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Abstract Background The 24-h urine protein (24-hUP) excretion is the gold standard for evaluating proteinuria. This study aimed to evaluate the diagnostic efficacy of protein/creatinine ratio (PCR) for estimating 24-hUP at various levels of renal function and proteinuria levels. Methods A cross-sectional study was conducted between December 2021 and December 2023 in Salvador, Bahia-Brazil, as an extension of previously published data from the TUNARI study. The study included 217 samples from 152 patients with various levels of renal function and proteinuria. PCR in isolated samples and 24-hUP were determined conventionally within a 24-h timeframe. Patients were classified into three groups according to the level of renal function (Group 1 = 10 to 60 mL/min) and level of proteinuria ( 3.5 g/day). The data were analyzed using the Spearman correlation (rs), coefficient of determination (r2), Bland–Altman plots and receiver operating characteristic (ROC) curve. Likelihood ratios, positive (LR +), and negative (LR-) were derived from the sensitivity and specificity of PCR. Results Mean age was 41.5 ± 15.7 years, 61.8% were women, 36.8% Black and 52% Mixed-race. Glomerulopathies constituted 80.3%; 46.1% with lupus nephritis. Of the total urine samples, we observed a high correlation between PCR in the total sample of 24-hUP sample (rs = 0.86, p 0.3–3.5 g/day, the sensitivity was 64.1%, the specificity was 84.6%, and the AUC was 0.76 (95% CI = 0.67; 0.84), PCR detected all cases > 3.5 g/day. Conclusions PCR is a suitable measure to be used as an indicator of 24-hUP at different levels of renal function, but may have limitations at higher levels of proteinuria. Analysis of PCR by proteinuria level found that agreement as well as sensitivity decreases at higher levels, but it maintains good specificity and is able to identify nephrotic range proteinuria.

Abstract Background Despite advances in pain management, cancer-related pain remains a critical issue for many patients. In recent years, there has been a growing interest in the use of fascial plane blocks, such as the Erector Spinae Plane Block (ESPB), for managing chronic pain, including in the oncology field. We conducted a systematic review to synthetize existing evidence on the use of ESPB for cancer pain management. Methods We selected studies published between January 2016 to April 2024. A systematic search in Pubmed and Embase databases was performed. The search strategy included the following keywords and/or MeSH terms according to the controlled vocabulary of the databases sought: ((erector spinae plane block) OR (ESP block) OR (ESPB) AND ((cancer pain). We considered eligible Randomized, nonrandomized studies, case series and case reports reporting data on the use of ESPB in patients with cancer pain. Results The search revealed 34 studies. Among these, we found one RCT, three retrospective studies, two case series, and 28 case reports for a total of 135 patients. Studies included described the use of ESPB for the management of various types of cancer pain across different conditions, including chronic thoracic cancer-related pain, abdominal visceral pain and pain related to bone metastases. Single-shot ESPB was performed in 26 studies while continuous ESPB and the use of a peripheral nerve catheter for continuous analgesia were described in 8 studies. Neurolytic ESPB was performed in 6 studies for a total of 10 patients There was a high clinical heterogeneity in terms of technique, drugs, and use of adjuvants. The lack of comparators was a major flaw, together with the low level of evidence in the majority of the included studies. Conclusions The evidence supporting the use of ESPB for cancer pain management is currently scarce, heterogeneous, and of low quality. To better understand its potential and provide robust clinical guidance, future research needs to focus on rigorous comparative studies, standardization of techniques and larger sample sizes.

