bluuebunny/crossref_metadata_2025 huggingface dataset:
Drosophila Calmodulin Mutants With Specific Defects in the Musculature or in the Nervous System
Authors: Wang Bo , Sullivan Kathleen M C , Beckingham Kathy
Published: April 2021

We have studied lethal mutations in the single calmodulin gene (Cam) of Drosophila to gain insight into the in vivo functions of this important calcium sensor. As a result of maternal calmodulin (CaM) in the mature egg, lethality is delayed until the postembryonic stages. Prior to death in the first larval instar, Cam nulls show a striking behavioral abnormality (spontaneous backward movement) whereas a mutation, Cam7, that results in a single amino acid change (V91G) produces a very different phenotype: short indented pupal cases and pupal death with head eversion defects. We show here that the null behavioral phenotype originates in the nervous system and involves a CaM function that requires calcium binding to all four sites of the protein. Further, backward movement can be induced in hypomorphic mutants by exposure to high light levels. In contrast, the V91G mutation specifically affects the musculature and causes abnormal calcium release in response to depolarization of the muscles. Genetic interaction studies suggest that failed regulation of the muscle calcium release channel, the ryanodine receptor, is the major defect underlying the Cam7 phenotype.
Patterns of Nucleotide Polymorphism and Divergence in the Odorant-Binding Protein Genes OS-E and OS-F: Analysis in the Melanogaster Species Subgroup of Drosophila
Authors: Sánchez-Gracia Alejandro , Aguadé Montserrat , Rozas Julio
Published: April 2021

The Olfactory Specific-E and -F genes (OS-E and OS-F) belong to the odorant-binding protein gene family, which includes the general odorant-binding proteins and the pheromone-binding proteins. In Drosophila melanogaster, these genes are arranged in tandem in a genomic region near the centromere of chromosome arm 3R. We examined the pattern of DNA sequence variation in an ∼7-kb genomic region encompassing the two OS genes in four species of the melanogaster subgroup of Drosophila and in a population sample of D. melanogaster. We found that both the OS-E and the OS-F gene are present in all surveyed species. Nucleotide divergence estimates would support that the two genes are functional, although they diverge in their functional constraint. The pattern of nucleotide variation in D. melanogaster also differed between genes. Variation in the OS-E gene region exhibited an unusual and distinctive pattern: (i) a relatively high number of fixed amino acid replacements in the encoded protein and (ii) a peak of nucleotide polymorphism around the OS-E gene. These results are unlikely under the neutral model and suggest the action of natural selection in the evolution of the two odorant-binding protein genes.
Genetic Modifier Screens in Drosophila Demonstrate a Role for Rho1 Signaling in Ecdysone-Triggered Imaginal Disc Morphogenesis
Authors: Ward Robert E , Evans Janelle , Thummel Carl S
Published: April 2021

Drosophila adult leg development provides an ideal model system for characterizing the molecular mechanisms of hormone-triggered morphogenesis. A pulse of the steroid hormone ecdysone at the onset of metamorphosis triggers the rapid transformation of a flat leg imaginal disc into an immature adult leg, largely through coordinated changes in cell shape. In an effort to identify links between the ecdysone signal and the cytoskeletal changes required for leg morphogenesis, we performed two large-scale genetic screens for dominant enhancers of the malformed leg phenotype associated with a mutation in the ecdysoneinducible broad early gene (br1). From a screen of >750 independent deficiency and candidate mutation stocks, we identified 17 loci on the autosomes that interact strongly with br1. In a complementary screen of ∼112,000 F1 progeny of EMS-treated br1 animals, we recovered 26 mutations that enhance the br1 leg phenotype [E(br) mutations]. Rho1, stubbloid, blistered (DSRF), and cytoplasmic Tropomyosin were identified from these screens as br1-interacting genes. Our findings suggest that ecdysone exerts its effects on leg morphogenesis through a Rho1 signaling cascade, a proposal that is supported by genetic interaction studies between the E(br) mutations and mutations in the Rho1 signaling pathway. In addition, several E(br) mutations produce unexpected defects in midembryonic morphogenetic movements. Coupled with recent evidence implicating ecdysone signaling in these embryonic morphogenetic events, our results suggest that a common ecdysone-dependent, Rho1-mediated regulatory pathway controls morphogenesis during the two major transitions in the life cycle, embryogenesis and metamorphosis.
Genetic Interactions Between the RhoA and Stubble-stubbloid Loci Suggest a Role for a Type II Transmembrane Serine Protease in Intracellular Signaling During Drosophila Imaginal Disc Morphogenesis
Authors: Bayer Cynthia A , Halsell Susan R , Fristrom James W , Kiehart Daniel P , von Kalm Laurence
Published: April 2021

