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Abstract Orofacial clefts are among the most prevalent birth defects, with severe medical and psychosocial consequences. Cleft lip with or without cleft palate (CL ± P) and cleft palate only (CPO) affect on average nearly 1/700 births worldwide. The cause of most non-syndromic cases is unknown. Maternal factors and disorders are assumed to modify the risk of orofacial clefting. In the present study, we performed a systematic review and meta-analysis to analyze the effects of maternal underweight, obesity, hypertension, diabetes, as well as smoking, and alcohol consumption on the development of orofacial clefts. As CL ± CP and CPO have distinct pathogenetic backgrounds, these cleft subtypes were assessed separately. Altogether, 5,830 studies were identified and 64 of them met the inclusion and exclusion criteria. Obesity significantly elevated the odds of clefting (OR = 1.28, CI:1.08–1.51) (ORCL±CP = 1.23, CI:1.01–1.50; ORCPO = 1.31, CI:0.97–1.77). Maternal underweight also significantly increased the odds of clefting (OR = 1.21 CI:1.06–1.38). In mothers with type 1 diabetes, the odds of cleft development were significantly elevated (OR = 1,75, CI:1.45–2.12). Essential hypertension was also associated with higher odds of developing cleft (OR = 1.55, CI:1.18–2.03). Smoking during pregnancy significantly elevated the odds of cleft development (OR = 1.55, CI:1.34–1.79) (ORCL±CP = 1.58, CI:1.36–1.83; ORCPO = 1.50, CI:1.15–1.96). Passive smoking was even more damaging than active tobacco use, but alcohol consumption had no effect. In conclusion, this study clearly showed the importance of maintaining normal maternal body weight and emphasized the importance of hypertension and type 1 diabetes care in the first months of pregnancy. It also highlighted similarnegative effects of passive and active smoking, while alcohol consumption did not seem to be a significant risk factor for cleft development. However, there is a complete lack of available studies on the interactions of these factors, which is an essential direction for improving prevention.

To the Editor, The perioperative risk associated with aortic stenosis during noncardiac surgery (NCS) depends on the presence of symptoms, the severity of aortic stenosis, concomitant cardiovascular diseases, and the risk associated with noncardiac comorbidity. Severe symptomatic aortic stenosis is a major risk factor for postoperative heart failure and a predictor of 30-day and long-term mortality after noncardiac surgery; therefore, an appropriate perioperative strategy is essential in patients undergoing intermediate- or high-risk noncardiac surgery.1,2 Hip and vertebral fractures, which are highly prevalent in the elderly population, are usually due to accidental falls and considered intermediate-risk interventions.3 Nonetheless, these patients are characterized by their advanced age and the presence of concomitant diseases, which increases their surgical risk. In this context, the management of aortic stenosis is associated with reduced morbidity and mortality rates in patients undergoing intermediate or high-risk noncardiac surgery.4,5 The perioperative management of patients with severe symptomatic aortic stenosis requiring uncertain trauma surgery is challenging. We present a series of 4 consecutive patients with a past medical history of severe symptomatic aortic stenosis with a trauma emergency, 3 of them due to hip fracture and 1 due to vertebral fracture, all after accidental falls, in whom perioperative management of aortic stenosis...

Introducción. La relación entre la obesidad y el consumo de alcohol es un tema de gran interés para la salud pública. Las bebidas alcohólicas aportan calorías adicionales a la dieta, lo que podría ser un factor relevante en el riesgo de sobrepeso. Sin embargo, su asociación con la ganancia de peso es controversial y está influenciada por múltiples factores. Objetivo. Analizar la relación entre la ingestión moderada de alcohol y el índice de masa corporal, y las variables que pueden influir en dicha relación. Materiales y métodos. La muestra estuvo constituida por 155 personas de Puerto Madryn (Argentina). Cada participante contestó un cuestionario sobre salud, estilo de vida, factores demográficos y socioeconómicos. Se tomaron medidas antropométricas y se tipificaron los polimorfismos de 18 genes relacionados con el metabolismo del alcohol. Resultados. Se encontró que el consumo moderado de alcohol está asociado con un índice de masa corporal más bajo, particularmente en el sexo femenino. Un aumento de 14 gramos de alcohol estuvo asociado con un riesgo de 0,68 para la obesidad y 0,71 para el sobrepeso. La variante T del marcador rs4646543 (ALDH1A1), un gen involucrado en el metabolismo del alcohol y en la adipogénesis, se asoció con una mayor frecuencia de consumo de bebidas alcohólicas. Conclusión. Los hallazgos del presente trabajo sugieren que el consumo moderado de alcohol no contribuye significativamente al peso corporal en la muestra estudiada. Además, la asociación con ciertas variantes genéticas, como las del gen ALDH1A1, podría explicar biológicamente la relación inversa observada entre el peso y el consumo de alcohol.

Abstract The Coma Recovery Scale-revised (CRS-r) is the gold standard for the behavioral assessment of patients with Disorders of Consciousness (DoCs). However, the misdiagnosis rate is around 40%. For this reason, recent guidelines suggested enhancing the assessment with neurophysiological measures: among these, surface electromyography (sEMG) represents a convenient bedside solution. This work presents the use of the STRIVEfc system, a wearable device that allows CRS-r administration while recording four sEMG signals. STRIVEfc was employed in 40 sessions on 33 DoCs patients and the sEMG was analyzed to look for voluntary and consistent over threshold (OT) muscular activities. Their duration, amplitude, and number were retained and compared between patients in Unresponsive Wakefulness Syndrome (UWS) and Minimally Conscious State (MCS), revealing more numerous and significantly longer OTs in the latter group. Lastly, the EMG information was exploited to enrich the behavioral assessment by building the instrumented CRS-r score (ICRS-r). In 9/16 UWS sessions, the ICRS-r score suggested a higher-level functioning, not translated into a behavioral response, compatible with MCS diagnosis. Overall, the use of STRIVEfc allows to reveal hidden muscular patterns not detectable by the clinician, thus improving the characterization of DoCs patient’s functional capabilities and supporting the diagnostic process.

Abstract Animated films are highly popular in society, particularly among children and adolescents. During film production, selecting an adequate colour palette and scene dynamism is crucial for creating a visual impact on the audience. However, the influence of visual aesthetics, such as colour and scene dynamism on visual fatigue remains unexplored. In the present study, visual fatigue was assessed and compared in 30 young participants after viewing two popular films: Spider-Man: Across the Spider-Verse, an active, fast-paced film, and My Neighbour Totoro, a more relaxed film. Both films were viewed twice, once with the original colour palette and once in greyscale. Watching Spider-Man film induced a greater degree of visual fatigue than My Neighbour Totoro in two subjective questionnaires evaluating visual fatigue, and in the vergence facility and binocular accommodative facility tests. Moreover, important differences in the visual dynamics and colour aspects between both films were found. These results demonstrate that the high-paced and high-colour aspects of films directly affect visual fatigue. Future animated film producers should consider these factors that are relevant to their audiences.

