bluuebunny/crossref_metadata_2025 huggingface dataset:
The Use of a Length-Structured Multispecies Model Fitted Directly to Data in Near-Real Time as a Viable Tool for Advice
Authors: Spence Michael A. , Dolder Paul J. , Nash Richard , Thorpe Robert B.
Published: September 2021

Fish communities are multispecies assemblages, so ideally multispecies models should be used directly for assessing this resource. However, progress in this direction has been slow, partly because these models are often more complex and take longer to fit, rendering them too slow to demonstrate near-real-time utility, and thus creating a perception that they are opaque to stakeholders. In this study we implemented a multispecies assessment for the Irish Sea, fitting a model of eight key stocks directly to catch and survey data. Two novel features of our approach allowed the multispecies model to be fitted within a few hours. Firstly, by using size-based theory and life-history invariants to specify many of the required properties of stocks, we reduced the number of general parameters that needed to be fitted directly to a more manageable 25. Secondly, by using state-of-the-art fitting methods, we found acceptable solutions quickly enough to provide assessments within the timescale of an advisory meeting. The outcomes were compared with the standard single species assessments of the same eight species. Model fits were generally good for either catch or at least one of the surveys, but not for all data sources at the same time, illustrating the challenges of fitting multiple stocks to different data sources simultaneously. Estimates of SSB and F agreed qualitatively with the assessments for most stocks with the exception of whiting. Estimates of natural mortality showed modest year to year variability, suggesting that single species assessments may be appropriate for short term tactical management. This method shows great promise for making multispecies assessments as a complement to existing assessments because of the rapid turnaround time and ability to respond at meetings to the requests of stakeholders. In addition, because these models avoid our current dependence on existing single species models they can be used to provide boundary conditions in natural mortality for standard assessment models and check for internal consistency in the assessment process. Furthermore, they are easily accessible because they are based upon freely available code.
A Framework for Compiling Quantifications of Marine Biosecurity Risk Factors Associated With Common Vessel Types
Authors: Tzeng Mimi W. , Floerl Oliver , Zaiko Anastasija
Published: September 2021

Globally, movements of commercial vessels can facilitate the spread of marine non-indigenous species (NIS) beyond their current biogeographic ranges. Authorities at potential destination locations employ a number of biosecurity risk assessment strategies to estimate threat levels from potential origin locations, vulnerability levels of specific destination regions, or the consequences of successful establishment of particular NIS species. Among the many factors and processes that have an influence on the probability that NIS will survive transport and establish successfully at new locations, vessel type has been identified as an important risk factor. Different vessel types have different structural and operational characteristics that affect their overall level of marine biosecurity risk. Several recent studies have examined subsets of vessel types or vessel characteristics for their ability to spread NIS. While high-quality information is available via these endeavors, it is fragmented and not readily available as an integrated resource to support biosecurity regulators or other end-users. In this study, we synthesize available empirical data on a wide range of vessel types and characteristics to develop a framework that allows systematic quantification of the relative risk of NIS transfer by common commercial vessel types. We explain our approach for constructing the framework, from selection of key risk factors for inclusion, to selection of which datasets to use for those risk factors. The framework output is a set of risk scores which denote the relative biosecurity risk of common commercial vessel types. To demonstrate a potential application of our framework, we applied the risk scores to vessel visit data for commercial ports around New Zealand and assigned a relative risk level per port based on the arrival frequencies of different vessel types. The resulting per-port risk levels matched closely with the results of a prior benchmark study that employed state-of-the-art risk modeling approaches. Our framework is based on globally relevant data, is simple to implement, and is adaptable as new empirical information arises. It can serve as a simple tool to determine the relative levels of vessel-related biosecurity risk associated with geographic shipping hubs, or it can be used as a vessel-specific “risk mask” for maritime transport models. It can be applied to any scientific or policy question that requires information on vessel type differences in relation to marine biosecurity risk.
Seasonal Acclimation Modulates the Impacts of Simulated Warming and Light Reduction on Temperate Seagrass Productivity and Biochemical Composition
Authors: Beca-Carretero Pedro , Azcárate-García Tomás , Julia-Miralles Marc , Stanschewski Clara S. , Guihéneuf Freddy , Stengel Dagmar B.
Published: September 2021

Increases in seawater temperature and reduction in light quality have emerged as some of the most important threats to marine coastal communities including seagrass ecosystems. Temperate seagrasses, including Zostera marina, typically have pronounced seasonal cycles which modulate seagrass growth, physiology and reproductive effort. These marked temporal patterns can affect experimental seagrass responses to climate change effects depending on the seasons of the year in which the experiments are conducted. This study aimed at evaluating how seasonal acclimatization modulates productivity and biochemical responses of Zostera marina to experimental warming and irradiance reduction. Seagrass shoots were exposed to different temperatures (6, 12, 16, 20, and 24°C), combined with high (180 μmol photons m–2 s–1) and low (60 μmol photons m–2 s–1) light conditions across four seasons (spring: April, summer: July, and autumn: November 2015, and winter: January 2016). Plants exhibited similar temperature growth rates between 16 and 20°C; at 24°C, a drastic reduction in growth was observed; this was more accentuated in colder months and under low irradiance conditions. Higher leaf growth rates occurred in winter while the largest rhizomes were reached in experiments conducted in spring and summer. Increases in temperature induced a significant reduction in polyunsaturated fatty acids (PUFA), particularly omega-3 (n-3 PUFA). Our results highlight that temperate seagrass populations currently living under temperature limitation will be favored by future increases in sea surface temperature in terms of leaf and rhizome productivity. Together with results from this study on Z. marina from a temperate region, a wider review of the reported impacts of experimental warming indicates the likely reduction in some compounds of nutritional importance for higher trophic levels in seagrass leaves. Our results further demonstrate that data derived from laboratory-based studies investigating environmental stress on seagrass growth and acclimation, and their subsequent interpretation, are strongly influenced by seasonality and in situ conditions that precede any experimental exposure.
Multiscale Geomechanical Behavior of Fiber-Reinforced Cementitious Composites Under Cyclic Loading Conditions—A Review
Authors: McLean Javaugh , Cui Liang
Published: September 2021

