bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectral analysis of the transition to turbulence downstream a delta winglet pair vortex generator in an airflow channel
Authors: Younes Eliane , Hamidouche Souria , Gautier Rémi , Russeil Serge
Published: December 2022

The purpose of this experimental study is to provide a detailed analysis of the transition to turbulence in an airflow channel perturbed by a delta winglet pair vortex generator. Measurements of instantaneous velocity are carried out by a laser Doppler anemometry technique. Experiments are conducted for Reynolds numbers (based on the hydraulic diameter) ranging from Re = 400 to Re=12 000 and at several axial position downstream of the vortex generator. The flow behavior is characterized in each regime by means of a frequency analysis. We identified the inlet conditions corresponding to laminar weakly unsteady, transitional, and fully turbulent flow regimes. Furthermore, we have constructed a correlation between the Strouhal number and the Reynolds number that characterizes the vortex instability mechanism. Finally, under turbulent flow conditions, the dissipation rate was estimated, which showed an increase followed by an exponential decrease with the distance downstream of the vortex generator.
Enabling multiple intercavity polariton coherences by adding quantum confinement to cavity molecular polaritons
Authors: Yang Zimo , Bhakta Harsh H. , Xiong Wei
Published: December 2022

In this study, the “particle in a box” idea, which was broadly developed in semiconductor quantum dot research, was extended into mid-infrared (IR) cavity modes by applying lateral confinement in an optical cavity. The discrete cavity modes hybridized with molecular vibrational modes, resulting in a quartet of polariton states that can support multiple coherence states in the IR regime. We applied tailored pump pulse sequences to selectively prepare these coherences and verified the multi-coherence existence. The simulation based on Lindblad equation showed that because the quartet of polariton states resided in the same cavity, they were specifically robust toward decoherence caused by fluctuations in space. The multiple robust coherences paved the way for entangled states and coherent interactions between cavity polaritons, which would be critical for advancing polariton-based quantum information technology.
SPOP loss of function protects against tauopathy
Authors: Eck Randall J. , Kow Rebecca L. , Black Aristide H. , Liachko Nicole F. , Kraemer Brian C.
Published: December 2022

The pathological accumulation of the microtubule binding protein tau drives age-related neurodegeneration in a variety of disorders, collectively called tauopathies. In the most common tauopathy, Alzheimer’s disease (AD), the accumulation of pathological tau strongly correlates with cognitive decline. The underlying molecular mechanisms that drive neurodegeneration in tauopathies remain incompletely understood and no effective disease modifying pharmacological interventions currently exist. Here, we show that tau toxicity depends on the highly conserved nuclear E3 ubiquitin ligase adaptor protein SPOP in aCaenorhabditis elegansmodel of tauopathy. Loss of function mutations in theC. elegans spop-1gene significantly improves behavioral deficits in tau transgenic animals, while neuronal overexpression of SPOP-1 protein significantly worsens behavioral deficits. In addition, loss ofspop-1rescues a variety of tau-related phenotypes including the accumulation of total and phosphorylated tau protein, neurodegeneration, and shortened lifespan. Knockdown of SPOP-1’s E3 ubiquitin ligasecul-3/Cullin3 does not improve tauopathy suggesting a non-degradative mechanism of action for SPOP-1. Suppression of disease-related phenotypes occurs independently of the nuclear speckle resident poly(A)-binding protein SUT-2/MSUT2. MSUT2 modifies tauopathy in mammalian neurons and in AD. Our work identifies SPOP as a novel modifier of tauopathy and a conceptual pathway for therapeutic intervention.
Inhibition of GPR39 restores defects in endothelial cell–mediated neovascularization under the duress of chronic hyperglycemia: Evidence for regulatory roles of the sonic hedgehog signaling axis
Authors: Meda Venkata Sai Pranathi , Li Hainan , Xu Liping , Koh Jia Yi , Nguyen Huong , Minjares Morgan , Li Chunying , Kowluru Anjaneyulu , Milligan Graeme , Wang Jie-Mei
Published: December 2022

Impaired endothelial cell (EC)–mediated angiogenesis contributes to critical limb ischemia in diabetic patients. The sonic hedgehog (SHH) pathway participates in angiogenesis but is repressed in hyperglycemia by obscure mechanisms. We investigated the orphan G protein–coupled receptor GPR39 on SHH pathway activation in ECs and ischemia-induced angiogenesis in animals with chronic hyperglycemia. Human aortic ECs from healthy and type 2 diabetic (T2D) donors were cultured in vitro. GPR39 mRNA expression was significantly elevated in T2D. The EC proliferation, migration, and tube formation were attenuated by adenovirus-mediated GPR39 overexpression (Ad-GPR39) or GPR39 agonist TC-G-1008 in vitro. The production of proangiogenic factors was reduced by Ad-GPR39. Conversely, human ECs transfected with GPR39 siRNA or the mouse aortic ECs isolated from GPR39 global knockout (GPR39
KO
) mice displayed enhanced migration and proliferation compared with their respective controls. GPR39 suppressed the basal and ligand-dependent activation of the SHH effector GLI1, leading to attenuated EC migration. Coimmunoprecipitation revealed that the GPR39 direct binding of the suppressor of fused (SUFU), the SHH pathway endogenous inhibitor, may achieve this. Furthermore, in ECs with GPR39 knockdown, the robust GLI1 activation and EC migration were abolished by SUFU overexpression. In a chronic diabetic model of diet-induced obesity (DIO) and low-dose streptozotocin (STZ)-induced hyperglycemia, the GPR39
KO
mice demonstrated a faster pace of revascularization from hind limb ischemia and lower incidence of tissue necrosis than GPR39 wild-type (GPR39
WT
) counterparts. These findings have provided a conceptual framework for developing therapeutic tools that ablate or inhibit GPR39 for ischemic tissue repair under metabolic stress.
Kidney-resident innate-like memory γδ T cells control chronic
Staphylococcus aureus
infection of mice
Authors: Bertram Tabea , Reimers Daniel , Lory Niels C. , Schmidt Constantin , Schmid Joanna , C. Heinig Lisa , Bradtke Peter , Rattay Guido , Zielinski Stephanie , Hellmig Malte , Bartsch Patricia , Rohde Holger , Nuñez Sarah , Rosemblatt Mariana V. , Bono Maria Rosa , Gagliani Nicola , Sandrock Inga , Panzer Ulf , Krebs Christian F. , Meyer-Schwesinger Catherine , Prinz Immo , Mittrücker Hans-Willi
Published: December 2022

