bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontostriatothalamic effective connectivity and dopaminergic function in the psychosis continuum
Authors: Sabaroedin Kristina , Razi Adeel , Chopra Sidhant , Tran Nancy , Pozaruk Andrii , Chen Zhaolin , Finlay Amy , Nelson Barnaby , Allott Kelly , Alvarez-Jimenez Mario , Graham Jessica , Yuen Hok P , Harrigan Susy , Cropley Vanessa , Sharma Sujit , Saluja Bharat , Williams Rob , Pantelis Christos , Wood Stephen J , O’Donoghue Brian , Francey Shona , McGorry Patrick , Aquino Kevin , Fornito Alex
Published: January 2022

Dysfunction of fronto-striato-thalamic (FST) circuits is thought to contribute to dopaminergic dysfunction and symptom onset in psychosis, but it remains unclear whether this dysfunction is driven by aberrant bottom-up subcortical signalling or impaired top-down cortical regulation.

We used spectral dynamic causal modelling of resting-state functional MRI to characterize the effective connectivity of dorsal and ventral FST circuits in a sample of 46 antipsychotic-naïve first-episode psychosis patients and 23 controls and an independent sample of 36 patients with established schizophrenia and 100 controls. We also investigated the association between FST effective connectivity and striatal 18F-DOPA uptake in an independent healthy cohort of 33 individuals who underwent concurrent functional MRI and PET.

Using a posterior probability threshold of 0.95, we found that midbrain and thalamic connectivity were implicated as dysfunctional across both patient groups. Dysconnectivity in first-episode psychosis patients was mainly restricted to the subcortex, with positive symptom severity being associated with midbrain connectivity. Dysconnectivity between the cortex and subcortical systems was only apparent in established schizophrenia patients. In the healthy 18F-DOPA cohort, we found that striatal dopamine synthesis capacity was associated with the effective connectivity of nigrostriatal and striatothalamic pathways, implicating similar circuits to those associated with psychotic symptom severity in patients.

Overall, our findings indicate that subcortical dysconnectivity is evident in the early stages of psychosis, that cortical dysfunction may emerge later in the illness, and that nigrostriatal and striatothalamic signalling are closely related to striatal dopamine synthesis capacity, which is a robust marker for psychosis.
Matrix metalloproteinase 10 is linked to the risk of progression to dementia of the Alzheimer’s type
Authors: Martino Adami Pamela V , Orellana Adelina , García Pablo , Kleineidam Luca , Alarcón-Martín Emilio , Montrreal Laura , Aguilera Nuria , Espinosa Ana , Abdelnour Carla , Rosende-Roca Maitee , Pablo Tartari Juan , Vargas Liliana , Mauleón Ana , Esteban-De Antonio Ester , López-Cuevas Rogelio , Dalmasso Maria Carolina , Campos Martin Rafael , Parveen Kayenat , Andrade Fuentes Victor M , Amin Najaf , Ahmad Shahzad , Ikram M Arfan , Lewczuk Piotr , Kornhuber Johannes , Peters Oliver , Frölich Lutz , Rüther Eckart , Wiltfang Jens , Tarraga Lluis , Boada Merce , Maier Wolfgang , de Rojas Itziar , Cano Amanda , Sanabria Angela , Alegret Montserrat , Hernández Isabel , Marquié Marta , Valero Sergi , van Duijn Cornelia M , Wagner Michael , Jessen Frank , Schneider Anja , Sáez Goñi María Eugenia , González Pérez Antonio , Ruiz Agustín , Ramírez Alfredo
Published: January 2022

Alzheimer’s disease has a long asymptomatic phase that offers a substantial time window for intervention. Using this window of opportunity will require early diagnostic and prognostic biomarkers to detect Alzheimer’s disease pathology at predementia stages, thus allowing identification of patients who will most probably progress to dementia of the Alzheimer’s type and benefit from specific disease-modifying therapies. Consequently, we searched for CSF proteins associated with disease progression along with the clinical disease staging.

We measured the levels of 184 proteins in CSF samples from 556 subjective cognitive decline and mild cognitive impairment patients from three independent memory clinic longitudinal studies (Spanish ACE, n = 410; German DCN, n = 93; German Mannheim, n = 53). We evaluated the association between protein levels and clinical stage, and the effect of protein levels on the progression from mild cognitive impairment to dementia of the Alzheimer’s type.

Mild cognitive impairment subjects with increased CSF level of matrix metalloproteinase 10 (MMP-10) showed a higher probability of progressing to dementia of the Alzheimer’s type and a faster cognitive decline. CSF MMP-10 increased the prediction accuracy of CSF amyloid-β 42 (Aβ42), phospho-tau 181 (P-tau181) and total tau (T-tau) for conversion to dementia of the Alzheimer’s type. Including MMP-10 to the [A/T/(N)] scheme improved considerably the prognostic value in mild cognitive impairment patients with abnormal Aβ42, but normal P-tau181 and T-tau, and in mild cognitive impairment patients with abnormal Aβ42, P-tau181 and T-tau. MMP-10 was correlated with age in subjects with normal Aβ42, P-tau181 and T-tau levels.

