bluuebunny/crossref_metadata_2025 huggingface dataset:
Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2
Authors: Wang Peijian , Yang Yi , Wang Dan , Yang Qiyuan , Wan Jindong , Liu Sen , Zhou Peng , Yang Yongjian
Published: April 2020

BACKGROUND

Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear.

METHODS

Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group.

RESULTS

CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-β1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice.

CONCLUSIONS

A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice.
Modern and Medieval Modal Spaces
Authors: Ahmed Arif
Published: March 2020

The interesting question about modality is not about its extension, but about its point. Everyone can agree (for instance) that the past is necessary in the Ockhamist sense but not in some ‘modern’ senses, and that the present is necessary in the Ockhamist sense but not in the Scotist sense. But why should it matter? These comments on Pasnau (2020) first set out a simple-minded explication in modern terms of some of these fourteenth-century ideas. Then I take issue with (a) Pasnau’s claim that the necessity of the past has something to do with the structure of ‘narrative history’, and (b) Duns Scotus’s claim that the contingency of the present has something to do with human freedom.
Climate change and maladaptive wing shortening in a long-distance migratory bird
Authors: Remacha Carolina , Rodríguez César , de la Puente Javier , Pérez-Tris Javier
Published: April 2020

Contemporary phenotypic trends associated with global change are widely documented, but whether such trends always denote trait optimization under changed conditions remains obscure. Natural selection has shaped the wings of long-distance migratory birds to minimize the costs of transport, and new optimal wing shapes could be promoted by migration patterns altered due to global change. Alternatively, wing shape could vary as a correlated response to selection on other traits favored in a changing environment, eventually moving away from the optimal shape for migration and increasing transport costs. Data from 20 yr of monitoring 2 Common Nightingale (Luscinia megarhynchos) populations breeding in central Spain, where environmental conditions for breeding have deteriorated during recent decades due to increased summer drought, show that birds have reduced wing length relative to body size over the period 1995–2014. However, long-winged nightingales survived their first round-trip migration better, and the shorter the average wing length of individuals, the stronger the survival-associated natural selection favoring longer wings. Maladaptive short wings may have arisen because the mortality costs of migration are outweighed by reproductive benefits accrued by short-winged nightingales in these populations. Assuming that the phenotypic integration of morphological and reproductive adaptations of migratory birds has a genetic basis, we hypothesize that the maladaptive trend towards shorter wings may be a correlated response to selection for moderate breeding investment in drying habitat. Our results provide evidence that contemporary phenotypic change may deviate average trait values from their optima, thereby increasing our understanding of the ecological constraints underpinning adaptation to rapid global change.
Detection of somatic structural variants from short-read next-generation sequencing data
Authors: Gong Tingting , Hayes Vanessa M , Chan Eva K F
Published: March 2020

Somatic structural variants (SVs), which are variants that typically impact >50 nucleotides, play a significant role in cancer development and evolution but are notoriously more difficult to detect than small variants from short-read next-generation sequencing (NGS) data. This is due to a combination of challenges attributed to the purity of tumour samples, tumour heterogeneity, limitations of short-read information from NGS and sequence alignment ambiguities. In spite of active development of SV detection tools (callers) over the past few years, each method has inherent advantages and limitations. In this review, we highlight some of the important factors affecting somatic SV detection and compared the performance of seven commonly used SV callers. In particular, we focus on the extent of change in sensitivity and precision for detecting different SV types and size ranges from samples with differing variant allele frequencies and sequencing depths of coverage. We highlight the reasons for why some SV callers perform well in some settings but not others, allowing our evaluation findings to be extended beyond the seven SV callers examined in this paper. As the importance of large SVs become increasingly recognized in cancer genomics, this paper provides a timely review on some of the most impactful factors influencing somatic SV detection that should be considered when choosing SV callers.
Toxoplasmosis Outbreak Associated With Toxoplasma gondii-Contaminated Venison—High Attack Rate, Unusual Clinical Presentation, and Atypical Genotype
Authors: Schumacher Amy C , Elbadawi Lina I , DeSalvo Traci , Straily Anne , Ajzenberg Daniel , Letzer David , Moldenhauer Ellen , Handly Tammy L , Hill Dolores , Dardé Marie-Laure , Pomares Christelle , Passebosc-Faure Karine , Bisgard Kristine , Gomez Carlos A , Press Cindy , Smiley Stephanie , Montoya José G , Kazmierczak James J
Published: March 2020

Background

During 2017, in response to a physician’s report, the Wisconsin Department of Health Services, Division of Public Health, began investigating an outbreak of febrile illness among attendees of a retreat where never frozen, intentionally undercooked, locally harvested venison was served. Preliminary testing tentatively identified the illness as toxoplasmosis.

Methods

Confirmatory human serology panels and testing of the venison to confirm and categorize the presence and type of Toxoplasma gondii were completed by French and American national reference laboratories. All 12 retreat attendees were interviewed; medical records were reviewed.

