bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Ascorbic Acid on Cardiac Surgery-Associated Acute Kidney Injury Incidence
Authors: Djordjevic Anze , Susak Stamenko , Kotnik Petra , Gorenjak Mario , Knez Zeljko , Antonic Miha
Published: May 2022

Objectives Acute kidney injury (AKI) is associated with higher perioperative mortality and morbidity. Oxidative stress has been proposed as a cause of postoperative AKI. Ascorbic acid (AA) supplementation was suggested as a novel and promising antioxidant. The aim of this study was to evaluate the capability of AA to reduce the incidence of postoperative AKI in cardiac surgery patients.

Methods A prospective randomized trial was conducted in patients scheduled for on-pump cardiac surgery. Subjects in the AA group received 2 g of AA intravenously during the induction of anesthesia, 2 g before aortic cross-clamp removal and 1 g every 8 hours for five postoperative days (the JERICA protocol). Postoperatively, the patients were monitored for AKI and other complications. Malondialdehyde levels were monitored in a subpopulation of 100 patients to evaluate the effect of AA on oxidative stress level.

Results The AA and control group consisted of 163 and 169 patients, respectively. The groups were well matched for baseline demographics and had similar intraoperative characteristics. The incidence of AKI in the AA and control group was 20.9 and 28.4%, respectively (p = 0.127). The estimated glomerular filtration rate did not differ between the study groups in the entire postoperative period. There was a trend toward higher malondialdehyde values with statistical significance on postoperative day 1 and lower in-hospital mortality in the AA group (0.6 vs. 4.1%, p = 0.067).

Conclusion Our results do not support the effectiveness of AA supplementation in reducing the incidence of postoperative AKI in on-pump cardiac surgery patients.

Clinical Registration Number This study was registered with the ISRCTN Registry under the trial registration number ISRCTN98572043.
Impact of Second Arterial Conduit on Outcomes Following Coronary Bypass Grafting
Authors: Aboul-Hassan Sleiman Sebastian , Marczak Jakub , Stankowski Tomasz , Moskal Lukasz , Stanislawski Ryszard , Perek Bartlomiej , Cichon Romuald
Published: May 2022

Background The aim of this study was to compare short-term outcomes and long-term survival in patients following coronary artery bypass grafting in whom second arterial conduit or saphenous vein was used as well as to find out the most optimal second arterial graft.

Methods Between January 2006 and June 2018, 7,857 patients met the inclusion criteria and were divided into two groups: single internal thoracic artery (SITA) + Vein group (n = 7,140) and second arterial conduit group (n = 717), of these 537 patients received right internal thoracic artery (RITA) and 180 patients received radial artery (RA). We obtained 701 propensity-matched pairs for final comparison. Short-term outcomes included: 30-day mortality and major adverse cardiac and cerebral events (MACCE), reoperation for bleeding, and deep sternal wound infection (DSWI). The long-term outcome was all-cause mortality.

Results No significant differences were observed between second arterial conduit versus SITA + Vein groups and between RITA versus RA groups in terms of 30-day mortality, 30-day MACCE, reoperation for bleeding, and incidence of DSWI in the matched cohort. The use of second arterial conduit was associated with a significant reduction in long-term mortality by 24% in the matched cohort (hazard ratio [HR]: 0.76; 95% confidence interval [CI]: 0.60–0.96; p = 0.02). RA and RITA as second arterial conduit had comparable long-term mortality (HR: 1.12; 95% CI: 0.69–1.82; p = 0.62).

Conclusion The use of second arterial conduit, irrespective of type, is safe and associated with improved long-term survival compared with the second venous aortocoronary graft.
A thermal convection limit of spiral state in wide-gap spherical Couette flow
Authors: Itano Tomoaki , Goto Fumitoshi , Yoshikawa Kazuki , Sugihara-Seki Masako
Published: May 2022

Symmetries of flow structures are often prescribed by their mechanical instability and geometry. In this study, as an example, we present the homotopy of a rotating threefold spiral state that is robust in a spherical Couette flow toward a hybrid system with thermal stratification effects. The rotating wave state has not yet been confirmed to smoothly connect to the thermal stratification system. Through continuation, the most dangerous mode at a purely spherical Couette flow of m = 4 modes of spherical harmonics is replaced by l = 4 and m = 3 in a purely thermal convective system. For the state obtained at the limit under only the thermal effect, the residual quantities of both the torque to the outer sphere and meridional circulation are discussed in detail.
Simulation of drop impact on substrate with micro-wells
Authors: Islam Ahmed , Sussman Mark , Hu Hui , Lian Yongsheng
Published: May 2022

In this paper, we numerically investigate drop impact on a micro-well substrate to understand the phenomena of non-wettability. The simulation is carried out by solving three-dimensional incompressible Navier–Stokes equations using a density projection method and an adaptive grid refinement algorithm. A very sharp interface reconstruction algorithm, known as the moment-of-fluid method, is utilized to identify the multi-materials and multi-phases present in the computation domain. Our simulations predicted that a micro-well with a deep cavity can significantly reduce a solid–liquid contact in the event of drop impact. The results from the drop impact on the micro-well substrate are compared with results from drop impact on a flat substrate. Significant differences are observed between these two cases in terms of wetted area, spreading ratio, and kinetic energy. Our simulation shows that under the same conditions, a drop is more apt to jump from a micro-well substrate than from a flat surface, resulting in smaller wetted area and shorter contact time. Based on the simulation results, we draw a drop jumping region map. The micro-well substrate has a larger region than the flat surface substrate. Finally, we present a comparative analysis between a flat substrate and a substrate constructed with a dense array of micro-wells and, therefore, show that the array of micro-wells outperforms the smooth substrate with regard to non-wettability and drop wicking capability.
Collisionless jet expanding into vacuum from a circular aperture
Authors: Cai Shiying , Cai Chunpei , Lin Edward , Cooke David L. , Li Jun
Published: May 2022

