bluuebunny/crossref_metadata_2025 huggingface dataset:
The incidence of Orientia tsutsugamushi infection in rural South India
Authors: Devamani Carol S. , Prakash John A. J. , Alexander Neal , Stenos John , Schmidt Wolf-Peter
Published: June 2022

Scrub typhus is a common bacterial infection in Asia caused by Orientia tsutsugamushi. This serological cohort study estimated the incidence of infection in a rural population in South India. Participants were enrolled through systematic sampling in 46 villages at baseline, and revisited the following year. Blood samples were tested for IgG antibodies using ELISA, followed by indirect immunofluorescence assays (IFA) in those positive for ELISA at both rounds. A case was defined as sero-conversion (ELISA), or at least a 4-fold titre increase (IFA), between the two time points. In addition to crude incidence rate estimates, we used piecewise linear rates across calendar months, with rates proportional to the monthly incidence of local hospital cases to address seasonality and unequal follow-up times. Of 402 participants, 61.7% were female. The mean age was 46.7 years, (range 13–88). 21 participants showed evidence for serological infection. The estimated incidence was 4.4 per 100 person-years (95% CI 2.8–6.7). The piecewise linear rates approach resulted in a similar estimate of 4.6 per 100 person years (95% CI 2.9–6.9). Considering previous estimates of symptomatic scrub typhus incidence in the same study population, only about 2–5% of infections may result in clinically relevant disease.
Evidence of steep declines in the heavily traded Javan White-eyeZosterops flavusfrom repeated standardised surveys
Authors: van Balen S. (Bas) , Saryanthi Ria , Marsden Stuart
Published: June 2022

Many Indonesian, and in particular Javan, birds are suspected to have declined dramatically as a result of unsustainable trapping for the cagebird trade, but quantitative evidence of the scale of declines is lacking for the great majority of species. We conducted field surveys of the heavily traded Javan White-eyeZosterops flavusat 19 key sites in 2018–2019 matching the methods and personnel used in baseline surveys done around 10 years earlier. Overall numbers counted were 84% lower in the later survey, and while more white-eyes were recorded at three sites in 2018–2019, there was a significant decline in numbers across all sites. The three sites with highest numbers in 2006–2019 (502 birds counted) had 22 individuals counted in 2018–2019, but there was no overall trend for ‘declines’ to be greater at sites that held more birds originally. Declines in white-eyes were much steeper than those of several lesser-traded bird species at the sites, suggesting that trapping has been a more important driver of declines than habitat changes such as conversion of mangrove to shrimp ponds. Small numbers of white-eyes were recorded at several previously unvisited sites, but we suggest that the species, on Java at least, has shown declines in the region of 80% over the last 10 years. Although since 2018 Javan White-eye is legally protected, we urge that this protection is extended to all white-eye species, because of their similarity.
Fragebogen zur Behandlungszufriedenheit in der stationären Kinder- und Jugendpsychiatrie (FBZ-KJP)
Authors: Della Casa André , Urben Sébastien , Hefti Stephanie , Wöckel Lars , Beutler Hélène , Holzer Laurent , Riedo Verena , Schimmelmann Benno G. , Schmid Marc
Published: June 2022

Zusammenfassung: Fragestellung: Die Patientenzufriedenheit ist ein etablierter Qualitätsindikator für medizinische Interventionen, welchen die Kostenträger im Gesundheitssystem zunehmend als Indikator heranziehen, um Unterschiede zwischen Kliniken sichtbar zu machen. Die Erfassung der Patientenzufriedenheit stellt die Kinder- und Jugendpsychiatrie/-psychotherapie (KJPP) vor besondere Herausforderungen (Entwicklungsstand, Rolle der Eltern). Die bestehenden Patientenzufriedenheitsinstrumente erwiesen sich als zu unspezifisch, um die verschiedenen Aspekte einer stationären KJPP-Behandlung abbilden zu können. Deshalb setzte sich eine Arbeitsgruppe im Auftrag der Schweizerischen Gesellschaft für Kinder und Jugendpsychiatrie (SGKJPP) zum Ziel, ein psychometrisches Instrument für die Patienten- und Elternzufriedenheit zu entwickeln, welches in den deutsch- und französischsprachigen Sprachregionen eingesetzt werden kann. Methodik: Die erste Anwendung und Überprüfung dieses Fragebogens in einer multizentrischen Pilotstudie mit einer Stichprobe von 174 Patientinnen und Patienten und 145 Eltern aus sechs Kliniken wird in diesem Artikel vorgestellt. Ergebnisse: Die Ergebnisse zeigen hervorragende Testgütekriterien des Instrumentariums (Cronbachs α = .93 bzw. α = .97 (Eltern-/Patientenversion). Die Fragebogenvarianten besitzen eine hohe konvergente Validität; die Korrelation zum Client Satisfaction Questionnaire (CSQ-8) beträgt p = .80 bzw. .83 (Patienten-, Elternurteil). Zudem differenzieren sie zwischen den einzelnen Kliniken. Die Korrelationen zwischen Patienten- und Elternurteil liegen bei moderaten p = .29 für den Gesamttest-Score und p = .39 für den CSQ-8. Schlussfolgerungen: Der Fragebogen eignet sich für die Beschreibung der Qualitätsentwicklung in der KJPP und kann als Standardverfahren für die Erfassung der Patientenzufriedenheit empfohlen werden.
Burnout-Symptome bei Fachkräften in der Kinder- und Jugendpsychiatrie/Psychotherapie während des Winter-Lockdowns 2020/2021 der COVID-19-Pandemie
Authors: Hähnle Sarah , Fegert Jörg M. , König Elsa , Hoffmann Ulrike
Published: June 2022