Our findings support the use of CSF MMP-10 as a prognostic marker for dementia of the Alzheimer’s type and its inclusion in the [A/T/(N)] scheme to incorporate pathologic aspects beyond amyloid and tau. CSF level of MMP-10 may reflect ageing and neuroinflammation.
Metabolomics identifies shared lipid pathways in independent amyotrophic lateral sclerosis cohorts
Authors: Goutman Stephen A , Guo Kai , Savelieff Masha G , Patterson Adam , Sakowski Stacey A , Habra Hani , Karnovsky Alla , Hur Junguk , Feldman Eva L
Published: January 2022

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease lacking effective treatments. This is due, in part, to a complex and incompletely understood pathophysiology. To shed light, we conducted untargeted metabolomics on plasma from two independent cross-sectional ALS cohorts versus control participants to identify recurrent dysregulated metabolic pathways. Untargeted metabolomics was performed on plasma from two ALS cohorts (cohort 1, n = 125; cohort 2, n = 225) and healthy controls (cohort 1, n = 71; cohort 2, n = 104). Individual differential metabolites in ALS cases versus controls were assessed by Wilcoxon, adjusted logistic regression and partial least squares-discriminant analysis, while group lasso explored sub-pathway level differences. Adjustment parameters included age, sex and body mass index. Metabolomics pathway enrichment analysis was performed on metabolites selected using the above methods. Additionally, we conducted a sex sensitivity analysis due to sex imbalance in the cohort 2 control arm. Finally, a data-driven approach, differential network enrichment analysis (DNEA), was performed on a combined dataset to further identify important ALS metabolic pathways. Cohort 2 ALS participants were slightly older than the controls (64.0 versus 62.0 years, P = 0.009). Cohort 2 controls were over-represented in females (68%, P < 0.001). The most concordant cohort 1 and 2 pathways centred heavily on lipid sub-pathways, including complex and signalling lipid species and metabolic intermediates. There were differences in sub-pathways that were enriched in ALS females versus males, including in lipid sub-pathways. Finally, DNEA of the merged metabolite dataset of both ALS and control cohorts identified nine significant subnetworks; three centred on lipids and two encompassed a range of sub-pathways. In our analysis, we saw consistent and important shared metabolic sub-pathways in both ALS cohorts, particularly in lipids, further supporting their importance as ALS pathomechanisms and therapeutics targets.
Gut Dysfunction Markers Are Associated With Body Composition in Youth Living With Perinatally Acquired Human Immunodeficiency Virus
Authors: Dirajlal-Fargo Sahera , Jacobson Denise L , Yu Wendy , Mirza Ayesha , Geffner Mitchell E , Jao Jennifer , McComsey Grace A
Published: January 2022

Background

The association between gut dysfunction and body fat composition in youth living with perinatal human immunodeficiency virus infection (YPHIV) has not been investigated.

Methods

We included YPHIV aged 7–19 years from the Pediatric HIV/AIDS Cohort Study Adolescent Master Protocol with plasma available within 6 months of baseline whole-body dual energy x-ray absorptiometry (DXA) and HIV RNA ≤1000 copies/mL within 3 months of baseline DXA and a second DXA 2 years later. Plasma markers of bacterial translocation and gut barrier dysfunction (lipopolysaccharide binding protein [LBP], zonulin, and intestinal fatty acid binding protein [I-FABP]) were measured at baseline by enzyme-linked immunosorbent assay and log10 transformed. Adiposity outcomes included percentage total body, truncal, and extremity fat in kilograms from DXA. Linear regression models were fit using generalized estimating equations to assess associations of baseline gut markers (log10) on adiposity outcomes at baseline and 2 years, adjusted for demographic variables, current antiretroviral therapy exposure, and physical activity.

Results

Two hundred sixty-one youth were included; 128 had a second DXA. Median age at first DXA was 12 years (interquartile range, 10–14 years), 49% were female, and 69% were Black. After adjustment for potential confounders, log10 LBP was positively associated with percentage total body fat at baseline (β = 4.08, P < .01) and zonulin with adiposity measures at both time points (β = .94 to 6.50, P ≤ .01). I-FABP was inversely associated with percentage total body fat at baseline and year 2 (β = –2.36 and –3.01, respectively, P ≤ .02).

Conclusions

Despite viral suppression, gut damage and the resultant bacterial translocation are associated with body composition measures in YPHIV.
Pediatric Hospitalizations After School Reopening During the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Alpha (B.1.1.7) Variant Spread: A Multicenter Cross-sectional Study in Israel
Authors: Friedman Nir , Levy Nitai , Kaplan Or , Padeh Gabi , Krupik Danna , Jacob Ron , Gamsu Shirly , Weiser Giora , Cohen Naama Kuchinski , Schnapp Zeev , Cohen Noy , Feldman Oren , Porat Danit , Gal Moran , Gleyzer Alexandra , Capua Tali , Klein Adi , Sharkansky Livnat , Shilo Smadar , Grotto Itamar , Kozer Eran , Shavit Itai
Published: January 2022

This multicenter, cross-sectional study provides evidence on severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–associated emergency department visits and hospitalizations in pediatric wards and intensive care units after school reopening during the SARS-CoV-2 Alpha (B.1.1.7) variant spread in Israel. Study findings suggest that school reopening was not followed by an increase in SARS-CoV-2–related pediatric morbidity.
Single-Tube Screen for Rapid Detection of Repeat Expansions in Seven Common Spinocerebellar Ataxias
Authors: Lian Mulias , Limwongse Chanin , Yoon Chui-Sheun , Lee Caroline G , Law Hai-Yang , Chong Samuel S
Published: January 2022

Background

The autosomal dominantly inherited and genetically heterogeneous spinocerebellar ataxias (SCAs) exhibit highly similar clinical presentations. Many are caused by repeat expansions, of which at least 8 involve CAG repeats. Repeat expansion detection is the only method to confirm disease status in symptomatic individuals. We present a novel strategy to simultaneously screen for the presence of CAG repeat expansion in the genes responsible for SCAs 1, 2, 3, 6, 7, 12, and dentatorubral-pallidoluysian atrophy using a simplified single-tube assay.

