bluuebunny/crossref_metadata_2025 huggingface dataset:
Epidemiology of neuropathic pain: an analysis of prevalence and associated factors in UK Biobank
Authors: Baskozos Georgios , Hébert Harry L. , Pascal Mathilde M.V. , Themistocleous Andreas C. , Macfarlane Gary J. , Wynick David , Bennett David L.H. , Smith Blair H.
Published: February 2023

Introduction:

Previous epidemiological studies of neuropathic pain have reported a range of prevalences and factors associated with the disorder.

Objectives:

This study aimed to verify these characteristics in a large UK cohort.

Methods:

A cross-sectional analysis was conducted of 148,828 UK Biobank participants who completed a detailed questionnaire on chronic pain. The Douleur Neuropathique en Quatre Questions (DN4) was used to distinguish between neuropathic pain (NeuP) and non-neuropathic pain (non-NeuP) in participants with pain of at least 3 months' duration. Participants were also identified with less than 3 months' pain or without pain (NoCP). Multivariable regression was used to identify factors associated with NeuP compared with non-NeuP and NoCP, respectively.

Results:

Chronic pain was present in 76,095 participants (51.1%). The overall prevalence of NeuP was 9.2%. Neuropathic pain was significantly associated with worse health-related quality of life, having a manual or personal service type occupation, and younger age compared with NoCP. As expected, NeuP was associated with diabetes and neuropathy, but also other pains (pelvic, postsurgical, and migraine) and musculoskeletal disorders (rheumatoid arthritis, osteoarthritis, and fibromyalgia). In addition, NeuP was associated with pain in the limbs and greater pain intensity and higher body mass index compared with non-NeuP. Female sex was associated with NeuP when compared with NoCP, whereas male sex was associated with NeuP when compared with non-NeuP.

Conclusion:

This is the largest epidemiological study of neuropathic pain to date. The results confirm that the disorder is common in a population of middle- to older-aged people with mixed aetiologies and is associated with a higher health impact than non-neuropathic pain.
New Horizons in Radioligand Therapy
Authors: Rosar Florian , Maus Stephan , Schaefer-Schuler Andrea , Burgard Caroline , Khreish Fadi , Ezziddin Samer
Published: February 2023

An 85-year-old man with advanced metastatic castration-resistant prostate cancer and progression after 8 cycles of 177Lu–prostate-specific membrane antigen (PSMA)–617 radioligand therapy (RLT) received 1 cycle of 161Tb-PSMA RLT. This one administration of 6.5 GBq 161Tb-PSMA-617 resulted in impressive partial remission with a PSA decline by 53.4% (from 474 to 221 ng/mL) and a concomitant decrease in tumor burden on PSMA PET/CT imaging. The presented case provides stunning initial evidence of the therapeutic potential of 161Tb-PSMA RLT in metastatic castration-resistant prostate cancer, even in patients progressing after extensive 177Lu-based RLT. 161Tb-labeled PSMA ligands may thus offer a promising alternative to standard PSMA RLT.
Differentiation of a Falcine Meningioma From Cerebral Venous Sinus Thrombosis Using DOTATATE PET
Authors: Stetter Isabelle , Werner Jan-Michael , Schroeter Michael , Baumann Claudia , Neuneier Janina , Schlamann Marc , Schmidt Matthias , Drzezga Alexander , Fink Gereon R. , Galldiks Norbert
Published: February 2023

Differentiating brain tumors from nonneoplastic lesions using conventional MRI may be challenging. Clinical symptoms often remain unspecific, and imaging findings from MRI may be inconclusive. We present the case of a 23-year-old woman in whom an MRI suggested a cerebral venous sinus thrombosis. On the other hand, additional atypical MRI findings raised doubts regarding the initial diagnosis. Given the need for a diagnostic procedure with higher sensitivity and specificity for neoplastic tissue, PET with the radiolabeled somatostatin receptor ligand DOTATATE (68Ga-DOTA-d-Phe1-Tyr3-octreotate) was performed. DOTATATE PET facilitated the diagnosis of a falcine meningioma consistent with its value for the differential diagnosis of meningioma.
Graduate Student Clinicians in Health Care Professions as Stakeholders in Intensive Comprehensive Aphasia Program (ICAP) Implementation and Research
Authors: Off Catherine A. , Scharp Victoria L. , Griffin-Musick Jenna R.
Published: February 2023

Purpose:

This article characterizes graduate student clinicians' (GSCs') understanding of their roles as stakeholders in clinical implementation and research before participating in an intensive comprehensive aphasia program (ICAP).

Method:

Seven GSCs participated in a pre-ICAP intervention focus group to characterize their perceived roles in stakeholder-engaged research. Following an extensive ICAP training orientation and clarification of key definitions, the focus group prompt asked GSCs to describe what they view as important issues for developing future research protocols that investigate student clinician outcomes in the context of an ICAP. Qualitative content analysis using an inductive coding approach was applied to the focus group transcript.

Results:

The GSCs preparing to participate in ICAPs report that they are highly invested in the clinical implementation and research of the ICAP service delivery model.

