Search

Periventricular heterotopia (PH), a common form of gray matter heterotopia associated with developmental delay and drug-resistant seizures, poses a challenge in understanding its neurophysiological basis. Human cerebral organoids (hCOs) derived from patients with causative mutations in FAT4 or DCHS1 mimic PH features. However, neuronal activity in these 3D models has not yet been investigated. Here we show that silicon probe recordings reveal exaggerated spontaneous spike activity in FAT4 and DCHS1 hCOs, suggesting functional changes in neuronal networks. Transcriptome and proteome analyses identify changes in neuronal morphology and synaptic function. Furthermore, patch-clamp recordings reveal a decreased spike threshold specifically in DCHS1 neurons, likely due to increased somatic voltage-gated sodium channels. Additional analyses reveal increased morphological complexity of PH neurons and synaptic alterations contributing to hyperactivity, with rescue observed in DCHS1 neurons by wild-type DCHS1 expression. Overall, we provide new comprehensive insights into the cellular changes underlying symptoms of gray matter heterotopia. Periventricular heterotopia (PH) is associated with neurodevelopmental delay. Here authors report patient-derived organoids with FAT4 and DCHS1 mutations mimic PH features, showing hyperactivity, synaptic changes and cell morphological alterations. [ABSTRACT FROM AUTHOR]

This study evaluates upadacitinib (UPA) effectiveness and drug retention rate (DRR) in patients with rheumatoid arthritis (RA). Multicentre prospective observational study. Consecutive patients with RA receiving UPA were evaluated at 0, 3, 6, 12, 18, and 24 months of treatment. Key outcomes included UPA DRR and changes in clinical and serological measures over time. The study included 215 patients (72.6% female sex, mean age 60.1 ± 11.7 years). The DRR of UPA was 91.6% (95% CI 88.0–95.4%) at 6 months, 84.6% (95% CI 79.8–89.7%) at 12 months, 80.3% (95% CI 75.0–86.0%) at 18 months and 80% (95% CI 75.0–86.0%) at 24 months. UPA DRR was similar between monotherapy and methotrexate combination (p = 0.47), and across different treatment lines (p = 0.58). A statistically significant improvement from baseline was observed over 24 months considering erythrocyte sedimentation rate, C-reactive protein (CRP), Health Assessment Questionnaire (HAQ), Disease Activity Score (DAS)28-CRP, Physician's (Ph) and Patient's (Pt) Global Assessment (GA), Visual Analogue Scale (VAS) Pain, Simplified and Clinical Disease Activity Index (SDAI and CDAI) (p < 0.00 for all of them). Patients discontinuing UPA were more likely to be male (p = 0.02), with a longer disease duration (p = 0.03), higher baseline values of VAS Pain (p < 0.00), PtGA (p < 0.00), PhGA (p < 0.00), CDAI (p < 0.00), SDAI (p < 0.00) and corticosteroid dosage (p = 0.04). This study confirms UPA effectiveness in managing RA in the real-world practice, demonstrating sustained drug retention and improvements in clinical and laboratory measures over time. Also, UPA could be a valuable option for patients with multi-refractory RA and when monotherapy is preferred. [ABSTRACT FROM AUTHOR]

Geological and lithological maps provide essential spatial data for various environmental assessments and studies. However, these maps lack detailed quantitative information on the geotechnical characteristics of rocks and soils, which limits their use for modelling purposes. This study addresses this gap by compiling a comprehensive database of over 2300 geotechnical parameter records searching the international literature. Focusing on cohesion, friction angle, and porosity, we analyse their distributions across different lithotypes, emphasising their significance in slope stability modelling. For the Italian territory, the collected information was used to associate geotechnical parameters to the lithological classes as identified by Bucci et al. 2022. These types of reclassified maps may provide researchers and stakeholders with a comprehensive dataset useful for slope stability assessment and land management at small scale. Descriptive statistics and validation from grey literature underscore the dataset's utility in enhancing geotechnical characterizations and supporting geological hazard assessments. [ABSTRACT FROM AUTHOR]

This research evaluated the storage characteristics of dried pumpkin packed in two different films: polylactic acid (PLA) and polyethylene (PE) by accelerated shelf-life testing (ASLT) at three storage temperatures: 30, 40, and 50 °C. Weight loss, pH, water activity, color, and total microbial count of the samples were monitored at fixed times during the experiments. After 2 days of storage at 50 °C, the weight loss for the PLA and PE packaging reached its maximum value at 9.15 ± 0.8% and 6.53 ± 1.6%, respectively. The microbiological results demonstrated that, with a total plate count of fewer than 4 log CFU/g, the dried pumpkin samples did not degrade while being stored at different temperatures. Bioactive compound content (total polyphenols, ascorbic acid content, and carotenoid content) and antioxidant activity were determined at the end of storage, and they significantly changed with higher temperatures. The largest total polyphenols losses were observed for samples PLA 40 °C and PLA 50 °C (40%) and samples PE 50 °C (55%). For both packaging under the same storage conditions, antioxidant activity and ascorbic acid concentration likewise showed a similar pattern. The color changes observed during the storage were described by the non-enzymatic browning process using a pseudo-first-order reaction in terms of Chroma. The activation energy in terms of Q10 (defined as the ratio of the rate constants when the temperature is raised by 10 °C) and the storage time at 25 °C were determined. The results showed that PLA film is an appropriate packaging for preserving the physico-chemical properties of dried pumpkin snacks. [ABSTRACT FROM AUTHOR]

Abstract Progressive myoclonus epilepsy (PME) of Unverricht–Lundborg type (EPM1) is an autosomal recessive neurodegenerative disorder with the highest incidence of PME worldwide. Mutations in the gene encoding cystatin B (CSTB) are the primary genetic cause of EPM1. Here, we investigate the role of CSTB during neurogenesis in vivo in the developing mouse brain and in vitro in human cerebral organoids (hCOs) derived from EPM1 patients. We find that CSTB (but not one of its pathological variants) is secreted into the mouse cerebral spinal fluid and the conditioned media from hCOs. In embryonic mouse brain, we find that functional CSTB influences progenitors’ proliferation and modulates neuronal distribution by attracting interneurons to the site of secretion via cell‐non‐autonomous mechanisms. Similarly, in patient‐derived hCOs, low levels of functional CSTB result in an alteration of progenitor's proliferation, premature differentiation, and changes in interneurons migration. Secretion and extracellular matrix organization are the biological processes particularly affected as suggested by a proteomic analysis in patients’ hCOs. Overall, our study sheds new light on the cellular mechanisms underlying the development of EPM1.

