bluuebunny/crossref_metadata_2025 huggingface dataset:
Antipassives in Nakh-Daghestanian languages
Authors: Comrie Bernard , Forker Diana , Khalilova Zaira , van den Berg Helma
Published: September 2020

Several Nakh-Daghestanian languages present
constructions that are candidate antipassives, in that the
construction is intransitive and is (at least sometimes) related to
a corresponding transitive construction, with A of the transitive
construction appearing as S of the intransitive, and P of the
transitive either corresponding to an oblique in the intransitive or
being omitted. All Nakh-Daghestanian antipassives are lexically
restricted, and their function is typically to shift aspectual value
in the direction of durativity, atelicity, iterativity, etc.
However, only Dargwa restricts the construction to transitive verbs,
while other languages also allow it with intransitive verbs, in
which case there is no change in argument structure. We explore the
implications of this for the definition of “antipassive” from the
perspective of canonical typology.
Antipassive and antipassive-like constructions in Mayan
languages
Authors: Heaton Raina
Published: September 2020

This chapter details the characteristics of the
various constructions found in Mayan languages that exhibit some
number of antipassive features (absolutive, incorporating, agent
focus, reflexives/reciprocals). Although the label ‘antipassive’ has
been applied to many of these structures historically, based on the
features presented in this volume as diagnostics for antipassives
cross-linguistically, only certain instantiations of the
‘absolutive’ antipassive qualify as antipassives.
When an antipassive isn’t an antipassive anymore
Authors: Hemmings Charlotte
Published: September 2020

This paper presents the Actor Voice
(av) construction in Kelabit, a Western Austronesian
language spoken in Northern Sarawak, Malaysia. It compares Kelabit
av with prototypical antipassives and related
constructions in the more conservative Western Austronesian
languages, using case studies of West Greenlandic and Tagalog. On
the basis of morphosyntactic, semantic and discourse diagnostics,
the paper demonstrates that Tagalog av constructions have
the semantic and discourse characteristics of antipassives but are
syntactically transitive. In contrast, Kelabit av, which is
also syntactically transitive, has a mixture of semantic and
discourse properties: some antipassive-like but many active-like.
This has important implications for Western Austronesian and the
theory of alignment shift, as well as the ways in which antipassives
vary and change over time.
Antipassivization in Basque revisited
Authors: Zúñiga Fernando , Fernández Beatriz
Published: September 2020

In this paper, we explore three phenomena that
have been considered to be antipassives in Basque linguistics.
First, we briefly review “ergative displacement” (Laka 1988),
related to antipassives as mentioned by Heath (1976). This is not a bona fide
instance of the antipassive, since the ergative displacement affects
only the agreement pattern (the A argument appears indexed as S in
finite verb forms) while the case frame and syntactic status of A
and P are as in the default transitive construction; besides, there
is no demotion or suppression of the P argument. Second, we review
two biclausal constructions, namely the
ari-progressive (Hualde & Ortiz de Urbina 1987;
Laka 2006) and
participial clauses (Ortiz
de Urbina & Uribe-Etxebarria 1991). Although regarded
as antipassives by Postal
(1977) and Coyos
(2002), respectively, their biclausality, long argued by
some Basque linguists, is incompatible with the antipassive, which
is monoclausal by definition. Finally, de Rijk (2003) labels as antipassives
some intransitive constructions that alternate with transitive ones.
This is the closest to true antipassives that can be found in
Basque, but these constructions are lexically constrained and
idiosyncratic, and unlike canonical antipassives attested in other
languages of the world.
Network-based identification genetic effect of SARS-CoV-2 infections to Idiopathic pulmonary fibrosis (IPF) patients
Authors: Taz Tasnimul Alam , Ahmed Kawsar , Paul Bikash Kumar , Kawsar Md , Aktar Nargis , Mahmud S M Hasan , Moni Mohammad Ali
Published: September 2020

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is accountable for the cause of coronavirus disease (COVID-19) that causes a major threat to humanity. As the spread of the virus is probably getting out of control on every day, the epidemic is now crossing the most dreadful phase. Idiopathic pulmonary fibrosis (IPF) is a risk factor for COVID-19 as patients with long-term lung injuries are more likely to suffer in the severity of the infection. Transcriptomic analyses of SARS-CoV-2 infection and IPF patients in lung epithelium cell datasets were selected to identify the synergistic effect of SARS-CoV-2 to IPF patients. Common genes were identified to find shared pathways and drug targets for IPF patients with COVID-19 infections. Using several enterprising Bioinformatics tools, protein–protein interactions (PPIs) network was designed. Hub genes and essential modules were detected based on the PPIs network. TF-genes and miRNA interaction with common differentially expressed genes and the activity of TFs are also identified. Functional analysis was performed using gene ontology terms and Kyoto Encyclopedia of Genes and Genomes pathway and found some shared associations that may cause the increased mortality of IPF patients for the SARS-CoV-2 infections. Drug molecules for the IPF were also suggested for the SARS-CoV-2 infections.
Examining the effect of feralization on craniomandibular morphology in pigs,Sus scrofa(Artiodactyla: Suidae)
Authors: Neaux Dimitri , Sansalone Gabriele , Lecompte François , Haruda Ashleigh , Schafberg Renate , Cucchi Thomas
Published: September 2020