γδ T cells are involved in the control of
Staphylococcus aureus
infection, but their importance in protection compared to other T cells is unclear. We used a mouse model of systemic
S. aureus
infection associated with high bacterial load and persistence in the kidney. Infection caused fulminant accumulation of γδ T cells in the kidney. Renal γδ T cells acquired tissue residency and were maintained in high numbers during chronic infection. At day 7, up to 50% of renal γδ T cells produced IL-17A in situ and a large fraction of renal γδ T cells remained IL-17A
+
during chronic infection. Controlled depletion revealed that γδ T cells restricted renal
S. aureus
replication in the acute infection and provided protection during chronic renal infection and upon reinfection. Our results demonstrate that kidney-resident γδ T cells are nonredundant in limiting local
S. aureus
growth during chronic infection and provide enhanced protection against reinfection.
Role of intracortical neuropil growth in the gyrification of the primate cerebral cortex
Authors: Rash Brian G. , Arellano Jon I. , Duque Alvaro , Rakic Pasko
Published: December 2022

The convolutions of the mammalian cerebral cortex allow the enlargement of its surface and addition of novel functional areas during evolution while minimizing expansion of the cranium. Cognitive neurodevelopmental disorders in humans, including microcephaly and lissencephaly, are often associated with impaired gyrification. In the classical model of gyrification, surface area is initially set by the number of radial units, and the forces driving cortical folding include neuronal growth, formation of neuropil, glial cell intercalation, and the patterned growth of subcortical white matter. An alternative model proposes that specified neurogenic hotspots in the outer subventricular zone (oSVZ) produce larger numbers of neurons that generate convexities in the cortex. This directly contradicts reports showing that cortical neurogenesis and settling of neurons into the cortical plate in primates, including humans, are completed well prior to the formation of secondary and tertiary gyri and indeed most primary gyri. In addition, during the main period of gyrification, the oSVZ produces mainly astrocytes and oligodendrocytes. Here we describe how rapid growth of intracortical neuropil, addition of glial cells, and enlargement of subcortical white matter in primates are the primary forces responsible for the post-neurogenic expansion of the cortical surface and formation of gyri during fetal development. Using immunohistochemistry for markers of proliferation and glial and neuronal progenitors combined with transcriptomic analysis, we show that neurogenesis in the ventricular zone and oSVZ is phased out and transitions to gliogenesis prior to gyral development. In summary, our data support the classical model of gyrification and provide insight into the pathogenesis of congenital cortical malformations.
KIR signaling is regulated by electrostatic interaction of its cytosolic tail with the plasma membrane despite being neutral polyampholyte
Authors: Sarangi Sitanshu Kumar , Lande Kashmiri M. , Kumar Santosh
Published: December 2022

Many receptors signal upon phosphorylation of tyrosine-based motifs in their cytosolic tail, with intrinsic disorder as a common feature. Studies on CD3ζ and CD3ε tails, which are disordered and polybasic, suggested regulation of phosphorylation through accessibility of tyrosines, governed by electrostatic interactions with membrane anionic lipids. We noticed characteristics of intrinsic disorder and previously unappreciated features in tyrosine-based motif-bearing cytosolic tails of many, especially, inhibitory receptors. They are neutral or acidic polyampholytes, with acidic and basic residues linearly segregated. To explore roles of these electrostatic features, we studied inhibitory killer-cell immunoglobulin-like receptor (KIR). Its cytosolic tail is a disordered neutrally charged polyampholyte, wherein juxtamembrane and membrane distal stretches are basic, and the intervening stretch is acidic. Despite lacking net charge, it interacted electrostatically with the plasma membrane. The juxtamembrane stretch was crucial for overall binding, which sequestered tyrosines in the lipid bilayer and restrained their constitutive phosphorylation. Human leukocyte antigen-C ligand binding to KIR released its tail from the plasma membrane to initiate signaling. Tail release occurred independently of KIR polymerization, clustering, or tyrosine phosphorylation, but required acidic residues of the acidic stretch. Tail interaction with the plasma membrane dictated signaling strength of KIR. These results revealed an electrostatic protein–lipid interaction that is unusual in being governed by segregated clusters of acidic and basic residues in polyampholytic disordered region of protein. In contrast to previously known, segregated distribution of oppositely charged residues made both binding and unbinding modules inherent to receptor tail, which could make the interaction an independent signaling switch.
Piezo mechanosensory channels regulate centrosome integrity and mitotic entry
Authors: David Liron , Martinez Laurel , Xi Qiongchao , Kooshesh Kameron A. , Zhang Ying , Shah Jagesh V. , Maas Richard L. , Wu Hao
Published: December 2022

