bluuebunny/crossref_metadata_2025 huggingface dataset:
15-month follow-up of anti-spike receptor binding domain (RBD) SARS-CoV-2 antibodies among healthcare workers in Boston, MA
Authors: Dodge Maura C. , Cole Manisha , Duffy Elizabeth R. , Werler Martha M. , Kataria Yachana
Published: March 2022

Over 15-months we found that anti-spike RBD SARS-CoV-2 antibody concentrations follow different trends with combinations and permutations of COVID-19 infection and vaccination among healthcare workers in Boston, MA. A majority of HCWs remain well above the positivity threshold for anti-spike RBD IgG antibodies for at least 9 months following vaccination regardless of infection history. Of interest, those with COVID-19 infection before vaccination had significantly higher median serum antibody concentrations in comparison to HCWs with no prior infection at each follow-up timepoint. These findings further support what is known regarding the decline in serum antibody concentrations following natural infection and vaccination, adding knowledge of serum antibodies up to 15 months post infection and 11 months post vaccination.

Importance

Boston Medical Center (BMC) is a safety net hospital in Boston and from the initial wave of COVID-19 there has been overwhelming concern about the exposure of healthcare workers to SARS-CoV-2. We conceived a longitudinal study to assess virus exposure and trends in SARS-CoV-2 antibodies amongst healthcare workers at BMC over 15 months. We have followed HCWs through three waves of COVID-19, including the Delta variant wave from June through mid-December 2021, assessing anti-spike receptor binding domain IgG, anti-nucleocapsid IgG, and anti-spike IgM at approximately three-month intervals. Current literature largely describes antibody durability six months post vaccination. These data add to the literature by describing antibody durability and trend differences according to infection history and vaccination status. These longitudinal data contribute to a greater understanding of the ongoing COVID-19 pandemic and can help inform future research and public health decision-making regarding vaccine uptake, breakthrough infections, and overall pandemic response.
Consent is a confounding factor in a prospective observational study of critically ill elderly patients
Authors: Flaatten Hans , Guidet Bertrand , Jung Christian , Boumendil Ariane , Leaver Susannah , Szczeklik Wojciech , Artigas Antonio , Andersen Finn , Moreno Rui , Walther Sten , Oeyen Sandra , Schefold Joerg C. , Marsh Brian , Joannidis Michael , Elhadi Muhammed , Nalapko Yuriy , Fjølner Jesper , de Lange Dylan W.
Published: March 2022

During analysis of a prospective multinational observation study of critically ill patients ≥80 years of age, the VIP2 study, we also studied the effects of differences in country consent for study inclusion. This is a post hoc analysis where the ICUs were analyzed according to requirement for study consent. Group A: ICUs in countries with no requirement for consent at admission but with deferred consent in survivors. Group B: ICUs where some form of active consent at admission was necessary either from the patient or surrogates. Patients’ characteristics, the severity of disease and outcome variables were compared. Totally 3098 patients were included from 21 countries. The median age was 84 years (IQR 81-87). England was not included because of changing criteria for consent during the study period. Group A (7 countries, 1220 patients), and group B (15 countries, 1878 patients) were comparable with age distribution, organ failure score, frailty score and activity of daily life. Cognition was better preserved prior to admission in group B. Group A suffered from more organ dysfunction at admission compared to group B with Sequential Organ Failure Assessment score median 8 and 5 respectively. Survival at 30-day was lower in group A, 50.8 % compared to 66.7% in group B (p<0.001). We found profound effects on outcomes according to differences in obtaining consent for this study. It seems that the most severely ill elderly patients were less often recruited to the study in group B. Hence the outcome measured as survival was higher in this group.

We therefore conclude that consent likely is an important confounding factor for outcome evaluation in international studies focusing on old patients.
Estimating diagnostic noise in panel-based genomic analysis
Authors: Beaumont Robin N. , Wright Caroline F.
Published: March 2022

Background

Gene panels with a series of strict variant filtering rules are often used for clinical analysis of exomes and genomes. Panels vary in size, which affects the sensitivity and specificity of the test. We sought to investigate the background rate of candidate diagnostic variants in a population setting using gene panels developed to diagnose a range of heterogeneous monogenic diseases.

Methods

We used the Genotype-2-Phenotype database with the Variant Effect Predictor plugin to identify rare non-synonymous variants in exome sequence data from 200,643 individuals in UK Biobank. We evaluated five clinically curated gene panels: developmental disorders (DD; 1708 genes), heritable eye disease (536 genes), skin disorders (293 genes), cancer syndromes (91 genes) and cardiac conditions (49 genes). We further tested the DD panel in 9,860 proband-parent trios from the Deciphering Developmental Disorders (DDD) study.

Results

As expected, bigger gene panels resulted in more variants being prioritised, varying from an average of ∼0.3 per person in the smallest panels, to ∼3.5 variants per person using the largest panel. The number of individuals with prioritised variants varied linearly with coding sequence length for monoallelic disease genes (∼300 individuals per 1000 base pairs) and quadratically for biallelic disease genes, with some notable outliers. Based on cancer registry data from UK Biobank, there was no detectable difference between cases and controls in the number of individuals with prioritised variants using the cancer panel, presumably due to the predominance of sporadic disease. However, we observed a marked increase in the number of prioritised variants in the DD panel in the DDD study (∼5 variants per proband). Phasing of compound heterozygotes in biallelic genes resulted in a modest reduction in the number of prioritised variants.

