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Abstract Background Neutrophils and lymphocytes represent the larger percentage of all white blood cells, they vary with age, with a progressive increase of the ratio in the first years of life, and then tend to remain at similar levels in steady state condition during adult age. Neutrophils to lymphocytes-ratio (NL-ratio) was proposed as an effective and low-cost marker to monitor and predict the evolution of several clinical conditions. The main objective of the study is to analyze its temporal trend variation, over twenty years’ follow-up, according to age, sex, and main clinical diagnosis, in a large representative Italian population. Methods The InCHIANTI study enrolled representative samples from the registry list of two towns in Tuscany, Italy. Baseline data were collected in 1998, and last follow-up visits were made in 2015-18. 1343 out of the 1453 participants enrolled were included, and consented to donate a blood sample. All subjects were assessed and followed for life-style, clinical condition, physical performance, and underwent an instrumental diagnostic session. Results The NL-ratio showed a statistically significant interaction between birth-cohort and time of the study (p-value = 0.005). A gender dimorphism was recognized in the neutrophils absolute count and in the NL-ratio. Moreover, in female participants only, those who reported CHF had lower neutrophil-count and NL-ratio; whereas an increase in creatinine clearance was directly associated with NL-ratio. In male subjects, an increase of BMI was inversely associated with both NL-ratio and neutrophils-count during the follow-up; a similar association but in the opposite direction was observed in female participants. Conclusion NL-ratio is a more reliable predictor of healthy aging than absolute lymphocytes and/or neutrophils counts. It is associated with the changes induced by disease, lifestyle, and environmental challenges in the immune system. NL-ratio confirms the gender dimorphism in the occurrence of inflammation-driven diseases, thus providing additional evidence for the necessity of tailored sex-specific measures to prevent and treat such diseases.

Background and Objectives: Irritable bowel syndrome (IBS) is an invasive and potentially disabling syndrome characterized by a multitude of symptoms capable of reducing the quality of life of patients. Among the most disabling symptoms of IBS is certainly physical pain, which manifests itself mainly at the abdominal level but can also appear in other areas of the body, particularly in the form of chronic low-back pain (CLBP). Among the non-invasive methods of treating organ-specific pathologies and organ-related musculoskeletal problems, the use of Bioresonance Therapy (BT)—based on the administration of self-modulating Extremely Low-Frequency Electromagnetic Fields, capable of determining a rebalance of bio-electrical and metabolic activity in the presence of various functional alterations—is currently gaining acceptance. Therefore, we decided to monitor results obtained from patients suffering from IBS and CLBP subjected to a cycle of treatments with BT. Materials and Methods: We monitored 20 patients (12 women and 8 men, average age of 51 years) suffering from CLBP and other visceral symptoms related to IBS. Patients were monitored through the use of the Bristol Stool Form Scale (BSFS), the Fecal Calprotectin test and the Short-Form Health Survey 36 (SF-36), collected before (T0) and after (T1) the execution of the cycle of treatments. They undertook a treatment protocol consisting of eight sessions of BT carried out over about a month. Results: At the end of the treatments with BT, it was possible to observe a general and significant improvement in all the parameters observed, as well as a close inversely proportional correlation between the Calprotectin values detected and the quality of life experienced by the patients in relation to their perceived IBS symptoms. Conclusions: Overall, our pilot study would seem to suggest a potential beneficial effect of BT in modulating organic and musculoskeletal symptoms derived from IBS.

Abstract Natural antibodies (nAbs) against aggregation-prone proteins have been found in healthy normal subjects. These proteins likely have a pathogenetic role in neurodegenerative diseases of ageing. They include the amyloid β (Aβ) protein which may play an important role in Alzheimer’s dementia (AD), and α-synuclein, a major determinant of Parkinson’s disease (PD). We measured nAbs to Aβ in a group of Italian patients with AD, vascular dementia, non-demented PD patients and healthy elderly controls. We found that Aβ antibody levels in AD were similar to age- and sex-matched controls, but contrary to our expectations, they were significantly reduced in PD. This may identify patients that could be more prone to amyloid aggregation.