Piezo1 and 2 are evolutionarily conserved mechanosensory cation channels known to function on the cell surface by responding to external pressure and transducing a mechanically activated Ca
2+
current. Here we show that both Piezo1 and 2 also exhibit concentrated intracellular localization at centrosomes. Both Piezo1 and 2 loss-of-function and Piezo1 activation by the small molecule Yoda1 result in supernumerary centrosomes, premature centriole disengagement, multi-polar spindles, and mitotic delay. By using a GFP, Calmodulin and M13 Protein fusion (GCaMP) Ca
2+
-sensitive reporter, we show that perturbations in Piezo modulate Ca
2+
flux at centrosomes. Moreover, the inhibition of Polo-like-kinase 1 eliminates Yoda1-induced centriole disengagement. Because previous studies have implicated force generation by microtubules as essential for maintaining centrosomal integrity, we propose that mechanotransduction by Piezo maintains pericentrosomal Ca
2+
within a defined range, possibly through sensing cell intrinsic forces from microtubules.
Unique ice dendrite morphology on state-of-the-art oil-impregnated surfaces
Authors: Gandee Hunter , Zhou Yimin , Lee John , Chomali Juan , Xu Haobo , Adera Solomon
Published: December 2022

Due to its multifaceted impact in various applications, icing and ice dendrite growth has been the focus of numerous studies in the past. Dendrites on wetting (hydrophilic) and nonwetting (hydrophobic) surfaces are sharp, pointy, branching, and hairy. Here, we show a unique dendrite morphology on state-of-the-art micro/nanostructured oil-impregnated surfaces, which are commonly referred to as slippery liquid-infused porous surfaces or liquid-infused surfaces. Unlike the dendrites on traditional textured hydrophilic and hydrophobic surfaces, the dendrites on oil-impregnated surfaces are thick and lumpy without pattern. Our experiments show that the unique ice dendrite morphology on lubricant-infused surfaces is due to oil wicking into the porous dendritic network because of the capillary pressure imbalance between the surface texture and the dendrites. We characterized the shape complexity of the ice dendrites using fractal analysis. Experiments show that ice dendrites on textured oil-impregnated surfaces have lower fractal dimensions than those on traditional lotus leaf-inspired air-filled porous structures. Furthermore, we developed a regime map that can be used as a design guideline for micro/nanostructured oil-impregnated surfaces by capturing the complex effects of oil chemistry, oil viscosity, and wetting ridge volume on dendrite growth and morphology. The insights gained from this work inform strategies to reduce lubricant depletion, a major bottleneck for the transition of micro/nanostructured oil-impregnated surfaces from bench-top laboratory prototypes to industrial use. This work will assist the development of next-generation depletion-resistant lubricant-infused ice-repellent surfaces.
Mec1 regulates PAS recruitment of Atg13 via direct binding with Atg13 during glucose starvation-induced autophagy
Authors: Yao Weijing , Li Yixing , Chen Yingcong , Chen Yuting , Zhao Pengwei , Zhang Yi , Jiang Qiang , Feng Yuyao , Yang Fan , Wu Choufei , Zhong Huiming , Zhou Yiting , Sun Qiming , Zhang Liqin , Liu Wei , Yi Cong
Published: December 2022

Mec1 is a DNA damage sensor, which performs an essential role in the DNA damage response pathway and glucose starvation-induced autophagy. However, the functions of Mec1 in autophagy remain unclear. In response to glucose starvation, Mec1 forms puncta, which are recruited to mitochondria through the adaptor protein Ggc1. Here, we show that Mec1 puncta also contact the phagophore assembly site (PAS) via direct binding with Atg13. Functional analysis of the Atg13–Mec1 interaction revealed two previously unrecognized protein regions, the
M
ec1-
B
inding
R
egion (MBR) on Atg13 and the
A
tg13-
B
inding
R
egion (ABR) on Mec1, which mediate their mutual association under glucose starvation conditions. Disruption of the MBR or ABR impairs the recruitment of Mec1 puncta and Atg13 to the PAS, consequently blocking glucose starvation-induced autophagy. Additionally, the MBR and ABR regions are also crucial for DNA damage-induced autophagy. We thus propose that Mec1 regulates glucose starvation-induced autophagy by controlling Atg13 recruitment to the PAS.
Mmp-induced fat body cell dissociation promotes pupal development and moderately averts pupal diapause by activating lipid metabolism
Authors: Jia Qiangqiang , Li Sheng
Published: December 2022