Zusammenfassung. Fragestellung: Fachkräfte in Kliniken und Abteilungen für Kinder- und Jugendpsychiatrie/Psychotherapie erleben in ihrem Arbeitsalltag häufig Belastungen, die sich in Form von Belastungssymptomen wie einer Burnout-Symptomatik äußern können. Ziel ist es, die bisher nicht ausreichend erforschten Folgen einer Burnout-Symptomatik auf institutioneller Ebene wie beispielsweise Personalfluktuation zu untersuchen. Methodik: An psychiatrischen Kliniken oder Abteilungen für Kinder und Jugendliche in Deutschland wurden die Zusammenhänge zwischen einer Burnout-Symptomatik der Fachkräfte und den institutionellen Folgen Präsentismus, Absentismus, Fluktuationsneigung und geminderte Qualität der Arbeitsleistung an einer Stichprobe von n = 172 Fachkräften während des Winter-Lockdowns (2020/2021) der COVID-19-Pandemie untersucht. Ergebnisse: Es zeigte sich, dass Anzeichen einer Burnout-Symptomatik einen Einfluss auf die Fluktuationsneigung, den Präsentismus sowie die Arbeitsleistung der Fachkräfte haben. Darüber hinaus ergaben sich Hinweise, dass die Fachkräfte während des Winter-Lockdowns (2020/2021) der COVID-19-Pandemie belasteter waren und dies die Fluktuationsneigung, den Präsentismus und Absentismus sowie die Qualität der Arbeitsleistung beeinflusst hat. Schlussfolgerung: Den berufsbedingten Belastungen der Fachkräfte gilt es frühzeitig zu begegnen, um die potenziellen Folgen für Kliniken und Abteilungen für Kinder- und Jugendpsychiatrie/Psychotherapie zu verhindern oder zu mindern und im Zuge dessen die Betreuungskonnektivität und -qualität gewährleisten zu können.
Nudging for Lockdown
Authors: Blayac Thierry , Dubois Dimitri , Duchêne Sébastien , Nguyen-Van Phu , Rafaï Ismaël , Ventelou Bruno , Willinger Marc
Published: June 2022

Abstract. We test the effectiveness of a social comparison nudge (SCN) to enhance lockdown compliance during the COVID-19 pandemic using a French representative sample ( N = 1,154). Respondents were randomly assigned to a favorable/unfavorable informational feedback (daily road traffic mobility patterns, in Normandy – a region of France) on peer lockdown compliance. Our dependent variable was the intention to comply with a possible future lockdown. We controlled for risk, time, and social preferences and tested the effectiveness of the nudge. We found no evidence of the effectiveness of the SCN among the whole French population, but the nudge was effective when its recipient and the reference population shared the same geographical location (Normandy). Exploratory results on this subsample ( N = 52) suggest that this effectiveness could be driven by noncooperative individuals.
Algorithmic Differentiation for Sensitivity Analysis in Cloud Microphysics
Authors: Hieronymus M. , Baumgartner M. , Miltenberger A. , Brinkmann A.
Published: June 2022

The role of clouds for radiative transfer, precipitation formation, and their interaction with atmospheric dynamics depends strongly on cloud microphysics. The parameterization of cloud microphysical processes in weather and climate models is a well‐known source of uncertainties. Hence, robust quantification of this uncertainty is mandatory. Sensitivity analysis to date has typically investigated only a few model parameters. We propose algorithmic differentiation (AD) as a tool to detect the magnitude and timing at which a model state variable is sensitive to any of the hundreds of uncertain model parameters in the cloud microphysics parameterization. AD increases the computational cost by roughly a third in our simulations. We explore this methodology as the example of warm conveyor belt trajectories, that is, air parcels rising rapidly from the planetary boundary layer to the upper troposphere in the vicinity of an extratropical cyclone. Based on the information of derivatives with respect to the uncertain parameters, the ten parameters contributing most to uncertainty are selected. These uncertain parameters are mostly related to the representation of hydrometeor diameter and fall velocity, the activation of cloud condensation nuclei, and heterogeneous freezing. We demonstrate the meaningfulness of the AD‐estimated sensitivities by comparing the AD results with ensemble simulations spawned at different points along the trajectories, where different parameter settings are used in the various ensemble members. The ranking of the most important parameters from these ensemble simulations is consistent with the results from AD. Thus, AD is a helpful tool for selecting parameters contributing most to cloud microphysics uncertainty.
Therapy response of glucocorticoid-refractory acute GVHD of the lower intestinal tract
Authors: Biavasco Francesca , Ihorst Gabriele , Wäsch Ralph , Wehr Claudia , Bertz Hartmut , Finke Jürgen , Zeiser Robert
Published: June 2022

Acute graft-versus-host disease (aGVHD) is a major life-threatening complication of allogeneic hematopoietic cell transplantation. While most studies report therapy-response of aGVHD including a cumulative grade of skin, liver and intestinal tract manifestations, there is a lack of information specifically on lower gastrointestinal tract aGVHD (GI-GVHD) therapy-response, which is highly relevant in light of novel therapies that target intestinal regeneration such as IL-22, R-spondin or GLP-2. Here we retrospectively analyzed patients who developed GI-GVHD over a 6-year period. A total of 144 patients developed GI-GVHD and 82 (57%) were resistant to glucocorticoid-therapy (SR). The most commonly used second-line therapy was ruxolitinib (74%). Overall and complete response (CR) to ruxolitinib on day 28 were 44.5% and 13%, respectively. SR-GVHD patients experienced a lower 5-year overall survival (OS) (34.8 vs 53.3%,p = 0.0014) and higher incidence of 12-months non-relapse-mortality (39.2 vs 14.3%,p = 0.016) compared to glucocorticoid-sensitive patients. SR-GI-GVHD patients, that achieved a CR on day 28 after ruxolitinib start, experienced a higher OS compared to non-CR patients (p = 0.04). These findings indicate that therapy response of SR-GI-GVHD to different immunosuppressive approaches is still low, and that novel therapies specifically aiming at enhanced intestinal regeneration should be tested in clinical trials.
Intracontinental deformation of the Tianshan Orogen in response to India-Asia collision
Authors: Li Wei , Chen Yun , Yuan Xiaohui , Xiao Wenjiao , Windley Brian F.
Published: June 2022