Methods

The method employs differentially labeled locus-specific primers and a common triplet-primed primer. Amplified products from each locus are distinguished by a combination of the product size and the fluorophore tag. The upper size limit of the normal allele range was used as the cutoff for distinguishing normal from potentially affected samples, with repeat expansion detected by presence of electrophoretic peaks extending beyond the cutoff.

Results

Blinded evaluation of the assay on 60 genotype-known DNA samples correctly detected repeat expansion in the expected SCA repeat locus for all 31 DNA samples.

Conclusions

In principle, this strategy can be applied to the simultaneous screening of any group of disease genes sharing the same repetitive units and/or their reverse complement.
Optimal Symmetric Ratcheting for Secure Communication
Authors: Yan Hailun , Vaudenay Serge , Collins Daniel , Caforio Andrea
Published: January 2022

To mitigate state exposure threats to long-lived instant messaging sessions, ratcheting was introduced, which is used in practice in protocols like Signal. However, existing ratcheting protocols generally come with a high cost. Recently, Caforio et al. proposed pragmatic constructions, which compose a weakly secure ‘light’ protocol and a strongly secure ‘heavy’ protocol, in order to achieve so-called ratcheting on-demand. The light protocol they proposed has still a high complexity.

In this paper, we propose the lightest possible protocol we could imagine, which essentially encrypts and then hashes the secret key. We prove it secure in the standard model by introducing a new security notion, which relates symmetric encryption with key updates by hashing. Our protocol composes well with the generic transformation techniques by Caforio et al. to offer high security and performance at the same time. In a second step, we propose another protocol based on a newly defined integrated primitive, extending standard one-time authenticated encryption with an additional output block used as a secret key for the next message. We instantiate this primitive firstly from any authenticated encryption with associated data, and then we propose an efficient instantiation using advanced encryption standard (AES) encryption to update the key and AES-Galois/Counter mode of operation to encrypt and decrypt messages.
Oedipus at Dover Cliff: Early Modern Receptions of Seneca’sPhoenissae
Authors: Engelmayer Caroline
Published: January 2022

Major accounts of Renaissance Senecanism argue that tragic protagonists in Seneca and his early modern imitators draw on overwhelming fury to achieve autarkic selfhood. Yet not all plays follow this mould: unlike the better-known Thyestes and Medea, Seneca’s Phoenissae locates tragic identity in the self-conscious rejection of a sudden resolution to violent strife. Oedipus, the play’s protagonist, temporarily relents in response to Antigone’s pleas against self-harm; despite his swift reversion to anger, this short-lived reconciliation aligns the tragedy with structural elements of comedy as understood by Renaissance genre theorists, inviting early modern authors to craft their own versions of the play’s ‘mixed mode’. In the New Arcadia, Philip Sidney rewrites the Phoenissae to privilege reconciliation over rage, but reframes this apparent comic gesture as the source of an escalating cycle of tragedy. In King Lear, William Shakespeare mobilizes the illusion of comic resolution that he found in Seneca’s play to heighten his protagonists’ irreversible suffering. Attending to the nuance and variety of Seneca’s tragic corpus as it was received by Renaissance readers reveals underexplored strands of Senecan influence on early modern literature, broadening the set of generic possibilities afforded by Seneca’s plays in the Renaissance to include tragicomedy and romance.
Impact of preoperative sarcopenia on postoperative complications and survival outcomes of patients with esophageal cancer: a meta-analysis of cohort studies
Authors: Chen Fei , Chi Junting , Zhao Bing , Mei Fan , Gao Qianqian , Zhao Li , Ma Bin
Published: January 2022

The effects of preoperative sarcopenia on postoperative complications and survival outcomes of patients undergoing esophageal cancer resection are controversial. From database establishment to 16 May 2021, we systematically searched PubMed, Embase, the Cochrane Library, Web of Science, and Chinese Biomedical Literature Database to collect relevant studies investigating the effects of preoperative sarcopenia on postoperative complications, survival outcomes, and the risk of a poor prognosis of patients undergoing esophagectomy. The Newcastle–Ottawa scale was used to evaluate the quality of the included literature, and RevMan 5.3 software was used for the meta-analysis. A total of 26 studies (3 prospective cohort studies and 23 retrospective cohort studies), involving 4,515 patients, were included. The meta-analysis showed that preoperative sarcopenia significantly increased the risk of overall complications (risk ratio [RR]: 1.15; 95% confidence interval [CI]: 1.08–1.22), pulmonary complications (RR: 1.78; 95% CI: 1.48–2.14), and anastomotic leakage (RR: 1.29; 95% CI: 1.04–1.59) and reduced the overall survival rate (hazard ratio: 1.12; 95% CI: 1.04–1.20) following esophageal cancer resection. Preoperative sarcopenia increased the risks of overall postoperative and pulmonary complications in patients undergoing esophageal cancer resection. For patients with esophageal cancer, assessing the preoperative risk of preoperative sarcopenia is necessary.
Clinical frailty is a risk factor of adverse outcomes in patients with esophageal cancer undergoing esophagectomy: analysis of 2011–2017 US hospitals
Authors: Lee David Uihwan , Hastie David Jeffrey , Fan Gregory Hongyuan , Addonizio Elyse Ann , Han John , Karagozian Raffi
Published: January 2022

