bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sensory Neuron Expressed TRPC3 Mediates Acute and Chronic Itch
Authors: Liu Yan , Liu Yutong , Narang Claire , Limjunyawong Nathachit , Jamaldeen Hanna , Yu Shimeng , Patiram Shivanie , Nie Hong , Caterina Michael J. , Dong Xinzhong , Qu Lintao 
Published: November 2021

Abstract
Background: Chronic pruritus is a prominent symptom of allergic contact dermatitis (ACD) and represent a huge unmet health problem. However, its underlying cellular and molecular mechanisms remain largely unexplored. TRPC3 is highly expressed in primary sensory neurons and has been implicated in peripheral sensitization induced by proinflammatory mediators. However, the role of TRPC3 in acute and chronic itch is still not well defined. Methods: RNAscope in situ hybridization and immunohistochemical staining were performed on mouse trigeminal ganglion (TG) neurons. Fura-2 calcium imaging was used to characterize the function of TRPC3 in dissociated TG neurons. In native mice, the TRPC3 agonist and pruritogens were subcutaneously injected to the cheek and nape of the neck of mice, respectively. Site directed scratching and/or wiping behaviors were video recorded. Contact hypersensitivity (CHS) model was induced in mouse ears by topical application of SADBE or DNCB. Spontaneous scratching behaviors were recorded by video monitoring. Global and conditional Trpc3 knockout mice were employed to determine the contribution of TRPC3 to acute and chronic itch. The mRNA expression levels of Trpc3 and proinflammatory cytokines were assayed by quantitative real-time PCR. H&E. staining was used for the evaluation of the thickness of mouse ears. Flow cytometry was performed to assess immune cell infiltration in mouse ear tissues. Results: Among mouse TG neurons, RNAscope assay revealed that Trpc3 mRNA was predominantly expressed in nonpeptidergic small diameter neurons. Moreover, Trpc3 mRNA signal was present in the majority of itch sensing neurons. TRPC3 agonism induced TG neuronal activation and acute nonhistaminergic itch- and pain-like behaviors in naïve mice. In addition, genetic deletion of Trpc3 attenuated acute itch evoked by certain common nonhistaminergic pruritogens, including endothelin-1 and SLIGRL-NH2. In a murine model of CHS, Trpc3 mRNA expression level and function were upregulated in the TG following CHS. Pharmacological inhibition and global knockout of Trpc3 significantly alleviated spontaneous scratching behaviors without affecting concurrent cutaneous inflammation in the CHS model. Furthermore, conditional deletion of Trpc3 in primary sensory neurons but not in keratinocytes produced similar antipruritic effects in this model. Conclusions: These findings suggest that TRPC3 expressed in primary sensory neurons may contribute to acute and chronic itch via a histamine independent mechanism and that targeting neuronal TRPC3 might benefit the treatment of chronic itch associated with ACD and other inflammatory skin disorders.
A Neurotechnological Aid For Semi-Autonomous Suction In Robotic-Assisted Surgery
Authors: Barragan Juan Antonio , Yang Jing , Yu Denny , Wachs Juan P. 
Published: November 2021

Abstract
Adoption of Robotic-Assisted Surgery has steadily increased as it improves the surgeon’s dexterity and visualization. Despite these advantages, the success of a robotic procedure is highly dependent on the availability of a proficient surgical assistant that can collaborate with the surgeon. With the introduction of novel medical devices, the surgeon has taken over some of the surgical assistant’s tasks to increase their independence. This, however, has also resulted in surgeons experiencing higher levels of cognitive demands that can lead to reduced performance. In this work, we proposed a neurotechnology-based semi-autonomous assistant to release the main surgeon of the additional cognitive demands of a critical support task: blood suction. To create a more synergistic collaboration between the surgeon and the robotic assistant, a real-time cognitive workload assessment system based on EEG signals and eye-tracking was introduced. A computational experiment demonstrates that cognitive workload can be effectively detected with an 80% accuracy. Then, we show how the surgical performance can be improved by using the neurotechnological autonomous assistant as a close feedback loop to prevent states of high cognitive demands. Our findings highlight the potential of utilizing real-time cognitive workload assessments to improve the collaboration between an autonomous algorithm and the surgeon.
Oral Candidiasis in Patients with Hematological Diseases: Diagnosis Through Clinical and Cytopathological Exams
Authors: Pereira Fernanda Guimarães de Azevedo , Milagres Adrianna , Werneck Juliana Tristão , Marques Letícia Côgo , Picciani Bruna Lavinas Sayed , Junior Arley Silva 
Published: November 2021

