bluuebunny/crossref_metadata_2025 huggingface dataset:
Immediate Postpartum Long-Acting Reversible Contraception: A Comparison Across Six Humanitarian Country Contexts
Authors: Gallagher Meghan C. , Morris Catherine N. , Fatima Aisha , Daniel Rebekah W. , Shire Abdikani Hirsi , Sangwa Bibiche Malilo Matala
Published: April 2021

Postpartum family planning (FP) could prevent more than 30% of maternal deaths by effectively spacing births; this is particularly relevant in humanitarian contexts given that disproportionate maternal death occurs in countries affected by crises. In humanitarian settings, where accessing functional facilities is challenging with security risks that constrain movement, many women are unable to return for their 6-week postpartum visits and thus unable to receive FP counseling and adopt a method that suits their fertility intentions. Thus, immediate postpartum family planning (IPPFP) interventions, focused on long-acting reversible contraception (LARC) and tailored toward humanitarian contexts, could contribute to healthy timing and spacing of pregnancy, particularly among postpartum women, and improve maternal and newborn health. In 2014, Save the Children integrated postpartum intrauterine device (IUD) services into its FP package in emergency settings. In 2017, this expanded to include postpartum implant uptake as well, given updated World Health Organization guidelines. Three countries (Democratic Republic of Congo, Somalia, and Pakistan) opted for higher-intensity programming for IPPFP with a specific focus on LARC. This involved training delivery-room providers on counseling and provision of IPPFP, as well as training antenatal care nurses in counseling pregnant women on IPPFP options. Three countries (Rwanda, Syria, and Yemen) did not implement notable IPPFP interventions, although they provided the standard of care and monitored provision via monthly service delivery data. Using data from 2016 to 2019, we examined trends in immediate postpartum LARC (IPP LARC) uptake and compared countries with higher-intensity IPP LARC interventions to countries providing standard care. Tests of association were performed to assess the significance of these differences. In the country programs with higher-intensity IPPFP interventions, IPP LARC as a percentage of all deliveries was much higher overall during the July 2016–December 2019 period. The IPP LARC intervention had a significant impact on the overall proportion of women and girls who adopted an IUD or implant within the first 48 h of delivery, F(1, 250) = 523.16, p < 0.001. The mean percentage of IPP LARC among all deliveries in intervention country programs was 10.01% as compared to 0.77% in countries providing standard care. Results suggest that there is demand for IPP LARC in humanitarian contexts and that uptake increases when multipronged solutions focusing on provider training, community outreach, and service integration are applied.
Stroma Involvement in Pancreatic Ductal Adenocarcinoma: An Overview Focusing on Extracellular Matrix Proteins
Authors: Liot Sophie , Balas Jonathan , Aubert Alexandre , Prigent Laura , Mercier-Gouy Perrine , Verrier Bernard , Bertolino Philippe , Hennino Ana , Valcourt Ulrich , Lambert Elise
Published: April 2021

Pancreatic cancer is the seventh leading cause of cancer-related deaths worldwide and is predicted to become second in 2030 in industrialized countries if no therapeutic progress is made. Among the different types of pancreatic cancers, Pancreatic Ductal Adenocarcinoma (PDAC) is by far the most represented one with an occurrence of more than 90%. This specific cancer is a devastating malignancy with an extremely poor prognosis, as shown by the 5-years survival rate of 2–9%, ranking firmly last amongst all cancer sites in terms of prognostic outcomes for patients. Pancreatic tumors progress with few specific symptoms and are thus at an advanced stage at diagnosis in most patients. This malignancy is characterized by an extremely dense stroma deposition around lesions, accompanied by tissue hypovascularization and a profound immune suppression. Altogether, these combined features make access to cancer cells almost impossible for conventional chemotherapeutics and new immunotherapeutic agents, thus contributing to the fatal outcomes of the disease. Initially ignored, the Tumor MicroEnvironment (TME) is now the subject of intensive research related to PDAC treatment and could contain new therapeutic targets. In this review, we will summarize the current state of knowledge in the field by focusing on TME composition to understand how this specific compartment could influence tumor progression and resistance to therapies. Attention will be paid to Tenascin-C, a matrix glycoprotein commonly upregulated during cancer that participates to PDAC progression and thus contributes to poor prognosis.
On a Reef Far, Far Away: Anthropogenic Impacts Following Extreme Storms Affect Sponge Health and Bacterial Communities
Authors: Shore Amanda , Sims Jordan A. , Grimes Michael , Howe-Kerr Lauren I. , Grupstra Carsten G. B. , Doyle Shawn M. , Stadler Lauren , Sylvan Jason B. , Shamberger Kathryn E. F. , Davies Sarah W. , Santiago-Vázquez Lory Z. , Correa Adrienne M. S.
Published: April 2021

