bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rheb promotes brown fat thermogenesis by Notch-dependent activation of the PKA signaling pathway
Authors: Meng Wen , Liang Xiuci , Xiao Ting , Wang Jing , Wen Jie , Luo Hairong , Teng Jianhui , Fei Yanquan , Zhang Qinghai , Liu Bilian , Hu Fang , Bai Juli , Liu Meilian , Zhou Zhiguang , Liu Feng 
Published: June 2019

AbstractIncreasing brown and beige fat thermogenesis have an anti-obesity effect and thus great metabolic benefits. However, the molecular mechanisms regulating brown and beige fat thermogenesis remain to be further elucidated. We recently found that fat-specific knockout of Rheb promoted beige fat thermogenesis. In the current study, we show that Rheb has distinct effects on thermogenic gene expression in brown and beige fat. Fat-specific knockout of Rheb decreased protein kinase A (PKA) activity and thermogenic gene expression in brown adipose tissue of high-fat diet-fed mice. On the other hand, overexpression of Rheb activated PKA and increased uncoupling protein 1 expression in brown adipocytes. Mechanistically, Rheb overexpression in brown adipocytes increased Notch expression, leading to disassociation of the regulatory subunit from the catalytic subunit of PKA and subsequent PKA activation. Our study demonstrates that Rheb, by selectively modulating thermogenic gene expression in brown and beige adipose tissues, plays an important role in regulating energy homeostasis.
A Review of Perspectives on the Use of Randomization in Phase II Oncology Trials
Authors: Grayling Michael J , Dimairo Munyaradzi , Mander Adrian P , Jaki Thomas F 
Published: June 2019

AbstractHistorically, phase II oncology trials assessed a treatment’s efficacy by examining its tumor response rate in a single-arm trial. Then, approximately 25 years ago, certain statistical and pharmacological considerations ignited a debate around whether randomized designs should be used instead. Here, based on an extensive literature review, we review the arguments on either side of this debate. In particular, we describe the numerous factors that relate to the reliance of single-arm trials on historical control data and detail the trial scenarios in which there was general agreement on preferential utilization of single-arm or randomized design frameworks, such as the use of single-arm designs when investigating treatments for rare cancers. We then summarize the latest figures on phase II oncology trial design, contrasting current design choices against historical recommendations on best practice. Ultimately, we find several ways in which the design of recently completed phase II trials does not appear to align with said recommendations. For example, despite advice to the contrary, only 66.2% of the assessed trials that employed progression-free survival as a primary or coprimary outcome used a randomized comparative design. In addition, we identify that just 28.2% of the considered randomized comparative trials came to a positive conclusion as opposed to 72.7% of the single-arm trials. We conclude by describing a selection of important issues influencing contemporary design, framing this discourse in light of current trends in phase II, such as the increased use of biomarkers and recent interest in novel adaptive designs.
Incidence of health problems in travelers to Southeast Asia: a prospective cohort study
Authors: Pisutsan Phimphan , Soonthornworasiri Ngamphol , Matsee Wasin , Phumratanaprapin Weerapong , Punrin Suda , Leowattana Wattana , Mansanguan Chayasin , Leshem Eyal , Piyaphanee Watcharapong 
Published: June 2019

Abstract

Background
There are few studies of the incidence of health problems among travelers to Southeast Asia. The current study sought to determine the incidence of self-reported health problems among travelers visiting the region.

Methods
A prospective questionnaire-based study was conducted among travelers from high-income countries who visited Southeast Asia. Participants were enrolled at time of their pre-travel visit at Mahidol University, Bangkok, Thailand. Travelers were prospectively followed by self-administered questionnaires 2 weeks after arrival, upon return to their home country and 2 weeks after return.

Results
During January 2018–February 2019, 359 travelers were enrolled in Bangkok, Thailand, and the first questionnaire was administered. Follow-up questionnaires were returned by 191, 96 and 64 participants 2 weeks later, at the end of the trip and 2 weeks after return, respectively. A total of 6094 travel days were included in the final analysis. The incidence of acute diarrhea per month per 1000 travelers was 217 [95% confidence interval (CI), 189–248] episodes; skin problems, 197 (95% CI, 170–227); respiratory symptoms, 133 (95% CI, 111–158); fever, 49 (95% CI, 36–65); and potential rabies exposure, 34 (95% CI, 24–48). The incidence of acute diarrhea episodes per month per 1000 travelers was significantly higher during the first 2 weeks of travel compared with subsequent weeks of travel: 325 (95% CI, 291–362) vs 132 (95% CI, 110–1157) (P < 0.05). The incidence of outpatient visits and hospitalizations per month per 1000 travelers was 49 (95% CI, 36–65) and 5 (95% CI, 2–10), respectively.

