bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic pattern of intratumor heterogeneity predicts the risk of progression in early stage diffuse large B-cell lymphoma
Authors: Wang Yue , Feng Wanjing , Liu Peng
Published: April 2019

Intratumor heterogeneity (ITH) plays an important role in tumor development, metastases, recurrence and has impact on clinical diagnosis, therapeutic responses. In this study, we used mutant-allele tumor heterogeneity (MATH) through whole-exome sequencing data to evaluate ITH in early stage diffuse large B-cell lymphoma (DLBCL). A discovery set of 22 patients and a validation set of 35 patients with primary DLBCL which staged I or II were chosen from The Cancer Genome Atlas database and The Gene Index Project database, respectively. Then patients were divided into low and high MATH score groups according to the median expression level. As a result, higher MATH score displayed an increasing risk of progression compared with lower MATH score both in the discovery set (P = 0.045) and the validation set (P = 0.025). Further, the genomic pattern according to MATH demonstrated that mutation rates of immunoglobulin lambda locus, B-cell translocation gene and membrane-associated guanylate kinase were the sites with the highest mutation rate. Moreover, Gene enrichment analysis showed that immunoglobulin lambda constant 2 (IGLC2) which belongs to immunoglobulin lambda locus was only enriched in high MATH group. Besides, BTG2 and Caspase recruitment domain-containing protein 11 were cancer driver genes which listed on the top three high rate of mutation. Our study revealed the prognostic value of MATH and relevant genomic pattern in early stage DLBCL. Potential mechanisms on genetic level of how genomic aberration influence the ITH of DLBCL are provided. MATH based on whole genome sequencing may be feasible for deciding clinical treatment of DLBCL patients in the future researches.
Interspecific relationships between Palmaria palmata and three Fucus species at the Murman Coast
Authors: Malavenda Sergey S , Malavenda Svetlana V , Chovgan Olga
Published: April 2019

The mutual influence of the dominant macroalgae species inhabiting the intertidal zone of the Murman Coast was studied. Particularly, the proposed negative effect of Palmaria palmata on the growth of Fucus algae was tested. The interspecific interactions of the Fucus vesiculosus, F. distichus, F. serratus, and P. palmata were studied experimentally. The species were cultivated pairwise in the laboratory. A field experiment with species removal was performed in the intertidal zone of the Zelenetskaya Bay, the Barents Sea. The growth rate, algae biomass, and the content of chlorophyll pigments was measured. Fucus species affected positively the growth of P. palmata. No effect of the other species on F. vesiculosus was recorded under the experimental conditions. Palmaria palmata affected negatively the growth of F. serratus; its presence led to an increase in the pigment content in F. serratus and F. distichus.
On Sevostyanov’s Construction of Quantum Difference Toda Lattices
Authors: Gonin Roman , Tsymbaliuk Alexander
Published: April 2019

We propose a natural generalization of the construction of the quantum difference Toda lattice [6, 22] associated with a simple Lie algebra $\mathfrak{g}$. Our construction depends on two orientations of the Dynkin diagram of $\mathfrak{g}$ and some other data (which we refer to as a pair of Sevostyanov triples). In types $A$ and $C$, we provide an alternative construction via Lax matrix formalism, cf. [15]. We also show that the generating function of the pairing of Whittaker vectors in the Verma modules is an eigenfunction of the corresponding modified quantum difference Toda system and derive fermionic formulas for the former in spirit of [7]. We give a geometric interpretation of all Whittaker vectors in type $A$ via line bundles on the Laumon moduli spaces and obtain an edge-weight path model for them, generalizing the construction of [4].
Balloon Catheter Dilatation for Treatment of a Patient With Cricopharyngeal Dysfunction After Thermal Burn Injury
Authors: Joo So Young , Lee Seung Yeol , Cho Yoon Soo , Seo Cheong Hoon
Published: April 2019

Deglutition disorder is a clinical symptom that has been associated with inhalation and cutaneous thermal burn injuries. Deglutition disorder is present in approximately 11% of patients with burn injury and is known to persist for weeks to months postinjury. Here, we report a case of deglutition disorder associated with cricopharyngeal dysfunction in a patient with thermal burn injury. Two patients presented with deglutition disorder lasting for several weeks after thermal injury. Clinically, it manifested as combined liquid and solid food dysphagia. The findings of videofluoroscopic swallow study (VFSS) were poor relaxation of the pharyngoesophageal sphincter (PES), decreased elevation of the laryngohyoid, and inadequate pharyngeal contraction. The PES was dilated with a 20-mm expansion balloon catheter multiple times. The symptoms of deglutition disorder were relieved immediately after the procedure. Balloon catheter dilatation was performed four times at 1- to 2-week intervals. Follow-up VFSS showed that poor relaxation of the PES was improved. The VFSS showed no recurrence at the 3-month follow-up. We found that balloon catheter dilatation for treatment of a patient with cricopharyngeal dysfunction after thermal burn injury was effective, ease of use, and safe.
A new species of Sunamphitoe (Amphipoda: Ampithoidae) that bores into the primary fronds of kelps in South Africa
Authors: Griffiths Charles L
Published: April 2019