Terrestrial runoff can negatively impact marine ecosystems through stressors including excess nutrients, freshwater, sediments, and contaminants. Severe storms, which are increasing with global climate change, generate massive inputs of runoff over short timescales (hours to days); such runoff impacted offshore reefs in the northwest Gulf of Mexico (NW GoM) following severe storms in 2016 and 2017. Several weeks after coastal flooding from these events, NW GoM reef corals, sponges, and other benthic invertebrates ∼185 km offshore experienced mortality (2016 only) and/or sub-lethal stress (both years). To assess the impact of storm-derived runoff on reef filter feeders, we characterized the bacterial communities of two sponges, Agelas clathrodes and Xestospongia muta, from offshore reefs during periods of sub-lethal stress and no stress over a three-year period (2016—2018). Sponge-associated and seawater-associated bacterial communities were altered during both flood years. Additionally, we found evidence of wastewater contamination (based on 16S rRNA gene libraries and quantitative PCR) in offshore sponge samples, but not in seawater samples, following these flood years. Signs of wastewater contamination were absent during the no-flood year. We show that flood events from severe storms have the capacity to reach offshore reef ecosystems and impact resident benthic organisms. Such impacts are most readily detected if baseline data on organismal physiology and associated microbiome composition are available. This highlights the need for molecular and microbial time series of benthic organisms in near- and offshore reef ecosystems, and the continued mitigation of stormwater runoff and climate change impacts.
The Barreirinhas Eddies: Stable Energetic Anticyclones in the Near-Equatorial South Atlantic
Authors: Simoes-Sousa Iury T. , Silveira Ilson Carlos A. , Tandon Amit , Flierl Glenn R. , Ribeiro Cesar H. A. , Martins Renato P.
Published: April 2021

We explore the Barreirinhas Eddies, submesoscale vortices generated by the North Brazil Current (NBC) off the Barreirinhas Bight (Brazil, centered at 1.75°S), using vessel-mounted and moored ADCP data, and a Global HYCOM reanalysis. These double-stacked anticyclones with incredibly high Rossby Number O (10)] occur independently at different depths (high Burger number). Anticyclones with Rossby number greater than unity are unstable according to inviscid linear theory, and hence these submesoscale features are not easily observable at mid latitudes. At these low latitudes, they last about a week, allowing characterization by oceanographic surveys. Our analyses suggest this increased stability is due to the joint effect of strong winds, stratification, proximity to the equator, and topography. Heretofore hypothesized via analytical studies and seen in numerical models, our study confirms this stabilization process in observations, and is also a starting point for the description of the submesoscale dynamics in the NBC domain.
Conjunctival Microbiota in Patients With Type 2 Diabetes Mellitus and Influences of Perioperative Use of Topical Levofloxacin in Ocular Surgery
Authors: Zhu Xiangjia , Wei Ling , Rong Xianfang , Zhang Yinglei , Zhang Qian , Wen Xiaofeng , He Wenwen , Zhang Keke , Chen Feng , Wei Lai , Lu Yi
Published: April 2021

Background: Patients with type 2 diabetes mellitus (T2DM) are prone to ocular surface infections. We therefore characterized the conjunctival microbiome of T2DM patients and the influence of topical levofloxacin to investigate whether a dysbiosis is associated with this phenomenon.

Methods: Conjunctival microbiome of 79 T2DM patients and 113 non-diabetic controls was profiled using the 16S rDNA sequencing approach. Furthermore, 21 T2DM and 14 non-diabetic patients who underwent cataract surgeries were followed up perioperatively and the influence of pre- and post-operative levofloxacin on the conjunctival microbiome was further investigated prospectively and compared longitudinally.

Results: The α-diversity of the conjunctival microbiota was significantly higher in T2DM patients than in controls (P < 0.05). Significant differences in both composition and function of the conjunctival microbiome were identified on the ocular surface of T2DM patients as compared to non-diabetic controls. Particularly, phylum Bacteroidetes and Fusobacteria, genus Pseudomonas, Haemophilus, and Empedobacter were enriched, while genus Streptococcus was reduced on the T2DM ocular surface. Microbial genes functioning of bacterial chemotaxis was elevated in the conjunctival microbiome of T2DM patients. Furthermore, compared to the initial status, several genera including Staphylococcus were more abundant in the conjunctival microbiome of T2DM patients after 3-days use of preoperative levofloxacin topically, while no genus was more abundant in the non-diabetic follow-up group. No difference was observed between initial status and 7 days after ceasing all postoperative medications in both diabetic and non-diabetic follow-up groups.

Conclusions: The conjunctival microbiome of T2DM patients was more complex and may respond differently to topical antibiotics.
Alterations of Phagocytic Activity and Capacity in Granulocytes and Monocytes Depend on the Pathogen Strain in Porcine Polytrauma
Authors: Vollrath Jan Tilmann , Klingebiel Felix , Bläsius Felix Marius , Greven Johannes , Bolierakis Eftychios , Janicova Andrea , Dunay Ildiko Rita , Hildebrand Frank , Marzi Ingo , Relja Borna
Published: April 2021

Background: Polytraumatized patients undergo a strong immunological stress upon insult. Phagocytes (granulocytes and monocytes) play a substantial role in immunological defense against bacteria, fungi and yeast, and in the clearance of cellular debris after tissue injury. We have reported a reduced monocytes phagocytic activity early after porcine polytrauma before. However, it is unknown if both phagocyte types undergo those functional alterations, and if there is a pathogen-specific phagocytic behavior. We characterized the phagocytic activity and capacity of granulocytes and monocytes after polytrauma.

Methods: Eight pigs (Sus scrofa) underwent polytrauma consisting of lung contusion, liver laceration, tibial fracture and hemorrhagic shock with fluid resuscitation and fracture fixation with external fixator. Intensive care treatment including mechanical ventilation for 72 h followed. Phagocytic activity and capacity were investigated using an in vitro ex vivo whole blood stimulation phagocytosis assays before trauma, after surgery, 24, 48, and 72 h after trauma. Blood samples were stimulated with Phorbol-12-myristate-13-acetate and incubated with FITC-labeled E. coli, S. aureus or S. cerevisiae for phagocytosis assessment by flow cytometry.