Abstract Vitamin D (vitD) deficiency is frequently observed in patients with pulmonary arterial hypertension (PAH) and, in these patients, low levels of vitD correlate with worse prognosis. The aim of this study was to examine the expression and the antiproliferative role of vitD receptor (VDR) and its signalling pathway in the human pulmonary vasculature. VDR presence and expression was analyzed in lungs, pulmonary artery smooth muscle cells (PASMC) and endothelial cells (PAEC) from controls and PAH-patients. VDR expression and VDR-target genes were examined in PASMC treated with calcitriol. The antiproliferative effect of 48 h-calcitriol was studied in PASMC by MTT and BrdU assays. VDR is expressed in PASMC. It is downregulated in lungs and in PASMC, but not in PAEC, from PAH-patients compared to non-hypertensive controls. Calcitriol strongly upregulated VDR expression in PASMC and the VDR target genes KCNK3 (encoding TASK1), BIRC5 (encoding survivin) and BMP4. Calcitriol produced an antiproliferative effect which was diminished by silencing or by pharmacological inhibition of survivin or BMPR2, but not of TASK1. In conclusion, the expression of VDR is low in PAH-patients and can be rescued by calcitriol. VDR exerts an antiproliferative effect in PASMC by modulating survivin and the BMP signalling pathway.

Abstract Inherited retinal degenerations are blinding genetic disorders characterized by high genetic and phenotypic heterogeneity. In this retrospective study, we describe sixteen families with early-onset non-syndromic retinal degenerations in which affected probands carried rare bi-allelic variants in CFAP410, a ciliary gene previously associated with recessive Jeune syndrome. We detected twelve variants, eight of which were novel, including c.373+91A>G, which led to aberrant splicing. To our knowledge this is the first likely pathogenic deep-intronic variant identified in this gene. Analysis of all reported and novel CFAP410 variants revealed no clear correlation between the severity of the CFAP410-associated phenotypes and the identified causal variants. This is supported by the fact that the frequently encountered missense variant p.(Arg73Pro), often found in syndromic cases, was also associated with non-syndromic retinal degeneration. This study expands the current knowledge of CFAP410-associated ciliopathy by enriching its mutational landscape and supports its association with non-syndromic retinal degeneration.

Abstract The effects of physical exercise on attentional performance have received considerable interest in recent years. Most of previous studies that assessed the effect of an acute bout of exercise on attentional performance have generally been approached by analysing single attentional functions in isolation, thus ignoring the functioning of other attentional functions, which characterizes the real perception-action environmental conditions. Here, we investigated the effect of two different intensities (light vs. vigorous) of acute exercise on attentional performance by using the ANTI-Vea, a behavioral task that simultaneously measures three attentional functions (phasic alertness, orienting, and cognitive control) and the executive and arousal components of vigilance. 30 young (age = 20.93; SD = 1.51 years) physically active participants (21 men and 9 women) completed three experimental sessions: the first one to assess their physical fitness and baseline performance in the ANTI-Vea, and the other two sessions (in counterbalanced order) to assess changes in attentional and vigilance performance after an acute bout of light- intensity vs. vigorous- intensity physical exercise. Beneficial effects on some accuracy scores (i.e., overall higher accuracy in the attentional sub-task and fewer false alarms in the executive vigilance sub-task) were observed in the light- intensity exercise condition compared to baseline and vigorous- intensity. Additionally, the RT score of phasic alertness was increased after the light- intensity exercise in comparison with baseline. The present findings suggest that a bout of acute exercise at light- intensity might induce some short-term beneficial effects on some aspects of attention and vigilance.

Abstract PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic mosaic variants that result in constitutive activation of the phosphatidylinositol-3-kinase/AKT/mTOR pathway. Promising responses to molecularly targeted therapy have been reported, although identification of an appropriate agent can be hampered by the mosaic nature and corresponding low variant allele frequency of the causal variant. Moreover, our understanding of the molecular consequences of these variants—for example how they affect gene expression profiles—remains limited. Here we describe in vitro expansion of a human capillary malformation followed by molecular characterization using exome sequencing, single cell gene expression, and targeted long-read single cell RNA-sequencing in a patient with clinical features consistent with Megalencephaly-Capillary Malformation Syndrome (MCAP, a PROS condition). These approaches identified a targetable PIK3CA variant with expression restricted to PAX3+ fibroblast and undifferentiated keratinocyte populations. This study highlights the innovative combination of next-generation single cell sequencing methods to better understand unique transcriptomic profiles and cell types associated with MCAP, revealing molecular intricacies of this genetic syndrome.

Abstract The SnRK1, hexokinase, and TORC1 (TOR, LST8, RAPTOR) are three pivotal kinases at the core of sugar level sensing, significantly impacting plant metabolism and development. We retrieved and analyzed protein sequences of these three kinase pathways from seven sugarcane transcriptome and genome datasets, identifying protein domains, phylogenetic relationships, sequence ancestry, and in silico expression levels. Additionally, we predicted HXK subcellular localization and assessed its enzymatic activity in sugarcane leaves and culms along development in the field. We retrieved 11 TOR, 23 RAPTOR, 55 LST8, 95 SnRK1α, 98 HXK, and 14 HXK-like putative full-length sequences containing all the conserved domains. Most of these transcripts seem to share a common origin with the three ancestral species of sugarcane: Saccharum officinarum, Saccharum spontaneum, and Saccharum barberi. We accessed the expression profile of sequences from one sugarcane transcriptome. We found the highest enzymatic activity of HXK in culms in the first month, which, at this stage, provides carbon (sucrose) and nitrogen (amino acids) for initial plant development. Our approach places novel sugar sensing sequences that work as a guideline for further research into the underlying signaling mechanisms and biotechnology applications in sugarcane.

Abstract Good data quality is vital for personalising plans in rehabilitation. Machine learning (ML) improves prognostics but integrating it with Multiple Imputation (MImp) for dealing missingness is an unexplored field. This work aims to provide post-stroke ambulation prognosis, integrating MImp with ML, and identify the prognostic influential factors. Stroke survivors in intensive rehabilitation were enrolled. Data on demographics, events, clinical, physiotherapy, and psycho-social assessment were collected. An independent ambulation at discharge, using the Functional Ambulation Category scale, was the outcome. After handling missingness using MImp, ML models were optimised, cross-validated, and tested. Interpretability techniques analysed predictor contributions. Pre-MImp, the dataset included 54.1% women, 79.2% ischaemic patients, median age 80.0 (interquartile range: 15.0). Post-MImp, 368 non-ambulatory patients on 10 imputed datasets were used for training, 80 for testing. The random forest (the validation best-performing algorithm) obtained 75.5% aggregated balanced accuracy on the test set. The main predictors included modified Barthel index, Fugl-Meyer assessment/motricity index, short physical performance battery, age, Charlson comorbidity index/cumulative illness rating scale, and trunk control test. This is among the first studies applying ML, together with MImp, to predict ambulation recovery in post-stroke rehabilitation. This pipeline reliably exploits the potential of incomplete datasets for healthcare prognosis, identifying relevant predictors.

