bluuebunny/crossref_metadata_2025 huggingface dataset:
Sibling competition in Blue Tits (Cyanistes caeruleus) is stronger in homozygous broods
Authors: Morales Judith , Acevedo Iván , Machordom Annie
Published: June 2019

Heterozygosity affects mate selection and can modulate interactions among family members and their fitness-related decisions. We studied whether nestling heterozygosity affected parent–offspring interactions and sib–sib competition in the Blue Tit (Cyanistes caeruleus) while controlling for the degree of relatedness among nestlings. Demanding environmental conditions might make the detection of heterozygosity-fitness correlations easier. Thus, we also investigated whether the decision rules of family members according to offspring heterozygosity were affected by brood size, as a proxy of the strength of sibling conflict. We found that chick individual heterozygosity was positively although weakly associated with individual body mass. Mean brood heterozygosity did not predict fledging success, but broods that fledged more chicks showed a higher number of less common alleles. Interestingly, fathers, but not mothers, favored heterozygous broods with many nestlings, that is, heterozygous broods with higher potential for sibling conflict. Moreover, the lower the mean brood heterozygosity the stronger the begging intensity when parents were absent, regardless of brood size. Finally, the degree of relatedness among nestlings was not associated with any behavioral parameter, supporting a more prominent role for heterozygosity in shaping intra-family interactions. Our findings suggest that offspring heterozygosity determines sex-specific rules of parental care and that genetic diversity is associated with lower sibling competition.
The influence of strain on the Verwey transition as a function of dopant concentration: towards a geobarometer for magnetite-bearing rocks
Authors: Biało Izabela , Kozłowski Andrzej , Wack Michael , Włodek Adam , Gondek Łukasz , Kąkol Zbigniew , Hochleitner Rupert , Żywczak Antoni , Chlan Vojtech , Gilder Stuart A
Published: June 2019

Magnetite is an abundant magnetic mineral that commonly records the ancient magnetic field in a wide variety of rock types. When cooled below ≈124 K, magnetite undergoes a phase transition, called the Verwey transition, whose characteristics are highly sensitive to grain size and stoichiometry. Studying the Verwey transition thus yields information on the formation conditions and compositions of rocks. The transition is also stress sensitive, thereby opening an avenue to understanding a rock’s strain history; however, the reason for the stress sensitivity is poorly understood. In particular, the temperature of the transition decreases when measured under pressure, yet mostly increases upon pressure release. Moreover, the stress sensitivity of the transition as a function of dopant concentration, especially after pressure cycling, was never systematically tested. We addressed these issues in order to further develop magnetite as a pressure gauge. Multidomain magnetite samples were pressure cycled up to maximum pressures of ∼5 GPa at room temperature to measure the influence of strain on the Verwey transition temperature as a function of dopant concentration after full decompression. The transition temperature measured via changes in magnetic remanence ($T_{\rm V}^{M}$) systematically increased with respect to pressure (P) in more doped samples, where domain wall pinning from impurities dominates $\mathrm{d}T_{\rm V} ^{\rm M}/\mathrm{d}P$. In less doped samples, no to only moderate pressure cycling dependence on $T_{\rm V}^{\rm M}$ was observed. Bulk coercive force (Bc) and magnetic remanence after saturation (Mrs) measured above or below the transition also increased with respect to pressure, but here effects related to permanent strain of the lattice structure prevail, and Bc versus P is steeper for less doped samples. Bc versus P increases in all cases, with a difference in slope dictated by dopant concentrations segregating the first to second-order nature of the transition. Thus, strain developed during pressure cycling controls $T_{\rm V}^{\rm M}$ and coercivity by a mechanism based on pinning of magnetic domains by both interstitial cations and structural lattice distortions. The combined observables, $T_{\rm V}^{\rm M}$ and Bc−Mrs, reflect both the dopant level and strain state of magnetite, which can quantify the pressure multidomain magnetite has experienced, especially in the range between 1 and 5 GPa. Based on these new results, we present a model that distinguishes between electronic versus defect-driven processes explaining the strain-related influences on the transition. Magnetite’s use as a geobarometer is thus a measure of its defect state, which is expressed through two somewhat independent mechanisms when sensed by magnetic observations.
The fruit fly at the interface of diagnosis and pathogenic mechanisms of rare and common human diseases
Authors: Bellen Hugo J , Wangler Michael F , Yamamoto Shinya
Published: June 2019

Drosophila melanogaster is a unique, powerful genetic model organism for studying a broad range of biological questions. Human studies that probe the genetic causes of rare and undiagnosed diseases using massive-parallel sequencing often require complementary gene function studies to determine if and how rare variants affect gene function. These studies also provide inroads to disease mechanisms and therapeutic targets. In this review we discuss strategies for functional studies of rare human variants in Drosophila. We focus on our experience in establishing a Drosophila core of the Model Organisms Screening Center for the Undiagnosed Diseases Network (UDN) and concurrent fly studies with other large genomic rare disease research efforts such as the Centers for Mendelian Genomics. We outline four major strategies that use the latest technology in fly genetics to understand the impact of human variants on gene function. We also mention general concepts in probing disease mechanisms, therapeutics and using rare disease to understand common diseases. Drosophila is and will continue to be a fundamental genetic model to identify new disease-causing variants, pathogenic mechanisms and drugs that will impact medicine.
Bacterial metabolism-inspired molecules to modulate antibiotic efficacy
Authors: Liu Yuan , Li Ruichao , Xiao Xia , Wang Zhiqiang
Published: June 2019

