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Background: Alcohol Use Disorder (AUD) is a major contributor to global morbidity, mortality, and socioeconomic burden. Cravings, defined as intense urges to consume alcohol, play a central role in relapse and are recognized as a diagnostic criterion in DSM-5. Pharmacological strategies targeting cravings may offer immediate or short-term relief, complementing existing long-term approaches. However, evidence on short-term (up to approximately three months) anti-craving interventions remains fragmented. Objective: To systematically review randomized, double-blind, placebo-controlled trials (RCTs) assessing the short-term effects of pharmacological treatments on cue-induced alcohol cravings. Methods: A systematic search was conducted in PubMed and PsycINFO using terms related to alcohol, craving, and randomized controlled designs. Eligibility included clinical trials on alcohol-dependent participants that evaluated craving as an outcome. Exclusion criteria encompassed non-clinical studies, non-pharmacological interventions, animal studies, single-blind trials, and studies with psychiatric comorbidities. Study quality was appraised using Cochrane and Joanna Briggs Institute tools. Results: From 442 studies screened, 26 RCTs fulfilled the inclusion criteria. In total, 1097 participants were enrolled across the trials (range = 16–125 per study; mean = 44), predominantly male outpatients aged 15–65 years. Craving was assessed primarily with the Visual Analog Scale and Alcohol Urge Questionnaire. Intervention duration ranged from 1 to 98 days. Naltrexone consistently reduced cue-induced craving across four trials, with additional benefit observed when combined with ondansetron. Varenicline and acamprosate also demonstrated reductions in craving and drinking. Memantine showed efficacy in craving reduction but was not assessed for abstinence. Topiramate was effective, whereas gabapentin showed limited short-term benefit. Other agents (e.g., citalopram, oxytocin, ondansetron, quetiapine) yielded mixed findings, often limited to single studies. Overall, 58% of trials reported positive anti-craving effects, 23% no difference, and 8% increased craving versus placebo. However, these findings should be interpreted in light of important methodological limitations, including small sample sizes and heterogeneous experimental paradigms. Conclusions: This review suggests that naltrexone and varenicline appear to be the most consistently supported short-term pharmacotherapies for alcohol craving within the available evidence, with promising but less consistent findings for memantine, acamprosate, and topiramate. These results highlight potential candidates for immediate craving management in AUD, while underscoring the need for larger and longer-term trials to confirm their efficacy and safety.

The present study deals with the development of a continuous cooling transformation diagram corresponding to the coarse-grained heat-affected zone of a high-strength all-weld metal with a minimum yield strength of 1100 MPa fabricated via gas metal arc welding. Dilatometry tests were conducted to determine the transition temperatures. High-resolution imaging methods, such as transmission electron microscopy and atom probe tomography, as well as nanoindentation, were employed to resolve the microstructural constituents. At fast cooling rates ( t 8/5 from 1.4 to 25 s), the microstructure comprises a mixture of martensite and coalesced bainite, with a slight increase in the content of coalesced bainite with faster cooling. This demonstrates that coalesced bainite cannot be avoided in the coarse-grained heat-affected zone of the current alloy by increasing the cooling rate. With slower cooling ( t 8/5  ≥ 50 s), the microstructure becomes increasingly bainitic, accompanied by a marginal drop in Vickers hardness. At t 8/5 times of 500 s and 1000 s, the all-weld metal consists of granular bainite with significant amounts of retained austenite and different shaped martensite-austenite constituents. The coarser massive-type constituents contain body-centered cubic grains, sized in the hundreds of nanometers, with a hardness approximately twice as high as that of the surrounding bainitic matrix.