Results

All attendees were male; median age was 51 years (range: 22–75). After a median incubation period of 7 days, 9 (82%) of 11 exposed persons experienced illness lasting a median of 12 days. All 9 sought outpatient healthcare for symptoms including fever, chills, sweats, and headache (100%) and ocular disturbances (33%). Testing confirmed the illness as toxoplasmosis and venison as the infection source. Multiple laboratory results were atypical for toxoplasmosis, including transaminitis (86%), lymphocytopenia (88%), thrombocytopenia (38%), and leukopenia (63%). One exposed but asymptomatic person was seronegative; the other had immunity from prior infection. The T. gondii strain was identified as closely related to an atypical genotype (haplogroup 12, polymerase chain reaction restriction fragment length polymorphism genotype 5) common in North American wildlife but with previously uncharacterized human clinical manifestations.

Conclusions

The T. gondii strain contaminating the venison might explain the unusual clinical presentations. In North America, clinicians and venison consumers should be aware of risk for severe or unusual presentations of acute toxoplasmosis after consuming undercooked game meat.
Differential Responses of White Adipose Tissue and Brown Adipose Tissue to Calorie Restriction During Aging
Authors: Sheng Yunlu , Xia Fan , Chen Lei , Lv Yifan , Lv Shan , Yu Jing , Liu Juan , Ding Guoxian
Published: March 2020

Age-related adipose tissue dysfunction is potentially important in the development of insulin resistance and metabolic disorder. Caloric restriction (CR) is a robust intervention to reduce adiposity, improve metabolic health, and extend healthy life span. Both white adipose tissue (WAT) and brown adipose tissue (BAT) are involved in energy homeostasis. CR triggers the beiging of WAT in young mice; however, the effects of CR on beiging of WAT and function of BAT during aging are unclear. This study aimed to investigate how age and CR impact the beiging of WAT, the function of BAT, and metabolic health in mice. C57BL/6 mice were fed CR diet (40% less than the ad libitum [AL] diet) for 3 months initiated in young (3 months), middle-aged (12 months), and old (19 months) stage. We found age-related changes in different types of adipose tissue, including adipocyte enlargement, declined beiging of WAT, and declined thermogenic and β-oxidational function of BAT. Moreover, CR attenuated age-associated adipocyte enlargement and prevented the age-related decline in beiging potential of WAT. These protective effects on the beiging potential were significant in inguinal WAT at all three ages, which were significant in epididymal WAT at young and old age. In contrast, thermogenic and β-oxidational function of BAT further declined after CR in the young age group. In conclusion, our findings reveal the contribution of WAT beiging decline to age-related metabolic disorder and suggest nutritional intervention, specifically targeting WAT beiging, as an effective approach to metabolic health during aging.
Recent Public Discourses on Anti-Jewish Violence in Moldovan History, 1991–2019
Authors: Felcher Anastasia
Published: April 2020

Efforts to commemorate the victims of the 1903 Chişinǎu (Kishinev) pogrom and the Holocaust in Bessarabia and Transnistria have achieved varying degrees of success in the Republic of Moldova. Gaining public recognition for these experiences has proven a convoluted process. Since the dissolution of the Soviet Union, the local Community has led an enduring memorialization campaign, which has steadily evolved with the shifting political climate. Though Community representatives have at times had a fraught relationship with Moldovan officials, they have continuously sought official acknowledgment of their efforts. This article analyzes how both the government and the Jewish Community have handled memory in public spaces and the local media of Chişinǎu.
Lower and Upper Bounds for Positive Bases of Skein Algebras
Authors: Lê Thang T Q , Thurston Dylan P , Yu Tao
Published: March 2020

We show that if a sequence of normalized polynomials gives rise to a positive basis of the skein algebra of a surface, then it is sandwiched between the two types of Chebyshev polynomials. For the closed torus, we show that the normalized sequence of Chebyshev polynomials of type one $(\hat{T}_n)$ is the only one that gives a positive basis.
A computational bio-chemo-mechanical model of in vivo tissue-engineered vascular graft development
Authors: Khosravi Ramak , Ramachandra Abhay B , Szafron Jason M , Schiavazzi Daniele E , Breuer Christopher K , Humphrey Jay D
Published: March 2020

Stenosis is the primary complication of current tissue-engineered vascular grafts used in pediatric congenital cardiac surgery. Murine models provide considerable insight into the possible mechanisms underlying this situation, but they are not efficient for identifying optimal changes in scaffold design or therapeutic strategies to prevent narrowing. In contrast, computational modeling promises to enable time- and cost-efficient examinations of factors leading to narrowing. Whereas past models have been limited by their phenomenological basis, we present a new mechanistic model that integrates molecular- and cellular-driven immuno- and mechano-mediated contributions to in vivo neotissue development within implanted polymeric scaffolds. Model parameters are inferred directly from in vivo measurements for an inferior vena cava interposition graft model in the mouse that are augmented by data from the literature. By complementing Bayesian estimation with identifiability analysis and simplex optimization, we found optimal parameter values that match model outputs with experimental targets and quantify variability due to measurement uncertainty. Utility is illustrated by parametrically exploring possible graft narrowing as a function of scaffold pore size, macrophage activity, and the immunomodulatory cytokine transforming growth factor beta 1 (TGF-β1). The model captures salient temporal profiles of infiltrating immune and synthetic cells and associated secretion of cytokines, proteases, and matrix constituents throughout neovessel evolution, and parametric studies suggest that modulating scaffold immunogenicity with early immunomodulatory therapies may reduce graft narrowing without compromising compliance.
On My Own: The Aversion to Being Observed during the Preference-Construction Stage
Authors: Zwebner Yonat , Schrift Rom Y
Published: March 2020