Frailty is an aggregate of medical and geriatric conditions that affect elderly and vulnerable patients; as frailty is known to affect postoperative outcomes, we evaluate the effects of frailty in patients undergoing esophageal resection surgery for esophageal cancer. 2011–2017 National Inpatient Sample was used to isolate younger (18 to <65) and older (65 or greater) patients undergoing esophagectomy for esophageal cancer, substratified using frailty (defined by Johns-Hopkins ACG frailty indicator) into frail patients and non-frail controls; the controls were 1:1 matched with frail patients using propensity score. Endpoints included mortality, length of stay (LOS), costs, discharge disposition, and postsurgical complications. Following the match, there were 363 and equal number controls in younger cohort; 383 and equal number controls in older cohort. For younger cohort, frail patients had higher mortality (odds ratio [OR] 3.14 95% confidence interval [CI] 1.39–7.09), LOS (20.5 vs. 13.6 days), costs ($320,074 vs. $190,235) and were likely to be discharged to skilled nursing facilities; however, there was no difference in postsurgical complications. In multivariate, frail patients had higher mortality (aOR 3.00 95%CI 1.29–6.99). In older cohort, frail patients had higher mortality (OR 1.96 95%CI 1.07–3.60), LOS (19.9 vs. 14.3 days), costs ($301,335 vs. $206,648) and were more likely to be discharged to short-term hospitals or skilled nursing facilities; the frail patients were more likely to suffer postsurgical respiratory failure (OR 2.03 95%CI 1.31–3.15). In multivariate, frail patients had higher mortality (aOR 1.93 95%CI 1.04–3.58). Clinical frailty adversely affects both younger and older patients undergoing esophagectomy for esophageal cancer.
Long-term evolution of N-terminal pro-brain natriuretic peptide levels and exercise capacity in 132 left ventricular assist device recipients
Authors: Van Edom Charlotte , Jacobs Steven , Fresiello Libera , Vandersmissen Katrien , Vandenbriele Christophe , Droogné Walter , Meyns Bart
Published: January 2022

OBJECTIVES

N-terminal pro-brain natriuretic peptide (NT-proBNP) is a widely used biomarker in clinical practice in the context of heart failure. Little is known about the long-term evolution of NT-proBNP levels in left ventricular assist device (LVAD) recipients. Besides this, the potential correlation of NT-proBNP with exercise capacity on the long term after LVAD implantation has not been previously studied.

METHODS

We retrospectively analysed 132 single-centre LVAD recipient records (HeartMate II/III; HeartWare; between March 2007 and January 2018; mean follow-up 559 days). Blood samples, 6-min walking test (6MWT) and maximal cardiopulmonary exercise test were performed in a standardized way.

RESULTS

Pre-LVAD NT-proBNP levels were increased (9736 ± 1072 ng/l) and dropped significantly after implantation [14 days: 4360 ± 545 ng/l (P < 0.0001), 6 months: 1485 ± 139 ng/l (P < 0.0001)]. Afterwards a steady state was reached during follow-up (after 1 year: 1592 ± 214 ng/l, after 5 years: 1679 ± 311 ng/l). Submaximal exercise capacity significantly improved postoperatively [percentage of the predicted distance walked during the 6MWT 50 ± 2% (0–3 months); 61 ± 2% (3–6 months, P < 0.001)], with a steady state afterwards [66 ± 2% (6–12 months, P = 0.08); 64 ± 3%, P = 0.70 later on]. We found a gradual increment of percentage of the expected peak oxygen consumption postoperatively [44 ± 2% (0–3 months); 49 ± 2% (3–6 months); 52 ± 2% (6–12 months); 53 ± 1% (after 12 months)] with a significant improvement between 0 and 3 months versus after the first year on LVAD. Furthermore, we showed a significant moderate correlation between NT-proBNP levels and results at both the 6MWT (correlation coefficient: −0.31, P < 0.0001) and cardiopulmonary exercise testing (correlation coefficient: −0.28, P < 0.0001).

CONCLUSIONS

NT-proBNP decreased on LVAD support. We showed that submaximal (6MWT) and maximal exercise capacity (cardiopulmonary exercise testing) improve after LVAD implantation and demonstrated an inverse correlation of both tests with NT-proBNP levels.
Everyday Discrimination in Public Spaces: A Field Experiment in the Milan Metro
Authors: Zhang Nan , Gereke Johanna , Baldassarri Delia
Published: January 2022

A large scholarship documents discrimination against immigrants and ethnic minorities in institutional settings such as labour and housing markets in Europe. We know less, however, about discrimination in informal and unstructured everyday encounters. To address this gap, we report results from a large-scale field experiment examining the physical avoidance of immigrants as an unobtrusive yet important measure of everyday discrimination in a multiethnic European metropolis. In addition to varying confederates’ migration background and race, we also vary signals of status (business versus casual attire) in order to shed light on the mechanisms underlying discriminatory patterns. We find that natives are averse to contact with Nigerian confederates, but do not discriminate against Chinese confederates. Furthermore, manipulating confederates’ attire has little effect on natives’ behaviour. Overall, our results highlight the everyday burdens borne particularly by individuals of African descent in commonplace, ‘street-level’ encounters.
Alcohol intake and bradyarrhythmia risk: a cohort study of 407 948 individuals
Authors: Tu Samuel J , Gallagher Celine , Elliott Adrian D , Linz Dominik , Pitman Bradley M , Hendriks Jeroen M L , Lau Dennis H , Sanders Prashanthan , Wong Christopher X
Published: January 2022

Aims 

There is a paucity of epidemiological evidence on alcohol and the risk of bradyarrhythmias. We thus characterized associations of total and beverage-specific alcohol consumption with incident bradyarrhythmias using data from the UK Biobank.