The decreasing antibiotic susceptibility of bacterial pathogens calls for novel antimicrobial therapies. Traditional screening pathways based on drug–target interaction have gradually reached the stage of diminishing returns. Thus, novel strategies are urgently needed in the fight against antibiotic-refractory bacteria, particularly for tolerant bacteria. Recently, evidence has accumulated demonstrating that microbial changes caused by bacterial metabolic processes significantly modulate antibiotic killing. A better understanding of these bacterial metabolic processes is indicating a need to screen novel metabolic modulators as potential antibiotic adjuvants. In this review, we describe the state of our current knowledge about how these bacterial metabolism-inspired molecules affect antibiotic efficacy, including potentiation and inhibition activity. In addition, the challenges faced and prospects for bringing them into clinic are also discussed. These examples may provide candidates or targets for the development of novel antibiotic adjuvants.
Clause tableaux for maximum and minimum satisfiability
Authors: Argelich Josep , Li Chu Min , Manyà Felip , Soler Joan Ramon
Published: June 2019

The inference systems proposed for solving SAT are unsound for solving MaxSAT and MinSAT, because they preserve satisfiability but not the minimum and maximum number of clauses that can be falsified, respectively. To address this problem, we first define a clause tableau calculus for MaxSAT and prove its soundness and completeness. We then define a clause tableau calculus for MinSAT and also prove its soundness and completeness. Finally, we define a complete clause tableau calculus for solving both MaxSAT and MinSAT, in that the minimum number of generated empty clauses provides an optimal MaxSAT solution and the maximum number provides an optimal MinSAT solution.
Assessing the legal duty to use or disclose interim data for ongoing clinical trials
Authors: Eckstein Lisa
Published: June 2019

Randomized controlled clinical trials, leading to large-scale meta-analyses, are considered the gold standard for research evaluating new drugs and other therapeutic interventions. To promote scientific integrity and prevent the adoption of potentially fallacious early trends, emerging information is commonly shielded from sponsors, investigators, and other clinical trial actors, including through the use of independent Data and Safety Monitoring Boards (DSMBs). Once established, a DSMB is usually the only body to have access to unblinded information until trial completion or the crossing of pre-specified, and often highly stringent, stopping boundaries. Yet, in certain circumstances, clinical trial actors have legal obligations to trial participants and others to use or disclose emerging information.

This paper canvasses potential legal obligations to use or disclose emerging clinical trial data, including through tort law and securities laws. The analysis is supplemented by a comprehensive search of US cases in which courts have adjudicated upon such allegations. Notably, available cases demonstrate widespread judicial deference to clinical trial practices designed to shield clinical trial actors from emerging information. As a result, despite a theoretical possibility of legal obligations of use or disclosure, it appears that these will rarely be enforceable.
Protein S-acyl transferase 15 is involved in seed triacylglycerol catabolism during early seedling growth in Arabidopsis
Authors: Li Yaxiao , Xu Jianfeng , Li Gang , Wan Si , Batistič Oliver , Sun Meihong , Zhang Yuxing , Scott Rod , Qi Baoxiu
Published: June 2019

Protein S-acyl transferase 15 is involved in β-oxidation of seed-storage triacylglycerol in Arabidopsis, which is required to provide sugars for normal post-germination growth of seedlings.
On the satisfiability problem for fragments of two-variable logic with one transitive relation
Authors: Szwast Wiesław , Tendera Lidia
Published: June 2019

We study the satisfiability problem for two-variable first-order logic over structures with one transitive relation. We show that the problem is decidable in 2-NExpTime for the fragment consisting of formulas where existential quantifiers are guarded by transitive atoms. As this fragment enjoys neither the finite model property nor the tree model property, to show decidability we introduce a novel model construction technique based on the infinite Ramsey theorem.

We also point out why the technique is not sufficient to obtain decidability for the full two-variable logic with one transitive relation; hence, contrary to our previous claim, [FO$^2$ with one transitive relation is decidable, STACS 2013: 317-328], the status of the latter problem remains open.
PAS stain based histological classification and severity grading of toenail onychomycosis
Authors: Hao Xingpei , Yim Joon , Freedman David , Siddiqui Sarwat , Levine David , Tritto Michael , Saffo Gina M , Isaac Adam , Mirkin Gene
Published: June 2019

Onychomycosis is a common world-wide health issue. Accurate detection is essential for treatment. Multiple studies have shown that PAS-stain based histological visualization of fungal elements is superior to either direct microscopy with 20% potassium hydroxide, or fungal culture. However, PAS stain based histological classification and severity grading of onychomycosis are lacking in the literature. Here we reported a fungal detection rate of 47.87% based on an analysis of 13,805 toenails processed for H&E and PAS stains over a three year period. Based on the analysis of fungal density, distribution and infiltrating depth level in 858 PAS-positive toenails, we created a novel PAS stain based histological classification system to classify onychomycosis as occult onychomycosis (OO), focal or diffuse subungual onychomycosis (FSO or DSO), focal or diffuse plate onychomycosis (FPO or DPO), focal or diffuse subungual and plate onychomycosis (FSPO or DSPO) and superficial onychomycosis (SO). The severities of OO, FSO and FPO were graded as mild, DSO and DPO as moderate, FSPO and DSPO as severe infections, which revealed that more than 75% PAS positive toenails were severe infections. Evaluation of 97 paired toenails biopsied pre- and post-treatment from 47 patients demonstrated that the severity of infection was significantly reduced from severe to mild and moderate levels. These data indicate that the current histological classification evaluates not only the severity of the fungal infection but also the response to treatment. We further propose a guideline for treatment of onychomycosis based on the histological classification and severity.
Testing the weak equivalence principle by differential measurements of fundamental constants in the Magellanic Clouds
Authors: Levshakov S A , Ng K-W , Henkel C , Mookerjea B , Agafonova I I , Liu S-Y , Wang W-H
Published: June 2019