As construction materials, cementitious composites such as cemented paste backfill (CPB), cemented soil, and concrete may be subjected to extreme dynamic loadings including impact, blast, and/or seismic loads during their service life. To improve mechanical performance under dynamic loadings, fiber reinforcement technique has been considered a promising approach and extensively used in practice. In this manuscript, a new perspective on the multiscale geomechanical behavior of fiber-reinforced cementitious composites (FRCC) is provided through a comprehensive review on the macroscale constitutive behavior and the associated mechanical properties, and microscale failure processes under cyclic tensile, shear, and compressive loading conditions. For the macroscale mechanical response, this review includes a detailed analysis of the state-of-the-art research in stress-strain behaviors including pre- and post-peak response and hysteretic behaviors. Moreover, the effects of pore water pressure on the dynamic response of soft FRCCs such as CPB are discussed. Furthermore, the link between microscale crack propagation (including the formation of the interfacial transition zone and fracture process zone) and damage accumulation is established for each type of cyclic loading condition. In addition, a critical discussion on the future development of fiber reinforcement is conducted as well. Therefore, this review not only offers guidance and references to the experimental investigation on the multiscale behavior of FRCCs under cyclic loadings, but also promotes the further development of fiber reinforcement techniques.
Novel Gene Signatures Predicting Primary Non-response to Infliximab in Ulcerative Colitis: Development and Validation Combining Random Forest With Artificial Neural Network
Authors: Feng Jing , Chen Yueying , Feng Qi , Ran Zhihua , Shen Jun
Published: September 2021

Background: While infliximab has revolutionized the treatment of ulcerative colitis, primary non-response is difficult to predict, which limits effective disease management. The study aimed to establish a novel genetic model to predict primary non-response to infliximab in patients with ulcerative colitis.

Methods: Publicly available mucosal expression profiles of infliximab-treated ulcerative colitis patients (GSE16879, GSE12251) were utilized to identify potential predictive gene panels. The random forest algorithm and artificial neural network were applied to further screen for predictive signatures and establish a model to predict primary non-response to infliximab.

Results: A total of 28 downregulated and 2 upregulated differentially expressed genes were identified as predictors. The novel model was successfully established on the basis of the molecular prognostic score system, with a significantly predictive value (AUC = 0.93), and was validated with an independent dataset GSE23597 (AUC = 0.81).

Conclusion: Machine learning was used to construct a predictive model based on the molecular prognostic score system. The novel model can predict primary non-response to infliximab in patients with ulcerative colitis, which aids in clinical-decision making.
Increased Risk of Chronic Kidney Disease Associated With Weight Gain in Healthy Adults: Insight From Metabolic Profiles and Body Composition
Authors: Yun Hae-Ryong , Kim Hyung Woo , Chang Tae Ik , Kang Ea Wha , Joo Young Su , Nam Ki Heon , Kim Hyoungnae , Park Jung Tak , Yoo Tae-Hyun , Kang Shin-Wook , Han Seung Hyeok
Published: September 2021

Objective: Obesity is an established risk factor for kidney damage. In this study, we explored the long-term association of changes in body mass index (BMI) over time with incident chronic kidney disease (CKD).

Methods: For this analysis, 5,393 middle-aged adults without comorbidities in the Korean Genome and Epidemiology Study (KoGES) were included. Group-based trajectory modeling was used to determine the patterns of BMI change (decreasing, stable, and increasing BMI) between baseline and year 4. The primary outcome was the subsequent development of CKD from year 4. A multivariable Cox proportional hazards model was constructed to determine the risk of incident CKD according to BMI trajectories.

Results: During 55,327 person-years, incident CKD occurred in 354 (6.5%) participants; 6.0, 6.1, and 7.8 per 1,000 person-years across the trajectories, respectively (P = 0.005). In the multivariable-adjusted Cox proportional hazards model, the increasing BMI trajectory was associated with a 1.4-fold [hazard ratio (HR), 1.41; 95% CI, 1.06–1.87] a higher risk of incident CKD compared with stable BMI trajectory. This association was stronger for overweight and obese individuals. The HRs for CKD development in these two groups were 1.6 (95% CI, 1.06–1.87) and 2.2 (95% CI, 1.40–3.48), respectively. While the increasing BMI group was gaining weight, there were concomitant increases in blood pressure, insulin resistance, serum concentrations of total cholesterol, triglyceride, and high-sensitivity C-reactive protein (hs-CRP), and fat mass, but high-density lipoprotein (HDL)-cholesterol level and muscle-to-fat (MF) ratio decreased.