Abstract Torque teno virus (TTV) viral load (VL), a component of the human virome, increases during immune suppression or dysregulation. This study aimed to explore TTV VL in youths living with vertically acquired HIV (YWVH) and its potential as an immunovirological marker. We performed an observational, retrospective study involving YWVH under antiretroviral treatment (ART) from the Spanish Cohort of HIV-infected children, adolescents, and vertically HIV-infected patients transferred to Adult Units (CoRISpe-FARO), compared to HIV-negative healthy donors (HD). Plasma TTV VL was assessed by qPCR. T-cell phenotype was analysed on cryopreserved peripheral blood mononuclear cells by flow cytometry. Correlations with baseline CD4 and CD8 and long-term virological evolution were examined. A total of 57 YWVH were compared with 23 HD. YWVH had a median CD4 T-cells of 736 cells/mm3 [IQR: 574–906], a median of 17 years [IQR: 14–20.5] since ART initiation, and 65 months [IQR: 39–116] under HIV-RNA virological control. TTV VL was higher among YWVH and in males compared with females (p

Abstract Background Understanding genetic-metabolite associations has translational implications for informing cardiovascular risk assessment. Interrogating functional genetic variants enhances our understanding of disease pathogenesis and the development and optimization of targeted interventions. Methods In this study, a total of 187 plasma metabolite levels were profiled in 4974 individuals of European ancestry of the GCAT| Genomes for Life cohort. Results of genetic analyses were meta-analysed with additional datasets, resulting in up to approximately 40,000 European individuals. Results of meta-analyses were integrated with reference gene expression panels from 58 tissues and cell types to identify predicted gene expression associated with metabolite levels. This approach was also performed for cardiovascular outcomes in three independent large European studies (N = 700,000) to identify predicted gene expression additionally associated with cardiovascular risk. Finally, genetically informed mediation analysis was performed to infer causal mediation in the relationship between gene expression, metabolite levels and cardiovascular risk. Results A total of 44 genetic loci were associated with 124 metabolites. Lead genetic variants included 11 non-synonymous variants. Predicted expression of 53 fine-mapped genes was associated with 108 metabolite levels; while predicted expression of 6 of these genes was also associated with cardiovascular outcomes, highlighting a new role for regulatory gene HCG27. Additionally, we found that atherogenic metabolite levels mediate the associations between gene expression and cardiovascular risk. Some of these genes showed stronger associations in immune tissues, providing further evidence of the role of immune cells in increasing cardiovascular risk. Conclusions These findings propose new gene targets that could be potential candidates for drug development aimed at lowering the risk of cardiovascular events through the modulation of blood atherogenic metabolite levels.

Abstract COVID-19 pandemic, caused by the novel SARS-CoV-2 virus, has raised significant interest in understanding potential cross-immunity mechanisms. Recent evidence suggests that T-cells associated with common cold coronaviruses (229E, NL63, OC43, HKU1) may provide some level of cross-immunity against SARS-CoV-2. It is also known that the prevalence of smokers among patients admitted to hospital for COVID-19 is lower than expected according to the corresponding country’s smoking prevalence, which is known as smoker’s paradox in COVID-19. No clear consensus to explain it has yet been reached. This phenomenon suggests a complex interaction between smoking and immune response. Nonetheless, very few works have studied the prevalence of smokers in those infected by common cold coronaviruses, and its relation to COVID-19 has not been investigated. We performed a systematic review and meta-analysis to study the prevalence of smokers among patients infected by common cold coronaviruses, and to compare them to the corresponding country’s smoking prevalence. L’Abbé plots were used to visually assess the consistency of the observed effects across the different studies included in the meta-analysis. Additionally, significant differences were found in smoking prevalence among the various types of ccCoV, indicating the need for further research into the biological mechanisms driving these disparities. The results show that smoking prevalence is higher among those patients infected by these coronaviruses than in the general population (OR = 1.37, 95% CI: 0.81–2.33). A study was separately done for the four coronavirus types, and the prevalence of smokers was higher in three of the four than that corresponding to country, gender and study year: OC43 (OR = 1.93, 95% CI: 0.64–5.82); HKU1 (OR = 3.62, 95% CI: 1.21–10.85); NL63 (OR = 1.93, 95% CI: 0.64–5.82); 229E (OR = 0.97, 95% CI: 0.50–1.90). The heterogeneity of the studies was assessed using the Cochrane Chi-squared test, I-squared (I2), and Tau-squared (τ2). This detailed statistical analysis enhances the robustness of our findings and highlights the variations in smoking prevalence among different ccCoVs. Our data suggest that COVID-19 might be less prevalent among smokers due to greater cross-immunity from a larger number or more recent infections by common cold coronaviruses than the non-smoking population, which would explain smoker’s paradox in COVID-19. IMPLICATIONS. The low prevalence of current smokers among SARS-CoV-2 patients is a finding recurrently repeated, even leading to postulate the “smoker’s paradox” in COVID-19. This fact compelled us to study the prevalence of smokers among patients infected by common cold coronaviruses, and to compare them to the corresponding country’s smoking prevalence. Our data could explain smoker’s paradox in COVID-19 by a greater cross immunity due to a larger number, or more recent infections by common cold coronaviruses than the non-smoking population. This manuscript allow understand potential unrevealed mechanism for low prevalence of current smokers among SARS-CoV-2 patients.

Abstract Benefits of neural mobilization (NM) have been described in musculoskeletal patients. The effects of NM on balance appear to be unclear in research, and no studies have tested the possible effects of NM on plantar pressures. Eighteen subjects were evaluated pre and post bilateral gliding of the sciatic nerve and its branches posterior tibial nerve, lateral dorsocutaneous, medial and intermediate dorsocutaneous nerves. Static variables of the plantar footprint and stabilometric variables were measured in a pre-post study. We found no differences in plantar pressure variables, Rearfoot maximum pressure (p = 0.376), Rearfoot medium pressure (p = 0.106), Rearfoot surface (p = 0.896), Midfoot maximum pressure (p = 0.975), Midfoot medium pressure (p = 0.950), Midfoot surface (p = 0.470) Forefoot maximum pressure (p = 0.559), Forefoot medium pressure(p = 0.481), Forefoot surface (p = 0.234), and stabilometric variables either, X-Displacement eyes-open (p = 0.086), Y-Displacement eyes-open (p = 0.544), Surface eyes-open (p = 0.411), Medium speed latero-lateral displacement eyes-open (p = 0.613), Medium speed anteroposterior displacement eyes-open (p = 0.442), X Displacement eyes-closed (p = 0.126), Y-Displacement eyes-closed (p = 0.077), Surface eyes-closed (p = 0.502), Medium speed latero-lateral displacement eyes-closed (p = 0.956), Medium speed anteroposterior displacement eyes-closed (p = 0.349). All variables don´t have significant differences however the measurements had a high reliability with at least an ICC of 0.769. NM doesn´t change plantar pressures or improve balance in healthy non-athletes subjects. NCT05190900.