Impulse oscillometry (IOS) has been proposed as an alternative test to evaluate the obstruction of small airways and to detect changes in airways earlier than spirometry. In this study, we sought to determine the utility and association of IOS parameters with spirometry and asthma control in an adult population. Adults 14-82 years of age with asthma were classified into uncontrolled asthma (n=48), partially controlled asthma (n=45), and controlled asthma (n=49) groups, and characterized with fractional exhaled nitric oxide (FE ), IOS, and spirometry in a transversal analysis planned as a one-visit study. The basic parameters evaluated in IOS are resistance at 5 Hz (R ), an index affected by the large and small airway; resistance at 20 Hz (R ), an index of the resistance of large airways; difference between R and R (R -R ), indicative of the function of the small peripheral airways; reactance at 5 Hz (X ), indicative of the capacitive reactance in the small peripheral airways; resonance frequency (Fres), the intermediate frequency at which the reactance is null, and reactance area (XA), which represents the total reactance (area under the curve) at all frequencies between 5 Hz to Fres. There were statistical differences between groups in standard spirometry and IOS parameters reflecting small peripheral airways (R , R , R -R , Fres, XA and X ) ( <0.001). Accuracy of IOS and/or spirometry to discriminate between controlled asthma vs partially controlled asthma and uncontrolled asthma was low (AUC=0.61). Using linear regression models, we found a good association between spirometry and IOS. In order to evaluate IOS as an alternative or supplementary method for spirometry, we designed a predictive model for spirometry from IOS applying a penalized regression model (Lasso). Then, we compared the original spirometry values with the values obtained from the predictive model using Bland-Altman plots, and the models showed an acceptable bias in the case of FEV /FVC, FEV %, and FVC%. IOS did not show a discriminative capacity to correctly classify patients according to the degree of asthma control. However, values of IOS showed good association with values of spirometry. IOS could be considered as an alternative and accurate complement to spirometry in adults. In a predictive model, spirometry values estimated from IOS tended to overestimate in low values of \"real\" spirometry and underestimate in high values.

Chimeric antigen receptor (CAR) T-cell therapy has emerged recently as a standard of care treatment for patients with relapsed or refractory acute lymphoblastic leukemia (ALL) and several subtypes of B-cell non-Hodgkin lymphoma (NHL). However, its use remains limited to highly specialized centers, given the complexity of its administration and its associated toxicities. We previously reported our experience in using a novel Sleeping Beauty (SB) CD19-specific CAR T-cell therapy in the peri-transplant setting, where it exhibited an excellent safety profile with encouraging survival outcomes. We have since modified the SB CD19 CAR construct to improve its efficacy and shorten its manufacturing time. We report here the phase 1 clinical trial safety results. Fourteen heavily treated patients with relapsed/refractory ALL and NHL were infused. Overall, no serious adverse events were directly attributed to the study treatment. Three patients developed grades 1-2 cytokine release syndrome and none of the study patients experienced neurotoxicity. All dose levels were well tolerated and no dose-limiting toxicities were reported. For efficacy, 3 of 8 (38%) patients with ALL achieved CR/CRi (complete remission with incomplete count recovery) and 1 (13%) patient had sustained molecular disease positivity. Of the 4 patients with DLBCL, 2 (50%) achieved CR. The SB-based CAR constructs allow manufacturing of targeted CAR T-cell therapies that are safe, cost-effective and with encouraging antitumor activity.

Mutations on Brauer configurations are introduced and associated with some suitable automata to solve generalizations of the Chicken McNugget problem. Additionally, based on marked order polytopes, the new Diophantine equations called Gelfand–Tsetlin equations are also solved. The approach allows algebraic descriptions of some properties of the AES key schedule via some Brauer configuration algebras and suitable non-deterministic finite automata (NFA).

Chronic graft-versus-host disease (cGvHD) remains a major complication of allogeneic hematopoietic stem cell transplantation (HSCT). A number of studies support a role for B cells in the pathogenesis of cGvHD. In this study, we report the presence of an expanded population of CD19+CD21- B cells with features of exhaustion in the peripheral blood of patients with cGvHD. CD21- B cells were significantly increased in patients with active cGvHD compared to patients without cGvHD and healthy controls (median 12.2 versus 2.12 versus 3%, respectively;  < 0.01). Compared with naïve (CD27-CD21+) and classical memory (CD27+CD21+) B cells, CD19+CD21- B cells in cGvHD were CD10 negative, CD27 negative and CD20hi, and exhibited features of exhaustion, including increased expression of multiple inhibitory receptors such as FCRL4, CD22, CD85J, and altered expression of chemokine and adhesion molecules such as CD11c, CXCR3, CCR7, and CD62L. Moreover, CD21- B cells in cGvHD patients were functionally exhausted and displayed poor proliferative response and calcium mobilization in response to B-cell receptor triggering and CD40 ligation. Finally, the frequencies of circulating CD21- B cells correlated with cGvHD severity in patients after HSCT. Our study further characterizes B cells in chronic cGVHD and supports the use of CD21-CD27-CD10- B cell frequencies as a biomarker of disease severity.

