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BACKGROUND: Enrichment strategies from clinical trials for progressive systemic sclerosis-associated interstitial lung disease (SSc-ILD) have not been tested in a real-life cohort.RESEARCH QUESTION: Do enrichment strategies for progressive ILD impact efficacy, repre-sentativeness, and feasibility in patients with SSc-ILD from the European Scleroderma Trials and Research (EUSTAR) database?STUDY DESIGN AND METHODS: We applied the inclusion criteria of major recent SSc-ILD trials (Study of the Efficacy and Safety of Tocilizumab in Participants With Systemic Sclerosis [focuSSced], Scleroderma Lung Study II [SLS II], and Safety and Efficacy of Nintedanib in Systemic Sclerosis [SENSCIS]) and assessed progressive ILD, which was defined as absolute change in FVC and as significant progression (FVC decline $10%). Data were compared with all patients and with patients who did not fulfill any inclusion criteria. RESULTS: In total, 2,258 patients with SSc-ILD were included: 31.2% of the patients met SENSCIS criteria; 5.8% of the patients met SLS II criteria; 1.6% of the patients met focuSSced criteria, and 67.7% (1,529) of the patients did not meet any criteria. In the first 12 + 3 months, the absolute FVC decline in all patients and in patients who fulfilled criteria from SENSCIS was -0.1%, in patients who fulfilled criteria from focuSSced was -3.7%, and in patients who fulfilled criteria from SLS II was 2.3%, with accompanying more progressors in focuSSced. The patient populations that fulfilled the different study inclusion criteria significantly differed in various clinical parameters. In the second 12-month period, SENSCIS-enriched patients had a further absolute FVC% decline as described for the total cohort. In contrast, patients who fulfilled the focuSSced and SLS II criteria showed numeric improvement of lung function. There were no significant associations of enrichment criteria and ILD progression.INTERPRETATION: The application of enrichment criteria from previous clinical trials showed enrichment for progression with variable success, which led to selected patient populations reducing feasibility of recruitment. These findings are important for future clinical trial design and interpretation of the results of published trials.CHEST 2023; 163(3):586-598

Galaxy clusters are assembled via merging of smaller structures, in a process that generates shocks and turbulence in the intra cluster medium and produces radio diffuse emission in the form of halos and relics. The cluster pair A 399–A 401 represents a special case: both clusters host a radio halo. Recent Low Frequency Array (LOFAR) observations at 140 MHz revealed the presence of a radio bridge connecting the two clusters along with two relic candidates. These relics include one South of A 399 and the other in between the two clusters, in proximity of a shock front detected in X-ray observations. In this paper we present observations of the A 399–A 401 cluster pair at 1.7, 1.4, 1.2 GHz, and 346 MHz from the Westerbork Synthesis Radio Telescope (WSRT). We detect the radio halo in the A 399 cluster at 346 MHz, extending up to ∼650 kpc and with a 125 ± 6 mJy flux density. Its spectral index between 140 MHz and 346 MHz is α = 1.75 ± 0.14. The two candidate relics are also seen at 346 MHz and we determine their spectral indices to be α = 1.10 ± 0.14 and α = 1.46 ± 0.14. The low surface brightness bridge connecting the two clusters is below the noise level at 346 MHz therefore we constrain the bridge average spectral index to be steep, i.e. α > 1.5 at 95 per cent confidence level. This result favours the scenario where dynamically-induced turbulence is a viable mechanism to reaccelerate a population of mildly relativistic particles and amplify magnetic fields on scales of a few Mpcs.

Precision agriculture (PA) is defined as an agricultural management based on the observation, measurement, and response of a set of quantitative and qualitative variables that affects agricultural production. The first step in the approach to precision agriculture is, therefore, the acquisition and collection of data from optical, multispectral, geophysical sensors, etc. aimed at obtaining knowledge and monitoring of the crop. In recent years UAVs are assuming an important role in precision agriculture. The possibility of mounting RGB, multispectral, LiDAR sensors on them make these systems fast, accurate, and usability compared other geomatic methods. In this study, we focus on a very low-cost UAV system to assess individual tree height and generate 3D Model and orthophoto of the study area. We used the DJI Mini2, a low-cost UAV that can be used without a flight rating and without restrictions due to its light weight of only 250 grams. The case study where the survey was performed is an agricultural area of about 1 hectare, where are some fruit trees and a small vineyard. The area was selected because it contained both tall and small trees. The study concerned the influence of the relative flight altitude and therefore of the GSD of the images on the extraction of the dimensional data of the trees. From the results obtained, it can be stated that the flight altitude has certainly more influence on the measurement of small tree (around one meter tall) compared to tall ones (around 4 m).

