bluuebunny/crossref_metadata_2025 huggingface dataset:
The cosmic evolution of binary black holes in young, globular, and nuclear star clusters: rates, masses, spins, and mixing fractions
Authors: Mapelli Michela , Bouffanais Yann , Santoliquido Filippo , Arca Sedda Manuel , Artale M Celeste
Published: February 2022

The growing population of binary black holes (BBHs) observed by gravitational wave (GW) detectors is a potential Rosetta stone for understanding their formation channels. Here, we use an upgraded version of our semi-analytical codes fastcluster and cosmo$\mathcal {R}$ate to investigate the cosmic evolution of four different BBH populations: isolated BBHs and dynamically formed BBHs in nuclear star clusters (NSCs), globular clusters (GCs), and young star clusters (YSCs). With our approach, we can study different channels assuming the same stellar and binary input physics. We find that the merger rate density of BBHs in GCs and NSCs is barely affected by stellar metallicity (Z), while the rate of isolated BBHs changes wildly with Z. BBHs in YSCs behave in an intermediate way between isolated and GC/NSC BBHs. The local merger rate density of Nth-generation black holes (BHs), obtained by summing up hierarchical mergers in GCs, NSCs, and YSCs, ranges from ∼1 to ∼4 Gpc−3 yr−1 and is mostly sensitive to the spin parameter. We find that the mass function of primary BHs evolves with redshift in GCs and NSCs, becoming more top-heavy at higher z. In contrast, the primary BH mass function almost does not change with redshift in YSCs and in the field. This signature of the BH mass function has relevant implications for Einstein Telescope and Cosmic Explorer. Finally, our analysis suggests that multiple channels contribute to the BBH population of the second GW transient catalogue.
Genesis of morpho-kinematic lopsidedness in minor merger of galaxies
Authors: Ghosh Soumavo , Saha Kanak , Jog Chanda J , Combes Francoise , Di Matteo Paola
Published: February 2022

An m = 1 lopsided asymmetry is common in disc galaxies. Here, we investigate the excitation of an m = 1 lopsidedness in host galaxies during minor mergers while choosing a set of 1:10 merger models (with varying orbital configurations, morphology of the host galaxy) from the GalMer galaxy merger library. We show that a minor merger triggers a prominent m = 1 lopsidedness in stars of the host galaxy. The strength of the m = 1 lopsidedness undergoes a transient amplification phase after each pericenter passage of the satellite, in concordance with past findings of exciting an m = 1 lopsidedness by tidal encounters. However, once the merger happens, and the post-merger remnant readjusts itself, the lopsidedness disappears in short time-scale (∼ 500 − 850 ${{\rm Myr}}$). Furthermore, a delayed merger can drive a prolonged (∼2 ${\rm Gyr}$) lopsidedness in the host galaxy. We demonstrate that the m = 1 lopsidedness rotates with a well-defined pattern speed which is much slower than the m = 2 bar pattern speed, and is retrograde with respect to the bar. This gives rise to a dynamical scenario where the Inner Lindblad resonance of the m = 1 lopsidedness falls in between the corotation and the Outer Lindblad resonance of the m = 2 bar mode. A kinematic lopsidedness also arises in the host galaxy; the resulting temporal variation closely follows that of the density lopsidedness. The minor merger also triggers a transient off-centred stellar disc-dark matter halo configuration due to the tidal encounter with the satellite.
KaRMMa– kappa reconstruction for mass mapping
Authors: Fiedorowicz Pier , Rozo Eduardo , Boruah Supranta S , Chang Chihway , Gatti Marco
Published: February 2022

We present KaRMMa, a novel method for performing mass map reconstruction from weak-lensing surveys. We employ a fully Bayesian approach with a physically motivated lognormal prior to sample from the posterior distribution of convergence maps. We test KaRMMa on a suite of dark matter N-body simulations with simulated DES Y1-like shear observations. We show that KaRMMa outperforms the basic Kaiser–Squires mass map reconstruction in two key ways: (1) our best map point estimate has lower residuals compared to Kaiser–Squires; and (2) unlike the Kaiser–Squires reconstruction, the posterior distribution of KaRMMa maps is nearly unbiased in all summary statistics we considered, namely: one-point and two-point functions, and peak/void counts. In particular, KaRMMa successfully captures the non-Gaussian nature of the distribution of κ values in the simulated maps. We further demonstrate that the KaRMMa posteriors correctly characterize the uncertainty in all summary statistics we considered.
A mobile restriction–modification system provides phage defence and resolves an epigenetic conflict with an antagonistic endonuclease
Authors: Birkholz Nils , Jackson Simon A , Fagerlund Robert D , Fineran Peter C
Published: February 2022