Previous research in consumer behavior and decision-making has explored many important aspects of social observation. However, the effect of social observation during the specific time wherein consumers construct their preferences remains relatively understudied. The present work seeks to fill this knowledge gap and adds to this literature by studying how consumers react to being observed during the preference-construction stage (i.e., prior to reaching their decision). While existing research on social observation focuses on accountability and self-presentation concerns, the present study uncovers an additional unique concern. Specifically, eight studies (three additional studies reported in the web appendix) find that being observed prior to reaching the decision threatens consumers’ sense of autonomy in making the decision, resulting in an aversion to being observed. Furthermore, we find that such threats lead consumers to terminate their decision by avoiding purchase or by choosing default options. Given the extent to which consumers are observed in the marketplace by other individuals and by online platforms, and given the rise in consumers’ privacy concerns associated with such practices, understanding consumer reactions to being observed in the pre-decisional stage is an important topic with practical implications.
Ecology of Sand Flies (Psychodidae: Phlebotominae) and Natural Infection of Pintomyia townsendi With Leishmania amazonensis in a Cutaneous Leishmaniasis Focus in Colombia
Authors: Hoyos Juliana , González Ranulfo , Cuellar Maria E , León Cielo
Published: March 2020

Humans have influenced the epidemiological patterns of American cutaneous leishmaniasis by habitat disturbance, which has led to the emergence of new transmission foci. In these transmission areas, detecting natural infection of sand fly species with Leishmania parasites is of prime importance in epidemiological studies. In this study, we examined the species composition, spatial distribution, seasonality, and natural infection with Leishmania of the sand fly fauna in an emergent leishmaniasis focus located in Colombia. Sand flies were collected from September 2014 to June 2015 using CDC light traps located in indoor, peridomestic, and outdoor habitats within areas with confirmed clinical patients. In total, 13,488 sand flies of 12 species and seven genera were collected. Among these, Pintomyia townsendi (Ortiz) was the most abundant species comprising 76.3% of total flies collected. The sand fly richness and abundance were influenced by habitat and weather conditions. Outdoor areas harbored the greatest diversity of sand flies. Rainfall negatively affected abundance, whereas increased temperature showed a low positive effect. We detected Leishmania amazonensis parasites in Pi. townsendi for the first time.
Limiting spread of COVID-19 in an orthopaedic department—a perspective from Spain
Authors: Gómez-Barrena Enrique , Rubio-Suárez Juan C , Fernández-Baillo Nicomedes , Antuña Samuel , Cruz-Pardos Ana , Blanco Manuel , Ortiz-Cruz Eduardo , González-Morán Gaspar , Gil-Garay Enrique
Published: March 2020

Besides national and international recommendations, orthopaedic departments face significant changes in daily activity and serious issues to maintain their standards in musculoskeletal care during the pandemic Covid-19 crisis that we are facing. This report retrospectively addresses measures that were progressively put in place to modify in a week time the activity of a busy orthopaedic department in a large tertiary university hospital in face of the pandemic. Surgical priorities and surgical outcomes are key aspects to consider. The experience may offer some insight to areas where the spread of the disease may be slower or delayed. Abrupt stop of scheduled surgery and clinics is useful to adapt an orthopaedic department to the overall hospital resource reorganization. Orthopaedic surgeons need to be aware of the risks to patients and personnel in view of underdiagnosed cases, which make pre-operative Covid-19 evaluation mandatory for all surgical cases.
A Neo-Aramaic Version of a Kurdish Folktale
Authors: Häberl Charles , Kuzin Nikita , Loesov Sergey , Lyavdansky Alexey
Published: March 2020

Versions of the folktale Zêrka Zêra (in Kurdish)/Stērka Zerá (in Ṭuroyo) circulate throughout southeastern Anatolia. The story belongs to a widely-disseminated tale type, the ‘Bear's Wife’, which concerns a young woman who is abducted by a bear (or other wilderness creature) and is forced to spawn and rear his children before escaping or being rescued. The following Ṭuroyo version was recorded during the 2018 winter field season of the Russian expedition to Ṭur Abdin in the village of Ḥaḥ/Anıtlı from a speaker of the dialect of Bequsyone. It represents the first scholarly publication not only of the Ṭuroyo version, but of any version of this folktale. In addition to the folktale and a translation, the study includes a glossary of the vocabulary used within the text, reflecting some Ṭuroyo words that have not been documented elsewhere. The paper also discusses the motifs of the Stērka Zerá folktale according to the standard classification scheme of folk motifs.
The Long Perplexing Mīmiyya of Ḥumayd B. Thawr Al-Hilālī: Which Version Is More Convincing?
Authors: Hussein Ali Ahmad
Published: March 2020

