bluuebunny/crossref_metadata_2025 huggingface dataset:
Disease Severity and Prognosis of SARS-CoV-2 Infection in Hospitalized Patients Is Not Associated With Viral Load in Nasopharyngeal Swab
Authors: Cocconcelli Elisabetta , Castelli Gioele , Onelia Francesco , Lavezzo Enrico , Giraudo Chiara , Bernardinello Nicol , Fichera Giulia , Leoni Davide , Trevenzoli Marco , Saetta Marina , Cattelan Annamaria , Crisanti Andrea , Spagnolo Paolo , Balestro Elisabetta
Published: September 2021

Background: The impact of viral burden on severity and prognosis of patients hospitalized for Coronavirus Disease 2019 (COVID-19) is still a matter of debate due to controversial results. Herein, we sought to assess viral load in the nasopharyngeal swab and its association with severity score indexes and prognostic parameters.

Methods: We included 127 symptomatic patients and 21 asymptomatic subjects with a diagnosis of SARS-CoV-2 infection obtained by reverse transcription polymerase chain reaction and presence of cycle threshold. According to the level of care needed during hospitalization, the population was categorized as high-intensity (HIMC, n = 76) or low intensity medical care setting (LIMC, n = 51).

Results: Viral load did not differ among asymptomatic, LIMC, and HIMC SARS-CoV-2 positive patients [4.4 (2.9–5.3) vs. 4.8 (3.6–6.1) vs. 4.6 (3.9–5.7) log10 copies/ml, respectively; p = 0.31]. Similar results were observed when asymptomatic individuals were compared to hospitalized patients [4.4 (2.9–5.3) vs. 4.68 (3.8–5.9) log10 copies/ml; p = 0.13]. When the study population was divided in High (HVL, n = 64) and Low Viral Load (LVL, n = 63) group no differences were observed in disease severity at diagnosis. Furthermore, LVL and HVL groups did not differ with regard to duration of hospital stay, number of bacterial co-infections, need for high-intensity medical care and number of deaths. The viral load was not an independent risk factor for HIMC in an adjusted multivariate regression model (OR: 1.59; 95% CI: 0.46–5.55, p = 0.46).

Conclusions: Viral load at diagnosis is similar in asymptomatic and hospitalized patients and is not associated with either worse outcomes during hospitalization. SARS CoV-2 viral load might not be the right tool to assist clinicians in risk-stratifying hospitalized patients.
Supporting Primary Care Professionals to Stay in Work During the COVID-19 Pandemic: Views on Personal Risk and Access to Testing During the First Wave of Pandemic in Europe
Authors: Wanat Marta , Hoste Melanie , Gobat Nina , Anastasaki Marilena , Böhmer Femke , Chlabicz Slawomir , Colliers Annelies , Farrell Karen , Karkana Maria-Nefeli , Kinsman John , Lionis Christos , Marcinowicz Ludmila , Reinhardt Katrin , Skoglund Ingmarie , Sundvall Pär-Daniel , Vellinga Akke , Goossens Herman , Butler Christopher C. , Velden Alike van der , Anthierens Sibyl , Tonkin-Crine Sarah
Published: September 2021

Background: Minimising primary care professionals' (PCPs) risk of SARS-CoV-2 infection is crucial to ensure their safety as well as functioning health care system. PCPs' perspectives on the support they needed in the early stages of a public health crisis can inform future preparedness.

Aim: To understand PCPs' experiences of providing care during the COVID-19 pandemic, with focus on personal risk from COVID-19 and testing.

Design and Setting: Qualitative study using semi-structured interviews with PCPs in England, Belgium, the Netherlands, Ireland, Germany, Poland, Greece and Sweden, between April and July 2020.

Method: Interviews were analysed using a combination of inductive and deductive thematic analysis techniques.

Results: Eighty interviews were conducted, showing that PCPs tried to make sense of their risk of both contracting and severity of COVID-19 by assessing individual risk factors and perceived effectiveness of Personal Protective Equipment (PPE). They had limited access to PPE yet continued providing care as their “duty.” Some PCPs felt that they were put in high-risk situations when patients or colleagues were not flagging symptoms of COVID-19. Not having access to testing in the initial stages of the pandemic was somewhat accepted but when available, was valued.

Conclusion: Access to adequate PPE and testing, as well as training for staff and education for patients about the importance of ensuring staff safety is crucial. Given PCPs' varied response in how they appraised personal risk and their tolerance for working, PCPs may benefit from the autonomy in deciding how they want to work during health emergencies.
Pregnancy Outcomes After Frozen-Thawed Embryo Transfer in the Absence of a Corpus Luteum
Authors: Waschkies Freya , Kroning Luka , Schill Thilo , Chandra Arvind , Schippert Cordula , Töpfer Dagmar , Ziert Yvonne , von Versen-Höynck Frauke
Published: September 2021

Background: Nowadays, frozen-thawed embryo transfer (FET) cycles represent a high proportion of fertility treatments worldwide. Recent studies suggest differences in pregnancy outcomes depending on the FET treatment protocol used. The reason for this is still unclear, but the number of corpora lutea (CL) at conception is discussed as a possible factor. This study aims to investigate whether maternal and neonatal outcomes for pregnancies following FET lacking a CL differ from FET with one or more CL in order to explore a potential link between CL absence and adverse pregnancy outcomes.