Collisionless flows expanding into a vacuum from a circular slit are investigated using the gaskinetic theory. Both accurate and approximate expressions to the plume fields along a centerline and a constant radius are obtained, including the density, velocity components, and translational temperature. Special non-dimensional parameters such as the exit semi-opening angle, gas speed ratio at the exit, and positions are included in these expressions. Particle simulations with the direct simulation Monte Carlo method are performed to validate the above results. These expressions are complex and may need computers for evaluations; however, the cost is minor when compared to particle simulations. With the assumptions of a high or low exit speed ratio and small exit angle, simple explicit expressions for properties along the centerline and a constant radius are obtained. The investigations also find out that the cosine law relations can provide fast and crude estimations, but it is not recommended to use the cosine law relation to compute collisionless plume flowfields with a large exit speed.
Dean flow velocity of shear-thickening SiO2 nanofluids in curved microchannels
Authors: Nikdoost Arsalan , Rezai Pouya
Published: May 2022

We report the effects of a curvilinear microchannel width, height, and radius of curvature, as well as the kinematic viscosity and axial velocity of shear-thickening nanofluids, on the average Dean velocity (VDe) of the secondary flow in the microchannel. Manipulation of inertial and Dean drag forces in curvilinear microchannels has enabled high-throughput and high-resolution size-based separation of microparticles and cells in various biomedical applications. VDe plays a deterministic role in the estimation of the Dean drag force and the design of these microfluidic devices. Despite the previous numerical and experimental studies on VDe of Newtonian and shear-thinning viscoelastic fluids, VDe of shear-thickening metallic nanofluids, such as SiO2 nanoparticles in water, in curved microchannels is still unknown. Such shear-thickening fluids are being used in thermal microsystem applications and are on the verge of entering the field of inertial microfluidics for particle and cell sorting. Our investigations have shown that VDe of shear-thickening SiO2–water nanofluids scales directly with the channel width and the fluid axial velocity, while being inversely proportional with the SiO2 concentration and the channel radius of curvature. Our non-dimensional analysis has led to the development of an empirical correlation that relates VDe-based Reynolds number of the nanofluid to the Dean number and the normalized kinematic viscosity of the nanofluid. It provides a significant accuracy in estimating VDe of shear-thickening fluids, compared to application of Newtonian or shear-thinning equations in the literature, which could be useful toward future design of particle and cell sorting and washing microdevices.
Interaction of a shock train with inherent isentropic waves in a curved isolator
Authors: He Li-hao , Chen Hao , Yue Lian-jie , Zhang Qi-fan , Wu Wan-nan
Published: May 2022

Shock-train transitions in simplified curved isolators are carefully studied by simulation. The results show the shock-train behavior is subject to the complex pressure field created by the duct deflection, eventually presenting five modes during a backpressure-varying process. Of them, the most special one is the abrupt shock-train leap. It appears as the leading shocks interact with an adverse pressure gradient and follows a different path after a reversal of the direction the backpressure takes, which causes a shock-train hysteresis. If the curvature increases, the leap phenomenon, together with the related hysteresis, grows in number and intensity. Analysis indicates the background pressure gradients stem from the inherent left-running expansion waves and right-running compression waves. They control alternately the near-wall flow state, provoking the cyclic changes in the pressure gradient sign. Unlike the former, the latter can enhance separation through a positive feedback mechanism, rendering the shock train highly sensitive to backpressure. This is why the leap occurs. Comparing with the previously reported shock-induced leap indicates that there is a marked similarity in their behaviors, suggesting the irrelevance of the occurrence of a leap to the category of incident waves. Nevertheless, a delay in the onset usually follows a compression-wave-typed leap, which reflects that there is a triggering threshold for an incident wave. Given the fact that no local separation is provoked by the compression waves, it is speculated that the threshold should lie below the criterion for causing a separation, as opposed to the impression from the previous research.
Characteristics, phenotypes, mechanisms and management of severe asthma
Authors: Chung Kian Fan , Dixey Piers , Abubakar-Waziri Hisham , Bhavsar Pankaj , Patel Pujan H. , Guo Sujuan , Ji Yang
Published: May 2022