The Drosophila RhoA (Rho1) GTPase is essential for postembryonic morphogenesis of leg and wing imaginal discs. Mutations in RhoA enhance leg and wing defects associated with mutations in zipper, the gene encoding the heavy chain of nonmuscle myosin II. We demonstrate here that mutations affecting the RhoA signaling pathway also interact genetically with mutations in the Stubble-stubbloid (Sb-sbd) locus that encodes an unusual type II transmembrane serine protease required for normal leg and wing morphogenesis. In addition, a leg malformation phenotype associated with overexpression of Sb-sbd in prepupal leg discs is suppressed when RhoA gene dose is reduced, suggesting that RhoA and Sb-sbd act in a common pathway during leg morphogenesis. We also characterized six mutations identified as enhancers of zipper mutant leg defects. Three of these genes encode known members of the RhoA signaling pathway (RhoA, DRhoGEF2, and zipper). The remaining three enhancer of zipper mutations interact genetically with both RhoA and Sb-sbd mutations, suggesting that they encode additional components of the RhoA signaling pathway in imaginal discs. Our results provide evidence that the type II transmembrane serine proteases, a class of proteins linked to human developmental abnormalities and pathology, may be associated with intracellular signaling required for normal development.
Detection and Effects of a Homeologous Reciprocal Transposition in Brassica napus
Authors: Osborn Thomas C , Butrulle David V , Sharpe Andrew G , Pickering Kathryn J , Parkin Isobel A P , Parker John S , Lydiate Derek J
Published: April 2021

A reciprocal chromosomal transposition was identified in several annual oilseed Brassica napus genotypes used as parents in crosses to biennial genotypes for genetic mapping studies. The transposition involved an exchange of interstitial homeologous regions on linkage groups N7 and N16, and its detection was made possible by the use of segregating populations of doubled haploid lines and codominant RFLP markers. RFLP probes detected pairs of homeologous loci on N7 and N16 for which the annual and biennial parents had identical alleles in regions expected to be homeologous. The existence of an interstitial reciprocal transposition was confirmed by cytological analysis of synaptonemal complexes of annual × biennial F1 hybrids. Although it included approximately one-third of the physical length of the N7 and N16 chromosomes, few recombination events within the region were recovered in the progenies of the hybrids. Significantly higher seed yields were associated with the parental configurations of the rearrangement in segregating progenies. These progenies contained complete complements of homeologous chromosomes from the diploid progenitors of B. napus, and thus their higher seed yields provide evidence for the selective advantage of allopolyploidy through the fixation of intergenomic heterozygosity.
Comparison of adaptive multiple phenotype association tests using summary statistics in genome-wide association studies
Authors: Sitlani Colleen M , Baldassari Antoine R , Highland Heather M , Hodonsky Chani J , McKnight Barbara , Avery Christy L
Published: April 2021

Genome-wide association studies have been successful mapping loci for individual phenotypes, but few studies have comprehensively interrogated evidence of shared genetic effects across multiple phenotypes simultaneously. Statistical methods have been proposed for analyzing multiple phenotypes using summary statistics, which enables studies of shared genetic effects while avoiding challenges associated with individual-level data sharing. Adaptive tests have been developed to maintain power against multiple alternative hypotheses because the most powerful single-alternative test depends on the underlying structure of the associations between the multiple phenotypes and a single nucleotide polymorphism (SNP). Here we compare the performance of six such adaptive tests: two adaptive sum of powered scores (aSPU) tests, the unified score association test (metaUSAT), the adaptive test in a mixed-models framework (mixAda) and two principal-component-based adaptive tests (PCAQ and PCO). Our simulations highlight practical challenges that arise when multivariate distributions of phenotypes do not satisfy assumptions of multivariate normality. Previous reports in this context focus on low minor allele count (MAC) and omit the aSPU test, which relies less than other methods on asymptotic and distributional assumptions. When these assumptions are not satisfied, particularly when MAC is low and/or phenotype covariance matrices are singular or nearly singular, aSPU better preserves type I error, sometimes at the cost of decreased power. We illustrate this trade-off with multiple phenotype analyses of six quantitative electrocardiogram traits in the Population Architecture using Genomics and Epidemiology (PAGE) study.
Effective Host-Directed Therapy for Tuberculosis by Depletion of Myeloid-Derived Suppressor Cells and Related Cells Using a Diphtheria Toxin Fusion Protein
Authors: Parveen Sadiya , Lun Shichun , Urbanowski Michael E , Cardin Mitchell , Shen Jessica , Murphy John R , Bishai William R
Published: April 2021

Myeloid-derived suppressor cells (MDSCs) are present in elevated numbers in tuberculosis patients and have been found to be permissive for Mycobacterium tuberculosis proliferation. To determine whether depletion of MDSCs may improve host control of tuberculosis, we used a novel diphtheria toxin-based fusion protein DABIL-4 that targets and depletes interleukin 4 (IL-4) receptor-positive cells. We show that DABIL-4 depletes both polymorphonuclear MDSCs and monocytic MDSCs, increases interferon-γ + T cells, and reduces the lung bacillary burden in a mouse tuberculosis model. These results indicate that MDSC-depleting therapies targeting the IL-4 receptor are beneficial in tuberculosis and offer an avenue towards host-directed tuberculosis therapy.
Mechanisms and regulation underlying membraneless organelle plasticity control
Authors: Ismail Hazrat , Liu Xu , Yang Fengrui , Li Junying , Zahid Ayesha , Dou Zhen , Liu Xing , Yao Xuebiao
Published: April 2021