Non-standard fields are assumed to be responsible for phenomena attributed to dark energy and dark matter. Being coupled to ordinary matter, these fields modify the masses and/or charges of the elementary particles, thereby violating the weak equivalence principle. Thus, values of fundamental constants such as the proton-to-electron mass ratio, μ, and/or the fine structure constant, α, measured in different environment conditions can be used as probes for this coupling. Here we perform differential measurements of F = μα2 to test a non-standard coupling in the Magellanic Clouds–dwarf galaxies where the overall mass budget is dominated by dark matter. The analysis is based on [C i] and CO lines observed with the Herschel Space Observatory. Since these lines have different sensitivities to changes in μ and α, the combined α and μ variations can be evaluated through the radial velocity offsets, ΔV, between the CO and [C i] lines. Averaging over nine positions in the Magellanic Clouds, we obtain 〈ΔV〉 = −0.02 ± 0.07 km s−1, leading to |ΔF/F| < 2 × 10−7 (1σ), where ΔF/F = (Fobs − Flab)/Flab. However, for one position observed with five times higher spectral resolution we find ΔV = −0.05 ± 0.02 km s−1, resulting in ΔF/F = (−1.7 ± 0.7) × 10−7. Whether this offset is due to changes in the fundamental constants, due to chemical segregation in the emitting gas, or merely due to Doppler noise requires further investigations.
Fast-rising blue optical transients and AT2018cow following electron-capture collapse of merged white dwarfs
Authors: Lyutikov Maxim , Toonen Silvia
Published: June 2019

We suggest that fast-rising blue optical transients (FBOTs) and the brightest event of the class, AT2018cow, result from an electron-capture collapse to a neutron star following the merger of a massive ONeMg white dwarf (WD) with another WD. Two distinct evolutionary channels lead to the disruption of the less-massive WD during the merger and the formation of a shell-burning non-degenerate star incorporating the ONeMg core. During the shell-burning stage, a large fraction of the envelope is lost to the wind, while mass and angular momentum are added to the core. As a result, the electron-capture collapse occurs with a small envelope mass, after ∼102–104 yr. During the formation of a neutron star, as little as ${\sim } 10^{-2} \, \mathrm{M}_\odot$ of the material is ejected at the bounce-off with mildly relativistic velocities and total energy of about a few 1050 erg. This ejecta becomes optically thin on a time-scale of days – this is the FBOT. During the collapse, the neutron star is spun up and the magnetic field is amplified. The ensuing fast magnetically dominated relativistic wind from the newly formed neutron star shocks against the ejecta, and later against the wind. The radiation-dominated forward shock produces the long-lasting optical afterglow, while the termination shock of the relativistic wind produces the high-energy emission in a manner similar to pulsar wind nebulae. If the secondary WD was of the DA type, the wind will likely have ${\sim } 10^{-4} \, \mathrm{M}_\odot$ of hydrogen; this explains the appearance of hydrogen late in the afterglow spectrum. The model explains many of the puzzling properties of FBOTs/AT2018cow: host galaxies, a fast and light anisotropic ejecta producing a bright optical peak, afterglow high-energy emission of similar luminosity to the optical, and late infrared features.
Dust in and around galaxies: dust in cluster environments and its impact on gas cooling
Authors: Vogelsberger Mark , McKinnon Ryan , O’Neil Stephanie , Marinacci Federico , Torrey Paul , Kannan Rahul
Published: June 2019

Simulating the dust content of galaxies and their surrounding gas is challenging due to the wide range of physical processes affecting the dust evolution. Here we present cosmological hydrodynamical simulations of a cluster of galaxies, $M_\text{200,crit}=6 \times 10^{14}{\, \rm M_\odot }$, including a novel dust model for the moving mesh code arepo. This model includes dust production, growth, supernova-shock-driven destruction, ion-collision-driven thermal sputtering, and high-temperature dust cooling through far-infrared reradiation of collisionally deposited electron energies. Adopting a rather low thermal sputtering rate, we find, consistent with observations, a present-day overall dust-to-gas ratio of ∼2 × 10−5, a total dust mass of ${\sim } 2\times 10^9{\, \rm M_\odot }$, and a dust mass fraction of ∼3 × 10−6. The typical thermal sputtering time-scales within ${\sim } 100\, {\rm kpc}$ are around ${\sim } 10\, {\rm Myr}$, and increase towards the outer parts of the cluster to ${\sim } 10^3\, {\rm Myr}$ at a cluster-centric distance of $1\, {\rm Mpc}$. The condensation of gas-phase metals into dust grains reduces high-temperature metal-line cooling, but also leads to additional dust infrared cooling. The additional infrared cooling changes the overall cooling rate in the outer parts of the cluster, beyond ${\sim } 1\, {\rm Mpc}$, by factors of a few. This results in noticeable changes of the entropy, temperature, and density profiles of cluster gas once dust formation is included. The emitted dust infrared emission due to dust cooling is consistent with observational constraints.
Structural insights into dimethylation of 12S rRNA by TFB1M: indispensable role in translation of mitochondrial genes and mitochondrial function
Authors: Liu Xiaodan , Shen Shengqi , Wu Pengzhi , Li Fudong , Liu Xing , Wang Chongyuan , Gong Qingguo , Wu Jihui , Yao Xuebiao , Zhang Huafeng , Shi Yunyu
Published: June 2019

