bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of antioxidants in itch treatment: lessons learned from pain management
Authors: Biazus Soares Georgia , Mahmoud Omar , Yosipovitch Gil
Published: March 2023

Chronic pain and chronic pruritus are both debilitating conditions that cause a significant burden to patients. Oxidative stress—driven by an imbalance between reactive oxygen species and antioxidants—has been shown to play a role both in pain disorders and conditions in which chronic itch is a prominent symptom. Antioxidants can be useful in treating oxidative stress-driven diseases and have shown promise in treating chronic pain conditions such as fibromyalgia and osteoarthritis. However, their role in treating pruritus and pruritic conditions such as psoriasis and atopic dermatitis remains unclear. Many of the current treatments for chronic itch are costly, associated with side effects, and have limited efficacy. Therefore, further controlled studies exploring antioxidants as a potential therapeutic option for chronic pruritus are warranted.
The dose-dependent effects of transcutaneous electrical nerve stimulation for pain relief in individuals with fibromyalgia: a systematic review and meta-analysis
Authors: Amer-Cuenca Juan J. , Badenes-Ribera Laura , Biviá-Roig Gemma , Arguisuelas María D. , Suso‐Martí Luis , Lisón Juan F.
Published: March 2023

Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological modality widely used to manage pain; however, its effectiveness for individuals with fibromyalgia (FM) has been questioned. In previous studies and systematic reviews, variables related to dose of TENS application have not been considered. The objectives of this meta-analysis were (1) to determine the effect of TENS on pain in individuals with FM and (2) determine the dose-dependent effect of TENS dose parameters on pain relief in individuals with FM. We searched the PubMed, PEDro, Cochrane, and EMBASE databases for relevant manuscripts. Data were extracted from 11 of the 1575 studies. The quality of the studies was assessed using the PEDro scale and RoB-2 assessment. This meta-analysis was performed using a random-effects model that, when not considering the TENS dosage applied, showed that the treatment had no overall effect on pain (d+ = 0.51, P > 0.050, k = 14). However, the moderator analyses, which were performed assuming a mixed-effect model, revealed that 3 of the categorical variables were significantly associated with effect sizes: the number of sessions (P = 0.005), the frequency (P = 0.014), and the intensity (P = 0.047). The electrode placement was not significantly associated with any effect sizes. Thus, there is evidence that TENS can effectively reduce pain in individuals with FM when applied at high or at mixed frequencies, a high intensity, or in long-term interventions involving 10 or more sessions. This review protocol was registered at PROSPERO (CRD42021252113).
Chronic pain in Chile: first prevalence report of noncancer chronic pain, fibromyalgia, and neuropathic pain and its associated factors
Authors: Durán Josefina , Tejos-Bravo Macarena , Cid Vicente , Ferreccio Catterina , Calvo Margarita
Published: March 2023

Although we know chronic pain (CP) affects approximately 30% of people in developed countries, data from Latin America are scarce. Moreover, prevalence of specific CP conditions, such as chronic noncancer pain (CNCP), fibromyalgia (FM), and neuropathic pain (NP), is unknown. To estimate them in Chile, we prospectively enrolled 1945 participants (61.4% women and 38.6% men), aged 38 to 74 years, from an agricultural town who answered a Pain Questionnaire, the Fibromyalgia Survey Questionnaire, and Douleur Neuropathique 4 (DN4) to identify CNCP, FM, and NP, respectively. The estimated prevalence of CNCP was 34.7% (95% CI 32.6; 36.8), with an average duration of 32.3 months (SD ± 56.3), producing deep impairments in daily activities, sleep, and mood. We estimated a prevalence of 3.3% for FM (95% CI 2.5; 4.1) and 12% for NP (95% CI 10.6; 13.4). Female sex, fewer school years, and depressive symptoms were associated with FM and NP, whereas diabetes was only associated with NP. We standardized the results from our sample against the whole Chilean population and found no significant difference to our crude estimates. This is in line with studies from developed countries, highlighting the idea that despite genetic and environmental differences, the conditions that confer risk to CNCP remain stable.
Nutrition after severe burn injury
Authors: Rousseau Anne-Françoise , Pantet Olivier , Heyland Daren K.
Published: March 2023

Purpose of review

Severe burn injury causes significant metabolic changes and demands that make nutritional support particularly important. Feeding the severe burn patient is a real challenge in regard to the specific needs and the clinical constraints. This review aims to challenge the existing recommendations in the light of the few recently published data on nutritional support in burn patients.

Recent findings

Some key macro- and micro-nutrients have been recently studied in severe burn patients. Repletion, complementation or supplementation of omega-3 fatty acids, vitamin C, vitamin D, antioxidant micronutrients may be promising from a physiologic perspective, but evidence of benefits on hard outcomes is still weak due to the studies’ design. On the contrary, the anticipated positive effects of glutamine on the time to discharge, mortality and bacteremias have been disproved in the largest randomized controlled trial investigating glutamine supplementation in burns. An individualized approach in term of nutrients quantity and quality may proof highly valuable and needs to be validated in adequate trials. The combination of nutrition and physical exercises is another studied strategy that could improve muscle outcomes.