Methods: The study was designed as a retrospective, multi-center observational study with two cohorts after singleton live birth [0 CL cohort (FET in a programmed cycle, n = 114) and ≥ 1 CL cohort (FET in a natural or stimulated cycle, n = 68)]. Participants completed a questionnaire on the outcome of pregnancy and birth records were analyzed in a descriptive way. Multivariable logistic and linear regressions were performed in order to explore associations between CL absence and pregnancy outcomes. The strength of the agreement between the information in the survey and the diagnoses extracted from the files was assessed by Cohen's Kappa.

Results: The risk of hypertensive disorders of pregnancy was higher after FET in the absence of a CL compared to FET with CL presence (aOR 5.56, 95% CI 1.12 – 27.72). Birthweights and birthweight percentiles were significantly higher in the 0 CL group. CL absence was a predictor of higher birthweight (adjusted coefficient B 179.74, 95% CI 13.03 – 346.44) and higher birthweight percentiles (adjusted coefficient B 10.23, 95%, 95% CI 2.28 – 18.40) particularly in female newborns of the 0 CL cohort. While the strength of the agreement between the reported information in the survey and the actual diagnoses extracted from the files was good for the majority of outcomes of interest it was fair in terms of hypertension (κ = 0.38).

Conclusion: This study supports observations suggesting a potential link between a lack of CL at conception and adverse maternal and neonatal outcomes. Further investigations on causes and pathophysiological relationships are yet to be conducted.
Content Analysis of Stroke Teleconsultation Recordings in the Moravian-Silesian Region, Czech Republic
Authors: Kasickova Linda , Lin Katie , Volny Ondrej , Cabal Martin , Holes David , Hill Michael D. , Bar Michal , Mikulik Robert
Published: September 2021

Background: Direct teleconsultations between emergency medical services (EMS) crews and hospital-based stroke neurologists are mandated in the Czech Republic as triage and prenotification tool in acute stroke patients. The main aim of this study was to analyze the efficacy as well as quality of such teleconsultations in daily clinical practice.

Methods: This is a descriptive analysis of teleconsultations between EMS paramedic crews and hospital-based neurologists in a geographically defined region of the Czech Republic (Moravian-Silesian region) between October 2018 to December 2018. All teleconsultations were analyzed for length and content. Content analysis included the following information: date, age, sex, prehospital neurological deficit(s), known/unknown time of symptom onset, anticoagulation status, vital signs, premorbid disability, and patient ID/insurance company number.

Results: Within the study period, paramedics conducted 522 calls across 6 stroke centers. Of these, 334 (64%) calls were conducted because patients met pre-established prehospital criteria for suspected acute stroke. Median call duration was 1 min 44 s ± 56 s (minimum 50 s, maximum 5 min 5 s). Amongst the analyzed prehospital teleconsultations, stroke onset time was reported in 95% of cases, neurological deficit in 96%, significant co-morbidities in 53%, premorbid disability in 37%, and anticoagulation status in 53%.

Conclusion: Teleconsultations between paramedics and hospital-based neurologists are not time-consuming. Stroke onset time and severity of neurological deficit are consistently communicated, however other important information such as comorbidities, premorbid disability, and anticoagulation status are reported inconsistently.
Association of Pericyte Loss With Microthrombosis After Subarachnoid Hemorrhage in ApoE-Deficient Mice
Authors: Pang Jinwei , Wu Yue , Peng Jianhua , Yang Ping , Chen Ligang , Jiang Yong
Published: September 2021

Background: The occurrence of microthrombosis contributes to not only delayed cerebral ischemia (DCI), but also early brain injury (EBI) after SAH. However, the underlying mechanism is not completely investigated. In the current study, we explored the underlying mechanism of microthrombosis in EBI stage after SAH in ApoE-deficient mice.

Methods: Experimental SAH was established by endovascular perforation in apolipoprotein E (ApoE)-deficient mice and wild type (WT) mice. Neurobehavioral, molecular biological and histopathological methods were used to assess the relationship between pericytes loss, neurobehavioral performance, and microthrombosis.

Results: We found that the number of microthrombi was significantly increased and peaked 48 h after SAH in WT mice. The increased microthrombosis was related to the decreased effective microcirculation perfusion area and EBI severity. ApoE-deficient mice showed more extensive microthrombosis than that of WT mice 48 h after SAH, which was thereby associated with greater neurobehavioral deficits. Immunohistochemical staining showed that microthrombi were predominantly located in microvessels where pericytes coverage was absent. Mechanistically, ApoE deficiency caused more extensive CypA-NF-κB-MMP-9 pathway activation than that observed in WT mice, which thereby led to more degradation of N-cadherin, and subsequently more pericytes loss. Thereafter, the major adhesion molecule that promoting microthrombi formation in microvessels, P-selectin, was considerably increased in WT mice and increased to a greater extent in the ApoE-deficient mice.

