bluuebunny/crossref_metadata_2025 huggingface dataset:
SuptoxD2.0: A second‐generation engineeredEscherichia colistrain achieving further enhanced levels of recombinant membrane protein production
Authors: Michou Myrsini , Stergios Angelos , Skretas Georgios
Published: May 2020

The bacteriumEscherichia coliis among the most popular hosts for recombinant protein production, including that of membrane proteins (MPs). We have recently generated the specialized MP‐producingE. colistrain SuptoxD, which upon co‐expression of the effector genedjlA, is capable of alleviating two major bottlenecks in bacterial recombinant MP production: it suppresses the toxicity that frequently accompanies the MP‐overexpression process and it markedly increases the cellular accumulation of membrane incorporated and properly folded recombinant MP. Combined, these two positive effects result in dramatically enhanced volumetric yields for various recombinant MPs of both prokaryotic and eukaryotic origin. Based on the observation thatdjlAis found in the genomes of various pathogenic bacteria, the aim of the present work was to investigate (a) whether other naturally occurring DjlA variants can exert the MP toxicity‐suppressing and production‐promoting effects similarly to theE. coliDjlA and (b) if we can identify a DjlA variant whose efficiency surpasses that of theE. coliDjlA of SuptoxD. We report that a quite surprisingly broad variety of homologous DjlA proteins exert beneficial effects on recombinant MP when overexpressed inE. coli. Furthermore, we demonstrate that theSalmonella entericaDjlA is an even more potent enhancer of MP productivity compared with theE. coliDjlA of SuptoxD. Based on this, we constructed a second‐generation SuptoxD strain, termed SuptoxD2.0, whose MP‐production capabilities surpass significantly those of the original SuptoxD, and we anticipate that SuptoxD2.0 will become a broadly utilized expression host for recombinant MP production in bacteria.
Serum metabolomic profiling in patients with Alzheimer disease and amnestic mild cognitive impairment by GC/MS
Authors: Sun Congcong , Gao Meimei , Wang Feifei , Yun Yan , Sun Qianwen , Guo Ruichen , Yan Chuanzhu , Sun Xiulian , Li Yi
Published: May 2020

The aim of this study was to characterize the serum metabolic profiles of patients with Alzheimer’s disease (AD) and amnestic mild cognitive impairment (AMCI) using metabolomics based on gas chromatography–mass spectrometry (GC/MS). Serum samples were collected from patients with AD (n = 30) and AMCI (n = 32), and normal healthy controls (NOR, n = 40). Metabolite profiles were performed with GC/MS in conjunction with multivariate statistical analysis, and possible biomarker metabolites were identified. Thirty‐one kinds of endogenous metabolites could be identified simultaneously. Eleven components were chosen as biomarker metabolites between AD and NOR groups, and these metabolites were closely related to seven biological pathways: arginine and proline metabolism, phenylalanine metabolism, β‐alanine metabolism, primary bile acid synthesis, glutathione metabolism, starch and sucrose metabolism, and steroid hormone biosynthesis. Meanwhile, 10 components were chosen as biomarker metabolites between AMCI and NOR groups and seven biological pathways were closely related: arginine and proline metabolism, phenylalanine metabolism, citrate cycle, alanine, aspartate and glutamate metabolism, taurine and hypotaurine metabolism, starch and sucrose metabolism, and steroid hormone biosynthesis. Our study distinguished serum metabotypes between AD, AMCI and NOR patients successfully. The implementation of this metabolomic strategy may help to develop biochemical insight into the metabolic alterations in AD/AMCI and will be helpful for the further understanding of pathogenesis.
Migration‐ and Proliferation‐Promoting Activities in Human Keratinocytes of Zea mays Flower Absolute and Its Chemical Composition
Authors: Kim Do Yoon , Won Kyung Jong , Hwang Dae Il , Kim Ha Bin , Li Yali , Lee Hwan Myung
Published: May 2020

Zea mays L. (ZM) has cytotoxic and anti‐inflammatory activities, but its biological activities such as skin regeneration and wound healing in human skin have not been reported. In the present study, we tested the effects of ZM flower (ZMF) absolute on proliferation and migration of human keratinocytes (HaCaTs) and identified its components by using gas chromatography/mass spectrometry (GC/MS) analysis. GC/MS analysis revealed that the ZMF absolute contained 13 constituents, and it increased HaCaT proliferation and migration. The ZMF absolute enhanced the phosphorylation levels of serine/threonine‐specific protein kinase (Akt), p38 mitogen‐activated protein kinase (MAPK), and extracellular signal‐regulated kinase1/2 in HaCaTs. In addition, the absolute induced an increase in sprout outgrowth of HaCaTs. The present study reports for the first time that ZMF absolute may promote skin wound healing and/or skin regeneration by stimulating proliferative and migratory activities in dermal keratinocytes through the Akt/MAPK pathway. Therefore, ZMF absolute may be a promising natural material for the use in skin regeneration and/or wound healing applications.
A Defect‐rich N, P Co‐doped Carbon Foam as Efficient Electrocatalyst toward Oxygen Reduction Reaction
Authors: Yang Maomao , Shu Xinxin , Zhang Jintao
Published: May 2020

