bluuebunny/crossref_metadata_2025 huggingface dataset:
Most recommended medical interventions reach P < 0.005 for their primary outcomes in meta-analyses
Authors: Koletsi Despina , Solmi Marco , Pandis Nikolaos , Fleming Padhraig S , Correll Christoph U , Ioannidis John P A
Published: November 2019

Background

It has been proposed that the threshold of statistical significance should shift from P-value < 0.05 to P-value < 0.005, but there is concern that this move may dismiss effective, useful interventions. We aimed to assess how often medical interventions are recommended although their evidence in meta-analyses of randomized trials lies between P-value = 0.05 and P-value = 0.005.

Methods

We included Cochrane systematic reviews (SRs) published from 1 January 2013 to 30 June 2014 that had at least one meta-analysis with GRADE (Grading of Recommendations Assessment, Development and Evaluation) assessment and at least one primary outcome having favourable results for efficacy at P-value < 0.05. Only comparisons of randomized trials between active versus no treatment/placebo were included. We then assessed the respective UpToDate recommendations for clinical practice from 22 May 2018 to 5 October 2018 and recorded how many treatments were recommended and what were the P-values in their meta-analysis evidence. The primary analysis was based on the first-listed outcomes.

Results

Of 608 screened SRs with GRADE assessment, 113 SRs were eligible, including 143 comparisons of which 128 comparisons had first-listed primary outcomes with UpToDate coverage. Altogether, 60% (58/97) of interventions with P-values < 0.005 for their evidence were recommended versus 32% (10/31) of those with P-value 0.005–0.05. Therefore, most (58/68, 85.2%) of the recommended interventions had P-values < 0.005 for the first-listed primary outcome. Of the 10 exceptions, 4 had other primary outcomes with P-values < 0.005 and another 4 had additional extensive evidence for similar indications that would allow extrapolation for practice recommendations.

Conclusions

Few interventions are recommended without their evidence from meta-analyses of randomized trials reaching P-value < 0.005.
An Integralgeometric Approach to Dorronsoro Estimates
Authors: Orponen Tuomas
Published: November 2019

A theorem of Dorronsoro from 1985 quantifies the fact that a Lipschitz function $f \colon \mathbb{R}^{n} \to \mathbb{R}$ can be approximated by affine functions almost everywhere, and at sufficiently small scales. This paper contains a new, purely geometric, proof of Dorronsoro’s theorem. In brief, it reduces the problem in $\mathbb{R}^{n}$ to a problem in $\mathbb{R}^{n - 1}$ via integralgeometric considerations. For the case $n = 1$, a short geometric proof already exists in the literature. A similar proof technique applies to parabolic Lipschitz functions $f \colon \mathbb{R}^{n - 1} \times \mathbb{R} \to \mathbb{R}$. A natural Dorronsoro estimate in this class is known, due to Hofmann. The method presented here allows one to reduce the parabolic problem to the Euclidean one and to obtain an elementary proof also in this setting. As a corollary, I deduce an analogue of Rademacher’s theorem for parabolic Lipschitz functions.
Targeting Parasite-Produced Macrophage Migration Inhibitory Factor as an Antivirulence Strategy With Antibiotic–Antibody Combination to Reduce Tissue Damage
Authors: Ghosh Swagata , Padalia Jay , Ngobeni Renay , Abendroth Jan , Farr Laura , Shirley Debbie-Ann , Edwards Thomas , Moonah Shannon
Published: November 2019

Targeting virulence factors represents a promising alternative approach to antimicrobial therapy, through the inhibition of pathogenic pathways that result in host tissue damage. Yet, virulence inhibition remains an understudied area in parasitology. Several medically important protozoan parasites such as Plasmodium, Entamoeba, Toxoplasma, and Leishmania secrete an inflammatory macrophage migration inhibitory factor (MIF) cytokine homolog, a virulence factor linked to severe disease. The aim of this study was to investigate the effectiveness of targeting parasite-produced MIF as combination therapy with standard antibiotics to reduce disease severity. Here, we used Entamoeba histolytica as the model MIF-secreting protozoan, and a mouse model that mirrors severe human infection. We found that intestinal inflammation and tissue damage were significantly reduced in mice treated with metronidazole when combined with anti–E. histolytica MIF antibodies, compared to metronidazole alone. Thus, this preclinical study provides proof-of-concept that combining antiparasite MIF-blocking antibodies with current standard-of-care antibiotics might improve outcomes in severe protozoan infections.
Emergence of an Empedobacter falsenii strain harbouring a tet(X)-variant-bearing novel plasmid conferring resistance to tigecycline
Authors: Zeng Yu , Dong Ning , Zhang Rong , Liu Congcong , Sun Qiaoling , Lu Jiayue , Shu Lingbin , Cheng Qipeng , Chan Edward Wai-Chi , Chen Sheng
Published: November 2019

Objectives

To investigate the genomic and phenotypic characteristics of an MDR Empedobacter falsenii strain isolated from a Chinese patient, which was phenotypically resistant to all last-line antibiotics (carbapenems, colistin and tigecycline).

Methods

Species identity was determined by MALDI-TOF MS analysis. The complete genome sequence of the isolate was determined by WGS and the genetic elements conferring antimicrobial resistance were determined. The origin of this strain was tracked by phylogenetic analysis.

