bluuebunny/crossref_metadata_2025 huggingface dataset:
Methods for Detecting Mycobacterial Mixed Strain Infections–A Systematic Review
Authors: Byrne Alexander Stephen , Goudreau Alex , Bissonnette Nathalie , Shamputa Isdore Chola , Tahlan Kapil
Published: December 2020

Mixed strain infection (MSI) refers to the concurrent infection of a susceptible host with multiple strains of a single pathogenic species. Known to occur in humans and animals, MSIs deserve special consideration when studying transmission dynamics, evolution, and treatment of mycobacterial diseases, notably tuberculosis in humans and paratuberculosis (or Johne's disease) in ruminants. Therefore, a systematic review was conducted to examine how MSIs are defined in the literature, how widespread the phenomenon is across the host species spectrum, and to document common methods used to detect such infections. Our search strategy identified 121 articles reporting MSIs in both humans and animals, the majority (78.5%) of which involved members of theMycobacterium tuberculosiscomplex, while only a few (21.5%) examined non-tuberculous mycobacteria (NTM). In addition, MSIs exist across various host species, but most reports focused on humans due to the extensive amount of work done on tuberculosis. We reviewed the strain typing methods that allowed for MSI detection and found a few that were commonly employed but were associated with specific challenges. Our review notes the need for standardization, as some highly discriminatory methods are not adapted to distinguish between microevolution of one strain and concurrent infection with multiple strains. Further research is also warranted to examine the prevalence of NTM MSIs in both humans and animals. In addition, it is envisioned that the accurate identification and a better understanding of the distribution of MSIs in the future will lead to important information on the epidemiology and pathophysiology of mycobacterial diseases.
Modeling and Analysis of a Screw Fitting Assembly Process Involving a Cast Magnesium Component
Authors: Salomonsson Kent , Svoboda Ales , Andersson Nils-Eric , Jarfors Anders E. W.
Published: December 2020

A finite element analysis of a complex assembly was made. The material description used was a physically based material model with dislocation density as an internal state variable. This analysis showed the importance of the materials’ behavior in the process as there is discrepancy between the bolt head contact pressure and the internals state of the materials where the assembly process allows for recovery. The end state is governed by both the tightening process and the thermal history and strongly influenced by the thermal expansion of the AZ91D alloy.
A Pilot Study on the Association of Mitochondrial Oxygen Metabolism and Gas Exchange During Cardiopulmonary Exercise Testing: Is There a Mitochondrial Threshold?
Authors: Baumbach Philipp , Schmidt-Winter Christiane , Hoefer Jan , Derlien Steffen , Best Norman , Herbsleb Marco , Coldewey Sina M.
Published: December 2020

Background:Mitochondria are the key players in aerobic energy generation via oxidative phosphorylation. Consequently, mitochondrial function has implications on physical performance in health and disease ranging from high performance sports to critical illness. The protoporphyrin IX-triplet state lifetime technique (PpIX-TSLT) allowsin vivomeasurements of mitochondrial oxygen tension (mitoPO2). Hitherto, few data exist on the relation of mitochondrial oxygen metabolism and ergospirometry-derived variables during physical performance. This study investigates the association of mitochondrial oxygen metabolism with gas exchange and blood gas analysis variables assessed during cardiopulmonary exercise testing (CPET) in aerobic and anaerobic metabolic phases.

Methods:Seventeen volunteers underwent an exhaustive CPET (graded multistage protocol, 50 W/5 min increase), of which 14 were included in the analysis. At baseline and for every load level PpIX-TSLT-derived mitoPO2measurements were performed every 10 s with 1 intermediate dynamic measurement to obtain mitochondrial oxygen consumption and delivery (mitoV.O2, mitoD.O2). In addition, variables of gas exchange and capillary blood gas analyses were obtained to determine ventilatory and lactate thresholds (VT, LT). Metabolic phases were defined in relation to VT1 and VT2 (aerobic: <VT1, aerobic-anaerobic transition: ≥VT1 and <VT2 and anaerobic: ≥VT2). We used linear mixed models to compare variables of PpIX-TSLT between metabolic phases and to analyze their associations with variables of gas exchange and capillary blood gas analyses.

Results:MitoPO2increased from the aerobic to the aerobic-anaerobic phase followed by a subsequent decline. A mitoPO2peak, termed mitochondrial threshold (MT), was observed in most subjects close to LT2. MitoD.O2increased during CPET, while no changes in mitoV.O2were observed. MitoPO2was negatively associated with partial pressure of end-tidal oxygen and capillary partial pressure of oxygen and positively associated with partial pressure of end-tidal carbon dioxide and capillary partial pressure of carbon dioxide. MitoD.O2was associated with cardiovascular variables. We found no consistent association for mitoV.O2.

Conclusion:Our results indicate an association between pulmonary respiration and cutaneous mitoPO2during physical exercise. The observed mitochondrial threshold, coinciding with the metabolic transition from an aerobic to an anaerobic state, might be of importance in critical care as well as in sports medicine.
WY195, a New Inducible Promoter From the Rubber Powdery Mildew Pathogen, Can Be Used as an Excellent Tool for Genetic Engineering
Authors: Wang Yi , Wang Chen , Rajaofera Mamy Jayne Nelly , Zhu Li , Xu Xinze , Liu Wenbo , Zheng Fucong , Miao Weiguo
Published: December 2020