Explore cost‐effective and efficient carbon‐based electrocatalysts toward oxygen reduction reaction is highly desired to replace high‐cost platinum group metal (PGM) catalysts. Herein we synthesized a N, P co‐doped carbon foam by direct blowing of glucose in the presence of phytic acid (blowing catalyst) and urea (self‐sacrificing template). This template‐free one‐step approach achieved high surface heteroatom content of N (5 at.%) and P (2.33 at.%), large surface area (1026 m2 g−1) and high ID/IG ratio. It was found that the edges‐rich activated carbon scaffold as well as the active N‐sites work synthetically to guarantee its efficient ORR performance with the half‐wave potential of 0.84 VRHE. Besides, the well‐balanced porous structure facilitates its practical application as an air cathode in zinc‐air cell, reaching power density of 145 mW cm−2 at the current density of 169 mA cm−2.
Considerations for Scaling Up the Synthesis of a Glycine‐Based Ionic Demulsifier
Authors: Guzmán‐Lucero Diego , Cerón‐Camacho Ricardo , Ocampo‐Barrera René , Martínez‐Palou Rafael
Published: May 2020

The operating conditions for scaling up the synthesis in semibatch‐type reactors of an ionic‐esterified amino acid salt, namely, 2‐(tetradecyloxy)‐2‐oxoethanaminium methanesulfonate, a demulsifier for breaking crude oil‐in‐water emulsions, were established. The conversion and reaction time were studied at different temperatures on a laboratory scale, and the best conditions for the reaction were found at 90 °C. At different reaction scales up to an industrial reactor, the influence of reaction variables such as temperature, order and rate of reagent addition, and reaction time were studied. This progressive scaling study found the most suitable and safest conditions to carry out the industrial‐level scaling of a high‐performance product for oilfield application.
Influence of Screening and Drying on Low‐Quality Wood Chips for Application in Small‐Scale Gasification Plants
Authors: Pollex Annett , Lesche Simon , Kuptz Daniel , Zeng Thomas , Kuffer Georg , Mühlenberg Jana , Hartmann Hans , Lenz Volker
Published: May 2020

Before using low‐quality wood chips for gasification on the small and medium scale (30–500 kWel), mechanical fuel pretreatment has to be employed to ensure the required fuel characteristics concerning particle size distribution and moisture. Two different low‐quality wood assortments (calamity wood and roadside maintenance wood) were subjected to three different mechanical fuel pretreatment strategies and a detailed analysis was realized along the supply chains. The results reveal the enrichment in elements characteristic of soil contamination in the removed fine fraction. Gasification tests were successfully performed with the upgraded low‐quality fuels in field trials and indicated comparable electrical efficiencies but higher supervision effort during plant operation.
Why we should be interested in P values and hypothesis tests
Authors: Brereton Richard G.
Published: May 2020

The origins of chemometrics in quantitative analytical chemistry is contrasted to the emerging growth points of statistically based hypothesis testing and generation such as in applications to metabolomics and heritage science.
Transfer of a human gene variant associated with exceptional longevity improves cardiac function in obese type 2 diabetic mice through induction of the SDF‐1/CXCR4 signalling pathway
Authors: Dang Zexu , Avolio Elisa , Thomas Anita C. , Faulkner Ashton , Beltrami Antonio P. , Cervellin Celeste , Carrizzo Albino , Maciag Anna , Gu Yue , Ciaglia Elena , Finato Nicoletta , Damato Antonio , Spinetti Gaia , Alenzi Aishah , Paisey Stephen J. , Vecchione Carmine , Puca Annibale A. , Madeddu Paolo
Published: May 2020

Aims

Homozygosity for a four‐missense single‐nucleotide polymorphism haplotype of the human BPIFB4 gene is enriched in long‐living individuals. Delivery of this longevity‐associated variant (LAV) improved revascularisation and reduced endothelial dysfunction and atherosclerosis in mice through a mechanism involving the stromal cell‐derived factor‐1 (SDF‐1). Here, we investigated if delivery of the LAV‐BPIFB4 gene may attenuate the progression of diabetic cardiomyopathy.

Methods and results

Compared with age‐matched lean controls, diabetic db/db mice showed altered echocardiographic indices of diastolic and systolic function and histological evidence of microvascular rarefaction, lipid accumulation, and fibrosis in the myocardium. All these alterations, as well as endothelial dysfunction, were prevented by systemic LAV‐BPIFB4 gene therapy using an adeno‐associated viral vector serotype 9 (AAV9). In contrast, AAV9 wild‐type‐BPIFB4 exerted no benefit. Interestingly, LAV‐BPIFB4‐treated mice showed increased SDF‐1 levels in peripheral blood and myocardium and up‐regulation of the cardiac myosin heavy chain isoform alpha, a contractile protein that was reduced in diabetic hearts. SDF‐1 up‐regulation was instrumental to LAV‐BPIFB4‐induced benefit as both haemodynamic and structural improvements were inhibited by an orally active antagonist of the SDF‐1 CXCR4 receptor.

Conclusions

In mice with type‐2 diabetes, LAV‐BPIFB4 gene therapy promotes an advantageous remodelling of the heart, allowing it to better withstand diabetes‐induced stress. These results support the viability of transferring healthy characteristics of longevity to attenuate diabetic cardiac disease.
Migration of murine intestinal dendritic cell subsets upon intrinsic and extrinsic TLR3 stimulation
Authors: Garcias López Agnès , Bekiaris Vasileios , Müller Luda Katarzyna , Hütter Julia , Ulmert Isabel , Getachew Muleta Konjit , Nakawesi Joy , Kotarsky Knut , Malissen Bernard , O'Keeffe Meredith , Holzmann Bernhard , Winston Agace William , Lahl Katharina
Published: May 2020