Mitochondria are essential molecular machinery for the maintenance of cellular energy supply by the oxidative phosphorylation system (OXPHOS). Mitochondrial transcription factor B1 (TFB1M) is a dimethyltransferase that maintains mitochondrial homeostasis by catalyzing dimethylation of two adjacent adenines located in helix45 (h45) of 12S rRNA. This m62A modification is indispensable for the assembly and maturation of human mitochondrial ribosomes. However, both the mechanism of TFB1M catalysis and the precise function of TFB1M in mitochondrial homeostasis are unknown. Here we report the crystal structures of a ternary complex of human (hs) TFB1M–h45–S-adenosyl-methionine and a binary complex hsTFB1M–h45. The structures revealed a distinct mode of hsTFB1M interaction with its rRNA substrate and with the initial enzymatic state involved in m62A modification. The suppression of hsTFB1M protein level or the overexpression of inactive hsTFB1M mutants resulted in decreased ATP production and reduced expression of components of the mitochondrial OXPHOS without affecting transcription of the corresponding genes and their localization to the mitochondria. Therefore, hsTFB1M regulated the translation of mitochondrial genes rather than their transcription via m62A modification in h45.
Automatic assessment of glioma burden: a deep learning algorithm for fully automated volumetric and bidimensional measurement
Authors: Chang Ken , Beers Andrew L , Bai Harrison X , Brown James M , Ly K Ina , Li Xuejun , Senders Joeky T , Kavouridis Vasileios K , Boaro Alessandro , Su Chang , Bi Wenya Linda , Rapalino Otto , Liao Weihua , Shen Qin , Zhou Hao , Xiao Bo , Wang Yinyan , Zhang Paul J , Pinho Marco C , Wen Patrick Y , Batchelor Tracy T , Boxerman Jerrold L , Arnaout Omar , Rosen Bruce R , Gerstner Elizabeth R , Yang Li , Huang Raymond Y , Kalpathy-Cramer Jayashree
Published: June 2019

Background

Longitudinal measurement of glioma burden with MRI is the basis for treatment response assessment. In this study, we developed a deep learning algorithm that automatically segments abnormal fluid attenuated inversion recovery (FLAIR) hyperintensity and contrast-enhancing tumor, quantitating tumor volumes as well as the product of maximum bidimensional diameters according to the Response Assessment in Neuro-Oncology (RANO) criteria (AutoRANO).

Methods

Two cohorts of patients were used for this study. One consisted of 843 preoperative MRIs from 843 patients with low- or high-grade gliomas from 4 institutions and the second consisted of 713 longitudinal postoperative MRI visits from 54 patients with newly diagnosed glioblastomas (each with 2 pretreatment “baseline” MRIs) from 1 institution.

Results

The automatically generated FLAIR hyperintensity volume, contrast-enhancing tumor volume, and AutoRANO were highly repeatable for the double-baseline visits, with an intraclass correlation coefficient (ICC) of 0.986, 0.991, and 0.977, respectively, on the cohort of postoperative GBM patients. Furthermore, there was high agreement between manually and automatically measured tumor volumes, with ICC values of 0.915, 0.924, and 0.965 for preoperative FLAIR hyperintensity, postoperative FLAIR hyperintensity, and postoperative contrast-enhancing tumor volumes, respectively. Lastly, the ICCs for comparing manually and automatically derived longitudinal changes in tumor burden were 0.917, 0.966, and 0.850 for FLAIR hyperintensity volume, contrast-enhancing tumor volume, and RANO measures, respectively.

Conclusions

Our automated algorithm demonstrates potential utility for evaluating tumor burden in complex posttreatment settings, although further validation in multicenter clinical trials will be needed prior to widespread implementation.
Transfusion-Transmitted Malaria: A Systematic Review and Meta-analysis
Authors: Ahmadpour Ehsan , Foroutan-Rad Masoud , Majidiani Hamidreza , Moghaddam Sirous Mehrani , Hatam-Nahavandi Kareem , Hosseini Seyed-Abdollah , Rahimi Mohammad Taghi , Barac Aleksandra , Rubino Salvatore , Zarean Mehdi , Mathioudakis Alexander G , Cevik Muge
Published: June 2019

Background

Malaria transmission through blood transfusion is an accidental but preventable cause of malaria infection and is increasingly becoming a matter of concern for blood transfusion services. This systematic review was conducted to provide a summary of evidence about the prevalence of Plasmodium infection in asymptomatic blood donors and the effectiveness of screening methods used based on the available literature.

Methods

PRISMA guidelines were followed. Scopus, PubMed, Science Direct, and EMBASE were searched from 1982 to October 10, 2017. All peer-reviewed original research articles describing the prevalence of malaria parasitemia in blood donors with different diagnostic methods were included. The random-effects model was applied to assess the effects of heterogeneity among the selected studies. Incoherence and heterogeneity between studies were quantified by I2 index and Cochran’s Q test. Publication and population bias was assessed with funnel plots and Egger’s regression asymmetry test. All statistical analyses were performed using Stata (version 2.7.2).