Abstract
Background: Candidiasis is a common opportunistic infection that may interfere with oncologic patients’ prognosis, especially those with hematologic diseases. This study is the first to analyse the prevalence of oral candidiasis in onco-hematological patients by physical and oral cytopathological exams. Methods: This is a cross-sectional and observational study with a retrospective sample composed of participants hospitalized in the hematology clinic, diagnosed with hematologic diseases. All patients were submitted to an oral mucosal exam and scraps from oral mucosa were obtained. Results: Of the 62 participants, 56.5% were male, 82.3% were white, with mean age of 57 years. Lymphoma was the most common hematologic disease (24.2%). In total, 48.3% of the sample was diagnosed with oral candidiasis. Of these participants with oral candidiasis, 13 (21.0%) had clinical diagnosis, where erythematous subtype was present in all cases and pseudomembranous subtype in 12 individuals. Cytopathological analysis revealed more 17 (27.4%) cases, without oral lesion indicative of candidiasis. Conclusions: Oral candidiasis is common among patients with hematologic disease, and the cytopathological exam proved to be a useful tool, confirming clinical diagnosis of candidiasis and identifying subclinical cases. These data are of great relevance considering the possible complications that these patients may develop such as longer hospitalizations, worsening of the general condition due to candidemia and even death.
Highly Active Antiretroviral Therapy-silver Nanoparticle Conjugate Alleviates Anxiety-like Behaviour in Streptozotocin-induced Diabetic Rats
Authors: Lawal Sodiq Kolawole , Olojede Samuel Oluwaseun , Dare Ayobami , Faborode Oluwaseun Samuel , Naidu Edwin C. Stephen , Rennie Carmen Olivia , Azu Onyemaechi Okpara 
Published: November 2021

Abstract
Background: The inception of highly active antiretroviral therapy (HAART) has changed the management of human immunodeficiency virus (HIV) positive patients, and their life expectancy has improved. However, neurological complications associated with chronic HAART administration has not been fully addressed. Therefore, this study aimed to evaluate the potential benefits of silver nanoparticles (AgNPs) conjugates on the anxiogenic effects of HAART in type-2 diabetic rats. Methods: Forty-two (42) adult male Sprague-Dawley rats (250 ± 13 g) were divided into non-diabetic and diabetic groups. After induction of diabetes, non-diabetic and diabetic animals were administered either with de-ionized water (DW), HAART (98.2 mg/kg, p.o) or AgNPs +HAART (24.5 mg/kg, i. p) for 8 weeks. Thereafter, metabolic biomarkers, oxidative injury, tissue inflammation, and behavioural changes were evaluated, while the prefrontal cortex was excised for neurochemical analysis. Results: The HAART-treated diabetic rats showed a significant increase in blood glucose level, number of faecal pellets, malondialdehyde (MDA), and pro-inflammatory cytokines (TNF-α, IL-1β) while locomotion, reduced glutathione (GSH), superoxide dismutase (SOD) activity, and PFC-GFAP positive cells were significantly reduced compared with diabetic control. However, administration of AgNPs +HAART to diabetic rats significantly improved the blood glucose level, metabolic activities, SOD, GSH, PFC-GFAP positive cells while reducing MDA and anxiety-like behaviour in the open field test. Conclusion: Administration of HAART aggravates anxiety-like behaviours and promotes neurotoxic effects in the PFC of diabetic rats. However, AgNPs +HAART alleviates the 3 anxiogenic effects of HAART and preserves PFC-GFAP positive cells by reducing oxidative and neuroinflammatory injury.
A Time-Incorporated SOFA-Based Explainable Machine Learning Model for Mortality Prediction in Critically Ill Patients
Authors: Liu Yang , Gao Kun , Deng Hongbin , Ling Tong , Lin Jiajia , Yu Xianqiang , Bo Xiangwei , Zhou Jing , Gao Lin , Wang Peng , Tong Zhihui , Liu Yuxiu , Shi Yinghuan , Ke Lu , Gao Yang , Li Weiqin 
Published: November 2021