Abstract Background Rotator cuff (RC) tendinopathy is a common shoulder pain condition. Extracorporeal shockwave therapy (ESWT) and hyaluronic acid peritendinous injection are viable treatment options for RC tendinopathy. The aim of this study is to evaluate the response in two different therapeutic rehabilitative approaches, the combined treatment ESWT plus hyaluronic acid injections (E + Hy) compared to ESWT alone (ESWT-al), in a cohort of patients with RC tendinopathy according to gender differences. Methods This is a retrospective longitudinal cohort study of patients with painful RC tendinopathy. Patients that had received a clinical evaluation, a shoulder ultra sound examination, as well as the Shoulder Pain and Disability Index (SPADI) questionnaire, and the Numerical Rating Scale (NRS) for pain at baseline, 1-month (T1) and 2-month follow-ups (T2) were included. Results Medical records of 53 patients were analyzed. In the comparison between baseline to T1 and similarly from baseline to T2, a statistically significant reduction has been reported in the NRS (p

Accurate and reproducible tissue identification is essential for understanding structural and functional changes that may occur naturally with aging, or because of a chronic disease, or in response to intervention therapies. Peripheral quantitative computed tomography (pQCT) is regularly employed for body composition studies, especially for the structural and material properties of the bone. Furthermore, pQCT acquisition requires low radiation dose and the scanner is compact and portable. However, pQCT scans have limited spatial resolution and moderate SNR. pQCT image quality is frequently degraded by involuntary subject movement during image acquisition. These limitations may often compromise the accuracy of tissue quantification, and emphasize the need for automated and robust quantification methods. We propose a tissue identification and quantification methodology that addresses image quality limitations and artifacts, with increased interest in subject movement. We introduce a multi-atlas image segmentation (MAIS) framework for semantic segmentation of hard and soft tissues in pQCT scans at multiple levels of the lower leg. We describe the stages of statistical atlas generation, deformable registration and multi-tissue classifier fusion. We evaluated the performance of our methodology using multiple deformable registration approaches against reference tissue masks. We also evaluated the performance of conventional model-based segmentation against the same reference data to facilitate comparisons. We studied the effect of subject movement on tissue segmentation quality. We also applied the top performing method to a larger out-of-sample dataset and report the quantification results. The results show that multi-atlas image segmentation with diffeomorphic deformation and probabilistic label fusion produces very good quality over all tissues, even for scans with significant quality degradation. The application of our technique to the larger dataset reveals trends of age-related body composition changes that are consistent with the literature. Because of its robustness to subject motion artifacts, our MAIS methodology enables analysis of larger number of scans than conventional state-of-the-art methods. Automated analysis of both soft and hard tissues in pQCT is another contribution of this work.

Vitamins, hormones, free radicals, and antioxidant substances significantly influence athletic performance. The aim of this study was to evaluate whether these biological mediators changed during the season and if this was associated with the rate of improvement in performance after training, assessed by means of a standardized test. Professional male soccer players took part in the study. Two evaluations were performed: the first in the pre-season period and the second at the mid-point of the official season, after about 6 months of intensive training and weekly matches. Blood levels of vitamins D, B12, and folic acid, testosterone and cortisol, free radicals, and antioxidant substances were measured. Two hours after breakfast, a Yo-Yo test was performed. The relationships between the biological mediators and the rate of improvement after training (i.e., the increase in meters run in the Yo-Yo test between the pre-season and mid-season periods) were evaluated by means of a linear mixed models analysis. Results: Eighty-two paired tests were performed. The athletes showed better performance after training, with an increase in the meters run of about 20%. No significant relationships between the vitamin and hormone values and the gain in the performance test were observed. Plasmatic levels of free radicals increased significantly, as did the blood antioxidant potential. An indirect relationship between oxidative stress and the improvement in performance was observed (free radicals β ± SE: = −0.33 ± 0.10; p-value = 0.001), with lower levels of oxidative stress being associated with higher levels of performance in the Yo-Yo test. Monitoring the measures of oxidative stress could be a useful additional tool for coaches in training and/or recovery programs tailored to each player.

Purpose: Brain tumor-related epilepsy (BTRE) is a condition characterized by the development of seizures in the context of an undergoing oncological background. Levetiracetam (LEV) is a third-generation anti-seizure medication (ASM) widely used in BTRE prophylaxis. The study evaluated LEV neuropsychiatric side effects (SEs) in BTRE prophylaxis.Method: Twenty-eight patients with brain tumors were retrospectively selected and divided into two groups. In one group, we evaluated patients with a BTRE diagnosis using LEV (BTRE-group). The other group included patients with brain tumors who never had epilepsy and used a prophylactic ASM regimen with LEV (PROPHYLAXIS-group). Neuropsychiatric SEs of LEV were monitored using the Neuropsychiatric Inventory Questionnaire (NPI-Q) at the baseline visit and the 6- and 12-month follow-up.Results: Eighteen patients of the BTRE-group and 10 patients of the PROPHYLAXIS-group were included. Compared to the BTRE-group, the PROPHYLAXIS-group showed a higher severity of neuropsychiatric symptoms. According to Linear Mixed Models (LMM), a multiplicative effect was observed for the interaction between group treatment and time. For the caregiver distress score (CDS), only a time-effect was observed.Conclusion: Prophylactic ASM with LEV is associated with an increased frequency of neuropsychiatric SE. Accurate epileptological evaluations in patients with brain tumors are mandatory to select who would benefit most from ASM.