Results

Seventy-one studies from 21 countries, 5 continents, were included in the present systematic review. The median prevalence of malaria parasitemia among 984 975 asymptomatic healthy blood donors was 10.54%, 5.36%, and 0.38% by microscopy, molecular methods (polymerase chain reaction), and rapid diagnostic tests, respectively. The most commonly detected Plasmodium species was P. falciparum.

Conclusions

This systematic review demonstrates that compared with other transfusion-linked infections, that is, HIV, HCV, and HBV, transfusion-transmitted malaria is one of the most significant transfusion-associated infections especially in Sub-Saharan Africa. Future work must aim to understand the clinical significance of transfusion-transmitted malaria in malaria-endemic settings.
Term Limits: What is a Term?
Authors: Wilmot-Smith Frederick
Published: June 2019

Contracts are constituted by their terms. The concept of a term has not received any theoretical attention. I present an analysis arguing that there are important normative reasons to attend to the conceptual analysis: unsound ideologies can be rooted out and the debate on contractual interpretation can be put on a surer foundation.
Alternative organizing with social purpose: revisiting institutional analysis of market-based activity
Authors: Mair Johanna , Rathert Nikolas
Published: June 2019

Given rampant economic inequality, social exclusion and overconsumption, organizing in markets increasingly focuses on leveraging commercial activity for a social purpose. Alternative forms of organizing have developed to overcome the deficiencies of contemporary capitalism. They have become prevalent in numerous institutional contexts through types of organizations such as social enterprises, cooperatives and platform-based sharing economy organizations. Our objective is to ignite research on alternative organizing. We build on two important institutional perspectives, Neo-institutionalism and Comparative Capitalism, to investigate how these organizations diverge from the archetypal corporation. In addition, we develop a framework to guide institutional analysis of the origins, enabling conditions and consequences of alternative organizing in contemporary markets and society. We conclude by laying out pathways for future research.
‘The Annexed Photos were Taken Today’:1 Photographing Patients in the Late-Nineteenth-century Asylum
Authors: Rawling Katherine D B
Published: June 2019

Photographing patients was a common practice in many asylums in the nineteenth century. Asylum casebooks contain thousands of patient photographs varying in style and content, but they have been paid relatively little attention by historians of medicine. When patient photographs have been considered, one type of photograph has been taken to represent all patient photography. Through a comparison of casebook photographs from two very different institutions, this article argues that photographic practices were fluid, ambiguous and diverse in the nineteenth century, and the camera was used in a variety of ways inside the asylum. Examining the visual patient record can enhance and even challenge established histories of mental illness and medico-psychiatric practices, as we consider the photographing of patients as a stage in the doctor–patient encounter, an important part of diagnosis and resulting treatment, and as a feature of patient experience.
A Simple, Inexpensive Method for Using Unmanned Aerial Vehicle Photograph Analysis to Quantify Green Color and Enhance Ratings in Field Research Plots
Authors: Price Trey , Brown Sebe , Price Randy
Published: June 2019

Agricultural small-plot research is necessary to determine pesticide efficacy and develop integrated pest management programs for stakeholders. Many efficacy trials are rated visually using scales of foliage affected by a given pest. Human estimations introduce variability, and researchers continue explore methods of reducing variability in research trials. Recent developments in unmanned aerial vehicle technology allow novices to outfit inexpensive drones with inexpensive modified cameras to obtain aerial photographs that can be analyzed with any number of free image manipulation programs. Measuring reflected color from photographs provides data with lower variability that can be correlated with foliar disease ratings.
Whole Genome Sequences of the Tea Leaf Spot Pathogen Didymella segeticola
Authors: Ren Yafeng , Li Dongxue , Zhao Xiaozhen , Wang Yong , Bao Xingtao , Wang Xue , Wu Xian , Wang Delu , Song Baoan , Chen Zhuo
Published: June 2019

The fungal pathogen Didymella segeticola (basionym Phoma segeticola) causes leaf spot on tea (Camellia sinensis), which leads to a loss in tea leaf production in Guizhou Province, China. D. segeticola isolate GZSQ-4 was sequenced using Illumina HiSeq and Pacific Biosciences (PacBio) RS technologies, and then assembled to approximately 33.4 Mbp with a scaffold N50 value of approximately 2.3 Mbp. In total, 10,893 genes were predicted using the Nonredundant, Gene Ontology, Clusters of Orthologous Groups, Kyoto Encyclopedia of Genes and Genomes, and SWISS-PROT databases. The whole-genome sequence of D. segeticola will provide a resource for future research on host−pathogen interactions, determination of trait-specific genes, pathogen evolution, and plant−host adaptation mechanisms.
Making a diagnosis in severe cutaneous drug hypersensitivity reactions
Authors: Ardern-Jones Michael R. , Mockenhaupt Maja
Published: June 2019

Purpose of review

Severe cutaneous adverse reactions (SCAR) are relatively uncommon but can be life-threatening. This review focuses on the nonanaphylactic (non-IgE-mediated) phenotypes of drug hypersensitivity, with specific reference to diagnosis and management of acute generalized exanthematous pustulosis (AGEP), drug reaction with eosinophilia and systemic symptoms (DRESS), Stevens–Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN).

Recent findings

Here, we review recent guidelines on optimal supportive care as well as publications of interventional treatment for SJS/TEN, including various immunomodulating therapies, and management strategies for severe ocular disease with the use of amniotic membrane transplantation. In DRESS, long-term autoimmune sequelae are increasingly recognized and modify strategies for treatment of the acute episode. If the causative drug is not apparent from careful inspection of the drug exposure history, in-vitro diagnostics, HLA testing and skin testing before drug challenge testing may be considered and we present an algorithm for investigation of complex cases.