How the continental lithosphere deforms far away from plate boundaries has been long debated. The Tianshan is a type-example of ongoing lithospheric deformation in an intracontinental setting. It formed during the Paleozoic accretion of the Altaids and was rejuvenated in the Cenozoic, which might be a far-field response to the India-Asia collision. Here we present seismic images of the lithosphere across the central Tianshan, which were constructed from receiver functions and Rayleigh wave dispersions along a N–S-trending linear seismic array. We observe an extensively deformed lithosphere in the Tianshan with inherited, structurally controlled brittle deformation in the shallow crust and plastic deformation near the Moho. We find that earlier multiple accretionary structures were preserved in the crust, which was deformed by pure-shear shortening in the south and thick-skinned tectonics in the north but was limitedly underthrusted by surrounding blocks. A balanced cross-section of Moho discontinuities supports the concept that intracontinental deformation in the Tianshan intensified synchronously with the direct contact between the underthrusting Indian slab and the Tarim Craton in the Late Miocene (~10 Ma). These findings provide a robust and unified seismic model for the Tianshan Orogen, and confirm that effective delivery of the India-Asia collision stress induced the rejuvenation of this intracontinental orogen.
Passive mode-locking and terahertz frequency comb generation in resonant-tunneling-diode oscillator
Authors: Hiraoka Tomoki , Inose Yuta , Arikawa Takashi , Ito Hiroshi , Tanaka Koichiro
Published: June 2022

Optical frequency combs in the terahertz frequency range are long-awaited frequency standards for spectroscopy of molecules and high-speed wireless communications. However, a terahertz frequency comb based on a low-cost, energy-efficient, and room-temperature-operating device remains unavailable especially in the frequency range of 0.1 to 3 THz. In this paper, we show that the resonant-tunneling-diode (RTD) oscillator can be passively mode-locked by optical feedback and generate a terahertz frequency comb. The standard deviation of the spacing between the comb lines, i.e., the repetition frequency, is reduced to less than 420 mHz by applying external bias modulation. A simulation model successfully reproduces the mode-locking behavior by including the nonlinear capacitance of RTD and multiple optical feedback. Since the mode-locked RTD oscillator is a simple semiconductor device that operates at room temperature and covers the frequency range of 0.1 to 2 THz (potentially up to 3 THz), it can be used as a frequency standard for future terahertz sensing and wireless communications.
Distinct nociception processing in the dysgranular and barrel regions of the mouse somatosensory cortex
Authors: Osaki Hironobu , Kanaya Moeko , Ueta Yoshifumi , Miyata Mariko
Published: June 2022

Nociception, a somatic discriminative aspect of pain, is, like touch, represented in the primary somatosensory cortex (S1), but the separation and interaction of the two modalities within S1 remain unclear. Here, we show spatially distinct tactile and nociceptive processing in the granular barrel field (BF) and adjacent dysgranular region (Dys) in mouse S1. Simultaneous recordings of the multiunit activity across subregions revealed that Dys neurons are more responsive to noxious input, whereas BF neurons prefer tactile input. At the single neuron level, nociceptive information is represented separately from the tactile information in Dys layer 2/3. In contrast, both modalities seem to converge on individual layer 5 neurons of each region, but to a different extent. Overall, these findings show layer-specific processing of nociceptive and tactile information between Dys and BF. We further demonstrated that Dys activity, but not BF activity, is critically involved in pain-like behavior. These findings provide new insights into the role of pain processing in S1.
Pervasive translation of circular RNAs driven by short IRES-like elements
Authors: Fan Xiaojuan , Yang Yun , Chen Chuyun , Wang Zefeng
Published: June 2022

Some circular RNAs (circRNAs) were found to be translated through IRES-driven mechanism, however the scope and functions of circRNA translation are unclear because endogenous IRESs are rare. To determine the prevalence and mechanism of circRNA translation, we develop a cell-based system to screen random sequences and identify 97 overrepresented hexamers that drive cap-independent circRNA translation. These IRES-like short elements are significantly enriched in endogenous circRNAs and sufficient to drive circRNA translation. We further identify multiple trans-acting factors that bind these IRES-like elements to initiate translation. Using mass-spectrometry data, hundreds of circRNA-coded peptides are identified, most of which have low abundance due to rapid degradation. As judged by mass-spectrometry, 50% of translatable endogenous circRNAs undergo rolling circle translation, several of which are experimentally validated. Consistently, mutations of the IRES-like element in one circRNA reduce its translation. Collectively, our findings suggest a pervasive translation of circRNAs, providing profound implications in translation control.
A guided multiverse study of neuroimaging analyses
Authors: Dafflon Jessica , F. Da Costa Pedro , Váša František , Monti Ricardo Pio , Bzdok Danilo , Hellyer Peter J. , Turkheimer Federico , Smallwood Jonathan , Jones Emily , Leech Robert
Published: June 2022

For most neuroimaging questions the range of possible analytic choices makes it unclear how to evaluate conclusions from any single analytic method. One possible way to address this issue is to evaluate all possible analyses using a multiverse approach, however, this can be computationally challenging and sequential analyses on the same data can compromise predictive power. Here, we establish how active learning on a low-dimensional space capturing the inter-relationships between pipelines can efficiently approximate the full spectrum of analyses. This approach balances the benefits of a multiverse analysis without incurring the cost on computational and predictive power. We illustrate this approach with two functional MRI datasets (predicting brain age and autism diagnosis) demonstrating how a multiverse of analyses can be efficiently navigated and mapped out using active learning. Furthermore, our presented approach not only identifies the subset of analysis techniques that are best able to predict age or classify individuals with autism spectrum disorder and healthy controls, but it also allows the relationships between analyses to be quantified.
Diverse mantle components with invariant oxygen isotopes in the 2021 Fagradalsfjall eruption, Iceland
Authors: Bindeman I. N. , Deegan F. M. , Troll V. R. , Thordarson T. , Höskuldsson Á. , Moreland W. M. , Zorn E. U. , Shevchenko A. V. , Walter T. R.
Published: June 2022