Ankle-brachial index and arterial stiffness are associated with leg function in the elderly and in patients with peripheral arterial disease. Little is known about the meaning of these parameters in young and trained subjects and how they are related to physical performance. The main objective was to evaluate the mediating role of arterial stiffness and ankle-brachial index in physical performance. In a cross-sectional, case-control study, 240 male athletes were consecutively enrolled from the Laboratory of Cardiology and Sports Medicine, “G. d’Annunzio” University (Italy). All the subjects underwent the examination protocol for the annual medical evaluation for sport participation. Soccer (football) players compared to runners showed a lower level of ankle-brachial index, higher arterial stiffness, and lower systolic and diastolic blood pressure. In the treadmill stress test, soccer players compared to runners showed a greater maximal aerobic capacity. Differences in cardiovascular performance between soccer players and runners were mediated by better arterial stiffness and low level of ankle-brachial index; the estimated effect was 0.11 ± 0.05 and 0.24 ± 0.06, respectively. Vigorous strength training drops blood pressure and increases arterial stiffness. Taken together, our findings would seem to suggest that ABI and CAVI could be used as markers for athletes’ performance.

Background and Objectives: The aim of this study was to investigate the impact of oral administration of the combination of astaxanthin (AXT), lutein, folic acid, vitamin D3, and bromelain with antioxidants on choroidal blood flow in patients with age-related intermediate macular degeneration (AMD). Materials and Methods: Patients affected by intermediate AMD and treated with daily oral nutritional supplement with AXT, bromelain, vitamin D3, folic acid, lutein, and antioxidants for a period of at least 6 months were included in this retrospective study. A control group homogenous for age and sex was also included in the analysis. All participants underwent a complete ophthalmologic examination, spectral domain optical coherence tomography (SD-OCT), and optical coherence tomography angiography (OCTA) evaluation. Outcome measures were choroidal thickness (CHT) and choriocapillary vessel density (CCVD) after six months of AXT assumption. Results: CCVD values showed statistically significant difference between cases and controls at baseline (p < 0.001) and in the cases during follow-up (p < 0.001). The CHT measurements showed statistically significant difference between cases and controls (p = 0.002) and in the cases during follow-up (p < 0.001). Conclusions: The combined use of structural OCT and OCTA allows for a detailed analysis in vivo of perfusion parameters of the choriocapillaris and choroid and evaluation of changes of choroidal blood flow after oral nutritional supplements that affect blood flow velocity.

The motor behaviour of patients with Upper Motor Neuron Syndrome (UMNS) is characterised by spasticity. The first-line treatment for this clinical condition is Botulinum neurotoxin A (BoNTA), but the number and key locations of muscles which need to be treated is not much discussed in the literature. Cross-sectional analysis of outpatient cohort with UMNS spasticity, who were potential candidates for BoNTA treatment, was performed. Between November 2020 and November 2021, all consecutive adult patients eligible for BoNTA treatment were enrolled. The inclusion criteria encompass UMNS spasticity (onset being ≥6 months), with disabling muscles hypertonia. Patients underwent a clinical evaluation, a comprehensive assessment with the Modified Ashworth Scale, with the Modified Rankin Scale, and a patients’ perception-centred questionnaire. In total, 68 participants were enrolled in the study, among them 40 (58.8%) were male; mean age 57.9 ± 15.1. In women, BoNTA was more frequently required for adductor group muscles, independently from potential confounders (OR = 7.03, 95%CI: 1.90–25.97). According to the pattern of disability, patients with hemiparesis more frequently need to be treated in the upper limb, whereas the diplegia/double-hemiparesis group needed to be treated more frequently at the adductor and crux muscles compared to their counterparts. UMNS spasticity in women could require more attention to be paid to the treatment of adductor muscle spasticity, potentially because the dysfunction of those muscles could influence sphincteric management, required for perineal hygiene and/or sexual life.