Conclusion: Weight gain is associated with an increased risk of incident CKD in healthy adults. This association is attributed to worsening metabolic profiles and increasing fat mass.
Molecular and Cellular Mediators of the Gut-Liver Axis in the Progression of Liver Diseases
Authors: Bruneau Alix , Hundertmark Jana , Guillot Adrien , Tacke Frank
Published: September 2021

The gut-liver axis covers the bidirectional communication between the gut and the liver, and thus includes signals from liver-to-gut (e.g., bile acids, immunoglobulins) and from gut-to-liver (e.g., nutrients, microbiota-derived products, and recirculating bile acids). In a healthy individual, liver homeostasis is tightly controlled by the mostly tolerogenic liver resident macrophages, the Kupffer cells, capturing the gut-derived antigens from the blood circulation. However, disturbances of the gut-liver axis have been associated to the progression of varying chronic liver diseases, such as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, and primary sclerosing cholangitis. Notably, changes of the gut microbiome, or intestinal dysbiosis, combined with increased intestinal permeability, leads to the translocation of gut-derived bacteria or their metabolites into the portal vein. In the context of concomitant or subsequent liver inflammation, the liver is then infiltrated by responsive immune cells (e.g., monocytes, neutrophils, lymphoid, or dendritic cells), and microbiota-derived products may provoke or exacerbate innate immune responses, hence perpetuating liver inflammation and fibrosis, and potentiating the risks of developing cirrhosis. Similarly, food derived antigens, bile acids, danger-, and pathogen-associated molecular patterns are able to reshape the liver immune microenvironment. Immune cell intracellular signaling components, such as inflammasome activation, toll-like receptor or nucleotide-binding oligomerization domain-like receptors signaling, are potent targets of interest for the modulation of the immune response. This review describes the current understanding of the cellular landscape and molecular pathways involved in the gut-liver axis and implicated in chronic liver disease progression. We also provide an overview of innovative therapeutic approaches and current clinical trials aiming at targeting the gut-liver axis for the treatment of patients with chronic liver and/or intestinal diseases.
Development and Validation of an Electronic Frailty Index Using Routine Electronic Health Records: An Observational Study From a General Hospital in China
Authors: Liang Yao-Dan , Xie Yi-Bo , Du Ming-Hui , Shi Jing , Yang Jie-Fu , Wang Hua
Published: September 2021

Background: This study aimed to develop and validate an electronic frailty index (eFI) based on routine electronic health records (EHR) for older adult inpatients and to analyze the correlations between frailty and hospitalized events and costs.

Methods: We created an eFI from routine EHR and validated the effectiveness by the consistency of the comprehensive geriatric assessment-frailty index (CGA-FI) with an independent prospective cohort. Then, we analyzed the correlations between frailty and hospitalized events and costs by regressions.

Results: During the study period, 49,226 inpatients were included in the analysis, 42,821 (87.0%) of which had enough data to calculate an eFI. A strong correlation between the CGA-FI and eFI was shown in the validation cohort of 685 subjects (Pearson's r = 0.716, P < 0.001). The sensitivity and specificity for an eFI≥0.15, the upper tertile, to identify frailty, defined as a CGA-FI≥0.25, were 64.8 and 88.7%, respectively. After adjusting for age, sex, and operation, an eFI≥0.15 showed an independent association with long hospital stay (odds ratio [OR] = 2.889, P < 0.001) and death in hospital (OR = 19.97, P < 0.001). Moreover, eFI values (per 0.1) were positively associated with total costs (β = 0.453, P < 0.001), examination costs (β = 0.269, P < 0.001), treatment costs (β = 0.414, P < 0.001), nursing costs (β = 0.381, P < 0.001), pharmacy costs (β = 0.524, P < 0.001), and material costs (β = 0.578, P < 0.001) after adjusting aforementioned factors.

Conclusions: We successfully developed an effective eFI from routine EHR from a general hospital in China. Frailty is an independent risk factor for long hospital stay and death in hospital. As the degree of frailty increases, the hospitalized costs increase accordingly.
Pneumonia Patients Caused by Co-infection With SARS-CoV-2 and Human Adenovirus in China
Authors: Qiu Shaofu , Zeng Ge , Li Peihan , Li Xiaohui , Liu Hongbo , Du Xinying , Liu Hongbo , Zhang Heng , Xiang Xingyu , Wang Hui , Chen Xiangbing , Yang Guangyao , Tian Sai , Wang Ligui , Yang Mingjuan , Yang Chaojie , Gao Lidong , Hu Shixiong , Song Hongbin , Zhan Zhifei
Published: September 2021

Objectives: To data, no patients with obvious epidemiological relationship co-infected with SARS-CoV-2 and other pathogens have been reported. Here, we investigated 10 patients caused by co-infection with SARS-CoV-2 and human adenovirus (HAdV), resulting in third-generation transmission.

Materials and Methods: From Jan 15, 2020, we enrolled 10 patients with pneumonia in Hunan Province, China. Epidemiological, clinical, and laboratory investigation results from these patients were analyzed. An epidemiological investigation was performed to assess whether patient infections were linked using conventional methods and metagenomic sequencing.