Repetitive negative thinking (RNT) may be defined as a reiterative, passive and uncontrollable thinking process. RNT has been recognized as a transdiagnostic phenomenon associated with the onset and maintenance of several clinical conditions including depression, generalised anxiety, psychosis and insomnia. We aimed to estimate a network model of mutual associations between RNT and the aforementioned indicators whilst controlling for other well-established transdiagnostic factors (i.e. perceived stress, loneliness). A total of 324 participants (Mage = 25.26 years, SD = 6.89; 69.3% females) completed a cross-sectional survey of self-report questionnaires. A Gaussian graphical model was estimated using the graphical LASSO in combination with the extended Bayesian information criterion. We found a dense network in which RNT exhibited substantial connections with the majority of the psychopathological domains. The centrality indices confirmed that RNT was one of the most important nodes in the network. Moreover, the estimated network showed satisfactory accuracy and stability. Findings emphasized RNT as a potentially good therapeutic target for psychopathology prevention and treatment protocols.

STUDY QUESTION Is there a possible etiologic link between cervical stiffness and adenomyosis? SUMMARY ANSWER Women with adenomyosis have a stiffer internal cervical os than those without adenomyosis. WHAT IS KNOWN ALREADY An increased myometrial contractility during menses, leading to breaches in the endometrial basal lamina and subsequent infiltration of endometrial cells into the myometrium, has been proposed as a possible pathogenic mechanism for adenomyosis. Intense menstrual pain has already been shown to be associated with an increased stiffness, at elastography, of the internal cervical os. STUDY DESIGN, SIZE, DURATION A cross-sectional study on 275 women was performed between 1 February and 31 July 2022. PARTICIPANTS/MATERIALS, SETTING, METHODS Among the participants, 103 were and 172 women were not affected by adenomyosis as evaluated by ultrasonography. General and clinical characteristics of the patients were collected. Strain elastography was used to document tissue stiffness at different regions of interest of the cervix, i.e. the internal cervical os, the middle cervical canal, the anterior and the posterior cervical compartment. Tissue stiffness was expressed as a colour score from 0.1 = blue/violet (high stiffness) to 3.0 = red (low stiffness). Simple and multiple logistic regression analyses were used to evaluate the relation between the presence of adenomyosis, as the dependent variable, and independent factors. MAIN RESULTS AND THE ROLE OF CHANCE Women with adenomyosis had a higher prevalence (P = 0.0001) and intensity (P = 0.0001) of pain during menses, between menses and at intercourse compared to control. The internal cervical os colour score was lower (higher stiffness) in women with adenomyosis (0.55 ± 0.29 versus 0.67 ± 0.26; P = 0.001) and the middle cervical canal/internal cervical os colour score ratio was greater (3.32 ± 4.36 versus 2.59 ± 4.99; P = 0.008), compared to controls. Upon logistic regression modelling (R2 = 0.077), the internal cervical os stiffness was an independent factor related to adenomyosis (odds ratio (OR) 0.220, 95% CI 0.077, 0.627; P = 0.005) along with age (P = 0.005) and the use of gonadal steroid therapies (P = 0.002). We obtained the same results using a different logistic regression model (R2 = 0.069), by substituting the internal cervical os stiffness with the ratio of the middle cervical canal/internal cervical os stiffness (OR 1.157, 95% CI 1.024, 1.309; P = 0.019). LIMITATIONS, REASONS FOR CAUTION Women did not undergo surgery therefore we have no histological confirmation of the adenomyosis diagnosis. Strain elastography is a semiquantitative analysis and can be conditioned by the force applied by the operator during the analysis. The data were obtained mainly in White women in a single centre. WIDER IMPLICATIONS OF THE FINDINGS To the best of our knowledge, this is the first study indicating that women with adenomyosis have an increased stiffness of the internal cervical os. The results indicate that a stiff internal cervical os, as determined by elastography, is a possible contributor to the development of adenomyosis. These findings may have clinical significance and should prompt further investigation. STUDY FUNDING/COMPETING INTEREST(S) None. TRIAL REGISTRATION NUMBER N/A.

Background: Minimally invasive sacral colpopexy is considered the gold standard for surgical treatment of Pelvic Organ Prolapse (POP), combining high success rates with low recurrence risk in comparison to other techniques. This is the first case of robotic sacral colpopexy (RSCP) performed with the innovative Hugo™ RAS robotic system. Objectives: The aim of this article is to show the surgical steps of a nerve sparing RSCP performed with the new Hugo™ RAS robotic system (Medtronic), by also evaluating the feasibility of this technique using this novel Robotic System. Materials and methods: A 50-year-old Caucasian woman with symptomatic pelvic organ prolapse (POP-Q): Aa: +2, Ba: +3, C: +4, D: +4, Bp: -2, Ap: -2 , TVL:10 GH: 3,5 BP:3 underwent RSCP as well as a subtotal hysterectomy with bilateral salpingo-oophorectomy, using the new surgical robot Hugo™ RAS in the Division of Urogynaecology and Pelvic Reconstructive Surgery, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Main outcome measures: Intraoperative data, docking specifics, objective and subjective outcomes at three months follow up. Results: Surgical procedure was carried out without intra-operative complications, operative time (OT) was 150 minutes, docking time was 9 minutes. No system errors or faults in the robotic arms were registered. Urogynaecological examination at three months follow up showed a complete resolution of the prolapse. Conclusion: RSCP using the Hugo™ RAS system seems to be a feasible and effective approach according to results in terms of operative time, cosmetic results, postoperative pain and length of hospitalisation. Large number of case reports as well as longer follow up are mandatory to better define its benefits, advantages, and costs.

