bluuebunny/crossref_metadata_2025 huggingface dataset:
The effect of serum luteinizing hormone on trigger day with a GnRH antagonist protocol in IVF/ICSI treatment
Authors: Hou Yanru , Tian Li , Liu Huixin , Ai Jiajia , Wang Yanbin , Shen Huan
Published: November 2021

Objective

To investigate the effect of serum luteinizing hormone (LH) on trigger day with a Gonadotrophin-releasing hormone (GnRH) antagonist protocol in patients receivingin vitrofertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment for pregnancy outcomes.

Methods

We retrospectively reviewed the medical documents of patients receiving IVF/ICSI with fresh embryo transfers from the Reproductive Medicine Center of Peking University People's Hospital between January 2016 and December 2018.730 patients were included and divided into three groups by their serum LH level determined on trigger day. All patients were categorized into Group A, Group B, and Group C based on LH concentrations <1.0 IU/L, 1.0–5.0 IU/L, and from 5.0 to 10.0 IU/L on trigger day during the cycle, respectively. Comparisons were made between the three groups.

Results

There was a significant difference in implantation rates between Group A and Group C (24.8% versus 40.1%, respectively,P ​< ​0.05). The clinical pregnancy rates (39.3% versus 54.3%, respectively,P ​= ​0.078) and live birth rate (LBR) (32.1% versus 46.5%, respectively,P ​= ​0.116), though the differences were not significant. Multivariate logistic regression analysis showed that the OR of Group C for clinical pregnancy (OR ​= ​1.849,P ​= ​0.040) and for LBR (OR ​= ​1.915,P ​= ​0.034) were significant using Group A as the base level.

Conclusions

Our study has demonstrated that patients with higher serum LH levels (5.0–10.0 IU/L) on trigger day in the GnRH antagonist protocol may confer better clinical outcomes than those with lower LH levels (<1.0 IU/L).
Living in Two Worlds
Authors: Behrend-Rosenfeld Else , Rosenfeld Siegfried , Evans Richard
Published: November 2021

This unique collection of diaries and letters offers a vivid personal account of the experiences of a Jewish couple living parallel lives during the Second World War. While their children left for England just before war broke out, and Siegfried soon followed, Else Behrend was unable to obtain her visa in time, and remained in Germany. This volume includes Else's account of her years of persecution under the Nazi dictatorship, and of her life underground in Berlin, before her eventual daring escape to Switzerland on foot in 1944. Her dramatic story is presented alongside Siegfried's account of his very different experience, living penniless and in isolation in England, as well as some of her letters to her close friend and confidante, Eva. Complemented by QR codes that allow readers to listen to Else's own voice from her 1963 BBC interviews. Published in English for the first time, Living in Two Worlds offers an unforgettable and moving insight into the impact of the Second World War on everyday life.
Transition in an infinite swept-wing boundary layer subject to surface roughness and free-stream turbulence
Authors: De Vincentiis Luca , Henningson Dan S. , Hanifi Ardeshir
Published: November 2021

The instability of an incompressible boundary-layer flow over an infinite swept wing in the presence of disc-type roughness elements and free-stream turbulence (FST) has been investigated by means of direct numerical simulations. Our study corresponds to the experiments by Örlü et al. (Tech. Rep., KTH Royal Institute of Technology, 2021, http://urn.kb.se/resolve?urn=urn:nbn:se:kth:diva-291874). Here, different dimensions of the roughness elements and levels of FST have been considered. The aim of the present work is to investigate the experimentally observed sensitivity of the transition to the FST intensity. In the absence of FST, flow behind the roughness elements with a height above a certain value immediately undergoes transition to turbulence. Impulse–response analyses of the steady flow have been performed to identify the mechanism behind the observed flow instability. For subcritical roughness, the generated wave packet experiences a weak transient growth behind the roughness and then its amplitude decays as it is advected out of the computational domain. In the supercritical case, in which the flow transitions to turbulence, flow as expected exhibits an absolute instability. The presence of FST is found to have a significant impact on the transition behind the roughness, in particular in the case of a subcritical roughness height. For a height corresponding to a roughness Reynolds number

$Re_{hh}=461$

, in the absence of FST the flow reaches a steady laminar state, while a very low FST intensity of

$Tu =0.03\,\%$

causes the appearance of turbulence spots in the wake of the roughness. These randomly generated spots are advected out of the computational domain. For a higher FST level of

$Tu=0.3\,\%$

, a turbulent wake is clearly visible behind the element, similar to that for the globally unstable case. The presented results confirm the experimental observations and explain the mechanisms behind the observed laminar–turbulent transition and its sensitivity to FST.
Instability of a planar fluid interface under a tangential electric field in a stagnation point flow
Authors: Firouznia Mohammadhossein , Miksis Michael J. , Vlahovska Petia M. , Saintillan David
Published: November 2021