Discussion/Conclusions:

The GSCs are crucial stakeholders in the development of GSC-run ICAPs across clinical implementation and all phases of research.
Advances in the management of acute ischemic stroke
Authors: Nair Radhika , Wagner Amanda N. , Buck Brian H.
Published: February 2023

Purpose of review

This review aims to summarize the therapeutic advances and evidence in the medical management of acute ischemic stroke (AIS). Recent evidence comparing the efficacy and safety of tenecteplase (TNK) with alteplase for intravenous thrombolysis (IVT) in AIS will be highlighted. Recent advances and evidence on improving micro-circulation following endovascular procedures and neuroprotection will be reviewed.

Recent findings

A significant number of randomized control studies now support the use of tenecteplase for IVT in AIS. TNK 0.25 mg/kg single bolus is as effective and well tolerated as alteplase 0.9 mg/kg infusion for IVT in AIS. Evidence from randomized control trials (RCTs) has shown effective and well tolerated expansion of the therapeutic window of IVT in the wake-up stroke and up to 9 h after last seen well, using advanced neuroimaging with computed tomography perfusion/MRI. Early evidence suggests that intra-arterial alteplase may help improve microcirculation in patients with large vessel occlusion following successful thrombectomy. However, more trials are required to confirm the results. Similarly, early evidence from a recent RCT showed that remote ischemic conditioning confers potential neuroprotection and improves outcomes in AIS.

Converging evidence has demonstrated that for patients with ischemic stroke presenting at under 4.5 h from the onset, TNK is comparable to alteplase. These data along with the practical advantages of TNK have resulted in a shift to replace intravenous TNK as the standard for thrombolysis. Ongoing studies of IVT with TNK are focussed on defining the optimal dose, expanding the time window with multimodal imaging and defining the role of thrombolysis for bridging patients with stroke due to large vessel occlusion.
The current landscape of epilepsy genetics: where are we, and where are we going?
Authors: Ruggiero Sarah M. , Xian Julie , Helbig Ingo
Published: February 2023

Purpose of review

In this review, we aim to analyse the progress in understanding the genetic basis of the epilepsies, as well as ongoing efforts to define the increasingly diverse and novel presentations, phenotypes and divergences from the expected that have continually characterized the field.

Recent findings

A genetic workup is now considered to be standard of care for individuals with an unexplained epilepsy, due to mounting evidence that genetic diagnoses significantly influence treatment choices, prognostication, community support, and increasingly, access to clinical trials. As more individuals with epilepsy are tested, novel presentations of known epilepsy genes are being discovered, and more individuals with self-limited epilepsy are able to attain genetic diagnoses. In addition, new genes causative of epilepsy are being uncovered through both traditional and novel methods, including large international data-sharing collaborations and massive sequencing efforts as well as computational methods and analyses driven by the Human Phenotype Ontology (HPO).

New approaches to gene discovery and characterization are advancing rapidly our understanding of the genetic and phenotypic architecture of the epilepsies. This review highlights relevant and groundbreaking studies published recently that have pushed forward the field of epilepsy genetics.
Stroke in the young
Authors: Fraser Stuart , Pabst Lisa , Smith Fiona
Published: February 2023

Purpose of review

The purpose of this review is to review recent findings regarding stroke epidemiology, etiologies, and treatment in children and young adults.

Recent findings

Incidence in young adults is increasing, and incidence, recurrence, and survival is worse in patients with cryptogenic stroke and in developing countries. Careful consideration of patent foramen ovale closure is now recommended in young adults with cryptogenic stroke. Thrombectomy has recently been extended to carefully selected children with acute ischemic stroke, and two recent publications strongly suggest that it can be beneficial for children. Sickle cell is also an important global contributor to stroke burden, but hydroxyurea can be a cost effective medication for stroke prevention in children. Recent advances in genetic testing and treatments may improve outcomes for patients with monogenic causes of stroke, such as deficiency of adenosine deaminase 2, hemophilia, and Fabry's disease.

Stroke in children and young adults is a morbid disease responsible for enormous indirect societal costs and a high burden of years with disability per affected patient. Recent advances have improved access to care for children with large vessel occlusion and adults with rare causes of stroke. Future research may bring effective treatments for other monogenic causes of stroke as well as increasing access to hyperacute therapies for young stroke patients.
Critical care EEG monitoring: improving access and unravelling potentially epileptic patterns
Authors: Fong Michael W.K.
Published: February 2023

Purpose of review

The major advances in critical care EEG have been the development of rapid response EEG, major revision of the American Clinical Neurophysiology Society's (ACNS) standardized critical care EEG terminology, and the commencement of treatment trials on rhythmic and periodic patterns (RPPs) that do not qualify as seizures.

Recent findings

Rapid response EEG (rEEG) has proven an important supplement to full montage continuous EEG monitoring (cEEG). This EEG can be applied in a few minutes and provides excellent ability to exclude seizures, selecting those where conversion to cEEG would have the greatest diagnostic yield. Once cEEG has been commenced, the durations required to adequately exclude seizures have been refined. The ACNS provided major revision and expansion to the standardized critical care EEG terminology, which paved the way for determining with great accuracy the RPPs that are associated with seizures and that are capable of causing neurologic symptoms and/or secondary neuronal injury. The current limitations to multicenter treatment trials of these patterns have been highlighted.

