bluuebunny/crossref_metadata_2025 huggingface dataset:
A machine learning algorithm to differentiate bipolar disorder from major depressive disorder using an online mental health questionnaire and blood biomarker data
Authors: Tomasik Jakub , Han Sung Yeon Sarah , Barton-Owen Giles , Mirea Dan-Mircea , Martin-Key Nayra A. , Rustogi Nitin , Lago Santiago G. , Olmert Tony , Cooper Jason D. , Ozcan Sureyya , Eljasz Pawel , Thomas Grégoire , Tuytten Robin , Metcalfe Tim , Schei Thea S. , Farrag Lynn P. , Friend Lauren V. , Bell Emily , Cowell Dan , Bahn Sabine
Published: January 2021

The vast personal and economic burden of mood disorders is largely caused by their under- and misdiagnosis, which is associated with ineffective treatment and worsening of outcomes. Here, we aimed to develop a diagnostic algorithm, based on an online questionnaire and blood biomarker data, to reduce the misdiagnosis of bipolar disorder (BD) as major depressive disorder (MDD). Individuals with depressive symptoms (Patient Health Questionnaire-9 score ≥5) aged 18–45 years were recruited online. After completing a purpose-built online mental health questionnaire, eligible participants provided dried blood spot samples for biomarker analysis and underwent the World Health Organization World Mental Health Composite International Diagnostic Interview via telephone, to establish their mental health diagnosis. Extreme Gradient Boosting and nested cross-validation were used to train and validate diagnostic models differentiating BD from MDD in participants who self-reported a current MDD diagnosis. Mean test area under the receiver operating characteristic curve (AUROC) for separating participants with BD diagnosed as MDD (N = 126) from those with correct MDD diagnosis (N = 187) was 0.92 (95% CI: 0.86–0.97). Core predictors included elevated mood, grandiosity, talkativeness, recklessness and risky behaviour. Additional validation in participants with no previous mood disorder diagnosis showed AUROCs of 0.89 (0.86–0.91) and 0.90 (0.87–0.91) for separating newly diagnosed BD (N = 98) from MDD (N = 112) and subclinical low mood (N = 120), respectively. Validation in participants with a previous diagnosis of BD (N = 45) demonstrated sensitivity of 0.86 (0.57–0.96). The diagnostic algorithm accurately identified patients with BD in various clinical scenarios, and could help expedite accurate clinical diagnosis and treatment of BD.
Comprehensive study of 28 individuals with SIN3A-related disorder underscoring the associated mild cognitive and distinctive facial phenotype
Authors: Balasubramanian Meena , Dingemans Alexander J. M. , Albaba Shadi , Richardson Ruth , Yates Thabo M. , Cox Helen , Douzgou Sofia , Armstrong Ruth , Sansbury Francis H. , Burke Katherine B. , Fry Andrew E. , Ragge Nicola , Sharif Saba , Foster Alison , De Sandre-Giovannoli Annachiara , Elouej Sahar , Vasudevan Pradeep , Mansour Sahar , Wilson Kate , Stewart Helen , Heide Solveig , Nava Caroline , Keren Boris , Demirdas Serwet , Brooks Alice S. , Vincent Marie , Isidor Bertrand , Küry Sebastien , Schouten Meyke , Leenders Erika , Chung Wendy K. , Haeringen Arie van , Scheffner Thomas , Debray Francois-Guillaume , White Susan M. , Palafoll Maria Irene Valenzuela , Pfundt Rolph , Newbury-Ecob Ruth , Kleefstra Tjitske
Published: January 2021

Witteveen-Kolk syndrome (OMIM 613406) is a recently defined neurodevelopmental syndrome caused by heterozygous loss-of-function variants in SIN3A. We define the clinical and neurodevelopmental phenotypes related to SIN3A-haploinsufficiency in 28 unreported patients. Patients with SIN3A variants adversely affecting protein function have mild intellectual disability, growth and feeding difficulties. Involvement of a multidisciplinary team including a geneticist, paediatrician and neurologist should be considered in managing these patients. Patients described here were identified through a combination of clinical evaluation and gene matching strategies (GeneMatcher and Decipher). All patients consented to participate in this study. Mean age of this cohort was 8.2 years (17 males, 11 females). Out of 16 patients ≥ 8 years old assessed, eight (50%) had mild intellectual disability (ID), four had moderate ID (22%), and one had severe ID (6%). Four (25%) did not have any cognitive impairment. Other neurological symptoms such as seizures (4/28) and hypotonia (12/28) were common. Behaviour problems were reported in a minority. In patients ≥2 years, three were diagnosed with Autism Spectrum Disorder (ASD) and four with Attention Deficit Hyperactivity Disorder (ADHD). We report 27 novel variants and one previously reported variant. 24 were truncating variants; three were missense variants and one large in-frame gain including exons 10–12.
In vivo intervertebral disc deformation: intratissue strain patterns within adjacent discs during flexion–extension
Authors: Wilson Robert L. , Bowen Leah , Kim Woong , Cai Luyao , Schneider Stephanie Ellyse , Nauman Eric A. , Neu Corey P.
Published: January 2021