Results: Early polytrauma-induced significant increase of granulocytes and monocytes declined to baseline values within 24 h. Percentage of E. coli-phagocytizing granulocytes significantly decreased after polytrauma and during further intensive care treatment, while their capacity significantly increased. Interestingly, both granulocytic phagocytic activity and capacity of S. aureus significantly decreased after trauma, although a recovery was observed after 24 h and yet was followed by another decrease. The percentage of S. cerevisiae-phagocytizing granulocytes significantly increased after 24 h, while their impaired capacity after surgery and 72 h later was detected. Monocytic E. coli-phagocytizing percentage did not change, while their capacity increased after 24–72 h. After a significant decrease in S. aureus-phagocytizing monocytes after surgery, a significant increase after 24 and 48 h was observed without capacity alterations. No significant changes in S. cerevisiae-phagocytizing monocytes occurred, but their capacity dropped 48 and 72 h.

Conclusion: Phagocytic activity and capacity of granulocytes and monocytes follow a different pattern and significantly change within 72 h after polytrauma. Both phagocytic activity and capacity show significantly different alterations depending on the pathogen strain, thus potentially indicating at certain and possibly more relevant infection causes after polytrauma.
SARS-CoV-2 Diagnostic Tests: Algorithm and Field Evaluation From the Near Patient Testing to the Automated Diagnostic Platform
Authors: Yin Nicolas , Debuysschere Cyril , Decroly Marc , Bouazza Fatima-Zohra , Collot Vincent , Martin Charlotte , Ponthieux Fanny , Dahma Hafid , Gilbert Marius , Wautier Magali , Duterme Cecile , De Vos Nathalie , Delforge Marie-Luce , Malinverni Stefano , Cotton Frédéric , Bartiaux Magali , Hallin Marie
Published: April 2021

Introduction:Since the first wave of COVID-19 in Europe, new diagnostic tools using antigen detection and rapid molecular techniques have been developed. Our objective was to elaborate a diagnostic algorithm combining antigen rapid diagnostic tests, automated antigen dosing and rapid molecular tests and to assess its performance under routine conditions.

Methods:An analytical performance evaluation of four antigen rapid tests, one automated antigen dosing and one molecular point-of-care test was performed on samples sent to our laboratory for a SARS-CoV-2 reverse transcription PCR. We then established a diagnostic algorithm by approaching median viral loads in target populations and evaluated the limit of detection of each test using the PCR cycle threshold values. A field performance evaluation including a clinical validation and a user-friendliness assessment was then conducted on the antigen rapid tests in point-of-care settings (general practitioners and emergency rooms) for outpatients who were symptomatic for <7 days. Automated antigen dosing was trialed for the screening of asymptomatic inpatients.

Results:Our diagnostic algorithm proposed to test recently symptomatic patients using rapid antigen tests, asymptomatic patients using automated tests, and patients requiring immediate admission using molecular point-of-care tests. Accordingly, the conventional reverse transcription PCR was kept as a second line tool. In this setting, antigen rapid tests yielded an overall sensitivity of 83.3% (not significantly different between the four assays) while the use of automated antigen dosing would have spared 93.5% of asymptomatic inpatient screening PCRs.

Conclusion:Using tests not considered the “gold standard” for COVID-19 diagnosis on well-defined target populations allowed for the optimization of their intrinsic performances, widening the scale of our testing arsenal while sparing molecular resources for more seriously ill patients.
Gentamicin Combined With Hypoionic Shock Rapidly Eradicates Aquaculture Bacteria in vitro and in vivo
Authors: Gao Yuanyuan , Chen Zhongyu , Yao Wei , Li Daliang , Fu Xinmiao
Published: April 2021

Bacterial pathogens are a major cause of infectious diseases in aquatic animals. The abuse of antibiotics in the aquatic industry has led to the proliferation of antibiotic resistance. It is therefore essential to develop more effective and safer strategies to increase the efficacy and extend the life span of the antibiotics used in aquaculture. In this study, we show that six aquaculture bacterial pathogens (i.e., Aeromonas hydrophila, Vibrio alginolyticus, Edwardsiella tarda, Streptococcus iniae, Vibrio harveyi, and Vibrio fluvialis) in the stationary phase can be rapidly killed after immersion in gentamicin- or neomycin-containing, ion-free solutions for a few minutes. Such hypoionic shock treatment enhances the bacterial uptake of gentamicin in an ATP-dependent manner. Importantly, we demonstrate, as a proof of concept, that gentamicin under hypoionic shock conditions can effectively kill A. hydrophila in vivo in a skin infection model of zebrafish (Danio rerio), completely curing the infected fish. Given that pathogenic bacteria generally adhere to the skin surface and gills of aquatic animals, our strategy is of potential significance for bacterial infection control, especially for small-scale economic fish farming and ornamental fish farming. Further, the combined treatment can be completed within 5 min with a relatively small volume of solution, thus minimizing the amount of residual antibiotics in both animals and the environment.
Pectin Induced Colony Expansion of Soil-Derived Flavobacterium Strains
Authors: Kraut-Cohen Judith , Shapiro Orr H. , Dror Barak , Cytryn Eddie
Published: April 2021

