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Background: Ectopic cell cycle reactivation in neurons is associated with neuronal death in Alzheimer’s disease. In cultured rodent neurons, synthetic β-amyloid (Aβ) reproduces the neuronal cell cycle re-entry observed in the Alzheimer’s brain, and blockade of the cycle prevents Aβ-induced neurodegeneration. DNA polymerase-β, whose expression is induced by Aβ, is responsible for the DNA replication process that ultimately leads to neuronal death, but the molecular mechanism(s) linking DNA replication to neuronal apoptosis are presently unknown. Aim: To explore the role of a conserved checkpoint pathway started by DNA replication stress, namely the ATM-ATR/Claspin/Chk-1 pathway, in switching the neuronal response from DNA replication to apoptosis. Methods: Experiments were carried out in cultured rat cortical neurons challenged with toxic oligomers of Aβ protein. Results: Small inhibitory molecules of ATM/ATR kinase or Chk-1 amplified Aβ-induced neuronal DNA replication and apoptosis, as they were permissive to the DNA polymerase-β activity triggered by Aβ oligomers. Claspin, i.e., the adaptor protein between ATM/ATR kinase and the downstream Chk-1, was present on DNA replication forks of neurons early after Aβ challenge, and decreased at times coinciding with neuronal apoptosis. The caspase-3/7 inhibitor I maintained overtime the amount of Claspin loaded on DNA replication forks and, concomitantly, reduced neuronal apoptosis by holding neurons in the S phase. Moreover, a short phosphopeptide mimicking the Chk-1-binding motif of Claspin was able to prevent Aβ-challenged neurons from entering apoptosis. Conclusion: We speculate that, in the Alzheimer’s brain, Claspin degradation by intervening factors may precipitate the death of neurons engaged into DNA replication.

Background: Despite its high prevalence, the clinical course of pediatric migraine has not been fully understood, and previous studies present conflicting results. We present here the findings of a 10-year follow-up study involving children with severe migraine pain admitted to our emergency department. Furthermore, all studies were carried out on selected outpatient clinical case studies. Our aim was to evaluate a population of migraine children admitted to an emergency department because of increased severity or frequency of pain or even because of very anxious parents concerning their child’s headache in order to describe their long-term outcomes, whether it differed from that of outpatient populations and to identify possible predictors of prognosis. Methods: We recruited 80 subjects with migraine headaches (mean age 8 years with a range of 4–14 years, 50% females), attending the baseline examination of a population admitted for a headache to the Emergency Department in the first half year of 2012. Of the 80 subjects, 48 (60%) were eligible for follow-up in 2022. We included in our study only patients diagnosed with migraine, according to the diagnostic criteria of the International Classification of Headache Disorders. All were contacted by telephone, and a semi-structured questionnaire was provided to them by email. The association between several possible prognostic factors (gender, familiar neurologic disorders, prenatal and perinatal disorders, social activities, sleep disorders, etc.) and the long-term persistence of migraine headaches were explored using logistic regression analysis. Results: Of 48 subjects with migraine headaches at baseline, 31 (65%) had persistent migraine, and 17 (35%) experienced remission. The preliminary results showed that the presence of neurologic disorders in parents (p < 0.01—odds ratio 9.34 (2.53–41.64) and sleep disorders (p < 0.01—odds ratio 13.18 (2.25–252.74) significantly predicted the 10-year persistence of migraine headaches, while the other considered predictors were found not to influence prognosis. Conclusions: To our knowledge, this was the first study conducted on a selected pediatric population upon admission to the emergency room. Our study suggests that a population of pediatric migraine selected for admission to the emergency department also shows a favorable long-term prognosis, like the studies conducted in the outpatient sample. Familial neurological comorbidity and sleep disorders were unfavorable factors for predicting good outcomes.

Objective: Studies on the relationship between depression and cognition on patients with multiple sclerosis (MS) are inconsistent and it is not clear whether higher depression levels are associated with impairment of specific cognitive domains or processes. This meta-analytic study aimed at evaluating the possible association between depressive symptomatology and performance on cognitive tests assessing several cognitive domains (global cognition, attention, processing speed, verbal, spatial and working memory, verbal fluency, inhibitory control, set-shifting) in individuals living with MS. Method: The literature search on three electronic databases yielded 5402 studies (4333 after the duplicates removal); after the evaluation of titles, abstracts full-text articles, 37 studies were included in the meta-analytic study. A random-effect model meta-analysis was performed and mean weighted effect sizes (ESs) were calculated using Hedges' g. Results: Small ESs were found for the relationship between depression and verbal memory (g = 0.25, p

Invasive alien species are among the main global drivers of biodiversity loss posing major challenges to nature conservation and to managers of protected areas. The present study applied a methodological framework that combined invasive Species Distribution Models, based on propagule pressure, abiotic and biotic factors for 14 invasive alien plants of Union concern in Italy, with the local interpretable model-agnostic explanation analysis aiming to map, evaluate and analyse the risk of plant invasions across the country, inside and outside the network of protected areas. Using a hierarchical invasive Species Distribution Model, we explored the combined effect of propagule pressure, abiotic and biotic factors on shaping invasive alien plant occurrence across three biogeographic regions (Alpine, Continental, and Mediterranean) and realms (terrestrial and aquatic) in Italy. We disentangled the role of propagule pressure, abiotic and biotic factors on invasive alien plant distribution and projected invasion risk maps. We compared the risk posed by invasive alien plants inside and outside protected areas. Invasive alien plant distribution varied across biogeographic regions and realms and unevenly threatens protected areas. As an alien's occurrence and risk on a national scale are linked with abiotic factors followed by propagule pressure, their local distribution in protected areas is shaped by propagule pressure and biotic filters. The proposed modelling framework for the assessment of the risk posed by invasive alien plants across spatial scales and under different protection regimes represents an attempt to fill the gap between theory and practice in conservation planning helping to identify scale, site, and species-specific priorities of management, monitoring and control actions. Based on solid theory and on free geographic information, it has great potential for application to wider networks of protected areas in the world and to any invasive alien plant, aiding improved management strategies claimed by the environmental legislation and national and global strategies.