Abstract
Background: Organ dysfunction (OD) assessment is essential in intensive care units (ICUs). However, no OD scoring system has so far considered the duration of OD, which is clinically relevant. This study aimed to develop and validate an ICU mortality prediction model based on the Sequential Organ Failure Assessment (SOFA) score, incorporating the time dimension with machine learning methods.Methods: Data from the eICU Collaborative Research Database and Medical Information Mart for Intensive Care (MIMIC) -III were mixed for model development, and the MIMIC-IV dataset and Nanjing Jinling Hospital Surgery ICU (SICU-JL) dataset were used for external testing. Adult patients in the ICUs for more than 72 hours were deemed eligible. The total SOFA score and individual scores were calculated every 12 hours for the first three days of ICU admission. Time-dimensional variables were derived from the consecutively recorded SOFA scores and individual scores for each organ. A modified SOFA model incorporating the time dimension (T-SOFA) was stepwise constructed to predict ICU mortality using multiple machine learning algorithms. The predictive performance was assessed with the area under the receiver operating characteristic curves (AUROC). Also, we utilized the SHapley Additive exPlanations (SHAP) algorithm for data visualization and model explainability.Results: We extracted a total of 66,709 ICU patients from the mixed datasets for model development and 15,423 patients for validation. The T-SOFA M3 that incorporated the time dimension features and age, using the XGBoost algorithm, significantly outperformed the original SOFA scores (AUROC 0.800 95% CI [0.787-0.813] vs. 0.693 95% CI [0.678-0.709], p<0.01) in the validation set. Good prediction performance was maintained for the T-SOFA M3 in test Set A and test Set B, with AUROC of 0.803, 95% CI[0.791-0.815], and 0.830, 95%CI [0.789-0.870], respectively. Significant contributors demonstrated by the SHAP analysis included total SOFA score, Respiration-score, CNS-score, age, Cardiovascular-score, and SOFA Organ dysfunction Unalleviated Time Index.Conclusions: A SOFA-based, time-incorporated prediction model was developed and validated by machine learning algorithms, showing satisfactory predictability and medical interpretability.
Sulfate-dependant microbially induced corrosion of mild steel in the deep-sea: a 10-year microbiome study
Authors: Rajala Pauliina , Cheng Dong-Qiang , Rice Scott , Lauro Federico 
Published: November 2021

Abstract
Background
Metal corrosion in seawater has been extensively studied in surface and shallow waters. However, infrastructure is increasingly being installed in deep-sea environments, where extremes of temperature, salinity and high hydrostatic pressure increase the costs and logistical challenges associated with monitoring corrosion. Moreover, there is currently only a rudimentary understanding of the role of microbially induced corrosion, which has rarely been studied in the deep-sea. We report here an integrative study of the biofilms growing on the surface of corroding mooring chain links that had been deployed for 10 years at ~2 km depth and developed a model of microbially induced corrosion based on flux-balance analysis.
Methods
We used optical emission spectrometry to analyse the chemical composition of the mooring chain and energy-dispersive X-ray spectrometry coupled with scanning electron microscopy to identify corrosion products and ultrastructural features. The taxonomic structure of the microbiome was determined using shotgun metagenomics and was confirmed by 16S amplicon analysis and quantitative PCR of the dsrB gene. The functional capacity was further analysed by generating binned, genomic assemblies and performing flux-balance analysis on the metabolism of the dominant taxa.
Results
The surface of the chain links showed intensive and localised corrosion with structural features typical of microbially induced corrosion. The microbiome on the links differed considerably from that of the surrounding sediment, suggesting selection for specific metal-corroding biofilms dominated by sulfur-cycling bacteria. The core metabolism of the microbiome was reconstructed to generate a mechanistic model that combines biotic and abiotic corrosion. Based on this metabolic model, we propose that sulfate reduction and sulfur disproportionation might play key roles in deep-sea corrosion.
Conclusions
The corrosion rate observed was higher than what could be expected from abiotic corrosion mechanisms under these environmental conditions. High corrosion rate and the form of corrosion (deep pitting) suggest that the corrosion of the chain links was driven by both abiotic and biotic processes. We posit that the corrosion is driven by deep-sea sulfur-cycling microorganisms which may gain energy by accelerating the reaction between metallic iron and elemental sulfur. The results of this field study provide important new insights on the ecophysiology of the corrosion process in the deep sea.
Transcriptome of Visceral Adipose Tissue Identifies an Inflammation-Related ceRNA Network That Regulates Obesity
Authors: Li GanBin , Zhang Haoyu , Cao Ke , Zhai Zhiwei , Wang Zhenjun , Yang Lei , Han JiaGang 
Published: November 2021