Conclusions
In this prospective cohort study we observed substantial burden of acute diarrhea and skin and respiratory symptoms among travelers to Southeast Asia. The higher incidence of diarrhea in the first 2 weeks of travel should be further investigated.
Transportable nuclear power plants: an enigma of international nuclear liability law
Authors: Handrlica Jakub 
Published: June 2019

Abstract
On 28th April 2018, the world’s only transportable nuclear power plant (TNPP) ‘Academic Lomonosov’ has left St Petersburg and headed to its base in Chukotka. These developments again triggered the attention of the legal community to various legal aspects of the TNPPs. In this context, different opinions concerning the applicability of the existing nuclear liability conventions vis-á-vis TNPPs were expressed. According to one line of interpretation, the existing nuclear liability conventions do apply also to a TNPP anchored at a coast to deliver electricity to the grid. This article questions such opinion. It argues, that a TNPP cannot be considered a ‘nuclear installation’ in the sense of the existing nuclear liability conventions, when anchored at the coast. In this respect, the article identifies bilateral agreements between the licensing State and the host State to only viable option to address the liability issues arising from a TNPP entering foreign waters to deliver electricity to the domestic grid there.
Evidence for the absorption of crystalline silicates at 11.1 $\mu$m in the spectra of the nucleus of the Circinus galaxy
Authors: Do Duy Tho , Lawson Warrick A 
Published: June 2019

Abstract
Several mid-infrared spectra of the Circinus galaxy nucleus taken with T-ReCS on Gemini South and MIDI on VLTI have consistently shown an inflection centred around 11 $\mu$m. We ascribe this feature to the absorption of crystalline silicate, based on their similarity in profile shape and improvement in fitting quality using a partially crystalline silicate model, compared to entirely amorphous models. Spectral fits reveal a fraction of 0.6–2.0 per cent of crystalline forsterite in the nucleus of the Circinus galaxy, which is similar to the values obtained for the interstellar medium (ISM) of the Milky Way. This is probably the first detection of crystalline silicate absorption in the nucleus of this Seyfert 2 galaxy. In addition, the presence of large grain-size amorphous silicates, together with the similarity in profile shape of the optical depth of Circinus with those of young stellar objects in the Milky Way, implies that most of the contribution to the spectra of Circinus comes from dust in the star formation regions near the centre of the nucleus or along the line of sight to the Earth, rather than in the ISM of Circinus. We also compare our optical depths of Circinus with those in previous studies.
Dural Ectasia in Neurofibromatosis 1: Case Series, Management, and Review
Authors: Polster Sean P , Dougherty Mark C , Zeineddine Hussein A , Lyne Seán B , Smith Heather L , MacKenzie Cynthia , Pytel Peter , Yang Carina W , Tonsgard James H , Warnke Peter C , Frim David M 
Published: June 2019

Abstract

BACKGROUND
The natural history and management of dural ectasia in Neurofibromatosis 1 (NF1) is still largely unknown. Dural ectasias are one of the common clinical manifestations of NF1; however, the treatment options for dural ectasias remain unstudied.

OBJECTIVE
To investigate the natural history, diagnosis, management, and outcome of the largest case series of patients with NF1-associated dural ectasia to date.

METHODS
Records from our NF1 clinic were reviewed to identify NF1 patients with computed tomography or magnetic resonance imaging evidence of dural ectasia(s) to determine their clinical course. Demographics, symptoms, radiographic and histopathologic findings, treatment, and clinical course were assessed.

RESULTS
Thirty-four of 37 patients were managed without surgery. Of the 18 initially asymptomatic patients, 5 (27.8%) progressed to symptoms attributable to a dural ectasia (onset of 2.7% per patient-year). Three patients required surgical intervention because of extraspinal mass effect. All 3 initially improved but had symptom recurrence within 2 yr. Reoperation involved shunt placement for cerebrospinal fluid (CSF) diversion. On imaging review, 26 (76.5%) of the nonsurgical patients harbored an associated nearby plexiform neurofibroma. Pathology of one surgical case revealed dural infiltration by diffuse neurofibroma.

