bluuebunny/crossref_metadata_2025 huggingface dataset:
Microstructure and Mechanical Properties of Aluminum Alloy/Stainless Steel Dissimilar Ring Joint Welded by Inertia Friction Welding
Authors: Qin Feng , Zhang Chunbo , Zhou Jun , Xu Kai , Wang Qi , Li Yunlei , Zhang Wenhan
Published: January 2022

In recent years, studying the weldability of a dissimilar metal hybrid structure, with the potential to make full use of their unique benefits, has been a research hotspot. In this article, inertia friction welding was utilized to join Φ130 forged ring of 2219 aluminum alloy with 304 stainless steel. Optical observation (OM), electron back scattering diffraction (EBSD), and scanning electron microscopy (SEM) were utilized to examine the joint microstructure in depth. Depending on the research, a significant thermal–mechanical coupling effect occurs during welding, resulting in inadequate recrystallization on aluminum-side thermo-mechanically affected zone (TMAZ) and forming zonal features. The crystal orientation and grain size of each TMAZ region reflect distinct differences. On the joint faying surface, the growth of intermetallic compounds (IMCs) is inhibited by a fast cooling rate and metallurgical bonding characteristics were found depending on the discontinuous distribution of IMCs. The average joint tensile strength can reach 161.3 MPa achieving 92.2% of 2219-O; fracture occurs on aluminum-side base metal presenting ductile fracture characteristics.
In vitro Characterization of Anti-SARS-CoV-2 Intravenous Immunoglobulins (IVIg) Produced From Plasma of Donors Immunized With the BNT162b2 Vaccine and Its Comparison With a Similar Formulation Produced From Plasma of COVID-19 Convalescent Donors
Authors: Rojas-Jiménez Gabriel , Solano Daniela , Segura Álvaro , Sánchez Andrés , Chaves-Araya Stephanie , Herrera María , Vargas Mariángela , Cerdas Maykel , Calvo Gerardo , Alfaro Jonathan , Molina Sebastián , Bolaños Kimberly , Moreira-Soto Andrés , Villalta Mauren , Sánchez Adriana , Cordero Daniel , Durán Gina , Solano Gabriela , Gómez Aarón , Hernández Andrés , Sánchez Laura , Vargas Marco , Drexler Jean Felix , Alape-Girón Alberto , Díaz Cecilia , León Guillermo
Published: January 2022

Despite vaccines are the main strategy to control the ongoing global COVID-19 pandemic, their effectiveness could not be enough for individuals with immunosuppression. In these cases, as well as in patients with moderate/severe COVID-19, passive immunization with anti-SARS-CoV-2 immunoglobulins could be a therapeutic alternative. We used caprylic acid precipitation to prepare a pilot-scale batch of anti-SARS-CoV-2 intravenous immunoglobulins (IVIg) from plasma of donors immunized with the BNT162b2 (Pfizer-BioNTech) anti-COVID-19 vaccine (VP-IVIg) and compared their in vitro efficacy and safety with those of a similar formulation produced from plasma of COVID-19 convalescent donors (CP-IVIg). Both formulations showed immunological, physicochemical, biochemical, and microbiological characteristics that meet the specifications of IVIg formulations. Moreover, the concentration of anti-RBD and ACE2-RBD neutralizing antibodies was higher in VP-IVIg than in CP-IVIg. In concordance, plaque reduction neutralization tests showed inhibitory concentrations of 0.03–0.09 g/L in VP-IVIg and of 0.06–0.13 in CP-IVIg. Thus, VP-IVIg has in vitro efficacy and safety profiles that justify their evaluation as therapeutic alternative for clinical cases of COVID-19. Precipitation with caprylic acid could be a simple, feasible, and affordable alternative to produce formulations of anti-SARS-CoV-2 IVIg to be used therapeutically or prophylactically to confront the COVID-19 pandemic in middle and low-income countries.
Antibiotic Resistance and Molecular Biological Characteristics of Non-13-Valent-Pneumococcal Conjugate Vaccine Serogroup 15 Streptococcus pneumoniae Isolated From Children in China
Authors: Shi Wei , Du Qianqian , Yuan Lin , Gao Wei , Wang Qing , Yao Kaihu
Published: January 2022

Background: The isolation rate of serogroup 15 Streptococcus pneumoniae has been increasing since developing countries began administering the 13-valent pneumococcal conjugate vaccine.

Methods: We detected the antibiotic resistance and molecular characteristics of 126 serogroup 15 S. pneumoniae strains isolated from children in China. Serotypes were determined via the Quellung reaction. Antibiotic resistance was tested using the E-test or disc diffusion method. Sequence types were assigned via multilocus sequence typing. Data were analyzed using WHONET 5.6 software.

Results: The frequencies of S. pneumoniae serotypes 15A, 15B, 15C, and 15F were 29.37, 40.48, 28.57, and 1.59%, respectively. Continuous-monitoring data from Beijing showed that the annual isolation rates of serogroup 15 S. pneumoniae were 7.64, 7.17, 2.58, 4.35, 3.85, 7.41, and 10.53%, respectively, from 2013 to 2019. All 126 serogroup 15 strains were susceptible to vancomycin and ceftriaxone. The non-susceptibility rate to penicillin was 78.57%. All strains were resistant to erythromycin with high minimum inhibitory concentrations (MICs). The multidrug resistance rate was 78.57%. The most common clonal complexes were CC3397, CC6011, CC10088, CC9785, and ST8589.