Abstract Controlling light at subwavelength scales is crucial in nanophotonics. Hyperbolic polaritons, supporting arbitrarily large wavevectors, enable extreme light confinement beyond the diffraction limit. Traditional hyperbolic metamaterials suffer from high losses due to metallic components, while natural low-loss hyperbolic phonon polaritons are limited to the mid-infrared range. Some hyperbolic materials at visible frequencies have been studied, but they are either very lossy or only feature out-of-plane hyperbolicity. Here, we demonstrate the presence of low-loss, in-plane hyperbolic plasmon polaritons in the visible and near-infrared in thin-films of MoOCl2, a natural van der Waals crystal. The polariton dispersion is predicted based on the framework of light propagation in biaxial media and experimentally confirmed by real space nano imaging on exfoliated flakes. MoOCl2 constitutes an ideal material platform for visible range applications leveraging the unboundedness of hyperbolic modes, such as hyperlensing, Purcell factor enhancement, and super-resolution imaging, without the drawbacks of metamaterials.

Introduction: Malignant paragangliomas (M-PGL) are a group of neuroendocrine tumors that originate from chromaffin cells. The most common location for PGL is the head and neck, which comprise 65–70% of all PGL, and the M-PGL accounts for 0.6% of all head and neck cancers. It is a rare tumor, with an incidence of 2–8 per million. Diagnosing PGL can be challenging, and treatment for metastatic disease is usually not curative. Case Presentation: A 66-year-old woman was diagnosed with left cervical pain and laterocervical mass in March 2015. Octreotide scintigraphy showed intense uptake in the cervical mass, two pulmonary micronodules of 4–5 mm, and another lesion in the lumbar region (L3–L4). The final diagnosis was malignant nonsecretory PGL with adjacent tissue involvement and distant metastases. After three different treatments with minimal symptomatic improvement, 177Lu-DOTATATE was requested off-label. With a dose of 7,400 MBq until January 2018, the patient showed remarkable symptomatic pain improvement and a decrease in tumor size. Conclusion: We believe that our case report provides relevant information that can be considered in similar cases. First, the patient tripled the expected survival in such a clinical setting, and this benefit seems to rely on 177Lu-DOTATATE treatment. Second, we documented an early symptomatic response to this treatment but a long-term delayed volumetric radiographic response.

Abstract Background Malaria is an infectious disease caused by the Plasmodium species and is a global burden. When not treated correctly, it can reemerge as a relapse or recrudescence. Malaria relapse cases can contribute to maintaining active transmission chains and can influence the patient to develop severe malaria, potentially leading to hospitalization or death. The objective of this study is to estimate the number of malaria relapse cases in the extra-Amazon region of Brazil and to investigate the associated factors. Methods This is a case–control study that analyses malaria infections caused by Plasmodium vivax, as reported in Notifiable Diseases Information System (Sinan) for the Brazilian extra-Amazon region (an area not endemic for the disease) from 2008 to 2019. For the identification of relapse cases, deduplication record linkage processes in R software were used. Malaria relapses were defined as the case group, and new malaria infections were defined as the control group. Logistic regression models were used to assess associated factors. Results Of the 711 malaria relapses, 589 (82.8%) were first relapses. Most relapses (71.6%) occurred between 30 and 120 days after the previous infection. Malaria relapses are spread throughout the extra-Amazon region, with a higher concentration near big cities. Driver occupation was found to be a common risk factor compared to other occupations, along with asymptomatic individuals. Other associated factors were: being infected in the Brazilian Amazon region, having follow-ups for malaria relapses, and having parasite density of the previous infection higher than 10,000 parasites per mm3. Conclusions This study provides evidence that allows malaria health surveillance services to direct their efforts to monitor cases of malaria in the highest risk segments identified in this study, particularly in the period between 30 and 120 days after being infected and treated. Relapses were associated to driver occupation, absence of symptoms, infection in endemic areas of Brazil, being detected through active surveillance or routine follow-up actions, and with parasitaemia greater than 10,000 parasites per mm3 in the previous infection. Improving cases follow-up is essential for preventing relapses.

