bluuebunny/crossref_metadata_2025 huggingface dataset:
Long-term winter food supplementation shows no significant impact on reproductive performance in Mountain Chickadees in the Sierra Nevada Mountains
Authors: Sonnenberg Benjamin R , Welklin Joseph F , Branch Carrie L , Pitera Angela M , Benedict Lauren M , Heinen Virginia K , Kozlovsky Dovid Y , Bridge Eli S , Pravosudov Vladimir V
Published: October 2022

Supplemental feeding of wild animal populations is popular across many areas of the world and has long been considered beneficial, especially to avian taxa. Over 4 billion dollars are spent by hobby bird feeders in the United States each year alone. However, there is mixed evidence whether wildlife feeding is beneficial, including when it is implemented as a conservation management tool, a targeted experimental design, or an avocation. Much of the current evidence suggests that providing supplemental food is advantageous to the reproductive output and general survival of focal taxa. However, many of these studies are limited in scope and duration, leaving possible negative impacts unaddressed. This is particularly true regarding passive backyard feeding, which describes the majority of supplemental feeding, including the immense effort of millions of public enthusiasts. Here we show that winter supplemental feeding prior to reproduction had no significant impact on a range of reproductive parameters in a resident, montane passerine species, the Mountain Chickadee (Poecile gambeli). This population resides in an intact natural environment with no exposure to supplemental food beyond our experimental treatments, and individual birds were tracked across six years using radio frequency identification technology. Our results add to the growing evidence that supplemental feeding alone, isolated from the effects of urban environments, may have little to no impact on the population dynamics of some avian taxa.
Observing how deep neural networks understand physics through the energy spectrum of 1D quantum mechanics
Authors: Ogure Kenzo
Published: October 2022

We investigate how neural networks (NNs) understand physics using 1D quantum mechanics. After training an NN to accurately predict energy eigenvalues from potentials, we used it to confirm the NN’s understanding of physics from four different aspects. The trained NN could predict energy eigenvalues of different kinds of potentials than the ones learned, predict the probability distribution of the existence of particles not used during training, reproduce untrained physical phenomena, and predict the energy eigenvalues of potentials with an unknown matter effect. These results show that NNs can learn physical laws from experimental data, predict the results of experiments under conditions different from those used for training, and predict physical quantities of types not provided during training. Because NNs understand physics in a different way than humans, they will be a powerful tool for advancing physics by complementing the human way of understanding.
Focal epilepsy impacts rapid eye movement sleep microstructure
Authors: Schiller Katharina , von Ellenrieder Nicolás , Avigdor Tamir , El Kosseifi Charbel , Abdallah Chifaou , Minato Erica , Gotman Jean , Frauscher Birgit
Published: October 2022

Study Objectives

Whereas there is plenty of evidence on the influence of epileptic activity on non-rapid eye movement (NREM) sleep macro- and micro-structure, data on the impact of epilepsy on rapid eye movement (REM) sleep remains sparse. Using high-density electroencephalography (HD-EEG), we assessed global and focal disturbances of sawtooth waves (STW) as cortically generated sleep oscillations of REM sleep in patients with focal epilepsy.

Methods

Twenty-two patients with drug-resistant focal epilepsy (13 females; mean age, 32.6 ± 10.7 years; 12 temporal lobe epilepsy) and 12 healthy controls (3 females; 24.0 ± 3.2 years) underwent combined overnight HD-EEG and polysomnography. STW rate, duration, frequency, power, spatial extent, IED rates and sleep homeostatic properties were analyzed.

Results

STW rate and duration were reduced in patients with focal epilepsy compared to healthy controls (rate: 0.64/min ± 0.46 vs. 1.12/min ± 0.41, p = .005, d = −0.98; duration: 3.60 s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = −1.01). Not surprisingly given the fronto-central maximum of STW, the reductions were driven by extratemporal lobe epilepsy patients (rate: 0.45/min ± 0.31 vs. 1.12/min ± 0.41, p = .0004, d = −1.35; duration: 3.49 s ± 0.92 vs. 4.57 ± 1.00, p = .017, d = −0.99) and were more pronounced in the first vs. the last sleep cycle (rate first cycle patients vs. controls: 0.60/min ± 0.49 vs. 1.10/min ± 0.55, p = .016, d = −0.90, rate last cycle patients vs. controls: 0.67/min ± 0.51 vs. 0.99/min ± 0.49, p = .11, d = −0.62; duration first cycle patients vs. controls: 3.60s ± 0.76 vs. 4.57 ± 1.00, p = .003, d = −1.01, duration last cycle patients vs. controls: 3.66s ± 0.84 vs. 4.51 ± 1.26, p = .039, d = −0.80). There was no regional decrease of STWs in the region with the epileptic focus vs. the contralateral side (all p > .05).

Conclusion

Patients with focal epilepsy and in particular extratemporal lobe epilepsy show a global reduction of STW activity in REM sleep. This may suggest that epilepsy impacts cortically generated sleep oscillations even in REM sleep when epileptic activity is low.
Cognitive-behavioral therapy for insomnia prevents and alleviates suicidal ideation: insomnia remission is a suicidolytic mechanism
Authors: Kalmbach David A , Cheng Philip , Ahmedani Brian K , Peterson Edward L , Reffi Anthony N , Sagong Chaewon , Seymour Grace M , Ruprich Melissa K , Drake Christopher L
Published: October 2022

Study Objectives

Insomnia is associated with elevated levels of suicidal thoughts and behaviors. Emerging evidence suggests that cognitive-behavioral therapy for insomnia (CBTI) may reduce suicidal ideation (SI). However, the role of digital therapeutics in both the alleviation and prevention of SI remains unclear, and treatment mechanisms facilitating SI reductions have not been clearly identified.

