bluuebunny/crossref_metadata_2025 huggingface dataset:
A dialogue-like cell communication mechanism is conserved in filamentous ascomycete fungi and mediates interspecies interactions
Authors: Haj Hammadeh Hamzeh , Serrano Antonio , Wernet Valentin , Stomberg Natascha , Hellmeier Davina , Weichert Martin , Brandt Ulrike , Sieg Bianca , Kanofsky Konstantin , Hehl Reinhard , Fischer Reinhard , Fleißner André
Published: March 2022

Significance

This study reveals that a dialogue-like communication mechanism, which mediates cell–cell fusion in filamentous fungi, is a conserved complex trait. It allows the communication and behavioral coordination of cells of distantly related species and mediates their mutual attraction and subsequent physical contact, although interspecies fusion does not occur. Through the activation of this signaling machinery, one species can reprogram the developmental program of the other fungus. These data promote our understanding of microbial communication, illustrate the mechanism of repurposing of existing building blocks in cellular evolution, revive the hypothesis of vegetative fusion as an avenue of horizontal gene transfer in fungi, and establish the idea of developmental reprogramming as a tool for controlling fungi.
Correlation between structure and function in phosphatidylinositol lipid–dependent Kir2.2 gating
Authors: Zhang Yuxi , Tao Xiao , MacKinnon Roderick
Published: March 2022

Significance

Phosphatidylinositol 4,5-bisphosphate (PI(4,5)P
2
) levels regulate cell membrane voltage by gluing two halves of a K
+
channel together and opening the pore. PI(4)P competes with this process. Because both of these lipids are relatively abundant in the plasma membrane and are directly interconvertible through the action of specific enzymes, they may function together to regulate channel activity.
Mitotic spindle formation in the absence of Polo kinase
Authors: Kim Juyoung , Goshima Gohta
Published: March 2022

Significance

Mitosis is an essential process in all eukaryotes, but paradoxically, genes required for mitosis vary among species. The essentiality of many mitotic genes was bypassed by activating alternative mechanisms during evolution. However, bypass events have rarely been recapitulated experimentally. Here, using the fission yeastSchizosaccharomyces pombe, the essentiality of a kinase (Plo1) required for bipolar spindle formation was bypassed by other mutations, many of which are associated with glucose metabolism. The Plo1 bypass by the reduction in glucose uptake was dependent on another kinase (casein kinase I), which potentiated spindle microtubule formation. This study illustrates a rare experimental bypass of essentiality for mitotic genes and provides insights into the molecular diversity of mitosis.
Rapid seafloor changes associated with the degradation of Arctic submarine permafrost
Authors: Paull Charles K. , Dallimore Scott R. , Jin Young Keun , Caress David W. , Lundsten Eve , Gwiazda Roberto , Anderson Krystle , Hughes Clarke John , Youngblut Scott , Melling Humfrey
Published: March 2022

Significance

Temperature increases in Arctic regions have focused attention on permafrost degradation on land, whereas little is known about the dynamics of extensive glacial-age permafrost bodies now submerged under the vast Arctic Continental shelves. Repeated high-resolution bathymetric surveys show that extraordinarily rapid morphologic changes are occurring at the edge of the continental slope of the Canadian Beaufort Sea along what was once the seaward limit of relict Pleistocene permafrost. How widespread similar changes are on the Arctic shelves is unknown, as this is one of the first areas in the Arctic subjected to multiple multibeam bathymetric surveys. Rapid morphologic changes associated with active submarine permafrost thawing may be an important process in sculpturing the seafloor in other submarine permafrost settings.
Injury-induced inflammatory signaling and hematopoiesis in
Drosophila
Authors: Evans Cory J. , Liu Ting , Girard Juliet R. , Banerjee Utpal
Published: March 2022

Significance

We explore mechanisms by which stress caused by acute injury affects blood cell development and inflammatory response in
Drosophila
. Similar to their mammalian myeloid counterparts, these cells are predisposed to sense and react to sterile injury at distant sites. Upon sterile injury, a breach of epidermis sets up a reactive oxygen species-based signal that bypasses the pathogen-sensing apparatus of septic immune challenge, but merges downstream to activate Toll. A number of autonomous and nonautonomous signaling pathways follow in a sequence and are mapped temporally by the appearance of their corresponding molecular phenotypes. A cell-type that fights deposited parasitic wasp eggs appears with sterile injury without the immune challenge, perhaps in anticipation, because in nature injury is usually followed by infection.
Activation of the UPR sensor ATF6α is regulated by its redox-dependent dimerization and ER retention by ERp18
Authors: Oka Ojore Benedict Valentine , Pierre Arvin Shedrach , Pringle Marie Anne , Tungkum Wanida , Cao Zhenbo , Fleming Bethany , Bulleid Neil John
Published: March 2022