Novel methods of EEG in critical care have been expanding access to all patients where clinically indicated. Standardized EEG terminology has provided the framework to determine what patterns in which presenting causes warrant treatment vs. those that do not.
Social contagion, violence, and suicide among adolescents
Authors: Martínez Vania , Jiménez-Molina Álvaro , Gerber Mónica M.
Published: February 2023

Purpose of review

Social Contagion is defined as the spread of behaviors, attitudes, and affect through crowds and other types of social aggregates from one member to another. Adolescents are prone to social contagion because they may be especially susceptible to peer influence and social media.

In this article, we provide a brief review of the most recent findings on social contagion, violence, and suicide among adolescents.

Recent findings

Recent evidence support social contagion in gun violence, bullying, cyberbullying, violent offending, and suicide, but is inconclusive on the role of violent video game exposure on aggressive behavior.

The mechanisms underlying the contagion effect of violence and suicide are currently unclear. It has been argued that social learning, identification with significant others, and the normalization of specific norms play a role. All these mechanisms require understanding social contagion as a complex interaction between individual, relational and social factors. This is key if the social contagion perspective is to be used not only to investigate negative outcomes, but also as a framework for promoting prosocial attitudes and behaviors. Additionally, more research is needed on psychosocial interventions and public policies to minimize the potential spillover effect of violence and suicide.
Formation and emergent dynamics of spatially organized microbial systems
Authors: Cremin Kelsey , Duxbury Sarah J. N. , Rosko Jerko , Soyer Orkun S.
Published: February 2023

Spatial organization is the norm rather than the exception in the microbial world. While the study of microbial physiology has been dominated by studies in well-mixed cultures, there is now increasing interest in understanding the role of spatial organization in microbial physiology, coexistence and evolution. Where studied, spatial organization has been shown to influence all three of these aspects. In this mini review and perspective article, we emphasize that the dynamics within spatially organized microbial systems (SOMS) are governed by feedbacks between local physico-chemical conditions, cell physiology and movement, and evolution. These feedbacks can give rise to emergent dynamics, which need to be studied through a combination of spatio-temporal measurements and mathematical models. We highlight the initial formation of SOMS and their emergent dynamics as two open areas of investigation for future studies. These studies will benefit from the development of model systems that can mimic natural ones in terms of species composition and spatial structure.
Evidence of cat-to-human transmission of Staphylococcus felis
Authors: Sips Gregorius J. , van Dijk Marloes A. M. , van Westreenen Mireille , van der Graaf - van Bloois Linda , Duim Birgitta , Broens Els M.
Published: February 2023

Introduction.

Staphylococcus felis

is a coagulase-negative staphylococcal species that is commonly isolated from healthy cats. Like other commensal staphylococci,

S. felis

can cause opportunistic infections, e.g. otitis externa, skin and urinary tract infections, in cats.

Gap Statement. Several studies have reported within-household transmission between humans and pets and human infections caused by coagulase-positive staphylococci. However, human infections with coagulase-negative staphylococci of zoonotic origin are relatively rare.

Methodology. Culture of a surgical site infection in a 58-year-old woman who underwent a laminectomy revealed dominant growth of

S. felis

. The three cats owned by the patient were sampled to investigate potential within-household transmission.

S. felis

isolates were sequenced to investigate the relatedness of the isolates and to look for virulence factors and host specific genes.

Results. All cats were colonized with

S. felis

. Comparative genomics of the isolates showed that each cat was colonized with a distinct genotype. The patient’s isolate clustered with isolates of one of the cats. Sequence analysis of the studied isolates together with 29 publicly available

S. felis

genomes detected putative virulence factors that can be crucial in potential interspecies transmission.

Conclusion. The current case is the first reported human infection caused by

S. felis

and highlights the zoonotic potential of this bacterial species. Evidence of cat-to-human transmission was shown by comparative genomics of isolates from the patient with isolates of her cats.
Rapid assembly of SARS-CoV-2 genomes reveals attenuation of the Omicron BA.1 variant through NSP6
Authors: Taha Taha Y. , Chen Irene P. , Hayashi Jennifer M. , Tabata Takako , Walcott Keith , Kimmerly Gabriella R. , Syed Abdullah M. , Ciling Alison , Suryawanshi Rahul K. , Martin Hannah S. , Bach Bryan H. , Tsou Chia-Lin , Montano Mauricio , Khalid Mir M. , Sreekumar Bharath K. , Kumar G. Renuka , Wyman Stacia , Doudna Jennifer A. , Ott Melanie
Published: February 2023