Conclusion: Taken together, these data suggest that pericytes loss is associated with EBI after SAH through promoting microthrombosis. Therapies that target ApoE to reduce microthrombosis may be a promising strategy for SAH treatment.
A Closed-Loop Optogenetic Platform
Authors: Firfilionis Dimitrios , Hutchings Frances , Tamadoni Reza , Walsh Darren , Turnbull Mark , Escobedo-Cousin Enrique , Bailey Richard G. , Gausden Johannes , Patel Aaliyah , Haci Dorian , Liu Yan , LeBeau Fiona E. N. , Trevelyan Andrew , Constandinou Timothy G. , O'Neill Anthony , Kaiser Marcus , Degenaar Patrick , Jackson Andrew
Published: September 2021

Neuromodulation is an established treatment for numerous neurological conditions, but to expand the therapeutic scope there is a need to improve the spatial, temporal and cell-type specificity of stimulation. Optogenetics is a promising area of current research, enabling optical stimulation of genetically-defined cell types without interfering with concurrent electrical recording for closed-loop control of neural activity. We are developing an open-source system to provide a platform for closed-loop optogenetic neuromodulation, incorporating custom integrated circuitry for recording and stimulation, real-time closed-loop algorithms running on a microcontroller and experimental control via a PC interface. We include commercial components to validate performance, with the ultimate aim of translating this approach to humans. In the meantime our system is flexible and expandable for use in a variety of preclinical neuroscientific applications. The platform consists of a Controlling Abnormal Network Dynamics using Optogenetics (CANDO) Control System (CS) that interfaces with up to four CANDO headstages responsible for electrical recording and optical stimulation through custom CANDO LED optrodes. Control of the hardware, inbuilt algorithms and data acquisition is enabled via the CANDO GUI (Graphical User Interface). Here we describe the design and implementation of this system, and demonstrate how it can be used to modulate neuronal oscillations in vitro and in vivo.
Protein, Calcium, Vitamin D Intake and 25(OH)D Status in Normal Weight, Overweight, and Obese Older Adults: A Systematic Review and Meta-Analysis
Authors: Dewansingh Priya , Reckman Gerlof A. R. , Mijlius Caspar F. , Krijnen Wim P. , van der Schans Cees P. , Jager-Wittenaar Harriët , van den Heuvel Ellen G. H. M.
Published: September 2021

The aging process is often accompanied by increase in body weight. Older adults with overweight or obesity might have an overconsumption in energy that is accompanied by inadequate intake of protein, vitamin D, and calcium. It is unclear if intake of protein and vitamin D and calcium is sufficient in older adults with overweight/obesity, and whether it differs from older adults with normal weight, since a recent overview of the literature review is lacking. Therefore, we systematically analyzed the current evidence on differences in nutrient intake/status of protein, vitamin D and calcium between older adults with different body mass index (BMI) categories. Randomized controlled trials and prospective cohort studies were identified from PubMed and EMBASE. Studies reporting nutrient intake/status in older adults aged ≥50 years with overweight/obesity and studies comparing between overweight/obesity and normal weight were included. Nutrient intake/status baseline values were reviewed and when possible calculated for one BMI category (single-group meta-analysis), or compared between BMI categories (meta-analysis). Nutrient intake/status was compared with international recommendations. Mean protein (N = 8) and calcium intake (N = 5) was 0.98 gram/kilogram body weight/day (g/kg/d) [95% Confidence Interval (CI) 0.89–1.08] and 965 mg [95% CI: 704–1225] in overweight/obese. Vitamin D intake was insufficient in all BMI categories (N = 5). The pooled mean for vitamin D intake was 6 ug [95% CI 4–9]. For 25(OH)D, the pooled mean was 54 nmol/L [95% CI 45–62], 52 nmol/L [95% CI 46–58], and 48 nmol/l [95% CI 33–62] in normal (N = 7), combined overweight and obese (N = 12), and obese older adults (N = 4), respectively. In conclusion, older adults with overweight and obesity have a borderline sufficient protein and sufficient calcium intake, but insufficient vitamin D intake. The 25(OH)D concentration is deficient for the obese older adults.
Is Elevated Choline on Magnetic Resonance Spectroscopy a Reliable Marker of Breast Lesion Malignancy?
Authors: Prvulovic Bunovic Natasa , Sveljo Olivera , Kozic Dusko , Boban Jasmina
Published: September 2021

Background

Contemporary magnetic resonance imaging (MRI) of the breast represents a powerful diagnostic modality for cancer detection, with excellent sensitivity and high specificity. Magnetic resonance spectroscopy (MRS) is being explored as an additional tool for improving specificity in breast cancer detection, using multiparametric MRI. The aim of this study was to examine the possibility of 1H-MRS to discriminate malignant from benign breast lesions, using elevated choline (Cho) peak as an imaging biomarker.

Methods

A total of 60 patients were included in this prospective study: 30 with malignant (average age, 55.2 years; average lesion size, 35 mm) and 30 with benign breast lesions (average age, 44.8 years; average lesion size, 20 mm), who underwent multiparametric MRI with multivoxel 3D 1H-MRS on a 1.5-T scanner in a 3-year period. Three patients with benign breast lesions were excluded from the study. All lesions were histologically verified. Peaks identified on 1H-MRS were lipid (0.9, 2.3, 2.8, and 5.2 ppm), choline (3.2 ppm), and water peaks (4.7 ppm). Sensitivity and specificity, as well as positive and negative predictive values, were defined using ROC curves. Cohen’s Kappa test of inter-test reliability was performed [testing the agreement between 1H-MRS and histologic finding, and 1H-MRS and MR mammography (MRM)].