Careful phenotypic analysis of the increasingly complex recognized patterns of SCAR facilitates the enhancement in our understanding of T-cell mediated drug hypersensitivity and allows the improvement of in-vitro diagnostic testing to minimize patient exposure to test substances in all but a very limited number of cases, thereby enhancing safety.
Diabetic Control Predicts Surgical Site Infection Risk in Orthopaedic Trauma Patients
Authors: Reich Michael S. , Fernandez Isaac , Mishra Abhinav , Kafchinski Lisa , Adler Adam , Nguyen Mai P.
Published: June 2019

Objectives:

(1) To determine the incidence of surgical site infections (SSIs) in diabetic orthopaedic trauma patients and (2) to establish a protocol for managing diabetes mellitus (DM) in orthopaedic trauma patients.

Design:

Retrospective cohort study.

Setting:

Level 1 Trauma Center.

Patients:

All diabetic orthopaedic trauma patients who underwent surgical intervention with at least 1 month follow-up. Patients were classified as poorly controlled or controlled diabetic patients based on admission hemoglobin A1c and blood glucose (BG) levels.

Interventions:

Orthopaedic surgical intervention in accordance with fracture type and a standardized diabetes management protocol with internal medicine comanagement.

Main Outcome Measurement:

SSI incidence.

Results:

There were 260 patients during the study period. Two hundred two (77.7%) were included in the final analysis. Seventy-five (37.1%) patients met the criteria for poorly controlled DM. The overall rate of SSI was 20.8%; 32.0% for poorly controlled diabetic patients, and 14.2% for controlled diabetic patients (P < 0.01). The admission blood glucose level (BG, P = 0.05), but not discharge BG, was associated with SSI incidence.

Conclusions:

Trauma patients with poorly controlled DM have a higher rate of SSIs than patients with controlled DM. Perioperative diabetes control does not seem to decrease infection rates in these patients.

Level of Evidence:

Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.
Trabecular bone score of postmenopausal women is positively correlated with bone mineral density and negatively correlated with age and body mass index
Authors: Torgutalp Şerife Ş. , Babayeva Naila , Kara Ömer S. , Özkan Ömer , Dönmez Gürhan , Korkusuz Feza
Published: June 2019

Objective:

Trabecular bone score (TBS), an indirect evaluation of skeletal microarchitecture, is calculated from dual-energy X-ray absorptiometry (DXA). This study aimed to determine the mean TBS values in healthy postmenopausal women and overall association between TBS and demographic features, bone mineral density (BMD) of the lumbar spine and femoral neck, and BMD to body mass index (BMI) ratio of the lumbar spine.

Methods:

Fifty-three postmenopausal healthy women were enrolled. The BMD of the lumbar spine and femoral neck was measured by DXA. Anteroposterior lumbar spine acquisitions were used to calculate the TBS for L1 to L4.

Results:

The mean BMD of the lumbar spine and femoral neck was 0.945 ± 0.133 and 0.785 ± 0.112 g/cm2, respectively. The mean TBS was 1.354 ± 0.107. There was a significant positive moderate correlation between TBS and total lumbar BMD to BMI ratio (r = 0.595, P < 0.001), and significant positive weak correlations between TBS and BMD of the lumbar spine (r = 0.347, P = 0.011) as well as between TBS and femoral neck (r = 0.305, P = 0.026), whereas significant negative moderate correlations were observed between TBS and age (r = −0.393, P = 0.004) as well as between TBS and BMI (r = −0.333, P = 0.015).

Conclusions:

TBS values of postmenopausal women were negatively correlated with age and BMI, and positively with BMD and BMD to BMI ratio.
Pseudoexfoliative Glaucoma, Endothelial Dysfunction, and Arterial Stiffness: The Role of Circulating Apoptotic Endothelial Microparticles
Authors: Bourouki Evgenia , Oikonomou Evangelos , Moschos Marilita , Siasos Gerasimos , Siasou Georgia , Gouliopoulos Nikos , Deftereos Spyridon , Miliou Antigoni , Zacharia Effimia , Tousoulis Dimitris
Published: June 2019

Précis:

Pseudoexfoliative glaucoma (PExG) patients present with not only endothelial dysfunction and arterial stiffness but also with a specific profile of circulating apoptotic endothelial microparticles which may be owing to the accumulation of pseudoexfoliative material in vessels walls.

Purpose:

PExG is characterized by the deposition of pseudoexfoliative material in several tissues and organs including in the cardiovascular system. This study aimed to evaluate the vascular endothelial function, arterial stiffness, inflammatory status, and circulating microparticle (MP) levels in PExG patients compared with those in primary open-angle glaucoma (POAG) patients and control subjects.

Methods:

Vascular endothelial function was evaluated by flow-mediated dilation. Pulse wave velocity and augmentation index were measured as indices of aortic stiffness and arterial wave reflections, respectively. Growth-differentiation factor-15 and intercellular adhesion molecule1 levels were measured to evaluate the systemic inflammatory status. Circulating MPs that constitute an emerging marker of vascular endothelial dysfunction and platelet activation were isolated and analyzed by flow cytometry.