Methods

A total of 658 adults with Diagnostic and Statistical Manual of Mental Disorders, 5th Edition insomnia disorder enrolled in a single-site randomized controlled trial evaluating the efficacy of digital CBTI relative to attention control. Outcomes were measured at pretreatment, posttreatment, and 1-year follow-up.

Results

Before treatment, 126 patients endorsed SI (19.1% prevalence). Among those with baseline SI, CBTI patients reported lower SI rates at posttreatment (30.0% vs 54.5%, p = .005) and 1-year follow-up (29.6% vs 46.8%, p = .042) relative to control. PRODCLIN analysis estimated that half of suicidolytic effects of CBTI were mediated through insomnia remission. Among those without baseline SI, CBTI did not directly prevent new onset SI. However, insomnia remitters reported lower rates of new-onset SI at posttreatment relative to non-remitters (1.5% vs 6.5%, p = .009). Mediation analysis supported a significant indirect effect wherein CBTI increased the likelihood of insomnia remission, which was associated with SI prevention (αβ = −3.20, 95% CI = −5.74 to −0.87).

Conclusion

Digital CBTI reduces insomnia symptoms, which promotes SI alleviation and prevention. For nonsuicidal patients, digital CBTI may serve as a highly accessible monotherapy for improving sleep, thereby reducing the risk for SI. For suicidal patients, digital CBTI may be appropriately administered as an adjunct treatment to support mainline intervention more directly targeting suicidogenic thoughts.
A Viability Analysis of Tumor-Bearing Frozen Autograft for the Reconstruction After Resection of Malignant Bone Tumors Using 99mTc-MDP Scintigraphy
Authors: Araki Yoshihiro , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Miwa Shinji , Igarashi Kentaro , Higuchi Takashi , Abe Kensaku , Taniguchi Yuta , Yonezawa Hirotaka , Morinaga Sei , Asano Yohei , Nojima Takayuki , Taki Junichi , Tsuchiya Hiroyuki
Published: October 2022

Purpose of the Report

Several methods are used to reconstruct bony defects after malignant tumor excision. Tumor-bearing frozen autograft reconstruction is a biological procedure in which tumor-bearing bone is reused after devitalization with liquid nitrogen to kill tumor cells. The viability of frozen autografts has not been fully evaluated over time. We therefore aimed to evaluate the viability of devitalized bone grafts, using 99mTc-MDP scintigraphy.

Patients and Methods

Seventy-four patients who underwent frozen autograft reconstruction after the excision of a malignant bone tumor were enrolled. Two hundred forty-two postoperative 99mTc-MDP scans were reviewed. For a quantitative analysis, the region of interest on the frozen bone segment and a symmetric region of interest on the contralateral normal area were manually set. The radioactive tracer uptake ratio was calculated by dividing the count density of the frozen bone segment by that of the contralateral normal area in each image. An uptake ratio of 0.9 to 1.1 was defined as a normalization of tracer uptake.

Results

Normalization of tracer uptake was achieved in 95% to 97% of the cases by 60 months postoperatively, and earlier in the middle zone and peripheral zone in the pedicle freezing group in comparison to the free freezing group (both P = 0.03). Fracture and nonunion was associated with a low uptake ratio, whereas infection was associated with a high uptake ratio before the occurrence of the event.

Conclusions

The calculation of the uptake ratio using 99mTc-MDP scans was an objective and accurate evaluation method. The period to normalization of tracer uptake in the pedicle frozen bone was significantly earlier than that in the free frozen bone. The postoperative complications can be also predicted.
Excellent Response to Multimodal Therapy Approach in Hyperfunctioning Metastatic Follicular Thyroid Carcinoma Diagnosed on 123I-SPECT/Ultrasound Fusion Imaging
Authors: Leder Theresa , Seifert Philipp , Drescher Robert , Gühne Falk , Freesmeyer Martin
Published: October 2022

An 83-year-old woman presented with new-onset hyperthyroidism and suspicious thyroid nodules on ultrasound (US). Conventional 99mTcO4 thyroid scintigraphy showed hyperfunctioning areas that could not be clearly assigned to the US findings. With the aid of 123I-SPECT/US fusion imaging, suspicious nodules were unambiguously identified as autonomously hyperfunctioning lesions. Additional 123I whole-body scan revealed iodine-avid lymphonodular and pulmonal metastases. Clinical diagnosis of hormone-active thyroid carcinoma was made and histologically confirmed. Because of significant hyperthyroidism as well as multiple partially iodine-negative metastases, a multimodal treatment regime consisting of 131I radioiodine therapy, surgery, and radiation therapy was conducted, leading to almost complete remission.
Sequential Brain Perfusion Findings in a Case of Osmotic Demyelination Syndrome
Authors: Ghomari Cherifa Fazila , Misgault Bastien , Diallo Alpha Oumar , Durand Helene , Bund Caroline , Namer Izzie Jacques
Published: October 2022

