bluuebunny/crossref_metadata_2025 huggingface dataset:
Praja1 RING‐finger E3 ubiquitin ligase suppresses neuronal cytoplasmic TDP‐43 aggregate formation
Authors: Watabe Kazuhiko , Kato Yoichiro , Sakuma Miho , Murata Makiko , Niida‐Kawaguchi Motoko , Takemura Taro , Hanagata Nobutaka , Tada Mari , Kakita Akiyoshi , Shibata Noriyuki
Published: July 2020

Transactivation response DNA‐binding protein of 43 kDa (TDP‐43) is a major constituent of cytoplasmic aggregates in neuronal and glial cells in cases of amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). We have previously shown neuronal cytoplasmic aggregate formation induced by recombinant adenoviruses expressing human wild‐type and C‐terminal fragment (CTF) TDP‐43 under the condition of proteasome inhibition in vitro and in vivo. In the present study, we demonstrated that the formation of the adenoviral TDP‐43 aggregates was markedly suppressed in rat neural stem cell‐derived neuronal cells by co‐infection of an adenovirus expressing heat shock transcription factor 1 (HSF1), a master regulator of heat shock response. We performed DNA microarray analysis and searched several candidate molecules, located downstream of HSF1, which counteract TDP‐43 aggregate formation. Among these, we identified Praja 1 RING‐finger E3 ubiquitin ligase (PJA1) as a suppressor of phosphorylation and aggregate formation of TDP‐43. Co‐immunoprecipitation assay revealed that PJA1 binds to CTF TDP‐43 and the E2‐conjugating enzyme UBE2E3. PJA1 also suppressed formation of cytoplasmic phosphorylated TDP‐43 aggregates in mouse facial motor neurons in vivo. Furthermore, phosphorylated TDP‐43 aggregates were detected in PJA1‐immunoreactive human ALS motor neurons. These results indicate that PJA1 is one of the principal E3 ubiquitin ligases for TDP‐43 to counteract its aggregation propensity and could be a potential therapeutic target for ALS and FTLD.
An accountability evaluation for the responsible use of celebrity endorsement by the food and beverage industry to promote healthy food environments for young Americans: A narrative review to inform obesity prevention policy
Authors: Zhou Mi , Rincón‐Gallardo Patiño Sofia , Hedrick Valisa E. , Kraak Vivica I.
Published: July 2020

Research has shown that celebrity endorsement is a marketing strategy primarily used to promote highly processed food and beverage products to children and adolescents, which negatively influences their diet quality and increases their risks of obesity. This study conducted an accountability evaluation to examine government, expert, and industry policies, guidelines, recommendations, and practices regarding using celebrity endorsement to support healthy marketing environment for young Americans. This study used the National Academy of Medicine's LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) to identify and synthesize relevant evidence between January 2000 and December 2019. We categorized the evidence in a five‐step accountability framework and assigned each step a progress score (i.e., none, limited, some, and extensive). The findings showed that the US government made no progress to appoint an independent empowered body to evaluate celebrity endorsement practices. Stakeholders made some progress to take and hold industry and government to account and limited progress to share the account and to strengthen accountability structures. We suggest actions for diverse stakeholders to substantially strengthen accountability structures to ensure that celebrity endorsement is used to promote only healthy food environments to reduce obesity risks for young Americans.
TightRope vs Clavicular Hook Plate for Rockwood III–V Acromioclavicular Dislocations: A Meta‐Analysis
Authors: Pan Xin , Lv Rui‐yan , Lv Ming‐gang , Zhang Da‐guang
Published: July 2020

Objective

To assess and compare the clinical outcomes and complications of TightRope® fixation vs hook plate fixation for the treatment of Rockwood III‐VI Acromioclavicular joint (ACJ) dislocations.

Methods

Relevant studies were identified by searching PubMed, Embase, and Web of Science databases, from their inception to 12 April, 2019. The main outcomes of interest included Constant Score, University of California Los Angeles (UCLA) Shoulder Score, Visual Analogue Scale (VAS), coracoclavicular distance (CCD), and complications. Weight mean difference (WMD) with 95% confidence intervals (95% CIs) or risk ratio (RR) with 95% CIs was used to calculate the data.

Results

Four studies with a total of 179 patients were included in this study. Compared with hook plate, TightRope® fixation was associated with a significantly less VAS score for pain (WMD = ‐0.69, 95% CI: −1.10, −0.27; P = 0.001). However, there were no significant differences between the two surgical techniques in terms of Constant Score (WMD = 6.12, 95% CI: −3.84, 16.08; P = 0.229), UCLA (WMD = 7.96, 95% CI: −5.76, 21.68; P = 0.256), CCD (WMD = 0.24, 95% CI: −0.67, 1.15; P = 0.602), and complication rate.