This article analyses the structure of four different versions of the long love poem by Ḥumayd b. Thawr al-Hilālī. The shortest of the four runs to 119 verses, and the longest is 185, each line ending with m as a rhyming letter. This structural analysis addresses two main questions: First, what is the story told in each version? Second, in light of this, which version is the most convincing? Answering these questions enabled a restructuring of the poem, which appears in Arabic below, followed by a full English translation, with footnotes to clarify lexicon and content. The study's main conclusion is that the most convincing version of the poem comprises the verses of al-Bayṭār (editor of its longest and most recent variant), structured to fit the narrative of al-Maymanī's edition.
Early Genizah Fragments Of Saadya Gaon's Bible Translation Copied By Samuel B. Shechaniah B. Amram
Authors: Zewi Tamar , Ashur Amir
Published: March 2020

The article presents a full transcription and discussion of eighteen early Genizah fragments of Saadya's Bible translation made of parchment (sixteen from the Pentateuch and two from the book of Daniel) and copied by the scribe Samuel b. Shechaniah b. Amram. Seventeen of them are long narrow pieces of parchment of uneven size, and some are two or more pieces sewn together. These fragments were bound in the form of a rotulus, that is, the pages are attached across their upper and lower margins to form a roll that is read vertically. The fragments are undated; nevertheless, codicological considerations, including their form and method of binding, the material onto which they were copied, and the type of handwriting allow us to assume that they were copied already in the tenth century, or at least no later than the beginning of the eleventh.
Immunotherapy based on Pythium insidiosum mycelia drives a Th1/Th17 response in mice
Authors: Tondolo Juliana S M , Loreto Erico S , de Jesus Francielli P K , Ledur Pauline C , Verdi Camila M , Santurio Janio M
Published: March 2020

Pythium insidiosum is an oomycete that affects mammals, especially humans and horses, causing a difficult-to-treat disease. Typically, surgical interventions associated with antimicrobial therapy, immunotherapy, or both are the preferred treatment choices. PitiumVac® is a therapeutic vaccine prepared from the mycelial mass of P. insidiosum and is used to treat Brazilian equine pythiosis. To better understand how PitiumVac® works, we analyzed the composition of PitiumVac® and the immune response triggered by this immunotherapy in mice. We performed an enzymatic quantification that showed a total glucan content of 21.05% ± 0.94 (α-glucan, 6.37% ± 0.77 and (1,3)(1,6)-β-glucan, 14.68% ± 0.60) and mannose content of 1.39% ± 0.26; the protein content was 0.52 mg ml−1 ± 0.07 mg ml−1. Healthy Swiss mice (n = 3) were subcutaneously preimmunized with one, two, or three shots of PitiumVac®, and immunization promoted a relevant Th1 and Th17 responses compared to nonimmunization of mice. The highest cytokine levels were observed after the third immunization, principally for IFN-γ, IL-17A, IL-6, and IL-10 levels. Results of infected untreated (Pythiosis) and infected treated (Pythiosis + PVAC) mice (n = 3) showed that PitiumVac® reinforces the Th1/Th17 response displayed by untreated mice. The (1,3)(1,6)-β-glucan content can be, at least in part, related to this Th1/Th17 response.
The biggest splash
Authors: Belokurov Vasily , Sanders Jason L , Fattahi Azadeh , Smith Martin C , Deason Alis J , Evans N Wyn , Grand Robert J J
Published: March 2020

Using a large sample of bright nearby stars with accurate Gaia Data Release 2 astrometry and auxiliary spectroscopy we map out the properties of the principle Galactic components such as the ‘thin’ and ‘thick’ discs and the halo. We confirm previous claims that in the Solar neighbourhood, there exists a large population of metal-rich ([Fe/H] > −0.7) stars on highly eccentric orbits. By studying the evolution of elemental abundances, kinematics, and stellar ages in the plane of azimuthal velocity vϕ and metallicity [Fe/H], we demonstrate that this metal-rich halo-like component, which we dub the Splash, is linked to the α-rich (or ‘thick’) disc. Splash stars have little to no angular momentum and many are on retrograde orbits. They are predominantly old, but not as old as the stars deposited into the Milky Way (MW) in the last major merger. We argue, in agreement with several recent studies, that the Splash stars may have been born in the MW’s protodisc prior to the massive ancient accretion event which drastically altered their orbits. We cannot, however, rule out other (alternative) formation channels. Taking advantage of the causal connection between the merger and the Splash, we put constraints of the epoch of the last massive accretion event to have finished 9.5 Gyr ago. The link between the local metal-rich and metal-poor retrograde stars is confirmed using a large suite of cutting-edge numerical simulations of the MW’s formation.
Clinical impact of combined epigenetic and molecular analysis of pediatric low-grade gliomas
Authors: Fukuoka Kohei , Mamatjan Yasin , Tatevossian Ruth , Zapotocky Michal , Ryall Scott , Stucklin Ana Guerreiro , Bennett Julie , Nobre Liana Figueiredo , Arnoldo Anthony , Luu Betty , Wen Ji , Zhu Kaicen , Leon Alberto , Torti Dax , Pugh Trevor J , Hazrati Lili-Naz , Laperriere Normand , Drake James , Rutka James T , Dirks Peter , Kulkarni Abhaya V , Taylor Michael D , Bartels Ute , Huang Annie , Zadeh Gelareh , Aldape Kenneth , Ramaswamy Vijay , Bouffet Eric , Snuderl Matija , Ellison David , Hawkins Cynthia , Tabori Uri
Published: March 2020

Background

Both genetic and methylation analysis have been shown to provide insight into the diagnosis and prognosis of many brain tumors. However, the implication of methylation profiling and its interaction with genetic alterations in pediatric low-grade gliomas (PLGGs) are unclear.