Until now, there are few studies and reports on the use of endogenous promoters of obligate biotrophic fungi. The WY195 promoter in the genome ofOidium heveae, the rubber powdery mildew pathogen, was predicted using PromoterScan and its promoter function was verified by the transient expression of the β-glucuronidase(GUS) gene. WY195 drove high levels ofGUSexpression in dicotyledons and monocotyledons. qRT-PCR indicated thatGUSexpression regulated by the WY195 promoter was 17.54-fold greater than that obtained using the CaMV 35S promoter in dicotyledons (Nicotiana tabacum), and 5.09-fold greater than that obtained using the ACT1 promoter in monocotyledons (Oryza sativa). Furthermore, WY195-regulatedGUSgene expression was induced under high-temperature and drought conditions. Soluble proteins extracted from WY195-hpaXmtransgenic tobacco was bioactive. Defensive micro-HR induced by the transgene expression ofhpaXmwas observed on transgenic tobacco leaves. Disease resistance bioassays showed that WY195-hpaXmtransgenic tobacco enhanced the resistance to tobacco mosaic virus (TMV). WY195 has great potential for development as a new tool for genetic engineering. Further in-depth studies will help to better understand the transcriptional regulation mechanisms and the pathogenic mechanisms ofO. heveae.
Microbe to Microbiome: A Paradigm Shift in the Application of Microorganisms for Sustainable Agriculture
Authors: Ray Prasun , Lakshmanan Venkatachalam , Labbé Jessy L. , Craven Kelly D.
Published: December 2020

Light, water and healthy soil are three essential natural resources required for agricultural productivity. Industrialization of agriculture has resulted in intensification of cropping practices using enormous amounts of chemical pesticides and fertilizers that damage these natural resources. Therefore, there is a need to embrace agriculture practices that do not depend on greater use of fertilizers and water to meet the growing demand of global food requirements. Plants and soil harbor millions of microorganisms, which collectively form a microbial community known as the microbiome. An effective microbiome can offer benefits to its host, including plant growth promotion, nutrient use efficiency, and control of pests and phytopathogens. Therefore, there is an immediate need to bring functional potential of plant-associated microbiome and its innovation into crop production. In addition to that, new scientific methodologies that can track the nutrient flux through the plant, its resident microbiome and surrounding soil, will offer new opportunities for the design of more efficient microbial consortia design. It is now increasingly acknowledged that the diversity of a microbial inoculum is as important as its plant growth promoting ability. Not surprisingly, outcomes from such plant and soil microbiome studies have resulted in a paradigm shift away from single, specific soil microbes to a more holistic microbiome approach for enhancing crop productivity and the restoration of soil health. Herein, we have reviewed this paradigm shift and discussed various aspects of benign microbiome-based approaches for sustainable agriculture.
Prevalence of Alzheimer's Disease and Parkinson's Disease in China: An Updated Systematical Analysis
Authors: Cui Lei , Hou Na-Na , Wu Hong-Mei , Zuo Xiang , Lian Yi-Zhi , Zhang Chao-Nan , Wang Zhen-Feng , Zhang Xiong , Zhu Jian-Hong
Published: December 2020

Background: Alzheimer's disease (AD) and Parkinson's disease (PD) are two major neurodegenerative diseases worldwide. Demographic aging is in rapid progress in China. Up-to-date estimates of AD and PD prevalence have not been provided.

Methods: Studies that reported the prevalence of AD and PD in China were identified via a systematic database search from 1985 to 2018. Meta-analysis, local polynomial regression and autoregressive integrated moving average model were used for analyses.

Results: A total of 99 studies were included in the study with populations of 385,312 and 227,228, respectively for AD and PD. The overall prevalence of AD and PD following age standardization was 3.20% [95% confidence interval (CI) = 3.17–3.23] and 1.06% (95% CI = 1.02–1.10), respectively in individuals over 60 years old. The rates increased drastically for every 10-years increment of age. The yearly prevalence of AD was predicted to increase from 3.81 to 6.17% in the next 5 years. Significant differences were observed between genders [male to female odds ratio (OR) for AD = 0.57, 95% CI = 0.51–0.64; OR for PD = 1.25, 95% CI = 1.06–1.46], and between education levels (Illiterate to non-illiterate OR for AD = 2.99, 95% CI = 2.38–3.75), but not between urban and rural settings.

Conclusion: Our results provide an updated insight into the epidemiology of AD and PD in China and their associated rates and ratios. The findings may facilitate China policy makers and health professionals mitigate the related health issues.
Preservation of Language Processing and Auditory Performance in Patients With Disorders of Consciousness: A Multimodal Assessment
Authors: Ferraro Stefania , Nigri Anna , D'Incerti Ludovico , Rosazza Cristina , Sattin Davide , Rossi Sebastiano Davide , Visani Elisa , Duran Dunja , Marotta Giorgio , Demichelis Greta , Catricala' Eleonora , Kotz Sonja , Verga Laura , Leonardi Matilde , Cappa Stefano , Bruzzone Maria Grazia
Published: December 2020

The impact of language impairment on the clinical assessment of patients suffering from disorders of consciousness (DOC) is unknown or underestimated and may mask the presence of conscious behavior. In a group of DOC patients (n = 11; time post-injury range: 5–252 months), we investigated the main neural functional and structural underpinnings of linguistic processing, and their relationship with the behavioral measures of the auditory function using the Coma Recovery Scale-Revised (CRS-R). We assessed the integrity of the brainstem auditory pathways, of the left superior temporal gyrus and arcuate fasciculus, the neural activity elicited by passive listening of an auditory language task, and the mean hemispheric glucose metabolism. Our results support the hypothesis of a relationship between the level of preservation of the investigated structures/functions and the CRS-R auditory subscale scores. Moreover, our findings indicate that patients in minimally conscious state minus (MCS−): (1) when presenting the auditory startle (at the CRS-R auditory subscale) might be aphasic in the receptive domain, being severely impaired in the core language structures/functions; (2) when presenting the localization to sound might retain language processing, being almost intact or intact in the core language structures/functions. Despite the small group of investigated patients, our findings provide a grounding of the clinical measures of the CRS-R auditory subscale in the integrity of the underlying auditory structures/functions. Future studies are needed to confirm our results that might have important consequences for the clinical practice.
Cytokines/Chemokines: Potential Biomarkers for Non-paraneoplastic Anti-N-Methyl-D-Aspartate Receptor Encephalitis
Authors: Liu Jingwen , Liu Lei , Kang Wenting , Peng Gongxin , Yu Di , Ma Qiuying , Li Yatong , Zhao Yan , Li Lin , Dai Feifei , Wang Jiawei
Published: December 2020