In Lepidoptera and Diptera, the fat body dissociates into single cells in nondiapause pupae, but it does not dissociate in diapause pupae until diapause termination. Using the cotton bollworm,
Helicoverpa armigera
, as a model of pupal diapause insects, we illustrated the catalytic mechanism and physiological importance of fat body cell dissociation in regulating pupal development and diapause. In nondiapause pupae, cathepsin L (CatL) activates matrix metalloproteinases (Mmps) that degrade extracellular matrix proteins and cause fat body cell dissociation. Mmp-induced fat body cell dissociation activates lipid metabolism through transcriptional regulation, and the resulting energetic supplies increase brain metabolic activity (i.e., mitochondria respiration and insulin signaling) and thus promote pupal development. In diapause pupae, low activities of CatL and Mmps prevent fat body cell dissociation and lipid metabolism from occurring, maintaining pupal diapause. Importantly, as demonstrated by chemical inhibitor treatments and CRISPR-mediated gene knockouts, Mmp inhibition delayed pupal development and moderately increased the incidence of pupal diapause, while Mmp stimulation promoted pupal development and moderately averted pupal diapause. This study advances our recent understanding of fat body biology and insect diapause regulation.
Top predator sea stars are the benthic equivalent to polar bears of the pelagic realm
Authors: Amiraux Rémi , Yurkowski David J. , Archambault Philippe , Pierrejean Marie , Mundy C. J.
Published: December 2022

The marine pelagic compartment spans numerous trophic levels and consists of numerous reticulate connections between species from primary producers to iconic apex predators, while the benthic compartment is perceived to be simpler in structure and comprised of only low trophic level species. Here, we challenge this paradigm by illustrating that the benthic compartment is home to a subweb of similar structure and complexity to that of the pelagic realm, including the benthic equivalent to iconic polar bears: megafaunal-predatory sea stars.
Crystal structure of LGR ligand α2/β5 from
Caenorhabditis elegans
with implications for the evolution of glycoprotein hormones
Authors: Gong Zhen , Wang Wei , El Omari Kamel , Lebedev Andrey A. , Clarke Oliver B. , Hendrickson Wayne A.
Published: December 2022

A family of leucine-rich-repeat-containing G-protein-coupled receptors (LGRs) mediate diverse physiological responses when complexed with their cognate ligands. LGRs are present in all metazoan animals. In humans, the LGR ligands include glycoprotein hormones (GPHs) chorionic gonadotropin (hCG), luteinizing hormone, follicle-stimulating hormone (hFSH), and thyroid-stimulating hormone (hTSH). These hormones are αβ heterodimers of cystine-knot protein chains. LGRs and their ligand chains have coevolved. Ancestral hormone homologs, present in both bilaterian animals and chordates, are identified as α2β5. We have used single-wavelength anomalous diffraction and molecular replacement to determine structures of the α2β5 hormone from
Caenorhabditis elegans
(
Ce
α2β5).
Ce
α2β5 is unglycosylated, as are many other α2β5 hormones. Both
Hs
α2β5, the human homolog of
Ce
α2β5, and hTSH activate the same receptor (hTSHR). Despite having little sequence similarity to vertebrate GPHs, apart from the cysteine patterns from core disulfide bridges,
Ce
α2β5 is generally similar in structure to these counterparts; however, its α2 and β5 subunits are more symmetric as compared with α and β of hCG and hFSH. This quasisymmetry suggests a hypothetical homodimeric antecedent of the α2β5 and αβ heterodimers. Known structures together with AlphaFold models from the sequences for other LGR ligands provide representatives for the molecular evolution of LGR ligands from early metazoans through the present-day GPHs. The experimental
Ce
α2β5 structure validates its AlphaFold model, and thus also that for
Hs
α2β5; and interfacial characteristics in a model for the
Hs
α2β5:hTSHR complex are similar to those found in an experimental hTSH:hTSHR structure.
Corrosion behaviour of Sn-9Zn-xS solders in 3.5 wt-% NaCl solution
Authors: Yu Xinyuan , Huang Huizhen , Zhang Qinghuan , Chen Weipeng , Shuai Gewang
Published: December 2022

The effects of S addition on the corrosion behaviour of Sn-9Zn solders in 3.5 wt-% NaCl solution were investigated using dynamic potential polarisation, electrochemical impedance spectroscopy techniques and weight loss measurement. The results indicate that S addition could obviously improve the corrosion resistance of Sn-9Zn solder alloy as revealed by much lower corrosion current density, higher impedance and the reduced weight loss. It is believed that the homogeneous microstructures of Sn-9Zn, especially the black refined Zn-rich phases are favourable to improve its corrosion resistance. SEM observations found that S addition might promote the formation of denser and more uniform corrosion products on the solder surface. The main corrosion product was Zn5(OH)8Cl2·H2O determined by EDS and XRD analysis.
Relativistic transformation of thermodynamic parameters and refined Saha equation
Authors: Hao Xin , Liu Shaofan , Zhao Liu
Published: December 2022

The relativistic transformation rule for temperature is a debated topic for more than 110 years. Several incompatible proposals exist in the literature but a final resolution is still missing. In this work, we reconsider the problem of relativistic transformation rules for a number of thermodynamic parameters including temperature, chemical potential, pressure, entropy and enthalpy densities for a relativistic perfect fluid using relativistic kinetic theory. The analysis is carried out in a fully relativistic covariant manner, and the explicit transformation rules for the above quantities are obtained in both Minkowski and Rindler spacetimes. Our results suggest that the temperature of a moving fluid appears to be colder, supporting the proposal by de Broglie, Einstein, and Planck, in contrast to other proposals. Moreover, in the case of a Rindler fluid, our findings suggest that the total number of particles and the total entropy of a perfect fluid in a box whose bottom is parallel to the Rindler horizon are proportional to the area of the bottom, but are independent of the height of the box, provided the bottom of the box is sufficiently close to the Rindler horizon. The area dependence of the particle number implies that the particles tend to be gathered toward the bottom of the box, and hence implicitly determines the distribution of the chemical potential of the system, whereas the area dependence of the entropy indicates that the entropy is still additive and may have potential applications in explaining the area law of black hole entropy. As a by-product, we also obtain a relativistically refined version of the famous Saha equation which holds in both Minkowski and Rindler spacetimes.
Interpretation of Lung Cancer PlasmaEGFRMutation Tests in the Clinical Setting
Authors: Cheung Alvin Ho-Kwan , Wong Kit-Yee , Chiang Cho-Han , Liu Xiaoli , Zhang Yihan , Hui Chris Ho-Lam , Chen Bonan , Wang Yifei , Chow Chit , Kang Wei , To Ka-Fai
Published: December 2022