Conclusion: Serogroup 15 S. pneumoniae is common among children in China, and these strains should be continuously monitored.
Development and Verification of a Hypoxic Gene Signature for Predicting Prognosis, Immune Microenvironment, and Chemosensitivity for Osteosarcoma
Authors: Wu Fengfeng , Xu Juntao , Jin Mingchao , Jiang Xuesheng , Li Jianyou , Li Xiongfeng , Chen Zhuo , Nie Jiangbo , Meng Zhipeng , Wang Guorong
Published: January 2022

Objective: Hypoxic tumors contribute to local failure and distant metastases. Nevertheless, the molecular hallmarks of hypoxia remain ill-defined in osteosarcoma. Here, we developed a hypoxic gene signature in osteosarcoma prognoses.

Methods: With the random survival forest algorithm, a prognostic hypoxia-related gene signature was constructed for osteosarcoma in the TARGET cohort. Overall survival (OS) analysis, receiver operating characteristic (ROC) curve, multivariate cox regression analysis, and subgroup analysis were utilized for assessing the predictive efficacy of this signature. Also, external validation was presented in the GSE21257 cohort. GSEA was applied for signaling pathways involved in the high- and low-risk samples. Correlation analyses between risk score and immune cells, stromal/immune score, immune checkpoints, and sensitivity of chemotherapy drugs were performed in osteosarcoma. Then, a nomogram was built by integrating risk score, age, and gender.

Results: A five-hypoxic gene signature was developed for predicting survival outcomes of osteosarcoma patients. ROC curves confirmed that this signature possessed the well predictive performance on osteosarcoma prognosis. Furthermore, it could be independently predictive of prognosis. Metabolism of xenobiotics by cytochrome P450 and nitrogen metabolism were activated in the high-risk samples while cell adhesion molecules cams and intestinal immune network for IgA production were enriched in the low-risk samples. The low-risk samples were characterized by elevated immune cell infiltrations, stromal/immune scores, TNFRSF4 expression, and sensitivity to cisplatin. The nomogram accurately predicted 1-, 3-, and 5-years survival duration.

Conclusion: These findings might offer an insight into the optimization of prognosis risk stratification and individualized therapy for osteosarcoma patients.
Motor–Cognitive Treadmill Training With Virtual Reality in Parkinson’s Disease: The Effect of Training Duration
Authors: Pelosin Elisa , Ponte Chiara , Putzolu Martina , Lagravinese Giovanna , Hausdorff Jeffrey M. , Nieuwboer Alice , Ginis Pieter , Rochester Lynn , Alcock Lisa , Bloem Bastiaan R. , Nieuwhof Freek , Cereatti Andrea , Della Croce Ugo , Mirelman Anat , Avanzino Laura
Published: January 2022

Treadmill training with virtual reality (TT + VR) has been shown to improve gait performance and to reduce fall risk in Parkinson’s disease (PD). However, there is no consensus on the optimal training duration. This study is a sub-study of the V-TIME randomized clinical trial (NCT01732653). In this study, we explored the effect of the duration of training based on the motor–cognitive interaction on motor and cognitive performance and on fall risk in subjects with PD. Patients in Hoehn and Yahr stages II–III, aged between 40 and 70 years, were included. In total, 96 patients with PD were assigned to 6 or 12 weeks of TT + VR intervention, and 77 patients completed the full protocol. Outcome measures for gait and cognitive performance were assessed at baseline, immediately after training, and at 1- and 6-month follow-up. The incident rate of falls in the 6-month pre-intervention was compared with that in the 6-month post-intervention. Dual-task gait performance (gait speed, gait speed variability and stride length under cognitive dual task and obstacle negotiation, and the leading foot clearance in obstacle negotiation) improved similarly in both groups with gains sustained at 6-month follow-up. A higher decrease in fall rate and fear of falling were observed in participants assigned to the 12-week intervention than the 6-week intervention. Improvements in cognitive functions (i.e., executive functions, visuospatial ability, and attention) were seen only in participants enrolled in 12-week training up to 1-month follow-up but vanished at the 6-month evaluation. Our results suggest that a longer TT + VR training leads to greater improvements in cognitive functions especially those directly addressed by the virtual environment.
Therapeutic Low-Intensity Ultrasound for Peripheral Nerve Regeneration – A Schwann Cell Perspective
Authors: Acheta Jenica , Stephens Shannon B. Z. , Belin Sophie , Poitelon Yannick
Published: January 2022

Peripheral nerve injuries are common conditions that can arise from trauma (e.g., compression, severance) and can lead to neuropathic pain as well as motor and sensory deficits. Although much knowledge exists on the mechanisms of injury and nerve regeneration, treatments that ensure functional recovery following peripheral nerve injury are limited. Schwann cells, the supporting glial cells in peripheral nerves, orchestrate the response to nerve injury, by converting to a “repair” phenotype. However, nerve regeneration is often suboptimal in humans as the repair Schwann cells do not sustain their repair phenotype long enough to support the prolonged regeneration times required for successful nerve regrowth. Thus, numerous strategies are currently focused on promoting and extending the Schwann cells repair phenotype. Low-intensity ultrasound (LIU) is a non-destructive therapeutic approach which has been shown to facilitate peripheral nerve regeneration following nerve injury in rodents. Still, clinical trials in humans are scarce and limited to small population sizes. The benefit of LIU on nerve regeneration could possibly be mediated through the repair Schwann cells. In this review, we discuss the known and possible molecular mechanisms activated in response to LIU in repair Schwann cells to draw support and attention to LIU as a compelling regenerative treatment for peripheral nerve injury.
Effects of Cortical Cooling on Sound Processing in Auditory Cortex and Thalamus of Awake Marmosets
Authors: Jeschke Marcus , Ohl Frank W. , Wang Xiaoqin
Published: January 2022