Abstract Background Non-village indigenous people may face urban lifestyle influences, impacting their nutritional profile. Therefore, this study aimed to analyze the temporal trends in the nutritional status (2008–2023) and food consumption (2015–2023) of non-village indigenous people in Brazil, using data from the Food and Nutrition Surveillance System (SISVAN). Methods In this time series study, secondary data available on the SISVAN online platform were used. All records of non-village indigenous people from all regions of Brazil were evaluated. Nutritional status was assessed using height-for-age (H/A) and Body Mass Index-for-age (BMI/A) for children and adolescents, and BMI for adults and the elderly. Food consumption trends were analyzed using food consumption screeners, based on specific food groups consumed the day before the assessment. An annual percentage change (APC) was calculated using Prais-Winsten regression models. Results There was a reduction in severe stunting among children aged 2 to 4 years old (APC = -0.80%; p = 0.025) and 5 to 9 years old (APC = -4.02%; p

Abstract Objective Epileptic seizures occurring in late adulthood often remain of unknown origin. Sporadic cerebral amyloid angiopathy (CAA) is a cerebral small vessel disease characterized by intracerebral hemorrhage, microhemorrhage and superficial siderosis, occurring mostly in elderly. This observational case–control study aimed to assess the occurrence of CAA in patients experiencing their first seizure in late adulthood. Methods We enrolled consecutive patients aged ≥55 years presenting with late‐onset seizures (LOS) to the emergency departments or outpatient clinics of two Italian centers, from April 2021 to October 2022. Two age‐matched control subjects with neurological symptoms other than epileptic seizure were recruited for each enrolled case. All participants underwent brain MRI (1.5 Tesla) including blood‐sensitive sequences and were assessed for probable CAA diagnosis according to Boston criteria 2.0. Chi‐squared test was performed to evaluate group differences. Univariate logistic regression analysis tested the association between clinical variables and CAA. Results We included 65 patients with LOS (27 females; mean age 72.2 ± 8.9 years) and 130 controls (49 females; mean age 70.3 ± 8.9 years). Diagnosis of probable CAA was achieved in 10.8% (7/65) of LOS patients and 2.3% (3/130) controls, with a statistically significant difference (p = 0.011). The OR for CAA in the LOS group was 5.2 as compared to the control group (95% CI = 1.3–20.6, p = 0.02). Significance The frequency of CAA is significatively higher in patients with LOS as compared to other neurological diseases, suggesting that a portion of LOS of unknown or vascular origin are associated with CAA. Plain Language Summary Late‐onset seizures (LOS) are very frequent in the elderly and often have no clear cause. Cerebral amyloid angiopathy (CAA) is a condition where amyloid proteins build up in the blood vessels of the brain, causing them to become weak and prone to bleeding. In this study, we explored the occurrence of CAA in people with LOS. We found that people with LOS were more likely to have a diagnosis of CAA than controls (i.e., people with other neurological diseases).

Abstract Background Metastatic pancreatic ductal adenocarcinoma (mPDAC) patients have very poor prognosis highlighting the urgent need of novel treatments. In this regard, repurposing non-oncology already-approved drugs might be an attractive strategy to offer more-effective treatment easily tested in clinical trials. Accumulating evidence suggests that epigenetic deregulation is a hallmark of cancer contributing to treatment resistance in several solid tumors, including PDAC. Histone deacetylase inhibitors (HDACi) are epigenetic drugs we have investigated preclinically and clinically as anticancer agents. Valproic acid (VPA) is a generic low-cost anticonvulsant and mood stabilizer with HDAC inhibitory activity, and anticancer properties also demonstrated in PDAC models. Statins use was reported to be associated with lower mortality risk in patients with pancreatic cancer and statins have been shown to have a direct antitumor effect when used alone or in combination therapy. We recently showed capability of VPA/Simvastatin (SIM) combination to potentiate the antitumor activity of gemcitabine/nab-paclitaxel in vitro and in vivo PDAC preclinical models. Methods/Design VESPA is a patient-centric open label randomized multicenter phase-II investigator-initiated trial, evaluating the feasibility, safety, and efficacy of VPA/SIM plus first line gemcitabine/nab-paclitaxel-based regimens (AG or PAXG) (experimental arm) versus chemotherapy alone (standard arm) in mPDAC patients. The study involves Italian and Spanish oncology centers and includes an initial 6-patients safety run-in-phase. A sample size of 240 patients (120 for each arm) was calculated under the hypothesis that the addition of VPA/SIM to gemcitabine and nab-paclitaxel-based regimens may extend progression free survival from 6 to 9 months in the experimental arm. Secondary endpoints are overall survival, response rate, disease control rate, duration of response, CA 19.9 reduction, toxicity, and quality of life. The study includes a patient engagement plan and complementary biomarkers studies on tumor and blood samples. Conclusions VESPA is the first trial evaluating efficacy and safety of two repurposed drugs in oncology such as VPA and SIM, in combination with standard chemotherapy, with the aim of improving mPDAC survival. The study is ongoing. Enrollment started in June 2023 and a total of 63 patients have been enrolled as of June 2024. Trial registration EudraCT number: 2022-004154-63; ClinicalTrials.gov identifier NCT05821556, posted 2023/04/20.