Evolution has enabled living cells to adopt their structural and functional complexity by organizing intricate cellular compartments, such as membrane-bound and membraneless organelles (MLOs), for spatiotemporal catalysis of physiochemical reactions essential for cell plasticity control. Emerging evidence and view support the notion that MLOs are built by multivalent interactions of biomolecules via phase separation and transition mechanisms. In healthy cells, dynamic chemical modifications regulate MLO plasticity, and reversible phase separation is essential for cell homeostasis. Emerging evidence revealed that aberrant phase separation results in numerous neurodegenerative disorders, cancer, and other diseases. In this review, we provide molecular underpinnings on (i) mechanistic understanding of phase separation, (ii) unifying structural and mechanistic principles that underlie this phenomenon, (iii) various mechanisms that are used by cells for the regulation of phase separation, and (iv) emerging therapeutic and other applications.
CoordinatingIfs
Authors: Khoo Justin
Published: April 2021

Accounting for the behavior of conjoined and disjoined if-clauses is not easy for standard theories of conditionals that treat if as either an operator or restrictor. In this paper, I discuss four observations about coordinated if-clauses, and motivate a semantics for conditionals that reorients the compositional structure of the restrictor theory. On my proposal, if-clauses provide restrictions on modal domains, but they do so by way of a higher type intermediary—a set of propositions—that is collapsed by the modal. I argue that combining this view with an independently plausible type-shifting operation applied to or and and predicts the range of data we find for conditionals with coordinated if-clauses.
Synopsis of the 2020 U.S. VA/DoD Clinical Practice Guideline for the Management of Adult Overweight and Obesity
Authors: Mayer Stéphanie B , Graybill Sky , Raffa Susan D , Tracy Christopher , Gaar Earl , Wisbach Gordon , Goldstein Michael G , Sall James
Published: April 2021

Introduction

In May of 2020, the U.S. Veterans Health Administration (VHA) and Department of Defense (DoD) approved a new joint clinical practice guideline for assessing and managing patients who have overweight and obesity. This guideline is intended to give healthcare teams a framework by which to screen, evaluate, treat, and manage the individual needs and preferences of VA and DoD patients who may have either of these conditions. It can be accessed at https://www.healthquality.va.gov/guidelines/CD/obesity/.

Materials and Methods

In January of 2019, the VA/DoD Evidence-Based Practice Work Group convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine’s tenets for trustworthy clinical practice guidelines.

Results

The guideline panel developed 12 key questions, systematically searched and evaluated the literature, created a 1-page algorithm, and advanced 18 recommendations using the Grading of Recommendations Assessment, Development, and Evaluation system.

Conclusions

This synopsis summarizes the key recommendations of the guideline regarding management of overweight and obesity, including referral to comprehensive lifestyle interventions that combine behavioral, dietary, and physical activity change, and additional tools of pharmacologic and procedural interventions. Additionally, recommendations based on evidence found in the literature for short-term weight loss are included. A clinical practice algorithm that is part of the guideline is also included. Additional materials, such as provider and patient summaries and a provider pocket card, are also available for public use, accessible at the U.S. Veterans Health Administration (VHA) Clinical Practice Guidelines (CPG) website listed above.
SpaceHub: A high-performance gravity integration toolkit for few-body problems in astrophysics
Authors: Wang Yi-Han , Leigh Nathan W C , Liu Bin , Perna Rosalba
Published: April 2021

We present the open source few-body gravity integration toolkit SpaceHub. SpaceHub offers a variety of algorithmic methods, including the unique algorithms AR-Radau, AR-Sym6, AR-ABITS, and AR-chain+ which we show outperform other methods in the literature and allow for fast, precise, and accurate computations to deal with few-body problems ranging from interacting black holes to planetary dynamics. We show that AR-Sym6 and AR-chain+, with algorithmic regularization, chain algorithm, active round-off error compensation and a symplectic kernel implementation, are the fastest and most accurate algorithms to treat black hole dynamics with extreme mass ratios, extreme eccentricities, and very close encounters. AR-Radau, the first regularized Radau integrator with round off error control down to 64 bits floating point machine precision, has the ability to handle extremely eccentric orbits and close approaches in long-term integrations. AR-ABITS, a bit efficient arbitrary precision method, achieves any precision with the least CPU cost compared to other open source arbitrary precision few-body codes. With the implementation of deep numerical and code optimization, these new algorithms in SpaceHub prove superior to other popular high precision few-body codes in terms of performance, accuracy, and speed.
The nature of sub-millimetre galaxies I: a comparison of AGN and star-forming galaxy SED fits
Authors: Shanks T , Ansarinejad B , Bielby R M , Heywood I , Metcalfe N , Wang L
Published: April 2021