Introduction: For several years, ropivacaine has been the standard-of-care for establishing postoperative femoral nerve block in total knee arthroplasty (TKA) setting and is still widely in use but new approaches such as the patient-controlled administration of sublingual sufentanil tablets system (SSTS) seem to offer good clinical results. Our aim is to compare the SSTS to single shot peri-nervous injection of ropivacaine (single shot) after TKA in terms of effectiveness in pain management and of time to recovery. Materials and methods: A total of 165 patients undergoing TKA were enrolled. Eighty-four patients were randomly allocated in the SSTS group and 81 patients in the single shot group. The primary objective of the study was to evaluate performance of Timed Up and Go test. Secondary objectives were to measure the length of stay, NRS pain scale, the adherence to the prescribed plan, the joint mobility, the frequency of rescue analgesic use, side effects and patients' satisfaction. Results: Of all patients of the single shot group, 64 were withdrawn from the study as they unable to achieve pain control; only one patient was withdrawn from the SSTS group. Times for the "Timed Up and Go" test on the 3rd postoperative day were 8.4 ± 1.6 and 11.8 ± 3.6 in the SSTS group (n = 83) and single shot group (n = 17), respectively (p <.001). Conclusions: SSTS provides better pain management when compared to peri-nervous ropivacaine single shot injection after TKA. [ABSTRACT FROM AUTHOR]

In this paper an efficient formulation of the Path integral (PI) approach is developed for determining the response probability density functions (PDFs) and first-passage statistics of nonlinear oscillators subject to stationary and time-modulated external Gaussian white noise excitations. Specifically, the evolution of the response PDF is obtained in short time steps, by using a discrete version of the Chapman-Kolmogorov equation and assuming a Gaussian form for the conditional response PDF. Next, the technique involves proceeding to treating the problem via an analytical asymptotic expansion procedure, namely the Laplace's method of integration. In this manner, the repetitive double integrals involved in the standard implementation of the PI approach are evaluated in a closed form, while the response and first-passage PDFs are obtained by mundane step-by-step application of the derived approximate analytical expression. It is shown that the herein proposed formulation can drastically decrease the associated computational cost by several orders of magnitude, as compared to both the standard PI technique and Monte Carlo solution (MCS) approach. A number of nonlinear oscillators are considered in the numerical examples. Notably, for these systems both response PDFs and first-passage probabilities are presented, whereas comparisons with pertinent MCS data demonstrate the efficiency and accuracy of the technique. [ABSTRACT FROM AUTHOR]

This paper documents the short-run macroeconomic impacts of influenza pandemics across 16 countries spanning 1871–2016 using the Jordà–Schularick–Taylor Macrohistory Database and the Human Mortality Database. We find pandemic-induced mortality contributed meaningfully to business cycle fluctuations in the post 1870 era. We identify negative causal impacts on the cyclical component of GDP using pandemics to instrument for working-age mortality. The analysis of short-run economic outcomes extends literature dominated by long-run economic growth outcomes and case studies of several specific health shocks such as the Black Death, Spanish Flu or COVID-19. Our findings illustrate that less catastrophic pandemics still have important economic implications. [ABSTRACT FROM AUTHOR]

The escalating drug resistance among microorganisms underscores the urgent need for innovative therapeutic strategies and a comprehensive understanding of bacteria's defense mechanisms against oxidative stress and antibiotics. Among the recently discovered barriers, the endogenous production of hydrogen sulfide (H2S) via the reverse transsulfuration pathway, emerges as a noteworthy factor. In this study, we have explored the catalytic capabilities and crystal structure of cystathionine γ-lyase from Pseudomonas aeruginosa (PaCGL), a multidrug-opportunistic pathogen chiefly responsible for nosocomial infections. In addition to a canonical l-cystathionine hydrolysis, PaCGL efficiently catalyzes the production of H2S using l-cysteine and/or l-homocysteine as alternative substrates. Comparative analysis with the human enzyme and counterparts from other pathogens revealed distinct structural features within the primary enzyme cavities. Specifically, a distinctly folded entrance loop could potentially modulate the access of substrates and/or inhibitors to the catalytic site. Our findings offer significant insights into the structural evolution of CGL enzymes across different pathogens and provide novel opportunities for developing specific inhibitors targeting PaCGL. [ABSTRACT FROM AUTHOR]

Introduction: Knee osteoarthritis (KOA) represents a widespread degenerative disease that causes pain and motor disability. Conservative treatments mainly focus on relieving symptoms, improving joint function, and trying to delay surgery. Safety and efficacy of hybrid cooperative complexes (2.4% sodium hyaluronate and 1.6% sodium chondroitin; HA-SC) for symptomatic KOA were investigated in a single-arm, prospective, pilot study. Methods: Patients with a visual analogue scale (VAS) pain score ≥ 4 and Kellgren–Lawrence Grade < 4 received a single intraarticular HA-SC injection. Patients with a VAS score change from baseline ≤ 1 received a second injection at day 30. Device-related adverse events (DR-AEs)/adverse events (AEs) were primary endpoints. Secondary endpoints included Western Ontario and McMaster Universities Osteoarthritis Index LK 3.1 (WOMAC LK 3.1), VAS, patient global assessment of disease status (PtGA), and patient proportion needing a second injection. Results: Of 83 patients with KOA (Kellgren–Lawrence Grade, 2–3), 34.9% had DR-AEs at day 7. No serious DR-AEs/AEs were reported. A significant (P < 0.0001) reduction over time in VAS pain score plus WOMAC pain, stiffness, physical function limitation, and total scores was reported. Median PtGA scores indicated a 'slight improvement' at most follow-up visits. Only 18.1% of patients required a second injection. Conclusions: A single intraarticular HA-SC injection was safe, well-tolerated, and did not lead to major deterioration in terms of reducing knee pain, stiffness, and physical function limitation in patients with symptomatic KOA. [ABSTRACT FROM AUTHOR]