Abstract Neoadjuvant endocrine therapy (NET) for hormone receptor-positive (HR+) breast cancer might be as effective as chemotherapy, with a better toxicity profile. Blocking a crucial process such as angiogenesis with sunitinib may have a synergistic effect with NET. We aimed to assess the efficacy and safety of neoadjuvant sunitinib plus exemestane in early-stage HR+/HER2-negative breast cancer. In this phase I/II study, postmenopausal women with HR+/HER2− stage II-III breast cancer received neoadjuvant exemestane at conventional dose of 25mg plus sunitinib in a 3 + 3 design at 25mg (3/1weeks scheme) or 37.5mg continuous dose, for 6 months. Coprimary endpoints were the recommended dose of sunitinib combined with exemestane and objective response. Secondary endpoints included safety and biomarkers of early response. For 15 months, 18 patients were enrolled, 15 at sunitinib 25mg and 3 at 37.5mg. Median age was 73, 77% of patients had T2 tumors and 67% node-positive disease. The most common grade 2 toxicity was asthenia (44%), as was hypertension (22%) for grade 3. No grade 4–5 were reported. Twelve patients (66%) achieved an objective response. VEGFR-2 levels significantly decreased after one month of treatment. Differential gene expression analysis showed downregulation of ESR1, PGR and NAT1 in post-treatment samples and upregulation of EGFR, MYC, SFRP1, and FOXC1. PAM50 analysis on 83% of patients showed a prevalence of luminal A subtype, both in pre-treatment (63.6%) and post-treatment tumors (54.5%). Sunitinib plus exemestane was associated with substantial yet reversible toxicities, providing safety, efficacy and biological impact insights of combining an antiangiogenic drug with hormone therapy in early-stage breast cancer. Trial registration: Registered with ClinicalTrials.gov, NCT00931450. 02/07/2009

Abstract To evaluate the hemodynamic effects and the safety profile of fluid bolus resuscitation with hypertonic saline albumin (HSA) in critically ill children, we performed a prospective observational pilot study between October 2018 and May 2021 in the pediatric intensive care unit (PICU) in a tertiary hospital in Madrid, Spain. Sixty-four HSA boluses were analyzed in 23 patients. A mean volume of 5.7 ml/kg (Standard Deviation, SD 2.3 ml/kg) per bolus was infused. Acute hypotension was the main indication. 91% of the patients had a cardiac disease, 56% of them had undergone cardiac surgery in the previous 72 h, and 47.8% associated right ventricular dysfunction. A significant increase in systolic, mean, and diastolic blood pressure and a decrease in the vasoactive index was observed after the infusion of HSA. This effect lasted for twenty-four hours (p

Abstract Human-based modelling and simulation offer an ideal testbed for novel medical therapies to guide experimental and clinical studies. Myocardial infarction (MI) is a common cause of heart failure and mortality, for which novel therapies are urgently needed. Although cell therapy offers promise, electrophysiological heterogeneity raises pro-arrhythmic safety concerns, where underlying complex spatio-temporal dynamics cannot be investigated experimentally. Here, after demonstrating credibility of the modelling and simulation framework, we investigate cell therapy in acute versus chronic MI and the role of cell heterogeneity, scar size and the Purkinje system. Simulations agreed with experimental and clinical recordings from ionic to ECG dynamics in acute and chronic infarction. Following cell delivery, spontaneous beats were facilitated by heterogeneity in cell populations, chronic MI due to tissue depolarisation and slow sinus rhythm. Subsequent re-entrant arrhythmias occurred, in some instances with Purkinje involvement and their susceptibility was enhanced by impaired Purkinje-myocardium coupling, large scars and acute infarction. We conclude that homogeneity in injected ventricular-like cell populations minimises their spontaneous beating, which is enhanced by chronic MI, whereas a healthy Purkinje-myocardium coupling is key to prevent subsequent re-entrant arrhythmias, particularly for large scars.

Abstract The combined release of the predatory mite Amblyseius swirskii (Athias-Henriot) and the mirid Nesidiocoris tenuis (Reuter) provides effective biological control of the tobacco whitefly (Bemisia tabaci (Gennadius)) in greenhouse eggplant. However, knowing how plants’ trichomes affect pest-predator interactions could improve whitefly management. Here, the effect of two varieties with either the presence or absence of trichomes was assessed on naturally occurring whitefly populations and predator abundance in a first experiment under field conditions. Predator-prey models were developed to assess the effect of trichomes on pest and predator population dynamics under field conditions. In a second semi-field experiment, the occurrence and oviposition preferences of B. tabaci and A. swirskii in the same eggplant varieties were compared. Significantly higher numbers of whitefly and mite, adults and eggs, were found on the hairy variety in both experiments. However, no differences were found in N. tenuis abundance between varieties under field conditions. Predator-prey models showed that whitefly growth rate increased in the hairy variety. N. tenuis and A. swirskii showed different fitness parameters according to the variety, with the former displaying better performance in the hairless variety and the latter in the hairy variety. Both predators effectively controlled the increase in whitefly populations in both varieties. Overall, the findings suggest that the hairless variety is more effective in deterring whiteflies. Additionally, the higher population of A. swirskii on the hairy variety indicates that this predator benefited from both the presence of trichomes and the prey.

Introduction: Preclinical and clinical evidence has elucidated that cannabis based medical formulations (CBMFs) may display anxiolytic, anti-depressive, and neuro-protective properties. CBMFs are often considered as novel therapeutic anxiolytic agents that can be prescribed as pharmacotherapy for symptomatic domains in anxiety disorders. Our aim was to explore effectiveness and tolerability of enriched cannabidiol (CBD) oil extract formulations in adults with anxiety symptoms in an outpatient mental health program in Colombia during the COIVD – 19 pandemic. Methods: We conducted an observational, retrospective, real world evidence (RWE) case-series at Zerenia Clinic in Bogotá, Colombia between June 2021 and December 2022. Our convenience sample consisted of people searching for CBMFs for the treatment of anxiety symptoms. A cohort of 24 adults was prescribed with enriched CBD in the form of non-sterile oral liquids suspended in sesame seed oil extracts unspecified anxiety disorder (UAD) and followed throughout the first year of treatment. Primary outcome measures established were the anxiety subscale in the hospital anxiety and depression scale (HADS – A), and the clinical global impression scale with regards to severity (CGI – S) at baseline, 6-month, and 12-month during follow-up. Secondary outcome measures established were HADS depression subscale (HADS – D) and the Epworth Sleepiness Scale (ESS) respectively. Results: After 6 months of treatment with sublingually administered enriched CBD oil extracts in a median dosage of 100mg, more than half (54.17%) of the sample continued to report significant anxiety symptoms. After 12 months, only 37.50% persisted with significant anxiety symptoms with a median dose of 120mgs of enriched CBD oil extracts. Similar subjective improvements were reported with regards to sleep disturbances (SDs) as a secondary outcome. At baseline, less than half (46,83%) of the sample reported significant daytime sleepiness. After 6-months of enriched CBD oil extract treatment, less than one third(29,17%) continued to report SDs. At end point, a high proportion of the sample (87.50%) were considered to have normal daytime sleepiness. No significant adverse–drug reactions or deaths were reported during the 12-month follow-up. Conclusions: Further research should determine the long-term efficacy, safety and appropriate dosages of enriched CBD oil extracts in treating specific anxiety disorders rather than broad and unspecified anxiety symptoms. The state of the art of MCBFs for anxiety disorders should be warranted and solidified through randomized controlled trials. The next stage for cannabis research should be focused in performing head-to-head trials comparing enriched CBD extracts or capsules versus first-line treatments proven to be effective in anxiety disorders.