Conclusion

Both TightRope® and hook plate techniques offered effective outcomes in relieving the pain of dislocation and improving function of ACJ. However, TightRope® fixation showed an advantage over hook plate in terms of postoperative pain. Further larger‐scale RCTs are needed to verify our findings.
Safety, speed, and effectiveness of air transportation for neonates
Authors: Hirakawa Eiji , Ibara Satoshi , Yoshihara Hideaki , Kamitomo Masato , Kodaira Yuichi , Kibe Masaya , Ishihara Chie , Naito Yoshiki , Yamamoto Masakatsu , Yamamoto Tsuyoshi , Takayama Tatsu , Kurimoto Tomonori , Mikami Yuta , Ohashi Hiroshi
Published: July 2020

Background : In Japan, 44.3% of neonates are delivered in private clinics without an attending pediatrician. Obstetricians in the clinics must resuscitate asphyxiated neonates in unstable condition, such as respiratory failure, and they are frequently transferred to tertiary perinatal medical centers. There has been no study comparing the physiological status and prognosis of neonates transported by ambulance with those transported by helicopter.

Methods: Medical and transport records were used to compare the physiological status of neonates transported to Kagoshima City Hospital by land and those transported by air between January 1, 2013, and December 31, 2017.

Results : Data from 425 neonates transferred by land and 143 by air were analyzed. There were no significant differences between the two groups in mean gestational age, mean birthweight, fetal blood pH, Apgar score, or the Score for Neonatal Acute Physiology with Perinatal Extension‐II (SNAPPE‐II) on arrival to the tertiary center (16.3 ± 15.4 [95% confidence interval (CI): 13.2–17.7] vs 16.4 ± 15.4 [95% CI: 13.9–19.0], respectively; P = 0.999); both groups had SNAPPE‐II score 10–19, indicating no difference in mortality risk. The times to starting first aid and to admission to the intensive care unit were significantly reduced in neonates transported by air than by land. In subgroup analysis of patients of a gestational age ≤28 weeks, all cases of severe intraventricular hemorrhage (IVH) were observed in the land transportation group.

Conclusions: Neonatal transportation by air is as safe as land transportation, and time to first aid and intensive care are significantly reduced by transportation by air than by land. Air transport could also contribute to the prevention of IVH in neonatal transportation.
Microsecretory adenocarcinoma of the hard palate: A case report of a recently described entity
Authors: Kawakami Fumi , Nagao Toshitaka , Honda Yumi , Sakata Junki , Yoshida Ryoji , Nakayama Hideki , Inoue Seijiro , Kitajima Mika , Ikeda Osamu , Nakaguro Masato , Mikami Yoshiki
Published: July 2020

We report a case of microsecretory adenocarcinoma of the hard palate. The patient is a 37‐year‐old woman with a 15 mm submucosal tumor, which was incidentally found by her primary care dentist, in her hard palate. Preoperative magnetic resonance imaging revealed a tumor exhibiting high signal on T2‐weighted image, which was gradually enhanced on dynamic study. Histologically, the tumor border was ill‐defined without fibrous capsule and adjoined minor salivary gland with permeative infiltration at the tumor periphery. The tumor comprised intercalated duct‐like cells with polygonal narrow eosinophilic to clear cytoplasm and small, uniform oval nuclei. These cells formed small infiltrative microcysts, tubules and fascicular cords collecting pale basophilic secretions and small vacuoles setting in an abundant fibromyxoid stroma. The tumor cells were positive for CK AE1+AE3, S‐100 protein, and p63, while are completely negative for p40, alpha‐SMA, and calponin. The MEF2C‐SS18 fusion was identified by reverse transcriptase‐polymerase chain reaction followed by Sanger sequencing. The combination of characteristic histology, immunophenotype, and presence of MEF2C‐SS18 fusion indicated the diagnosis of microsecretory adenocarcinoma of the hard palate, an entity described only recently. Post‐operative course was uneventful and there was no evidence of disease at 4 months after surgery.
Can self‐pain sensitivity quantify empathy for others' pain?
Authors: Ren Qiaoyue , Lu Xuejing , Zhao Qing , Zhang Huijuan , Hu Li
Published: July 2020

Empathy is essential for the survival of social species. In many studies, especially those with animal models, empathy for pain was evaluated by the modulation of pain sensitivity. However, the relationship between pain sensitivity and empathy for pain is not well established. Here, by performing two experiments, we aimed to investigate their relationship at both behavioral and electrophysiological levels. In Experiment 1, we characterized individual pain sensitivity using pain threshold and tolerance in a cold pressor test, self‐report empathy using Interpersonal Reactivity Index, and pain‐related psychological factors, including pain‐related anxiety, depression, pain catastrophizing, and pain‐related fear, using well‐validated questionnaires. We observed that pain sensitivity was positively correlated with emotional empathy, and their relationship was mediated by pain‐related anxiety, pain catastrophizing, and pain‐related fear. In Experiment 2, we quantified empathy for pain using pain intensity and unpleasantness as well as event‐related potentials (ERPs) in an empathy for pain task. Positive correlations were observed between pain sensitivity and psychophysiological empathic responses (i.e., the P3 component and the late positive potential in ERPs), and their relationship was mediated by pain‐related fear. These results suggested that being influenced by some pain‐related psychological factors, individuals with higher pain sensitivity tended to have stronger empathy for pain, manifested as stronger emotional reactions to others' pain. Our results indicated that the conventional strategy of using pain sensitivity to quantify empathy should be treated with caution, as their relationship could be disturbed by experimental manipulations or pathological modulations that could influence individual emotional states or cognitive processes.
Compassion without pity: Buddhist dāna as charity, humanitarianism, and altruism
Authors: Swenson Sara Ann
Published: July 2020