Results:

There was a stepwise impairment from the control to the POAG patients and PExG subjects in the flow-mediated dilation (8.21%±2.94% vs. 7.56%±3.12% vs. 5.79±3.13, P=0.005), pulse wave velocity (8.14±1.79 vs. 9.21±2.27 vs. 9.95±3.28 m/s, P=0.007), augmentation index (24.71%±7.84% vs. 26.78%±7.21% vs. 29.96%±7.58%, P=0.02), and growth-differentiation factor-15 (P=0.001) and intercellular adhesion molecule1 levels (P=0.08). PExG patients expressed greater levels of total circulating MPs (Annexin V+) (P=0.004) and endothelial-derived MPs (CD144+) (P<0.001) compared with POAG and control subjects.

Conclusions:

PExG patients with an accumulation of pseudoexfoliative microfibrillar material presented with vascular endothelial dysfunction and arterial wall impairment associated with the levels of circulating proinflammatory molecules and circulating apoptotic endothelial MPs. These findings highlight the underlying systemic pathophysiological mechanisms associated with the progress of the pseudoexfoliative syndrome.
A randomized controlled trial testing a virtual perspective-taking intervention to reduce race and socioeconomic status disparities in pain care
Authors: Hirsh Adam T. , Miller Megan M. , Hollingshead Nicole A. , Anastas Tracy , Carnell Stephanie T. , Lok Benjamin C. , Chu Chenghao , Zhang Ying , Robinson Michael E. , Kroenke Kurt , Ashburn-Nardo Leslie
Published: June 2019

We conducted a randomized controlled trial of an individually tailored, virtual perspective-taking intervention to reduce race and socioeconomic status (SES) disparities in providers' pain treatment decisions. Physician residents and fellows (n = 436) were recruited from across the United States for this two-part online study. Providers first completed a bias assessment task in which they made treatment decisions for virtual patients with chronic pain who varied by race (black/white) and SES (low/high). Providers who demonstrated a treatment bias were randomized to the intervention or control group. The intervention consisted of personalized feedback about their bias, real-time dynamic interactions with virtual patients, and videos depicting how pain impacts the patients' lives. Treatment bias was re-assessed 1 week later. Compared with the control group, providers who received the tailored intervention had 85% lower odds of demonstrating a treatment bias against black patients and 76% lower odds of demonstrating a treatment bias against low SES patients at follow-up. Providers who received the intervention for racial bias also showed increased compassion for patients compared with providers in the control condition. Group differences did not emerge for provider comfort in treating patients. Results suggest an online intervention that is tailored to providers according to their individual treatment biases, delivers feedback about these biases, and provides opportunities for increased contact with black and low SES patients, can produce substantial changes in providers' treatment decisions, resulting in more equitable pain care. Future studies should examine how these effects translate to real-world patient care and the optimal timing/dose of the intervention.
A Proof-of-Concept Study Evaluating the Phosphodiesterase 10A Inhibitor PF-02545920 in the Adjunctive Treatment of Suboptimally Controlled Symptoms of Schizophrenia
Authors: DeMartinis Nicholas , Lopez Rene N. , Pickering Eve H. , Schmidt Christopher J. , Gertsik Lev , Walling David P. , Ogden Adam
Published: June 2019

Background

Effective treatments for managing suboptimal clinical responses to current therapy for schizophrenia remain a critical unmet need. Phosphodiesterase 10A (PDE10A) inhibition represents a mechanistically novel approach to the treatment of schizophrenia, with preclinical studies suggesting improvements in partially responsive symptoms could be achieved via adjunctive use of the PDE10A inhibitor PF-02545920. Therefore, the adjunctive safety, tolerability, pharmacokinetics, and efficacy of multiple repeat doses of PF-02545920 were investigated in a phase 1b study and subsequent phase 2 study.

Methods

The phase 1b study randomized 37 adult patients with stable symptomatology and stable antipsychotic regimens within 3 cohorts. Study participants received ascending doses of PF-02545920 or placebo for 10 to 18 days. The phase 2 study randomized 240 outpatients with stable symptomatology but suboptimal response to current antipsychotic regimens 1:1:1 to PF-02545920 5 mg, PF-02545920 15 mg, or placebo every 12 hours for 12 weeks. The primary efficacy end point of the phase 2 study was change in the Positive and Negative Syndrome Scale total score from baseline to week 12, with changes in other clinical assessments as secondary end points.

Results

Treatment was well tolerated, and observed PF-02545920 exposures were within the range predicted to be adequate for demonstrating efficacy. However, no significant differences in the prespecified efficacy end points between the 2 PF-02545920 treatment arms and placebo were observed.

Conclusions

Current data and results of a prior monotherapy study in which PF-02545920 failed to differentiate from placebo refute the hypothesis that PDE10A inhibitors have use as antipsychotic agents for schizophrenia.
Estimating the Risk of Pneumonia in Patients With Schizophrenia Newly Receiving Clozapine
Authors: Wu Chi-Shin , Chen Tien-Yu , Tsai Shang-Ying , Chen Chiao-Chicy , Kuo Chian-Jue
Published: June 2019

Purpose/Background

Patients with schizophrenia are vulnerable to pneumonia. Clozapine is associated with the greatest risk of pneumonia. We investigated the risk factors of pneumonia in patients with schizophrenia who use clozapine.

Methods/Procedures

We used a large cohort of patients with schizophrenia (N = 22,774) who newly use clozapine (baseline). We divided the data set into a training cohort (entry between 1998 and 2008, n = 18,496) and test cohort (entry between 2009 and 2012, n = 4278), where 483 and 168 patients developed pneumonia requiring hospitalization within 1 year after baseline, respectively. For prediction, we developed a static model using Cox proportional hazards regression and a dynamic model using Cox regression with time-dependent modeling. Areas under receiver operating curves (AUCs) for the predictive model were estimated in the training cohort and then in the test cohort for validation.