Epigenetic DNA methylation plays an important role in bacteria by influencing gene expression and allowing discrimination between self-DNA and intruders such as phages and plasmids. Restriction–modification (RM) systems use a methyltransferase (MTase) to modify a specific sequence motif, thus protecting host DNA from cleavage by a cognate restriction endonuclease (REase) while leaving invading DNA vulnerable. Other REases occur solitarily and cleave methylated DNA. REases and RM systems are frequently mobile, influencing horizontal gene transfer by altering the compatibility of the host for foreign DNA uptake. However, whether mobile defence systems affect pre-existing host defences remains obscure. Here, we reveal an epigenetic conflict between an RM system (PcaRCI) and a methylation-dependent REase (PcaRCII) in the plant pathogen Pectobacterium carotovorum RC5297. The PcaRCI RM system provides potent protection against unmethylated plasmids and phages, but its methylation motif is targeted by the methylation-dependent PcaRCII. This potentially lethal co-existence is enabled through epigenetic silencing of the PcaRCII-encoding gene via promoter methylation by the PcaRCI MTase. Comparative genome analyses suggest that the PcaRCII-encoding gene was already present and was silenced upon establishment of the PcaRCI system. These findings provide a striking example for selfishness of RM systems and intracellular competition between different defences.
Cardiac magnetic resonance in systemic sclerosis myocarditis: the value of T2 mapping to detect myocardial inflammation
Authors: De Luca Giacomo , Palmisano Anna , Campochiaro Corrado , Vignale Davide , Cavalli Giulio , Bruno Elisa , Sartorelli Silvia , Ferlito Arianna , Peretto Giovanni , Sala Simone , Matucci-Cerinic Marco , Dagna Lorenzo , Esposito Antonio
Published: February 2022

Objectives

Myocarditis in SSc is associated with a poor prognosis. Cardiac magnetic resonance (CMR) is the non-invasive diagnostic modality of choice for SSc myocarditis. Our study investigates the performance of the mapping techniques included in the revised Lake Louise criteria (LLC) for the identification of SSc myocarditis.

Methods

CMR data (right and left ventricular function and morphology, early and late gadolinium enhancement [LGE], T2 ratio, and T1 mapping, extracellular volume [ECV] and T2 mapping) of SSc patients diagnosed with myocarditis were reviewed. Myocarditis was defined by the presence of symptoms of SSc heart involvement with increased high-sensitive troponin T (hs-TnT) and/or NT-proBNP and at least an abnormality at 24 h ECG Holter and/or echocardiography and/or CMR. A P-value < 0.05 was considered as statistically significant.

Results

Nineteen patients (median age 54 [46–70] years; females 78.9%; diffuse SSc 52.6%; anti-Scl70+ 52.6%) were identified: 11 (57.9%) had echocardiographic, and 8 (42.8%) 24 h ECG Holter abnormalities. All patients had at least one CMR abnormality: LGE in 18 (94.7%), increased ECV in 10 (52.6%) and T2 mapping >50 ms in 15 (78.9%). Median T1 and T2 mapping were 1085 [1069–1110] ms and 53.1 [52–54] ms, respectively. T1 mapping directly correlated with NT-proBNP (r = 0.620; P = 0.005), ESR (r = 0.601; P = 0.008), CRP (r = 0.685; P = 0.001) and skin score (r = 0.507; P = 0.027); ECV correlated with NT-proBNP serum levels (r = 0.702; P = 0.001). No correlations emerged between T2 mapping and other parameters. Ten patients satisfied the 2009 LLC, 17 the 2018 LLC. With the new criteria including T2 mapping, the sensitivity improved from 52.6% to 89.5%.

Conclusion

The CMR mapping techniques improve the sensitivity to detect myocardial inflammation in patients with SSc heart involvement. The evaluation of T2 mapping increases diagnostic accuracy for the recognition of myocardial inflammation in SSc.
Semaglutide for weight loss and cardiometabolic risk reduction in overweight/obesity
Authors: Mares Adriana C. , Chatterjee Saurav , Mukherjee Debabrata
Published: February 2022

Purpose of review

Cardiovascular disease is the most common cause of morbidity and mortality worldwide, and the risk is heightened in the presence of obesity. We review semaglutide, a drug recently approved for chronic weight management in adults with obesity or who are overweight.

Recent findings

On 4 June 2021, the US Food and Drug Administration approved semaglutide injection at 2.4 mg once weekly for chronic weight management in adults with obesity or overweight with at least one weight-related condition such as high blood pressure, type 2 diabetes mellitus, or high cholesterol. This subcutaneous injection is the first approved drug for chronic weight management in adults with general obesity or overweight since 2014. The drug is indicated for weight management in patients with a BMI of 27 kg/m2 or greater who have at least one weight-related ailment or in patients with a BMI of 30 kg/m2 or greater.

Semaglutide offers adults with obesity or overweight a new treatment in conjunction with a weight management program consisting of reduced calorie diet and increased physical activity.
OUTCOMES OF RETROPUPILLARY IRIS CLAW INTRAOCULAR LENS IMPLANTATION COMBINED WITH PARS PLANA VITRECTOMY
Authors: Zaleski Marta , Stahel Marc , Eberhard Roman , Alexander Blum Robert , Barthelmes Daniel
Published: February 2022

Purpose:

To report 12-month visual outcomes, incidence of intraocular pressure (IOP) changes and postoperative complications after pars plana vitrectomy with retropupillary implantation of an iris claw intraocular lens (IOL) in aphakic eyes after complicated cataract surgery and eyes with a dislocation of the IOL.

Methods:

This is a retrospective analysis of eyes undergoing implantation of an iris claw IOL combined with pars plana vitrectomy from 1st of January 2009 until 30th of June 2018 after complicated cataract extraction with capsular loss (Group A) or dislocation of an IOL (Group B). Corrected distance visual acuity was analyzed in logarithm of the minimum angle of resolution (logMAR) units, IOP was recorded in mmHg.

Results:

Eyes in Group A (n = 49) improved from a preoperative median visual acuity of 0.523 logMAR (Snellen 20/65) to 0.201 logMAR (Snellen 20/30), P < 0.01. Eyes in Group B (n = 126) showed stable median visual acuity, preoperative 0.301 logMAR (Snellen 20/40) versus postoperative 0.222 logMAR (Snellen 20/30), P > 0.05. During 12 months in Group A, IOP >21 mmHg occurred in 9 (18.4%) eyes; no eye had an IOP <6 mmHg. In Group B, IOP >21 mmHg occurred in 15 (11.9%) eyes, IOP <6 mmHg in 5 (4%) cases. None of the eyes in Group A and B had IOP >21 mmHg or <6 mmHg at 12 months follow-up.