The interface between two immiscible fluids can become unstable under the effect of an imposed tangential electric field along with a stagnation point flow. This canonical situation, which arises in a wide range of electrohydrodynamic systems including at the equator of electrified droplets, can result in unstable interface deflections where the perturbed interface gets drawn along the extensional axis of the flow while experiencing strong charge build-up. Here, we present analytical and numerical analyses of the stability of a planar interface separating two immiscible fluid layers subject to a tangential electric field and a stagnation point flow. The interfacial charge dynamics is captured by a conservation equation accounting for Ohmic conduction, advection by the flow and finite charge relaxation. Using this model, we perform a local linear stability analysis in the vicinity of the stagnation point to study the behaviour of the system in terms of the relevant dimensionless groups of the problem. The local theory is complemented with a numerical normal-mode linear stability analysis based on the full system of equations and boundary conditions using the boundary element method. Our analysis demonstrates the subtle interplay of charge convection and conduction in the dynamics of the system, which oppose one another in the dominant unstable eigenmode. Finally, numerical simulations of the full nonlinear problem demonstrate how the coupling of flow and interfacial charge dynamics can give rise to nonlinear phenomena such as tip formation and the growth of charge density shocks.
Approach to the 4/3 law for turbulent pipe and channel flows examined through a reformulated scale-by-scale energy budget
Authors: Zimmerman Spencer J. , Antonia R.A. , Djenidi L. , Philip J. , Klewicki J.C.
Published: November 2021

In this study, we propose a scale-by-scale (SBS) energy budget equation for flows with homogeneity in at least one direction. This SBS budget represents a modified form of the equation first proposed by Danaila et al. (J. Fluid Mech., vol. 430, 2001, pp. 87–109) for the channel centreline – the primary difference is that, here, we consider the role of pressure along with the errors associated with the isotropic approximations of the interscale divergence and Laplacian of the squared velocity increment. The term encompassing the effects of mean shear is also characterised such that the present analysis can be extended straightforwardly to locations away from the centreline. We show, based on a detailed analysis of previously published channel flow direct numerical simulations and pipe flow experiments near the centreline, how several terms in the present SBS budget equation (including the third-order velocity structure function) behave with increasing Reynolds number. The behaviour of these terms is shown to imply a rate of emergence and subsequent growth of the 4/3 law scale subrange at the channel centreline and pipe axis. The analysis also suggests that the peak magnitude of the third-order velocity structure function occurs at a scale that is fixed in proportion to the Taylor microscale at sufficiently high Reynolds number.
Defining performance levels in undergraduate otolaryngology education
Authors: Steven R A , McAleer S , Jones S E , Lloyd S K , Spielmann P M , Eynon-Lewis N , Mires G J
Published: November 2021

Objectives

This study seeks the opinions of qualified doctors on what they feel medical students should learn about otolaryngology. It aims to identify both the content deemed relevant and the performance levels for medical students in otolaryngology.

Methods

A national survey developed from a content analysis of undergraduate otolaryngology curricula from the UK was undertaken, accompanied by a review of the literature and input from an expert group. Data were collected from a wide range of doctors.

Results

Participants felt that graduating students should be able to: recognise, assess and initiate management for common and life-threatening acute conditions; take an appropriate patient history; and perform an appropriate examination for the majority of otolaryngology clinical conditions but manage only a select few.

Conclusion

This study reports performance levels for otolaryngology topics at an undergraduate level. Participating doctors felt that a higher level of performance should be expected of students treating life-threatening, acute and common otolaryngology conditions.
Moving beyond Weiss and Springer’sRepatriation and Erasing the Past:Indigenous values, relationships, and research
Authors: Halcrow Siân , Aranui Amber , Halmhofer Stephanie , Heppner Annalisa , Johnson Norma , Killgrove Kristina , Schug Gwen Robbins
Published: November 2021

This commentary debunks the poor scholarship inRepatriation and Erasing the Pastby Elizabeth Weiss and James Springer. We show that modern bioarchaeological practice with Indigenous remains places ethics, partnership, and collaboration at the fore and that the authors’ misconstructed dichotomous fallacy between “objective science” and Indigenous knowledge and repatriation hinders the very argument they are espousing. We demonstrate that bioarchaeology, when conducted in collaboration with stakeholders, enriches research, with concepts and methodologies brought forward to address common questions, and builds a richer historical and archaeological context. As anthropologists, we need to acknowledge anti-Indigenous (and anti-Black) ideology and the insidious trauma and civil rights violations that have been afflicted and re-afflicted through Indigenous remains being illegally or unethically obtained, curated, transferred, and used for research and teaching in museums and universities. If we could go so far as to say that anything good has come out of this book, it has been the stimulation in countering these beliefs and developing and strengthening ethical approaches and standards in our field.
Quantitative Analysis of Nitrogen by Atom Probe Tomography Using Stoichiometric γ′-Fe4N Consisting of 15N Isotope
Authors: Takahashi Jun , Kawakami Kazuto , Miura Koyo , Hirano Mitsuhiro , Ohtsu Naofumi
Published: November 2021

The nitrogen deficiency in steels measured by atom probe tomography (APT) is considered to arise from the obscurement of singly charged dimer nitrogen ions (N2+) by the iron-dominant peak (56Fe2+) at 28 Da. To verify this by quantifying the amount of N2+ ions, γ′-Fe4N consisting of the 15N isotope was prepared on iron substrates by plasma nitriding using a nitrogen isotopic gas (15N2). Although considerable amounts of 15N2+ were observed at 30 Da without overlap with any iron peak, the observed nitrogen concentrations of γ′-Fe4N were clearly lower than the stoichiometric composition (19–20 at%), using both pulsed voltage and pulsed laser atom probes. The origin of the missing nitrogen, excluding nitrogen obscured by other ion species, was predicted to be the occurrence of neutral nitrogen or nitrogen gas molecules in field evaporation. The generation rate of iron nitride ions (FeN2+) for 15N was significantly lower than that for 14N in γ′-Fe4N, which affected the amount of the missing nitrogen. The isotope effect suggests that the isotopic ratio cannot always be determined from only one ion species among the multiple species observed in the APT analysis. We discuss the mechanism of the isotope effect in FeN2+ formation by field evaporation.
Preliminary evaluation of a culturally adapted CBT-based online programme for depression and anxiety from a lower middle-income country
Authors: Latif Madeeha , Awan Falahat , Gul Mirrat , Husain M. Omair , Husain M. Ishrat , Sayyed Kumail , Magsi Taj , Naz Saiqa , Aylem Ozlem , Phiri Peter , Irfan Muhammad , Ayub Muhammad , Naeem Farooq
Published: November 2021