The herbivorous amphipod Sunamphitoe robertan. sp. is described from the canopy of kelp beds in False Bay, South Africa. The new species has unusual habits, small family groups burrowing directly into the margins of the swollen primary fronds of the kelp Ecklonia maxima (Osbeck) Papenfuss, 1940. Morphologically, the new species is best distinguished from other species of Sunamphitoe by strong rows of dorsal spines on the outer rami of uropods 1 and 2. These spine rows appear to be employed as ‘drill-bits’ to excavate kelp tissue and create the burrows. Damage to hosts does not appear to be fatal, but requires further investigation.
Blood DNA Methylation and Breast Cancer: A Prospective Case-Cohort Analysis in the Sister Study
Authors: Xu Zongli , Sandler Dale P , Taylor Jack A
Published: April 2019

Background

Peripheral blood DNA methylation may be associated with breast cancer, but studies of candidate genes and global and genome-wide DNA methylation have been inconsistent.

Methods

We performed an epigenome-wide study using Infinium HumanMethylation450 BeadChips with prospectively collected blood DNA samples from the Sister Study (1552 cases, 1224 subcohort). Differentially methylated cytosine-phosphate-guanine sites (dmCpGs) were identified using case-cohort proportional hazard models and replicated using deposited data from European Prospective Investigation into Cancer and Nutrition in Italy (EPIC-Italy) (n = 329). The correlation between methylation and time to diagnosis was examined using robust linear regression. Causal or consequential relationships of methylation to breast cancer were examined by Mendelian randomization using OncoArray 500 K single-nucleotide polymorphism data. All statistical tests were two-sided.

Results

We identified 9601 CpG markers associated with invasive breast cancer (false discovery rate = q < 0.01), with 510 meeting a strict Bonferroni correction threshold (10–7). A total of 2095 of these CpGs replicated in the independent EPIC-Italy dataset, including 144 meeting the Bonferroni threshold. Sister Study women who developed ductal carcinoma in situ had methylation similar to noncases. Most (1501, 71.6%) dmCpGs showed lower methylation in invasive cases. In case-only analysis, methylation was statistically significantly associated (false discovery rate = q < 0.05) with time to diagnosis for 892 (42.6%) of the dmCpGs. Analyses based on genetic association suggest that methylation differences are likely a consequence rather than a cause of breast cancer. Pathway analysis shows enrichment of breast cancer-related gene pathways, and dmCpGs are overrepresented in known breast cancer susceptibility genes.

Conclusions

Our findings suggest that the DNA methylation profile of blood starts to change in response to invasive breast cancer years before the tumor is clinically detected.
A fast radio burst with frequency-dependent polarization detected during Breakthrough Listen observations
Authors: Price D C , Foster G , Geyer M , van Straten W , Gajjar V , Hellbourg G , Karastergiou A , Keane E F , Siemion A P V , Arcavi I , Bhat R , Caleb M , Chang S-W , Croft S , DeBoer D , de Pater I , Drew J , Enriquez J E , Farah W , Gizani N , Green J A , Isaacson H , Hickish J , Jameson A , Lebofsky M , MacMahon D H E , Möller A , Onken C A , Petroff E , Werthimer D , Wolf C , Worden S P , Zhang Y G
Published: April 2019

Here, we report on the detection and verification of fast radio burst FRB 180301, which occurred on utc 2018 March 1 during the Breakthrough Listen observations with the Parkes telescope. Full-polarization voltage data of the detection were captured – a first for non-repeating FRBs – allowing for coherent de-dispersion and additional verification tests. The coherently de-dispersed dynamic spectrum of FRB 180301 shows complex, polarized frequency structure over a small fractional bandwidth. As FRB 180301 was detected close to the geosynchronous satellite band during a time of known 1–2 GHz satellite transmissions, we consider whether the burst was due to radio interference emitted or reflected from an orbiting object. Based on the pre-ponderance of our verification tests, we cannot conclusively determine FRB 180301 to be either astrophysical or anthropogenic in origin.
Formation of short-period planets by disc migration
Authors: Carrera Daniel , Ford Eric B , Izidoro Andre
Published: April 2019

Protoplanetary discs are thought to be truncated at orbital periods of around 10 d. Therefore, the origin of rocky short-period planets with P < 10 d is a puzzle. We propose that many of these planets may form through the Type-I migration of planets locked into a chain of mutual mean motion resonances. We ran N-body simulations of planetary embryos embedded in a protoplanetary disc. The embryos experienced gravitational scatterings, collisions, disc torques, and dampening of orbital eccentricity and inclination. We then modelled Kepler observations of these planets using a forward model of both the transit probability and the detection efficiency of the Kepler pipeline. We found that planets become locked into long chains of mean motion resonances that migrate in unison. When the chain reaches the edge of the disc, the inner planets are pushed past the edge due to the disc torques acting on the planets farther out in the chain. Our simulated systems successfully reproduce the observed period distribution of short-period Kepler planets between 1 and 2 R⊕. However, we obtain fewer closely packed short-period planets than in the Kepler sample. Our results provide valuable insight into the planet formation process, and suggests that resonance locks, migration, and dynamical instabilities play important roles in the formation and evolution of close-in small exoplanets.
Hunting for brown dwarfs in the globular cluster M4: second epoch HST NIR observations
Authors: Dieball A , Bedin L R , Knigge C , Geffert M , Rich R M , Dotter A , Richer H , Zurek D
Published: April 2019