Conclusion:

The retropupillary implantation of an iris claw IOL with pars plana vitrectomy provides adequate visual rehabilitation and seems to be safe in IOP changes.
Risk Factors and Treatment of Clostridioides difficile in Pediatric Patients
Authors: Nang Catherine
Published: February 2022

The purpose of this article is to discuss the pharmacological causes of pediatric Clostridioides difficile infection (CDI) and the treatment options available to clinicians. The authors identify antibiotic classes and antacids and how they interfere with normal gastrointestinal processes to cause CDI. In addition, the treatment algorithm for pediatric patients, which differs slightly from adults, is presented. Choosing the appropriate medication is imperative in reducing symptoms, recurrence, and optimizing treatment of CDI. This article will discuss the medications that contribute to CDI and not cover infectious causes or structural causes.
Biomechanical and Musculoskeletal Differences Between Postpartum Runners and Nulliparous Controls
Authors: Christopher Shefali Mathur , Bauer Lindsey , Maylone Rebba , Bullock Garrett S. , Chinworth Susan A. , Snodgrass Suzanne J. , Vallabhajosula Srikant
Published: February 2022

Background:

Women are running as soon as 8 weeks postpartum and there is currently little understanding of the effects of pregnancy and childbirth on the postpartum runner (PPR). Pregnancy-related musculoskeletal and physiological changes could impact running gait postpartum.

Objective:

The purpose of the current study was to investigate differences in overground running kinetics, strength and flexibility in PPRs, and age-matched nulliparous controls.

Methods:

Vertical and anteroposterior ground reaction force (APGRF) data were collected during overground running and normalized to body weight (NBW). Hip and knee strength, and hamstring flexibility measures were collected using a handheld dynamometer and inclinometer, respectively. Data were averaged for both legs. Independent-samples t tests and effect size (ES) estimations were conducted using α = .05.

Findings:

Nine PPRs (33.10 ± 5.60 years; ≤2 years postpartum) and 9 age-matched nulliparous women (31.67 ± 4.55 years) participated. PPRs had 24.3% greater braking loading rate for APGRF than controls (mean difference [MD] 3.41 NBW/s, 95% confidence interval [CI] 0.08, 6.74; P = .046; ES 1.08). PPRs had 14% less hamstring flexibility (MD 10.98°, 95% CI 0.97, 20.99; P = .034; ES 1.14), 25.9% less hip abduction strength (MD 0.04 NBW, 95% CI 0.00, 0.08; P = .045; ES 1.07) and 51.6% less hip adduction strength (MD 0.06 NBW, 95% CI 0.02, 0.10; P = .003; ES 1.68).

Interpretation:

These preliminary findings suggest that PPRs demonstrate altered running braking strategies and decreased hamstring flexibility and hip strength compared with nulliparous controls. As running guidelines for PPRs have been derived mostly from expert opinion, this exploratory cohort study suggests that PPRs should be evaluated for musculoskeletal impairments before initiating or returning to running. (See the Video, Supplemental Digital Content A, available at: http://links.lww.com/JWHPT/A67, which discusses the significance, innovation, and clinical applicability of this study.)
Systemic Vasculitis Following SARS-CoV-2 mRNA Vaccination Demonstrated on FDG PET/CT
Authors: Nakatani Koya , Sakata Etsuro , Fujihara Masakazu , Mizukawa Kaoru , Koyama Takashi
Published: February 2022

Causality regarding adverse events following SARS-CoV-2 mRNA vaccine is undetermined for vasculitis. Herein, we report the case of an 80-year-old man who presented with a persistent high fever of 7 days' duration that began shortly after receiving a COVID-19 vaccination. There was also a complaint of persistent lower limb pain and walking difficulty on emergency transportation. FDG PET/CT demonstrated extensive linear hypermetabolic foci along the vessels of both legs, including the hips, and the arms, supraclavicular area, chest wall, and temporal regions, suggesting systemic vasculitis. Subsequent temporal artery biopsy revealed arteritis, which is not typical of giant cell arteritis.
Germline intergenic duplications at Xq26.1 underlie Bazex-Dupré-Christol syndrome, an inherited basal cell carcinoma susceptibility condition
Authors: Liu Yanshan , Banka Siddharth , Huang Yingzhi , Hardman-Smart Jonathan , Pye Derek , Torrelo Antonio , Beaman Glenda M. , Kazanietz Marcelo G. , Baker Martin J , Ferrazzano Carlo , Shi Chenfu , Orozco Gisela , Eyre Stephen , van Geel Michel , Bygum Anette , Fischer Judith , Miedzybrodzka Zosia , Abuzahra Faris , Rübben Albert , Cuvertino Sara , Ellingford Jamie M. , Smith Miriam J. , Evans D. Gareth , Weppner-Parren Lizelotte J.M.T , van Steensel Maurice A.M. , Chaudhary Iskander H. , Mangham D. Chas , Lear John T. , Paus Ralf , Frank Jorge , Newman William G. , Zhang Xue
Published: February 2022

Background

Bazex-Dupré-Christol syndrome (BDCS; MIM301845) is a rare X-linked dominant genodermatosis characterized by follicular atrophoderma, congenital hypotrichosis and multiple basal cell carcinomas (BCCs). Previous studies have linked BDCS to an 11.4 Mb interval on chromosome Xq25-27.1. However, the genetic mechanism of BDCS remains an open question.