Methods

We performed a comprehensive analysis of PLGG with long-term clinical follow-up. In total 152 PLGGs were analyzed from a range of pathological subtypes, including 40 gangliogliomas. Complete molecular analysis was compared with genome-wide methylation data and outcome in all patients. For further analysis of specific PLGG groups, including BRAF p.V600E mutant gliomas, we compiled an additional cohort of clinically and genetically defined tumors from 3 large centers.

Results

Unsupervised hierarchical clustering revealed 5 novel subgroups of PLGG. These were dominated by nonneoplastic factors such as tumor location and lymphocytic infiltration. Midline PLGG clustered together while deep hemispheric lesions differed from lesions in the periphery. Mutations were distributed throughout these location-driven clusters of PLGG. A novel methylation cluster suggesting high lymphocyte infiltration was confirmed pathologically and exhibited worse progression-free survival compared with PLGG harboring similar molecular alterations (P = 0.008; multivariate analysis: P = 0.035). Although the current methylation classifier revealed low confidence in 44% of cases and failed to add information in most PLGG, it was helpful in reclassifying rare cases. The addition of histopathological and molecular information to specific methylation subgroups such as pleomorphic xanthoastrocytoma–like tumors could stratify these tumors into low and high risk (P = 0.0014).

Conclusion

The PLGG methylome is affected by multiple nonneoplastic factors. Combined molecular and pathological analysis is key to provide additional information when methylation classification is used for PLGG in the clinical setting.
Pediatric Spine Trauma: A Brief Review
Authors: Alexiades Nikita G , Parisi Frank , Anderson Richard C E
Published: March 2020

Pediatric spinal trauma is a broad topic with nuances specific to each anatomic region of the spinal column. The purpose of this report is to provide a brief review highlighting the most important and common clinical issues regarding the diagnosis and management of pediatric spine trauma. Detailed descriptions of imaging findings along with specific operative and nonoperative management of each fracture and dislocation type are beyond the scope of this review.
Use of virtual reality for symptom management in solid-tumor patients with implications for primary brain tumor research: a systematic review
Authors: Leggiero Nicole M , Armstrong Terri S , Gilbert Mark R , King Amanda L
Published: March 2020

Background

Primary brain tumors (PBTs) remain incurable, with a typically poor prognosis and significant symptom burden for patients. Virtual reality (VR) can potentially alleviate some of the negative aspects of illness by allowing individuals to escape to environments where they can experience more positive thoughts and emotions. Given promising findings for VR use in other clinical populations, there is increasing interest to use VR for symptomatic improvement in oncology patients. The purpose of this review was to analyze the literature of VR-related interventions for symptom management in adult PBT and other solid-tumor patients, which will guide development of future VR interventions in these populations.

Methods

A systematic search of EMBASE, PubMed, Scopus, and Web of Science was performed using PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines with predefined eligibility criteria. Thirteen studies met the inclusion criteria and were selected for review.

Results

Findings showed promising evidence that VR can improve anxiety for solid-tumor patients, with mixed results reported for pain, distress, depression, and mood. There was significant heterogeneity in methodological approaches across the literature and the majority of studies were underpowered and lacked rigorous study designs. Qualitative findings demonstrated a high degree of participant satisfaction with VR use, with very few adverse side effects reported.

Conclusions

Findings from this review suggest that VR can be used as an innovative delivery system for targeted interventions to improve symptoms in PBTs and other solid-tumor patient populations, though additional well-designed clinical trials are needed to better establish its efficacy.
Circulating CD19+CD24hiCD38hi regulatory B cells as biomarkers of response to methotrexate in early rheumatoid arthritis
Authors: Fortea-Gordo Paula , Villalba Alejandro , Nuño Laura , Santos-Bórnez María José , Peiteado Diana , Monjo Irene , Puig-Kröger Amaya , Sánchez-Mateos Paloma , Martín-Mola Emilio , Balsa Alejandro , Miranda-Carús María-Eugenia
Published: March 2020

Objective

The protagonism of regulatory B cells seems to vary along the course of the disease in murine models of inflammatory conditions. Decreased numbers of circulating regulatory CD19+CD24hiCD38hi transitional (cTr) B cells have been described in patients with long-standing RA, thus our objective was to examine the frequency and evolution of cTr B cells in the peripheral blood of early RA (ERA) patients.

Methods

Freshly isolated peripheral blood mononuclear cells from 48 steroid- and DMARD-naïve ERA patients with a disease duration of <24 weeks and 48 healthy controls (HCs) were examined by flow cytometry. Co-cultures of isolated memory B cells were established with autologous T cells in the absence or presence of Tr B cells.

Results

As compared with HCs, ERA patients demonstrated an increased frequency of cTr B cells. cTr B cells of ERA patients and HCs displayed an anti-inflammatory cytokine profile and were able to downregulate T cell IFN-γ and IL-21 production, together with ACPA secretion in autologous B/T cell co-cultures. Basal frequencies of cTr B cells above the median value observed in HCs were associated with a good EULAR response to MTX at 12 months [relative risk 2.91 (95% CI 1.37, 6.47)]. A significant reduction of cTr B cells was observed 12 months after initiating MTX, when the cTr B cell frequency was no longer elevated but decreased, and this was independent of the degree of clinical response or the intake of prednisone.