Abstract
Obesity is becoming an epidemic of widespread concern, but the underlying causes remain elusive. In this study, whole transcriptome RNA sequencing (RNA-seq) revealed differential profiles of noncoding (nc) RNAs and mRNAs in visceral adipose tissue (VAT) from obese (BMI >32.5 kg/m2) and lean (BMI < 20 kg/m2) individuals, with 1920 differentially expressed (DE) genes, 1466 long noncoding (lnc)RNAs, 122 micro (mi)RNAs, and 52 circular (circ)RNAs identified. Gene Set Enrichment Analysis, Gene Ontology analysis, Kyoto Encyclopedia of Genes and Genomes analysis revealed that these ncRNAs were involved in inflammation-related pathways that included cytokine-cytokine receptor interaction, the tumor necrosis factor and nuclear factor kappa B signaling pathways. The results indicated a critical role of inflammation in the pathogenesis of obesity. The network interaction of lncRNA, circRNA, and miRNA revealed a competing endogenous (ce)RNA network that was associated with inflammation. The ceRNA network included circORC5/miR-197-5p/TNFRSF10D and circNTRK2/miR-760/LAT, which were dysregulated in obese patients. Notably, the overexpression of TNFRSF10D and LAT were significantly positively associated with body weight in obese patients. In conclusion, this whole transcriptome study provided a pool of data that will be useful for identifying biomarkers of obesity and identified an obesity-associated ceRNA network that is regulated by circORC5 and circNTRK2.
Quercetin Alleviates Demyelination to Mitigate Neuropsychiatric Symptoms Through Promoting Microglia M2 Polarization in Mice with Vascular Dementia
Authors: Tan Zihu , Yang Guang , Qiu Jing , Yan Wenjing , Liu Yu , Ma Zhengling , Li Jia , Liu Jing , Shan Nan 
Published: November 2021

Abstract
Cerebral hypoperfusion plays a pivotal role in the ictus and development of vascular dementia (VaD) with neuropsychiatric symptoms. To date, few pharmacological interventions for neuropsychiatric symptoms are available in the VaD patients with neuropsychiatric impairments. Here, our results demonstrated that the extent of demyelination was dramatically deteriorated and the thickness of myelin sheath were evidently decreased in the presence of cerebral hypoperfusion, whereas Quercetin possessed the potential of abrogating these effects at least in part, then relieving anxiety and depression-like behavior when mice exposed to bilateral carotid artery stenosis (BCAS)/chronic restraint stress (CRS). The underlying mechanism was that Quercetin facilitated microglia transformation into M2 phenotype, which expedited secretion of anti-inflammatory cytokines (IL-4 and IL-10), and in turn decreased production of pro-inflammatory factors (TNF-α and IL-1β), thereafter enhancing the microglial engulfment ability of myelin fragments in vitro and in vivo. Collectively, the results demonstrated that that Quercetin facilitated microglia transition into M2 phenotype to reduce demyelination in ventral hippocampus (vHIP), thereafter mitigating neuropsychiatric deficits (including anxiety and depression). The present research broadens the therapeutic scope of Quercetin in central nervous system (CNS) disorders with presence of white matter damage and/or the insufficient activation of M2 microglia, particularly for vascular dementia with/without neuropsychiatric symptoms.
Heterologous production of glycine betaine using Synechocystis sp. PCC 6803-based chassis lacking native compatible solutes
Authors: Ferreira Eunice A. , Pacheco Catarina C. , Rodrigues João , Pinto Filipe , Lamosa Pedro , Fuente David , Urchueguía Javier , Tamagnini Paula 
Published: November 2021

