, in turn, inhibits fluid transport into the lumen. This negative feedback loop between pressure and transport allows the otic vesicle to change growth rate to control natural or experimentally-induced size variation. Spatiotemporal patterning of contractility modulates pressure-driven strain for regional tissue thinning. Our work connects moleculardriven mechanisms, such as osmotic pressure driven strain and actomyosin tension, to the regulation of tissue morphogenesis via hydraulic feedback to ensure robust control of organ size.
Atypical neurogenesis in induced pluripotent stem cell (iPSC) from autistic individuals
Authors: Adhya Dwaipayan , Swarup Vivek , Nagy Roland , Dutan Lucia , Shum Carole , Valencia-Alarcón Eva P. , Jozwik Kamila Maria , Mendez Maria Andreina , Horder Jamie , Loth Eva , Nowosiad Paulina , Lee Irene , Skuse David , Flinter Frances A. , Murphy Declan , McAlonan Grainne , Geschwind Daniel H. , Price Jack , Carroll Jason , Srivastava Deepak P. , Baron-Cohen Simon 
Published: June 2018

AbstractBackgroundAutism is a heterogenous collection of disorders with a complex molecular underpinning. Evidence from post-mortem brain studies using adult brains have indicated that early prenatal development may be altered in autism. Induced pluripotent stem cells (iPSCs) generated from autistic individuals with macrocephaly also indicate prenatal development as a critical period for this condition. But little is known about early altered cellular events during prenatal stages in autism.MethodsIPSCs were generated from 9 unrelated autistic individuals without macrocephaly and with heterogeneous genetic backgrounds, and 6 typically developing, control, individuals. IPSCs were differentiated towards either cortical or midbrain fates. Gene expression and high throughput cellular phenotyping was used to characterise iPSCs at different stage of differentiation.ResultsA subset of autism-iPSC cortical neurons were RNA-sequenced to reveal autism-specific signatures similar to post-mortem brain studies, indicating a potential common biological mechanism. Autism-iPSCs differentiated towards a cortical fate displayed impairments in the ability to self-form into neural rosettes. In addition, autism-iPSCs demonstrated significant differences in rate of cell type assignment of cortical precursors, and dorsal and ventral forebrain precursors. These cellular phenotypes occurred in the absence of alterations in cell proliferation during cortical differentiation, differing from previous studies. Acquisition of cell fate during midbrain differentiation was not different between control- and autism-iPSCs.ConclusionsTaken together, our data indicate that autism-iPSCs diverge from control-iPSCs at a cellular level during early stage of neurodevelopment. This suggests that unique developmental differences associated with autism may be established at early prenatal stages.
Objective Classification of Neocortical Pyramidal Cells
Authors: Kanari Lida , Ramaswamy Srikanth , Shi Ying , Morand Sebastien , Meystre Julie , Perin Rodrigo , Abdellah Marwan , Wang Yun , Hess Kathryn , Markram Henry 
Published: June 2018

AbstractA consensus on the number of morphologically different types of pyramidal cells (PCs) in the neocortex has not yet been reached, despite over a century of anatomical studies. This is because of a lack of agreement on the subjective classifications of neuron types, which is based on expert analyses of neuronal morphologies: the shapes of somata, dendrites, and axons. Even for neurons that are visually different to non-experts, there is no common ground to consistently distinguish morphological types. We found that objective classification is possible with methods from algebraic topology, and that the dendritic arbor is sufficient for reliable identification of distinct types of PCs. We also provide a solution for the more challenging problem of whether two similar neurons belong to different types or to a continuum of the same type. Using this scheme, we objectively identify seventeen types of PCs in the rat somatosensory cortex. Our topological classification does not require expert input, is stable, and helps settle the long-standing debate on whether cell-types are discrete or continuous morphological variations of each other.
Spatiotemporal Gene Coexpression and Regulation in Mouse Cardiomyocytes of Early Cardiac Morphogenesis
Authors: Liu Yang , Lu Pengfei , Wang Yidong , Morrow Bernice E. , Zhou Bin , Zheng Deyou 
Published: June 2018

AbstractCardiac looping is an early morphogenic process critical for the formation of four-chambered mammalian hearts. To study the roles of signaling pathways, transcription factors (TFs) and genetic networks in the process, we constructed gene co-expression networks and identified gene modules highly activated in individual cardiomyocytes (CMs) at multiple anatomical regions and developmental stages. Function analyses of the module genes uncovered major pathways important for spatiotemporal CM differentiation. Interestingly, about half of the pathways were highly active in cardiomyocytes at outflow tract (OFT) and atrioventricular canal (AVC), including many well-known signaling pathways for cardiac development and several newly identified ones. Most of the OFT-AVC pathways were predicted to be regulated by 6 6 transcription factors (TFs) actively expressed at the OFT-AVC locations, with the prediction supported by motif enrichment analysis of the TF targets, including 10 TFs that have not been previously associated with cardiac development, e.g.,Etv5,Rbpms,andBaz2b. Finally, our study showed that the OFT-AVC TF targets were significantly enriched with genes associated with mouse heart developmental abnormalities and human congenital heart defects.
Transcriptome Profiling Reveals Inhibitory Effect of Down-regulated ZBTB38 gene on the Transcriptional Regulation of Tumor Cells Proliferation
Authors: Chen Jie , Xing Chaofeng , Wang Haosen , Zhang Zengmeng , Yu Daolun , Li Jie , Li Honglin , Li Jun , Cai Yafei 
Published: June 2018