Methods and results 

Alcohol consumption reported at baseline was calculated as UK standard drinks (8 g alcohol)/week. Bradyarrhythmia events were defined as sinus node dysfunction (SND), high-level atrioventricular block (AVB), and permanent pacemaker implantations. Outcomes were assessed through hospitalization and death records, and dose–response associations were characterized using Cox regression models with correction for regression dilution bias. We studied 407 948 middle-aged individuals (52.4% female). Over a median follow-up time of 11.5 years, a total of 8 344 incident bradyarrhythmia events occurred. Increasing total alcohol consumption was not associated with an increased risk of bradyarrhythmias. Beer and cider intake were associated with increased bradyarrhythmia risk up to 12 drinks/week; however, no significant associations were observed with red wine, white wine, or spirit intake. When bradyarrhythmia outcomes were analysed separately, a negative curvilinear was observed for total alcohol consumption and risk of SND, but no clear association with AVB was observed.

Conclusion 

In this predominantly White British cohort, increasing total alcohol consumption was not associated with an increased risk of bradyarrhythmias. Associations appeared to vary according to the type of alcoholic beverage and between different types of bradyarrhythmias. Further epidemiological and experimental studies are required to clarify these findings.
Long-term quality of life and acceptance of implantable cardioverter-defibrillator therapy: results of the European Heart Rhythm Association survey
Authors: Januszkiewicz Łukasz , Barra Sérgio , Providencia Rui , Conte Giulio , de Asmundis Carlo , Chun Julian K R , Farkowski Michał M , Guerra Jose M , Marijon Eloi , Boveda Serge
Published: January 2022

Implantable cardioverter-defibrillator (ICD) may impact patients’ life significantly. The aim of this survey was to analyse the impact of the ICD on quality of life (QoL) metrics from the patient’s perspective. ‘Living with an ICD’ was a prospective, multicentre study with an online questionnaire submitted to the European Heart Rhythm Association (EHRA) Research Network centres as well as patient associations from 10 European countries; it was filled-in directly and personally by the patients that were invited to participate, with a minimal interaction or influence from the healthcare professionals. Overall, the questionnaire was completed by 1809 patients (624 women, 34.5%). Patients in their 60s and 70s and from Western Europe were the most represented. The median time from first ICD implantation was 5 years (IQR 2–10). Device-related complications were reported by 505 patients (22.4%), including one or more inappropriate shocks (n = 209, 11.6%). Almost half the respondents reported improved QoL, with a more favourable impact for those receiving cardiac resynchronization therapy-defibrillator (CRT-D), and only a 10th experienced a significant decrease in QoL. The occurrence of complications remained a major predictor of deteriorated QoL (odds ratio 2.1, 95% confidence interval 1.4–3.0, P < 0.001). In conclusion, most patients have a globally positive view and acceptance of ICD therapy, reporting preserved to improved QoL after device implantation. Complications, namely inappropriate shocks, affect the expectation of living a normal life post-implant and are associated with a significant decrease in QoL. Our findings also highlight the importance of a detailed informed consent process and the involvement of the patient in the decision-making process.
The exploitation of human glycans by Group AStreptococcus
Authors: Indraratna Anuk D , Everest-Dass Arun , Skropeta Danielle , Sanderson-Smith Martina
Published: January 2022

Host carbohydrates, or glycans, have been implicated in the pathogenesis of many bacterial infections. Group A Streptococcus (GAS) is a Gram-positive bacterium that readily colonises the skin and oropharynx, and is a significant cause of mortality in humans. While the glycointeractions orchestrated by many other pathogens are increasingly well-described, the understanding of the role of human glycans in GAS disease remains incomplete. Although basic investigation into the mechanisms of GAS disease is ongoing, several glycointeractions have been identified and are examined herein. The majority of research in this context has focussed on bacterial adherence, however, glycointeractions have also been implicated in carbohydrate metabolism; evasion of host immunity; biofilm adaptations; and toxin-mediated haemolysis. The involvement of human glycans in these diverse avenues of pathogenesis highlights the clinical value of understanding glycointeractions in combatting GAS disease.
A Highly Contiguous Genome Assembly of Arthrinium puccinoides
Authors: Sørensen Trine , Petersen Celine , Fechete Lavinia I , Nielsen Kåre L , Sondergaard Teis E
Published: January 2022

The phylogenetic relationship of the Arthrinium genus has changed throughout the years. For many years, the Arthrinium genus included the Apiospora genus as well. New evidence has now showed that these two genera in fact are phylogenetically different and belong to two different clades. Here, we present the first genome draft within the Arthrinium genus. This genome was sequenced using the MinION platform from Oxford Nanopore Technologies and the assembly was contiguous. The assembly comprises ten contigs totaling 39.8 Mb with an N50 length of 7.9. In the assembly, 11,602 genes were predicted whereof 10,784 were functionally annotated. A total of 37 rRNA genes were observed in the assembly and repeat elements spanning 7.39% of the genome were found. A total of 99 secondary metabolite gene clusters were predicted, showing a high potential of novel secondary metabolites. This genome sequence will not only be useful for further investigation of the Arthrinium clade, but also for discovery of novel secondary metabolite compounds that could be of high interest for the food, agricultural, or pharmaceutical industry.
Social Disconnectedness and Loneliness: Do Self-Perceptions of Aging Play a Role?
Authors: Hu Rita Xiaochen , Li Lydia W
Published: January 2022

Objectives

Research suggests that self-perceptions of aging (SPA) have effects on physical, mental, cognitive, and emotional well-being among older adults. Few studies have examined the effects of SPA on social well-being. This study investigates the association of SPA with trajectories of social disconnectedness and loneliness in older Americans and explores mechanisms linking SPA and the 2 forms of social isolation.