Due to the low number of clinical trials focused on severe burn injury, most often including limited number of patients, developing new evidence-based guidelines is challenging. More high-quality trials are needed to improve the existing recommendations in the very next future.
EEG Correlates of Spikes in Intracranial Pressure Caused by Transient Ventriculoperitoneal Shunt Malfunction
Authors: Wang Paul , Dona Allison , Khetarpal Nikita , Reeder Stephanie , Robertson Jetter , Patel Sima
Published: March 2023

A 30-year-old man with recurrent headaches and seizure-like activity and a 26-year-old woman with worsening headaches were admitted to the hospital. Both had ventriculoperitoneal shunts and history of several shunt revisions for congenital hydrocephalus. The ventricle size visualized on computed tomography scans was unremarkable, and shunt series were negative in both cases. Both patients began to present with brief periods of unresponsiveness, and video electroencephalography at that time showed periods of diffuse delta slowing. Lumbar punctures revealed increased opening pressures. Despite normal imaging and shunt series, both patients ultimately had increased intracranial pressure caused by shunt malfunction. This series demonstrates the difficulty of diagnosing potential transient increases in intracranial pressure based on standard-of-care diagnostics/examination and the potentially critical role for EEG in the identification of shunt malfunction.
Injury of the Corticofugal Tract from the Secondary Motor Area in Middle Cerebral Territory Infarction: A DTI Study
Authors: Seo Jeong Pyo , Yun Seong Ho
Published: March 2023

Background and Purpose

Middle cerebral artery (MCA) territory infarction commonly induces a variety of motor function deficits because it involves multiple descending motor pathways, including the corticospinal tract (CST) and corticofugal tract (CFT). Despite the importance of the MCA territory for motor function, there is currently insufficient evidence regarding an injury of the CFT from the secondary motor area in MCA territory infarctions. We investigated injury of the CFT from the secondary motor area and CST in patients with MCA using diffusion tensor tractography (DTT).

Methods

Thirty-five patients with MCA territory infarctions and 30 controls were recruited. DTT parameters, including fractional anisotropy (FA) and tract volume (TV), of the CST and CFTs from the dorsal premotor cortex (dPMC) and supplementary motor area (SMA), were analyzed.

Results

In the affected hemisphere, the FA values of the CFTs from the secondary motor areas and CST were significantly lower than those in the unaffected hemisphere and control groups. Additionally, the TV of the CFTs from the dPMC and SMA were significantly lower than those from the unaffected hemisphere.

Conclusion

We observed concurrent injury to the CFTs from the secondary motor area and CST after MCA territory infarction. Our findings explain the neural mechanisms underlying motor weakness and limb kinetic apraxia in patients with MCA.
What has brain diffusion MRI taught us about chronic pain: a narrative review
Authors: Bautin Paul , Fortier Marc-Antoine , Sean Monica , Little Graham , Martel Marylie , Descoteaux Maxime , Léonard Guillaume , Tétreault Pascal
Published: March 2023

Chronic pain is a pervasive and debilitating condition with increasing implications for public health, affecting millions of individuals worldwide. Despite its high prevalence, the underlying neural mechanisms and pathophysiology remain only partly understood. Since its introduction 35 years ago, brain diffusion MRI has emerged as a powerful tool to investigate changes in white matter microstructure and connectivity associated with chronic pain. This review synthesizes findings from 58 articles that constitute the current research landscape, covering methodologies and key discoveries.

We discuss the evidence supporting the role of altered white matter microstructure and connectivity in chronic pain conditions, highlighting the importance of studying multiple chronic pain syndromes to identify common neurobiological pathways. We also explore the prospective clinical utility of diffusion MRI, such as its role in identifying diagnostic, prognostic, and therapeutic biomarkers.

Further, we address shortcomings and challenges associated with brain diffusion MRI in chronic pain studies, emphasizing the need for the harmonization of data acquisition and analysis methods. We conclude by highlighting emerging approaches and prospective avenues in the field that may provide new insights into the pathophysiology of chronic pain and potential new therapeutic targets.

Due to the limited current body of research and unidentified targeted therapeutic strategies, we are forced to conclude that further research is required. However, we believe that brain diffusion MRI presents a promising opportunity for enhancing our understanding of chronic pain and improving clinical outcomes.
Viral kinetics of sequential SARS-CoV-2 infections
Authors: Kissler Stephen M , Hay James A , Fauver Joseph R , Mack Christina , Tai Caroline G , Anderson Deverick J , Ho David D , Grubaugh Nathan D , Grad Yonatan H
Published: March 2023

The impact of a prior SARS-CoV-2 infection on the progression of subsequent infections has been unclear. Using a convenience sample of 94,812 longitudinal RT-qPCR measurements from anterior nares and oropharyngeal swabs, we compared the SARS-CoV-2 viral kinetics of firstvs. second infections, adjusting for viral variant, vaccination status, and age. Relative to first infections, second infections usually featured a lower peak viral concentration and faster clearance time, especially in individuals who received a vaccine dose between their first and second infection. Furthermore, a person’s relative (rank-order) viral clearance time, compared to others infected with the same variant, was similar across first and second infections; that is, individuals who had a relatively fast clearance time in their first infection tended to also have a relatively fast clearance time in their second infection. These findings provide evidence that, like vaccination, immunity from a prior SARS-CoV-2 infection shortens the duration of subsequent acute SARS-CoV-2 infections principally by reducing viral clearance time. Additionally, there appears to be an inherent element of the immune response, or some other host factor, that shapes a person’s relative ability to clear SARS-CoV-2 infection that persists across sequential infections.
Relationship between blood pressure and the risk of acute myocardial infarction in Chinese adults: a prospective study
Authors: Zhang Xin , He Xiaoyong , Mao Fan , Zhang Run , You Xiaoqing , Li Jianhong
Published: March 2023

Objective

To explore the relationship between blood pressure and the risk of acute myocardial infarction (AMI) in Chinese adults.