High-redshift sub-millimetre galaxies (SMGs) are usually assumed to be powered by star formation. However, it has been clear for some time that >20 per cent of such sourcesbrighter than ≈3 mJy host quasars. Here, we analyse a complete sample of 12 sub-mm LABOCA/ALMA 870-μm sources in the centre of the William Herschel Deep Field (WHDF) with multiwavelength data available from the X-ray to the radio bands. Previously, two sources were identified as X-ray-absorbed quasars at z = 1.32 and z = 2.12. By comparing their spectral energy distributions (SEDs) with unabsorbed quasars in the same field, we confirm that they are dust reddened although at a level significantly lower than implied by their X-ray absorption. Then, we compare the SEDs of all the sources to dust-reddened AGN and star-forming galaxy models. This optical/NIR comparison combined with Spitzer MIR colours and faint Chandra X-ray detections shows that 7/12 SMGs are best fitted with an obscured quasar model, a further 3/12 show no preference between AGN and star-forming templates, leaving only a z = 0.046 spiral galaxy and one unidentified source. So in our complete sample, the majority (10/12) of bright SMGs are at least as likely to fit an AGN as a star-forming galaxy template, although no claim is made to rule out the latter as SMG power sources. We then suggest modifications to a previous SMG number count model and conclude that obscured AGN in SMGs may still provide the dominant contribution to both the hard X-ray and sub-millimetre backgrounds.
ALMA imaging of the M-dwarf Fomalhaut C’s debris disc
Authors: Cronin-Coltsmann Patrick F , Kennedy Grant M , Kalas Paul , Milli Julien , Clarke Cathie J , Duchêne Gaspard , Greaves Jane , Lawler Samantha M , Lestrade Jean-François , Matthews Brenda C , Shannon Andrew , Wyatt Mark C
Published: April 2021

Fomalhaut C (LP 876-10) is a low mass M4V star in the intriguing Fomalhaut triple system and, like Fomalhaut A, possesses a debris disc. It is one of very few nearby M-dwarfs known to host a debris disc and of these has by far the lowest stellar mass. We present new resolved observations of the debris disc around Fomalhaut C with the Atacama Large Millimetre Array that allow us to model its properties and investigate the system’s unique history. The ring has a radius of 26 au and a narrow full width at half-maximum of at most 4.2 au. We find a 3σ upper limit on the eccentricity of 0.14, neither confirming nor ruling out previous dynamic interactions with Fomalhaut A that could have affected Fomalhaut C’s disc. We detect no 12CO J = 3-2 emission in the system and do not detect the disc in scattered light with HST/STIS or VLT/SPHERE. We find the original Herschel detection to be consistent with our ALMA model’s radial size. We place the disc in the context of the wider debris disc population and find that its radius is as expected from previous disc radius-host luminosity trends. Higher signal-to-noise observations of the system would be required to further constrain the disc properties and provide further insight to the history of the Fomalhaut triple system as a whole.
In vivo stabilization of endogenous chloroplast RNAs by customized artificial pentatricopeptide repeat proteins
Authors: Manavski Nikolay , Mathieu Sébastien , Rojas Margarita , Méteignier Louis-Valentin , Brachmann Andreas , Barkan Alice , Hammani Kamel
Published: April 2021

Pentatricopeptide repeat (PPR) proteins are helical repeat-proteins that bind RNA in a modular fashion with a sequence-specificity that can be manipulated by the use of an amino acid code. As such, PPR repeats are promising scaffolds for the design of RNA binding proteins for synthetic biology applications. However, the in vivo functional capabilities of artificial PPR proteins built from consensus PPR motifs are just starting to be explored. Here, we report in vivo functions of an artificial PPR protein, dPPRrbcL, made of consensus PPR motifs that were designed to bind a sequence near the 5′ end of rbcL transcripts in Arabidopsis chloroplasts. We used a functional complementation assay to demonstrate that this protein bound its intended RNA target with specificity in vivo and that it substituted for a natural PPR protein by stabilizing processed rbcL mRNA. We targeted a second protein of analogous design to the petL 5′ UTR, where it substituted for the native stabilizing PPR protein PGR3, albeit inefficiently. These results showed that artificial PPR proteins can be engineered to functionally mimic the class of native PPR proteins that serve as physical barriers against exoribonucleases.
Endotrophin, a collagen type VI-derived matrikine, reflects the degree of renal fibrosis in patients with IgA nephropathy and in patients with ANCA-associated vasculitis
Authors: Sparding Nadja , Genovese Federica , Rasmussen Daniel Guldager Kring , Karsdal Morten Asser , Neprasova Michaela , Maixnerova Dita , Satrapova Veronika , Frausova Doubravka , Hornum Mads , Bartonova Lenka , Honsova Eva , Kollar Marek , Koprivova Helena , Hruskova Zdenka , Tesar Vladimir
Published: April 2021

Background

Renal fibrosis is the hallmark of chronic kidney disease (CKD) and is characterized by an imbalanced extracellular matrix remodelling. Endotrophin (ETP) is a signalling molecule released from collagen type VI (COL VI). ETP can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation. ETP levels were previously associated with mortality and disease progression in patients with CKD. We hypothesized that serum and urinary ETP levels correlate with the degree of interstitial fibrosis in kidney biopsies from patients with immunoglobulin A nephropathy (IgAN) and patients with anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV).

Methods

We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. ETP was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the enzyme-linked immunosorbent assay PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores.

Results

S-ETP and U-ETP/Cr levels correlated with kidney function, increased CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort.