The biomechanical function of the intervertebral disc (IVD) is a critical indicator of tissue health and pathology. The mechanical responses (displacements, strain) of the IVD to physiologic movement can be spatially complex and depend on tissue architecture, consisting of distinct compositional regions and integrity; however, IVD biomechanics are predominately uncharacterized in vivo. Here, we measured voxel-level displacement and strain patterns in adjacent IVDs in vivo by coupling magnetic resonance imaging (MRI) with cyclic motion of the cervical spine. Across adjacent disc segments, cervical flexion–extension of 10° resulted in first principal and maximum shear strains approaching 10%. Intratissue spatial analysis of the cervical IVDs, not possible with conventional techniques, revealed elevated maximum shear strains located in the posterior disc (nucleus pulposus) regions. IVD structure, based on relaxometric patterns of T2 and T1ρ images, did not correlate spatially with functional metrics of strain. Our approach enables a comprehensive IVD biomechanical analysis of voxel-level, intratissue strain patterns in adjacent discs in vivo, which are largely independent of MRI relaxometry. The spatial mapping of IVD biomechanics in vivo provides a functional assessment of adjacent IVDs in subjects, and provides foundational biomarkers for elastography, differentiation of disease state, and evaluation of treatment efficacy.
Mining and analysis of multiple association rules between the Xining loess collapsibility and physical parameters
Authors: Li Zhikun , Li Xiaojun , Zhu Yanyan , Dong Shi , Hu Chenzhi , Fan Jixin
Published: January 2021

Collapsibility determination in loess area is expensive, and it also requires a large amount of experimentation. This paper aims to find the association rules between physical parameters and collapsibility of the loess in Xining through the method of data mining, so to help researchers predict the collapsibility of loess. Related physical parameters of loess collapsibility, collected from 1039 samples, involve 13 potential influence factors. According to Grey Relational Analysis, the key influence factors that lead to collapsing are identified from these potential influence factors. Subsequently, take the key influence factors, δs (coefficient of collapsibility) and δzs (coefficient of collapsibility under overburden pressure) as input items, and use the Apriori algorithm to find multiple association rules between them. Then, through analysing the results of association rules between these key influence factors and collapsibility, the evaluation criteria for collapsibility in this area is proposed, which can be used to simplify the workload of determining collapsibility. Finally, based on these research results, recommendations for projects construction were made to ensure the safety of construction in the area.
Mesh patch and anchors can improve clinical results of prosthetic replacement after resection of primary proximal humerus malignant tumor
Authors: Yang Yongkun , Li Yuan , Liu Weifeng , Niu Xiaohui
Published: January 2021

The purpose of this study was to evaluate the functional results, complications and related factors of prosthesis reconstruction after malignant tumor resection of primary proximal humeral, and also evaluate whether soft tissue reconstruction with mesh patch and anchors can improve clinical results. From 2002 to 2016, forty-one patients were enrolled in this study. The pathological diagnosis contained 27 cases of osteosarcoma, 7 cases of chondrosarcoma and other primary malignant bone tumors. Both mesh patch and anchors were used in the reconstruction of joint capsule and the surrounding soft tissues in 27 cases. The mean postoperative follow-up was 60.6 months. The average active abduction angle and passive abduction angle was 33.5 (5–71) degrees and 72.4 (52–104) degrees. The prosthetic humeral head displacement was over 2 cm in 5 cases (12.2%). The average MSTS score was 23.1. The overall 5-year survival rate of prosthesis was 88.2%. The length of osteotomy, whether preserving deltoid muscle, whether applying mesh patch and anchors had significant effects on the abduction angle of shoulder joint; the length of osteotomy, whether applying mesh patch and anchors had significant effects on the degree of upward displacement of prosthesis. The application of both mesh patch and anchors in prosthesis reconstruction achieved more stable result and better function of shoulder joint. To ensure the stability of shoulder joint and the firm wrapping of surrounding soft tissue are key factors affecting the postoperative function.
Prospective evaluation of metabolic intratumoral heterogeneity in patients with advanced gastric cancer receiving palliative chemotherapy
Authors: Yoo Shin Hye , Kang Seo Young , Yoon Jeesun , Kim Tae-Yong , Cheon Gi Jeong , Oh Do-Youn
Published: January 2021

Although metabolic intratumoral heterogeneity (ITH) gives important value on treatment responses and prognoses, its association with treatment outcomes have not been reported in gastric cancer (GC). We aimed to evaluate temporal changes in metabolic ITH and the associations with treatment responses, progression-free survival (PFS), and overall survival (OS) in advanced GC patients. Eighty-five patients with unresectable, locally advanced, or metastatic GC were prospectively enrolled before the first-line palliative chemotherapy and underwent [18F]FDG PET at baseline (TP1) and the first response follow-up evaluation (TP2). Standardized uptake values (SUVs), volumetric parameters, and textural features were evaluated in primary gastric tumor at TP1 and TP2. Of 85 patients, 44 had partial response, 33 had stable disease, and 8 progressed. From TP1 to TP2, metabolic ITH was significantly reduced (P < 0.01), and the degree of the decrease was greater in responders than in non-responders (P < 0.01). Using multiple Cox regression analyses, a low SUVmax at TP2, a high kurtosis at TP2 and larger decreases in the coefficient of variance were associated with better PFS. A low SUVmax at TP2, larger decreases in the metabolic tumor volume and larger decreased in the energy were associated with better OS. Age older than 60 years and responders also showed better OS. An early reduction in metabolic ITH is useful to predict treatment outcomes in advanced GC patients.
An open access dataset for developing automated detectors of Antarctic baleen whale sounds and performance evaluation of two commonly used detectors
Authors: Miller Brian S. ,   The IWC-SORP/SOOS Acoustic Trends Working Group, Miller Brian S. , Stafford Kathleen M. , Van Opzeeland Ilse , Harris Danielle , Samaran Flore , Širović Ana , Buchan Susannah , Findlay Ken , Balcazar Naysa , Nieukirk Sharon , Leroy Emmanuelle C. , Aulich Meghan , Shabangu Fannie W. , Dziak Robert P. , Lee Won Sang , Hong Jong Kuk
Published: January 2021