We present an analysis of the second epoch Hubble Space TelescopeWide Field Camera 3 F110W near-infrared (NIR) imaging data of the globular cluster M 4. The new data set suggests that one of the previously suggested four brown dwarf candidates in this cluster is indeed a high-probability cluster member. The position of this object in the NIR colour–magnitude diagrams (CMDs) is in the white dwarf/brown dwarf area. The source is too faint to be a low-mass main-sequence (MS) star, but, according to theoretical considerations, also most likely somewhat too bright to be a bona-fide brown dwarf. Since we know that the source is a cluster member, we determined a new optical magnitude estimate at the position the source should have in the optical image. This new estimate places the source closer to the white dwarf sequence in the optical–NIR CMD and suggests that it might be a very cool (Teff ≤ 4500 K) white dwarf at the bottom of the white dwarf cooling sequence in M 4, or a white dwarf/brown dwarf binary. We cannot entirely exclude the possibility that the source is a very massive, bright brown dwarf, or a very low-mass MS star, however, we conclude that we still have not convincingly detected a brown dwarf in a globular cluster, but we expect to be very close to the start of the brown dwarf cooling sequence in this cluster. We also note that the MS ends at F110W ≈ 22.5 mag in the proper-motion cleaned CMDs, where completeness is still high.
Jediism: Religion at Law?
Authors: Cheung Tommy
Published: April 2019

This article explores whether Jediism, one of the ‘fiction-based religions’ in contemporary times, meets the requirements of religion under the English charity law. This article argues that the reasons gave by the Charity Commission of the UK in rejecting the application of the Jediist religious group the Temple of The Jedi Order (TOTJO) as a Charitable Incorporation Organization in 2016 was not made under solid legal grounds but on a moral judgment that Jediism, in their opinion, is not serious. This article argues that the principles adopted by the Charity Commission is wrong and they could reach the same conclusion by using a correct legal approach.

Through a detailed study on the origin and the current situation of Jediism as a ‘fiction-based religious group’ and TOTJO, this article suggests that for Jediism to be considered as a bona fide religion, it needs to complete its belief system and bring back the concept of Dark Side from Star Wars. It was absent because of the Jediists’ deliberate effort to distance themselves from the Star Wars fandom. Finally, through looking at the history and evolvement of the English charity law, argues that there is room for the current English charity law to give a more liberal interpretation to allow a better balance between regulation of charity and the freedom of religion. It is necessary because of the public benefit brought by any bona fide religion.
Expression and characterization of functional domains of FK506-binding protein 35 from Plasmodium knowlesi
Authors: Goh Carlmond Kah Wun , Silvester Jovi , Wan Mahadi Wan Nur Shuhaida , Chin Lee Ping , Ying Lau Tiek , Leow Thean Chor , Kurahashi Ryo , Takano Kazufumi , Budiman Cahyo
Published: April 2019

The FK506-binding protein of Plasmodium knowlesi (Pk-FKBP35) is considerably a viable antimalarial drug target, which belongs to the peptidyl-prolyl cis-trans isomerase (PPIase) protein family member. Structurally, this protein consists of an N-terminal FK506-binding domain (FKBD) and a C-terminal tetratricopeptide repeat domain (TPRD). This study aims to decipher functional properties of these domains as a platform for development of novel antimalarial drugs. Accordingly, full-length Pk-FKBP35 as well as its isolated domains, Pk-FKBD and Pk-TPRD were overexpressed, purified, and characterized. The results showed that catalytic PPIase activity was confined to the full-length Pk-FKBP35 and Pk-FKBD, suggesting that the catalytic activity is structurally regulated by the FKBD. Meanwhile, oligomerization analysis revealed that Pk-TPRD is essential for dimerization. Asp55, Arg60, Trp77 and Phe117 in the Pk-FKBD were considerably important for catalysis as underlined by significant reduction of PPIase activity upon mutations at these residues. Further, inhibition activity of Pk-FKBP35 towards calcineurin phosphatase activity revealed that the presence of FKBD is essential for the inhibitory property, while TPRD may be important for efficient binding to calcineurin. We then discussed possible roles of FKBP35 in Plasmodium cells and proposed mechanisms by which the immunosuppressive drug, FK506, interacts with the protein.
The Rate of Return on Everything, 1870–2015*
Authors: Jordà Òscar , Knoll Katharina , Kuvshinov Dmitry , Schularick Moritz , Taylor Alan M
Published: April 2019

What is the aggregate real rate of return in the economy? Is it higher than the growth rate of the economy and, if so, by how much? Is there a tendency for returns to fall in the long run? Which particular assets have the highest long-run returns? We answer these questions on the basis of a new and comprehensive data set for all major asset classes, including housing. The annual data on total returns for equity, housing, bonds, and bills cover 16 advanced economies from 1870 to 2015, and our new evidence reveals many new findings and puzzles.
Inhibition of Autophagy Alleviates Cadmium-Induced Mouse Spleen and Human B Cells Apoptosis
Authors: Gu Jie , Wang Yanwei , Liu Yanmin , Shi Meilin , Yin Liangdong , Hou Yongzhong , Zhou Yang , Chu Wong Chris Kong , Chen Dongfeng , Guo Zhigang , Shi Haifeng
Published: April 2019

