bluuebunny/crossref_metadata_2025 huggingface dataset:
Technical feasibility and clinical success of direct “free hand” EUS-guided gastroenterostomy in patients with gastric outlet obstruction
Authors: Fischer Hanna , Rüther Katharina , Abdelhafez Mohamed , Götzberger Manuela , Dollhopf Markus , Schlag Christoph
Published: July 2022

Background and study aims Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) with lumen-apposing metal stents (LAMS) appears to be a promising intervention in management of gastroduodenal out obstruction (GOO), particularly for patients for whom surgery is high risk or in a palliative setting. This study aimed to evaluate the technical feasibility, procedure-associated adverse events (AEs), and clinical outcome of direct “free hand” EUS-GE.

Patients and methods This retrospective two-center study included patients who underwent direct “free hand” EUS-GE (April 2017 to March 2021) investigating technical success (correctly placed LAMS), clinical outcome (successful oral nutrition), and management of procedure-associated AEs. “Free hand” was defined as the use of the electrocautery enhanced stent delivery system alone without additional guidewire-assistance for EUS-GE creation.

Results Forty-five patients (58 % women/42 % men; mean age 65 years) with malignant (n = 39), benign (n = 4) or unclear (n = 2) GOO underwent direct “free hand” EUS-GE. The technical success rate was 98 % (44/45). Of the patients, 95% (42/44) had less vomiting and increased ability to tolerate oral food intake after the intervention. In one patient, a second EUS-GE was necessary to achieve sufficient clinical improvement. Procedure-associated AEs were observed in 24 % (11/45) of cases including stent misplacement (n = 7), leakage (n = 1), development of a gastrojejunocolic fistula (n = 1), and bleeding (n = 2), which could be all managed endoscopically.

Conclusions Direct EUS-GE has a favorable risk-benefit profile for patients with GOO, showing high technical success rates, manageable AEs, and rapid symptom relief.
Impression management attenuates the effect of ability on trust in economic exchange
Authors: Reimann Martin , Hüller Christoph , Schilke Oliver , Cook Karen S.
Published: July 2022

Are competent actors still trusted when they promote themselves? The answer to this question could have far-reaching implications for understanding trust production in a variety of economic exchange settings in which ability and impression management play vital roles, from succeeding in one’s job to excelling in the sales of goods and services. Much social science research assumes an unconditional positive impact of an actor’s ability on the trust placed in that actor: in other words, competence breeds trust. In this report, however, we challenge this assumption. Across a series of experiments, we manipulated both the ability and the self-promotion of a trustee and measured the level of trust received. Employing both online laboratory studies (n= 5,606) and a field experiment (n= 101,520), we find that impression management tactics (i.e., self-promotion and intimidation) can substantially backfire, at least for those with high ability. An explanation for this effect is encapsuled in attribution theory, which argues that capable actors are held to higher standards in terms of how kind and honest they are expected to be. Consistent with our social attribution account, mediation analyses show that competence combined with self-promotion decreases the trustee’s perceived benevolence and integrity and, in turn, the level of trust placed in that actor.
Escherichia coli
RclA is a highly active hypothiocyanite reductase
Authors: Meredith Julia D. , Chapman Irina , Ulrich Kathrin , Sebastian Caitlyn , Stull Frederick , Gray Michael J.
Published: July 2022

Hypothiocyanite and hypothiocyanous acid (OSCN
−
/HOSCN) are pseudohypohalous acids released by the innate immune system which are capable of rapidly oxidizing sulfur-containing amino acids, causing significant protein aggregation and damage to invading bacteria. HOSCN is abundant in saliva and airway secretions and has long been considered a highly specific antimicrobial that is nearly harmless to mammalian cells. However, certain bacteria, commensal and pathogenic, are able to escape damage by HOSCN and other harmful antimicrobials during inflammation, which allows them to continue to grow and, in some cases, cause severe disease. The exact genes or mechanisms by which bacteria respond to HOSCN have not yet been elucidated. We have found, in
Escherichia coli
, that the flavoprotein RclA, previously implicated in reactive chlorine resistance, reduces HOSCN to thiocyanate with near-perfect catalytic efficiency and strongly protects
E. coli
against HOSCN toxicity. This is notable in
E. coli
because this species thrives in the chronically inflamed environment found in patients with inflammatory bowel disease and is able to compete with and outgrow other important commensal organisms, suggesting that HOSCN may be a relevant antimicrobial in the gut, which has not previously been explored. RclA is conserved in a variety of epithelium-colonizing bacteria, implicating its HOSCN reductase activity in a variety of host–microbe interactions. We show that an
rclA
mutant of the probiotic
Limosilactobacillus reuteri
is sensitive to HOSCN and that RclA homologs from
Staphylococcus aureus
,
Streptococcus pneumoniae
, and
Bacteroides thetaiotaomicron
all have potent protective activity against HOSCN when expressed in
E. coli
.
The emergence of interstellar molecular complexity explained by interacting networks
Authors: García-Sánchez Miguel , Jiménez-Serra Izaskun , Puente-Sánchez Fernando , Aguirre Jacobo
Published: July 2022

