bluuebunny/crossref_metadata_2025 huggingface dataset:
Two-dimensional simulations of internal gravity waves in the radiation zones of intermediate-mass stars
Authors: Ratnasingam R P , Edelmann P V F , Rogers T M
Published: July 2020

Intermediate-mass main-sequence stars have large radiative envelopes overlying convective cores. This configuration allows internal gravity waves (IGWs) generated at the convective–radiative interface to propagate towards the stellar surface. The signatures of these waves can be observed in the photometric and spectroscopic data from stars. We have studied the propagation of these IGWs using two-dimensional (2D) fully non-linear hydrodynamical simulations with realistic stellar reference states from the 1D stellar evolution code, Modules for Stellar Astrophysics (mesa). When a single wave is forced, we observe wave self-interaction. When two waves are forced, we observe non-linear interaction (i.e. triadic interaction) between these waves forming waves at different wavelengths and frequencies. When a spectrum of waves similar to that found in numerical simulations is forced, we find that the surface IGW frequency slope is consistent with recent observations. This power law is similar to that predicted by linear theory for the wave propagation, with small deviations that can be an effect of non-linearities. When the same generation spectrum is applied to 3 M⊙ models at different stellar rotation and ages, the surface IGW spectrum slope is very similar to the generation spectrum slope.
A library of self-consistent simulated exoplanet atmospheres
Authors: Goyal Jayesh M , Mayne Nathan , Drummond Benjamin , Sing David K , Hébrard Eric , Lewis Nikole , Tremblin Pascal , Phillips Mark W , Mikal-Evans Thomas , Wakeford Hannah R
Published: July 2020

We present a publicly available library of model atmospheres with radiative-convective equilibrium pressure–temperature (P-T) profiles fully consistent with equilibrium chemical abundances, and the corresponding emission and transmission spectrum with R ∼ 5000 at 0.2 µm decreasing to R ∼ 35 at 30 µm, for 89 hot Jupiter exoplanets, for four recirculation factors, six metallicities, and six C/O ratios. We find the choice of condensation process (local/rainout) alters the P-T profile and thereby the spectrum substantially, potentially detectable by James Webb Space Telescope. We find H− opacity can contribute to form a strong temperature inversion in ultrahot Jupiters for C/O ratios ≥ 1 and can make transmission spectra features flat in the optical, alongside altering the entire emission spectra. We highlight how adopting different model choices such as thermal ionization, opacities, line-wing profiles and the methodology of varying the C/O ratio, effects the P-T structure, and the spectrum. We show the role of Fe opacity to form primary/secondary inversion in the atmosphere. We use WASP-17b and WASP-121b as test cases to demonstrate the effect of grid parameters across their full range, while highlighting some important findings, concerning the overall atmospheric structure, chemical transition regimes, and their observables. Finally, we apply this library to the current transmission and emission spectra observations of WASP-121b, which shows H2O and tentative evidence for VO at the limb, and H2O emission feature indicative of inversion on the dayside, with very low energy redistribution, thereby demonstrating the applicability of library for planning and interpreting observations of transmission and emission spectrum.
Relevance of Higher-Order Epistasis in Drug Resistance
Authors: Lozovsky Elena R , Daniels Rachel F , Heffernan Gavin D , Jacobus David P , Hartl Daniel L
Published: July 2020

We studied five chemically distinct but related 1,3,5-triazine antifolates with regard to their effects on growth of a set of mutants in dihydrofolate reductase. The mutants comprise a combinatorially complete data set of all 16 possible combinations of four amino acid replacements associated with resistance to pyrimethamine in the malaria parasite Plasmodium falciparum. Pyrimethamine was a mainstay medication for malaria for many years, and it is still in use in intermittent treatment during pregnancy or as a partner drug in artemisinin combination therapy. Our goal was to investigate the extent to which the alleles yield similar adaptive topographies and patterns of epistasis across chemically related drugs. We find that the adaptive topographies are indeed similar with the same or closely related alleles being fixed in computer simulations of stepwise evolution. For all but one of the drugs the topography features at least one suboptimal fitness peak. Our data are consistent with earlier results indicating that third order and higher epistatic interactions appear to contribute only modestly to the overall adaptive topography, and they are largely conserved. In regard to drug development, our data suggest that higher-order interactions are likely to be of little value as an advisory tool in the choice of lead compounds.
A Comparison of Three Music Therapy Introduction Dialogues on Acceptance of Music Therapy Services by Patients in an Outpatient Cancer Center
Authors: Barck Leanne , McDougal Miller Dawn
Published: July 2020

Music therapy is not often well understood by patients with cancer; therefore, patients may be initially hesitant to accept music therapy services. The purpose of this study was to compare the effectiveness of three different scripts (described from here on as “introduction dialogues”) used to offer music therapy services to patients in an outpatient cancer center. Relationships between patient-reported anxiety levels, gender, and age with the acceptance rate of music therapy services were also examined. Patients (n = 59) were offered music therapy using one of three different introduction dialogues, asked to complete an anxiety Visual Analogue Scale (VAS), and provided with music therapy services if accepted. Results showed that introduction dialogue #2 (benefits of music therapy explained, including research) had the greatest acceptance rate. Moderate anxiety levels, males, and individuals 61+ years of age also showed greatest acceptance rates. A breakdown of different variables influencing patient response, limitations of the study, and future recommendations are also discussed.
A multiplexed bioluminescent reporter for sensitive and non-invasive tracking of DNA double strand break repair dynamics in vitro and in vivo
Authors: Chien Jasper Che-Yung , Tabet Elie , Pinkham Kelsey , da Hora Cintia Carla , Chang Jason Cheng-Yu , Lin Steven , Badr Christian E , Lai Charles Pin-Kuang
Published: July 2020

