Miracle-dz/UniFAR-FTUs huggingface dataset:
Existing semantic knowledge provides a schematic scaffold for inference in early cognitive decline, but not in amnestic MCI

ABSTRACT Healthy older adults show impaired relational learning, but improved transitive expression when inferences are made across pre-experimentally known premise relations. Here, we used the transitivity paradigm to ask whether the organizational structure within schemas facilitates the bridging of relations for novel inference for otherwise healthy older adults who are exhibiting early signs of cognitive decline (“at-risk” older adults), and individuals with single- or multiple-domain amnestic mild cognitive impairment (aMCI). Relational learning was impaired in the two older adult groups, but transitive expression was facilitated by prior semantic knowledge of relations. Prior semantic knowledge did not improve novel inference for aMCI individuals. Schematic scaffolding can successfully support inference in preclinical cognitive decline, but such cognitive support may no longer be useful later in the disease process when dysfunction in neural circuitry may be too severe. The findings encourage future work of semantic knowledge and inference in larger samples of aMCI cases.
Do socioeconomic factors play a role in nonadherence to follow-up colonoscopy after a positive faecal immunochemical test in the Flemish colorectal cancer screening programme?

Objective In Flanders (Belgium), a population-based colorectal cancer (CRC) screening programme was started in 2013, coordinated by the Centre for Cancer Detection (CCD) in cooperation with the Belgian Cancer Registry (BCR). The CCD offers a biennial faecal immunochemical test (FIT) to Flemish citizens aged 56–74 years and recommends a colonoscopy when screened positive by FIT. The study objective is to investigate sociodemographic differences in follow-up colonoscopy adherence after a positive FIT. Methods Characteristics of the study population were derived by linkage of data from the CCD and BCR, linked with data of the Intermutualistic Agency and the Crossroads Bank for Social Security, resulting in aggregated tables to ensure anonymity. A total of 37 834 men and women aged 56–74 years with a positive FIT in 2013–2014 were included. Adherence to follow-up colonoscopy was calculated for age, sex, work intensity at household level, preferential reimbursement status, and first and current nationality. Descriptive analyses and logistic regressions were performed. Results Nonadherence to follow-up colonoscopy was associated with increasing age, and was significantly higher in men [odds ratio (OR), 1.08], participants with a preferential reimbursement status (OR, 1.34), very low work intensity (OR, 1.41), no payed work (OR, 1.38) and other than Belgian nationality by birth (OR, 1.6–4.66). Conclusion Adherence to follow-up colonoscopy after a positive FIT differs according to sociodemographic variables. Additional research is needed to explore reasons for nonadherence to colonoscopy and tackle barriers by exploring interventions to increase colonoscopy follow-up adherence after a positive FIT in the Flemish colorectal cancer screening programme.
Microbiome modulation to correct uremic toxins and to preserve kidney functions.

PURPOSE OF REVIEW The association between dysbiosis and CKD is well established. This review focuses on the current understanding of microbiome, in normal individuals and CKD patients, in order to hypothesize how to correct uremic toxins levels and preserve the renal function and reduce associated comorbidities. Here we discuss our current opinion on microbiome modulation in order to manage the CKD-associated dysbiosis. RECENT FINDINGS Emerging evidence confirms the role of gut microbiome in the progression of CKD. In this scenario, the need is felt to set up multifaceted approaches for dysbiosis management. Among many strategies able to improve gut wellness, a crucial approach is represented by the functional nutrition. At the same time, drug-based treatments show significant results in microbiome modulation. Furthermore, we examine here the potentialities of fecal microbiome transplantation (FMT) in CKD, an approach currently applied in Clostridium difficile infection. SUMMARY The gut microbiome plays a pivotal role in the pathophysiology of CKD. The vicious cycle triggered by kidney function decline leads to gut dysbiosis. Considering the gut microbiome as a therapeutic target in CKD, multiple approaches aimed at its modulation should be envisioned to preserve kidney function. Dietary interventions and pharmacological strategies are able to improve microbiome dysbiosis, oxidative stress and fibrosis. Additionally, FMT could represent a promising novel therapy in the management of CKD-associated dysbiosis.
Management of locally advanced non-small cell lung cancer in the modern era: A national Italian survey on diagnosis, treatment and multidisciplinary approach