Recent years have witnessed the detection of an increasing number of complex organic molecules in interstellar space, some of them being of prebiotic interest. Disentangling the origin of interstellar prebiotic chemistry and its connection to biochemistry and ultimately, to biology is an enormously challenging scientific goal where the application of complexity theory and network science has not been fully exploited. Encouraged by this idea, we present a theoretical and computational framework to model the evolution of simple networked structures toward complexity. In our environment, complex networks represent simplified chemical compounds and interact optimizing the dynamical importance of their nodes. We describe the emergence of a transition from simple networks toward complexity when the parameter representing the environment reaches a critical value. Notably, although our system does not attempt to model the rules of real chemistry nor is dependent on external input data, the results describe the emergence of complexity in the evolution of chemical diversity in the interstellar medium. Furthermore, they reveal an as yet unknown relationship between the abundances of molecules in dark clouds and the potential number of chemical reactions that yield them as products, supporting the ability of the conceptual framework presented here to shed light on real scenarios. Our work reinforces the notion that some of the properties that condition the extremely complex journey from the chemistry in space to prebiotic chemistry and finally, to life could show relatively simple and universal patterns.
Superresolution microscopy localizes endogenous Dvl2 to Wnt signaling-responsive biomolecular condensates
Authors: Schubert Antonia , Voloshanenko Oksana , Ragaller Franziska , Gmach Philipp , Kranz Dominique , Scheeder Christian , Miersch Thilo , Schulz Matthias , Trümper Lorenz , Binder Claudia , Lampe Marko , Engel Ulrike , Boutros Michael
Published: July 2022

During organismal development, homeostasis, and disease, Dishevelled (Dvl) proteins act as key signaling factors in beta-catenin–dependent and beta-catenin–independent Wnt pathways. While their importance for signal transmission has been genetically demonstrated in many organisms, our mechanistic understanding is still limited. Previous studies using overexpressed proteins showed Dvl localization to large, punctate-like cytoplasmic structures that are dependent on its DIX domain. To study Dvl’s role in Wnt signaling, we genome engineered an endogenously expressed Dvl2 protein tagged with an mEos3.2 fluorescent protein for superresolution imaging. First, we demonstrate the functionality and specificity of the fusion protein in beta-catenin–dependent and beta-catenin–independent signaling using multiple independent assays. We performed live-cell imaging of Dvl2 to analyze the dynamic formation of the supramolecular cytoplasmic Dvl2_mEos3.2 condensates. While overexpression of Dvl2_mEos3.2 mimics the previously reported formation of abundant large “puncta,” supramolecular condensate formation at physiological protein levels is only observed in a subset of cells with approximately one per cell. We show that, in these condensates, Dvl2 colocalizes with Wnt pathway components at gamma-tubulin and CEP164-positive centrosomal structures and that the localization of Dvl2 to these condensates is Wnt dependent. Single-molecule localization microscopy using photoactivated localization microscopy (PALM) of mEos3.2 in combination with DNA-PAINT demonstrates the organization and repetitive patterns of these condensates in a cell cycle–dependent manner. Our results indicate that the localization of Dvl2 in supramolecular condensates is coordinated dynamically and dependent on cell state and Wnt signaling levels. Our study highlights the formation of endogenous and physiologically regulated biomolecular condensates in the Wnt pathways at single-molecule resolution.
Active emulsions in living cell membranes driven by contractile stresses and transbilayer coupling
Authors: Saha Suvrajit , Das Amit , Patra Chandrima , Anilkumar Anupama Ambika , Sil Parijat , Mayor Satyajit , Rao Madan
Published: July 2022

The spatiotemporal organization of proteins and lipids on the cell surface has direct functional consequences for signaling, sorting, and endocytosis. Earlier studies have shown that multiple types of membrane proteins, including transmembrane proteins that have cytoplasmic actin binding capacity and lipid-tethered glycosylphosphatidylinositol-anchored proteins (GPI-APs), form nanoscale clusters driven by active contractile flows generated by the actin cortex. To gain insight into the role of lipids in organizing membrane domains in living cells, we study the molecular interactions that promote the actively generated nanoclusters of GPI-APs and transmembrane proteins. This motivates a theoretical description, wherein a combination of active contractile stresses and transbilayer coupling drives the creation of active emulsions, mesoscale liquid order (lo) domains of the GPI-APs and lipids, at temperatures greater than equilibrium lipid phase segregation. To test these ideas, we use spatial imaging of molecular clustering combined with local membrane order, and we demonstrate that mesoscopic domains enriched in nanoclusters of GPI-APs are maintained by cortical actin activity and transbilayer interactions and exhibit significant lipid order, consistent with predictions of the active composite model.
Plant genetic effects on microbial hubs impact host fitness in repeated field trials
Authors: Brachi Benjamin , Filiault Daniele , Whitehurst Hannah , Darme Paul , Le Gars Pierre , Le Mentec Marine , Morton Timothy C. , Kerdaffrec Envel , Rabanal Fernando , Anastasio Alison , Box Mathew S. , Duncan Susan , Huang Feng , Leff Riley , Novikova Polina , Perisin Matthew , Tsuchimatsu Takashi , Woolley Roderick , Dean Caroline , Nordborg Magnus , Holm Svante , Bergelson Joy
Published: July 2022