Objectives

Comprehensive data synthesis of the clinical parameters that affect plasma EGFR mutation test results in non–small cell lung carcinoma is lacking. Although individual studies have suggested a variety of patient characteristics that can affect diagnostic accuracy, no unified conclusion has been reached.

Methods

We analyzed 170 plasma EGFR mutation tests performed between 2015 and 2021 at our institution and carried out a systematic review and meta-analysis to identify clinical and imaging features that correlate with plasma EGFR mutation test sensitivity.

Results

Data synthesis from 14 studies of 2,576 patients revealed that patients with stage IV disease had a significantly lower false-negative rate than those with stage I through III disease. For our institutional cohort, which consisted of 75 paired plasma and tissue tests that were assessable for diagnostic accuracy, the overall sensitivity was 70.59% (95% confidence interval, 56.17%-82.51%). Patients who had distant metastases and more suspicious lymph nodes on imaging findings correlated with a low false-negative rate.

Conclusions

While interpreting plasma EGFR mutation results, extra caution should be exercised for patients with early-stage, localized disease to accommodate the possibility of false-negative results. These meta-analyses and clinical data may enable clinicians to make evidence-based judgments for individual patients.
Correlation Between Short-Term Blood Pressure Variability After Primary Percutaneous Coronary Intervention and Adverse Cardiovascular Events in Patients With ST Segment Elevation Myocardial Infarction
Authors: Huang Liu-hai , Tan Si-lu , Fang Zhen , Wei Xin , Li Ya-nian , Zhou Jian-wei , He Sheng-hu
Published: December 2022

Background

To investigate the relationship between short-term blood pressure variability (BPV) after primary percutaneous coronary intervention (PPCI) and adverse cardiovascular outcomes 1 year after operation in patients with acute ST segment elevation myocardial infarction (STEMI).

Methods

The clinical and prognostic data of 331 patients with STEMI who underwent PPCI and drug-eluting stent implantation were collected retrospectively from 2016 to 2019. The correlation between BPV within 4 days and adverse cardiovascular outcome 1 year after operation was analyzed. Blood pressure SD was used to evaluate individual systolic blood pressure variability (SBPV) and diastolic blood pressure variability (DBPV). The high SBPV and DBPV groups were defined as SD ≥11.42 and ≥8.49 mm Hg, respectively. Multivariate bivariate logistic regression model was used to explore the correlation between SBPV, DBPV, and major adverse cardiovascular events (MACE) 1 year after operation.

Results

The incidence of heart failure in the high SBPV group (21.1% vs. 10.3%) was significantly higher than the low SBPV group. Also, the incidence of heart failure (23.5% vs. 7.9%) and the cumulative incidence of MACE (29.5% vs. 13.9%) in the high DBPV group were higher than those in the low DBPV group (all P < 0.05). After adjusting for age, sex, body mass index, antihypertensive drugs, left ventricular ejection fraction, Gensini score, and other influencing factors, multivariate binary logistic regression analysis showed that high SBPV was a risk factor for heart failure (odds ratio [OR] = 3.462, 95% confidence interval [CI] 1.476–8.117, P = 0.004), and high DBPV was a risk factor for heart failure and cumulative MACE (OR = 4.535, 95% CI 1.725–11.926, P = 0.002; OR = 3.412, 95% CI 1.627–7.152, P = 0.001, respectively) and in the subgroup hypertensives using oral antihypertensive drugs (OR = 4.328, 95% CI 1.619–11.572, P = 0.004), as well as high DBPV for heart failure and cumulative MACE (OR = 4.600, 95% CI 1.518–13.934, P = 0.007; OR = 4.942, 95% CI 1.851–13.198, P = 0.001, respectively).

Conclusions

High BPV within 4 days after PPCI and drug-eluting stent implantation in STEMI patients is a cardiovascular risk factor within 1 year after operation.
Absence of evidence against belief as credence 1
Authors: del Rio Andrew
Published: December 2022

On one view of the traditional doxastic attitudes, belief is credence 1, disbelief is credence 0 and suspension is any precise credence between 0 and 1. In ‘Rational agnosticism and degrees of belief’ (2013) Jane Friedman argues, against this view, that there are cases where a credence of 0 is required but where suspension is permitted. If this were so, belief, disbelief and suspension could not be identified or reduced to the aforementioned credences. I argue that Friedman relies on two different notions of epistemic rationality and two different kinds of evidential absence. I clarify these distinctions and show that her argument is either not valid or includes implausible premisses, twice over. If this is so, the view that belief is credence 1, disbelief is credence 0 and suspension is any precise credence between 0 and 1 cannot be rejected on the grounds that Friedman proposes.
Proximal reflux frequency not correlated with atypical gastroesophageal reflux disease (GERD) symptoms
Authors: Liu Kelli , Evans Joni , Clayton Steven
Published: December 2022