Abstract Invasive alien insects have the potential to pose a significant threat to global agriculture, with their distinctive traits enabling rapid reproduction, successful adaptation to new environments and high distribution capability. These pests can devastate crops, livestock, biodiversity and ecosystem functioning, resulting in ecological damage and substantial economic losses. Climate change plays a crucial role in driving the invasion of these pests, creating favorable conditions for their development, and negatively impacting global biodiversity. Among invasive alien insects, fall armyworm (FAW) (Spodoptera frugiperda) (JE Smith) (Lepidoptera: Noctuidae) has emerged as a major pest species, causing significant yield losses in maize cropping outside his native range. Initially, reliance on pesticides for control proved ineffective and led to pesticide resistance. Significant progress has been made in implementing integrated pest management (IPM) strategies that integrate agro-ecological and biological approaches. This review article focuses on the compilation of IPM methods, combining agro-ecological practices and biological control agents such as parasitoids and viruses, for the effective management of FAW. Approaches such as intercropping, agronomic practices, and the use of parasitoids and viruses have shown promising results in controlling FAW. This review article provides insights into successful management methods, recommendations and suggestions for the sustainable control of FAW using agro-ecological practices, biological control agents or their combination.

Abstract Intratumoral injections have the potential for enhanced cancer treatment efficacy while reducing costs and systemic exposure. However, intratumoral drug injections can result in substantial off-target leakage and are invisible under standard imaging modalities like ultrasound (US) and x-ray. A thermosensitive poloxamer-based gel for drug delivery was developed that is visible using x-ray imaging (computed tomography (CT), cone beam CT, fluoroscopy), as well as using US by means of integrating perfluorobutane-filled microbubbles (MBs). MBs content was optimized using tissue mimicking phantoms and ex vivo bovine livers. Gel formulations less than 1% MBs provided gel depositions that were clearly identifiable on US and distinguishable from tissue background and with minimal acoustic artifacts. The cross-sectional areas of gel depositions obtained with US and CT imaging were similar in studies using ex vivo bovine liver and postmortem in situ swine liver. The gel formulation enhanced multimodal image-guided navigation, enabling fusion of ultrasound and x-ray/CT imaging, which may enhance targeting, definition of spatial delivery, and overlap of tumor and gel. Although speculative, such a paradigm for intratumoral drug delivery might streamline clinical workflows, reduce radiation exposure by reliance on US, and boost the precision and accuracy of drug delivery targeting during procedures. Imageable gels may also provide enhanced temporal and spatial control of intratumoral conformal drug delivery.