A 60-year-old man with chronic alcoholism for 30 years was admitted to the hospital for an acute alcoholic syndrome with global confusional state, cognitive disorders, and ataxia. MRI detected bilateral mamillary bodies T2 hypersignal related to Wernicke encephalopathy. It was treated by oral thiamine supplementation with clinical improvement. Two months later, he was rehospitalized for rapidly progressive dementia symptoms. Brain perfusion scintigraphy revealed pontine hyperperfusion and right hippocampal hypoperfusion. One month after IV thiamine supplementation, brain perfusion scintigraphy showed normalization of perfusion abnormalities in the pons and right hippocampus, leading to the diagnosis of alcoholic-related osmotic demyelination syndrome.
Extensive Drop Metastases From Pineal Gland Tumor
Authors: Saini Vivek Kumar , Ora Manish
Published: October 2022

Pineal gland tumors are an infrequent central nervous system manifestation. Their prevalence is only less than 1% of all central nervous system tumors. They generally involve children or young adults aged younger than 40 years. Extracranial or spinal drop metastases are very rare from pineal gland tumors. In this case, 18FDG PET/CT demonstrates drops in metastases involving the entire length of the spinal as well as multiple other intracranial metastatic lesions.
A NURSING PHILOSOPHY OF CHRONIC DISEASE SERVICES-BASED PALLIATIVE CARE NURSING DURING COVID-19
Authors: Nimah Lailatun , Pandin Moses Glorino Rumambo , Nursalam
Published: October 2022

Introduction

Palliative care is a special service particularly in the cases of chronic disease. The scope of palliative care includes populations with old age, chronic diseases, and processes of facing death. The COVID-19 pandemic has changed the health system, including palliative care.The purpose of this study is to explain nursing palliative care during the COVID-19 pandemic.

Method

This paper is result of a literature review. The data bases used were Scopus, Springerlink, Science direct. The search is limited to publications in 2020-2022, open acces, and English language. Then selected using Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) diagram and obtained 13 articles.

Result

Palliative care as a special care aims to reduce suffering and improve the quality of life of patient and family. Palliative care can be applied to acute hospital, community, nursing care, as well as residential care homes and hospices. The goal of palliative care is to prevent and reduce suffering in any form, including reducing pain through early identification, correct assessment, as well as treatment of pain and other problems. Many barries are felt by patients and families in accessing health services during the COVID-19 pandemic due to social restrictions.

Conclusion

Palliative care requires the involvement of various parties, including the government, health workers, and the community to overcome various barriers. During the COVID-19 pandemic in palliative care, special health policies are needed that are able to maintain the health status of patients so that the patient’s illness does not get worse.
Personalized Functional Brain Network Topography Predicts Individual Differences in Youth Cognition
Authors: Keller Arielle S. , Pines Adam R. , Sydnor Valerie J. , Cui Zaixu , Bertolero Maxwell A. , Barzilay Ran , Alexander-Bloch Aaron F. , Byington Nora , Chen Andrew , Conan Gregory M. , Davatazikos Christos , Feczko Eric , Hendrickson Timothy J. , Houghton Audrey , Larsen Bart , Li Hongming , Miranda-Dominguez Oscar , Roalf David R. , Perrone Anders , Shanmugan Sheila , Shinohara Russell T. , Fan Yong , Fair Damien A. , Satterthwaite Theodore D.
Published: October 2022

Individual differences in cognition during childhood are associated with important social, physical, and mental health outcomes in adolescence and adulthood. Given that cortical surface arealization during development reflects the brain’s functional prioritization, quantifying variation in the topography of functional brain networks across the developing cortex may provide insight regarding individual differences in cognition. We test this idea by defining personalized functional networks (PFNs) that account for interindividual heterogeneity in functional brain network topography in 9-10 year olds from the Adolescent Brain Cognitive DevelopmentSMStudy. Across matched discovery (n=3,525) and replication (n=3,447) samples, the total cortical representation of fronto-parietal PFNs positively correlated with general cognition. Cross-validated ridge regressions trained on PFN topography predicted cognition across domains, with prediction accuracy increasing along the cortex’s sensorimotor-association organizational axis. These results establish that functional network topography heterogeneity is associated with individual differences in cognition before the critical transition into adolescence.
Patterns of convergent somatic hypermutations in the adaptive immune response of Mus musculus
Authors: Wenner Alexander C. , Mettler Charles A. , Sharp Ellie M. , Hansen Thomas C. , Vari Isabella B. , Le Alexander V. , Zimmermann Jörg
Published: October 2022

We analyzed a dataset of 964 clonally unrelated murine antibodies for which structures have been deposited in the PDB. 454 of the 964 antibodies have gapless germline assignments and do not have excessive numbers of computationally identified somatic hypermutations (SHMs). About 5,500 SHMs were identified, of which approximately 3,500 are in the framework. We then searched for correlated convergent SHMs, i.e. groups of SHMs that arose independently in different antibodies but at the same sequence position and with the same germline and mature amino acid identity. A surprisingly large number of groups of correlated convergent SHMs were found. 329 antibodies share at least two, 161 antibodies share at least three, 87 antibodies share at least four, and 53 antibodies share at least five identical SHMs with another antibody in the dataset. We then analyzed whether any of the correlated SHMs are forming structural cluster. Approximately 400 clusters where CFWMs are located within 10 Å of each other were identified. 158 of these clusters are in the framework region. Identification of such structural clusters of correlated convergent SHMs may help identify adaptive mutations that act in an antigen-independent manner.
Triggered functional dynamics of AsLOV2 by time-resolved electron paramagnetic resonance at high magnetic fields
Authors: Maity Shiny , Price Brad D. , Wilson C. Blake , Mukherjee Arnab , Starck Matthieu , Parker David , Wilson Maxwell Z. , Lovett Janet E. , Han Songi , Sherwin Mark S.
Published: October 2022