Abstract Background CD155 is a transmembrane protein that inhibits antitumor immune response and represents a predictor of worse prognosis in non-small-cell lung cancer (NSCLC). However, it remains unexplored its association with clinical characteristics and genomic status of Latin American patients. This study characterizes the CD155 expression and its clinical implications in this population. Methods Tissue biopsies from 86 patients with locally-advanced or metastatic NSCLC were assessed for CD155 protein expression, ALK rearrangements and EGFR mutations. Cutoff values for high CD155 expression (CD155high) were determined from receiver operating characteristic (ROC) curves according to 2-year survival. It was evaluated its association with clinicopathological features, median progression-free survival (mPFS) and overall survival (mOS). Results the cutoff score for CD155high was 155 in the entire cohort and in patients without oncogenic alterations, and it was 110 in patients with oncogenic alterations. Eighty-four patients (97.7%) were CD155 positive, of which fifty-six (65.0%) had CD155high. EGFR L858R mutation related to lower CD155 IHC score than exon 19 deletion. Individuals with CD155high showed a shorter mOS (13.0 vs. 30.8 months; HR: 1.96 [95% CI, 1.15–3.35]; p = 0.014). Patients without oncogenic alterations having a CD155high displayed shorter mPFS (1.6 vs. 6.4 months, HR: 2.09 [95% CI, 1.06–4.20]; p = 0.034) and mOS (2.9 vs. 23.1 months; HR: 1.27 [95% CI, 1.07– 4.42]; p = 0.032). Patients with oncogenic alterations having CD155high only showed a trend to shorter mOS (26.3 vs. 52.0 months; HR: 2.39 [95% CI, 0.98–5.83]; p = 0.058). Conclusion CD155high is a predictor of worse outcomes in patients with advanced NSCLC, predominantly among those without oncogenic alterations. CD155 could be a potential biomarker and a molecular target in patients with poor responses to current therapies.

Introduction: Neuropsychiatric symptoms (NPS) may be disruptive and problematic for patients with Alzheimer’s disease (AD) and for their caregivers. Cannabidiol (CBD) may be a safer alternative. The objective was to evaluate whether CBD-rich oil was effective, and safe in adults with NPS secondary to AD. Methods: An open-label, prospective cohort, single-center study in patients with AD onset after the age of 65 with untreated NPS. A CBD-rich oil was administrated 0.1 mL sublingually every 8–12 h, up-titrated weekly. The primary outcome was to establish a reduction in the NPI-Q severity score of >30% at 12 weeks compared with the baseline. A p value of 30% was 94.9%, while a reduction of >50% was achieved by 54.2%. The improvement was maintained for up to 24 months. Conclusion: This study shows that CBD-rich oil is an effective and safe therapy for treating NPS in AD patients, while also reducing the caregivers’ distress.

Abstract The present study aims to investigate the low-energy consumption and high-efficiency removal of arsenic from aqueous solutions. The designed adsorbent Fe/TBC was synthesized by impregnating iron on torrefaction henequen fibers. Isothermal adsorption experiments indicated maximum adsorption capacities of 7.30 mg/g and 8.98 mg/g for arsenic(V) at 25.0 °C and 40.0 °C, respectively. The interference testing showed that elevated levels of pH, HCO3 − concentration, and humic acid content in the solution could inhibit the adsorption of arsenic by Fe/TBC. Characterization of the adsorbent before and after adsorption using FTIR and SEM–EDS techniques confirmed arsenic adsorption mechanisms, including pore filling, electrostatic interaction, surface complexation, and H-bond adhesion. Column experiments were conducted to treat arsenic-spiked water and natural groundwater, with effective treatment volumes of 550 mL and 8792 mL, respectively. Lastly, the life cycle assessment (LCA) using OpenLCA 2.0.3 software was performed to treat 1 m3 of natural groundwater as the functional unit. The results indicated relatively significant environmental impacts during the Fe/TBC synthesis stage. The global warming potential resulting from the entire life cycle process was determined to be 0.8 kg CO2-eq. The results from batch and column experiments, regeneration studies, and LCA analysis indicate that Fe/TBC could be a promising adsorbent for arsenic(V).

Abstract Maintaining patients’ temperature during surgery is beneficial since hypothermia has been linked with perioperative complications. Laparoscopic surgery involves the insufflation of carbon dioxide (CO2) into the peritoneal cavity and has become the standard in many surgical indications since it is associated with better and faster recovery. However, the use of cold and dry CO2 insufflation can lead to perioperative hypothermia. We aimed to assess the difference between intraperitoneal and core temperatures during laparoscopic surgery and evaluate the influence of duration and CO2 insufflation volume by fitting a mixed generalized additive model. In this prospective observational single-center cohort trial, we included patients aged over 17 with American Society of Anesthesiology risk scores I to III undergoing laparoscopic surgery. Anesthesia, ventilation, and analgesia followed standard protocols, while patients received active warming using blankets and warmed fluids. Temperature data, CO2 ventilation parameters, and intraabdominal pressure were collected. We recruited 51 patients. The core temperature was maintained above 36 °C and progressively raised toward 37 °C as pneumoperitoneum time passed. In contrast, the intraperitoneal temperature decreased, thus creating a widening difference from 0.4 [25th–75th percentile: 0.2–0.8] °C at the beginning to 2.3 [2.1–2.3] °C after 240 min. Pneumoperitoneum duration and CO2 insufflation volume significantly increased this temperature difference (P

Aims: Addiction treatment training has been recognized to be an essential part of the curriculum in psychiatry and general medicine. Our objective in this study was to measure the knowledge and attitudes towards addictions among medical residents of a general hospital in Catalonia, Spain. Methods: Within a sample of medical residents, we administered a questionnaire based on previous literature including attitudes towards patients with drug use problems, evaluation of knowledge and beliefs about harm reduction policies. Additionally, basic professional data, and personal as well as family consumption history were recorded. Findings: Four dimensions were found within the beliefs of medical residents about drug treatment and training: judgement of medical treatment of addictions and harm reduction, attitudes toward patients, importance given to training and assessment of training received. When correlating these dimensions with personal characteristics, we found those residents with personal or family history of drug use to have higher positive attitudes towards patients with addictions, and also better predisposition towards harm reduction policies. Residents working with these patients tended to give more importance to training and knowledge, and to have a better perception of the training already received, compared with residents without this contact. Conclusions: Although residents working often with addicted patients appear to have positive attitudes towards addiction treatment, according to our results, it seems very important to improve training policies, awareness and attitudes towards addiction among the whole medical community.