Methods

This prospective cohort study included 26,794 participants which were recruited from 60 surveillance sites in 2010 China Chronic Disease Risk Factor Surveillance and followed-up survey was conducted from 2016 to 2017. Data were collected by questionnaires, physical measurements and laboratory tests. Blood pressure was grouped by systolic blood pressure and diastolic blood pressure, and cox proportional hazards regression models were used to analyze the relationship between blood pressure and risk of AMI.

Results

A total of 256 AMI events occurred among 160,386.38 person-years follow-up and the incidence of AMI was 159.6/100,000 person-years. After adjusting for age, sex, income, education, marital status, physical activity, drinking, abdominal obesity, BMI, dyslipidemia and diabetes, compared with normotension group, the risk of AMI onset was increased by 61% (HR=1.61, 95%CI: 1.17∼2.21), 60% (HR=1.60, 95%CI: 1.17∼2.20), 84% (HR=1.84, 95%CI: 1.26∼2.68) and 120% (HR=2.20, 95%CI: 1.43∼3.38) in systolic diastolic hypertension(SDH), hypertension grade 1(mild), hypertension grade 2(moderate), hypertension grade 3(severe), respectively. In addition, after adjusting for relevant factors, the relationship between hypertension and the risk of AMI may be influenced by abdominal obesity, diabetes and lack of physical activity.

Conclusions

The incidence of AMI appears to be considerable among Chinese adults and hypertension is an independent risk factor for its onset. The risk of AMI is higher in participants with more severe hypertension.
Stress-induced brain responses are associated with BMI in women
Authors: Kühnel Anne , Hagenberg Jonas , Knauer-Arloth Janine , Ködel Maik , Czisch Michael , Sämann Philipp G. ,   BeCOME working group, Binder Elisabeth B. , Kroemer Nils B.
Published: March 2023

Background

Stress is associated with elevated risk for overweight and obesity, especially in women. Since body mass index (BMI) is correlated with increased inflammation and reduced baseline cortisol, obesity may lead to altered stress responses. However, it is not well understood whether stress-induced changes in brain function scale with BMI and if peripheral inflammation contributes to this.

Methods

We investigated the subjective, autonomous, endocrine, and neural stress response in a transdiagnostic sample (N=192, 120 women, MBMI=23.7±4.0 kg/m2; N=148, 89 women, with cytokines). First, we used regression models to examine effects of BMI on stress reactivity. Second, we predicted BMI based on stress-induced changes in activation and connectivity using cross-validated elastic-nets. Third, to link stress responses with inflammation, we quantified the association of BMI-related cytokines with model predictions.

Results

BMI was associated with higher negative affect after stress and an increased response to stress in the substantia nigra and the bilateral posterior insula (pFWE<.05). Moreover, stress-induced changes in activation of the hippocampus, dACC, and posterior insula predicted BMI in women (pperm<.001), but not in men. BMI was associated with higher baseline cortisol while cytokines were not associated with predicted BMI scores.

Conclusions

Stress-induced changes in the hippocampus and posterior insula predicted BMI in women, indicating that acute brain responses to stress might be more strongly related to a higher BMI in women compared to men. Altered stress-induced changes were associated with baseline cortisol but independent of cytokines, suggesting that the endocrine system and not inflammation contributes to stress-related changes in BMI.
Treatment seeking behaviours, antibiotic use and relationships to multi-drug resistance: A study of urinary tract infection patients in Kenya, Tanzania and Uganda
Authors: Sado Keina , Keenan Katherine , Manataki Areti , Kesby Mike , Mushi Martha F , Mshana Stephen E , Mwanga Joseph , Neema Stella , Asiimwe Benon , Bazira Joel , Kiiru John , Green Dominique L , Ke Xuejia , Maldonado-Barragán Antonio , Abed Al Ahad Mary , Fredricks Kathryn , Gillespie Stephen H , Sabiiti Wilber , Mmbaga Blandina T , Kibiki Gibson , Aanensen David , Smith V Anne , Sandeman Alison , Sloan Derek J , Holden Matthew TG
Published: March 2023

Antibacterial resistance (ABR) is a major public health threat. An important accelerating factor is treatment-seeking behaviours, including inappropriate antibiotic (AB) use. In many low- and middle-income countries (LMICs) this includes taking ABs with and without prescription sourced from various providers, including health facilities and community drug sellers. However, investigations of complex treatment-seeking, AB use and drug resistance in LMICs are scarce.

The Holistic Approach to Unravel Antibacterial Resistance in East Africa (HATUA) Consortium collected questionnaire and microbiological data from 6,827 adult outpatients with urinary tract infection (UTI)-like symptoms presenting at healthcare facilities in Kenya, Tanzania and Uganda. Among 6,388 patients we analysed patterns of self-reported treatment seeking behaviours (‘patient pathways’) using process mining and single-channel sequence analysis. Of those with microbiologically confirmed UTI (n=1,946), we used logistic regression to assessed the relationship between treatment seeking behaviour, AB use, and likelihood of having a multi-drug resistant (MDR) UTI.