Significance

Membrane and secretory proteins are synthesized in the endoplasmic reticulum (ER). Perturbations to ER function disrupts protein folding, causing misfolded proteins to accumulate, a condition known as ER stress. Cells adapt to stress by activating the unfolded protein response (UPR), which ultimately restores proteostasis. A key player in the UPR response is ATF6α, which requires release from ER retention and modulation of its redox status during activation. Here, we report that ER stress promotes formation of a specific ATF6α dimer, which is preferentially trafficked to the Golgi for processing. We show that ERp18 regulates ATF6α by mitigating its dimerization and trafficking to the Golgi and identify redox-dependent oligomerization of ATF6α as a key mechanism regulating its function during the UPR.
A recombinant VSV-vectored vaccine rapidly protects nonhuman primates against lethal Nipah virus disease
Authors: Foster Stephanie L. , Woolsey Courtney , Borisevich Viktoriya , Agans Krystle N. , Prasad Abhishek N. , Deer Daniel J. , Geisbert Joan B. , Dobias Natalie S. , Fenton Karla A. , Cross Robert W. , Geisbert Thomas W.
Published: March 2022

Significance

Concern has increased about the pandemic potential of Nipah virus (NiV). Similar to SARS-CoV-2, NiV is an RNA virus that is transmitted by respiratory droplets. There are currently no NiV vaccines licensed for human use. While several preventive vaccines have shown promise in protecting animals against lethal NiV disease, most studies have assessed protection 1 mo after vaccination. However, in order to contain and control outbreaks, vaccines that can rapidly confer protection in days rather than months are needed. Here, we show that a recombinant vesicular stomatitis virus vector expressing the NiV glycoprotein can completely protect monkeys vaccinated 7 d prior to NiV exposure and 67% of animals vaccinated 3 d before NiV challenge.
Skin effect as a probe of transport regimes in Weyl semimetals
Authors: Matus Paweł , Dantas Renato M. A. , Moessner Roderich , Surówka Piotr
Published: March 2022

Significance

Weyl semimetals are a class of three-dimensional materials, whose low-energy excitations mimic massless fermions. In consequence they exhibit various unusual transport properties related to the presence of chiral anomalies, a subtle quantum phenomenon that denotes the breaking of the classical chiral symmetry by quantum fluctuations. In this work we present a universal description of transport in weakly disordered Weyl semimetals with several scattering mechanisms taken into account. Our work predicts the existence of a new anomaly-induced transport regime in these materials and gives a crisp experimental signature of a chiral anomaly in optical conductivity measurements. Finally, by also capturing the hydrodynamic regime of quasiparticles, our construction bridges the gap between developments in electronic fluid mechanics and three-dimensional semimetals.
Sprayed water microdroplets containing dissolved pyridine spontaneously generate pyridyl anions
Authors: Zhao Lingling , Song Xiaowei , Gong Chu , Zhang Dongmei , Wang Ruijing , Zare Richard N. , Zhang Xinxing
Published: March 2022

Significance

Water microdroplets can accelerate chemical reactions by orders of magnitude compared to the same reactions in bulk water and/or trigger spontaneous reactions that do not occur in bulk solution. Among the properties of water microdroplets, the unique redox ability resulting from the spontaneous dissociation of OH
−
into a released electron and •OH at the air–water interfaces is especially intriguing. At the air–water interface, OH
−
exhibits a strong reducing potential, and the resulting •OH is highly oxidative, making water microdroplets a unity of opposites. We report the reduction of pyridine into pyridyl anions (C
5
H
5
N
−
) and the oxidation of pyridine into hydroxypyridine, which extends what we know about the redox power of water microdroplets.
The X-word
Authors: Morse Ainsley
Published: March 2022

This article describes changes in the use of profanity in contemporary Russian poetry and its implications for translation into English. While Russian poetry now more closely resembles English-language poetry in embracing the profanity typical of conversational speech, the highly taboo nature of Russian profanity is still relevant, including gender-specific taboos. Using examples from a range of female and male poets from the 2000s and 2010s (including Dina Gatina, Elena Fanailova, Dmitri Prigov, Andrei Rodionov, Alexander Skidan, Oksana Vasyakina, Lida Yusupova and others), the article explores the ambivalent status of profane language today, whereby the same phrase for different speakers can be considered entirely unremarkable or profoundly taboo. In addition to the exigencies of poetic form, this is the most relevant factor (and vexing problem) for Russian-to-English translation. Special attention is also paid to specifically queer uses of profanity, with the suggestion that profanity is perhaps best translated in a maximally expressive sociolect-specific way.
Solidification cracking test of aluminium alloy 5052
Authors: Soysal Tayfun , Kou Sindo
Published: March 2022

The recently developed transverse-motion weldability (TMW) test, in which a motor pushes the lower sheet in lap welding at velocity V to induce solidification cracking, has been applied to the 2000-, 6000- and 7000-series Al alloys but not the 5000-series. Here, alloy 5052 was TMW-tested under essentially identical conditions including the motor torque that caused the pushing force on the lower sheet. Surprisingly, the fracture surface of the fusion zone was flat instead of dendritic as expected from solidification cracking. When the torque was set at lower levels, a higher V was required to cause cracking, but the fracture surface became dendritic. The torque effect on cracking in alloy 5052 was discussed, and alloy 2219 was also tested for comparison.
Allo-reactive tissue-resident T cells causing damage: An inside job
Authors: van Lier René A.W. , Hombrink Pleun
Published: March 2022