We present time-resolved Gd-Gd electron paramagnetic resonance (TiGGER) at 240 GHz for tracking inter-residue distances during a protein’s mechanical cycle in the solution state. TiGGER makes use of Gd-sTPATCN as spin labels, whose favorable qualities include a spin-7/2 EPR-active center, short linker, narrow intrinsic linewidth, and virtually no anisotropy at high fields (8.6 T) when compared to nitroxide spin labels. Using TiGGER, we determined that upon light activation, the C-terminus and N-terminus of AsLOV2 separate in less than 1 s and relax back to equilibrium with a time constant of approximately 60 s. TiGGER revealed that the light-activated long-range mechanical motion is slowed in the Q513A variant of AsLOV2 and is correlated to the similarly slowed relaxation of the optically excited chromophore as described in recent literature. TiGGER has the potential to valuably complement existing methods for the study of triggered functional dynamics in proteins.
Disease-causing variant recommendation system for clinical genome interpretation with adjusted scores for artefactual variants
Authors: Kim Ho Heon , Woo Junwoo , Kim Dong-Wook , Lee Jungsul , Seo Go Hun , Lee Hane , Lee Kyoungyeul
Published: October 2022

Background

In the process of finding the causative variant of rare diseases (RD), accurate assessment and prioritization of genetic variants is essential. Although quality control (QC) of genetic variants is strictly performed, the presence of artefactual variants in the remaining set of variants can deteriorate the process. Variant QC and prioritization have been treated as separate processes, leading to limited efficiency and risk of misdiagnosis.

Results

We developed a disease-causing variant recommendation system that integrates quality control into variant prioritization by adjusting scores for artefactual variants. We confirmed that the QC-related features of the variants contribute to a significant performance improvement. For genomic data from 2,878 patients with rare disorders, the recall rate of finding causative variants was 0.961 for the top 5 ranked variants. We also found that our system recognized the anomaly of QC-related features, so that the scores of artifactual variants to be disease-causing were assessed relatively low.

Conclusions

Integration of variant QC and prioritization help reduce the risk of misdiagnosis based on artefactual variants and increase the effectiveness of clinical genome interpretation.
Visual experience instructs the organization of cortical feedback inputs to primary visual cortex
Authors: Dias Rodrigo F. , Rajan Radhika , Baeta Margarida , Marques Tiago , Petreanu Leopoldo
Published: October 2022

Cortical feedback (FB) projections are thought to modulate lower-order activity depending on learned expectations. However, whether FB inputs become bound to specific lower-order neurons depending on experience is unknown. We measured the effects of dark rearing and manipulations of experienced visual statistics on the retinotopic specificity of projections from the lateromedial (LM) visual area to layer 1 of the mouse primary visual cortex (V1). LM inputs were, on average, retinotopically matched with V1 neurons irrespective of visual experience. While the orientation tuning of LM axons determined the retinotopic position of the V1 neurons they innervated, this organization was absent in dark-reared mice. Restricting visual experience to a narrow range of orientations revealed that visual experience exerts an instructive role in the retinotopic organization of LM inputs in V1. Our observations support theories of hierarchical computation proposing that inputs from higher-order neurons to lower-order ones reflect learned hierarchical associations.
Building Transformers from Neurons and Astrocytes
Authors: Kozachkov Leo , Kastanenka Ksenia V. , Krotov Dmitry
Published: October 2022

Glial cells account for roughly 90% of all human brain cells, and serve a variety of important developmental, structural, and metabolic functions. Recent experimental efforts suggest that astrocytes, a type of glial cell, are also directly involved in core cognitive processes such as learning and memory. While it is well-established that astrocytes and neurons are connected to one another in feedback loops across many time scales and spatial scales, there is a gap in understanding the computational role of neuron-astrocyte interactions. To help bridge this gap, we draw on recent advances in artificial intelligence (AI) and astrocyte imaging technology. In particular, we show that neuron-astrocyte networks can naturally perform the core computation of a Transformer, a particularly successful type of AI architecture. In doing so, we provide a concrete and experimentally testable account of neuron-astrocyte communication. Because Transformers are so successful across a wide variety of task domains, such as language, vision, and audition, our analysis may help explain the ubiquity, flexibility, and power of the brain’s neuron-astrocyte networks.

Significance Statement

Transformers have become the default choice of neural architecture for many machine learning applications. Their success across multiple domains such as language, vision, and speech raises the question: how can one build Transformers using biological computational units? At the same time, in the glial community there is a gradually accumulating evidence that astrocytes, formerly believed to be passive house-keeping cells in the brain, in fact play important role in brain’s information processing and computation. In this work we hypothesize that neuron-astrocyte networks can naturally implement the core computation performed by the Transformer block in AI. The omnipresence of astrocytes in almost any brain area may explain the success of Transformers across a diverse set of information domains and computational tasks.
Ventral subiculum inputs to nucleus accumbens medial shell preferentially innervate D2R medium spiny neurons and contain calcium permeable AMPARs
Authors: Boxer Emma E , Kim JungMin , Dunn Brett , Aoto Jason
Published: October 2022