This article provides an overview of the changing role of dāna in contemporary Buddhism through ethnographic research on Buddhist charities in Vietnam. I begin by briefly describing how the concept of dāna has developed through Buddhist history and philosophy. Then, I explore how Vietnamese Buddhists reinterpret the concept of dāna amid (a) shifting trends in Buddhist humanitarianism and volunteering, (b) critiques of corruption in Buddhist monasticism, and (c) changing forms of religious community, charity, and altruism via social media. I conclude by demonstrating how nonordained or lay volunteers in Vietnam adapt notions of dāna to include informal charity events organized online. These examples demonstrate how Buddhism operates as a highly adaptable, living ethical resource for both lay and monastic practitioners.
An integrated spatial econometric approach in valuing soil conservation using contingent valuation
Authors: Dimal Matthew Oliver Ralp , Jetten Victor
Published: July 2020

The integration of soil value in agronomic micro‐level decision‐making and macro‐scale policy development has grown immensely in recent years. Major threats to soil resources and their impact on human well‐being require a comprehensive estimation of soil's economic worth, highlighting the need for sustainable and pragmatic conservation strategies. However, the absence of formal markets for numerous soil amenities, coupled with the heterogeneity of stakeholder cognition and spatio‐environmental factors, obfuscates the valuation process for soil and similar public goods. This paper aims to address such concerns by evaluating stakeholders’ willingness to pay (WTP) for soil conservation as a proxy indicator for its explicit value. Two contingent valuation method (CVM) formats, the payment card (PC) and the dichotomous choice (DC), were used to analyse WTP in Norzagaray, Philippines. Results suggest farmers’ income, education, land tenure type, level of environmental consciousness and proximity to amenities influence their inclination to spend on soil conservation measures. Econometric analyses indicate a compensating surplus corresponding to the mean WTP estimate of ₱79.98 (PC‐CVM) and a Turnbull WTP estimate of ₱99.47 (DC‐CVM). Estimated WTP values can be used in future benefit‐transfer studies, and the findings of the econometric models can be used in developing strategies that would promote greater stakeholder acceptance and participation. The approach presented here provides another step towards a more comprehensive characterization of soil value that integrates environmental valuation and econometric modelling with geospatial data.
STME: An effective method for discovering spatiotemporal multi‐type clusters containing events with different densities
Authors: Wang Chao , Du Zhenhong , Gu Yuhua , Zhang Feng , Liu Renyi
Published: July 2020

Clustering on spatiotemporal point events with multiple types is an important step for exploratory data mining and can help us reveal the correlation of event types. In this article, we present an effective method for discovering spatiotemporal multi‐type clusters containing events with different densities and event types (STME). Particularly, the type of events in a cluster can be different, and clusters with similar densities but different internal compositions should be distinguished. We use the distance to the kth nearest neighbour to define the size of the searched neighbourhood, and expand clusters by the concept of cluster reachable, ensuring that the proportion of various types of events in the cluster remains stable. The concept of clustering priority is also proposed to make the cluster always expand from the region with the highest density, which improves the robustness of clustering. Moreover, the density of multiple types of events in clusters is estimated to discover the internal structure of clusters and further explore the correlation between events. The effectiveness of the STME algorithm is demonstrated in several simulated and real data sets, including points of interest data in Beijing and the origins and destinations of taxi trips in New York.
COVID‐19 in solid organ transplant recipients: No difference in survival compared to general population
Authors: Rinaldi Matteo , Bartoletti Michele , Bussini Linda , Pancaldi Livia , Pascale Renato , Comai Giorgia , Morelli Mariacristina , Ravaioli Matteo , Cescon Matteo , Cristini Francesco , Viale Pierluigi , Giannella Maddalena
Published: July 2020

Coronavirus disease 2019 (COVID‐19) may be associated with worse outcome in solid organ transplant (SOT) recipients. We performed a prospective cohort study of hospitalized patients with confirmed diagnosis of COVID‐19, from March 15 to April 30, 2020, at two tertiary hospitals in Emilia‐Romagna Region. SOT recipients were compared with non‐SOT patients. Primary endpoint was all‐cause 30‐day mortality. Relationship between SOT status and mortality was investigated by univariable and multivariable Cox regression analysis. Patients were assessed from COVID‐19 diagnosis to death or 30‐day whichever occurred first. Study cohort consisted of 885 patients, of them 24 SOT recipients (n = 22, kidney, n = 2 liver). SOT recipients were younger, had lower BMI, but higher Charlson Index. At admission they presented less frequently with fever and respiratory failure. No difference in 30‐day mortality between the two groups (19% vs 22.1%) was found; however, there was a trend toward higher rate of respiratory failure (50% vs 33.1%, P = .07) in SOT recipients. Superinfections were more represented in SOT recipients, (50% vs 15.5%, P < .001). At multivariate analysis adjusted for main covariates, there was no association between SOT and 30‐day mortality HR 1.15 (95% CI 0.39‐3.35) P = .79. Our data suggest that mortality among COVID‐19 SOT recipients is similar to general population.
Ophthalmopathologic characterization of multicentric or metastatic neoplasms with an extraocular origin in dogs and cats
Authors: Bandinelli Marcele Bettim , Viezzer Bianchi Matheus , Wronski Júlia Gabriela , Santos de Mello Lauren , Blanco DeMartini Renata , Savi Caroline , Sonne Luciana , Driemeier David , Petinatti Pavarini Saulo
Published: July 2020

Objective

To characterize the frequency and distribution of secondary ocular neoplasms in dogs and cats identified during necropsy.