Findings/Results

Based on the baseline characteristics, the static model for predicting pneumonia in 3 periods (90, 180, and 365 days) was unsatisfactory (AUCs, 0.64, 0.64, and 0.65, respectively). The predictors were older age, male sex, history of nonpsychiatric hospitalization, dementia, asthma, and tuberculosis within 1 year before baseline. However, the results were improved (AUCs, 0.83, 0.79, and 0.77, respectively) after control for time-dependent variables, namely, duration of clozapine use and concomitant medications (ie, benzodiazepines, valproic acid, systemic corticosteroids).

Implications/Conclusions

Several risk factors for predicting subsequent pneumonia after initial use of clozapine were explored, including older age, male, history of nonpsychiatric hospitalization, dementia, asthma, tuberculosis, benzodiazepines, valproic acid, systemic corticosteroids, and the use duration of clozapine. Clinical staff can use the risk factors to administer evidence-based treatment.
Quetiapine Poisoning and Factors Influencing Severity
Authors: Peridy Elise , Hamel Jean-François , Rolland Anne-Lise , Gohier Bénédicte , Boels David
Published: June 2019

Purpose/Background

Quetiapine is a relatively new atypical antipsychotic with fewer adverse effects. It is increasingly prescribed to patients. The purpose of this study was to describe the cases of poisoning observed at the western France Poison Control Centre and identify potential risk factors that increase the severity of the cases.

Methods

This was a retrospective study of self-poisoning with quetiapine as reported by the western France Poison Control Centre between 2007 and 2017.

Results

There were 372 cases of quetiapine poisoning. Circumstances are known in 367 of 372 cases. There were 75 cases of null severity (grade 0), 133 cases of mild severity (grade 1), 85 cases of moderate severity (grade 2), and 79 cases of high severity (grade 3). Five deaths were listed in this series. The most commonly observed symptoms were neurological and cardiovascular in nature (drowsiness, coma, tachycardia, hypotension). Of these cases, 79.8% included voluntary ingestions. Among 302 cases with coagents, the most common coagents were benzodiazepines (56%), other psychotropic drugs (41%), and antidepressants (37%). An evaluated ingested dose 1500 mg or greater and 2 or more coagents increase the risk of severe poisoning. In particular, concomitant ingestion of benzodiazepines and antidepressants with quetiapine was associated with high severity (odds ratio, 2.478 [confidence interval, 1.3–4.723]; odds ratio, 1.820 [confidence interval, 1.010–3.316]).

Conclusions

Quetiapine may lead to severe poisoning for which there is currently no specific treatment. Patients and practitioners should be aware of this when quetiapine is prescribed, particularly when used in combination with other medications, and in order to deal with cases of poisoning.
Efficacy of Varenicline in Patients With Severe Alcohol Dependence
Authors: Pfeifer Philippe , Fehr Christoph
Published: June 2019

Purpose/Background

Varenicline has proven its efficacy in the treatment of nicotine dependence, and there is also evidence that it could be helpful in the treatment of alcohol dependence. In our pilot study, we investigated the feasibility and acceptability of varenicline for the treatment of a population of patients with severe alcohol dependence and multiple somatic comorbidities after alcohol detoxification.

Methods/Procedures

We conducted a phase II, double-blind, placebo-controlled randomized trial of daily oral varenicline versus a placebo in alcohol-dependent men and women after alcohol detoxification (n = 28). Following our study protocol, somatic conditions and adverse events were thoroughly monitored and several study end points were investigated (percentage of abstinent days for both alcohol and nicotine, number of standardized drinks and cigarettes per day, days of heavy drinking).

Findings/Results

Compared with the placebo, varenicline did not have more side effects and did not provoke more adverse events. Patients in the varenicline group did not show a significantly higher percentage of alcohol abstinent days or fewer heavy drinking days. A trend significance was found for a reduced number of standard drinks per day (P = 0.06) in the varenicline group.

Implications/Conclusions

In this pilot trial, varenicline was shown to be well tolerated by our study population of severely alcohol-dependent patients with somatic conditions. Varenicline did not sustain alcohol abstinence or reduce the number of heavy drinking days, but it did reduce the daily amount of alcohol consumed.
The stigma of skin disease
Authors: Wu Julie H. , Cohen Bernard A.
Published: June 2019

Purpose of review

The effects of skin disease on stigmatization are important but understudied in the pediatric population. Given the highly visible nature of dermatologic conditions, stigmatization is a common problem that requires significant attention in patients with skin diseases. In this review, we examine the recent literature addressing stigmatization of patients suffering from common dermatologic diseases with the goal to increase clinician awareness of these issues and identify new avenues for future research.

Recent findings

A number of studies have examined the impact of skin disease on psychosocial well being and quality of life. Although some skin diseases are often overlooked medically and considered to be primarily cosmetic issues, the long-term consequences of skin diseases on psychosocial health, especially in pediatric patients, can be profound.

The precipitating factors for stigma vary widely depending on age, sex, and culture. In order to effectively reduce the impact of pediatric skin diseases on psychosocial health, physicians should be able to identify specific characteristics that may increase risks for stigmatization in chidlren. Carefully monitoring psychosocial development in pediatric patients with dermatological conditions in addition to proactively guiding patients and families to appropriate resources can benefit the child's development and overall long-term well being.