Cadmium (Cd) is a toxic heavy metal that can accumulate and cause severe damage to many organs, such as liver, kidney, lung, etc. Cd also significantly suppresses immunity, however, the underlying mechanism involved in Cd-induced immunnotoxicity is still unclear. The present study indicated that semichronic Cd exposure (7 days) induced apoptotic damage of mouse spleen. In human Ramos B cells, Cd exposure also induced apoptosis, which was dependent on Cd-induced vacuole membrane protein 1 (VMP1) expression and autophagy. Cd-induced autophagy and apoptosis were abated when VMP1 expression was knockdown. In addition, Cd-induced VMP1 expression, autophagy, and apoptosis were dependent on the elevation of Ca2+ and reactive oxygen species (ROS). More important, Cd exposure also induced VMP1 expression and autophagy in mouse spleen tissue, and the intraperitoneal injection of the autophagy inhibitor chloroquine (CQ) into mice effectively reduced Cd-induced spleen apoptotic damage. Taken together, these results indicate Cd-induced autophagy, promotes apoptosis in immune cells, and inhibition of autophagy can alleviate Cd-induced spleen and immune cell apoptosis. This study might provide the groundwork for future studies on Cd-induced immunomodulatory effects and immune diseases.
Effects of Hemodynamic Factors and Oxygenation on the Incidence of Pressure Ulcers in the ICU
Authors: Soodmand Mostafa , Moghadamnia Mohammad Taghi , Aghaei Iraj , Ghasemzadeh Golshan , Kazemnejad Lili Ehsan , Homaie Rad Enayatollah
Published: April 2019

OBJECTIVE

To investigate the roles of hemodynamic factors and oxygenation on the incidence of pressure ulcers in patients in the ICU on mechanical ventilation.

METHODS

This prospective analytical cross-sectional study was performed in several ICUs for a period of 8 months in Iran. Researchers checked patients for pressure ulcers on a daily basis. They collected demographic, hemodynamic, and oxygenation data until a pressure ulcer occurred, the patient’s artificial airway was removed, the patient died, or the patient was discharged.

RESULTS

From August 2017 to February 2018, a total of 2,581 patients were admitted to the study ICUs; of these, 133 patients were eligible for the study. The results indicated that 41.4% (n = 55) of the patients ended up with pressure ulcers. Investigation of the variables using a Cox regression model showed that, among other variables considered in this study, age, mean arterial pressure, and positive end-expiratory pressure in the mechanical ventilator can contribute to the risk of pressure ulcers.

CONCLUSIONS

Providers should pay attention to changes in hemodynamic parameters, especially mean arterial pressure; carefully determine the most appropriate positive end-expiratory pressure for patients connected to mechanical ventilation; and take special care of susceptible groups such as older adults and hospitalized patients to decrease the incidence of pressure ulcers.
Cognitive Behavioral Therapy for Prenatal Insomnia
Authors: Manber Rachel , Bei Bei , Simpson Norah , Asarnow Lauren , Rangel Elizabeth , Sit Anita , Lyell Deirdre
Published: April 2019

OBJECTIVE:

To evaluate the effectiveness of cognitive behavioral therapy for insomnia during pregnancy.

METHODS:

Randomized, unmasked, 3-site controlled trial. Participants were randomly allocated to cognitive behavioral therapy for insomnia (a first-line, empirically supported psychosocial intervention that addresses sleep-related behaviors and cognitions) or a control intervention consisting of imagery exercises that paired patient-identified distressing nighttime experiences with patient-identified neutral images. Participants were eligible if they met diagnostic criteria for insomnia disorder and were between 18 and 32 weeks of gestation. Patients were ineligible if they met diagnostic criteria for major psychiatric disorders, including depression, or were receiving nonstudy treatments that could affect sleep (or both). The primary outcome was the Insomnia Severity Index score, a validated brief questionnaire, with scores between 14 and 21 representing clinically meaningful insomnia of moderate severity, scores higher than 21 representing severe insomnia, and scores less than 8 representing no insomnia. Secondary outcomes included remission of insomnia (Insomnia Severity Index score less than 8), objectively measured and self-reported time awake (ie, total wake time), and the Edinburgh Postnatal Depression Scale score. All outcomes were measured weekly. Analysis included 48 participants who did not complete treatment. We estimated that 184 women would be required to have 80% power, with a two-tailed test, to detect a moderate Cohen's d effect size (.5) with α=.05.

RESULTS:

Between May 2013 and April 2017, 194 pregnant women were randomized and 149 completed treatment; 179 with available baseline data (92%) were ultimately analyzed, 89 in the cognitive therapy group and 90 in the control group. Women assigned to cognitive behavioral therapy for insomnia experienced significantly greater reductions in insomnia severity (scores decreased from 15.4±4.3 to 8.0±5.2 in the cognitive behavioral therapy group vs from 15.9±4.4 to 11.2±4.9 in the control therapy group [P<.001, d=0.5]). Remission of insomnia (to an Insomnia Severity Index score less than 8) disorder was attained by 64% of women in the cognitive behavioral therapy for insomnia group vs 52% in the control group. Women receiving cognitive behavioral therapy for insomnia experienced faster remission of insomnia disorder, with a median of 31 days vs 48 days in the control therapy (P<.001). Cognitive behavioral therapy for insomnia led to significantly greater reduction in self-reported but not objective total wake time and a small but significantly greater decline in Edinburgh Postnatal Depression Scale scores vs the control group.