Heart failure patients often experience respiratory symptoms due to diaphragmatic involvement, but the diaphragmatic motion in heart failure remains understudied. This research aimed to investigate the correlation between ultrasonographically assessed diaphragmatic motion and thickness with cardiac performance indexes in an emergency setting. Seventy-two acutely decompensated heart failure patients and 100 non-heart failure individuals were enrolled. Diaphragmatic motion and thickness were assessed via ultrasound. Cardiac and respiratory parameters were recorded, and regression analysis was performed. Heart failure patients exhibited reduced diaphragmatic motion at total lung capacity compared to controls, and an inverse association was found between motion and heart failure severity (NYHA stage). Diaphragmatic thickness was also higher in heart failure patients at tidal volume and total lung capacity. Notably, diaphragmatic motion inversely correlated with systolic pulmonary artery pressure. The study highlights diaphragmatic dysfunction in acutely decompensated heart failure, with reduced motion and increased thickness. These changes were associated with cardio-respiratory parameters, specifically systolic pulmonary artery pressure. Monitoring diaphragmatic motion via ultrasound may aid in evaluating heart failure severity and prognosis in emergency settings. Additionally, interventions targeting diaphragmatic function could improve heart failure management. Further research is warranted to enhance heart failure management and patient outcomes. [ABSTRACT FROM AUTHOR]

Purpose: The use of biophysical stimuli produced by extracorporeal shock wave therapy (ESWT) can improve the rehabilitation treatment of patients undergoing total knee arthroplasty (TKA). The aim of our study is to evaluate the short-term efficacy of early postoperative ESWT in combination with physiotherapy in terms of pain reduction and motor function recovery of patients undergoing TKA and compare it with conventional physiotherapy treatment. Methods: Fifty-six patients undergoing TKA were enrolled in the study from January 2019 to February 2020. Patients received two sessions of physiotherapy daily, with (experimental group) or without (control group) four sessions of ESWT within seven days after surgery. Patients were prospectively evaluated at baseline and at post-operative day two and seven. Assessment included active knee range of motion (aROM), timed up and go (TUG) test, visual analogue scale (VAS) for pain, and Borg scale. Results: Fifty patients completed the study. Both treatments proved to be effective in reducing pain and improving the knee range of motion and functional scores at seven days after surgery: the aROM in the ESWT group was 36.8 ± 11.0 grades (p < 0.001), while in control group was 19.8 ± 7.8 grades (p < 0.001). TUG, VAS, and BORG scores showed a similar trend. Comparative analysis revealed superior clinical results for the experimental group in all the outcomes, in particular aROM (96.0 ± 5.40 vs. 81.20 ± 11.01, p < 0.001) and TUG test (17.4 ± 5.61 vs. 21.24 ± 5.88, p < 0.001), at day seven after surgery. Conclusion: Early application of ESWT in addition to physiotherapy can positively influence the rehabilitation process after TKA. The treatment proved to be well tolerated and safe. Preliminary results demonstrated better pain control and functional scores compared to physiotherapy alone. [ABSTRACT FROM AUTHOR]

Periventricular neuronal heterotopia (PH) is one of the most common forms of cortical malformation in the human cortex. We show that human neuronal progenitor cells (hNPCs) derived from PH patients with a DCHS1 or FAT4 mutation as well as isogenic lines had altered migratory dynamics when grafted in the mouse brain. The affected migration was linked to altered autophagy as observed in vivo with an electron microscopic analysis of grafted hNPCs, a Western blot analysis of cortical organoids, and time‐lapse imaging of hNPCs in the presence of bafilomycin A1. We further show that deficits in autophagy resulted in the accumulation of paxillin, a focal adhesion protein involved in cell migration. Strikingly, a single‐cell RNA‐seq analysis of hNPCs revealed similar expression levels of autophagy‐related genes. Bolstering AMPK‐dependent autophagy by metformin, an FDA‐approved drug, promoted migration of PH patients‐derived hNPCs. Our data indicate that transcription‐independent homeostatic modifications in autophagy contributed to the defective migratory behavior of hNPCs in vivo and suggest that modulating autophagy in hNPCs might rescue neuronal migration deficits in some forms of PH. Synopsis: Time‐lapse imaging of hNPCs derived from patients with periventricular neuronal heterotopia grafted in the mouse brain revealed abnormal migratory dynamics due to the longer duration of the stationary phases. These changes were linked to altered autophagic flux leading to the accumulation of focal adhesion molecules. Bolstering autophagy by metformin, an FDA‐approved drug, rescued neuronal migration.Affected migration of hNPCs with a DCHS1 or FAT4 mutation in vivo.Transcription‐independent dysregulation of autophagy in hNPCs with a DCHS1 or FAT4 mutation.Metformin bolsters autophagy and rescues migratory deficits of hNPCs with a DCHS1 or FAT4 mutation. [ABSTRACT FROM AUTHOR]

It is estimated that almost one-third of all adults have radiological signs of osteoarthritis (OA), with the knee being the most common site affected [[1]]: the global scientific community is providing a tremendous effort to allow an early diagnosis and a timely treatment to spare the joint from metal [[2]]. To this regard, we are also including in our Special Issue two papers which both concluded how lateral meniscus changes surprisingly did not jeopardize the clinical outcomes in patients who underwent medial unicompartmental knee arthroplasty [[17]]. On the opposite side of the continuum of lesions that could affect the meniscus, we include the degenerative meniscus. Int Orthop. https://doi.org/10.1007/s00264-023-05907-6 19 Beaufils P, Becker R, Kopf S, Englund M, Verdonk R, Ollivier M, Seil R. Surgical management of degenerative meniscus lesions: The 2016 ESSKA Meniscus Consensus. [Extracted from the article]

This is a review about financial dependencies which merges efforts in econophysics and financial economics during the last few years. We focus on the most relevant contributions to the analysis of asset markets' dependencies, especially correlational studies, which in our opinion are beneficial for researchers in both fields. In econophysics, these dependencies can be modeled to describe financial markets as evolving complex networks. In particular, we show that a useful way to describe dependencies is by means of information filtering networks that are able to retrieve relevant and meaningful information in complex financial datasets. In financial economics these dependencies can describe asset comovement and spill-overs. In particular, several models are presented that show how network and factor model approaches are related to modeling of multivariate volatility and asset returns, respectively. Finally, we sketch out how these studies can inspire future research and how they contribute to support researchers in both fields to find a better and a stronger common language. [ABSTRACT FROM AUTHOR]