CONCLUSION
Using the largest NF1-associated dural ectasia group to date, we report the first symptom-onset rate for nonsurgical patients. In the few cases requiring surgery for decompression, primary resection, and patching of ectasias failed, subsequently requiring CSF shunting. We demonstrate imaging evidence of nearby plexiform neurofibroma in a majority of cases, which, when combined with histopathology, provides a novel explanation for the formation of dural ectasias.
Mechanical Thrombectomy in Acute Ischemic Stroke: A Meta-Analysis of Stent Retrievers vs Direct Aspiration vs a Combined Approach
Authors: Texakalidis Pavlos , Giannopoulos Stefanos , Karasavvidis Theofilos , Rangel-Castilla Leonardo , Rivet Dennis J , Reavey-Cantwell John 
Published: June 2019

Abstract

BACKGROUND
Recent randomized control trials (RCTs) established that mechanical thrombectomy is superior to medical therapy for patients with stroke due to a large vessel occlusion.

OBJECTIVE
To compare the safety and efficacy profile of the different mechanical thrombectomy strategies.

METHODS
A random-effects meta-analysis was performed and the I2 statistic was used to assess heterogeneity according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines.

RESULTS
Nineteen studies with a total of 2449 patients were included. No differences were identified between the stent retrieval and direct aspiration groups in terms of modified Thrombolysis in Cerebral Infarction (mTICI) 2b/3 and mTICI 3 recanalization rates, and favorable outcomes (modified Rankin Scale [mRS] ≤ 2). Adverse event rates, including 90-d mortality, symptomatic intracerebral hemorrhage (sICH), and subarachnoid hemorrhage (SAH), were similar between the stent retrieval and direct aspiration groups. The use of the stent retrieval was associated with a higher risk of vasospasm (odds ratio [OR]: 2.98; 95% confidence interval [CI]: 1.10-8.09; I2: 0%) compared to direct aspiration. When compared with the direct aspiration group, the subgroup of patients who underwent thrombectomy with the combined approach as a first-line strategy had a higher likelihood of successful mTICI 2b/3 (OR: 1.47; 95% CI: 1.02-2.12; I2: 0%) and mTICI 3 recanalization (OR: 3.65; 95% CI: 1.56-8.54), although with a higher risk of SAH (OR: 4.33; 95% CI: 1.15-16.32).

CONCLUSION
Stent retrieval thrombectomy and direct aspiration did not show significant differences. Current available evidence is not sufficient to draw conclusions on the best surgical approach. The combined use of a stent retriever and aspiration as a first-line strategy was associated with higher mTICI 2b/3 and mTICI 3 recanalization rates, although with a higher risk of 24-h SAH, when compared with direct aspiration.
Re-Evaluation of the Size Limitation in Single-Session Stereotactic Radiosurgery for Brain Arteriovenous Malformations: Detailed Analyses on the Outcomes with Focusing on Radiosurgical Doses
Authors: Hasegawa Hirotaka , Hanakita Shunya , Shin Masahiro , Sugiyama Takehiro , Kawashima Mariko , Takahashi Wataru , Ishikawa Osamu , Nakatomi Hirofumi , Saito Nobuhito 
Published: June 2019

Abstract

BACKGROUND
Single-session stereotactic radiosurgery (SRS) for large arteriovenous malformations (AVMs) ≥10 mL remains controversial, which is considered as the current size limitation.

OBJECTIVE
To reconsider the size limitation of SRS for AVMs by profoundly analyzing dose-volume relationship.

METHODS
Data on 610 consecutive patients with AVM treated with SRS using regular (18-22 Gy) or low (<18 Gy) prescription doses were retrospectively analyzed. AVMs were classified into 4 groups: small (<5 mL), medium (≥5 and <10 mL), medium-large (≥10 and <15 mL), and large (≥15 mL). The maximum volumes were 22.5 mL (regular-dose group) and 23.5 mL (low-dose group).

RESULTS
When treated with regular doses, the cumulative 6-yr obliteration rates for each of the 4 AVM groups were 86%, 80%, 87%, and 79%, respectively; the cumulative 10-yr significant neurological event (SNE) rates were 2.6%, 3.9%, 6.8%, and 5.3%, respectively. Regarding large AVMs, regular-dose SRS resulted in marginally better obliteration rate (6-yr cumulative rate, 79% vs 48%, P = .111) and significantly lower SNE (5-yr cumulative rate, 5% vs 31%, P = .038) and post-SRS hemorrhage rate (8-yr cumulative rate, 0% vs 54%, P = .002) compared to low-dose SRS. Multivariate analyses revealed that regular-dose SRS significantly contributed to increase in the obliteration rate and decrease in SNEs and hemorrhage.