CONCLUSION:

Cognitive behavioral therapy for insomnia is an effective nonpharmacologic treatment for insomnia during pregnancy.

CLINICAL TRIAL REGISTRATION:

ClinicalTrials.gov, NCT01846585.
Use of Active Learning and Sequencing in a Weekly Continuing Medical Education/Graduate Medical Education Conference
Authors: Austin Jared P. , Carney Patricia A. , Thayer Erin K. , Rozansky David J.
Published: April 2019

Introduction:

Active learning and sequencing have been described as effective techniques for improving educational conferences. However, few departmental continuing medical education/graduate medical education (CME/GME) conferences, such as Grand Rounds (GR), have adopted these techniques. The purpose of this study was to describe the development, implementation, and evaluation of Friday Forum (FF), a weekly CME/GME conference that incorporated active learning and sequencing techniques into a new educational offering, complementary to GR, within a medium-sized academic pediatrics department.

Methods:

Implemented in 2013, FF was designed to address 5 medically relevant themes in a sequential, rotating, interactive format, and included: (1) clinical reasoning, (2) evidence-based medicine, (3) morbidity & mortality, (4) research in progress, and (5) ethics. In 2018, at the conclusion of its fifth year, a survey and focus groups of faculty, residents, and fellows explored the relative value of FF compared with the departmental GR.

Results:

Survey response rates for residents/fellows and faculty were 37/76 (48.7%) and 57/112 (50.9%), respectively. FF was rated highly for helping participants develop rapport with colleagues, exposing participants to interactive strategies for large-group teaching and value for time spent. GR was rated highly for helping participants learn about academic endeavors outside the department and emerging challenges in pediatrics. Qualitatively, two key themes emerged for FF: desire for interaction (community building) and topical variety.

Discussion:

Using active learning and sequencing techniques, we implemented a novel CME/GME conference that enhanced our learning community by integrating the education of faculty and trainees, and achieved complementary objectives to GR.
Effects of 90Sr on Tree Swallow Nestlings Near Groundwater Contaminant Plumes
Authors: Lee David R. , Haughton Jennifer , Valente Andrew , Bellan Lee , Stuart Marilyne , Beaton Danielle , Chen Hui Qun , Gosselin Isabelle , Festarini Amy
Published: April 2019

Discharge of groundwater contaminant plumes has created elevated concentrations of 90Sr in some aquatic sediments at Chalk River Laboratories. Tree swallows (Tachycenita bicolor) feed and supply their nestlings almost exclusively with airborne insects that developed as larvae in aquatic sediments. To monitor the uptake and test for potential detriment due to 90Sr in a terrestrial animal, we measured the gross beta concentrations in the bone of 12-d-old tree swallow nestlings in areas having sediments with elevated levels of gross beta (90Sr and 90Y) and in several control areas where sediment gross beta was primarily due to naturally occurring 40K. Nesting behavior and reproductive success of the tree swallows were similar regardless of the gross beta concentrations in sediments near their nest boxes. Radiation can damage DNA and cause micronuclei to form in cells, so we examined the frequency of micronuclei in erythrocytes of nestlings. The formation of micronuclei in the erythrocytes of the nestlings was also similar wherever nestlings were analyzed. The results revealed no significant increases even near sediments with the highest gross beta levels. At Perch Lake, where Chalk River Laboratories has a large area of 90Sr-contaminated sediments, the bones of 12-d-old nestlings contained gross beta concentrations as high as 29 Bq g−1. This would produce a skeletal dose rate of 9 μGy h−1, which is one-fourth of the threshold dose rate of 40 μGy h−1, above which detriment could occur. Failing to find any indication of detriment in the field study, we irradiated wild eggs in the lab and returned them to their nest for natural incubation, hatching, and feeding by the parents. There was an increase in formation of micronuclei following a dose of 3.2 Gy, and the other results were consistent with existing literature.
EARLY VITAMIN A SUPPLEMENTATION IMPROVES THE OUTCOME OF RETINOPATHY OF PREMATURITY IN EXTREMELY PRETERM INFANTS
Authors: Sun Huiqing , Cheng Rui , Wang Zhansheng
Published: April 2019

Purpose:

This study assessed the efficacy and safety of early vitamin A (VA) supplementation to improve outcomes of retinopathy of prematurity in extremely preterm infants.

Methods:

A total of 262 eligible extremely preterm infants underwent randomization; of these, 132 were assigned to the VA group and 130 to the control group. The infants were administered a solution of VA (1,500 IU/day), added to their enteral feeds as soon as minimal feeding was introduced and continued for 28 days or until discharge.