Recent works have proposed that spatial mechanisms in the hippocampal–entorhinal system might have originally developed to represent distances and positions in the physical space and successively evolved to represent experience and memory in the mental space (Bellmund et al. 2018; Bottini and Doeller 2020). Within this phylogenetic continuity hypothesis (Buzsáki and Moser 2013), mechanisms supporting episodic and semantic memory would have evolved from egocentric and allocentric spatial navigation mechanisms, respectively. Recent studies have described a specific relationship between human performance in egocentric navigation and episodic memory (Committeri et al. 2020; Fragueiro et al. 2021), representing the first behavioral support to this hypothesis. Here, we tested the causal relationship among egocentric navigation and both episodic and semantic components of declarative memory. We conducted two experiments on healthy young adults: in the first experiment, participants were submitted to a navigational training based on path integration, while in the second experiment, participants completed a control training based on visual–perceptual learning. Performance in a set of memory tasks assessing episodic, semantic and short-term memory was compared among the pre- vs. post-training sessions. The results indicated a significant improvement of the episodic memory but not of the semantic or the short-term memory performance following the navigational training. In addition, no modulations of performance across the three memory tasks were observed following the control perceptual training. Our findings provide brand-new evidence of a potential causal association between mechanisms of egocentric navigation and episodic memory, thereby further supporting the phylogenetic continuity hypothesis between navigation and memory mechanisms as well as offering new insights about possible clinical applications of navigational trainings for memory functions/dysfunctions. [ABSTRACT FROM AUTHOR]

Laser-induced thermotherapy has shown promising potential for the treatment of unresectable primary pancreatic ductal adenocarcinoma tumors. Nevertheless, heterogeneous tumor environment and complex thermal interaction phenomena that are established under hyperthermic conditions can lead to under/over estimation of laser thermotherapy efficacy. Using numerical modeling, this paper presents an optimized laser setting for Nd:YAG laser delivered by a bare optical fiber (300 µm in diameter) at 1064 nm working in continuous mode within a power range of 2–10 W. For the thermal analysis, patient-specific 3D models were used, consisting of tumors in different portions of the pancreas. The optimized laser power and time for ablating the tumor completely and producing thermal toxic effects on the possible residual tumor cells beyond the tumor margins were found to be 5 W for 550 s, 7 W for 550 s, and 8 W for 550 s for the pancreatic tail, body, and head tumors, respectively. Based on the results, during the laser irradiation at the optimized doses, thermal injury was not evident either in the 15 mm lateral distances from the optical fiber or in the nearby healthy organs. The present computational-based predictions are also in line with the previous ex vivo and in vivo studies, hence, they can assist in the estimation of the therapeutic outcome of laser ablation for pancreatic neoplasms prior to clinical trials. [ABSTRACT FROM AUTHOR]

Multiple statistical and event studies based on in situ observations have shown that the solar wind contains mesoscale (∼ 100 – 10,000 Mm) periodic structures in the proton number density. Remote observations of such structures and event studies of concurrent variations in composition have demonstrated that they can form in the solar atmosphere and be preserved while advecting outwards through the heliosphere. Viall, Kepko, and Spence (J. Geophys. Res. (Space Phys.)113, A07101, 2008; J. Geophys. Res. (Space Phys.)114, A01201, 2009) and Kepko, Viall, and Wolfinger (J. Geophys. Res. (Space Phys.)125(8), e28037, 2020) have reported that periodic proton density structures preferentially occur at specific radial length scales and have published their distributions from Wind measurements near L1. Here, we conduct a statistical study of 14 years (1998 – 2011) of 12-minute composition data measured by the Solar Wind Ion Composition Spectrometer instrument aboard the Advanced Composition Explorer spacecraft. We found that the elemental and ionic composition also contain statistically significant mesoscale periodic structures and, for the first time, present occurrence distributions for elemental abundance ratios with low, intermediate, and high first ionization potentials as well as for key solar wind charge states. These distributions set important constraints on solar wind formation in general and the formation of periodic mesoscale solar wind structures specifically, as the elemental and ionic composition are known to be determined at the Sun and to not evolve during advection. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to evaluate the clinical and imaging findings up to 24 months of follow-up in patients treated with combined subchondral and intra-articular bone marrow aspirate concentrate (BMAC) injections for the treatment of knee osteoarthritis (OA). Methods: Thirty consecutive patients (19 males, 11 females) aged between 40 and 75 years (mean age 56.4 ± 8.1 years) with unilateral symptomatic knee OA (Kellgren–Lawrence 2–3) were included in the study. Patients were treated with combined intra-articular and subchondral bone BMAC injections (total 9 ml) under fluoroscopic control. IKDC subjective score, VAS for pain, KOOS, and EQ-VAS were prospectively evaluated up to 24 months. Radiographs were performed at baseline and at 24 months after the procedure. MRI was evaluated with the WORMS score at baseline, 6–12 months, and 24 months of follow-up. The statistical analysis was performed using SPSS v.19.0 and for all tests p < 0.05 was considered significant. Results: No major complications and a 13% failure rate were reported. The IKDC subjective score remained stable from 62.6 ± 19.4 at 12 months to 63.4 ± 17.1 at 24 months (both p < 0.0005 compared to baseline, 40.5 ± 12.5). Similar improvements were reported for all KOOS subscales, while EQ-VAS did not report any significant improvement. VAS pain worsened from 3.0 ± 1.9 at 12 months to 4.4 ± 1.8 at the final follow-up (p = 0.0001), although remaining lower compared to the baseline value of 6.3 ± 1.8 (p = 0.002). The radiographic evaluation did not reveal signs of improvement or deterioration of the OA grade. The MRI findings showed a worsening in marginal osteophytes and synovitis, but a significant reduction of bone marrow edema at 24 months (p < 0.0005). Conclusion: Combined intra-articular and subchondral BMAC injections provided clinical and imaging benefits up to 24 months for the treatment of symptomatic knee OA, with durable clinical results, a low failure rate, and a significant reduction of bone marrow edema. [ABSTRACT FROM AUTHOR]