Online cognitive behaviour therapy (CBT), self-help and guided self-help (GSH) interventions have been found to be efficacious and cost-effective for treatment of anxiety and depression, but there are limited data from low- and middle-income countries on culturally adapted digital interventions for these common mental disorders. The aim of this study was to investigate the feasibility and acceptability of an online culturally adapted CBT-based guided self-help (CaCBT-GSH) for patients with anxiety and depression in Pakistan. This randomized controlled trial recruited 39 participants from primary care in Karachi, Pakistan and randomized them to two groups. The intervention group received seven modules of CaCBT-GSH plus treatment as usual (TAU) over 12 weeks. The control group was a waitlist control plus TAU. The primary outcomes were feasibility and acceptability. Clinical outcomes included results from the Hospital Anxiety and Depression Scale (HADS) and the WHO Disability Assessment Schedule 2 (WHODAS 2). Assessments were carried out at baseline and at 12 weeks. All 39 individuals who met eligibility criteria for the study agreed to participate. Adherence to the intervention was excellent, with 85% (17/20) completing more than five modules. Statistically significant improvements were found in all clinical outcomes in the intervention group. This was the first trial of an online CaCBT-GSH intervention, which was found to be feasible and acceptable to Pakistani patients with anxiety and depression. CaCBT-GSH may help improve symptoms, depression, anxiety and overall functioning in this population. The results provide rationale for a larger, confirmatory randomized controlled trial of digital CaCBT-GSH.

Key learning aims

(1)

Leveraging digital and virtual platforms to deliver psychosocial interventions may contribute to addressing the significant treatment gap in low-resource settings.

(2)

CBT-informed guided self-help is feasible and acceptable in the treatment of common mental disorders in Pakistan.

(3)

The results of this study merit a larger, appropriately powered confirmatory randomized controlled trial to determine clinical and cost effectiveness.
Detecting and Evaluating Dust‐Events in North China With Ground Air Quality Data
Authors: Tong Pei Feng , Chen Song Xi , Tang Cheng Yong
Published: November 2021

We propose a dust‐event detection and tracking procedure based on air quality data from the ground monitoring network by detecting temporal and spatial change‐points in PM10 concentration. It supplements the existing remote sensing based approach with high temporal resolution and better weather adaptivity. Applications of the procedure on the labeled data showed its having high discriminating power for dust events, pollution events, and clean periods. Our study finds changing correlation patterns between PM10 and other air pollutants at the start of the dust events, which are utilized to enhance the discriminating power of the dust‐event detection procedure. The detection and tracking procedure allows the construction of transport networks of the dust‐events as well as the identification of the source regions and the transportation pattern, and assess the intensity and severity of the dust‐events in North China. Our analysis find the dust‐events contributed to 23.3%–34.6% for PM10 and 18.2–33.2% for PM2.5 in the source regions and 2.0%–7.3% and 0.8%–4.0%, respectively, in the down‐stream provinces in the spring season from 2015 to 2020.
Determining Parameters of Whistler Waves Trapped in High‐Density Ducts
Authors: Williams Daniel D. , Streltsov Anatoly V.
Published: November 2021

We investigate the possibility of identifying the perpendicular and parallel wavelengths (or wave numbers) of the very‐low‐frequency (VLF) whistler‐mode waves trapped inside the high‐density duct. This will be done by using information about the wave frequency, background magnetic field, and plasma density inside and outside of the duct. This data is collected from observations by the Van Allen Probes satellites. We developed a three‐step procedure based on the analysis of the whistler wave dispersion relation and numerical simulations of the electron‐magnetohydrodynamics model. We use this model to identify the parallel and perpendicular wave numbers of the “most trapped” wave. The first two steps of this procedure identify the ranges of the parallel and perpendicular wavelengths of the waves trapped inside the duct. The third step uses numerical simulations to determine the parameters of the “most trapped” wave from the aforementioned ranges. This procedure has been applied to the retrieved data from the Van Allen Probes in order to analyze the structure of VLF waves observed in the equatorial magnetosphere.
Quasilinear Model of Jovian Whistler Mode Emission
Authors: Yoon P. H. , Menietti J. D. , Kurth W. S. , Allegrini F. , Bolton S. J.
Published: November 2021