Tracking DNA double strand break (DSB) repair is paramount for the understanding and therapeutic development of various diseases including cancers. Herein, we describe a multiplexed bioluminescent repair reporter (BLRR) for non-invasive monitoring of DSB repair pathways in living cells and animals. The BLRR approach employs secreted Gaussia and Vargula luciferases to simultaneously detect homology-directed repair (HDR) and non-homologous end joining (NHEJ), respectively. BLRR data are consistent with next-generation sequencing results for reporting HDR (R2 = 0.9722) and NHEJ (R2 = 0.919) events. Moreover, BLRR analysis allows longitudinal tracking of HDR and NHEJ activities in cells, and enables detection of DSB repairs in xenografted tumours in vivo. Using the BLRR system, we observed a significant difference in the efficiency of CRISPR/Cas9-mediated editing with guide RNAs only 1–10 bp apart. Moreover, BLRR analysis detected altered dynamics for DSB repair induced by small-molecule modulators. Finally, we discovered HDR-suppressing functions of anticancer cardiac glycosides in human glioblastomas and glioma cancer stem-like cells via inhibition of DNA repair protein RAD51 homolog 1 (RAD51). The BLRR method provides a highly sensitive platform to simultaneously and longitudinally track HDR and NHEJ dynamics that is sufficiently versatile for elucidating the physiology and therapeutic development of DSB repair.
Synthetic circular miR-21 RNA decoys enhance tumor suppressor expression and impair tumor growth in mice
Authors: Müller Simon , Wedler Alice , Breuer Janina , Glaß Markus , Bley Nadine , Lederer Marcell , Haase Jacob , Misiak Claudia , Fuchs Tommy , Ottmann Alina , Schmachtel Tessa , Shalamova Lyudmila , Ewe Alexander , Aigner Achim , Rossbach Oliver , Hüttelmaier Stefan
Published: July 2020

Naturally occurring circular RNAs efficiently impair miRNA functions. Synthetic circular RNAs may thus serve as potent agents for miRNA inhibition. Their therapeutic effect critically relies on (i) the identification of optimal miRNA targets, (ii) the optimization of decoy structures and (iii) the development of efficient formulations for their use as drugs. In this study, we extensively explored the functional relevance of miR-21-5p in cancer cells. Analyses of cancer transcriptomes reveal that miR-21-5p is the by far most abundant miRNA in human cancers. Deletion of the MIR21 locus in cancer-derived cells identifies several direct and indirect miR-21-5p targets, including major tumor suppressors with prognostic value across cancers. To impair miR-21-5p activities, we evaluate synthetic, circular RNA decoys containing four repetitive binding elements. In cancer cells, these decoys efficiently elevate tumor suppressor expression and impair tumor cell vitality. For their in vivo delivery, we for the first time evaluate the formulation of decoys in polyethylenimine (PEI)-based nanoparticles. We demonstrate that PEI/decoy nanoparticles lead to a significant inhibition of tumor growth in a lung adenocarcinoma xenograft mouse model via the upregulation of tumor suppressor expression. These findings introduce nanoparticle-delivered circular miRNA decoys as a powerful potential therapeutic strategy in cancer treatment.
Integration of genetic and histopathology data in interpretation of kidney disease
Authors: Murray Susan L , Fennelly Neil K , Doyle Brendan , Lynch Sally Ann , Conlon Peter J
Published: July 2020

For many years renal biopsy has been the gold standard for diagnosis in many forms of kidney disease. It provides rapid, accurate and clinically useful information in most individuals with kidney disease. However, in recent years, other diagnostic modalities have become available that may provide more detailed and specific diagnostic information in addition to, or instead of, renal biopsy. Genomics is one of these modalities. Previously prohibitively expensive and time consuming, it is now increasingly available and practical in a clinical setting for the diagnosis of inherited kidney disease. Inherited kidney disease is a significant cause of kidney disease, in both the adult and paediatric populations. While individual inherited kidney diseases are rare, together they represent a significant burden of disease. Because of the heterogenicity of inherited kidney disease, diagnosis and management can be a challenge and often multiple diagnostic modalities are needed to arrive at a diagnosis. We present updates in genomic medicine for renal disease, how genetic testing integrates with our knowledge of renal histopathology and how the two modalities may interact to enhance patient care.
One-Year Efficacy and Incremental Cost-effectiveness of Contingency Management for Cigarette Smokers With Depression
Authors: González-Roz Alba , Weidberg Sara , García-Pérez Ángel , Martínez-Loredo Víctor , Secades-Villa Roberto
Published: July 2020

Introduction

Contingency management (CM) is efficacious for smoking cessation. To date, the number of cost-effectiveness evaluations of behavioral and pharmacological smoking cessation treatments far outnumbers the ones on CM. This study estimated 1-year efficacy and incremental cost-effectiveness of adding CM in relation to abstinence outcomes for a cognitive-behavioral therapy (CBT)+behavioral activation (BA) treatment.