The genus Flavobacterium is characterized by the capacity to metabolize complex organic compounds and a unique gliding motility mechanism. Flavobacteria are often abundant in root microbiomes of various plants, but the factors contributing to this high abundance are currently unknown. In this study, we evaluated the effect of various plant-associated poly- and mono-saccharides on colony expansion of two Flavobacterium strains. Both strains were able to spread on pectin and other polysaccharides such as microcrystalline cellulose. However, only pectin (but not pectin monomers), a component of plant cell walls, enhanced colony expansion on solid surfaces in a dose- and substrate-dependent manner. On pectin, flavobacteria exhibited bi-phasic motility, with an initial phase of rapid expansion, followed by growth within the colonized area. Proteomic and gene expression analyses revealed significant induction of carbohydrate metabolism related proteins when flavobacteria were grown on pectin, including selected SusC/D, TonB-dependent glycan transport operons. Our results show a positive correlation between colony expansion and the upregulation of proteins involved in sugar uptake, suggesting an unknown linkage between specific operons encoding for glycan uptake and metabolism and flavobacterial expansion. Furthermore, within the context of flavobacterial-plant interactions, they suggest that pectin may facilitate flavobacterial expansion on plant surfaces in addition to serving as an essential carbon source.
Transneuronal Degeneration in the Brain During Glaucoma
Authors: You Mengling , Rong Rong , Zeng Zhou , Xia Xiaobo , Ji Dan
Published: April 2021

The death of retinal ganglion cells (RGCs) is a key factor in the pathophysiology of all types of glaucoma, but the mechanism of pathogenesis of glaucoma remains unclear. RGCs are a group of central nervous system (CNS) neurons whose soma are in the inner retina. The axons of RGCs form the optic nerve and converge at the optic chiasma; from there, they project to the visual cortex via the lateral geniculate nucleus (LGN). In recent years, there has been increasing interest in the dysfunction and death of CNS and retinal neurons caused by transneuronal degeneration of RGCs, and the view that glaucoma is a widespread neurodegenerative disease involving CNS damage appears more and more frequently in the literature. In this review, we summarize the current knowledge of LGN and visual cortex neuron damage in glaucoma and possible mechanisms behind the damage. This review presents an updated and expanded view of neuronal damage in glaucoma, and reveals new and potential targets for neuroprotection and treatment.
A Semi-active Exoskeleton Based on EMGs Reduces Muscle Fatigue When Squatting
Authors: Wang Zhuo , Wu Xinyu , Zhang Yu , Chen Chunjie , Liu Shoubin , Liu Yida , Peng Ansi , Ma Yue
Published: April 2021

In dynamic manufacturing and warehousing environments, the work scene made it impossible for workers to sit, so workers suffer from muscle fatigue of the lower limb caused by standing or squatting for a long period of time. In this paper, a semi-active exoskeleton used to reduce the muscle fatigue of the lower limb was designed and evaluated. (i) Background: The advantages and disadvantages of assistive exoskeletons developed for industrial purposes were introduced. (ii) Simulation: The process of squatting was simulated in the AnyBody.7.1 software, the result showed that muscle activity of the gluteus maximus, rectus femoris, vastus medialis, vastus lateralis, vastus intermedius, and erector spinae increased with increasing of knee flexion angle. (iii) Design: The exoskeleton was designed with three working modes: rigid-support mode, elastic-support mode and follow mode. Rigid-support mode was suitable for scenes where the squatting posture is stable, while elastic-support mode was beneficial for working environments where the height of squatting varied frequently.The working environments were identified intelligently based on the EMGs of the gluteus maximus, and quadriceps, and the motor was controlled to switch the working mode between rigid-support mode and elastic-support mode. In follow mode, the exoskeleton moves freely with users without interfering with activities such as walking, ascending and descending stairs. (iv) Experiments: Three sets of experiments were conducted to evaluate the effect of exoskeleton. Experiment one was conducted to measure the surface electromyography signal (EMGs) in both condition of with and without exoskeleton, the root mean square of EMGs amplitude of soleus, vastus lateralis, vastus medialis, gastrocnemius, vastus intermedius, rectus femoris, gluteus maximus, and erector spinae were reduced by 98.5, 97.89, 80.09, 77.27, 96.73, 94.17, 70.71, and 36.32%, respectively, with the assistance of the exoskeleton. The purpose of experiment two was aimed to measure the plantar pressure with and without exoskeleton. With exoskeleton, the percentage of weight through subject's feet was reduced by 63.94, 64.52, and 65.61% respectively at 60°, 90°, and 120° of knee flexion angle, compared to the condition of without exoskeleton. Experiment three was purposed to measure the metabolic cost at a speed of 4 and 5 km/h with and without exoskeleton. Experiment results showed that the average additional metabolic cost introduced by exoskeleton was 2.525 and 2.85%. It indicated that the exoskeleton would not interfere with the movement of the wearer Seriously in follow mode. (v) Conclusion: The exoskeleton not only effectively reduced muscle fatigue, but also avoided interfering with the free movement of the wearer.
Gene Therapy in Movement Disorders: A Systematic Review of Ongoing and Completed Clinical Trials
Authors: Merola Aristide , Kobayashi Noelle , Romagnolo Alberto , Wright Brenton A. , Artusi Carlo Alberto , Imbalzano Gabriele , Litvan Irene , Van Laar Amber D. , Bankiewicz Krystof
Published: April 2021

Introduction:We sought to provide an overview of the published and currently ongoing movement disorders clinical trials employing gene therapy, defined as a technology aiming to modulate the expression of one or more genes to achieve a therapeutic benefit.