The whistler mode chorus emissions are pervasively detected by the Juno satellite in Jupiter’s magnetospheric environment. This article pays particular attention to a sample observation made by the Juno on 3 November 2019, where typical whistler mode chorus waves are measured. The emission is characterized by a broad range of wave frequencies from below fce/2, where fce denotes the local electron cyclotron frequency, down to the lower‐hybrid frequency, with a gradually downshifting frequency over time. The excitation appears to coincide with the detection of a “butterfly” pitch‐angle distribution and the expected loss‐cone feature associated with the energetic electrons. These anisotropic features, especially the butterfly pitch‐angle distribution, gradually disappear as the waves are excited and the electron phase space distribution becomes isotropic. The aim of this article is to model the characteristics by means of quasilinear kinetic theory of the whistler instability driven by a loss‐cone electron distribution function with a narrow loss‐cone angle, which is to be expected from low‐latitude regions of the Jovian magnetosphere. It is shown that the theoretically constructed dynamic wave spectrum is consistent with the observation made on 3 November 2019. The present finding demonstrates that the quasilinear theory can be a powerful theoretical tool for interpreting various Jovian plasma wave emissions, which includes the whistler waves, but also other wave modes.
Ocean Model Formulation Influences Transient Climate Response
Authors: Semmler Tido , Jungclaus Johann , Danek Christopher , Goessling Helge F. , Koldunov Nikolay V. , Rackow Thomas , Sidorenko Dmitry
Published: November 2021

The transient climate response (TCR) is 20% higher in the Alfred Wegener Institute Climate Model (AWI‐CM) compared to the Max Planck Institute Earth System Model (MPI‐ESM) whereas the equilibrium climate sensitivity (ECS) is by up to 10% higher in AWI‐CM. These results are largely independent of the two considered model resolutions for each model. The two coupled CMIP6 models share the same atmosphere‐land component ECHAM6.3 developed at the Max Planck Institute for Meteorology (MPI‐M). However, ECHAM6.3 is coupled to two different ocean models, namely the MPIOM sea ice‐ocean model developed at MPI‐M and the FESOM sea ice‐ocean model developed at the Alfred Wegener Institute, Helmholtz Centre for Polar and Marine Research (AWI). A reason for the different TCR is related to ocean heat uptake in response to greenhouse gas forcing. Specifically, AWI‐CM simulations show stronger surface heating than MPI‐ESM simulations while the latter accumulate more heat in the deeper ocean. The vertically integrated ocean heat content is increasing slower in AWI‐CM model configurations compared to MPI‐ESM model configurations in the high latitudes. Weaker vertical mixing in AWI‐CM model configurations compared to MPI‐ESM model configurations seems to be key for these differences. The strongest difference in vertical ocean mixing occurs inside the Weddell and Ross Gyres and the northern North Atlantic. Over the North Atlantic, these differences materialize in a lack of a warming hole in AWI‐CM model configurations and the presence of a warming hole in MPI‐ESM model configurations. All these differences occur largely independent of the considered model resolutions.
Multiphase Volatilization of Halogens at the Soil‐Atmosphere Interface on Mars
Authors: Wang Xiyu , Zhao Yu‐Yan Sara , Hood Don R. , Karunatillake Suniti , Laczniak Dara , Schmidt Mariek E. , Vithanage Meththika
Published: November 2021

The Martian critical zone, especially its soil‐atmosphere interface, may host an active halogen cycle affecting habitability, as inferred from halogen trends observed in situ at Gusev and Meridiani, along with oxychlorine species detected in situ. However, the sinks and sources of the Martian halogen cycle remain poorly constrained, especially for Br, including the broader geographic significance of halogen volatility in soils. Here, we statistically analyze Br, Cl, and S distribution and associated cations in the soils of Gale Crater and compare the results with soils of Gusev Crater and Meridiani Planum. We further place the overall in situ soil trends in the framework of terrestrial natural evaporative halides and Mars‐analog evaporative experiments. We observe three lines of evidence that support preferential volatilization of Br versus Cl and S in Martian soils: (a) Unlike Cl and S, Br abundance decreases from subsurface to surface. (b) Br and Cl abundances correlate strongly at the relatively dust‐free and freshly exposed surface of the active Bagnold dunes, but Br‐Cl correlations weaken and Br concentrations decrease in less mobile surface soil. (c) Laboratory experiments show preferential Br loss over Cl and S under ultraviolet (UV) irradiation, consistent with the observed Br loss relative to Cl in Martian soil samples. Overall, these findings generally suggest that soil serves as a source for volatilized halogens. Specifically, soil‐atmosphere multiphase reaction pathways constitute a crucial component missing from purely gas‐phase photochemical models of the halogen cycle.
Machine Learning Mid‐Infrared Spectral Models for Predicting Modal Mineralogy of CI/CM Chondritic Asteroids and Bennu
Authors: Breitenfeld L. B. , Rogers A. D. , Glotch T. D. , Hamilton V. E. , Christensen P. R. , Lauretta D. S. , Gemma M. E. , Howard K. T. , Ebel D. S. , Kim G. , Kling A. M. , Nekvasil H. , DiFrancesco N.
Published: November 2021