The auditory thalamus is the central nexus of bottom-up connections from the inferior colliculus and top-down connections from auditory cortical areas. While considerable efforts have been made to investigate feedforward processing of sounds in the auditory thalamus (medial geniculate body, MGB) of non-human primates, little is known about the role of corticofugal feedback in the MGB of awake non-human primates. Therefore, we developed a small, repositionable cooling probe to manipulate corticofugal feedback and studied neural responses in both auditory cortex and thalamus to sounds under conditions of normal and reduced cortical temperature. Cooling-induced increases in the width of extracellularly recorded spikes in auditory cortex were observed over the distance of several hundred micrometers away from the cooling probe. Cortical neurons displayed reduction in both spontaneous and stimulus driven firing rates with decreased cortical temperatures. In thalamus, cortical cooling led to increased spontaneous firing and either increased or decreased stimulus driven activity. Furthermore, response tuning to modulation frequencies of temporally modulated sounds and spatial tuning to sound source location could be altered (increased or decreased) by cortical cooling. Specifically, best modulation frequencies of individual MGB neurons could shift either toward higher or lower frequencies based on the vector strength or the firing rate. The tuning of MGB neurons for spatial location could both sharpen or widen. Elevation preference could shift toward higher or lower elevations and azimuth tuning could move toward ipsilateral or contralateral locations. Such bidirectional changes were observed in many parameters which suggests that the auditory thalamus acts as a filter that could be adjusted according to behaviorally driven signals from auditory cortex. Future work will have to delineate the circuit elements responsible for the observed effects.
A Platform for Spatiotemporal “Matrix” Stimulation in Brain Networks Reveals Novel Forms of Circuit Plasticity
Authors: Wilson Nathan R. , Wang Forea L. , Chen Naiyan , Yan Sherry X. , Daitch Amy L. , Shi Bo , Sharma Samvaran , Sur Mriganka
Published: January 2022

Here we demonstrate a facile method by which to deliver complex spatiotemporal stimulation to neural networks in fast patterns, to trigger interesting forms of circuit-level plasticity in cortical areas. We present a complete platform by which patterns of electricity can be arbitrarily defined and distributed across a brain circuit, either simultaneously, asynchronously, or in complex patterns that can be easily designed and orchestrated with precise timing. Interfacing with acute slices of mouse cortex, we show that our system can be used to activate neurons at many locations and drive synaptic transmission in distributed patterns, and that this elicits new forms of plasticity that may not be observable via traditional methods, including interesting measurements of associational and sequence plasticity. Finally, we introduce an automated “network assay” for imaging activation and plasticity across a circuit. Spatiotemporal stimulation opens the door for high-throughput explorations of plasticity at the circuit level, and may provide a basis for new types of adaptive neural prosthetics.
Evaluation of a Newly Developed Smartphone App for Risk Factor Management in Young Patients With Ischemic Stroke: A Pilot Study
Authors: Fruhwirth Viktoria , Berger Lisa , Gattringer Thomas , Fandler-Höfler Simon , Kneihsl Markus , Schwerdtfeger Andreas , Weiss Elisabeth Margarete , Enzinger Christian , Pinter Daniela
Published: January 2022

Background: Efficient treatment of modifiable vascular risk factors decreases reoccurrence of ischemic stroke, which is of uttermost importance in younger patients. In this longitudinal pilot study, we thus assessed the effect of a newly developed smartphone app for risk factor management in such a cohort.

Methods: The app conveys key facts about stroke, provides motivational support for a healthy lifestyle, and a reminder function for medication intake and blood pressure measurement. Between January 2019 and February 2020, we consecutively invited patients with ischemic stroke aged between 18 and 55 years to participate. Patients in the intervention group used the app between hospital discharge and 3-month follow-up. The control group received standard clinical care. Modifiable risk factors (physical activity, nutrition, alcohol consumption, smoking behavior, obesity, and hypertension) were assessed during the initial hospital stay and at a dedicated stroke outpatient department three months post-stroke.

Results: The study cohort comprised 21 patients in the app intervention group (62% male; age = 41 ± 11 years; education = 12 ± 3 years) and 21 sex-, age- and education-matched control patients with a comparable stroke risk factor profile. Baseline stroke severity was comparable between groups (intervention: median NIHSS = 3; control: median NIHSS = 4; p = 0.604). Three months post-stroke, patients in the intervention group reported to be physically almost twice as active (13 ± 9 h/week) compared to controls (7 ± 5 h/week; p = 0.022). More intense app usage was strongly associated with higher physical activity (r = 0.60, p = 0.005) and lower consumption of unhealthy food (r = −0.51, p = 0.023). Smoking behavior (p = 0.001) and hypertension (p = 0.003) improved in all patients. Patients in the intervention group described better self-reported health-related quality of life three months post-stroke (p = 0.003).

Conclusions: Specifically designed app interventions can be an easily to implement and cost-efficient approach to promote a healthier lifestyle in younger patients with a stroke.
Alterations in Neural Networks During Working Memory Encoding Related to Cognitive Impairment in Temporal Lobe Epilepsy
Authors: Pan Liping , Wu Yakun , Bao Jie , Guo Dandan , Zhang Xin , Wang Jiajing , Deng Meili , Yu Peiran , Wei Gaoxu , Zhang Lulin , Qin Xiao , Song Yijun
Published: January 2022

Objective: The aim of the current study was to investigate the alterations in the neural networks of patients with temporal lobe epilepsy (TLE) during working memory (WM) encoding.

Methods: Patients with TLE (n = 52) and healthy volunteers (n = 35) completed a WM task, during which 34-channel electroencephalogram signals were recorded. The neural networks during WM encoding were calculated in TLE patients with (TLE-WM) and without (TLE-N) WM deficits.