Methods

A retrospective analysis of necropsy records of dogs and cats was conducted, and cases with metastatic/multicentric neoplasms with an extraocular origin, involving the eyes, were selected.

Results

From January 2015 to January 2019, we identified a total of 233 dogs and 100 cats with metastatic disease. Of these, 11.6% (27/233) of the dogs and 13% (13/100) of the cats had ocular metastases. Lymphoma was the most common multicentric neoplasm involving the eyes of both species. In dogs, these neoplasms occurred bilaterally, predominantly in the anterior uvea, and were diffuse large B‐cell, T‐lymphoblastic, peripheral T‐cell not otherwise specified, and lymphocytic B‐cell lymphomas. In cats, feline leukemia virus (FeLV)‐associated T‐cell lymphoma was the most common. Mammary carcinoma was the second most common ocular metastatic neoplasm in bitches, with a predominantly unilateral involvement of the uveal tract. In cats, following lymphoma, pulmonary and squamous cell carcinomas were the most common multicentric/metastatic neoplasms of the eyes. Individual cases of cholangiocarcinoma, hemangiosarcoma, and chemodectoma in dogs, as well as mammary gland cribriform carcinoma, salivary gland carcinoma, and histiocytic sarcoma in cats were detected.

Conclusions

The eyes of dogs were mostly affected by lymphoma or mammary gland carcinoma, while those of cats mostly had lymphoma, pulmonary carcinoma, or squamous cell carcinoma as the main metastatic/multicentric neoplasm. To the best of our knowledge, this is the first study to identify intraocular metastatic cholangiocarcinoma and chemodectoma in dogs, aside from identifying salivary gland carcinoma in cats.
Incidence and risk factors for surgical glove perforation in small animal ophthalmic surgery
Authors: Massidda Paola A. , Diaz Jesus , Tetas Pont Roser , Grundon Rachael , Corletto Federico , Blacklock Ben
Published: July 2020

Objective

To determine the incidence of perforation of surgical gloves and identify associated risk factors that contribute to glove perforation in small animal ophthalmic surgery.

Study design

Observational cohort study.

Sample population

Surgical gloves (n = 2000) collected following 765 small animal ophthalmic procedures.

Methods

All the gloves were tested for perforation at the end of the procedure using a water leak test. The potential risk factors for glove perforation were recorded, and associations between these risk factors and perforation were explored using univariable (Fisher's exact test) and mixed effect logistic regression analysis. Results were considered significant if P < .05.

Results

Glove perforation was detected in 6% of procedures. Glove perforation was 1.97 (95% CI: 0.98‐4.22) times more likely in extraocular than in intraocular surgeries (7.3% vs 3.9%; P = .0462). The incidence of perforations was not statistically different between main and assistant surgeon (P = .86). No significant association was found between the risk of glove perforation and duration of the procedure (P = .13). Perforation of the nondominant hand was 2.6 (95% CI: 1.38‐4.98) times more likely than the dominant hand (74% vs 26%; P = .0028). Only 22% of the perforations were detected intraoperatively. Multivariable analysis identified only extraocular surgery as a risk factor for perforations.

Conclusions

There is a low incidence of glove perforation in small animal ophthalmic surgery, but extra care of the nondominant hand is required, especially during extraocular procedures.
The Branching Redesign Technique Used for Upgrading Steel-Pipes-Based Hydraulic Systems: Re-Examined
Authors: Chaker Mohamed Amir , Triki Ali
Published: July 2020

The branching technique demonstrated an effective ability to attenuate severe hydraulic-head magnitudes into existing steel-pipes-based hydraulic systems. However, there was no detailed exploration of circumferential-stress, radial-strain, and wave-oscillation period behaviors, which are equally embedded in the design stage of hydraulic systems. Accordingly, this paper examined these last parameters to provide relevant information on the entire design key parameters. The numerical solver used the Method of Characteristics for discretizing the extended one-dimensional water-hammer model incorporating the Vitkovsky and the Kelvin–Voigt formulations along with the discrete gas cavity model to represent column separation. The plastic short-penstock material types utilized in this study included high- or low-density polyethylene (HDPE or LDPE). Results demonstrated that the branching technique is promising in terms of hydraulic-head attenuation waves; however, this research emphasized the limitation of this technique, not previously delineated, including the amplification of the radial-strain peaks or crests and the spreading of the wave-oscillation period. Ultimately, a methodology was suggested for optimizing the plastic short-penstock diameter and length parameters.
A Bionic Hierarchy Generative Design for Conductive Heat Transfer
Authors: Lin Qiyin , Liu Lian , Wang Jihong , Yan Ke , Guo Junkang , Su Wenjun
Published: July 2020

A bionic hierarchy generative design algorithm inspired by the leaf vein growth process is presented for the layout design of heat conduction channels. The design domain is discretized based on the element-free Galerkin (EFG) method. The generations of main channels and lateral channels are separated. The effectiveness of the developed bionic hierarchy generative design approach is investigated based on the general “volume-to-point” heat conduction problem.
Rotational Effect on Flow Field and Thermal Characteristics of a Turboexpander for Helium Liquefaction System: A Numerical Perspective
Authors: Kumar Manoj , Behera Suraj K. , Kumar Amitesh , Sahoo Ranjit K.
Published: July 2020