Feralization is the process by which domestic animals return to the wild and produce self-sustaining populations. It is often considered as a model in understanding the permanence of morphological changes associated with domestication; however, it is still unclear how much the release of anthropogenic selective pressures affects domestic traits. Here, we assessed the influence of feralization on the domestic morphological traits acquired through selective breeding using craniomandibular differences in shape and size between populations of feral pigs, wild boar and domestic pigs, using landmark-based geometric morphometrics. Our results suggest that numerous cranial and mandibular traits associated with domestication still exist in feral specimens, corroborating that domestication-induced changes in the shape of morphological elements are broadly maintained in feral populations. This is not the case for size variations, however, as the cranium is significantly smaller in feral pigs than in domesticated breeds, which could be due to the selective pressures associated with founding events. Our exploratory study, therefore, underlines the complexity of feral population history, the intricate influence of variations in genetic diversity, and novel selection pressures in the morphology of these groups. Future studies will need to expand the sample to take into account the diversity of morphotypes.
Female fiddler crabs,Austruca lactea(Decapoda: Ocypodidae), adjust their rate of mate sampling based on remaining days until oviposition under a size-dependent temperature constraint
Authors: Takeshita Fumio
Published: September 2020

Rate of mate sampling is one of the critical components associated with sampling costs in female mate choice. In ectotherms, environmental temperature generally constrains locomotion performance. In addition, females will adjust the mate sampling rate depending on their breeding schedule because of the risk of remaining unfertilized eggs or a loss of benefits related to mating, if they lose the opportunity to copulate. This study investigated how these effects influence the rate of female mate sampling in the temperate fiddler crab (Austruca lactea) in the field. The number of sampled males per searching duration formed a convex curve against environmental temperature. The optimal environmental temperature increased with the female body size. These results suggest that mate sampling rate is under a size-dependent temperature constraint, and sampling costs are lower for larger females than smaller individuals under high-temperature conditions. Furthermore, when there were fewer remaining days, the mate sampling rate increased. Females would hasten the sampling rate to ensure a suitable burrow for breeding. Mate sampling rate in female A. lactea is therefore associated with environmental temperature, female body size and remaining days until oviposition.
Mural vegetation in left ventricular apex caused by Staphylococcus aureus
Authors: Uzuka Takeshi , Nakamura Masanori , Kondo Mayo , Sakata Junichi
Published: September 2020

A 77-year-old male on chronic haemodialysis was admitted for repeated episodes of stroke and a high fever. The patient’s blood culture was positive for Staphylococcus aureus and echocardiogram results revealed moderate mitral valve regurgitation, small masses in the left atrial appendage and a 20-mm mobile, spherical structure attached to the apical cavity of the left ventricle. Surgery was conducted to successfully excise these masses and pathological investigation confirmed the diagnosis of infective endocarditis. The attachment of mobile, spherical vegetation to the apex of the left ventricle is a rare manifestation of infective endocarditis.
Outcome of transcatheter aortic valve replacement in bicuspid aortic valve stenosis with new-generation devices
Authors: Gorla Riccardo , Casenghi Matteo , Finotello Alice , De Marco Federico , Morganti Simone , Regazzoli Damiano , Bianchi Giovanni , Acerbi Elena , Popolo Rubbio Antonio , Brambilla Nedy , Testa Luca , Castriota Fausto , Auricchio Ferdinando , Reimers Bernhard , Bedogni Francesco
Published: September 2020

OBJECTIVES

To compare device success and paravalvular leak rates of 3 new-generation transcatheter aortic valve replacement devices in patients with bicuspid aortic valve stenosis and to test their biomechanical performance in a computer-based simulation model of aortic root with increasing ellipticity.

METHODS

This retrospective multicentre study included 56 bicuspid aortic valve patients undergoing transcatheter aortic valve replacement with new-generation devices: Lotus/Lotus Edge (N = 15; 27%), Evolut-R (N = 20; 36%) and ACURATE neo (N = 21; 37%). Three virtual simulation models of aortic root with increasing index of eccentricity (0–0.25–0.5) were implemented. Stress distribution, stent–root contact area and paravalvular orifice area were computed.

RESULTS

Device success was achieved in 43/56 patients (77%) with comparable rates among Lotus (87%), Evolut-R (60%) and ACURATE neo (86%; P = 0.085). Moderate paravalvular leak rate was significantly lower in the Lotus group as compared to Evolut-R group (0% vs 30%; P = 0.027) and comparable to the ACURATE neo group (0% vs 10%; P = 0.33). By index of eccentricity = 0.5, Lotus showed a uniform and symmetric pattern of stress distribution with absent paravalvular orifice area, ACURATE neo showed a mild asymmetry with small paravalvular orifice area (1.1 mm2), whereas a severely asymmetric pattern was evident with Evolut-R, resulting in a large paravalvular orifice area (12.0 mm2).

CONCLUSIONS

Transcatheter aortic valve replacement in bicuspid aortic valve patients with new-generation devices showed comparable device success rates. Lotus showed moderate paravalvular leak rate comparable to that of ACURATE neo and significantly lower than Evolut-R. On simulation, Lotus and ACURATE neo showed optimal adaptability to elliptic anatomies as compared to Evolut-R.
Optimizing pharmacokinetics/pharmacodynamics of β-lactam/β-lactamase inhibitor combinations against high inocula of ESBL-producing bacteria
Authors: Tam Vincent H , Abodakpi Henrietta , Wang Weiqun , Ledesma Kimberly R , Merlau Paul R , Chan Katrina , Altman Rachel , Tran Truc T , Nikolaou Michael , Sofjan Amelia K
Published: September 2020

Objectives

Reduced in vitro β-lactam activity against a dense bacterial population is well recognized. It is commonly attributed to the presence of β-lactamase(s) and it is unknown whether the inoculum effect could be diminished by a β-lactamase inhibitor. We evaluated different β-lactam/β-lactamase inhibitor combinations in suppressing a high inoculum of ESBL-producing bacteria.