Although complex interactions between hosts and microbial associates are increasingly well documented, we still know little about how and why hosts shape microbial communities in nature. In addition, host genetic effects on microbial communities vary widely depending on the environment, obscuring conclusions about which microbes are impacted and which plant functions are important. We characterized the leaf microbiota of 200Arabidopsis thalianagenotypes in eight field experiments and detected consistent host effects on specific, broadly distributed microbial species (operational taxonomic unit [OTUs]). Host genetic effects disproportionately influenced central ecological hubs, with heritability of particular OTUs declining with their distance from the nearest hub within the microbial network. These host effects could reflect either OTUs preferentially associating with specific genotypes or differential microbial success within them. Host genetics associated with microbial hubs explained over 10% of the variation in lifetime seed production among host genotypes across sites and years. We successfully cultured one of these microbial hubs and demonstrated its growth-promoting effects on plants in sterile conditions. Finally, genome-wide association mapping identified many putatively causal genes with small effects on the relative abundance of microbial hubs across sites and years, and these genes were enriched for those involved in the synthesis of specialized metabolites, auxins, and the immune system. Using untargeted metabolomics, we corroborate the consistent association between variation in specialized metabolites and microbial hubs across field sites. Together, our results reveal that host genetic variation impacts the microbial communities in consistent ways across environments and that these effects contribute to fitness variation among host genotypes.
Shock-formed carbon materials with intergrown sp
3
- and sp
2
-bonded nanostructured units
Authors: Németh Péter , Lancaster Hector J. , Salzmann Christoph G. , McColl Kit , Fogarassy Zsolt , Garvie Laurence A. J. , Illés Levente , Pécz Béla , Murri Mara , Corà Furio , Smith Rachael L. , Mezouar Mohamed , Howard Christopher A. , McMillan Paul F.
Published: July 2022

Studies of dense carbon materials formed by bolide impacts or produced by laboratory compression provide key information on the high-pressure behavior of carbon and for identifying and designing unique structures for technological applications. However, a major obstacle to studying and designing these materials is an incomplete understanding of their fundamental structures. Here, we report the remarkable structural diversity of cubic/hexagonally (
c
/
h
) stacked diamond and their association with diamond-graphite nanocomposites containing sp
3
-/sp
2
-bonding patterns, i.e., diaphites, from hard carbon materials formed by shock impact of graphite in the Canyon Diablo iron meteorite. We show evidence for a range of intergrowth types and nanostructures containing unusually short (0.31 nm) graphene spacings and demonstrate that previously neglected or misinterpreted Raman bands can be associated with diaphite structures. Our study provides a structural understanding of the material known as lonsdaleite, previously described as hexagonal diamond, and extends this understanding to other natural and synthetic ultrahard carbon phases. The unique three-dimensional carbon architectures encountered in shock-formed samples can place constraints on the pressure–temperature conditions experienced during an impact and provide exceptional opportunities to engineer the properties of carbon nanocomposite materials and phase assemblages.
WNK1 collaborates with TGF-β in endothelial cell junction turnover and angiogenesis
Authors: Jaykumar Ankita B. , Plumber Sakina , Barry David M. , Binns Derk , Wichaidit Chonlarat , Grzemska Magdalena , Earnest Svetlana , Goldsmith Elizabeth J. , Cleaver Ondine , Cobb Melanie H.
Published: July 2022

Angiogenesis is essential for growth of new blood vessels, remodeling existing vessels, and repair of damaged vessels, and these require reorganization of endothelial cell–cell junctions through a partial endothelial–mesenchymal transition. Homozygous disruption of the gene encoding the protein kinase WNK1 results in lethality in mice near embryonic day (E) 12 due to impaired angiogenesis. This angiogenesis defect can be rescued by endothelial-specific expression of an activated form of the WNK1 substrate kinase OSR1. We show that inhibition of WNK1 kinase activity not only prevents sprouting of endothelial cells from aortic slices but also vessel extension in inhibitor-treated embryos ex vivo. Mutations affecting TGF-β signaling also result in abnormal vascular development beginning by E10 and, ultimately, embryonic lethality. Previously, we demonstrated cross-talk of WNK1 with TGF-β–regulated SMAD signaling, and OSR1 was identified as a component of the TGF-β interactome. However, molecular events jointly regulated by TGF-β and WNK1/OSR1 have not been delineated. Here, we show that inhibition of WNK1 promotes TGF-β–dependent degradation of the tyrosine kinase receptor AXL, which is involved in TGF-β–mediated cell migration and angiogenesis. We also show that interaction between OSR1 and occludin, a protein associated with endothelial tight junctions, is an essential step to enable tight junction turnover. Furthermore, we show that these phenomena are WNK1 dependent, and sensitive to TGF-β. These findings demonstrate intimate connections between WNK1/OSR1 and multiple TGF-β–sensitive molecules controlling angiogenesis and suggest that WNK1 may modulate many TGF-β–regulated functions.
Tribological behaviour of TiB2 ceramic based composite coating deposited on stainless steel AISI 304 by gas tungsten arc (GTA) cladding process
Authors: Kumar Ravi , Das Anil Kumar
Published: July 2022