Results

Choline peak was elevated in 24/30 malignant lesions and in 20/27 benign breast lesions. The sensitivity of 1H-MRS was 0.8, specificity was 0.741, positive predictive value was 0.774, and negative predictive value was 0.769. Area under ROC was 0.77 (CI 0.640–0.871). Inter-test reliability between 1H-MRS and histologic finding was 0.543 (moderate agreement) and that between 1H-MRS and MRM was 0.573 (moderate agreement). False-negative findings were most frequently observed in invasive lobular cancers, while false-positive findings were most frequently observed in adenoid fibroadenomas.

Conclusion

Although elevation of the choline peak has a good sensitivity and specificity in breast cancer detection, both are significantly lower than those of multiparametric MRM. Inclusion of spectra located on tumor margins as well as analysis of lipid peaks could aid both sensitivity and specificity. An important ratio of false-positive and false-negative findings in specific types of breast lesions (lobular cancer and adenoid fibroadenoma) suggests interpreting these lesions with a caveat.
Prediction of Clinical Outcome for High-Intensity Focused Ultrasound Ablation of Uterine Leiomyomas Using Multiparametric MRI Radiomics-Based Machine Leaning Model
Authors: Zheng Yineng , Chen Liping , Liu Mengqi , Wu Jiahui , Yu Renqiang , Lv Fajin
Published: September 2021

Objectives

This study sought to develop a multiparametric MRI radiomics-based machine learning model for the preoperative prediction of clinical success for high-intensity-focused ultrasound (HIFU) ablation of uterine leiomyomas.

Methods

One hundred and thirty patients who received HIFU ablation therapy for uterine leiomyomas were enrolled in this retrospective study. Radiomics features were extracted from T2-weighted (T2WI) image and ADC map derived from diffusion-weighted imaging (DWI). Three feature selection algorithms including least absolute shrinkage and selection operator (LASSO), recursive feature elimination (RFE), and ReliefF algorithm were used to select radiomics features, respectively, which were fed into four machine learning classifiers including k-nearest neighbors (KNN), logistic regression (LR), random forest (RF), and support vector machine (SVM) for the construction of outcome prediction models before HIFU treatment. The performance, predication ability, and clinical usefulness of these models were verified and evaluated using receiver operating characteristics (ROC), calibration, and decision curve analyses.

Results

The radiomics analysis provided an effective preoperative prediction for HIFU ablation of uterine leiomyomas. Using SVM with ReliefF algorithm, the multiparametric MRI radiomics model showed the favorable performance with average accuracy of 0.849, sensitivity of 0.814, specificity of 0.896, positive predictive value (PPV) of 0.903, negative predictive value (NPV) of 0.823, and the area under the ROC curve (AUC) of 0.887 (95% CI = 0.848–0.939) in fivefold cross-validation, followed by RF with ReliefF. Calibration and decision curve analyses confirmed the potential of model in predication ability and clinical usefulness.

Conclusions

The radiomics-based machine learning model can predict preoperatively HIFU ablation response for the patients with uterine leiomyomas and contribute to determining individual treatment strategies.
Construction of Novel Methylation-Driven Gene Model and Investigation of PARVB Function in Glioblastoma
Authors: Yu Wanli , Wu Pengfei , Wang Fang , Miao Li , Han Bo , Jiang Zhiqun
Published: September 2021

Background

Glioblastoma multiforme (GBM) is characterized by widespread genetic and transcriptional heterogeneity. Aberrant DNA methylation plays a vital role in GBM progression by regulating gene expression. However, little is known about the role of methylation and its association with prognosis in GBM. Our aim was to explore DNA methylation-driven genes (DMDGs) and provide evidence for survival prediction and individualized treatment of GBM patients.

Methods

Use of the MethylMix R package identified DMDGs in GBM. The prognostic signature of DMDGs based on the risk score was constructed by multivariate Cox regression analysis. Receiver operating characteristics (ROC) curve and C-index were applied to assess the predictive performance of the DMDG prognostic signature. The predictive ability of the multigene signature model was validated in TCGA and CGGA cohorts. Finally, the role of DMDG β-Parvin (PARVB) was explored in vitro.

Results

The prognostic signature of DMDGs was constructed based on six genes (MDK, NMNAT3, PDPN, PARVB, SERPINB1, and UPP1). The low-risk cohort had significantly better survival than the high-risk cohort (p < 0.001). The area under the curve of the ROC of the six-gene signature was 0.832, 0.927, and 0.980 within 1, 2, and 3 years, respectively. The C-index of 0.704 indicated superior specificity and sensitivity. The six-gene model has been demonstrated to be an independent prognostic factor for GBM. In addition, joint survival analysis indicated that the MDK, NMNAT3, PARVB, SERPINB1, and UPP1 genes were significantly associated with prognosis and therapeutic targets for GBM. Importantly, our DMDG prognostic model was more suitable and accurate for low-grade gliomas. Finally, we verified that PARVB induced epithelial-mesenchymal transition partially through the JAK2/STAT3 pathway, which in turn promoted GBM cell proliferation, migration, and invasion.