Methods

To investigate the genetic etiology of BDCS, we ascertained eight families with individuals affected with BDCS (F1-F8). Whole exome (F1 and F2) and genome sequencing (F3) were performed to identify putative disease-causing variants within the linkage region. Array-comparative genomic hybridization and quantitative PCR were used to explore copy number variations (CNV) in BDCS families, followed by long-range gap-PCR and Sanger sequencing to amplify duplication junction and define the precise head-tail junctions, respectively. Immunofluorescence was performed in hair follicles, BCCs and trichoepitheliomas from BDCS patients and sporadic BCCs to detect the expression of corresponding genes. The ACTRT1 variant (p.Met183Asnfs*17), previously proposed to cause BDCS, was evaluated with allele frequency calculator.

Results

In eight BDCS families, we identified overlapping 18-135kb duplications (six inherited and two de novo) at Xq26.1, flanked by ARHGAP36 and IGSF1. We detected ARHGAP36 expression near the control hair follicular stem cells compartment, and found increased ARHGAP36 levels in hair follicles in telogen, BCCs and trichoepitheliomas from patients with BDCS. ARHGAP36 was also detected in sporadic BCCs from individuals without BDCS. Our modelling showed the predicted ACTRT1 variants maximum tolerated minor allele frequency in control populations to be orders of magnitude higher than expected for a high-penetrant ultra-rare disorder, suggesting loss-of-function of ACTRT1 is unlikely to cause BDCS.

Conclusions

Our data support the pathogenicity of intergenic duplications at Xq26.1, most likely leading to dysregulation of ARHGAP36, establish BDCS as a genomic disorder, and provide a potential therapeutic target for both inherited and sporadic BCCs.
An optimized reference tissue method for quantification of tau protein depositions in diverse neurodegenerative disorders by PET with 18F-PM-PBB3 (18F-APN-1607)
Authors: Tagai Kenji , Ikoma Yoko , Endo Hironobu , Debnath Oiendrila Bhowmik , Seki Chie , Matsuoka Kiwamu , Matsumoto Hideki , Oya Masaki , Hirata Kosei , Shinotoh Hitoshi , Takahata Keisuke , Kurose Shin , Sano Yasunori , Ono Maiko , Shimada Hitoshi , Kawamura Kazunori , Zhang Ming-Rong , Takado Yuhei , Higuchi Makoto
Published: February 2022

Positron emission tomography (PET) with 18F-PM-PBB3 (18F-APN-1607) enables high-contrast detection of tau depositions in various neurodegenerative dementias, including Alzheimer’s disease (AD) and frontotemporal lobar degeneration (FTLD). A simplified method for quantifying the radioligand binding in target regions is to employ the cerebellum as a reference (CB-ref) on the assumption that the cerebellum has minimal tau pathologies. This procedure could be valid in AD, while FTLD disorders exemplified by progressive supranuclear palsy (PSP) are characterized by occasional tau accumulations in the cerebellum, hampering the application of CB-ref. The present study aimed to establish an optimal method for defining reference tissues on 18F-PM-PBB3-PET images of the AD and non-AD tauopathy brains. We developed a new algorithm to extract reference voxels with a low likelihood of containing tau deposits from gray matter (GM-ref) or white matter (WM-ref) by a bimodal fit to an individual, voxel-wise histogram of the radioligand retentions and applied it to 18F-PM-PBB3-PET data obtained from age-matched 40 healthy controls (HCs) and 23 AD, 40 PSP, and five other tau-positive FTLD patients. PET images acquired at 90-110 min after injection were averaged and co-registered to corresponding magnetic resonance imaging space. Subsequently, we generated standardized uptake value ratio (SUVR) images estimated by CB-ref, GM-ref and WM-ref respectively, and then compared the diagnostic performances. GM-ref and WM-ref covered a broad area in HCs and free of voxels located in regions known to bear high tau burdens in AD and PSP patients. GM-ref allowed the most robust separation of AD and PSP patients from HCs according to the area under the curves in receiver operating characteristic curve analyses. GM-ref also provided SUVR images with higher contrast than CB-ref in FTLD patients with suspected and confirmed corticobasal degeneration. The methodology for determining reference tissues as optimized here reinforces the accuracy of 18F-PM-PBB3-PET measurements of tau burdens in a wide range of neurodegenerative illnesses.
Transition to siblinghood causes substantial and long-lasting physiological stress reactions in wild bonobos
Authors: Behringer Verena , Berghänel Andreas , Lee Sean M. , Fruth Barbara , Hohmann Gottfried
Published: February 2022

In mammals with a slow ontogeny, the birth of a sibling marks a major developmental transition. Behavioral studies suggest that this event is stressful for the older offspring, but physiological evidence for this is lacking, and it remains unknown whether the birth of a sibling is stressful beyond mere weaning stress. Studying transition to siblinghood in wild bonobos, we investigated physiological changes in urinary cortisol (stress response), neopterin (cell-mediated immunity), and total triiodothyronine (metabolic rate), and related them to behavioral changes in mother-infant relationship and feeding (suckling, riding, proximity, body contact, independent foraging). With sibling’s birth, cortisol levels increased fivefold in the older offspring and remained elevated for seven months, independent of age. This was associated with diminished immunity but not with behavioral or metabolic changes. Our results indicate that transition to siblinghood is stressful beyond nutritional and social weaning and suggest that this effect is evolutionary old.
‘4-Aminoquinazoline-6, 7-diol’ derivatives for enhanced EGFR binding (as inhibitor) against Lung cancer
Authors: Maurya Pratibha Preeti
Published: February 2022