In this study, Titanium (Ti)-Titanium diboride (TiB2) metal matrix composite (MMC) cladding layers were fabricated on an AISI 304 stainless steel substrate by the gas tungsten arc (GTA) cladding process. The composite cladding layer was produced using different powder mixtures: 85 wt% TiB2−15 wt% Ti, 75 wt% TiB2−25 wt% Ti, and 65 wt% TiB2 −35 wt% Ti. During cladding, the GTA process currents were used in the range of 70 A to 90 A with 10 A interval differences and the scan speed in the range of 1.1 mm sec−1 to 1.9 mm s−1 with 0.4 mm s−1 interval differences. All samples were investigated for mechanical properties, microstructure, and phase analysis by Vickers microhardness, scanning electron microscopy (SEM), Energy dispersive x-ray spectroscopy (EDX), and x-ray diffraction (XRD) respectively. The x-ray diffraction (XRD) findings indicate that the composite coatings consist of TiB2, TiB, Ti, Fe3C, B4C, and NiTi phases. The presence of elements B, C, Ti, Cr, Mn, Fe, and Ni in the coating was confirmed by x-ray energy dispersive spectroscopy (EDX). The maximum microhardness value of the composite coating was enhanced in the range of 1639 HV0.1 to 3781 HV0.1, whereas the microhardness of the AISI 304 stainless steel substrate was 194 HV0.1. The average wear rate of the coated samples was determined in the range of 11.09 × 10−9 g N−1-m−1 to 27.63 × 10−9 g N−1m−1, whereas the average wear rate of the AISI 304 steel substrate was 88.414 × 10−9 g N−1m−1. It can be concluded that the maximum micro-hardness of the composite coating increased by 9-19 times than that of the nominal substrate (AISI 304 stainless steel). Also, the wear resistance of the composite coating enhanced by 8 times as compared to AISI 304 steel substrate. It is demonstrated in this study that the processing current, TiB2 content, and scanning speed have significant effect on the microstructure, mechanical, and tribological features of the cladding layers under consideration.
Simulation of crack growth for metal plates with holes based on cohesive zone model
Authors: Ma Lian-hua , Song Zi-zhen , Zhang Kun , Wang Lin , Zhou Wei , Zhang Qiang
Published: July 2022

Hole defects are very common in metal plates. The propagation of cracks in engineering structural members will be affected by the holes of the members, which will not only change the propagation direction of cracks, but also have the ability to limit the growth of cracks. Therefore, the study of material fracture crack propagation caused by the distribution of holes and other factors under loading conditions has become a problem that needs to be considered in structural design. The cohesive zone model (CZM) can effectively avoid the singularity problem of crack tip stress when simulating crack growth, and at the same time can clearly show the crack growth path. Based on exponential CZM, the finite element analysis of tensile test for metallic materials with hole defects was carried out. The crack propagation law under constant load was obtained. It was proved that CZM could simulate the crack propagation in metallic materials with holes more accurately. The influence of the pore size, shape, distribution on the crack propagation is discussed. The results show that the smaller the distance difference between holes, the greater the supporting reaction force. The smaller the radius of the hole, the higher the fracture toughness and the maximum supporting reaction force of the metal plate. And it also can be seen that as the number of holes increases, the maximum supporting reaction force and fracture toughness of the metal plate decrease. The use of staggered holes distribution has greater supporting force and better toughness. The research results of this paper provide a theoretical basis and reference for investigating the propagation and propagation of cracks in the process of damage and failure of materials and for structural design and performance evaluation of engineering materials.
Silver nanowires: a focused review of their synthesis, properties, and major factors limiting their commercialization
Authors: Muhmood Tahir , Ahmad Farooq , Hu Xiaobin , Yang Xiaofei
Published: July 2022

Metallic nanostructures play a vital role in the nanoscale engineering of flexible optoelectronic devices as active units. Due to the limited flexibility properties of nanoparticles, researchers are devoting much more attention nowadays to nanowires (NWs) for designing flexible transparent electrodes for different electronic devices. Silver NW (AgNW) possesses a 1D structure with a changeable aspect ratio. It also includes up-to-date properties for future optoelectronic devices, such as low cost, high conductivity, high transparency, and mechanical flexibility. In view of the increasing demand for AgNWs, commercial-scale synthesis of AgNWs is inevitable. However, high discrepancies among the published data have resulted in a major delay in its commercialization. Therefore, this review critically discusses the ignored factors that limit AgNW commercialization and provide possible solutions.
The crossing multiplier for solvable lattice models
Authors: Belavin Vladimir , Gepner Doron , Ramos Cabezas J
Published: July 2022

We study the large class of solvable lattice models, based on the data of conformal field theory. These models are constructed from any conformal field theory. We consider the lattice models based on affine algebras described by Jimbo et al, for the algebras ABCD and by Kuniba et al for G
2. We find a general formula for the crossing multipliers of these models. It is shown that these crossing multipliers are also given by the principally specialized characters of the model in question. Therefore we conjecture that the crossing multipliers in this large class of solvable interaction round the face lattice models are given by the characters of the conformal field theory on which they are based. We use this result to study the local state probabilities of these models and show that they are given by the branching rule, in regime III.
Fitting China in: local elite collusion and contestation along Kenya’s standard Gauge Railway
Authors: Alden Chris , Otele Oscar M
Published: July 2022