Planetary surfaces can be complex mixtures of coarse and fine particles that exhibit linear and nonlinear mixing behaviors at mid‐infrared (MIR) wavelengths. Machine learning multivariate analysis can estimate modal mineralogy of mixtures and is favorable because it does not assume linear mixing across wavelengths. We used partial least squares (PLS) and least absolute shrinkage and selection operator (lasso), two types of machine learning, to build MIR spectral models to determine the surface mineralogy of the asteroid (101955) Bennu using OSIRIS‐REx Thermal Emission Spectrometer (OTES) data. We find that PLS models outperform lasso models. The cross‐validated root‐mean‐square error of our final PLS models (consisting of 317 unique spectra of samples derived from 13 analog mineral samples and eight meteorites) range from ∼4 to 13 vol% depending on the mineral group. PLS predictions in vol% of Bennu's average global composition are 78% phyllosilicate, 9% olivine, 11% carbonates, and 6% magnetite. Pyroxene is not predicted for the global average spectrum, though it has been detected in small amounts on Bennu. These mineral abundances confirm previous findings that the composition of Bennu is consistent with CI/CM chondrites with high degrees of aqueous alteration. The predicted mineralogy of two previously identified OTES spectral types vary minimally from the global average. In agreement with previous work, we interpret OTES spectral differences as primarily caused by relative abundances of fine particulates rather than major compositional variations.
Neoadjuvant PD-1 blockade induces T cell and cDC1 activation but fails to overcome the immunosuppressive tumor associated macrophages in recurrent glioblastoma
Authors: Lee Alexander H. , Sun Lu , Mochizuki Aaron Y. , Reynoso Jeremy G. , Orpilla Joey , Chow Frances , Kienzler Jenny C. , Everson Richard G. , Nathanson David A. , Bensinger Steven J. , Liau Linda M. , Cloughesy Timothy , Hugo Willy , Prins Robert M.
Published: November 2021

Primary brain tumors, such as glioblastoma (GBM), are remarkably resistant to immunotherapy, even though pre-clinical models suggest effectiveness. To understand this better in patients, here we take advantage of our recent neoadjuvant treatment paradigm to map the infiltrating immune cell landscape of GBM and how this is altered following PD-1 checkpoint blockade using high dimensional proteomics, single cell transcriptomics, and quantitative multiplex immunofluorescence. Neoadjuvant PD-1 blockade increases T cell infiltration and the proportion of a progenitor exhausted population of T cells found within the tumor. We identify an early activated and clonally expanded CD8+ T cell cluster whose TCR overlaps with a CD8+ PBMC population. Distinct changes are also observed in conventional type 1 dendritic cells that may facilitate T cell recruitment. Macrophages and monocytes still constitute the majority of infiltrating immune cells, even after anti-PD-1 therapy. Interferon-mediated changes in the myeloid population are consistently observed following PD-1 blockade; these also mediate an increase in chemotactic factors that recruit T cells. However, sustained high expression of T-cell-suppressive checkpoints in these myeloid cells continue to prevent the optimal activation of the tumor infiltrating T cells. Therefore, future immunotherapeutic strategies may need to incorporate the targeting of these cells for clinical benefit.
Fat mass and obesity-associated protein regulates RNA methylation associated with depression-like behavior in mice
Authors: Liu Shu , Xiu Jianbo , Zhu Caiyun , Meng Kexin , Li Chen , Han Rongrong , Du Tingfu , Li Lanlan , Xu Lingdan , Liu Renjie , Zhu Wanwan , Shen Yan , Xu Qi
Published: November 2021

Post-transcriptional modifications of RNA, such as RNA methylation, can epigenetically regulate behavior, for instance learning and memory. However, it is unclear whether RNA methylation plays a critical role in the pathophysiology of major depression disorder (MDD). Here, we report that expression of the fat mass and obesity associated gene (FTO), an RNA demethylase, is downregulated in the hippocampus of patients with MDD and mouse models of depression. Suppressing Fto expression in the mouse hippocampus results in depression-like behaviors in adult mice, whereas overexpression of FTO expression leads to rescue of the depression-like phenotype. Epitranscriptomic profiling of N6-methyladenosine (m6A) RNA methylation in the hippocampus of Fto knockdown (KD), Fto knockout (cKO), and FTO-overexpressing (OE) mice allows us to identify adrenoceptor beta 2 (Adrb2) mRNA as a target of FTO. ADRB2 stimulation rescues the depression-like behaviors in mice and spine loss induced by hippocampal Fto deficiency, possibly via the modulation of hippocampal SIRT1 expression by c-MYC. Our findings suggest that FTO is a regulator of a mechanism underlying depression-like behavior in mice.
Cryo-EM snapshots of a native lysate provide structural insights into a metabolon-embedded transacetylase reaction
Authors: Tüting Christian , Kyrilis Fotis L. , Müller Johannes , Sorokina Marija , Skalidis Ioannis , Hamdi Farzad , Sadian Yashar , Kastritis Panagiotis L.
Published: November 2021

Found across all kingdoms of life, 2-keto acid dehydrogenase complexes possess prominent metabolic roles and form major regulatory sites. Although their component structures are known, their higher-order organization is highly heterogeneous, not only across species or tissues but also even within a single cell. Here, we report a cryo-EM structure of the fully active Chaetomium thermophilum pyruvate dehydrogenase complex (PDHc) core scaffold at 3.85 Å resolution (FSC = 0.143) from native cell extracts. By combining cryo-EM with macromolecular docking and molecular dynamics simulations, we resolve all PDHc core scaffold interfaces and dissect the residing transacetylase reaction. Electrostatics attract the lipoyl domain to the transacetylase active site and stabilize the coenzyme A, while apolar interactions position the lipoate in its binding cleft. Our results have direct implications on the structural determinants of the transacetylase reaction and the role of flexible regions in the context of the overall 10 MDa PDHc metabolon architecture.
Transcriptional responses of skeletal stem/progenitor cells to hindlimb unloading and recovery correlate with localized but not systemic multi-systems impacts
Authors: Booker Cori N. , Haga Christopher L. , Boregowda Siddaraju V. , Strivelli Jacqueline , Phinney Donald G.
Published: November 2021