Abstract HPV-positive and HPV-negative head and neck squamous cell carcinoma (HNSCC) are recognized as distinct entities. There remains uncertainty surrounding the causal effects of smoking and alcohol on the development of these two cancer types. Here we perform multivariable Mendelian randomization (MR) to evaluate the causal effects of smoking and alcohol on the risk of HPV-positive and HPV-negative HNSCC in 3431 cases and 3469 controls. Lifetime smoking exposure, as measured by the Comprehensive Smoking Index (CSI), is associated with increased risk of both HPV-negative HNSCC (OR = 3.03, 95%CI:1.75-5.24, P = 7.00E-05) and HPV-positive HNSCC (OR = 2.73, 95%CI:1.39-5.36, P = 0.003). Drinks Per Week is also linked with increased risk of both HPV-negative HNSCC (OR = 7.72, 95%CI:3.63-16.4, P = 1.00E-07) and HPV-positive HNSCC (OR = 2.66, 95%CI:1.06-6.68, P = 0.038). Smoking and alcohol independently increase the risk of both HPV-positive and HPV-negative HNSCC. These findings have important implications for understanding the modifying risk factors between HNSCC subtypes.

Bony hemangiomas are benign vascular lesions with an expansive growth; usually they tend to obliterate the entire bony cavity. They are typical lesion of the spinal bones, but they can rarely arise within other bones of the neurocranium. Diabetic microangiopathy is a condition characterized by the development of aberrant vessel tangles anastomosed to each other due to dysregulated neoangiogenesis. We report the case of a 56-year-old woman, suffering from type 2 diabetes mellitus, admitted to the neurology department due to a reported worsening of paresthesias and dysesthesias of the upper and lower limbs. She performed a contrast-enhanced brain CT scan that showed the presence, at the level of the right mastoid process, of an hypervascular angioma. A subsequent MRI study of the brain and spine showed the presence of multiple bone angiomas, at the level of the right frontal theca and C7, Th3, and Th7 vertebral bodies. Due to the absence of further symptoms and clinical and radiological signs of intracranial compression, the patient did not perform surgery. A radiological follow-up was advised. Although possible pathophysiological correlations between diabetes and vertebral hemangiomas are mentioned in literature, vascular lesions of this type involving vertebrae and skull base simultaneously can be discovered in a patient with chronic diabetic disease. As long as these lesions remain asymptomatic, surgical treatment is not indicated, and the patient is followed over time with radiological follow-up.

Abstract Background Chronic pelvic pain is a common disease that affects approximately 4% of women of reproductive age in developed countries. This number is estimated to be higher in developing countries, with a significant negative personal and socioeconomic impact on women. The lack of data on this condition in several countries, particularly those in development and in socially and biologically vulnerable populations such as the indigenous, makes it difficult to guide public policies. Objectives To evaluate the prevalence of chronic pelvic pain (dysmenorrhea, dyspareunia, non-cyclical pain) and identify which variables are independently associated with the presence of the condition in indigenous women from Otavalo-Ecuador. Design A cross-sectional study was carried out including a sample of 2429 women of reproductive age between 14 and 49 years old, obtained from April 2022 to March 2023. A directed questionnaire was used, collected by bilingual interviewers (Kichwa and Spanish) belonging to the community itself; the number of patients was selected by random sampling proportional to the number of women estimated by sample calculation. Data are presented as case prevalence, odds ratio, and 95% confidence interval, with p

Objetivo da Investigação: Este artigo explora as principais teorias sobre o processo de industrialização no Brasil que mais influíram na Geografia brasileira e os seus respectivos desdobramentos em termos de produção científica na área. Metodologia: No plano metodológico, trata-se de um esforço de revisitar a produção sobre o tema no sentido de mostrar as principais formulações teóricas sobre esse processo no país. Inicialmente, discutiu-se algumas das principais teorias desenvolvidas no âmbito das ciências humanas e sociais sobre a industrialização no Brasil. Em seguida, a abordagem se direciona para algumas formulações consideradas centrais no âmbito da geografia. Resultados: Como resultados, evidenciou-se um interesse significativo na temática e um constante crescimento na produção científica e, consequentemente, a diversificação das intepretações capazes de explicar o processo de industrialização brasileira e o quadro de dependência às luz do seu acarbouço teórico e conceitual. Originalidade/Valor: Conclui-se que a produção científica na Geografia – e em outros campos do conhecimento em outras perspectivas – desempenha um papel crucial na compreensão e no planejamento do desenvolvimento econômico do território, enfatizando a importância da atuação estatal na concessão de incentivos fiscais e na criação de infraestrutura para as indústrias, ou seja, na dotação e/ou renovação da materialidade do território brasileiro.