Ventral subiculum (vSUB) is the major output region of ventral hippocampus (vHIPP) and sends major projections to nucleus accumbens medial shell (NAcMS). Hyperactivity of the vSUB-NAcMS circuit is associated with substance use disorders (SUDs) and the modulation of vSUB activity alters drug seeking and drug reinstatement behavior in rodents. However, to the best of our knowledge, the cell-type specific connectivity and synaptic transmission properties of the vSUB-NAcMS circuit have never been directly examined. Instead, previous functional studies have focused on total ventral hippocampal (vHIPP) output to NAcMS without distinguishing vSUB from other subregions of vHIPP, including ventral CA1 (vCA1). Usingex vivoelectrophysiology, we systematically characterized the vSUB-NAcMS circuit with cell-type and synapse specific resolution in male and female mice and found that vSUB output to dopamine receptor type-1 (D1R) and type-2 (D2R) expressing medium spiny neurons (MSNs) displays a functional connectivity bias for D2R MSNs. Furthermore, we found that vSUB-D1R and -D2R MSN synapses contain calcium-permeable AMPA receptors in drug-naïve mice. Finally, we find that, distinct from other glutamatergic inputs, cocaine exposure selectively induces plasticity at vSUB-D2R synapses. Importantly, we directly compared vSUB and vCA1 output to NAcMS and found that vSUB synapses are functionally distinct and that vCA1 output recapitulated the synaptic properties previously ascribed to vHIPP. Our work highlights the need to consider the contributions of individual subregions of vHIPP to SUDs and represents an important first step toward understanding how the vSUB-NAcMS circuit contributes to the etiologies that underlie SUDs.
Pf Bacteriophage Inhibits Neutrophil Migration in the Lung
Authors: Popescu Medeea C. , Pennetzdorfer Nina , Hargil Aviv , Kaber Gernot , Bollyky Paul L.
Published: October 2022

Bacteriophages are abundant in the human body, including at sites of infection. We report that Pf4 phage, a filamentous bacteriophage produced byPseudomonas aeruginosa, dampens inflammatory responses in response to eitherP. aeruginosaairway infection in a mouse model of acute pneumonia or bacterial endotoxin treatment. Pf4 triggers TLR3-dependent type I interferon production and antagonize production of anti-bacterial cytokines and chemokines. In particular, Pf4 phages inhibit CXCL5, preventing efficient neutrophil chemotaxis in response to endotoxin. These results suggest that Pf4 phages alter innate immunity to bacteria potentially dampening inflammation and neutrophil migration at sites of bacterial colonization or infection.
Rapid transmission and tight bottlenecks constrain the evolution of highly transmissible SARS-CoV-2 variants
Authors: Bendall Emily E. , Callear Amy , Getz Amy , Goforth Kendra , Edwards Drew , Monto Arnold S. , Martin Emily T. , Lauring Adam S.
Published: October 2022

Transmission bottlenecks limit the spread of novel mutations and reduce the efficiency of natural selection along a transmission chain. Many viruses exhibit tight bottlenecks, and studies of early SARS-CoV-2 lineages identified a bottleneck of 1-3 infectious virions. While increased force of infection, host receptor binding, or immune evasion may influence bottleneck size, the relationship between transmissibility and the transmission bottleneck is unclear. Here, we compare the transmission bottleneck of non-variant-of-concern (non-VOC) SARS-CoV-2 lineages to those of the Alpha, Delta, and Omicron variants. We sequenced viruses from 168 individuals in 65 multiply infected households in duplicate to high depth of coverage. In 110 specimens collected close to the time of transmission, within-host diversity was extremely low. At a 2% frequency threshold, 51% had no intrahost single nucleotide variants (iSNV), and 42% had 1-2 iSNV. In 64 possible transmission pairs with detectable iSNV, we identified a bottleneck of 1 infectious virion (95% CI 1-1) for Alpha, Delta, and Omicron lineages and 2 (95% CI 2-2) in non-VOC lineages. The latter was driven by a single iSNV shared in one non-VOC household. The tight transmission bottleneck in SARS-CoV-2 is due to low genetic diversity at the time of transmission, a relationship that may be more pronounced in rapidly transmissible variants. The tight bottlenecks identified here will limit the development of highly mutated VOC in typical transmission chains, adding to the evidence that selection over prolonged infections in immunocompromised patients may drive their evolution.
Serology assays used in SARS-CoV-2 seroprevalence surveys worldwide: a systematic review and meta-analysis of assay features, testing algorithms, and performance
Authors: Ma Xiaomeng , Li Zihan , Whelan Mairead G. , Kim Dayoung , Cao Christian , Yanes-Lane Mercedes , Yan Tingting , Jaenisch Thomas , Chu May , Clifton David A. , Subissi Lorenzo , Bobrovitz Niklas , Arora Rahul K.
Published: October 2022

Background

Many serological assays to detect SARS-CoV-2 antibodies were developed during the COVID-19 pandemic. Differences in the detection mechanism of SARS-CoV-2 serological assays limited the comparability of seroprevalence estimates for populations being tested.

Methods

We conducted a systematic review and meta-analysis of serological assays used in SARS-CoV-2 population seroprevalence surveys, searching for published articles, preprints, institutional sources, and grey literature between January 1, 2020, and November 19, 2021. We described features of all identified assays and mapped performance metrics by the manufacturers, third-party head-to-head, and independent group evaluations. We compared the reported assay performance by evaluation source with a mixed-effect beta regression model. A simulation was run to quantify how biased assay performance affects population seroprevalence estimates with test adjustment.

Results

Among 1807 included serosurveys, 192 distinctive commercial assays and 380 self-developed assays were identified. According to manufacturers, 28.6% of all commercial assays met WHO criteria for emergency use (sensitivity [Sn.] >= 90.0%, specificity [Sp.] >= 97.0%). However, manufacturers overstated the absolute values of Sn. of commercial assays by 1.0% [0.1, 1.4%] and 3.3% [2.7, 3.4%], and Sp. by 0.9% [0.9, 0.9%] and 0.2% [-0.1, 0.4%] compared to third-party and independent evaluations, respectively. Reported performance data was not sufficient to support a similar analysis for self-developed assays. Simulations indicate that inaccurate Sn. and Sp. can bias seroprevalence estimates adjusted for assay performance; the error level changes with the background seroprevalence.