Conclusions

We demonstrated that high levels of circulating and excreted ETP are not only indicative of lower kidney function, but also reflect the burden of fibrosis in the kidneys.
Atomically precise metal chalcogenide supertetrahedral clusters: frameworks to molecules, and structure to function
Authors: Zhang Jiaxu , Feng Pingyun , Bu Xianhui , Wu Tao
Published: April 2021

Metal chalcogenide supertetrahedral clusters (MCSCs) are of significance for developing crystalline porous framework materials and atomically precise cluster chemistry. Early research interest focused on the synthetic and structural chemistry of MCSC-based porous semiconductor materials with different cluster sizes/compositions and their applications in adsorption-based separation and optoelectronics. More recently, focus has shifted to the cluster chemistry of MCSCs to establish atomically precise structure–composition–property relationships, which are critical for regulating the properties and expanding the applications of MCSCs. Importantly, MCSCs are similar to II–VI or I–III–VI semiconductor nanocrystals (also called quantum dots, QDs) but avoid their inherent size polydispersity and structural ambiguity. Thus, discrete MCSCs, especially those that are solution-processable, could provide models for understanding various issues that cannot be easily clarified using QDs. This review covers three decades of efforts on MCSCs, including advancements in MCSC-based open frameworks (reticular chemistry), the precise structure–property relationships of MCSCs (cluster chemistry), and the functionalization and applications of MCSC-based microcrystals. An outlook on remaining problems to be solved and future trends is also presented.
Epidermolysis bullosa acquisita: an uncommon cause of esophageal stricture
Authors: Figueredo Carlos , Boroda Konstantin , Hertan Hilary
Published: April 2021

Epidermolysis bullosa acquisita (EBA) encompasses a wide spectrum of rare diseases with a common genetic origin transmitted in an autosomal recessive fashion. Mild forms of non-inflammatory EBA are characterized by skin lesions and have gained great relevance in the literature. However, resistant inflammatory EBA with widespread mucosal involvement remains a rare entity given its low prevalence. It commonly represents a great burden for the patient’s quality of life with most cases being resistant to different therapeutic modalities. We present a case of resistant inflammatory EBA with esophageal strictures that improved after therapy with intravenous immunoglobulin and rituximab.
A challenging case of arrhythmogenic right ventricular cardiomyopathy presenting as fulminant myocarditis
Authors: Mahdavi Mohammad , Hosseini Leila , Mozzaffari Kambiz , Zadehbagheri Fatemeh , Rezaeian Nahid
Published: April 2021

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is known as a primary genetic heart disease that leading to the myocardial deposition of fibrofatty tissue in right ventricular (RV) wall. Sometimes, it occurs in the left ventricular (LV) subepicardial wall.

This study introduces a child referred to our hospital with influenza-like symptoms and ventricular tachyarrhythmia, followed by cardiac failure. However, in our subsequent evaluation, there was evidence of severe LV and RV dysfunction based on the echocardiography. Moreover, cardiac magnetic resonance showed not only the major criteria of ARVC but also those of Lake Luise seen in myocarditis. Regarding the deteriorating condition during the hospital course, he was later scheduled for heart transplantation.

Finally, the histopathological study of explanted heart revealed RV myocyte atrophy with the infiltration of fibrofatty tissue in myocardium diagnostic of ARVC, resolving dilemma between ARVC and myocarditis.
Sertraline as a rare cause of interstitial lung disease
Authors: Lepore Mario , Campbell Niall
Published: April 2021

Sertraline, a selective serotonin reuptake inhibitor, is commonly prescribed for the treatment of moderate-to-severe depression. We report a case of a 36-year-old male taking sertraline for 7 weeks prior to developing a dry cough, pleuritic chest pain, hypoxia and diffuse ground-glass attenuation with mediastinal lymphadenopathy on imaging. No infectious aetiology was identified and multiple causes of pneumonitis excluded. Sertraline-induced interstitial lung disease was subsequently diagnosed. Sertraline was discontinued and treatment commenced with a weaning course of oral dexamethasone, leading to a rapid reduction in oxygen requirement and successful discharge. Given the increasing prevalence of selective serotonin reuptake inhibitor use, it is vital that medical professionals can recognize sertraline as a rare, albeit potentially life-threatening, cause of interstitial lung disease—allowing for the rapid diagnosis and appropriate management of this condition.
Non-IgE-mediated food allergy: Evaluation and management
Authors: Abrams Elissa M , Hildebrand Kyla J , Chan Edmond S
Published: April 2021

The most common types of non-IgE-mediated food allergy are food protein-induced enterocolitis syndrome (FPIES) and food protein-induced allergic proctocolitis (FPIAP). FPIES presents with delayed refractory emesis, while FPIAP presents with hematochezia in otherwise healthy infants. Acute management of FPIES includes rehydration or ondansetron, or both. No acute management is required for FPIAP. Long-term management of both disorders includes avoidance of the trigger food. The prognosis for both conditions is a high rate of resolution within a few years’ time.
Customizing CAT Administration of the PROMIS Misuse of Prescription Pain Medication Item Bank for Patients with Chronic Pain
Authors: You Dokyoung S , Cook Karon F , Domingue Benjamin W , Ziadni Maisa S , Hah Jennifer M , Darnall Beth D , Mackey Sean C
Published: April 2021

Objective

The 22-item PROMIS®-Rx Pain Medication Misuse item bank (Bank-22) imposes a high response burden. This study aimed to characterize the performance of the Bank-22 in a computer adaptive testing (CAT) setting based on varied stopping rules.