Methods

The study sample comprised 120 smokers with depression (% females: 70.8%; mean age: 51.67 [SD = 9.59]) enrolled in an 8-week randomized controlled clinical trial. Clinical effectiveness variables were point-prevalence abstinence, continuous abstinence, longest duration of abstinence (LDA), and Beck-Depression Inventory-II (BDI-II) scores at 1-year follow-up. Cost-effectiveness analyses were based on resource utilization, unit costs per patient, and incremental cost per additional LDA week at 1 year.

Results

There was a significant effect of time by treatment group interaction, which indicated superior effects of CBT+BA+CM across time. Point-prevalence abstinence (53.3% [32/60]) was superior in participants receiving CBT+BA+CM compared with those in CBT+BA (23.3% [14/60]), but both groups were equally likely to present sustained reductions in depression. The average cost per patient was €208.85 (US$236.57) for CBT+BA and €410.64 (US$465.14) for CBT+BA+CM, p < .001. The incremental cost of using CM to enhance 1-year abstinence by one extra LDA week was €18 (US$20.39) (95% confidence interval: 17.75–18.25).

Conclusions

Behavioral treatments addressing both smoking and depression are efficacious for sustaining high quit rates at 1 year. Adding CM to CBT+BA for smoking cessation is highly cost-effective, with an estimated net benefit of €4704 (US$5344.80).

Implications

Informing on the cost-effectiveness of CM might expedite the translation of research findings into clinical practice. Findings suggested that CM is feasible and highly cost-effective, confirming that its implementation is worthwhile. At a CM cost per patient of €410.64 (US$465.14), the net benefit equals €4704 (US$5344.80), although even starting from a minimum investment of €20 (US$22.72) was cost-effective.

ClinicalTrials-gov Identifier

NCT03163056.
Mixed occupational and iatrogenic allergic contact dermatitis in a hairdresser
Authors: Koblinski J E , Hamann D
Published: July 2020

Allergic contact dermatitis (ACD) is a common occupational disease. Hairdressers and beauticians are at increased risk of occupational chronic hand eczema. We present a case of mixed occupational, non-occupational and iatrogenic ACD in a hairdresser which illustrates that delayed diagnosis can result in high morbidity, and unnecessary treatment and cost. A hairdresser with chronic hand and facial eczema failed medical management with topical steroids and dupilumab. Patch testing revealed contact allergy to multiple occupational exposures, home exposures and topical medicaments.
Diffuse Idiopathic calcinosis cutis: a case report in a 13-year-old Syrian boy
Authors: Tawekji Talha , Abdul-Baki Mohammad-Nasan , Dhemesh Yaseen , Douri Thaer
Published: July 2020

Calcinosis cutis is characterized by the deposition of calcium salts in the skin and subcutaneous tissue. It is divided into the following subtypes: dystrophic, metastatic, iatrogenic, idiopathic and calciphylaxis. In this case, we report a 13-year-old Syrian boy with idiopathic calcinosis cutis, the lesions were unusually widespread, unlike the common condition which is usually localized to one area. The case was unrelated to any systemic or local disorders, and the patient had no complications, so no treatment was planned.

As the best of our knowledge, there are very few cases of diffuse or widespread idiopathic calcinosis cutis. We analyzed the clinical, laboratory, radiographical and pathological characteristics of our patient, which helped us to reach the final diagnosis. We will discuss the pathogenesis, investigation and management of this disease.
A recessive case of Thévenard’s disease, aka. ulcero-mutilating acropathology syndrome with hypodontia
Authors: Turk Tarek , Haitham Al Husseini M H D , Al Assil Houda
Published: July 2020

Thévenard’s disease, aka. ulcero-mutilating acropathology syndrome, is a rare hereditary disorder. In this report, we describe the case of a 6-year old patient with deep, non-healing ulcers on her lower extremities that progressed to spontaneous mutilation of her toes and distal phalanges. In this case, seldom-reported features were encountered such as hands’ involvement, absence of family history and congenital absence of teeth eruption. Diagnosing this case can be challenging due to the rarity of the disease. Early detection and appropriate approach help to better-control complications and further-delay disability, especially that no cure has been identified for this case yet. Therefore, it is vital to keep this syndrome as part of a deferential diagnosis when approaching patients with similar symptoms. It is also important to emphasize that regular examinations and rapid response to new lesions are crucial and should be combined with education and support to patients and their families.
The VvSUPERMAN-like Gene Is Differentially Expressed between Bicarpellate and Tricarpellate Florets of Vitis vinifera L. Cv. ‘Xiangfei’ and Its Heterologous Expression Reduces Carpel Number in Tomato
Authors: Liang Jinjun , Guan Pingyin , Liu Zhenhua , Wang Yan , Xing Jiayi , Hu Jianfang
Published: July 2020