Scholarship examining African agency towards Chinese development projects typically focuses on negotiations between African national elites and Chinese actors at the inception and policy formulation phase, a period which excludes local elites and public participation more generally. This gap between the policy formulation and policy implementation phases in the project cycle can, however, be exploited by local elites at the periphery of power to serve as a channel of influence over the distribution of foreign-derived patronage. Using opportunities posed by elections, these local elites assert their claims to the spoils of patronage with national elites through strategies like protest, bargaining and co-optation. This article investigates how the implementation phase of the Chinese-funded Standard Gauge Railway presented opportunities for collusion and contestation over foreign economic largesse amongst Kenya’s national and local elites, underscoring the multi-actor aspects of African agency and, concurrently, those structural and temporal factors that enable and shape such agency.
Oral β-lactams vs fluoroquinolones and trimethoprim/sulfamethoxazole for step-down therapy forEscherichia coli,Proteus mirabilis, andKlebsiella pneumoniaebacteremia
Authors: McAlister Michael J , Rose Dusten T , Hudson F Parker , Padilla-Tolentino Eimeira , Jaso Theresa C
Published: July 2022

Purpose

To compare rates of treatment failure for patients with bloodstream infections (BSIs) due to Escherichia coli, Klebsiella pneumoniae, or Proteus mirabilis who received oral step-down antibiotic therapy with either a fluoroquinolone (FQ) or trimethoprim/sulfamethoxazole (SXT) to rates for those who received an oral β-lactam (BL).

Methods

This retrospective, multicenter, cohort study included 397 unique adult hospitalized patients with a BSI due to E. coli, K. pneumoniae, or P. mirabilis at 6 hospitals in central Texas between July 11, 2016, and July 11, 2018. The primary outcome was a composite of treatment failure comprising 30-day readmission due to recurrence, 30-day all-cause mortality, and change in oral antibiotic. Secondary outcomes included 90-day development of Clostridioides difficile infection, 90-day colonization with a multidrug-resistant organism, 90-day all-cause readmission, hospital length of stay, and the individual components of the primary outcome.

Results

Of the 397 patients included, 200 received oral step-down therapy with a BL while 197 received an FQ or SXT. Most patients had an infection due to E. coli (82.8%) and a urinary source of infection (85%). Median total duration of therapy was 14 days in both groups. No difference in treatment failure was identified between the groups treated with a BL and FQ/SXT (7% vs 5.8%, P = 0.561). Median hospital length of stay was the only secondary endpoint in which there was an observed difference (6 vs 5 days, P = 0.04).

Conclusion

We observed no difference in treatment failure rates for patients receiving an oral BL compared to an oral FQ or SXT for step-down therapy of BSIs due to E. coli, K. pneumoniae, and P. mirabilis.
VII—Reflecting, Registering, Recording and Representing: From Light Image to Photographic Picture
Authors: Wilson Dawn M
Published: July 2022

Photography is valued as a medium for recording and visually reproducing features of the world. I seek to challenge the view that photography is fundamentally a recording process and that every photograph is a record—a view that I claim is based on a ‘single-stage’ misconception of the process. I propose an alternative, ‘multi-stage’ account in which I argue that causal registration of light is not equivalent to recording and reproducing an image. Intervention or non-intervention by photographers is more sophisticated than the traditional view allows. Using the multi-stage account, I describe four models for producing photographic images and pictures.
Structural features of free N-glycans in α1,3/4-fucosidase-deficient Arabidopsis thaliana: deletion of α1,3/4-fucosidase activity induced accumulation of plant complex type GN1 free N-glycans
Authors: Takata Shun , Hayashi Megumi , Maeda Megumi , Ishimizu Takeshi , Kimura Yoshinobu
Published: July 2022

Deletion of α-1,3/4-fucosidase activity in Arabidopsis thaliana resulted in the accumulation of GN1-type free N-glycans with the Lewis a epitope (GN1-FNG). This suggests that the release of α-fucose residue(s) may trigger rapid degradation of the plant complex-type (PCT) GN1-FNG. The fact that PCT-GN1-FNG has rarely been detected to date is probably due to its easier degradation compared with PCT-GN2-FNG.
Expression analysis of gibberellin-regulated protein in peach by reverse transcription-quantitative PCR
Authors: Kawai Natsuki , Hirakawa Yuki , Matsumoto Shinya , Itai Akihiro , Matsunaga Kayoko , Narita Hiroshi , Momma Keiko
Published: July 2022

Gibberellin-regulated protein (GRP) is a fruit severe allergen. The amounts of GRP expression normalized against actin in peach were determined by reverse transcription-quantitative PCR (RT-qPCR). The results were consistent with those determined by enzyme-linked immunosorbent assay (ELISA). The GRP expression was more evident in flesh than peel and increased rapidly in the maturing period. This approach is applicable to estimate the amount of GRP in other plants.
Anti-melanogenic effect of furanoeremophilanes identified from edible wild plants belonging to the genus Cacalia
Authors: Uesugi Shota , Hakozaki Mayuka , Kanno Yuko , Takahashi Yuta , Shindo Kazutoshi , Kimura Ken-ichi , Yano Akira
Published: July 2022

Cacalia delphiniifolia and Cacalia hastata are edible wild plants in Japan. We found that these plants have anti-melanogenic activity in B16F10 mouse melanoma cells. Three furanoeremophilanes, cacalol (from C. delphiniifolia), dehydrocacalohastin, and cacalohastin (from C. hastata), were identified as the main active components. The genus Cacalia may be a good source of beneficial materials with anti-melanogenic effects.
Impact of endometrial claudin-3 deletion on murine implantation, decidualization, and embryo development
Authors: Grund Susanne C , Wu Xin Xin , Müller Dominik , Wennemuth Gunther , Grümmer Ruth
Published: July 2022