Results: Functional connectivity strength decreased, and the theta network was altered in the TLE-WM group, although no significant differences in clinical features were observed between the TLE-N and TLE-WM groups.

Conclusions: Not all patients with TLE present with cognitive impairments and alterations in the theta network were identified in TLE patients with functional cognitive deficits.

Significance: The theta network may represent a sensitive measure of cognitive impairment and could predict cognitive outcomes among patients with TLE.
If You Are Old, Videos Look Slow. The Paradoxical Effect of Age-Related Motor Decline on the Kinematic Interpretation of Visual Scenes
Authors: de’Sperati Claudio , Granato Marco , Moretti Michela
Published: January 2022

Perception and action are tightly coupled. However, there is still little recognition of how individual motor constraints impact perception in everyday life. Here we asked whether and how the motor slowing that accompanies aging influences the sense of visual speed. Ninety-four participants aged between 18 and 90 judged the natural speed of video clips reproducing real human or physical motion (SoS, Sense-of-Speed adjustment task). They also performed a finger tapping task and a visual search task, which estimated their motor speed and visuospatial attention speed, respectively. Remarkably, aged people judged videos to be too slow (speed underestimation), as compared to younger people: the Point of Subjective Equality (PSE), which estimated the speed bias in the SoS task, was +4% in young adults (<40), +12% in old adults (40–70) and +16% in elders. On average, PSE increased with age at a rate of 0.2% per year, with perceptual precision, adjustment rate, and completion time progressively worsening. Crucially, low motor speed, but not low attentional speed, turned out to be the key predictor of video speed underestimation. These findings suggest the existence of a counterintuitive compensatory coupling between action and perception in judging dynamic scenes, an effect that becomes particularly germane during aging.
Single Image-Based Vignetting Correction for Improving the Consistency of Neural Activity Analysis in 2-Photon Functional Microscopy
Authors: Li Dong , Wang Guangyu , Werner René , Xie Hong , Guan Ji-Song , Hilgetag Claus C.
Published: January 2022

High-resolution functional 2-photon microscopy of neural activity is a cornerstone technique in current neuroscience, enabling, for instance, the image-based analysis of relations of the organization of local neuron populations and their temporal neural activity patterns. Interpreting local image intensity as a direct quantitative measure of neural activity presumes, however, a consistent within- and across-image relationship between the image intensity and neural activity, which may be subject to interference by illumination artifacts. In particular, the so-called vignetting artifact—the decrease of image intensity toward the edges of an image—is, at the moment, widely neglected in the context of functional microscopy analyses of neural activity, but potentially introduces a substantial center-periphery bias of derived functional measures. In the present report, we propose a straightforward protocol for single image-based vignetting correction. Using immediate-early gene-based 2-photon microscopic neural image data of the mouse brain, we show the necessity of correcting both image brightness and contrast to improve within- and across-image intensity consistency and demonstrate the plausibility of the resulting functional data.
Combined Structural MR and Diffusion Tensor Imaging Classify the Presence of Alzheimer’s Disease With the Same Performance as MR Combined With Amyloid Positron Emission Tomography: A Data Integration Approach
Authors: Agostinho Daniel , Caramelo Francisco , Moreira Ana Paula , Santana Isabel , Abrunhosa Antero , Castelo-Branco Miguel
Published: January 2022

Background: In recent years, classification frameworks using imaging data have shown that multimodal classification methods perform favorably over the use of a single imaging modality for the diagnosis of Alzheimer’s Disease. The currently used clinical approach often emphasizes the use of qualitative MRI and/or PET data for clinical diagnosis. Based on the hypothesis that classification of isolated imaging modalities is not predictive of their respective value in combined approaches, we investigate whether the combination of T1 Weighted MRI and diffusion tensor imaging (DTI) can yield an equivalent performance as the combination of quantitative structural MRI (sMRI) with amyloid-PET.

Methods: We parcellated the brain into regions of interest (ROI) following different anatomical labeling atlases. For each region of interest different metrics were extracted from the different imaging modalities (sMRI, PiB-PET, and DTI) to be used as features. Thereafter, the feature sets were reduced using an embedded-based feature selection method. The final reduced sets were then used as input in support vector machine (SVM) classifiers. Three different base classifiers were created, one for each imaging modality, and validated using internal (n = 41) and external data from the ADNI initiative (n = 330 for sMRI, n = 148 for DTI and n = 55 for PiB-PET) sources. Finally, the classifiers were ensembled using a weighted method in order to evaluate the performance of different combinations.

Results: For the base classifiers the following performance levels were found: sMRI-based classifier (accuracy, 92%; specificity, 97% and sensitivity, 87%), PiB-PET (accuracy, 91%; specificity, 89%; and sensitivity, 92%) and the lowest performance was attained with DTI (accuracy, 80%; specificity, 76%; and sensitivity, 82%). From the multimodal approaches, when integrating two modalities, the following results were observed: sMRI+PiB-PET (accuracy, 98%; specificity, 98%; and sensitivity, 99%), sMRI+DTI (accuracy, 97%; specificity, 99%; and sensitivity, 94%) and PiB-PET+DTI (accuracy, 91%; specificity, 90%; and sensitivity, 93%). Finally, the combination of all imaging modalities yielded an accuracy of 98%, specificity of 97% and sensitivity of 99%.