The basalts of the 2021 Fagradalsfjall eruption were the first erupted on the Reykjanes Peninsula in 781 years and offer a unique opportunity to determine the composition of the mantle underlying Iceland, in particular its oxygen isotope composition (δ18O values). The basalts show compositional variations in Zr/Y, Nb/Zr and Nb/Y values that span roughly half of the previously described range for Icelandic basaltic magmas and signal involvement of Icelandic plume (OIB) and Enriched Mid-Ocean Ridge Basalt (EMORB) in magma genesis. Here we show that Fagradalsfjall δ18O values are invariable (mean δ18O = 5.4 ± 0.3‰ 2 SD, N = 47) and indistinguishable from “normal” upper mantle, in contrast to significantly lower δ18O values reported for erupted materials elsewhere in Iceland (e.g., the 2014–2015 eruption at Holuhraun, Central Iceland). Thus, despite differing trace element characteristics, the melts that supplied the Fagradalsfjall eruption show no evidence for 18O-depleted mantle or interaction with low-δ18O crust and may therefore represent a useful mantle reference value in this part of the Icelandic plume system.
Rhythmic interactions between the mediodorsal thalamus and prefrontal cortex precede human visual perception
Authors: Griffiths Benjamin J. , Zaehle Tino , Repplinger Stefan , Schmitt Friedhelm C. , Voges Jürgen , Hanslmayr Simon , Staudigl Tobias
Published: June 2022

The thalamus is much more than a simple sensory relay. High-order thalamic nuclei, such as the mediodorsal thalamus, exert a profound influence over animal cognition. However, given the difficulty of directly recording from the thalamus in humans, next-to-nothing is known about thalamic and thalamocortical contributions to human cognition. To address this, we analysed simultaneously-recorded thalamic iEEG and whole-head MEG in six patients (plus MEG recordings from twelve healthy controls) as they completed a visual detection task. We observed that the phase of both ongoing mediodorsal thalamic and prefrontal low-frequency activity was predictive of perceptual performance. Critically however, mediodorsal thalamic activity mediated prefrontal contributions to perceptual performance. These results suggest that it is thalamocortical interactions, rather than cortical activity alone, that is predictive of upcoming perceptual performance and, more generally, highlights the importance of accounting for the thalamus when theorising about cortical contributions to human cognition.
WASp modulates RPA function on single-stranded DNA in response to replication stress and DNA damage
Authors: Han Seong-Su , Wen Kuo-Kuang , García-Rubio María L. , Wold Marc S. , Aguilera Andrés , Niedzwiedz Wojciech , Vyas Yatin M.
Published: June 2022

Perturbation in the replication-stress response (RSR) and DNA-damage response (DDR) causes genomic instability. Genomic instability occurs in Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency disorder, yet the mechanism remains largely uncharacterized. Replication protein A (RPA), a single-strand DNA (ssDNA) binding protein, has key roles in the RSR and DDR. Here we show that human WAS-protein (WASp) modulates RPA functions at perturbed replication forks (RFs). Following genotoxic insult, WASp accumulates at RFs, associates with RPA, and promotes RPA:ssDNA complexation. WASp deficiency in human lymphocytes destabilizes RPA:ssDNA-complexes, impairs accumulation of RPA, ATR, ETAA1, and TOPBP1 at genotoxin-perturbed RFs, decreases CHK1 activation, and provokes global RF dysfunction.las17(yeastWAS-homolog)-deficientS. cerevisiaealso show decreased ScRPA accumulation at perturbed RFs, impaired DNA recombination, and increased frequency of DNA double-strand break (DSB)-induced single-strand annealing (SSA). Consequently, WASp (or Las17)-deficient cells show increased frequency of DSBs upon genotoxic insult. Our study reveals an evolutionarily conserved, essential role of WASp in the DNA stress-resolution pathway, such that WASp deficiency provokes RPA dysfunction-coupled genomic instability.
Scanning gradiometry with a single spin quantum magnetometer
Authors: Huxter W. S. , Palm M. L. , Davis M. L. , Welter P. , Lambert C.-H. , Trassin M. , Degen C. L.
Published: June 2022