Initiation of adaptive immunity to particulate antigens in lymph nodes largely depends on their presentation by migratory dendritic cells (DCs). DC subsets differ in their capacity to induce specific types of immunity, allowing subset‐specific DC‐targeting to influence vaccination and therapy outcomes. Faithful drug design, however, requires exact understanding of subset‐specific versus global activation mechanisms. cDC1, the subset of DCs that excel in supporting immunity toward viruses, intracellular bacteria, and tumors, express uniquely high levels of the pattern recognition receptor TLR3. Using various murine genetic models, we show here that both, the cDC1 and cDC2 subsets of cDCs are activated and migrate equally well in response to TLR3 stimulation in a cell extrinsic and TNF‐α dependent manner, but that cDC1 show a unique requirement for type I interferon signaling. Our findings reveal common and differing pathways regulating DC subset migration, offering important insights for the design of DC‐based vaccination and therapy approaches.
Multinuclear Copper Hydride Complexes Supported by Polyphosphine Ligands
Authors: Nakajima Takayuki , Nakamae Kanako , Ura Yasuyuki , Tanase Tomoaki
Published: May 2020

Copper hydride compounds have attracted interest in diverse fields as base metallic material in place of rare and noble metals, which have widely been utilized in hydrogenation catalysts, hydrogen storage, and electrochemical materials. Since the first report on the synthesis of copper hydride complex [Cu6H6(PPh3)6] in 1971, copper hydride reagents have been utilized in a variety of organic transformation. While well‐characterized copper hydride complexes have been long limited to a few examples, recently several research groups have reported the synthesis of phosphine‐stabilized copper hydride complexes with various metal‐frameworks and unique reactivity. Here we review recent progress on the synthesis and structures of copper hydride complexes supported by phosphine ligands, including di‐, tri‐, and tetraphosphines, and also describe their reactivity with CO2.
One‐Pot Preparation of Functionalized Azabicyclo[6.3.0]alkanone Amino Acids by Tandem Cross Enyne Metathesis/Ring‐Closing Metathesis
Authors: Bernardi Eric , Colombo Lino , De Lorenzi Ersilia , Carraro Massimo , Serra Massimo
Published: May 2020

Here we report an efficient one‐pot procedure for the preparation of functionalized azabicyclo[6.3.0]alkanone amino acid derivatives. The synthetic protocol exploits an ethylene‐mediated cross enyne metathesis followed by a ring closing metathesis. The reactivity of the newly synthesized 8,5‐fused bicyclic scaffolds has then been investigated to obtain variously functionalized derivatives with potential applications in the field of peptides/peptidomimetics.
Multiple Reversible Dynamics of Pyrimidine Based Acylhydrazones
Authors: Arango Alejandra M. , Wist Julien , Ellena Javier , D'Vries Richard , Chaur Manuel N.
Published: May 2020

We employed (Z)‐N'‐[phenyl(pyrimidin‐2‐yl)methylene]nicotinohydrazide (2) and (Z)‐4‐(dimethylamino)‐N'‐[phenyl(pyrimidin‐2‐yl)methylene]benzohydrazide (3) as cores of dynamic chemical systems whose different states are modulated, in a reversible fashion, through specific physical and chemical stimuli. The structure of the compounds was determined by Nuclear Magnetic Resonance (NMR) techniques (1D and 2D) and confirmed by single‐crystal X‐ray diffraction. By Variable temperature (VT) 1H NMR experiments and DFT calculations, the conformational isomerism of 2 was studied and added as an additional input for the dynamic system. Additionally, 2 exhibits configurational E/Z isomerization mediated by pH variations and UV light. On the other hand, configurational isomerism locks an unlocks a tridentate pocket for metal cation coordination in both 2 and 3. All the different dynamic states configurational/conformational isomerism and locked and unlocked coordination constitute a development in the field of systems of multiple dynamics suitable for molecular machines.
Cobalt‐Catalyzed Direct C(sp2)–H Alkylation with Unactivated Alkenes
Authors: Kim Ye Lim , Park Sun‐a , Kim Ju Hyun
Published: May 2020

A facile and efficient method for Cp*CoIII‐catalyzed C(sp2)–H bond alkylation was developed using 2‐aryl pyridines and unactivated alkenes. The reaction proceeded atom‐economically with readily available styrene derivatives and an abundant cobalt catalyst. This reaction tolerates a broad range of functional groups, directing groups, styrenes and affords mono‐diarylethane products with high linear selectivity. To demonstrate the synthetic utility and the potential application in organic synthesis, a gram‐scale reaction and further C–H bond functionalizations of the mono‐alkylated product were performed.
Association of quantitative sensory testing parameters with clinical outcome in patients with lumbar radiculopathy undergoing microdiscectomy
Authors: Tampin Brigitte , Slater Helen , Jacques Angela , Lind Christopher R. P.
Published: May 2020

Background/Aim

This study aimed to establish the somatosensory profile of patients with lumbar radiculopathy at pre‐and post‐microdiscectomy and to explore any association between pre‐surgical quantitative sensory test (QST) parameters and post‐surgical clinical outcomes.

Methods

A standardized QST protocol was performed in 53 patients (mean age 38 ± 11 years, 26 females) with unilateral L5/S1 radiculopathy in the main pain area (MPA), affected dermatome and contralateral mirror sites and in age‐ and gender‐,and body site‐matched healthy controls. Repeat measures at 3 months included QST, the Oswestry Disability Index (ODI) and numerous other clinical measures; at 12 months, only clinical measures were repeated. A change <30% on the ODI was defined as ‘no clinically meaningful improvement’.