Conclusion

This study demonstrated the potential value of the prognostic signature of DMDGs and provided important bioinformatic and potential therapeutic target data to facilitate individualized treatment for GBM, and to elucidate the specific mechanism by which PARVB promotes GBM progression.
A Multicentric Randomized Trial to Evaluate the ROle of Uterine MANipulator on Laparoscopic/Robotic HYsterectomy for the Treatment of Early-Stage Endometrial Cancer: The ROMANHY Trial
Authors: Gueli Alletti Salvatore , Perrone Emanuele , Fedele Camilla , Cianci Stefano , Pasciuto Tina , Chiantera Vito , Uccella Stefano , Ercoli Alfredo , Vizzielli Giuseppe , Fagotti Anna , Gallotta Valerio , Cosentino Francesco , Costantini Barbara , Restaino Stefano , Monterossi Giorgia , Rosati Andrea , Turco Luigi Carlo , Capozzi Vito Andrea , Fanfani Francesco , Scambia Giovanni
Published: September 2021

Objective

This prospective randomized trial aimed to assess the impact of the uterine manipulator in terms of lymph vascular space invasion (LVSI) in patients undergoing minimally invasive staging for early-stage endometrial cancer.

Methods

In this multicentric randomized trial, enrolled patients were randomly allocated in two groups according to the no use (arm A) or the use (arm B) of the uterine manipulator. Inclusion criteria were G1-G2 early-stage endometrial cancer at preoperative evaluation. The variables collected included baseline demographic characteristics, perioperative data, final pathology report, adjuvant treatment, and follow-up.

Results

In the study, 154 patients (76 in arm A and 78 in arm B) were finally included. No significant differences were recorded regarding the baseline characteristics. A statistically significant difference was found in operative time for the laparoscopic staging (p=0.005), while no differences were reported for the robotic procedures (p=0.419). The estimated blood loss was significantly lower in arm A (p=0.030). No statistically significant differences were recorded between the two study groups in terms of peritoneal cytology, LVSI (p=0.501), and pattern of LVSI (p=0.790). No differences were detected in terms of overall survival and disease-free survival (p=0.996 and p=0.480, respectively). Similarly, no differences were recorded in the number of recurrences, 6 (7.9%) in arm A and 4 (5.2%) in arm B (p=0.486). The use of the uterine manipulator had no impact on DFS both at univariable and multivariable analyses.

Conclusions

The intrauterine manipulator does not affect the LVSI in early-stage endometrial cancer patients undergoing laparoscopic/robotic staging.

Clinical Trial Registration

https://clinicaltrials.gov, identifier (NCT: 02762214)
Urinary Exosomes Diagnosis of Urological Tumors: A Systematic Review and Meta-Analysis
Authors: Xu Yipeng , Lou Jianmin , Yu Mingke , Jiang Yingjun , Xu Han , Huang Yueyu , Gao Yun , Wang Hua , Li Guorong , Wang Zongping , Zhao An
Published: September 2021

Purpose

Exosomes could be released directly into the urine by the urological tumoral cells, so testing urinary exosomes has great potential for non-invasive diagnosis and monitor of urological tumors. The objective of this study is to systematically review and meta-analysis of urinary exosome for urological tumors diagnosis.

Materials and Methods

A systematic review of the recent English-language literature was conducted according to the PRISMA statement recommendations (CRD42021250613) using PubMed, Embase, Cochrane Library, Web of Science, and Scopus databases up to April 30, 2021. Risk-of-bias assessment was performed according to the QUADAS 2 tool. The true diagnostic value of urinary exosomes by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature.

Results

Sixteen eligible studies enrolling 3224 patients were identified. The pooled sensitivity and specificity of urinary exosomes as a diagnostic tool in urological tumors were 83% and 88%, respectively. The area under the summary receiver operating characteristic curve was 0.92 (95% CI: 0.89–0.94). Further subgroup analyses showed that our results were stable irrespective of the urinary exosome content type and tumor type.

Conclusion

Urinary exosomes may serve as novel non-invasive biomarkers for urological cancer detection. Future clinical trial designs must validate and explore their utility in treatment decision-making.

Systematic Review Registration

[
https://www.crd.york.ac.uk/prospero/], identifier [CRD42021250613].
GPR171 Agonist Reduces Chronic Neuropathic and Inflammatory Pain in Male, But Not Female Mice
Authors: Ram Akila , Edwards Taylor , McCarty Ashley , Afrose Leela , McDermott Max V. , Bobeck Erin N.
Published: September 2021

Chronic pain is a growing public health crisis that requires exigent and efficacious therapeutics. GPR171 is a promising therapeutic target that is widely expressed through the brain, including within the descending pain modulatory regions. Here, we explore the therapeutic potential of the GPR171 agonist, MS15203, in its ability to alleviate chronic pain in male and female mice using a once-daily systemic dose (10 mg/kg, i.p.) of MS15203 over the course of 5 days. We found that in our models of Complete Freund's Adjuvant (CFA)-induced inflammatory pain and chemotherapy-induced peripheral neuropathy (CIPN), MS15203 did not alleviate thermal hypersensitivity and allodynia, respectively, in female mice. On the other hand, MS15203 treatment decreased the duration of thermal hypersensitivity in CFA-treated male mice following 3 days of once-daily administration. MS15203 treatment also produced an improvement in allodynia in male mice, but not female mice, in neuropathic pain after 5 days of treatment. Gene expression of GPR171 and that of its endogenous ligand BigLEN, encoded by the gene PCSK1N, were unaltered within the periaqueductal gray (PAG) in both male and female mice following inflammatory and neuropathic pain. However, following neuropathic pain in male mice, the protein levels of GPR171 were decreased in the PAG. Treatment with MS15203 then rescued the protein levels of GPR171 in the PAG of these mice. Taken together, our results identify GPR171 as a GPCR that displays sexual dimorphism in alleviation of chronic pain. Further, our results suggest that GPR171 and MS15203 have demonstrable therapeutic potential in the treatment of chronic pain.
Investigating the Role of Ly6G+ Neutrophils in Incisional and Inflammatory Pain by Multidimensional Pain-Related Behavioral Assessments: Bridging the Translational Gap
Authors: Segelcke Daniel , Pradier Bruno , Reichl Sylvia , Schäfer Lukas C. , Pogatzki-Zahn Esther M.
Published: September 2021