Methods

Three clinical isolates expressing representative ESBLs (CTX-M-15 and SHV-12) were examined. The impact of escalating β-lactamase inhibitor (tazobactam or avibactam) concentrations on β-lactam (piperacillin or ceftazidime) MIC reduction was characterized by an inhibitory sigmoid Emax model. The effect of various dosing regimens of β-lactam/β-lactamase inhibitor combinations was predicted using %T>MICi and selected exposures were experimentally validated in a hollow-fibre infection model over 120 h. The threshold exposure to suppress bacterial regrowth was identified using recursive partitioning.

Results

A concentration-dependent reduction in β-lactam MIC was observed (r2 ≥0.93). Regrowth could be suppressed in all six experiments using %T>MICi ≥73.6%, but only one out of six experiments below the threshold (P = 0.015). The exposures to suppress regrowth might be attained using the clinical dose of avibactam, but a much higher dose than the standard dose would be needed for tazobactam.

Conclusions

A dense population of ESBL-producing bacteria could be suppressed by an optimized dosing regimen of selected β-lactam/β-lactamase inhibitor combinations. The reversibility of enzyme inhibition could play an important role in diminishing the inoculum effect. In vivo investigations to validate these findings are warranted.
Comparison of Bone Turnover Biomarkers in Serum and Urine Measured on an Automated Analytical Platform
Authors: Wilson Brittany M , Ross Ryan D , Jacobs Joshua J , Sumner Dale Rick
Published: September 2020

Background

Matched serum and urine samples from patients who had total hip replacement were used to assess serum-validated immunoassay reagents for use in urine.

Methods

Samples were evaluated by an automated electrochemiluminescent immunoassay (cobas e411; Roche Diagnostics) for C-terminal telopeptide of type I collagen isoform β (β-Crosslaps), osteocalcin N-terminal midfragment (N-MID OC), N-terminal propeptide of type I collagen (PINP), and interleukin 6 (IL-6). Spike and recovery experiments were utilized to assess urinary matrix effects. Correlations between serum and both raw and creatinine-corrected urinary measures were assessed. Short-term precision was assessed.

Results

Spike and recovery experiments indicated minimal matrix effects of urine for the β-Crosslaps assay. Potential matrix effects were observed for the other analytes because N-MID OC and IL-6 tended to be slightly overrecovered, whereas PINP was underrecovered. There were strong correlations between serum β-Crosslaps and raw (Spearman ρ [rs] = 0.725, P < 0.0001) and creatinine-corrected (rs = 0.793, P < 0.0001) urinary measures and moderate correlations between serum N-MID OC and raw (rs = 0.582, P < 0.0001) and creatinine-corrected (rs = 0.482, P < 0.0001) urinary measures. PINP was not detected in urine, and no significant serum–urine correlations were found for IL-6. Short-term precision for urinary levels of β-Crosslaps, N-MID OC, and IL-6 were 1.6%, 6.3% and 14.4%, respectively.

Conclusions

Urinary measurements of β-Crosslaps and N-MID OC assays were correlated with serum measurements and had good short-term precision. Urinary PINP was not detectable. IL-6 can be measured in urine using this technology, but the levels did not correlate with serum levels, and the short-term precision was variable.
A Rapid and Accurate 1HNMR Method for the Identification and Quantification of Major Constituents in Qishen Yiqi Dripping Pills
Authors: Xie Qingling , Gong Limin , Huang Feibing , Cao Mengru , Liu Yongbei , Yuan Hanwen , Li Bin , Jian Yuqing , Peng Caiyun , Zhou Shuiping , Chu Yang , Wang Wei
Published: September 2020

Background

Qishen Yiqi dripping pills (QSYQ), composed of four herbal medicines—Salvia miltiorrhiza, Astragalus membranaceus, Panax notoginseng, and Dalbergiaodorifera—are widely used to treat ischemic cerebrovascular and hemorrhagic cerebrovascular conditions.

Objective

In this study, a rapid and accurate proton NMR (1HNMR) spectroscopy method was established to control the quality of QSYQ and ensure their clinical efficacy.

Method

Firstly, different types of metabolites were identified based on the proton signal peaks of chemical shifts, coupling constants, and related information provided through two-dimensional NMR spectroscopy. Secondly, a quantitative 1HNMR method was established for the simultaneous determination of major constituents in QSYQ samples. In addition, an HPLC method was performed to verify the results obtained by the quantitative proton NMR (qHNMR)  method.

Results

In the present study, 26 metabolites were identified in the 1HNMR spectra of QSYQ. In addition, a rapid and accruate qHNMR method was established for the simultaneous determination of protocatechualdehyde, rosmarinic acid, danshensu, calycosin-7-O-β-D-glucoside, and ononin in ten batches of QSYQ samples for the first time. Moreover, the proposed qHNMR method and HPLC method were compared using Bland-Altman and plots Passing-Bablok regression, indicating no significant differences and a strong correlation between the two analytical methods.

Conclusions

This method is an important tool for the identification and quantification of major constituents in QSYQ.