Concurrent chemotherapy and radiotherapy (cCRT) is considered the standard treatment of locally advanced non-small cell lung cancer (LA-NSCLC). Unfortunately, management is still heterogeneous across different specialists. A multidisciplinary approach is needed in this setting due to recent, promising results obtained by consolidative immunotherapy. The aim of this survey is to assess current LA-NSCLC management in Italy. From January to April 2018, a 15-question survey focusing on diagnostic/therapeutic LA-NSCLC management was sent to 1,478 e-mail addresses that belonged to pneumologists, thoracic surgeons, and radiation and medical oncologists. 421 answers were analyzed: 176 radiation oncologists, 86 medical oncologists, 92 pneumologists, 64 thoracic surgeons and 3 other specialists. More than a half of the respondents had been practicing for >10 years after completing residency training. Some discrepancies were observed in clinical LA-NSCLC management: the lack of a regularly planned multidisciplinary tumor board, the use of upfront surgery in multistation stage IIIA, and territorial diffusion of cCRT in unresectable LA-NSCLC. Our analysis demonstrated good compliance with international guidelines in the diagnostic workup of LA-NSCLC. We observed a relationship between high clinical experience and good clinical practice. A multidisciplinary approach is mandatory for managing LA-NSCLC.
The influence of fibrillin‐1 and physical activity upon tendon tissue morphology and mechanical properties in mice

Fibrillin‐1 mutations cause pathological changes in connective tissue that constitute the complex phenotype of Marfan syndrome. In this study, we used fibrillin‐1 hypomorphic and haploinsufficient mice (Fbn1mgr/mgR and Fbn1+/− mice, respectively) to investigate the impact of fibrillin‐1 deficiency alone or in combination with regular physical activity on tendon tissue morphology and mechanical properties. Morphological and biomechanical analyses revealed that Fbn1mgr/mgR but not Fbn1+/− mice displayed smaller tendons with physical properties that were unremarkable when normalized to tendon size. Fbn1mgR/mgR mice (n = 43) Fbn1+/−mice (n = 27) and wild‐type mice (WT, n = 25) were randomly assigned to either control cage conditions (n = 54) or to a running on a running wheel for 4 weeks (n = 41). Both fibrillin‐1‐deficient mice ran voluntarily on the running wheel in a manner similar to WT mice (3–4 km/24 h). Regular exercise did not mitigate aneurysm progression in Fbn1mgR/mgR mice (P < 0.05) as evidenced by unmodified median survival. In spite of the smaller size, tendons of fibrillin‐1‐deficient mice subjected to regular exercise showed no evidence of overt histopathological changes or tissue overload. We therefore concluded that lack of optimal fibrillin‐1 synthesis leads to a down regulation of integrated tendon formation, rather than to a loss of tendon quality, which also implies that fibrillin‐1 deficiency in combination with exercise is not a suitable animal model for studying the development of tendon overuse (tendinopathy).
Effect of nongenetic factors on reproduction traits in Jamunapari goats under semiintensive management

Data on 256 Jamunapari goats maintained at Central Institute for Research on Goats, Makhdoom, Mathura, UP during the period 1993 to 2000 were analysed to study reproductive traits. The least squares means of age at first kidding (AFK), kidding interval (KI), service period (SP), dry period (DP) and gestation period (GP) were 773.44±13.28, 388.80±6.26, 255.76±6.95, 213.25±6.55 and 147.62±0.11 days, respectively. Year of kidding had significant influence on AFK, DP, GP and KI. The does kidded during October–November showed lower service period than those kidded in March–April. The optimization of age at first service with respect to weight is important for improving age at first kidding. Does with multiple births had 1% lower gestation period than does with singles. Breeding efficiency and prolificacy were statistically same over the seasons with average litter size of 1.21. Maximum kidding occurred in October followed by February, March, November and December, which accounted for 83% of total kidding.
Adult growth hormone deficiency: clinical advances and approaches to improve adherence