The present study, based on microsatellite markers, describes a population genetic analysis of the small-spotted catshark Scyliorhinus canicula (Linnaeus, 1758), representing one of the most abundant and commonly caught cartilaginous fishes in the Mediterranean Sea and adjacent areas. The analyses were performed to unravel the genetic features (variability, connectivity, sex-biased dispersal) of their relative geographic populations, both at the small (around the coast of Sardinia, Western Mediterranean Sea) and at a larger spatial scale (pan-Mediterranean level and between the Atlantic Ocean and the Mediterranean Sea). Individual clustering, multivariate and variance analyses rejected the hypothesis of genetic homogeneity, with significant genetic differences mainly within the Mediterranean between the Western and Eastern basins, as well as between the Mediterranean and the NE Atlantic Ocean. In detail, our results seem to confirm that the Strait of Gibraltar could not represent a complete barrier to the exchange of individuals of small-spotted catshark between the Atlantic Ocean and the Mediterranean Sea. In the latter area, a complex genetic structuring for S. canicula was found. Apart from differences among the Western, Eastern and Adriatic sites, within the Western basin the small-spotted catsharks around Sardinian waters are strongly differentiated from all others (both from the eastern Tyrrhenian Sea and southernmost part of the Algerian basin) and are demographically stable. Several possible mechanisms, both biological and abiotic (e.g., migratory behavior, waterfronts, and oceanographic discontinuities), are discussed here to explain their peculiar characteristics. Overall, the genetic data presented, both at the local and regional level, could represent a baseline information, useful for the temporal monitoring of populations, and to assess the effects of present or future fishing/management/conservation measures.

Objective To develop and validate the prognostic prediction model DU-VASC to assist the clinicians in decision-making regarding the use of platelet inhibitors (PIs) for the management of digital ulcers in patients with systemic sclerosis. Secondly, to assess the incremental value of PIs as predictor. Methods We analysed patient data from the European Scleroderma Trials and Research group registry (one time point assessed). Three sets of derivation/validation cohorts were obtained from the original cohort. Using logistic regression, we developed a model for prediction of digital ulcers (DUs). C-Statistics and calibration plots were calculated to evaluate the prediction performance. Variable importance plots and the decrease in C-statistics were used to address the importance of the predictors. Results Of 3710 patients in the original cohort, 487 had DUs and 90 were exposed to PIs. For the DU-VASC model, which includes 27 predictors, we observed good calibration and discrimination in all cohorts (C-statistic = 81.1% [95% CI: 78.9%, 83.4%] for the derivation and 82.3% [95% CI: 779.3%, 85.3%] for the independent temporal validation cohort). Exposure to PIs was associated with absence of DUs and was the most important therapeutic predictor. Further important factors associated with absence of DUs were lower modified Rodnan skin score, anti-Scl-70 negativity and normal CRP. Conversely, the exposure to phosphodiesterase-5 inhibitor, prostacyclin analogues or endothelin receptor antagonists seemed to be associated with the occurrence of DUs. Nonetheless, previous DUs remains the most impactful predictor of DUs. Conclusion The DU-VASC model, with good calibration and discrimination ability, revealed that PI treatment was the most important therapy-related predictor associated with reduced DU occurrence.

Abnormalities in cortical sources of resting-state eyes-closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10–20 electrode montage) with 19 scalp electrodes provide useful markers of neurophysiological dysfunctions in the vigilance regulation in patients with Alzheimer's disease dementia (ADD). Here we tested whether these markers may be effective from a few scalp electrodes towards the use of low-cost recording devices. Clinical and rsEEG data acquired in hospital settings (10–20 electrode montage) from 88 ADD participants and 68 age-, education-, and sex-matched normal elderly controls (Nold) were available in an international Eurasian database. Standard spectral FFT analysis of rsEEG data for individual delta, theta, and alpha frequency bands was from C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels. As compared to the Nold group, the ADD group showed increased delta, theta, low-frequency alpha power density and decreased high-frequency alpha power density at all those bipolar channels. The highest classification accuracy between the ADD and Nold individuals reached 90 % (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from a few posterior bipolar channels successfully classified Nold and ADD individuals, thus encouraging a massive prescreening of neurophysiological mechanisms underpinning the vigilance dysregulation in underserved old seniors. Ministero della Salute