TRP channels are important pharmacological targets in physiopathology. TRPV2 plays distinct roles in cardiac and neuromuscular function, immunity, and metabolism, and is associated with pathologies like muscular dystrophy and cancer. However, TRPV2 pharmacology is unspecific and scarce at best. Using in silico similarity-based chemoinformatics we obtained a set of 270 potential hits for TRPV2 categorized into families based on chemical nature and similarity. Docking the compounds on available rat TRPV2 structures allowed the clustering of drug families in specific ligand binding sites. Starting from a probenecid docking pose in the piperlongumine binding site and using a Gaussian accelerated molecular dynamics approach we have assigned a putative probenecid binding site. In parallel, we measured the EC50 of 7 probenecid derivatives on TRPV2 expressed in Pichia pastoris using a novel medium-throughput Ca2+ influx assay in yeast membranes together with an unbiased and unsupervised data analysis method. We found that 4-(piperidine-1-sulfonyl)-benzoic acid had a better EC50 than probenecid, which is one of the most specific TRPV2 agonists to date. Exploring the TRPV2-dependent anti-hypertensive potential in vivo, we found that 4-(piperidine-1-sulfonyl)-benzoic acid shows a sex-biased vasodilator effect producing larger vascular relaxations in female mice. Overall, this study expands the pharmacological toolbox for TRPV2, a widely expressed membrane protein and orphan drug target.

Adult-onset cases of idiopathic hypogonadotropic hypogonadism (IHH) are characterized by partial or normal puberty development until adolescence and by the impairment of the hypothalamic–pituitary–gonadal (HPG) axis in adulthood. WDR11 and DCC genes are known to be involved in axonal development, particularly of hypothalamic GnRH neurons, and ciliogenesis. We report a female case of adult-onset hypogonadism and cerebellar ataxia, in which we identified two gene mutations. A panel of 48 genes was set up to search for variants in the causative genes of CHH. The variants found were analyzed following the American College of Medical Genetics and Genomics (ACMG) criteria to define their pathogenicity. We identified a missense heterozygous variant in the WDR11 gene NM_018117.12:c.2306T>G (p.Met769Arg) and a mutation in a second gene DCC resulting in amino acid substitutions NM_005215.4:c.3533C>T (p.Ser1178Phe). These variants were classified as being of uncertain clinical significance. We assume that there is a link between the variants found and the impairment of the gonadotrophic and neurological phenotype of the patient. Therefore, we propose the genetic test to identify the best therapeutic approach to identify infertility in female patients with IHH; we believe it is necessary to test WDR11 and DCC genes in larger populations with the same condition to introduce it in future protocols of assessment.

The Mediterranean, a global hotspot for rare ant species, hosts a significant representation of the global diversity of the mainly Holarctic ant genus Temnothorax. However, several groups still require significant taxonomic efforts. The taxonomy of the T. luteus complex species was revised in 2014 when morphometrics allowed distinguishing two valid species and two synonyms out of four taxa that had been originally described from France. The two species recognized since then are T. luteus, distributed from Iberia to the Alps, and the largely sympatric but much more xerothermophilic T. racovitzai. In Italy, only a few records of the complex were ever published, and the identity of the Italian population was never thoroughly assessed. We combined morphometrics with phylogenomic data to assess the identity of the T. luteus populations that spanned from Sicily to the Italian Alps and discovered that all Italian samples belong to a new cryptic species, which we describe as T. apenninicus sp. nov. whose glacial refugium was probably in the southern Apennines.