Conclusions

Although large gene panels may be the best strategy to maximize diagnostic yield in genetically heterogeneous diseases, they will frequently prioritise false positive candidate variants potentially requiring additional clinical follow-up. Most individuals will have at least one rare nonsynonymous variant in panels containing >500 monogenic disease genes. Extreme caution should therefore be applied when interpreting potentially pathogenic variants found in the absence of relevant phenotypes.
Exploring stroke survivors’ and physiotherapists’ perspectives of the potential for markerless motion capture technology in community rehabilitation
Authors: Faux-Nightingale Alice , Philp Fraser , Leone Enza , Helliwell Brinton Boreman , Pandyan Anand
Published: March 2022

INTRODUCTION

Many stroke survivors do not receive optimal levels of personalised therapy to support their recovery. Use of technology stroke rehabilitation has increased in recent years to help minimise gaps in service provision. Markerless motion capture technology is currently being used for musculoskeletal and occupational health screening and could offer a means to provide personalised guidance to stroke survivors struggling to access rehabilitation.

AIMS

This study considered context, stakeholders, and key uncertainties surrounding the use of markerless motion capture technology in community stroke rehabilitation from the perspectives of stroke survivors and physiotherapists with a view to adapting an existing intervention in a new context.

METHODS

Three focus groups were conducted with eight stroke survivors and five therapists. Data were analysed using reflexive thematic analysis.

RESULTS

Five themes were identified: limited access to community care; personal motivation; pandemic changed rehabilitation practice; perceptions of technology; and role of markerless technology for providing feedback.

CONCLUSIONS

Participants identified problems associated with the access of community stroke rehabilitation, exacerbated by Covid-19 restrictions. Participants were positive about the potential for the use of markerless motion capture technology as a means to support personalised, effective stroke rehabilitation in the future, providing it is developed to meet stroke survivor specific needs.
Toward a preventive approach to prolonged grief disorder in palliative care: Insecure attachment moderates the impact of perceived support on the severity of symptoms
Authors: Lenzo Vittorio , Sardella Alberto , Faraone Cristina , Quattropani Maria C.
Published: March 2022

Objective

This study aimed to investigate the relationships between the perceived support at the time of assistance, insecure attachment (i.e., avoidance and anxious attachment factors), and the prolonged grief symptoms in family caregivers of palliative care patients deceased for at least one year. We also investigated the moderating role of insecure attachment in the relationship between perceived support and intensity of prolonged grief symptoms.

Method

A sample of 157 participants completed the Prolonged Grief Scale (PG-13) and the Attachment Style Questionnaire (ASQ).

Results

Correlational analysis indicated that prolonged grief symptoms were positively correlated with the Avoidance attachment factor but not with the Anxious one. The perceived support was negatively related to both the Avoidance and the Anxious attachment factors. Lastly, the two insecure attachment factors were moderately and positively correlated with each other. Results of moderation analysis showed that the high Avoidance attachment moderated the effect of the perceived family and social support on the intensity of prolonged grief symptoms among family caregivers of patients assisted in palliative home care. Results also showed that the Anxious attachment factor had a significant effect on prolonged grief symptoms, even though the interaction with the perceived support was not significant.

Conclusions

Overall, these results underline that a high level of avoidance attachment may moderate the relationship between the perceived support and intensity of grief symptoms and thereby increasing the risk of developing a mental disorder. Intervention to prevent prolonged grief disorder among family caregivers should take into account these findings.
Projected impact on blood pressure, chronic kidney disease burden and healthcare costs of achieving the Australian sodium reduction targets: a modelling study
Authors: Aminde Leopold N. , Wanjau Mary , Cobiac Linda J. , Veerman J. Lennert
Published: March 2022

Background

Excess sodium intake increases blood pressure and risk of vascular complications. Most studies have focused on heart disease and stroke, but the impact on chronic kidney disease (CKD) is less well-characterised. The aim of this study was to estimate the impact of sodium intake on CKD burden in Australia.

Methods

A dynamic epidemiological model was developed to estimate the potential impact on CKD if the Australian Suggested Dietary Target (SDT) and the National Preventive Health Strategy 2021-2030 (NPHS) sodium target were achieved. Outcomes were estimated between 2019 (base year) and 2030, and lifetime.

Findings

Achieving the SDT and NPHS target could lower overall mean systolic blood pressure by 2.1 mmHg and 1.7 mmHg respectively. Compared to current sodium intake levels, attaining the SDT could prevent 59,220 (95% UI, 53,140 – 65,500) incident CKD cases and 568 (95% UI, 479 – 652) CKD deaths by 2030. Over the lifetime, this is projected to generate 199,488 (95% UI, 180,910 – 218,340) HALYs and AU$ 644 million in CKD health expenditure savings. Similarly, if achieved, the NPHS is estimated to prevent 49,890 (95% UI, 44,377 – 55,569) incident CKD cases and 511 (95% UI, 426 – 590) CKD deaths by 2030. Over the lifetime, this could produce 170,425 (95% UI, 155,017 – 186,559) HALYs and AU$ 514 million in CKD health expenditure savings.