Results

The E. falsenii strain was genetically most closely related to an Empedobacter sp. strain isolated from the USA. Members of E. falsenii are speculated to be intrinsically resistant to colistin. The carbapenem resistance of this strain was conferred by a chromosomal blaEBR-2 variant gene. Phylogenetic analysis indicated that the gene encoding the EBR β-lactamase was widely distributed in Empedobacter spp. Tigecycline resistance was mediated by a tet(X) variant gene encoded by a non-conjugative and non-typeable plasmid.

Conclusions

The MDR phenotype of the E. falsenii isolate was conferred by different mechanisms. Findings from us and others indicate that E. falsenii may serve as a reservoir for carbapenem and tigecycline resistance determinants.
Insights into the Evolutionary History of the Hawaiian Bidens (Asteraceae) Adaptive Radiation Revealed Through Phylogenomics
Authors: Knope Matthew L , Bellinger M Renee , Datlof Erin M , Gallaher Timothy J , Johnson Melissa A
Published: November 2019

Hawaiian plant radiations often result in lineages with exceptionally high species richness and extreme morphological and ecological differentiation. However, they typically display low levels of genetic variation, hindering the use of classic DNA markers to resolve their evolutionary histories. Here we utilize a phylogenomic approach to generate the first generally well-resolved phylogenetic hypothesis for the evolution of the Hawaiian Bidens (Asteraceae) adaptive radiation, including refined initial colonization and divergence time estimates. We sequenced the chloroplast genome (plastome) and nuclear ribosomal complex for 18 of the 19 endemic species of Hawaiian Bidens and 4 outgroup species. Phylogenomic analyses based on the concatenated dataset (plastome and nuclear) resulted in identical Bayesian and Maximum Likelihood trees with high statistical support at most nodes. Estimates from dating analyses were similar across datasets, with the crown group emerging ~1.76–1.82 Mya. Biogeographic analyses based on the nuclear and concatenated datasets indicated that colonization within the Hawaiian Islands generally followed the progression rule with 67–80% of colonization events from older to younger islands, while only 53% of events followed the progression rule in the plastome analysis. We find strong evidence for nuclear-plastome conflict indicating a potentially important role for hybridization in the evolution of the group. However, incomplete lineage sorting cannot be ruled out due to the small number of independent loci analyzed. This study contributes new insights into species relationships and the biogeographic history of the explosive Hawaiian Bidens adaptive radiation.
Cholecystitis and hemobilia
Authors: Staszak Jessica K , Buechner David , Helmick Ryan A
Published: November 2019

Hemobilia, or hemorrhage into the biliary system, is an unusual cause of gastrointestinal bleeding most commonly seen in accidental or iatrogenic trauma. We present the rare case of a 43-year-old gentleman who presents with an intrahepatic pseudoaneurysm caused by cholecystitis. The management of the hemobilia was technically challenging requiring multiple interventional procedures. We review the pathophysiology and treatment strategies for this rare case of gastrointestinal hemorrhage.
Sugar sensing responses to low and high light in leaves of the C4 model grass Setaria viridis
Authors: Henry Clémence , Watson-Lazowski Alexander , Oszvald Maria , Griffiths Cara , Paul Matthew J , Furbank Robert T , Ghannoum Oula
Published: November 2019

ABSTRACT :Although sugar regulate photosynthesis, the signalling pathways underlying this process remain elusive, especially for C4 crops. To address this knowledge gap and identify potential candidate genes, we treated Setaria viridis (C4 model) plants acclimated to medium light intensity (ML, 500 µmol m-2 s-1) with low (LL, 50 µmol m-2 s-1) or high (HL, 1000 µmol m-2 s-1) light for 4 days and observed the consequences on carbon metabolism and the transcriptome of source leaves. LL impaired photosynthesis and reduced leaf content of signalling sugars (glucose, sucrose and trehalose-6-phosphate). Contrastingly, HL strongly induced sugar accumulation without repressing photosynthesis. LL more profoundly impacted leaf transcriptome, including photosynthetic genes. LL and HL contrastingly altered the expression of HXK and SnRK1 sugar sensors and trehalose pathway genes. The expression of key target genes of HXK and SnRK1 were affected by LL and sugar depletion, while surprisingly HL and strong sugar accumulation only slightly repressed the SnRK1 signalling pathway. In conclusion, we demonstrate that LL profoundly impacted photosynthesis and the transcriptome of S. viridis source leaves, while HL altered sugar levels more than LL. We also present the first evidence that sugar signalling pathways in C4 source leaves may respond to light intensity and sugar accumulation differently to C3 source leaves.
A search for heavy-metal stars: abundance analyses of hot subdwarfs with Subaru★
Authors: N Naslim , Jeffery C S , Woolf V M
Published: November 2019

The discovery of extremely zirconium- and lead-rich surfaces amongst a small subgroup of hot subdwarfs has provoked questions pertaining to chemical peculiarity in hot star atmospheres and about their evolutionary origin. With only three known in 2014, a limited search for additional ‘heavy-metal’ subdwarfs was initiated with the Subaru telescope. Five hot subdwarfs having intermediate to high surface enrichment of helium were observed at high-resolution and analyzed for surface properties and abundances. This paper reports the analyses of four of these stars. PG 1559+048 and FBS 1749+373, having only intermediate helium enrichment, show strong lines of triply ionized lead. PG 1559+048 also shows a strong overabundance of germanium and yttrium. With more helium-rich surfaces, Ton 414 and J17554+5012, do not show evidence of heavy-metal enrichment. This limited survey suggests that extreme enrichment of ‘heavy metals’ by selective radiative levitation in hot subdwarf atmospheres is suppressed if the star is too helium-rich.
Cosmological evolution of orientations of cluster-sized dark matter haloes and their central galaxies in the Horizon-AGN simulation
Authors: Okabe Taizo , Nishimichi Takahiro , Oguri Masamune , Peirani Sébastien , Kitayama Tetsu , Sasaki Shin , Suto Yasushi , Pichon Christophe , Dubois Yohan
Published: November 2019