Objective:Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is the most common type of autoimmune encephalitis. This study focuses on finding new biomarkers to evaluate the clinical condition and provide new directions for treatment.

Methods:A total of 44 cytokines/chemokines in the cerebrospinal fluid of 10 non-paraneoplastic patients and nine controls were measured. We selected some of the cytokines/chemokines that significantly increased in patients. Six selected cytokines/chemokines, including IL-10, CXCL10, CCL22, CCL3, IL-7, TNF-α, and three previously reported (IL-2, IL-6, and IL-17A), were measured in seven other patients who provided repeat samples. We compared their levels and explored correlations with severity of disease and antibody titers.

Results:The levels of Th1 axis (CXCL10, TNF-α, IFN-γ, CCL3), Th2 axis (CCL1, CCL8, CCL17, CCL22), Treg axis (IL-10), Th17 axis (IL-7), and B cell axis (CXCL13) cytokines, as well as IL-12 p40 and IL-16, were significantly higher in patients compared to those in controls. The level of IL-2 was significantly decreased at the intermediate stage of treatment compared with that before treatment. The severity of disease is positively correlated with levels of CXCL10, CCL3, IL-10, CCL22, and IL-6. The level of CCL3 in the high antibody titer group was greater than that in the low antibody titer group.

Conclusion:The pathogenesis of anti-NMDAR encephalitis involves T cell and B cell cytokines. T cells likely assist B cells to produce antibodies. IL-2, CXCL10, CCL3, IL-10, CCL22, and IL-6 may represent new biomarkers in anti-NMDAR encephalitis. Given the lack of research on IL-10, CCL3, and CCL22 in this disease, it will be informative to explore their potential role in pathogenesis in larger studies.
Neuroprotective and Neurorestorative Effects of Holothuria scabra Extract in the MPTP/MPP+-Induced Mouse and Cellular Models of Parkinson’s Disease
Authors: Noonong Kunwadee , Sobhon Prasert , Sroyraya Morakot , Chaithirayanon Kulathida
Published: December 2020

Extracts from Holothuria scabra (HS) have been shown to possess anti-inflammation, anti-oxidant and anti-cancer activities. More recently, it was shown to have neuroprotective potential in Caenorhabditis elegans PD model. Here, we assessed whether HS has neuroprotective and neurorestorative effects on dopaminergic neurons in both mouse and cellular models of PD. We found that both pre-treatment and post-treatment with HS improved motor deficits in PD mouse model induced with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) as determined by grid walk test. This was likely mediated by HS protective and restorative effects on maintaining the numbers of dopaminergic neurons and fibers in both substantia nigra pars compacta (SNpc) and striatum. In a cellular model of PD, HS significantly attenuated 1-methyl-4-phenylpyridinium (MPP+)-induced apoptosis of DAergic-like neurons differentiated from SH-SY5Y cells by enhancing the expression of Bcl-2, suppressing the expression of cleaved Caspase 3 and preventing depolarization of mitochondrial membrane. In addition, HS could stimulate the expression of tyrosine hydroxylase (TH) and suppressed the formation of α-synuclein protein. Taken together, our in vivo and in vitro findings suggested that HS is an attractive candidate for the neuroprotection rather than neurorestoration in PD.
Clinical Assessment of Ultrasound-Guided Local Lauromacrogol Injection Combined With Curettage and Hysteroscopy for Cesarean Scar Pregnancy
Authors: Wu Qing , Liu Xia , Zhu Lin , Zhu Yichen , Mei Tingting , Cao Shanshan , Shen Yan , Ding Jun , Lin Tan
Published: December 2020

Background: To evaluate the efficacy, safeness and cost of ultrasound-guided local lauromacrogol injection (USG-LLI) combined with curettage and hysteroscopy for cesarean scar pregnancy (CSP).

Methods: This was a retrospective study included 151 CSP patients diagnosed with CSP from June 2017 to December 2019, and treated by USG-LLI (n = 86) or uterine artery embolization (UAE) (n = 65) combined with curettage and hysteroscopy. Clinical data and outcome were analyzed.

Results: There were no significant differences in basic clinical characteristics in the two groups. Two groups showed the similar success rates. USG-LLI group, compared with UAE group had significantly lower complication rates (9.30 vs. 44.62%), lower total costs (both medical and non-medication cost) (p < 0.05).