Ichthyomyini, a morphologically distinctive group of Neotropical cricetid rodents, lacks an integrative study of its systematics and biogeography. Since this tribe is a crucial element of the Sigmodontinae, the most speciose subfamily of the Cricetidae, we conducted a study that includes most of its recognized diversity (five genera and 19 species distributed from southern Mexico to northern Bolivia). For this report we analyzed a combined matrix composed of four molecular markers ( RBP3 , GHR , RAG1 , Cytb ) and 56 morphological traits, the latter including 15 external, 14 cranial, 19 dental, five soft-anatomical and three postcranial features. A variety of results were obtained, some of which are inconsistent with the currently accepted classification and understanding of the tribe. Ichthyomyini is retrieved as monophyletic, and it is divided into two main clades that are here recognized as subtribes: one to contain the genus Anotomys and the other composed by the remaining genera. Neusticomys (as currently recognized) was found to consist of two well supported clades, one of which corresponds to the original concept of Daptomys . Accordingly, we propose the resurrection of the latter as a valid genus to include several species from low to middle elevations and restrict Neusticomys to several highland forms. Numerous other revisions are necessary to reconcile the alpha taxonomy of ichthyomyines with our phylogenetic results, including placement of the Cajas Plateau water rat (formerly Chibchanomys orcesi ) in the genus Neusticomys ( sensu stricto ), and the recognition of at least two new species (one in Neusticomys , one in Daptomys ). Additional work is necessary to confirm other unanticipated results, such as the non-monophyletic nature of Rheomys and the presence of a possible new genus and species from Peru. Our results also suggest that ichthyomyines are one of the main Andean radiations of sigmodontine cricetids, with an evolutionary history dating to the Late Miocene and subsequent cladogenesis during the Pleistocene.

The “la Caixa” Foundation has been experimenting with artificial intelligence (AI)-assisted decision-making geared toward alleviating the administrative burden associated with the evaluation pipeline of its flagship funding program, piloting an algorithm to detect immature project proposals before they reach the peer review stage, and suggest their removal from the selection process to a human overseer. In this article, we explore existing uses of AI by publishers and research funding organizations to automate their selection pipelines, in addition to analyzing the conditions under which the focal case corresponds to a responsible use of AI and the extent to which these conditions are met by the current implementation, highlighting challenges and areas of improvement.

The growing ageing population and prevalence of comorbidities pose significant healthcare challenges, from increasing hospitalisations to dementia risk. Healthcare systems primarily treat single conditions, overlooking the complex interplay of chronic diseases. Advances in wearable technology and remote healthcare monitoring technologies offer opportunities to enhance management of comorbidities and early intervention to improve healthcare outcomes. This study presents the RESILIENT dataset, a collection of physiological, sleep, and mental health assessment data conducted as part of an ageing-related comorbidities and dementia study. The RESILIENT study has developed a digital platform to integrate data from wearable devices and in-home monitoring technologies to track physiological, sleep, and cognitive patterns. The validation analysis using the Resilient data highlights correlations between cognitive function, mental health, physical activity, and sleep, aligning with existing literature. By leveraging this dataset, researchers can develop predictive models for early detection and personalised interventions aimed at reducing unplanned hospital admissions and improving health outcomes. The study provides technical foundations and pilot validation for constructing virtual wards to support and complement healthcare services.

The objective of this work was to quantify and characterize the lipid fraction of coffee beans grown in different agroclimatic zones of the department of Quindío, seeking to provide coffee growers with useful information about the coffee produced on their farms and the ability to determine coffee quality and sensory attributes. The lipid extraction process was carried out using two different methods: Soxhlet and Soxtec. The bias was established through concordance analysis using the Bland–Altman test to determine the correlation between the two extraction methods. The final results were compared for each agroclimatic zone, and no significant differences were found between the values for average lipid content of the coffee, which varied between 12.01% and 12.90%. When characterizing the profile of fatty acids present in the lipid fraction of coffee using the technique of gas chromatography coupled to mass spectrometry, it was evidenced that the major acids present in the green coffee bean were linoleic acid and palmitic acid, with an average content between 39.83–40.83% and 36.92–37.90%, respectively, and that these fatty acid contents presented statistically significant differences in areas with higher elevations, higher relative humidity and less sunlight (zones 3 and 4). Stearic acid presented differences in all of the agroclimatic zones.