Disuse osteoporosis (DO) results from mechanical unloading of weight-bearing bones and causes structural changes that compromise skeletal integrity, leading to increased fracture risk. Although bone loss in DO results from imbalances in osteoblast vs. osteoclast activity, its effects on skeletal stem/progenitor cells (SSCs) is indeterminate. We modeled DO in mice by 8 and 14 weeks of hindlimb unloading (HU) or 8 weeks of unloading followed by 8 weeks of recovery (HUR) and monitored impacts on animal physiology and behavior, metabolism, marrow adipose tissue (MAT) volume, bone density and micro-architecture, and bone marrow (BM) leptin and tyrosine hydroxylase (TH) protein expression, and correlated multi-systems impacts of HU and HUR with the transcript profiles of Lin−LEPR+ SSCs and mesenchymal stem cells (MSCs) purified from BM. Using this integrative approach, we demonstrate that prolonged HU induces muscle atrophy, progressive bone loss, and MAT accumulation that paralleled increases in BM but not systemic leptin levels, which remained low in lipodystrophic HU mice. HU also induced SSC quiescence and downregulated bone anabolic and neurogenic pathways, which paralleled increases in BM TH expression, but had minimal impacts on MSCs, indicating a lack of HU memory in culture-expanded populations. Although most impacts of HU were reversed by HUR, trabecular micro-architecture remained compromised and time-resolved changes in the SSC transcriptome identified various signaling pathways implicated in bone formation that were unresponsive to HUR. These findings indicate that HU-induced alterations to the SSC transcriptome that persist after reloading may contribute to poor bone recovery.
The herd-immunity threshold must be updated for multi-vaccine strategies and multiple variants
Authors: Yadegari Iraj , Omidi Mehdi , Smith Stacey R.
Published: November 2021

Several vaccines with different efficacies and effectivenesses are currently being distributed across the world to control the COVID-19 pandemic. Having enough doses from the most efficient vaccines in a short time is not possible for all countries. Hence, policymakers may propose using various combinations of available vaccines to control the pandemic with vaccine-induced herd immunity by vaccinating a fraction of the population. The classic vaccine-induced herd-immunity threshold suggests that we can stop spreading the disease by vaccinating a fraction of the population. However, that classic threshold is defined only for a single vaccine and may be invalid and biased when we have multi-vaccine strategies for a disease or multiple variants, potentially leading policymakers to suboptimal vaccine-allocation policies. Here, we determine which combination of multiple vaccines may lead to herd immunity. We show that simplifying the problem and considering the vaccination of the population as a single-vaccine strategy whose effectiveness is the sample mean of all effectivenesses would not be ideal, because many multi-vaccine strategies with a smaller herd-immunity threshold can be proposed. We show that the herd-immunity threshold may vary due to changes in vaccine-uptake proportions. Moreover, we propose methods to determine the optimal combination of multiple vaccines in order to achieve herd immunity and apply our results to the issue of multiple variants. In addition, we determine a condition for reaching herd immunity in the presence of new emerging variants of concern. We show by example that new variants could influence our estimation of the vaccination reproduction number. It follows that the herd-immunity threshold must be updated not only when multi-vaccine strategies are used but also when multiple variants coexist in the population.
A register-based study comparing planned rehabilitation following acute stroke in 2011 and 2017
Authors: Nylén Malin C. , Persson Hanna C. , Abzhandadze Tamar , Sunnerhagen Katharina S.
Published: November 2021

This cross-sectional, register-based study aimed to explore patterns of planned rehabilitation at discharge from stroke units in Sweden in 2011 and 2017 and identify explanatory variables for planned rehabilitation. Multivariable binary logistic regression was used to identify variables that could explain planned rehabilitation. There were 19,158 patients in 2011 and 16,508 patients in 2017 with stroke, included in the study. In 2011, 57% of patients were planned for some form of rehabilitation at discharge from stroke unit, which increased to 72% in 2017 (p < 0.001). Patients with impaired consciousness at admission had increased odds for planned rehabilitation (hemorrhage 2011 OR 1.43, 95% CI 1.13–1.81, 2017 OR 1.66, 95% CI 1.20–2.32), (IS 2011 OR 1.21, 95% CI 1.08–1.34, 2017 OR 1.49, 95% CI 1.28–1.75). Admission to a community hospital (hemorrhage 2011 OR 0.56, 95% CI 0.43–0.74, 2017 OR 0.39, 95% CI 0.27–0.56) (IS 2011 OR 0.63, 95% CI 0.58–0.69, 2017 OR 0.54, 95% CI 0.49–0.61) or to a specialized non-university hospital (hemorrhage 2017 OR 0.66, 95% CI 0.46–0.94), (IS 2011 OR 0.90, 95% CI 0.82–0.98, 2017 OR 0.76, 95% CI 0.68–0.84) was associated with decreased odds of receiving planned rehabilitation compared to admission to a university hospital. As a conclusion severe stroke was associated with increased odds for planned rehabilitation and patients discharged from non-university hospitals had consistently decreased odds for planned rehabilitation.
The reserve of joint torque determines movement coordination
Authors: Faity Germain , Mottet Denis , Pla Simon , Froger Jérôme
Published: November 2021