Though most known for heartburn and regurgitation, gastroesophageal reflux disease (GERD) is attributed to countless atypical, extra-esophageal (EE) manifestations like cough and throat clearing. While GERD has been studied extensively, the relationship between reflux character and symptom manifestation remains poorly understood. The aim of this study was to examine proximal reflux frequency and its relationship with typical or atypical symptoms. 540 (75.1% female, 24.9% male) pH-impedance monitoring studies from the last 3-years were divided by symptom indication and retrospectively reviewed for proximal reflux frequency, total acid exposure time, mean nocturnal baseline impedance, and total reflux episodes in both abnormal and normal, and borderline studies. Baseline characteristics were also collected. Both total reflux events and mean proximal reflux frequency were found to differ significantly between those with typical versus atypical symptoms. Total reflux events [median (IQR)] were 43.5 (24.0–74.0) in typical patients and 35.0 (20.0–57.0) in atypical patients (P-value 0.0369). Proximal reflux frequency [median (IQR)] was 12.0 (4.0–19.0) typical and 7.0 (3.0–17.0) atypical (P-value 0.0348). Results for exclusively abnormal studies also favored typical patients but not significantly. Baseline characteristics and use of gastric acid control did not differ significantly. Proximal reflux frequency was observed to increase among those with typical GERD symptoms. Total acid reflux events were also significantly higher on average with typical patients. Our findings that proximal reflux frequency is reduced in patients with atypical symptoms compared with patients with typical symptoms suggest that proximal reflux exposure may play a significant role in the symptom presentation of typical classic heartburn and regurgitation symptoms. The differential diagnosis for atypical EE symptoms is vast and can be multifactorial. Our results indicate proximal reflux events may contribute to atypical EE symptoms less than previously reported.
Early outcomes following EndoFLIP-tailored peroral endoscopic myotomy (POEM): the establishment of POEM services in two UK centers
Authors: Knight William , Kandiah Kaveetha , Vrakopoulou Zoi , White Annabel , Barbieri Lavinia , Tewari Nilanjana , Couch Jennifer , DiMaggio Francesco , Barley Mark , Ragunath Krish , Catton James , Botha Abraham
Published: December 2022

Peroral endoscopic myotomy (POEM) is a safe and effective minimally invasive treatment for achalasia. Postoperative reflux rates remain high. The functional luminal imaging probe (FLIP) allows intraoperative measurement of lower esophageal distensibility during POEM. In theory, this enables a tailoring of myotomies to ensure adequate distensibility while minimizing postoperative reflux risk. Two prospectively collected POEM databases were analyzed from two UK tertiary upper GI centers. The operators in each center used FLIP measurements to ensure adequate myotomy. Outcome measures included Eckardt score (where <3 indicated clinical success) and proton-pump inhibitor use (PPI), collected at the first postoperative appointment. Length of stay was recorded as were complications. In all, 142 patients underwent POEM between 2015 and 2019. Overall, 90% (128/142) had postoperative Eckardt scores of <3 at 6 weeks. Clinical success improved to 93% (66/71) in the latter half of each series with a significantly higher rate of complete symptom resolution (53 versus 26%, P = 0.003). In all, 79% of the poor responders had previous interventions compared with 55% of responders (P = 0.09). Median post-myotomy distensibility index was 4.0 mm2/mmHg in responders and 2.9 in nonresponders (P = 0.16). Myotomy length of <7 cm was associated with 93% clinical success and 40% post op PPI use compared with 60% PPI use with longer myotomies. There were two type IIIa, two type IIIb, and one IV Clavien–Dindo complications. This is the largest series of endoluminal functional lumen imaging probe (EndoFLIP)-tailored POEM in the UK to date. The shorter myotomies, allowed through EndoFLIP tailoring, remained clinically effective at 6 weeks. Complete symptom response rates improved in the latter half of each series. More data will be needed from high-volume collaborations to decipher optimal myotomy profiles based on EndoFLIP parameters.
Surface microdialysis measures local tissue metabolism after Ivor Lewis esophagectomy; an attempt to predict anastomotic defect
Authors: Åkesson Oscar , Abrahamsson Pernilla , Johansson Göran , Haney Michael , Falkenback Dan , Hermansson Michael , Jeremiasen Martin , Johansson Jan
Published: December 2022

Anastomotic defect (AD) after esophagectomy can lead to severe complications with need for surgical or endoscopic intervention. Early detection enables early treatment and can limit the consequences of the AD. As of today, there are limited methods to predict AD. In this study, we have used microdialysis (MD) to measure local metabolism at the intrathoracic anastomosis. Feasibility and possible diagnostic use were investigated. Sixty patients planned for Ivor Lewis esophagectomy were enrolled. After construction of the anastomosis, surface MD (S-MD) probes were attached to the outer surface of the esophageal remnant and the gastric conduit in close vicinity of the anastomosis and left in place for 7 postoperative days (PODs). Continuous sampling of local tissue concentrations of metabolic substances (glucose, lactate, and pyruvate) was performed postoperatively. Outcome, defined as AD or not according to Esophagectomy Complications Consensus Group definitions, was recorded at discharge or at first postoperative follow up. Difference in concentrations of metabolic substances was analyzed retrospectively between the two groups by means of artificial neural network technique. S-MD probes can be attached and removed from the gastric tube reconstruction without any adverse events. Deviating metabolite concentrations on POD 1 were associated with later development of AD. In subjects who developed AD, no difference in metabolic concentrations between the esophageal and the gastric probe was recorded. The technical failure rate of the MD probes/procedure was high. S-MD can be used in a clinical setting after Ivor Lewis esophagectomy. Deviation in local tissue metabolism on POD 1 seems to be associated with development of AD. Further development of MD probes and procedure is required to reduce technical failure.
Acute LDL-C reduction post ACS: strike early and strike strong: from evidence to clinical practice. A clinical consensus statement of the Association for Acute CardioVascular Care (ACVC), in collaboration with the European Association of Preventive Cardiology (EAPC) and the European Society of Cardiology Working Group on Cardiovascular Pharmacotherapy
Authors: Krychtiuk Konstantin A , Ahrens Ingo , Drexel Heinz , Halvorsen Sigrun , Hassager Christian , Huber Kurt , Kurpas Donata , Niessner Alexander , Schiele Francois , Semb Anne Grete , Sionis Alessandro , Claeys Marc J , Barrabes José , Montero Santiago , Sinnaeve Peter , Pedretti Roberto , Catapano Alberico
Published: December 2022