Methods:We systematically reviewed movement disorders gene therapy clinical trials from PubMed andClinicalTrials.govusing a searching strategy that included Parkinson disease (PD), Huntington disease (HD), amino acid decarboxylase (AADC) deficiency, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), dystonia, tremor, ataxia, and other movement disorders. Data extracted included study characteristics, investigational product, route of administration, safety/tolerability, motor endpoints, and secondary outcomes (i.e., neuroimaging, biomarkers).

Results:We identified a total of 46 studies focusing on PD (21 published and nine ongoing), HD (2 published and 5 ongoing), AADC deficiency (4 published and 2 ongoing), MSA (2 ongoing), and PSP (1 ongoing). In PD, intraparenchymal infusion of viral vector-mediated gene therapies demonstrated to be safe and showed promising preliminary data in trials aiming at restoring the synthesis of dopamine, enhancing the production of neurotrophic factors, or modifying the functional interaction between different nodes of the basal ganglia. In HD, monthly intrathecal delivery of an antisense oligonucleotide (ASO) targeting the huntingtin protein (HTT) mRNA proved to be safe and tolerable, and demonstrated a dose-dependent reduction of the cerebrospinal fluid levels of mutated HTT, while a small phase-I study testing implantable capsules of cells engineered to synthesize ciliary neurotrophic factor failed to show consistent drug delivery. In AADC deficiency, gene replacement studies demonstrated to be relatively safe in restoring catecholamine and serotonin synthesis, with promising outcomes. Ongoing movement disorders clinical trials are focusing on a variety of gene therapy approaches including alternative viral vector serotypes, novel recombinant genes, novel delivery techniques, and ASOs for the treatment of HD, MSA, and distinct subtypes of PD (LRRK2 mutation or GBA1 mutation carriers).

Conclusion:Initial phase-I and -II studies tested the safety and feasibility of gene therapy in PD, HD, and AADC deficiency. The ongoing generation of clinical trials aims to test the efficacy of these approaches and explore additional applications for gene therapy in movement disorders.
Phosphate Brain Energy Metabolism and Cognition in Alzheimer’s Disease: A Spectroscopy Study Using Whole-Brain Volume-Coil 31Phosphorus Magnetic Resonance Spectroscopy at 7Tesla
Authors: Das Namrata , Ren Jimin , Spence Jeffrey , Chapman Sandra Bond
Published: April 2021

Introduction

Mitochondrial dysfunction is a neurometabolic hallmark signaling abnormal brain energy metabolism (BEM) targeted as a potential early marker of Alzheimer’s disease (AD). Advanced imaging technologies, such as 31phosphorus magnetic resonance spectroscopy (31P MRS) at ultra-high-field (UHF) magnetic strength 7T, provide sensitive phosphate-BEM (p-BEM) data with precision. The study’s first goal was to develop a methodology to measure phosphate energy and membrane metabolites simultaneously across the whole-brain using volume-coil 31P MRS at 7T in three groups-cognitively normal (CN), amnestic mild cognitive impairment (aMCI), and AD. The second aim investigated whether p-BEM markers in the four brain regions-frontal, temporal, parietal, and occipital were significantly different across the three groups. The final goal examined correspondence between the p-BEM markers and cognition in the three groups.

Methods

Forty-one participants (CN = 15, aMCI = 15, AD = 11) were enrolled and completed cognitive assessment and scan. The cognitive domains included executive function (EF), memory, attention, visuospatial skills, and language. The p-BEM markers were measured using energy reserve index (PCr/t-ATP), energy consumption index (intracellular_Pi/t-ATP), metabolic state indicator (intracellular_Pi/PCr), and regulatory co-factors [magnesium (Mg2+) and intracellular pH].

Results

Thirteen metabolites were measured simultaneously from the whole brain for all three group with high spectral resolution at UHF. In the aMCI group, a lower p-BEM was observed compared to CN group based on two markers, i.e., energy reserve (p = 0.009) and energy consumption (p = 0.05) indices; whereas in AD a significant increase was found in metabolic stress indicator (p = 0.007) and lower Mg2+ (p = 0.004) in the temporal lobes compared to aMCI using ANOVA between group analytical approach. Finally, using a linear mixed model, a significant positive correlation was found between Mg2+ and cognitive performance of memory (p = 0.013), EF (p = 0.023), and attention (p = 0.0003) in CN but not in aMCI or AD.