Severe asthma is “asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy.” The state of control was defined by symptoms, exacerbations and the degree of airflow obstruction. Therefore, for the diagnosis of severe asthma, it is important to have evidence for a diagnosis of asthma with an assessment of its severity, followed by a review of comorbidities, risk factors, triggers and an assessment of whether treatment is commensurate with severity, whether the prescribed treatments have been adhered to and whether inhaled therapy has been properly administered. Phenotyping of severe asthma has been introduced with the definition of a severe eosinophilic asthma phenotype characterized by recurrent exacerbations despite being on high dose ICS and sometimes oral corticosteroids, with a high blood eosinophil count and a raised level of nitric oxide in exhaled breath. This phenotype has been associated with a Type-2 (T2) inflammatory profile with expression of interleukin (IL)-4, IL-5, and IL-13. Molecular phenotyping has also revealed non-T2 inflammatory phenotypes such as Type-1 or Type-17 driven phenotypes. Antibody treatments targeted at the T2 targets such as anti-IL5, anti-IL5Rα, and anti-IL4Rα antibodies are now available for treating severe eosinophilic asthma, in addition to anti-immunoglobulin E antibody for severe allergic asthma. No targeted treatments are currently available for non-T2 inflammatory phenotypes. Long-term azithromycin and bronchial thermoplasty may be considered. The future lies with molecular phenotyping of the airway inflammatory process to refine asthma endotypes for precision medicine.
Virologic characterization of symptom rebound following nirmatrelvir-ritonavir treatment for COVID-19
Authors: Boucau Julie , Uddin Rockib , Marino Caitlin , Regan James , Flynn James P. , Choudhary Manish C. , Chen Geoffrey , Stuckwisch Ashley M. , Mathews Josh , Liew May Y. , Singh Arshdeep , Reynolds Zahra , Iyer Surabhi L. , Chamberlin Grace C. , Vyas Tammy D. , Vyas Jatin M. , Turbett Sarah E. , Li Jonathan Z. , Lemieux Jacob E. , Barczak Amy K. , Siedner Mark J.
Published: May 2022

We enrolled seven individuals with recurrent symptoms following nirmatrelvir-ritonavir treatment. High viral loads (median 6.1 log10 copies/mL) were detected at enrollment and for a median of 17 days after initial diagnosis. Three of seven had culturable virus for up to 16 days after initial diagnosis. No known resistance-associated mutations were identified.
Computerized biofeedback to characterize Pupil Cycle Time (PCT) in neuropathies and retinopathies
Authors: Ajasse Suzon , Vignal-Clermont Catherine , Mohand-Saïd Saddek , Coen Cecilia , Romand Carole , Lorenceau Jean
Published: May 2022

Pupillary responses to light offer a convenient and objective way to quickly assess the functional health of the anterior afferent visual pathways. We here present the characteristics of Pupil Cycle Time (PCT) obtained with a computerized biofeedback setting in patients with retinal and optic nerve diseases. The spectral analysis of the sustained pupillary oscillations elicited over 45 seconds of passive fixation of colored displays with different spatial configurations provides relevant information that allow distinguishing patients from healthy participants with good sensitivity and specificity. PCT measures done with this method could complement the current functional examination of chronic ophthalmic diseases whose prevalence worryingly increases worldwide.
Omicron BA.1 and BA.2 Neutralizing Activity Following Pre-Exposure Prophylaxis with Tixagevimab plus Cilgavimab in Vaccinated Solid Organ Transplant Recipients
Authors: Karaba Andrew H. , Kim Jake D. , Chiang Teresa P-Y , Alejo Jennifer L. , Abedon Aura T. , Mitchell Jonathan , Chang Amy , Eby Yolanda , Johnston Trevor Scott , Aytenfisu Tihitina , Hussey Casey , Jefferis Alexa , Fortune Nicole , Abedon Rivka , Thomas Letitia , Warren Daniel S. , Sitaras Ioannis , Pekosz Andrew , Avery Robin K. , Massie Allan B. , Clarke William A. , Tobian Aaron A.R. , Segev Dorry L. , Werbel William A.
Published: May 2022

Neutralizing antibody responses are attenuated in many solid organ transplant recipients (SOTRs) despite SARS-CoV-2 vaccination. Pre-exposure prophylaxis (PrEP) with the monoclonal antibody combination Tixagevimab and Cilgavimab (T+C) might augment immunoprotection, yet activity against Omicron sublineages in vaccinated SOTRs is unknown. Vaccinated SOTRs who received 300+300mg T+C (either single dose or two 150+150mg doses) within a prospective observational cohort submitted pre- and post-injection samples between 1/10/2022-4/4/2022. Binding antibody (anti-receptor binding domain [RBD], Roche) and surrogate neutralization (%ACE2 inhibition; ≥20% connoting neutralizing inhibition, Meso Scale Discovery) were measured against variants including Omicron sublineages BA.1 and BA.2. Data were analyzed using the Wilcoxon matched-pairs signed-rank test and McNemar’s test. Among 61 participants, median (IQR) anti-RBD increased from 424 (IQR <0.8-2322.5) to 3394.5 (IQR 1403.9-7002.5) U/ml post T+C (p<0.001). The proportion demonstrating vaccine strain neutralizing inhibition increased from 46% to 100% post-T+C (p<0.001). BA.1 neutralization was low and did not increase (8% to 16% of participants post-T+C, p=0.06). In contrast, BA.2 neutralization increased from 7% to 72% of participants post-T+C (p<0.001). T+C increased anti-RBD levels, yet BA.1 neutralizing activity was minimal. Encouragingly, BA.2 neutralization was augmented and in the current variant climate T+C PrEP may serve as a useful complement to vaccination in high-risk SOTRs.
Flexible specificity of memory in Drosophila depends on a comparison between choices
Authors: Modi Mehrab N , Rajagopalan Adithya , Rouault Hervé , Aso Yoshinori , Turner Glenn C
Published: May 2022

Memory guides behavior across widely varying environments and must therefore be both sufficiently specific and general. A memory too specific will be useless in even a slightly different environment, while an overly general memory may lead to suboptimal choices. Animals successfully learn to both distinguish between very similar stimuli and generalize across cues. Rather than forming memories that strike a balance between specificity and generality,Drosophilacan flexibly categorize a given stimulus into different groups depending on the options available. We asked how this flexibility manifests itself in the well-characterized learning and memory pathways of the fruit fly. We show that flexible categorization in neuronal activity as well as behavior depends on the order and identity of the perceived stimuli. Our results identify the neural correlates of flexible stimulus-categorization in the fruit fly.