Sunflower press cake is a protein-rich sidestream from oil production, that is potentially suitable for human consumption, but its utilisation is hindered by the high content of chlorogenic acid (CGA), an abundant anti-nutritional factor. Here we show that processing sunflower protein concentrate (SP) by fermentation (fSP) reduces the CGA content while increasing the level of free amino acids, but impairs the formation of fibrillar structures and generates a sour taste. After fermentation of SP pH was shifted to neutral (fSP7). Meat analogues based on SP, fSP, fSP7, and pea protein isolate were prepared by high-moisture extrusion processing, which reduced CGA levels further. The texture and colour of the extrudates were both improved by the neutral pH shift. Finally, the odour, flavour and structure were assessed by a trained sensory panel. We found that fermentation followed by a neutral pH shift encouraged the formation of fibrillar structures and prevented sour taste attributes in the meat analogue. Our data will facilitate the development of sunflower protein products that are more palatable and nutritionally beneficial for humans.

Full list of authors: Doroshenko, Victor; Poutanen, Juri; Tsygankov, Sergey S.; Suleimanov, Valery F.; Bachetti, Matteo; Caiazzo, Ilaria; Costa, Enrico; Di Marco, Alessandro; Heyl, Jeremy; La Monaca, Fabio; Muleri, Fabio; Mushtukov, Alexander A.; Pavlov, George G.; Ramsey, Brian D.; Rankin, John; Santangelo, Andrea; Soffitta, Paolo; Staubert, Rüdiger; Weisskopf, Martin C.; Zane, Silvia; Agudo, Iván; Antonelli, Lucio A.; Baldini, Luca; Baumgartner, Wayne H.; Bellazzini, Ronaldo; Bianchi, Stefano; Bongiorno, Stephen D.; Bonino, Raffaella; Brez, Alessandro; Bucciantini, Niccolò; Capitanio, Fiamma; Castellano, Simone; Cavazzuti, Elisabetta; Ciprini, Stefano; De Rosa, Alessandra; Del Monte, Ettore; Di Gesu, Laura; Di Lalla, Niccolò; Donnarumma, Immacolata; Dovčiak, Michal; Ehlert, Steven R.; Enoto, Teruaki; Evangelista, Yuri; Fabiani, Sergio; Ferrazzoli, Riccardo; Garcia, Javier A.; Gunji, Shuichi; Hayashida, Kiyoshi; Iwakiri, Wataru; Jorstad, Svetlana G.; Karas, Vladimir; Kitaguchi, Takao; Kolodziejczak, Jeffery J.; Krawczynski, Henric; Latronico, Luca; Liodakis, Ioannis; Maldera, Simone; Manfreda, Alberto; Marin, Frédéric; Marinucci, Andrea; Marscher, Alan P.; Marshall, Herman L.; Matt, Giorgio; Mitsuishi, Ikuyuki; Mizuno, Tsunefumi; Ng, Chi-Yung; O'Dell, Stephen L.; Omodei, Nicola; Oppedisano, Chiara; Papitto, Alessandro; Peirson, Abel L.; Perri, Matteo; Pesce-Rollins, Melissa; Pilia, Maura; Possenti, Andrea; Puccetti, Simonetta; Ratheesh, Ajay; Romani, Roger W.; Sgrò, Carmelo; Slane, Patrick; Spandre, Gloria; Sunyaev, Rashid A.; Tamagawa, Toru; Tavecchio, Fabrizio; Taverna, Roberto; Tawara, Yuzuru; Tennant, Allyn F.; Thomas, Nicolas E.; Tombesi, Francesco; Trois, Alessio; Turolla, Roberto; Vink, Jacco; Wu, Kinwah; Xie, Fei., Using observations of X-ray pulsar Hercules X-1 by the Imaging X-ray Polarimetry Explorer we report a highly significant (>17σ) detection of the polarization signal from an accreting neutron star. The observed degree of linear polarization of ~10% is far below theoretical expectations for this object, and stays low throughout the spin cycle of the pulsar. Both the degree and angle of polarization exhibit variability with the pulse phase, allowing us to measure the pulsar spin position angle 57(2) deg and the magnetic obliquity 12(4) deg, which is an essential step towards detailed modelling of the intrinsic emission of X-ray pulsars. Combining our results with the optical polarimetric data, we find that the spin axis of the neutron star and the angular momentum of the binary orbit are misaligned by at least ~20 deg, which is a strong argument in support of the models explaining the stability of the observed superorbital variability with the precession of the neutron star. © 2022, The Author(s), under exclusive licence to Springer Nature Limited., This Article is based on observations made by IXPE, a joint US and Italian mission. This research used data products provided by the IXPE Team (MSFC, SSDC, INAF and INFN) and distributed with additional software tools by the High-Energy Astrophysics Science Archive Research Center (HEASARC), at the NASA Goddard Space Flight Center (GSFC). The US contribution is supported by NASA and led and managed by its Marshall Space Flight Center (MSFC), with industry partner Ball Aerospace (contract number NNM15AA18C). The Italian contribution is supported by the Italian Space Agency (Agenzia Spaziale Italiana, ASI) through contract number ASI-OHBI-2017-12-I.0, agreement numbers ASI-INAF-2017-12-H0 and ASI-INFN-2017.13-H0, and its Space Science Data Center (SSDC) and by the Istituto Nazionale di Astrofisica (INAF) and the Istituto Nazionale di Fisica Nucleare (INFN) in Italy. V.D. and V.F.S. acknowledge support from the German Academic Exchange Service (DAAD) under travel grant number 57525212. J.P. and S.S.T. thank the Russian Science Foundation for support under grant number 20-12-00364 and the Academy of Finland for support under grant numbers 333112, 349144, 349373 and 349906. V.F.S. thanks the German Research Foundation (DFG) for grant number WE 1312/53-1. I.C. is a Sherman Fairchild Fellow at Caltech and thanks the Burke Institute at Caltech for supporting her research. A.A.M. acknowledges support from the Netherlands Organization for Scientific Research Veni Fellowship., info:eu-repo/grantAgreement/MICINN//SEV-2017-0709