Results: The presence of co-infection with SARS-CoV-2 and HAdV was determined via RT-PCR and metagenomic sequencing. Phylogenetic analysis revealed that SARS-CoV-2 and HAdV genomes clustered together, with similar genetic relationships. The first patient likely became co-infected during meetings or travel in Wuhan. The patient transmitted the virus via dinners and meetings, which resulted in four second-generation cases. Then, a second-generation case transmitted the virus to her family members or relatives via presymptomatic transmission.

Conclusions: This study described an example of co-infection with SARS-CoV-2 and HAdV in pneumonia patients, which caused third-generation cases and inter-regional transmission via meetings, household interactions, and dinner parties. We also observed the persistent and presymptomatic transmission of co-infection, which has the potential to make the continued control of the COVID-19 pandemic challenging. Continuous surveillance is needed to monitor the prevalence, infectivity, transmissibility, and pathogenicity of SARS-CoV-2 co-infection with other pathogens to evaluate its real risk.
Intrinsic Capacity vs. Multimorbidity: A Function-Centered Construct Predicts Disability Better Than a Disease-Based Approach in a Community-Dwelling Older Population Cohort
Authors: Zhao Jing , Chhetri Jagadish K. , Chang Yi , Zheng Zheng , Ma Lina , Chan Piu
Published: September 2021

Objective: This study aimed to assess the status of intrinsic capacity (IC)—a novel function-centered construct proposed by the WHO and examine whether impairment in IC predicts subsequent 1-year activities of daily living (ADL) disability better than a disease-based approach, i. e., multimorbidity status.

Methods: This study included data of community-dwelling older adults from the Beijing Longitudinal Study on Aging II aged 65 years or older who were followed up at 1 year. Multivariate logistic regressions were performed to estimate the odds of ADL disability at baseline and 1-year follow-up.

Results: A total of 7,298 older participants aged 65 years or older were included in the current study. About 4,742 older adults were followed up at 1 year. At baseline, subjects with a higher impairment in IC domains showed higher odds of ADL disability [adj. odds ratio (OR) = 9.51 for impairment in ≥3 domains, area under the curve (AUC) = 0.751] compared to much lower odds of ADL disability in subjects with a higher number (≥3) of chronic diseases (adj. OR 3.92, AUC = 0.712). At 1-year follow-up, the overall incidence of ADL disability increased with the impairment in IC domains higher than the increase in multimorbidity status. A higher impairment in IC domains showed higher odds of incidence ADL disability for impairment in 2 or ≥3 IC domains (adj. OR 2.32 for impairment in ≥3 domains, adj. OR 1.43 for impairment in two domains, AUC = 0.685). Only subjects who had ≥3 chronic diseases had higher odds of 1-year incident ADL disability (adj. OR 1.73, AUC = 0.681) that was statistically significant.

Conclusion: Our results imply that a function-centered construct could have higher predictability of disability compared to the multimorbidity status in community older people. Our results need to be confirmed by studies with longer follow-up.
Lactic Acid Bacteria – A Promising Tool for Controlling Chicken Campylobacter Infection
Authors: Wyszyńska Agnieszka Krystyna , Godlewska Renata
Published: September 2021

Since 2005, campylobacteriosis has been the most common zoonotic disease in Europe. The main reservoir of pathogenic Campylobacter strains is broilers, which makes raw and undercooked poultry meat two major sources of disease. Infection in chicken flocks is most often asymptomatic, despite a high level of colonization reaching 106–109cfu/g in animal ceca. It is widely believed that controlling the level of colonization of the birds’ digestive tract by pathogenic strains is a good way to increase food safety. Many treatments have been proposed to combat or at least reduce the level of colonization in animals reservoirs: probiotics, bacteriophages, vaccines, and anti-Campylobacter bacteriocins. This review focuses on the effects of Campylobacter infection on the chicken microbiome and colonization control strategies using probiotics (mostly lactic acid bacteria, LAB), which are live microorganisms included in the diet of animals as feed additives or supplements. Probiotics are not only an alternative to antibiotics, which were used for years as animal growth promoters, but they also constitute an effective protective barrier against excessive colonization of the digestive system by pathogenic bacteria, including Campylobacter. Moreover, one of the many beneficial functions of probiotics is the ability to manipulate the host’s microbiota. Recently, there have also been some promising attempts to use lactic acid bacteria as a delivery system of oral vaccine against Campylobacter. Recombinant LAB strains induce primarily a mucosal immune response against foreign antigens, accompanied by at most a low-level immune response against carrier strains. Since the main barrier against the invasion of pathogens in the gastrointestinal tract is the intestinal mucosal membrane, the development of effective oral vaccines to protect animals against enteric infection is very reasonable.
Novel Symbiotic Association Between Euwallacea Ambrosia Beetle and Fusarium Fungus on Fig Trees in Japan
Authors: Jiang Zi-Ru , Masuya Hayato , Kajimura Hisashi
Published: September 2021