Impact Statement

Flies can optimally recall a memory with high specificity by comparing options close in time, or default to generalization when they cannot.
The N-terminal subunit of vitellogenin in planthopper eggs and saliva acts as a reliable elicitor that induces defenses in rice
Authors: Zeng Jiamei , Ye Wenfeng , Hu Wenhui , Jin Xiaochen , Kuai Peng , Xiao Wenhan , Jian Yukun , Turlings Ted C. J. , Lou Yonggen
Published: May 2022

Vitellogenins are essential for the development and fecundity of insects, but these proteins may also betray them, as we show here. We found that the small N-terminal subunit of vitellogenins of the planthopper Nilaparvata lugens (NlVgN) triggers strong defense responses in rice plants when it enters the plant during feeding or oviposition by the insect. The defenses induced by NlVgN in plants not only decreased the hatching rate of N. lugens eggs, but also induced volatile emissions in rice plants, which rendered them attractive to a common egg parasitoid. VgN of other planthoppers were found to trigger the same defense responses in rice. We further show that VgN deposited during planthopper feeding compared to during oviposition induces a somewhat different response, probably targeting the appropriate developmental stage of the insect. The key importance of VgN for planthopper performance precludes possible evolutionary adaptions to prevent detection by rice plants.
Changes in oscillations in anterior cingulate and medial prefrontal cortex are associated with altered signatures of Bayesian predictive coding in trait anxiety
Authors: Hein Thomas P , Gong Zheng , Ivanova Marina , Fedele Tommaso , Nikulin Vadim , Ruiz Maria Herrojo
Published: May 2022

Recent advances in the computational understanding of decision-making processes have led to proposals that anxiety biases how individuals form beliefs and estimate uncertainty. The anxiety and decision-making circuitry broadly overlap in regions such as the medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), and orbitofrontal cortex (OFC). Changes in activity across these brain areas could help explain how misestimation of uncertainty and altered belief updating can lead to impaired learning in anxiety. To test this prediction, this study built on recent progress in rhythm-based formulations of Bayesian predictive coding to identify sources of oscillatory modulations across the ACC, mPFC, and OFC that are associated with altered learning in subclinical trait anxiety. In a magnetoencephalography (MEG) experiment, two groups of human participants pre-screened with high and low trait anxiety (HTA, LTA: 39) performed a volatile probabilistic reward-based learning task. We modelled behaviour using a hierarchical Bayesian learning model. Furthermore, we quantified the parametric effects of trial-wise estimates of unsigned precision-weighted prediction errors (pwPEs) and, separately, precision weights and surprise on source-reconstructed MEG time-frequency responses using convolution modelling. We showed that HTA interferes with overall reward-based learning performance associated with more stochastic decisions and more pronounced lose-shift tendencies. These behavioural effects were explained by an overestimation of volatility and faster belief updating in HTA when compared to LTA. On a neural level, we observed enhanced gamma responses and decreased alpha/beta activity in HTA during the encoding of unsigned pwPEs about about stimulus outcomes relative to LTA. These effects emerged primarily in the ACC and dorsomedial PFC (dmPFC), and they were accompanied by additional ACC alpha/beta modulations representing differential encoding of precision weights in each anxiety group. Our study supports the association between subclinical trait anxiety and faster updating of beliefs in a volatile environment through gamma and alpha/beta activity changes in the ACC and dmPFC.
Establishment of a colony of Anopheles darlingi from French Guiana for vector competence studies on malaria transmission
Authors: Puchot Nicolas , Lecoq Marie-Thérèse , Carinci Romuald , Duchemin Jean Bernard , Gendrin Mathilde , Bourgouin Catherine
Published: May 2022

Anopheles darlingi is a major vector of both Plasmodium falciparum and Plasmodium vivax in South and Central America. However, vector competence and physiology of this mosquito species have been scarcely studied due to difficulties in rearing it in the laboratory. Here, we report the successful establishment of a robust colony, from mosquito collection in French Guiana. We describe our mosquito colonization procedure with relevant information on environmental conditions, mating ability, larval development and survival, recorded over the first six critical generations. Experimental infection showed that our An. darlingi colony has a moderate permissiveness to in vitro produced gametocytes of the P. falciparum NF54 strain originating from Africa. This colony, that has reached its 20th generation, will allow further characterization of An. darlingi life-history traits and of Plasmodium-mosquito interactions with South American malaria parasites.
Lesion Localization of Time Disorientation in Patients With Focal Brain Damage
Authors: Skye J. , Bruss J. , Herbet G. , Tranel D. , Boes AD.
Published: May 2022

Background and Objectives

Time orientation is a fundamental cognitive process in which one’s personal sense of time is matched with a universal reference. Assessment of time orientation is a ubiquitous component of neurological mental status examinations and neuropsychological assessments, yet its neural correlates remain unclear. Large bilateral lesions have been associated with deficits in time orientation, but more specific regions of the brain implicated in time disorientation following focal unilateral damage are relatively unknown. The current study investigates the anatomy of time disorientation and its network correlates in patients with focal brain lesions.