Conclusion

To our knowledge, this is the first study to show that it is possible to measure p-BEM in vivo with precision at UHF across the three groups. Moreover, the findings suggest that p-BEM may be compromised in aMCI even before an AD diagnosis, which in future studies should explore to examine whether this energy crisis contributes to some of the earliest neuropathophysiologic changes in AD.
Behaviors Related to Psychiatric Disorders and Pain Perception in C57BL/6J Mice During Different Phases of Estrous Cycle
Authors: Zhao Weinan , Li Qing , Ma Yu , Wang Zhiyong , Fan Bingqian , Zhai Xiaojing , Hu Mengfan , Wang Qing , Zhang Moruo , Zhang Chunyan , Qin Yixue , Sha Sha , Gan Zhonghao , Ye Fan , Xia Yihan , Zhang Guangchao , Yang Li , Zou Shiya , Xu Zheng , Xia Sunhui , Yu Yumei , Abdul Mannan , Yang Jun-Xia , Cao Jun-Li , Zhou Fang , Zhang Hongxing
Published: April 2021

Robust sex difference among humans regarding psychiatry- and pain-related behaviors is being researched; however, the use of female mice in preclinical research is relatively rare due to an unchecked potential behavioral variation over the estrous cycle. In the present study, a battery of psychiatry- and pain-related behaviors are examined under physiological condition in female C57BL/6J mice over different estrous cycle phases: proestrus, estrous, metestrous, diestrous. Our behavioral results reveal that there is no significant difference over different phases of the estrous cycle in social interaction test, sucrose preference test, tail suspension test, open field test, marble burying test, novelty-suppressed feeding test, Hargreaves thermal pain test, and Von Frey mechanical pain test. These findings implicate those psychiatry- and pain-related behaviors in normal female C57BL/6J mice appear to be relatively consistent throughout the estrous cycle; the estrous cycle might not be a main contributor to female C57BL/6J mice’s variability of behaviors.
Comparison of Artificial and Spiking Neural Networks on Digital Hardware
Authors: Davidson Simon , Furber Steve B.
Published: April 2021

Despite the success of Deep Neural Networks—a type of Artificial Neural Network (ANN)—in problem domains such as image recognition and speech processing, the energy and processing demands during both training and deployment are growing at an unsustainable rate in the push for greater accuracy. There is a temptation to look for radical new approaches to these applications, and one such approach is the notion that replacing the abstract neuron used in most deep networks with a more biologically-plausible spiking neuron might lead to savings in both energy and resource cost. The most common spiking networks use rate-coded neurons for which a simple translation from a pre-trained ANN to an equivalent spike-based network (SNN) is readily achievable. But does the spike-based network offer an improvement of energy efficiency over the original deep network? In this work, we consider the digital implementations of the core steps in an ANN and the equivalent steps in a rate-coded spiking neural network. We establish a simple method of assessing the relative advantages of rate-based spike encoding over a conventional ANN model. Assuming identical underlying silicon technology we show that most rate-coded spiking network implementations will not be more energy or resource efficient than the original ANN, concluding that more imaginative uses of spikes are required to displace conventional ANNs as the dominant computing framework for neural computation.
Cerebrospinal Fluid Neurofilament Light Chain (NfL) Predicts Disease Aggressiveness in Amyotrophic Lateral Sclerosis: An Application of the D50 Disease Progression Model
Authors: Dreger Marie , Steinbach Robert , Gaur Nayana , Metzner Klara , Stubendorff Beatrice , Witte Otto W. , Grosskreutz Julian
Published: April 2021

Amyotrophic lateral sclerosis (ALS) is a relentlessly progressive neurodegenerative disorder. As previous therapeutic trials in ALS have been severely hampered by patients’ heterogeneity, the identification of biomarkers that reliably reflect disease progression represents a priority in ALS research. Here, we used the D50 disease progression model to investigate correlations between cerebrospinal fluid (CSF) neurofilament light chain (NfL) levels and disease aggressiveness. The D50 model quantifies individual disease trajectories for each ALS patient. The value D50 provides a unified measure of a patient’s overall disease aggressiveness (defined as time taken in months to lose 50% of functionality). The relative D50 (rD50) reflects the individual disease covered and can be calculated for any time point in the disease course. We analyzed clinical data from a well-defined cohort of 156 patients with ALS. The concentration of NfL in CSF samples was measured at two different laboratories using the same procedure. Based on patients’ individual D50 values, we defined subgroups with high (<20), intermediate (20–40), or low (>40) disease aggressiveness. NfL levels were compared between these subgroups via analysis of covariance, using an array of confounding factors: age, gender, clinical phenotype, frontotemporal dementia, rD50-derived disease phase, and analyzing laboratory. We found highly significant differences in NfL concentrations between all three D50 subgroups (p < 0.001), representing an increase of NfL levels with increasing disease aggressiveness. The conducted analysis of covariance showed that this correlation was independent of gender, disease phenotype, and phase; however, age, analyzing laboratory, and dementia significantly influenced NfL concentration. We could show that CSF NfL is independent of patients’ disease covered at the time of sampling. The present study provides strong evidence for the potential of NfL to reflect disease aggressiveness in ALS and in addition proofed to remain at stable levels throughout the disease course. Implementation of CSF NfL as a potential read-out for future therapeutic trials in ALS is currently constrained by its demonstrated susceptibility to (pre-)analytical variations. Here we show that the D50 model enables the discovery of correlations between clinical characteristics and CSF analytes and can be recommended for future studies evaluating potential biomarkers.
Effect of Long-Term Frozen Storage on Health-Promoting Compounds and Antioxidant Capacity in Baby Mustard
Authors: Zhang Fen , Zhang Jiaqi , Di Hongmei , Xia Pingxin , Zhang Chenlu , Wang Zihan , Li Zhiqing , Huang Shuya , Li Mengyao , Tang Yi , Luo Ya , Li Huanxiu , Sun Bo
Published: April 2021