Highlights

Compared with traditional HPLC, the established qHNMR method has the advantages of simple sample preparation, short analysis time, and non-destructive analysis.
Implementing Group Parent Training in Telepsychology: Lessons Learned During the COVID-19 Pandemic
Authors: Fogler Jason M , Normand Sébastien , O’Dea Nicole , Mautone Jennifer A , Featherston Marilyn , Power Thomas J , Nissley-Tsiopinis Jenelle
Published: September 2020

Objective

We recently transitioned from in-person delivery of a brief behavioral parent intervention to telepsychology delivery to meet families’ needs during the COVID-19 pandemic. In this topical review, we describe how we used treatment fidelity as a guiding principle to orient adaptations for telepsychology, as well as preliminary findings and early lessons learned in this implementation. Methods: Using rapid-cycle quality improvement methods, we adapted a brief parent training group (Bootcamp for Attention-Deficit/Hyperactivity Disorder; BC-ADHD) to three groups of caregivers (i.e., 5–7 families) of school-aged children with ADHD (n = 20; 85% males). Families were from the following ethnic backgrounds: 75% White non-Hispanic, 15% White Hispanic, and 10% Black. Clinicians completed measures on their implementation experience. Observers completed measures on content/process fidelity and attendance. Caregivers completed measures on demographics, treatment satisfaction, and telepsychology experience.

Results

Telepsychology BC-ADHD can be implemented with comparably high levels of content and process fidelity and treatment satisfaction to in-person groups; and it appears to be feasible and acceptable to caregivers. Caregiver and clinician qualitative feedback revealed themes of appreciating the convenience of telepsychology, while experiencing some challenges in relating to others and sharing over video.

Conclusions

When treatment fidelity is used as a guiding tool, telepsychology parent training groups can be delivered with high fidelity and appear to be acceptable and feasible to caregivers and clinicians. Future research using larger and more diverse samples, multimethod and multi-informant measurement approaches, and controlled designs is needed to further assess the generalizability and efficacy of telepsychology parent training groups.
Psychosocial Functioning Among Children With and Without Differences of Sex Development
Authors: Hansen-Moore Jennifer A , Kapa Hillary M , Litteral Jennifer L , Nahata Leena , Indyk Justin A , Jayanthi Venkata R , Chan Yee-Ming , Tishelman Amy C , Crerand Canice E
Published: September 2020

Objective

 To assess health-related quality of life (HRQoL), psychosocial adjustment, and family functioning of children with differences of sex development (DSD) or cleft lip and/or palate (CL/P).

Methods

 In this cross-sectional study, parents of children with DSD (n = 67), CL/P (n = 121), and a comparison group of unaffected youth (n = 126) completed standardized measures assessing family functioning and their children’s HRQoL and psychosocial adjustment. Medical charts were abstracted for youth with either congenital condition.

Results

 Children with DSD were rated as having significantly lower HRQoL and greater internalizing problems compared to youth with CL/P and unaffected youth. Children in the DSD group were also significantly more likely to fall into the clinical risk categories for total and internalizing problems relative to the CL/P and unaffected groups. Caregivers of children with DSD were significantly more likely to endorse items about child suicidality compared with caregivers in the CL/P and unaffected groups. No significant differences were found between groups for externalizing problems or the expressiveness domain of family functioning; parents of children with DSD reported significantly less family conflict relative to the other groups and greater cohesion relative to the unaffected group. Conclusions Youth with DSD appear to be at greater risk for psychosocial problems relative to children with CL/P and unaffected peers. Results underscore the need for integrated interdisciplinary care and ongoing psychosocial risk monitoring in youth with DSD.
A slice classification model-facilitated 3D encoder–decoder network for segmenting organs at risk in head and neck cancer
Authors: Zhang Shuming , Wang Hao , Tian Suqing , Zhang Xuyang , Li Jiaqi , Lei Runhong , Gao Mingze , Liu Chunlei , Yang Li , Bi Xinfang , Zhu Linlin , Zhu Senhua , Xu Ting , Yang Ruijie
Published: September 2020

For deep learning networks used to segment organs at risk (OARs) in head and neck (H&N) cancers, the class-imbalance problem between small volume OARs and whole computed tomography (CT) images results in delineation with serious false-positives on irrelevant slices and unnecessary time-consuming calculations. To alleviate this problem, a slice classification model-facilitated 3D encoder–decoder network was developed and validated. In the developed two-step segmentation model, a slice classification model was firstly utilized to classify CT slices into six categories in the craniocaudal direction. Then the target categories for different OARs were pushed to the different 3D encoder–decoder segmentation networks, respectively. All the patients were divided into training (n = 120), validation (n = 30) and testing (n = 20) datasets. The average accuracy of the slice classification model was 95.99%. The Dice similarity coefficient and 95% Hausdorff distance, respectively, for each OAR were as follows: right eye (0.88 ± 0.03 and 1.57 ± 0.92 mm), left eye (0.89 ± 0.03 and 1.35 ± 0.43 mm), right optic nerve (0.72 ± 0.09 and 1.79 ± 1.01 mm), left optic nerve (0.73 ± 0.09 and 1.60 ± 0.71 mm), brainstem (0.87 ± 0.04 and 2.28 ± 0.99 mm), right temporal lobe (0.81 ± 0.12 and 3.28 ± 2.27 mm), left temporal lobe (0.82 ± 0.09 and 3.73 ± 2.08 mm), right temporomandibular joint (0.70 ± 0.13 and 1.79 ± 0.79 mm), left temporomandibular joint (0.70 ± 0.16 and 1.98 ± 1.48 mm), mandible (0.89 ± 0.02 and 1.66 ± 0.51 mm), right parotid (0.77 ± 0.07 and 7.30 ± 4.19 mm) and left parotid (0.71 ± 0.12 and 8.41 ± 4.84 mm). The total segmentation time was 40.13 s. The 3D encoder–decoder network facilitated by the slice classification model demonstrated superior performance in accuracy and efficiency in segmenting OARs in H&N CT images. This may significantly reduce the workload for radiation oncologists.
Pudendal flap—a good option for creating neo-scrotum after Fournier’s gangrene: a case series
Authors: Khanal Bhawani , Agrawal Sunit , Gurung Roshan , Sah Suresh , Gupta Rakesh Kumar
Published: September 2020

Scrotal skin loss following Fournier’s gangrene is very distressing to the patients. The management is complex and challenging shown by the multiplicity of flaps and techniques described in the literature.

