bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of 18F-fluorodeoxyglucose PET/CT in the management of patients with plasma cell disorders
Authors: Shachar Ben , Prica Anca , Anconina Reut , Hawsawy Asmaa , MacCrostie Pamela , Langer Deanna , Metser Ur 
Published: November 2019

Objectives
To evaluate the impact of 18F-fluorodeoxyglucose PET/CT examinations on the management of patients with plasma cell disorders.

Methods
This is a retrospective review of patients in a provincial database with PET/CT performed for plasma cell disorders between 2011 and 2018. The impact of PET/CT on actual patient management and outcome was assessed by two independent readers who compared planned pre-PET/CT management, documented at time of PET/CT requisition, to actual management received through linkages to administrative databases. PET/CT was considered of high impact if it altered the provision of active treatment, changed the modality of treatment or chemotherapy regimen. Change in management and the proportion of patients with high impact PET/CT were assessed.

Results
There were 44 patients with plasma cell disorders, including multiple myeloma, solitary plasmacytoma, Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal protein, Skin changes syndrome, or monoclonal gammopathy of undetermined significance or biclonal gammopathy of undetermined significance. Management was altered after 38/56 (67.9%) PET/CT scans. Considering just the initial PET/CT scan in patients who underwent multiple scans, 31/44 (70.5%) patients had their management altered subsequent to PET/CT.

Conclusion
PET/CT resulted in a change in planned management in more than two-thirds of patients with plasma cell disorders in the current selected patient cohort. These results should be validated in a larger prospective trial.
A New Video Aid for Communicating Risk in the Treatment of Pediatric Inflammatory Bowel Disease
Authors: Newman Noah E. , Williams Kathryn L. , Zikmund‐Fisher Brian J. , Adler Jeremy 
Published: November 2019

ABSTRACTBalancing risks of immune suppressive medications against risk of chronic disease is challenging for clinicians and families. Available aids commonly lack comparative information needed to inform treatment decisions. We developed a simple video aid to illustrate competing risks associated with medications and underlying disease in context of pediatric inflammatory bowel disease. Those who viewed the video aid had more realistic risk perceptions than those who did not view it. The video aid is adaptable for other conditions. It required only commonly accessible software and little cost, thereby making an aid of this style an attractive option for health care professionals interested in communicating comparative risk data to patients.
New Insights on Lipedema: The Enigmatic Disease of the Peripheral Fat
Authors: Bauer Anna-Theresa , von Lukowicz Dominik , Lossagk Katrin , Aitzetmueller Matthias , Moog Philipp , Cerny Michael , Erne Holger , Schmauss Daniel , Duscher Dominik , Machens Hans-Guenther 
Published: November 2019

Background:
Although a large number of adult women worldwide are affected by lipedema, the physiologic conditions triggering onset and progression of this chronic disease remain enigmatic. In the present study, a descriptive epidemiologic situation of postoperative lipedema patients is presented.

Methods:
The authors developed an online survey questionnaire for lipedema patients in Germany. The survey was conducted on 209 female patients who had been diagnosed with lipedema and had undergone tumescent liposuction.

Results:
Most of the participants (average age, 38.5 years) had noticed a first manifestation of the disease at the age of 16. It took a mean of 15 years to accomplish diagnosis. Liposuction led to a significant reduction of pain, swelling, tenderness, and easy bruising as confirmed by the majority of patients. Hypothyroidism [n = 75 (35.9 percent) and depression [n = 48 (23.0 percent)] occurred at a frequency far beyond the average prevalence in the German population. The prevalence of diabetes type 1 [n = 3 (1.4 percent)], and diabetes type 2 [n = 2 (1 percent)] was particularly low among the respondents. Forty-seven of the lipedema patients (approximately 22.5 percent) suffered from a diagnosed migraine. Following liposuction, the frequency and/or intensity of migraine attacks became markedly reduced, as stated by 32 patients (68.1 percent).