Since 2001, hundreds of thousands of hours of underwater acoustic recordings have been made throughout the Southern Ocean south of 60° S. Detailed analysis of the occurrence of marine mammal sounds in these circumpolar recordings could provide novel insights into their ecology, but manual inspection of the entirety of all recordings would be prohibitively time consuming and expensive. Automated signal processing methods have now developed to the point that they can be applied to these data in a cost-effective manner. However training and evaluating the efficacy of these automated signal processing methods still requires a representative annotated library of sounds to identify the true presence and absence of different sound types. This work presents such a library of annotated recordings for the purpose of training and evaluating automated detectors of Antarctic blue and fin whale calls. Creation of the library has focused on the annotation of a representative sample of recordings to ensure that automated algorithms can be developed and tested across a broad range of instruments, locations, environmental conditions, and years. To demonstrate the utility of the library, we characterise the performance of two automated detection algorithms that have been commonly used to detect stereotyped calls of blue and fin whales. The availability of this library will facilitate development of improved detectors for the acoustic presence of Southern Ocean blue and fin whales. It can also be expanded upon to facilitate standardization of subsequent analysis of spatiotemporal trends in call-density of these circumpolar species.
Molecular and biophysical mechanisms behind the enhancement of lung surfactant function during controlled therapeutic hypothermia
Authors: Autilio C. , Echaide M. , Cruz A. , García-Mouton C. , Hidalgo A. , Da Silva E. , De Luca D. , Sørli Jorid B. , Pérez-Gil J.
Published: January 2021

Therapeutic hypothermia (TH) enhances pulmonary surfactant performance in vivo by molecular mechanisms still unknown. Here, the interfacial structure and the composition of lung surfactant films have been analysed in vitro under TH as well as the molecular basis of its improved performance both under physiological and inhibitory conditions. The biophysical activity of a purified porcine surfactant was tested under slow and breathing-like dynamics by constrained drop surfactometry (CDS) and in the captive bubble surfactometer (CBS) at both 33 and 37 °C. Additionally, the temperature-dependent surfactant activity was also analysed upon inhibition by plasma and subsequent restoration by further surfactant supplementation. Interfacial performance was correlated with lateral structure and lipid composition of films made of native surfactant. Lipid/protein mixtures designed as models to mimic different surfactant contexts were also studied. The capability of surfactant to drastically reduce surface tension was enhanced at 33 °C. Larger DPPC-enriched domains and lower percentages of less active lipids were detected in surfactant films exposed to TH-like conditions. Surfactant resistance to plasma inhibition was boosted and restoration therapies were more effective at 33 °C. This may explain the improved respiratory outcomes observed in cooled patients with acute respiratory distress syndrome and opens new opportunities in the treatment of acute lung injury.
Complex of human Melanotransferrin and SC57.32 Fab fragment reveals novel interdomain arrangement with ferric N-lobe and open C-lobe
Authors: Hayashi Kristyn , Longenecker Kenton L. , Liu Yi-Liang , Faust Bryan , Prashar Aditi , Hampl Johannes , Stoll Vincent , Vivona Sandro
Published: January 2021

Melanotransferrin (MTf) is an iron-binding member of the transferrin superfamily that can be membrane-anchored or secreted in serum. On cells, it can mediate transferrin-independent iron uptake and promote proliferation. In serum, it is a transcytotic iron transporter across the blood–brain barrier. MTf has been exploited as a drug delivery carrier to the brain and as an antibody-drug conjugate (ADC) target due to its oncogenic role in melanoma and its elevated expression in triple-negative breast cancer (TNBC). For treatment of TNBC, an MTf-targeting ADC completed a phase I clinical trial (NCT03316794). The structure of its murine, unconjugated Fab fragment (SC57.32) is revealed here in complex with MTf. The MTf N-lobe is in an active and iron-bound, closed conformation while the C-lobe is in an open conformation incompatible with iron binding. This combination of active and inactive domains displays a novel inter-domain arrangement in which the C2 subdomain angles away from the N-lobe. The C2 subdomain also contains the SC57.32 glyco-epitope, which comprises ten protein residues and two N-acetylglucosamines. Our report reveals novel features of MTf and provides a point of reference for MTf-targeting, structure-guided drug design.
Uraemic toxins impair skeletal muscle regeneration by inhibiting myoblast proliferation, reducing myogenic differentiation, and promoting muscular fibrosis
Authors: Alcalde-Estévez Elena , Sosa Patricia , Asenjo-Bueno Ana , Plaza Patricia , Olmos Gemma , Naves-Díaz Manuel , Rodríguez-Puyol Diego , López-Ongil Susana , Ruiz-Torres María P.
Published: January 2021

Uraemic toxins increase in serum parallel to a decline in the glomerular filtration rate and the development of sarcopenia in patients with chronic kidney disease (CKD). This study analyses the role of uraemic toxins in sarcopenia at different stages of CKD, evaluating changes in the muscular regeneration process. Cultured C2C12 cells were incubated with a combination of indoxyl sulphate and p-cresol at high doses (100 µg/mL) or low doses (25 µg/mL and 10 µg/mL) resembling late or early CKD stages, respectively. Cell proliferation (analysed by scratch assays and flow cytometry) was inhibited only by high doses of uraemic toxins, which inactivated the cdc2-cyclin B complex, inhibiting mitosis and inducing apoptosis (analysed by annexin V staining). By contrast, low doses of uraemic toxins did not affect proliferation, but reduced myogenic differentiation, primed with 2% horse serum, by inhibiting myogenin expression and promoting fibro-adipogenic differentiation. Finally, to assess the in vivo relevance of these results, studies were performed in gastrocnemii from uraemic rats, which showed higher collagen expression and lower myosin heavy chain expression than those from healthy rats. In conclusion, uraemic toxins impair the skeletal muscular regeneration process, even at low concentrations, suggesting that sarcopenia can progress from the early stages of CKD.
Heat diffusion-related damping process in a highly precise coarse-grained model for nonlinear motion of SWCNT
Authors: Koh Heeyuen , Chiashi Shohei , Shiomi Junichiro , Maruyama Shigeo
Published: January 2021