The Epidermal growth factor receptor (EGFR) have been considered as potential targets for cancer therapy due to their role in regulating proliferation and survival of cancer cells. In the present study, the four ‘4-aminoquinazoline-6, 7-diol’ derivative molecules were selected to the theoretically investigate their inhibitory activity against EGFR protein. Molecules were evaluated on the basis of: (i) in-silico cytotoxic assay on human cancer cell lines expressing EGFR (A549 and A431), (ii) in-silico kinase assay, (iii) impact of molecular interaction on EGFR, (iv) molecular interaction stability, (v) inhibitory impact of molecules on combined expression of EGF-EGFR and (v) ADME observations. Studies were observed on the scale of two known EGFR inhibitors. In-silico cytotoxicity screening results demonstrated that the A431 lung cancer cell line was vulnerable to compound abc1-4. However, A549 cells were less sensitive to our designed molecules. From kinase inhibition assay results, compound abc1&2 were found to be an inhibitor against EGFR. According to the molecular interaction analysis, compounds abc1-4 performed in similar fashion of positive controls, acting at the catalytic site of EGFR. Altogether, these potent compounds, with compromised bioavailability, could likely be developed as a promising EGFR targeted drug(s) for cancer therapy.
Comparative transmission of SARS-CoV-2 Omicron (B.1.1.529) and Delta (B.1.617.2) variants and the impact of vaccination: national cohort study, England
Authors: Allen Hester , Tessier Elise , Turner Charlie , Anderson Charlotte , Blomquist Paula , Simons David , Løchen Alessandra , Jarvis Christopher I , Groves Natalie , Capelastegui Fernando , Flannagan Joe , Zaidi Asad , Chen Cong , Rawlinson Christopher , Hughes Gareth J. , Chudasama Dimple , Nash Sophie , Thelwall Simon , Lopez-Bernal Jamie , Dabrera Gavin , Charlett André , Kall Meaghan , Lamagni Theresa
Published: February 2022

Background

The SARS-CoV-2 Omicron variant (B.1.1.529) has rapidly replaced the Delta variant (B.1.617.2) to become dominant in England. This epidemiological study assessed differences in transmissibility between the Omicron and Delta using two methods and data sources.

Methods

Omicron and Delta cases were identified through genomic sequencing, genotyping and S-gene target failure in England from 5-11 December 2021. Secondary attack rates for Omicron and Delta using named contacts and household clustering were calculated using national surveillance and contact tracing data. We used multivariable logistic regression was used to control for factors associated with transmission.

Findings

Analysis of contact tracing data identified elevated secondary attack rates for Omicron vs Delta in household (15.0% vs 10.8%) and non-household (8.2% vs 3.7%) settings. The proportion of index cases resulting in residential clustering was twice as high for Omicron (16.1%) compared to Delta (7.3%). Transmission was significantly less likely from cases, or in named contacts, in receipt of three compared to two vaccine doses in household settings, but less pronounced for Omicron (aRR 0.78 and 0.88) compared to Delta (aRR 0.62 and 0.68). In non-household settings, a similar reduction was observed for Delta cases and contacts (aRR 0.84 and 0.51) but only for Omicron contacts (aRR 0.76, 95% CI: 0.58-0.93) and not cases in receipt of three vs two doses (aRR 0.95, 0.77-1.16).

Interpretation

Our study identified increased risk of onward transmission of Omicron, consistent with its successful global displacement of Delta. We identified a reduced effectiveness of vaccination in lowering risk of transmission, a likely contributor for the rapid propagation of Omicron.

Funding

Study funded by the UK Health Security Agency.
High-throughput profiling of natural acquired humoral immune response to a large panel of known and novel full length ectodomain P. falciparum merozoite vaccine candidates under reduced malaria transmission
Authors: Ndungu Duncan Ndegwa , Tuju James , Chepsat Emily , Mwai Rinter , Mwai Kennedy , Nyamako Lydia , Mosobo Moses , Deme Awa B. , Dieye Baba , Ndiaye Ibrahima Mbaye , Sy Mouhamad , Diallo Mamadou Alpha , Diedhiou Younous , Mbaye Amadou Moctar , Wirth Dyann , Ndiaye Daouda , Osier Faith , Bei Amy K.
Published: February 2022

Despite recent progress in the fight against malaria, it still remains a global health challenge necessitating development of intervention strategies. However, the search for malaria vaccine(s) has so far been very challenging. Multiple targets have been tested and so far only a few show promise with one having been endorsed by the WHO. In this study we explore the development of immunity in a low transmission setting, with very few documented re-infections, in order to understand the kinetics of the development and waning of immunity to current and novel blood-stage vaccine candidate antigens. To do this we performed a high-throughput measurement of natural acquired immunity against P. falciparum antigens utilizing a well-established micro-array platform based on the mammalian protein expression system. This large panel of known and novel recombinant full length ectodomain P. falciparum merozoite vaccine candidates were differently recognized by the immune system. Based on the overal spread of the data, some of these antigens induced the acquisition of high levels (1st tertile) of antibodies, among which included novel antigens such as PF3D7_1025300, PF3D7_1105800, PF3D7_1334400, PF3D7_0911300, PF3D7_1252300, PF3D7_1460600, PF3D7_1453100, PF3D7_0831400 and some induced low levels of antibodies (3rd tertile) while others induced moderate levels (4th tertile). In this longitudinal cohort with low level of malaria endemicity, acquisition of humoral immunity to these full length ectodomains P. falciparum antigens demonstrate different dynamics over-time, whereby it was either not acquired or if it was acquired it was either maintained or lost at different rates. These various identified novel antigens are potentially ideal candidates to be prioritized for further functional and or serological studies.
FACS-assisted single-cell lipidome analysis of phosphatidylcholines and sphingomyelins
Authors: Hancock Sarah E , Ding Eileen , Beves Emma Johansson , Mitchell Todd , Turner Nigel
Published: February 2022