Results

Patients showed a significant loss of function in their symptomatic leg both in the dermatome (thermal, mechanical, vibration detection p < .002), and MPA (thermal, mechanical, vibration detection, mechanical pain threshold, mechanical pain sensitivity p < .041) and increased cold sensitivity in the MPA (p < .001). Pre‐surgical altered QST parameters improved significantly post‐surgery in the dermatome (p < .018) in the symptomatic leg and in the MPA (p < .010), except for thermal detection thresholds and cold sensitivity. Clinical outcomes improved at 3 and 12 months (p < .001). Seven patients demonstrated <30% change on the ODI at 12 months. Baseline loss of function in mechanical detection in the MPA was associated with <30% change on the ODI at 12 months (OR 2.63, 95% CI 1.09–6.37, p = .032).

Conclusion

Microdiscectomy resulted in improvements in affected somatosensory parameters and clinical outcomes. Pre‐surgical mechanical detection thresholds may be predictive of clinical outcome.

Significance

This study documented quantitative sensory testing (QST) profiles in patients with lumbar radiculopathy in their main pain area (MPA) and dermatome pre‐ and post‐microdiscectomy and explored associations between QST parameters and clinical outcome. Lumbar radiculopathy was associated with loss of function in modalities mediated by large and small sensory fibres. Microdiscectomy resulted in significant improvements in loss of function and clinical outcomes in 85% of our cohort. Pre‐surgical mechanical detection thresholds in the MPA may be predictive of clinical outcome.
Nested control loop design for differential boost inverter using generalized averaged model in photovoltaic applications
Authors: Amirparast Ali , Gholizade‐narm Hossein
Published: May 2020

To use photovoltaic energy, voltage source inverters are playing an important role. The most of local AC loads such as AC motors need higher voltage than solar panel output voltage. Differential boost inverter produces an AC voltage that is greater than the DC input voltage in a single power stage. This inverter consists of two DC‐DC bilateral boost converters in which work via time‐variant duty cycles to produce sinusoidal voltage, and this feature causes complexity in control design. To deal with this complexity, new modeling so‐called generalized averaged model is used to achieve a linear time‐invariant model. In this paper, a nested control loop is designed. This control strategy consists of two control loops in which the inner loop is designed by linear quadratic regulator theory to displace poles in proper location and the second loop uses a PI‐PR controller to track desired voltage and reject disturbances. To evaluate the proposed control method, the sliding mode controller is applied and compared as well. As shown by simulations, the proposed control strategy has more reliable performance and provides higher robustness in comparison with sliding mode control technique in rigid situations such as dealing with nonlinear load, parameters values changes, and external disturbances.
Tracheostomy time‐out: New safety tool in the setting of COVID‐19
Authors: Dharmarajan Harish , Snyderman Carl H.
Published: May 2020

Tracheostomy procedures have a high risk of aerosol generation. Airway providers have reflected on ways to mitigate the severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission risks when approaching a surgical airway. To standardize institutional safety measures with tracheostomy, we advocate using a dedicated tracheostomy time‐out applicable to all patients including those suspected of having COVID‐19. The aim of the tracheostomy time‐out is to reduce preventable errors that may increase the risk of transmission of SARS‐CoV‐2.
Use of Hepatocellular Carcinoma Surveillance in Patients With Cirrhosis: A Systematic Review and Meta‐Analysis
Authors: Wolf Erin , Rich Nicole E. , Marrero Jorge A. , Parikh Neehar D. , Singal Amit G.
Published: May 2020

Background and Aims

Hepatocellular carcinoma (HCC) surveillance is associated with early tumor detection and improved survival; however, it is often underused in clinical practice. We aimed to characterize surveillance use among patients with cirrhosis and the efficacy of interventions to increase surveillance.

Approach and Results

We performed a systematic literature review using the MEDLINE database from January 2010 through August 2018 to identify cohort studies evaluating HCC surveillance receipt or interventions to increase surveillance in patients with cirrhosis. A pooled estimate for surveillance receipt with 95% confidence intervals was calculated. Correlates of surveillance use were defined from each study and prespecified subgroup analyses. Twenty‐nine studies, with a total of 118,799 patients, met inclusion criteria, with a pooled estimate for surveillance use of 24.0% (95% confidence interval, 18.4‐30.1). In subgroup analyses, the highest surveillance receipt was reported in studies with patients enrolled from subspecialty gastroenterology/hepatology clinics and lowest in studies characterizing surveillance in population‐based cohorts (73.7% versus 8.8%, P < 0.001). Commonly reported correlates of surveillance included higher receipt among patients followed by subspecialists and lower receipt among those with alcohol‐associated or nonalcoholic steatohepatitis (NASH)–related cirrhosis. All eight studies (n = 5,229) evaluating interventions including patient/provider education, inreach (e.g., reminder and recall systems), and population health outreach strategies reported significant increases (range 9.4%‐63.6%) in surveillance receipt.

Conclusions

HCC surveillance remains underused in clinical practice, particularly among patients with alcohol‐associated or NASH‐related cirrhosis and those not followed in subspecialty gastroenterology clinics. Interventions such as provider education, inreach including reminder systems, and population health outreach efforts can significantly increase HCC surveillance.
Protective effect of carnosic acid on acrylamide‐induced liver toxicity in rats: Mechanistic approach over Nrf2‐Keap1 pathway
Authors: Donmez Dilek B. , Kacar Sedat , Bagci Ridvan , Sahinturk Varol
Published: May 2020