Multicarpellate fruits are larger and produce more seeds than mono- or bicarpellate fruits, enhancing the reproductive capacity of the plant. To identify the phenotypic and molecular differences among florets of different carpel types, we studied carpel formation and fusion in the grapevine (Vitis vinifera) cultivar ‘Xiangfei’, which produces a high proportion of multicarpellate fruit. We also determined the function of VvSUPERMAN-like (VvSUP-like) and explored its relationship with VvWUS (VvWUSCHEL) and VvAG1 (VvAGAMOUS), which is related to the formation of carpel primordia. We showed that carpel formation and fusion were largely consistent between bicarpellate and tricarpellate ovaries, which both involve congenital fusion; rather, the differences between these ovary types arose from variation in carpel primordia number and location. Transgenic tomato (Solanum lycopersicum) plants expressing VvSUP-like produced significantly fewer carpels and other floral organs than the wild type. Moreover, transcriptome sequencing results indicate that VvSUP-like was more highly expressed in bicarpellate than in tricarpellate ‘Xiangfei’ florets. Luciferase reporter assays indicated that VvSUP-like inhibits the expression of VvAG1 and VvWUS by directly binding to their promoters, and VvWUS promotes VvAG1 expression by directly binding to its promoter. VvSUP-like inhibits the feedback signaling between VvWUS and VvAG1. Together, these results suggest that VvSUP-like negatively regulates the number of carpels that develop by inhibiting VvAG1 and VvWUS expression.
Evaluation of warm season annual forages for forage yield and quality in the north-central United States
Authors: Bleier Jonathan S , Coblentz Wayne K , Kalscheur Kenneth F , Panke-Buisse Kevin , Brink Geoffrey E
Published: July 2020

Grazing-based dairy operations require productive, high-quality forages capable of supporting the nutritional needs of mid-lactation dairy cows. Our objectives were to evaluate primary and regrowth harvests of two cultivars of sudangrass (SU), sorghum-sudangrass (S×SU), and pearl millet (PM) forages for growth and nutritive characteristics within the specific context of suitability for grazing by dairy cows. Three harvest cycles, including primary and regrowth cycles in 2016, and a single harvest cycle of primary growth in 2017, were evaluated at two locations (Prairie du Sac and Marshfield, WI). Within each cycle, sampling was initiated when canopy height was about 41 cm and continued thereafter on weekly intervals for 5 weeks, resulting in six equally spaced sampling dates per harvest cycle. Data were analyzed as a split-plot design with cultivars (6) as whole-plots arranged in randomized complete blocks and weekly harvest dates (6) as subplots. Yields of dry matter (DM) were less consistent at the more northern location (Marshfield), which is known for its heavier, poorly drained soils. Despite locational differences, the taller-growing cultivar within each forage type frequently exhibited yield advantages over dwarf or shorter-growing cultivars; this occurred for 7 of 9 intra-forage-type comparisons (P ≤ 0.021) across three harvest cycles at Prairie du Sac, and for 6 of 9 similar comparisons (P ≤ 0.032) at Marshfield. In 2016, shorter-growing cultivars had greater percentages of leaf in 4 of 6 intra-forage-type comparisons at both locations (P ≤ 0.004), which is especially relevant for grazing. Similarly, PM cultivars exhibited shorter canopy heights (P ≤ 0.002), but greater percentages of leaf (P < 0.001), than all other cultivars during all harvest cycles at both locations. However, the greater leaf percentages exhibited by PM cultivars did not translate into reduced percentages of structural plant fiber (asNDFom) on a whole-plant basis during any harvest cycle at either location; furthermore, asNDFom concentrations for PM cultivars were greater (P ≤ 0.047) than observed for other cultivars within 3 of 6 harvest cycles across both locations. Ruminal in-situ degradation of asNDFom for whole-plant forages based on a 48-h incubation was significantly greater (P ≤ 0.006) for PM compared with other cultivars in 4 of 6 harvest cycles. Pearl millet cultivars generally exhibited more suitable characteristics for grazing livestock than SU or S×SU cultivars.
Development of a DNA-Based Real-Time PCR Assay To Quantify Allorhizobium vitis Over Time in Grapevine (Vitis vinifera L.) Plantlets
Authors: Nguyen-Huu Trong , Doré Jeanne , Aït Barka Essaïd , Lavire Céline , Clément Christophe , Vial Ludovic , Sanchez Lisa
Published: July 2020

Allorhizobium vitis is the primary causal pathogen of grapevine crown gall disease. Because this endophytic bacterium can survive as a systemic latent (symptomless) infection in grapevine, detecting and monitoring its development in planta is of great importance. In plant bacteria studies, plate counting is routinely used as a simple and reliable method to evaluate the bacterial population level in planta. However, isolation techniques are time-consuming and present some disadvantages such as the risk of contamination and the need for fresh samples for research. In this study, we developed a DNA-based real-time PCR assay that can replace the classical method to monitor the development of Allorhizobium vitis in grapevine plantlets. Primers targeting Allorhizobium vitis chromosomic genes and the virulent tumor-inducing plasmid were validated. The proposed quantitative real-time PCR technique is highly reliable and reproducible to assess Allorhizobium vitis numeration at the earliest stage of infection until tumor development in grapevine plantlets. Moreover, this low-cost technique provides rapid and robust in planta quantification of the pathogen and is suitable for fundamental research to monitor bacterial development over time.
Retrocalcaneal Spur Removal and Achilles Tendon Reattachment for the Treatment of Haglund Deformity
Authors: Akoh Craig C. , DeOrio James K.
Published: July 2020

Insertional Achilles tendinopathy frequently involves intratendinous calcification of the Achilles tendon insertion and a prominent superolateral calcaneus tuberosity known as a Haglund’s deformity. The incidence of insertional Achilles tendinopathy is up to 30%, affecting both recreational and elite athletes. The indications for surgical treatment of insertional Achilles tendinopathy is appropriate when a patient’s symptoms are recalcitrant to nonoperative therapies. Advancements in surgical treatment include the utilization of the midline longitudinal incision, improved soft tissue handling, and minimizing the detachment of the Achilles tendon insertion during surgery. Surgical treatment includes removal of the Haglund’s deformity, debridement of the Achilles insertion, and bone to tendon repair utilizing a double-row suture anchor construct. The authors are presenting a unique surgical technique for Haglund’s deformity excision, Achilles debridement, and repair without flexor hallucis longus augmentation.