ABSTRACT Introduction: There have been significant clinical advances in the understanding of the diagnosis and benefits of long-term recombinant human growth hormone (rhGH) replacement in adults with GH deficiency (GHD) since its approval in 1996 by the United States Food and Drug Administration. Areas covered: We searched PubMed, Medline, CINAHL, EMBASE and PsychInfo databases between January 2000 and June 2019 for published studies evaluating adults with GHD. We reviewed the data of the oral macimorelin test compared to the GHRH plus arginine and the insulin tolerance tests that led to its approval by the United States FDA and European Medicines Agency for adult diagnostic testing. We summarize the clinical advances of long-term benefits of rhGH therapy and the potential effects of GH receptor polymorphisms on individual treatment responsiveness. We identify that non-adherence and discontinuation rates are high and recommend strategies to support patients to improve adherence. We also provide an overview of several long-acting GH (LAGH) preparations currently under development and their potential role in improving treatment adherence. Expert opinion: This article summarizes recent clinical advances in rhGH replacement therapy, the biological and molecular aspects that may influence rhGH action, and offers practical strategies to enhance adherence in adults with GHD.
Molecular cloning of Gibel carp (Carassius auratus gibelio) complement component C3 and its expression profile after Cyprinid herpesvirus 2 infection

The complement systems play an important role in innate and adaptive immunity. In this study, the complement C3 gene, designated CagC3, was cloned and sequenced from Gibel carp (Carassius auratus gibelio). The expression pattern of CagC3 in different tissues of healthy Gibel carp and after challenge with Cyprinid herpesvirus 2 (CyHV-2) were evaluated using quantitative real-time PCR. The full-length CagC3 cDNA was 5131 bp with an ORF of 4950 bp, encoding a predicted protein of 1649 amino acids. The deduced amino acid sequence showed that CagC3 has conserved domains and residues known to be critical for C3 function. Phylogenetic analysis demonstrated that CagC3 clustered with homologs from common carp and grass carp (Ctenopharyngodon idella). CagC3 is expressed in all examined tissues of healthy Gibel carp, with the highest expression in liver. In vivo, after CyHV-2 challenge, CagC3 transcription was significantly upregulated in liver, spleen and kidney with the peaks at 24 hr, 2 d, and 2 d, respectively. In vitro, CagC3 expression in the Gibel carp brain cell line showed the same pattern as that in vivo after stimulation with CyHV-2 or poly(I:C). However, CagC3 expression was downregulated at 24 hr after induction with lipopolysaccharide (LPS), and then reached the peak at 2 d. These results suggest that CagC3 is involved in the innate immune response of Gibel carp to viral infection.
Antiviral bioactivity of renewable polysaccharides against Varicella Zoster

ABSTRACT Although several effective treatments exist against Varicella zoster virus (VZV), resistant strains have emerged and the treatment is usually not definite and may have various undesired side effects. Thus, alternative treatment options are necessary. Here we studied the inhibitory effects of natural polysaccharides (PSs) obtained from renewable sources, varied by their structure and charge, on VZV infection in vitro, using a plaque assay. In terms of selectivity indices, almost all the tested PSs were very active; in the order of λ > ἰ > G > κ > P against VZV compared to Acyclovir as a reference drug and exhibited dose-dependent behavior. Our results, which showed a strong inhibition of VZV infection when the cells were treated with ἰ only at the time of infection or only post infection may indicate a multistep inhibitory effect. It seems that ἰ may block different stages of the virus replication cycle including early steps such as absorption and penetration to the host cells and also late steps after the penetration into the host cells. These results are part of an on-going research that highlights the PSs as potential novel nontoxic candidates that can be used against VZV, and contributes to the elucidation of their mode of action.
Transcriptional regulatory divergence underpinning species-specific learned vocalization in songbirds