AimsClimate change imposes adaptation of viticulture in risk areas, such as the Mediterranean. Mycorrhization is a valid tool to reduce the impact of the expected temperature/drought increase. Aim of this work was to test the effects of mycorrhization on grapevine vegetative growth, element composition of soil/leaves, and microbiota of bulk soil/rhizosphere/endorhiza, in the field, under exacerbated summer stress conditions obtained by planting the rootstocks in June.Methods118 rooted cuttings of 1103-Paulsen (Vitis berlandieri×Vitis rupestris) were planted in Salento (Apulia, Southern Italy); about half of them were mycorrhized. Leaf Area Index, shoot growth and survival rate were monitored across two growing seasons. Leaf/shoot weight, chemical analysis of 25 elements, and 16S rRNA gene metabarcoding of bulk soil/rhizosphere/endorhiza were performed on subsamples.ResultsMycorrhized plants showed significantly higher survival rate and growth, and accumulated significantly higher amounts of 18 elements. 27 endorhizal OTUs (representing ~20% of total sequences) were differently distributed (20 OTUs more abundant in mycorrhized plants); in the rhizosphere, instead, 12 OTUs (~2.5% of total sequences) were differently distributed. A few Actinobacterial OTUs were enriched by mycorrhization in the root endosphere; the same OTUs were the most correlated with the chemical elements, suggesting a role in element dynamics. These OTUs were not hub taxa of the co-occurrence network.ConclusionsThis work shed light onto the interactions between mycorrhiza and microbiome, in the context of plant element dynamics, which is useful to identify potential target candidates for biotechnological applications, thus moving towards a more sustainable, ecosystem-based viticulture.

Objectives To characterize patients with positive anti-topoisomerase I (ATA) in lcSSc. Methods SSc patients enrolled in the EUSTAR cohort with a disease duration of ≤3 years at database entry were considered. We assessed the risk of major organ involvement in the following groups: ATA-lcSSc vs ACA-lcSSc and vs ANA without specificity (ANA)-lcSSc, and ATA-lcSSc vs ATA-dcSSc. Cox regression models with time-dependent covariates were performed with the following outcomes: new-onset interstitial lung disease (ILD), ILD progression [forced vital capacity (FVC) decline ≥10% and ≥5% vs values at ILD diagnosis), primary myocardial involvement (PMI), pulmonary hypertension (PH), any organ involvement and all-cause mortality. Results We included 1252 patients [194 ATA-lcSSc (15.5%)], with 7.7 years (s.d. 3.5) of follow-up. ILD risk was higher in ATA-lcSSc vs ACA- and ANA-lcSSc and similar to ATA-dcSSc, although with less frequent restrictive lung disease. The risk of FVC decline ≥10% (35% of ATA-lcSSc) was lower in ATA-lcSSc than in ATA-dcSSc, whereas FVC decline ≥5% occurs similarly between ATA-lcSSc (58% of patients) and other SSc subsets, including ATA-dcSSc. The risk of PMI was similar in ATA-lcSSc and ANA-lcSSc but lower than in ACA-lcSSc; no difference in PH and mortality risk was observed among lcSSc subsets. The risk of any organ involvement, PMI and PH was lower and the mortality tended to be lower in ATA-lcSSc vs ATA-dcSSc. Conclusion ATA-lcSSc patients have a high risk of ILD, albeit with a lower risk of progression compared with ATA-dcSSc, supporting careful screening for ILD in this subgroup.

Purpose Since the term orthorexia nervosa (ON) was coined from the Greek (ὀρθός, right and ὄρεξις, appetite) in 1997 to describe an obsession with “correct” eating, it has been used worldwide without a consistent definition. Although multiple authors have proposed diagnostic criteria, and many theoretical papers have been published, no consensus definition of ON exists, empirical primary evidence is limited, and ON is not a standardized diagnosis. These gaps prevent research to identify risk and protective factors, pathophysiology, functional consequences, and evidence-based therapeutic treatments. The aims of the current study are to categorize the common observations and presentations of ON pathology among experts in the eating disorder field, propose tentative diagnostic criteria, and consider which DSM chapter and category would be most appropriate for ON should it be included. Methods 47 eating disorder researchers and multidisciplinary treatment specialists from 14 different countries across four continents completed a three-phase modified Delphi process, with 75% agreement determined as the threshold for a statement to be included in the final consensus document. In phase I, participants were asked via online survey to agree or disagree with 67 statements about ON in four categories: A–Definition, Clinical Aspects, Duration; B–Consequences; C–Onset; D–Exclusion Criteria, and comment on their rationale. Responses were used to modify the statements which were then provided to the same participants for phase II, a second round of feedback, again in online survey form. Responses to phase II were used to modify and improve the statements for phase III, in which statements that met the predetermined 75% of agreement threshold were provided for review and commentary by all participants. Results 27 statements met or exceeded the consensus threshold and were compiled into proposed diagnostic criteria for ON. Conclusions This is the first time a standardized definition of ON has been developed from a worldwide, multidisciplinary cohort of experts. It represents a summary of observations, clinical expertise, and research findings from a wide base of knowledge. It may be used as a base for diagnosis, treatment protocols, and further research to answer the open questions that remain, particularly the functional consequences of ON and how it might be prevented or identified and intervened upon in its early stages. Although the participants encompass many countries and disciplines, further research will be needed to determine if these diagnostic criteria are applicable to the experience of ON in geographic areas not represented in the current expert panel. Level of evidence Level V: opinions of expert committees