Conclusion: Although DTI in isolation shows relatively poor performance, when combined with structural MR, it showed a surprising classification performance which was comparable to MR combined with amyloid PET. These results are consistent with the notion that white matter changes are also important in Alzheimer’s Disease.
rs62139665 Polymorphism in the Promoter Region of EpCAM Is Associated With Hepatitis C Virus-Related Hepatocellular Carcinoma Risk in Egyptians
Authors: Motawi Tarek Mohamed Kamal , Sadik Nermin Abdel Hamid , Sabry Dina , Fahim Sally Atef , Shahin Nancy Nabil
Published: January 2022

Hepatocellular carcinoma (HCC) is a universal health problem that is particularly alarming in Egypt. The major risk factor for HCC is hepatitis C virus (HCV) infection which is a main burden in Egypt. The epithelial cell adhesion molecule (EpCAM) is a stem cell marker involved in the tumorigenesis and progression of many malignancies, including HCC. We investigated the association of -935 C/G single nucleotide polymorphism in EpCAM promoter region (rs62139665) with HCC risk, EpCAM expression and overall survival in Egyptians. A total of 266 patients (128 HCV and 138 HCC cases) and 117 age- and sex-matched controls participated in this study. Genotyping, performed using allelic discrimination and confirmed by sequencing, revealed a significant association between EpCAM rs62139665 and HCC susceptibility, with higher GG genotype and G allele distribution in HCC patients than in non-HCC subjects. Such association was not detected in HCV patients compared to controls. EpCAM gene expression levels, determined in blood by RT-qPCR, and its serum protein expression levels, determined by ELISA, were significantly higher in GG relative to GC+CC genotype carriers in HCV and HCC patients in a recessive model. ROC analysis of EpCAM protein levels revealed significant discriminatory power between HCC patients and non-HCC subjects, with improved diagnostic accuracy when combining α-fetoprotein and EpCAM compared to that of α-fetoprotein alone. Altogether, EpCAM rs62139665 polymorphism is significantly associated with HCC and with EpCAM gene and protein expression levels in the Egyptian population. Moreover, serum EpCAM levels may hold promise for HCC diagnosis and for improving the diagnostic accuracy of α-fetoprotein.
Mapping of Recurrence Sites Following Adjuvant or Salvage Radiotherapy for Prostate Cancer Patients
Authors: Gonzalez-Moya Ana , Supiot Stéphane , Seegers Valérie , Lizée Thibaut , Legouté Florence , Perennec Tanguy , Calais Gilles
Published: January 2022

Introduction

Although salvage and adjuvant radiotherapy (RT) are effective in prostate cancer (PC) patients, 30%–40% of men will have disease progression. The objective was to describe the pattern of recurrence in PC patients with biochemical failure (BF) following postoperative RT.

Methods

We retrospectively analyzed 935 PC patients treated from 2009 to 2019 with adjuvant or salvage RT at the Institut de Cancérologie de l’Ouest. Of these, 205 (22%) developed BF of whom 166 underwent imaging. Patients with identified radiologic failure prior any specific treatment were included to determine the site of relapse categorized as local (L)-only, locoregional (LR), or metastatic (M) recurrence. Main disease characteristics and RT fields were examined in relation to sites of recurrence.

Results

One hundred forty-one patients were identified with 244 sites of failure on imaging. Of these, 108 patients had received RT to the PB alone and 33 RT to the PB and pelvic lymph nodes (PB+PLN). Androgen-deprivation therapy was used concomitantly in 50 patients (35%). The median PSA at imaging was 1.6 ng/ml (range, 0–86.7). In all, 74 patients (52%) had M disease (44% in the PB group and 79% in the PB+PLN group), 61 (43%) had LR failure (52% in the PB alone group and 15% in the PB+PLN group), and six (4%) had L-only failure, at a median of 26.7 months (range, 5–110.3) from RT. Metastases were in extra-pelvic LN (37 (15%)), bones (66 (27%)), and visceral organs (eight (3%)). Fifty-three (48%) of the pelvic LN failures in the PB group would have been encompassed by standard PLN RT volume.

Conclusion

We found that most patients evaluated for BF after postoperative RT recurred outside the RT field. Isolated pelvic nodal failure was rare in those receiving RT to the PB+PLN but accounted for half of failures in those receiving PB alone RT. Imaging directed salvage treatment could be helpful to personalize radiation therapy plan.
Variations in the Consumption of Antimicrobial Medicines in the European Region, 2014–2018: Findings and Implications from ESAC-Net and WHO Europe
Authors: Robertson Jane , Vlahović-Palčevski Vera , Iwamoto Kotoji , Högberg Liselotte Diaz , Godman Brian , Monnet Dominique L. , Garner Sarah , Weist Klaus ,   ESAC-Net Study Group,   WHO Europe AMC Network Study Group
Published: January 2022

Background: Surveillance of antimicrobial consumption (AMC) is important to address inappropriate use. AMC data for countries in the European Union (EU) and European Economic Area (EEA) and Eastern European and Central Asian countries were compared to provide future guidance.

Methods: Analyses of 2014–2018 data from 30 EU/EEA countries of the European Surveillance of Antibiotic Consumption network (ESAC-Net) and 15 countries of the WHO Regional Office for Europe (WHO Europe) AMC Network were conducted using the Anatomical Therapeutic Chemical (ATC) classification and Defined Daily Dose (DDD) methodology. Total consumption (DDD per 1000 inhabitants per day) of antibacterials for systemic use (ATC group J01), relative use (percentages), trends over time, alignment with the WHO Access, Watch, Reserve (AWaRe) classification, concordance with the WHO global indicator (60% of total consumption should be Access agents), and composition of the drug utilization 75% (DU75%) were calculated.