Ficus carica plantations in Japan were first reported to be infested by an ambrosia beetle species, identified as Euwallacea interjectus, in 1996. The purpose of this study was to determine the symbiotic fungi of female adults of E. interjectus emerging from F. carica trees infected with fig wilt disease (FWD). Dispersal adults (51 females) of E. interjectus, which were collected from logs of an infested fig tree in Hiroshima Prefecture, Western Japan, were separated into three respective body parts (head, thorax, and abdomen) and used for fungal isolation. Isolated fungi were identified based on the morphological characteristics and DNA sequence data. Over 13 species of associated fungi were detected, of which a specific fungus, Fusarium kuroshium, was dominant in female head (including oral mycangia). The plant-pathogenic fungus of FWD, Ceratocystis ficicola, was not observed within any body parts of E. interjectus. We further discussed the relationship among E. interjectus and its associated fungi in fig tree.
The Role of Short-Chain Fatty Acids of Gut Microbiota Origin in Hypertension
Authors: Wu Yeshun , Xu Hongqing , Tu Xiaoming , Gao Zhenyan
Published: September 2021

Hypertension is a significant risk factor for cardiovascular and cerebrovascular diseases, and its development involves multiple mechanisms. Gut microbiota has been reported to be closely linked to hypertension. Short-chain fatty acids (SCFAs)—the metabolites of gut microbiota—participate in hypertension development through various pathways, including specific receptors, immune system, autonomic nervous system, metabolic regulation and gene transcription. This article reviews the possible mechanisms of SCFAs in regulating blood pressure and the prospects of SCFAs as a target to prevent and treat hypertension.
Low Concentrations of Chlorhexidine Inhibit the Formation and Structural Integrity of Enzyme-Treated Multispecies Oral Biofilms
Authors: Gränicher Kay Andrin , Karygianni Lamprini , Attin Thomas , Thurnheer Thomas
Published: September 2021

The self-produced matrix of biofilms, consisting of extracellular polymeric substances, plays an important role in biofilm adhesion to surfaces and the structural integrity of biofilms. In dentistry, biofilms cause multiple diseases such as caries, periodontitis, and pulpitis. Disruption of these biofilms adhering to dental hard tissues may pose a major challenge since biofilms show higher tolerance to antimicrobials and antibiotics than planktonic cells. In this study, the effect of low concentrations of chlorhexidine (CHX) on enzyme-treated multispecies oral biofilm was investigated in an in vitro model. Six-species biofilms were enzymatically treated by anaerobic growth in a medium containing DNase I and proteinase K. Biofilms were exposed to a low concentration of CHX at defined time points. After 64h, biofilms were either harvested and quantified by cultural analyses or stained for confocal laser scanning microscopy (CLSM) analyses using either Live/Dead kit or different fluorescent dyes. A mixture of YoPro1 and SYTOX™ Green, Fluorescent Brightener 28 (Calcofluor), and SYPRO™ Ruby Protein Gel Stain was used to stain total DNA, exopolysaccharides, and extracellular proteins, respectively. Extracellular DNA (eDNA) was visualized via an indirect immunofluorescence assay (Mouse anti-DNA IgG, Goat anti-Mouse IgG, Streptavidin-Cy3). Overall, the total colony-forming units significantly decreased after combined treatment with a low concentration of CHX and enzymes compared to the group treated with CHX alone (p<0.001). These findings also apply to five species individually (Streptococcus mutans, Streptococcus oralis, Actinomyces oris, Veillonella dispar, and Candida albicans) occurring in the biofilms, with Fusobacterium nucleatum being the only exception. Furthermore, CLSM images showed less dense biofilms and a reduction in cell numbers after combined treatment compared to the group without enzymes. The combination of enzymes capable of disturbing the matrix integrity with antimicrobial agents thus appears to be a promising approach for biofilm disruption and killing.
Hypertension With High Homocysteine Is Associated With Default Network Gray Matter Loss
Authors: Kong Yanliang , Li Xin , Chang Lina , Liu Yuwei , Jia Lin , Gao Lei , Ren Lijuan
Published: September 2021

Hypertension with high homocysteine (Hcy, ≥10 μmol/L) is also known as H-type hypertension (HHT) and proposed as an independent risk factor for stroke and cognitive impairment. Although previous studies have established the relationships among hypertension, Hcy levels, and cognitive impairment, how they affect brain neuroanatomy remains unclear. Thus, we aimed to investigate whether and to what extent hypertension and high Hcy may affect gray matter volume in 52 middle-aged HHT patients and 51 demographically matched normotensive subjects. Voxel-based morphological analysis suggested that HHT patients experienced significant gray matter loss in the default network. The default network atrophy was significantly correlated with Hcy level and global cognitive function. These findings provide, to our knowledge, novel insights into how HHT affects brain gray matter morphology through blood pressure and Hcy.
Clinical Features in Patients With PANDAS/PANS and Therapeutic Approaches: A Retrospective Study
Authors: Rea Isabella , Guido Cristiana Alessia , Spalice Alberto
Published: September 2021

Objective: The clinical characteristics of patients with PANDAS (pediatric autoimmune neuropsychiatric disorders associated with streptococcal infection) and PANS (pediatric acute-onset neuropsychiatric syndrome) and the efficacy of antibiotic therapy with psychotherapy and antipsychotics were investigated to improve neurological symptoms as well as obsessive compulsive disorder (OCD).