Abnormalities in cortical sources of resting-state eyes closed electroencephalographic (rsEEG) rhythms recorded by hospital settings (10-20 montage) with 19 scalp electrodes characterized Alzheimer's disease (AD) from preclinical to dementia stages. An intriguing rsEEG application is the monitoring and evaluation of AD progression in large populations with few electrodes in low-cost devices. Here we evaluated whether the above-mentioned abnormalities can be observed from fewer scalp electrodes in patients with mild cognitive impairment due to AD (ADMCI). Clinical and rsEEG data acquired in hospital settings (10-20 montage) from 75 ADMCI participants and 70 age-, education-, and sex-matched normal elderly controls (Nold) were available in an Italian-Turkish archive (PDWAVES Consortium; www.pdwaves.eu ). Standard spectral fast fourier transform (FFT) analysis of rsEEG data for individual delta, theta, and alpha frequency bands was computed from 6 monopolar scalp electrodes to derive bipolar C3-P3, C4-P4, P3-O1, and P4-O2 markers. The ADMCI group showed increased delta and decreased alpha power density at the C3-P3, C4-P4, P3-O1, and P4-O2 bipolar channels compared to the Nold group. Increased theta power density for ADMCI patients was observed only at the C3-P3 bipolar channel. Best classification accuracy between the ADMCI and Nold individuals reached 81% (area under the receiver operating characteristic curve) using Alpha2/Theta power density computed at the C3-P3 bipolar channel. Standard rsEEG power density computed from six posterior bipolar channels characterized ADMCI status. These results may pave the way toward diffuse clinical applications in health monitoring of dementia using low-cost EEG systems with a strict number of electrodes in lower- and middle-income countries.

We measure the local correlation between radio emission and Compton-$y$ signal across two galaxy clusters, Abell~399 and Abell~401, using maps from the Low-Frequency Array (LOFAR) and the Atacama Cosmology Telescope (ACT) + \Planck. These datasets allow us to make the first measurement of this kind at $\sim$arcminute resolution. We find that the radio brightness scales as $F_{\mathrm{radio}} \propto y^{1.5}$ for Abell~401 and $F_{\mathrm{radio}} \propto y^{2.8}$ for Abell~399. Furthermore, using \XMM data, we derive a sublinear correlation between radio and X-ray brightness for both the clusters ($F_{\mathrm{radio}} \propto F_{\rm X}^{0.7}$). Finally, we correlate the Compton-$y$ and X-ray data, finding that an isothermal model is consistent with the cluster profiles, $y \propto F_{\rm X}^{0.5}$. By adopting an isothermal--$\beta$ model, we are able, for the first time, to jointly use radio, X-ray, and Compton-$y$ data to estimate the scaling index for the magnetic field profile, $B(r) \propto n_{\mathrm{e}}(r)^{\eta}$ in the injection and re-acceleration scenarios. Applying this model, we find that the combined radio and Compton-$y$ signal exhibits a significantly tighter correlation with the X-ray across the clusters than when the datasets are independently correlated. We find $\eta \sim 0.6{-}0.8$. These results are consistent with the upper limit we derive for the scaling index of the magnetic field using rotation measure values for two radio galaxies in Abell~401. We also measure the radio, Compton-$y$, and X-ray correlations in the filament between the clusters but conclude that deeper data are required for a convincing determination of the correlations in the filament., Comment: 16 pages, 8 figures, Accepted for publication in Monthly Notices of the Royal Astronomical Society Main Journal

Laparoscopic uterosacral ligament suspension (LUSLS) of the vaginal apex for the treatment of pelvic organ prolapse (POP) has gained popularity. The aim of this systematic review is to investigate perioperative outcomes and complications, subjective and objective success rates and recurrence rates in women undergoing this surgical procedure.A systematic literature search was performed in December 2021. The critical appraisal skills program (CASP) was used to assess the methodological quality of the selected studies. The Clavien-Dindo (CD) scale and the Satava scale were used to classify periprocedural complications. Continuous variables were described as means and standard deviations while categorical were expressed as percentages of the whole group. Statistical significance was set at p 0.05.26 articles were selected and analysed, with a total population of 1401 patients. Anatomical and subjective success rates after LUSLS ranged from 79% and 100% and from 76.2% to 100% respectively. The re-operation rate varied from 2% to 4.5% in the largest cohorts. The overall complication rate was 13.6%, however grade III CD complications occurred only in 1% of patients. Ureteral complications were described in only 2 cases.LUSLS represent a safe and effective technique for vaginal apex resuspension in women with POP. Further larger prospective randomized studies are required to confirm these data.