Level of Evidence: Diagnostic Level V. See Instructions for Authors for a complete description of levels of evidence.
Tibialis Anterior Tendon Partial Release and Plantar Implant Placement for Midfoot Arthrodesis: Technique Tip
Authors: Fraser Tyler , Miles Daniel T. , Doty Jesse
Published: July 2020

Midfoot arthrodesis is generally a reliable and commonly performed operative procedure for deformity correction and pain relief. Biomechanical studies suggest the superior strength of plantar-based plates compared with traditional dorsally placed plates and screws. Multiple structures must be considered when accessing the medial column on the plantar surface, including the saphenous neurovascular bundle and the tibialis anterior tendon insertional footprint. Some skeptics are concerned over possible tibialis tendon rupture after placing plantar-based plates. This novel technique demonstrates the ability to safely apply for plantar plates with no tibialis anterior ruptures.

Level of Evidence: Diagnostic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Increasing Tuberculosis Rates and Association With Migration in Children Living in Campania Region, Southern Italy: A 10-Year Cohort Study
Authors: Lo Vecchio Andrea , Smarrazzo Andrea , Amato Chiara , Palladino Raffaele , Scarano Sara Maria , Spagnuolo Maria Immacolata , Bruzzese Eugenia , Guarino Alfredo
Published: July 2020

Background:

Italy is classified as a low tuberculosis (TB) incidence country (rate 6.5/100,000 inhabitants). However, the Campania Region Pediatric Reference Centre (CRRC) observed an increase in TB, contemporarily with a rise in migration.

Our aim was to investigate trends in TB notification rates, association with migration, and changes in clinical outcomes of children living in Campania.

Methods:

We conducted a prospective cohort study (January 1, 2009–December 31, 2018), including children <18 years who received diagnosis of TB at the CRRC. Yearly crude TB incidence rates and relative confidence interval (95% CI) were calculated. Two main outcome measures were considered: loss to follow-up and poor clinical outcome, including prolonged or second-line treatment, sequelae, or death.

Results:

Overall 146 children (52.1% male; median age, 50 months; interquartile range, 96.33) received a diagnosis of TB. TB incidence rates increased from 0.44 cases (95% CI: 0.16–0.97) per 100,000 inhabitants <18 years of age in 2009 to 1.84 cases (95% CI: 1.15–2.79) in 2018 (P < 0.05) and linearly correlated with the rate of migrants (R2 = 0.9272; P < 0.0001). Ziehl-Neelsen-positive children had an increased likelihood of poor clinical outcomes (odds ratio, 4.83; 95% CI: 1.28–18.2; P = 0.020). Compared with Italians, foreign children showed a lower likelihood of cure without sequelae (49.3% versus 67.9%; P < 0.001; odds ratio, 0.45; 95% CI: 0.23–0.89; P = 0.02). They accounted for all fatal cases and loss to follow-up.

Conclusion:

Pediatric TB rate in Campania increased in the last 10 years in association with the increase in migration. Emphasizing national TB rates may disregard important differences in local infection trends and limit medical awareness about TB. Foreign children may need tailored management programs.
Surgical Treatment of Combined ACL, PCL, and Lateral Side Injuries
Authors: Stannard James P. , Stannard James T. , Cook James L.
Published: July 2020

A knee dislocation that involves at least 2 of the 4 major ligament groups—such as the anterior cruciate ligament, the posterior cruciate ligament, or the posterolateral corner—is a catastrophic event for an athlete or trauma patient. Careful evaluation of these patients is needed to avoid disastrous outcomes. Surgeons must be cognizant of a number of key treatment concerns—such as tunnel crowding, controversies over graft fixation methods, and sparsity of level I clinical data—to make proper ligament repair decisions. This manuscript will review treatment principles that govern high-quality care of this complex injury.
The Southern Diet
Authors: Pucciarelli Deanna
Published: July 2020

Cultural considerations of food consider the way people evaluate regional foodstuffs both by the residents of the region and from those outside. The Southern diet has been studied by historians, health professionals, and independent scholars in myriad approaches to the topic. Eating Southern has been criticized and demonized as unhealthy because people who live in the region have some of the highest rates of chronic disease in the United States. Health professionals across the spectrum design food consumption behavioral programs to alter eating patterns. Particular attention is given to African Americans' food consumption patterns dating back to the turn of the 20th century when food scarcity was rampant. The current situation involves food insecurity with excess kilocalories intake. Not the primary determinant of the so-called Southern diet to the health problems of the region; rather, poverty and inequality have a far greater impact on the health and wellness in the South, or elsewhere.
Risk Factors for Peri-Intubation Cardiac Arrest in Pediatric Cardiac Intensive Care Patients: A Multicenter Study*
Authors: Esangbedo Ivie D. , Byrnes Jonathan , Brandewie Katie , Ebraheem Mohammad , Yu Priscilla , Zhang Song , Raymond Tia
Published: July 2020