This study investigated the effects of blanching and subsequent long-term frozen storage on the retention of health-promoting compounds and antioxidant capacity in frozen lateral buds of baby mustard. Results showed that all glucosinolates were well preserved during frozen storage, and 72.48% of total glucosinolate content was retained in the unblanched treatment group after 8 months, as were chlorophylls, carotenoids, ascorbic acid, total phenolics, soluble sugars, soluble proteins, and antioxidant capacity. The loss of nutritional qualities mainly occurred in the 1st month of frozen storage, and nutritional qualities in the unblanched treatment group were significantly better than those in the blanched treatment group during frozen storage. Blanching before freezing reduced contents of high-content glucosinolates and ascorbic acid, as well as antioxidant capacity levels. Therefore, we recommend using long-term frozen storage to preserve the quality of baby mustard to achieve annual supply, and freezing without blanching.
Multi-Omics Analysis of Brain Metastasis Outcomes Following Craniotomy
Authors: Su Jing , Song Qianqian , Qasem Shadi , O’Neill Stacey , Lee Jingyun , Furdui Cristina M. , Pasche Boris , Metheny-Barlow Linda , Masters Adrianna H. , Lo Hui-Wen , Xing Fei , Watabe Kounosuke , Miller Lance D. , Tatter Stephen B. , Laxton Adrian W. , Whitlow Christopher T. , Chan Michael D. , Soike Michael H. , Ruiz Jimmy
Published: April 2021

Background

The incidence of brain metastasis continues to increase as therapeutic strategies have improved for a number of solid tumors. The presence of brain metastasis is associated with worse prognosis but it is unclear if distinctive biomarkers can separate patients at risk for CNS related death.

Methods

We executed a single institution retrospective collection of brain metastasis from patients who were diagnosed with lung, breast, and other primary tumors. The brain metastatic samples were sent for RNA sequencing, proteomic and metabolomic analysis of brain metastasis. The primary outcome was distant brain failure after definitive therapies that included craniotomy resection and radiation to surgical bed. Novel prognostic subtypes were discovered using transcriptomic data and sparse non-negative matrix factorization.

Results

We discovered two molecular subtypes showing statistically significant differential prognosis irrespective of tumor subtype. The median survival time of the good and the poor prognostic subtypes were 7.89 and 42.27 months, respectively. Further integrated characterization and analysis of these two distinctive prognostic subtypes using transcriptomic, proteomic, and metabolomic molecular profiles of patients identified key pathways and metabolites. The analysis suggested that immune microenvironment landscape as well as proliferation and migration signaling pathways may be responsible to the observed survival difference.

Conclusion

A multi-omics approach to characterization of brain metastasis provides an opportunity to identify clinically impactful biomarkers and associated prognostic subtypes and generate provocative integrative understanding of disease.
Development of a Prognostic AI-Monitor for Metastatic Urothelial Cancer Patients Receiving Immunotherapy
Authors: Trebeschi Stefano , Bodalal Zuhir , van Dijk Nick , Boellaard Thierry N. , Apfaltrer Paul , Tareco Bucho Teresa M. , Nguyen-Kim Thi Dan Linh , van der Heijden Michiel S. , Aerts Hugo J. W. L. , Beets-Tan Regina G. H.
Published: April 2021

Background: Immune checkpoint inhibitor efficacy in advanced cancer patients remains difficult to predict. Imaging is the only technique available that can non-invasively provide whole body information of a patient's response to treatment. We hypothesize that quantitative whole-body prognostic information can be extracted by leveraging artificial intelligence (AI) for treatment monitoring, superior and complementary to the current response evaluation methods.

Methods: To test this, a cohort of 74 stage-IV urothelial cancer patients (37 in the discovery set, 37 in the independent test, 1087 CTs), who received anti-PD1 or anti-PDL1 were retrospectively collected. We designed an AI system [named prognostic AI-monitor (PAM)] able to identify morphological changes in chest and abdominal CT scans acquired during follow-up, and link them to survival.

Results: Our findings showed significant performance of PAM in the independent test set to predict 1-year overall survival from the date of image acquisition, with an average area under the curve (AUC) of 0.73 (p < 0.001) for abdominal imaging, and 0.67 AUC (p < 0.001) for chest imaging. Subanalysis revealed higher accuracy of abdominal imaging around and in the first 6 months of treatment, reaching an AUC of 0.82 (p < 0.001). Similar accuracy was found by chest imaging, 5–11 months after start of treatment. Univariate comparison with current monitoring methods (laboratory results and radiological assessments) revealed higher or similar prognostic performance. In multivariate analysis, PAM remained significant against all other methods (p < 0.001), suggesting its complementary value in current clinical settings.

Conclusions: Our study demonstrates that a comprehensive AI-based method such as PAM, can provide prognostic information in advanced urothelial cancer patients receiving immunotherapy, leveraging morphological changes not only in tumor lesions, but also tumor spread, and side-effects. Further investigations should focus beyond anatomical imaging. Prospective studies are warranted to test and validate our findings.
Neurological and Cognitive Performance After Childhood Encephalitis
Authors: Pöyhönen Heidi , Setänen Sirkku , Isaksson Nea , Nyman Mikko , Nyman Anna , Peltola Ville , Lähdesmäki Tuire
Published: April 2021

Background: Children with encephalitis have increased risk for long-term neurological sequelae. We investigated minor neurological dysfunction (MND) and cognitive performance as a measurement for long-term outcome of encephalitis in childhood.