Differential scanning calorimetry (DSC) was used as an efficient and rapid tool in studying the conformational transitions between the folded and unfolded structures of cellulolytic enzymes. The thermal properties of two crude hydrolytic enzyme cocktails containing extracellular cellulases from Trichoderma longibrachiatum DIBAF-10 were analyzed and compared with three commercial cellulase preparations. Differences in the thermal behavior of fungal cellulases in the liquid phase, freeze-dried state, liquid formulations in sodium citrate buffer (pH 4.8), and contact with cellulose, carboxymethyl cellulose, and cellobiose were evaluated. DSC profiles of cellulases from the DIBAF-10 strain provided important thermodynamic information about the thermal stability of the included proteins. Crude enzyme cocktails underwent a reproducible and irreversible exothermic aggregation phenomenon at 52.45 ± 0.90 °C like commercial β-glucosidase. Freeze-dried and resuspended in a sodium citrate buffer, cellulases from T. longibrachiatum showed an endothermic peak dependent on buffer and enzyme concentration. In the enzyme-substrates systems, a shift of the same peak was recorded for all substrates tested. The thermal analysis of freeze-dried cellulase samples in the range of 20–150 °C gave information on the denaturation process. In conclusion, we demonstrated that DSC is a cost-effective tool for obtaining "conformational fingerprinting" of crude fungal cellulase preparations. [ABSTRACT FROM AUTHOR]

Galaxy mergers produce pairs of supermassive black holes (SMBHs), which may be witnessed as dual quasars if both SMBHs are rapidly accreting. The kiloparsec (kpc)-scale separation represents a physical regime sufficiently close for merger-induced effects to be important1 yet wide enough to be directly resolvable with the facilities currently available. Whereas many kpc-scale, dual active galactic nuclei—the low-luminosity counterparts of quasars—have been observed in low-redshift mergers2, no unambiguous dual quasar is known at cosmic noon (z ≈ 2), the peak of global star formation and quasar activity3,4. Here we report multiwavelength observations of Sloan Digital Sky Survey (SDSS) J0749 + 2255 as a kpc-scale, dual-quasar system hosted by a galaxy merger at cosmic noon (z = 2.17). We discover extended host galaxies associated with the much brighter compact quasar nuclei (separated by 0.46″ or 3.8 kpc) and low-surface-brightness tidal features as evidence for galactic interactions. Unlike its low-redshift and low-luminosity counterparts, SDSS J0749 + 2255 is hosted by massive compact disk-dominated galaxies. The apparent lack of stellar bulges and the fact that SDSS J0749 + 2255 already follows the local SMBH mass–host stellar mass relation, suggest that at least some SMBHs may have formed before their host stellar bulges. While still at kpc-scale separations where the host-galaxy gravitational potential dominates, the two SMBHs may evolve into a gravitationally bound binary system in around 0.22 Gyr.The authors report multiwavelength observations of SDSS J0749 + 2255, hosted by massive compact disk-dominated galaxies, as a kpc-scale, dual-quasar system hosted by a galaxy merger at cosmic noon. [ABSTRACT FROM AUTHOR]

As classically captured in the notion of affordance, the natural environment presents animals with multiple opportunities for action and locomotion appears as the privileged form of action to cover distance in the extrapersonal space/environment. We have recently described a facilitation effect, known as "macro-affordance", for the execution of walking-related actions in response to distant vs. near objects/locations in the extrapersonal space. However, since the manipulation of distance was coextensive to landmark-objects contained in the environment and to the environmental layout per se, the relative contribution of these two factors remains undetermined. In addition, since the effect was originally described in the context of an incidental priming paradigm, it is still unknown whether it was specifically associated with an implicit coding of environmental distance. Here, across three experiments, we examined the degree to which the "macro-affordance" effect reflects (i) the encoding of environmental vs. landmark-objects' distance, (ii) the involvement of an implicit vs. controlled system, (iii) a foot-effector specificity. The results showed that the "macro-affordance" effect is more efficiently triggered by the framing distance of the environmental layout (far/wide/panoramic vs. near/close/restricted) rather than of isolated landmark-objects in the environment and that it only emerges when the distance dimension is implicitly processed within the incidental priming paradigm. The results additionally suggested a specificity of the effect for foot- vs. hand-related actions. The present findings suggest that macro-affordances reflect an implicit coding of spatial features of the environmental layout and viewer–environment relationships that preferentially guide a walking-related exploration of the spatial environment. [ABSTRACT FROM AUTHOR]

Frailty is a new concept in rheumatology that can help identify people more likely to have less favorable outcomes. Sarcopenia and inflammaging can be regarded as the biological foundations of physical frailty. Frailty is becoming more widely accepted as an indicator of ageing and is linked to an increased risk of negative outcomes such as falls, injuries, and mortality. Frailty identifies a group of older adults that seem poorer and more fragile than their age-matched counterparts, despite sharing similar comorbidities, demography, sex, and age. Several studies suggest that inflammation affects immune-mediated pathways, multimorbidity, and frailty by inhibiting growth factors, increasing catabolism, and by disrupting homeostatic signaling. Frailty is more common in the community-dwelling population as people get older, ranging from 7 to 10% in those over 65 years up to 40% in those who are octogenarians. Different parameters have been validated to identify frailty. These primarily relate to two conceptual models: Fried's physical frailty phenotype and Rockwood's cumulative deficit method. Immune-mediated rheumatic diseases (IMRDs), such as rheumatoid arthritis, spondyloarthritis, systemic lupus erythematosus, systemic sclerosis, and vasculitis, are leading causes of frailty in developing countries. The aim of this review was to quantitatively synthesize published literature on the prevalence of frailty in IMRDs and to summarize current evidence on the relevance and applicability of the most widely used frailty screening tools. [ABSTRACT FROM AUTHOR]

Old-growth forests play a key-role in reducing atmospheric carbon dioxide (CO2) concentrations by storing large CO2 amounts in biomass and soil over time. This quantifies the carbon pool into different forest compartments in three Mediterranean old-growth forests of Southern Italy populated by Pinus laricio, Fagus sylvatica and Abies alba. Ecosystem carbon pools have been assessed per compartment, i.e., living trees, deadwood, litterfall (foliar and woody), roots and 0–20 cm topsoil, combining the whole old-growth forest mass, (i.e., using tree allometric relationships, deadwood factor conversions, root-to-shoot ratios, litterfall and soil samplings) by the respective organic carbon concentrations. The results show the considerable capacity of these forest ecosystems in storing CO2 in biomass and soil, with carbon pool values ranging from 532.2 to 596.5 Mg C ha−1. Living trees and 0–20 cm topsoil had larger carbon pool, contributing 53.0 and 22.1%, respectively. In most cases, organic carbon concentration was higher (more than 60%) than the average carbon conversion rate of 50%, especially in living trees, deadwood, and woody litterfall. This study contributes further scientific evidence of the capacity of old-growth forests in storing CO2 in their different compartments, with special evidence on tree biomass, litterfall and mineral soil, thereby highlighting the key role of old-growth forests within the challenge of climate change mitigation. [ABSTRACT FROM AUTHOR]