Second sound and heat diffusion in single-walled carbon nanotubes (SWCNT) are well-known phenomena which is related to the high thermal conductivity of this material. In this paper, we have shown that the heat diffusion along the tube axis affects the macroscopic motion of SWCNT and adapting this phenomena to coarse-grained (CG) model can improve the precision of the coarse-grained molecular dynamics (CGMD) exceptionally. The nonlinear macroscopic motion of SWCNT in the free thermal vibration condition in adiabatic environment is demonstrated in the most simplified version of CG modeling as maintaining finite temperature and total energy with suggested dissipation process derived from internal heat diffusion. The internal heat diffusion related to the cross correlated momentum from different potential energy functions is considered, and it can reproduce the nonlinear dynamic nature of SWCNTs without external thermostatting in CG model. Memory effect and thermostat with random noise distribution are not included, and the effect of heat diffusion on memory effect is quantified through Mori–Zwanzig formalism. This diffusion shows perfect syncronization of the motion between that of CGMD and MD simulation, which is started with initial conditions from the molecular dynamics (MD) simulation. The heat diffusion related to this process has shown the same dispersive characteristics to second wave in SWCNT. This replication with good precision indicates that the internal heat diffusion process is the essential cause of the nonlinearity of the tube. The nonlinear dynamic characteristics from the various scale of simple beads systems are examined with expanding its time step and node length.
Complete genomic sequence and analysis of β2 toxin gene mapping of Clostridium perfringens JXJA17 isolated from piglets in China
Authors: Zeng Xiu , Liu Baosheng , Zhou Jiao , Dai Yimin , Han Chunsheng , Wang Linkang , Wu Yunzheng , Zhang Jinhua
Published: January 2021

Clostridium perfringens (Cp) is a ubiquitous opportunistic pathogen of humans and animals in the natural environment and animal intestines. The pathogenicity of Cp depends on the production of toxins encoded by genes on the chromosomes or plasmids. In contemporary literature, there is no clear consensus about the pathogenicity of CpA β2 toxin. To analyze the homology of the genome of piglet source CpA and its β2 toxin, we sequenced the whole genome of strain JXJA17 isolated from diarrhea piglets using the Illumina Miseq and Pacbio Sequel platforms. The genome was composed of a circular chromosome with 3,324,072 bp (G + C content: 28.51%) and nine plasmids. Genome and 16S rDNA homology analysis revealed a close relation of the JXJA17 strain with the JGS1495, Cp-06, Cp-16, and FORC_003 strains. These strains were isolated from different samples and belonged to different toxin-types. JXJA17 strain was found to carry two toxin genes (plc and cpb2). In contrast to other Cp strains, the cpb2 of JXJA17 was located on a large plasmid (58 kb) with no co-localization of other toxin genes or antibiotic resistance genes. Analysis of JXJA17 genome homology and its cpb2 would facilitate our further study the relationship between β2 toxin and piglet diarrhea.
Galanin receptor 3 attenuates inflammation and influences the gut microbiota in an experimental murine colitis model
Authors: Brunner Susanne M. , Reichmann Florian , Leitner Julia , Wölfl Soraya , Bereswill Stefan , Farzi Aitak , Schneider Anna-Maria , Klieser Eckhard , Neureiter Daniel , Emberger Michael , Heimesaat Markus M. , Weghuber Daniel , Lang Roland , Holzer Peter , Kofler Barbara
Published: January 2021

The regulatory (neuro)peptide galanin and its three receptors (GAL1–3R) are involved in immunity and inflammation. Galanin alleviated inflammatory bowel disease (IBD) in rats. However, studies on the galanin receptors involved are lacking. We aimed to determine galanin receptor expression in IBD patients and to evaluate if GAL2R and GAL3R contribute to murine colitis. Immunohistochemical analysis revealed that granulocytes in colon specimens of IBD patients (Crohn’s disease and ulcerative colitis) expressed GAL2R and GAL3R but not GAL1R. After colitis induction with 2% dextran sulfate sodium (DSS) for 7 days, mice lacking GAL3R (GAL3R-KO) lost more body weight, exhibited more severe colonic inflammation and aggravated histologic damage, with increased infiltration of neutrophils compared to wild-type animals. Loss of GAL3R resulted in higher local and systemic inflammatory cytokine/chemokine levels. Remarkably, colitis-associated changes to the intestinal microbiota, as assessed by quantitative culture-independent techniques, were most pronounced in GAL3R-KO mice, characterized by elevated numbers of enterobacteria and bifidobacteria. In contrast, GAL2R deletion did not influence the course of colitis. In conclusion, granulocyte GAL2R and GAL3R expression is related to IBD activity in humans, and DSS-induced colitis in mice is strongly affected by GAL3R loss. Consequently, GAL3R poses a novel therapeutic target for IBD.
Association of bacterial vaginosis with periodontitis in a cross-sectional American nationwide survey
Authors: Escalda Cláudia , Botelho João , Mendes José João , Machado Vanessa
Published: January 2021