Materials and Methods: Children with encephalitis (n = 98) treated in Turku University Hospital during the years 1995–2016 were retrospectively identified. We included the patients without severe developmental delay before the encephalitis and without recorded neurological disability caused by encephalitis. MND was assessed using the Touwen examination. Age-appropriate Wechsler Intelligence Scale was used to determine the full-scale intelligence quotient (IQ). Residual symptoms in everyday life were evaluated using a questionnaire.

Results: Forty-two subjects participated in the study and returned the questionnaire regarding residual symptoms. The median age was 4.3 years at the time of encephalitis, and 11.3 years at the time of the Touwen examination (n = 41) and the cognitive assessment (n = 38). The Touwen examination indicated MND in 29 of 41 participants (71%; simple MND in 16 and complex MND in 13 patients). The median full-scale IQ was lower in participants with MND compared with participants without MND (98 vs. 110, p = 0.02). Participants with IQ < 85 (n = 5) had lower median age at acute encephalitis compared to participants with IQ ≥ 85 (n = 33) (1.8 vs. 5.3 years, p = 0.03). Problems in daily performance were reported in participant with MND (p = 0.2) and low full-scale IQ (p = 0.008).

Conclusions: The prevalence of MND was high and it was related to lower cognitive performance after childhood encephalitis. Younger age at acute encephalitis was a risk factor for lower cognitive performance.
Job Insecurity and Employees’ Extra-Role Behavior: Moderated Mediation Model of Negative Emotion and Workplace Friendship
Authors: Yu Shengxian , Wu Na , Liu Shanshi , Gong Xiaoxiao
Published: April 2021

Based on the affective events theory, this paper discusses the influence of job insecurity on employees’ extra-role behavior. The mediating effect of negative emotion and the moderating effect of workplace friendship are also tested. The results of an empirical analysis, based on the data of 327 employees, show that job insecurity has a significant negative impact on employees’ extra-role behavior. Negative emotion plays a mediating role in the relationship between job insecurity and extra-role behavior. Workplace friendship moderated the relationship between job insecurity and negative emotions, as well as between job insecurity and extra-role behavior. Workplace friendship also moderates the mediating effect of negative emotion on the relationship between job insecurity and extra-role behavior, that is, the higher the level of the workplace friendship is, the weaker the mediation role mentioned above will be. The research results have implications for the sustainable development of the organization.
Young People Who Meaningfully Improve Are More Likely to Mutually Agree to End Treatment
Authors: Edbrooke-Childs Julian , Costa da Silva Luís , Čuš Anja , Liverpool Shaun , Pinheiro Mota Catarina , Pietrabissa Giada , Bardsley Thomas , Sales Celia M. D. , Ulberg Randi , Jacob Jenna , Ferreira Nuno
Published: April 2021

Objective: Symptom improvement is often examined as an indicator of a good outcome of accessing mental health services. However, there is little evidence of whether symptom improvement is associated with other indicators of a good outcome, such as a mutual agreement to end treatment. The aim of this study was to examine whether young people accessing mental health services who meaningfully improved were more likely to mutually agree to end treatment.

Methods: Multilevel multinomial regression analysis controlling for age, gender, ethnicity, and referral source was conducted on N = 8,995 episodes of care [Female = 5,469, 61%; meanAge = 13.66 (SD = 2.87) years] using anonymised administrative data from young people's mental health services.

Results: Compared to young people with no change in mental health difficulties, those showing positive meaningful changes in mental health difficulties were less likely to have case closure due to non-mutual agreement (Odds Ratio or OR = 0.58, 95% Confidence Interval or CI = 0.50–0.61). Similarly, they were less likely to transfer (OR = 0.61, 95% CI = 0.49–0.74) or end treatment for other reasons (OR = 0.59, 95% CI = 0.50–0.70) than by case closure due to mutual agreement.

Conclusion: The findings suggest that young people accessing mental health services whose symptoms meaningfully improve are more likely to mutually agree to end treatment, adding to the evidence that symptom improvement may be appropriate to examine as an indicator of a good outcome of accessing mental health services.
Impulsivity-Compulsivity Axis: Evidence of Its Clinical Validity to Individually Classify Subjects on the Use/Abuse of Information and Communication Technologies
Authors: Cassú-Ponsatí Daniel , Pedrero-Pérez Eduardo J. , Morales-Alonso Sara , Ruiz-Sánchez de León José María
Published: April 2021

The compulsive habit model proposed by Everitt and Robbins has accumulated important empirical evidence. One of their proposals is the existence of an axis, on which each a person with a particular addiction can be located depending on the evolutionary moment of his/her addictive process. The objective of the present study is to contribute in addressing the identification of such axis, as few studies related to it have been published to date. To do so, the use/abuse of Information and Communication Technologies (ICT) was quantified on an initial sample of 807 subjects. Questionnaires were also delivered to measure impulsivity, compulsivity and symptoms of prefrontal dysfunction. Evidence of the existence of the proposed axis was obtained by means of Machine Learning techniques, thus allowing the classification of each subject along the continuum. The present study provides preliminary evidence of the existence of the Impulsivity-Compulsivity axis, as well as an IT tool so that each patient that starts getting treatment for an addiction can be statistically classified as “impulsive” or “compulsive.” This would allow the matching of each person with the most appropriate treatment depending on his/her moment in the addiction/abuse process, thus facilitating the individualized design of each therapeutic process and a possible improvement of the results of the treatment.