Recent advances in single-cell genomics and transcriptomics technologies have transformed our understanding of cellular heterogeneity in growth, development, ageing and disease; however, methods for single-cell lipidomics have comparatively lagged behind in development. We have developed a high-throughput method for the detection and quantification of a wide range of phosphatidylcholine (PC) and sphingomyelin (SM) species from single cells that combines fluorescence-assisted cell sorting (FACS) with automated chip-based nanoelectrospray ionization (nanoESI) and shotgun lipidomics. We show herein that our method is capable of quantifying more than 50 different PC and SM species from single cells and can easily distinguish between cells of different lineages or cells treated with exogenous fatty acids. Moreover, our method can detect more subtle differences in the lipidome between cell lines of the same cancer type. Our approach can be run in parallel with other single-cell technologies to deliver near-complete multi-omics data on cells with a similar phenotype and has the capacity to significantly advance our current knowledge on cellular heterogeneity.
Botulinum neurotoxin accurately separates tonic vs phasic transmission and reveals heterosynaptic plasticity rules in Drosophila
Authors: Han Yifu , Chien Chun , Goel Pragya , He Kaikai , Pinales Cristian , Buser Chris , Dickman Dion
Published: February 2022

In developing and mature nervous systems, diverse neuronal subtypes innervate common targets to establish and maintain functional neural circuits. A major challenge towards understanding the structural and functional architecture of neural circuits is to separate these inputs and determine their intrinsic and heterosynaptic relationships. The Drosophila larval neuromuscular junction is a powerful model system to study these questions, where two glutamatergic motor neurons, the strong phasic-like Is and weak tonic-like Ib, co-innervate individual muscle targets to coordinate locomotor behavior. However, complete neurotransmission from each input has never been electrophysiologically separated. We have developed a botulinum neurotoxin, BoNT-C, that eliminates both spontaneous and evoked neurotransmission without perturbing synaptic growth or structure, enabling the first approach that accurately isolates input-specific neurotransmission. Selective expression of BoNT-C in Is or Ib motor inputs disambiguates functional properties of each input. Importantly, the composite values of Is and Ib neurotransmission can be fully recapitulated by isolated physiology from each input. Finally, selective silencing by BoNT-C does not induce heterosynaptic structural or functional plasticity at the convergent input. Thus, BoNT-C establishes the first approach to cleanly separate neurotransmission between tonic vs phasic neurons and defines heterosynaptic plasticity rules in a powerful model glutamatergic circuit.
An umbrella review of randomized control trials on the effects of physical exercise on cognition
Authors: Ciria Luis F. , Román-Caballero Rafael , Vadillo Miguel A. , Holgado Darias , Luque-Casado Antonio , Perakakis Pandelis , Sanabria Daniel
Published: February 2022

Extensive research links regular physical exercise to an overall enhancement of cognitive function across the lifespan. Here, we assess the causal evidence supporting this relationship in the healthy population, using an umbrella review of meta-analyses limited to randomized controlled trials (RCTs). Despite most of the 24 reviewed meta-analyses reporting a positive overall effect, our assessment reveals evidence of low statistical power in the primary RCTs, selective inclusion of studies, publication bias, and large variation in combinations of preprocessing and analytic decisions. In addition, our meta-analysis of all the primary RCTs included in the revised meta-analyses shows small exercise-related benefits (d= 0.22, 95% CI [0.16, 0.28]) that became substantially smaller after accounting for key moderators (i.e., active control and baseline differences;d= 0.13, 95% CI [0.07, 0.20), and negligible after correcting for publication bias (d= 0.05, 95% CrI [−0.09, 0.14]). These findings suggest caution in claims and recommendations linking regular physical exercise to cognitive benefits in the healthy human population until more reliable causal evidence accumulates.
Awake responses suggest inefficient dense coding in the mouse retina
Authors: Boissonnet Tom , Tripodi Matteo , Asari Hiroki
Published: February 2022

The structure and function of the vertebrate retina have been extensively studied across species with an isolated,ex vivopreparation. Retinal functionin vivo, however, remains elusive, especially in awake animals. Here we performed single-unit extracellular recordings in the optic tract of head-fixed mice to compare the output of awake, anesthetized, andex vivoretinas. While the visual response properties were overall similar across conditions, we found that awake retinal output had in general 1) faster kinetics with less variability in the response latencies; 2) a larger dynamic range; and 3) higher firing activity, by ∼20 Hz on average, for both baseline and visually evoked responses. Our modeling analyses further showed that such awake response patterns convey comparable total information but less efficiently, and allow for a linear population decoder to perform significantly better than the anesthetized orex vivoresponses. These results highlight distinct retinal behavior in awake states, in particular suggesting that the retina employs dense codingin vivo, rather than sparse efficient coding as has been often assumed fromex vivostudies.
Conflict- and error-related theta activities are coupled to BOLD signals in different brain regions
Authors: Beldzik Ewa , Ullsperger Markus , Domagalik Aleksandra , Marek Tadeusz
Published: February 2022