Conclusion

An increased frequency of regulatory cTr B cells is apparent in untreated ERA and the baseline cTr B cell frequency is associated with the clinical response to MTX at 12 months.
Ultradian modulation of cortical arousals during sleep: effects of age and exposure to nighttime transportation noise
Authors: Rudzik Franziska , Thiesse Laurie , Pieren Reto , Héritier Harris , Eze Ikenna C , Foraster Maria , Vienneau Danielle , Brink Mark , Wunderli Jean Marc , Probst-Hensch Nicole , Röösli Martin , Fulda Stephany , Cajochen Christian
Published: March 2020

Study Objectives

The present study aimed at assessing the temporal non-rapid eye movement (NREM) EEG arousal distribution within and across sleep cycles and its modifications with aging and nighttime transportation noise exposure, factors that typically increase the incidence of EEG arousals.

Methods

Twenty-six young (19–33 years, 12 women) and 16 older (52–70 years, 8 women) healthy volunteers underwent a 6-day polysomnographic laboratory study. Participants spent two noise-free nights and four transportation noise exposure nights, two with continuous and two characterized by eventful noise (average sound levels of 45 dB, maximum sound levels between 50 and 62 dB for eventful noise). Generalized mixed models were used to model the time course of EEG arousal rates during NREM sleep and included cycle, age, and noise as independent variables.

Results

Arousal rate variation within NREM sleep cycles was best described by a u-shaped course with variations across cycles. Older participants had higher overall arousal rates than the younger individuals with differences for the first and the fourth cycle depending on the age group. During eventful noise nights, overall arousal rates were increased compared to noise-free nights. Additional analyses suggested that the arousal rate time course was partially mediated by slow wave sleep (SWS).

Conclusions

The characteristic u-shaped arousal rate time course indicates phases of reduced physiological sleep stability both at the beginning and end of NREM cycles. Small effects on the overall arousal rate by eventful noise exposure suggest a preserved physiological within- and across-cycle arousal evolution with noise exposure, while aging affected the shape depending on the cycle.
Psychometric Properties of the Revised Clinical Institute Withdrawal Alcohol Assessment and the Brief Alcohol Withdrawal Scale in a Psychiatric Population
Authors: Elefante Raymond Julius , Batkis Marcelo , Nelliot Archana , Abernathy Karen , Rocha Kristi , Jenkins Freddie , Rastegar Darius Anthony , Neufeld Karin Jane
Published: March 2020

Objective:

Psychiatric illness complicates the assessment of alcohol and sedative withdrawal (ASW). This study measured the diagnostic characteristics of the Revised Clinical Institute Withdrawal Alcohol Assessment (CIWA-Ar) and the Brief Alcohol Withdrawal Scale (BAWS) compared with a reference standard in patients with psychiatric illness and evaluated their administration time.

Methods:

This prospective quality improvement (QI) project conducted in November, 2016 evaluated 35 consecutive unique patients in psychiatric settings. Each patient was evaluated on 1 occasion, sequentially by 2 independent examiners with the CIWA-Ar and BAWS. A Diagnostic Statistical Manual of Mental Disorders, Fifth Edition diagnosis of ASW derived after medical record review by 2 psychiatrists blind to the screening results served as a reference standard. Psychometric properties of the CIWA-Ar and BAWS were measured against the reference.

Results:

Nineteen (54%) patients had ASW diagnosis by the reference standard. The sensitivity (95% confidence interval [CI]) of the CIWA-Ar was 47% (25%–71%) at a cut-off score ≥8; sensitivity of the BAWS was 79% (54%–94%) at a cut-off score ≥3. Specificity (95% CI) for CIWA-Ar and BAWS was 88% (62%–98%) and 88% (62%–98%), respectively. Administration times (interquartile range) for the CIWA-Ar and BAWS were 120 (60–180) and 65 (50–75) seconds, respectively. Receiver operator characteristic area under the curve for CIWA-Ar was 0.77 and for BAWS was 0.76 (P = 0.86).

Conclusion:

Both instruments performed similarly in assessing for mild to moderate ASW in a sample of patients with psychiatric illness. The BAWS took 65 seconds to administer—almost half as much time as the CIWA-Ar.
Use of PROMIS in Assessment of Children With Ponseti-treated Idiopathic Clubfoot: Better Scores With Greater Than 3 Years of Brace Use
Authors: Khan Ahsan A. , Abarca Nancy , Cung Nina Q. , Lerman Joel A.
Published: April 2020

Background:

Patient-Reported Outcomes Measurement Information System (PROMIS) is a well-validated tool used to measure health-related quality of life for children and adolescents with chronic medical conditions. The current study evaluates PROMIS scores in 3 domains for children with Ponseti-treated idiopathic clubfoot.

Methods:

This is a retrospective cohort study of 77 children, ages 5 to 16 years, treated by Ponseti protocol for idiopathic clubfoot. Three pediatric PROMIS domains (Mobility, Pain Interference, and Peer Relationships) were administered between April 2017 and June 2018. One-way analysis of variance with Bonferroni post hoc and independent sample t tests were performed to explore differences across PROMIS domain scores by sex, age, initial Dimeglio score, laterality, bracing duration, and whether the child underwent tibialis anterior transfer.