We included a total of 14 patients with the diagnosis of Fournier’s gangrene over a period of 1 year in our department. We used a modified pudendal thigh flap to reconstruct neo-scrotum in patients with scrotal defects resulting from excision and debridement of Fournier’s gangrene. The average age group of the patients in our study was 41.8 years. The average body mass index in our study was 22.36 kg/m2. The average defect size in our study was 7.05 × 13.07 cm2. There was a single case of flap necrosis. Modified pudendal thigh flap produces a neo-scrotum that looks natural in appearance, provides good quality skin cover and cushion to the testes as well as protective sensation.
A new adenylyl cyclase, putative disease-resistance RPP13-like protein 3, participates in abscisic acid-mediated resistance to heat stress in maize
Authors: Yang Hao , Zhao Yulong , Chen Ning , Liu Yanpei , Yang Shaoyu , Du Hanwei , Wang Wei , Wu Jianyu , Tai Fuju , Chen Feng , Hu Xiuli
Published: September 2020

In plants, 3´,5´-cyclic adenosine monophosphate (cAMP) is an important second messenger with varied functions; however, only a few adenylyl cyclases (ACs) that synthesize cAMP have been identified. Moreover, the biological roles of ACs/cAMP in response to stress remain largely unclear. In this study, we used quantitative proteomics techniques to identify a maize heat-induced putative disease-resistance RPP13-like protein 3 (ZmRPP13-LK3), which has three conserved catalytic AC centres. The AC activity of ZmRPP13-LK3 was confirmed by in vitro enzyme activity analysis, in vivo RNAi experiments, and functional complementation in the E. coli cyaA mutant. ZmRPP13-LK3 is located in the mitochondria. The results of in vitro and in vivo experiments indicated that ZmRPP13-LK3 interacts with ZmABC2, a possible cAMP exporter. Under heat stress, the concentrations of ZmRPP13-LK3 and cAMP in the ABA-deficient mutant vp5 were significantly less than those in the wild-type, and treatment with ABA and an ABA inhibitor affected ZmRPP13-LK3 expression in the wild-type. Application of 8-Br-cAMP, a cAMP analogue, increased heat-induced expression of heat-shock proteins in wild-type plants and alleviated heat-activated oxidative stress. Taken together, our results indicate that ZmRPP13-LK3, a new AC, can catalyse ATP for the production of cAMP and may be involved in ABA-regulated heat resistance.
Higher order spectra of weak lensing convergence maps in parametrized theories of modified gravity
Authors: Munshi D , McEwen J D
Published: September 2020

We compute the low-ℓ limit of the family of higher order spectra for projected (2D) weak lensing convergence maps. In this limit these spectra are computed to an arbitrary order using tree-level perturbative calculations. We use the flat-sky approximation and Eulerian perturbative results based on a generating function approach. We test these results for the lower order members of this family, i.e. the skew- and kurt-spectra against state-of-the-art simulated all-sky weak lensing convergence maps and find our results to be in very good agreement. We also show how these spectra can be computed in the presence of a realistic sky-mask and Gaussian noise. We generalize these results to 3D and compute the equal-time higher order spectra. These results will be valuable in analysing higher order statistics from future all-sky weak lensing surveys such as the Euclid survey at low-ℓ modes. As illustrative examples, we compute these statistics in the context of the Horndeski and beyond Horndeski theories of modified gravity. They will be especially useful in constraining theories such as the Gleyzes–Langlois–Piazza–Vernizzi (GLPV) theories and degenerate higher order scalar-tensor theories as well as the commonly used normal-branch of Dvali–Gabadadze–Porrati model, clustering quintessence models and scenarios with massive neutrinos.
Weak lensing skew-spectrum
Authors: Munshi D , Namikawa T , Kitching T D , McEwen J D , Bouchet F R
Published: September 2020

We introduce the skew-spectrum statistic for weak lensing convergence κ maps and test it against state-of-the-art high-resolution all-sky numerical simulations. We perform the analysis as a function of source redshift and smoothing angular scale for individual tomographic bins. We also analyse the cross-correlation between different tomographic bins. We compare the numerical results to fitting-functions used to model the bispectrum of the underlying density field as a function of redshift and scale. We derive a closed form expression for the skew-spectrum for gravity-induced secondary non-Gaussianity. We also compute the skew-spectrum for the projected κ inferred from cosmic microwave background (CMB) studies. As opposed to the low redshift case, we find the post-Born corrections to be important in the modelling of the skew-spectrum for such studies. We show how the presence of a mask and noise can be incorporated in the estimation of a skew-spectrum.
The Genomic Basis of Rapid Adaptation to Antibiotic Combination Therapy in Pseudomonas aeruginosa
Authors: Barbosa Camilo , Mahrt Niels , Bunk Julia , Graßer Matthias , Rosenstiel Philip , Jansen Gunther , Schulenburg Hinrich
Published: September 2020