Conclusions: USG-LLI combined with curettage and hysteroscopy is a feasible method to treat CSP with minimal invasion and high efficacy. Moreover, compared with curettage after UAE, USG-LLI exhibited lower complication rate and required fewer expenses.
Regulation of Peroxisome Proliferator-Activated Receptor Pathway During Torpor in the Garden Dormouse, Eliomys quercinus
Authors: Watts Alexander J. , Logan Samantha M. , Kübber-Heiss Anna , Posautz Annika , Stalder Gabrielle , Painer Johanna , Gasch Kristina , Giroud Sylvain , Storey Kenneth B.
Published: December 2020

Differential levels of n-6 and n-3 essential polyunsaturated fatty acids (PUFAs) are incorporated into the hibernator’s diet in the fall season preceding prolonged, multi-days bouts of torpor, known as hibernation. Peroxisome proliferator-activated receptor (PPAR) transcriptional activators bind lipids and regulate genes involved in fatty acid transport, beta-oxidation, ketogenesis, and insulin sensitivity; essential processes for survival during torpor. Thus, the DNA-binding activity of PPARα, PPARδ, PPARγ, as well as the levels of PPARγ coactivator 1α (PGC-1α) and L-fatty acid binding protein (L-FABP) were investigated in the hibernating garden dormouse (Eliomys quercinus). We found that dormice were hibernating in a similar way regardless of the n-6/n-3 PUFA diets fed to the animals during the fattening phase prior to hibernation. Further, metabolic rates and body mass loss during hibernation did not differ between dietary groups, despite marked differences in fatty acid profiles observed in white adipose tissue prior and at mid-hibernation. Overall, maintenance of PPAR DNA-binding activity was observed during torpor, and across three n-6/n-3 ratios, suggesting alternate mechanisms for the prioritization of lipid catabolism during torpor. Additionally, while no change was seen in L-FABP, significantly altered levels of PGC-1α were observed within the white adipose tissue and likely contributes to enhanced lipid metabolism when the diet favors n-6 PUFAs, i.e., high n-6/n-3 ratio, in both the torpid and euthermic state. Altogether, the maintenance of lipid metabolism during torpor makes it likely that consistent activity or levels of the investigated proteins are in aid of this metabolic profile.
Recollecting Cross-Cultural Evidences: Are Decision Makers Really Foresighted in Iowa Gambling Task?
Authors: Lee We-Kang , Lin Ching-Jen , Liu Li-Hua , Lin Ching-Hung , Chiu Yao-Chu
Published: December 2020

The Iowa Gambling Task (IGT) has become a remarkable experimental paradigm of dynamic emotion decision making. In recent years, research has emphasized the “prominent deck B (PDB) phenomenon” among normal (control group) participants, in which they favor “bad” deck B with its high-frequency gain structure—a finding that is incongruent with the original IGT hypothesis concerning foresightedness. Some studies have attributed such performance inconsistencies to cultural differences. In the present review, 86 studies featuring data on individual deck selections were drawn from an initial sample of 958 IGT-related studies published from 1994 to 2017 for further investigation. The PDB phenomenon was found in 67.44% of the studies (58 of 86), and most participants were recorded as having adopted the “gain-stay loss-randomize” strategy to cope with uncertainty. Notably, participants in our sample of studies originated from 16 areas across North America, South America, Europe, Oceania, and Asia, and the findings suggest that the PDB phenomenon may be cross-cultural.
The Stress of Caring—Resilience and HPA-Axis Activity in Hair Samples of Youth Residential Caregivers
Authors: Bürgin David , Kind Nina , Schröder Martin , Clemens Vera , Fegert Jörg M. , Eckert Anne , Buchheim Anna , O'Donovan Aoife , Boonmann Cyril , Schmid Marc
Published: December 2020

Background: Professional caregivers in youth residential care institutions experience frequent verbal and physical aggression as well as multiple stressors as part of their everyday work, leading to high levels of burnout and staff turnover. Resilience might buffer against psychophysiological stress response and therefore be crucial for well-being in professional caregivers.

Objectives: We aimed to investigate if measures related to resilience [sense of coherence (SoC), self-efficacy and self-care] and attachment security of caregivers were cross-sectionally associated with stress markers in hair samples [cortisol and dehydroepiandrosterone (DHEA)].

Method: Participants (n = 134; 64.2% women) reported on individual resilience measures and provided hair samples for cortisol and DHEA assays. Attachment was assessed in a subsample using the Adult Attachment Projective Picture System (AAP, n = 69). Linear regression models were fitted to estimate the association between resilience measures and the Cortisol:DHEA ratio, cortisol and DHEA, controlling for gender and age.

Results: SoC was associated with a lower Cortisol:DHEA ratio (β = −0.36, p < 0.001), driven by a positive association between SoC and DHEA levels (β = 0.28, p = 0.002). Self-care was also associated with lower Cortisol:DHEA ratios (β = −0.24, p = 0.005), due to self-care being associated with higher DHEA (β = 0.21, p = 0.016). HPA-axis measures were not associated with self-efficacy nor with attachment patterns in a subsample.

Conclusions: Our findings imply that youth residential care institutions might benefit from programs focusing on enhancing SoC and self-care practices. Fostering a meaningful, comprehensible and manageable professional climate in caregiving environments and implementing self-care in routine practices might enhance not only well-being but also physical health of professional caregivers and in this way buffer adverse health effects of chronic stressors.
Risk Factors Underlying COVID-19 Lockdown-Induced Mental Distress
Authors: Novotný Jan Sebastian , Gonzalez-Rivas Juan Pablo , Kunzová Šárka , Skladaná Mária , Pospíšilová Anna , Polcrová Anna , Medina-Inojosa Jose Ramon , Lopez-Jimenez Francisco , Geda Yonas Endale , Stokin Gorazd Bernard
Published: December 2020