Objectives:

Endotracheal intubation is associated with hemodynamic adverse events, including cardiac arrest, especially in patients with cardiac disease. There are only a few studies that have evaluated the rate of and risk factors for endotracheal intubation hemodynamic complications in critically ill pediatric patients. Although some of these studies have assessed hemodynamic complications during intubation in pediatric cardiac patients, the frequency of and risk factors for peri-intubation cardiac arrest have not been adequately described in high acuity cardiac patients. This study aims to describe the frequency of and risk factors for peri-intubation cardiac arrest in critically ill pediatric cardiac patients admitted to specialized cardiac ICUs.

Design:

Multicenter retrospective cohort study.

Setting:

Three pediatric cardiac ICUs in the United States.

Patients:

Critically ill pediatric patients with congenital or acquired heart disease requiring endotracheal intubation.

Interventions:

None.

Measurements and Main Results:

Endotracheal intubations performed in three cardiac ICUs between January 2015 and December 2017 were reviewed. Clinical variables—including data on patients, clinical providers, and procedure—were evaluated for their association with peri-intubation cardiac arrest. There was a total of 186 intubation events studied, occurring in 151 individual (index) patients. The rates of peri-intubation cardiac arrest and peri-intubation mortality in this cohort were 7% and 1.6%, respectively. Among those patients with moderate or severe systolic dysfunction of the systemic ventricle, peri-intubation cardiac arrest rate was 20.7%. Statistically significant risk factors for peri-intubation cardiac arrest included: significant systolic dysfunction of the systemic ventricle, pre-intubation hypotension, pre-intubation lactate elevation, lower pre-intubation pH, and documented oxygen desaturations (> 10%) during intubation procedure.

Conclusions:

Our most significant finding was a peri-intubation cardiac arrest rate which was much higher than previously published rates for both cardiac and noncardiac children who underwent endotracheal intubation in ICUs. Peri-intubation mortality was also high in our cohort. Regarding risk factors for peri-intubation arrest, significant systolic dysfunction of the systemic ventricle was strongly associated with cardiac arrest in this cohort.
Prevotella vespertina sp. nov., isolated from an abscess of a hospital patient
Authors: Buhl Michael , Marschal Matthias
Published: July 2020

A strain of an obligately anaerobic, Gram-stain-negative rod-shaped bacterium is described by phenotypical, biochemical and genotypical characterization. This strain A2879T was isolated from an abscess swab of a patient sampled during routine care at hospital. Phylogenetic analyses (full-length 16S rRNA gene and whole-genome sequence) revealed the strain to belong to the genus

Prevotella

, but to be distant from recognized species, with the closest relationship to

Prevotella veroralis

. Unambiguous identification also proved possible by MALDI-TOF MS. The genomic DNA G+C content was 41.5 mol%. Strain A2879T was moderately saccharolytic and proteolytic. The most abundant cellular long-chain fatty acids were anteiso-C15 : 0 and iso-C15 : 0. In view of these data, strain A2879T is considered to represent a novel species within the genus

Prevotella

, for which the name Prevotella vespertina sp. nov. is proposed. The type strain is A2879T (=DSM 108027T=CCOS 1233T=CCUG72808T). As this strain has been isolated from a clinical sample, it is considered relevant for human medicine and health in general, and in particular for the fields of clinical microbiology and infectious diseases. This description will enable routine and research laboratories alike to easily identify the novel taxon, allowing its role in the context of human health and disease or microbiota to be further elucidated.
Viral interactions with non-homologous end-joining: a game of hide-and-seek
Authors: Hristova Dayana B. , Lauer Katharina B. , Ferguson Brian J.
Published: July 2020

There are extensive interactions between viruses and the host DNA damage response (DDR) machinery. The outcome of these interactions includes not only direct effects on viral nucleic acids and genome replication, but also the activation of host stress response signalling pathways that can have further, indirect effects on viral life cycles. The non-homologous end-joining (NHEJ) pathway is responsible for the rapid and imprecise repair of DNA double-stranded breaks in the nucleus that would otherwise be highly toxic. Whilst directly repairing DNA, components of the NHEJ machinery, in particular the DNA-dependent protein kinase (DNA-PK), can activate a raft of downstream signalling events that activate antiviral, cell cycle checkpoint and apoptosis pathways. This combination of possible outcomes results in NHEJ being pro- or antiviral depending on the infection. In this review we will describe the broad range of interactions between NHEJ components and viruses and their consequences for both host and pathogen.
Single-Cell Transcriptomics Identifies Dysregulated Metabolic Programs of Aging Alveolar Progenitor Cells in Lung Fibrosis
Authors: Liang Jiurong , Huang Guanling , Liu Xue , Taghavifar Forough , Liu Ningshan , Yao Changfu , Deng Nan , Wang Yizhou , Burman Ankita , Xie Ting , Rowan Simon , Chen Peter , Hogaboam Cory , Stripp Barry , Weigt S. Samuel , Belperio John , Parks William C. , Noble Paul W. , Jiang Dianhua
Published: July 2020