Methods

550 patients with acquired, focal brain lesions participated in this study, identified retrospectively from the Iowa Neurological Patient Registry. Time orientation was assessed 3 months or more after lesion onset using the Benton Temporal Orientation Test (BTOT), and 39 patients were identified as having chronic impairment in time orientation defined as a score of 3 or worse on the BTOT. Multivariate lesion-symptom mapping and lesion network mapping were used to evaluate the anatomy and networks associated with time disorientation. Performance on a variety of neuropsychological tests was compared between the time oriented and time disoriented group.

Results

39 patients were identified as having chronic impairment in time orientation. Multivariate lesion-symptom mapping showed that lesions of the posterior cortices were associated with impaired time orientation, including medial temporal lobes, occipitotemporal cortex, and precuneus (r=0.21, p<.001). Individuals with time disorientation tended to have concomitant impairments in memory, visuospatial ability, and naming. Follow-up analyses of individuals with unilateral lesions and those with relatively unimpaired cognition in other domains implicated the precuneus and parahippocampal gyrus in time orientation. Lesion network mapping demonstrated that these regional findings occurred at nodes of the default mode and visual networks. Individuals with time disorientation tended to have concomitant impairments in memory, visuospatial ability, and naming.

Discussion

We interpret these findings as novel evidence for the role of posteromedial cortices extending from the precuneus to the medial temporal lobe in supporting time orientation.
Immunogenicity and Safety of Beta Adjuvanted Recombinant Booster Vaccine
Authors: Launay Odile , Cachanado Marine , Nguyen Liem B Luong , Ninove Laetitia , Lachâtre Marie , Ben Ghezala Inès , Bardou Marc , Schmidt-Mutter Catherine , Felten Renaud , Lacombe Karine , Surgers Laure , Laine Fabrice , Allain Jean-Sébastien , Botelho-Nevers Elisabeth , Tavolacci Marie-Pierre , Chidiac Christian , Pavese Patricia , Dussol Bertrand , Priet Stéphane , Deplanque Dominique , Touati Amel , Curci Laureen , Konate Eleine , Hamouda Nadine Ben , Besbes Anissa , Nubret Eunice , Capelle Florence , Berard Laurence , Rousseau Alexandra , Tartour Eric , Simon Tabassome , de Lamballerie Xavier
Published: May 2022

Background

Variant-adaptated vaccines against coronavirus disease 2019 (COVID-19) as boosters are needed to increase a broader protection against SARS CoV-2 variants. New adjuvanted recombinant protein vaccines as heterologous boosters could maximize the response.

Methods

In this randomized, single-blinded, multicenter trial, adults who had received two doses of Pfizer-BioNTech mRNA vaccine (BNT162b2) 3 to7 months before were randomly assigned to receive a boost of BNT162b2, Sanofi/GSK SARS-CoV-2 adjuvanted recombinant protein MV D614 (monovalent parental formulation) or SARS-CoV-2 adjuvanted recombinant protein MV B.1.351 vaccine (monovalent Beta formulation). The primary endpoint was the percentage of subjects with a ≥10-fold increase in neutralizing antibody titers for the Wuhan (D614) and B.1.351 (Beta) SARS-CoV-2 viral strains between day 0 and day 15.

Findings

The percentages of participants whose neutralizing antibody titers against the Wuhan (D614) SARS-CoV-2 strain increased by a factor ≥10 between day 0 and day 15 was 55.3% (95% CI 43.4-66.7) in MV D614 group (n=76), 76.1% (64.5-85.4) in MV B.1.351 (Beta) group (n=71) and 63.2% (51.3-73.9) in BNT162b2 group (n=76). These percentages were 44.7% (33.3-56.6), 84.5% (74.0-92.0) and 51.3% (39.6-63.0) for the B.1.351 (Beta) viral strain, respectively. Higher neutralizing antibodies rates against Delta and Omicron BA.1 variants were also elicited after Sanofi/GSK MV Beta vaccine compared to the other vaccines. Comparable reactogenicity profile was observed with the three vaccines.

Interpretation

Heterologous boosting with the Sanofi/GSK Beta formulation vaccine resulted in a higher neutralizing antibody response against Beta variant but also the original strain and Delta and Omicron BA.1 variants, compared with mRNA BNT162b2 vaccine or the Sanofi/GSK MVD614 formulation. New vaccines containing Beta spike protein may represent an interesting strategy for broader protection against SARS CoV-2 variants.

Funding

French Ministries of Solidarity and Health and Research and Sanofi

Trial registration number

ClinicalTrials.gov identifier NCT05124171; EudraCT identifier 2021-004550-33.
Altered brain activity and functional connectivity after MDMA-assisted therapy for post-traumatic stress disorder
Authors: Singleton S. Parker , Wang Julie B. , Mithoefer Michael , Hanlon Colleen , George Mark S. , Mithoefer Annie , Mithoefer Oliver , Coker Allison R. , Yazar-Klosinski Berra , Emerson Amy , Doblin Rick , Kuceyeski Amy
Published: May 2022