The most common treatment pathways for UTI-like symptoms included attending health facilities, rather than other providers (e.g. drug sellers). Patients from the sites sampled in Tanzania and Uganda, where prevalence of MDR UTI was over 50%, were more likely to report treatment failures, and have repeated visits to clinics/other providers, than those from Kenyan sites, where MDR UTI rates were lower (33%). There was no strong or consistent relationship between individual AB use and risk of MDR UTI, after accounting for country context.

The results highlight challenges East African patients face in accessing effective UTI treatment. These challenges increase where rates of MDR UTI are higher, suggesting a reinforcing circle of failed treatment attempts and sustained selection for drug resistance. Whilst individual behaviours may contribute to the risk of MDR UTI, our data show that factors related to context are stronger drivers of ABR.
Machines learn ecological networks: automated discovery of ecological networks based on empirical data
Authors: Ko Hongseok , Kim Ahyoung Amy , Zhang Hao Helen
Published: March 2023

Constructing ecological networks is known to be important and challenging in community ecology. In particular, to construct the holistic structure of ecological networks, identifying species interaction is essential but often costly and impalpable. Recent studies providing major challenges in assembling ecological networks have highlighted the need of new and more powerful approaches to reconstruct biological networks, including species interaction networks. In literature, there are no promising verifications in using machine leaning (ML) approaches to reconstruct ecological networks. In this work, we develop and employ a variety of ML methods, including penalized regression and graphical tools, to reconstruct ecological networks. For evaluation, we apply the methods to empirical time series data sets of 20 species abundances collected at Lake Constance in central Europe. We use resampled data to identify highly-ranked interactions among species and measure their consistency across 7 ML methods and 5,000 learning processes. We show that the best precision, recall, and F1 score were 0.48, 0.97, and 0.64, respectively, among all penalized regression methods under comparison. In summary, our study shows that machine learning methods offer promising data-driven and automated tools for reconstructing ecological networks and discovering underlying biological interactions among species.
Using risk advancement periods to derive starting ages of colorectal cancer screening according to sex and polygenic risk score: Results from the UK Biobank
Authors: Chen Xuechen , Heisser Thomas , Cardoso Rafael , Hoffmeister Michael , Brenner Hermann
Published: March 2023

Objective

Polygenic risk scores (PRSs) derived from genome-wide association studies are strong predictors of colorectal cancer (CRC) risk. We applied the straightforward approach of risk advancement periods (RAPs) to derive risk-adapted starting ages of CRC screening according to sex and PRS in the UK Biobank.

Methods

Among 242,779 participants (40-69 years; no previous CRC screening; no family history of CRC), we assessed associations of sex and a PRS with CRC risk and mortality using Cox regression models. Hazard ratios (HRs) were translated to RAPs to quantify how many years of age earlier men and women in defined PRS deciles reach comparable risks as those in the reference group (5thand 6thPRS deciles).

Results

During a median follow-up of 11.2 and 12.8 years, 2,714 participants were diagnosed with CRC and 758 died from CRC, respectively. HRs (95% CIs) of CRC risk were 1.57 (1.46, 1.70) for men versus women and ranged from 0.51 (0.41, 0.62) to 2.29 (2.01, 2.62) across PRS deciles compared to the reference. RAPs (95% CI) were 5.6 (4.6, 6.6) years for men versus women, and ranged from -8.4 (-11.0, -5.9) to 10.3 (8.5, 12.1) years across PRS deciles compared to the reference. Risk-adapted starting ages would vary by 24 years between men in the highest PRS decile and women in the lowest PRS decile. Very similar results were obtained regarding CRC mortality.

Conclusion

Consideration of sex and a standard PRS alone could have far-reaching implications for starting ages of CRC screening in the “average risk population”.

SUMMARY BOX

What is already known on this topic

Polygenic risk scores (PRSs) are strong predictors of colorectal cancer (CRC) risk.

Men have substantially higher CRC incidence and mortality than women.

CRC risk information from the combination of PRS and genetically determined sex, which are constant factors over lifetime, is so far not used for risk-adapted CRC screening in the “average risk population”.

What this study adds

Risk advancement periods (RAPs) of CRC by PRS and sex were derived at high levels of precision from the large database of the UK Biobank.

By joint consideration of PRS and genetically defined sex, risk-adapted starting ages would vary by as much as 24 years between men in the highest PRS decile and women in the lowest PRS decile.

How this study might affect research, practice or policy

Our study demonstrates a straightforward way to translate CRC risk information from a large population-based cohort into risk-adapted starting ages of screening.

Personalized, risk-adapted starting ages of CRC screening could be derived from a single blood test performed in middle adulthood.

The RAP approach could be easily extended for defining personalized starting ages by incorporating additional risk factors in the regression models.
PromoR and PromoS forE. colipromoter recognition and classification
Authors: Wang Xinglong , Zhou Jingwen
Published: March 2023

Recognition of promoters is important for novel promoter identification, which can be used for genome annotation. Classification of strong and weak promoters can be used for screening high activity promoters. This study introduced PomoR for promoter recognition and PromoS for promoter strong and weak classification. The given two network were built based on ResNet and Attention and validated by cross-validation. PromoR and PromoS displayed an accuracy of 0.887 and 0.781, respectively.
Novel determinants of NOTCH1 trafficking and signaling in breast epithelial cells
Authors: Kobia Francis M. , Castro e Almeida Luis , Carminati Francesca , Andronache Adrian , Lavezzari Francesco , Wade Mark , Vaccari Thomas
Published: March 2023