To explore the association between bacterial vaginosis (BV) and periodontitis (PD) and to determine whether PD and BV might be linked with systemic serum alterations. We used the National Health and Nutrition Examination Survey 2001–2004, with women aged 18–49 years old and diagnosed with or without BV according to Nugent’s method. PD was defined according to the 2012 case definition. We compared serum counts according to the presence of PD and the presence of BV. Multivariable regression was used to explore and identify relevant variables towards the presence of BV. 961 women fulfilled the inclusion criteria. In women with BV, PD was associated with higher inflammation, characterized by increased white blood cells (p = 0.006) and lymphocyte (p = 0.009) counts. Predictive models presented a statistically significant association between PD and BV [Odds Ratio (OD) = 1.69, 95% Confidence Interval (CI): 1.09–2.61 for periodontitis; OD = 2.37, 95% CI: 1.30–4.29 for severe PD]. Fully adjusted models for age, smoking, body mass index, diabetes mellitus and number of systemic conditions reinforced this association [OD = 1.71, 95% CI: 1.06–2.76 for PD; OD = 2.21, 95% CI: 1.15–4.25 for severe PD]. An association between BV and PD is conceivable. PD was associated with higher systemic markers of inflammation in women with BV. Our data is novel and could serve as a foundation to guide future studies in the confirmation of this association and the underlying mechanisms.
Negative index metamaterial through multi-wave interactions: numerical proof of the concept of low-frequency Lamb-wave multiplexing
Authors: Lott Martin , Roux Philippe , Rupin Matthieu , Colquitt Daniel , Colombi Andrea
Published: January 2021

We study numerically the potential of a multimodal elastic metamaterial to filter and guide Lamb waves in a plate. Using a sub-wavelength array of elongated beams attached to the plate, and combining the coupling effects of the longitudinal and flexural motion of these resonators, we create narrow transmission bands at the flexural resonances of the beams inside the wide frequency bandgap induced by their longitudinal resonance. The diameter of the beams becomes the tuning parameter for selection of the flexural leakage frequency, without affecting the main bandgap. Finally, by combination of the monopolar and dipolar scattering effects associated with the coupled beam and plate system, we create a frequency-based multiplexer waveguide in a locally resonant metamaterial.
The prognostic roles of the prognostic nutritional index in patients with intraductal papillary mucinous neoplasm
Authors: Okamura Yukiyasu , Sugiura Teiichi , Ito Takaaki , Yamamoto Yusuke , Ashida Ryo , Ohgi Katsuhisa , Sasaki Keiko , Narimatsu Hiroto , Uesaka Katsuhiko
Published: January 2021

The preoperative accurate diagnosis is difficult in the patients with intraductal papillary mucinous neoplasm (IPMN). The aim of the present study was to elucidate the roles of systemic inflammation responses and nutritional status indexes in IPMN. High-grade dysplasia was classified as a malignant neoplasm in the study. We retrospectively reviewed 155 patients who underwent pancreatectomy. The correlation between the clinical factors and several indexes of a systemic inflammation response and nutritional status was analyzed. Among the biomarkers, prognostic nutritional index (PNI) value of malignant IPMN patients was significantly lower than that of benign IPMN patients (P = 0.023), whereas PNI was not significant predictor for malignant IPMN. The multivariate analysis showed that a PNI < 43.5 (odds ratio [OR] 16.1, 95% CI 1.88–138.5, P = 0.011) and a carbohydrate antigen (CA) 19–9 level > 22.5 U/mL (OR 6.64, 95% CI 1.73–25.6, P = 0.006) were significant independent predictors of the presence of lymph node metastasis (LNM). Our scoring system developed based on these two factors. Patients with a score of 0 had no LNM and zero disease-related death. The present study suggested the roles of PNI on the IPMN patients who undergo curative pancreatectomy.
Effect of chrysophanic acid on immune response and immune genes transcriptomic profile in Catla catla against Aeromonas hydrophila
Authors: Harikrishnan Ramasamy , Devi Gunapathy , Balasundaram Chellam , Van Doan Hien , Jaturasitha Sanchai , Ringø Einar , Faggio Caterina
Published: January 2021

The effect of chrysophanic acid (CA) (2, 4, and 8 mg kg−1) on the immunity and immune-related gene profile of Catla catla against Aeromonas hydrophila is reported. In both control and treated groups fed with 2 mg kg−1 (2 CA), the phagocytosis, hemolytic, myeloperoxidase content, and superoxide anion production decreased significantly between 6th and 8th weeks, whereas when fed with 4 mg kg−1 CA (4 CA) the H2O2 production and nitric oxide synthase increased significantly between 4th and 8th week. When fed with 2 CA and 4 CA diets, the total protein, bactericidal, and antibody titer increased significantly from the 4th week onwards. When fed with 2 CA, the IL-1β and IL-10 mRNA expression of head kidney leucocytes were significant between weeks 6 and 8. The expressions of toll-like receptors significantly increased when fed with a 4 CA diet from 4th week onwards. The 4 CA group significantly increased in TNF-α, TNF receptor-associated factor 6 (NOD), which influences protein expression, after the 4th week. The mRNA transcription of MHCI, lysozyme-chicken and goose type expressions significantly increased in 4 CA group within the 4th week. In summary, the dietary administration of 4 mg kg−1 of CA (4 CA) provides better immunity and enhances the up-regulation of immune-related genes in Catla against A. hydrophila.
A prospective, randomised study of the effect of fixation sutures during phacotrabeculectomy on intraocular pressure and incidence of ptosis
Authors: Konopińska Joanna , Lisowski Łukasz , Mariak Zofia , Wojnar Małgorzata , Obuchowska Iwona , Rękas Marek
Published: January 2021