Results:

With no adverse effects occurring, serum VA of the VA-supplemented infants on Days 14, 28, and postmenstrual 36 weeks was higher than that of the placebo group (P < 0.001). No signs of VA toxicity or increased intracranial pressure were reported. The VA group had lower unadjusted rates of Type 1 retinopathy of prematurity (1.6 vs. 6.9%, P = 0.030) and bronchopulmonary dysplasia (18.9 vs. 33.8%, P = 0.008) than the control group. Regression analysis revealed an association between serum VA levels and risk of Type 1 retinopathy of prematurity (beta = −2.37).

Conclusion:

Vitamin A supplementation reduced VA deficiency in extremely preterm infants; it was associated with a decreased incidence of Type 1 retinopathy of prematurity and may also have a positive impact on reducing bronchopulmonary dysplasia.
Bilateral Orbital Compartment Syndrome Preceding Cerebellar Herniation in Neuropsychiatric Systemic Lupus Erythematosus
Authors: Hamill Eric B. , Weber Adam C. , Patel Kalyani R. , Yen Michael T.
Published: April 2019

Orbital compartment syndrome poses a significant risk for vision loss if not promptly treated. The authors report a patient with neuropsychiatric systemic lupus erythematosus presenting with bilateral orbital compartment syndrome and rapid decompensation leading to uncal and tonsillar herniation. While extremely rare, bilateral orbital compartment syndrome should prompt consideration of systemic etiologies including neuropsychiatric systemic lupus erythematosus.
Development of a Question Prompt List for Patients Living With HIV and Assessment of Their Information Needs
Authors: Kim Gwang Suk , Choi Jae-Phil , Yi Jeong Min , Shim Mi-So
Published: April 2019

A question prompt list (QPL) is an efficient method to facilitate patient active participation and communication by providing patients with questions to ask their health care providers. We developed a QPL based on the information needs of patients living with HIV in Korea. A mixed method study design was used, involving five sequential steps: literature review, focus group interview with experienced nurses, in-depth interviews with patients, expert reviews, and a survey of 170 patients. A QPL with 27 questions was developed through literature reviews and expert reviews, and 12 questions were identified based on the Borich needs assessment model. Questions included items regarding diagnosis and prognosis, medication, depressive symptoms, sexual relationships, and family and social life. Our findings suggest that a QPL should be used as a tool to encourage effective communication for patients living with HIV.
Heads Up Football Training Decreases Concussion Rates in High School Football Players
Authors: Shanley Ellen , Thigpen Charles , Kissenberth Michael , Gilliland Robert Gil , Thorpe John , Nance Darryl , Register-Mihalik Johna K. , Tokish John
Published: April 2019

Objective:

The objective of this study was to determine whether football players receiving heads up (HU) training would display a lower rate of sport-related concussion (SRC) compared to those without HU training.

Design:

Prospective cohort.

Setting:

Scholastic football fields.

Patients:

Two thousand five hundred fourteen scholastic football players during the 2015 to 2016 football season were monitored throughout the football season.

Interventions:

Before the preseason, 1 coach from 14 schools received HU training from US football. These schools were matched with 10 control schools performing standard football training [non–heads up (NHU)]. Random monitoring for proper coaching instruction was performed during the season. School athletic trainers monitored injuries and return to sport over the season for all schools.

Main Outcome Measures:

The outcome measures of concussions and associated time loss were determined before data collection began. Injury incidence and rate ratios were calculated to determine program effectiveness.

Results:

During the season, football players sustained 117 concussions (HU = 75; NHU = 42). The HU players displayed a significantly lower concussion rate (4.1 vs 6.0/100 players) compared with NHU teams [rate ratio = 1.5; 95% confidence interval (CI), 1.1-5.4]. The HU group returned to full participation 27% faster than athletes in the NHU group [time loss: 18.2 days (95% CI, 15.8-20.6) vs 24.8 days (95% CI, 19.9-29.7)], respectively.

Conclusions:

This is the first study to evaluate the impact of the HU program on the incidence of SRC in high school football players. Our data demonstrated that the HU program reduced SRC rates by 33% supporting the use of US HU football training as an effective method to decrease the rate of SRCs in scholastic football.

Clinical Relevance:

This study is the first to prospectively explore the effect of HU training on the incidence and recovery from SRC in high school football players.
Androgens and depression: a review and update
Authors: Nead Kevin T.
Published: April 2019

Purpose of review

The aim of this study is to summarize recently published literature examining androgens and depression.

Recent findings

The impact of androgen levels, androgen replacement therapy and pharmacologic androgen deprivation on depression and depressive symptoms remain active areas of investigation. Recent publications support the finding that testosterone replacement therapy in men with low testosterone may improve depression, and that androgen deprivation therapy in men with prostate cancer may contribute to depression.