Quantum sensors based on spin defects in diamond have recently enabled detailed imaging of nanoscale magnetic patterns, such as chiral spin textures, two-dimensional ferromagnets, or superconducting vortices, based on a measurement of the static magnetic stray field. Here, we demonstrate a gradiometry technique that significantly enhances the measurement sensitivity of such static fields, leading to new opportunities in the imaging of weakly magnetic systems. Our method relies on the mechanical oscillation of a single nitrogen-vacancy center at the tip of a scanning diamond probe, which up-converts the local spatial gradients into ac magnetic fields enabling the use of sensitive ac quantum protocols. We show that gradiometry provides important advantages over static field imaging: (i) an order-of-magnitude better sensitivity, (ii) a more localized and sharper image, and (iii) a strong suppression of field drifts. We demonstrate the capabilities of gradiometry by imaging the nanotesla fields appearing above topographic defects and atomic steps in an antiferromagnet, direct currents in a graphene device, and para- and diamagnetic metals.
SARS-CoV-2 antibody trajectories after a single COVID-19 vaccination with and without prior infection
Authors: Wei Jia , Matthews Philippa C. , Stoesser Nicole , Diamond Ian , Studley Ruth , Rourke Emma , Cook Duncan , Bell John I. , Newton John N. , Farrar Jeremy , Howarth Alison , Marsden Brian D. , Hoosdally Sarah , Jones E. Yvonne , Stuart David I. , Crook Derrick W. , Peto Tim E. A. , Walker A. Sarah , Eyre David W. , Pouwels Koen B. ,   The COVID-19 Infection Survey team, Thomas Tina , Ayoubkhani Daniel , Black Russell , Felton Antonio , Crees Megan , Jones Joel , Lloyd Lina , Sutherland Esther , Pritchard Emma , Vihta Karina-Doris , Doherty George , Kavanagh James , Chau Kevin K. , Hatch Stephanie B. , Ebner Daniel , Ferreira Lucas Martins , Christott Thomas , Dejnirattisai Wanwisa , Mongkolsapaya Juthathip , Cameron Sarah , Tamblin-Hopper Phoebe , Wolna Magda , Brown Rachael , Cornall Richard , Screaton Gavin , Lythgoe Katrina , Bonsall David , Golubchik Tanya , Fryer Helen , Cox Stuart , Paddon Kevin , James Tim , House Thomas , Robotham Julie , Birrell Paul , Jordan Helena , Sheppard Tim , Athey Graham , Moody Dan , Curry Leigh , Brereton Pamela , Jarvis Ian , Godsmark Anna , Morris George , Mallick Bobby , Eeles Phil , Hay Jodie , VanSteenhouse Harper , Lee Jessica , White Sean , Evans Tim , Bloemberg Lisa , Allison Katie , Pandya Anouska , Davis Sophie , Conway David I. , MacLeod Margaret , Cunningham Chris
Published: June 2022

Given high SARS-CoV-2 incidence, coupled with slow and inequitable vaccine roll-out in many settings, there is a need for evidence to underpin optimum vaccine deployment, aiming to maximise global population immunity. We evaluate whether a single vaccination in individuals who have already been infected with SARS-CoV-2 generates similar initial and subsequent antibody responses to two vaccinations in those without prior infection. We compared anti-spike IgG antibody responses after a single vaccination with ChAdOx1, BNT162b2, or mRNA-1273 SARS-CoV-2 vaccines in the COVID-19 Infection Survey in the UK general population. In 100,849 adults median (50 (IQR: 37–63) years) receiving at least one vaccination, 13,404 (13.3%) had serological/PCR evidence of prior infection. Prior infection significantly boosted antibody responses, producing higher peak levels and/or longer half-lives after one dose of all three vaccines than those without prior infection receiving one or two vaccinations. In those with prior infection, the median time above the positivity threshold was >1 year after the first vaccination. Single-dose vaccination targeted to those previously infected may provide at least as good protection to two-dose vaccination among those without previous infection.
Genome-wide siRNA screening reveals several host receptors for the binding of human gut commensal Bifidobacterium bifidum
Authors: Kainulainen Veera , von Schantz-Fant Carina , Kovanen Ruusu-Maria , Potdar Swapnil , Laamanen Karoliina , Saarela Jani , Satokari Reetta
Published: June 2022

Bifidobacterium spp. are abundant gut commensals, especially in breast-fed infants. Bifidobacteria are associated with many health-promoting effects including maintenance of epithelial barrier and integrity as well as immunomodulation. However, the protective mechanisms of bifidobacteria on intestinal epithelium at molecular level are poorly understood. In this study, we developed a high-throughput in vitro screening assay to explore binding receptors of intestinal epithelial cells for Bifidobacterium bifidum. Short interfering RNAs (siRNA) were used to silence expression of each gene in the Caco-2 cell line one by one. The screen yielded four cell surface proteins, SERPINB3, LGICZ1, PKD1 and PAQR6, which were identified as potential receptors as the siRNA knock-down of their expression decreased adhesion of B. bifidum to the cell line repeatedly during the three rounds of siRNA screening. Furthermore, blocking of these host cell proteins by specific antibodies decreased the binding of B. bifidum significantly to Caco-2 and HT29 cell lines. All these molecules are located on the surface of epithelial cells and three out of four, SERPINB3, PKD1 and PAQR6, are involved in the regulation of cellular processes related to proliferation, differentiation and apoptosis as well as inflammation and immunity. Our results provide leads to the first steps in the mechanistic cascade of B. bifidum-host interactions leading to regulatory effects in the epithelium and may partly explain how this commensal bacterium is able to promote intestinal homeostasis.
Electrochemical characterization and degradation of carbon fibre reinforced polymer in quiescent near neutral chloride media
Authors: Ofoegbu Stanley Udochukwu , Quevedo Marcela C. , Bastos A. C. , Ferreira M. G. S. , Zheludkevich M. L.
Published: June 2022

In a quest for a better understanding of the mechanism and contribution(s) of fresh (“un-degraded”) and degraded CFRP surfaces to galvanic corrosion of coupled metals in multi-material assemblies the electrochemical behaviour of CFRP in quiescent 50 mM NaCl was studied using electrochemical techniques. Tests using ferricyanide/ferrocyanide redox couple revealed a quasi-reversible behaviour. Under cathodic polarization, CFRP is active electrochemically evidenced by the increase in pH (to pH ≥ 10). Galvanic current densities and potentials for Al-CFRP couple comprised of freshly polished CFRP sample ranged from 15–25 µA cm−2 and ≈−660 to −850 mVSCE respectively, while the corresponding parameter for Al-CFRP couple comprised of degraded CFRP were in the range 10–25 µA cm−2 and ≈−670 to −900 mVSCE. Contrary to expectations, CFRP prior exposure to degradative high pH media before galvanic coupling did not result in an increase in the intensity of galvanic corrosion of the coupled metal.
Genomic, transcriptomic, and metabolomic profiles of hiPSC-derived dopamine neurons from clinically discordant brothers with identical PRKN deletions
Authors: Cukier Holly N. , Kim Hyunjin , Griswold Anthony J. , Codreanu Simona G. , Prince Lisa M. , Sherrod Stacy D. , McLean John A. , Dykxhoorn Derek M. , Ess Kevin C. , Hedera Peter , Bowman Aaron B. , Neely M. Diana
Published: June 2022