In recent years, preclinical pain research has failed to develop genuinely new analgesics for clinical use. This fact is reflected by a high number of patients, limited drug efficacy accompanied by side effects, and a long-term opioid intake. Two main aspects have been addressed, which hinder translation: the use of non-relevant pain models and a mismatch between pain-related outcomes in preclinical and clinical studies. Conversely, disease-specific pain models that mirror more closely the clinical situation and multidimensional behavioral outcome measures that objectively and reproducibly assess relevant pain-related symptoms in a preclinical setting could improve translation. Mechanistically, a matter of debate is the role of Ly6G+neutrophil granulocytes (NGs) for pain. NGs are essential to eliminate pathogens and promote the wound healing process. For this purpose, there is a need to release various pro- and anti-inflammatory mediators, some of which could ameliorate or enhance pain. However, the contribution of NGs to different pain entities is contradictory for reflex-based tests, and completely unknown in the context of non-evoked pain (NEP) and movement-evoked pain (MEP). First, we combined withdrawal reflex-based assays with novel video-based assessments for NEP- and MEP-related behavior in two mouse pain models. The pain models utilized in this study were incision (INC) and pathogen/adjuvant-induced inflammation (CFA), translating well to postsurgical and inflammatory pain entities. Second, we depleted NGs and applied a set of behavioral assessments to investigate the role of NG migration in different pain modalities. Our comprehensive behavioral approach identified pain-related behaviors in mice that resemble (NEP) or differentiate (MEP) behavioral trajectories in comparison to mechanical and heat hypersensitivity, thereby indicating modality-dependent mechanisms. Further, we show that injury-induced accumulation of NGs minimally affects pain-related behaviors in both pain models. In conclusion, we report a novel assessment to detect NEP in mice after unilateral injuries using a more unbiased approach. Additionally, we are capable of detecting an antalgic gait for both pain entities with unique trajectories. The different trajectories between MEP and other pain modalities suggest that the underlying mechanisms differ. We further conclude that NGs play a subordinate role in pain-related behaviors in incisional and inflammatory pain.
Global Trends and Future Prospects of Child Nutrition: A Bibliometric Analysis of Highly Cited Papers
Authors: Wang Yunhua , Liu Qiaorong , Chen Yongcong , Qian Yaling , Pan Bei , Ge Long , Wang Qi , Ding Guowu , Wang Jiancheng
Published: September 2021

Child nutrition has always been a global concern. This study performed visual analysis of 1,398 child nutrition highly cited papers (HCPs) from 2009 to 2019. The purpose of the study was to evaluate and present the performances of authors, journals, countries, institutions, top cited papers; to explore the hot topics, prospects, and to propose the future research directions on child nutrition. We used bibliometric methods to conduct in-depth statistical analysis of HCPs on child nutrition, showing research progress, trends and hot spots. We included HCPs on child nutrition from the Science Citation Index-Expanded (SCI-E) database February 7, 2020. Two tools, CiteSpace and VOSviewer, were used to conduct the bibliometric analyses. The results showed that, since 2011, the number of HCPs on child nutrition has increased rapidly. The top three contributors in this field were the USA, the UK and Canada. However, the contribution of developing countries was very limited. Intestinal microflora, food allergy, overweight and obesity were the three major research hotspots in this field. Results of this study provide valuable references for ongoing child nutrition related research, which may be interesting and noteworthy to the researchers involved.
Heart's Ease: Eudaimonia, Musicking in the Pandemic, and Its Implications for Music Education
Authors: Boyce-Tillman June
Published: September 2021

This article will review the themes found in the literature on eudaimonia: ethical behaviour, a sense of meaning and purpose, autonomy – being able to make wise decisions and manage behaviour, contemplation, relationship with spirits of the ancestors and celestial beings and relationships of mutuality, respect. It will use these to critique various events online during the pandemic, such as the Embodiment conference, the SHIFT conference and the ZOOM peace choir. These developments related to music and wellbeing will be used to interrogate the purposes of music education and what might be learned from these new developments in relation to technology in relation to themes, such as values, orality and literacy, process and product.
The Validity of Physiological Measures to Identify Differences in Intrinsic Cognitive Load
Authors: Ayres Paul , Lee Joy Yeonjoo , Paas Fred , van Merriënboer Jeroen J. G.
Published: September 2021

A sample of 33 experiments was extracted from the Web-of-Science database over a 5-year period (2016–2020) that used physiological measures to measure intrinsic cognitive load. Only studies that required participants to solve tasks of varying complexities using a within-subjects design were included. The sample identified a number of different physiological measures obtained by recording signals from four main body categories (heart and lungs, eyes, skin, and brain), as well as subjective measures. The overall validity of the measures was assessed by examining construct validity and sensitivity. It was found that the vast majority of physiological measures had some level of validity, but varied considerably in sensitivity to detect subtle changes in intrinsic cognitive load. Validity was also influenced by the type of task. Eye-measures were found to be the most sensitive followed by the heart and lungs, skin, and brain. However, subjective measures had the highest levels of validity. It is concluded that a combination of physiological and subjective measures is most effective in detecting changes in intrinsic cognitive load.
The Lutheran Imaginary That Underpins Social Democracy
Authors: Larsen Mads
Published: September 2021