Although the SARS-CoV-2 Omicron variant (BA.1) spread rapidly across the world and effectively evaded immune responses, its viral fitness in cell and animal models was reduced. The precise nature of this attenuation remains unknown as generating replication-competent viral genomes is challenging because of the length of the viral genome (30kb). Here, we designed a plasmid-based viral genome assembly and rescuestrategy (pGLUE) that constructs complete infectious viruses or noninfectious subgenomic replicons in a single ligation reaction with >80% efficiency. Fully sequenced replicons and infectious viral stocks can be generated in 1 and 3 weeks, respectively. By testing a series of naturally occurring viruses as well as Delta-Omicron chimeric replicons, we show that Omicron nonstructural protein 6 harbors critical attenuating mutations, which dampen viral RNA replication and reduce lipid droplet consumption. Thus, pGLUE overcomes remaining barriers to broadly study SARS-CoV-2 replication and reveals deficits in nonstructural protein function underlying Omicron attenuation.
Clinical Validation of a Multi-protein, Serum-based Assay for Disease Activity Assessments in Multiple Sclerosis
Authors: Chitnis Tanuja , Foley John , Ionete Carolina , Ayoubi Nabil K. El , Saxena Shrishti , Gaitan-Walsh Patricia , Lokhande Hrishikesh , Paul Anu , Saleh Fermisk , Weiner Howard , Venzie Jennifer L. , Qureshi Ferhan , Becich Michael J. , da Costa Fatima Rubio , Gehman Victor M. , Zhang Fujun , Keshavan Anisha , Jalaleddini Kian , Ghoreyshi Ati , Khoury Samia J.
Published: February 2023

Background and objectives

An unmet need exists for validated quantitative tools to measure multiple sclerosis (MS) disease activity and progression. We developed a custom immunoassay-based MS disease activity (MSDA) Test incorporating 18 protein concentrations into an algorithm to calculate four Disease Pathway scores (Immunomodulation, Neuroinflammation, Myelin Biology, and Neuroaxonal Integrity) and an overall Disease Activity score. The objective was to clinically validate the MSDA Test based on associations between scores and clinical/radiographic assessments.

Methods

Serum samples (N=614) from patients with MS at multiple sites were split into Train (n=426; algorithm development) and Test (n=188; evaluation) subsets. Subsets were stratified by demographics, sample counts per site, and gadolinium-positive (Gd+) lesion counts; age and sex were used to demographically adjust protein concentrations. MSDA Test results were evaluated for potential association with Gd+ lesion presence/absence, new and enlarging (N/E) T2 lesion presence, and active versus stable disease status (composite endpoint combining radiographic and clinical evidence of disease activity).

Results

A multi-protein model was developed (trained and cross-validated) using the Train subset. When applied to the Test subset, the model classified the Gd+ lesion presence/absence, N/E T2 lesion presence, and active versus stable disease status assessments with an area under the receiver operating characteristic (AUROC) of 0.781, 0.750, and 0.768, respectively. In each case, the multi-protein model had significantly (bootstrapped, one-sidedp<0.05) greater AUROC performance when compared with the top-performing, demographically adjusted (by age and sex) single-protein model based on neurofilament light polypeptide chain. Algorithmic score thresholds corresponded to low, moderate, or high levels of disease activity. Based on the Test subset, the diagnostic odds ratios determined that the odds of having ≥1 Gd+ lesions among samples with a moderate/high Disease Activity score were 4.49 times that of a low Disease Activity score. The odds of having ≥2 Gd+ lesions among samples with a high Disease Activity score were 20.99 times that of a low/moderate Disease Activity score.

Discussion

The MSDA Test was clinically validated; the multi-protein model had greater performance compared with the top-performing single-protein model. The MSDA Test may serve as a quantitative and objective tool to enhance care for MS.
Derivation and external validation of a clinical prognostic model identifying children at risk of death following presentation for diarrheal care
Authors: Ahmed Sharia M. , Brintz Ben J. , Talbert Alison , Ngari Moses , Pavlinac Patricia B. , Platts-Mills James A. , Levine Adam C. , Nelson Eric J. , Walson Judd L. , Kotloff Karen L. , Berkley James A. , Leung Daniel T.
Published: February 2023

Diarrhea continues to be a leading cause of death for children under-five. Amongst children treated for acute diarrhea, mortality risk remains elevated during and after acute medical management. Identification of those at highest risk would enable better targeting of interventions, but available prognostic tools lack validation. We used clinical and demographic data from the Global Enteric Multicenter Study (GEMS) to build predictive models for death (in-treatment, after discharge, or either) in children aged ≤59 months presenting with moderate-to-severe diarrhea (MSD), in Africa and Asia. We screened variables using random forests, and assessed predictive performance with random forest regression and logistic regression using repeated cross-validation. We used data from the Kilifi Health and Demographic Surveillance System (KHDSS) and Kilifi County Hospital (KCH) in Kenya to externally validate our GEMS-derived clinical prognostic model (CPM). Of 8060 MSD cases, 43 (0.5%) children died in treatment and 122 (1.5% of remaining) died after discharge. MUAC at presentation, respiratory rate, age, temperature, number of days with diarrhea at presentation, number of people living in household, number of children <60 months old living in household, and how much the child had been offered to drink since diarrhea started were predictive of death both in treatment and after discharge. Using a parsimonious 2-variable prediction model, we achieve an AUC=0.84 (95% CI: 0.82, 0.86) in the derivation dataset, and an AUC=0.74 (95% CI 0.71, 0.77) in the external dataset. Our findings suggest it is possible to identify children most likely to die after presenting to care for acute diarrhea. This could represent a novel and cost-effective way to target resources for the prevention of childhood mortality.
Mental health, gender, and care-seeking behavior during the COVID-19 pandemic in Sweden: An exploratory study
Authors: Vincze Katalin , Murphy Gillian , Barker Mary , González-Hijón Juan , Kähler Anna K. , Frans Emma M. , Sullivan Patrick F. , Valdimarsdóttir Unnur A. , Fang Fang , Lovik Anikó
Published: February 2023

Objective

To explore the prevalence of care-seeking avoidance behavior in relation to gender and to describe the effect of (and potential interaction between) gender and care-seeking on mental health during the COVID-19 pandemic in Sweden.