Methods

We conducted Latent Growth Curve Modeling and path analysis using 3-wave data spanning 8 years (2008/2010–2016/2018) from the Health and Retirement Study. The sample included respondents aged 65 and older (N = 3,597) at baseline (2008/2010). SPA was measured by the Attitudes Toward Own Aging Scale. Social disconnectedness was an index including 6 indicators of social networks and social engagement. Loneliness was measured using the 11-item UCLA Loneliness Scale.

Results

Older adults with more negative SPA at baseline were more lonely but had slower rates of increase in loneliness during the 8-year study period. More negative SPA also predicted greater social disconnectedness but was not significantly related to the rate of change in social disconnectedness over time. The effects of SPA on social disconnectedness were primarily indirect through loneliness, whereas SPA had direct effects on loneliness. Overall, SPA had a stronger association with loneliness than with social disconnectedness.

Discussion

The results suggest that older adults with negative SPA are at risk of loneliness which then leads to social disconnectedness. Asking about SPA during individual assessment with older adults may help to discern issues with loneliness.
How Welfare Regimes Moderate the Associations Between Cognitive Aging, Education, and Occupation
Authors: Orsholits Dan , Cullati Stéphane , Ghisletta Paolo , Aartsen Marja J , Oris Michel , Studer Matthias , Maurer Jürgen , Perna Laura , Gouveia Élvio R , Gouveia Bruna R , Marques Adilson , Peralta Miguel , Marconcin Priscila , Kliegel Matthias , Ihle Andreas
Published: January 2022

Objectives

Previous studies have shown the importance of individual markers of cognitive reserve, such as education and occupation, for cognitive health in old age. However, there has been only little investigation so far on how this relationship varies across contexts.

Methods

We analyzed data from the Survey of Health, Ageing, and Retirement in Europe, using second-order latent growth models, to assess the moderating role of welfare regimes on the relationship between education and occupation skill level in explaining overall cognitive functioning and decline in old age. Our sample includes 13 European countries using data from 5 regular waves of the survey (2004–2007 and 2011–2015) and 2 retrospective ones (2008–2009 and 2017). Cognitive functioning was modeled as a latent variable measured by immediate and delayed recall, verbal fluency, and numeracy.

Results

74,193 participants were included from the survey. Our analysis showed that the association of education with cognition was weaker overall in Scandinavian countries, but stronger in Southern European countries, relative to Bismarckian ones. However, educational differences in the decline of cognition were more pronounced only in Scandinavian compared to Bismarckian countries. Additionally, higher-skilled occupations in Scandinavian countries had better overall functioning compared to the same occupations in Bismarckian countries, but there was no difference in the decline in cognitive functioning.

Discussion

Our findings indicate that the associations of cognitive functioning and its decline with individuals’ cognitive reserve markers (education and occupational skill level) vary according to welfare regimes, showing the importance of contextual factors in cognitive aging processes.
How Do Area Agencies on Aging Build Partnerships With Health Care Organizations?
Authors: Curry Leslie , Cherlin Emily , Ayedun Adeola , Rubeo Chris , Straker Jane , Wilson Traci L , Brewster Amanda
Published: January 2022

Background and Objectives

Partnerships between health care and social service organizations may contribute to lower health care use and spending. Such partnerships are increasing, including Area Agencies on Aging (AAAs) working and contracting with health care organizations. Nevertheless, knowledge about how AAAs establish and manage successful collaborations is limited. We sought to understand how AAAs establish and manage partnerships with health care organizations.

Research Design and Methods

We conducted an explanatory sequential mixed-methods study using a positive deviance approach. We used national-level data to identify AAAs with multiple health care partners serving areas with low utilization of nursing homes by residents with low-care needs (n = 9) and AAAs with few health care partners and high utilization for comparison (n = 3). We conducted in-depth interviews with key informants from these 12 AAAs and their partner organizations (total n = 130). A 5-person multidisciplinary team used the constant comparative method of analysis, supported by Atlas.ti software.

Results

Highly partnered AAAs were characterized by 3 distinctive features of organizational culture: (a) attention to external environments, (b) openness to innovation and change, and (c) risk-taking to learn, improve, and grow. AAAs and partners describe a broad set of organizational strategies and partnership development tactics, depending on their local contexts. These features were underdeveloped in AAAs with few health care partnerships.