Scandinavian social democracy is increasingly upheld as an alternative that could reform capitalism. The Nordic Model produces income equality, low-conflict politics, and happy people. When half of young Americans express that they would prefer “socialism,” they generally mean to live in a society that provides for its citizens as the Nordics do. Such aspirations are complicated by how social democracy can be viewed as a secularized form of Lutheranism, the Protestant creed that the Nordic region embraced in the 16th century. Lutheran norms and values carried into the modern era and made possible social democracy's two distinguishing features: fascist corporatism and socialist redistribution. A strong state facilitatesstatist individualism, which empowers individuals vis-à-vis employers, parents, and spouses. The outcome could be cross-culturally salient, as it brings people closer to our species' fission-fusion baseline. Yet in the modern environment, only Nordics seem to have a cultural imaginary that makes compelling the politics that drive such high levels of both productivity and egalitarianism. The region's storytelling reflects this Lutheran past and is used to negotiate modern adaptations. A better understanding of social democracy could help prevent that demands for “socialism” motivate a turn to actual socialism.
Predictors of Prenatal Depression: A Cross-Sectional Study in Rural Pakistan
Authors: Khan Rukhsana , Waqas Ahmed , Mustehsan Zille Huma , Khan Amna Saeed , Sikander Siham , Ahmad Ikhlaq , Jamil Anam , Sharif Maria , Bilal Samina , Zulfiqar Shafaq , Bibi Amina , Rahman Atif
Published: September 2021

Objective: To determine the prevalence and association of prenatal depression with socioeconomic, demographic and personal factors among pregnant women living in Kallar Syedan, Rawalpindi, Pakistan.

Methods: Five hundred women in the second and third trimester of pregnancy, living in Kallar Syedan, a rural area of district Rawalpindi Pakistan, were included in the study. Depression was assessed using “Patient health questionnaire” (PHQ9) in Urdu, with a cut-off score of 10. Multi-dimensional scale of perceived social support (MSPSS) was used to assess perceived social support. Life Events and Difficulties Schedule (LEDS) were used to measure stressful life events in past 1 year. Tool to assess intimate partner violence (IPV) was based on WHO Multi Country Study on “Women's Health and Domestic Violence against Women.”

Results: Prevalence of prenatal depression was found to be 27%. Number of pregnancies was significantly associated with prenatal depression (p < 0.01). Women living in a joint family and those who perceived themselves as moderately satisfied or not satisfied with their life in the next 4 years were found to be depressed (p < 0.01, OR 6.9, CI 1.77–26.73). Depressive symptomatology in women who experienced more than five stressful life events in last 1 year was three times higher (p < 0.001, OR 3.2, CI 1.68–5.98) than in women with 1–2 stressful events. Women who were supported by their significant others or their family members had 0.9 times (p < 0.01, OR 0.9, CI 0.85–0.96) less chance of getting depressed. Pregnant women who were psychologically abused by their partners were 1.5 times more depressed (p < 0.05 CI 1.12–2.51). Odds of having depression was also high in women who had less mean score of MSSI (p < 0.05, OR 1.1, CI 1.01–1.09). Women who had suitable accommodation had 0.5 times less chance of having depression than others (p < 0.05, OR 0.5, CI 0.27–0.92).

Conclusion: Over a quarter of the women in the study population reported prenatal depression, which were predicted predominantly by psychosocial variables.
Case Report: Changes in Regional Cerebral Blood Flow in Chronic Akathisia of a Depressed Patient Before and After Electroconvulsive Therapy Treatment
Authors: Suzuki Akihito , Kobayashi Ryota , Shirata Toshinori , Komoriya Hitomi , Kanoto Masafumi , Otani Koichi
Published: September 2021

Akathisia, which characterized by subjective restlessness and objective hyperactivity, is induced mostly by antipsychotics and antidepressants. Chronic akathisia is defined as persistence of symptoms for more than 3 months. The pathophysiology of chronic akathisia remains unclear. This report describes a depressed patient, a 66-year-old woman with a diagnosis of major depressive disorder, with chronic akathisia. Her regional cerebral blood flow (rCBF) was measured using single photon emission computed tomography (SPECT) before and after the treatment with electroconvulsive therapy (ECT). She had experienced akathisia-like symptoms three times prior because of risperidone, escitalopram, and clomipramine administration, accompanied by major depression. After levomepromazine was added to quetiapine to treat insomnia, she developed akathisia symptoms such as a sense of restlessness and inability to sit in one place for a few minutes. These antipsychotics were withdrawn. Propranolol was administered, leading to no apparent improvement for 8 months. After she was diagnosed as having major depressive disorder and chronic akathisia, she received 10 sessions of bilateral ECT. Her depressive symptoms improved greatly. Akathisia disappeared completely after ECT. SPECT revealed that rCBF was decreased in the middle frontal gyrus and parietal lobe, that it was increased in the thalamus, fusiform gyrus, and cerebellum before ECT, and that these abnormalities in rCBF were approaching normal levels after ECT. Findings presented in this report suggest ECT as a beneficial treatment for chronic akathisia. Altered rCBF in the middle frontal gyrus, parietal lobe, thalamus, fusiform gyrus, and cerebellum, and especially decreased rCBF in the parietal lobe, may be related to the pathophysiology of chronic akathisia.
Sex Differences in Molecular Mechanisms of Cardiovascular Aging
Authors: Dela Justina Vanessa , Miguez Jéssica S. G. , Priviero Fernanda , Sullivan Jennifer C. , Giachini Fernanda R. , Webb R. Clinton
Published: September 2021