Conclusions:
Quality of life increases significantly after surgery with a reduction of pain and swelling and decreased tendency to easy bruising. The high prevalence of hypothyroidism in lipedema patients could be related to the frequently observed lipedema-associated obesity. The low prevalence of diabetes, dyslipidemia, and hypertension appears to be a specific characteristic distinguishing lipedema from lifestyle-induced obesity.
Virological and immunological impact of integrase inhibitor-based regimens initiated during primary HIV-1 infection
Authors: Veil Raphael , Poizot-Martin Isabelle , Reynes Jacques , Goujard Cecile , Seng Remonie , Delobel Pierre , Cotte Laurent , Duvivier Claudine , Rey David , Tran Laurent , Surgers Laure , Allavena Clotilde , Lascoux Combe Caroline , Cheret Antoine , Meyer Laurence 
Published: November 2019

Design:Current international guidelines recommend either boosted protease inhibitor (PI/r)-based or integrase inhibitors (INSTI)-based regimens during primary HIV infection (PHI), even though the latter have only demonstrated their superiority at the chronic stage. We compared the effectiveness of INSTI-based versus PI/r-based combined antiretroviral therapy (cART) initiated during PHI.Methods:This study was conducted among patients who initiated cART between 2013 and 2017, using data from the ANRS-PRIMO cohort and the Dat’AIDS study. Cumulative proportions of patients reaching viral suppression (HIV-1 RNA <50 copies/ml) were calculated using Turnbull's estimator for interval-censored data. CD4+cells and CD4+/CD8+ratio increases were estimated using mixed linear models. Results were adjusted for the data source.Results:Among the 712 study patients, 299 received an INSTI-based cART. Patients’ baseline characteristics were similar between groups. Viral suppression was reached more rapidly in INSTI-treated versus PI/r-treated patients (P < 0.01), with cumulative proportions of 32 versus 6% at 4 weeks, 72 versus 31% at 12 weeks, 91 versus 78% at 24 weeks and about 95% in both groups at 48 weeks. At 4 weeks, INSTI-treated patients had gained on average 40 CD4+cells/μl (P = 0.05) over PI/r-treated ones; mean CD4+counts were similar in the two groups at 48 weeks. The CD4+/CD8+ratio followed the same pattern. Results were similar when restricted to a comparison between dolutegravir-based versus darunavir-based cART.Conclusion:On the basis of this study and available literature, we recommend the use of INSTI-based cART for treatment initiation during PHI, as it leads to faster viral suppression and immune restoration.
Public Health Practice-Driven Research to Improve HIV Prevention in the United States
Authors: Dombrowski Julia C. , Irvine Mary , Nash Denis , Harriman Graham , Golden Matthew R. 
Published: November 2019

Background:
The evidence-practice gap in HIV prevention and the care continuum in the United States often reflects a mismatch between the perspectives of researchers and public health practitioners. The traditional research paradigm of sequential progress from efficacy research to implementation in practice and widespread scale-up is not well-aligned with the reality of health department program implementation.

Setting:
This article focuses on public health practice carried out by state and local health departments in the United States and the research intended to inform it.

Methods and Results:
In this narrative review, we discuss approaches to HIV prevention and care continuum research that are shaped by and responsive to public health practice implementation priorities and what is needed to promote productive and successful university–health department research partnerships. We review research methods of particular relevance to health departments to evaluate the effectiveness of HIV prevention and care continuum interventions and how these approaches diverge from traditional research approaches. Finally, we highlight the roles of federal agencies in supporting practice-driven HIV implementation research.

Conclusions:
Health departments are key stakeholders, consumers, and generators of the evidence base for public health practice. High-impact research to improve HIV prevention and the care continuum is informed by health department priorities and current practice from the start. Long-term, equitable relationships between universities and health departments are crucial to advance practice-driven research.
Artificial intelligence for detection of optic disc abnormalities
Authors: Milea Dan , Singhal Shweta , Najjar Raymond P. 
Published: November 2019

Purpose of review
The aim of this review is to highlight novel artificial intelligence-based methods for the detection of optic disc abnormalities, with particular focus on neurology and neuro-ophthalmology.

Recent findings
Methods for detection of optic disc abnormalities on retinal fundus images have evolved considerably over the last few years, from classical ophthalmoscopy to artificial intelligence-based identification methods being applied to retinal imaging with the aim of predicting sight and life-threatening complications of underlying brain or optic nerve conditions.