The evolutionarily conserved Notch pathway controls cell–cell communication during development and in adult metazoans. It influences cell fate decisions, cell proliferation and cell differentiation, and contributes to the maintenance of normal tissue homeostasis. Consequently, misregulation of the Notch pathway is associated with a wide range of diseases, including congenital disorders and cancers with little to no cure. Signaling by Notch receptors is regulated by a complex set of cellular processes that include maturation and trafficking to the plasma membrane, endocytic uptake and sorting, lysosomal and proteasomal degradation, and ligand-dependent and independent proteolytic cleavages. We devised assays to follow quantitively the lifetime of endogenous human NOTCH1 receptor in breast epithelial cells in culture. Based on such analysis, we executed a high-content screen of 2749 human genes for which modulatory compounds exist, to identify new regulators of Notch signaling activation that might be amenable to pharmacologic intervention. We uncovered 39 new NOTCH1 genetic modulators that affect different steps of NOTCH1 cellular dynamics. In particular, we find thatPTPN23andHCN2act as positive NOTCH1 regulators by promoting endocytic trafficking and NOTCH1 maturation in the Golgi apparatus, respectively, whileSGK3serves as a negative regulator that can be modulated by pharmacologic inhibition. Our findings might be relevant in the search of new strategies to counteract pathologic Notch signaling.
High-Capacity Sample Multiplexing for Single Cell Chromatin Accessibility Profiling
Authors: Booth Gregory T. , Daza Riza M. , Srivatsan Sanjay R. , McFaline-Figueroa José L. , Gladden Rula Green , Furlan Scott N. , Shendure Jay , Trapnell Cole
Published: March 2023

Single-cell chromatin accessibility has emerged as a powerful means of understanding the epigenetic landscape of diverse tissues and cell types, but profiling cells from many independent specimens is challenging and costly. Here we describe a novel approach, sciPlex-ATAC-seq, which uses unmodified DNA oligos as sample-specific nuclear labels, enabling the concurrent profiling of chromatin accessibility within single nuclei from virtually unlimited specimens or experimental conditions. We first demonstrate our method with a chemical epigenomics screen, in which we identify drug-altered distal regulatory sites predictive of compound- and dose-dependent effects on transcription. We then analyze cell type-specific chromatin changes in PBMCs from multiple donors responding to synthetic and allogeneic immune stimulation. We quantify stimulation-altered immune cell compositions and isolate the unique effects of allogeneic stimulation on chromatin accessibility specific to T-lymphocytes. Finally, we observe that impaired global chromatin decondensation often coincides with chemical inhibition of allogeneic T-cell activation.
Vitamin D signaling orchestrates skeletal muscle metabolic flexibility by regulating its fuel choice
Authors: Das Anamica , Jawla Neha , Gopinath Suchitra D. , Arimbasseri G. Aneeshkumar
Published: March 2023

Vitamin D deficiency is associated with skeletal muscle pathologies. However, the role of vitamin D signaling in maintenance of muscle function is not well understood. Mice lacking vitamin D receptor (VDR) exhibit severe muscle wasting after weaning and this is associated with accumulation of muscle glycogen and energy deprivation. Here we show that the skeletal muscles of vdr-/- mice exhibit upregulation of fatty acid oxidation pathway and PPAR pathway and are predisposed to utilize fatty acids as the energy source even in a carbohydrate-enriched diet. As a result, fat-enriched diets could alleviate energy deprivation and atrophy of vdr-/- skeletal muscles. However, the complete restoration of muscle mass and systemic metabolism of vdr-/- mice depended on the quality of diets. Despite increasing muscle energy levels, a lard-based high-fat diet (HFD) disrupted glucose homeostasis by specifically inhibiting the insulin synthesis in pancreatic islets. Surprisingly, milk-based high-fat diets (MBD) could restore both muscle mass and pancreatic insulin response. This study reveals a micronutrient-macronutrient interaction network that connects vitamin D signaling with muscle fuel selection and pancreatic insulin response to enable energy homeostasis under different metabolic landscapes.
Modeling Biases in SARS-CoV-2 infections Prediction using Genome Copies Concentration in Wastewater
Authors: Mattei Mattia , Pinto Rosa M. , Guix Susana , Bosch Albert , Arenas Alex
Published: March 2023

Background

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, can be detected in stool samples and subsequently shed in the sewage system. The field of Wastewater-based epidemiology (WBE) aims to use this valuable source of data for epidemiological surveillance, as it has the potential to identify unreported infections and to anticipate the need for diagnostic tests.

Objectives

The objectives of this study were to analyze the absolute concentration of genome copies of SARS-CoV-2 shed in Catalonia’s wastewater during the Omicron peak in January 2022, and to develop a mathematical model capable of using wastewater data to estimate the actual number of infections and the temporal relationship between reported and unreported infections.

Methods

We collected twenty-four-hour composite 1-liter samples of wastewater from 16 wastewater treatment plants (WWTPs) in Catalonia on a weekly basis. We incorporated this data into a compartmental epidemiological model that distinguishes between reported and unreported infections and uses a convolution process to estimate the genome copies shed in sewage.