Both conflict and error processing have been linked to the midfrontal theta power (4-8 Hz) increase as indicated by EEG studies and greater hemodynamic activity in the anterior midcingulate cortex (aMCC) as indicated by fMRI studies. Conveniently, the source of the midfrontal theta power was estimated in or nearby aMCC. However, previous studies using concurrent EEG and fMRI recordings in resting-state or other cognitive tasks observed only a negative relationship between theta power and BOLD signal in the brain regions typically showing task-related deactivations. In this study, we used a simultaneous EEG-fMRI technique to investigate a trial-by-trial coupling between theta power and hemodynamic activity during the performance of two conflict tasks. Independent component analysis (ICA) was applied to denoise the EEG signal and select individual midfrontal EEG components, whereas group ICA was applied to fMRI data to obtain a functional parcellation of the frontal cortex. Using a linear mixed- effect model, theta power was coupled with the peak of hemodynamic responses from various frontal, cingulate, and insular cortical sites to unravel the potential brain sources that contribute to conflict- and error-related theta variability. Although several brain regions exhibited conflict-related increases in hemodynamic activity, the conflict pre-response theta showed only a negative correlation to BOLD signal in the midline area 9 (MA9), a region exhibiting conflict-sensitive deactivation. Conversely, and more expectedly, error-related theta showed a positive relationship to activity in the aMCC. Our results provide novel evidence suggesting that the amplitude of pre-response theta reflects the process of active inhibition that suppresses the MA9 activity. This process is affected independently by the stimulus congruency, reaction times variance, and is susceptible to the time-on-task effect. Finally, it predicts the commitment of an omission error. Together, our findings highlight that conflict- and error-related theta oscillations represent fundamentally different processes.
Dissociable misconfigurations of striatal functional connectivity profiles in smokers
Authors: Korponay Cole , Stein Elliot A , Ross Thomas J
Published: February 2022

Corticostriatal circuits are central to reward processing and reinforcement learning functions that often become dysregulated in substance use disorder (SUD) and drive compulsive drug use. Human neuroimaging research seeking to identify how corticostriatal circuits become altered in SUD has primarily focused on evaluating connectivity between cortex-striatum node-pairs. Yet, striatal nodes receive appreciable input from many cortical nodes, and the morphological and electrophysiological properties of striatal nodes dictate that combinational features of their multivariate “connectivity profiles” shape their activity more so than any individual cortical node. Here, we introduce an approach for quantifying and statistically evaluating different types of multivariate connectivity profile configuration differences (i.e., aggregate divergence, rank order arrangement, and entropy shift) that may reflect different forms of circuit plasticity, and apply it to nicotine dependent smokers (n=46) as an exemplar SUD. Foremost, we find evidence of significant connectivity profile misconfiguration throughout much of the striatum, suggesting that prior findings of abnormal connections between individual striatal-cortical node-pairs may only represent the “tip of the iceberg” of corticostriatal circuit alteration in nicotine dependence. Moreover, we find that dorsolateral and ventromedial striatum display distinct types of connectivity profile misconfiguration. Whereas dorsolateral striatum almost exclusively displays abnormal rank order arrangement that is present in both the nicotine sated and acutely abstinent states – indicative of a “trait” misconfiguration – ventromedial striatum almost exclusively displays abnormal aggregate divergence that only manifests during acute abstinence – indicative of a “state” misconfiguration. Further, we identify a unique striatal site in the right caudal ventral putamen that displays multiple forms of connectivity profile misconfiguration, where connections with cognitive processing cortical areas overtake those with motor/premotor control cortical areas as the strongest in the connectivity profile, and acute abstinence significantly strengthens this abnormal arrangement. Moreover, the interactive magnitude of these misconfigurations during acute abstinence is significantly linked to dependence severity. Collectively, the present findings underscore the need for increased examination of connectivity profile misconfigurations as a mechanism of SUD etiology and as a potential guide for identifying therapeutic intervention targets.
Mask up! Testing strategies to increase mask usage in Kenya*
Authors: Egger Dennis , Jakubowski Aleskandra , Nekesa Carolyne , Walker Michael
Published: February 2022

Background

COVID-19 continues to pose a major threat to countries around the world, and non-pharmaceutical interventions such as social distancing and face coverings remain important to reduce transmission, especially in settings with low vaccination rates. Despite a nationwide mask mandate in Kenya during the pandemic, proper masking remained low in Siaya County. We conducted a pilot study with the Siaya County Ministry of Health to improve mask adoption within Ugunja subcounty, and present initial findings on mask usage effects.

Methods

The study took place across 72 villages in Ugunja subcounty, which were randomly assigned to receive: (i) free mask and education on mask usage; (ii) only education on mask usage; or (iii) no mask or education by community health workers. A “role model” intervention was also cross-randomized across half of the villages, along with SMS messages reinforcing a variety of messages around masking. The intervention was administered in January 2021. Data collection was done via phone survey and direct observation of mask usage.

Findings

Preliminary analysis of the pilot study suggests providing free face masks may improve compliance, particularly in settings with higher COVID-19 risks. Two weeks to three months after the intervention, the free mask and education arm increased directly-observed correct mask usage by 3.1 percentage points (95% confidence interval 1.9, 6.0) on a control mean of 6.8 percent. Some treatment arms also improved COVID-19 knowledge and mask attitudes.