Methods

We performed a cross-sectional study among 27,562 participants of the Omtanke2020 Study, using data collected at three time points concerning sociodemographic factors, mental health symptoms, and care-seeking behavior. Network analysis and prevalence ratios calculated from modified Poisson regressions were used to explore the relationship between gender, care-seeking behavior, and mental health symptoms (depression, anxiety, and COVID-19-related distress).

Results

In our study, women reported a higher prevalence of mental health symptoms and avoidance of care-seeking due to COVID-19, compared to men. At baseline and six months thereafter, female gender was positively associated with COVID-19-related distress and previous mental health diagnosis. At 12 months after baseline, female gender was positively associated with anxiety and avoidance of care-seeking for mental health. However, previous mental health diagnosis and care avoidance were more strongly associated with a higher prevalence of mental health symptoms among men, compared to women.

Conclusion

This study highlights gender differences in mental health outcomes and care-seeking behavior during the COVID-19 pandemic in Sweden.

Funding

This work was supported with grants from Nordforsk (COVIDMENT, 105668 and 138929).
Polysubstance addiction and psychiatric, somatic comorbidities among 7,989 individuals with cocaine use disorder: a latent class analysis
Authors: Stiltner Brendan , Pietrzak Robert H. , Tylee Daniel S. , Nunez Yaira Z. , Adhikari Keyrun , Kranzler Henry R. , Gelernter Joel , Polimanti Renato
Published: February 2023

Aims

We performed a latent class analysis (LCA) in a sample ascertained for addiction phenotypes to investigate cocaine use disorder (CoUD) subgroups related to polysubstance addiction (PSA) patterns and characterized their differences with respect to psychiatric and somatic comorbidities.

Design

Cross-sectional study

Setting

United States

Participants

Adult participants aged 18-76, 39% female, 47% African American, 36% European American with a lifetime DSM-5 diagnosis of CoUD (N=7,989) enrolled in the Yale-Penn cohort. The control group included 2,952 Yale-Penn participants who did not meet for alcohol, cannabis, cocaine, opioid, or tobacco use disorders.

Measurements

Psychiatric disorders and related traits were assessed via the Semi-structured Assessment for Drug Dependence and Alcoholism. These features included substance use disorders (SUD), family history of substance use, sociodemographic information, traumatic events, suicidal behaviors, psychopathology, and medical history. LCA was conducted using diagnoses and diagnostic criteria of alcohol, cannabis, opioid, and tobacco use disorders.

Findings

Our LCA identified three subgroups of PSA (i.e., low, 17%; intermediate, 38%; high, 45%) among 7,989 CoUD participants. While these subgroups varied by age, sex, and racial-ethnic distribution (p<0.001), there was no difference on education or income (p>0.05). After accounting for sex, age, and race-ethnicity, the CoUD subgroup with high PSA had higher odds of antisocial personality disorder (OR=21.96 vs. 6.39, difference-p=8.08×10−6), agoraphobia (OR=4.58 vs. 2.05, difference-p=7.04×10−4), mixed bipolar episode (OR=10.36 vs. 2.61, difference-p=7.04×10−4), posttraumatic stress disorder (OR=11.54 vs. 5.86, difference-p=2.67×10−4), antidepressant medication use (OR=13.49 vs. 8.02, difference-p=1.42×10−4), and sexually transmitted diseases (OR=5.92 vs. 3.38, difference-p=1.81×10−5) than the low-PSA CoUD subgroup.

Conclusions

We found different patterns of PSA in association with psychiatric and somatic comorbidities among CoUD cases within the Yale-Penn cohort. These findings underscore the importance of modeling PSA severity and comorbidities when examining the clinical, molecular, and neuroimaging correlates of CoUD.
Backward masking reveals coarse-to-fine dynamics in human V1
Authors: Schuurmans Jolien P. , Bennett Matthew A. , Petras Kirsten , Goffaux Valérie
Published: February 2023

Natural images exhibit luminance variations aligned across a broad spectrum of spatial frequencies (SFs). It has been proposed that, at early stages of processing, the coarse signals carried by the low SF (LSF) of the visual input are sent rapidly from primary visual cortex (V1) to ventral, dorsal and frontal regions to form a coarse representation of the input, which is later sent back to V1 to guide the processing of fine-grained high SFs (i.e., HSF). We used functional resonance imaging (fMRI) to investigate the role of human V1 in the coarse-to-fine integration of visual input. We disrupted the processing of the coarse and fine content of full-spectrum human face stimuli via backward masking of selective SF ranges (LSFs: <1.75cpd and HSFs: >1.75cpd) at specific times (50, 83, 100 or 150ms). In line with coarse-to-fine proposals, we found that (1) the selective masking of stimulus LSF disrupted V1 activity in the earliest time window, and progressively decreased in influence, while (2) an opposite trend was observed for the masking of a stimulus’ HSF. This pattern of activity was found in V1, as well as in ventral (i.e. the Fusiform Face area, FFA), dorsal and orbitofrontal regions. We additionally presented participants with contrast negated stimuli. While contrast negation significantly reduced response amplitudes in the FFA, as well as coupling between FFA and V1, coarse-to-fine dynamics were not affected by this manipulation. The fact that V1 response dynamics to strictly identical stimulus sets differed depending on the masked scale adds to growing evidence that V1 role goes beyond the early and quasi-passive transmission of visual information to the rest of the brain. It instead indicates that V1 may yield a ‘spatially registered common forum’ or ‘blackboard’ that integrates top-down inferences with incoming visual signals through its recurrent interaction with high-level regions located in the inferotemporal, dorsal and frontal regions.
Transgenerational coexistence history attenuates negative direct interactions and strengthens facilitation
Authors: Schmutz Anja , Schöb Christian
Published: February 2023