Acrylamide is a food contaminant with a range of toxic effects. Carnosic acid (C20H28O4) is a phenolic compound found in plants and has many beneficial effects. In this study, we aimed at investigating the effect of carnosic acid on acrylamide‐induced liver damage. Rats (n = 7) were allotted to control, carnosic acid, acrylamide, acrylamide + carnosic acid groups. Animals were euthanized. Their blood was taken for biochemical analysis, and liver tissue was excised for morphological, immunohistochemical, and immunoblotting analyses. As a result, acrylamide reduced bodyweight, liver weight, catalase, and total antioxidant capacity levels but increased alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, malondialdehyde, total oxidant status, oxidative stress index levels, Nrf2, and Keap1 protein levels. In addition, acrylamide disrupted liver histology leading to vascular congestion, cellular infiltration, necrotic cells, and so forth. Carnosic acid cotreatment ameliorated the altered biochemical parameters, liver histology, Nrf2, and Keap1 enzyme levels. In conclusion, carnosic acid has the potential to be used as a protective agent against acrylamide‐induced liver damage.
Immune checkpoints in hematologic malignancies: What made the immune cells and clinicians exhausted!
Authors: Hajifathali Abbas , Parkhideh Sayeh , Kazemi Mohammad H. , Chegeni Rouzbeh , Roshandel Elham , Gholizadeh Majid
Published: May 2020

Hematologic malignancies comprise a considerable part of cancers with high mortality at any age. Since the introduction of hematopoietic stem cell transplantation (HSCT), the overall survival of patients dramatically increased. The main goal of HSCT is the induction of a graft‐versus‐leukemia effect to eradicate the residual cancer cells and also reconstitute a healthy immune system for patients. However, relapse is a nettlesome challenge of HSCT. Like many other tumors, hematologic cancer cells induce immune exhaustion leading to immune escape and relapses after HSCT. Besides malignant cells, inhibitory cells such as tumor‐associated macrophages and myeloid‐derived suppressor cells express various inhibitory receptors capable of inducing exhaustion in immune cells, especially T and natural killer cells. The significance of immune checkpoint blocking in tumor regression in clinical trials led to the 2018 Nobel Prize in Physiology/Medicine. Here, we reviewed the clinical roles of immune checkpoints in hematologic malignancies and post‐HSCT relapses.
Feasibility, face validity, and sensitivity of a web‐based simulation tool for assessing genetic counseling communication
Authors: Setzer Michael R. , Roter Debra L.
Published: May 2020

We conducted a test of concept study to explore feasibility, face validity, and sensitivity of an interactive web‐based video tool designed to assess communication practices of genetic counselors in response to standardized video prompts. A convenience sample of genetic counselors was recruited from the National Society of Genetic Counselors to respond verbally to a set of brief standardized video prompts from a virtual client in a prenatal genetic counseling session and a cancer genetic counseling session, embedded in an interactive online platform. Participant verbal responses to prompts were captured through a secure voicemail service. A total of 89 participants attempted to use the online tool and 51 (57%) successfully completed the simulation and produced an audio record of their responses. The average length of recordings was 12.2 min. Face validity was high; participants rated the virtual client as similar to clients seen in practice (75% agree; 12% strongly agree, 7% neutral, 6% disagree) and rated their own responses to the virtual client prompts as similar to those in practice (63% agree; 19% strongly agree; 12% neutral, 6% disagree). Feasibility was assessed by ratings of ease of use (57% agreed, 24% strongly agreed, 17% were neutral, and none disagreed). Content checklists showed that the tool was sensitive enough to detect variation in frequency of certain topics discussed by participants that was similar to previous descriptive studies. The test of concept demonstrated feasibility, face validity, and sensitivity of this communication tool with possible applications in research, training, and program evaluation.
A biallelic pathogenic variant in the OGDH gene results in a neurological disorder with features of a mitochondrial disease
Authors: Yap Zheng Yie , Strucinska Klaudia , Matsuzaki Satoshi , Lee Sukyeong , Si Yue , Humphries Kenneth , Tarnopolsky Mark A. , Yoon Wan Hee
Published: May 2020

2‐Oxoglutarate dehydrogenase (OGDH) is a rate‐limiting enzyme in the mitochondrial TCA cycle, encoded by the OGDH gene. α‐Ketoglutarate dehydrogenase (OGDH) deficiency was previously reported in association with developmental delay, hypotonia, and movement disorders and metabolic decompensation, with no genetic data provided. Using whole exome sequencing, we identified two individuals carrying a homozygous missense variant c.959A>G (p.N320S) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure. Fibroblast analysis and modeling of the mutation in Drosophila were used to evaluate pathogenicity of the variant. Skin fibroblasts from subject # 2 showed a decrease in both OGDH protein and enzyme activity. Transfection of human OGDH cDNA in HEK293 cells carrying p.N320S also produced significantly lower protein levels compared to those with wild‐type cDNA. Loss of Drosophila Ogdh (dOgdh) caused early developmental lethality, rescued by expressing wild‐type dOgdh (dOgdhWT) or human OGDH (OGDHWT) cDNA. In contrast, expression to the mutant OGDH (OGDHN320S) or dOgdh carrying homologous mutations to human OGDH p.N320S variant (dOgdhN324S) failed to rescue lethality of dOgdh null mutants. Knockdown of dOgdh in the nervous system resulted in locomotion defects which were rescued by dOgdhWT expression but not by dOgdhN324S expression. Collectively, the results indicate that c.959A>G variant in OGDH leads to an amino acid change (p.N320S) causing a severe loss of OGDH protein function. Our study establishes in the first time a genetic link between an OGDH gene mutation and OGDH deficiency.
The morphology of mating plugs and its formation in scorpions: Implications for intersexual participation
Authors: Oviedo‐Diego Mariela A. , Mattoni Camilo I. , Vrech David E. , Michalik Peter , Peretti Alfredo V.
Published: May 2020