We previously reported on two brothers who carry identical compound heterozygousPRKNmutations yet present with significantly different Parkinson’s Disease (PD) clinical phenotypes. Juvenile cases demonstrate that PD is not necessarily an aging-associated disease. Indeed, evidence for a developmental component to PD pathogenesis is accumulating. Thus, we hypothesized that the presence of additional genetic modifiers, including genetic loci relevant to mesencephalic dopamine neuron development, could potentially contribute to the different clinical manifestations of the two brothers. We differentiated human-induced pluripotent stem cells (hiPSCs) derived from the two brothers into mesencephalic neural precursor cells and early postmitotic dopaminergic neurons and performed wholeexome sequencing and transcriptomic and metabolomic analyses. No significant differences in the expression of canonical dopamine neuron differentiation markers were observed. Yet our transcriptomic analysis revealed a significant downregulation of the expression of three neurodevelopmentally relevant cell adhesion molecules,CNTN6,CNTN4andCHL1, in the cultures of the more severely affected brother. In addition, severalHLAgenes, known to play a role in neurodevelopment, were differentially regulated. The expression ofEN2, a transcription factor crucial for mesencephalic dopamine neuron development, was also differentially regulated. We further identified differences in cellular processes relevant to dopamine metabolism. Lastly, wholeexome sequencing, transcriptomics and metabolomics data all revealed differences in glutathione (GSH) homeostasis, the dysregulation of which has been previously associated with PD. In summary, we identified genetic differences which could potentially, at least partially, contribute to the discordant clinical PD presentation of the two brothers.
STN-DBS does not increase the risk of sialorrhea in patients with advanced Parkinson’s disease
Authors: Bove Francesco , Genovese Danilo , Petracca Martina , Tufo Tommaso , Pisani Danila , Lo Monaco Maria Rita , Bentivoglio Anna Rita , Calabresi Paolo , Piano Carla
Published: June 2022

The aims of this study were to assess the incidence rate and risk factors for sialorrhea in the long-term follow-up in a cohort of 132 patients with advanced Parkinson’s disease [88 with deep brain stimulation (DBS) and 44 on medical treatment]. The incidence rate of sialorrhea did not differ between the two groups; male sex, Hoehn and Yahr stage and dysphagia resulted risk factors for sialorrhea. These findings indicate that DBS does not increase the risk of developing sialorrhea.
Structural insights into dsRNA processing by Drosophila Dicer-2–Loqs-PD
Authors: Su Shichen , Wang Jia , Deng Ting , Yuan Xun , He Jinqiu , Liu Nan , Li Xiaomin , Huang Ying , Wang Hong-Wei , Ma Jinbiao
Published: June 2022

Small interfering RNAs (siRNAs) are the key components for RNA interference (RNAi), a conserved RNA-silencing mechanism in many eukaryotes1,2. In Drosophila, an RNase III enzyme Dicer-2 (Dcr-2), aided by its cofactor Loquacious-PD (Loqs-PD), has an important role in generating 21 bp siRNA duplexes from long double-stranded RNAs (dsRNAs)3,4. ATP hydrolysis by the helicase domain of Dcr-2 is critical to the successful processing of a long dsRNA into consecutive siRNA duplexes5,6. Here we report the cryo-electron microscopy structures of Dcr-2–Loqs-PD in the apo state and in multiple states in which it is processing a 50 bp dsRNA substrate. The structures elucidated interactions between Dcr-2 and Loqs-PD, and substantial conformational changes of Dcr-2 during a dsRNA-processing cycle. The N-terminal helicase and domain of unknown function 283 (DUF283) domains undergo conformational changes after initial dsRNA binding, forming an ATP-binding pocket and a 5′-phosphate-binding pocket. The overall conformation of Dcr-2–Loqs-PD is relatively rigid during translocating along the dsRNA in the presence of ATP, whereas the interactions between the DUF283 and RIIIDb domains prevent non-specific cleavage during translocation by blocking the access of dsRNA to the RNase active centre. Additional ATP-dependent conformational changes are required to form an active dicing state and precisely cleave the dsRNA into a 21 bp siRNA duplex as confirmed by the structure in the post-dicing state. Collectively, this study revealed the molecular mechanism for the full cycle of ATP-dependent dsRNA processing by Dcr-2–Loqs-PD.
High spatial and temporal variability in Antarctic ice discharge linked to ice shelf buttressing and bed geometry
Authors: Miles Bertie W. J. , Stokes Chris R. , Jamieson Stewart S. R. , Jordan Jim R. , Gudmundsson G. Hilmar , Jenkins Adrian
Published: June 2022

Antarctica’s contribution to global mean sea level rise has been driven by an increase in ice discharge into the oceans. The rate of change and the mechanisms that drive variability in ice discharge are therefore important to consider in the context of projected future warming. Here, we report observations of both decadal trends and inter-annual variability in ice discharge across the Antarctic Ice Sheet at a variety of spatial scales that range from large drainage basins to individual outlet glacier catchments. Overall, we find a 37 ± 11 Gt year−1 increase in discharge between 1999 and 2010, but a much smaller increase of 4 ± 8 Gt year−1 between 2010 and 2018. Furthermore, comparisons reveal that neighbouring outlet glaciers can behave synchronously, but others show opposing trends, despite their close proximity. We link this spatial and temporal variability to changes in ice shelf buttressing and the modulating effect of local glacier geometry.
The disruption of elective procedures due to COVID-19 in Brazil in 2020
Authors: Frio Gustavo Saraiva , Russo Letícia Xander , de Albuquerque Cleandro Pires , da Mota Licia Maria Henrique , Barros-Areal Adriana Ferreira , Oliveira Andréa Pedrosa Ribeiro Alves , Firmino-Machado João , da Silva Everton Nunes
Published: June 2022