After experiencing an acute coronary syndrome (ACS), patients are at a high risk of suffering from recurrent ischaemic cardiovascular events, especially in the very early phase. Low density lipoprotein-cholesterol (LDL-C) is causally involved in atherosclerosis and a clear, monotonic relationship between pharmacologic LDL-C lowering and a reduction in cardiovascular events post-ACS has been shown, a concept termed ‘the lower, the better’. Current ESC guidelines suggest an LDL-C guided, step-wise initiation and escalation of lipid-lowering therapy (LLT). Observational studies consistently show low rates of guideline-recommended LLT adaptions and concomitant low rates of LDL-C target goal achievement, leaving patients at residual risk, especially in the vulnerable post-ACS phase. In addition to the well-established ‘the lower, the better’ approach, a ‘strike early and strike strong’ approach in the early post-ACS phase with upfront initiation of a combined lipid-lowering approach using high-intensity statins and ezetimibe seems reasonable. We discuss the rationale, clinical trial evidence and experience for such an approach and highlight existing knowledge gaps. In addition, the concept of acute initiation of PCSK9 inhibition in the early phase is reviewed. Ultimately, we focus on hurdles and solutions to provide high-quality, evidence-based follow-up care in post-ACS patients.
Glimepiride use is associated with reduced cardiovascular mortality in patients with type 2 diabetes and chronic heart failure: a prospective cohort study
Authors: He Wu , Yuan Gang , Han Yu , Yan Yongcui , Li Gen , Zhao Chengcheng , Shen Jingshan , Jiang Xiangrui , Chen Chen , Ni Li , Wang Dao Wen
Published: December 2022

Aims

Glimepiride has good cardiovascular safety. However, whether glimepiride benefits clinical cardiovascular outcomes is unclear.

Methods and results

A total of 21 451 inpatients with type 2 diabetes (T2D) and chronic heart failure (CHF) were analysed, including 638 who received glimepiride treatment and 20 813 who did not. Propensity score matching yielded 509 pairs (glimepiride and non-glimepiride groups), and both groups were followed up. Kaplan–Meier and Cox regression analyses were used to compare all-cause mortality, cardiovascular mortality, hospitalizations and emergency visits for heart failure, and hospitalizations for acute myocardial infarction or stroke. During follow-up, the all-cause mortality [adjusted hazard ratio (HR), 0.47; 95% confidence interval (CI), 0.35–0.63; P < 0.001], cardiovascular mortality (adjusted HR, 0.34; 95% CI, 0.24–0.48; P < 0.001), and number of hospitalizations and emergency visits for heart failure (adjusted HR, 0.42; 95% CI, 0.36–0.50; P < 0.001) and hospitalizations for acute myocardial infarction or stroke (adjusted HR, 0.53; 95% CI, 0.38–0.73; P < 0.001) were significantly lower in the glimepiride group; the conclusion remained similar in all subgroups. Furthermore, high-dose glimepiride use (2–4 mg/day) was associated with lower cardiovascular mortality than low-dose (1 mg/day) (adjusted HR, 0.55; 95% CI, 0.31–0.99; P = 0.047). Glimepiride exhibited good molecular docking with soluble epoxide hydrolase (sEH) and increased the level epoxyeicosatrienoic acid (EET).

Conclusion

Long-term continuous glimepiride use is associated with better survival, fewer hospitalizations and emergency visits for heart failure, and fewer hospitalizations for acute myocardial infarction or stroke in patients with T2D and CHF. High-dose glimepiride has greater cardiovascular protective advantages than low-dose glimepiride. The cardiovascular protective effect of glimepiride may be related to the EET level increase through sEH inhibition.