Conclusions

The Sn. and Sp. of the serological assay are not fixed properties, but varying features depending on the testing population. To achieve precise population estimates and to ensure the comparability of seroprevalence, serosurveys should select assays with high performance validated not only by their manufacturers and adjust seroprevalence estimates based on assured performance data. More investigation should be directed to consolidating the performance of self-developed assays.
Sexual dimorphic regulation of recombination by the synaptonemal complex
Authors: Cahoon Cori K. , Richter Colette M. , Dayton Amelia E. , Libuda Diana E.
Published: October 2022

In sexually reproducing organisms, germ cells faithfully transmit the genome to the next generation by forming haploid gametes, such as eggs and sperm. Although most meiotic proteins are conserved between eggs and sperm, many aspects of meiosis are sexually dimorphic. The mechanisms regulating recombination display sex-specific differences in multiple organisms such that the same proteins in each sex are being utilized in different ways to produce sexually dimorphic outcomes. The synaptonemal complex (SC), a large ladder-like structure that forms between homologous chromosomes, is essential for regulating meiotic chromosome organization and promoting recombination. To assess whether sex-specific differences in the SC underpin sexually dimorphic aspects of meiosis, we examined twoCaenorhabditis elegansSC central region proteins, SYP-2 and SYP-3, in oogenesis and spermatogenesis and uncovered sex-specific roles for the SYPs in regulating meiotic recombination. We find that SC composition is regulated by sex-specific mechanisms throughout meiotic prophase I. During pachytene, both oocytes and spermatocytes differentially regulate the stability of SYP-2 and SYP-3 within an assembled SC, with increased SYP-2 dynamics in spermatocytes and increased SYP-3 dynamics in oocytes. Further, we uncover that the relative amount of SYP-2 and SYP-3 within the SC is independently regulated in both a sex-specific and a recombination-dependent manner. Specifically, we find that SYP-2 regulates the early steps of recombination in both sexes, while SYP-3 controls the timing and positioning of crossover recombination events across the genomic landscape in only oocytes. Taken together, we demonstrate dosage-dependent regulation of individual SC components with sex-specific functions in recombination. These sexual dimorphic features of the SC provide insights into how spermatogenesis and oogenesis adapted similar chromosome structures to differentially regulate and execute recombination.
SARS-CoV-2 immune complex triggers human monocyte necroptosis
Authors: Santos Leonardo Duarte , Antunes Krist Helen , Cassão Gisele , Gonçalves João Ismael , Abbadi Bruno Lopes , Bizarro Cristiano Valim , Basso Luiz Augusto , Machado Pablo , de Souza Ana Paula Duarte , Porto Bárbara Nery
Published: October 2022

We analyzed the ability of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) itself and SARS-CoV-2-IgG immune complexes to trigger human monocyte necroptosis. SARS-CoV-2 was able to induce monocyte necroptosis dependently of MLKL activation. Necroptosis-associated proteins (RIPK1, RIPK3 and MLKL) were involved in SARS-CoV-2 N1 gene expression in monocytes. SARS-CoV-2 immune complexes promoted monocyte necroptosis in a RIPK3- and MLKL-dependent manner, and Syk tyrosine kinase was necessary for SARS-CoV-2 immune complex-induced monocyte necroptosis, indicating the involvement of Fcγ receptors on necroptosis. Finally, we provide evidence that elevated LDH levels as a marker of lytic cell death are associated with COVID-19 pathogenesis.
Maternal omega-3 fatty acid deficiency affects fetal thermogenic development and postnatal musculoskeletal growth in mice
Authors: Srinivas Vilasagaram , Molangiri Archana , Varma Saikanth , Mallepogu Aswani , Kona Suryam Reddy , Ibrahim Ahamed , Duttaroy Asim K , Basak Sanjay
Published: October 2022

Maternal omega-3 (n-3) polyunsaturated fatty acids (PUFAs) deficiency can affect offspring’s adiposity and metabolism by modulating lipid and glucose metabolism. However, the impact of n-3 PUFA deficiency on the development of fetal thermogenesis and its consequences is not reported. Using an n-3 PUFA deficient mice, we assessed fetal interscapular brown adipose tissue (iBAT), body fat composition, insulin growth factor-1 (IGF-1), glucose transporters (GLUTs), and expression of lipid storage & metabolic proteins in the offspring. The n-3 PUFA deficiency did not change the pups’ calorie intake, organ weight, and body weight. However, the offspring’s skeletal growth was altered due to excess fat to lean mass, reduced tibia & femur elongation, dysregulated IGF-1 in the mother and pups (p<0.05). Localization of uncoupling protein 1 (UCP1) in iBAT exhibited a reduced expression in the deficient fetus. Further, UCP1, GLUT1,GPR120were downregulated while FABP3, ADRP, GLUT4 expressions were upregulated in the BAT of the deficient offspring (p<0.05). The deficiency decreased endogenous conversion of the n-3 LCPUFAs from their precursors and upregulatedSCD1, FASN, andMFSD2AmRNAs in the liver (p<0.05). An altered musculoskeletal growth in the offspring is associated with impaired browning of the fetal adipose, dysregulated thermogenesis, growth hormone, and expression of glucose and fatty acid metabolic mediators due to maternal n-3 PUFA deficiency. BAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiency. Maternal n-3 PUFA intake may prevent excess adiposity by modulating fetal development of thermogenesis and skeletal growth dynamics in the mice offspring.