It is known observationally that the major axes of galaxy clusters and their brightest cluster galaxies are roughly aligned with each other. To understand the origin of the alignment, we identify 40 cluster-sized dark matter (DM) haloes with masses higher than 5 × 1013 M⊙ and their central galaxies (CGs) at z ≈ 0 in the Horizon-AGN cosmological hydrodynamical simulation. We trace the progenitors at 50 different epochs between 0 < z < 5. We then fit their shapes and orientations with a triaxial ellipsoid model. While the orientations of both DM haloes and CGs change significantly due to repeated mergers and mass accretions, their relative orientations are well aligned at each epoch even at high redshifts, z > 1. The alignment becomes tighter with cosmic time; the major axes of the CGs and their host DM haloes at present are aligned on average within ∼30○ in the three dimensional space and ∼20○ in the projected plane. The orientations of the major axes of DM haloes on average follow one of the eigen-vectors of the surrounding tidal field that corresponds to the slowest collapsing (or even stretching) mode, and the alignment with the tidal field also becomes tighter. This implies that the orientations of CGs and DM haloes at the present epoch are largely imprinted in the primordial density field of the Universe, whereas strong dynamical interactions such as mergers are important to explain their mutual alignment at each epoch.
Spiral arms in the protoplanetary disc HD100453 detected with ALMA: evidence for binary–disc interaction and a vertical temperature gradient
Authors: Rosotti G P , Benisty M , Juhász A , Teague R , Clarke C , Dominik C , Dullemond C P , Klaassen P D , Matrà L , Stolker T
Published: November 2019

Scattered light high-resolution imaging of the protoplanetary disc orbiting HD100453 shows two symmetric spiral arms, possibly launched by an external stellar companion. In this paper, we present new, sensitive high-resolution (∼30 mas) Band 7 ALMA observations of this source. This is the first source where we find counterparts in the sub-mm continuum to both scattered light spirals. The CO J = 3–2 emission line also shows two spiral arms; in this case, they can be traced over a more extended radial range, indicating that the southern spiral arm connects to the companion position. This is clear evidence that the companion is responsible for launching the spirals. The pitch angle of the submillimetre continuum spirals (∼6°) is lower than the one in scattered light (∼16°). We show that hydrodynamical simulations of binary–disc interaction can account for the difference in pitch angle only if one takes into account that the mid-plane is colder than the upper layers of the disc, as expected for the case of externally irradiated discs.
Pinnacles on the surface of the comet 67P/Churyumov-Gerasimenko: regional distribution and morphology
Authors: Krasilnikov S S , Skorov Y V , Basilevsky A T , Hviid S F , Mall U , Keller H U
Published: November 2019

Pinnacles are local topographic promontories of different shapes considered to be formed due to uneven surface erosion. In the case of comets, areal changes in the degree of erosion could be related to inhomogeneities of the nucleus. However, the amount of solar radiation and the thermal gradient is different across the orbit for geomorphological regions, which can result in different erosion and shape for a similar composition among two differently illuminated areas. Therefore, a study of the areal distribution of pinnacles on the nucleus surface and their morphology may help to understand the structure and properties of the nucleus material. We mapped 166 pinnacles on the comet nucleus surface of 67P/Churyumov-Gerasimenko. About a third of them have planimetrically rounded shape (rounded pinnacles) and the rest are planimetrically elongated (local ridges). In the southern hemisphere, number of both round pinnacles and local ridges is larger than in the northern hemisphere. This difference possibly indicates the higher effectiveness of the pinnacles’ formation in the southern hemisphere. At the same time the mean values of the measured parameters, including the height, show no statistically reliable difference between the north and south. We found that the maximum height of the pinnacles is about a hundred meters. Suggesting that they have been formed by sublimational erosion, this value allows estimating the minimum thickness of the eroded material and thus the degree of the evolutionary changes of the nucleus. In our future study, we will model pinnacles formation based on the here presented analysis of observations.
Can sodium fluorescein cause contrast-induced nephropathy?
Authors: Yun Donghwan , Kim Dong Ki , Lee Jung Pyo , Kim Yon Su , Oh Sohee , Lim Chun Soo
Published: November 2019

Background

Contrast-induced nephropathy (CIN) is a common cause of acute kidney injury (AKI), and can be diagnosed when the etiology of AKI is unclear other than via a contrast agent. Fluorescent angiography (FAG) with fluorescein sodium dye is generally considered to be safe for patients with kidney diseases. However, it remains unresolved whether or not FAG can induce CIN.

Methods

Patients from two tertiary hospitals who underwent FAG and had serum creatinine results within 4 weeks before FAG and 3 days after FAG between 2001 and 2017 were retrieved. Cases with concurrent iodinated contrast imaging or undergoing dialysis were excluded from the analysis. CIN was defined by two criteria: CIN criteria as >0.5 mg/dL or >25% increase in serum creatinine (sCr) level within 3 days after FAG, and contrast-induced acute kidney injury (CIAKI) criteria as ≥0.3 mg/dL increase within 2 days or ≥50% increase within 7 days after FAG.