Abstract
Background: Among compatible solutes, glycine betaine has various applications in the fields of nutrition, pharmaceuticals and cosmetics. Currently, this compound can be extracted from sugar beet plants or obtained by chemical synthesis, resulting in low yields or high carbon footprint, respectively. Hence, in this work we aimed at exploring the production of glycine betaine using the unicellular cyanobacterium Synechocystis sp. PCC 6803 as a photoautotrophic chassis. Results: Synechocystis mutants lacking the native compatible solutes sucrose or/and glucosylglycerol - ∆ sps , ∆ ggpS and ∆ sps ∆ ggpS - were generated and characterized. Under salt stress conditions, the growth was impaired and accumulation of glycogen decreased by ~50% whereas the production of compatible solutes and extracellular polymeric substances (capsular and released ones) increased with salinity. These mutants were used as chassis for the implementation of a synthetic device based on the metabolic pathway described for the halophilic cyanobacterium Aphanothece halophytica for the production of the compatible solute glycine betaine. Transcription of ORFs comprising the device was shown to be stable and insulated from Synechocystis’ native regulatory network. The production of glycine betaine was successfully obtained in all chassis tested, and was shown to increase with salinity. The introduction of the glycine betaine synthetic device into the ∆ ggpS background improved its growth and enabled survival under 5% NaCl, which was not observed in the absence of the device. The maximum glycine betaine production was 64.29 µmol/gDW (1.89 µmol/mg protein) that was reached in the ∆ ggpS chassis grown under 3% NaCl. Conclusions: Taking into consideration the heterologous production of glycine betaine by our Synechocystis ∆ ggpS chassis under seawater-like salinity, and the identification of main key players involved in the carbon fluxes, this work paves the way for a feasible production of this/or other compatible solutes, using optimized Synechocystis chassis in a pilot-scale.
Treatment of Persistent Post-Traumatic Headache with the Anti-CGRP Receptor Antibody Erenumab: A Case Report
Authors: Papenhoff Mike , Dudda Marcel 
Published: November 2021

Abstract
Introduction: Calcitonin gene-related peptide (CGRP) has only recently emerged as a potential target in posttraumatic headache. To our knowledge this is the first description of a patient with persistent posttraumatic headache following severe traumatic head injury who has been treated with the CGRP-receptor-monoclonal antibody erenumab.Case presentation: A 56-year-old man presented with a 30-year history of frequent migraine-like posttraumatic headaches following a high-voltage head injury that he treated with an excessive intake of peripheral analgesics. Although amitriptyline was reasonably effective, it had to be discontinued when the patient developed restless legs syndrome in the second year of treatment. Under therapy with erenumab he achieved a rapid and stable reduction in his symptoms down to only 2–3 headache days per month without adverse events.Conclusions: This case demonstrates that the inhibition of the CGRP-receptor with erenumab could be an effective treatment option in migraine-like post-traumatic headache even decades after the traumatic event.
Mental health resilience in offspring of depressed parents: a systematic literature review protocol
Authors: Padaigaitė Eglė , Maruyama Jessica Mayumi , Hammerton Gemma , Rice Frances , Collishaw Stephan 
Published: November 2021

Abstract
Background

Parental depression is associated with a range of mental health conditions and other difficulties in the offspring. Nevertheless, about one in five offspring exposed to parental depression do not develop mental health problems, indicating the presence of protective factors that may buffer parental depression-related risk effects. However, evidence of protective factors that might explain good sustained mental health in offspring of depressed parents is limited and systematic synthesis of these factors is still needed. Therefore, as far as we are aware, this will be the first systematic review that will define mental health resilience in the parental depression context and identify parental/ caregivers’, child, family, and social factors associated with mental health resilience in offspring exposed to parental depression. As a secondary aim, evidence for sex-, developmental stage-, and outcome domain-specific factors associated with mental health resilience will also be examined.
Methods

A two-step search strategy will be performed. Electronic searches will be performed for articles published up to March 2021 in PsycINFO, Embase, MEDLINE, Web of Science Core Collection, and Cochrane Library. Additional articles will be identified by manually screening the references and citations of included studies. Two reviewers will independently screen titles, abstracts and full texts of articles against pre-determined eligibility criteria, extract data and perform risk of bias assessments. Reviewers will be blinded to the other’s decisions, and discrepancies between reviewers will be resolved during consensus meetings with a senior researcher. Results will be narratively synthesised to address primary and secondary aims.
Discussion

This systematic review will provide a comprehensive overview of protective factors associated with mental health resilience in offspring exposed to parental depression. Results will help better understand mental health resilience and factors associated with it and identify future research directions. The findings are also expected to identify targets for evidence-based prevention and intervention strategies for those in need.
Systematic review registration:

This systematic review has been registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (www.crd.york.ac.uk/PROSPERO, CRD42021229955).