Methods: We retrospectively analyzed 62 patients with a clinical diagnosis of PANDAS/PANS enrolled from May 14, 2013 to September 15, 2020 in the Neurology Childhood Division, Department of Pediatrics at Sapienza, Rome. Clinical manifestations, neurological and psychiatric, laboratory investigations, and familiar history were collected to evaluate the differences between the two groups. The effects of various therapeutic approaches were examined. Descriptive and comparative statistical analyses were performed.

Results: The mean age at onset of PANDAS/PANS symptoms was 6.2 ± 1.2 years. The most common diagnosis was PANDAS, followed by PANS. Neurological and psychiatric symptoms were mostly evident in both groups (>70% of the population), with no significant difference between them (P = 0.52 and P = 0.15, respectively). Irritability, aggressivity, and food restriction were more prevalent in children with PANS than in those with PANDAS (P = 0.024 and P = 0.0023, respectively). The levels of anti-streptolysin O and anti-DNAse B 10-fold higher in PANDAS than those in PANS (P < 0.0001). Antibiotics or psychotherapy were administered in most cases (90.3 and 53.2%, respectively), followed by antipsychotic treatments (24.2%). In the multivariate analysis, among the therapies used, psychotherapy significantly resulted in the most efficacious relief of OCD, reducing stress in patients and their parents (P = 0.042).

Conclusion: Our findings confirm a clear clinical difference between the two groups, PANDAS and PANS, using different approaches. In fact, irritability, aggressivity, and food restriction were significantly more frequent in children with PANS and the levels of anti-streptolysin O and anti-DNAse B were higher in PANDAS. Another relevant finding is the efficacy of psychotherapy, especially for obsessive-compulsive disorder, and of antibiotic prophylaxis in managing acute neurological symptoms.
Lateralization of Color Discrimination Performance and Lexical Effects in Patients With Chronic Schizophrenia
Authors: Kogata Tomohiro , Iidaka Tetsuya
Published: September 2021

Introduction:Patients with schizophrenia experience various visual disturbances. However, information regarding color perception in these patients is rare. In this study, we used a lateralized color search task to investigate whether difference in color name affects color recognition in patients with schizophrenia.

Methods:In a color search task, we controlled the position of the target that emerged from the left visual field (LVF) or right visual field (RVF) as well as the color category. In this task, both the target and the distractors had the same or different color name (e.g., blue or green).

Results:Patients with schizophrenia showed faster performance in the color search task with different color names for target-distractors when the target emerged from the LVF than when it emerged from the RVF. However, the same laterality was not observed in healthy controls. This finding indicates that semantic processing for color name differences influenced visual discrimination performance in patients with schizophrenia more profoundly in the LVF than in the RVF.

Conclusion:This lateralized performance could imply the failure of the left hemisphere language processing dominance in schizophrenia. A search paradigm combining target position and category may indicate that automatic language processing depends on imbalanced hemispheric function in schizophrenia.
Efficiency Evaluation of Neuroprotection for Therapeutic Hypothermia to Neonatal Hypoxic-Ischemic Encephalopathy
Authors: Weng Bowen , Yan Chongbing , Chen Yihuan , Gong Xiaohui , Cai Cheng
Published: September 2021

Background: To evaluate the safety and neurological outcomes of therapeutic hypothermia to neonatal hypoxic-ischemic encephalopathy (HIE).

Materials and Methods: Medical records of 61 neonates with moderate to severe HIE were retrospectively enrolled and divided into a therapeutic hypothermia group (n = 36) and conventional therapy group (n = 25).

Results: No significant difference in the incidence of severe adverse events was found between the two groups. Minimum and maximum voltages of amplitude-integrated electroencephalography (aEEG) recording results showed statistically significant differences in therapeutic hypothermia group after 72 h. The neonatal behavioral neurological assessment (NBNA) on the 28th day after birth and Bayley Scales of Infant Development, second edition (BSID II) scores at 18 months old were significant higher in the therapeutic hypothermia group than the conventional therapy group.

Conclusion: Therapeutic hypothermia for neonates with moderate to severe HIE improved the development of the nervous system in 0–18-month-old infants and showed a predominant role in reducing death and major neuron development-associated disabilities.
The Proliferation of Dentate Gyrus Progenitors in the Ferret Hippocampus by Neonatal Exposure to Valproic Acid
Authors: Sawada Kazuhiko , Kamiya Shiori , Aoki Ichio
Published: September 2021