Mating plugs have been proposed as a mechanism that has evolved to avoid sperm competition. Their structure and composition vary across taxa and are related to the effectiveness of its function. This effectiveness could be related to different evolutionary interests of the sexes.Urophonius brachycentrusandUrophonius achalensis(Scorpiones, Bothriuridae) are highly suitable species to study mating plugs because both are monandrous species with specific morphological and physiological responses in the female's genitalia. Here, we analyze (a) the morphology and fine structure of the mating plugs of both species, (b) the site of production in males and the formation process of the mating plug, and (c) the changes that it undergoes over time in the female's reproductive tract. In both species, a complex mating plug obliterates the female's genital aperture and fills the genital atrium. We observed considerable interspecific variation in the mating plug morphology. A mating hemi‐plug was found surrounding the capsular lobes of the hemispermatophore, which could have a mixed composition (involving portions of the hemispermatophore and glandular products). The glandular portion was transferred in a semi‐solid state filling the female's genital atrium and then hardening. Changes that the plug undergoes in the female's genitalia (darkening and increase of the “distal” area of the plug) indicate a participation of the female to the formation of this type of plug. Our study provides new insights into the plugging phenomenon in scorpions, and we discussed the adaptive significance as a post‐copulatory mechanism to avoid sperm competition.
Asymptomatic cases with SARS‐CoV‐2 infection
Authors: Wang Yishan , Kang Hanyujie , Liu Xuefeng , Tong Zhaohui
Published: May 2020

On 31 March 2020, Chinese Health Authorization announced that numbers of asymptomatic cases with severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection will be made to the public daily. This was a very important step since different counties have different capacities for the detection of SARS‐CoV‐2 infection and control strategy for the Coronavirus Disease 2019 outbreak. We summarized the characteristics of asymptomatic SARS‐CoV‐2 infections and the transmission potential of asymptomatic cases. Then we provided guidelines for the management of asymptomatic cases through quarantine and nucleic acid/serology tests.
Variability of southwest Pacific tropical cyclone track geometry over the last 70 years
Authors: Sharma Krishneel K. , Magee Andrew D. , Verdon‐Kidd Danielle C.
Published: May 2020

Variability in tropical cyclone (TC) track morphology, as it evolves post genesis, presents continued challenges in accurately forecasting TC movement. Therefore, an improved understanding of TC track climatology is essential, given that TCs are one of the most critical natural hazards in the southwest Pacific (SWP) region. We examine the historical variability of TC tracks within the SWP over the last 70 years (1948–2017) using 6‐hourly track data obtained from the South Pacific Enhanced Archive of Tropical Cyclones (SPEArTC) database. A probabilistic clustering technique is applied to separate TC tracks into distinct groups in order to assess the primary cyclone trajectories for the region and its relationship with the El Niño–Southern Oscillation (ENSO). TC tracks are also classified into four sinuosity categories: straight, recurving, sinuous and highly sinuous; and their spatial and temporal characteristics subsequently analysed. The results of the cluster analysis identified five optimal groups of TC tracks, four of which exhibited southeast propagation, except for the southwest moving tracks in Cluster 5. Temporally, significant trends were observed over the last seven decades, with Clusters 1, 3 and 4 becoming less frequent with a substantial increase in the occurrence of Cluster 2 tracks (representing TCs east of dateline), a geometry favoured by El Niño conditions. Further, the sinuosity analysis revealed continued dominance of straight TCs within the eastern SWP with a tendency of encountering TCs of other morphology types. Conversely, the western SWP region is typically exposed to highly sinuous tracks. We also observed a significant decrease (increase) in TCs with straight and quasi‐straight (highly sinuous) tracks, particularly during the last decade. These findings suggest that combined cluster analysis and TC track sinuosity analysis is an important tool in generalising the TC track regimes, refining predicted trajectories and understanding impacts on SWP island nations.
Identifying hotspots cities vulnerable to climate change in Pakistan under CMIP5 climate projections
Authors: Ali Shaukat , Kiani Rida S. , Reboita Michelle S. , Dan Li , Eum Hyung‐Il , Cho Jaepil , Dairaku K. , Khan Firdos , Shreshta Madan L.
Published: May 2020

In this study, an ensemble of statistically downscaled 14 multi‐global climate models for RCP4.5 and RCP8.5 emission scenarios was employed to implement a comprehensive assessment of climate change impacts over Pakistan in order to identify the future hotspots cities in terms of changes in temperature and precipitation. The analyses focused on the minimum, maximum and average temperature and precipitation in three time‐slices: 2006–2035, 2041–2070, and 2071–2,100. Average temperature is projected to increase by 2.6°C under RCP4.5 while 5.1°C under RCP8.5 by the end of this century with the north side of Pakistan (mainly over North Pakistan—NP, Monsoon Region—MR and Khyber Pakhtunkhwa—KP) presenting the highest changes in the temperatures. Wetter conditions are expected in the future over Pakistan, mainly over the MR. In general, air temperature and precipitation showed linear positive correlation over Pakistan in both RCP scenarios. Hotspot cities where extreme climate, that is, the hottest, dryer and wetter, exists were also identified. Hyderabad will likely become the hottest city of Pakistan by end century with the highest average temperature reaching 29.9°C under RCP4.5 and 32.0°C under RCP8.5 followed by Jacobabad, Bahawalnagar, and Bahawalpur. Most of the hottest cities are detected in areas on the southern side of Pakistan. On the other hand, the wettest cities, Murree, Balakot and Muzaffarabad, are located in the MR. Dry conditions are likely to be prevalent in Dalbandin followed by Khanpur and Jacobabad under both RCPs. The uncertainties of the projections were also evaluated. For precipitation, for example, there are a large number of outliers indicating the high variability/uncertainties of the projections. These uncertainties are clearer when the probability density functions are analysed for individual sub‐domains in Pakistan.
Delay of Fetal Anatomy Ultrasound Assessment Based on Maternal Body Mass Index Does Not Reduce the Rate of Inadequate Visualization
Authors: Khaikin Yannay , Bishop Kelly A. , Munawar Saleha , Pudwell Jessica , Davies Gregory A. L.
Published: May 2020

Objectives

To determine whether delay of initial anatomy ultrasound based on the maternal body mass index (BMI) reduces the rate of inadequate visualization compared to standard timing at 180/7 to 196/7 weeks.