We analyzed here how formin-like 1 β (FMNL1β), an actin cytoskeleton-regulatory protein, regulates microtubule-organizing center (MTOC) and multivesicular bodies (MVB) polarization and exosome secretion at an immune synapse (IS) model in a phosphorylation-dependent manner. IS formation was associated with transient recruitment of FMNL1β to the IS, which was independent of protein kinase C δ (PKCδ). Simultaneous RNA interference of all FMNL1 isoforms prevented MTOC/MVB polarization and exosome secretion, which were restored by FMNL1βWT expression. However, expression of the non-phosphorylatable mutant FMNL1βS1086A did not restore neither MTOC/MVB polarization nor exosome secretion to control levels, supporting the crucial role of S1086 phosphorylation in MTOC/MVB polarization and exosome secretion. In contrast, the phosphomimetic mutant, FMNL1βS1086D, restored MTOC/MVB polarization and exosome secretion. Conversely, FMNL1βS1086D mutant did not recover the deficient MTOC/MVB polarization occurring in PKCδ-interfered clones, indicating that S1086 FMNL1β phosphorylation alone is not sufficient for MTOC/MVB polarization and exosome secretion. FMNL1 interference inhibited the depletion of F-actin at the central region of the immune synapse (cIS), which is necessary for MTOC/MVB polarization. FMNL1βWT and FMNL1βS1086D, but not FMNL1βS1086A expression, restored F-actin depletion at the cIS. Thus, actin cytoskeleton reorganization at the IS underlies the effects of all these FMNL1β variants on polarized secretory traffic. FMNL1 was found in the IS made by primary T lymphocytes, both in T cell receptor (TCR) and chimeric antigen receptor (CAR)-evoked synapses. Taken together, these results point out a crucial role of S1086 phosphorylation in FMNL1β activation, leading to cortical actin reorganization and subsequent control of MTOC/MVB polarization and exosome secretion.

Abstract Systemic lupus erythematosus (SLE) is a multifactorial disease characterized by the convergence of genetic, immunological, and viral elements resulting in a complex interaction of both internal and external factors. The role of the Epstein-Barr virus (EBV) and human endogenous retroviruses (HERV-E) as triggers and maintenance elements in the pathogenesis of SLE has been widely recognized. Previous studies have independently evaluated the effects of EBV and HERV-E in this disease. In this work, for the first time, these viral factors are jointly investigated in SLE patients. This study aimed at assessing the differential expression of immune regulatory genes and the incidence of specific viral pathogens (EBV and HERV-E), alongside the detailed characterization of surface markers in T- and B-lymphocytes in patients with SLE and control participants. A comparative analysis between patients with SLE and control participants was performed, evaluating the expression of phenotypic markers and genes involved in the immune response (TNF-α, IL-2, IL-6, IL-10, IFNG, TLR3), as well as HERV-E gag and EBV viral genes (LMP1 and BZLF1).A significant association between SLE and EBV was found in this study. A notable increase in EBV LMP1 gene expression was observed in patients with SLE . Also, a significant overexpression of HERV-E was observed, in addition to a considerable increase in the distribution of the cell surface marker CD27 + on T- and B-lymphocytes, observed in individuals with SLE compared to the control group. This study provides evidence regarding the role that EBV virus plays in lymphocytes in the context of SLE, highlighting how both the virus and the host gene expression may influence disease pathogenesis by altering immune regulatory pathways mediated by TNF-α, IFN-γ, and IL-10, as well as parallel overexpression of HERV-E gag. The decrease in TLR3 could indicate a compromised antiviral response, which could facilitate viral reactivation and contribute to disease activity.

Abstract Skin inflammation with the potential sequel of moist epitheliolysis and edema constitute the most frequent breast radiotherapy (RT) acute side effects. The aim of this study was to compare the predictive value of tissue-derived radiomics features to the total breast volume (TBV) for the moist cells epitheliolysis as a surrogate for skin inflammation, and edema. Radiomics features were extracted from computed tomography (CT) scans of 252 breast cancer patients from two volumes of interest: TBV and glandular tissue (GT). Machine learning classifiers were trained on radiomics and clinical features, which were evaluated for both side effects. The best radiomics model was a least absolute shrinkage and selection operator (LASSO) classifier, using TBV features, predicting moist cells epitheliolysis, achieving an area under the receiver operating characteristic (AUROC) of 0.74. This was comparable to TBV breast volume (AUROC of 0.75). Combined models of radiomics and clinical features did not improve performance. Exclusion of volume-correlated features slightly reduced the predictive performance (AUROC 0.71). We could demonstrate the general propensity of planning CT-based radiomics models to predict breast RT-dependent side effects. Mammary tissue was more predictive than glandular tissue. The radiomics features performance was influenced by their high correlation to TBV volume.

Abstract Background The incidence of sexually transmitted infections (STIs) is increasing, especially among young people. Tools are needed to increase knowledge about sex education and STI prevention and treatment. Gamification can be a good training tool for both young people and health professionals. The primary objective of this study is to assess the impact of a training intervention on STI prevention, detection, and treatment in primary care professionals. Methods/design Multicentre cluster randomized controlled trial. Groups of primary care professionals will receive an intervention (online video game on sex education and STIs [SEXIT]) and will be compared with control groups that will not receive the intervention. Group assignments will be randomized by clusters. The study will consist of a pre-post evaluation of the intervention: a knowledge test will be administered before and after the intervention and 3 months after the intervention. This test will also be carried out on the same time sequence in the control groups. The impact of the training intervention will be assessed over a 6-month period, focusing on various variables associated with the clinical management of STIs. This evaluation entails the clinical records of diagnostic tests and antibiotic prescriptions related to the clinical approach to STIs. The required sample size is 262 (131 per group). Discussion Compared with those in the control group, improvements in knowledge and clinical behavioural outcomes after the intervention are expected for participants in the intervention groups. We plan to develop an educational video game to increase the knowledge about sexuality, STIs and violence. Protocol registered at ISRCTN with reference number ISRCTN17783607.

Abstract Eye tracking technology is a high-potential tool for different mathematic cognition research areas. Moreover, there is a dire need for more studies that provide detailed information on the quality of registered eye data. This study aimed to illustrate the applicability of eye tracking in the examination of mathematical cognition, focusing specifically on primary school students completing a computerized mental arithmetic task. Results suggested that the eye tracking device effectively captured high-quality eye movement data when primary school children engaged in this specific task. Furthermore, significant negative correlations have been found between task performance and number of eye fixations. Finally, eye movements distinctions between “Areas of Interest” have been found, indicating different visual tracking associated with different components of arithmetic calculations. This study underscores the extensive possibilities for future research employing eye tracking devices during computerized calculation tasks as assessment tools to explore the complex visual and cognitive processes.

It is recommended to implement the teaching of Basic Life Support (BLS) in schools; however, studies on the best training method are limited and have been a priority in recent years. The objective of this study was to analyze the attitudes and practical skills learned during BLS training using a gamified proposal. A comparative study was carried out, consisting of Compulsory Secondary Education students [control group (CG; classical teaching) and experimental group (EG; gamified proposal)]. The instruments used were the CPR and AED action sequence observation sheet, data from the Laerdal Resusci Anne manikin and AED and Attitude Questionnaire towards Basic Life Support and the Use of the Automated External Defibrillator. Sixty-eight students (33 girls) with a mean age of 13.91 ± 0.70 years were recruited. Results were significantly better in the EG (n = 37) [i.e., breathing control (p = 0.037); call to emergency services (p = 0.049); mean compression depth (p = 0.001); self-confidence (p = 0.006); intention to perform BLS and AED (p = 0.002)]; and significantly better in the CG (n = 31) [Total percentage of CPR (p < 0.001); percentage of correct compression (p < 0.001); time to apply effective shock with AED (p < 0.001); demotivation (p = 0.005). We can conclude that the group that was trained with the training method through the gamified proposal presents better intentions and attitudes to act in the event of cardiac arrest than those of the classic method. This training method allows for similar results in terms of CPR and AED skills to classical teaching, so it should be taken into account as a method for teaching BLS to secondary education students.