Results

A total of 979 patients were screened, and we found 124 patients with AKI after FAG. After excluding 32 patients with clear causes of AKI other than FAG, the incidence rates of CIN were 7.3% by CIN criteria and 6.4% by CIAKI criteria. CIN incidence had a U-shaped distribution according to chronic kidney disease (CKD) stages in CIN criteria, while linear association between CIN incidence and CKD stages were found in CIAKI criteria. Kaplan–Meier curves showed the CIN group was significantly associated with end-stage renal disease (ESRD) progression (log-rank P < 0.001, in both CIN criteria and CIAKI criteria), and adjusted hazard ratios by multivariable Cox regression were 2.23 [95% confidence interval (CI) 1.468–3.378] in CIN criteria and 2.17 (95% CI 1.462–3.232) in CIAKI criteria.

Conclusions

According to CIN and CIAKI criteria, FAG may cause CIN and appeared to be a possible risk factor for ESRD progression. However, CIN or CIAKI criteria themselves may overestimate AKI and require meticulous attention to the interpretation of results.
Atypical Clinical Manifestations of Loiasis and Their Relevance for Endemic Populations
Authors: Buell Kevin G , Whittaker Charles , Chesnais Cédric B , Jewell Paul D , Pion Sébastien D S , Walker Martin , Basáñez Maria-Gloria , Boussinesq Michel
Published: November 2019

Background

Loiasis is mostly considered a relatively benign infection when compared with other filarial and parasitic diseases, with Calabar swellings and eyeworm being the most common signs. Yet, there are numerous reports in the literature of more serious sequelae. Establishing the relationship between infection and disease is a crucial first step toward estimating the burden of loiasis.

Methods

We conducted a systematic review of case reports containing 329 individuals and detailing clinical manifestations of loiasis with a focus on nonclassical, atypical presentations.

Results

Results indicate a high proportion (47%) of atypical presentations in the case reports identified, encompassing a wide range of cardiac, respiratory, gastrointestinal, renal, neurological, ophthalmological, and dermatological pathologies. Individuals with high microfilarial densities and residing in an endemic country were at greater risk of suffering from atypical manifestations.

Conclusions

Our findings have important implications for understanding the clinical spectrum of conditions associated with Loa loa infection, which extends well beyond the classical eyeworm and Calabar swellings. As case reports may overestimate the true rate of atypical manifestations in endemic populations, large-scale, longitudinal clinico-epidemiological studies will be required to refine our estimates and demonstrate causality between loiasis and the breadth of clinical manifestations reported. Even if the rates of atypical presentations were found to be lower, given that residents of loiasis-endemic areas are both numerous and the group most at risk of severe atypical manifestations, our conclusions support the recognition of loiasis as a significant public health burden across Central Africa.
Microsurgical Resection of a Middle Cerebellar Peduncle Cavernous Malformation: 3-Dimensional Operative Video
Authors: Rassi Marcio S , Ceccato Guilherme H W , Schindler Emerson , Fagundes Felipe G , Beiras Matias N P , Ferreira André L C , Sufianov Albert A , Borba Luis A B
Published: November 2019

Brainstem cavernous malformations are frequently surrounded by vital structures, which often makes surgical treatment a challenging task even to the most skilled surgeon. Accordingly, microsurgical excision is preferably offered to symptomatic patients and superficial lesions.
1-3
We present the case of a 41-yr-old male presenting with progressive dizziness and diplopia. Neurological examination showed horizontal nystagmus, dysmetria, and unbalance. Preoperative magnetic resonance imaging (MRI) suggested a cavernous malformation in the right middle cerebellar peduncle. A telovelar approach was employed with the guidance of intraoperative neurophysiological monitoring. An exophytic lesion was identified in the right middle cerebellar peduncle and a clear cleavage plane was obtained allowing circumferential dissection around the capsule. The lesion was removed en bloc. Postoperative MRI confirmed a complete excision of the malformation. The patient presented an improvement in his initial symptoms, with no new neurological deficit. Cavernous malformations related with the fourth ventricle can be successfully resected through a telovelar approach in select cases, especially when exophytic, where the surgeon might take advantage of the path created by the lesion. Informed consent was obtained from the patient for the procedure and publication of this operative video. Anatomic images were a courtesy of the Rhoton Collection, American Association of Neurological Surgeons (AANS)/Neurosurgical Research and Education Foundation (NREF).
ESTABLISHMENT OF LOCAL DIAGNOSTIC REFERENCE LEVELS FOR COMMON PROCEDURES OF COMPUTED TOMOGRAPHY IN YAZD PROVINCE
Authors: Zamani Hamed , Masjedi Hamidreza , Omidi Reza , Hosein Zare Mohammad
Published: November 2019

Objective: The aim of this study was to propose first established diagnostic reference levels (DRLs) in computed tomography (CT) for adults, based on volume-averaged CTDI and dose length product (DLP) metrics in Yazd Province. Materials and Methods: Six multislice CT scanners located at diverse areas of Yazd Province and seven common procedures were selected for the present study. For each procedure, at least twenty patients 18 years and older were sampled at each institution. For each patient, dose report data and scan parameters as well as patient’s information were abstracted from picture archiving and communication system. Results: Proposed DRLs in terms of computed tomography dose index (mGy) and DLP (mGy.cm) were as follows: brain (42, 527), sinus (25, 220), neck (14, 264), abdomen-pelvis (11, 295), routine chest (8, 247), CT pulmonary angiogram (32, 261) and chest HRCT (11, 455), respectively, slightly lower compared to other investigations. Conclusion: The proposed DRLs in this study should be considered as the local DRLs for the seven most common adult CT examinations in Yazd province so as to optimize the patient dose while maintaining acceptable image quality for the clinical task.
The rule in Saunders v Vautier: to the ‘residuary beneficiary’, the spoils?
Authors: Beynon Charlotte
Published: November 2019