Tissue-resident memory T cells (TRM cells) reside in the epithelium and contribute to the first line defense against invading pathogens. Snyder et al. (2022. J. Exp. Med.https://doi.org/10.1084/jem.20212059) now report that clonally expanded, recipient T cells persist as TRM cells in human lung allografts despite intensive immunosuppression. Their persistence may contribute to chronic allograft dysfunction.
Interfacial adhesion assessment of SiN/GaAs film/substrate system using microcantilever bending technique
Authors: Lin Weikang , Zhao Yitian , Wang Feng , Huang Han , Lu Mingyuan
Published: March 2022

In this study, a microcantilever bending technique was applied to evaluate the interfacial adhesion of a silicon nitride (SiN) film on a gallium arsenide (GaAs) substrate. Miniaturised cantilevers in micrometre scale were machined on the SiN/GaAs cross-section using focused ion beam milling. Subsequent bending tests was performed on a nanomechanical testing system. Static and cyclic loadings were applied to bend the cantilevers until they fractured. All cantilevers failed at the SiN/GaAs interface. A finite element analysis (FEA) model was used to simulate the deflection of the cantilevers and the stress state at the locus of failure was analysed. Interfacial fracture strength σ
in was derived from the FEA model. The mean values of σ
in from the static and cyclic loading tests were 0.8 ± 0.2 and 0.5 ± 0.1 GPa, respectively. An energy balance analysis was then used to evaluate an interfacial toughness of G
in = 0.18 ± 0.05 J m−2.
Effect of residual strain on magnetic properties and Hall effect in chiral antiferromagnet Mn3Sn
Authors: Deng J J , Zhao M Y , Wang Y , Wu X , Niu X T , Ma L , Zhao D W , Zhen C M , Hou D L
Published: March 2022

Here, the effect of residual strain (RS) generated by uniaxial stress on the magnetic properties and Hall effect of polycrystalline Mn3Sn is investigated. Contrary to the role of pressure in Mn3Sn, both Hall measurements and our theoretically calculated kagome lattice distortions suggest that RS is beneficial for suppressing the magnetic transition from an inverse triangular antiferromagnetic (AFM) state to a helical AFM state. Furthermore, the topological Hall effect (THE) is observed in Mn3Sn over the entire temperature range from 5 K to 400 K due to RS. Combined with the magnetic measurements, we speculate that the THE originates from a RS-induced non-coplanar AFM structure. Our findings point out a method to realize a chiral non-coplanar AFM structure through strain engineering, thereby providing a path for the construction of topological antiferromagnets.
Integrity monitoring for kinematic precise point positioning in open-sky environments with improved computational performance
Authors: El-Mowafy Ahmed , Wang Kan
Published: March 2022

Positioning integrity monitoring (IM) is essential for liability- and safety-critical land applications such as road transport. IM methods such as solution separation apply multiple filters, which necessitates the use of computationally efficient algorithms in real-time applications. In this contribution, a new approach that significantly improves the computation time of the measurement update of the Kalman filter is presented, where only one matrix inversion is applied for all filters with measurement subsets. The fault detection and identification method and computation of the protection levels (PLs) are discussed. The computational improvement comes at the expense of a small increase in the PL. Test results for precise point positioning (PPP) with float ambiguities in an open-sky and suburban environment demonstrate the reduced computation time using the proposed approach compared to the traditional method, with 23%–42% improvement. The availability of IM for PPP, i.e. when the PL is less than a selected alert limit of 1.625 m, ranged between 92% and 99%, depending on the allowable integrity risk, tested at 10−5 and 10−6, and the observation environment.
Multi FBG sensor-based impact localization with a hybrid correlation interpolation method
Authors: Du Liangya , Jiang Wensong , Luo Zai , Song Hao , Yang Li , Li Hongyang
Published: March 2022

To locate the impact source of a composite material structure with a series of fiber Bragg grating (FBG) sensors, a hybrid correlation interpolation method is proposed, in this paper, based on a weighted correlation analysis and a unidirectional cubic spline interpolation. First, the signals collected by FBG sensors are preprocessed on the frequency domain to reduce noise interference. Second, the impact similarity map is built by using the weighted cross-correlation value to estimate the location of the impact roughly. Third, the similarity map is further subdivided by the unidirectional cubic spline interpolation to increase the impact localization. Fourth, the FBG sensor network is experimental analyzed to optimize the layout and the structure of the FBG sensor network. The validity of the multi FBG sensor-based impact localization method is verified on a carbon fiber composite plate with a size of 650 × 500 (mm). The experimental result shows that the mean absolute error is 9.74 mm for our suggested method and 15.51 mm for the bicubic polynomial interpolation (BPI) algorithm, which is reduced by 5.77 mm. The maximum errors are 36.40 mm for the BPI algorithm while are reduced to 21.55 mm for our suggested method. Furthermore, the effect of FBG sensor combination layout and number on impact location accuracy is analyzed and compared. It shows that the sensor network layout of rectangular structure using four FBG sensors is a better choice after the comprehensive consideration of economic benefits, localization accuracy, and error rate.
H-SegNet: hybrid segmentation network for lung segmentation in chest radiographs using mask region-based convolutional neural network and adaptive closed polyline searching method
Authors: Peng Tao , Wang Caishan , Zhang You , Wang Jing
Published: March 2022