Results

The 16 WWTPs showed an average correlation of 0.88±0.08 (ranging from 0.96 to 0.71) and an average delay of 8.7±5.4 days (ranging from 0 to 20 days). Our model estimates that about 53% of the population in our study had been infected during the period under investigation, compared to the 19% of cases that were detected. This under-reporting was especially high between November and December 2021, with values up to 10. Our model also allowed us to estimate the maximum quantity of genome copies shed in a gram of feces by an infected individual, which ranged from 4.15×107gc/gto 1.33×108gc/g.

Discussion

Although wastewater data can be affected by uncertainties and may be subject to fluctuations, it can provide useful insights into the current trend of an epidemic. As a complementary tool, WBE can help account for unreported infections and anticipate the need for diagnostic tests, particularly when testing rates are affected by human behavior-related biases.
The single item burnout measure is a reliable and valid tool to measure occupational burnout
Authors: Galanis P. , Katsiroumpa A. , Vraka I. , Siskou O. , Konstantakopoulou O. , Katsoulas T. , Gallos P. , Kaitelidou Daphne
Published: March 2023

OBJECTIVE

To estimate the reliability and the validity of the single item burnout measure in a sample of nurses in Greece.

METHOD

We conducted an online cross-sectional study in Greece with 963 nurses. Data were collected during October 2022. We measured demographic and work-related variables of nurses, i.e. gender, age, chronic disease, self-rated health status, years of experience, and working in COVID-19 ward/intensive care unit. We used the single item burnout (SIB) and the Copenhagen Burnout Inventory (CBI) to measure occupational burnout. Moreover, we used the COVID-19 burnout scale (COVID-19-BS) to measure nurses’ burnout during the pandemic, and the Patient Health Questionnaire-4 (PHQ-4) to measure anxiety and depression among nurses.

RESULTS

Intraclass correlation coefficient between the two measurements of the SIB during the test-retest study was 0.986 indicating excellent reliability of the SIB. We found a high correlation between CBI factors and SIB (p<0.001), a moderate correlation between PHQ-4 and SIB (p<0.001), and a low to moderate correlation between COVID-19-BS and SIB (p<0.001). Therefore, concurrent validity of SIB was excellent. Moreover, SIB had high discriminant validity. In particular, nurses with a chronic disease, those with a very poor/poor/moderate health status, and those working in COVID-19 ward/intensive care unit had higher levels of burnout according to the SIB (p<0.001 in all cases). Moreover, we found a positive relationship between years of experience and SIB score (r=0.13, p<0.001).

CONCLUSIONS

The single item burnout measure is a brief, reliable, and valid tool that we can use as a screening measure to identify individuals at high risk of burnout.
Associative plasticity of granule cell inputs to cerebellar Purkinje cells
Authors: Conti Rossella , Auger Céline
Published: March 2023

Granule cells of the cerebellum make up to 175 000 excitatory synapses on a single Purkinje cell, encoding the wide variety of information from the mossy fibre inputs into the cerebellar cortex. The granule cell axon is made of an ascending portion and a long parallel fibre extending at right angles, an architecture suggesting that synapses formed by the two segments of the axon could encode different information. There are controversial indications that ascending axon (AA) and parallel fibre (PF) synapse properties and modalities of plasticity are different. We tested the hypothesis that AA and PF synapses encode different information, and that association of these distinct inputs to Purkinje cells might be relevant to the circuit and trigger plasticity, similarly to the coincident activation of PF and climbing fibre inputs. Here, by recording synaptic currents in Purkinje cells from either proximal or distal granule cells (mostly AA and PF synapses respectively), we describe a new form of associative plasticity between these two distinct granule cell inputs. We show for the first time that synchronous AA and PF repetitive train stimulation, with inhibition intact, triggers long term potentiation (LTP) at AA synapses specifically. Furthermore, the timing of presentation of the two inputs controls the outcome of plasticity and induction requires NMDAR and mGluR1 activation. The long length of the PFs allows us to preferentially activate the two inputs independently, and despite a lack of morphological reconstruction of the connections, these observations reinforce the suggestion that AA and PF synapses have different coding capabilities and plasticity that is associative, enabling effective association of information transmitted via granule cells.
Bioinformatics-Guided Discovery of Biaryl-Tailored Lasso Peptides
Authors: Saad Hamada , Majer Thomas , Bhattarai Keshab , Lampe Sarah , Nguyen Dinh T. , Kramer Markus , Straetener Jan , Brötz-Oesterhelt Heike , Mitchell Douglas A. , Gross Harald
Published: March 2023

Lasso peptides are a class of ribosomally synthesized and post-translationally modified peptides (RiPPs) that feature an isopeptide bond and a distinct lariat fold. A growing number of secondary modifications have been described that further decorate lasso peptide scaffolds. Using genome mining, we have discovered a pair of lasso peptide biosynthetic gene clusters (BGCs) that include cytochrome P450 genes. Here, we report the structural characterization of two unique examples of (C-N) biaryl-containing lasso peptides. Nocapeptin A, from Nocardia terpenica, is tailored with Trp-Tyr crosslink while longipepetin A, from Longimycelium tulufanense, features Trp-Trp linkage. Besides the unusual bicyclic frame, longipepetin A receives an S-methylation by a new Met methyltransferase resulting in unprecedented sulfonium-bearing RiPP. Our bioinformatic survey revealed P450(s) and further maturating enzyme(s)-containing lasso BGCs awaiting future characterization.
TRansit ACessibility Tool (TRACT): Developing a novel scoring system for public transportation system accessibility
Authors: Twardzik Erica , Schrack Jennifer A , Pollack Porter Keshia M , Coleman Taylor , Washington Kathryn , Swenor Bonnielin K.
Published: March 2023