Cryogenic turboexpander is an essential component to produce the refrigeration effect in various helium liquefaction systems. The convergent nozzle and small-scale radial inflow turbine (turboexpander) are the important components that are responsible for increasing the performance of the cycle. In this paper, an optimum preliminary design approach of the turbine and nozzle is explained using real gas properties. Initially, the Sobol method is used to determine the sensitivity indices and optimized range of ten important nondimensional and geometrical variables for better performance of the radial turbine. Three turboexpanders of a modified Collins cycle-based helium liquefaction system have been designed considering the optimized ranges. The proposed method improves the isentropic efficiency and power output of the turbine up to 3.86% and 5.14%, respectively, as compared to the initial design. Hereafter, a comparative three-dimensional numerical analysis is conducted to characterize the flow physics and thermal properties of three turboexpander systems (16 bar and 40 K, 6 bar and 20 K, and 16 bar and 10 K). The thermal and fluid flow properties such as temperature, Prandtl number, static enthalpy, entropy, velocity vectors, Reynolds number, and turbulence kinetic energy are determined at different spans and streamwise locations. Moreover, the present numerical results are also verified with the experimental and numerical results obtained from the existing literature. The study highlights the optimal range of design variables for helium turbine, the methodology for helium liquefaction system, and the numerical analysis to understand the flow physics and thermal properties of helium near its boiling point.
Effects of consonantal constrictions on voice quality
Authors: Chong Adam J. , Risdal Megan , Aly Ann , Zymet Jesse , Keating Patricia
Published: July 2020

A speech production experiment with electroglottography investigated how voicing is affected by consonants of differing degrees of constriction. Measures of glottal contact [closed quotient (CQ)] and strength of voicing [strength of excitation (SoE)] were used in conditional inference tree analyses. Broadly, the results show that as the degree of constriction increases, both CQ and SoE values decrease, indicating breathier and weaker voicing. Similar changes in voicing quality are observed throughout the course of the production of a given segment. Implications of these results for a greater understanding of source-tract interactions and for the phonological notion of sonority are discussed.
Preserved Efficacy and Reduced Toxicity with Intermittent Linezolid Dosing in Combination with Bedaquiline and Pretomanid in a Murine Tuberculosis Model
Authors: Bigelow Kristina M. , Tasneen Rokeya , Chang Yong S. , Dooley Kelly E. , Nuermberger Eric L.
Published: July 2020

The novel regimen of bedaquiline, pretomanid, and linezolid (BPaL) is highly effective against drug-resistant tuberculosis, but linezolid toxicities are frequent. We hypothesized that, for a similar total weekly cumulative dose, thrice-weekly administration of linezolid would preserve efficacy while reducing toxicity compared with daily dosing, in the context of the BPaL regimen. Using C3HeB/FeJ and BALB/c mouse models of tuberculosis disease, thrice-weekly linezolid dosing was compared with daily dosing, with intermittent dosing introduced (i) from treatment initiation or (ii) after an initial period of daily dosing.
DNA Thermo-Protection Facilitates Whole-Genome Sequencing of Mycobacteria Direct from Clinical Samples
Authors: George Sophie , Xu Yifei , Rodger Gillian , Morgan Marcus , Sanderson Nicholas D. , Hoosdally Sarah J. , Thulborn Samantha , Robinson Esther , Rathod Priti , Walker A. Sarah , Peto Timothy E. A. , Crook Derrick W. , Dingle Kate E.
Published: July 2020

Mycobacterium tuberculosis
is the leading cause of death from bacterial infection. Improved rapid diagnosis and antimicrobial resistance determination, such as by whole-genome sequencing, are required. Our aim was to develop a simple, low-cost method of preparing DNA for sequencing direct from
M. tuberculosis
-positive clinical samples (without culture). Simultaneous sputum liquefaction, bacteria heat inactivation (99°C/30 min), and enrichment for mycobacteria DNA were achieved using an equal volume of thermo-protection buffer (4 M KCl, 0.
Analysis of Virus Population Profiles within Pigs Infected with Virulent Classical Swine Fever Viruses: Evidence for Bottlenecks in Transmission but Absence of Tissue-Specific Virus Variants
Authors: Johnston Camille Melissa , Fahnøe Ulrik , Lohse Louise , Bukh Jens , Belsham Graham J. , Rasmussen Thomas Bruun
Published: July 2020

The surface-exposed E2 protein of classical swine fever virus is required for its interaction with host cells. A short motif within this protein varies between strains of different virulence. The importance of two particular amino acid residues in determining the properties of a highly virulent strain of the virus has been analyzed. Each of the different viruses tested proved highly virulent, but one of them produced earlier, but not more severe, disease. By analyzing the virus genomes present within infected pigs, it was found that the viruses which replicated within inoculated animals were only a subset of those within the virus inoculum. Furthermore, following contact transmission, it was shown that a very restricted set of viruses had transferred between animals. There were no significant differences in the virus populations present in various tissues of the infected animals. These results indicate mechanisms of virus population change during transmission between animals.
Microbial Species Coexistence Depends on the Host Environment
Authors: Deines Peter , Hammerschmidt Katrin , Bosch Thomas C. G.
Published: July 2020