In this study, the results of a vast experimental campaign on the applicability of a smartphone-based technique for bridge monitoring are presented. Specifically, the vehicle–bridge interaction (VBI)-based approach is exploited as a cost-effective means to estimate the natural frequencies of bridges, with the final aim of possibly developing low-cost and diffused infrastructure monitoring system. The analysis is performed using a common hybrid vehicle, fully equipped with classical piezoelectric accelerometers and a smartphone MEMS accelerometer, to record its vertical accelerations while passing over the bridge. In this regard, the experimental campaign is carried out considering the vehicle moving with a constant velocity on a bridge in the city of Palermo (Italy). Appropriate identification procedures are then employed to determine the modal data of the bridge from the recorded accelerations. Further, comparisons with the results of a standard Operational Modal Analysis procedure, using accelerometers directly mounted on the structure, are presented. Experimental VBI-based analyses are performed also considering the effect of several different vehicle velocities. Further, the applicability of smartphone-based sensor data is investigated, exploiting the possibility of using up-to-date smartphone accelerometers for recording the vehicle accelerations. In this regard, comparison between piezoelectric accelerometers and MEMS ones is performed to assess the reliability of these sensors for the determination of bridge modal properties. [ABSTRACT FROM AUTHOR]

The well-known health beneficial properties of beer are mainly due to phenolic antioxidants. Citrus-flavored beers represent a growing side-market in the beer industry, sparingly investigated to date. The phenolic profile of commercial radler beers (R1, R2) was investigated to evaluate the impact of the lemon juice added to beer in the industrial production. Results were compared to those obtained for opportunely chosen commercial beer (B) and lemonade (L). The study was carried out by an HPLC-MS/MS with an electrospray ionization source in selected ion recording mode, analyzing in a single chromatographic run 26 compounds belonging to the different phenolic classes of hydroxybenzoic, hydroxycinnamic and caffeoylquinic acids, flavonoids and prenylflavonoids. Different phenolic profiles were found for R1 and R2, mainly ascribed to different malt/hop/recipe used for the beer. High to very high level of hesperidin were found in the radlers, so that a major impact on phenolic antioxidants of the radlers was due to the lemon. Similarly, a major impact of the lemon aromas was found, D-limonene being the dominant peak resulting from the GC-MS analysis of the volatile fraction of the radlers. [ABSTRACT FROM AUTHOR]

Sarcopenia is characterized by loss of muscle mass, altered muscle composition, fat and fibrous tissue infiltration, and abnormal innervation, especially in older individuals with immune-mediated rheumatic diseases (IMRDs). Several techniques for measuring muscle mass, strength, and performance have emerged in recent decades. The portable dynamometer and gait speed represent the most frequently used tools for the evaluation of muscle strength and physical efficiency, respectively. Aside from dual-energy, X-ray, absorptiometry, and bioelectrical impedance analysis, ultrasound (US) and magnetic resonance imaging (MRI) techniques appear to have a potential role in evaluating muscle mass and composition. US and MRI have been shown to accurately identify sarcopenic biomarkers such as inflammation (edema), fatty infiltration (myosteatosis), alterations in muscle fibers, and muscular atrophy in patients with IMRDs. US is a low-cost, easy-to-use, and safe imaging method for assessing muscle mass, quality, architecture, and biomechanical function. This review summarizes the evidence for using US and MRI to assess sarcopenia. [ABSTRACT FROM AUTHOR]

The aim of this paper is to map the emergence and development of a research field around the topic of "gender-based violence (GBV) against women with precarious legal status and their access to social protection in advanced welfare societies". We explore the academic knowledge production around this topic as a specific research field by using bibliometric data. We investigate the place occupied by scholars who publish in well-established journals, and their disciplines, in order to understand the relevance of different disciplines and groups of researchers in the knowledge production within the field. Our methodology includes analysis of co-authorship, cross-country collaboration, and co-citation. The search strategy is informed by discursive practices and knowledge production by influential international civil society actors (CSAs) involved in framing welfare responses to GBV against women with precarious legal status. Our results suggest that the knowledge produced in the field increased in terms of number of publications between 2010 and 2021, indicating a process of institutionalisation. Disciplines oriented towards certain groups of professionals such as clinical psychology, medicine, health, nursing, and social work, affiliated mainly to institutions in the US, Canada, and the EU, have a prominent role in knowledge production in this field. In our conclusions, we discuss the implications of these results in relation to gender studies and migration studies, along with some limitations of the use of bibliometrics software combined with an intersectionality approach. [ABSTRACT FROM AUTHOR]

The design of engineering measures during emergency phases is crucial in mitigating the river flow impacts on landslide dams, avoiding dam breaks and related downstream flooding. Man-made hydraulic facilities represent a possible mitigation strategy for reducing the occurrence of dam breaching by diverting river inflow. Semi-empirical equations published in the literature may help define the landslide dam evolution and design the discharge to be diverted into the hydraulic works assuring the dam's stability. These approaches need to be carefully validated with case studies, an important step in evaluating the accuracy of predictive models. The work presents and discusses the pre- and post-seismic hydrologic conditions along the Nera River gorge focusing on the role of the pre-existing anthropic works in mitigating the impact of river discharge on the Sasso Pizzuto landslide dam triggered by the October 30, 2016 earthquake (Central Italy). Considering historical data, the upper part of the river catchment has experienced the highest discharge values during the landslide dam lifetime. The discriminant analysis approach of the hydro-geomorphometric characteristics supported the definition of the critical peak flow, avoiding the dam's instability. Thanks to an upstream hydropower bypass, about 80% of the river discharge increase have been diverted into an underground pipeline built in 1928 to feed the Preci hydroelectric plant (located a few kilometers downstream of the landslide dam). The discriminant analysis model, developed in the literature on other landslides worldwide, had a good performance in managing the upstream river discharge of Sasso Pizzuto dam, expanding its validity on other landslide dams. [ABSTRACT FROM AUTHOR]