Extracellular vesicles (EVs) enriched with bioactive molecules have gained considerable attention in nanotechnology because they are critical to intercellular communication while maintaining low immunological impact. Among biological matrices, urine has emerged as a noninvasive source of extracellular-contained liquid biopsy, currently of interest as a readout for physiological adaptations. Therefore, we aimed to evaluate chronic adaptations of endurance sport practice in terms of urinary EV parameters and evaluated by food consumption assessment. Two balanced groups of 13 inactive controls vs. triathlon athletes were enrolled; their urinary EVs were obtained by differential ultracentrifugation and analyzed by dynamic light scattering and transmission electron and atomic force microscopy. The cargo was analyzed by means of purine and miRNA content through HPLC-UV and qRT-PCR. Specific urinary EV signatures differentiated inactive versus endurance-trained in terms of peculiar shape. Particularly, a spheroid shape, smaller size, and lower roughness characterize EVs from triathletes. Metabolic and regulatory miRNAs often associated with skeletal muscle (i.e., miR378a-5p, miR27a-3p, miR133a, and miR206) also accounted for a differential signature. These miRNAs and guanosine in urinary EVs can be used as a readout for metabolic status along with the shape and roughness of EVs, novel informative parameters that are rarely considered. The network models allow scholars to entangle nutritional and exercise factors related to EVs’ miRNA and purine content to depict metabolic signatures. All in all, multiplex biophysical and molecular analyses of urinary EVs may serve as promising prospects for research in exercise physiology.

Longitudinal models suited for the analysis of panel data, such as cross-lagged panel or autoregressive latent-state trait models, assume population homogeneity with respect to the temporal dynamics of the variables under investigation. This assumption is likely to be too restrictive in a myriad of research areas. We propose an extension of autoregressive and cross-lagged latent state-trait models to mixture distribution models. The models allow researchers to model unobserved person heterogeneity and qualitative differences in longitudinal dynamics based on comparatively few observations per person, while taking into account temporal dependencies between observations as well as measurement error in the variables. The models are extended to include categorical covariates, to investigate the distribution of encountered latent classes across observed groups. The potential of the models is illustrated with an application to self-esteem and affect data in patients with borderline personality disorder, an anxiety disorder, and healthy control participants. Requirements for the models’ applicability are investigated in an extensive simulation study and recommendations for model applications are derived.

In this work, using Neutron star Interior Composition Explorer and Insight-Hard X-ray Modulation Telescope observations, we present a study of the broad-band spectral and timing evolution of the source throughout the first reflare, which occurred about 4-month after the major outburst. Our findings suggest that during the reflare, below a critical luminosity Lcrit ∼ 2.5 × 1036 (D/2.2 kpc)2 erg s−1, the scale of the corona shrinks in the radial direction, whereas the inner radius of the disc does not change considerably; however, the inner radius of the disc starts to move inward when the source exceeds the critical luminosity. We conclude that at low luminosity the increase in accretion rate only heats up the inner zone of the accretion disc without the transfer of angular momentum which occurs above a certain luminosity.

A pesquisa tem por objetivo verificar os reflexos da pandemia da COVID-19 na situação econômico-financeira das Fundações de Apoio vinculadas à UFSC. A pesquisa caracteriza-se como descritiva com abordagem qualitativa por meio de pesquisa documental. O banco de dados da pesquisa contempla demonstrações contábeis, relatórios de gestão, relatórios de auditoria e notas explicativas do período entre 2017 a 2020. Os resultados da pesquisa mostraram que as três Fundações - FAPEU, FEPESE e FEESC - apresentaram em 2020, indicadores econômico-financeiros inferiores aos anos anteriores, com redução relevante em várias contas do balanço patrimonial e da demonstração de resultado. Também houve reflexos na operação, com a redução de volume de compras, demissões de colaboradores e demora nos repasses de recursos e resultados deficitários. Diante dos resultados, conclui-se que houve um agravamento na situação econômico-financeira das fundações, visto que todas as fundações tiveram redução significativa, principalmente de contratos de projetos. Nesse cenário de crise econômica e de Pandemia da COVID-19, o acompanhamento da situação econômico-financeira das fundações é fundamental, visto que desempenham papel importante no apoio e fomento aos projetos e atividades multidisciplinares acadêmicas e de extensão, gerando benefícios para a sociedade.