Introduction: Although federal laws require equal access to public transportation for people with disabilities, access barriers persist. Lack of sharing accessibility information on public transportation websites restricts people with disabilities from making transportation plans and effectively using public transportation systems. This project aims to document information provided about public transportation systems accessibility and share this information using an open data platform. Methods: We reviewed the top twenty-six public transportation systems in the United States based on federal funding in fiscal year 2020. Information about accessibility was abstracted from the webpages of each public transportation system by two independent reviewers from February-March 2022. Informed by universal design principles, public transportation systems were scored across six dimensions: facility accessibility (0-22 points), vehicle accessibility (0-11 points), inclusive policies (0-12 points), rider accommodations (0-9 points), paratransit services (0-6 points), and website accessibility (0-2 points). Total scores were calculated as the sum of each dimension and ranged from 0-62 points. Data and findings were publicly disseminated (https://disabilityhealth.jhu.edu/tract-dashboard/). Results: The average overall accessibility information score was 31.9 (SD=6.2) out of 62 possible points. Mean scores were 8.4 (SD=2.9) for facility accessibility, 4.5 (SD=2.1) for vehicle accessibility, 7.8 (SD=1.6) for inclusive policies, 4.9 (SD=1.6) for rider accommodations, 4.5 (SD=2.0) for paratransit services, and 1.8 (SD=0.4) for website accessibility. Eleven public transportation systems (42%) received the maximum score for paratransit services and 20 (77%) received the maximum score for website accessibility. No public transportation system received the maximum score for any of the other dimensions. Conclusions: Using a novel scoring system, we found significant variation in the accessibility information presented on public transportation system websites. Websites are a primary mode where users obtain objective information about public transportation systems and are therefore important platforms for communication. Absence of accessibility information creates barriers for the disability community and restricts equal access to public transportation.
Antibacterial Effect of Oral Care Gel-Containing Hinokitiol and 4-isopropyl-3-methylphenol Against Intraoral Pathogenic Microorganisms
Authors: Ohara Hiroshi , Odanaka Keita , Shiine Miku , Hayasaka Masataka
Published: March 2023

Objective

Deterioration of oral hygiene is closely related to increase severity and mortality of corona virus disease-19 (COVID-19), and also contribute to the development of various diseases such as aspiration pneumonia or Alzheimer’s. Oral care is attracting high interest in Japan, which has entered a super-aging society. In this study, we aimed to investigate whether commercially available Hinora®(HO) that oral care gels-containing hinokitiol and 4-isopropyl-3-methylphenol (IPMP) have biofilm formation inhibitory and antibacterial activities against various intraoral pathogen microorganisms.

Method

Candidaspp.,Aggregatibacter actinomycetemcomitans, Staphylococcus aureus, andPseudomonas aeruginosawere selected during the study period, all which were analyzed using antimicrobial disc, microorganism turbidity, and crystal violet assays. In addition, the germ tube test usingC. albicanswas performed with a modification of Mackenzie’s method. Images for morphological observation of the germ tubes were acquired with an inverted microscope. For comparison between products, we used Refrecare®(RC), which contains only hinokitiol (not containing IPMP).

Results

All the intraoral pathogenic microorganisms showed drug susceptibility against undiluted form HO and/or RC. In particular, HO was more effective at lower concentrations than RC. In the HO-added group, inhibition circles were observed in all bacteria exceptP. aeruginosawhen added at a concentration of 0.5 g/mL or more. The optical density values at 590 nm (crystal violet) and/or 600 nm (microorganism turbidity) of all the fungi and bacteria were significantly lower when cultured in medium with HO. Inhibition of growth or biofilm formation was observed when HO was added at a concentration of 0.05 g/mL or higher. To investigate the action mechanism of HO, germ tube tests were performed inC. albicans. The results show that culturingC. albicansin soyabean-casein digest broth with HO (0.05 g/mL) significantly suppressed germ tube formation.

Conclusions

These data suggest that oral care gel-containing hinokitiol and IPMP has strong biofilm formation inhibitory, antifungal and antibacterial effects againstCandidafungi and multiple intraoral pathogenic microorganisms. Therefore, it may be a promising treatment option for oral infections.
Embracing firefly flash pattern variability with data-driven species classification
Authors: Martin Owen , Nguyen Chantal , Sarfati Raphael , Chowdhury Murad , Iuzzolino Michael L. , Nguyen Dieu My T. , Layer Ryan M. , Peleg Orit
Published: March 2023

Many nocturnally active fireflies use precisely timed bioluminescent patterns to identify mates, making them especially vulnerable to light pollution. As urbanization continues to brighten the night sky, firefly populations are under constant stress, and close to half of the species are now threatened. Ensuring the survival of firefly biodiversity depends on a large-scale conservation effort to monitor and protect thousands of populations. While species can be identified by their flash patterns, current methods require expert measurement and manual classification and are infeasible given the number and geographic distribution of fireflies. Here we present the application of a recurrent neural network (RNN) for accurate automated firefly flash pattern classification. Using recordings from commodity cameras, we can extract flash trajectories of individuals within a swarm and classify their species with a precision and recall of approximately seventy percent. In addition to scaling population monitoring, automated classification provides the means to study firefly behavior at the population level. We employ the classifier to measure and characterize the variability within and between swarms, unlocking a new dimension of their behavior. Our method is open source, and deployment in community science applications could revolutionize our ability to monitor and understand firefly populations.
Comprehensive analysis of autophagic functions of WIPI family proteins and their implications for the pathogenesis of β-propeller associated neurodegeneration
Authors: Shimizu Takahiro , Tamura Norito , Nishimura Taki , Saito Chieko , Yamamoto Hayashi , Mizushima Noboru
Published: March 2023