Combination therapy is a common antibiotic treatment strategy that aims at minimizing the risk of resistance evolution in several infectious diseases. Nonetheless, evidence supporting its efficacy against the nosocomial opportunistic pathogen Pseudomonas aeruginosa remains elusive. Identification of the possible evolutionary paths to resistance in multidrug environments can help to explain treatment outcome. For this purpose, we here performed whole-genome sequencing of 127 previously evolved populations of P. aeruginosa adapted to sublethal doses of distinct antibiotic combinations and corresponding single-drug treatments, and experimentally characterized several of the identified variants. We found that alterations in the regulation of efflux pumps are the most favored mechanism of resistance, regardless of the environment. Unexpectedly, we repeatedly identified intergenic variants in the adapted populations, often with no additional mutations and usually associated with genes involved in efflux pump expression, possibly indicating a regulatory function of the intergenic regions. The experimental analysis of these variants demonstrated that the intergenic changes caused similar increases in resistance against single and multidrug treatments as those seen for efflux regulatory gene mutants. Surprisingly, we could find no substantial fitness costs for a majority of these variants, most likely enhancing their competitiveness toward sensitive cells, even in antibiotic-free environments. We conclude that the regulation of efflux is a central target of antibiotic-mediated selection in P. aeruginosa and that, importantly, changes in intergenic regions may represent a usually neglected alternative process underlying bacterial resistance evolution, which clearly deserves further attention in the future.
Rewiring of growth-dependent transcription regulation by a point mutation in region 1.1 of the housekeeping σ factor
Authors: Pletnev Philipp , Pupov Danil , Pshanichnaya Lizaveta , Esyunina Daria , Petushkov Ivan , Nesterchuk Mikhail , Osterman Ilya , Rubtsova Maria , Mardanov Andrey , Ravin Nikolai , Sergiev Petr , Kulbachinskiy Andrey , Dontsova Olga
Published: September 2020

In bacteria, rapid adaptation to changing environmental conditions depends on the interplay between housekeeping and alternative σ factors, responsible for transcription of specific regulons by RNA polymerase (RNAP). In comparison with alternative σ factors, primary σs contain poorly conserved region 1.1, whose functions in transcription are only partially understood. We found that a single mutation in region 1.1 in Escherichia coli σ70 rewires transcription regulation during cell growth resulting in profound phenotypic changes. Despite its destabilizing effect on promoter complexes, this mutation increases the activity of rRNA promoters and also decreases RNAP sensitivity to the major regulator of stringent response DksA. Using total RNA sequencing combined with single-cell analysis of gene expression we showed that changes in region 1.1 disrupt the balance between the "greed" and "fear" strategies thus making the cells more susceptible to environmental threats and antibiotics. Our results reveal an unexpected role of σ region 1.1 in growth-dependent transcription regulation and suggest that changes in this region may facilitate rapid switching of RNAP properties in evolving bacterial populations.
Functional Impairment of Skin Appendages Due to Peripheral Nerve Involvement by Mycobacterium leprae
Authors: Granger Donald L , Rosado-Santos Harry , Lo Tze Shien , Florell Scott R , Shimwella Rehema A T
Published: September 2020

In the earliest stage of Mycobacterium leprae infection, bacteria parasitize fine fiber twigs of autonomic peripheral nerves supplying efferent impulses to appendages of the skin. This obligate intracellular pathogen invades Schwann cells, the glial cells of peripheral nerves. Intracellular events inhibit Schwann cell physiology in complex ways, which include demyelination and dedifferentiation. Ultimately, axons embraced by their surrounding dysfunctional glia are damaged by poorly understood mechanisms. Loss of nerve conduction impairs the functions of skin appendages including hair growth, sebaceous gland secretion, sweating, and skin pigmentation. At the clinical level, these changes may be subtle and may precede the more obvious anesthetic skin lesions associated with Hansen’s disease. Recognizing the early signs of skin appendage malfunction may aid in diagnosis leading to initiation of antimycobacterial treatment. Effective therapy administered early during infection may prevent irreversible peripheral nerve destruction, the presage for morbid complications of leprosy.
Characterization of Prolonged COVID-19 Symptoms in an Outpatient Telemedicine Clinic
Authors: Cellai Michele , O’Keefe James B
Published: September 2020

We identified patients with coronavirus disease 2019 in a telemedicine clinic who requested ongoing follow-up calls 6 weeks after symptom onset. In this group, respiratory symptoms are the most common complaints, asthma and lung disease are frequent comorbidities, and patients often have not returned to work or usual activity.
Prolonged Low-Dose Methylprednisolone in Patients With Severe COVID-19 Pneumonia
Authors: Salton Francesco , Confalonieri Paola , Meduri G Umberto , Santus Pierachille , Harari Sergio , Scala Raffaele , Lanini Simone , Vertui Valentina , Oggionni Tiberio , Caminati Antonella , Patruno Vincenzo , Tamburrini Mario , Scartabellati Alessandro , Parati Mara , Villani Massimiliano , Radovanovic Dejan , Tomassetti Sara , Ravaglia Claudia , Poletti Venerino , Vianello Andrea , Gaccione Anna Talia , Guidelli Luca , Raccanelli Rita , Lucernoni Paolo , Lacedonia Donato , Foschino Barbaro Maria Pia , Centanni Stefano , Mondoni Michele , Davì Matteo , Fantin Alberto , Cao Xueyuan , Torelli Lucio , Zucchetto Antonella , Montico Marcella , Casarin Annalisa , Romagnoli Micaela , Gasparini Stefano , Bonifazi Martina , D’Agaro Pierlanfranco , Marcello Alessandro , Licastro Danilo , Ruaro Barbara , Volpe Maria Concetta , Umberger Reba , Confalonieri Marco
Published: September 2020

Background

In hospitalized patients with coronavirus disease 2019 (COVID-19) pneumonia, progression to acute respiratory failure requiring invasive mechanical ventilation (MV) is associated with significant morbidity and mortality. Severe dysregulated systemic inflammation is the putative mechanism. We hypothesize that early prolonged methylprednisolone (MP) treatment could accelerate disease resolution, decreasing the need for intensive care unit (ICU) admission and mortality.