Recent reports suggest that the COVID-19 lockdown resulted in changes in mental health, however, potential age-related changes and risk factors remain unknown. We measured COVID-19 lockdown-induced stress levels and the severity of depressive symptoms prior to and during the COVID-19 lockdown in different age groups and then searched for potential risk factors in a well-characterized general population-based sample. A total of 715 participants were tested for mental distress and related risk factors at two time-points, baseline testing prior to COVID-19 and follow-up testing during COVID-19, using a battery of validated psychological tests including the Perceived Stress Scale and the Patient Health Questionnaire. Longitudinal measurements revealed that the prevalence of moderate to high stress and the severity of depressive symptoms increased 1.4- and 5.5-fold, respectively, during the COVID-19 lockdown. This surge in mental distress was more severe in women, but was present in all age groups with the older age group exhibiting, cross-sectionally, the lowest levels of mental distress prior to and during the lockdown. Illness perception, personality characteristics such as a feeling of loneliness, and several lifestyle components were found to be associated with a significant increase in mental distress. The observed changes in mental health and the identified potential risk factors underlying these changes provide critical data justifying timely and public emergency-tailored preventive, diagnostic, and therapeutic mental health interventions, which should be integrated into future public health policies globally.
Economic and Behavioral Influencers of Vaccination and Antimicrobial Use
Authors: Wagner Caroline E. , Prentice Joseph A. , Saad-Roy Chadi M. , Yang Luojun , Grenfell Bryan T. , Levin Simon A. , Laxminarayan Ramanan
Published: December 2020

Despite vast improvements in global vaccination coverage during the last decade, there is a growing trend in vaccine hesitancy and/or refusal globally. This has implications for the acceptance and coverage of a potential vaccine against COVID-19. In the United States, the number of children exempt from vaccination for “philosophical belief-based” non-medical reasons increased in 12 of the 18 states that allowed this policy from 2009 to 2017 (1). Meanwhile, the overuse and misuse of antibiotics, especially in young children, have led to increasing rates of drug resistance that threaten our ability to treat infectious diseases. Vaccine hesitancy and antibiotic overuse exist side-by-side in the same population of young children, and it is unclear why one modality (antibiotics) is universally seen as safe and effective, while the other (vaccines) is seen as potentially hazardous by some. In this review, we consider the drivers shaping the use of vaccines and antibiotics in the context of three factors: individual incentives, risk perceptions, and social norms and group dynamics. We illustrate how these factors contribute to the societal and individual costs of vaccine underuse and antimicrobial overuse. Ultimately, we seek to understand these factors that are at the nexus of infectious disease epidemiology and social science to inform policy-making.
Multimodal Risk-Adapted Treatment in Surgical Patients With Synovial Sarcoma: A Preoperative Nomogram-Guided Adjuvant Treatment Strategy
Authors: Zeng Ziliang , Yao Hao , Lv Dongming , Jin Qinglin , Bian Yiying , Zou Yutong , Tu Jian , Wang Bo , Wen Lili , Xie Xianbiao
Published: December 2020

Background: Synovial sarcoma is characterized by heterogeneous clinical manifestations, making it difficult to evaluate individual patients' prognoses and design personal treatment schemes. We established an effective preoperative nomogram to predict cancer-specific survival (CSS) and present a risk-adapted adjuvant treatment strategy in surgical patients with synovial sarcoma.

Methods: This retrospective study included patients from the Surveillance, Epidemiology, and End Results (SEER) database who were diagnosed with synovial sarcoma between 1996 and 2015. The patients were randomly divided into training and validation groups. The predictors were selected using univariate and multivariate Cox hazards models. The nomogram performance was verified for its discriminatory ability and calibration. We further stratified the patients into different risk groups according to the nomogram scores and compared the efficacy of chemotherapy, radiotherapy, and combination of radiotherapy and chemotherapy.

Results: There were 915 patients enrolled in our study, with 874 patients either alive or dead due to synovial sarcoma. We established a nomogram to predict 5-year CSS based on independent factors, including sex, age, grade, tumor size, location, and extent (all p < 0.05). Our model showed a consistently good discriminatory ability and calibration for predicting 5-year CSS in both the training (c-index = 0.78, 95% CI 0.75–0.81) and validation (c-index = 0.73, 95% CI 0.68–0.78). Based on their nomogram scores, we divided patients into 5 groups. Compared to patients without adjuvant treatment, nomogram I patients with adjuvant treatment had no improvements in 5-year CSS (100.0% vs. 100.0%), nomogram II patients had higher 5-year CSS with radiotherapy or chemotherapy (92.9% vs. 72.2%, p = 0.015), nomogram III patients had higher 5-year CSS with combination of chemotherapy and radiotherapy (70.1% vs. 47.2%, p = 0.004), nomogram IV patients had higher 5-year CSS with radiotherapy (41.3% vs. 15.6%, p = 0.015), and nomogram V patients had no improvements in 5-year CSS rates with adjuvant treatment (28.9% vs. 16.9%, p = 0.18).

Conclusion: The nomogram showed a satisfactory discriminatory ability and calibration for predicting 5-year CSS in synovial sarcoma patients. Based on this nomogram, we stratified synovial sarcoma patients according to risk levels, which enabled us to provide a useful grouping scheme that can inform multimodal risk-adapted treatment in synovial sarcoma.
Targeting Kinases in Fasciola hepatica: Anthelminthic Effects and Tissue Distribution of Selected Kinase Inhibitors
Authors: Morawietz Carolin M. , Houhou Hicham , Puckelwaldt Oliver , Hehr Laura , Dreisbach Domenic , Mokosch Annika , Roeb Elke , Roderfeld Martin , Spengler Bernhard , Haeberlein Simone
Published: December 2020