The Royal Court of Guernsey was recently called upon to interpret Guernsey’s statutory incarnation of the rule in Saunders v Vautier in order to decide whether the sole beneficiary of a discretionary trust was entitled to collapse the trust and have the property distributed to it notwithstanding that, as a result of the trustee’s wide powers to appoint additional beneficiaries, it could be argued that the class of objects was not closed. The Royal Court held that the beneficiary could collapse the trust in those circumstances. This article considers the potential impact of this decision, particularly for ‘Red Cross’ trusts in Guernsey and beyond.
Virologic failure and switch to second-line antiretroviral therapy in children with HIV in Lilongwe, Malawi: an observational cohort study
Authors: Tweya Hannock , Feldacker Caryl , Kiruthu-Kamamia Christine , Billion Lucion , Gumulira Joe , Nhlema Angellina , Phiri Sam
Published: November 2019

Background

As routine viral load testing among HIV-infected individuals on antiretroviral therapy (ART) expands, virologic failure (VF) among children in developing countries remains poorly understood. We assessed the rate of VF, the proportion failing who were subsequently switched to second-line ART and factors associated with VF among children ≤18 y.

Methods

An observation cohort study among 1312 children at two public clinics in Lilongwe, Malawi who initiated a first-line ART regimen between January 2014 and December 2017 and remained on treatment for ≥6 mo was conducted. Kaplan-Meier methods estimated the probabilities of VF. Univariable and multivariable Poisson regression models were used to explore predictors of VF.

Result

Overall, 16% (208/1312) of children experienced VF with an incidence rate of 10.1 events per 100 person-years. Of the 208, 184 (88%) were switched to second-line ART: 68 (43%) switched the same day VF was confirmed and 106 (66%) switched within 90 d of confirmed VF. Use of a Nevirapine (NVP)-based regimen and initiating ART in 2016–2017 compared with 2014–2015 were independent predictors of VF.

Conclusion

VF is common among children receiving ART. The findings suggest that VF can be reduced by phasing out NVP-based regimen and by ensuring optimal adherence to ART.
Fibronectin is up‐regulated in podocytes by mechanical stress
Authors: Kliewe Felix , Kaling Sören , Lötzsch Henriette , Artelt Nadine , Schindler Maximilian , Rogge Henrik , Schröder Sindy , Scharf Christian , Amann Kerstin , Daniel Christoph , Lindenmeyer Maja T. , Cohen Clemens D. , Endlich Karlhans , Endlich Nicole
Published: November 2019

Hypertension is one of the central causes of kidney damage. In the past it was shown that glomerular hypertension leads to morphologic changes of podocytes and effacement and is responsible for detachment of these postmitotic cells. Because we have shown that podocytes are mechanosensitive and respond to mechanical stress by reorganization of the actin cytoskeleton in vitro, we look for mechanotransducers in podocytes. In this study, we demonstrate that the extracellular matrix protein fibronectin (Fn1) might be a potential candidate. The present study shows that Fn1 is essential for the attachment of podocytes during mechanical stress. By real‐time quantitative PCR as well as by liquid chromatography‐mass spectrometry, we found a significant up‐regulation of Fn1 caused by mechanical stretch (3 d, 0.5 Hz, and 5% extension). To study the role of Fn1 in cultured podocytes under mechanical stress, Fn1 was knocked down (Fn1 KD) by a specific small interfering RNA. Additionally, we established a Fn1 knockout (KO) podocyte cell line (Fn1 KO) by clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR‐associated protein 9 (Cas9). During mechanical stress, a significant loss of podocytes (>80%) was observed in Fn1 KD as well as Fn1 KO podocytes compared with control cells. Furthermore, Fn1 KO podocytes showed a significant down‐regulation of the focal adhesion proteins talin, vinculin, and paxillin and a reduced cell spreading, indicating an important role of Fn1 in adhesion. Analyses of kidney sections from patients with diabetic nephropathy have shown a significant up‐regulation of FN1 in contrast to control biopsies. In summary, we show that Fn1 plays an important role in the adaptation of podocytes to mechanical stress.—Kliewe, F., Kaling, S., Lötzsch, H., Artelt, N., Schindler, M., Rogge, H., Schröder, S., Scharf, C., Amann, K., Daniel, C., Lindenmeyer, M. T., Cohen, C. D., Endlich, K., Endlich, N. Fibronectin is up‐regulated in podocytes by mechanical stress. FASEB J. 33, 14450‐14460 (2019). www.fasebj.org
Rare case report of infective endocarditis due to Kocuria kristinae in a patient with ventricular septal defect
Authors: Ali Arif Maqsood , Waseem Gule Raana , Arif Shazia
Published: November 2019

Background. Infective endocarditis (IE) is an uncommon but life-threatening infection. It is commonly associated with diseased or damaged valves. Patients with congenital heart disease are more prone to getting IE than the general population. The typical organisms that cause IE include

Staphylococcus

, Coagulase-negative Staphylococcus, Streptococcus viridians and Enterococci. However, the importance of rare micro-organisms like

Kocuria kristinae

should not be underestimated especially when isolated from multiple blood cultures in patients suspected of IE.