Findings: In 2018, total consumption of antibacterials for systemic use (ATC J01) ranged from 8.9 to 34.1 DDD per 1000 inhabitants per day (population-weighted mean for ESAC-Net 20.0, WHO Europe AMC Network 19.6, ESAC-Net Study Group, and WHO Europe AMC Network Study Group). ESAC-Net countries consumed more penicillins (J01C; 8.7 versus 6.3 DDD per 1000 inhabitants per day), more tetracyclines (J01A; 2.2 versus 1.2), less cephalosporins (J01D; 2.3 versus 3.8) and less quinolones (J01M; 1.7 versus 3.4) than WHO Europe AMC Network countries. Between 2014 and 2018, there were statistically significant reductions in total consumption in eight ESAC-Net countries. In 2018, the relative population-weighted mean consumption of Access agents was 57.9% for ESAC-Net and 47.4% for the WHO Europe AMC Network. For each year during 2014–2018, 14 ESAC-Net and one WHO Europe AMC Network countries met the WHO global monitoring target of 60% of total consumption being Access agents. DU75% analyses showed differences in the choices of agents in the two networks.

Interpretation: Although total consumption of antibacterials for systemic use was similar in the two networks, the composition of agents varied substantially. The greater consumption of Watch group agents in WHO Europe AMC Network countries suggests opportunities for improved prescribing. Significant decreases in consumption in several ESAC-Net countries illustrate the value of sustained actions to address antimicrobial resistance.
Seizures Caused by Exposure to Hyperbaric Oxygen in Rats Can Be Predicted by Early Changes in Electrodermal Activity
Authors: Posada-Quintero Hugo F. , Landon Carol S. , Stavitzski Nicole M. , Dean Jay B. , Chon Ki H.
Published: January 2022

Hyperbaric oxygen (HBO2) is breathed during undersea operations and in hyperbaric medicine. However, breathing HBO2 by divers and patients increases the risk of central nervous system oxygen toxicity (CNS-OT), which ultimately manifests as sympathetic stimulation producing tachycardia and hypertension, hyperventilation, and ultimately generalized seizures and cardiogenic pulmonary edema. In this study, we have tested the hypothesis that changes in electrodermal activity (EDA), a measure of sympathetic nervous system activation, precedes seizures in rats breathing 5 atmospheres absolute (ATA) HBO2. Radio telemetry and a rodent tether apparatus were adapted for use inside a sealed hyperbaric chamber. The tethered rat was free to move inside a ventilated animal chamber that was flushed with air or 100% O2. The animal chamber and hyperbaric chamber (air) were pressurized in parallel at ~1 atmosphere/min. EDA activity was recorded simultaneously with cortical electroencephalogram (EEG) activity, core body temperature, and ambient pressure. We have captured the dynamics of EDA using time-varying spectral analysis of raw EDA (TVSymp), previously developed as a tool for sympathetic tone assessment in humans, adjusted to detect the dynamic changes of EDA in rats that occur prior to onset of CNS-OT seizures. The results show that a significant increase in the amplitude of TVSymp values derived from EDA recordings occurs on average (±SD) 1.9 ± 1.6 min before HBO2-induced seizures. These results, if corroborated in humans, support the use of changes in TVSymp activity as an early “physio-marker” of impending and potentially fatal seizures in divers and patients.
Psychological Health Conditions and COVID-19-Related Stressors Among University Students: A Repeated Cross-Sectional Survey
Authors: Zurlo Maria Clelia , Cattaneo Della Volta Maria Francesca , Vallone Federica
Published: January 2022

The Coronavirus Disease 2019 (COVID-19) pandemic has broadly impacted university students’ customary life, resulting in remarkable levels of stress and psychological suffering. Although the acute phase of the crisis has been overcome, it does not imply that perceived stress related to the risk of contagion and to the changes in the relational life experienced over more than 1 year of the pandemic will promptly and abruptly decrease. This study aims at comparing university students’ psychological health conditions before and during the COVID-19 pandemic, but also at providing information on how psychological health conditions evolved over the 1 year of the pandemic. We analyzed data from a repeated cross-sectional survey on different samples of university students before the pandemic in 2017 (n = 545) and during the pandemic (n = 671). During the pandemic, data were collected at three stages (Stage 1, April 2020 n = 197; Stage 2, November 2020 n = 274; and Stage 3, April 2021 n = 200). The COVID-19 Student Stress Questionnaire (CSSQ) and the Symptom-Checklist-90-Revised (SCL-90-R) were used to assess, respectively, COVID-19-related stressors (Relationships and Academic Life, Isolation, and Fear of Contagion) and the presence of psychological symptoms. Psychological health conditions were compared at baseline and during the pandemic, whereas both psychological health conditions and perceived levels of COVID-19-related stressors were compared over the three pandemic stages. In addition, Logistic Regression was used to explore the associations between COVID-19-related stressors and psychological symptoms. Findings revealed a significant increase in symptoms of Depression (DEP), Phobic-Anxiety (PHOB), Obsessive-Compulsive (O-C), and Psychoticism (PSY) from pre to during the pandemic. Perceived levels of COVID-19-related stress and specific psychological symptoms significantly increased as the pandemic was progressing. COVID-19-related stressors emerged as significantly associated with several psychopathological symptoms. Findings are discussed with the aim of providing tailored interventions to prevent mental disease and promote psychological adjustment in this specific stage of transition within this exceptional global emergency.
Sexual Dimorphism in the Brain Correlates of Adult-Onset Depression: A Pilot Structural and Functional 3T MRI Study
Authors: Piani Maria Chiara , Maggioni Eleonora , Delvecchio Giuseppe , Ferro Adele , Gritti Davide , Pozzoli Sara M. , Fontana Elisa , Enrico Paolo , Cinnante Claudia M. , Triulzi Fabio M. , Stanley Jeffrey A. , Battaglioli Elena , Brambilla Paolo
Published: January 2022