Chest x-ray (CXR) is one of the most commonly used imaging techniques for the detection and diagnosis of pulmonary diseases. One critical component in many computer-aided systems, for either detection or diagnosis in digital CXR, is the accurate segmentation of the lung. Due to low-intensity contrast around lung boundary and large inter-subject variance, it has been challenging to segment lung from structural CXR images accurately. In this work, we propose an automatic Hybrid Segmentation Network (H-SegNet) for lung segmentation on CXR. The proposed H-SegNet consists of two key steps: (1) an image preprocessing step based on a deep learning model to automatically extract coarse lung contours; (2) a refinement step to fine-tune the coarse segmentation results based on an improved principal curve-based method coupled with an improved machine learning method. Experimental results on several public datasets show that the proposed method achieves superior segmentation results in lung CXRs, compared with several state-of-the-art methods.
Evaluation of continuous fiber Bragg grating and signal processing method for hotspot detection at cryogenic temperatures
Authors: Fisser Maximilian , Huang Xiyong , Moseley Dominic A , Bumby Chris , Badcock Rodney A
Published: March 2022

The recent adoption of high-T
c superconductor (HTS) wires for ultra-high field magnet windings provide great promise for future applications, such as high-power generators and Tokamak fusion reactors. However, an open issue with the use of HTS is the challenge of rapidly detecting a hot spot which could lead to a quench. Optical fiber sensors have been shown to be promising alternatives to the voltage-based quench detection method. In this paper, we report on ultra-long fiber Bragg gratings (ULFBG) for hotspot detection at cryogenic temperatures using a new detection algorithm. This novel sensing system is suitable for applications in which solely the occurrence of a hotspot but not its precise location is of importance. This is the case e.g. for quench detection in HTS. The developed system provides the advantages of cost reduction and faster response time compared to conventional FBGs with wavelength-division multiplexing and continuous FBGs with time-division multiplexing, respectively. We demonstrate the functionality of the system for the ULFBG with a grating length of 100 mm and 500 mm at 77 K and 90 K respectively. The ULFBG is shown to respond as fast as conventional FBG, to a hot spot as small as 1 K temperature rise. Furthermore, using the proposed signal processing algorithm, ULFBG exhibits much higher signal to noise ratio than that from the conventional FBG. It is believed that artificial intelligence based technique can assist the signal processing algorithm in detecting a small hot spot more rapidly from the big spectral data in real-time.
Gravitational waves from the vacuum decay with LISA *
Authors: Lee Bum-Hoon , Lee Wonwoo , Yeom Dong-han , Yin Lu
Published: March 2022

We investigate the gravitational wave spectrum originating from the cosmological first-order phase transition. We compare two models: one is a scalar field model without gravitation, while the other is a scalar field model with gravitation. Based on the sensitivity curves of the LISA space-based interferometer on the stochastic gravitational-wave background, we compare the difference between the gravitational wave spectra of the former and the latter cases obtained from the bubble collision process. In particular, we numerically calculate the speed of the bubble wall before collision for the two models. We demonstrate that the difference between the amplitudes of these spectra can clearly distinguish between the two models. We expect that the LISA with Signal to Noise Ratio = 10 could observe the spectrum as the fast first-order phase transition.
Toroidal modeling of runaway electron loss due to 3D fields in ITER
Authors: Liu Yueqiang , Aleynikova K. , Paz-Soldan C. , Aleynikov P. , Lukash V. , Khayrutdinov R.
Published: March 2022

Mitigation of runaway electrons (REs) by three-dimensional (3D) magnetic field perturbations is numerically investigated for the ITER 15 MA baseline D–T scenario, utilizing the MARS-F code (Liu et al Phys. Plasmas
7 3681) with a drift orbit test particle tracing module. Considered are two types of 3D fields: the n = 3 (n is the toroidal mode number) resonant magnetic perturbation (RMP) utilized for the purpose of controlling the edge localized modes in ITER, and perturbations generated by the n = 1 magneto-hydrodynamic (MHD) instabilities in a post-disruption plasma. The RMP field, applied to a pre-disruption plasma, is found to be moderately effective in mitigating the RE seeds in ITER when vacuum field model is assumed. Up to ∼40% loss fraction is possible at 90 kA-turn coil current. The mitigation efficiency is however substantially reduced, down to less than 5%, when the plasma response is taken into account. This is due to strong screening of the resonant magnetic field components by the plasma response resulting in much less field line stochasticity. On the other hand, the MARS-F modeling, based on the DINA-simulated post-disruption equilibria, shows that the n = 1 resistive kink instabilities develop in these plasmas, as the edge safety factor q

a
evolves and drops below integer numbers. RE mitigation by these MHD instabilities is sensitive to the eigenmode structure. The best mitigation is achieved as q

a
drops below 3, when a global kink instability occurs that encompasses both internal and external components. This global instability is found to be capable of mitigating over 80% MeV-level passing RE orbits at a field perturbation |δB|/B
0 that is comparable to that observed in DIII-D experiments, and full mitigation if the perturbation amplitude is doubled. The ‘wetted’ area on the ITER limiting surface, due to MHD instability induced RE loss, generally increases with the perturbation amplitude (together with increasing loss fraction). At the highest perturbation level assumed in this study, the wetted area reaches ∼60% of the total limiting surface area. The lost RE orbits mainly strike the outer divertor region of the limiting surface, with some fraction also hitting a wide area along the inboard side of the surface.
Multivariate generating functions for information spread on multi-type random graphs
Authors: Oz Yaron , Rubinstein Ittai , Safra Muli
Published: March 2022