Case presentation. We report a rare case of right-sided infective endocarditis due to

K. kristinae

in a young non-diabetic, non-addict female of low socioeconomic class who presented with undiagnosed fever for 1 year. She was investigated and treated for fever by several general practitioners without relief. Later on, she was diagnosed by a local cardiologist to have perimembranous ventricular septal defect with a small pulmonary valve vegetation. She was referred to a tertiary care cardiac hospital in Rawalpindi, Pakistan for further management. Transthoracic and transesophageal echocardiography confirmed IE secondary to preexisting congenital heart disease complicated with a small pulmonary vegetation. Her blood cultures yielded growth of K. kristanae, a rare micro-organism to cause IE. The patient responded to the antibiotic therapy.

Conclusion. Clinicians should have a high index of suspicion for K. kristanae IE as a possible cause of a prolonged fever especially in the presence of congenital heart disease. Antibiotic susceptibility is required for adequate therapy.
Mixta tenebrionis sp. nov., isolated from the gut of the plastic-eating mealworm Tenebrio molitor L.
Authors: Xia Mengli , Wang Jialei , Huo Yi-Xin , Yang Yu
Published: November 2019

A bacterial strain, BIT-26T, was isolated from the gut of plastic-eating mealworm Tenebrio molitor L. The taxonomic position of this new isolate was investigated by using a polyphasic approach. Cells of the strain were Gram-stain-negative, facultatively anaerobic, motile rods with peritrichous flagella. The 16S rRNA gene sequence (1412 bp) of strain BIT-26T showed the highest similarity (97.4 %) to

Erwinia piriflorinigrans

CFBP 5888T, followed by

Citrobacter sedlakii

NBRC 105722T (97.3 %),

Mixta calida

LMG 25383T (97.3 %),

Cronobacter muytjensii

ATCC 51329T (97.2 %) and

Mixta theicola

QC88-366 T (97.2 %). The results of phylogenetic analyses, based on the 16S rRNA gene and concatenated sequences of four housekeeping genes (atpD﻿, gyrB, infB ﻿and rpoB), placed strain BIT-26T within the genus

Mixta

of the family

Erwiniaceae

. This affiliation was also supported by the chemotaxonomic data. Strain BIT-26T had similar predominant fatty acids, including C12 : 0, C14 : 0, C16 : 0, C17 : 0 cyclo and C19 : 0 cyclo ω8c, to species of the genus

Mixta

. In silico DNA–DNA hybridization and average nucleotide identity calculations plus physiological and biochemical tests allowed the genotypic and phenotypic differentiation of strain BIT-26T from other species of the genus

Mixta

with validly published names. Therefore, strain BIT-26T is considered to represent a novel species, for which the name Mixta tenebrionis sp. nov is proposed. The type strain is BIT-26T (=CGMCC 1.17041T=KCTC 72449T).
Sphingobium fluviale sp. nov., isolated from a river
Authors: Sheu Shih-Yi , Guo Ya-Ping , Kwon Soon-Wo , Chen Wen-Ming
Published: November 2019

A Gram-stain-negative, rod-shaped, non-motile, poly-β-hydroxybutyrate-accumulating and aerobic bacterial strain, designated CHR27T, was isolated and characterized by using the polyphasic taxonomy approach. The results of phylogenetic analyses based on 16S rRNA gene sequences and coding sequences of an up-to-date bacterial core gene set (92 protein clusters) indicated that strain CHR27Tis affiliated with species in the genusSphingobium. 16S rRNA gene sequence similarity results indicated that strain CHR27Twas closely related to species of the genusSphingobium(94.3–97.0 %), and had the highest sequence similarity toSphingobium qiguoniiX23T(97.0 %). Strain CHR27Tshowed 19.4–22.1 % digital DNA–DNA hybridization values and 73.2–74.8 % average nucleotide identity values with the strains of otherSphingobiumspecies. Optimal growth occurred at 25 °C, pH 7.5 and in the absence of NaCl. The major fatty acids of strain CHR27Twere C18 : 1ω7cand summed feature 3 (C16 : 1ω7cand/or C16 : 1ω6c). The predominant hydroxy fatty acid was C14 : 02-OH. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidyldimethylethanolamine, two unidentified sphingoglycolipids and an unidentified aminophospholipid. Strain CHR27Tcontained spermidine as the major polyamine and putrescine as a minor component. The only isoprenoid quinone was ubiquinone-10. The genomic DNA G+C content of strain CHR27Twas 61.8 mol%. On the basis of the phylogenetic inference and phenotypic data, strain CHR27Twas considered a representative of a novel species within the genusSphingobium. The nameSphingobium fluvialesp. nov. is proposed, with strain CHR27T(=BCRC 81121T=LMG 30596T=KCTC 62510T) as the type strain.
Agua Salud alphavirus defines a novel lineage of insect-specific alphaviruses discovered in the New World
Authors: Hermanns Kyra , Marklewitz Marco , Zirkel Florian , Overheul Gijs J. , Page Rachel A. , Loaiza Jose R. , Drosten Christian , van Rij Ronald P. , Junglen Sandra
Published: November 2019