Methods

We conducted a multicenter observational study to explore the association between exposure to prolonged, low-dose MP treatment and need for ICU referral, intubation, or death within 28 days (composite primary end point) in patients with severe COVID-19 pneumonia admitted to Italian respiratory high-dependency units. Secondary outcomes were invasive MV-free days and changes in C-reactive protein (CRP) levels.

Results

Findings are reported as MP (n = 83) vs control (n = 90). The composite primary end point was met by 19 vs 40 (adjusted hazard ratio [aHR], 0.41; 95% CI, 0.24–0.72). Transfer to ICU and invasive MV were necessary in 15 vs 27 (P = .07) and 14 vs 26 (P = .10), respectively. By day 28, the MP group had fewer deaths (6 vs 21; aHR, 0.29; 95% CI, 0.12–0.73) and more days off invasive MV (24.0 ± 9.0 vs 17.5 ± 12.8; P = .001). Study treatment was associated with rapid improvement in PaO2:FiO2 and CRP levels. The complication rate was similar for the 2 groups (P = .84).

Conclusion

In patients with severe COVID-19 pneumonia, early administration of prolonged, low dose MP treatment was associated with a significantly lower hazard of death (71%) and decreased ventilator dependence. Treatment was safe and did not impact viral clearance. A large randomized controlled trial (RECOVERY trial) has been performed that validates these findings.

Clinical trial registration. ClinicalTrials.gov NCT04323592.
Occult Colonic Perforation in a Patient With Coronavirus Disease 2019 After Interleukin-6 Receptor Antagonist Therapy
Authors: Schwab Kristin , Hamidi Sepehr , Chung Augustine , Lim Raymond J , Khanlou Negar , Hoesterey Daniel , Dumitras Camelia , Adeyiga Oladunni B , Phan-Tang Michelle , Wang Tisha S , Saggar Rajan , Goldstein Jeffrey , Belperio John A , Dubinett Steven M , Kim Jocelyn T , Salehi-Rad Ramin
Published: September 2020

Background

Interleukin-6 blockade (IL-6) has become a focus of therapeutic investigation for the coronavirus disease 2019 (COVID-19).

Methods

We report a case of a 34-year-old with COVID-19 pneumonia receiving an IL-6 receptor antagonist (IL-6Ra) who developed spontaneous colonic perforation. This perforation occurred despite a benign abdominal exam and in the absence of other known risk factors associated with colonic perforation.

Results

Examination of the colon by electron microscopy revealed numerous intact severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virions abutting the microvilli of the colonic mucosa. Multiplex immunofluorescent staining revealed the presence of the SARS-CoV-2 spike protein on the brush borders of colonic enterocytes that expressed angiotensin-converting enzyme 2. However, no viral particles were observed within the enterocytes to suggest direct viral injury as the cause of colonic perforation.

Conclusions

These data and absence of known risk factors for spontaneous colonic perforation implicate IL-6Ra therapy as the potential mediator of colonic injury in this case. Furthermore, this report provides the first in situ visual evidence of the virus in the colon of a patient presenting with colonic perforation adding to growing evidence that intact infectious virus can be present in the stool.
Endothelial Dysfunction Is Related to Monocyte Activation in Antiretroviral-Treated People With HIV and HIV-Negative Adults in Kenya
Authors: Temu Tecla M , Polyak Stephen J , Zifodya Jerry S , Wanjalla Celestine N , Koethe John R , Masyuko Sarah , Nyabiage Jerusha , Kinuthia John , Gervassi Ana L , Oyugi Julius , Page Stephanie , Farquhar Carey
Published: September 2020

Background

Residual monocyte activation may contribute to increased risk for endothelial dysfunction and subsequent atherosclerotic cardiovascular diseases (CVDs) among people with HIV (PWH) on antiretroviral therapy (ART). We examined the relationship between monocyte activation and endothelial activation in PWH in Kenya.

Methods

Serum levels of markers of endothelial activation (soluble/circulating intercellular [sICAM-1] and vascular [sVCAM-1] cell adhesion molecule–1), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and monocyte activation (soluble CD14 [sCD14]) were measured in 275 PWH on ART and 266 HIV-negative persons. Linear regression was used to evaluate associations, adjusting for demographic and traditional CVD risk factors.

Results

Among 541 participants, the median age was 43 years, 50% were female, and most PWH were virally suppressed (97%). sICAM-1 and sVCAM-1 levels were significantly higher in PWH than in HIV-negative participants (P < .001 for both). After further adjustment for traditional CVD risk factors, HIV infection remained associated with 49% (95% CI, 33% to 67%) greater sICAM-1 and 30% (95% CI, 14% to 48%) greater sVCAM-1 relative to uninfected controls. Adjustment for sCD14 substantially attenuated the difference between PWH and HIV-negative individuals. In a stratified analysis of PWH, both sICAM-1 and sVCAM-1 were positively associated with sCD14 (P < .001).

Conclusions

Despite viral suppression, African PWH have evidence of enhanced endothelial activation associated with sCD14, suggesting that monocyte activation plays a role in atherosclerotic plaque development. Future studies are needed to determine mechanistic pathways leading to monocyte activation in this population.
Solar Ultraviolet Radiation and Vitamin D Deficiency on Epstein-Barr Virus Reactivation: Observational and Genetic Evidence From a Nasopharyngeal Carcinoma-Endemic Population
Authors: Mai Zhi-Ming , Lin Jia-Huang , Ngan Roger Kai-Cheong , Kwong Dora Lai-Wan , Ng Wai-Tong , Ng Alice Wan-Ying , Ip Kai-Ming , Chan Yap-Hang , Lee Anne Wing-Mui , Ho Sai-Yin , Lung Maria Li , Lam Tai-Hing
Published: September 2020

Background

We investigated the relationship of Epstein-Barr virus viral capsid antigen (EBV VCA-IgA) serostatus with ambient and personal ultraviolet radiation (UVR) and vitamin D exposure.