We study the spread of information on multi-type directed random graphs. In such graphs the vertices are partitioned into distinct types (communities) that have different transmission rates between themselves and with other types. We construct multivariate generating functions and use multi-type branching processes to derive an equation for the size of the large out-components in multi-type random graphs with a general class of degree distributions. We use our methods to analyse the spread of epidemics and verify the results with population based simulations.
Impact of the Geometric Form of the Building Envelopes on The efficiency of Natural Lighting in the Office Space.
Authors: Bhai Mohammad A Y , Abdelkader M , Neseem A , Mustafa A
Published: March 2022

Envelopes play an important role in Office Buildings.They affect visual comfort for the user Driven by architectural trends and the need to maximize natural light In order to realize required visual comfort conditions. advanced glazing systems, Geometric formation of the outer building envelope proper self- shading properties and control and lighting controls should be studied comprehensively Optimized fenestration system design may improve exploitation of daylight. and it can be controlled to harvest maximum daylight thus reaching the maximum depth naturally illuminated. The paper explains the design relationship between both configuration of office space and between the system of the glazing and the transmission of natural light inside the space, in terms of the design characteristics of the office space (proportions, dimensions), in order to achieve visual comfort to improve the efficiency of the environmental performance of Office Buildings. This paper discusses the study of the environmental effects of the glazing façades of office buildings and their impact on the efficiency of natural lighting and visual comfort. The paper relies on simulation using, the Grasshopper program, in analyzing of the building’s Envelopes and its external elements and the architectural space, in order to find the proper form for improving visual performance.
The Influence of Using Responsive Façade as a Tool for Improving the Built Environment: Case study: Attaba – Opera square
Authors: Eltanboly M F , Afify M M
Published: March 2022

The path we are currently following to improve the physics of construction due to the destruction of our environment through the negative impact of the built environment around us. Current efforts to decrease carbon and energy are noted by modifying and improving modern “layered” envelopes and improving a misunderstanding of thermal comfort that has become much less effective than expected. Understanding construction physics is an important factor in improving the quality of life indoor and outdoor, relying primarily on theoretical and computational aspects, then applying the practical part to reduce excessive use of carbon and energy and hinder the elaboration of a sustainable and built environment. This paper shows how the problem stems from neglecting to think about the first principles and basic construction physics. Similarly, we show how combining good construction physics with reassessing old methodologies to construction and structure use provides some powerful and effective tools to address the climate emergency. The use of construction physics methods supports the search for new solutions to express the most important factors affecting thermal conduction and minimum surface temperatures. However, buildings have integrated concepts in which advanced systems work together to optimize energy, comfort, and health performance. Convergence between various engineering fields and the overlapping field of construction techniques and services has great potential in the future to achieve the next step in energy saving. As a result, the research highlights new methods that make our buildings interact with the external environment using climate data, responsive envelope design, simulation software, thereby achieving architectural response to surrounding variables, improving building physics to reduce environmental pollution, thermal comfort, and achieving the highest energy efficiency and performance in buildings. This is illustrated by the presentation of a case study of an existing building (Opera Garage Building) – Cairo, it will review solutions to enhance the envelope of the building and its impact on the built environment to come up with some recommendations and solutions which we can apply it on the existing buildings in Egypt.
Large-scale CuS nanotube arrays@graphdiyne for high-performance sodium ion battery
Authors: Zhai Xiangang , Zuo Zicheng , Xiong Zecheng , Pan Houhe , Gao Xiaoya , Li Yuliang
Published: March 2022

Copper sulfide (CuS) is emerged as a promising electrode material for Na-ion batteries due to its high theoretical specific capacity, environmental friendliness and abundant resource. However, the conversion type mechanism for storing the Na+ causes huge volume variations, irreversible phase changes and disintegration of the structure during charge and discharge processes. These intractable issues lead to the fast capacity degradation, and sluggish reaction kinetics, and performances are hard to fulfill the criteria in practical applications. Herein, the large-scale free-standing CuS nanotube arrays sandwiched by successive graphdiyne (GDY) nanofilm are readily prepared using a simple and efficient strategy. The in-situ protection of GDY nanofilm successfully enhances the structural stability and the network conductivity of the free-standing electrode. The as-obtained CuS electrode protected by GDY exhibits excellent electrochemical sodium storage capability, in the term of long-term reversibility (After 1000 cycles at 2 C, the capacity retention is 78.7%.) and rate performance.
Impact of modifiable healthy lifestyle adoption on lifetime gain from middle to older age
Authors: Sakaniwa Ryoto , Noguchi Midori , Imano Hironori , Shirai Kokoro , Tamakoshi Akiko , Iso Hiroyasu ,   The JACC Study Group
Published: March 2022

Objective

this study explored whether the modification of selected lifestyles is likely to increase life expectancy from middle age onwards, regardless of the presence of major comorbidities.