Conclusion

Achieving the national sodium reduction targets could deliver substantial health and economic benefits for people with CKD in Australia. Robust government action is required in order to achieve the projected outcomes of these policy targets.
Cannabinoids regulate an insula circuit controlling water intake
Authors: Zhao Zhe , Covelo Ana , Mitra Arojit , Varilh Marjorie , Wu Yifan , Jacky Débora , Cannich Astrid , Bellocchio Luigi , Marsicano Giovanni , Beyeler Anna
Published: March 2022

The insular cortex, or insula, is a large brain region involved in the detection of thirst and the control of water intake. However our understanding of the topographical, circuit and molecular mechanisms the controlling water intake within the insula remains parcellated. We found that type-1 cannabinoid receptors (CB1) within the insular cortex participate to the regulation of water intake, and deconstructed circuit mechanisms of this control. Topographically, we revealed that the activity of excitatory neurons in both anterior (aIC) and posterior (pIC) insula increases in response to water intake, yet removal of CB1 receptors only in the pIC decreases water intake. Interestingly, we found that CB1 receptors are highly expressed in insula projections to the basolateral amygdala (BLA), while undetectable in the neighboring central part of the amygdala. Thus, we imaged the neurons of the anterior or posterior insula targeting the BLA (aIC-BLA and pIC-BLA), and found they oppositely respond to water intake, respectively decreasing and increasing their activity upon water drinking. Consistently, chemogenetic activation of pIC-BLA neurons decreased water intake. Finally, we uncovered CB1-dependent short term synaptic plasticity (depolarization-induced suppression of excitation, DSE) selectively in pIC-BLA, compared to aIC-BLA synapses. Altogether, our results support a model where CB1 signaling in the pIC-BLA pathway exerts a positive control on water intake.
Persistent Immune and Clotting Dysfunction Detected in Saliva and Blood Plasma after COVID-19
Authors: Jang Hyesun , Choudhury Saibyasachi , Yu Yanbao , Sievers Benjamin L. , Gelbart Terri , Singh Harinder , Rawlings Stephen A. , Proal Amy , Tan Gene S. , Smith Davey , Freire Marcelo
Published: March 2022

A growing number of studies indicate that coronavirus disease 2019 (COVID-19) is associated with inflammatory sequelae, but molecular signatures governing the normal vs. pathologic convalescence process have not been well-delineated. We characterized global immune and proteome responses in matched plasma and saliva samples obtained from COVID-19 patients collected between 4-6 weeks after initial clinical symptoms resolved. Convalescent subjects showed robust IgA and IgG responses and positive antibody correlations between matched saliva and plasma samples. However, global shotgun proteomics revealed persistent inflammatory patterns in convalescent samples including dysfunction of salivary innate immune cells and clotting factors in plasma (e.g., fibrinogen and antithrombin), with positive correlations to acute COVID-19 disease severity. Saliva samples were characterized by higher concentrations of IgA, and proteomics showed altered pathways that correlated positively with IgA levels. Our study positions saliva as a viable fluid to monitor immunity beyond plasma to document COVID-19 immune, inflammatory, and coagulation-related sequelae.
Ultrasound Neuromodulation and Correlation Change in the Rat Somatosensory Cortex
Authors: Ramachandran Sandhya , Niu Xiaodan , Yu Kai , He Bin
Published: March 2022

Transcranial focused ultrasound (tFUS) is a neuromodulation technique which has been the focus of increasing interest for noninvasive brain stimulation with high spatial specificity. Its ability to excite and inhibit neural circuits as well as to modulate perception and behavior has been demonstrated, however, we currently lack understanding of how tFUS modulates the ways neurons interact with each other. This understanding would help explain tFUS’s mechanism of high-level neuromodulation and allow future development of therapies for neurological disorders. In this study we investigate how tFUS modulates neural interaction and response to peripheral electrical limb stimulation through intracranial multi-electrode recordings in the rat somatosensory cortex. We deliver ultrasound in a pulsed pattern to attempt to induce frequency dependent plasticity in a manner similar to that found following electrical stimulation. We show that neural firing in response to peripheral electrical stimulation is increased after ultrasound stimulation at all frequencies, showing tFUS induced excitation in individual neurons in vivo. We demonstrate tFUS frequency dependent pairwise correlation changes between neurons, with both potentiation and depression observed at different frequencies. These results extend previous research showing tFUS to be capable of inducing synaptic depression and demonstrate its ability to modulate network dynamics as a whole.
Human Galectin-9 Potently Enhances SARS-CoV-2 Replication and Inflammation in Airway Epithelial Cells
Authors: Du Li , Bouzidi Mohamed S. , Gala Akshay , Deiter Fred , Billaud Jean-Noël , Yeung Stephen T. , Dabral Prerna , Jin Jing , Simmons Graham , Dossani Zain , Niki Toshiro , Ndhlovu Lishomwa C. , Greenland John R. , Pillai Satish K.
Published: March 2022

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic has caused a global economic and health crisis. Recently, plasma levels of galectin-9 (Gal-9), a β-galactoside-binding lectin involved in immune regulation and viral immunopathogenesis, were reported to be elevated in the setting of severe COVID-19 disease. However, the impact of Gal-9 on SARS-CoV-2 infection and immunopathology remained to be elucidated. Here, we demonstrate that Gal-9 treatment potently enhances SARS-CoV-2 replication in human airway epithelial cells (AECs), including primary AECs in air-liquid interface (ALI) culture. Gal-9-glycan interactions promote SARS-CoV-2 attachment and entry into AECs in an ACE2-dependent manner, enhancing the binding affinity of the viral spike protein to ACE2. Transcriptomic analysis revealed that Gal-9 and SARS-CoV-2 infection synergistically induce the expression of key pro-inflammatory programs in AECs including the IL-6, IL-8, IL-17, EIF2, and TNFα signaling pathways. Our findings suggest that manipulation of Gal-9 should be explored as a therapeutic strategy for SARS-CoV-2 infection.