Major Depressive Disorder (MDD) is a disabling illness affecting more than 5% of the elderly population. Higher female prevalence and sex-specific symptomatology have been observed, suggesting that biologically-determined dimensions might affect the disease onset and outcome. Rumination and executive dysfunction characterize adult-onset MDD, but sex differences in these domains and in the related brain mechanisms are still largely unexplored. The present pilot study aimed to explore any interactions between adult-onset MDD and sex on brain morphology and brain function during a Go/No-Go paradigm. We hypothesized to detect diagnosis by sex effects on brain regions involved in self-referential processes and cognitive control. Twenty-four subjects, 12 healthy (HC) (mean age 68.7 y, 7 females and 5 males) and 12 affected by adult-onset MDD (mean age 66.5 y, 5 females and 7 males), underwent clinical evaluations and a 3T magnetic resonance imaging (MRI) session. Diagnosis and diagnosis by sex effects were assessed on regional gray matter (GM) volumes and task-related functional MRI (fMRI) activations. The GM volume analyses showed diagnosis effects in left mid frontal cortex (p < 0.01), and diagnosis by sex effects in orbitofrontal, olfactory, and calcarine regions (p < 0.05). The Go/No-Go fMRI analyses showed MDD effects on fMRI activations in left precuneus and right lingual gyrus, and diagnosis by sex effects on fMRI activations in right parahippocampal gyrus and right calcarine cortex (p < 0.001, ≥ 40 voxels). Our exploratory results suggest the presence of sex-specific brain correlates of adult-onset MDD–especially in regions involved in attention processing and in the brain default mode–potentially supporting cognitive and symptom differences between sexes.
Diagnostic Contribution of the DSM-5 Criteria for Internet Gaming Disorder
Authors: Luo Tao , Wei Dan , Guo Jiangfan , Hu Maorong , Chao Xuelin , Sun Yan , Sun Qian , Xiao Shuiyuan , Liao Yanhui
Published: January 2022

Background: Internet gaming disorder (IGD) can have long-term severe consequences in affected individuals, especially adolescents and young people. Empirical studies of IGD using the DSM-5 criteria are still lacking. This study aimed to evaluate the contribution of specific criteria to the diagnosis of IGD based on the DSM-5 in the context of Chinese culture.

Methods: The Chinese version of the Internet Gaming Disorder Scale–Short Form (IGDS9-SF) was applied to investigate the prevalence of IGD in a general sample of 28,689 middle school students aged 12–19 years from two cities in China.

Results: The prevalence of IGD was 4.6% among this adolescent sample. The group of IGD students reported longer weekly gaming times and worse academic performance than the group of non-IGD students. Although “preoccupation” and “playing to escape” were the most frequently reported criteria, the conditional inference trees showed that “give up other activities,” ‘negative consequences,” and “continue despite problems” contributed most to the diagnosis of IGD based on the DSM-5.

Conclusions: The prevalence of IGD among Chinese adolescents (ages 12–19) was 4.6%. This study provides evidence for retaining or deleting specific diagnostic criteria by the DSM framework in the future.
Effect of Clothing Fabric on 20-km Cycling Performance in Endurance Athletes
Authors: Ferguson Jared , Hadid Amir , Epstein Yoram , Jensen Dennis
Published: January 2022

Purpose: Examine the effect of synthetic fabrics (SYN, 60% polyester: 40% nylon) vs. 100% cotton fabric (CTN) on the 20-km cycling time trial (20 kmCTT) performance of competitive cyclists and triathletes.

Methods: In this randomized controlled crossover study, 15 adults (5 women) aged 29.6 ± 2.7 years (mean ± SE) with a peak rate of O2 consumption of 60.0 ± 2.0 ml/kg/min completed a 20 kmCTT under ambient laboratory conditions (24.3 ± 0.7°C and 17 ± 7% relative humidity) with a simulated wind of ~3 m/s while wearing SYN or CTN clothing ensembles. Both ensembles were of snowflake mesh bi-layer construction and consisted of a loose-fitting long-sleeved shirt with full-length trousers.

Results: Participants maintained a significantly (p < 0.05) higher cycling speed and power output over the last 6-km of the 20 kmCTT while wearing the SYN vs. CTN ensemble (e.g., by 0.98 km/h and 18.4 watts at the 20-km mark). Consequently, 20 kmCTT duration was significantly reduced by 15.7 ± 6.8 sec or 0.8 ± 0.3% during SYN vs. CTN trials (p < 0.05). Improved 20 kmCTT performance with SYN vs. CTN clothing could not be explained by concurrent differences in esophageal temperature, sweat rate, ratings of perceived exertion and/or cardiometabolic responses to exercise. However, it was accompanied by significantly lower mean skin temperatures (~1°C) and more favorable ratings of perceived clothing comfort and thermal sensation during exercise.