Protein kinases have been discussed as promising druggable targets in various parasitic helminths. New drugs are also needed for control of fascioliasis, a food-borne trematode infection and worldwide spread zoonosis, caused by the liver fluke Fasciola hepatica and related species. In this study, we intended to move protein kinases more into the spotlight of Fasciola drug research and characterized the fasciolicidal activity of two small-molecule inhibitors from human cancer research: the Abelson tyrosine kinase (ABL-TK) inhibitor imatinib and the polo-like 1 (PLK1) inhibitor BI2536. BI2536 reduced viability of 4-week-old immature flukes in vitro, while adult worms showed a blockade of egg production. Together with a significantly higher transcriptional expression of PLK1 in adult compared to immature worms, this argues for a role of PLK1 in fluke reproduction. Both fluke stages expressed ABL1-TK transcripts at similar high levels and were affected by imatinib. To study the uptake kinetic and tissue distribution of imatinib in F. hepatica, we applied matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MSI) for the first time in this parasite. Drug imaging revealed the accumulation of imatinib in different fluke tissues from 20 min to 12 h of exposure. Furthermore, we show that imatinib is metabolized to N-desmethyl imatinib by F. hepatica, a bioactive metabolite also found in humans. Besides the vitellarium, gastrodermal tissue showed strong signal intensities. In situ hybridization demonstrated the gastrodermal presence of abl1 transcripts. Finally, we assessed transcriptional changes of physiologically important genes in imatinib-treated flukes. Moderately increased transcript levels of a gene encoding a multidrug resistance protein were detected, which may reflect an attempt to defend against imatinib. Increased expression levels of the cell cycle dependently expressed histone h2b and of two genes encoding superoxide dismutases (SODs) were also observed. In summary, our pilot study demonstrated cross-stage activity of imatinib but not BI2536 against immature and adult F. hepatica in vitro; a fast incorporation of imatinib within minutes, probably via the oral route; and imatinib-induced expression changes of physiologically relevant genes. We conclude that kinases are worth analyzing in more detail to evaluate the potential as therapeutic targets in F. hepatica.
Edible Environmental Enrichments in Littered Housing Systems: Do Their Effects on Integument Condition Differ Between Commercial Laying Hen Strains?
Authors: Schreiter Ruben , Damme Klaus , Freick Markus
Published: December 2020

The aim of this study was to investigate the effect of additional enrichment materials (EMs; pecking stones and alfalfa bales) on the occurrence of plumage damage, skin injuries, and toe injuries, with an emphasis on the possible differences between commercial hybrid strains of laying hens. During rearing (weeks 1–18, 16 compartments, 4000 pullets) and laying periods (weeks 21–72, 24 compartments, 2808 hens) in a littered housing system, EMs were permanently provided to the study groups (EXP), while control groups (CON) did not receive additional EM. In a two-factorial study design (two groups with four strains) with 351 hens per variant, the brown egg-laying Lohmann Brown classic (LB) and Bovans Brown (BB) strains as well as the white egg-laying Lohmann Selected Leghorn classic (LSL) and Dekalb White (DW) strains were investigated. Compared to the CON, the EXP showed reduced body mass during rearing (p < 0.001) and reduced albumen consistency in the laying period (p < 0.001). Regarding integument condition, the LSL in the EXP showed more toe injuries than in the CON (p = 0.018). Remarkably, genotype-environment interactions between strains and groups were evident (p < 0.001). In groups with an EM supply, plumage damage decreased in LB (p ≤ 0.033) and LSL (p ≤ 0.005) but increased in BB (p ≤ 0.003). Moreover, there were fewer skin injuries in LSL (p = 0.001) but more in BB (p = 0.001) in groups with access to EM. In view of the diverging effects between strains, future practical recommendations for laying hen husbandry should be strain-specific.
Effect of Varying Dietary Crude Protein Level on Feed Intake, Nutrient Digestibility, Milk Production, and Nitrogen Use Efficiency by Lactating Holstein-Friesian Cows
Authors: Katongole Constantine Bakyusa , Yan Tianhai
Published: December 2020

The effect of dietary crude protein (CP) level on intake, digestibility, milk production, and nitrogen (N) use efficiency was studied. Twenty-four Holstein-Friesian cows (17 multiparous and seven primiparous) were grouped by parity, days in milk, milk yield, and live weight into six blocks of four, and randomly assigned to four total mixed ration (TMR) treatments, containing 141, 151, 177, or 210 g CP/kg dry matter (DM), over 28 day experimental periods. Apparent total-tract DM and fiber digestibilities and milk fat composition were similar across treatments. Milk protein and urea-N compositions, and urinary and manure N excretion increased linearly, while milk N efficiency (MNE) decreased linearly with increasing CP. DM intake was highest with the 177 diet, while CP intake increased linearly with increasing CP, peaking at 200 g/kg DM. Milk yield increased with CP intake for the three lower CP levels, peaking at 176 g CP/kg DM. The further increase in CP level from 177 to 210 g/kg DM did not result in improved milk yield, but resulted in decreased milk N secretion and increased urinary N excretion. In summary, milk protein composition increased linearly with increasing CP, accompanied by a linear decrease in MNE, resulting in a bell-shaped relationship between milk yield and dietary CP level.
Comparative Assessment of Thermotolerance in Dorper and Second-Cross (Poll Dorset/Merino × Border Leicester) Lambs
Authors: Joy Aleena , Dunshea Frank R. , Leury Brian J. , DiGiacomo Kristy , Clarke Iain J. , Zhang Minghao H. , Abhijith Archana , Osei-Amponsah Richard , Chauhan Surinder S.
Published: December 2020