Methods

Using data from a multicenter case-control study, we included 1026 controls subjects in 2014–2017 in Hong Kong, China. Odds ratios (ORs) and 95% confidence intervals (CIs) of the association between UVR exposure and EBV VCA-IgA (seropositivity vs seronegativity) were calculated using unconditional logistic regression models adjusted for potential confounders.

Results

We observed a large increase in seropositivity of EBV VCA-IgA in association with duration of sunlight exposures at both 10 years before recruitment and age 19–30 years (adjusted OR = 3.59, 95% CI = 1.46–8.77; and adjusted OR = 2.44, 95% CI = 1.04–5.73 for ≥8 vs <2 hours/day; P for trend = .005 and .048, respectively). However, no association of EBV VCA-IgA serostatus with other indicators of UVR exposure was found. In addition, both circulating 25-hydroxyvitamin D (25OHD) and genetic predicted 25OHD were not associated with EBV VCA-IgA serostatus.

Conclusions

Our results suggest that personal UVR exposure may be associated with higher risk of EBV reactivation, but we did not find clear evidence of vitamin D exposure (observational or genetic), a molecular mediator of UVR exposure. Further prospective studies in other populations are needed to confirm this finding and to explore the underlying biological mechanisms. Information on photosensitizing agents, and serological markers of EBV, and biomarkers related to systemic immunity and inflammation should be collected and are also highly relevant in future studies.
Management of Gram-Negative Bloodstream Infections in the Era of Rapid Diagnostic Testing: Impact With and Without Antibiotic Stewardship
Authors: Claeys Kimberly C , Heil Emily L , Hitchcock Stephanie , Johnson J Kristie , Leekha Surbhi
Published: September 2020

Background

Verigene Blood-Culture Gram-Negative is a rapid diagnostic test (RDT) that detects gram-negatives (GNs) and resistance within hours from gram stain. The majority of the data support the use of RDTs with antimicrobial stewardship (AMS) intervention in gram-positive bloodstream infection (BSI). Less is known about GN BSI.

Methods

This was a retrospective quasi-experimental (nonrandomized) study of adult patients with RDT-target GN BSI comparing patients pre-RDT/AMS vs post-RDT/pre-AMS vs post-RDT/AMS. Optimal therapy was defined as appropriate coverage with the narrowest spectrum, accounting for source and co-infecting organisms. Time to optimal therapy was analyzed using Kaplan-Meier and multivariable Cox proportional hazards regression.

Results

Eight-hundred thirty-two patients were included; 237 pre-RDT/AMS vs 308 post-RDT/pre-AMS vs 237 post-RDT/AMS, respectively. The proportion of patients on optimal antibiotic therapy increased with each intervention (66.5% vs 78.9% vs 83.2%; P < .0001). Time to optimal therapy (interquartile range) decreased with introduction of RDT: 47 (7.9–67.7) hours vs 24.9 (12.4–55.2) hours vs 26.5 (10.3–66.5) hours (P = .09). Using multivariable modeling, infectious diseases (ID) consult was an effect modifier. Within the ID consult stratum, controlling for source and ICU stay, compared with the pre-RDT/AMS group, both post-RDT/pre-AMS (adjusted hazard ratio [aHR], 1.34; 95% CI, 1.04–1.72) and post-RDT/AMS (aHR, 1.28; 95% CI, 1.01–1.64), improved time to optimal therapy. This effect was not seen in the stratum without ID consult.

Conclusions

With the introduction of RDT and AMS, both proportion and time to optimal antibiotic therapy improved, especially among those with an existing ID consult. This study highlights the beneficial role of RDTs in GN BSI.
Surprisingly Low Levels of Measles Immunity in Persons With HIV: A Seroprevalence Survey in a United States HIV Clinic
Authors: Rearigh Lindsey , O’Neill Jennifer , Kubat Maureen , Sayles Harlan , Swindells Susan , Bares Sara H
Published: September 2020

Background

Measles outbreaks have become increasingly common due to deteriorating vaccination rates, fluctuating herd immunity, and varying antibody decline. Limited knowledge exists regarding prevalence and risk factors associated with measles seronegativity among persons with HIV (PWH).

Methods

This was a cross-sectional study conducted at an academic HIV clinic in Omaha, Nebraska. Participants were screened for the presence of measles IgG antibody. Demographic and clinical information was obtained through electronic medical record review. Simple and multivariable logistic regressions were performed to identify risk factors for measles seronegativity.

Results

Three hundred fifty-one participants were enrolled, with a measles seroprevalence rate of 70.3%. The mean age (range) was 48 (20–74) years, 77% were male, and 53% were Caucasian. The mean CD4 nadir (range) was 334 (1–1675) cells/mm3. At the time of testing, 86% and 87% of the seronegative and seropositive participants had an HIV RNA <50 copies/mL, respectively. Younger age was significantly associated with measles seronegativity (P = .003), as was birth year after 1957 (P = .021). Prior history of measles infection was associated with seropositivity (P = .011). All other risk factors evaluated, including written documentation of adequate vaccination, were not associated with seronegativity.

Conclusions

Our study demonstrates a measles seroprevalence rate that is remarkably lower than previously reported in PWH (92%), and, more importantly, is considerably lower than the rate needed to maintain herd immunity (95%). With higher than expected seronegativity and absence of notable risk factors aside from age, our findings support expanded measles immunity screening for PWH who are at risk of measles exposure.