Methods

The 22 items were administered to 288 patients. We performed a CAT simulation using default stopping rules (CATPROMIS). In 5 other simulations, a “best health” response rule was added to decrease response burden. This rule stopped CAT administration when a participant selected “never” to a specified number of initial Bank-22 items (2–6 in this study, designated CATAlt2-Alt6). The Bank-22 and 7-item short form (SF-7) scores were compared to scores based on CATPROMIS, and the 5 CAT variations.

Results

Bank-22 scores correlated highly with the SF-7 and CATPROMIS, Alt5, Alt6 scores (r=0.87–0.95) and moderately with CATAlt2- Alt4 scores (r=0.63–0.74). In all CAT conditions, the greatest differences with Bank-22 scores were at the lower end of misuse T-scores. The smallest differences with Bank-22 and CATPROMIS scores were observed with CATAlt5 and CATAlt6. Compared to the SF-7, CATAlt5 and CATAlt6 reduced overall response burden by about 42%. Finally, the correlations between PROMIS-Rx Misuse and Anxiety T-scores remained relatively unchanged across the conditions (r=0.31–0.43, Ps < .001).

Conclusions

Applying a stopping rule based on number of initial “best health” responses reduced response burden for respondents with lower levels of misuse. The tradeoff was less measurement precision for those individuals, which could be an acceptable tradeoff when the chief concern is in discriminating higher levels of misuse.
The Daily Experience of Subjective Tinnitus: Ecological Momentary Assessment Versus End-of-Day Diary
Authors: Lourenco Matheus P. C. G. , Simoes Jorge , Vlaeyen Johan W. S. , Cima Rilana F. F.
Published: April 2021

Objective:

Traditional methods of self-report assessments are susceptible to bias (i.e., memory, recall, and recency). Ecological momentary assessment (EMA) may curb these biases by repeated momentary assessment of the participant throughout the day. High costs and participant burden may, however, impede the use of EMA. End-of-day diary (EDD) provides an attractive alternative to EMA, though no direct comparison has been performed in the tinnitus field.

Design:

Four thousand seven-hundred thirty-two data entries were collected from nine participants undergoing cognitive behavioral treatment for tinnitus. Eleven equivalent EMA and EDD items were collected for approximately 3 months. Tinnitus experience (i.e., anger, annoyance, avoidance, distraction, fear, invasiveness, pleasantness, and sadness) and well-being (i.e., anxiety, happiness, and stress) were correlated and means compared (t-tests).

Results:

All variables presented adequate correlation (r > 0.68) between the EMA and EDD counterparts. Small (<3.9%) significant daily mean differences between EMA and EDD were found for six variables (tinnitus anger, invasiveness, pleasantness, sadness, as well as anxiety and stress) with worse results reported in EDD.

Conclusion:

The small significant effects found may be attributed to the large number of data points. When EMA is not possible or recommended, EDD provides a viable alternative to assess tinnitus experience daily. Further research on the underlying mechanisms of tinnitus experience and recollection is warranted.
Bacteria in Surgical Smoke: A Self-controlled Laboratory Study Using Porcine Spinal Tissues
Authors: Zhu Zhenqi , Liu Ning , Xia Weiwei , Liu Haiying , Wood Kirkham B. , Wang Kaifeng
Published: April 2021

Study Design.

A laboratory study performed in a self-controlled fashion.

Objective.

The aim of this study was to examine whether “surgical smoke” generated by using the electrocautery on porcine spinal tissues could contain viable bacteria.

Summary of Background Data.

The year 2020 has seen a surge in legislation regarding surgical smoke evacuation in the operating room across the United States. Surgical smoke contains numerous toxic and carcinogenic substances, which spine surgeons and operating room staff are regularly exposed to. Although the smoke's chemical toxicity has been extensively studied, little is known about its biohazard level.

Methods.

The electrocautery was used to “operate on” 20 segments of porcine spinal tissues on a clean bench. In each operation, the generated smoke was captured with a swab, which was positioned above the surgical site and within the smoke, to obtain bacteria cultures. Two other swabs—a tissue swab (swabbing the porcine tissue itself) and a blank swab (swabbing an empty sterile bowl)—were collected as controls. The culture results were compared among the three groups. An additional experiment was conducted to see whether using a mask can reduce the “infection rate” of the swab.

Results.

Although all blank swabs tested negative, 95% (19/20) of the smoke swabs tested positive, with a total of nine bacteria species identified. The most prevalent species observed in the smoke swabs included Serratia liquefaciens, Lactococcus garvieae, and Hafnia alvei, and so on. Among the positive smoke swabs, 84% (16/19) had one or more bacteria species that were consistent with the cultures of their corresponding tissue swabs. Using a surgical or N95 mask reduced the “infection rate” of the swab.

Conclusion.

“Surgical smoke” generated by electrocauterization of porcine spinal tissues contains viable bacteria. Further research in actual spine surgery is needed next.