Methods

we examined a prospective cohort of 20,373 men and 26,247 women aged 40–80 years. Eight modifiable lifestyle factors were assessed: consumption of fruit, fish and milk, walking and/or sports participation, body-mass index, smoking status, alcohol consumption and sleep duration. Modifiable healthy lifestyle factors scored one point each, for a maximum of eight points. The impact of modifiable healthy lifestyle adoption on lifetime gain during the ages of 40–102 years was analysed.

Findings

during the median 21 years of follow-up, 8,966 individuals (3,683 men and 5,283 women) died. Life expectancy at 40 years (95% confidence intervals) for 7–8 health lifestyle points was 46.8 (45.6–48.1) and 51.3 (50.0–52.6) years for men and women, respectively. The potential impact of modifiable healthy lifestyle adoption on lifetime gain persisted over the age of 80 years or more, in individuals with ≥5 factors (P < 0.001), particularly older men. The benefits were more pronounced among patients with major comorbidities, such as cardiovascular disease, cancer, hypertension, diabetes, kidney disease and those with multimorbidity throughout all age categories.

Conclusion

adopting modifiable healthy lifestyles was associated with lifetime gain, even in individuals aged 80 years or more, regardless of the presence of any major comorbidities in each life stage since middle age. The findings imply the importance of improving the one’s lifestyle for an increased lifespan, even among older patients and/or those with multimorbidity.
Casting New Light on Statistical Power: An Illuminating Analogy and Strategies to Avoid Underpowered Trials
Authors: Kiernan Michaela , Baiocchi Michael T
Published: March 2022

Current standards for methodological rigor and trial reporting underscore the critical issue of statistical power. Still, the chance of detecting most effects reported in randomized controlled trials in medicine and other disciplines is currently lower than winning a toss of a fair coin. Here we propose that investigators who retain a practical understanding of how statistical power works can proactively avoid the potentially devastating consequences of underpowered trials. We first offer a vivid, carefully constructed analogy that illuminates the underlying relationships among 3 of the 5 essential parameters—namely, statistical power, effect size, and sample size—while holding the remaining 2 parameters constant (type of statistical test and significance level). Second, we extend the analogy to a set of critical scenarios in which investigators commonly miss detecting intervention effects due to insufficient statistical power. Third, we highlight effective pragmatic strategies for the design and conduct of sufficiently powered trials, without increasing sample size.
Perfluoroalkyl Substances and Incident Natural Menopause in Midlife Women: The Mediating Role of Sex Hormones
Authors: Ding Ning , Harlow Siobán D , Randolph John F , Mukherjee Bhramar , Batterman Stuart , Gold Ellen B , Park Sung Kyun
Published: March 2022

Perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been associated with earlier natural menopause; however, the underlying mechanisms are not well understood, particularly the extent to which this relationship is mediated by sex hormones. We analyzed data (1999–2017) on 1,120 premenopausal women from the Study of Women’s Health Across the Nation (SWAN). Causal mediation analysis was applied to quantify the degree to which follicle-stimulating hormone (FSH) and estradiol levels could mediate the associations between PFAS and incident natural menopause. Participants with higher PFAS concentrations had shorter times to natural menopause, with a relative survival of 0.82 (95% confidence interval (CI): 0.69, 0.96) for linear perfluorooctane sulfonate (n-PFOS), 0.84 (95% CI: 0.69, 1.00) for sum of branched-chain perfluorooctane sulfonate (Sm-PFOS), 0.79 (95% CI: 0.66, 0.93) for linear-chain perfluorooctanoate (n-PFOA), and 0.84 (95% CI: 0.71, 0.97) for perfluorononanoate (PFNA), comparing the highest tertile of PFAS concentrations with the lowest. The proportion of the effect mediated through FSH was 8.5% (95% CI: −11.7, 24.0) for n-PFOS, 13.2% (95% CI: 0.0, 24.5) for Sm-PFOS, 26.9% (95% CI: 15.6, 38.4) for n-PFOA, and 21.7% (6.8, 37.0) for PFNA. No significant mediation by estradiol was observed. The effect of PFAS on natural menopause may be partially explained by variations in FSH concentrations.
Self-association status-dependent inactivation of the endoplasmic reticulum stress sensor Ire1 by C-terminal tagging with artificial peptides
Authors: Ishiwata-Kimata Yuki , Hata Tatsuya , Kimata Yukio
Published: March 2022

Upon endoplasmic reticulum (ER) stress, eukaryotic cells commonly induce unfolded protein response (UPR), which is triggered, at least partly, by the ER stress sensor Ire1. Upon ER stress, Ire1 is dimerized or forms oligomeric clusters, resulting in the activation of Ire1 as an endoribonuclease. In ER-stressed Saccharomyces cerevisiae cells, HAC1 mRNA is spliced by Ire1 and then translated into a transcription factor that promotes the UPR. Herein, we report that Ire1 tagged artificially with irrelevant peptides at the C terminus is almost completely inactive when only dimerized, while it induced the UPR as well as untagged Ire1 when clustered. This finding suggests a fundamental difference between the dimeric and clustered forms of Ire1. By comparing UPR levels in S. cerevisiae cells carrying artificially peptide-tagged Ire1 to that in cells carrying untagged Ire1, we estimated the self-association status of Ire1 under various ER stress conditions.
Prediction and early biomarkers of cognitive decline in Parkinson disease and atypical parkinsonism: a population-based study
Authors: Bäckström David , Granåsen Gabriel , Mo Susanna Jakobson , Riklund Katrine , Trupp Miles , Zetterberg Henrik , Blennow Kaj , Forsgren Lars , Domellöf Magdalena Eriksson
Published: March 2022