Highlight

Maternal n-3 PUFA deficiency dysregulated the development of fetal adipose browning

N-3 PUFA regulates fetal thermogenic development by altering UCP1 expression

BAT had higher metabolic sensitivity compared to WAT in n-3 PUFA deficiency

Increased fat mass and IGF-1 played a role in promoting adiposity in n-3 PUFA deficiency
Streptococcus pyogenesϕ1207.3 is a temperate bacteriophage carrying the macrolide efflux gene pairmef(A)-msr(D) and capable to lysogenise different Streptococci
Authors: Santoro Francesco , Pastore Gabiria , Fox Valeria , Petit Marie-Agnes , Iannelli Francesco , Pozzi Gianni
Published: October 2022

Streptococcus pyogenesprophage ϕ1207.3 (formerly Tn1207.3) carries themef(A)-msr(D) efflux resistance genes, responsible for type M macrolide resistance. To investigate if ϕ1207.3 is a functional bacteriophage, we transferred the element from the originalS. pyogeneshost in a prophage-free and competence-deficientS. pneumoniaestrain. Pneumococcal cultures of the ϕ1207.3-carrying lysogen were treated with mitomycin C to assess if ϕ1207.3 enters the lytic cycle. Mitomycin C induced a limited phage burst and a growth impairment resulting in early entrance in the stationary phase. To determine if ϕ1207.3 is able to produce mature phage particles we prepared concentrated supernatants recovered from a mitomycin C induced pneumococcal culture by sequential centrifugation and ultracentrifugation steps. Negative staining Transmission Electron Microscopy (TEM) of supernatants revealed the presence of phage particles with an icosahedral, electron dense capsid and a long, non-contractile tail, typical of a siphovirus. Quantification of ϕ1207.3 was performed by qPCR and semi-quantitatively by TEM. PCR quantified 3.34 × 104and 6.06 × 104excised forms of phage genome per ml of supernatant obtained from the untreated and mitomycin C treated cultures, respectively. By TEM, we estimated 3.02 × 103and 7.68 × 103phage particles per ml of supernatant. The phage preparations of ϕ1207.3 infected and lysogenised pneumococcal recipient strains at a frequency of 7.5 × 10−6lysogens/recipient, but did not show sufficient lytic activity to form plaques. Phage lysogenisation efficiently occurred after 30 minutes of contact of the phages with the recipient cells and required a minimum of 103phage particles.

Importance

Bacteriophages play an important role in bacterial physiology and genome evolution. The widespread use of genome sequencing revealed that bacterial genomes can contain several different integrated temperate bacteriophages, which can constitute up to 20% of the genome. Most of these bacteriophages are only predictedin silicoand never shown to be functional. In fact, it is often difficult to induce the lytic cycle of temperate bacteriophages. In this work, we show that ϕ1207.3, a peculiar bacteriophage originally fromStreptococcus pyogenes, which can lysogenise different Streptococci and carries the macrolide resistancemef(A)-msr(D) gene pair, is capable of producing mature virions, but only at a low level, while not being able to produce plaques. This temperate phage is probably a partially functional phage, which seems to have lost lytic characteristics to specialize into lysogenisation. While we are not used to conceive phages separately from lysis, this behavior could actually be more frequent than expected.
DNA transposons ofmaTfamily in the Cnidaria
Authors: Puzakov Mikhail V. , Puzakova Lyudmila V. , Cheresiz Sergey V. , Shi Shasha
Published: October 2022

Transposable elements exert a significant influence on the structure and size of eukaryotic genomes. Representatives ofTc1/marinersuperfamily of DNA transposons form a prevalent and highly variable group, which includes the relatively well studiedTLE/DD34-38E,MLE/DD34D,maT/DD37D,Visitor/DD41D,Guest/DD39D,mosquito/DD37E andL18/DD37E families. A detailed study of distribution and diversity ofTc1/marinertransposons will help us to better investigate the co-evolution of TEs and eukaryotic genomes. We performed a profound analysis ofmaT/DD37D family in the cnidarians. maT transposons were shown to exist in a limited number of cnidarian species belonging to Cubozoa, Hydrozoa and Scyphozoa classes.maTtransposons of the cnidarians are thought to be the descendants of several individual invasion events, which have occurred at different times in the past. Themosquito/DD37E transposons of the cnidarians have also been described. These TEs were shown to be present in Hydridae family (class Hydrozoa) only. An analysis of TE distribution, diversity, evolutionary history and phylogeny established that theTEs undergo their unique evolution not only in different species, but also within a particular species. These results improve our knowledge ofTc1/marinerdiversity and evolution, as well as their influence of eukaryotic genomes.
Standardising Breast Radiotherapy Structure Naming Conventions: A Machine Learning Approach
Authors: Haidar Ali , Field Matthew , Batumalai Vikneswary , Cloak Kirrily , Mouiee Daniel Al , Chlap Phillip , Huang Xiaoshui , Chin Vicky , Aly Farhannah , Carolan Martin , Sykes Jonathan , Vinod Shalini K. , Delaney Geoffrey P , Holloway Lois
Published: October 2022