Importance

COVID-19 continues to have a major global health and economic impact. Identifying host molecular determinants that modulate SARS-CoV-2 infectivity and pathology is a key step in discovering novel therapeutic approaches for COVID-19. Several recent studies have revealed that plasma concentrations of the human β-galactoside-binding protein galectin-9 (Gal-9) are highly elevated in COVID-19 patients. In this study, we investigated the impact of Gal-9 on SARS-CoV-2 pathogenesis ex vivo in airway epithelial cells (AECs), the critical initial targets of SARS-CoV-2 infection. Our findings reveal that Gal-9 potently enhances SARS-CoV-2 replication in AECs, interacting with glycans to enhance the binding between viral particles and entry receptors on the target cell surface. Moreover, we determined that Gal-9 accelerates and exacerbates several virus-induced pro-inflammatory programs in AECs that are established signature characteristics of COVID-19 disease and SARS-CoV-2-induced acute respiratory distress syndrome (ARDS). Our findings suggest that Gal-9 is a promising pharmacological target for COVID-19 therapies.
Transposon activities drive the selection and diversification of sweet orange (Citrus × sinensis) cultivars in the last 500 years
Authors: Wu Bo , Cui Yiping , Duan Yongping , Gmitter Frederick G. , Luo Feng
Published: March 2022

Sweet orange (SWO) has one of the largest numbers of cultivar groups inCitruswith diverse horticultural traits just through asexual breeding. However, the molecular mechanism driving its fast selection and diversification is unclear. In this study, we completely surveyed the transposon activities in SWO genomes and unraveled six transposon families with up to 8,974.2-fold activity increase in modern SWO cultivars. Based on the transposon insertion phylogenetic tree, we inferred that modern SWOs date back to a common ancestor ∼500 years ago and reconstructed three major spread events in SWO cultivation history. Activation, acceleration, and silencing of the six families have recurred in distinct lineages. Their insertions are presented as tag mutations for all SWO cultivar groups and can distinguish over 99% of all analyzed SWO accessions. The insertions are enriched in impacting plant development and hormone signaling. This study demonstrated the importance of transposon activities in asexual breeding.
STING controls T cell memory fitness during infection through T cell intrinsic and IDO dependent mechanisms
Authors: Quaney Michael J. , Newth Rebecca J. , Karin Knudson M. , Saxena Vikas , Pritzl Curtis J. , Rae Chris S. , Lauer Peter , Daniels Mark A. , Teixeiro Emma
Published: March 2022

Stimulator of interferon genes (STING) signaling has been extensively studied in inflammatory diseases and cancer while its role in T cell responses to infection is unclear. UsingListeria monocytogenesstrains engineered to induce different levels of c-di-AMP, we found that strong STING signals impaired T cell memory upon infection via increased Bim levels and apoptosis. Unexpectedly, reduction of TCR signal strength or T cell-STING expression decreased Bim expression, T cell apoptosis and recovered T cell memory. We found that TCR signal intensity coupled STING signal strength to the Unfolded Protein Response (UPR) and T cell survival. Under strong STING signaling, IDO inhibition also reduced apoptosis and led to a recovery of T cell memory in STING sufficient CD8 T cells. Thus, STING signaling regulates CD8 T cell memory fitness through both cell-intrinsic and extrinsic mechanisms. These studies provide insight into how IDO and STING therapies could improve long-term T cell protective immunity.

Significance Statement

STING signaling is an innate pathway that triggers host immunity against pathogens and cancer in response to cytosolic DNA. Additionally, STING signaling overactivation has been linked to autoimmunity. Yet, the interaction between antigenic and STING signaling and its impact in the development of protective immunity has remained unexplored. We found that strong levels of STING signaling impair CD8 T cell memory but only in response to high affinity TCR-pMHC interactions. Here, we provide evidence of how TCR signal strength controls STING signaling and IDO metabolism to regulate T cells’ survival as they mature to memory. These data have important implications for the design of STING and IDO combination immunotherapies
Cloning of Nine Glucocorticoid Receptor Isoforms from the Slender African lungfish (Protopterus dolloi)
Authors: Katsu Yoshinao , Oana Shin , Lin Xiaozhi , Hyodo Susumu , Bianchetti Laurent , Baker Michael E.
Published: March 2022