Background and objectives: Non-alcoholic fatty liver disease (NAFLD) develops due to impaired hepatic lipid fluxes and is a risk factor for chronic liver disease and atherosclerosis. Lipidomic studies consistently reported characteristic hepatic/VLDL “lipid signatures” in NAFLD; whole plasma traits are more debated. Surprisingly, the HDL lipid composition by mass spectrometry has not been characterised across the NAFLD spectrum, despite HDL being a possible source of hepatic lipids delivered from peripheral tissues alongside free fatty acids (FFA). This study characterises the HDL lipidomic signature in NAFLD, and its correlation with metabolic and liver disease markers. Methods: We used liquid chromatography-mass spectrometry to determine the whole serum and HDL lipidomic profile in 89 biopsy-proven NAFLD patients and 20 sex and age-matched controls. Results: In the whole serum of NAFLD versus controls, we report a depletion in polyunsaturated (PUFA) phospholipids (PL) and FFA; with PUFA PL being also lower in HDL, and negatively correlated with BMI, insulin resistance, triglycerides, and hepatocyte ballooning. In the HDL of the NAFLD group we also describe higher saturated ceramides, which positively correlate with insulin resistance and transaminases. Conclusion: NAFLD features lower serum lipid species containing polyunsaturated fatty acids; the most affected lipid fractions are FFA and (HDL) phospholipids; our data suggest a possible defect in the transfer of PUFA from peripheral tissues to the liver in NAFLD. Mechanistic studies are required to explore the biological implications of our findings addressing if HDL composition can influence liver metabolism and damage, thus contributing to NAFLD pathophysiology.

Purpose With the aim of characterizing the gastrointestinal (GI) microbiota and contextually determine how different prenatal, perinatal, and postnatal factors affected its composition in early childhood, infants were enrolled in a longitudinal-prospective study named “A.MA.MI.” (Alimentazione MAmma e bambino nei primi MIlle giorni; NCT04122612, October 2019). Methods Forty-five fecal samples were collected at 12 months of infants’ age, identified as the 3rd follow-up (T3). The evaluated variables were pre-gestational weight and weight gain during pregnancy, delivery mode, feeding, timing of weaning, and presence/absence of older siblings. Fecal alpha and beta-diversities were analyzed. Noteworthy, to determine the impact of the influencing factors, multivariate analyses were conducted. Results At T3, all prenatal and perinatal variables did not result to be significant whereas, among the postnatal variables, type of milk-feeding and weaning showed the greatest contribution in shaping the microbiota. Although aged 1 year, infants exclusively breastfed until 6 months were mainly colonized by Lactobacillaceae and Enterobacteriaceae. Differently, Bacteroidaceae characterized the microbiota of infants that were never breastfed in an exclusive way. Moreover, although an early introduction of solid foods determined higher values of Faith’s PD, high abundances of Ruminococcaceae and Faecalibacterium mainly associated with infants weaned after the 4th month of age. Conclusion The microbial colonization during the first year of life is likely affected by a simultaneous effect of multiple variables playing a significant role at different times. Therefore, these data contribute to add evidence concerning the complex multifactorial interaction between GI microbiota and various stimuli affecting infants during the early stages of life.

The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article. CA extern

We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38 × 106 sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.

At the global level, the quantity of goat milk produced and its gross production value have increased considerably over the last 2 decades. Although many scientific papers on this topic have been published, few studies have been carried out on bulk goat milk samples. The aim of the present study was to investigate in the field the effects of farming system, breed type, individual flock, and stage of production on the composition, coagulation properties (MCP), curd firming over time parameters (CF

The aim of this article was to describe the definition process of a joint master’s degree program as a proposal for the training of professional smart designers on the skills needed to contribute to the current green and digital transition of the European industry context. Arising from the framework of the INTRIDE European project, this article has been structured starting from an introductory analysis of the demanded skills of designers and the needs of European Union (EU) companies in the current contemporary scenario. As such, the reflection extends to the research methodology established for the development of a state of the art on soft, digital, and green skills as a scientific basis for the definition of a cross and interdisciplinary training course entitled Strategic design for innovation in the manufacturing sector. Thus, focusing on the Bologna Declaration (June 19, 1999) in which the need to build a "European Higher Education Area" has been declared. Based on the achieved research results, the authors propose the INTRIDE Joint Master’s Degree Program (JMDP) as a cross and interdisciplinary training course for smart designers that will become the future innovation triggers for small- and medium-sized enterprises (SMEs) in the EU manufacturing sector. This, together with added competencies related to soft, digital, and green skills – as general ones – and design and technological – as specific ones. At the end of this scientific contribution, a discussion has been reported regarding a general reflection on the developed design process and the lessons learned in the application of the design methodology, combined with the suggestions for a sustainable use and implementation of the proposed training program.

Background: We report the case of a 43-year-old Chinese male with Tophaceous gout who had been living in Italy for some years. Case Presentation: Previous treatments with allopurinol had induced Steven Johnson syndrome, dictating a switch to febuxostat 80 mg daily. After two years of treatment with febuxostat, he developed a diffuse maculopapular rash with severe itching. Rheumatologists stopped febuxostat; however, gout worsened over the following years despite treatment with kalnicitrate and colchicine. Therefore, an allergy consultation was called for. A slow desensitization protocol with febuxostat was started, with a low oral dosage scheme to be increased up to 80 mg/day. Febuxostat was prepared in a solid formulation by the consultation pharmacist as pills instead of the more frequently used liquid suspension. Conclusion: The patient is currently receiving febuxostat 80 mg, and he has shown no side effects as of now, while his gout has improved. This is the first reported example and he has shown no side effect till now, while his gout improved of a successful desensitization protocol using a solid preparation of diluted febuxostat given as pills.