The composition of cell contacts in the endometrium plays an important role in the process of embryo implantation and the establishment of pregnancy. In previous studies, we showed an induction of the tight junction protein claudin-3 in the developing decidua from day 6.5 of pregnancy onward. To evaluate the role of this specific claudin-3 distribution, we here evaluated the effect of an endometrial claudin-3 deletion in implantation and embryo development in claudin-3 knockout mice. Claudin-3 knockout mice were fertile but revealed a slightly reduced amount of implantation sites as well as of litter size. Though implantation sites showed morphologically regularly developed embryos and deciduas, depth of ectoplacental cone invasion was reduced in tendency compared to controls. The weight of the implantation sites on day 6.5 and 8.5 of pregnancy as well as the weight of the embryos on day 17.5 of pregnancy, but not of the placentas, was significantly reduced in claudin-3 knockout mice due to a maternal effect. This could be due to an impairment of decidualization as substantiated by a downregulation of the transcription of various decidua-associated genes in the early implantation sites of claudin-3 knockout mice. The fact that claudin-3 knockout mice are nevertheless fertile possibly may be compensated by the presence of other claudins like claudin-4 and claudin-10.
Healthcare resource utilisation and related costs of patients with CKD from the UK: a report from the DISCOVER CKD retrospective cohort
Authors: Pollock Carol , James Glen , Garcia Sanchez Juan Jose , Carrero Juan Jesus , Arnold Matthew , Lam Carolyn S P , Chen Hungta (Tony) , Nolan Stephen , Pecoits-Filho Roberto , Wheeler David C
Published: July 2022

Background

Chronic kidney disease (CKD) is widely reported to decrease quality of life, increase morbidity and mortality and cause increased healthcare resource utilisation (HCRU) as the disease progresses. However, there is a relative paucity of accurate and recent estimates of HCRU in this patient population. Our aim was to address this evidence gap by reporting HCRU and related costs in patients with CKD from the UK primary and secondary care settings.

Methods

HCRU and cost estimates of CKD were derived for UK patients included in the DISCOVER CKD cohort study using clinical records from the Clinical Practice Research Datalink linked to external databases. Patients with a history of transplant or undergoing dialysis were not included. HCRU and costs were stratified by CKD severity using the urinary albumin:creatinine ratio (UACR) and estimated glomerular filtration rate.

Results

Hospitalisation rates more than tripled between low (A1) and high (A3) UACR categories and the mean annual per-patient costs ranged from £4966 (A1) to £9196 (A3) and from £4997 (G2) to £7595 (G5), demonstrating that a large healthcare burden can be attributed to a relatively small number of patients with later stage CKD, including those with kidney failure and/or albuminuria.

Conclusions

HCRU and costs associated with CKD impose a substantial burden on the healthcare system, particularly in the more advanced stages of CKD. New interventions that can delay the progression of CKD to kidney failure may not only prolong the patient’s life, but would also provide significant resource and cost savings to healthcare providers.
Prediction of right ventricular failure after left ventricular assist device implantation: role of vasodilator challenge
Authors: Cacioli Giulio , Polizzi Vincenzo , Ciabatti Michele , Cristiano Ernesto , Pergolini Amedeo , Distefano Giada , Lilla Della Monica Paola , Comisso Marina , Piazza Vito , Sbaraglia Fabio , Musumeci Francesco
Published: July 2022

Aims

Pulmonary artery pulsatility index (PAPi) is an indicator of right ventricular (RV) function and an independent predictor of right ventricular failure (RVF) following left ventricular assist device (LVAD) implantation. Administration of vasodilator challenge during right heart catheterization (RHC) could reduce RV workload allowing a better assessment of its functional reserve.

Methods and results

Patients undergoing LVAD implantation at our Institution between May 2013 and August 2021 were enrolled. Only patients who had undergone RHC and vasodilator challenge with sodium nitroprusside were analyzed. We collected all available clinical, instrumental, and haemodynamic parameters, at baseline and after nitroprusside infusion and evaluated potential associations with post-LVAD RVF. Of the 54 patients analyzed, 19 (35%) developed RVF after LVAD implantation. Fractional area change (FAC) (OR: 0.647, CI: 0.481–0.871; P = 0.004), pulmonary artery systolic pressure (PASP) (OR: 0.856, CI: 0.761–0.964; P = 0.010), and post-sodium nitroprusside (NTP) PAPi (OR: 0.218, CI: 0.073–0.653; P = 0.006) were independent predictors of post-LVAD RVF. The model combining FAC, PASP, and post-NTP PAPi demonstrated a predictive accuracy of 90.7%. Addition of post-NTP PAPi significantly increased the predictive accuracy of the European Registry for Patients with Mechanical Circulatory Support right-sided heart failure risk score [79.4 vs. 70.4%; area under the curve (AUC): 0.841 vs. 0.724, P = 0.022] and the CRITT score (79.6% vs. 74%; AUC: 0.861 vs. 0.767 P = 0.033).