We wanted to clone the glucocorticoid receptor (GR) from slender African lungfish (Protopterus dolloi) for comparison to P. dolloi MR, which we had cloned and were characterizing, as well as for comparison to the GRs from humans, elephant shark and zebrafish. However, although sequencing of the genome of the Australian lungfish (Neoceratodus forsteri), as well as, that of the West African lungfish (Protopterus annectens) were reported in the first three months of 2021, we could not retrieve a GR sequence with a BLAST search of GenBank, when we submitted our research for publication in July 2021. Moreover, we were unsuccessful in cloning the GR from slender African lungfish using a cDNA from the ovary of P. dolloi and PCR primers that had successfully cloned a GR from elephant shark, Xenopus and gar GRs. On October 21, 2021 the nucleotide sequence of West African lungfish (P. annectens) GR was deposited in GenBank. We used this GR sequence to construct PCR primers that successfully cloned the GR from the slender spotted lungfish. Here, we report the sequences of nine P. dolloi GR isoforms and explain the basis for the previous failure to clone a GR from slender African lungfish using PCR primers that cloned the GR from elephant shark, Xenopus and gar. Studies are underway to determine corticosteroid activation of these slender African lungfish GRs.
Correlations between human mating partners: a comprehensive meta-analysis of 22 traits and raw data analysis of 133 traits in the UK Biobank
Authors: Horwitz Tanya B. , Balbona Jared V. , Paulich Katie N. , Keller Matthew C.
Published: March 2022

Positive correlations between human mating partners are consistently observed across traits. Such correlations can increase phenotypic variation and, to the extent that they reflect genetic similarity in co-parents, can also increase prevalence for rare phenotypes and bias estimates in genetic designs. We conducted the largest set of meta-analyses on human partner correlations to date, incorporating 480 partner correlations across 22 traits. We also calculated 133 trait correlations between up to 79,074 male-female couples in the UK Biobank (UKB). Estimates of the mean meta-analyzed correlations ranged fromrmeta=.08 for extraversion tormeta=.58 for political values. UKB correlations ranged fromrUKB=-.18 for chronotype torUKB=.87 for birth year. Overall, attitudes, education, and substance use traits mostly showed the highest correlations, while psychological and biological traits generally yielded lower but still positive correlations. We observed high between-study heterogeneity for most meta-analyzed traits, likely because of both systematic differences between samples and true differences in partner correlations across populations.
Directional anchor genes refine polygenic informed treatment selection in schizophrenia and bipolar disorder
Authors: Reay William R , Geaghan Michael P , Atkins Joshua Ronald , Carr Vaughan J , Green Melissa J , Cairns Murray J
Published: March 2022

Genetically informed drug development and repurposing is an attractive prospect for improving outcomes in patients with psychiatric illness; however, the effectiveness of these endeavours can be confounded by heterogeneity. In this study, we propose a novel approach that links interventions implicated by disorder-associated genetic risk, at the population level, to a framework that can target these compounds to individuals. Specifically, results from genome-wide association studies are integrated with expression data to prioritise individual 'directional anchor' genes for which the predicted risk-increasing direction of expression could be counteracted by an existing drug. While these compounds represent plausible therapeutic candidates, they are not likely to be equally efficacious for all individuals. To account for this heterogeneity, we constructed polygenic scores restricted to variants annotated to the network of genes that interact with each directional anchor gene. These metrics, we call pharmagenic enrichment scores (PES), identify individuals with a higher burden of genetic risk, localised in biological processes related to the candidate drug target, to inform precision drug repurposing. We used this approach to investigate schizophrenia and bipolar disorder and reveal several compounds targeting specific directional anchor genes that could be plausibly repurposed, including antioxidants, vitamins, antiarrhythmics, and lipid modifying agents. These genetic risk scores, mapped to the networks associated with target genes, revealed biological insights that cannot be observed in undifferentiated genome-wide polygenic risk score (PRS). For example, an enrichment of these partitioned scores in schizophrenia cases with otherwise low PRS and distinct correlations with measured biochemical traits. In summary, genetic risk could be used more specifically to direct drug repurposing candidates that target particular genes implicated in psychiatric and other complex disorders.
The Outcome of Gynecologic Cancer Patients With Covid-19 Infection: A Systematic Review And Meta-Analysis
Authors: Sastra Winata I Gde , Simatupang Januar , Polim Arie A , Togar Yakob , Tondang Advenny Elisabeth
Published: March 2022

Objective

Cancer is a comorbidity that leads to progressive worsening of Covid-19 with increased mortality. This is a systematic review and meta-analysis to yield evidence of adverse outcomes of Covid-19 in gynecologic cancer.

Methods

Searches through PubMed, Google Scholar, ScienceDirect, and medRxiv to find articles on the outcome of gynecologic cancer with Covid-19 (24 July 2021-19 February 2022). Newcastle-Ottawa Scale tool is used to evaluate the quality of included studies. Pooled odds ratio (OR), 95% confidence interval (CI), random-effects model were presented. This study was registered to PROSPERO (CRD42021256557).

Results

We accepted 51 studies (1991 gynecologic cancer with Covid-19). Covid-19 infection was lower in gynecologic cancer vs hematologic cancer (OR 0.71, CI 0.56-0.90, p 0.005). Severe Covid and death were lower in gynecologic cancer vs lung and hematologic cancer (OR 0.36, CI 0.16-0.80, p 0.01), (OR 0.52, CI 0.44-0.62, p <0.0001), (OR 0.26, CI 0.10-0.67 p 0.005), (OR 0.63, CI 0.47-0.83, p 0.001) respectively. Increased Covid death is seen in gynecologic cancer vs breast, non-covid cancer, and non-cancer covid (OR 1.50, CI 1.20-1.88, p 0.0004), (OR 11.83, CI 8.20-17.07, p <0.0001), (OR 2.98, CI 2.23-3.98, p <0.0001) respectively.