Background: To prevent and fight the increase of daily sedentary time and to promote and stimulate the positive effects of physical activity and exercise on health, both traditional interventions and new strategies are important for breast cancer survivors (BCS). The research goal was to compare the effects of weekly personal feedback, based on objectively measured physical activity, on the trends of both daily sedentary time and on the physical activity of BCS (E− group) with those of an intervention also including online supervised physical exercise sessions (E+ group), during the Italy COVID-19 lockdown. Methods: The Italian COVID-19 emergency allowed the possibility to also observe the effects of social and personal limitations. A total of 51 BCS were studied over an 18-week period and had an objective registration of day-to-day sedentary time, physical activity, and sleep. Both subsamples received weekly or fortnight personal feedback. Data were analysed considering four key periods, according to the COVID-19 emergency steps. Results: Statistical analysis showed an additive effect for sedentary time and a multiplicative effect both for light-to vigorous and light-intensity physical activities. The E− group had a high overall sedentary time and a different trend of light-to vigorous and light-intensity physical activities, with a reduction from the 1st to the 2nd periods (national and personal restrictions), showing a significant rise just at the end of the national restrictions. Conclusions: The use of an activity tracker and its accompanying app, with the reception of weekly tailored advice and supervised online physical exercise sessions, can elicit proper physical activity recomposition in BCS in the COVID-19 era.

Objective: The aim of this study was to analyze quantitative sleep changes and their implication on subjective cognitive decline (SCD). Objective sleep patterns were investigated by an actigraph and recorded at the baseline and 2-year after in order to examine specific sleep alterations in SCD.Background: Sleep disorders are very common among average elderly adults and an altered sleep pattern is known to be a risk factor for future development of mild cognitive impairment (MCI) and dementia. Recent studies have shown how sleep is objectively altered in average senior adults with SCD, without any other significant change in cognition and behavior or brain structure. Considering that both SCD and disrupted sleep are risk factors for future MCI and dementia, with sleep only as a modifiable risk factor, further research is required to deeply investigate the interaction between sleep and SCD.Methods: Among 70 community-dwelling elderly individuals who had been enrolled at baseline, 35 (64.6 ± 5.6 years, 15 M/20 F) underwent a complete neuropsychological battery and 1-week wrist actigraphy recording 2 years later during the follow-up stage. Individuals were divided into two groups according to their SCD Questionnaire (SCD-Q) score. Sleep hours, sleep efficiency and onset latency, napping and time awake after sleep onset (WASO) were collected. All individuals underwent structural magnetic resonance imaging (MRI) examination to exclude brain disorders. Data collection was performed at baseline and after 2 years at the follow-up phase.Results: A significantly different night sleep time between the two groups was observed: SCD showed a lower total sleep time (TST) than non-SCD subjects. Moreover, a total time spent in bed (TIB) was significantly lower in SCD subjects over 2 years of observation.Conclusions: Objective changes over time of the sleep pattern, specifically TIB and TST, are present in SCD individuals. The results of the study show that sleep alterations are common in SCD and underline the clinical importance of screening in order to assess sleep alterations as well as improve sleep in average adults with SCD complaints.

Background: Brain-Computer Interface (BCI) is becoming more reliable, thanks to the advantages of Artificial Intelligence (AI). Recently, hybrid Deep Learning (hDL), which combines different DL algorithms, has gained momentum over the past five years. In this work, we proposed a review on hDL-based BCI starting from the seminal studies in 2015. Objectives: We have reviewed 47 papers that apply hDL to the BCI system published between 2015 and 2020 extracting trends and highlighting relevant aspects to the topic. Methods: We have queried four scientific search engines (Google Scholar, PubMed, IEEE Xplore and Elsevier Science Direct) and different data items were extracted from each paper such as the database used, kind of application, online/offline training, tasks used for the BCI, pre-processing methodology adopted, type of normalization used, which kind of features were extracted, type of DL architecture used, number of layers implemented and which optimization approach were used as well. All these items were then investigated one by one to uncover trends. Results: Our investigation reveals that Electroencephalography (EEG) has been the most used technique. Interestingly, despite the lower Signal-to-Noise Ratio (SNR) of the EEG data that makes pre-processing of that data mandatory, we have found that the pre-processing has only been used in 21.28% of the cases by showing that hDL seems to be able to overcome this intrinsic drawback of the EEG data. Temporal-features seem to be the most effective with 93.94% accuracy, while spatial-temporal features are the most used with 33.33% of the cases investigated. The most used architecture has been Convolutional Neural Network-Recurrent Neural Network CNN-RNN with 47% of the cases. Moreover, half of the studies have used a low number of layers to achieve a good compromise between the complexity of the network and computational efficiency. Significance: To give useful information to the scientific community, we make our summary table of hDL-based BCI papers available and invite the community to published work to contribute to it directly. We have indicated a list of open challenges, emphasizing the need to use neuroimaging techniques other than EEG, such as functional Near-Infrared Spectroscopy (fNIRS), deeper investigate the advantages and disadvantages of using pre-processing and the relationship with the accuracy obtained. To implement new combinations of architectures, such as RNN-based and Deep Belief Network DBN-based, it is necessary to better explore the frequency and temporal-frequency features of the data at hand.