The genus Alphavirus harbours mostly insect-transmitted viruses that cause severe disease in humans, livestock and wildlife. Thus far, only three alphaviruses with a host range restricted to insects have been found in mosquitoes from the Old World, namely Eilat virus (EILV), Taï Forest alphavirus (TALV) and Mwinilunga alphavirus (MWAV). In this study, we found a novel alphavirus in one Culex declarator mosquito sampled in Panama. The virus was isolated in C6/36 mosquito cells, and full genome sequencing revealed an 11 468 nt long genome with maximum pairwise nucleotide identity of 62.7 % to Sindbis virus. Phylogenetic analyses placed the virus as a solitary deep rooting lineage in a basal relationship to the Western equine encephalitis antigenic complex and to the clade comprising EILV, TALV and MWAV, indicating the detection of a novel alphavirus, tentatively named Agua Salud alphavirus (ASALV). No growth of ASALV was detected in vertebrate cell lines, including cell lines derived from ectothermic animals, and replication of ASALV was strongly impaired above 31 °C, suggesting that ASALV represents the first insect-restricted alphavirus of the New World.
A pilot exploratory study of the potentials of deep learning methods in cancer image segmentation and classification
Authors: Yi Eric , Liu Yanling
Published: November 2019

The authors have withdrawn their manuscript while recent data-sharing permission questions are addressed. Therefore, the authors do not wish this work to be cited as a reference for the project. If you have any questions, please contact the corresponding author.
Ghost QTL and hotspots in experimental crosses - novel solution by mixed model with nonzero mean
Authors: Szulc Piotr A. , Wallin Jonas , Bogdan Małgorzata , Doerge R.W. , Siegmund David O.
Published: November 2019

“Ghost-QTL” are the false discoveries in QTL mapping, that arise due to the “accumulation” of the polygenic effects, uniformly distributed over the genome. The locations on the chromosome which are strongly correlated with the summary polygenic effect depend on a specific sample correlation structure determined by the genotype at all loci. During the analysis of e-QTL data or recombinant inbred lines this correlation structure is preserved for all traits under consideration, and may lead to the so called “hot-spots” via the detection of the summary polygenic effect at exactly the same positions for most of the considered traits. We illustrate that the problem can be solved by the application of the extended mixed effect model, where the random effects are allowed to have a nonzero mean. We provide formulas for estimating the thresholds for the corresponding t-test statistics and use them in the stepwise selection strategy, which allows for a simultaneous detection of several QTL. Extensive simulation studies illustrate that our approach allows to eliminate ghost-QTL/false hot spot effects, while preserving a high power of detection of true QTL effects.
Label-free horizontal EMSA for analysis of protein-RNA interactions
Authors: Perea William , Greenbaum Nancy L.
Published: November 2019

We describe a method to analyze the affinity and specificity of interactions between proteins and RNA using horizontal PAGE under non-denaturing conditions. The method permits tracking of migration of anionic and cationic biomolecules and complexes toward anode and cathode, respectively, therefore enabling quantification of bound and free biomolecules of different charges and affinity of their intermolecular interactions. The gel is stained with a fluorescent intercalating dye (SYBR®Gold or ethidium bromide) for visualization of nucleic acids followed by Coomassie® Brilliant Blue R-250 for visualizations of proteins; the dissociation constant is determined separately from the intensity of unshifted and shifted bands visualized by each dye. The method permits calculation of bound and unbound anionic nucleic acid and cationic protein components in the same gel, regardless of charge, under identical conditions, and avoids the need for radioisotope or fluorescent labeling of either component.
Lokiarchaeon exhibits homoacetogenesis
Authors: Orsi William D. , Vuillemin Aurèle , Rodriguez Paula , Coskun Ömer K. , Gomez-Saez Gonzalo V. , Lavik Gaute , Morholz Volker , Ferdelman Timothy G.
Published: November 2019

The proposed Asgard superphylum of Archaea comprises the closest archaeal relatives of eukaryotes, whose genomes hold clues pertaining to the nature host cell that acquired the mitochondrion at the origin of eukaryotes1-4. Genomes of the Asgard candidate Phylum ‘CandidatusLokiarchaeota’ [Lokiarchaeon] suggest an acetogenic H2–dependent lifestyle5and mixotrophic capabilities6. However, data on the activity of Lokiarchaeon are currently lacking, and the ecology of the host cell that acquired the mitochondrion is debated4,7. Here, we show that in anoxic marine sediments underlying highly productive waters on the Namibian continental shelf Lokiarchaeon gene expression increases with depth below the seafloor, and was significantly different across a redox gradient spanning hypoxic to sulfidic conditions. Notably, Lokiarchaeon increased expression of genes involved in growth, carbohydrate metabolism, and the H2-dependent Wood-Ljungdahl (WLP) carbon fixation pathway under the most reducing (sulfidic) conditions. Quantitative stable isotope probing experiments revealed multiple populations of Lokiarchaeota utilizing both CO2and diatomaceous extracellular polymeric substances (dEPS) as carbon sources over a 10-day incubation under anoxic conditions. This apparent anaerobic mixotrophic metabolism was consistent with the expression of Lokiarchaeon genes involved in transport and fermentation of sugars and amino acids. Remarkably, several Asgard populations were more enriched with13C-dEPS compared to the community average, indicating a preference for dEPS as a growth substrate. The qSIP and gene expression data indicate a metabolism of “CandidatusLokiarchaeota” similar to that of sugar fermenting homoacetogenic bacteria8, namely that Lokiarchaeon can couple fermentative H2production from organic substrates with electron bifurcation and the autotrophic and H2-dependent WLP. Homoacetogenesis allows to access a wide range of substrates and relatively high ATP gain during acetogenic sugar fermentation8thereby providing an ecological advantage for Lokiarchaeon in anoxic, energy limited settings.
Air pollution mediates diabetes by disrupting gut innate mucosal immunity
Authors: Bosch Angela J. T. , Rohm Theresa V. , AlAsfoor Shefaa , Baumann Zora , Stawiski Marc , Dervos Thomas , Mitrovic Sandra , Roux Julien , Meier Daniel T. , Cavelti-Weder Claudia
Published: November 2019