CONCLUSION
The outcomes for large AVMs were generally favorable when treated with ablative doses. Single-session SRS could be acceptable for AVMs up to ≈20 mL if treated with ablative doses.
Trace elements in schizophrenia: a systematic review and meta-analysis of 39 studies (N = 5151 participants)
Authors: Saghazadeh Amene , Mahmoudi Maryam , Shahrokhi Shayan , Mojarrad Maryam , Dastmardi Maedeh , Mirbeyk Mona , Rezaei Nima 
Published: June 2019

AbstractContextThe pathogenesis of schizophrenia appears to be multifaceted.ObjectiveThe aim of this meta-analysis of studies that investigated blood and hair concentrations of trace elements in people diagnosed with schizophrenia was to determine whether levels of trace elements in patients with schizophrenia differ from those in healthy individuals.Data SourcesThe PubMed, Scopus, and Web of Science databases were searched to January 2018.Study SelectionStudies that compared concentrations of trace elements in patients with schizophrenia with those in healthy controls, in patients with schizophrenia under different treatment regimens, or in patients with schizophrenia at different stages of disease were included.Data ExtractionData on study and sample characteristics and measures of trace elements were extracted.ResultsThirty-nine studies with a total of 5151 participants were included. Meta-analysis of combined plasma and serum data showed higher levels of copper, lower levels of iron, and lower levels of zinc among patients with schizophrenia vs controls without schizophrenia. Subgroup analyses confirmed the following: higher levels of copper in plasma, in users of typical antipsychotic drugs, and in males; lower levels of zinc in serum, in patients in Asia, in drug-naive/drug-free patients, and in inpatients; lower levels of iron in serum, in patients in Asia, in drug-naive/drug-free patients, in patients on antipsychotic drugs, in inpatients, in patients with acute or newly diagnosed schizophrenia, in patients with chronic or previously diagnosed schizophrenia, and in males; and lower levels of manganese in plasma and in patients with chronic or previously diagnosed schizophrenia.ConclusionsThis meta-analysis provides evidence of an excess of copper, along with deficiencies of zinc, iron, and manganese, in patients with schizophrenia.
Return to work after kidney transplant: a systematic review
Authors: D’Egidio V , Mannocci A , Ciaccio D , Sestili C , Cocchiara R A , Del Cimmuto A , La Torre G 
Published: June 2019

Abstract

Background
Renal transplant is the gold standard treatment for patients with end-stage renal disease. Employment after transplant is an important marker of recovery and a key component of general well-being with important social implications.

Aims
To evaluate employment status after renal transplant and to investigate facilitators of and barriers to return to work for renal transplant patients.

Methods
We searched PubMed, Scopus and the Cochrane Library in March 2019 using the following algorithms: ‘return to work’ AND kidney AND transplant. Eligible studies were selected by two independent researchers. Quality assessment was performed using the following tools: International Narrative Systematic Assessment (INSA) and Newcastle–Ottawa Scale (NOS) for cross-sectional and cohort studies.

Results
The review included 18 papers: 10 cross-sectional studies, 6 cohort studies and 2 narrative reviews. The weighted mean percentage for return to work within 1 year was 39.4% (95% CI 39.3–39.6%). Employment status was influenced by modifiable and non-modifiable factors, such as pre-transplant employment, sociodemographic characteristics, clinical conditions and comorbidities, operative technique (invasive or not), type of transplants (living donor or cadaver), pre-transplant dialysis, psychosocial support, educational level and participation in education programmes.

Conclusion
Return to work after kidney transplant is a dynamic process influenced by numerous factors. It is vital to implement multidimensional interventions focused on rehabilitation and influencing modifiable factors to improve return to work after kidney transplant. This systematic review updates knowledge in the field of transplant and of disability management.
Next generation sequencing panel in undifferentiated autoinflammatory diseases identifies patients with colchicine-responder recurrent fevers
Authors: Papa Riccardo , Rusmini Marta , Volpi Stefano , Caorsi Roberta , Picco Paolo , Grossi Alice , Caroli Francesco , Bovis Francesca , Musso Valeria , Obici Laura , Castana Cinzia , Ravelli Angelo , Van Gijn Marielle E , Ceccherini Isabella , Gattorno Marco 
Published: June 2019

Abstract

Objectives
The number of innate immune system disorders classified as systemic autoinflammatory diseases (SAID) has increased in recent years. More than 70% of patients with clinical manifestations of SAID did not receive a molecular diagnosis, thus being classed as so-called undifferentiated or undefined SAID (uSAID). The aim of the present study was to evaluate a next-generation sequencing (NGS)-based clinically oriented protocol in patients with uSAID.