Discussion and Implications

While federal and state policies can create more favorable environments for AAA–health care partnerships, AAAs can also work internally to foster an organizational culture that allows them to thrive in dynamic and challenging environments.
Animal-assisted interventions in universities: a scoping review of implementation and associated outcomes
Authors: Cooke Emily , Henderson-Wilson Claire , Warner Elyse , LaMontagne Anthony
Published: January 2022

With levels of stress and anxiety rising among the university community, universities worldwide are implementing animal-assisted interventions (AAIs) on campus. However, to date, little is known about how to implement these initiatives. Questions also remain as to the impact of evaluated AAIs on health and wellbeing. Therefore, this study sought to review the implementation and effectiveness of previous AAIs in university settings. Electronic databases ProQuest Central, Gale and 16 databases within EBSCOHost were searched with key words, such as AAI, and university or college students for relevant articles. Inclusion criteria included primary research studies that measured a health, wellbeing or behavioural outcome. A total of 47 articles met inclusion criteria, including 24 RCTs. There was limited reporting on the implementation of AAIs in the higher education setting. A total of 11 different mental health and behavioural outcomes have been summarized, with stress, anxiety and mood providing favourable results. An AAI on campus may provide a form of stress and anxiety relief for the university community. Other mental health and behavioural outcomes require further research to determine their effectiveness. These findings highlight that an AAI on campus could potentially provide a form of stress and anxiety relief, and could be a strategy for addressing rising levels of psychological stress and mental health issues among university students and staff in Australia and internationally.
A randomized controlled trial of the impact of the Teen Council peer education program on youth development
Authors: Foss L , Brown S A , Sutherland S , Miller C J , Philliber S
Published: January 2022

This paper presents results of an impact evaluation of Teen Council, a program that trains youth as peer educators. Teen Council is designed to help peer educators make healthy sexual and reproductive decisions, increase their confidence and abilities to educate their peers and inspire them to advocate for just sexual policies. The program’s impact on these educators was evaluated using a randomized controlled trial. Over 5 years, interested high school students in seven states were randomly assigned to a study condition. An intent-to-treat framework using ordinary least square (OLS) regression was employed to measure program effects. Relative to control, Teen Council youth showed enhanced comfort with their own sexuality, greater comfort with and more frequent communication with parents about sexuality and more positive sexual health behaviors, including accessing reproductive health care and adopting more effective means of contraception. Teen Council youth also reported greater confidence in talking with peers about sexuality and more confidence in their civic engagement skills.
Dehn Surgery and Hyperbolic Knot Complements without Hidden Symmetries
Authors: Chesebro Eric , DeBlois Jason , R Hoffman Neil , Millichap Christian , Mondal Priyadip , Worden William
Published: January 2022

Neumann and Reid conjectured that only three hyperbolic knot complements admit hidden symmetries. Here, we provide evidence for the conjecture, giving obstructions for a manifold to have infinitely many fillings that are knot complements with hidden symmetries. Applying these, we show that at most finitely many fillings of any hyperbolic two-bridge link complement can be covered by knot complements with hidden symmetries. We then make our tools effective, showing first that the only knot complement with hidden symmetries and volume less than $6v_0 \approx 6.0896496$ is the complement of the figure-eight. We conclude with two proofs that if a hyperbolic knot’s complement admits hidden symmetries and covers a filling of the complement of the $6_2^2$ link, it is the figure-eight.
Overcrowding Estimates for the Nodal Volume of Stationary Gaussian Processes
Authors: M E Lakshmi Priya
Published: January 2022

For smooth centered stationary Gaussian processes on ${{\mathbb {R}}}^d$ ($d \geq 1$), we study the unlikely event of overcrowding of the nodal set; this is the event that the volume of the nodal set in a region is much larger than its expected value. Under some mild assumptions on the spectral measure of the process, we obtain estimates for the probability of the overcrowding event.
Impaired Intrauterine Growth in the Context of Maternal Hookworm Infection During Gestation
Authors: Barry Meagan A , Colt Susannah , Vargas Zorimel , Barry Christopher V , Tallo Veronica , Sagliba Marianne J , Amoylen Amabelle J , Friedman Jennifer F , McDonald Emily A
Published: January 2022

Hookworm infection is associated with poor nutritional outcomes, anemia, and impaired cognitive performance. We examined the association between maternal hookworm infection and birth outcomes in a cohort of women in Leyte, Philippines. We observed poor intrauterine growth characteristics associated with maternal hookworm only among male offspring, with lower birth weight, head circumference, and placental surface area. Male neonates also had higher insulin-like growth factor 2 (IGF-2) and lower adiponectin in cord blood. These data intriguingly suggest nutritional impacts of maternal hookworm infection during pregnancy may be divergent based on sex of the offspring.
Phylogenomics and Fossil Data Inform the Systematics and Geographic Range Evolution of a Diverse Neotropical Ant Lineage
Authors: Price Shauna L , Blanchard Benjamin D , Powell Scott , Blaimer Bonnie B , Moreau Corrie S
Published: January 2022

Recent advances in phylogenomics allow for the use of large amounts of genetic information in phylogenetic inference. Ideally, the increased resolution and accuracy of such inferences facilitate improved understanding of macroevolutionary processes. Here, we integrate ultraconserved elements (UCEs) with fossil and biogeographic range data to explore diversification and geographic range evolution in the diverse turtle ant genus Cephalotes Latreille, 1802 (Hymenoptera: Formicidae). We focus on the potential role of the uplift of the Panamanian land bridge and the putative ephemeral GAARlandia land bridge linking South America and the Antilles in shaping evolution in this group. Our phylogenetic analyses provide new resolution to the backbone of the turtle ant phylogeny. We further found that most geographic range shifts between South America and Central America regions were temporally consistent with the development of the Panamanian land bridge, while we did not find support for the GAARlandia land bridge. Additionally, we did not infer any shifts in diversification rates associated with our focal land bridges, or any other historical events (we inferred a single diversification rate regime across the genus). Our findings highlight the impact of the Panamanian land bridge for Cephalotes geographic range evolution as well as the influence of taxonomic sampling on macroevolutionary inferences.
Performance of the Rotation Gesture Based on Electrostatic Tactile Feedback Devices
Authors: Liu Guohong , Lv Shuai , Wang Xiaocui , Sun Xiaoying
Published: January 2022