AbstractTranscription factor ZBTB38 belongs to the zinc finger protein family and contains the typical BTB domains. Only several predicted BTB domain-containing proteins encoded in the human genome have been functionally characterized. No relevant studies have been reported concerning the effect of down-regulated ZBTB38 gene expression on tumor cells through transcriptome analysis. In the present study, 2,438 differentially expressed genes in ZBTB38−/− SH-SY5Y cells were obtained via high-throughput transcriptome sequencing analysis, 83.5% of which was down-regulated. Furthermore, GO functional clustering and KEGG pathway enrichment analysis of these differentially expressed genes (DEGs) revealed that the knocked-down transcription factor ZBTB38 interacted with p53 and arrested cell cycles to inhibit the proliferation of the tumor cells. Besides, it also significantly down-regulated the expressions of PTEN, a “molecular switch” of the PI3K/Akt signaling pathway, and RB1CC1, the key gene for autophagy initiation, and blocked autophagy to accelerate the apoptosis of tumor cells. ZBTB38−/− SH-SY5Y cells were investigated at the whole transcriptome level and key DEGs were screened in the present study for the first time, providing a theoretical foundation for exploring the molecular mechanism of inhibition of tumor cell proliferation and targeted anti-tumor therapies.
Diffusion-weighted magnetic resonance spectroscopy enables cell-specific monitoring of astrocyte reactivity in vivo
Authors: Ligneul Clémence , Hernández-Garzón Edwin , Palombo Marco , Carrillo-de Sauvage María-Angeles , Flament Julien , Hantraye Philippe , Brouillet Emmanuel , Bonvento Gilles , Escartin Carole , Valette Julien 
Published: June 2018

AbstractThe diffusion of brain intracellular metabolites, as measured using diffusion-weighted magnetic resonance spectroscopy in vivo, is thought to specifically depend on the cellular structure constraining them. However, it has never been established that variations of metabolite diffusion, e.g. as observed in some diseases, could indeed be linked to alterations of cellular morphology. Here we demonstrate, in a mouse model of reactive astrocytes, that advanced diffusion-weighted magnetic resonance spectroscopy acquisition and modeling techniques enable non-invasive detection of reactive astrocyte hypertrophy (increased soma radius, increased fiber radius and length), as inferred from variations of myo-inositol diffusion, and as confirmed by confocal microscopy ex vivo. This establishes that specific alterations of intracellular metabolite diffusion can be measured and related to cell-specific morphological alterations. Furthermore, as reactive astrocytes are a hallmark of many brain pathologies, this work opens exciting perspectives for neuroscience and clinical research.
Genetic architecture of collective behaviors in zebrafish
Authors: Tang Wenlong , Zhang Guoqiang , Serluca Fabrizio , Li Jingyao , Xiong Xiaorui , Coble Matthew , Tsai Tingwei , Li Zhuyun , Molind Gregory , Zhu Peixin , Fishman Mark C. 
Published: June 2018

AbstractCollective behaviors of groups of animals, such as schooling and shoaling of fish, are central to species survival, but genes that regulate these activities are not known. Here we parsed collective behavior of groups of adult zebrafish using computer vision and unsupervised machine learning into a set of highly reproducible, unitary, several hundred millisecond states and transitions, which together can account for the entirety of relative positions and postures of groups of fish. Using CRISPR-Cas9 we then targeted for knockout 35 genes associated with autism and schizophrenia. We found mutations in three genes had distinctive effects on the amount of time spent in the specific states or transitions between states. Mutation inimmp2l(inner mitochondrial membrane peptidase 2-like gene) enhances states of cohesion, so increases shoaling; mutation in in the Nav1.1 sodium channel,scn1lab+/− causes the fish to remain scattered without evident social interaction; and mutation in the adrenergic receptor,adra1aa−/−, keeps fish close together and retards transitions between states, leaving fish motionless for long periods. Motor and visual functions seemed relatively well-preserved. This work shows that the behaviors of fish engaged in collective activities are built from a set of stereotypical states. Single gene mutations can alter propensities to collective actions by changing the proportion of time spent in these states or the tendency to transition between states. This provides an approach to begin dissection of the molecular pathways used to generate and guide collective actions of groups of animals.