This work studies microbial interactions within the microbiome of the simple cnidarian
Hydra
and investigates whether microbial species coexistence and community stability depend on the host environment. We find that the outcome of the interaction between the two most dominant bacterial species in
Hydra
’s microbiome differs depending on the environment and results in a stable coexistence only in the host context. The interactive ecology between the host and the two most dominant microbes, but also the less abundant members of the microbiome, is critically important for achieving the native community composition. This indicates that the metaorganism environment needs to be taken into account when studying microbial interactions.
Evolutionary Stabilization of Cooperative Toxin Production through a Bacterium-Plasmid-Phage Interplay
Authors: Spriewald Stefanie , Stadler Eva , Hense Burkhard A. , Münch Philipp C. , McHardy Alice C. , Weiss Anna S. , Obeng Nancy , Müller Johannes , Stecher Bärbel
Published: July 2020

Bacteria are excellent model organisms to study mechanisms of social evolution. The production of public goods, e.g., toxin release by cell lysis in clonal bacterial populations, is a frequently studied example of cooperative behavior. Here, we analyze evolutionary stabilization of toxin release by the enteric pathogen
Salmonella
. The release of colicin Ib (ColIb), which is used by
Salmonella
to gain an edge against competing microbiota following infection, is coupled to bacterial lysis mediated by temperate phages. Here, we show that phage-dependent lysis and subsequent release of colicin and phage particles occurs only in part of the ColIb-expressing
Salmonella
population. This phenotypic heterogeneity in lysis, which represents an essential step in the temperate phage life cycle, has evolved as a bet-hedging strategy under fluctuating environments such as the gastrointestinal tract. Our findings suggest that prophages can thereby evolutionarily stabilize costly toxin release in bacterial populations.
An Antivirulence Approach for Preventing Cryptococcus neoformans from Crossing the Blood-Brain Barrier via Novel Natural Product Inhibitors of a Fungal Metalloprotease
Authors: Aaron Phylicia A. , Vu Kiem , Gelli Angie
Published: July 2020

Fungal infections like cryptococcal meningitis are difficult to resolve because of the limited therapies available. The small arsenal of antifungal drugs reflect the difficulty in finding available targets in fungi because like mammalian cells, fungi are eukaryotes. The limited efficacy, toxicity, and rising resistance of antifungals contribute to the high morbidity and mortality of fungal infections and further underscore the dire but unmet need for new antifungal drugs. The traditional approach in antifungal drug development has been to target fungal growth, but an attractive alternative is to target mechanisms of pathogenesis. An important attribute of
Cryptococcus neoformans
(
Cn
) pathogenesis is its ability to enter the central nervous system. Here, we describe a large-scale screen that identified three natural products that prevented
Cn
from crossing the blood-brain barrier by inhibiting the virulence factor Mpr1 without affecting the growth of
Cn
. We propose that compounds identified here could be further developed as antivirulence therapy that would be administered preemptively or serve as a prophylactic in patients at high risk for developing cryptococcal meningitis.
ClbR Is the Key Transcriptional Activator of Colibactin Gene Expression in Escherichia coli
Authors: Wallenstein Alexander , Rehm Nadine , Brinkmann Marina , Selle Martina , Bossuet-Greif Nadège , Sauer Daniel , Bunk Boyke , Spröer Cathrin , Wami Haleluya Tesfaye , Homburg Stefan , von Bünau Rudolf , König Simone , Nougayrède Jean-Philippe , Overmann Jörg , Oswald Eric , Müller Rolf , Dobrindt Ulrich
Published: July 2020

The nonribosomal peptide/polyketide hybrid colibactin can be considered a bacterial virulence factor involved in extraintestinal infection and also a procarcinogen. Nevertheless, and despite its genotoxic effect, colibactin expression can also inhibit bacterial or tumor growth and correlates with probiotic anti-inflammatory and analgesic properties. Although the biological function of this natural compound has been studied extensively, our understanding of the regulation of colibactin expression is still far from complete. We investigated in detail the role of regulatory elements involved in colibactin expression and in the growth conditions that promote colibactin expression. In this way, our data shed light on the regulatory mechanisms involved in colibactin expression and may support the expression and purification of this interesting nonribosomal peptide/polyketide hybrid for further molecular characterization.
Genome-Scale Transcription-Translation Mapping Reveals Features of Zymomonas mobilis Transcription Units and Promoters
Authors: Vera Jessica M. , Ghosh Indro Neil , Zhang Yaoping , Hebert Alex S. , Coon Joshua J. , Landick Robert
Published: July 2020

Efforts to rationally engineer synthetic pathways in
Zymomonas mobilis
are impeded by a lack of knowledge and tools for predictable and quantitative programming of gene regulation at the transcriptional, posttranscriptional, and posttranslational levels. With the detailed functional characterization of the
Z. mobilis
genome presented in this work, we provide crucial knowledge for the development of synthetic genetic parts tailored to
Z. mobilis
. This information is vital as researchers continue to develop
Z. mobilis
for synthetic biology applications. Our methods and statistical analyses also provide ways to rapidly advance the understanding of poorly characterized bacteria via empirical data that enable the experimental validation of sequence-based prediction for genome characterization and annotation.
Soil Bacterial Communities Exhibit Strong Biogeographic Patterns at Fine Taxonomic Resolution
Authors: Bay Sean K. , McGeoch Melodie A. , Gillor Osnat , Wieler Nimrod , Palmer David J. , Baker David J. , Chown Steven L. , Greening Chris
Published: July 2020