Conclusion

Post-NTP PAPi has observed to be an independent predictor of RVF following LVAD implantation. Dynamic assessment of PAPi using a vasodilator challenge may represent a method of testing RV functional reserve in candidates for LVAD implantation. Larger and prospective studies are needed to confirm this hypothesis.
Differentially Active and Conserved Neural Enhancers Define Two Forms of Adaptive Noncoding Evolution in Humans
Authors: Pizzollo Jason , Zintel Trisha M , Babbitt Courtney C
Published: July 2022

The human and chimpanzee genomes are strikingly similar, but our neural phenotypes are very different. Many of these differences are likely driven by changes in gene expression, and some of those changes may have been adaptive during human evolution. Yet, the relative contributions of positive selection on regulatory regions or other functional regulatory changes are unclear. Where are these changes located throughout the human genome? Are functional regulatory changes near genes or are they in distal enhancer regions? In this study, we experimentally combined both human and chimpanzee cis-regulatory elements (CREs) that showed either (1) signs of accelerated evolution in humans or (2) that have been shown to be active in the human brain. Using a massively parallel reporter assay, we tested the ability of orthologous human and chimpanzee CREs to activate transcription in induced pluripotent stem-cell-derived neural progenitor cells and neurons. With this assay, we identified 179 CREs with differential activity between human and chimpanzee; in contrast, we found 722 CREs with signs of positive selection in humans. Selection and differentially expressed CREs strikingly differ in level of expression, size, and genomic location. We found a subset of 69 CREs in loci with genetic variants associated with neuropsychiatric diseases, which underscores the consequence of regulatory activity in these loci for proper neural development and function. By combining CREs that either experienced recent selection in humans or CREs that are functional brain enhancers, presents a novel way of studying the evolution of noncoding elements that contribute to human neural phenotypes.
Stop Codon Usage as a Window into Genome Evolution: Mutation, Selection, Biased Gene Conversion and the TAG Paradox
Authors: Ho Alexander T , Hurst Laurence D
Published: July 2022

Protein coding genes terminate with one of three stop codons (TAA, TGA, or TAG) that, like synonymous codons, are not employed equally. With TGA and TAG having identical nucleotide content, analysis of their differential usage provides an unusual window into the forces operating on what are ostensibly functionally identical residues. Across genomes and between isochores within the human genome, TGA usage increases with G + C content but, with a common G + C → A + T mutation bias, this cannot be explained by mutation bias-drift equilibrium. Increased usage of TGA in G + C-rich genomes or genomic regions is also unlikely to reflect selection for the optimal stop codon, as TAA appears to be universally optimal, probably because it has the lowest read-through rate. Despite TAA being favored by selection and mutation bias, as with codon usage bias G + C pressure is the prime determinant of between-species TGA usage trends. In species with strong G + C-biased gene conversion (gBGC), such as mammals and birds, the high usage and conservation of TGA is best explained by an A + T → G + C repair bias. How to explain TGA enrichment in other G + C-rich genomes is less clear. Enigmatically, across bacterial and archaeal species and between human isochores TAG usage is mostly unresponsive to G + C pressure. This unresponsiveness we dub the TAG paradox as currently no mutational, selective, or gBGC model provides a well-supported explanation. That TAG does increase with G + C usage across eukaryotes makes the usage elsewhere yet more enigmatic. We suggest resolution of the TAG paradox may provide insights into either an unknown but common selective preference (probably at the DNA/RNA level) or an unrecognized complexity to the action of gBGC.
Pathological Set of Initial Data for Scaling-Supercritical Nonlinear Schrödinger Equations
Authors: Camps Nicolas , Gassot Louise
Published: July 2022

The purpose of this work is to evidence a pathological set of initial data for which the regularized solutions by convolution experience a norm-inflation mechanism, in arbitrarily short time. The result is in the spirit of the construction from Sun and Tzvetkov, where the pathological set contains a superposition of profiles that concentrate at different points. Thanks to finite propagation speed of the wave equation, and given a certain time, at most one profile exhibits significant growth. However, for Schrödinger-type equations, we cannot preclude the profiles from interacting between each other. Instead, we propose a method that exploits the regularizing effect of the approximate identity, which, at a given scale, rules out the norm inflation of the profiles that are concentrated at smaller scales.
Galois Distribution on Tori—A Refinement, Examples, and Applications
Authors: Baker Roger , Masser David
Published: July 2022

In this paper we give a refinement of the one-dimensional form of Bilu’s Equidistribution Theorem together with some examples and applications. These include an explicit bound for the sum of the $e^{i\theta }$ taken over all conjugates $re^{i\theta }$ of an algebraic number $\alpha $ in terms of its height $h$ and degree $d$. That is applied to show that a certain discrepancy of $\alpha $ is at most $8000h^{1/3}$, which removes an extra term involving $d$ from previous bounds; this cannot be done simply by using a lower bound for $h$ in terms of $d$, even assuming the Lehmer Conjecture. And we give a new estimate for the norm of $1-\alpha $. We also improve existing upper bounds for the height of $\xi $ when $\xi ,1-\xi $ are multiplicatively dependent.
Nonwaivability of Labour Rights, Individual Waivers and the Emancipatory Function of Labour Law
Authors: Bogoeski Vladimir
Published: July 2022