Prenatal and neonatal exposure to valproic acid (VPA) is associated with human autism spectrum disorder (ASD) and can alter the development of several brain regions, such as the cerebral cortex, cerebellum, and amygdala. Neonatal VPA exposure induces ASD-like behavioral abnormalities in a gyrencephalic mammal, ferret, but it has not been evaluated in brain regions other than the cerebral cortex in this animal. This study aimed to facilitate a comprehensive understanding of brain abnormalities induced by developmental VPA exposure in ferrets. We examined gross structural changes in the hippocampus and tracked proliferative cells by 5-bromo-2-deoxyuridine (BrdU) labeling following VPA administration to ferret infants on postnatal days (PDs) 6 and 7 at 200 μg/g of body weight. Ex vivo short repetition time/time to echo magnetic resonance imaging (MRI) with high spatial resolution at 7-T was obtained from the fixed brain of PD 20 ferrets. The hippocampal volume estimated using MRI-based volumetry was not significantly different between the two groups of ferrets, and optical comparisons on coronal magnetic resonance images revealed no differences in gross structures of the hippocampus between VPA-treated and control ferrets. BrdU-labeled cells were observed throughout the hippocampus of both two groups at PD 20. BrdU-labeled cells were immunopositive for Sox2 (>70%) and almost immunonegative for NeuN, S100 protein, and glial fibrillary acidic protein. BrdU-labeled Sox2-positive progenitors were abundant, particularly in the subgranular layer of the dentate gyrus (DG), and were denser in VPA-treated ferrets. When BrdU-labeled Sox2-positive progenitors were examined at 2 h after the second VPA administration on PD 7, their density in the granular/subgranular layer and hilus of the DG was significantly greater in VPA-treated ferrets compared to controls. The findings suggest that VPA exposure to ferret infants facilitates the proliferation of DG progenitors, supplying excessive progenitors for hippocampal adult neurogenesis to the subgranular layer.
Excretion of Heavy Metals and Glyphosate in Urine and Hair Before and After Long-Term Fasting in Humans
Authors: Grundler Franziska , Séralini Gilles-Eric , Mesnage Robin , Peynet Vincent , Wilhelmi de Toledo Françoise
Published: September 2021

Background: Dietary exposure to environmental pollutants in humans is an important public health concern. While long-term fasting interrupts the dietary exposure to these substances, fat mobilization as an energy source may also release bioaccumulated substances. This was, to our knowledge, only investigated in obese people decades ago. This study explored the effects of 10-days fasting on the excretion of heavy metals and glyphosate.

Methods: Urinary levels of arsenic, chromium, cobalt, lead, nickel, mercury and glyphosate were measured before and after 10 fasting days in 109 healthy subjects. Additionally, hair analysis was done before and ten weeks after fasting in 22 subjects.

Results: Fasting caused a decrease in body weight, and in urinary arsenic (by 72%) and nickel (by 15%) concentrations. A decrease in lead hair concentrations (by 30%) was documented. Urinary mercury levels were unchanged for chromium, cobalt and glyphosate, which were undetectable in most of the subjects. Additionally, fatigue, sleep disorders, headache and hunger were reduced. Body discomfort symptoms diminished four weeks after food reintroduction.

Conclusions: The results of this study provide the first insights into the changes in heavy metal excretion caused by long-term fasting. Further studies focusing on the kinetics of efflux between different compartments of the body are needed.

Clinical Trial Registration:https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00016657, identifier: DRKS00016657.
Determination of the Heterogeneity of Intramuscular Fat and Visceral Adipose Tissue From Dezhou Donkey by Lipidomics and Transcriptomics Profiling
Authors: Li Mengmeng , Zhu Mingxia , Chai Wenqiong , Wang Yonghui , Song Yinghua , Liu Baoxiu , Cai Changyun , Song Yingzi , Sun Xue , Xue Peng , Wang Changfa
Published: September 2021

Intramuscular fat (IMF) and visceral adipose tissue (VAT) are both lipids, but have significantly different deposition processes. Furthermore, the heterogeneity of lipid molecular characteristics and mechanisms is unclear. Accordingly, this study used non-targeted lipidomics and transcriptomics to analyze the lipid profiles and metabolism of longissimus dorsi muscle (LDM) and VAT from donkeys. A total of 1,146 and 1,134 lipids belonging to 18 subclasses were identified in LDM and VAT, respectively, with LDM having higher glycerophospholipid (GP) and lower glycerolipid (GL) contents. Polyunsaturated fatty acids (PUFAs) were distributed preferentially at the sn-1 positions in triglycerides (TGs), and sn-2 positions in phosphatidylcholine (PC) and phosphatidylethanolamine (PE). The percentage PUFA content in TGs was significantly lower in LDM than in VAT, while the opposite trend was observed for PUFAs in PC and PE. A total of 110 different lipid molecules (72 downregulated and 38 upregulated) were identified in LDM compared with VAT, of which 11 were considered potential lipid markers. These different lipids were involved in 17 metabolic pathways, including GL and GP metabolisms. Of the 578 differentially expressed genes screened, 311 were downregulated and 267 were upregulated in LDM compared with VAT. Enriched ontology analysis of the differentially expressed genes mainly involved sphingolipid signaling pathways, and GP, GL, and sphingolipid metabolisms. Overall, lipidomics and transcriptomics indicated differences in lipid profiles and metabolism in LDM and VAT, providing new perspectives for the study of heterogeneity in IMF and VAT.
RNA Sequencing Data for FFPE Tumor Blocks Can Be Used for Robust Estimation of Tumor Mutation Burden in Individual Biosamples
Authors: Sorokin Maxim , Gorelyshev Alexander , Efimov Victor , Zotova Evgenia , Zolotovskaia Marianna , Rabushko Elizaveta , Kuzmin Denis , Seryakov Alexander , Kamashev Dmitry , Li Xinmin , Poddubskaya Elena , Suntsova Maria , Buzdin Anton
Published: September 2021