Elective procedures were temporarily suspended several times over the course of the pandemic of COVID-19. Monthly data from the Unified Health System (SUS) were used for the period between January 2008 and December 2020 and the interrupted time series method was used to estimate the effect of the pandemic on the number of elective surgeries and elective procedures that were not performed. Considering a 9-month period, a reduction of 46% in the number of elective procedures carried out in the SUS could be attributed to COVID-19, corresponding to about 828,429 elective procedures cancelled, ranging from 549,921 to 1,106,936. To a full recovery of pre-pandemic performance, SUS would need to increase about 21,362 hospital beds, ranging from 12,370 to 36,392 hospital beds during a 6 month-period. This effort would represent an increase of 8.48% (ranging from 4.91 to 14.45%) in relation to the total number of SUS’s hospital beds in 2019. As a result, the pandemic will leave a large number of elective procedures to be carried out, which will require efforts by health agencies to meet this demand.
Randomized double-blind placebo-controlled proof-of-concept trial of resveratrol for outpatient treatment of mild coronavirus disease (COVID-19)
Authors: McCreary Marvin R. , Schnell Patrick M. , Rhoda Dale A.
Published: June 2022

Resveratrol is a polyphenol that has been well studied and has demonstrated anti-viral and anti-inflammatory properties that might mitigate the effects of COVID-19. Outpatients (N = 105) were recruited from central Ohio in late 2020. Participants were randomly assigned to receive placebo or resveratrol. Both groups received a single dose of Vitamin D3 which was used as an adjunct. The primary outcome measure was hospitalization within 21 days of symptom onset; secondary measures were ER visits, incidence of pneumonia, and incidence of pulmonary embolism. Five patients chose not to participate after randomization. Twenty-one-day outcome was determined of all one hundred participants (mean [SD] age 55.6 [8.8] years; 61% female). There were no clinically significant adverse events attributed to resveratrol. Outpatients in this phase 2 study treated with resveratrol had a lower incidence compared to placebo of: hospitalization (2% vs. 6%, RR 0.33, 95% CI 0.04–3.10), COVID-19 related ER visits (8% vs. 14%, RR 0.57, 95% CI 0.18–1.83), and pneumonia (8% vs. 16%, RR 0.5, 95% CI 0.16–1.55). One patient (2%) in each group developed pulmonary embolism (RR 1.00, 95% CI: 0.06–15.55). This underpowered study was limited by small sample size and low incidence of primary adverse events consequently the results are statistically similar between treatment arms. A larger trial could determine efficacy.

Trial Registrations: ClinicalTrials.gov NCT04400890 26/05/2020; FDA IND #150033 05/05/2020.
The cheetah optimizer: a nature-inspired metaheuristic algorithm for large-scale optimization problems
Authors: Akbari Mohammad Amin , Zare Mohsen , Azizipanah-abarghooee Rasoul , Mirjalili Seyedali , Deriche Mohamed
Published: June 2022

Motivated by the hunting strategies of cheetahs, this paper proposes a nature-inspired algorithm called the cheetah optimizer (CO). Cheetahs generally utilize three main strategies for hunting prey, i.e., searching, sitting-and-waiting, and attacking. These strategies are adopted in this work. Additionally, the leave the pray and go back home strategy is also incorporated in the hunting process to improve the proposed framework's population diversification, convergence performance, and robustness. We perform intensive testing over 14 shifted-rotated CEC-2005 benchmark functions to evaluate the performance of the proposed CO in comparison to state-of-the-art algorithms. Moreover, to test the power of the proposed CO algorithm over large-scale optimization problems, the CEC2010 and the CEC2013 benchmarks are considered. The proposed algorithm is also tested in solving one of the well-known and complex engineering problems, i.e., the economic load dispatch problem. For all considered problems, the results are shown to outperform those obtained using other conventional and improved algorithms. The simulation results demonstrate that the CO algorithm can successfully solve large-scale and challenging optimization problems and offers a significant advantage over different standards and improved and hybrid existing algorithms. Note that the source code of the CO algorithm is publicly available athttps://www.optim-app.com/projects/co.
Altered ocular microvasculature in patients with systemic sclerosis and very early disease of systemic sclerosis using optical coherence tomography angiography
Authors: Mihailovic Nataša , Lahme Larissa , Braasch Sonja , Rosenberger Friederike , Eter Nicole , Ehrchen Jan , Alnawaiseh Maged
Published: June 2022

The vascular hypothesis of systemic sclerosis (SSc) would predict microvascular alterations should also affect anatomical regions like ocular microvasculature. The objective of this study was to evaluate retinal and choriocapillary vessel density (VD) in patients with definite SSc and very early disease of systemic sclerosis (VEDOSS) using optical coherence tomography angiography (OCTA). 22 eyes of 22 patients and 22 eyes of 22 healthy subjects were included in this study. Patients were classified into patients with definite SSc and patients with VEDOSS. VD data of the superficial OCT angiogram (OCTA-SCP), deep OCT angiogram (OCTA-DCP) and choriocapillaris (OCTA-CC) were analysed. VD in the OCTA-SCP and OCTA-CC was lower in patients with SSc (p < 0.05). In VEDOSS patients, VD in the OCTA-CC was still reduced compared to controls (p < 0.05). Correlation analysis revealed a positive correlation between nailfold capillaroscopy and VD of OCTA-CC (Spearman correlation coefficient (rSp) 0.456, p < 0.05) and a negative correlation between skin score and VD of OCTA-SCP (p < 0.05). Ocular perfusion seems to be impaired in patients with SSc and even VEDOSS. VD correlated with disease severity. OCTA could be a new useful diagnostic and predictive parameter for monitoring patients with different stages of the disease.
Lean non-alcoholic fatty liver disease (Lean-NAFLD) and the development of metabolic syndrome: a retrospective study
Authors: Wang Wenting , Ren Jianping , Zhou Wenzhao , Huang Jinyu , Wu Guomin , Yang Fenfang , Yuan Shuang , Fang Juan , Liu Jing , Jin Yao , Qi Haiyang , Miao Yuyang , Le Yanna , Ge Cenhong , Qiu Xiantao , Wang JinJing , Huang Ping , Liu Zixin , Wang Sheng
Published: June 2022