Background

Interactions among species are a fundamental aspect of biodiversity and driving ecosystem functioning and services. Species interactions include direct (pairwise) interactions among two species and indirect interactions that occur when a third species interacts with the two others and changes the direct interactions between the two. In a three-species interaction network, these interactions can be transitive (where one species outperforms all others) or intransitive (where each species outperforms another). How direct and indirect interactions influence ecosystem functions in crop systems, and how diversification and evolutionary adaptation can influence those interactions and therefore ecosystem functions has not been studied.

Methods

A common garden experiment was conducted with crop communities in monocultures, 2- and 3-species mixtures that had either a common or no coexistence history (i.e. community adaptation) for three years. Net, direct and indirect interaction intensities were estimated and compared between the diversity levels and coexistence histories. Furthermore, species interaction networks were inspected for transitive/intransitive interactions.

Results

We found evidence for lower competition in mixtures and for reduced negative direct interaction intensity and enhance facilitative effects upon community adaptation. We could further show that indirect interactions were generally less important for community adaptation than direct interactions. Additionally, we showed that community adaptation has the potential to shift interactions in the species interaction networks from competitive intransitive into pairwise competitive interactions where interactions occurred mainly between two species.

Synthesis

Co-adapted crop species with reduced negative interactions might have the potential to enhance productivity especially in more diverse cropping systems. This supports the notion that intercropping is a vital part towards a more sustainable agriculture and one with further yield potential when developing cultivars adapted to grow in mixtures.
Mass Mortality of Marine Mammals Associated to Highly Pathogenic Influenza Virus (H5N1) in South America
Authors: Gamarra-Toledo Víctor , Plaza Pablo I. , Gutiérrez Roberto , Inga-Diaz Giancarlo , Saravia-Guevara Patricia , Pereyra-Meza Oliver , Coronado-Flores Elver , Calderón-Cerrón Antonio , Quiroz-Jiménez Gonzalo , Martinez Paola , Huamán-Mendoza Deyvis , Nieto-Navarrete José C. , Ventura Sandra , Lambertucci Sergio A.
Published: February 2023

We report a massive mortality of more than 3,000 sea lions (Otaria flavescens) of Peru associated with a Highly Pathogenic Influenza Virus (H5N1). The transmission pathway of H5N1 may have been through the close contact of sea lions with infected wild birds. We cannot rule out direct transmission among sea lions.
Variable Power Functional Dilution Adjustment of Spot Urine
Authors: Carmine Thomas Clemens
Published: February 2023

Spot-urinary biomarkers are essential for medical, epidemiological, and environmental research. However, they are affected by hydration-dependent diuresis, requiring precise dilution adjustments. Traditional methods, like conventional creatinine correction (CCRC), have limitations and introduce errors due to residual diuresis dependence. To address this, the WHO recommends a valid creatinine (CRN) range of 0.3-3 g/L. The present study introduces a novel numerical variable power functional CRN correction method (V-PFCRC). It was developed using 5553 spot urinary samples for total weight arsenic from a diverse population with generally low background exposure to inorganic arsenic from drinking water. The innovative V-PFCRC formula normalizes analytes (A) to 1 g/L CRN using uncorrected analyte levels and two analyte-specific coefficients, c and d: A normalized = A uncorrected / CRN[c · Ln(A uncorrected) + d] / [c · Ln(CRN) + 1]When applied to spot urinary arsenic, iodine, cesium, molybdenum, strontium, and zinc, the V-PFCRC method significantly reduced residual CRN bias. It performed better compared to uncorrected, conventionally (CCRC), and simple power functionally CRN-corrected (S-PFCRC) urine samples. V-PFCRC enhanced CRN-bias removal in entire datasets and within seven separately analyzed analyte levels (septiles), adequately compensating for non-linear, exposure-differentiated skews, including complex metabolic and excretory interactions between analytes and CRN. These advancements were supported by improved blood-urine correlations for iodine and arsenic in both sexes, suggesting a more accurate representation of supply and exposure than traditional urinary dilution corrections. The results underscore the superior performance of the V-PFCRC method in adjusting for hydration-dependent variability, surpassing traditional correction methods. The resource-efficient and versatile V-PFCRC method is easy to implement and holds immense potential for broader applications in various scientific and medical fields. This study advocates for the wider adoption of V-PFCRC to enhance the accuracy and reliability of urinary biomarkers, ensuring superior diagnostic and research outcomes. Keywords: Non-linear dilution adjustment, variable power-functional dilution adjustment, creatinine correction, spot urine, biomarkers, arsenic, iodine, metal analytics, exposure studies.
Microbiota Predict Infections and Acute Graft-Versus-Host Disease after Pediatric Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Margolis Elisa B , Alfaro Gabriela Maron , Sun Yilun , Dallas Ronald H , Allison Kim J , Ferrolino Jose , Ross Hailey S , Davis Amy E , Jia Qidong , Turner Paige , Mackay Victoria , Morin Cara E. , Triplett Brandon M , Tang Li , Hayden Randall T
Published: February 2023