This paper intervenes in ongoing discussions on emerging legislation and jurisprudence across jurisdictions offering employees the possibility to renounce established labour rights through individual labour rights waivers. Building on discussions about consent and coercion in the employment relationship, the paper argues that individual labour rights waivers in most cases undermine labour law’s overall emancipatory potential, as they reverse the decommodifying effects of nonwaivable labour rights by re-appropriating the capitalist market logic that those very rights seek to offset. The paper’s intervention is twofold. It first develops the argument about the emancipatory function of labour law, and uses it to examine the negative effects of individual waivers on labour law’s capacity to emancipate working people and society at large. Second, the paper introduces a jurisdiction that until now has not been considered in the discussions on individual waivers, namely Germany. Although discussions on individual waivers in the scholarly discourse in Germany are marginal, the paper examines what current exceptions to nonwaivability might qualify as waivers, and argues that the reasons why individual labour rights waivers are less present lie in the strong collective dimension of the ideational framework that underpins German labour law.
Effect of Adulteration on Quality and Preliminary Risk Assessment of the Decoction Pieces of Farfarae Flos Based on the Determination of Hepatotoxic Pyrrolizidine Alkaloids by UHPLC–MS/MS
Authors: Li An-Ping , Shi Yan-Ping
Published: July 2022

Background

Farfarae Flos (FF) is a frequently used traditional herbal medicine with outstanding antitussive actions. The adulteration of FF decoction pieces is common.

Objective

This study aimed to study the effect of adulteration on the safety and quality of FF decoction pieces.

Methods

The proportion of impurities was conducted by cone quartering method. A simple and accurate ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method was established to simultaneous determinate three pyrrolizidine alkaloids (PAs) as endogenous toxic compounds in FF. The traditional medicinal parts (flower bud), impurities (pedicel and rhizome) and unselected samples were determined respectively. The values of estimated daily intake (EDI) and margin of exposure (MOE) were used for risk assessment.

Results

Twenty batches of samples were collected from different habitats, and the proportion of impurities ranged from 17.51% to 41.27%. Pedicel and rhizome were the main impurities, accounting for more than 87.40% of the total impurities. The content of PAs in impurities was significantly higher. The EDI value range was 5.34 to 16.59 μg/kg bw/day, which was much higher than the standard safety value of 7.00 × 10−3 μg/kg bw/day. The MOE values ranges for life long time and shorter exposure were 14.29 to 44.37 and 371.53 to 1153.63, respectively, indicating that at least 80% of the samples had safety risks. Correlation analysis showed that the proportion of adulterated impurities had significant correlation with the values of EDI and MOE.

Conclusions

Adulteration of non medicinal parts may significantly increase the risk of medications of FF decoction pieces.

Highlights

This study provides an efficient methodology reference for the control of PAs and a basis for adulteration to affect the safety and quality of FF decoction pieces.
Determination of Cross-Reactivity of Contemporary Cannabinoids with THC Direct Immunoassay (ELISA) in Whole Blood
Authors: Moody Marykathryn T , Ringel Meaghan M , Mathews Colleen M , Midthun Kari M
Published: July 2022

Immunoassay procedures, such as enzyme-linked immunosorbent assay (ELISA), are widely used for screening samples in both driving under the influence of drugs (DUID) and postmortem (PM) investigations. While these are sensitive and widely used techniques, they lack specificity compared to more novel instrumental screening platforms. In this study, the cross-reactivities of several cannabinoid isomers and related compounds were evaluated in whole blood using the Cannabinoids Direct ELISA kit from Immunalysis. The compounds of interest were supplemented individually at three different concentrations, ranging from 10 to 100 ng/mL or 10 to 1,000 ng/mL depending on analyte, to determine initial feasibility. Compounds exhibiting cross-reactivity were then tested to create dose–response curves to calculate the percent cross-reactivity. The cross-reactivity was determined to be 200% for delta-8-carboxy-tetrahydrocannabinol (THC) (delta-8-carboxy-THC), 25% for delta-9,11-THC, 13% for delta-10-THC, 7% for delta-6a(10a)-THC, 3% for THC-O-acetate and 0.5% for tetrahydrocannabiphorol. To determine potential impacts on forensic laboratory casework, a review of DUID and PM casework was also performed. From November 2020 to June 2021, a random sampling of DUID and PM cases was selected monthly and evaluated for the presence of cannabinoid isomer(s) in the absence of a reportable delta-9-carboxy-THC result. While validated techniques for the identification and confirmation of these isomer(s) did not exist at the time of routine testing, delta-8-carboxy-THC was believed to be the most common isomer finding based on current testing capability. This study demonstrated a noticeable increase in the presence of isomeric cannabinoid compounds in both forensic DUID and PM casework sampled during this period and suggests potential impacts for clinical casework as well.
Automated and High-Throughput Urine Drug Screening Using Paper Spray Mass Spectrometry
Authors: Rydberg Magnus , Dowling Sarah , Manicke Nicholas E
Published: July 2022

Paper spray mass spectrometry (PS-MS) has been shown to be a rapid, simple and inexpensive alternative to traditional forensic drug screening methods. It can address the limitations of both immunoassays and chromatography-based techniques due to its non-reliance on sample preparation and its ability to rapidly screen for a wide array of compounds. In this study, an automated PS-MS system was employed to semi-quantitatively screen for 40 commonly abused drugs and metabolites in urine after a 15-min glucuronidase reaction. The target compounds included common prescription opioids, fentanyl and norfentanyl, stimulants including methamphetamine and cocaine, benzodiazepines and antidepressants. The enzyme, buffer and internal standard solution were combined in one spiking solution to minimize sample handling. Analysis was carried out using a commercially available automated paper spray system coupled to a triple quadrupole mass spectrometer. This method may prove useful for clinical and forensic toxicology laboratories as it allows for automated screening of complex samples for drugs without extraction, separation and sample cleanup.