Abstract Humans modify their environment to grant or prevent others’ access to valuable resources, for example by using locks. We tested whether sanctuary-living chimpanzees (N = 10) would flexibly modify their environment to either allow or deny a dominant conspecific access to a shared food source by giving them the option to change a food reward’s pathway prior to releasing it. The food could end up in one of two locations: one was accessible to both the subject and a dominant conspecific, the other one was only accessible to the subject. We further manipulated the extent of inhibitory control needed for modifying the pathway by varying the subjects’ starting position. Our subjects reoriented the pathway competitively to monopolize food but changed the pathway less often in trials with high inhibitory demands. We further show how inhibitory task demands in a social context influence chimpanzees’ future planning. Our results show that chimpanzees will strategically manipulate their environment to maximize their own and deny a dominant conspecific access to food.

Abstract Adeno-associated viruses (AAVs) are promising gene therapy vectors, but challenges arise when treating patients with preexisting neutralizing antibodies. Worldwide seroprevalence studies provide snapshots of existing immunity in diverse populations. Owing to the uniqueness of the Basque socio-geographical landscape, we investigated the seroprevalence of eight AAV serotypes in residents of the Basque Country. We found the highest seroprevalence of AAV3, and the lowest seroprevalence of AAV9. Additionally, less than 50% of the Basque population has neutralizing antibodies against AAV4, AAV6, and AAV9. Our findings provide insight into AAV infections in the Basque region, public health, and the development of AAV-based therapeutics.

Abstract The human intestinal tract is colonized with microorganisms, which present a diverse array of immunological challenges. A number of antimicrobial mechanisms have evolved to cope with these challenges. A key defense mechanism is the expression of inducible antimicrobial peptides (AMPs), such as beta-defensins, which rapidly inactivate microorganisms. We currently have a limited knowledge of mechanisms regulating the inducible expression of AMP genes, especially factors from the host required in these regulatory mechanisms. To identify the host factors required for expression of the beta-defensin-2 gene (HBD2) in intestinal epithelial cells upon a bacterial challenge, we performed a RNAi screen using a siRNA library spanning the whole human genome. The screening was performed in duplicate to select the strongest 79 and 110 hit genes whose silencing promoted or inhibited HBD2 expression, respectively. A set of 57 hits selected among the two groups of genes was subjected to a counter-screening and a subset was subsequently validated for its impact onto HBD2 expression. Among the 57 confirmed hits, we brought out the TLR5-MYD88 signaling pathway, but above all new signaling proteins, epigenetic regulators and transcription factors so far unrevealed in the HBD2 regulatory circuits, like the GATA6 transcription factor involved in inflammatory bowel diseases. This study represents a significant step toward unveiling the key molecular requirements to promote AMP expression in human intestinal epithelial cells, and revealing new potential targets for the development of an innovative therapeutic strategy aiming at stimulating the host AMP expression, at the era of antimicrobial resistance.

Introduction: This study investigates the impact of smart refrigerators on the logistics and management of biological samples, emphasizing the critical phases of transport and storage to enhance the pre-analytical quality of blood samples. Efficient sample management is crucial for ensuring diagnostic accuracy. Objective: The primary objective is to evaluate the efficiency of smart refrigerators equipped with cloud technology in optimizing the transport and storage of biological samples. The secondary objective is to assess healthcare personnel's perceptions and satisfaction with these technologies. Method: A longitudinal prospective analysis was conducted to assess both the quantitative incidence of pre-analytical errors and the qualitative perceptions of healthcare personnel regarding these technologies. Samples were collected from six primary care centers within the Elche General Health Department, with one center using smart refrigerators and five using conventional methods. The refrigerators featured GPS, real-time temperature sensors, alert systems for cold chain interruptions, and RFID technology. Training on refrigerator use, systematic data collection on pre-analytical errors, and surveys and semi-structured interviews with healthcare personnel were conducted. Descriptive methods and hypothesis testing, including Z-statistics and logistic regression models, were used for statistical analysis. Results: The analysis revealed a significant decrease in the incidence of coagulated and hemolyzed samples at the center using smart refrigerators. Specifically, the rate of coagulated samples was reduced by 69.39%, while hemolyzed samples decreased by 78.12%. This improvement contrasts with trends observed in centers using conventional practices. A significant 94.62% of the staff reported a positive experience with the smart refrigerators, highlighting high satisfaction and the importance of stricter control in handling and transporting samples to prevent errors. Conclusions: The use of smart refrigerators in the transport and storage of biological samples effectively improves the pre-analytical quality of blood samples, reduces pre-analytical errors, and enhances staff satisfaction. These findings underscore the importance of incorporating advanced technologies in the management of biological samples in primary care settings.

Abstract Huntington’s disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene (HTT). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resulting in an amelioration of some motor and cognitive functions. During physical training, extracellular vesicles (EVs) are released in many tissues, including the brain, as a potential means for inter-tissue communication. To investigate how motor skill learning, involving acute physical training, modulates EVs crosstalk between cells in the striatum, we trained wild-type (WT) and R6/1 mice, the latter with motor and cognitive deficits, on the accelerating rotarod test, and we isolated their striatal EVs. EVs from R6/1 mice presented alterations in the small exosome population when compared to WT. Proteomic analyses revealed that striatal R6/1 EVs recapitulated signaling and energy deficiencies present in HD. Motor skill learning in R6/1 mice restored the amount of EVs and their protein content in comparison to naïve R6/1 mice. Furthermore, motor skill learning modulated crucial pathways in metabolism and neurodegeneration. All these data provide new insights into the pathogenesis of HD and put striatal EVs in the spotlight to understand the signaling and metabolic alterations in neurodegenerative diseases. Moreover, our results suggest that motor learning is a crucial modulator of cell-to-cell communication in the striatum.

Abstract Humoral immunity in COVID-19 includes antibodies (Abs) targeting spike (S) and nucleocapsid (N) SARS-CoV-2 proteins. Antibody levels are known to correlate with disease severity, but titers are poorly reported in mild or asymptomatic cases. Here, we analyzed the titers of IgA and IgG against SARS-CoV-2 proteins in samples from 200 unvaccinated Hospital Workers (HWs) with mild COVID-19 at two time points after infection. We analyzed the relationship between Ab titers and patient characteristics, clinical features, and evolution over time. Significant differences in IgG and IgA titers against N, S1 and S2 proteins were found when samples were segregated according to time T1 after infection, seroprevalence at T1, sex and age of HWs and symptoms at infection. We found that IgM + samples had higher titers of IgG against N antigen and IgA against S1 and S2 antigens than IgM − samples. There were significant correlations between anti-S1 and S2 Abs. Interestingly, IgM + patients with dyspnea had lower titers of IgG and IgA against N, S1 and S2 than those without dyspnea. Comparing T1 and T2, we found that IgA against N, S1 and S2 but only IgG against certain Ag decreased significantly. In conclusion, an association was established between Ab titers and the development of infection symptoms.