Humans coordinate biomechanical degrees of freedom to perform tasks at minimum cost. When reaching a target from a seated position, the trunk-arm-forearm coordination moves the hand to the well-defined spatial goal, while typically minimising hand jerk and trunk motion. However, due to fatigue or stroke, people visibly move the trunk more, and it is unclear what cost can account for this. Here we show that people recruit their trunk when the torque at the shoulder is too close to the maximum. We asked 26 healthy participants to reach a target while seated and we found that the trunk contribution to hand displacement increases from 11 to 27% when an additional load is handled. By flexing and rotating the trunk, participants spontaneously increase the reserve of anti-gravitational torque at the shoulder from 25 to 40% of maximal voluntary torque. Our findings provide hints on how to include the reserve of torque in the cost function of optimal control models of human coordination in healthy fatigued persons or in stroke victims.
Traumatic brain injury in the presence of Aβ pathology affects neuronal survival, glial activation and autophagy
Authors: Streubel-Gallasch Linn , Zyśk Marlena , Beretta Chiara , Erlandsson Anna
Published: November 2021

Traumatic brain injury (TBI) presents a widespread health problem in the elderly population. In addition to the acute injury, epidemiological studies have observed an increased probability and earlier onset of dementias in the elderly following TBI. However, the underlying mechanisms of the connection between TBI and Alzheimer’s disease in the aged brain and potential exacerbating factors is still evolving. The aim of this study was to investigate cellular injury-induced processes in the presence of amyloid β (Aβ) pathology. For this purpose, a co-culture system of cortical stem-cell derived astrocytes, neurons and oligodendrocytes were exposed to Aβ42 protofibrils prior to a mechanically induced scratch injury. Cellular responses, including neurodegeneration, glial activation and autophagy was assessed by immunoblotting, immunocytochemistry, ELISA and transmission electron microscopy. Our results demonstrate that the combined burden of Aβ exposure and experimental TBI causes a decline in the number of neurons, the differential expression of the key astrocytic markers glial fibrillary acidic protein and S100 calcium-binding protein beta, mitochondrial alterations and prevents the upregulation of autophagy. Our study provides valuable information about the impact of TBI sustained in the presence of Aβ deposits and helps to advance the understanding of geriatric TBI on the cellular level.
Faces and words are both associated and dissociated as evidenced by visual problems in dyslexia
Authors: Sigurdardottir Heida Maria , Arnardottir Alexandra , Halldorsdottir Eydis Thuridur
Published: November 2021

Faces and words are traditionally assumed to be independently processed. Dyslexia is also traditionally thought to be a non-visual deficit. Counter to both ideas, face perception deficits in dyslexia have been reported. Others report no such deficits. We sought to resolve this discrepancy. 60 adults participated in the study (24 dyslexic, 36 typical readers). Feature-based processing and configural or global form processing of faces was measured with a face matching task. Opposite laterality effects in these tasks, dependent on left–right orientation of faces, supported that they tapped into separable visual mechanisms. Dyslexic readers tended to be poorer than typical readers at feature-based face matching while no differences were found for global form face matching. We conclude that word and face perception are associated when the latter requires the processing of visual features of a face, while processing the global form of faces apparently shares minimal—if any—resources with visual word processing. The current results indicate that visual word and face processing are both associated and dissociated—but this depends on what visual mechanisms are task-relevant. We suggest that reading deficits could stem from multiple factors, and that one such factor is a problem with feature-based processing of visual objects.
Investigations of proximity-induced superconductivity in the topological insulator Bi2Te3 by microRaman spectroscopy
Authors: Kiphart D. , Harkavyi Y. , Balin K. , Szade J. , Mróz B. , Kuświk P. , Jurga S. , Wiesner M.
Published: November 2021

We used the topological insulator (TI) Bi2Te3 and a high-temperature superconductor (HTSC) hybrid device for investigations of proximity-induced superconductivity (PS) in the TI. Application of the superconductor YBa2Cu3O7-δ (YBCO) enabled us to access higher temperature and energy scales for this phenomenon. The HTSC in the hybrid device exhibits emergence of a pseudogap state for T > Tc that converts into a superconducting state with a reduced gap for T < Tc. The conversion process has been reflected in Raman spectra collected from the TI. Complementary charge transport experiments revealed emergence of the proximity-induced superconducting gap in the TI and the reduced superconducting gap in the HTSC, but no signature of the pseudogap. This allowed us to conclude that Raman spectroscopy reveals formation of the pseudogap state but cannot distinguish the proximity-induced superconducting state in the TI from the superconducting state in the HTSC characterised by the reduced gap. Results of our experiments have shown that Raman spectroscopy is a complementary technique to classic charge transport experiments and is a powerful tool for investigation of the proximity-induced superconductivity in the Bi2Te3.
Megahertz scan rates enabled by optical sampling by repetition-rate tuning
Authors: Bajek D. , Cataluna M. A.
Published: November 2021