Theory of mind (ToM), the ability to understand other minds-that is, their beliefs, intentions (cognitive ToM), or emotions (affective ToM)-and its neuropsychological mechanisms in migraine have been poorly investigated. The aim of the study was to explore the deficit of cognitive and affective ToM and its possible associations with cognitive functioning in patients with chronic migraine (CM).Forty participants with CM and 40 age-, education-, and sex-matched healthy controls (HC) underwent clinical assessment, cognitive (the ToM Pictures Sequencing Task and the Advanced Test of ToM) and affective ToM (the Reading the Mind in the Eyes Task and the Emotion Attribution Task) tasks, and a comprehensive neuropsychological battery.Patients with CM significantly reported a lower performance on tasks assessing ToM compared to HC, with an impairment demonstrated for cognitive ToM. Moreover, patients with CM achieved significantly lower scores on tests assessing cognitive flexibility, planning, abstract reasoning, and long-term memory with respect to HC. ToM abilities were significantly related to migraine severity, executive, and memory functions in CM patients.The findings demonstrated that patients with CM present difficulties in inferring others' mental states, which would be related to clinical and cognitive functioning. The clinical importance of these findings, implications for clinical practice, and future research are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Neutrophil-to-lymphocyte ratio (NLR) recently demonstrated predictive value for hepatocellular carcinoma (HCC) recurrence after thermal ablation. Microwave ablation (MWA) has been shown to induce changes in the immune landscape after HCC treatment. This study aims at identifying predictors of local tumor progression (LTP) and post-treatment NLR kinetics after MWA.Data from 108 consecutive patients who underwent percutaneous MWA of 119 HCCs with a 2450 Hz/100 W generator in two institutions from October 2014 to September 2021 were retrospectively reviewed. Forty-five HCCs (42 patients) met inclusion criteria for analysis (technique efficacy, pre- and post-treatment NLR availability, follow-up 6 months, absence of complications). NLR was analyzed prior to therapy and at 1-month follow-up; difference between the two time points was defined as ΔNLRAfter a median follow-up of 25 months, LTP occurred in 18 HCCs (40%) and 18 patients (42.9%). Multivariate competing risk regression comprising ΔNLRNLR increase after ablation was the only independent predictor of LTP, supporting the role of balance between systemic inflammation and immunity in recurrence after MWA. Ablation energy/tumor size predicted NLR increase, reinforcing the concept of immune ablation.III.

Sydenham’s chorea (SC) is a post-streptococcal autoimmune disorder of the central nervous system, and it is a major criterium for the diagnosis of acute rheumatic fever (ARF). SC typically improves in 12–15 weeks, but patients can be affected for years by persistence and recurrencies of both neurological and neuropsychiatric symptoms. We enrolled 48 patients with a previous diagnosis of ARF, with or without SC, in a national multicenter prospective study, to evaluate the presence of neuropsychiatric symptoms several years after SC’s onset. Our population was divided in a SC group (n = 21), consisting of patients who had SC, and a nSC group (n = 27), consisting of patients who had ARF without SC. Both groups were evaluated by the administration of 8 different neuropsychiatric tests. The Work and Social Adjustment Scale (WSAS) showed significantly (p = 0.021) higher alterations in the SC group than in the nSC group. Furthermore, 60.4% (n = 29) of the overall population experienced neuropsychiatric symptoms other than choreic movements at diagnosis and this finding was significantly more common (p = 0.00) in SC patients (95.2%) than in nSC patients (33.3%). The other neuropsychiatric tests also produced significant results, indicating that SC can exert a strong psychopathological impact on patients even years after its onset.

Atypical Parkinsonism (AP) syndromes are characterized by a wide spectrum of non-motor symptoms including prominent attentional and executive deficits. However, the cognitive profile of AP and its differences and similarities with that of Parkinson's Disease (PD) are still a matter of debate. The present meta-analysis aimed at identifying patterns of cognitive impairment in AP by comparing global cognitive functioning, memory, executive functions, visuospatial abilities, language, non-verbal reasoning, and processing speed test performances of patients with AP relative to healthy controls and patients with PD. All investigated cognitive domains showed a substantial impairment in patients with AP compared to healthy controls. When AP syndromes were considered separately, their cognitive functioning was distributed along a continuum from Multiple Systemic Atrophy at one extreme, with the least impaired cognitive profile (similar to that observed in PD) to Progressive Supranuclear Palsy, with the greatest decline in global cognitive and executive functioning (similar to Corticobasal Syndrome). These findings indicate that widespread cognitive impairment could represent an important clinical indicator to distinguish AP from other movement disorders.

Background. The orofacial pain syndromes (OFPs) are a heterogeneous group of syndromes characterized by painful attacks involving the orofacial structures. They may be summarily subdivided into two great categories: (1) orofacial pain mainly attributed to dental disorders such as dentoalveolar and myofascial orofacial pain or temporomandibular joint (TM) pain; (2) orofacial pain mainly attributed to non-dental pain as neuralgias, facial localization of primary headaches or idiopathic orofacial pain. The second group is uncommon, often described by single case reports, can often show overlapping symptoms with the first group, and represents a clinical challenge, carrying the risk of undervaluation and possibly invasive odontoiatric treatment. We aimed to describe a clinical pediatric series of non-dental orofacial pain and better to underline some topographic and clinical features associated with them. We retrospectively collected the data of children admitted to our headache centers (Bari, Palermo, Torino) from 2017 to 2021. Our inclusion criterion was the presence of non-dental orofacial pain following the topographic criteria of 3° International Classification of Headache Disorders (ICHD-3), and exclusion criteria included the pain syndromes attributed to the dental disorders and pain syndromes due to the secondary etiologies Results. Our sample comprised 43 subjects (23/20 M/F, in the range of ages 5–17). We classified them int: 23 primary headaches involving the facial territory during attacks, 2 facial trigeminal autonomic cephalalgias, 1 facial primary stabbing headache, 1 facial linear headache, 6 trochlear migraines, 1 orbital migraine 3 red ear syndrome and 6 atypical facial pain. All patients described debilitating pain for intensity (moderate/severe), 31 children had episodic attacks, and 12 had continuous pain. Almost all received drugs for acute treatment (less than 50% were satisfied), and some received non-pharmacological treatment associated with drug therapy Conclusion. Although rare OFP can occur in pediatric age, it can be debilitating if unrecognized and untreated, affecting the psychophysical well-being of young patients. We highlight the specific characteristics of the disorder for a more correct and earlier identification during the diagnostic process, already difficult in pediatric age, and to define the approach and possible treatment to prevent negative outcomes in adulthood.