Summary
Artificial intelligence and in particular newly developed deep-learning systems are playing an increasingly important role for the detection and classification of acquired neuro-ophthalmic optic disc abnormalities on ocular fundus images. The implementation of automatic deep-learning methods for detection of abnormal optic discs, coupled with innovative hardware solutions for fundus imaging, could revolutionize the practice of neurologists and other non-ophthalmic healthcare providers.
The HMGB1-RAGE axis modulates the growth of autophagy-deficient hepatic tumors
Authors: Khambu Bilon , Hong Honghai , Liu Sheng , Liu Gang , Chen Xiaoyun , Dong Zheng , Wan Jun , Yin Xiao-Ming 
Published: November 2019

AbstractAutophagy is an intracellular lysosomal degradative pathway important for tumor surveillance. Autophagy deficiency can lead to tumorigenesis. Autophagy is also known to be important for the aggressive growth of tumors, yet the mechanism that sustains the growth of autophagy-deficient tumors is not known. We previously reported that progression of hepatic tumors developed in autophagy-deficient livers required high mobility group box 1 (HMGB1) that is released from autophagy-deficient hepatocytes. However, the mechanism by which HMGB1 promotes hepatic tumorigenesis is not understood. In this study we examined the pathological features of the hepatic tumors and the mechanism of HMGB1-mediated tumorigenesis using liver-specific autophagy-deficient (Atg7-/-) and Atg7-/-/Hmgb1-/- mice. We found that in Atg7-/- mice the tumors cells were still deficient in autophagy and could also release HMGB1. Histological analysis using cell-specific markers suggested that fibroblast and ductular cells were present only outside the tumor whereas macrophages were present both inside and outside the tumor. Genetic deletion of HMGB1 or one of its receptors, receptor for advanced glycated end product (Rage), retarded liver tumor development. In addition, we found that expression of RAGE was only on ductual cells and Kupffer’s cells but not on hepatoctyes, which suggested that HMGB1 might promote hepatic tumor growth through a paracrine mode that altered the tumor microenvironment. Furthermore, HMGB1 and RAGE enhanced the proliferation capability of the autophagy-deficient hepatocytes and tumors. Finally, RNAseq analysis of the tumors indicated that HMGB1 induced a much broad changes in tumors. In particular, genes related to mitochondrial structures or functions were enriched among those differentially expressed in tumors in the presence or absence of HMGB1, revealing a potential key role of mitochondria in sustaining the growth of autophagy-deficient liver tumors via HMGB1 stimulation.
Obstacles to the reuse of study metadata in ClinicalTrials.gov
Authors: Miron Laura , Gonçalves Rafael S. , Musen Mark A. 
Published: November 2019

AbstractMetadata that are structured using principled schemas and that use terms from ontologies are essential to making biomedical data findable and reusable for downstream analyses. The largest source of metadata that describes the experimental protocol, funding, and scientific leadership of clinical studies is ClinicalTrials.gov. We evaluated whether values in 302,091 trial records adhere to expected data types and use terms from biomedical ontologies, whether records contain fields required by government regulations, and whether structured elements could replace free-text elements. Contact information, outcome measures, and study design are frequently missing or underspecified. Important fields for search, such as condition and intervention, are not restricted to ontologies, and almost half of the conditions are not denoted by MeSH terms, as recommended. Eligibility criteria are stored as semi-structured free text. Enforcing the presence of all required elements, requiring values for certain fields to be drawn from ontologies, and creating a structured eligibility criteria element would improve the reusability of data from ClinicalTrials.gov in systematic reviews, metanalyses, and matching of eligible patients to trials.
Biological data questions the support of the self inhibition required for pattern generation in the half center model
Authors: Kohler Matthias , Stratmann Philipp , Röhrbein Florian , Knoll Alois , Albu-Schäffer Alin , Jörntell Henrik 
Published: November 2019