Methods

A retrospective study of singleton anatomy assessments was conducted at a tertiary care center in the 2‐year period before (A, 2012–2014) and after (B, 2014–2016) protocol initiation. Assessments in period B were scheduled on the basis of the BMI in the first trimester: lower than 25 kg/m2, 180/7 to 196/7 weeks; 25 to 29.9 kg/m2, 190/7 to 206/7 weeks; 30 to 34.9 kg/m2, 200/7 to 216/7 weeks; 35 to 39.9 kg/m2, 210/7 to 226/7 weeks; and 40 kg/m2 or higher, 220/7 to 236/7 weeks. In period A, assessments were scheduled between 180/7 and 196/7 weeks. The rate of inadequate visualization and repeated assessments in periods A and B were compared. Multivariable logistic regression, per‐protocol, and BMI subgroup analyses were completed.

Results

In total, 3491 pregnancies in period A and 3672 in period B were included. In period B, 74% were scheduled per protocol; however, this rate decreased for higher‐BMI categories (52% for BMI ≥40 kg/m2). The inadequate visualization rate was slightly higher in period B versus A (16.9% versus 15.0%; P = .03) and exceeded 35% for a BMI of 40 kg/m2 or higher, with or without delay. After adjusting for maternal age and fetal presentation, period B had small increased odds of inadequate visualization versus period A (adjusted odds ratio, 1.2; 95% confidence interval, 1.02–1.38). Repeated assessment rates were similar in periods B and A (14.0% versus 13.1%; P = .25).

Conclusions

In pregnancies with obesity, a protocol delaying the initial assessment beyond 196/7 weeks based on the maternal BMI does not reduce the rate of inadequate visualization.
Discharge by Noon: A Checklist Initiative by the Otolaryngology Service
Authors: Tamaki Akina , Cabrera Claudia , Hoppe Kathryn , Maronian Nicole
Published: May 2020

Objectives/Hypothesis

Hospital length of stay (LOS) and throughput are critical issues for hospitals. Late hospital discharges contribute to bottlenecks in the emergency department, overcrowd surgical and procedural areas, and limit patient tertiary‐care center transfers. Our goal was to increase discharge by noon (DCBN) percentage from 8% to over 50% in a sustainable manner.

Study Design

Retrospective Review.

Methods

We used a multiple time series design and a quality improvement approach. An interdisciplinary improvement team (IIT) identified the main causes contributing to late discharge and then developed and implemented multiple interventions to increase the percentage of DCBN. Admissions and discharge information were obtained for all patients in the otolaryngology service (January 2014–September 2017). The intervention was implemented in July 2015. The primary outcome was the percentage of DCBN per month. Secondary outcomes were LOS, case‐mix index (CMI), patient experience, and 30‐day readmissions. We analyzed the impact of our intervention and outcomes at the preintervention, peri‐intervention, and postintervention periods.

Results

One thousand four hundred sixty‐four admissions to the otolaryngology service were included. Throughout the intervention period, the percentage of patients DCBN increased. Analysis of the intervention showed significant DCBN change of 15% in the first versus 42% in the last 12‐months (P < .001), and shorter LOS (−1.4 days, P < .001) and lower CMI (−0.6, P < .001) in the DCBN group. Patient satisfaction scores improved by 4% (P < .05), and no difference in 30‐day readmission rates (P = .29) was shown.

Conclusions

This multifaceted intervention improved early discharge and patient experience. Our checklist of key behaviors could be applied throughout other services and hospitals with reproducible success.

Level of Evidence

4 Laryngoscope, 131:E76–E82, 2021
Long‐term outcomes of children with extracutaneous juvenile xanthogranulomas in Japan
Authors: Maeda Miho , Morimoto Akira , Shioda Yoko , Asano Takeshi , Koga Yuhki , Nakazawa Yozo , Kanegane Hirokazu , Kudo Kazuko , Ohga Shouichi , Ishii Eiichi ,   Histiocytosis Study Group of the Japanese Society of Pediatric Hematology/Oncology
Published: May 2020

Background

Juvenile xanthogranuloma (JXG) is the most common non‐Langerhans cell histiocytosis in children. The mortality and morbidity of JXG with extracutaneous lesions remain unclear.

Methods

Data of patients aged < 18 years who were diagnosed with JXG between 2001 and 2010 were retrospectively collected through a nationwide survey.

Results

Twenty patients (11 male and nine female) had extracutaneous lesions. The median observation time was 10 years (range, 0‐17). Six patients presented with symptoms at birth. The median age at diagnosis was 8.5 months (range, 0 month‐13 years). Fifteen patients underwent treatment for JXG, including chemotherapy (n = 11), and five did not receive treatment. All patients except one survived; 17 were disease‐free and two survived with disease. One newborn‐onset patient with liver, spleen, and bone marrow involvement died of the disease. Permanent sequelae included central diabetes insipidus, growth hormone deficiency, and panhypopituitarism detected at diagnosis in three, one, and two patients, respectively. Four patients had visual impairment (optic nerve compression and intraocular invasion in two each), three had epilepsy, one had mental retardation, and one had a skin scar. Eight patients who had intracranial lesions were older at diagnosis, and had a higher frequency of disease‐related comorbidities and permanent sequelae than those without intracranial involvement.