β-propellers that bind polyphosphoinositides (PROPPINs) are an autophagy-related protein family conserved throughout eukaryotes. The PROPPIN family includes Atg18, Atg21, and Hsv2 in yeast and WD-repeat protein interacting with phosphoinositides (WIPI)1–4 in mammals. Mutations in theWIPIgenes are associated with human neuronal diseases, including β-propeller associated neurodegeneration (BPAN) caused by mutations inWDR45(encoding WIPI4). In contrast to yeast PROPPINs, the functions of mammalian WIPI1–WIPI4 have not been systematically investigated. Although the involvement of WIPI2 in autophagy has been clearly shown, the functions of WIPI1, WIPI3, and WIPI4 in autophagy remain poorly understood. In this study, we comprehensively analyzed the roles of WIPI proteins by usingWIPI-knockout (single, double, and quadruple knockout) HEK293T cells and recently developed HaloTag-based reporters, which enable us to monitor autophagic flux sensitively and quantitatively. We found that WIPI2 was nearly essential for autophagy and partially redundant with WIPI1. Autophagic flux was unaffected or only slightly reduced by single deletion of WIPI3 (encoded byWDR45B) or WIPI4 but was profoundly reduced by double deletion of WIPI3 and WIPI4. Furthermore, we revealed variable effects of BPAN-related missense mutations on the autophagic activity of WIPI4. BPAN is characterized by neurodevelopmental and neurodegenerative abnormalities, and we found a possible association between the magnitude of the defect of the autophagic activity of WIPI4 mutants and the severity of neurodevelopmental symptoms. However, some of the BPAN-related missense mutations, which produce neurodegenerative signs, showed almost normal autophagic activity, suggesting that non-autophagic functions of WIPI4 may be related to neurodegeneration in BPAN.
KCNN4 links PIEZO-dependent mechanotransduction to NLRP3 inflammasome activation
Authors: Ran Li , Ye Tao , Erbs Eric , Ehl Stephan , Spassky Nathalie , Sumara Izabela , Zhang Zhirong , Ricci Romeo
Published: March 2023

Immune cells sense the microenvironment to fine-tune their inflammatory responses. Patients with cryopyrin associated periodic syndrome (CAPS), caused by mutations in theNLRP3gene, develop auto-inflammation triggered by non-antigenic, e.g. environmental cues. However, the underlying mechanisms are poorly understood. Here, we uncover that KCNN4, a calcium-activated potassium channel, links PIEZO-mediated mechanotransduction to NLRP3 inflammasome activation. Yoda1, a PIEZO1 agonist, lowers the threshold for NLRP3 inflammasome activation. PIEZO-mediated sensing of stiffness and shear stress increases NLRP3-dependent inflammation. Myeloid-specific deletion ofPIEZO1/2protects mice from gouty arthritis. Activation of PIEZO1 triggers calcium influx, which activates KCNN4 to evoke potassium efflux promoting NLRP3 inflammasome activation. Activation of PIEZO signaling is sufficient to activate the inflammasome in cells expressing CAPS-causing NLRP3 mutants via KCNN4. Finally, pharmacologic inhibition of KCNN4 alleviates auto-inflammation in CAPS patient cells and in CAPS-mimicking mice. Thus, PIEZO-dependent mechanical inputs augment inflammation in NLRP3-dependent diseases including CAPS.

One Sentence Summary

PIEZO-mediated mechanotransduction stimulates KCNN4-dependent potassium efflux to potentiate NLRP3 inflammasome activation.
The ABI3-ERF1 module mediates ABA-auxin crosstalk to regulate lateral root emergence
Authors: Zhang Jing , Zhao Pingxia , Chen Siyan , Sun Liangqi , Mao Jieli , Tan Shutang , Xiang Chengbin
Published: March 2023

Lateral root (LR) development is regulated by hormones and environmental signals. Abscisic acid (ABA) is involved in LR development, but it is not well understood how ABA signaling interacts with auxin to regulate LR formation. Here, we report thatArabidopsis ERF1is responsive to ABA during LR development and mediates the crosstalk between ABA and auxin signaling to regulate LR emergence. ABA attenuates ERF1-mediated excessive auxin accumulation with altered distribution known to inhibit LR emergence. ABI3 acts as a negative factor in LR emergence and transcriptionally activatesERF1by binding to the RY motif in its promoter, and reciprocally, ERF1 activatesABI3, which forms a positive regulatory loop that enables rapid signal amplification. Notably, ABI3 physically interacts with ERF1, consequently reducing theciselement-binding activities of both ERF1 and ABI3 and thus attenuating ERF1-regulated transcription ofPIN1,AUX1, andARF7involved in the modulation of LR emergence and ABI3-regulatedABI5in ABA signaling, which may provide a molecular rheostat to avoid overamplification of auxin and ABA signaling. Taken together, our findings unveil the pivotal ABI3-ERF1 module that mediates the crosstalk between ABA and auxin signaling in LR emergence.