Learning of most motor skills is constrained in a species-specific manner. However, the proximate mechanisms underlying species-specific learned behaviors remain poorly understood. Songbirds acquire species-specific songs through learning, which is hypothesized to depend on species-specific patterns of gene expression in functionally specialized brain regions for vocal learning and production, called song nuclei. Here, we leveraged two closely related songbird species, zebra finch, owl finch, and their interspecific first-generation (F1) hybrids, to relate transcriptional regulatory divergence between species with the production of species-specific songs. We quantified genome-wide gene expression in both species and compared this with allele-specific expression in F1 hybrids to identify genes whose expression in song nuclei is regulated by species divergence in either cis- or trans-regulation. We found that divergence in transcriptional regulation altered the expression of approximately 10% of total transcribed genes and was linked to differential gene expression between the two species. Furthermore, trans-regulatory changes were more prevalent than cis-regulatory and were associated with synaptic formation and transmission in song nucleus RA, the avian analog of the mammalian laryngeal motor cortex. We identified brain-derived neurotrophic factor (BDNF) as an upstream mediator of trans-regulated genes in RA, with a significant correlation between individual variation in BDNF expression level and species-specific song phenotypes in F1 hybrids. This was supported by the fact that the pharmacological overactivation of BDNF receptors altered the expression of its trans-regulated genes in the RA, thus disrupting the learned song structures of adult zebra finch songs at the acoustic and sequence levels. These results demonstrate functional neurogenetic associations between divergence in region-specific transcriptional regulation and species-specific learned behaviors.
Robustness analysis of decoding SSVEPs in humans with head movements using a moving visual flicker

Objective. The emergence of mobile electroencephalogram (EEG) platforms have expanded the use cases of brain–computer interfaces (BCIs) from laboratory-oriented experiments to our daily life. In challenging situations where humans’ natural behaviors such as head movements are unrestrained, various artifacts could deteriorate the performance of BCI applications. This paper explored the effect of muscular artifacts generated by participants’ head movements on the signal characteristics and classification performance of steady-state visual evoked potentials (SSVEPs). Approach. A moving visual flicker was employed to induce not only SSVEPs but also horizontal and vertical head movements at controlled speeds, leading to acquiring EEG signals with intensity-manipulated muscular artifacts. To properly induce neck muscular activities, a laser light was attached to participants’ heads to give visual feedback; the laser light indicates the direction of the head independently from eye movements. The visual stimulus was also modulated by four distinct frequencies (10, 11, 12, and 13 Hz). The amplitude and signal-to-noise ratio (SNR) were estimated to quantify the effects of head movements on the signal characteristics of the elicited SSVEPs. The frequency identification accuracy was also estimated by using well-established decoding algorithms including calibration-free and fully-calibrated approaches. Main results. The amplitude and SNR of SSVEPs tended to deteriorate when the participants moved their heads, and this tendency was significantly stronger in the vertical head movements than in the horizontal movements. The frequency identification accuracy also deteriorated in proportion to the speed of head movements. Importantly, the accuracy was significantly higher than its chance-level regardless of the level of artifact contamination and algorithms. Significance. The results suggested the feasibility of decoding SSVEPs in humans freely moving their head directions, facilitating the real-world applications of mobile BCIs.
Utility of Elastography with Endoscopic Ultrasonography Shear-Wave Measurement for Diagnosing Chronic Pancreatitis