Interpretation

Interventions designed to increase adoption of health measures can be successful, but behavioral change is challenging and may require more intensive treatment.
Effects of auditory sleep modulation approaches on brain oscillatory and cardiovascular dynamics
Authors: Huwiler Stephanie , Dominguez Manuel Carro , Huwyler Silja , Kiener Luca , Stich Fabia , Sala Rossella , Aziri Florent , Trippel Anna , Schmied Christian , Huber Reto , Wenderoth Nicole , Lustenberger Caroline
Published: February 2022

Sleep modulation techniques to elucidate the functional role of sleep brain oscillations in brain and body functions have gained large interest. Slow waves, the hallmark feature of deep non-rapid eye movement sleep, do potentially drive restorative effects on brain and cardiovascular functions. Auditory stimulation to modulate slow waves is a promising tool, however, directly comparing different auditory stimulation approaches within a night and analyzing induced dynamic brain and cardiovascular effects are yet missing. Here, we tested various auditory stimulation approaches in a windowed, 10 s ON (stimulations) followed by 10 s OFF (no stimulations), within-night stimulation design and compared them to a SHAM control condition. We report the results of three studies and a total of 51 included stimulation nights. We found a large and global increase in slow wave activity (SWA) in the stimulation window compared to SHAM. Furthermore, slow wave dynamics were most pronouncedly increased at the start of the stimulation and declined across the stimulation window. Beyond the changes in brain oscillations, we observed, for some conditions, a significant increase in the mean interval between two heartbeats within a stimulation window, indicating a slowing of the heart rate, and increased heart rate variability derived parasympathetic activity. Those cardiovascular changes were positively correlated with the change in SWA and thus, our findings provide mechanistic insight into the potential of auditory slow wave enhancement to modulate cardiovascular restorative conditions during sleep. However, future studies need to investigate whether the potentially increased restorative capacity through slow wave enhancements translates into a more rested cardiovascular system on the subsequent day.
Pro-resolving Lipid Mediators Within Brain Esterified Lipid Pools are Reduced in Female Rats Chronically Exposed to Traffic-Related Air Pollution or Genetically Susceptible to Alzheimer’s Disease Phenotype
Authors: Shen Qing , Liang Nuanyi , Patten Kelley T. , Otoki Yurika , Valenzuela Anthony E. , Wallis Christopher , Bein Keith J. , Wexler Anthony S. , Lein Pamela J. , Taha Ameer Y.
Published: February 2022

Traffic-related air pollution (TRAP) is a risk factor for Alzheimer’s disease (AD) where neuroinflammation underlies disease progression and pathogenesis. Unresolved inflammation in AD is known to be exacerbated by brain deficits in unesterified pro-resolving lipid mediators enzymatically synthesized from polyunsaturated fatty acids. Recently, we reported that in the brain, unesterified pro-resolving lipid mediators which are bioactive, can also be supplied from less bioactive esterified lipid pools such as neutral lipids (NLs) and phospholipids (PLs). It is not known whether esterified pro-resolving lipid mediators are affected by AD pathology and exacerbated by TRAP exposure. In the present study we addressed this data gap using TgF344-AD male and female rats that express human AD risk genes and their wildtype littermates exposed to filtered air (FA) or TRAP from 1 to 15 months of age. Esterified lipid mediators within NLs and PLs were quantified by mass-spectrometry. We observed a significant reduction in pro-resolving lipid mediators in both NLs and PLs of female TgF344-AD rats compared to wildtype controls. TRAP exposure also reduced pro-resolving lipids in the female brain, mainly in PL pools, but did not exacerbate changes observed in TgF344-AD rats. Minimal changes were observed in males. Our findings indicate that AD genotype and chronic TRAP exposure result in sex-specific deficits in brain esterified pro-resolving lipid mediators, the pool that supplies free and bioactive lipid mediators. These data provide new information on lipid-mediated mechanisms regulating impaired inflammation resolution in AD, and show for the first time that chronic TRAP exposure targets the same lipid network implicated in AD.
Oligodendrocytes form paranodal bridges that generate chains of myelin sheaths that are vulnerable to degeneration with age
Authors: Call Cody L. , Neely Sarah A. , Early Jason J. , James Owen G. , Zoupi Lida , Williams Anna C. , Chandran Siddharthan , Lyons David A. , Bergles Dwight E.
Published: February 2022

Myelin sheaths in the CNS are generated by the tips of oligodendrocyte processes, which wrap axons to accelerate action potential conduction, provide metabolic support and control excitability. Here we identify a distinct mode of myelination, conserved between zebrafish, mouse and human, in which oligodendrocytes extend myelin along individual axons by linking myelin sheaths across nodes of Ranvier (NoR). By forming thin extensions that cross NoR, which we term paranodal bridges, multiple sheaths can be connected to the soma by a single cytoplasmic process. Extensive in vivo live imaging-based analyses, complemented by serial electron microscopic reconstruction of paranodal bridges, revealed that many oligodendrocytes use this strategy to generate longer stretches of myelin along individual axons. In the mouse somatosensory cortex, paranodal bridges were particularly prevalent along the highly branched axons of parvalbumin expressing (PV) interneurons, which enabled oligodendrocytes to extend myelin sheaths around axon bifurcations. Sheaths at the distal ends of these chains of myelin degenerated more frequently in aged mice, suggesting that they may be more vulnerable to the aging brain environment. This previously undescribed and evolutionarily conserved feature of oligodendrocytes extends myelin coverage of individual axons without new oligodendrogenesis, which may reduce metabolic demand and preserve the fidelity of action potential propagation at axon branch points.