Abstract Introduction Personalised prevention aims to delay or avoid disease occurrence, progression, and recurrence of disease through the adoption of targeted interventions that consider the individual biological, including genetic data, environmental and behavioural characteristics, as well as the socio-cultural context. This protocol summarises the main features of a rapid scoping review to show the research landscape on biomarkers or a combination of biomarkers that may help to better identify subgroups of individuals with different risks of developing specific diseases in which specific preventive strategies could have an impact on clinical outcomes. This review is part of the “Personalised Prevention Roadmap for the future HEalThcare” (PROPHET) project, which seeks to highlight the gaps in current personalised preventive approaches, in order to develop a Strategic Research and Innovation Agenda for the European Union. Objective To systematically map and review the evidence of biomarkers that are available or under development in cancer, cardiovascular and neurodegenerative diseases that are or can be used for personalised prevention in the general population, in clinical or public health settings. Methods Three rapid scoping reviews are being conducted in parallel (February–June 2023), based on a common framework with some adjustments to suit each specific condition (cancer, cardiovascular or neurodegenerative diseases). Medline and Embase will be searched to identify publications between 2020 and 2023. To shorten the time frames, 10% of the papers will undergo screening by two reviewers and only English-language papers will be considered. The following information will be extracted by two reviewers from all the publications selected for inclusion: source type, citation details, country, inclusion/exclusion criteria (population, concept, context, type of evidence source), study methods, and key findings relevant to the review question/s. The selection criteria and the extraction sheet will be pre-tested. Relevant biomarkers for risk prediction and stratification will be recorded. Results will be presented graphically using an evidence map. Inclusion criteria Population: general adult populations or adults from specific pre-defined high-risk subgroups; concept: all studies focusing on molecular, cellular, physiological, or imaging biomarkers used for individualised primary or secondary prevention of the diseases of interest; context: clinical or public health settings. Systematic review registration https://doi.org/10.17605/OSF.IO/7JRWD (OSF registration DOI).

Introduction: Retained permanent maxillary canines can cause aesthetic and functional alterations in the pediatric population. Objective: To clinically and epidemiologically characterize adolescents with retained permanent maxillary canines and identify the risk factors involved in the etiology of this dentomaxillofacial anomaly. Methods: An analytical case-control study was carried out in adolescents treated in the orthodontic services of the Plaza de la Revolución municipality in the period from 2018 to 2023. A probabilistic sample of 64 cases and 128 controls was obtained.The variables studied were: sex, skin color, direction anomalies, position and microdontia of the maxillary lateral incisors, anterior diastemas, negative bone-tooth discrepancy, anterior sector trauma, premature loss of temporary teeth, persistence of temporary maxillary canines and genetic factors. Contingency tables were made to calculate the odds ratio and the chi-square hypothesis test for homogeneity was performed, with a confidence interval of 95%. Results: An association was evident between the retention of permanent maxillary canines and the presence of interincisors diastemas (OR=2.88; p=0.0015), the persistence of temporary maxillary canines (OR=45.97; p=0.0000) and genetic factors (OR=12.01; p=0.0000). Conclusions: In the outbreak control of permanent maxillary canines, emphasis should be placed on monitoring risk factors: such as the presence of interincisors diastemas, hereditary factors and the persistence of temporary canines.

Male germ cells share a common origin across animal species, therefore they likely retain a conserved genetic program that defines their cellular identity. However, the unique evolutionary dynamics of male germ cells coupled with their widespread leaky transcription pose significant obstacles to the identification of the core spermatogenic program. Through network analysis of the spermatocyte transcriptome of vertebrate and invertebrate species, we describe the conserved evolutionary origin of metazoan male germ cells at the molecular level. We estimate the average functional requirement of a metazoan male germ cell to correspond to the expression of approximately 10,000 protein-coding genes, a third of which defines a genetic scaffold of deeply conserved genes that has been retained throughout evolution. Such scaffold contains a set of 79 functional associations between 104 gene expression regulators that represent a core component of the conserved genetic program of metazoan spermatogenesis. By genetically interfering with the acquisition and maintenance of male germ cell identity, we uncover 161 previously unknown spermatogenesis genes and three new potential genetic causes of human infertility. These findings emphasize the importance of evolutionary history on human reproductive disease and establish a cross-species analytical pipeline that can be repurposed to other cell types and pathologies.

Summary: Background: We studied the poorly-known dynamics of circulating DNA (cir-nDNA), as monitored prospectively over an extended post-surgery period, in patients with cancer. Methods: On patients with stage III colon cancer (N = 120), using personalised molecular tags we carried out the prospective, multicenter, blinded cohort study of the post-surgery serial analysis of cir-nDNA concentration. 74 patients were included and 357 plasma samples tested. Findings: During post-operative follow-up, the patients’ median cir-nDNA concentration was greater (P 18 months post-surgery, the data suggest that the persistence of NETs formation is not due to the adjuvant CT. Interpretation: (1), Given the inter-patient heterogeneity, the post-surgery cir-nDNA level cannot be considered a reliable value, and caution must be exercised when determining mutation allele frequency or the mutation status; and (2), specific studies must be undertaken to investigate the possible clinical impact of the persistent, low-grade inflammation resulting from elevated NETs levels, such as observed in these post-surgery patients, given that such levels are known to potentially induce adverse cardiovascular or thrombotic events. Funding: This work was supported by the H2020 European ERA-NET grant on Translational Cancer Research (TRANSCAN-2).

The Xerces Blue (Glaucopsyche xerces) is considered to be the first butterfly to become extinct in historical times. It was notable for its chalky lavender wings with conspicuous white spots on the ventral wings. The last individuals were collected in their restricted habitat, in the dunes near the Presidio military base in San Francisco, in 1941. We sequenced the genomes of four 80- to 100-year-old Xerces Blue, and seven historical and one modern specimens of its closest relative, the Silvery Blue (Glaucopsyche lygdamus). We compared these to a novel annotated genome of the Green-Underside Blue (Glaucopsyche alexis). Phylogenetic relationships inferred from complete mitochondrial genomes indicate that Xerces Blue was a distinct species that diverged from the Silvery Blue lineage at least 850,000 years ago. Using nuclear genomes, both species experienced population growth during the Eemian interglacial period, but the Xerces Blue decreased to a very low effective population size subsequently, a trend opposite to that observed in the Silvery Blue. Runs of homozygosity and deleterious load in the former were significantly greater than in the later, suggesting a higher incidence of inbreeding. These signals of population decline observed in Xerces Blue could be used to identify and monitor other insects threatened by human activities, whose extinction patterns are still not well known.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Introduction Sleep deprivation has a great impact on the learning process in physicians in training. Therefore, inquiring on this phenomenon in the most recent investigations will facilitate the provision of evidence on the influence regarding the absence of sleep on the learning process in health personnel.