Hyper-/hypoglycemic states are rare but well-established causes of hyperkinetic movements, including chorea and ballismus, usually associated with brain lesions in the basal ganglia. We report a case of hemichorea-hemiballismus (HCHB) syndrome that developed after a severe hypoglycemic episode in a 71-year-old man with poorly controlled type 2 diabetes mellitus. Uncommonly, brain MRI showed contralateral cortical-subcortical T2 and T2-FLAIR-hyperintense frontoparietal lesions, with cingulate gyrus involved, while the basal ganglia were unaffected. In patients with hypoglycemic encephalopathy associated with cortical lesions, the long-term prognosis is usually poor. Nevertheless, in our patient, the dyskinesias and the cerebral lesions progressively regressed by achieving good glycemic control. After four and 12 months, the patient’s neurological examination was normal. To our knowledge, this is the first evidence of hypoglycemic etiology of cortical HCHB syndrome, supporting recent theories that cortical circuitries may independently contribute to the pathogenesis of chorea and ballismus. This is also the first report of cingulate gyrus involvement in hypoglycemic encephalopathy. Finally, this case may indicate that a subset of patients with cortical lesions due to hypoglycemia could present a good clinical outcome, likely depending on the size of the lesions and the duration and severity of the hypoglycemic episode.

ObjectiveWhile human papillomavirus (HPV) has been shown to play a significant role in cervical cancer carcinogenesis (HPV associated cases), a considerable percentage of cervical cancers occur independently of HPV status (HPV independent).MethodsIn this retrospective study of 254 locally advanced cervical cancer patients treated with chemoradiotherapy and radical surgery, HPV genotypes were determined using the Anyplex II HPV28 kit that uses multiplex, real time polymerase chain reaction technology. The primary endpoints of this study were to evaluate the complete response to chemoradiotherapy (pathologic complete response), the presence of microscopic (<3 mm, pathologic micro partial response, group 1) and macroscopic (>3 mm, pathologic macro partial response, group 2) residual carcinoma in the cervix, and the persistence of metastatic lymph nodes (group 3) in HPV independent cervical cancers. Secondary endpoints were evaluation of disease-free survival and overall survival.ResultsOf 254 patients studied, 21 cases (8.3%) of cervical cancer were determined to be HPV independent. The percentage of pathologic complete response was found to be higher in the HPV associated group compared with the HPV independent group (pConclusionsThis study showed that HPV status at diagnosis could be a relevant factor for clinical outcomes in locally advanced cervical cancer patients.

To evaluate latency and duration of a brachial plexus block technique in eastern box turtles performed with 2% lidocaine at three dose rates.Prospective, randomized, blinded crossover study.Adult eastern box turtles, two for drug dose evaluation and a group of six (three male, three female) weighing 432 ± 40 g (mean ± standard deviation) for the main study.Animals were randomly assigned to four brachial plexus blocks with lidocaine at 5, 10 and 20 mg kgMotor and sensory blockade was achieved in treatments LID10 and LID20 in one turtle, with a latency of 10 minutes and duration of 50 minutes for both doses. Raising of the ipsilateral lower palpebra occurred with both blocks. Turtles administered lidocaine experienced higher HR compared with CON, and HR decreased over time for all individuals. Mentation and fThe technique was unreliable in producing brachial plexus motor and sensory blockade at the lidocaine doses evaluated in this study. HR was higher in lidocaine-administered turtles but remained within normal limits for the species. No change in mentation or fGeneral anesthesia with systemic analgesia is recommended for surgical procedures involving the chelonian thoracic limb. Further studies are needed to optimize a brachial plexus block in this species.

During acute health decompensations for seriously ill patients, emergency clinicians often determine the intensity end-of-life care. Little is known about how emergency clinicians conduct these conversations, especially among those who have received serious illness communication training.To determine the self-reported practice patterns of code status conversations by emergency clinicians with and without serious illness communication training.A cross-sectional survey was conducted among emergency clinicians with and without a recent evidence-based, serious illness communication training tailored for emergency clinicians. Emergency clinicians were included from two academic medical centers. A five-point Likert scale ("very unlikely" to "very likely" to ask) was used to assess the self-reported likelihood of asking about patients' preferences for medical procedures and patients' values and goals.Among 161 respondents (71% response rate), 77 (48%) received the training. A total of 70% of emergency clinicians reported asking about procedure-based questions, and only 38% reported asking about patient's values regarding end-of-life care. For value-based questions, statistically significant differences were observed between emergency clinicians who underwent the training and those who did not in four of the seven questions asked (e.g., the higher odds of exploring the patient's life priorities [adjusted OR = 4.34, 95% CI = 1.95-9.65, P-value0.001]). No difference was observed in the self-reported rates of all procedure-based questions between the two groups.Most emergency clinicians reported asking about procedure-based questions, and some asked about patient's value-based questions. Clinicians with recent serious illness communication training may ask more about some values and priorities.

The magnetism of electrospun porous high-entropy spinel oxides can be tuned by changing a single cation.

Oxygen vacancy-rich high-entropy (Cr0.2Mn0.2Fe0.2Co0.2Ni0.2)3O4 oxide nanofibres with granular structure are good candidates for the preparation of electrocatalytic inks.

Geopolitical shifts are having an increased impact on multinational enterprises. We propose a framework that illustrates how corporate responses to geopolitical shifts vary with operational and reputational considerations. We build our framework from evidence of how five Danish multinationals with operations in Russia responded to the Russian invasion of Ukraine. The selected cases highlight several drivers of operational and reputational considerations that offer reasons for MNEs’ heterogeneity in strategic responses. Based on our framework, we derive recommendations for managers in terms of increased preparedness and awareness. We also recommend that policymakers reconsider their strategies for using corporations as geopolitical instruments.