The objective of this study was to compare the thermotolerance of second-cross (SC; Poll Dorset × Merino × Border Leicester) and Dorper lambs. Dorper and SC lambs (4–5 months of age) were subjected to cyclic heat stress (HS) (28–40 °C). The temperature was increased to 38–40 °C between 800 and 1700 h daily and maintained at 28 °C for the remainder of the day (30–60% relative humidity (RH)) in climatic chambers for 2 weeks (n = 12/group), with controls maintained in a thermoneutral (TN) (18–21 °C, 40–50% RH) environment (n = 12/group). Basal respiration rate (RR), rectal temperature (RT) and skin temperature (ST) were higher (p < 0.01) in SC lambs than in Dorpers. HS increased RR, RT and ST (p < 0.01) in both genotypes, but the levels reached during HS were lower (p < 0.01) in Dorpers. HS increased (p < 0.01) water intake to a greater extent in SC lambs, while feed intake was reduced (p < 0.05) by HS in SC lambs but not in Dorpers. HS increased (p < 0.01) blood urea nitrogen and creatinine in SC lambs only. Plasma non-esterified fatty acid concentrations were reduced (p < 0.05) by HS in SC lambs but increased (p < 0.05) in Dorpers. There was no effect of HS on pO2, cHCO3− and cSO2, but higher (p < 0.01) blood pH and lower (p < 0.01) pCO2 were recorded under HS in both genotypes. Blood electrolytes and base excess were reduced (p < 0.01) under HS, while a genotype difference (p < 0.05) was only observed in blood K+ and hemoglobin concentrations. Basal plasma prolactin concentrations were lower (p < 0.01) in Dorpers but were elevated at a similar level during HS (p < 0.01) in both genotypes. Dorper lambs are more resilient to HS than SC lambs. Future research should focus on confirming whether the better heat tolerance of Dorpers is translated to better returns in terms of growth performance and carcass traits over the summer months.
The LEPR Gene Is Associated with Reproductive Seasonality Traits in Rasa Aragonesa Sheep
Authors: Lakhssassi Kenza , Serrano Malena , Lahoz Belén , Sarto María Pilar , Iguácel Laura Pilar , Folch José , Alabart José Luis , Calvo Jorge Hugo
Published: December 2020

The aim of this study was to characterize and identify causative polymorphisms in the leptin receptor (LEPR) gene responsible for the seasonal variation of reproductive traits in sheep. Three reproductive seasonality traits were studied: the total days of anoestrous (TDA), the progesterone cycling months (P4CM) and the oestrous cycling months (OCM). In total, 18 SNPs were detected in 33 ewes with extreme values for TDA and OCM. Six SNPs were non-synonymous substitutions and two of them were predicted in silico as deleterious: rs596133197 and rs403578195. These polymorphisms were then validated in 239 ewes. The SNP rs403578195, located in exon 8 and leading to a change of alanine to glycine (Ala284Gly) in the extracellular domain of the protein, was associated with the OCM trait, being the G allele associated with a decrease of 12 percent of the OCM trait. Haplotype analyses also suggested the involvement of other non-synonymous SNP located in exon 20 (rs405459906). This SNP also produces an amino acid change (Lys1069Glu) in the intracellular domain of the protein and segregates independently of rs403578195. These results confirm for the first time the role of the LEPR gene in sheep reproductive seasonality.
Fatty Acid Binding Protein 5 Mediates Cell Death by Psychosine Exposure through Mitochondrial Macropores Formation in Oligodendrocytes
Authors: Cheng An , Kawahata Ichiro , Fukunaga Kohji
Published: December 2020

Oligodendrocytes, the myelinating cells in the central nervous system (CNS), are critical for producing myelin throughout the CNS. The loss of oligodendrocytes is associated with multiple neurodegenerative disorders mediated by psychosine. However, the involvement of psychosine in the critical biochemical pathogenetic mechanism of the loss of oligodendrocytes and myelin in krabbe disease (KD) remains unclear. Here, we addressed how oligodendrocytes are induced by psychosine treatment in both KG-1C human oligodendroglial cells and mouse oligodendrocyte precursor cells. We found that fatty acid binding protein 5 (FABP5) expressed in oligodendrocytes accelerates mitochondria-induced glial death by inducing mitochondrial macropore formation through voltage-dependent anion channels (VDAC-1) and BAX. These two proteins mediate mitochondrial outer membrane permeabilization, thereby leading to the release of mitochondrial DNA and cytochrome C into the cytosol, and the activation of apoptotic caspases. Furthermore, we confirmed that the inhibition of FABP5 functions by shRNA and FABP5-specific ligands blocking mitochondrial macropore formation, thereby rescuing psychosine-induced oligodendrocyte death. Taken together, we identified FABP5 as a critical factor in mitochondrial injury associated with psychosine-induced apoptosis in oligodendrocytes.
Biocompatibility and Immune Response of a Newly Developed Volume-Stable Magnesium-Based Barrier Membrane in Combination with a PVD Coating for Guided Bone Regeneration (GBR)
Authors: Steigmann Larissa , Jung Ole , Kieferle Wolfgang , Stojanovic Sanja , Proehl Annica , Görke Oliver , Emmert Steffen , Najman Stevo , Barbeck Mike , Rothamel Daniel
Published: December 2020