AbstractLocomotion control in mammals has been hypothesized to be governed by a central pattern generator (CPG) located in the circuitry of the spinal cord. The most common model of the CPG is the half center model, where two pools of neurons generate alternating, oscillatory activity. In this model, the pools reciprocally inhibit each other ensuring alternating activity. There is experimental support for reciprocal inhibition. However another crucial part of the half center model is a self inhibitory mechanism which prevents the neurons of each individual pool from infinite firing. Self-inhibition is hence necessary to obtain alternating activity. But critical parts of the experimental bases for the proposed mechanisms for self-inhibition were obtained in vitro, in preparations of juvenile animals. The commonly used adaptation of spike firing does not appear to be present in adult animals in vivo. We therefore modeled several possible self inhibitory mechanisms for locomotor control. Based on currently published data, previously proposed hypotheses of the self inhibitory mechanism, necessary to support the CPG hypothesis, seems to be put into question by functional evaluation tests or by in vivo data. This opens for alternative explanations of how locomotion activity patterns in the adult mammal could be generated.Author summaryLocomotion control in animals is hypothesized to be controlled through an intrinsic central pattern generator in the spinal cord. This was proposed over a hundred years ago and has subsequently been formed into a consistent theory, through experimentation and computer modeling. However, critical data that support the neuronal circuitry mechanisms underpinning this theory has been obtained in experiments that greatly differ from intact animals. We propose, after trying to fill in this critical part, that new ideas are required to explain locomotion of intact animals.
Host-adaptation inLegionellalesis 2.4 Ga, coincident with eukaryogenesis
Authors: Hugoson Eric , Ammunét Tea , Guy Lionel 
Published: November 2019

AbstractBacteria adapting to living in a host cell caused the most salient events in the evolution of eukaryotes, namely the seminal fusion with an archaeon1, and the emergence of both the mitochondrion and the chloroplast2. A bacterial clade that may hold the key to understanding these events is the deep-branching gammaproteobacterial orderLegionellales– containing among othersCoxiellaandLegionella– of which all known members grow inside eukaryotic cells3. Here, by analyzing 35 novelLegionellalesgenomes mainly acquired through metagenomics, we show that this group is much more diverse than previously thought, and that key host-adaptation events took place very early in its evolution. Crucial virulence factors like the Type IVB secretion (Dot/Icm) system and two shared effector proteins were gained in the lastLegionellalescommon ancestor (LLCA), while many metabolic gene families were lost in LLCA and its immediate descendants. We estimate that LLCA lived circa 2.4 Ga ago, predating the last eukaryotic common ancestor (LECA) by at least 0.5 Ga4. These elements strongly indicate that host-adaptation arose only once inLegionellales, and that these bacteria were using advanced molecular machinery to exploit and manipulate host cells very early in eukaryogenesis.
Predicting Latent Links from Incomplete Network Data Using Exponential Random Graph Model with Outcome Misclassification
Authors: Wu Qiong , Zhang Zhen , Waltz James , Ma Tianzhou , Milton Donald , Chen Shuo 
Published: November 2019

SummaryLink prediction is a fundamental problem in network analysis. In a complex network, links can be unreported and/or under detection limits due to heterogeneous noises and technical challenges during data collection. The incomplete network data can lead to an inaccurate inference of network based data analysis. We propose a new link prediction model that builds on the exponential random graph model (ERGM) by considering latent links as misclassified binary outcomes. We develop new algorithms to optimize model parameters and yield robust predictions of unobserved links. The new method is applied to a partially observed social network data and incomplete brain network data. The results demonstrate that our method outperforms the existing latent-contact prediction methods.
Atypical spatial frequency dependence of visual metacognition among schizophrenia patients
Authors: Koizumi Ai , Hori Tomoki , Maniscalco Brian , Hayase Makoto , Mishima Ryou , Kawashima Takahiko , Miyata Jun , Aso Toshihiko , Lau Hakwan , Takahashi Hidehiko , Amano Kaoru 
Published: November 2019