Conclusion: Under the experimental conditions of the current study, athletic clothing made of synthetic fabrics significantly improved the 20 kmCTT performance of endurance-trained athletes by optimizing selected thermoregulatory and perceptual responses to exercise.
Inhibition of LRRK2-Rab10 Pathway Improves Secondary Brain Injury After Surgical Brain Injury in Rats
Authors: Li Jie , Wu Muyao , Gong Yating , Tang Jiafeng , Shen Jinchao , Xu Li , Dang Baoqi , Chen Gang
Published: January 2022

Leucine-rich repeat kinase 2 (LRRK2) is considered as a potential target for the treatment of Parkinson's disease. This protein is expressed in the brain and has been associated with various diseases and lysosomal maintenance. Rab10 is a member of the Rab protein GTPase family that has been recently shown to be a kinase substrate of LRRK2. In addition, LRRK2 and its kinase substrate Rab10 constitute a key stress response pathway during lysosomal overload stress. This study aimed to investigate the potential role and mechanism underlying LRRK2 and its kinase substrate Rab10 involving surgical brain injury (SBI). One hundred and forty-four male Sprague-Dawley rats were examined using an SBI model, and some had received the LRRK2-specific inhibitor PF-06447475. Thereafter, western blotting, immunofluorescence, brain water content analysis, neuronal apoptosis assay, and neurological score analysis were conducted. The results showed that after SBI, LRRK2 and phosphorylated Rab10 (p-Rab10) expression in neuronal cells were upregulated, and administration of PF-06447475 significantly reduced neuronal apoptosis, neuroinflammation, and brain water content 12 h after SBI and improved neurological deficit 72 h after SBI, which is related to the decreased expression of LRRK2 and p-Rab10, and the lessening of lysosomal overload stress. Our research suggests that the inhibition of LRRK2 can effectively interfere with the role of p-Rab10 in promoting the secretion of lysosomal hydrolase in lysosomal overload stress after SBI, thereby reducing neuronal apoptosis and inflammation after SBI and playing a major role in brain protection.
Advantages and Limitations of Clinical Scores for Donation After Circulatory Death Liver Transplantation
Authors: Meier Raphael P. H. , Kelly Yvonne , Yamaguchi Seiji , Braun Hillary J. , Lunow-Luke Tyler , Adelmann Dieter , Niemann Claus , Maluf Daniel G. , Dietch Zachary C. , Stock Peter G. , Kang Sang-Mo , Feng Sandy , Posselt Andrew M. , Gardner James M. , Syed Shareef M. , Hirose Ryutaro , Freise Chris E. , Ascher Nancy L. , Roberts John P. , Roll Garrett R.
Published: January 2022

Background: Scoring systems have been proposed to select donation after circulatory death (DCD) donors and recipients for liver transplantation (LT). We hypothesized that complex scoring systems derived in large datasets might not predict outcomes locally.

Methods: Based on 1-year DCD-LT graft survival predictors in multivariate logistic regression models, we designed, validated, and compared a simple index using the University of California, San Francisco (UCSF) cohort (n = 136) and a universal-comprehensive (UC)-DCD score using the United Network for Organ Sharing (UNOS) cohort (n = 5,792) to previously published DCD scoring systems.

Results: The total warm ischemia time (WIT)-index included donor WIT (dWIT) and hepatectomy time (dHep). The UC-DCD score included dWIT, dHep, recipient on mechanical ventilation, transjugular-intrahepatic-portosystemic-shunt, cause of liver disease, model for end-stage liver disease, body mass index, donor/recipient age, and cold ischemia time. In the UNOS cohort, the UC-score outperformed all previously published scores in predicting DCD-LT graft survival (AUC: 0.635 vs. ≤0.562). In the UCSF cohort, the total WIT index successfully stratified survival and biliary complications, whereas other scores did not.

Conclusion: DCD risk scores generated in large cohorts provide general guidance for safe recipient/donor selection, but they must be tailored based on non-/partially-modifiable local circumstances to expand DCD utilization.
DETERMINANTS OF NEET (NOT IN EMPLOYMENT, EDUCATION OR TRAINING) ON THE POLISH LABOUR MARKET
Authors: Rak Anna M.
Published: January 2022

The principal purpose of the study is to identify the individual risk factors of young people becoming the NEET generation on the Polish labour market. The first part of the paper comprises a literature-based overview of definitions of the NEET category based and a presentation of the risk factors of young people becoming NEET. The second part presents the results of empirical analyses conducted employing a questionnaire on a group of 120 individuals, aged 15 through 30, who met all criteria of the NEET definition set forth by the Employment Committee of the EU. The research demonstrates that among the major determinants of young people becoming NEET are financial hardship of their households, low motivation to continue formal education or change professional qualifications, and low level of job-seeking activity.
THE PROBLEM OF ABANDONED PROPERTY AFTER THE ENTRY INTO FORCE OF THE DECREE ON OWNERSHIP AND USE OF LANDS IN THE CAPITAL CITY OF WARSAW
Authors: Amramowska Monika
Published: January 2022

This article attempts to answer the question of whether abandoned property existed in Warsaw after the entry into force of the Decree on Warsaw Lands. Contemporary case law is consistent in the position that within the territory of the capital of Poland, after the entry into force of the Decree on Warsaw Lands, there was no abandoned property given the categorical wording of Article 1 of the Decree that on the date of entry into force, all Warsaw lands are transferred to the municipality of the Capital City of Warsaw. However, post-war doctrine is of the opinion that for the transfer of ownership it was necessary to enter the new owner in the land and mortgage register.
Política exterior como política pública: reflexiones teóricas y metodológicas en marco del caso de la República Argentina
Authors: Fernández Alonso José , Zelicovich Julieta
Published: January 2022

El presente artículo se propone analizar las referencias a la política exterior como política pública en la producción científica contemporánea de la República Argentina. De modo específico, escruta el modo en el que dicha noción fue definida y operacionalizada por la academia durante las últimas décadas. En el análisis de los alcances y limitaciones de tales definiciones y operacionalizaciones, el trabajo proyecta contribuir a las discusiones teórico-metodológicas en torno a la identificación de la política exterior como política pública, y tras ello, a la construcción de puentes entre los campos de estudio dedicados al Análisis de la Política Exterior (APE) dentro de las Relaciones Internacionales (RRII) y de las políticas públicas en la Ciencia Política.