A major function of the intrahepatic biliary epithelium is bicarbonate excretion in bile. Recent reports indicate that budesonide, a corticosteroid with high receptor affinity and hepatic first pass clearance, increases the efficacy of ursodeoxycholic acid, a choleretic agent, in primary biliary cholangitis patients. We have previously reported that bile ducts isolated from rats treated with dexamethasone or budesonide showed an enhanced activity of the Na+/H+ exchanger isoform 1 (NHE1) and Cl−/HCO3− exchanger protein 2 (AE2). Increasing the delivery of steroids to the liver may result in three beneficial effects: increase in the choleresis, treatment of the autoimmune or inflammatory liver injury and reduction of steroids' systemic harmful effects. In this study, the steroid dexamethasone was loaded into nanohydrogels (or nanogels, NHs), in order to investigate corticosteroid-induced increased activities of transport processes driving bicarbonate excretion in the biliary epithelium (NHE-1 isoform) and to evaluate the effects of dexamethasone-loaded NHs (NHs/dex) on liver injury induced by experimental cholestatis. Our results showed that NHs and NHs/dex do not reduce cell viability in vitro in human cholangiocyte cell lines. Primary and immortalized human cholangiocytes treated with NHs/dex show an increase in the functional marker expression of NHE1 cholangiocytes compared to control groups. A mouse model of cholangiopathy treated with NHs/dex shows a reduction in markers of hepatocellular injury compared to control groups (NHs, dex, or sham group). In conclusion, we believe that the NHs/dex formulation is a suitable candidate to be investigated in preclinical models of cholangiopathies. [ABSTRACT FROM AUTHOR]

National and international research documents a relationship between greater economic inequality and higher homicide rates. However, much of this work uses simple cross sections at high levels of aggregation rather than longer time series of cities or districts and lacks controls for a more substantial range of confounding factors. Using longitudinal Canadian provincial-level data over the period 1982 to 2017, we occasionally find a positive correlation between inequality and homicides rates. However, the relationship between income inequality and homicide rates in Canada reverses to become negative when looking at Canadian census metropolitan areas (CMAs). Moreover, the province-level result between greater inequality and homicide rates also appears to break down once accounting for regional effects. We conclude that much of the literature that finds a relationship between greater economic inequality and homicide rates needs to be re-examined within a longer time and more disaggregated framework. [ABSTRACT FROM AUTHOR]

We develop a refined singularity analysis for the Ricci flow by investigating curvature blow-up rates locally. We first introduce general definitions of Type I and Type II singular points and show that these are indeed the only possible types of singular points. In particular, near any singular point the Riemannian curvature tensor has to blow up at least at a Type I rate, generalising a result of Enders, Topping and the first author that relied on a global Type I assumption. We also prove analogous results for the Ricci tensor, as well as a localised version of Sesum's result, namely that the Ricci curvature must blow up near every singular point of a Ricci flow, again at least at a Type I rate. Finally, we show some applications of the theory to Ricci flows with bounded scalar curvature. [ABSTRACT FROM AUTHOR]

Systemic liquidity risk, defined by the International Monetary Fund as "the risk of simultaneous liquidity difficulties at multiple financial institutions," is a key topic in financial stability studies and macroprudential policy-making. In this context, the complex web of interconnections of the interbank market plays the crucial role of allowing funding liquidity shortages to propagate between financial institutions. Here, we introduce a simple yet effective model of the interbank market in which liquidity shortages propagate through an epidemic-like contagion mechanism on the network of interbank loans. The model is defined by using aggregate balance sheet information of European banks, and it exploits country and bank-specific risk features to account for the heterogeneity of financial institutions. Moreover, in order to obtain the European-wide topology of the interbank network, we define a block reconstruction method based on the exchange flows between the various countries. We show that the proposed contagion model is able to estimate systemic liquidity risk across different years and countries. Results suggest that our effective contagion approach can be successfully used as a viable alternative to more realistic but complicated models, which not only require more specific balance sheet variables with high time resolution but also need assumptions on how banks respond to liquidity shocks. [ABSTRACT FROM AUTHOR]

In this study, an innovative procedure is presented for the analysis of the static behavior of plates at the micro and nano scale, with arbitrary shape and various boundary conditions. In this regard, the well-known Eringen's nonlocal elasticity theory is used to appropriately model small length scale effects. The proposed mesh-free procedure, namely the Line Element-Less Method (LEM), only requires the evaluation of simple line integrals along the plate boundary parametric equation. Further, variations of appropriately introduced functionals eventually lead to a linear system of algebraic equations in terms of the expansion coefficients of the deflection function. Notably, the proposed procedure yields approximate analytical solutions for general shapes and boundary conditions, and even exact solutions for some plate geometries. In addition, several applications are discussed to show the simplicity and applicability of the procedure, and comparison with pertinent data in the literature assesses the accuracy of the proposed approach. [ABSTRACT FROM AUTHOR]

The late Middle Pleistocene, starting at around 300 ka, witnessed large-scale biological and cultural dynamics in hominin evolution across Africa including the onset of the Middle Stone Age that is closely associated with the evolution of our species—Homo sapiens. However, archaeological and geochronological data of its earliest appearance are scarce. Here we report on the late Middle Pleistocene sequence of Wadi Lazalim, in the Sahara of Southern Tunisia, which has yielded evidence for human occupations bracketed between ca. 300–130 ka. Wadi Lazalim contributes valuable information on the spread of early MSA technocomplexes across North Africa, that likely were an expression of large-scale diffusion processes. [ABSTRACT FROM AUTHOR]

Mesenteric cysts are defined as a heterogeneous group of intra-abdominal cystic lesions of the mesentery or omentum that may be found in any portion of the gastrointestinal tract from the duodenum to the rectum. The clinical condition is entirely asymptomatic in many patients, particularly with small cysts. The diagnosis is typically incidental and secondary to imaging performed for other purposes. In symptomatic patients, the clinical picture is characterized by nonspecific gastrointestinal signs and symptoms. Treatment may be surgical or via interventional radiology. We report the case of a 55-year-old female patient complaining of left-sided abdominal discomfort and constipation lasting three months. An abdominal ultrasound showed the presence of a 10 × 14 × 16 cm anechoic cystic mass filling the whole anterior and left abdominal cavity, confirmed by CT and MRI. The cyst, removed laparoscopically, was histologically a simple mesothelial cyst. We reviewed the international literature over the last 10 years of all cases with mesenteric cysts > 10 cm in evaluating gastrointestinal symptoms at diagnosis, histology, performed treatment, and outcome. [ABSTRACT FROM AUTHOR]