We investigated the effects of different intraoperative eyeball fixation techniques (superior rectus muscle suture [MS] and traction suture at the corneal limbus [CS]), on intraocular pressure (IOP) and the incidence of ptosis after phacotrabeculectomy. Forty-one eyes with different glaucoma types which qualified for phacotrabeculectomy were included. Twenty-three and eighteen patients were included in the CS and MS groups, respectively. The IOP, best-corrected visual acuity (BCVA), and margin reflex distance were assessed preoperatively and 3, 6, and 12 months post-operatively. Preoperatively, the mean IOPs (± standard deviation) in the CS and MS groups were 23.6 ± 7.3 mmHg and 24.3 ± 6.6 mmHg (p > 0.05), respectively. At 3 and 6 months post-surgery, the mean IOPs were significantly lower in the CS group than in the MS group: 13.9 ± 3.0 mmHg vs. 17.7 ± 3.5 mmHg (p = 0.001), and 13.9 ± 4.9 mmHg vs. 17.2 ± 3.5 mmHg (p = 0.005), respectively (mean difference: 3.9, 95% confidence interval 1.7–6.1). At 12 months, the mean postoperative IOPs were 15.2 ± 3.5 mmHg and 14.9 ± 3.6 mmHg in the CS and MS groups, respectively (p > 0.05). At 6 months, the BCVAs were 0.91 ± 0.15 and 0.71 ± 0.3 (p = 0.029) in the CS and MS groups, respectively; BCVAs were 0.91 ± 0.15 and 0.71 ± 0.3 (p = 0.029) in the CS and MS groups, respectively; the difference was non-significant 12 months post-surgery (0.78 ± 0.32 vs. 0.74 ± 0.30, p = 0.553). Postoperative ptosis was observed in 4 (17%) and zero patients in the CS and MS groups, respectively, but the difference was not statistically significant (p = 0.118). The study was not powered sufficiently to detect statistically significant changes in exploratory endpoints. The study was not powered sufficiently to detect statistically significant differences between groups in exploratory endpoints.
Genome wide methylation profiling of selected matched soft tissue sarcomas identifies methylation changes in metastatic and recurrent disease
Authors: Vargas Ana Cristina , Gray Lesley-Ann , White Christine L. , Maclean Fiona M. , Grimison Peter , Ardakani Nima Mesbah , Bonar Fiona , Algar Elizabeth M. , Cheah Alison L. , Russell Peter , Mahar Annabelle , Gill Anthony J.
Published: January 2021

In this study we used the Illumina Infinium Methylation array to investigate in a cohort of matched archival human tissue samples (n = 32) from 14 individuals with soft tissue sarcomas if genome-wide methylation changes occur during metastatic and recurrent (Met/Rec) disease. A range of sarcoma types were selected for this study: leiomyosarcoma (LMS), myxofibrosarcoma (MFS), rhabdomyosarcoma (RMS) and synovial sarcoma (SS). We identified differential methylation in all Met/Rec matched samples, demonstrating that epigenomic differences develop during the clonal evolution of sarcomas. Differentially methylated regions and genes were detected, not been previously implicated in sarcoma progression, including at PTPRN2 and DAXX in LMS, WT1-AS and TNXB in SS, VENTX and NTRK3 in pleomorphic RMS and MEST and the C14MC / miR-379/miR-656 in MFS. Our overall findings indicate the presence of objective epigenetic differences across primary and Met/Rec human tissue samples not previously reported.
Microbiota analysis and transient elastography reveal new extra-hepatic components of liver steatosis and fibrosis in obese patients
Authors: Lanthier Nicolas , Rodriguez Julie , Nachit Maxime , Hiel Sophie , Trefois Pierre , Neyrinck Audrey M. , Cani Patrice D. , Bindels Laure B. , Thissen Jean-Paul , Delzenne Nathalie M.
Published: January 2021

Obesity could lead to metabolic dysfunction-associated fatty liver disease (MAFLD), which severity could be linked to muscle and gut microbiota disturbances. Our prospective study enrolled 52 obese patients whose MAFLD severity was estimated by transient elastography. Patients with severe steatosis (n = 36) had higher ALAT values, fasting blood glucose levels as well as higher visceral adipose tissue area and skeletal muscle index evaluated by computed tomography. Patients with fibrosis (n = 13) had higher ASAT values, increased whole muscle area and lower skeletal muscle density index. In a multivariate logistic regression analysis, myosteatosis was the strongest factor associated with fibrosis. Illumina sequencing of 16S rRNA gene amplicon was performed on fecal samples. The relative abundance of fecal Clostridium sensu stricto was significantly decreased with the presence of liver fibrosis and was negatively associated with liver stiffness measurement and myosteatosis. In addition, 19 amplicon sequence variants were regulated according to the severity of the disease. Linear discriminant analysis effect size (LEfSe) also highlighted discriminant microbes in patients with fibrosis, such as an enrichment of Enterobacteriaceae and Escherichia/Shigella compared to patients with severe steatosis without fibrosis. All those data suggest a gut-liver-muscle axis in the pathogenesis of MAFLD complications.
Comparative genomics and metabolomics analysis of Riemerella anatipestifer strain CH-1 and CH-2
Authors: Liu Jibin , Cheng Anchun , Wang Mingshu , Liu Mafeng , Zhu Dekang , Yang Qiao , Wu Ying , Jia Renyong , Chen Shun , Zhao Xinxin , Zhang Shaqiu , Huang Juan , Ou Xumin , Mao Sai , Gao Qun , Wen Xingjian , Zhang Ling , Liu Yunya , Yu Yanling , Tian Bin , Pan Leichang , Ur Rehman Mujeeb , Chen Xiaoyue
Published: January 2021