The objective of this study was to develop formulas based on milk composition of individual goat samples for predicting cheese yield (%CY) traits (fresh curd, milk solids, and water retained in the curd). The specific aims were to assess and quantify (1) the contribution of major milk components (fat, protein, and casein) and udder health indicators (lactose, somatic cell count, pH, and bacterial count) on %CY traits (fresh curd, milk solids, and water retained in the curd); (2) the cheese-making method; and (3) goat breed effects on prediction accuracy of the %CY formulas. The %CY traits were analyzed in duplicate from 600 goats, using an individual laboratory cheese-making procedure (9-MilCA method; 9 mL of milk per observation) for a total of 1,200 observations. Goats were reared in 36 herds and belonged to 6 breeds (Saanen, Murciano-Granadina, Camosciata delle Alpi, Maltese, Sarda, and Sarda Primitiva). Fresh %CY (%CY

The foot has 28 bones, 30 joints, and more than 100 muscles, ligaments, and tendons. These structures work together to carry out two main functions: weight-bearing and propulsion. Plus, the foot must be flexible to adapt to uneven surfaces and remain stable. In this article, we briefly illustrate the anatomy of the foot and its various structures

The kappa agonist structure-activity relationship around the novel, pyrrolidinyl substituted pyranopiperazine scaffold was developed. More specifically, the dichloroPhenylAcetamide-Pyrrolidinyl-PyranoPiperazine (PAPPP) core A was the focus of our work. The modulation of kappa receptor potency/G-protein activation and arrestin recruitment with respect to changes of the piperazine R group in A was demonstrated. Reduced β

Multiple studies have occurred to determine if a patient's blood type, Rhesus factor (Rh), and sociodemographic attributes contribute to contracting SARS-CoV-2. True association remains unknown.Inclusion criteria included in-patients who were tested for SARS-CoV-2 with blood type assessed. Study endpoints combined ABO, Rh and all-cause inpatient mortality (ACIM) with testing positivity. Pregnancy status was one of several secondary endpoints evaluated. A logistic regression analysis was used to estimate association.Of the 27,662 patients who met inclusion criteria, Type A blood was associated with increased positivity [1.01 (1.0-1.21), P = .03]. Type B [1.10 (0.99-1.23), P = .08] and AB [0.98 (0.81-1.19), P = .84] showed no association. When evaluating ACIM, type A [1.18 (0.91-1.52), P = .22], B [1.13 (0.82- 1.56), P = .480], and AB [1.06 (0.62-1.81), P = .839] were not associated with increased mortality. The female subgroup was less likely to test positive [0.88 (0.82-0.986), P = .002]. Black patients demonstrated a higher likelihood of positivity when compared to White [1.96 (1.79-2.14), P.001]. Non-pregnant women exhibited a 2.5 times greater likelihood of testing positive [2.49 (2.04-3.04), P.001].This study confirms results of previous research which showed SARS-Co-V-2 positivity related to blood type. It also confirms more recent research demonstrating inequities related to acquisition of SARS-CoV-2 for certain sociodemographic groups. Larger studies are warranted to confirm and further explore novel pregnancy findings.

BACKGROUND: Elotuzumab plus lenalidomide and dexamethasone has shown improved progression-free and overall survival versus lenalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. We aimed to assess these regimens in patients with newly diagnosed multiple myeloma who are ineligible for haematopoietic stem-cell transplantation (HSCT). METHODS: ELOQUENT-1 is an open-label, multicentre, randomised, phase 3 trial conducted at 185 hospitals, oncology practices, and research centres in 19 countries. Eligible patients were aged 18 years or older with newly diagnosed, untreated, symptomatic myeloma and not candidates for high-dose therapy plus HSCT, and an Eastern Cooperative Oncology Group (ECOG) performance status of 2 or lower. Patients were randomly assigned (1:1) to receive elotuzumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone using an interactive voice response system, stratified by the International Staging System (ISS; stage I-II vs III), age (

This study conducted stable isotope analysis (δ13C, δ15N, and δ34S) on the epidermis and two skeletal elements (rib and squamosal bones) of Hawaiian green turtles (Chelonia mydas) and putative diet items obtained from two neritic sites: the Kona/Kohala coast and Oahu. Turtle tissues were collected in 2018–2020 and diet samples in 2018, 2019, and 2021. The effect of body size and sampling locality on individual bulk tissue isotope values was evaluated, and stable isotope mixing models based on δ13C, δ15N, and δ34S values from those tissues and four groups of food sources were used to reconstruct diet histories of the turtles. Mixing models indicated that green turtles along the Kona/Kohala coast consumed an omnivorous diet, whereas those from Oahu had an herbivorous diet. These diet make-ups are consistent with published gut content analyses. However, mixing models using the stable isotope ratios in rib and squamosal bone failed to yield reasonable diet histories, probably due to inadequacies of the applied trophic discrimination factor (TDF), a key model parameter. These results further establish that stable isotope ratios in the epidermis can be used effectively to study green turtle diet, but also reveal that more validation—and establishment of appropriate TDFs—is needed before bone can be used reliably to assess green turtle diet.