Conclusion

Gynecologic cancer has higher Covid-19 adverse outcomes compared to non-cancer, breast cancer, non-metastatic, and Covid-19 negative population. Gynecologic cancer has fewer Covid-19 adverse outcomes compared to other cancer types, lung cancer, and hematologic cancer. These findings may aid health policies and services during the ongoing global pandemic.
A computational model for individual differences in non-reinforced learning for individual items
Authors: Salomon Tom , Itzkovitch Alon , Daw Nathaniel D. , Schonberg Tom
Published: March 2022

Cue-Approach Training (CAT) is a paradigm that enhances preferences without external reinforcmeents, suggesting a potential role for internal learning processes. Here, we developed a novel Bayesian computational model to quantify anticipatory response patterns during the training phase of CAT. This phase includes individual items and thus this marker is potentially of internal learning signals at the item level. Our model, fitted to meta-analysis data from 29 prior CAT experiments, was able to predict individual differences in non-reinforced preference changes using a key computational marker. Crucially, two new experiments manipulated the training procedure to influence the model’s predicted learning marker. As predicted and preregistered, the manipulation successfully induced differential preference changes, supporting a causal role of our model. These findings demonstrate powerful potential of our computational framework for investigating intrinsic learning processes. This framework could be used to predict preference changes and opens new avenues for understanding intrinsic motivation and decision-making.

Teaser

Bayesian modeling of response time predicts individual differences in non reinforced preference change.
Syrah, a Slide-seqV2 pipeline augmentation
Authors: Brewster C.E. , Mann F.G. , Benham-Pyle B.W. , Sánchez Alvarado A.
Published: March 2022

Spatial transcriptomic techniques such as Slide-seqV2 uncover novel relationships and interactions between cell types by coupling gene expression and spatial data. Here we discuss two unexpected sources of error in Slide-seqV2 data, one physical and one computational. To address this we present an analysis pipeline augmentation, Syrah, which corrects for these errors and show that it improves both data quantity and quality over the standard pipeline alone or in combination with additional sequencing.
Planarians employ diverse and dynamic stem cell microenvironments to support whole-body regeneration
Authors: Benham-Pyle Blair W. , Mann Frederick G. , Brewster Carolyn E. , Dewars Enya R. , Vuu Dung M. , Nowotarski Stephanie H. , Guerrero-Hernández Carlos , Malloy Seth , Hall Kate E. , Maddera Lucinda E. , Chen Shiyuan , Morrison Jason A. , McKinney Sean A. , Slaughter Brian D. , Perera Anoja , Alvarado Alejandro Sánchez
Published: March 2022

Stem cells enable regeneration by self-renewing and differentiating as instructed by a local microenvironment called a niche1–3. In most cases, the repair or replacement of tissues is fueled by tissue-specific or lineage-restricted stem cells that proliferate in response to local injury and apoptosis4–11. However, in organisms that regenerate using abundant adult pluripotent stem cells, the stem cell niches that support tissue repair have not been identified or characterized. Since these adult pluripotent stem cells are often more widely distributed and plentiful than lineage-restricted stem cells of other organisms, defining their microenvironments may uncover alternative forms of stem cell regulation12–14. Here we used unbiased spatial transcriptomics to define the cellular and molecular environments that support pluripotency in the highly regenerative freshwater planarianSchmidtea mediterranea. We determined that stem cells associate with a diverse collection of differentiated cell types, and these associations are highly dynamic during regeneration. We explored associations with two distinct cell types: secretory cells we term ‘hecatonoblasts,’ and intestinal cells. While both cell types regulate stem cell proliferation, their spatial relationships to stem cells defy the concept of a single regenerative niche. Thus, the planarian stem cell pool is likely maintained by a dynamic collection of distinct microenvironments that cooperatively power whole-body regeneration.
Eusocial insect queens show costs of reproduction and transcriptomic signatures of reduced longevity
Authors: Collins David H. , Prince David C. , Donelan Jenny L. , Chapman Tracey , Bourke Andrew F. G.
Published: March 2022

Eusocial insect queens have been suggested to be counter-examples to the standard evolutionary theory of ageing through lacking costs of reproduction. Using the bumblebee (Bombus terrestris), we tested this hypothesis experimentally against the alternative that costs of reproduction exist in eusocial insect queens, but are latent, resulting in the positive fecundity-longevity relationship typically found in unmanipulated queens. We experimentally increased queens’ costs of reproduction by removing their eggs, which causes queens to increase their egg-laying rate. Treatment queens had significantly reduced longevity relative to control queens whose egg-laying rate was not increased. In addition, treatment and control queens differed in age-related gene expression based on mRNA-seq in both their overall expression profiles and the expression of ageing-related genes. Remarkably, this occurred principally with respect to relative age, not chronological age. These results provide the first simultaneously phenotypic and transcriptomic experimental evidence of costs of reproduction in queens of eusocial insects and suggest how the genetic pathways underpinning ageing might become remodelled during eusocial evolution.
A Tailored Approach To Study Legionella Infection Using Lattice Light Sheet Microscope (LLSM)
Authors: Yi Xiyu , Miao Haichao , Lo Jacky Kai-Yin , Elsheikh Maher M. , Lee Tek Hyung , Jiang Chenfanfu , Zhang Yuliang , Segelke Brent W. , Overton K. Wesley , Bremer Peer-Timo , Laurence Ted A.
Published: March 2022