To date, there are no bioresorbable alternatives to non-resorbable and volume-stable membranes in the field of dentistry for guided bone or tissue regeneration (GBR/GTR). Even magnesium (Mg) has been shown to constitute a favorable biomaterial for the development of stabilizing structures. However, it has been described that it is necessary to prevent premature degradation to ensure both the functionality and the biocompatibility of such Mg implants. Different coating strategies have already been developed, but most of them did not provide the desired functionality. The present study analyses a new approach based on ion implantation (II) with PVD coating for the passivation of a newly developed Mg membrane for GBR/GTR procedures. To demonstrate comprehensive biocompatibility and successful passivation of the Mg membranes, untreated Mg (MG) and coated Mg (MG-Co) were investigated in vitro and in vivo. Thereby a collagen membrane with an already shown biocompatibility was used as control material. All investigations were performed according to EN ISO 10993 regulations. The in vitro results showed that both the untreated and PVD-coated membranes were not cytocompatible. However, both membrane types fulfilled the requirements for in vivo biocompatibility. Interestingly, the PVD coating did not have an influence on the gas cavity formation compared to the uncoated membrane, but it induced lower numbers of anti-inflammatory macrophages in comparison to the pure Mg membrane and the collagen membrane. In contrast, the pure Mg membrane provoked an immune response that was fully comparable to the collagen membrane. Altogether, this study shows that pure magnesium membranes represent a promising alternative compared to the nonresorbable volume-stable materials for GBR/GTR therapy.
Age-Related Structural and Functional Changes of the Hippocampus and the Relationship with Inhibitory Control
Authors: Hu Sien , Li Chiang-shan R.
Published: December 2020

Aging is associated with structural and functional changes in the hippocampus, and hippocampal dysfunction represents a risk marker of Alzheimer’s disease. Previously, we demonstrated age-related changes in reactive and proactive control in the stop signal task, each quantified by the stop signal reaction time (SSRT) and sequential effect computed as the correlation between the estimated stop signal probability and go trial reaction time. Age was positively correlated with the SSRT, but not with the sequential effect. Here, we explored hippocampal gray matter volume (GMV) and activation to response inhibition and to p(Stop) in healthy adults 18 to 72 years of age. The results showed age-related reduction of right anterior hippocampal activation during stop success vs. go trials, and the hippocampal activities correlated negatively with the SSRT. In contrast, the right posterior hippocampus showed higher age-related responses to p(Stop), but the activities did not correlate with the sequential effect. Further, we observed diminished GMVs of the anterior and posterior hippocampus. However, the GMVs were not related to behavioral performance or regional activities. Together, these findings suggest that hippocampal GMVs and regional activities represent distinct neural markers of cognitive aging, and distinguish the roles of the anterior and posterior hippocampus in age-related changes in cognitive control.
Patterns of Intrahemispheric EEG Asymmetry in Insomnia Sufferers: An Exploratory Study
Authors: Provencher Thierry , Fecteau Shirley , Bastien Célyne
Published: December 2020

Individuals with insomnia present unique patterns of electroencephalographic (EEG) asymmetry between homologous regions of each brain hemisphere, yet few studies have assessed asymmetry within the same hemisphere. Increase in intrahemispheric asymmetry during rapid eye movement (REM) sleep in good sleepers (GS) and disruption of REM sleep in insomnia sufferers (INS) both point out that this activity may be involved in the pathology of insomnia. The objective of the present exploratory study was to evaluate and quantify patterns of fronto-central, fronto-parietal, fronto-occipital, centro-parietal, centro-occipital and parieto-occipital intrahemispheric asymmetry in GS and INS, and to assess their association with sleep-wake misperception, daytime anxiety and depressive symptoms, as well as insomnia severity. This paper provides secondary analysis of standard EEG recorded in 43 INS and 19 GS for three nights in a sleep laboratory. Asymmetry measures were based on EEG power spectral analysis within 0.3–60 Hz computed between pairs of regions at frontal, central, parietal and occipital derivations. Repeated-measures ANOVAs were performed to assess group differences. Exploratory correlations were then performed on asymmetry and sleep-wake misperception, as well as self-reported daytime anxiety and depressive symptoms, and insomnia severity. INS presented increased delta and theta F3/P3 asymmetry during REM sleep compared with GS, positively associated with depressive and insomnia complaints. INS also exhibited decreased centro-occipital (C3/O1, C4/O2) and parieto-occipital (P3–O1, P4/O2) theta asymmetry during REM. These findings suggest that INS present specific patterns of intrahemispheric asymmetry, partially related to their clinical symptoms. Future studies may investigate the extent to which asymmetry is related to sleep-wake misperception or memory impairments.
Role of Fibroblast Growth Factors Receptors (FGFRs) in Brain Tumors, Focus on Astrocytoma and Glioblastoma
Authors: Ardizzone Alessio , Scuderi Sarah A. , Giuffrida Dario , Colarossi Cristina , Puglisi Caterina , Campolo Michela , Cuzzocrea Salvatore , Esposito Emanuela , Paterniti Irene
Published: December 2020

Despite pharmacological treatments and surgical practice options, the mortality rate of astrocytomas and glioblastomas remains high, thus representing a medical emergency for which it is necessary to find new therapeutic strategies. Fibroblast growth factors (FGFs) act through their associated receptors (FGFRs), a family of tyrosine kinase receptors consisting of four members (FGFR1–4), regulators of tissue development and repair. In particular, FGFRs play an important role in cell proliferation, survival, and migration, as well as angiogenesis, thus their gene alteration is certainly related to the development of the most common diseases, including cancer. FGFRs are subjected to multiple somatic aberrations such as chromosomal amplification of FGFR1; mutations and multiple dysregulations of FGFR2; and mutations, translocations, and significant amplifications of FGFR3 and FGFR4 that correlate to oncogenesis process. Therefore, the in-depth study of these receptor systems could help to understand the etiology of both astrocytoma and glioblastoma so as to achieve notable advances in more effective target therapies. Furthermore, the discovery of FGFR inhibitors revealed how these biological compounds improve the neoplastic condition by demonstrating efficacy and safety. On this basis, this review focuses on the role and involvement of FGFRs in brain tumors such as astrocytoma and glioblastoma.