We demonstrate, for the first time, optical sampling by repetition-rate tuning (OSBERT) at record megahertz scan rates. A low-cost, tunable and extremely compact 2-section passively mode-locked laser diode (MLLD) is used as the pulsed laser source, whose repetition rate can be modulated electronically through biasing of the saturable absorber section. The pulsed output is split into two arms comparable to an imbalanced Michelson interferometer, where one arm is significantly longer than the other (a passive delay line, or PDL). The resulting electronic detuning of the repetition rate gives rise to a temporal delay between pulse pairs at a detector; the basis for time-resolved spectroscopy. Through impedance-matching, we developed a new system whereby a sinusoidal electrical bias could be applied to the absorber section of the MLLD via a signal generator, whose frequency could be instantly increased from sub-hertz through to megahertz modulation frequencies, corresponding to a ground-breaking megahertz optical sampling scan rate, which was experimentally demonstrated by the real-time acquisition of a cross-correlation trace of two ultrashort optical pulses within just 1 microsecond of real time. This represents scan rates which are three orders of magnitude greater than the recorded demonstrations of OSBERT to date, and paves the way for highly competitive scan rates across the field of time-resolved spectroscopy and applications therein which range from pump probe spectroscopy to metrology.
Observational and genetic evidence highlight the association of human sleep behaviors with the incidence of fracture
Authors: Qian Yu , Xia Jiangwei , Liu Ke-Qi , Xu Lin , Xie Shu-Yang , Chen Guo-Bo , Cong Pei-Kuan , Khederzadeh Saber , Zheng Hou-Feng
Published: November 2021

We combined conventional evidence from longitudinal data in UK Biobank and genetic evidence from Mendelian randomization (MR) approach to infer the causality between sleep behaviors and fracture risk. We found that participants with insomnia showed 6.4% higher risk of fracture (hazard ratio [HR] = 1.064, 95% CI = 1.038–1.090, P = 7.84 × 10−7), falls and bone mineral density (BMD) mediated 24.6% and 10.6% of the intermediary effect; the MR analyses provided the consistent evidence. A U-shape relationship was observed between sleep duration and fracture risk (P < 0.001) with the lowest risk at sleeping 7–8 h per day. The excessive daytime sleepiness and “evening” chronotype were associated with fracture risk in observational study, but the association between chronotype and fracture did not show in MR analyses. We further generated a sleep risk score (SRS) with potential risk factors (i.e., insomnia, sleep duration, chronotype, and daytime sleepiness). We found that the risk of fracture increased with an increasing SRS (HR = 1.087, 95% CI = 1.065–1.111, P = 1.27 × 10−14). Moreover, 17.4% of the fracture cases would be removed if all participants exhibited a healthy sleep pattern. In conclusion, insomnia had a causal effect on fracture, falls had a larger intermediary effect than BMD in this association. Individuals with fracture risk could benefit from the intervention on unhealthy sleep pattern.
In defence of oxidation states
Authors: Norman Nicholas C. , Pringle Paul G.
Published: November 2021

In this Perspective, some of the criticisms which have been made concerning the use of oxidation states are addressed, particularly in the context of the teaching of inorganic chemistry.
Tuning the sumanene receptor structure towards the development of potentiometric sensors
Authors: Kasprzak Artur , Tobolska Aleksandra , Sakurai Hidehiro , Wróblewski Wojciech
Published: November 2021

The structure of sumanene was tuned to enable its application as a receptor molecule in a potentiometric sensor for caesium cations detection.
Atomic layer deposition of thin-film sodium manganese oxide cathode materials for sodium ion batteries
Authors: Paranamana Nikhila C. , He Xiaoqing , Young Matthias J.
Published: November 2021

Insights into atomic layer deposition chemistries enable sodium manganese oxide thin film cathodes for sodium ion battery research.
Reprogramming natural proteins using unnatural amino acids
Authors: Adhikari Anup , Bhattarai Bibek Raj , Aryal Ashika , Thapa Niru , KC Puja , Adhikari Ashma , Maharjan Sushila , Chanda Prem B. , Regmi Bishnu P. , Parajuli Niranjan
Published: November 2021

Incorporation of unnatural amino acids into protein offers wide array of applications in fundamental and applied science.
Investigation of shear-induced rearrangement of carbon nanotube bundles using Taylor–Couette flow
Authors: Lee Haemin , Park Jinhwan , Cho Hyunjung , Lee Jaegeun , Lee Kun-Hong
Published: November 2021

The rearrangement of CNT bundles depends on the flow pattern and flow-induced shear stress. When the Taylor–Couette flow is stable and laminar, and has sufficiently low shear stress, CNT assemblies assume a highly aligned and densified structure.
Self-supervised clustering of mass spectrometry imaging data using contrastive learning
Authors: Hu Hang , Bindu Jyothsna Padmakumar , Laskin Julia
Published: November 2021

Contrastive learning is used to train a deep convolutional neural network to identify high-level features in mass spectrometry imaging data. These features enable self-supervised clustering of ion images without manual annotation.
Computational and experimental investigation of the effect of cation structure on the solubility of anionic flow battery active-materials
Authors: Visayas Benjoe Rey B. , Pahari Shyam K. , Gokoglan Tugba Ceren , Golen James A. , Agar Ertan , Cappillino Patrick J. , Mayes Maricris L.
Published: November 2021

Active-material solubility is critical in determining NRFB energy density, yet a predictive model accounting for solid-state cohesion energy has remained elusive. Herein we present such, based on an empirically calibrated computational framework.
Iterative addition of carbon nucleophiles to N,N-dialkyl carboxamides for synthesis of α-tertiary amines
Authors: Chen Jiahua , Lim Jun Wei , Ong Derek Yiren , Chiba Shunsuke
Published: November 2021

We herein report a concise protocol for iterative addition of carbon nucleophiles to N,N-dialkyl carboxamides for the synthesis of α-tertiary amines.