Despite intensive prophylactic and pre-emptive measures, infections remain an important cause of morbidity and mortality in pediatric recipients of allogeneic hematopoietic cell transplantation (allo-HCT). Disruption of the gut microbiota has been linked to clinical outcomes after adult allo-HCT. The objective was to evaluate whether these or differing microbiota disruptions or signatures were associated with risk of infection in pediatric allo-HCT.

In a prospective observational study, fecal samples from 74 children were collected prior to conditioning and at the time of neutrophil recovery and profiled by means of 16S ribosomal rRNA sequencing. The associations between microbiome signatures and infections or acute graft-versus-host disease (aGVHD) were examined using Cox proportional-hazards analysis.

Previously associated indices of microbiome disruption in adults, including diversity and butyrate producer frequency, did not predict infection risk in pediatric allo-HCT. Unique microbiota signatures were associated with different infections or aGVHD. A ratio of strict and facultative anaerobes (e.g.Lachnoclostridium, Parabacteroides, Clostridium spp.) prior to conditioning predicted likelihood of bacteremia (cox hazards ratio 3.89) in first year post HCT. A distinct ratio of oral (e.g.Rothia, Veillonellaspp.) to colonic anaerobes (e.g.Anaerobutyricum, Dorea, Romboutsiaspp.) at neutrophil recovery predicted likelihood of bacterial infections (cox hazards ratio 1.81) and viral enterocolitis (cox hazards ratio 1.96) through first year post transplant.

Interactions between medical interventions, pediatric hosts and microbial communities may be responsible for these consistent microbiota signatures that predict infections. A future multi-center investigation will be needed to demonstrate whether these ratios can be generalized to other pediatric cohorts.

Key Points

(1 or 2, <140 characters): Gut microbial communities can predict which children after HCT will have infections or acute graft versus host disease. These ratios of gut community members can be used to focus prevention and treatment on children at highest risks for complications.
Prevalence and Factors Associated with Renal Disease Among HIV Infected Children on Antiretroviral Therapy Attending Joint Clinical Research Center, Lubowa, Kampala
Authors: Bagoloire Lynn Kolosi , Sheilla Ansiima , Kalyango Joan , Mugerwa Henry , Bruhan Kaggwa , Waiswa Peter , Barungi Nicolette Nabukeera , Musiime Victor
Published: February 2023

Introduction

Renal disease is asymptomatic in its early stages but on progression into advanced stage is expensive to manage requiring renal replacement therapy. Monitoring of children’s renal functionality is not routinely done but only on a doctor’s request. However, there is currently no published study on renal disease prevalence among children living with HIV in Uganda and the associated factors.

Objective

To determine the prevalence of renal disease and its associated factors among HIV positive children on ART at the Joint Clinical Research Center (JCRC) Pediatric clinic.

Methods

We conducted a cross sectional study from JCRC Pediatrics Clinic. Children attending the clinic between January and August, 2020 were recruited using consecutive sampling. Information on age, sex, z sore for age, Blood pressure, route of transmission, clinical stage of the disease, ART regimen, duration on ART, non-ART drugs, Viral load and comorbidities was obtained. Blood and urine samples were also collected from the participants and sent to the laboratory for analysis. Renal disease was diagnosed using either proteinuria on urine dipstick or reduced estimated Glomerular Filtration Rate, (eGFR).

Results

The study participants were 261, of which 51% were female and 49% male, with a median age of 12 years. The prevalence of renal diseases was 21.5% as proteinuria and 9.6% with low eGFR. Factors associated with proteinuria were; age (p-value =0.01), clinical stage of the disease (p=0.035) and diastolic blood pressure (DBP, p = 0.001) and with low eGFR were; DBP (p < 0.001) and clinical stage of disease (p < 0.001).

Conclusion

The prevalence of proteinuria was high (21.5%) and that of low eGFR was (9.1%). Early screening for renal disease when still asymptomatic as a preventive strategy for renal disease should be considered, especially using affordable yet effective methods like urinalysis. This is because all the participants were asymptomatic at the time of enrollment.
Identification of circulating apolipoprotein M as a new determinant of insulin sensitivity and relationship with adiponectin
Authors: Frances Laurie , Croyal Mikaël , Ruidavets Jean-Bernard , Maraninchi Marie , Combes Guillaume , Raffin Jérémy , de Souto Barreto Philippe , Ferrières Jean , Blaak Ellen E. , Perret Bertrand , Moro Cédric , Valéro René , Martinez Laurent O. , Viguerie Nathalie
Published: February 2023

Background

Adiponectin and apolipoprotein M (apoM) are adipokines indicatives of healthy adipose tissue and down-regulated with obesity. We compared circulating apoM with adiponectin regarding their relationship with metabolic parameters and insulin sensitivity and examined their gene expression patterns in adipocytes and in the adipose tissue.