The progression of cognitive decline is heterogeneous in the three most common idiopathic parkinsonian diseases: Parkinson disease, multiple system atrophy and progressive supranuclear palsy. The causes for this heterogeneity are not fully understood, and there are no validated biomarkers that can accurately identify patients who will develop dementia and when. In this population-based, prospective study, comprehensive neuropsychological testing was performed repeatedly in new-onset, idiopathic parkinsonism. Dementia was diagnosed until 10 years and participants (N = 210) were deeply phenotyped by multimodal clinical, biochemical, genetic and brain imaging measures. At baseline, before the start of dopaminergic treatment, mild cognitive impairment was prevalent in 43.4% of the patients with Parkinson disease, 23.1% of the patients with multiple system atrophy and 77.8% of the patients with progressive supranuclear palsy. Longitudinally, all three diseases had a higher incidence of cognitive decline compared with healthy controls, but the types and severity of cognitive dysfunctions differed. In Parkinson disease, psychomotor speed and attention showed signs of improvement after dopaminergic treatment, while no such improvement was seen in other diseases. The 10-year cumulative probability of dementia was 54% in Parkinson disease and 71% in progressive supranuclear palsy, while there were no cases of dementia in multiple system atrophy. An easy-to-use, multivariable model that predicts the risk of dementia in Parkinson disease within 10 years with high accuracy (area under the curve: 0.86, P < 0.001) was developed. The optimized model adds CSF biomarkers to four easily measurable clinical features at baseline (mild cognitive impairment, olfactory function, motor disease severity and age). The model demonstrates a highly variable but predictable risk of dementia in Parkinson disease, e.g. a 9% risk within 10 years in a patient with normal cognition and CSF amyloid-β42 in the highest tertile, compared with an 85% risk in a patient with mild cognitive impairment and CSF amyloid-β42 in the lowest tertile. Only small or no associations with cognitive decline were found for factors that could be easily modifiable (such as thyroid dysfunction). Risk factors for cognitive decline in multiple system atrophy and progressive supranuclear palsy included signs of systemic inflammation and eye movement abnormalities. The predictive model has high accuracy in Parkinson disease and might be used for the selection of patients into clinical trials or as an aid to improve the prevention of dementia.
A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282
Authors: Wilkin Timothy , Chen Huichao , Sahasrabuddhe Vikrant , Matining Roy , Mngqibisa Rosie , Chinula Lameck , Mbilizi Yamikani , Magure Tsitsi , Omoz-Oarhe Ayotunde E , Rassool Mohammed , Riviere Cynthia , Bhosale Rhamesh , Godbole Sheela , Naranjo Reena , Coombs Robert , Michelow Pamela , Godfrey Catherine , Firnhaber Cynthia
Published: March 2022

Background

Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes.

Methods

Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion.

Results

In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13).

Conclusions

HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs.

Clinical Trials Registration

NCT01315363.
Clinical Course and Impact of Immune Checkpoint Inhibitor Colitis Resembling Microscopic Colitis
Authors: Fredrick Thomas W , Ramos Guilherme P , Braga Neto Manuel B , Kane Sunanda , Faubion William A , Loftus Edward V , Pardi Darrell S , Pasha Shabana F , Farraye Francis A , Zhang Lizhi , Raffals Laura E
Published: March 2022

Background

Microscopic colitis (MC) is suspected to result from increased immune activity in gut mucosa. Immune checkpoint inhibitors (ICIs) treat cancer by activating the immune system, and further investigation is needed regarding their role in the development of MC.

Methods

A retrospective case series investigated cases of endoscopically and histologically confirmed MC developing after administration of ICIs. Clinical notes and medication administration records were reviewed for demographics, symptom duration, and treatment response.

Results

Nineteen cases of de novo MC were identified, with 95% of cases requiring steroid treatment, 53% presenting with hospitalization, and colitis-related mortality in 1 individual. Symptom onset occurred a median of 160 days after initiation of ICI therapy and 53 days after their most recent dose of therapy. Patients had a median of 125 days of symptoms, and ICI therapy was held in 70% of individuals due for treatment.

Conclusions

MC can develop after ICI administration, and presents with severe symptoms, often requiring hospitalization and steroid treatment. In certain individuals this can require a prolonged treatment course of steroid therapy or immunomodulators. Individuals developing diarrhea after ICI therapy warrant thorough workup including endoscopy and rapid treatment initiation given the disease severity observed in this series.
Transcatheter aortic valve replacement in a patient with critical bicuspid aortic stenosis and cardiogenic shock: case report
Authors: El Tahlawy Walid , Bader Feras , Traina Mahmoud Idris , Edris Ahmad
Published: March 2022

Background

Cardiogenic shock (CS) is associated with significant morbidity and mortality (27–51%). Little is known about the feasibility and safety of emergency transcatheter aortic valve replacement (TAVR) for critical aortic stenosis (AS) in acute myocardial infarction (AMI) with CS.