Results:

In the self-reported group (ages 8 to 16), mean T-scores for all 3 domains in both unilaterally and bilaterally affected groups were within the normal range, with respect to the general reference pediatric population. However, children with unilateral clubfoot had a significantly higher mean Mobility T-score (54.77) than children with bilateral clubfoot (47.81, P=0.005). Children with unilateral clubfoot also had significantly lower mean pain scores (39.16) than their bilateral counterparts (46.56, P=0.005). Children who had braced >36 months had a significantly higher mean Mobility T-score (53.68) than children who braced ≤36 months (46.28, P=0.004).

In the proxy group (ages 5 to 7), mean T-scores for all 3 domains in both laterality groups were within the normal range, with respect to the reference population. Children who had braced >36 months had a significantly higher mean Mobility T-score (52.75 vs. 49.15, P=0.014) and lower Pain Interference score (43.04 vs. 49.15, P=0.020) than children who braced ≤36 months.

Conclusions:

Children treated by Ponseti protocol for idiopathic clubfoot yielded PROMIS scores for Mobility, Pain Interference, and Peer Relationships domains similar to the reference population. Bracing duration >36 months and unilaterality were associated with less mobility impairment than their counterparts. These findings may help guide parent recommendations.

Level of Evidence:

Level III.
Giant Ethmoid Sinus Osteoma Protruding into the Maxillary Sinus
Authors: Yazici Demet , Kuran Gökhan
Published: March 2020

Ethmoid sinus osteomas are rare, benign, encapsulated neoplasms of the paranasal region. They can lead to various complications such as sinusitis, orbital cellulitis, proptosis, and diplopia. The treatment protocol of these lesions changed remarkably as powered instrumentation of functional endoscopic sinus surgery evolved and otolaryngologists gained experience. Here, the authors report a 30-year-old female who was diagnosed with a giant right-sided ethmoid sinus osteoma and discuss diagnostic and treatment modalities of these lesions in consonance with the current literature.
Analysis of Neoclassical Facial Canons for Brazilian White Young Adults and Comparison With North American Caucasian Population
Authors: Gonzales Paola Sampaio , Machado Carlos Eduardo Palhares , Michel-Crosato Edgard
Published: March 2020

An indirect anthropometric study was conducted to find out whether neoclassical facial canons could be applied to the population of Brazilian white young adults. The study was based on standardized facial photographs of 689 women and 666 men aged 30 years ± 6 months. The findings were compared to those observed for the North American Caucasian population. The frequency of 5 canons was assessed: facial thirds; interorbital width; nose and eye widths; mouth and nose widths; and face and nose widths. The assessed population showed the following ratios: tr-n > n-sn (96.01%), n-sn < sn-gn (95.90%), tr-n = sn-gn (42.06%), en-en < al-al (58.08%), en-en < ec-en (59.92%), ch-ch = 1½ al-al (52.61%), and al-al = 1/4 zy-zy (56.67%). When compared to North American Caucasians, only tr-n/n-sn and n-sn/sn-gn were identical. In conclusion, neoclassical facial canons cannot be applied to the Brazilian population, but they could serve as parameters for application in clinical practice and in forensic sciences.
Microsurgery for Head and Neck Reconstruction
Authors: Onoda Satoshi , Masahito Kinoshita
Published: March 2020

The most serious complication of free flap transfer is total flap necrosis, which is usually due to a microvascular problem. The development of a microsurgical instrument has greatly lowered the prevalence of postoperative vascular trouble to a rate of 1% to 3%. However, necrosis of the transferred flap in head and neck reconstruction can cause serious complications and postoperative functional deficiency. Therefore, for blood circulation disorder of the flap following free flap transfer, it is necessary to perform re-operation, as soon as possible, in order to attempt salvaging the flap after the disorder has been diagnosed.

The goal of this study was to analyze the microsurgery for head and neck reconstruction. The author, with an experience of more than 500 microsurgical anastomoses, discusses microsurgery in head and neck reconstruction through the choices of recipient vessels, aspects that require attention in order to prevent vascular complications, and correspondence when complications occur.
Experience With “Jaw in a Day” Technique
Authors: Sukato Daniel C. , Hammer Daniel , Wang Weitao , Shokri Tom , Williams Fayette , Ducic Yadranko
Published: March 2020

The “Jaw in a Day” (JIAD) technique, first described by Levine and colleagues, establishes immediate functional occlusion through a single-stage maxillomandibular reconstruction with concurrent implant placement and provisional prosthesis delivery. In this study, the authors describe 2 cases exemplifying the reconstructive principles of JIAD. One patient underwent mandibular reconstruction with the JIAD technique and another patient underwent JIAD with an optimized rapid sequence computer-aided design and computer-aided manufacturing (CAD-CAM) for composite maxillomandibular reconstruction. Immediate implant-borne prosthesis was fixated and all implants osseointegrated into the neomandible. Although the authors’ patient outcomes are consistent with the literature, the published reports of JIAD remain limited, and further studies are required to assess the long-term functional and aesthetic outcomes as well as cost-effectiveness of this approach.
Effect of Deviated Nasal Septum on Choriodal Thickness
Authors: Şahin Ender , Songur Murat Serkan , Kantekin Yunus , Bayhan Hasan Ali , Can Ilknur Haberal
Published: March 2020

Introduction:

Nasal septal deviation (NSD) is one of the major causes of upper airway obstruction. Chronic hypoxia and hypercapnia due to NSD may affect the choroidal blood flow and may change the choroidal thickness (CT). In this study, the authors aimed to research the assessment of CT before and after septoplasty in patients with NSD.