The Atlantic meridional overturning circulation (AMOC) is a vital component of the global climate system regulating heat, carbon, and freshwater distribution. Most models predict a weakening of the AMOC throughout the 21st century, although there is significant uncertainty about its magnitude and the related regional climate impacts. In particular, the response of large-scale atmospheric circulation to the AMOC slowdown is still largely unknown, with implications for weather extremes and associated societal risks. The purpose of this study is to enhance our understanding of the impacts of an AMOC slowdown on atmospheric patterns with a focus on the Euro-Atlantic region, where the influence of AMOC is particularly relevant.We analyse changes in an ensemble of idealised abrupt-4xCO2 climate model simulations from the CMIP archives with respect to the preindustrial climate. We split the models into groups according to their AMOC response to the 4xCO2. Through rigorous statistical testing, we attribute the differences in the simulated climate impacts to the difference in the AMOC response. Specifically, we find that models that simulate a larger AMOC decline feature minimum warming in the subpolar North Atlantic (North Atlantic Warming Hole or NAWH), a southward shift of the ITCZ, and a poleward strengthening of the mid-latitude jet stream. Instead, models that simulate a smaller AMOC decline feature enhanced North Atlantic warming, an intensification of the hydrological cycle but no southward shift in the ITCZ, and smaller displacements of the mid-latitude jet. To better characterize the large-scale atmospheric response at daily timescales, we use k-means clustering and self-organising maps to assess the changes in weather regimes over the Euro-Atlanic sector, including the NAO. We further compare weather regimes’ frequency of occurrence and persistence between the two groups, attributing the differences to the AMOC decline. Our results indicate that the AMOC is a key source of large inter-model uncertainty in the simulation of future climate change impacts. Further observational campaigns may thus help us alleviate model biases and provide constraints on a number of societally relevant climate change impacts.

The focus of this paper is to show the process of developing a condition monitoring system for an axial piston pump mounted on a mini excavator. This work outlines some previous condition monitoring work on axial piston pumps but addresses the lack of research conducted on mobile hydraulics. The valve plate of the pump is chosen as a case study to demonstrate varying degrees of wear and damage to represent healthy and faulty pump conditions. The wear and damage of these valve plates is measured using an optical profilometer, and efficiency measurements were conducted to characterize the fault levels. Once the faults were characterized, the mini excavator was introduced and instrumented to demonstrate what parameters were being considered. Next, three duty cycles were introduced: controlled, digging, and different operator cycles. The controlled cycles are a very repeatable condition that eliminated the need of an operator. The digging cycle was more of a realistic cycle where an operator dug into a loose pile of soil. The different operator cycle is the same as the digging cycle, but a different operator was employed. The sensors that proved to be the most useful in detecting valve plate faults were the drain pressure, pump port pressures, engine speed, and pump displacement. Fault detectability accuracies of 100% were achievable under the controlled cycle utilizing the Fine KNN classification machine learning algorithm. The digging cycle could achieve a fault detection accuracy of 93.6% using the same algorithm and sensors. Finally, the cross-compatibility between a model trained under once cycle and using data from another cycle as an input was investigated. This study showed that a model trained under the controlled duty cycle does not give reliable and accurate fault detectability for data run in a digging cycle, below 60% accuracies. However, cross-compatibility may be achievable if more extreme faults are present. This work concluded by recommending a diagnostic function for mobile machines to perform a preprogrammed operation to reliably and accurately detect pump faults.

This paper proposes an electro-hydraulic actuator (EHA) system, and a novel-designed electro-hydraulic unit (EHU) consisting of a fixed-displacement hydraulic gear machine and a variable-speed electric machine. The novel EHU design integrates an electric machine and a hydraulic machine in a single housing, targeting optimal compactness, power density, and component reduction. The EHA system features an open circuit design, where hydraulic hoses connect the EHU with a tank, a valve manifold, and the hydraulic cylinder. In this way, the proposed EHA technology can be used to implement distributed hydraulic actuation in a vehicle without requiring changes to the hydraulic actuators or at the overall layout of the hydraulic components with respect to the original vehicle design. A dedicated test rig is developed to verify the performance of the proposed EHA system. The efficiency of the EHA is measured in a steady state and under a realistic duty cycle of a commercial compact loader. The efficiency of the EHA system based on the measurements on the test rig can reach 54% with up to 20 kN load and 6 kW power level. Furthermore, the EHU is implemented on the reference machine to drive the boom function. Preliminary results on the performance of the EHU show an efficiency of up to 68% under different loading conditions.