In progressing the use of big data in health systems, standardised nomenclature is required to enable data pooling and analyses. In many radiotherapy planning systems and their data archives, target volumes (TV) and organ-at-risk (OAR) structure nomenclature has not been standardised. Machine learning (ML) have been utilized to standardise volumes nomenclature in retrospective datasets. However, only subsets of the structures have been targeted. Within this paper, we proposed a new approach for standardizing all the structures nomenclature by using multi-modal artificial neural networks. A cohort consisting of 1613 breast cancer patients treated with radiotherapy was identified from Liverpool & Macarthur Cancer Therapy Centres, NSW, Australia. Four types of volume characteristics were generated to represent each target and OAR volume: textual features, geometric features, dosimetry features, and imaging data. Five datasets were created from the original cohort, the first four represented different subsets of volumes and the last one represented the whole list of volumes. For each dataset, 15 sets of combinations of features were generated to investigate the effect of using different characteristics on the standardisation performance. The best model reported 99.416% classification accuracy over the hold-out sample when used to standardise all the nomenclatures in a breast cancer radiotherapy plan into 21 classes. Our results showed that ML based automation methods can be used for standardising naming conventions in a radiotherapy plan taking into consideration the inclusion of multiple modalities to better represent each volume.
Dog-related deaths registered in England and Wales from 2001 to 2021
Authors: Tulloch John SP , Oxley James A , Christley Robert M , Westgarth Carri
Published: October 2022

Introduction

This study aimed to describe the incidence and demographics of fatal dog bites or strikes, as defined in English and Welsh mortality data (2001-2021).

Methods

Data from the Office for National Statistics registered deaths dataset were used to identify individuals whose cause of death was defined as ‘bitten or struck by a dog’. The average annual number of dog-related deaths and trends in incidence were calculated. Age and sex demographics of victims were described.

Results

There were 3.3 (95%CI 0.3-6.3) dog-related deaths per year, a mean annual incidence of 0.59 (95%CI 0.06-1.11) deaths per 10 million population. There was no obvious trend in incidence. Of victims, 59% were male, 10% were <5 years, and 30% were ≥75 years.

Discussion

Dog-related deaths are rare in England and Wales and have not increased between 2001 and 2021. Further contextual information about the incidents is needed to be able to develop public health strategies and interventions.

What is already known on this subject?

Dog attacks can cause severe physical injury and psychological trauma, and can be fatal.

Hospital admissions due to ‘dog bites or strikes’ in England have doubled between 1998 and 2018, with males and young children the most likely to be bitten.

What this study adds?

Deaths attributed to dog bites or strikes in England and Wales over a 20-year period are rare events and do not appear to be increasing in incidence.

Registered deaths were more common in the very young and old, and in males.

Further contextual information concerning dog-related deaths is needed to develop public health strategies and interventions.
Precisely patterned nanofibers made from extendable protein multiplexes
Authors: Bethel Neville P. , Borst Andrew J. , Parmeggiani Fabio , Bick Matthew J. , Brunette TJ , Nguyen Hannah , Kang Alex , Bera Asim K. , Carter Lauren , Miranda Marcos C. , Kibler Ryan , Lamb Mila , Li Xinting , Sankaran Banumathi , Baker David
Published: October 2022

Molecular systems with coincident cyclic and superhelical symmetry axes have considerable advantages for materials design as they can be readily lengthened or shortened by changing the length of the constituent monomers. Among proteins, alpha helical coiled coils have such symmetric extendable architectures, but are limited by the relatively fixed geometry and flexibility of the helical protomers. Here, we describe a systematic approach to generating modular and rigid repeat protein oligomers with coincident C2to C8and superhelical symmetry axes that can be readily extended by repeat propagation. From these building blocks, we demonstrate that a wide range of unbounded fibers can be systematically designed by introducing hydrophilic surface patches that force staggering of the monomers; the geometry of such fibers can be precisely tuned by varying the number of repeat units in the monomer and the placement of the hydrophilic patches.
Differential chondrogenic differentiation between iPSC-derived from healthy and OA cartilage is associated with changes in epigenetic regulation and metabolic transcriptomic signatures
Authors: Khan Nazir M. , Diaz-Hernandez Martha Elena , Chihab Samir , Priyadarshani Priyanka , Bhattaram Pallavi , Mortensen Luke J. , Guzzo Rosa M , Drissi Hicham
Published: October 2022

Induced pluripotent stem cells (iPSCs) are potential cell sources for regenerative medicine. The iPSCs exhibit a preference for lineage differentiation to the donor cell type indicating the existence of memory of origin. Although the intrinsic effect of the donor cell type on differentiation of iPSCs is well recognized, whether disease-specific factors of donor cells influence the differentiation capacity of iPSC remains unknown. Using viral based reprogramming, we demonstrated the generation of iPSCs from chondrocytes isolated from healthy (AC-iPSCs) and osteoarthritis cartilage (OA-iPSCs). These reprogrammed cells acquired markers of pluripotency and differentiated into uncommitted-mesenchymal progenitors. Interestingly, AC-iPSCs exhibited enhanced chondrogenic potential as compared OA-iPSCs and showed increased expression of chondrogenic genes. Pan-transcriptome analysis showed that chondrocytes derived from AC-iPSCs were enriched in molecular pathways related to energy metabolism and epigenetic regulation, together with distinct expression signature that distinguishes them from OA-iPSCs. The molecular tracing data demonstrated that epigenetic and metabolic marks were imprint of original cell sources from healthy and OA-chondrocytes. Our results suggest that the epigenetic and metabolic memory of disease may predispose OA-iPSCs for their reduced chondrogenic differentiation and thus regulation at epigenetic and metabolic level may be an effective strategy for controlling the chondrogenic potential of iPSCs.