Case summary

A 57-year-old male with history of tobacco dependence and diabetes mellitus presented with acute posterior ST-segment elevation myocardial infarction and CS. The patient initially underwent successful primary percutaneous intervention to an anomalous circumflex artery coming off the right cusp. It was noted to have advanced CS out of proportion to his coronary anatomy. Echocardiographic assessment noted critical AS. Heart team decided to perform percutaneous aortic balloon valvuloplasty under support of extracorporeal membrane oxygenation. Percutaneous aortic balloon valvuloplasty was performed and was complicated by severe aortic regurgitation (AR). A balloon-expandable transcatheter heart valve was then placed with resolution of AR and stabilization of the patient. Then, the patient was subsequently decannulated within a week then was able to go home after 47 days (32 days intensive care unit). His course was notable for a minor stroke due to initial period of hypotension and CS. He was extubated and remained hospitalized for several weeks participating in rehabilitation. Follow-up echo showed a well-seated and functioning transcatheter heart valve. His left ventricular systolic function improved from 21% to 45%.

Conclusion

Emergency TAVR is feasible and can be performed in a patient with AMI and CS. Early initiation of mechanical support allowed the patient to receive definitive treatment. The multidisciplinary heart team is essential and reflected in the ultimate outcome of our patient.
Sex differences in associations of comorbidities with incident cardiovascular disease: focus on absolute risk
Authors: Dronkers Just , Meems Laura M G , van Veldhuisen Dirk J , Meyer Sven , Kieneker Lyanne M , Gansevoort Ron T , Bakker Stephan J L , Rienstra Michiel , de Boer Rudolf A , Suthahar Navin
Published: March 2022

Aim

To examine sex differences in associations of obesity, type-2 diabetes, hypertension, and atrial fibrillation (AF) with incident cardiovascular disease (CVD), focusing on absolute risk measures.

Methods and results

We included a total of 7994 individuals (mean age 49.1 years; 51.2% women) without prior CVD from the PREVEND (Prevention of Renal and Vascular End-stage Disease) cohort with a median follow-up of 12.5 years. Using Poisson regression, we calculated the increase in absolute as well as relative CVD risk associated with a comorbidity using incidence rate differences (IRD = IRcomorbidity−IRno-comorbidity) and incidence rate ratios (IRR = IRcomorbidity/IRno-comorbidity), respectively. Sex differences were presented as women-to-men differences (WMD = IRDwomen−IRDmen) and women-to-men ratios (WMR = IRRwomen/IRRmen). Absolute CVD risk was lower in women than in men (IRwomen: 6.73 vs. IRmen: 14.58 per 1000 person-years). While increase in absolute CVD risk associated with prevalent hypertension was lower in women than in men [WMD: −6.12, 95% confidence interval: (−9.84 to −2.40), P = 0.001], increase in absolute CVD risk associated with prevalent obesity [WMD: −4.25 (−9.11 to 0.61), P = 0.087], type-2 diabetes [WMD: −1.04 (−14.36 to 12.29), P = 0.879] and AF [WMD: 18.39 (−39.65 to 76.43), P = 0.535] did not significantly differ between the sexes. Using relative risk measures, prevalent hypertension [WMR: 1.49%, 95% confidence interval: (1.12–1.99), P = 0.006], type-2 diabetes [WMR: 1.73 (1.09–2.73), P = 0.019], and AF [WMR: 2.53 (1.12–5.70), P = 0.025] were all associated with higher CVD risk in women than in men.

Conclusion

Increase in absolute risk of developing CVD is higher in hypertensive men than in hypertensive women, but no substantial sex-related differences were observed among individuals with obesity, type-2 diabetes and AF. On a relative risk scale, comorbidities, in general, confer a higher CVD risk in women than in men.
GeneCup: mining PubMed and GWAS catalog for gene–keyword relationships
Authors: Gunturkun Mustafa H , Flashner Efraim , Wang Tengfei , Mulligan Megan K , Williams Robert W , Prins Pjotr , Chen Hao
Published: March 2022

Interpreting and integrating results from omics studies typically requires a comprehensive and time consuming survey of extant literature. GeneCup is a literature mining web service that retrieves sentences containing user-provided gene symbols and keywords from PubMed abstracts. The keywords are organized into an ontology and can be extended to include results from human genome-wide association studies. We provide a drug addiction keyword ontology that contains over 300 keywords as an example. The literature search is conducted by querying the PubMed server using a programming interface, which is followed by retrieving abstracts from a local copy of the PubMed archive. The main results presented to the user are sentences where gene symbol and keywords co-occur. These sentences are presented through an interactive graphical interface or as tables. All results are linked to the original abstract in PubMed. In addition, a convolutional neural network is employed to distinguish sentences describing systemic stress from those describing cellular stress. The automated and comprehensive search strategy provided by GeneCup facilitates the integration of new discoveries from omic studies with existing literature. GeneCup is free and open source software. The source code of GeneCup and the link to a running instance is available at https://github.com/hakangunturkun/GeneCup.