Conclusions

Patients with extracutaneous JXG had good outcomes, although those with intracranial lesions had serious permanent sequelae. Effective and safe treatment regimens for patients with intracranial JXG need to be developed.
A single supratentorial high‐grade neuroepithelial tumor with two distinct BCOR mutations, exceptionally long complete remission and survival
Authors: Bremer Juliane , Kottke Raimund , Johann Pascal D. , von Hoff Katja , Brazzola Pierluigi , Grotzer Michael A. , Kool Marcel , Rushing Elisabeth , Gerber Nicolas U.
Published: May 2020

Here, we present a patient with high‐grade neuroepithelial tumors with mutations in the BCL6 corepressor BCOR (HGNET‐BCOR), a rare, highly malignant brain tumor with poor prognosis. The patient underwent gross total tumor resection (GTR), high‐dose chemotherapy, and, after local relapse, GTR, proton radiation, and chemotherapy. After a 7.5 year‐long complete remission, the tumor recurred locally, was treated by GTR, and responded to temozolomide treatment. In addition to an internal tandem duplication in BCOR common to the majority of HGNET‐BCOR cases, molecular analysis revealed a second BCOR mutation in this tumor: a frame shift mutation. The combination of these mutations was associated with relatively low BCOR expression compared to other HGNET‐BCOR cases.
Becoming More Conscientious or More Open to Experience? Effects of a Two–Week Smartphone–Based Intervention for Personality Change
Authors: Stieger Mirjam , Wepfer Sandro , Rüegger Dominik , Kowatsch Tobias , Roberts Brent W. , Allemand Mathias
Published: May 2020

Research indicates that it might be possible to change personality traits through intervention, but this clinical research has primarily focused on changing neuroticism. To date, there are no established, proven techniques for changing other domains of personality, such as conscientiousness and openness. This research examined the effects of a two–week smartphone–based intervention to either change one facet of conscientiousness (i.e. self–discipline) or one facet of openness to experience (i.e. openness to action). Two intervention studies (total N = 255) with two active intervention groups for mutual comparisons were conducted. Results of self–reports and observer reports showed that people who wanted to become more self–disciplined were less self–disciplined at pretest. Similarly, people who wanted to become more open to action were less open to action at pretest. The results showed that people who chose the self–discipline intervention showed greater increases in self–discipline, and people who chose the openness to action intervention showed greater increases in openness to action compared with the other group. Changes were maintained until follow–up two and six weeks after the end of the intervention. Future work is needed to examine whether these personality changes are enduring or reflect temporary accentuation as a result of participation in the intervention. © 2020 European Association of Personality Psychology
In Depth Quantitative Proteomic and Transcriptomic Characterization of Human Adipocyte Differentiation using the SGBS Cell Line
Authors: Kalkhof Stefan , Büttner Petra , Krieg Laura , Wabitsch Martin , Küntzel Carolin , Friebe Daniela , Landgraf Kathrin , Hanschkow Martha , Schubert Kristin , Kiess Wieland , Krohn Knut , Blüher Matthias , von Bergen Martin , Körner Antje
Published: May 2020

Most information on molecular processes accompanying and driving adipocyte differentiation are derived from rodent models. Here, a comprehensive analysis of combined transcriptomic and proteomic alterations during adipocyte differentiation in Simpson–Golabi–Behmel Syndrome (SGBS) cells is provided. The SGBS cells are a well‐established and the most widely applied cell model to study human adipocyte differentiation and cell biology. However, the molecular alterations during human adipocyte differentiation in SGBS cells have not yet been described in a combined analysis of proteome and transcriptome. Here a global proteomic and transcriptomic data set comprising relative quantification of a total of 14372 mRNA transcripts and 2641 intracellular and secreted proteins is presented. 1153 proteins and 313 genes are determined as differentially expressed between preadipocytes and the fully differentiated cells including adiponectin, lipoprotein lipase, fatty acid binding protein 4, fatty acid synthase, stearoyl‐CoA desaturase, and apolipoprotein E and many other proteins from the fatty acid synthesis, amino acid synthesis as well as glucose and lipid metabolic pathways. Preadipocyte markers, such as latexin, GATA6, and CXCL6, are found to be significantly downregulated at the protein and transcript level. This multi‐omics data set provides a deep molecular profile of adipogenesis and will support future studies to understand adipocyte function.
Heterostructures of Graphene and Topological Insulators Bi2Se3, Bi2Te3, and Sb2Te3
Authors: Zollner Klaus , Fabian Jaroslav
Published: May 2020

Prototypical 3D topological insulators of the Bi2Se3 family provide a beautiful example of the appearance of the surface states inside the bulk bandgap caused by spin‐orbit coupling‐induced topology. The surface states are protected against backscattering by time reversal symmetry, and exhibit spin‐momentum locking whereby the electron spin is polarized perpendicular to the momentum, typically in the plane of the surface. In contrast, graphene is a prototypical 2D material, with negligible spin‐orbit coupling. When graphene is placed on the surface of a topological insulator, giant spin‐orbit coupling is induced by the proximity effect, enabling interesting novel electronic properties of its Dirac electrons. A detailed theoretical study of the proximity effects of monolayer graphene and topological insulators Bi2Se3, Bi2Te3, and Sb2Te3 is presented, and the appearance of the qualitatively new spin‐orbit splittings, well described by a phenomenological Hamiltonian, is elucidated by analyzing the orbital decomposition of the involved band structures. This should be useful for building microscopic models of the proximity effects between the surfaces of the topological insulators and graphene.