Riemerella anatipestifer is a major pathogenic microorganism in poultry causing serositis with significant mortality. Serotype 1 and 2 were most pathogenic, prevalent, and liable over the world. In this study, the intracellular metabolites in R. anatipestifer strains RA-CH-1 (serotype 1) and RA-CH-2 (serotype 2) were identified by gas chromatography-mass spectrometer (GC–MS). The metabolic profiles were performed using hierarchical clustering and partial least squares discriminant analysis (PLS-DA). The results of hierarchical cluster analysis showed that the amounts of the detected metabolites were more abundant in RA-CH-2. RA-CH-1 and RA-CH-2 were separated by the PLS-DA model. 24 potential biomarkers participated in nine metabolisms were contributed predominantly to the separation. Based on the complete genome sequence database and metabolite data, the first large-scale metabolic models of iJL463 (RA-CH-1) and iDZ470 (RA-CH-2) were reconstructed. In addition, we explained the change of purine metabolism combined with the transcriptome and metabolomics data. The study showed that it is possible to detect and differentiate between these two organisms based on their intracellular metabolites using GC–MS. The present research fills a gap in the metabolomics characteristics of R. anatipestifer.
Effects of vestibular neurectomy and neural compensation on head movements in patients undergoing vestibular schwannoma resection
Authors: Zobeiri Omid A. , Mischler Gavin M. , King Susan A. , Lewis Richard F. , Cullen Kathleen E.
Published: January 2021

The vestibular system is vital for maintaining balance and stabilizing gaze and vestibular damage causes impaired postural and gaze control. Here we examined the effects of vestibular loss and subsequent compensation on head motion kinematics during voluntary behavior. Head movements were measured in vestibular schwannoma patients before, and then 6 weeks and 6 months after surgical tumor removal, requiring sectioning of the involved vestibular nerve (vestibular neurectomy). Head movements were recorded in six dimensions using a small head-mounted sensor while patients performed the Functional Gait Assessment (FGA). Kinematic measures differed between patients (at all three time points) and normal subjects on several challenging FGA tasks, indicating that vestibular damage (caused by the tumor or neurectomy) alters head movements in a manner that is not normalized by central compensation. Kinematics measured at different time points relative to vestibular neurectomy differed substantially between pre-operative and 6-week post-operative states but changed little between 6-week and > 6-month post-operative states, demonstrating that compensation affecting head kinematics is relatively rapid. Our results indicate that quantifying head kinematics during self-generated gait tasks provides valuable information about vestibular damage and compensation, suggesting that early changes in patient head motion strategy may be maladaptive for long-term vestibular compensation.
A pre-operative prognostic score for the selection of patients for salvage surgery after recurrent head and neck squamous cell carcinomas
Authors: Lupato Valentina , Polesel Jerry , La Torre Fabio Biagio , Fanetti Giuseppe , Fratta Elisabetta , Gobitti Carlo , Baldassarre Gustavo , Vaccher Emanuela , Franchin Giovanni , Giacomarra Vittorio
Published: January 2021

Salvage surgery in recurrent head and neck squamous cell carcinoma has a poor outcome, both in terms of survival and quality of life. Therefore, the identification of pre-operative prognostic factors to improve the selection of patients who could benefit the most from salvage surgery is clinically relevant. The present study is a single-center retrospective analysis of 164 patients treated with salvage surgery after recurrence of head and neck cancer. Progression free survival and overall survival were calculated through Kaplan–Meier method. Hazard risk (HR) and corresponding confidence intervals (CI) were estimated through Cox proportional hazard model, adjusting for potential confounders. Significant predictors were combined into a prognostic score, attributing one point to each factor. Progression-free survival and overall survival were respectively 50.3% and 56.5% at 2 years, and 36.6% and 44.2% at 5 years. Four pre-operative factors were independently associated with poor prognosis: age > 70 years (HR = 2.18; 95% CI 1.27–3.73), initial stage IV (HR = 2.37; 95% CI 1.18–4.76), disease free interval < 12 months (HR = 1.72; 95% CI 1.01–2.94), and loco-regional recurrence (HR = 2.22; 95% CI 1.22–4.04). No post operative factor was associated with oncologic outcomes. Patients with 3–4 unfavorable factors showed a 5-year overall survival of 0.0% compared to 65.7% in those with 0–1 unfavorable factors (HR = 5.61; 95% CI 2.89–10.92). Despite the low number of patients, 3–4 unfavorable factors were associated to worse prognosis in all sub-sites. In conclusion, age > 70 years, initial stage IV, disease-free interval < 12 months, and loco-regional recurrence are strong independent pre-operative predictors of poor outcome in patients undergoing salvage surgery. Patients with two or more of these factors should be informed about the low success rate after salvage surgery and alternative treatments should be considered.
The evaluation of pituitary damage associated with cardiac arrest: An experimental rodent model
Authors: Okuma Yu , Aoki Tomoaki , Miyara Santiago J. , Hayashida Kei , Nishikimi Mitsuaki , Takegawa Ryosuke , Yin Tai , Kim Junhwan , Becker Lance B. , Shinozaki Koichiro
Published: January 2021

The pituitary gland plays an important endocrinal role, however its damage after cardiac arrest (CA) has not been well elucidated. The aim of this study was to determine a pituitary gland damage induced by CA. Rats were subjected to 10-min asphyxia and cardiopulmonary resuscitation (CPR). Immunohistochemistry and ELISA assays were used to evaluate the pituitary damage and endocrine function. Samples were collected at pre-CA, and 30 and 120 min after cardio pulmonary resuscitation. Triphenyltetrazolium chloride (TTC) staining demonstrated the expansion of the pituitary damage over time. There was phenotypic validity between the pars distalis and nervosa. Both CT-proAVP (pars nervosa hormone) and GH/IGF-1 (pars distalis hormone) decreased over time, and a different expression pattern corresponding to the damaged areas was noted (CT-proAVP, 30.2 ± 6.2, 31.5 ± 5.9, and 16.3 ± 7.6 pg/mg protein, p < 0.01; GH/IGF-1, 2.63 ± 0.61, 0.62 ± 0.36, and 2.01 ± 0.41 ng/mg protein, p < 0.01 respectively). Similarly, the expression pattern between these hormones in the end-organ systems showed phenotypic validity. Plasma CT-proAVP (r = 0.771, p = 0.025) and IGF-1 (r = −0.775, p = 0.024) demonstrated a strong correlation with TTC staining area. Our data suggested that CA induces pathological and functional damage to the pituitary gland.
Design of fractional evolutionary processing for reactive power planning with FACTS devices
Authors: Muhammad Yasir , Akhtar Rizwan , Khan Rahimdad , Ullah Farman , Raja Muhammad Asif Zahoor , Machado J. A. Tenreiro
Published: January 2021