We review the recent literature on androgens and depression and highlight key developments.
The Rise and Fall of the Diagnosis of Psychoneurosis of Childhood
Authors: Hirshbein Laura D.
Published: April 2019

American child and adolescent psychiatry was dominated in most of its first century by a psychoanalytic framework. Child psychiatrists, as well as their treatment team partners in social work and psychology, assumed that children developed mood and behavior problems based on unconscious conflicts, which were driven by difficulties in early childhood experiences within their families. Treatment depended on a painstaking untangling of the strands of the conflict in each individual child. Diagnosis per se was not initially a goal for child mental health providers. Instead, a broad concept of psychoneurosis was central to emphasize the depth and complexity of childhood psychiatric problems. Psychoneurosis did not translate into the 1980 nosology of the American Psychiatric Association (Diagnostic and Statistical Manual of Mental Disorders, 3rd Edition [DSM-III]), however, and mostly disappeared from child psychiatry by the 1990s. The loss of the developmental, individual, and contextual perspective embedded in psychoneurosis (and other childhood disorders) has been a loss because the widespread use of the DSM symptom criteria has unintended consequences when applied to children.
Most of the variation in length of stay in emergency general surgery is not related to clinical factors of patient care
Authors: Achanta Aditya , Nordestgaard Ask , Kongkaewpaisan Napaporn , Han Kelsey , Mendoza April , Saillant Noelle , Rosenthal Martin , Fagenholz Peter , Velmahos George , Kaafarani Haytham M.A.
Published: April 2019

BACKGROUND

Hospital length of stay (LOS) is currently recognized as a key quality indicator. We sought to investigate how much of the LOS variation in the high-risk group of patients undergoing Emergency general surgery could be explained by clinical versus nonclinical factors.

METHODS

Using the 2007 to 2015 American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database, we included all patients who underwent an emergency appendectomy, cholecystectomy, colectomy, small intestine resection, enterolysis, or hernia repair. American College of Surgeons National Surgical Quality Improvement Program defines emergency surgery as one that is performed no later than 12 hours after admission or symptom onset. Using all the ACS-NSQIP demographic, preoperative (comorbidities, laboratory variables), intraoperative (e.g., duration of surgery, wound classification), and postoperative variables (i.e., complications), we created multivariable linear regression models to predict LOS. LOS was treated as a continuous variable, and the degree to which the models could explain the variation in LOS for each type of surgery was measured using the coefficient of determination (R
2).

RESULTS

A total of 215,724 patients were included. The mean age was 47.1 years; 52.0% were female. In summary, the median LOS ranged between 1 day for appendectomies (n = 124, 426) and cholecystectomies (n = 21,699) and 8 days for colectomies (n = 19,557) and small intestine resections (n = 7,782). The R
2 for all clinical factors ranged between 0.28 for cholecystectomy and 0.44 for hernia repair, suggesting that 56% to 72% of the LOS variation for each of the six procedures studied cannot be explained by the wide range of clinical factors included in ACS-NSQIP.

CONCLUSION

Most of the LOS variation is not explained by clinical factors and may be explained by nonclinical factors (e.g., logistical delays, insurance type). Further studies should evaluate these nonclinical factors to identify target areas for quality improvement.

LEVELS OF EVIDENCE

Epidemiological study, level III.
Identifying risk factors involved in the common versus specific liabilities to substance abuse: A genetically informed approach
Authors: Iob Eleonora , Schoeler Tabea , Cecil Charlotte M. , Walton Esther , McQuillin Andrew , Pingault Jean-Baptiste
Published: April 2019

The co-occurrence of abuse of multiple substances is thought to stem from a common liability that is partly genetic in origin. Genetic risk may indirectly contribute to a common liability through genetically influenced individual vulnerabilities and traits. To disentangle the aetiology of common versus specific liabilities to substance abuse, polygenic scores can be used as genetic proxies indexing such risk and protective individual vulnerabilities or traits. In this study, we used genomic data from a UK birth cohort study (ALSPAC, N=4218) to generate 18 polygenic scores indexing mental health vulnerabilities, personality traits, cognition, physical traits, and substance abuse. Common and substance-specific factors were identified based on four classes of substance abuse (alcohol, cigarettes, cannabis, other illicit substances) assessed over time (age 17, 20, and 22). In multivariable regressions, we then tested the independent contribution of selected polygenic scores to the common and substance-specific factors. Our findings implicated several genetically influenced traits and vulnerabilities in the common liability to substance abuse, most notably risk taking (bstandardized=0.14; 95%CI: 0.10,0.17), followed by extraversion (bstandardized =-0.10; 95%CI: −0.13,-0.06), and schizophrenia risk (bstandardized=0.06; 95%CI: 0.02;0.09). Educational attainment (EA) and body mass index (BMI) had opposite effects on substance-specific liabilities such as cigarettes (bstandardized-EA= −0.15; 95%CI: −0.19,-0.12; bstandardized-BMI=0.05; 95%CI: 0.02,0.09), alcohol (bstandardized-EA=0.07; 95%CI: 0.03,0.11; bstandardized-BMI= −0.06; 95%CI: −0.10, −0.02), and other illicit substances (bstandardized-EA=0.12; 95%CI: 0.07,0.17; bstandardized-BMI= −0.08; 95%CI:-0.13,-0.04). This is the first study based on genomic data that clarifies the aetiological architecture underlying the common versus substance-specific liabilities, providing novel insights for the prevention and treatment of substance abuse.
Discovery of UFO Proteins: Human-Virus Chimeric Proteins Generated During Influenza Virus Infection
Authors: Ma Yixuan , Angel Matthew , Wang Guojun , Ho Jessica Sook Yuin , Zhao Nan , Noel Justine , Moshkina Natasha , Gibbs James , Wei Jiajie , Rosenberg Brad , Johnson Jeffrey , Chang Max , Peralta Zuleyma , Krogan Nevan , Benner Christopher , van Bakel Harm , Łuksza Marta , Greenbaum Benjamin D. , Miraldi Emily R. , Garcìa-Sastre Adolfo , Yewdell Jonathan W. , Marazzi Ivan
Published: April 2019