There is converging evidence that abnormal thalamocortical interactions contribute to attention deficits and sensory sensitivities in autism spectrum disorder (ASD). However, previous functional MRI studies of thalamocortical connectivity in ASD have produced inconsistent findings in terms of both the direction (hyper vs. hypoconnectivity) and location of group differences. This may reflect, in part, the confounding effects of head motion during scans. In the present study, we investigated resting-state thalamocortical functional connectivity in 8-25 year-olds with ASD and their typically developing (TD) peers. We used pre-scan training, on-line motion correction, and rigorous data quality assurance protocols to minimize motion confounds. ASD participants showed increased thalamic connectivity with temporal cortex relative to TD. Both groups showed similar age-related decreases in thalamic connectivity with occipital cortex, consistent with a process of circuit refinement. Findings of thalamocortical hyperconnectivity in ASD are consistent with other evidence that decreased thalamic inhibition leads to increase and less filtered sensory information reaching the cortex where it disrupts attention and contributes to sensory sensitivity. This literature motivates studies of mechanisms, functional consequences, and treatment of thalamocortical circuit dysfunction in ASD.

Resumen Se buscó adaptar al contexto argentino dos escalas que evalúan preferencias psicoterapéuticas: el Inventario de Preferencias de Cooper-Norcross (C-NIP-v1.1) y el Cuestionario de Preferencias y Experiencias de Psicoterapia para el Paciente (PEX-1). Ambas escalas fueron administradas a 600 personas (muestra no probabilística). Se realizaron análisis de consistencia interna, dimensionales, y sobre los ítems. Los coeficientes de consistencia interna fueron adecuados para las escalas y sus dimensiones. Los análisis factoriales confirmatorios demostraron un ajuste aceptable a sus estructuras originales. El desempeño de los ítems fue óptimo, con algunas excepciones. Las características psicométricas del PEX-1 y C-NIP-v1.1 indicarían que se ajustan a la aplicación en nuestro contexto. Abstract We sought to adapt to the Argentine context two scales that assess psychotherapeutic preferences: The Cooper-Norcross Preferences Inventory (C-NIP-v1.1) and the Questionnaire of Preferences and Experiences of Psychotherapy for the Patient (PEX-1). We administered both scales in a sample of N=600 people (non-probabilistic). We performed internal consistency, dimensional, and item level analyzes. The internal consistency coefficients were adequate for the total scale and, in general, for each dimension. The confirmatory factor analysis evidenced an adequate fit to the original structures. The performance of the items for the scale and its dimensions was acceptable with few exceptions. The psychometric properties of the C-NIP-v1.1 and the PEX-1 are suitable for their application in our context. Resumo Procuramos adaptar duas escalas que avaliam as preferências psicoterapêuticas ao contexto argentino: o Inventário de Preferências Cooper-Norcross (C-NIP-v1.1) e o Questionário de Preferências e Experiências de Psicoterapia do Paciente (PEX-1). Ambas as escalas foram aplicadas a N = 600 pessoas (amostra não probabilística). Foram realizadas análises de consistência interna, dimensional e sobre os itens. Os coeficientes de consistência interna foram adequados para as escalas e suas dimensões. As análises fatoriais confirmatórias demonstraram um ajuste aceitável às suas estruturas originais. O desempenho dos itens foi ótimo, com algumas exceções. As características psicométricas do PEX-1 e C-NIP-v1.1 indicariam que eles se encaixam na aplicação em nosso contexto. Résumé Nous avons cherché à adapter deux échelles qui évaluent les préférences psychothérapeutiques au contexte argentin: le Cooper-Norcross Preferences Inventory (C-NIP-v1.1) et le Patient Psychotherapy Preferences and Experiences Questionnaire (PEX-1). Les deux échelles ont été administrées à N = 600 personnes (échantillon non probabiliste). Des analyses de cohérence interne, dimensionnelle et sur les éléments ont été réalisées. Les coefficients de cohérence interne étaient adéquats pour les échelles et leurs dimensions. Les analyses factorielles de confirmation ont démontré un ajustement acceptable à leurs structures d’origine. La performance des articles était optimale, à quelques exceptions près. Les caractéristiques psychométriques du PEX-1 et du C-NIP-v1.1 indiqueraient qu’ils correspondent à l’application dans notre contexte.

The editors of most scholarly journals in business and management, including international business (IB) journals such as JIBS, expect authors to make a ‘theory-related’ contribution. Many submissions are rejected outright by the journal’s reviewing editor or after review by field experts because of an insufficient theory-related contribution. In this article, we provide ten actionable guidelines to help authors clarify their theory-related contribution to an extant body of scholarly research, thereby avoiding commonly made mistakes.As a preamble to our ten guidelines, we should like to note that it matters much to frame an empirical phenomenon, a research gap and a research question by using field-specific ‘language’. Appropriate framing means that the author demonstrates adequate knowledge (even when adopting a critical perspective) of the field’s main building blocks, including the shared assumptions and common variables viewed relevant by scholars in the field, to examine a series of phenomena of interest. In the case of IB research, these shared assumptions and variables are related to the purposes and goals of IB activities. Shared assumptions and variables are also related to the characteristics and motivations of the parties involved. These parties include the actors steering the internationally operating firm and those affecting the achievement of its goals, as well as the market and non-market institutions that can influence IB. Finally, shared assumptions and variables are linked to a myriad of outcomes of IB activities, both intended and unintended ones.