Aging is a critical risk factor in progressive lung fibrotic diseases such as idiopathic pulmonary fibrosis (IPF). Loss of integrity of type 2 alveolar epithelial cells (AEC2s) is the main causal event in the pathogenesis of IPF. To systematically examine the genomic program changes of AEC2s with aging and lung injury, we performed unbiased single cell RNA-seq analyses of lung epithelial cells from either uninjured or bleomycin-injured young and old mice. Major lung epithelial cell types were readily identified with canonical cell markers in our dataset. Heterogenecity of AEC2s was apparent, and AEC2s were then classified into three subsets according to their gene signatures. Genes related to lipid metabolism and glycolysis were significantly altered within these three clusters of AEC2s, and also affected by aging and lung injury. Importantly, IPF AEC2s showed similar genomic programming and metabolic changes as that of AEC2s from bleomycin injured old mouse lungs relative to controls. Furthermore, perturbation of both lipid metabolism and glycolysis significantly changed progenitor renewal capacity in 3-Demensional organoid culture of AEC2s. Taken togather, this work identified metabolic defects of AEC2s in aging and during lung injury. Strategies to rectify these altered programs would promote AEC2 renewal which in turn improves lung repair.

One sentence summary

Metabolic defects of alveolar progenitors in aging and during lung injury impair their renewal.
Endoplasmic reticulum visits highly active spines and prevents runaway potentiation of synapses
Authors: Perez-Alvarez Alberto , Yin Shuting , Schulze Christian , Hammer John A. , Wagner Wolfgang , Oertner Thomas G.
Published: July 2020

In hippocampal pyramidal cells, a small subset of dendritic spines contain endoplasmic reticulum (ER). In large spines, ER frequently forms aspine apparatus, while smaller spines contain just a single tubule of smooth ER. Here we show that the ER visits dendritic spines in a non-random manner, targeting spines during periods of high synaptic activity. When we blocked ER motility using a dominant negative approach against myosin V, spine synapses became stronger compared to controls. We were not able to further potentiate these maxed-out synapses, but LTD was readily induced by low-frequency stimulation. We conclude that the brief ER visits to active spines have the important function of preventing runaway potentiation of individual spine synapses, keeping most of them at an intermediate strength level from which both LTP and LTD are possible.
No SARS-CoV-2 cross-neutralization by intravenous immunoglobulins produced from plasma collected before the 2020 pandemic
Authors: Schwaiger Julia , Karbiener Michael , Aberham Claudia , Farcet Maria R. , Kreil Thomas R.
Published: July 2020

The 2020 SARS-CoV-2 pandemic is caused by a zoonotic coronavirus transmitted to humans, similar to earlier events. Whether the other, seasonally circulating coronaviruses induce cross-reactive, potentially even cross-neutralizing antibodies to the new species in humans is unclear. The question is of particular relevance for people with immune deficiencies, as their health depends on treatment with immunoglobulin preparations that need to contain neutralizing antibodies against the pathogens in their environment. Testing 54 IVIG preparations, produced from plasma collected in Europe and the US, highly potent neutralization of a seasonal coronavirus was confirmed, yet no cross-neutralization of the new SARS-CoV-2 was seen.

IVIG products manufactured from pre-pandemic plasma do not neutralize SARS-CoV-2 but contain high neutralizing titers for seasonal coronavirus hCoV-229E.
Why do pathway methods work better than they should?
Authors: Szalai Bence , Saez-Rodriguez Julio
Published: July 2020

Different pathway analysis methods are frequently applied to cancer gene expression data to identify dysregulated pathways. In most cases these methods infer pathway activity changes based on the gene expression of pathway members. However, pathways are constituted by signaling proteins, and their activity - not their abundance - defines the activity of the pathway; the association between gene expression and protein activity is in turn limited and not well characterised. Other methods infer pathway activity from the expression of the genes whose transcription is regulated by the pathway of interest, which seems a more adequate proxy of activity. Despite these potential limitations, membership based pathway methods are frequently used and often provide statistically significant results.

Here, we submit that pathway based methods are not effective because of the correlation between the gene expression of pathway members and the activity of the pathway, but because pathway member gene sets overlap with the genes regulated by transcription factors (regulons). This implies that pathway methods do not inform about the activity of the pathway of interest, but instead the downstream effects of changes in the activities of transcription factors.

To support our hypothesis, we show that the higher the overlap to transcription factor regulons, the higher the information value of pathway gene sets. Furthermore, removing these overlapping genes reduces the information content of pathway gene sets, but not vice versa. Our results suggest that results of classical pathway analysis methods should be interpreted with caution, and instead methods using pathway regulated genes for activity inference should be prioritised.