3,4-methylenedioxymethamphetamine-assisted therapy (MDMA-AT) for post-traumatic stress disorder (PTSD) has demonstrated promise in multiple clinical trials. MDMA is hypothesized to facilitate the therapeutic process, in part, by decreasing fear response during fear memory processing while increasing extinction learning. The acute administration of MDMA in healthy controls modifies recruitment of brain regions involved in the hyperactive fear response in PTSD such as the amygdala, hippocampus, and insula. However, to date there have been no neuroimaging studies aimed at directly elucidating the neural impact of MDMA-AT in PTSD patients. We analyzed brain activity and connectivity via functional MRI during both rest and autobiographical memory (trauma and neutral) response before and two-months after MDMA-AT in nine veterans and first-responders with chronic PTSD of 6 months or more. We hypothesized that MDMA-AT would increase amygdala-hippocampus resting-state functional connectivity, however we only found evidence of a trend in the left amygdala – left hippocampus (t= -2.91, uncorrected p = 0.0225, corrected p = 0.0901). We also found reduced activation contrast (trauma > neutral) after MDMA-AT in the cuneus. Finally, the amount of recovery from PTSD after MDMA-AT correlated with changes in four functional connections during autobiographical memory recall: the left amygdala – left posterior cingulate cortex (PCC), left amygdala – right PCC, left amygdala – left insula, and left isthmus cingulate – left posterior hippocampus. Amygdala – insular functional connectivity is reliably implicated in PTSD and anxiety, and both regions are impacted by MDMA administration. These findings compliment previous research indicating that amygdala, hippocampus, and insula functional connectivity is a potential target of MDMA-AT, and highlights other regions of interest related to memory processes. More research is necessary to determine if these findings are specific to MDMA-AT compared to other types of treatment for PTSD.

This study:NCT02102802Parent-study:NCT01211405
Modelling the impacts of public health interventions and weather on SARS-CoV-2 Omicron outbreak in Hong Kong
Authors: Yuan Hsiang-Yu , Liang Jingbo
Published: May 2022

Background

Hong Kong, has operated under a zero-Covid policy in the past few years. As a result, population immunity from natural infections has been low. The ‘fifth wave’ in Hong Kong, caused by the Omicron variant, grew substantially in February 2022 during the transition from winter into spring. The daily number of reported cases began to decline quickly in a few days after social distancing regulations were tightened and rapid antigen test (RAT) kits were largely distributed. How the non-pharmaceutical interventions (NPIs) and seasonal factors (temperature and relative humidity) could affect the spread of Omicron remains unknown.

Methods

We developed a model with stratified immunity, to incorporate antibody responses, together with changes in mobility and seasonal factors. After taking into account the detection rates of PCR test and RAT, we fitted the model to the daily number of reported cases between 1 February and 31 March, and quantified the associated effects of individual NPIs and seasonal factors on infection dynamics.

Findings

Although NPIs and vaccine boosters were critical in reducing the number of infections, temperature was associated with a larger change in transmissibility. Cold days appeared to drive Re from about 2–3 sharply to 10.6 (95%CI: 9.9–11.4). But this number reduced quickly below one a week later when the temperature got warmer. The model projected that if weather in March maintained as February’s average level, the estimated cumulative incidence could increase double to about 80% of total population.

Interpretation

Temperature should be taken into account when making public health decisions (e.g. a more relaxed (or tightened) social distancing during a warmer (or colder) season).
Multi-omics empowered deep phenotyping of ulcerative colitis
Authors: Janker Lukas , Schuster Dina , Bortel Patricia , Hagn Gerhard , Brunmair Julia , Meier-Menches Samuel M. , Mader Johanna C. , Slany Astrid , Bileck Andrea , Madl Christian , Unger Lukas , Hennlich Barbara , Weitmayr Barbara , Del Favero Giorgia , Pils Dietmar , Pukrop Tobias , Pfisterer Nikolaus , Feichtenschlager Thomas , Gerner Christopher
Published: May 2022

Objective

Ulcerative colitis (UC) is a chronic disease with rising incidence and unclear etiology. The application of mass spectrometry-based analysis methods shall support the establishment of systemic molecular biomarker signatures providing status information with regard to individual UC pathomechanisms.

Design

UC pathomechanisms were assessed by proteome profiling of human tissue specimen, obtained from five distinct colon locations each of 12 patients. Systemic disease-associated alterations were investigated in a cross-sectional setting by mass spectrometry-based multi-omics analyses comprising proteins, metabolites and eicosanoids of plasma obtained from UC patients during disease and upon remission in comparison to healthy controls.

Results

Tissue proteome profiling identified colitis-associated activation of neutrophils, macrophages, B- and T-cells, fibroblasts, endothelial cells and platelets, and indicated hypoxic stress, as well as a general downregulation of mitochondrial proteins accompanying the establishment of apparent wound healing-promoting activities including scar formation. While the immune cells mainly contributed pro-inflammatory proteins, the colitis-associated epithelial cells, fibroblasts, endothelial cells and platelets predominantly formed anti-inflammatory and wound healing-promoting proteins. Blood plasma proteomics indicated chronic inflammation and platelet activation, whereas plasma metabolomics identified disease-associated deregulation of bile acids, eicosanoids and gut microbiome-derived metabolites. Upon remission, several, but not all, molecular candidate biomarker levels recovered to normal levels. These findings may indicate that pathomechanisms related to gut functions, gut microbiome status, microvascular damage and metabolic dysregulation associated with hypoxia may not resolve uniformly during remission.