Air pollution has emerged as an unexpected risk factor for diabetes1–6. The mechanisms linking air pollution and diabetes remain, however, unknown. It has been postulated that lung exposure mediates diabetes via systemic inflammation and insulin resistance7–9. By contrast, gut exposure to pollutants has received little attention, even though a large proportion of air pollution particles are swallowed after mucociliary clearance from the upper airways10. Here, we identified intestinal macrophages as key mediators linking air pollutants with impaired beta-cell function. Upon oral exposure to air pollution, intestinal macrophages up-regulated inflammatory- and interferon-response pathways, which disrupted their normal differentiation towards an anti-inflammatory/resident phenotype. The resulting pro-inflammatory milieu in the gut impaired beta-cell identity and function via local cytokine secretion from macrophages as genetic and pharmacological macrophage or IL-1β ablation protected mice from developing air pollution-induced diabetes. These data establish intestinal macrophage-derived cytokines as key mediators of air pollution associated beta-cell dysfunction, thus pointing towards novel therapeutic strategies.
Large-Scale Preparation and Linearization of Bacterial Artificial Chromosome (BAC) DNA
Authors: Heintz Nathaniel , Gong Shiaoching
Published: November 2019

A critical step for creating bacterial artificial chromosome (BAC) transgenic organisms is the production of high-quality BAC DNA. The method described here provides a source of DNA for further manipulation and modification, but can also be used for preparing modified BAC DNA, resulting from the one-step or two-step strategy, for use in other applications such as BAC transgenesis. An analysis of precautions to take when working with large DNA molecules is also provided.
Examination of Bacterial Artificial Chromosome (BAC) DNA Quality and Quantity by Pulsed-Field Gel Electrophoresis
Authors: Heintz Nathaniel , Gong Shiaoching
Published: November 2019

Pulsed-field gel electrophoresis (PFGE) is the preferred method to measure the size of an insert in a high-capacity vector. After digestion with a restriction enzyme (e.g., PI-SceI or NotI), the DNA fragments are separated by PFGE through a 1% agarose gel.
Single-Cell Cloning of Hybridoma Cells by Growth in Soft Agar
Authors: Greenfield Edward A.
Published: November 2019

Single-cell cloning during hybridoma production ensures that cells that produce the antibody of interest are truly monoclonal and that the secretion of this antibody can be stably maintained. Cloning of hybridoma cells in semisolid medium is one of the most commonly used methods for producing single-cell clones. The technique is easy, but, because it is performed in two stages, it does take longer than other methods. Not all cells will grow in soft agar, and there may be a bias on the type of colony that appears. However, most of the commonly used myeloma fusion partners have relatively good cloning efficiencies in soft agar, and, consequently, so do most hybridomas. Even though every attempt is made to ensure that the cells are in a single-cell suspension before plating, there is no way to guarantee that the colonies do not arise from two cells that were stuck together. Therefore, single-cell cloning in soft agar should be repeated at least twice before the cells are considered clonal.
Introducing Genes into Cultured Mammalian Cells
Authors: Kumar Priti , Nagarajan Arvindhan , Uchil Pradeep D.
Published: November 2019

Strategies for the delivery of genes into eukaryotic cells fall into three categories: transfection by biochemical methods, transfection by physical methods, and virus-mediated transduction. This introduction deals with the first two categories.
Job embeddedness of manufacturing SME employees in Indonesia
Authors: Martdianty Fanny , Coetzer Alan , Susomrith Pattanee
Published: November 2019

Purpose

The purpose of this paper is to explore the applicability of job embeddedness (JE) theory to employees in manufacturing SMEs in Central Java, Indonesia, and to qualitatively assess the transferability of the JE framework and its measure to these distinctive contexts.

Design/methodology/approach

Data were collected using semi-structured interviews with 42 employees from 13 SMEs. The JE framework informed development of the interview questions, which focussed on participants’ lived experiences. Thematic analysis of the textual data was conducted.

Findings

Distinctive characteristics of SMEs, such as resource constraints and managerial informality, and cultural factors influenced employees’ perceptions of the forces that embedded them in their jobs. For example, participants perceived the psychological costs associated with severing ties with co-workers as a more salient embedding force than the material costs associated with leaving a job. Additionally, lack of job fit was not an important turnover determinant, because work was perceived as a duty or obligation, rather than a personal choice.

Research limitations/implications

The findings imply that the JE framework and its measure only partially explain why employees stay in manufacturing SMEs in Central Java. Accordingly, the original JE scale items would need to be significantly modified to accurately assess employees’ levels of embeddedness in Indonesian manufacturing SMEs.

Originality/value

Limited research has examined how SME owner-managers can retain key employees, particularly in Indonesia. This study contributes to an understanding of factors that embed employees in the cultural context of Indonesia and enhances our understanding of how JE theory operates in SMEs.