The application of electrostatic tactile feedback to a touchscreen can provide a real sense of immersion to enhance the user interaction experience. With a custom-designed electrostatic tactile feedback device, we explore the effect of electrostatic tactile feedback on performing rotation gestures. Specifically, we design three-part experiments that include no tactile feedback, tactile feedback in the target area and tactile feedback increased linearly in the process. The effect of electrostatic tactile feedback on performing rotation gestures is then examined. The results with 12 participants indicate that adding tactile feedback to the process or the target area significantly enhances the efficiency and accuracy of rotation operations. In addition, the relationship between the index of difficulty (ID) and rotation time (RT) is studied by applying electrostatic tactile feedback in the process and the target area. The results indicate that the relations between ID and RT under the above two conditions satisfy Fitts’ Law with correlation coefficients >0.96.
Linezolid toxicity in patients with drug-resistant tuberculosis: a prospective cohort study
Authors: Wasserman Sean , Brust James C. M. , Abdelwahab Mahmoud T. , Little Francesca , Denti Paolo , Wiesner Lubbe , Gandhi Neel R. , Meintjes Graeme , Maartens Gary
Published: January 2022

Background

Linezolid is recommended for treating drug-resistant TB. Adverse events are a concern to prescribers but have not been systematically studied at the standard dose, and the relationship between linezolid exposure and clinical toxicity is not completely elucidated.

Patients and methods

We conducted an observational cohort study to describe the incidence and determinants of linezolid toxicity, and to determine a drug exposure threshold for toxicity, among patients with rifampicin-resistant TB in South Africa. Linezolid exposures were estimated from a population pharmacokinetic model. Mixed-effects modelling was used to analyse toxicity outcomes.

Results

One hundred and fifty-one participants, 63% HIV positive, were enrolled and followed for a median of 86 weeks. Linezolid was permanently discontinued for toxicity in 32 (21%) participants. Grade 3 or 4 linezolid-associated adverse events occurred in 21 (14%) participants. Mean haemoglobin concentrations increased with time on treatment (0.03 g/dL per week; 95% CI 0.02–0.03). Linezolid trough concentration, male sex and age (but not HIV positivity) were independently associated with a decrease in haemoglobin >2 g/dL. Trough linezolid concentration of 2.5 mg/L or higher resulted in optimal model performance to describe changing haemoglobin and treatment-emergent anaemia (adjusted OR 2.9; 95% CI 1.3–6.8). SNPs 2706A > G and 3010G > A in mitochondrial DNA were not associated with linezolid toxicity.

Conclusions

Permanent discontinuation of linezolid was common, but linezolid-containing therapy was associated with average improvement in toxicity measures. HIV co-infection was not independently associated with linezolid toxicity. Linezolid trough concentration of 2.5 mg/L should be evaluated as a target for therapeutic drug monitoring.
Long noncoding RNA and phase separation in cellular stress response
Authors: Onoguchi-Mizutani Rena , Akimitsu Nobuyoshi
Published: January 2022

Stress response is important for sensing and adapting to environmental changes. Recently, RNA-protein (RNP) condensates, which are a type of membrane-less organelle formed by liquid–liquid phase separation, have been proposed to regulate the stress response. Because RNP condensates are formed through interactions between positively charged proteins and negatively charged RNAs, the ratio of proteins to RNAs is critical for phase-separated condensate formation. In particular, long noncoding RNAs (lncRNAs) can efficiently nucleate phase-separated RNP condensates because of their secondary structure and long length. Therefore, increased attention has been paid to lncRNAs because of their potential role as a regulator of biological condensates by phase separation under stress response. In this review, we summarize the current research on the involvement of lncRNAs in the formation of RNP condensates under stress response. We also demonstrate that lncRNA-driven phase separation provides a useful basis to understanding the response to several kinds of cellular stresses.
Lithium in International Law: Trade, Investment, and the Pursuit of Supply Chain Justice
Authors: Hailes Oliver
Published: January 2022

Projected demand for renewable energy storage has underlined the importance of lithium-ion batteries, reflected in concern over ‘supply chain security’ for critical minerals. Yet, other voices have called for ‘supply chain justice’ among governments, firms, and communities affected by the social and environmental externalities of lithium extraction. To anticipate disputes and draw a baseline for further research, this article surveys the relevant rules of international law that presently regulate major operations of the lithium industry. First, the material dimensions of lithium are transformed into a workable object of international law, focusing on viable reserves (as opposed to all proven resources) and the analytical priority of territorial jurisdiction. Second, the regulatory regimes of four States with major reserves—Chile, Australia, Argentina, and China—illustrate recurring challenges, such as incentivizing investment in value-added production and the discontent of Indigenous communities. Third, the trade and investment treaties of these States help us to map an international legal framework for the lithium industry, focusing on the World Trade Organization, the Comprehensive and Progressive Agreement for Trans-Pacific Partnership, and the Regional Comprehensive Economic Partnership. But such treaties may be interpreted in light of a State’s obligations concerning human rights, environmental protection, and Indigenous peoples, giving legal form to the pursuit of supply chain justice in the energy transition.