It is commonly thought that bacterial distributions show lower spatial variation than for multicellular organisms. In this article, we present evidence that these inferences are artifacts caused by methodological limitations. Through leveraging innovations in sampling design, sequence processing, and diversity analysis, we provide multifaceted evidence that bacterial communities in fact exhibit strong distribution patterns. This is driven by selection due to factors such as local soil characteristics. Altogether, these findings suggest that the processes underpinning diversity patterns are more unified across all domains of life than previously thought, which has broad implications for the understanding and management of soil biodiversity.
Supplemental Material: Rapid eruption of silicic magmas from the Paraná magmatic province (Brazil) did not trigger the Valanginian event
Authors: Rocha B.C. , al. et
Published: July 2020

Sample description, sample preparation, analytical protocols, zircon U-Pb and Hf data, and additional interpretations on zircon ages.
Supplemental Material: Flooding induced by rising atmospheric carbon dioxide
Authors: Retallack G.J. , Conde G.D.
Published: July 2020

Stomatal data for Ginkgo biloba
Children with type 1 diabetes have elevated high-sensitivity C-reactive protein compared with a control group
Authors: Pérez-Segura Pilar , de Dios Olaya , Herrero Leticia , Vales-Villamarín Claudia , Aragón-Gómez Isabel , Gavela-Pérez Teresa , Garcés Carmen , Soriano-Guillén Leandro
Published: July 2020

Introduction

Our objective was to compare high-sensitivity C-reactive protein (hsCRP) levels in children with type 1 diabetes, healthy controls, and children with obesity. Additionally, we aimed to analyze the association between hsCRP levels and glycemic control measured by glycohemoglobin A (HbA1c) and anthropometric and biochemical variables.

Research design and methods

We conducted a non-randomized descriptive study of children with type 1 diabetes matched for sex and age with a control group and group with obesity. We recorded anthropometric parameters and studied variables related to diabetes, blood pressure, lipid profile, and HbA1c. hsCRP was measured by ELISA.

Results

We included 49 children with type 1 diabetes, 46 controls, and 40 children with obesity. hsCRP levels were significantly higher in the group with type 1 diabetes compared with controls and nearly significantly lower than in the group comprising children with obesity. We found no correlation between hsCRP and HbA1c and characteristics of type 1 diabetes with the exception of albumin to creatinine ratio. Statistically significant association was found between hsCRP and body mass index (BMI) and waist circumference Z-score.

Conclusions

The higher hsCRP levels observed in children with type 1 diabetes compared with a control group with a similar BMI suggest a basal inflammatory state that could increase cardiovascular risk. The main factors related to hsCRP are BMI and waist circumference, so obesity prevention should be a priority when performing follow-up in children with type 1 diabetes.
Moving beyond the Cox proportional hazards model in survival data analysis: a cervical cancer study
Authors: Li Lixian , Yang Zijing , Hou Yawen , Chen Zheng
Published: July 2020

Objectives

This study explored the prognostic factors and developed a prediction model for Chinese-American (CA) cervical cancer (CC) patients. We compared two alternative models (the restricted mean survival time (RMST) model and the proportional baselines landmark supermodel (PBLS model, producing dynamic prediction)) versus the Cox proportional hazards model in the context of time-varying effects.

Setting and data sources

A total of 713 CA women with CC and available covariates (age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, lymph node metastasis and radiation) from the Surveillance, Epidemiology and End Results database were included.

Design

We applied the Cox proportional hazards model to analyse the all-cause mortality with the proportional hazards assumption. Additionally, we applied two alternative models to analyse covariates with time-varying effects. The performances of the models were compared using the C-index for discrimination and the shrinkage slope for calibration.

Results

Older patients had a worse survival rate than younger patients. Advanced FIGO stage patients showed a relatively poor survival rate and low life expectancy. Lymph node metastasis was an unfavourable prognostic factor in our models. Age at diagnosis, FIGO stage and lymph node metastasis represented time-varying effects from the PBLS model. Additionally, radiation showed no impact on survival in any model. Dynamic prediction presented a better performance for 5-year dynamic death rates than did the Cox proportional hazards model.

Conclusions

With the time-varying effects, the RMST model was suggested to explore diagnosis factors, and the PBLS model was recommended to predict a patient’s w-year dynamic death rate.
Multimorbidity patterns in low-middle and high income regions: a multiregion latent class analysis using ATHLOS harmonised cohorts
Authors: Bayes-Marin Ivet , Sanchez-Niubo Albert , Egea-Cortés Laia , Nguyen Hai , Prina Matthew , Fernández Daniel , Haro Josep Maria , Olaya Beatriz
Published: July 2020

Objectives

Our aim was to determine clusters of non-communicable diseases (NCDs) in a very large, population-based sample of middle-aged and older adults from low- and middle-income (LMICs) and high-income (HICs) regions. Additionally, we explored the associations with several covariates.