Legionella is a genus of ubiquitous environmental pathogens found in freshwater systems, moist soil, and composted materials. More than four decades of Legionella research has provided important insights into Legionella pathogenesis [1]. Although standard commercial microscopes have led to significant advances in understanding Legionella pathogenesis [2,3], great potential exists in the deployment of more advanced imaging techniques to provide additional insights. The Lattice Light Sheet Microscope (LLSM) is a recently developed microscope for 4D live cell imaging with high resolution and minimum photo-damage [4]. We built a LLSM with an improved version for the optical layout with two path-stretching mirror sets and a novel Reconfigurable Galvanometer Scanner (RGS) module to improve the reproducibility and reliability of the alignment and maintenance of the LLSM. We commissioned this LLSM to study Legionella pneumophila infection with a tailored workflow designed over instrumentation, experiments, and data processing methods. Our results indicate that Legionella pneumophila infection is correlated with a series of morphological signatures such as smoothness, migration pattern and polarity both statistically and dynamically. Our work demonstrates the benefits of using LLSM for studying long-term questions in bacterial infection. Our free-for-use modifications and workflow designs on the use of LLSM system contributes to the adoption and promotion of the state-of-the-art LLSM technology for both academic and commercial applications.
Quantitation, base identity and distribution of stably incorporated ribonucleotides in nuclear and mitochondrial DNA from murine tissues
Authors: Kreisel Katrin , Kalm Josephine , Bandaru Sashidar , Ala Chandu , Akyürek Levent M. , Clausen Anders R. Ranegaard
Published: March 2022

Ribonucleotides are estimated to be the most common non-canonical nucleotides transiently incorporated in DNA. Their presence or failure of their removal can affect genome stability and mutations in factors involved in dNTP pool maintenance or ribonucleotide removal can cause Aicardi-Goutières syndrome or promote certain human cancers. Here, we have mapped and quantitated ribonucleotides genome-wide, in nine tissues of wild-type mice. We observed tissue-specific variation in number and base identity of incorporated ribonucleotides and present evidence that a number of genomic features, such as tRNA genes, transcription start sites and G-quadruplexes, can increase the frequency of stably incorporated ribonucleotides in their proximity. Moreover, we present the non-random distribution of incorporated ribonucleotides in mtDNA and identified ribonucleotide hotspots. The study presents a framework to understand the physiological role of ribonucleotides in mammalian DNA.
Regional importation and asymmetric within-country spread of SARS-CoV-2 variants of concern in the Netherlands
Authors: Han Alvin X. , Kozanli Eva , Koopsen Jelle , Vennema Harry ,   RIVM COVID-19 molecular epidemiology group, Hajji Karim , Kroneman Annelies , van Walle Ivo , Klinkenberg Don , Wallinga Jacco , Russell Colin A. , Eggink Dirk , Reusken Chantal B.E.M.
Published: March 2022

Variants of concern (VOCs) of SARS-CoV-2 have caused resurging waves of infections worldwide. In the Netherlands, Alpha, Beta, Gamma and Delta variants circulated widely between September 2020 and August 2021. To understand how various control measures had impacted the spread of these VOCs, we analyzed 39,844 SARS-CoV-2 genomes collected under the Dutch national surveillance program. We found that all four VOCs were introduced before targeted flight restrictions were imposed on countries where the VOCs first emerged. Importantly, foreign introductions, predominantly from other European countries, continued during these restrictions. Our findings show that flight restrictions had limited effectiveness in deterring VOC introductions due to the strength of regional land travel importation risks. We also found that the Alpha and Delta variants largely circulated more populous regions
with international connections after their respective introduction before asymmetric bidirectional transmissions occurred with the rest of the country and the variant dominated infections in the Netherlands. As countries consider scaling down SARS-CoV-2 surveillance efforts in the post-crisis phase of the pandemic, our results highlight that robust surveillance in regions of early spread is important for providing timely information for variant detection and outbreak control.
Cost-effectiveness of antigen testing for ending COVID-19 isolation
Authors: Maya Sigal , Kahn James G.
Published: March 2022

Background

The Omicron variant of SARS-CoV-2 led to a steep rise in transmissions. Recently, as public tolerance for isolation abated, CDC guidance on duration of at-home isolation of COVID-19 cases was shortened to five days if no symptoms, with no lab test requirement, despite more cautious approaches advocated by other federal experts.

Methods

We conducted a decision tree analysis of alternative protocols for ending COVID-19 isolation, estimating net costs (direct and productivity), secondary infections, and incremental cost-effectiveness ratios. Sensitivity analyses assessed the impact of input uncertainty.