Purpose This paper introduces the Research Articles in Simplified HTML (or RASH), which is a Web-first format for writing HTML-based scholarly papers; it is accompanied by the RASH Framework, a set of tools for interacting with RASH-based articles. The paper also presents an evaluation that involved authors and reviewers of RASH articles submitted to the SAVE-SD 2015 and SAVE-SD 2016 workshops. Design RASH has been developed aiming to: be easy to learn and use; share scholarly documents (and embedded semantic annotations) through the Web; support its adoption within the existing publishing workflow. Findings The evaluation study confirmed that RASH is ready to be adopted in workshops, conferences, and journals and can be quickly learnt by researchers who are familiar with HTML. Research Limitations The evaluation study also highlighted some issues in the adoption of RASH, and in general of HTML formats, especially by less technically savvy users. Moreover, additional tools are needed, e.g., for enabling additional conversions from/to existing formats such as OpenXML. Practical Implications RASH (and its Framework) is another step towards enabling the definition of formal representations of the meaning of the content of an article, facilitating its automatic discovery, enabling its linking to semantically related articles, providing access to data within the article in actionable form, and allowing integration of data between papers. Social Implications RASH addresses the intrinsic needs related to the various users of a scholarly article: researchers (focussing on its content), readers (experiencing new ways for browsing it), citizen scientists (reusing available data formally defined within it through semantic annotations), publishers (using the advantages of new technologies as envisioned by the Semantic Publishing movement). Value RASH helps authors to focus on the organisation of their texts, supports them in the task of semantically enriching the content of articles, and leaves all the issues about validation, visualisation, conversion, and semantic data extraction to the various tools developed within its Framework.

While most challenges organized so far in the Semantic Web domain are focused on comparing tools with respect to different criteria such as their features and competencies, or exploiting semantically enriched data, the Semantic Web Evaluation Challenges series, co-located with the ESWC Semantic Web Conference, aims to compare them based on their output, namely the produced dataset. The Semantic Publishing Challenge is one of these challenges. Its goal is to involve participants in extracting data from heterogeneous sources on scholarly publications, and producing Linked Data that can be exploited by the community itself. This paper reviews lessons learned from both (i) the overall organization of the Semantic Publishing Challenge, regarding the definition of the tasks, building the input dataset and forming the evaluation, and (ii) the results produced by the participants, regarding the proposed approaches, the used tools, the preferred vocabularies and the results produced in the three editions of 2014, 2015 and 2016. We compared these lessons to other Semantic Web Evaluation Challenges. In this paper, we (i) distill best practices for organizing such challenges that could be applied to similar events, and (ii) report observations on Linked Data publishing derived from the submitted solutions. We conclude that higher quality may be achieved when Linked Data is produced as a result of a challenge, because the competition becomes an incentive, while solutions become better with respect to Linked Data publishing best practices when they are evaluated against the rules of the challenge.

The «Anywhere, Anytime, Anyway» slogan is frequently associated to e-learning with the aim to emphasize the wide access offered by on-line education to students. Our aim is to extend the reach of this sentence to content authors as well. Our idea is to produce tools to simplify drastically the task of creating, updating and publishing content for e-learning courses, and to allow them to produce learning objects of extremely high technical sophistication directly from off-the-shelf desktop application. Thus we introduce ISA-BeL, a conversion engine that can generate standard-based, visually homogeneous, accessible and graphically sophisticated SCORM learning objects by analyzing the internal structure and content of word processing fi les and generating the required output without requiring particular technical awareness by the user.

The “WikiWay” is the open editing philosophy of wikis meant to foster open collaboration and continuous improvement of their content. Just like other online communities, wikis often introduce and enforce conventions, constraints, and rules for their content, but do so in a considerably softer way, expecting authors to deliver content that satisfies the conventions and the constraints, or, failing that, having volunteers of the community, the WikiGnomes, fix others' content accordingly. Constrained wikis is our generic framework for wikis to implement validators of community-specific constraints and conventions that preserve the WikiWay and their open collaboration features. To this end, specific requirements need to be observed by validators and a specific software architecture can be used for their implementation, that is, as independent functions (implemented as internal modules or external services) used in a nonintrusive way. Two separate proof-of-concept validators have been implemented for MediaWiki and MoinMoin, respectively, providing an annotated view functions, that is, presenting content authors with violation warnings, rather than preventing them from saving a noncompliant text.