Influenza A virus (IAV) is a threat to mankind because it generates yearly epidemics and poorly predictable sporadic pandemics with catastrophic potential. IAV has a small RNA genome composed of 8 mini-chromosomes (segments) that constitute a 5’UTR followed by a coding region and a 3’UTR. Transcription of IAV RNA into mRNA depends on host mRNA, as the viral polymerase cleaves 5’m7G-capped nascent transcripts to use as primers to initiate viral mRNA synthesis. We hypothesized that captured host transcripts bearing AUG could drive the expression of upstream ORFs in the viral segments, a phenomenon that would depend on the translatability of the viral 5’UTRs. Here we report the existence of this mechanism, which generates host-virus chimeric proteins. We label these proteins asUpstreamFluORFs (UFO). Depending on the frame, two types of host-virus UFO proteins are made: canonical viral proteins with human-derived N term extensions or novel uncharacterized proteins. Here we show that both types are made during IAV infection. Sequences that enable chimeric protein synthesis are conserved across IAV strains, indicating that selection allowed the expansion of the proteome diversity of IAV in infected cells to include multiple human-virus proteins.
Murine cytomegalovirus infection of melanoma lesions delays tumor growth by recruiting and re-polarizing monocytic phagocytes in the tumor
Authors: Wilski Nicole A , Del Casale Christina , Purwin Timothy J , Aplin Andrew E , Snyder Christopher M
Published: April 2019

Cytomegalovirus (CMV) is a ubiquitous β-herpesvirus that infects many different cell types. CMV has been found in several solid tumors and it has been hypothesized that it may promote cellular transformation or exacerbate tumor growth. Paradoxically, in some experimental situations, CMV infection delays tumor growth. We previously showed that wild-type murine (M)CMV delayed the growth of poorly immunogenic B16 melanomas via an undefined mechanism. Here we show that MCMV delayed the growth of these immunologically “cold” tumors by recruiting and modulating tumor-associated macrophages. Depletion of monocytic phagocytes with clodronate completely prevented MCMV from delaying tumor growth. Mechanistically, our data suggest that MCMV recruits new macrophages to the tumor via the virus-encoded chemokine MCK2, and viruses lacking this chemokine were unable to delay tumor growth. Moreover, MCMV infection of macrophages drove them toward an M1-like state. Importantly, adaptive immune responses were also necessary for MCMV to delay tumor growth as the effect was substantially blunted in Rag-deficient animals. However, viral spread was not needed and a spread-defective MCMV strain was equally effective. In most mice, the anti-tumor effect of MCMV was transient. Although the recruited macrophages persisted, tumor regrowth correlated with a loss of viral activity in the tumor. However, an additional round of MCMV infection further delayed tumor growth, suggesting that tumor growth delay was dependent on active viral infection. Together, our results suggest that MCMV infection delayed the growth of an immunologically “cold” tumor by recruiting and modulating macrophages in order to promote anti-tumor immune responses.

Importance

Cytomegalovirus (CMV) is an exciting new platform for vaccines and cancer therapy. Although CMV may delay tumor growth in some settings, there is also evidence that CMV may promote cancer development and progression. Thus, defining the impact of CMV on tumors is critical. Using a mouse model of melanoma, we previously found that murine (M)CMV delayed tumor growth and activated tumor-specific immunity, although the mechanism was unclear. We now show that MCMV delayed tumor growth not by infecting and killing tumor cells, but rather by recruiting macrophages to the tumor. A viral chemokine was necessary to recruit macrophages and delay tumor growth. Furthermore, MCMV infection altered the functional state of the macrophages. Finally, we found that repeated MCMV injections sustained the anti-tumor effect suggesting that active viral infection was needed. Thus, MCMV altered tumor growth by actively recruiting and infecting macrophages in the tumor.
Resting state cerebral networks in mouse lemur primates: from multilevel validation to comparison with humans
Authors: Garin Clément M. , Nadkarni Nachiket A. , Landeau Brigitte , Chételat Gaël , Picq Jean-Luc , Bougacha Salma , Dhenain Marc
Published: April 2019

Measures of resting-state functional connectivity allow the description of neuronal networks in humans and provide a window on brain function in normal and pathological conditions. Animal models are critical to further address experimentally the function of brain networks and their roles in pathologies. Here we describe for the first time brain network organization in the mouse lemur (Microcebus murinus), a small primate attracting increased attention as a model for neuroscience. Resting-state functional MR images were recorded at 11.7 Tesla. Forty-eight functional regions were identified and used to identify networks using graph theory, dictionary learning and seed-based analyses. Comparison of results issued from these three complementary methods allowed the description of the most robust networks from mouse lemurs. Large scale networks were then identified from resting-state functional MR images of humans using the same method as for lemurs. Strong homologies were outlined between cerebral networks in mouse lemurs and humans.