Methods
We designed a NGS panel that included 41 genes clustered in seven subpanels. Patients with uSAID were classified into different groups according to their clinical features and sequenced for the coding portions of the 41 genes.

Results
Fifty patients were enrolled in the study. Thirty-four patients (72%) displayed recurrent fevers not consistent with a PFAPA phenotype. Sixteen patients displayed a chronic inflammatory disease course. A total of 100 gene variants were found (mean 2 per patient; range 0–6), a quarter of which affected suspected genes. Mutations with a definitive diagnostic impact were detected in two patients. Patients with genetically negative recurrent fevers displayed a prevalent gastrointestinal, skin and articular involvement. Patients responded to steroids on demands (94%) and colchicine, with a response rate of 78%.

Conclusion
Even with a low molecular diagnostic rate, a NGS-based approach is able to provide a final diagnosis in a proportion of uSAID patients with evident cost-effectiveness. It also allows the identification of a subgroup of genetically negative patients with recurrent fever responding to steroid on demand and colchicine.
Diversity of Eocene Ripiphoridae with descriptions of the first species of Pelecotominae and larva of Ripidiinae (Coleoptera)
Authors: Batelka Jan , Perkovsky Evgeny E , Prokop Jakub 
Published: June 2019

AbstractThe Eocene records of the beetle family Ripiphoridae are evaluated and summarized. A new species of Pelecotominae belonging to the genus Clinops, C. svachaisp. nov. from Baltic amber, is described and figured. The female holotype of C. svachai is the first Palaeogene member of this subfamily to be identified. In addition, a male of a different unidentified genus of Pelecotominae, preserved as an inclusion in Baltic amber, is documented. The first Palaeogene primary larva of Ripiphoridae is described from Sakhalin amber and is compared with all other primary larvae of this family. The larva is attributed to Ripidius (Ripidiinae) and bears some unique characters absent in larvae of this extant genus. A putative record of Ripiphorus (Ripiphorinae) in the Berendt collection is identified as a member of Ripidius. Distribution of Eocene species are compared with those of their closest extant relatives and mapped. Based on the fossil record and the distribution of extant South African species of Clinops, this genus is tentatively thought to be an example of an Eocene relict, while the extant pelecotomine genus Scotoscopus from the East Mediterranean is considered to be an Oligocene–Miocene relict as its distribution corresponds with the geological history of the Aegais landmass.
Neurovascular anatomy of the protostegid turtle Rhinochelys pulchriceps and comparisons of membranous and endosseous labyrinth shape in an extant turtle
Authors: Evers Serjoscha W , Neenan James M , Ferreira Gabriel S , Werneburg Ingmar , Barrett Paul M , Benson Roger B J 
Published: June 2019

AbstractChelonioid turtles are the only surviving group of reptiles that secondarily evolved marine lifestyles during the Mesozoic Early chelonioid evolution is documented by fossils of their stem group, such as protostegids, which yield insights into the evolution of marine adaptation. Neuroanatomical features are commonly used to infer palaeoecology owing to the functional adaptation of the senses of an organism to its environment. We investigated the neuroanatomy and carotid circulation of the early Late Cretaceous protostegid Rhinochelys pulchriceps based on micro-computed tomography data. We show that the trigeminal foramen of turtles is not homologous to that of other reptiles. The endosseous labyrinth of R. pulchriceps has thick semicircular canals and a high aspect ratio. Comparisons among turtles and other reptiles show that the endosseous labyrinth aspect ratio is not a reliable predictor of the degree of aquatic adaptation, contradicting previous hypotheses. We provide the first models of neuroanatomical soft tissues of an extant turtle. Turtle brain morphology is not reflected by the brain cavity, and the endosseous labyrinth provides an incomplete reflection of membranous semicircular duct morphology. Membranous labyrinth geometry is conserved across gnathostomes, which allows approximate reconstruction of the total membranous labyrinth morphology from the endosseous labyrinth despite their poor reflection of duct morphology.