Level of Evidence: N/A
Surgery-related Factors Do Not Affect Short-term Adjacent Segment Kinematics After Anterior Cervical Arthrodesis
Authors: Chen Stephen R. , LeVasseur Clarissa M. , Pitcairn Samuel , Kanter Adam S. , Okonkwo David O. , Shaw Jeremy D. , Donaldson William F. , Lee Joon Y. , Anderst William J.
Published: April 2021

Study Design.

Prospective cohort study.

Objective.

The aim of this study was to identify surgical factors that affect adjacent segment kinematics after anterior cervical discectomy and fusion (ACDF) as measured by biplane radiography.

Summary of Background Data.

Previous studies investigated the effect of surgical factors on spine kinematics as a potential etiology for adjacent segment disease (ASD). Those studies used static flexion-extension radiographs to evaluate range of motion. However, measurements from static radiographs are known to be unreliable. Furthermore, those studies were unable to evaluate the effect of ACDF on adjacent segment axial rotation.

Methods.

Patients had continuous cervical spine flexion/exten- sion and axial rotation movements captured at 30 images per second in a dynamic biplane radiography system preoperatively and 1 year after ACDF. Digitally reconstructed radiographs generated from subject-specific CT scans were matched to biplane radiographs using a previously validated tracking process. Dynamic kinematics, postoperative segmental kyphosis, and disc distraction were calculated from this tracking process. Plate-to-disc distance was measured on postoperative radiographs. Graft type was collected from the medical record. Multivariate linear regression was performed to identify surgical factors associated with 1-year post-surgery changes in adjacent segment kinematics. A secondary analysis was also performed to compare adjacent segment kinematics between each of the surgical factors and previously defined thresholds believed to be associated with adjacent segment degeneration.

Results.

Fifty-nine patients completed preoperative and postoperative testing. No association was found between any of the surgical factors and change in adjacent segment flexion/exten- sion or axial rotation range of motion (all P > 0.09). The secondary analysis also did not identify differences between adjacent segment kinematics and surgical factors (all P > 0.07).

Conclusion.

Following ACDF for cervical spondylosis, factors related to surgical technique were not associated with short-term changes in adjacent segment kinematics that reflect the hypermobility hypothesized to lead to the development of ASD.

Level of Evidence: 2
Examining the Bidirectional Association Between Body Esteem and Body Mass Index During Adolescence
Authors: Lamb Megan , Buchholz Annick , Gunnell Katie E. , Valois Darcie D. , Obeid Nicole , Henderson Katherine , Flament Martine , Goldfield Gary S.
Published: April 2021

Objective:

Research on body esteem (weight and appearance esteem) and weight suggests that having a positive body esteem may be associated with more stable weight trajectories during adolescence, and adolescents with higher weight report lower levels of body esteem. However, bidirectional relationships between body esteem and weight have not yet been examined. This 3-year longitudinal study examined (1) bidirectional relationships between body esteem and body mass index (BMI) and (2) how BMI and body esteem changed together throughout adolescence.

Methods:

Participants (N = 1163 adolescents, at time 1 [T1] baseline; 60.3% female) from a school-based community sample completed surveys approximately annually for 3 years.

Results:

Latent growth modeling revealed that (a) among boys and girls, appearance and weight esteem scores decreased over time, (b) higher initial BMI scores were associated with slower decreases in appearance esteem over time. However, evidence for bidirectionality was not found, in which baseline appearance and weight esteem did not predict changes in BMI over time and vice versa.

Conclusion:

Results suggest that changes in BMI and body esteem are co-occurring (rather than predictive) throughout adolescence. The decreasing trajectory of body esteem over time suggests the need for prevention efforts to improve body esteem throughout adolescence.
Importance of Family Connection for Healthy Weight Behaviors Amid Adverse Family Experiences and Behavioral Difficulties
Authors: Hayes Katey , Davis Angelia , Zlomke Kimberly , Fruh Sharon
Published: April 2021

Objective:

Adverse family experiences (AFEs), including parent divorce and domestic violence, negatively affect obesogenic behaviors and engagement in healthy weight behaviors (HWBs). The current study used a moderated mediation model to investigate the role of family connection in the relationship between AFEs and HWBs for children with behavioral difficulties.

Method:

Youth (6–17 years old; n = 13,921) from the 2016 National Survey of Children's Health data set were included in the study.

Results:

Family connection mediated the relationship between AFEs and each HWB. The models of physical activity and screen time had significant direct effects. Behavioral difficulties moderated the direct effect of AFEs and screen time and physical activity.

Conclusion:

Family connection mediated the relationships between each HWB and AFEs. The findings suggest that for children without behavioral difficulties, family connection was a stronger protective factor for adequate physical activity and decreased screen time.
The Role of Parents in Reducing Academic, Health, and Behavioral Problems for Native American, African American, and Latinx Adolescents
Authors: Bradley Robert H. , Bryce Crystal I.
Published: April 2021

Objective:

The aim of the study was to determine how parental modeling of thoughtful behavior and the home physical environment may reduce the number of developmental problems exhibited by Native American, African American, and Latinx adolescents.

Method:

Demographic and home environmental data were collected from 54 Native American, 131 African American, and 159 Latinx families living in 4 states as part of a home visit. Parents and adolescents were administered surveys that captured adolescent health, social skills, problem behavior, self-efficacy beliefs, vocabulary attainment, and school grades. Scores from the surveys were combined to construct both an adolescent problems index and a household risk index. For each of the 3 racial/ethnic groups examined, the adolescent problems index was regressed on parental modeling and encouragement of mature behavior, the home physical environment, and the household risk index.