Massima In caso di sequestro preventivo ex art. 321, comma 1, cod. proc. pen., che abbia a oggetto le quote sociali e il patrimonio della società, la disposizione di un blind trust sulle sole partecipazioni, ancorché totalitarie, non condiziona la titolarità delle componenti patrimoniali riferibili alla società e, per l’effetto, la legittimazione a impugnare il provvedimento cautelare.

The results of the 4th National Report for the Italian flora under the 92/43/EEC ‘Habitats’ Directive are presented. The outcomes showed a general negative conservation status for plant species, with the worst situation being in the Mediterranean bioregion. At the National level, significant monitoring and conservation activities are required.

Iron accumulation is emerging as a player in aging-related disorders due to its propensity for generating reactive oxygen species (ROS). Studies investigating the role of iron in the pathogenesis of primary osteoarthritis (OA) are limited. We designed a proof-of-principle study to determine the effect of systemic iron deficiency, via an iron deficient diet, on knee OA in an animal model.Twelve-week-old male Hartley guinea pigs received the standard diet (n = 6) or a diet devoid of iron (n = 6) for 19-weeks. Iron levels were determined in the serum, liver, and articular cartilage. Knees were collected to assess structural changes related to OA (microcomputed tomography, histopathology). Immunohistochemistry was performed to evaluate the presence and distribution of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) and ROS-driven 4-hydroxynonenal (4-HNE)-induced protein adducts. Transcript expression was also assessed.Relative to control animals, an iron deficient diet reduced the concentration of this mineral in serum, liver, and articular cartilage. Iron deficient animals had lower histologic OA scores; decreased subchondral bone mineral density was also noted. This reduction in knee joint pathology was accompanied by a decrease in: ADAMTS4 in synovium; and 4-HNE protein adducts from lipid peroxidation in both the menisci and articular cartilage of iron deficient animals. Expression of iron-related genes in these tissues was also altered in treated animals.Results from this study suggest that systemic iron levels may play a role in knee OA pathogenesis, with a short-term deficit in dietary iron reducing the severity of knee cartilage lesions.

Considerar la terminación prematura en psicoterapia es esencial cuando hablamos de eficacia y efectividad. El objetivo de este trabajo fue evaluar la relación entre las características demográficas de los pacientes y el nivel de severidad al inicio del tratamiento con la terminación prematura en psicoterapia. Método. Estudio longitudinal, con una muestra clínica de N = 134 pacientes. Se administraron en el proceso de admisión el PID – 5 y el OQ.45.2 y en la tercera sesión de psicoterapia, octava y última sesión el OQ.45.2. Se realizaron análisis de regresión logística con deserción como variable de resultado, y correlaciones de Spearman para estimar la relación entre las características personales y la cantidad de sesiones en el grupo que abandonó el proceso psicoterapéutico. Resultados. El malestar al inicio del proceso psicoterapéutico no se relacionó con la deserción. La única faceta de personalidad relacionada con la deserción fue Labilidad Emocional, a menor Labilidad Emocional, hubo una probabilidad 16% menor de deserción. Un mayor nivel socioeconómico y nivel de instrucción redujeron en un 42% y 16% las probabilidades de deserción, respectivamente. Los varones, por su parte, tuvieron 3 veces más probabilidad de abandonar el tratamiento que las mujeres.

This study explored the impact of Strengths Model training, supervision and mentorship on the practice of a group of multi-disciplinary mental health clinicians that included mental health nurses, social workers, psychologists, and occupational therapists. A qualitative approach that combined critical realism and grounded theory was used. The findings demonstrated how a substantive category, Getting to Know Clients Better, facilitated participants' progression through a basic social psychological process, Becoming a Strengths-Informed Practitioner. This process consisted of a discernible and sustained change towards more person-centred, hopeful, and recovery-oriented practice. The findings also described an underlying generative mechanism for this, the Client Becomes Visible, which accorded with theoretical models of empathy, based on enhanced cognitive processing. The strength-based approach to practice facilitated the establishment of a collaborative relationship and a stronger therapeutic alliance between the client and clinician. The research demonstrated that Strengths Model is an effective vehicle for improving recovery-orientated mental health services.

Hypothermia is a promising therapeutic strategy for severe vasospasm and other types of non-thrombotic cerebral ischemia, but its clinical application is limited by significant systemic side effects. We aimed to develop an intraventricular device for the controlled cooling of the cerebrospinal fluid, to produce a targeted hypothermia in the affected cerebral hemisphere with a minimal effect on systemic temperature. An intraventricular cooling device (acronym: V-COOL) was developed by in silico modelling, in vitro testing, and in vivo proof-of-concept application in healthy Wistar rats (n = 42). Cerebral cortical temperature, rectal temperature, and intracranial pressure were monitored at increasing flow rate (0.2 to 0.8 mL/min) and duration of application (10 to 60 min). Survival, neurological outcome, and MRI volumetric analysis of the ventricular system were assessed during the first 24 h. The V-COOL prototyping was designed to minimize extra-cranial heat transfer and intra-cranial pressure load. In vivo application of the V-COOL device produced a flow rate-dependent decrease in cerebral cortical temperature, without affecting systemic temperature. The target degree of cerebral cooling (− 3.0 °C) was obtained in 4.48 min at the flow rate of 0.4 mL/min, without significant changes in intracranial pressure. Survival and neurological outcome at 24 h showed no significant difference compared to sham-treated rats. MRI study showed a transient dilation of the ventricular system (+ 38%) in a subset of animals. The V-COOL technology provides an effective, rapid, selective, and safe cerebral cooling to a clinically relevant degree of − 3.0 °C.