Background/Aims Rosemont classification (RC) with endoscopic ultrasonography (EUS) is important for diagnosing chronic pancreatitis (CP) but is based only on subjective judgement. EUS shear wave measurement (EUS-SWM) is a precise modality based on objective judgment, but its usefulness has not been extensively studied yet. This study evaluated the utility of EUS-SWM for diagnosing CP and estimating CP severity by determining the presence of endocrine dysfunction along with diabetes mellitus (DM). Methods Between June 2018 and December 2018, 52 patients who underwent EUS and EUS-SWM were classified into two groups according to RC non-CP (indeterminate CP and normal) and CP (consistent and suggestive of CP). The EUS-SWM value by shear wave velocity was evaluated with a median value. The EUS-SWM value was compared with RC and the number of EUS features. The diagnostic accuracy and cutoff value of EUS-SWM for CP and DM and its sensitivity and specificity were calculated. Results The EUS-SWM value significantly positively correlated with the RC and the number of EUS features. The EUS-SWM values that were consistent and suggestive of CP were significantly higher than that of normal. The area under the receiver operating characteristic (AUROC) curve for the diagnostic accuracy of EUS-SWM for CP was 0.97. The cutoff value of 2.19 had 100% sensitivity and 94% specificity. For endocrine dysfunction in CP, the AUROC was 0.75. The cutoff value of 2.78 had 70% sensitivity and 56% specificity. Conclusions EUS-SWM provides an objective assessment and can be an alternative diagnostic tool for diagnosing CP. EUS-SWM may also be useful for predicting the presence of endocrine dysfunction.
Health Promotion: Principles and Practice in the Australian Context (Third Edition) [Book Review]

Review(s) of: Health Promotion: Principles and Practice in the Australian Context (Third Edition), by Mary Louise Fleming and Elizabeth Parker, Published by Allen and Unwin, Sydney, 2006, Paperback, 386 pages with index, RRP $55, ISBN 1-74175-017-2. Includes references.
Efficacies and Related Issues of Ustekinumab in Japanese Patients with Crohn’s Disease: A Preliminary Study

Introduction: Ustekinumab (UST) is an antibody to the p40 subunit of interleukins 12 and 23 in Crohn’s disease (CD) patients. Few reports are available on CD in the Asian scenario. Objective: We evaluated UST’s efficacy in inducing remission and its maintenance in Japanese CD patients. Methods: This retrospective study was conducted in UST-treated CD patients at our center. The primary endpoint was the clinical remission rate at week 8; the major secondary endpoints were the clinical remission rate at week 24 or 48, change in CD activity index (CDAI) and biomarkers, endoscopic efficacy, and cumulative remission maintenance rate. Results: The clinical remission rates at weeks 8, 24, and 48 were 44.4, 66.7, and 50.0%, respectively. Delayed response was shown by 22.2% of the patients; they achieved remission by week 24. The baseline CDAI was significantly lower in the remission group than in the nonremission group at week 8 (95% CI 0.89–0.99; p = 0.03). The cumulative remission maintenance rates at 6 and 12 months were 82.4 and 49.8%, respectively. Loss of response (LOR) was noted in 22.2% of the patients within 1 year. The endoscopic response and mucosal healing rate were 52.6 and 5.3%, respectively. Rapid improvements in serum albumin levels were observed at weeks 8 (p = 0.06), 24 (p < 0.01), and 48 (p = 0.01) from the baseline in active cases at baseline. Conclusions: UST is effective for remission induction and maintenance, especially in those with lower CD activity, however, may result in delayed response or LOR.
Comparison of cortisol concentrations in plasma and saliva in dairy cattle following ACTH stimulation

Abstract The experiments described in this research communication compared cortisol concentrations in plasma and saliva samples collected from dairy cattle before and after an adrenocorticotropic hormone (ACTH) application. For that purpose, blood and saliva samples were collected from five dairy cows at determined time intervals before (490 min and down to 0 min) and after (10 min and up to 500 min) an ACTH application. Mean baseline cortisol concentrations were greater in plasma compared to saliva. The relative increases and decreases in plasma and salivary cortisol concentrations following ACTH were similar. After ACTH, we observed an increase in cortisol concentrations in plasma after 10 min and in saliva after 20 min. The time of peak concentrations after ACTH were reached at 70 and 80 min for plasma and saliva, respectively. After peak concentrations, values steadily declined and returned to baseline values at 169 ± 15 min in plasma and 170 ± 14 min in saliva. Ratios between salivary and plasma cortisol concentrations were on average 0.09 and did not change substantially during the ACTH challenge. There was a strong positive relationship between salivary and plasma cortisol concentrations. These results indicate that salivary cortisol concentrations can be a good indicator of ACTH-induced plasma cortisol concentrations in dairy cattle.