Conclusions

This study integrates and expands the knowledge about local and systemic effects of UC and identifies biomarker profiles related to molecular UC pathomechanisms.
Impact of the COVID-19 pandemic on Latino families with Alzheimer’s disease and related dementias: Perceptions of family caregivers and primary care providers
Authors: Perales-Puchalt Jaime , Peltzer Jill , Fracachan-Cabrera Monica , Perez Adriana , Ramirez-Mantilla Mariana , Greiner K Allen , Burns Jeffrey M
Published: May 2022

Latinos experience disproportionately poor outcomes in dementia and COVID-19, which may synergistically impact their health. We explored the impact of the COVID-19 pandemic among Latino families with dementia via a qualitative descriptive study of 21 informal caregivers of Latinos with dementia and 24 primary care providers. Two themes arose: The impact of a global pandemic (e.g., accelerated cognitive and physical decline, or caregivers choosing between risking finances and the family’s infection given the work situation) and Developing resilience to the effects of the pandemic (e.g., caregivers seeking vaccination sites, moving in with the care recipient and adopting telehealth).
Associations of Sputum Biomarkers with Clinical Outcomes in People with Cystic Fibrosis
Authors: Liou Theodore G , Argel Natalia , Asfour Fadi , Brown Perry S , Chatfield Barbara A , Cox David R , Daines Cori L , Durham Dixie , Francis Jessica A , Glover Barbara , Helms My , Heynekamp Theresa , Hoidal John R , Jensen Judy L , Kartsonaki Christiana , Keogh Ruth , Kopecky Carol M , Lechtzin Noah , Li Yanping , Lysinger Jerimiah , Molina Osmara , Nakamura Craig , Packer Kristyn A , Paine Robert , Poch Katie R , Quittner Alexandra L , Radford Peggy , Redway Abby J , Sagel Scott D , Szczesniak Rhonda D , Sprandel Shawna , Taylor-Cousar Jennifer L , Vroom Jane B , Yoshikawa Ryan , Clancy John P , Elborn J Stuart , Olivier Kenneth N , Adler Frederick R
Published: May 2022

Background

Airway inflammation promotes bronchiectasis and lung injury in cystic fibrosis (CF). Amplification of inflammation underlies pulmonary exacerbations of disease. We asked whether sputum inflammatory biomarkers provide explanatory information on pulmonary exacerbations.

Patients and Methods

We collected sputum from randomly chosen stable adolescents and adults and prospectively observed time to next exacerbation, our primary outcome. We evaluated relationships between potential biomarkers of inflammation, clinical characteristics and outcomes and assessed clinical variables as potential confounders or mediators of explanatory models. We assessed associations between the markers and time to next exacerbation using proportional hazard models adjusting for confounders.

Results

We enrolled 114 patients, collected data on clinical variables [December 8, 2014 to January 16, 2016; 46% male, mean age 28 years (SD 12), mean percent predicted forced expiratory volume in 1 s (FEV1%) 70 (SD 22)] and measured 24 inflammatory markers. Half of the inflammatory markers were plausibly associated with time to next exacerbation. Age and sex were confounders while we found that FEV1% was a mediator.

Three potential biomarkers of RAGE axis inflammation were associated with time to next exacerbation while six potential neutrophil-associated biomarkers indicate associations between protease activity or reactive oxygen species with time to next exacerbation.

Conclusion

Pulmonary exacerbation biomarkers are part of the RAGE proinflammatory axis or reflect neutrophil activity, specifically implicating protease and oxidative stress injury. Further investigations or development of novel anti-inflammatory agents should consider RAGE axis, protease and oxidant stress antagonists.

Tweetable abstract

Sputum from 114 randomly chosen people with CF show RAGE axis inflammation, protease and oxidative stress injury are associated with time to next pulmonary exacerbation and may be targets for bench or factorial design interventional studies. (242 characters)
Correlates of Daytime Sleepiness and Insomnia among Adults in Samoa
Authors: Heinsberg Lacey W. , Carlson Jenna C. , Pomer Alysa , Cade Brian E. , Naseri Take , Reupena Muagututia Sefuiva , Weeks Daniel E. , McGarvey Stephen T. , Redline Susan , Hawley Nicola L.
Published: May 2022

Objective

To describe daytime sleepiness and insomnia among adults in Samoa and identify modifiable factors associated with these measures.

Design/setting

Cross-sectional analysis of data from the Soifua Manuia (“Good Health”) study (n=519, 55.1% female); Upolu island, Samoa.

Methods

Daytime sleepiness and insomnia were assessed with the Epworth Sleepiness Scale (ESS) and the Women’s Health Initiative Insomnia Rating Scale (WHIIRS), respectively. Detailed physical, sociodemographic, and behavioral factors were collected. Sleep measures were characterized using multiple linear regression with backwards elimination and a bootstrap stability investigation.

Results

Excessive daytime sleepiness (ESS>10) and insomnia (WHIIRS>10) were reported by 20% and 6.3% of the sample, respectively. ESS scores were higher in individuals reporting more physical activity (Estimate=1.88; 95% CI=1.12 to 2.75), higher material wealth (0.18; 0.09 to 0.28), and asthma (2.85; 1.25 to 4.51). ESS scores were lower in individuals residing in periurban versus urban regions (−1.43; −2.39 to −0.41), reporting no work versus day shift work (−2.26; −3.07 to −1.41), and reporting greater perceived stress (−0.14; −0.23 to −0.06). WHIIRS scores were lower in individuals reporting “other” shift work (split/irregular/on-call/rotating) versus day shift work (−1.96; −2.89 to −1.14) and those who perceived their village’s wealth to be poor/average versus wealthy (−0.94; −1.50 to −0.34).