Design

The total sample was 72 140 people aged 50+ years from three population-based studies (English Longitudinal Study of Ageing, Survey of Health, Ageing and Retirement in Europe Study and Study on Global Ageing and Adult Health) included in the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) project and representing eight regions with LMICs and HICs. Variables were previously harmonised using an ex-post strategy. Eight NCDs were used in latent class analysis. Multinomial models were made to calculate associations with covariates. All the analyses were stratified by age (50–64 and 65+ years old).

Results

Three clusters were identified: ‘cardio-metabolic’ (8.93% in participants aged 50–64 years and 27.22% in those aged 65+ years), ‘respiratory-mental-articular’ (3.91% and 5.27%) and ‘healthy’ (87.16% and 67.51%). In the younger group, Russia presented the highest prevalence of the ‘cardio-metabolic’ group (18.8%) and England the ‘respiratory-mental-articular’ (5.1%). In the older group, Russia had the highest proportion of both classes (48.3% and 9%). Both the younger and older African participants presented the highest proportion of the ‘healthy’ class. Older age, being woman, widowed and with low levels of education and income were related to an increased risk of multimorbidity. Physical activity was a protective factor in both age groups and smoking a risk factor for the ‘respiratory-mental-articular’.

Conclusion

Multimorbidity is common worldwide, especially in HICs and Russia. Health policies in each country addressing coordination and support are needed to face the complexity of a pattern of growing multimorbidity.
Abductor muscle strength deficit in patients after total hip arthroplasty for hip osteoarthritis: a protocol for a systematic review and meta-analysis
Authors: Ismailidis Petros , Kvarda Peter , Vach Werner , Appenzeller-Herzog Christian , Mündermann Annegret
Published: July 2020

Introduction

Conservation of abductor muscle strength is directly associated with physical function after total hip replacement (THA). Although many studies have tried to explore and quantify a potential abductor muscle strength deficit after THA as well as identify possible causes and treatment options, this topic has not been addressed systematically.

Methods and analysis

Human-based studies reporting measurements of hip abductor strength will be included in this review. Studies reporting on hip abductor strength measured manually or isometric measurements at an abduction angle other than 0° will not be considered. No restriction will be placed on study design, publication date operative approach, prosthesis design, age and sex of the patients or severity of OA. Data sources will be Embase via embase.com, Medline ALL via Ovid and the Cochrane Central Register of Controlled Trials. The preliminary search was conducted on 5 May 2019. Data regarding absolute values or torque ratio of hip abductor torque between sides as well as patient demographic data, surgical approaches and rehabilitation protocols will be extracted. The assessment of quality and risk of bias will be performed with the modified Newcastle-Ottawa Scale. The screening, data extraction and quality assessment will be performed by two reviewers independently. Where necessary, a third review author will make a final judgement. Narrative synthesis as well as tabular presentation of the extracted data will be included. Whenever possible, metaregression and subgroup specific meta-analyses will be used to investigate the influence of time since THA and type of measurement (isokinetic or isometric) on the different outcomes. In case of sufficient information, these analyses will be extended to include characteristics such as age, sex, surgical approach or rehabilitation programme.

Ethics and dissemination

No ethics approval is required. The results will be disseminated through peer-reviewed publications and conference presentations.

PROSPERO registration number

CRD42020153185.
Effectiveness of intraoperative peritoneal lavage (IOPL) with saline in patient with intra-abdominal infections: a systematic review and meta-analysis protocol
Authors: Zhou Qi , Shi Qianling , Yu Xuan , Wang Zijun , Zhang Jingyi , Yang Nan , Wang Jianjian , Ma Yanfang , Luo Xufei , Xun Yangqin , Zhao Siya , Zheng Bobo , Meng Wenbo , Yang Kehu , Chen Yaolong , Sawyer Robert
Published: July 2020

Introduction

Intra-abdominal infections (IAIs) are common surgical emergencies and cause a significant worldwide burden per year. Since the concept of intraoperative peritoneal lavage (IOPL) was proposed in 1905, it has been widely used in the surgery practice. However, the effectiveness of IOPL in patients with IAIs has always been controversial. Our objective is to identify whether it is beneficial to flush the abdominal cavity with saline in IAIs surgery through a comprehensive systematic review and meta-analysis.

Methods and analysis

This protocol is reported in line with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. Electronic databases (including the Cochrane library, MEDLINE, EMBASE, Web of Science, etc) and clinical trial registry platforms will be searched from inception to 8 September 2019. Randomised controlled trials, quasi-randomised clinical trials and cohort studies comparing IOPL and suction alone in IAIs will be included. The primary outcomes are mortality and abscess rate. Two independent reviewers will screen literature, collect data and assess risk of bias of included studies. Discussion or a third reviewer will be referred for any disagreements. The Grading of Recommendations Assessment, Development and Evaluation approach will be used to assess the quality of the evidence. We will perform meta-analysis using random-effects model. Subgroup analysis, sensitivity analysis and publication bias will be conducted if data are enough.

Ethics and dissemination

Ethical approval is not required for this systematic review and meta-analysis protocol. Results of this study will be published in a peer-reviewed journal, presented at relevant conferences and disseminated to local and international policy makers.

PROSPERO registration number

CRD42019145109.