Purpose: The aims of the present study were: (1) to characterize the bone-marrow aspirate (BMA) obtained with a centrifuge-free process, employing a dedicated aspiration device; (2) to test the in vitro efficacy of BMA in a model of cartilage inflammation; and (3) to report the preliminary clinical results in a small cohort of patients affected by knee OA. Methods: Ten patients (4 M, 6 W; mean age: 51.9 ± 9.2 yy) affected by mild to moderate unicompartmental knee OA (KL grade 2–3) were treated by intra-articular and subchondral injections of BMA obtained by a centrifuge-free process. To evaluate the effectiveness of the device in harvesting mesenchymal stem cells (MSCs), samples of the obtained BMA were tested by flow cytometry before and after subculture; BMA ability to counteract inflammation was also tested in an in vitro model of cartilage cell inflammation, evaluating the expression of MMP1, MMP3, TGFβ and TIMP-1 by real-time PCR. Patients were also evaluated up to two years' follow-up by using: VAS for pain, IKDC-subjective and KOOS scores. Results: The laboratory analysis showed that BMSCs accounted for 0.011% of BMA cells, similar to what had been expected in native bone marrow. The paracrine activity of BMA was able to reduce in vitro the catabolic response of human chondrocyte, as shown by the decrease in metalloproteases concentration and increase in anti-inflammatory mediators. Moreover, the clinical evaluation showed significant improvements in all scores adopted, with stable results up to two years. Conclusion: The present data showed the effectiveness of the study device to harvest pure bone marrow with minimal peripheral blood contamination. The relevant content of MSCs resulted in the ability to counteract the catabolic cascade through a paracrine action. The clinical outcomes in patients affected by unicompartmental knee OA were encouraging in terms of pain reduction and functional improvement up to mid-term evaluation. [ABSTRACT FROM AUTHOR]

Chronic granulomatous disease (CGD) is a rare inborn error of immunity (IEI), characterized by a deficient phagocyte killing due to the inability of NADPH oxidase to produce reactive oxygen species in the phagosome. Patients with CGD suffer from severe and recurrent infections and chronic inflammatory disorders. Onset of CGD has been rarely reported in neonates and only as single case reports or small case series. We report here the cases of three newborns from two different kindreds, presenting with novel infectious and inflammatory phenotypes associated with CGD. A girl with CYBA deficiency presented with necrotizing pneumonia, requiring a prolonged antibiotic treatment and resulting in fibrotic pulmonary changes. From the second kindred, the first of two brothers developed a fatal Burkholderia multivorans sepsis and died at 24 days of life. His younger brother had a diagnosis of CYBB deficiency and presented with Macrophage Activation Syndrome/Hemophagocytic Lympho-Histiocytosis (MAS/HLH) without any infection, that could be controlled with steroids. We further report the findings of a review of the literature and show that the spectrum of microorganisms causing infections in neonates with CGD is similar to that of older patients, but the clinical manifestations are more diverse, especially those related to the inflammatory syndromes. Our findings extend the spectrum of the clinical presentation of CGD to include unusual neonatal phenotypes. The recognition of the very early, potentially life-threatening manifestations of CGD is crucial for a prompt diagnosis, improvement of survival and reduction of the risk of long-term sequelae. [ABSTRACT FROM AUTHOR]

Purpose: We described clinical, immunological, and molecular characterization within a cohort of 22 RAG patients focused on the possible correlation between clinical and genetic data. Methods: Immunological and genetic features were investigated by multiparametric flow cytometry and by Sanger or next generation sequencing (NGS) as appropriate. Results: Patients represented a broad spectrum of RAG deficiencies: SCID, OS, LS/AS, and CID. Three novel mutations in RAG1 gene and one in RAG2 were reported. The primary symptom at presentation was infections (81.8%). Infections and autoimmunity occurred together in the majority of cases (63.6%). Fifteen out of 22 (68.2%) patients presented autoimmune or inflammatory manifestations. Five patients experienced severe autoimmune cytopenia refractory to different lines of therapy. Total lymphocytes count was reduced or almost lacking in SCID group and higher in OS patients. B lymphocytes were variably detected in LS/AS and CID groups. Eighteen patients underwent HSCT permitting definitive control of autoimmune/hyperinflammatory manifestations in twelve of them (80%). Conclusion: We reinforce the notion that different clinical phenotype can be found in patients with identical mutations even within the same family. Infections may influence genotype–phenotype correlation and function as trigger for immune dysregulation or autoimmune manifestations. Severe and early autoimmune refractory cytopenia is frequent and could be the first symptom of onset. Prompt recognition of RAG deficiency in patients with early onset of autoimmune/hyperinflammatory manifestations could contribute to the choice of a timely and specific treatment preventing the onset of other complications. [ABSTRACT FROM AUTHOR]

Purpose: Subchondral bone is becoming a treatment target for knee OA patients, with promising early findings on the use of bone marrow aspirate concentrate (BMAC). The aim of this prospective, multi-centric pilot study was to evaluate safety as well as clinical and MRI outcomes of a combined approach of intra-articular and subchondral BMAC injections. Methods: Thirty patients (19 men, 11 women, 56.4 ± 8.1 years) with symptomatic knee OA were treated with a combination of an intra-articular and two subchondral BMAC injections (femoral condyle and tibial plateau). Patients were evaluated at baseline and at 1–3–6–12 months of follow-up with the IKDC subjective, VAS, KOOS, and EQ-VAS scores. The MRI evaluation was performed with the WORMS score. Results: No major complications were reported and only two patients were considered treatment failures, requiring a new injective or surgical treatment. The IKDC subjective score improved significantly from 40.5 ± 12.5 to 59.9 ± 16.1 at 3 months, 59.1 ± 12.2 at 6 months, and 62.6 ± 19.4 at 12 months (p < 0.0005). A similar improvement was reported for VAS pain and all KOOS subscales at all follow-ups, while EQ-VAS did not show any significant improvement. The MRI analysis showed a significant bone marrow edema reduction (p = 0.003), while the remaining WORMS parameters did not show any significant changes. Conclusion: The pilot evaluation of this combined BMAC injective treatment showed safety and positive outcome up to 12 months of follow-up in patients with symptomatic knee OA associated with subchondral bone alterations. These findings suggest that targeting both subchondral bone and joint environment can provide promising results, and that BMAC can be a valid option for this combined approach to treat knee OA. [ABSTRACT FROM AUTHOR]