Results

Per 100 individuals, five-day isolation had 23 predicted secondary infections and a net cost of $33,000. Symptom check on day five (CDC guidance) yielded a 23% decrease in secondary infections (to 17.8), with a net cost of $45,000. Antigen testing on day six yielded 2.9 secondary infections and $63,000 in net costs. This protocol, compared to the next best protocol of antigen testing on day five of a maximum eight-day isolation, cost an additional $1,300 per secondary infection averted. Antigen or polymerase chain reaction testing on day five were dominated (more expensive and less effective) versus antigen testing on day six. Results were qualitatively robust to uncertainty in key inputs.

Conclusions

A six-day isolation with antigen testing to confirm the absence of contagious virus appears the most effective and cost-effective de-isolation protocol to shorten at-home isolation of individuals with COVID-19.
Altered Brain Responses to Noxious Dentoalveolar Stimuli in High-Impact Temporomandibular Disorder Pain Patients
Authors: Peck Connor , Bereiter David A. , Eberly Lynn E. , Lenglet Christophe , Moana-Filho Estephan
Published: March 2022

High-impact temporomandibular disorder (TMD) pain may involve brain mechanisms related to central sensitization. We investigated brain responses to stimulation of trigeminal sites not typically associated with TMD pain by applying noxious dentoalveolar pressure to high- and low-impact TMD pain cases and pain-free controls during functional magnetic resonance imaging (fMRI). Fifty female participants were recruited and assigned to one of three groups based on the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) and Graded Chronic Pain Scale: controls (n=17), low-impact (n=17) and high-impact TMD (n=16). Multimodal whole-brain MRI was acquired following the Human Connectome Project protocol, including stimulus-evoked fMRI scans during which painful dentoalveolar pressure was applied to the buccal gingiva of participants. Group analyses were performed using non-parametric permutation tests for parcellated cortical and subcortical neuroimaging data. There were no significant between-group differences for brain activations/deactivations evoked by the noxious dentoalveolar pressure. For individual group mean activations/deactivations, a gradient in the number of parcels surviving thresholding was found according to the TMD pain grade, with the highest number seen in the high-impact group. Among the brain regions activated in chronic TMD pain groups were those previously implicated in sensory-discriminative and motivational-affective pain processing. These results suggest that dentoalveolar pressure pain evokes abnormal brain responses to sensory processing of noxious stimuli in high-impact TMD pain participants, which supports the presence of maladaptive brain plasticity in chronic TMD pain.
Social information-mediated population dynamics in non-grouping prey
Authors: Tóth Zoltán , Csöppü Gabriella
Published: March 2022

Inadvertent social information (ISI) use, i.e., the exploitation of social cues including the presence and behaviour of others, has been predicted to mediate population-level processes even in the absence of cohesive grouping. However, we know little about how such effects may arise when the prey population lacks social structure beyond the spatiotemporal autocorrelation originating from the random movement of individuals. In this study, we built an individual-based model where predator avoidance behaviour could spread among randomly moving prey through the network of nearby observers. We qualitatively assessed how ISI use may affect prey population size when cue detection was associated with different probabilities and fitness costs, and characterised the structural properties of the emerging detection networks that would provide pathways for information spread in prey. We found that ISI use was among the most influential model parameters affecting prey abundance and increased equilibrium population sizes in most examined scenarios. Moreover, it could substantially contribute to population survival under high predation pressure, but this effect strongly depended on the level of predator detection ability. When prey exploited social cues in the presence of high predation risk, the observed detection networks consisted of a large number of connected components with small sizes and small ego networks; this resulted in efficient information spread among connected individuals in the detection networks. Our study provides hypothetical mechanisms about how temporary local densities may allow information diffusion about predation threats among conspecifics and facilitate population stability and persistence in non-grouping animals.

Significance Statement

The exploitation of inadvertently produced social cues may not only modify individual behaviour but also fundamentally influence population dynamics and species interactions. Using an individual-based model, we investigated how the detection and spread of adaptive antipredator behaviour may cascade to changes in the demographic performance of randomly moving (i.e., non-grouping) prey. We found that social information use contributed to population stability and persistence by reducing predation-related per capita mortality and raising equilibrium population sizes when predator detection ability reached a sufficient level. We also showed that temporary detection networks had structural properties that allowed efficient information spread among prey under high predation pressure. Our work represents a general modelling approach that could be adapted to specific predator-prey systems and scrutinize how temporary local densities allow dynamic information diffusion about predation threats and facilitate population stability in non-grouping animals.
Estimating the time structure of descending activation that generates movements at different speeds
Authors: Ramadan Rachid , Hummert Cora , Jokeit Jean-Stephane , Schöner Gregor
Published: March 2022

In targeted movements of the hand, descending activation patterns must not only generate muscle activation, but must also adjust spinal reflexes from stabilizing the initial to stabilizing the final postural state. We estimate descending activation patterns that change minimally while generating a targeted movement within a given movement time based on a model of the biomechanics, muscle dynamics, and the stretch reflex. The estimated descending activation patterns predict human movement trajectories quite well. Their temporal structure varies across workspace and with movement speed,  from monotonic profiles for slow movements to non-monotonic profiles for fast movements. Descending activation patterns at different speeds thus do not result from a not mere rescaling of invariant templates, but reflect varying needs to compensate for interaction torques and muscle dynamics. The virtual attractor trajectories, on which active muscle torques are zero, lie within reachable workspace and are largely invariant movements when represented in end-effector coordinates. Their temporal structure along movement direction changes from linear ramps to ''N-shaped'' profiles with increasing movement speed.