Reactive power dispatch is a vital problem in the operation, planning and control of power system for obtaining a fixed economic load expedition. An optimal dispatch reduces the grid congestion through the minimization of the active power loss. This strategy involves adjusting the transformer tap settings, generator voltages and reactive power sources, such as flexible alternating current transmission systems (FACTS). The optimal dispatch improves the system security, voltage profile, power transfer capability and overall network efficiency. In the present work, a fractional evolutionary approach achieves the desired objectives of reactive power planning by incorporating FACTS devices. Two compensation arrangements are possible: the shunt type compensation, through Static Var compensator (SVC) and the series compensation through the Thyristor controlled series compensator (TCSC). The fractional order Darwinian Particle Swarm Optimization (FO-DPSO) is implemented on the standard IEEE 30, IEEE 57 and IEEE 118 bus test systems. The power flow analysis is used for determining the location of TCSC, while the voltage collapse proximity indication (VCPI) method identifies the location of the SVC. The superiority of the FO-DPSO is demonstrated by comparing the results with those obtained by other techniques in terms of measure of central tendency, variation indices and time complexity.
Engineering calcium signaling of astrocytes for neural–molecular computing logic gates
Authors: Barros Michael Taynnan , Doan Phuong , Kandhavelu Meenakshisundaram , Jennings Brendan , Balasubramaniam Sasitharan
Published: January 2021

This paper proposes the use of astrocytes to realize Boolean logic gates, through manipulation of the threshold of $$\hbox {Ca}^{2+}$$

Ca

2
+

ion flows between the cells based on the input signals. Through wet-lab experiments that engineer the astrocytes cells with pcDNA3.1-hGPR17 genes as well as chemical compounds, we show that both AND and OR gates can be implemented by controlling $$\hbox {Ca}^{2+}$$

Ca

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signals that flow through the population. A reinforced learning platform is also presented in the paper to optimize the $$\hbox {Ca}^{2+}$$

Ca

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activated level and time slot of input signals $$T_b$$

T
b

into the gate. This design platform caters for any size and connectivity of the cell population, by taking into consideration the delay and noise produced from the signalling between the cells. To validate the effectiveness of the reinforced learning platform, a $$\hbox {Ca}^{2+}$$

Ca

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signalling simulator was used to simulate the signalling between the astrocyte cells. The results from the simulation show that an optimum value for both the $$\hbox {Ca}^{2+}$$

Ca

2
+

activated level and time slot of input signals $$T_b$$

T
b

is required to achieve up to 90% accuracy for both the AND and OR gates. Our method can be used as the basis for future Neural–Molecular Computing chips, constructed from engineered astrocyte cells, which can form the basis for a new generation of brain implants.
UV-C mediated accumulation of pharmacologically significant phytochemicals under light regimes in in vitro culture of Fagonia indica (L.)
Authors: Abbasi Bilal Haider , Khan Taimoor , Khurshid Razia , Nadeem Muhammad , Drouet Samantha , Hano Christophe
Published: January 2021

Fagonia indica(L.) is an important medicinal plant with multitude of therapeutic potentials. Such application has been attributed to the presence of various pharmacological important phytochemicals. However, the inadequate biosynthesis of such metabolites in intact plants has hampered scalable production. Thus, herein, we have established an in vitro based elicitation strategy to enhance such metabolites in callus culture ofF. indica. Cultures were exposed to various doses of UV radiation (UV-C) and grown in different photoperiod regimes and their impact was evaluated on biomass accumulation, biosynthesis of phytochemicals along antioxidant expression. Cultures grown under photoperiod (16L/8D h) after exposure to UV-C (5.4 kJ/m2) accumulated optimal biomass (438.3 g/L FW; 16.4 g/L DW), phenolics contents (TPC: 11.8 μgGAE/mg) and flavonoids contents (TFC: 4.05 μgQE/mg). Similarly, HPLC quantification revealed that total production (6.967 μg/mg DW) of phytochemicals wherein kaempferol (1.377 μg/mg DW), apigenin (1.057 μg/mg DW), myricetin (1.022 μg/mg DW) and isorhamnetin (1.022 μg/mg DW) were recorded highly accumulated compounds in cultures at UV-C (5.4 kJ/m2) dose than other UV-C radiations and light regimes.. The antioxidants activities examined as DPPH (92.8%), FRAP (182.3 µM TEAC) and ABTS (489.1 µM TEAC) were also recorded highly expressed by cultures under photoperiod after treatment with UV-C dose 5.4 kJ/m2. Moreover, same cultures also expressed maximum % inhibition towards phospholipase A2 (sPLA2: 35.8%), lipoxygenase (15-LOX: 43.3%) and cyclooxygenases (COX-1: 55.3% and COX-2: 39.9%) with 1.0-, 1.3-, 1.3- and 2.8-fold increased levels as compared with control, respectively. Hence, findings suggest that light and UV can synergistically improve the metabolism ofF. indicaand could be used to produce such valuable metabolites on commercial scale.