Cardiovascular disease (CVD) is still the leading cause of illness and death in the Western world. Cardiovascular aging is a progressive modification occurring in cardiac and vascular morphology and physiology where increased endothelial dysfunction and arterial stiffness are observed, generally accompanied by increased systolic blood pressure and augmented pulse pressure. The effects of biological sex on cardiovascular pathophysiology have long been known. The incidence of hypertension is higher in men, and it increases in postmenopausal women. Premenopausal women are protected from CVD compared with age-matched men and this protective effect is lost with menopause, suggesting that sex-hormones influence blood pressure regulation. In parallel, the heart progressively remodels over the course of life and the pattern of cardiac remodeling also differs between the sexes. Lower autonomic tone, reduced baroreceptor response, and greater vascular function are observed in premenopausal women than men of similar age. However, postmenopausal women have stiffer arteries than their male counterparts. The biological mechanisms responsible for sex-related differences observed in cardiovascular aging are being unraveled over the last several decades. This review focuses on molecular mechanisms underlying the sex-differences of CVD in aging.
Agent-Supported Peer Collaboration in MOOCs
Authors: Tegos Stergios , Mavridis Apostolos , Demetriadis Stavros
Published: September 2021

While massive open online courses (MOOCs) can be effective in scaling education, orchestrating collaborative learning activities for large audiences remains a non-trivial task that introduces a series of practical challenges, such as the lack of adequate human support. Even when collaboration takes place, there is uncertainty whether meaningful interactions will occur among learners. This work presents the architecture of a prototype system called PeerTalk. The system was created to enable instructors to easily incorporate real-time collaborative learning activities into their online courses. Furthermore, PeerTalk employs a conversational agent service that aims to scaffold students’ online collaboration and provide valuable guidance, which can be configured by the course instructor. In order to investigate the user-acceptance of the system, two evaluation studies took place. The first one involved a group of experts, i.e., MOOC instructors who are expected to use such a system in their course, whereas the second study featured 44 postgraduate students. The study findings were encouraging in terms of the system efficiency and usability levels, laying the foundation for a conversational agent service, which can effectively scale the support of the teaching staff and be easily integrated in MOOC platforms, creating further opportunities for valuable social interaction among learners.
Features and Applications of Urine Stabilization Methods: A Review
Authors: Yang Wei , Li Jianan , Yang Xuejing
Published: September 2021

The recovery of nutrients from unconventional water such as domestic sewage is considered as a sustainable solution to environmental sanitation, personal hygiene, water, and food safety issues. Source separation of urine and the sequenced treatment techniques are the promising approaches to recover the resources from this unconventional water. However, in the storage of urine, urea is hydrolyzed under the action of urease, resulting in odor, precipitation and the loss of ammonia, which is a challenge to be overcome in the process of urine recycling. This review collates research related to urine stabilization, and aims to summarize the characteristics and applications of existing urine stabilization methods, such as acidification, alkalization, electrochemistry, inhibitors and etc. Overall, acidification and alkalization have higher dosage requirements and have an attentional impact on the environment; electrochemical technology is suitable for decentralized sanitation facilities, but the inhibition duration is short; inhibitors are the least effective and are usually used to regulate urease activities in soil environment rather than for urine stabilization. Choosing the appropriate approaches of urine stabilization should focus on the overall perspective of urine resource utilization, consider the separation method and recovery form, and combine it with the concentration technology.
Take the Opportunity Afforded by the COVID-19 Experiences: Progressive Non-growth Policies for Sustainable Lifestyles
Authors: Boström Magnus
Published: September 2021

The COVID-19 pandemic has led to significant restrictions on lifestyles and consumption everywhere. Many consumer practices have been disrupted due to the shutting down of economic and social activities, limiting of mobility in public places, closing of shopping centers and non-essential stores, and closing of borders. These restrictions have had a significant impact on climate emissions. Much public and scholarly attention has been given to the question of whether the pandemic also offers a window of opportunity for long-term sustainability transformation. The article elaborates on this issue by specifically discussing progressive non-growth policies for sustainable lifestyles and reduced consumption. What potential for long-term transformative change results from lifestyle changes like these? How can societies be restructured to take advantage of the experiences from the pandemic? Bottom-up drivers and possibilities for top-down enforcement are both important to consider. The article limits its focus to top-down policy measures with transformative potential related to sustainable lifestyles (reduced consumption) by summarizing and discussing some key policy lessons identified in recent COVID-19 literature. It considers the need to address likely rebound effects and the vested interests in bouncing practices back toward the previous unsustainable “normality.” The argument is generally inspired by post-growth and degrowth perspectives, as the dominant pro-growth, neo-liberal doctrines are seen as unable to transform societies and guide them onto sustainable paths.