Trial registration

ClinicalTrials.gov NCT05538819. https://www.clinicaltrials.gov/ct2/show/NCT05538819
German narratives about the Saint Bartholomew’s Day massacre
Authors: van Tol Jonas
Published: December 2022

In Germany, the Saint Bartholomew’s Day massacre was seen as special but not unique. Confronted with the first news reports, German audiences turned to existing understandings of the nature of religious conflict to make sense of the traumatic stories. This article examines four broad and interrelated narrative frameworks that were used to explain the massacre. First, German Catholics and Lutherans, treasuring the orderly Peace of Augsburg, condemned the sedition of the Huguenots and saw the massacre as a regrettable but logical consequence of their rebellion. Secondly, rumours of conspiracy and equivocation abounded in the empire. These seemed to be confirmed by the massacre. Thirdly, fearing the erosion of noble prerogatives and the creation of ‘Turkish’ tyrannies, the massacre of the French nobility chimed in with German aristocratic anxieties. Finally, the horrific fate of so many fellow Christians in France led some to see the massacre as an eschatological event.
Global Gene Expression Analysis Reveals Complex Cuticle Organization of the Tribolium Compound Eye
Authors: Chen Qing , Sasikala-Appukuttan Arun Kirshna , Husain Zahabiya , Shrivastava Anura , Spain Marla , Sendler Edward D , Daines Bryce , Fischer Stefan , Chen Rui , Cook Tiffany A , Friedrich Markus
Published: December 2022

The red flour beetle Tribolium castaneum is a resource-rich model for genomic and developmental studies. To extend previous studies on Tribolium eye development, we produced transcriptomes for normal-eyed and eye-depleted heads of pupae and adults to identify differentially transcript-enriched (DE) genes in the visual system. Unexpectedly, cuticle-related genes were the largest functional class in the pupal compound eye DE gene population, indicating differential enrichment in three distinct cuticle components: clear lens facet cuticle, highly melanized cuticle of the ocular diaphragm, which surrounds the Tribolium compound eye for internal fortification, and newly identified facet margins of the tanned cuticle, possibly enhancing external fortification. Phylogenetic, linkage, and high-throughput gene knockdown data suggest that most cuticle proteins (CPs) expressed in the Tribolium compound eye stem from the deployment of ancient CP genes. Consistent with this, TcasCPR15, which we identified as the major lens CP gene in Tribolium, is a beetle-specific but pleiotropic paralog of the ancient CPR RR-2 CP gene family. The less abundant yet most likely even more lens-specific TcasCP63 is a member of a sprawling family of noncanonical CP genes, documenting a role of local gene family expansions in the emergence of the Tribolium compound eye CP repertoire. Comparisons with Drosophila and the mosquito Anopheles gambiae reveal a steady turnover of lens-enriched CP genes during insect evolution.
Reconceptualizing Stigmas in Aged Care: A Typology of Stigmatizing Discourses in the Aged-Care Context
Authors: Manchha Asmita V , Tann Ken , Way Kïrsten A , Thai Michael
Published: December 2022

Background and Objectives

Stigmatizing discourses surrounding aged care is complex. The stigma associated with people working in aged care is often conflated with negative evaluations about older adults who receive care and/or the institutions and systems that provide these services. This lack of nuance hampers productive dialogue in gerontology required for making sense of the stigmas attached to entities and systems. We propose that an interdisciplinary approach drawing on gerontology, psychology, and linguistics would facilitate a greater understanding of the stigma of aged care. Specifically, a discourse approach underpinned by Stigma Theory and Systemic Functional Linguistics can clarify the different stigmatizing discourses associated with aged-care entities and systems, and inform priorities for interventions targeting each discourse category identified.

Research Design and Methods

APPRAISAL, a linguistics framework, was employed to analyze evaluative language in 660 submissions published in the Australian Royal Commission into Aged Care. Through applying predefined language-based criteria, we distinguished between multiple stigmatizing discourses that were interrelated but conceptually distinct in terms of attitude types and targets.

Results

Twelve categories of stigmatizing discourses derived from the linguistic analysis established a typology. This typology conceptualized different ways stigma can be meaningfully understood in the aged-care context. By employing this typology, 12 intervention priorities were also identified.

Discussion and Implications

This interdisciplinary approach enabled us to examine the diversity and complexity of the social construction of stigma in the public domain. We argue that understanding these linguistic patterns can assist with designing targeted aged-care interventions and policies.
Evaluating Changes in Surgical Outcomes for Patients With Inflammatory Bowel Disease Following Medicaid Expansion
Authors: Tong Jason K C , Mascuilli Tory , Wirtalla Christopher , Aarons Cary B , Saur Nicole M , Mahmoud Najjia N , Karakousis Giorgos C , Kelz Rachel R
Published: December 2022

Background

Little is known about the impact of Medicaid expansion on the surgical care of inflammatory bowel disease. We sought to determine whether Medicaid expansion is associated with improved postsurgical outcomes for patients with inflammatory bowel disease undergoing a colorectal resection.

Methods

We performed a risk-adjusted difference-in-difference study examining postsurgical outcomes for patients ages 26 to 64 with Crohn’s disease or ulcerative colitis undergoing a colorectal resection across 15 states that did and did not expand Medicaid before (2012-2013) and after (2016-2018) policy reform. Primary study outcomes included 30-day readmission and postoperative complication.

Results

Study population included 11 394 patients with inflammatory bowel disease that underwent a colorectal resection. States that underwent Medicaid expansion were associated with a rise in Medicaid enrollment following policy reform (11.8% pre-Medicaid expansion vs 19.7% post-Medicaid expansion). Difference-in-difference analysis revealed a statistically significant lower odds of 30-day readmission in patients undergoing a colorectal resection in expansion states following policy reform relative to patients in nonexpansion states prior to reform (odds ratio, 0.56; 95% confidence interval, 0.36-0.86). No changes in odds of postoperative complication were noted across expansion and nonexpansion states.

Conclusions

Medicaid expansion is associated with a rise in Medicaid enrollment in expansion states following policy reform. There were greater improvements in postoperative outcomes associated with patients in expansion states following policy reform relative to patients in nonexpansion states prior to reform, which may have been related to improved perioperative care and medical management.