Results:

Modeling and encouragement of mature behavior was a significant bivariate predictor of overall problems in all 3 groups of adolescents—albeit the overall regression model was nonsignificant for Native Americans. By contrast, the other 2 predictors were nonsignificant in regression models for all 3 groups.

Conclusion:

Native American, African American, and Latinx adolescents often face a multitude of risks, including poverty and discrimination. As a consequence, adolescents from these 3 racial/ethnic groups frequently display problems pertaining to health, competence, and adaptive behavior. The results from this study suggest that adolescents from such demographic groups are less likely to manifest developmental problems if their parents model mature behavior and encourage the adolescent to act in thoughtful ways.
Omega-3 Fatty Acid Supplementation in the Primary and Secondary Prevention of Cardiovascular Events
Authors: O'Connell Thomas F. , Trivax Justin , Franklin Barry A.
Published: April 2021

Omega-3 fatty acid (O-3FA) supplementation has garnered interest since cardioprotective properties of dietary fish consumption were observed. In the general population, O-3FA supplementation has not improved cardiovascular outcomes. However, icosapent ethyl, a high-dose, purified form of eicosapentaenoic acid, has demonstrated additive cardioprotection to statins in high-risk patients with elevated triglycerides.
Pink and Crusted Crateriform Nodule on the Arm
Authors: Park Ariel , Serabyn Cynthia
Published: April 2021

Teledermatology is a term to describe the provision of dermatological medical services through telecommunication technology. This is a teledermatology case of a pink and crusted crateriform nodule on the arm.
Guidelines for Management of Psoriasis
Authors: Ramos Vanessa L. , Van Voorhees Abby S.
Published: April 2021

Psoriasis is a common, inflammatory disease that can significantly impact patients' quality of life and well-being. In recent years, psoriasis has been found to be associated with several comorbidities including psoriatic arthritis, cardiovascular disease, metabolic conditions, mental health disorders, and other inflammatory disorders. This article reviews current literature about emerging comorbidities and provides screening recommendations based on available evidence in an effort to improve the overall management of psoriatic patients.
Increased alarm pheromone component is associated withNosema ceranaeinfected honeybee colonies
Authors: Mayack Christopher , Broadrup Robert L. , Schick Sassicaia J. , Eppley Elizabeth J. , Khan Zaeema , Macherone Anthony
Published: April 2021

Use of chemicals, such as alarm pheromones, for rapid communication with conspecifics is widespread throughout evolutionary history. Such chemicals are particularly important for social insects, such as the honeybee (Apis mellifera), because they are used for collective decision-making, coordinating activities and self-organization of the group. What is less understood is how these pheromones change due to an infection and what the implications might be for social communication. We used semiquantitative polymerase chain reaction (sqPCR) to screen for a common microsporidian gut parasite,Nosema ceranae, for 30 hives, across 10 different locations. We then used high-resolution accurate mass gas chromatography–quadrupole time of flight mass spectrometry to generate an exposome profile for each hive. Of the 2352 chemical features identified, chemicals associated with infection were filtered for cosanes or cosenes. A significant association was found betweenN. ceranaeand the presence of (Z)-11-eicosen-1-ol, a known alarm pheromone component. The increase in (Z)-11-eicosen-1-ol could be the recognition mechanism for healthy individuals to care for, kill, or quarantine infected nestmates.Nosema ceranaehas contributed to the global decline in bee health. Therefore, altered alarm pheromones might play a role in disrupting social harmony and have potential impacts on colony health.
Whole genome sequencing of a clinical drug resistant Candida albicans isolate reveals known and novel mutations in genes involved in resistance acquisition mechanisms
Authors: Khalaf Roy A. , Fattouh Nour , Medvecky Matej , Hrabak Jaroslav
Published: April 2021

Candida albicans is an opportunistic pathogen accounting for the majority of cases of Candida infections. Currently, C. albicans are developing resistance towards different classes of antifungal drugs and this has become a global health burden that does not spare Lebanon. This study aims at determining point mutations in genes known to be involved in resistance acquisition and correlating resistance to virulence and ergosterol content in the azole resistant C. albicans isolate CA77 from Lebanon. This pilot study is the first of its kind to be implemented in Lebanon. We carried out whole genome sequencing of the azole resistant C. albicans isolate CA77 and examined 18 genes involved in antifungal resistance. To correlate genotype to phenotype, we evaluated the virulence potential of this isolate by injecting it into BALB/c mice and we quantified membrane ergosterol. Whole genome sequencing revealed that eight out of 18 genes involved in antifungal resistance were mutated in previously reported and novel residues. These genotypic changes were associated with an increase in ergosterol content but no discrepancy in virulence potential was observed between our isolate and the susceptible C. albicans control strain SC5314. This suggests that antifungal resistance and virulence potential in this antifungal resistant isolate are not correlated and that resistance is a result of an increase in membrane ergosterol content and the occurrence of point mutations in genes involved in the ergosterol biosynthesis pathway.