Osteoarthritis (OA) is a leading cause of morbidity among aging populations, yet symptom and/or disease-modification remains elusive. Adipose-derived mesenchymal stromal cells (adMSCs) have demonstrated immunomodulatory and anti-inflammatory properties that may alleviate clinical signs and interrupt disease onset and progression. Indeed, multiple manuscripts have evaluated intra-articular administration of adMSCs as a therapeutic; however, comparatively few evaluations of systemic delivery methods have been published. Therefore, the aim of this study was to evaluate the short-term impact of intravenous (IV) delivery of allogeneic adMSCs in an established model of spontaneous OA, the Hartley guinea pig. Animals with moderate OA received once weekly injections of 2 × 10

Background Multiple sclerosis (MS) is characterized by phenotypical heterogeneity, partly resulting from demographic and environmental risk factors. Socio-economic factors and the characteristics of local MS facilities might also play a part. Methods This study included patients with a confirmed MS diagnosis enrolled in the Italian MS and Related Disorders Register in 2000–2021. Patients at first visit were classified as having a clinically isolated syndrome (CIS), relapsing–remitting (RR), primary progressive (PP), progressive-relapsing (PR), or secondary progressive MS (SP). Demographic and clinical characteristics were analyzed, with centers’ characteristics, geographic macro-areas, and Deprivation Index. We computed the odds ratios (OR) for CIS, PP/PR, and SP phenotypes, compared to the RR, using multivariate, multinomial, mixed effects logistic regression models. Results In all 35,243 patients from 106 centers were included. The OR of presenting more advanced MS phenotypes than the RR phenotype at first visit significantly diminished in relation to calendar period. Females were at a significantly lower risk of a PP/PR or SP phenotype. Older age was associated with CIS, PP/PR, and SP. The risk of a longer interval between disease onset and first visit was lower for the CIS phenotype, but higher for PP/PR and SP. The probability of SP at first visit was greater in the South of Italy. Discussion Differences in the phenotype of MS patients first seen in Italian centers can be only partly explained by differences in the centers’ characteristics. The demographic and socio-economic characteristics of MS patients seem to be the main determinants of the phenotypes at first referral.

Initial release of repo for GBE manuscript acceptance

In this chapter, we briefly review the history of X-ray astronomy through its missions. We follow a temporal development, from the first instruments onboard rockets and balloons to the most recent and complex space missions. We intend to provide the reader with detailed information and references on the many missions and instruments that have contributed to the success of the exploration of the X-ray universe. We have not included missions that are still operating, providing the worldwide community with high-quality observations. Specific chapters for these missions are included in a dedicated section of the handbook.

We report on multiwavelength target-of-opportunity observations of the blazar PKS 0735+178, located 2.2$^\circ$ away from the best-fit position of the IceCube neutrino event IceCube-211208A detected on December 8, 2021. The source was in a high-flux state in the optical, ultraviolet, X-ray, and GeV gamma-ray bands around the time of the neutrino event, exhibiting daily variability in the soft X-ray flux. The X-ray data from Swift-XRT and NuSTAR characterize the transition between the low-energy and high-energy components of the broadband spectral energy distribution (SED), and the gamma-ray data from Fermi -LAT, VERITAS, and H.E.S.S. require a spectral cut-off near 100 GeV. Both X-ray and gamma-ray measurements provide strong constraints on the leptonic and hadronic models. We analytically explore a synchrotron self-Compton model, an external Compton model, and a lepto-hadronic model. Models that are entirely based on internal photon fields face serious difficulties in matching the observed SED. The existence of an external photon field in the source would instead explain the observed gamma-ray spectral cut-off in both leptonic and lepto-hadronic models and allow a proton jet power that marginally agrees with the Eddington limit in the lepto-hadronic model. We show a numerical lepto-hadronic model with external target photons that reproduces the observed SED and is reasonably consistent with the neutrino event despite requiring a high jet power., 21 pages, 3 figures, accepted by ApJ

Translational research requires data at multiple scales of biological organization. Advancements in sequencing and multi-omics technologies have increased the availability of these data but researchers face significant integration challenges. Knowledge graphs (KGs) are used to model complex phenomena, and methods exist to automatically construct them. However, tackling complex biomedical integration problems requires flexibility in the way knowledge is modeled. Moreover, existing KG construction methods provide robust tooling at the cost of fixed or limited choices among knowledge representation models. PheKnowLator (Phenotype Knowledge Translator) is a semantic ecosystem for automating the FAIR (Findable, Accessible, Interoperable, and Reusable) construction of ontologically grounded KGs with fully customizable knowledge representation. The ecosystem includes KG construction resources (e.g., data preparation APIs), analysis tools (e.g., SPARQL endpoints and abstraction algorithms), and benchmarks (e.g., prebuilt KGs and embeddings). We evaluate the ecosystem by surveying open-source KG construction methods and analyzing its computational performance when constructing 12 large-scale KGs. With flexible knowledge representation, PheKnowLator enables fully customizable KGs without compromising performance or usability.

In July 2021, PKS 1510-089 exhibited a significant flux drop in the high-energy gamma-ray (by a factor 10) and optical (by a factor 5) bands and remained in this low state throughout 2022. Similarly, the optical polarization in the source vanished, resulting in the optical spectrum being fully explained through the steady flux of the accretion disk and the broad-line region. Unlike the aforementioned bands, the very-high-energy gamma-ray and X-ray fluxes did not exhibit a significant flux drop from year to year. This suggests that the steady-state very-high-energy gamma-ray and X-ray fluxes originate from a different emission region than the vanished parts of the high-energy gamma-ray and optical jet fluxes. The latter component has disappeared through either a swing of the jet away from the line-of-sight or a significant drop in the photon production efficiency of the jet close to the black hole. Either change could become visible in high-resolution radio images., 18 pages, 4 figures, 6 tables; accepted for publication in ApJ Letters; corresponding authors: Joleen Barnard, Markus Boettcher, Hester Schutte, Michael Zacharias