AbstractAlthough altered early stages of visual processing have been reported among schizophrenia patients, how such atypical visual processing may affect higher-level cognition remains largely unknown. Here we tested the hypothesis that metacognitive performance may be atypically modulated by spatial frequency (SF) of visual stimuli among individuals with schizophrenia, given their altered magnocellular function. To study the effect of SF on metacognitive performance, we asked patients and controls to perform a visual detection task on gratings with different SFs and report confidence, and analyzed the data using the signal detection theoretic measure meta-d’. Control subjects showed better metacognitive performance after yes- (stimulus-presence) than after no- (stimulus-absence) responses (‘yes-response advantage’) for high SF (HSF) stimuli but not for low SF (LSF) stimuli. The patients, to the contrary, showed a ‘yes-response advantage’ not only for HSF but also for LSF stimuli, indicating atypical SF dependency of metacognition. An fMRI experiment using the same task revealed that the dorsolateral prefrontal cortex (DLPFC), known to be crucial for metacognition, shows activity mirroring the behavioral results: decoding accuracy of perceptual confidence in DLPFC was significantly higher for HSF than for LSF stimuli in controls, whereas this decoding accuracy was independent of SF in patients. While individuals without schizophrenia may flexibly adapt metacognitive computations across SF ranges, patients may employ a different mechanism that is independent of SF. Because visual stimuli of low SF have been linked to top-down processing in predictive coding, this may reflect atypical functioning in these processes in schizophrenia.HighlightsVisual metacognition of controls was dependent on spatial frequency.Visual metacognition of schizophrenia patients was independent of spatial frequency.Patients and controls differently rely on the dorsolateral prefrontal cortex.Sensory inputs may reach metacognitive circuits in an atypical manner among patients.
Micro-pellet culture reveals that bone marrow mesenchymal stromal cell (BMSC) chondrogenic induction is triggered by a single day of TGF-β1 exposure
Authors: Futrega Kathryn , Robey Pamela G. , Klein Travis J. , Crawford Ross W. , Doran Michael R. 
Published: November 2019

AbstractDespite immense promise, engineering of stable cartilage tissue from bone marrow-derived stromal cells (BMSCs, also known as bone marrow-derived “mesenchymal stem cells”) remains elusive. Relative cartilage-like matrix deposition is commonly used to guide BMSC chondrogenic optimisation efforts. However, matrix deposition is heterogeneous in most models, and notably, it lags behind cell fate decisions. We reason that the lag time between cell fate decision and matrix accumulation, coupled with matrix heterogeneity, has obscured basic BMSC biological characteristics, such as differentiation kinetics. Here, we utilize a customized microwell platform to assemble hundreds of small-diameter BMSCmicro-pellets and characterized chondrogenic differentiation kinetics in response to the canonical signaling molecule, transforming growth factor-β1 (TGF-β1).Micro-pellets provide a homogeneous readout, and our experimental design accounts for the significant time delay between growth factor signal and deposition of cartilage-like matrix. While 14-to-21-day induction protocols are routine, BMSCmicro-pellet cultures reveal that a single day of TGF-β1 exposure was sufficient to trigger chondrogenic differentiation cascades resulting in outcomes similar tomicro-pellets exposed to TGF-β1 for 21 days. RNA-sequencing analysis demonstrated that one day of TGF-β1 exposure was also sufficient to induce hypertrophic cascades in BMSC, not observed in articular chondrocytes. Refocusing chondrogenic induction optimisation efforts from weeks to the first hours or days of culture, using homogeneous model systems, may benefit efforts to build stable cartilage formed by BMSCs.SignificanceThemacro-pellet model, and assumptions generated using it, have permeated BMSC-based cartilage tissue engineering strategies since the 1990s. Using amicro-pellet model, we show that BMSC chondrogenic kinetics are significantly more rapid than historicalmacro-pellets data suggests, and that BMSC chondrogenic and hypertrophic commitment is instructed by a single day of TGF-β1 exposure. This highly relevant study demonstrates that: (1)macro-pellets, which are large heterogeneous tissue models confound the differentiation kinetics visible inmicro-pellet models; (2) induction strategies should focus on the first hours or days of culture; (3) even a single day of TGF-β1 exposure drives BMSC to form hypertrophic tissuein vivo, requiring early intervention to prevent hypertrophy; and (4) articular chondrocytes and BMSCs respond distinctly to TGF-β1.