Conclusions

Participants had a generally higher prevalence of excessive daytime sleepiness, but lower prevalence of insomnia, compared with individuals from high-income countries. Factors associated with sleep health differed compared with prior studies, emphasizing potential cultural/environmental differences and the need for targeted interventions to improve sleep health in this setting.
Research topics and trends of lumbar spondylolisthesis: a bibliometric study with machine-learning based text mining
Authors: Fan Guoxin , Qin Jiaqi , Li Yufeng , Yang Sheng , Huang Longfei , Liu Huaqing , He Shisheng , Liao Xiang
Published: May 2022

Objectives

The study aimed to conduct a bibliometric analysis of publications concerning lumbar spondylolisthesis, as well as explore its research topics and trends with machine-learning based text mining.

Methods

The data were extracted from the Web of Science Core Collection (WoSCC) database and analyzed in Rstudio1.3.1. Annual publication production and the top 20 productive authors over time were presented. Additionally, top 20 productive journals and top 20 impact journals were compared by spine-subspecialty or not. Similarly, top 20 productive countries/regions and top 20 impact countries/regions were compared by developed countries/regions or not. The collaborative relationship among countries and the research trends in the past decade were presented by R package “Bibliometrix”. Latent Dirichlet allocation (LDA) analysis was conducted to classify main topics of lumbar spondylolisthesis.

Result

Up to 2021, a total number of 4990 articles concerning lumbar spondylolisthesis were finally included for analysis. Spine-subspecialty journals were found to be dominant in productivity and impact of the field, and SPINE, EUROPEAN SPINE JOURNAL and JOURNAL OF NEUROSURGERY-SPINE were the top 3 productive and the top 3 impact journals in this field. USA, China and Japan have contributed to over half of the publication productivity, but European countries seemed to publish more influential articles. It seemed that developed countries/regions tended to produce more articles as well as high influential articles, and international collaborations focused on USA, Europe and eastern Asia. Publications concerning emerging surgical technique was the major topic, followed by radiographic measurement and epidemiology for this field. Cortical bone trajectory, oblique lumbar interbody fusion, oblique lateral lumbar interbody fusion, lateral lumbar interbody fusion, degenerative lumbar spondylolisthesis, adjacent segment disease, spinal canal stenosis, minimally invasive transforaminal lumbar interbody fusion and percutaneous pedicle screw were the recent hotspots over the past 5 years.

Conclusions

The study successfully summarized the productivity and impact of different countries/regions and journals, which should benefit the journal selection and pursuit of international collaboration for researcher who were interested in the field of lumbar spondylolisthesis. Additionally, the current study may encourage more researchers in the field and somewhat inform their research direction in the future.
Development and Validation of a Metabolite Index for Obstructive Sleep Apnea across Race/Ethnicities
Authors: Zhang Ying , Ngo Debby , Yu Bing , Shah Neomi A. , Chen Han , Ramos Alberto R. , Zee Phyllis C. , Tracy Russell , Durda Peter , Kaplan Robert , Daviglus Martha L. , Rich Stephen S. , Rotter Jerome I. , Cai Jianwen , Clish Clary , Gerszten Robert , Kristal Bruce S. , Gharib Sina A. , Redline Susan , Sofer Tamar
Published: May 2022

Background

Obstructive sleep apnea (OSA) is a common disorder characterized by recurrent episodes of upper airway obstruction during sleep resulting in oxygen desaturation and sleep fragmentation, and associated with increased risk of adverse health outcomes. Metabolites are being increasingly used for biomarker discovery and evaluation of disease processes and progression. Studying metabolomic associations with OSA in a diverse community-based cohort may provide insights into the pathophysiology of OSA. We aimed to develop and replicate a metabolite index for OSA and identify individual metabolites associated with OSA.

Methods and Findings

We studied 219 metabolites and their associations with the apnea hypopnea index (AHI) and with moderate-severe OSA (AHI≥15) in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) (n=3507) using two methods: (1) association analysis of individual metabolites, and (2) least absolute shrinkage and selection operator (LASSO) regression to identify a subset of metabolites jointly associated with OSA, and develop a metabolite index for OSA. Results were validated in the Multi-Ethnic Study of Atherosclerosis (MESA) (n=475). When assessing the associations with individual metabolites, we identified seven metabolites significantly positively associated with OSA in HCHS/SOL (FDR p<0.05), of which four associations - glutamate, oleoyl-linoleoyl-glycerol (18:1/18:2), linoleoyl-linoleoyl- glycerol (18:2/18:2) and phenylalanine, replicated in MESA (one sided-p<0.05). The OSA metabolite index, composed of 14 metabolites, was associated with 50% increase of risk for moderate-severe OSA (OR=1.50 [95% CI: 1.21-1.85] per 1 SD of OSA metabolite index,p<.001) in HCHS/SOL and 44% increased risk (OR=1.55 [95% CI: 1.10-2.20] per 1 SD of OSA metabolite index,p=0.013) in MESA, both adjusted for demographics, lifestyle, and comorbidities. Similar albeit less significant associations were observed for AHI.

Conclusions

We developed a metabolite index that replicated in an independent multi-ethnic dataset, demonstrating the robustness of metabolomic-based OSA index to population heterogeneity. Replicated metabolite associations may provide insights into OSA-related molecular and metabolic mechanisms.