Graphical abstract
Direct Antimicrobial Resistance Prediction from clinical MALDI-TOF mass spectra using Machine Learning
Authors: Weis Caroline , Cuénod Aline , Rieck Bastian , Llinares-López Felipe , Dubuis Olivier , Graf Susanne , Lang Claudia , Oberle Michael , Brackmann Maximilian , Søgaard Kirstine K. , Osthoff Michael , Borgwardt Karsten , Egli Adrian
Published: July 2020

Early administration of effective antimicrobial treatments is critical for the outcome of infections. Antimicrobial resistance testing enables the selection of optimal antibiotic treatments, but current culture-based techniques take up to 72 hours. We have developed a novel machine learning approach to predict antimicrobial resistance directly from MALDI-TOF mass spectra profiles of clinical samples. We trained calibrated classifiers on a newly-created publicly available database of mass spectra profiles from clinically most relevant isolates with linked antimicrobial susceptibility phenotypes. The dataset combines more than 300,000 mass spectra with more than 750,000 antimicrobial resistance phenotypes from four medical institutions. Validation against a panel of clinically important pathogens, includingStaphylococcus aureus,Escherichia coli, andKlebsiella pneumoniae, resulting in AUROC values of 0.8, 0.74, and 0.74 respectively, demonstrated the potential of using machine learning to substantially accelerate antimicrobial resistance determination and change of clinical management. Furthermore, a retrospective clinical case study found that implementation of this approach would have resulted in a beneficial change in the clinical treatment in 88% (8/9) of cases. MALDI-TOF mass spectra based machine learning may thus be an important new tool for antibiotic stewardship.
Targeted downregulation of estradiol binding Na+/H+exchangernhx-2,mimics calorie restriction, extends reproductive longevity and ameliorates effects associated with alpha synuclein aggregation inC. elegans
Authors: Shukla Shikha , Kumar Lalit , Sarkar Arunabh , Srividya Kottapalli , Nazir Aamir
Published: July 2020

Setting in of reproductive senescence (RS) gives rise to several changes, making aged individuals susceptible to multiple disorders including neurodegenerative diseases, cardiovascular ailments and bone disorders amongst others. The present study, employing transgenicC. elegansthat expresses ‘human’ alpha synuclein, endeavors to decipher the association of reproductive senescence with age-associated neurodegenerative diseases and behavioral ageing, under normal conditions and after being probed with estradiol. We carried out RNAi induced silencing of a subset of 22 genes that are known to delay RS, followed by studies on alpha-Synuclein aggregation and associated effects. These studies led us to functional characterization of the Na+/H+exchanger;nhx-2, expressed exclusively in gut. We found that RNAi ofnhx-2not only ameliorates the effects associated with alpha-Synuclein aggregation, but it also attunes effects related to behavioral aging including that of reproductive health-span and neuroprotection via mimicking dietary restriction, as it alters food absorption from the gut. We further elucidated that these effects are Sir-2.1 driven asnhx-2knock out did not delay reproductive senescence in knock down condition ofsir-2.1.To substantiate our findings, we performed whole transcriptome analysis innhx-2mutant strain. Our data revealed differential expression of 61 out of 62 hallmark genes of CR described by GenDR, in knock out condition ofnhx-2.As estradiol plays a central role in both reproductive health as well as neuronal health, we subjected worms to exogenous estradiol treatment and observed that it led to elevated levels ofnhx-2. Studies on structural binding analysis demonstrated significant binding potential of estradiol receptor NHR-14 withnhx-2gene and ChIP analysis revealed that estradiol treatment gives rise to enhanced NHX-2 levels through inducing the promoter specific histone H3 acetylation (H3K9) and lysine methylation (H3K4me3). These studies identifynhx-2as an important modulator that extends reproductive longevity and ameliorates effects associated with alpha synuclein aggregation inC elegans.

Graphical abstract

HIGHLIGHTS

Silencing of sodium proton antiporternhx-2affords neuroprotection and ameliorates effects associated with alpha-Synuclein aggregation via mimicking dietary restriction inC. elegans.

Exogenous 17-β-Estradiol treatment induces the expression ofnhx-2,through inducing the promoter specific histone H3 acetylation (H3K9) and lysine methylation (H3K4me3).

Effects associated withnhx-2,including prolonged reproductive span and neuroprotective effects, are SIR-2.1 driven.

nhx-2silencing decreases alpha-Synuclein aggregation, however; estradiol mediated overexpression above the endogenous levels, does not amend the aggregation any further.
Cross-reactivity of SARS-CoV structural protein antibodies against SARS-CoV-2
Authors: Bates Timothy A. , Weinstein Jules B. , Farley Scotland E. , Leier Hans C. , Messer William B. , Tafesse Fikadu G.
Published: July 2020

There is currently a lack of biological tools to study the replication cycle and pathogenesis of SARS-CoV-2, the etiological agent of COVID-19. Repurposing the existing tools, including antibodies of SARS-CoV, is an effective way to accelerate the development of therapeutics for COVID-19. Here, we extensively characterized antibodies of the SARS-CoV structural proteins for their cross-reactivity, experimental utility, and neutralization of SARS-CoV-2. We assessed a total of 10 antibodies (six for Spike, two for Membrane, and one for Nucleocapsid and Envelope viral protein). We evaluated the utility of these antibodies against SARS-CoV-2 in a variety of assays, including immunofluorescence, ELISA, biolayer interferometry, western blots, and micro-neutralization. Remarkably, a high proportion of the antibodies we tested showed cross-reactivity, indicating a potentially generalizable theme of cross-reactivity between SARS-CoV and SARS-CoV-2 antibodies. These antibodies should help facilitate further research into SARS-CoV-2 basic biology. Moreover, our study provides critical information about the propensity of SARS-CoV antibodies to cross-react with SARS-CoV-2 and highlights its relevance in defining the clinical significance of such antibodies to improve testing and guide the development of novel vaccines and therapeutics.