Tumor mutation burden (TMB) is a well-known efficacy predictor for checkpoint inhibitor immunotherapies. Currently, TMB assessment relies on DNA sequencing data. Gene expression profiling by RNA sequencing (RNAseq) is another type of analysis that can inform clinical decision-making and including TMB estimation may strongly benefit this approach, especially for the formalin-fixed, paraffin-embedded (FFPE) tissue samples. Here, we for the first time compared TMB levels deduced from whole exome sequencing (WES) and RNAseq profiles of the same FFPE biosamples in single-sample mode. We took TCGA project data with mean sequencing depth 23 million gene-mapped reads (MGMRs) and found 0.46 (Pearson)–0.59 (Spearman) correlation with standard mutation calling pipelines. This was converted into low (<10) and high (>10) TMB per megabase classifier with area under the curve (AUC) 0.757, and application of machine learning increased AUC till 0.854. We then compared 73 experimental pairs of WES and RNAseq profiles with lower (mean 11 MGMRs) and higher (mean 68 MGMRs) RNA sequencing depths. For higher depth, we observed ~1 AUC for the high/low TMB classifier and 0.85 (Pearson)–0.95 (Spearman) correlation with standard mutation calling pipelines. For the lower depth, the AUC was below the high-quality threshold of 0.7. Thus, we conclude that using RNA sequencing of tumor materials from FFPE blocks with enough coverage can afford for high-quality discrimination of tumors with high and low TMB levels in a single-sample mode.
Efficacy and Safety of First-Line Chemotherapies for Patients With Advanced Biliary Tract Carcinoma: A Systematic Review and Network Meta-Analysis
Authors: Jiang Yanfeng , Zeng Zhiming , Zeng Jie , Liu Cuizhen , Qiu Jinfeng , Li Ye , Tang Jing , Mo Ning , Du Lihua , Ma Jie
Published: September 2021

Background

At present, chemotherapy is still the primary treatment for advanced biliary tract carcinoma, but it is challenging to balance the efficacy and side effects. Network meta-analysis (NMA) is a better way to identify the protocol, and the advantage is that it can be combined with direct and indirect evidence to judge the best treatment regimens. Therefore, we conducted NMA on the searched randomized controlled trials (RCTs).

Methods

NMA was conducted regarding the searched RCTs by comparing progression-free survival (PFS), overall survival (OS), objective remission rates (ORRs), and adverse events (AEs) of different chemotherapy protocols.

Results

We screened 24 studies that met the inclusion criteria for further analysis. Compared with other regimens, the best supportive care (BSC) or FUFA protocol has a worse OS. Folfox4, GEMOX+erlotinib, and C+GEMOX can improve patients’ PFS compared with BSC. Patients receiving GP+cediranib protocol have higher ORRs. There was reduced neutropenia grade ≥3 when adopting GP+cediranib, GS, C+GEMOX, RAM+GP, and MER+GP than when using FUFA protocol. The probability of vomiting of XELOX is lower than that of GEM+XELOX. There is a lower diarrhea incidence of XELOX than that of GEMOX+erlotinib. The results of cluster grade analysis illustrated that GEMOX+erlotinib owned a higher ORR and a higher surface under the cumulative ranking (SUCRA) of neutropenia and vomiting but also had a lower SUCRA of diarrhea and fatigue. Meanwhile, both GEMOX and C+GEMOX have a better ORR and a higher AE SUCRA.

Conclusion

The NMA demonstrated that chemotherapy combined with targeted therapy has better efficacy and lower incidence of AEs than chemotherapy alone.
Dosimetric Impact of Inter-Fraction Anatomical Changes in Carbon Ion Boost Treatment for High-Risk Prostate Cancer (AIRC IG 14300)
Authors: Russo Stefania , Ricotti Rosalinda , Molinelli Silvia , Patti Filippo , Barcellini Amelia , Mastella Edoardo , Pella Andrea , Paganelli Chiara , Marvaso Giulia , Pepa Matteo , Comi Stefania , Zaffaroni Mattia , Avuzzi Barbara , Giandini Tommaso , Pignoli Emanuele , Valdagni Riccardo , Baroni Guido , Cattani Federica , Ciocca Mario , Jereczek-Fossa Barbara Alicja , Orlandi Ester , Orecchia Roberto , Vischioni Barbara
Published: September 2021

Rectum and bladder volumes play an important role in the dose distribution reproducibility in prostate cancer adenocarcinoma (PCa) radiotherapy, especially for particle therapy, where density variation can strongly affect the dose distribution. We investigated the reliability and reproducibility of our image-guided radiotherapy (IGRT) and treatment planning protocol for carbon ion radiotherapy (CIRT) within the phase II mixed beam study (AIRC IG 14300) for the treatment of high-risk PCa. In order to calculate the daily dose distribution, a set of synthetic computed tomography (sCT) images was generated from the cone beam computed tomography (CBCT) images acquired in each treatment session. Planning target volume (PTV) together with rectum and bladder volume variation was evaluated with sCT dose-volume histogram (DVH) metric deviations from the planning values. The correlations between the bladder and rectum volumes, and the corresponding DVH metrics, were also assessed. No significant difference in the bladder, rectum, and PTV median volumes between the planning computed tomography (pCT) and the sCT was found. In addition, no significant difference was assessed when comparing the average DVHs and median DVH metrics between pCT and sCT. Dose deviations determined by bladder and rectum filling variations demonstrated that dose distributions were reproducible in terms of both target coverage and organs at risk (OARs) sparing.