Methods

Circulating apoM and adiponectin were examined in 169 men with overweight in a cross-sectional study, and 13 patients with obesity during a surgery-induced slimming program. Correlations with clinical parameters including the insulin resistance index (HOMA-IR) were analyzed. Multiple regression analyses were performed on HOMA-IR. TheAPOMandADIPOQgene expression were measured in the adipose tissue from 267 individuals with obesity and a human adipocyte cell line.

Results

Participants with type 2 diabetes had lower circulating adiponectin and apoM, while apoM was higher in individuals with dyslipidemia. Similar to adiponectin, apoM showed negative associations with HOMA-IR and hs-CRP (r>-0.2), and positive correlations with HDL markers (HDL-C and apoA-I, r>0.3). Unlike adiponectin, apoM was positively associated with LDL markers (LDL-C and apoB100, r< 0.20) and negatively correlated with insulin and age (r>-0.2). The apoM was the sole negative determinant of HOMA-IR in multiple regression models, while adiponectin not contributing significantly. After surgery, the change in HOMA-IR was negatively associated with the change in circulating apoM (r=-0.71), but not with the change in adiponectin. TheAPOMandADIPOQgene expression positively correlated in adipose tissue (r>0.44) as well as in adipocytes (r>0.81). In adipocytes,APOMwas downregulated by inflammatory factors and upregulated by adiponectin.

Conclusions

The apoM rises as a new partner of adiponectin regarding insulin sensitivity. At the adipose tissue level, the adiponectin may be supported by apoM to promote a healthy adipose tissue.
Reconstructing colonization dynamics to establish how human activities transformed island biodiversity
Authors: Tomlinson Sean , Lomolino Mark , Haythorne Sean , Anderson Atholl , Austin Jeremy J. , Brown Stuart , Perry George , Wilmshurst Janet , Wood Jamie R. , Fordham Damien A.
Published: February 2023

Aim

The drivers and dynamics of initial human migrations across individual islands and archipelagos are poorly understood, affecting assessments of human-modification of island biodiversity. Here, we describe and test a process-explicit approach for reconstructing human arrival and expansion on islands, which combines archaeological and climate records with high-resolution spatial population models. Using Polynesian colonisation of New Zealand as an example, we show that our new method can generate information crucial for assessing how humans affected biodiversity on islands.

Innovation

The transition of islands from prehuman to human dominated ecosystems has typically been assessed by comparing biodiversity before and after time of first arrival, without considering the potential importance of the spatiotemporal dynamics of the human expansion event. Our new approach, which uses pattern-oriented modelling methods to combine inferences of human colonisation dynamics from dated archaeological material with spatially explicit population models, produces validated reconstructions of the pattern and pace of human migration across islands at high spatiotemporal resolutions. From these reconstructions, demographic and environmental drivers of human colonization can be identified, and the role that people had on biodiversity established. Using this technique, we show that closely reconciling inferences of Polynesian colonisation of New Zealand requires there to have been a single founding population of approximately 500 people, arriving between 1233 and 1257 AD, settling multiple areas, and expanding quickly over both North and South islands. The resultant maps of Māori colonisation dynamics provide new opportunities to better determine how human activities transformed biodiversity of New Zealand in space and time.

Main conclusions

Process-explicit models can reconstruct human migration across large islands, producing validated, high resolution spatiotemporal projections of human occupancy and abundance that account for dispersal and population dynamics. This modelling framework should prove effective across any islands and archipelagos where climate and archaeological records are available.
Structural-Functional Brain Network Coupling Predicts Human Cognitive Ability
Authors: Popp Johanna L. , Thiele Jonas A. , Faskowitz Joshua , Seguin Caio , Sporns Olaf , Hilger Kirsten
Published: February 2023

Individual differences in general cognitive ability (GCA) have a biological basis within the structure and function of the human brain. Network neuroscience investigations revealed neural correlates of GCA in structural as well as in functional brain networks. However, whether the relationship between structural and functional networks, the structural-functional brain network coupling (SC-FC coupling), is related to individual differences in GCA remains an open question. We used data from 1030 adults of the Human Connectome Project, derived structural connectivity from diffusion weighted imaging, functional connectivity from resting-state fMRI, and assessed GCA as a latentg-factor from 12 cognitive tasks. Two similarity measures and six communication measures were used to model possible functional interactions arising from structural brain networks. SC-FC coupling was estimated as the degree to which these measures align with the actual functional connectivity, providing insights into different neural communication strategies. At the whole-brain level, higher GCA was associated with higher SC-FC coupling, but only when considering path transitivity as neural communication strategy. Taking region-specific variations in the SC-FC coupling strategy into account and differentiating between positive and negative associations with GCA, allows for prediction of individual cognitive ability scores in a cross-validated prediction framework (correlation between predicted and observed scores:r= .25,p< .001). The same model also predicts GCA scores in a completely independent sample (N= 567,r= .19,p< .001). Our results propose structural-functional brain network coupling as a neurobiological correlate of GCA and suggest brain region-specific coupling strategies as neural basis of efficient information processing predictive of cognitive ability.