Lean NAFLD is a special phenotypic closely correlated with metabolic syndrome (MS). The aim of this study is to investigate the MS development and the gender differences in lean NAFLD population. Participants were divided into 4 groups by BMI and NAFLD status. Descriptive analysis was performed to characterize baseline information. A total of 18,395 subjects were participated, and 1524 incident cases of MS were documented. Then, Kaplan–Meier curves were used to present the MS outcomes in different groups, and the NAFLD was found to be a riskier factor than obesity for MS. Subgroup analysis showed significantly higher MS incidence in female than male among lean NAFLD group, which is different from other groups. Although with higher prevalence in male, lean NAFLD seems to be a more harmful phenotype for females according to the TG, ALT and GGT levels. The logistic regressive analysis was performed to show the impact of NAFLD status and BMI changes on MS risk. Lean non-NAFLD subjects merely developed to NAFLD with no BMI status changes exhibited highest MS risk (ORs = 1.879, 95% CI 1.610–2.292) than that with both BMI increase and NAFLD development (ORs = 1.669, 95% CI 1.325–2.104). It also suggests the metabolic specificity of this population.
Microstructure and mechanical properties of the Mg–Gd–Zn alloy prepared by sintering of rapidly-solidified ribbons
Authors: Luo Wenbo , Guo Yanke , Xue Zhiyong , Han Xiuzhu , Kong Qinke , Mu Minghao , Zhang Gaolong , Mao Weimin , Ren Yu
Published: June 2022

Mg–15Gd–1Zn (wt.%) alloy was successfully prepared via the spark plasma sintering rapid solidification ribbons process. Microstructure investigation showed that the sintered alloys consisted of fine grains, the β1 phase, and long-perioded stacking ordered phase (LPSO). The sintering temperature and time have a significant effect on the microstructural evolution. A lower sintering temperature (430 °C ) was beneficial for obtaining finer grain sizes with less than 5 μm and a higher content of β1 phase with a content of 3–15 vol.% and a size-distribution of (10–600) nm. A higher temperature for a longer sintering time, 450–470 °C and 5–10 min, helpfully promoted precipitating the abundantly lamellar LPSO phase, and its content was 2–10 vol.% for LPSO phase with the width of (10–100) nm. The mechanical properties indicated that the fine grain size and supersaturated solid solution contributed at least 50% of the yield stress, and the residual contribution was related to the β1 phase and LPSO phase strengthening, which were based on their contents and the sizes.
Enhanced propagation of Granulicatella adiacens from human oral microbiota by hyaluronan
Authors: Yabuuchi Shun , Oiki Sayoko , Minami Shuma , Takase Ryuichi , Watanabe Daisuke , Hashimoto Wataru
Published: June 2022

Host determinants for formation/composition of human oral microbiota remain to be clarified, although microorganisms entering the mouth cannot necessarily colonize the oral environment. Here we show that human oral-abundant bacteria degraded host glycosaminoglycans (GAGs) in saliva and gingiva, and certain bacteria significantly grew on hyaluronan (HA), a kind of GAGs. Microbial communities from teeth or gingiva of healthy donors assimilated HA. Metagenomic analysis of human oral microbiota under different carbon sources revealed HA-driven Granulicatella growth. HA-degrading bacterial strains independently isolated from teeth and gingiva were identified as Granulicatella adiacens producing extracellular 130 kDa polysaccharide lyase as a HA-degrading enzyme encoded in a peculiar GAG genetic cluster containing genes for isomerase KduI and dehydrogenase DhuD. These findings demonstrated that GAGs are one of the host determinants for formation/composition of oral microbiota not only for colonization but also for the adaptation to the host niche. Especially, HA enhanced the G. adiacens propagation.
A method for AI assisted human interpretation of neonatal EEG
Authors: Gomez-Quintana Sergi , O’Shea Alison , Factor Andreea , Popovici Emanuel , Temko Andriy
Published: June 2022

The study proposes a novel method to empower healthcare professionals to interact and leverage AI decision support in an intuitive manner using auditory senses. The method’s suitability is assessed through acoustic detection of the presence of neonatal seizures in electroencephalography (EEG). Neurophysiologists use EEG recordings to identify seizures visually. However, neurophysiological expertise is expensive and not available 24/7, even in tertiary hospitals. Other neonatal and pediatric medical professionals (nurses, doctors, etc.) can make erroneous interpretations of highly complex EEG signals. While artificial intelligence (AI) has been widely used to provide objective decision support for EEG analysis, AI decisions are not always explainable. This work developed a solution to combine AI algorithms with a human-centric intuitive EEG interpretation method. Specifically, EEG is converted to sound using an AI-driven attention mechanism. The perceptual characteristics of seizure events can be heard using this method, and an hour of EEG can be analysed in five seconds. A survey that has been conducted among targeted end-users on a publicly available dataset has demonstrated that not only does it drastically reduce the burden of reviewing the EEG data, but also the obtained accuracy is on par with experienced neurophysiologists trained to interpret neonatal EEG. It is also shown that the proposed communion of a medical professional and AI outperforms AI alone by empowering the human with little or no experience to leverage AI attention mechanisms to enhance the perceptual characteristics of seizure events.