Methods:

Ninety-two patients who underwent septoplasty surgery with the diagnose of nasal septum deviation and 58 patients for control group were enrolled to the study. CT values measured before and three months after septoplasty surgery.

Results:

CT values were subfoveal 272.51 ± 27.62, nasal 245.50 ± 21.22, temporal 248.35 ± 30.25 and subfoveal 232.09 ± 44.17, nasal 222.09 ± 38.82,temporal 227.12 ± 28.80 for the control and NSD groups, respectively (P < 0.001). Also choroid thickness values (subfoveal 232.09 ± 44.17, nasal 222.09 ± 38.82, temporal 227.12 ± 28.80; subfoveal 252 ± 18.90, nasal 228 ± 22.12, temporal 240 ± 25.80) were significantly different in patients with NSD, before and after septoplasty procedure, respectively (P < 0.001).

Conclusion:

To the authors’ knowledge this is the first study investigating choroid thickness measurements before and after septoplasty in patients with NSD. We found significant correlation between NSD and CT. After septoplasty surgery at 3rd month, CT increased significantly in comparision with the preoperative values.
Elevated Intracranial Pressure Associated With Exogenous Hormonal Therapy Used for Gender Affirmation
Authors: Nguyen Huy V. , Gilbert Aubrey L. , Fortin Elizabeth , Vodopivec Ivana , Torun Nurhan , Chwalisz Bart K. , Cestari Dean M. , Rizzo Joseph F.
Published: April 2020

Background:

Addison disease, corticosteroid withdrawal, and taking synthetic growth hormone have been linked with development of intracranial hypertension, but there is still debate on whether administration of other exogenous hormones plays a role in precipitating elevated pressure. The growing use of hormonal therapy for gender affirmation provides an opportunity to explore this possibility.

Methods:

All transgender patients taking exogenous hormones for female-to-male (FTM) and male-to-female (MTF) transitions who were diagnosed with intracranial hypertension at Massachusetts Eye and Ear Infirmary, Massachusetts General Hospital and Beth Israel Deaconess Medical Center between August 2014 and November 2018 were included in a retrospective review. Visual acuity, type, and dose of exogenous hormone, visual field testing, clinical exam, results of neuroimaging and lumbar puncture, and treatment modalities were catalogued and analyzed.

Results:

Six transgender individuals were identified. Five were FTM, with an average hormone treatment time of 18.4 months, and one was MTF who had been treated with hormones for 4 years. The average age of all patients was 23.5 years. The average time between onset of symptoms and presentation was 5 months. Fifty percent of the patients reported pulse-synchronous tinnitus, 83% reported positional headache, 33% reported transient visual obscurations, and 16% reported diplopia. Lumbar punctures performed on 4 of the patients revealed elevated opening pressures and normal cerebrospinal fluid constituents. MRI findings consistent with elevated intracranial pressure (ICP) were present in the other 2 patients in whom lumbar puncture was unsuccessful. Four patients were treated with acetazolamide and one was treated with topiramate, with an average follow-up time of 15.7 months. All patients demonstrated bilateral optic disc swelling, and all maintained normal acuity and color vision. Performance on visual field testing was not significantly affected in any patient.

Conclusions:

This is the largest reported series to date of gender-transitioning patients with intracranial hypertension, including one novel MTF conversion. These observations warrant further investigation into the possible link of exogenous hormonal therapy and elevated ICP and any mechanisms or confounders underlying this potential association.
A novel germline mutation in thePOT1gene predisposes to familial non-medullary thyroid cancer
Authors: Srivastava Aayushi , Miao Beiping , Skopelitou Diamanto , Kumar Varun , Kumar Abhishek , Paramasivam Nagarajan , Bonora Elena , Hemminki Kari , Försti Asta , Bandapalli Obul Reddy
Published: March 2020

Non-medullary thyroid cancer (NMTC) is a common endocrine malignancy with a genetic basis that has yet to be unequivocally established. In a recent whole genome sequencing study of five families with recurrence of NMTCs, we shortlisted promising variants with the help of bioinformatics tools. Here, we reportin silicoanalyses andin vitroexperiments on a novel germline variant (p.V29L) in the highly conserved oligonucleotide/oligosaccharide binding domain of theProtection of Telomeres 1 (POT1)gene in one of the families. The results showed that the variant demonstrates a reduction in telomere-bound POT1 levels in the mutant protein as compared to its wild-type counterpart. HEK293Tcells carryingPOT1V29Lshowed increased telomere length in comparison to wild type cells, strongly suggesting that the mutation causes telomere dysfunction and may play a role in predisposition to NMTC in this family. This study reports the first germlinePOT1mutation in a family with a predominance of thyroid cancer, thereby expanding the spectrum of cancers associated with mutations in the shelterin complex.