Nematode surveys in natural environments in the Iberian Peninsula detected three unidentified Xenocriconemella populations that closely resembled the X. macrodora-species complex, but utilization of integrative taxonomy confirmed that they comprised a new taxon described in this paper as X. andreae sp. nov. Only females were detected in the new species (considered parthenogenetic) and delineated with a bare body (274–353 µm); lip region with two annuli, continuous with body delineation; second lip annulus enclosed by the first one. Flexible and thin stylet (88.0–99.0 µm), representing 30.4–47.8% of total body length. The excretory pore is positioned 2–3 annuli posterior to the level of stylet knobs, at 101.5 (87–107) µm from the lip region. Female genital tract: monodelphic, prodelphic, large, and representing 34.4–52.4% of the body length; vagina slightly ventrally curved. The anus is located at (6–9) annuli from the rear end. Tail short, conoid, and blunt round terminus. Ribosomal and mitochondrial markers (D2-D3 expansion domains of 28S, ITS, partial 18S rRNA, and COI), as well as molecular phylogenetic analyses of sequences, confirmed this new taxon, and it was clearly delineated from X. macrodora and species within the species complex (X. costaricense, X. iberica, X. paraiberica, and X. pradense).

Abstract Background Prompt and effective management with maintenance therapy (single or dual bronchodilator therapy) is recommended after the initial diagnosis of chronic obstructive pulmonary disease (COPD) to maintain lung function and prevent exacerbations. Contrary to guideline-based recommendations, most patients are not prescribed maintenance treatment at initial diagnosis. The current study assessed the pharmacologic treatment patterns and outcomes of newly diagnosed patients with COPD in the USA. Methods This retrospective, noninterventional study used de-identified data from the Inovalon Insights’ database (Commercial, Medicaid Managed Care, and Medicare Advantage–insured individuals) between January 1, 2015, and December 31, 2021. The “patient journey” from initial diagnosis was followed over a 4-year period. The primary outcome measure was the number of moderate or severe exacerbations. Secondary outcome measures included the cumulative incidence of exacerbations, mean cumulative count of moderate and severe exacerbations, rates of moderate and severe exacerbations in patients who remained untreated after diagnosis in 12-month time periods for 4 years, sociodemographic and clinical characteristics, and pharmacologic treatment patterns. Results The cohort consisted of 238,158 newly diagnosed patients with COPD (female [52.9%]; mean age 63.8 years). The majority of patients with COPD had Medicaid as their primary insurance (46.2%). Overall, during the 4-year follow-up period, 32.9% of the patients had at least one moderate or severe exacerbation, and 25.8% and 13.8% experienced moderate and severe exacerbations, respectively. At diagnosis, 86.2% of the patients were untreated and most remained untreated by the end of the follow-up (63.8%). Most patients (62.0%) received long-acting beta-agonist (LABA)/inhaled corticosteroids (ICS) as their initial treatment at diagnosis, and LABA/ICS continued to be the most common initial treatment during the 4-year period (64.0% at year 1; 58.0% at year 4). Conclusions Most patients with COPD were not treated at initial diagnosis and remained untreated during follow-up. Our data highlight a lack of adherence to recommendations for clinical practice.

Abstract Identification of Aedes aegypti breeding hotspots is essential for the implementation of targeted vector control strategies and thus the prevention of several mosquito-borne diseases worldwide. Training computer vision models on satellite and street view imagery in the municipality of Rio de Janeiro, we analyzed the correlation between the density of common breeding grounds and Aedes aegypti infestation measured by ovitraps on a monthly basis between 2019 and 2022. Our findings emphasized the significance (p ≤ 0.05) of micro-habitat proxies generated through object detection, allowing to explain high spatial variance in urban abundance of Aedes aegypti immatures. Water tanks, non-mounted car tires, plastic bags, potted plants, and storm drains positively correlated with Aedes aegypti egg and larva counts considering a 1000 m mosquito flight range buffer around 2700 ovitrap locations, while dumpsters, small trash bins, and large trash bins exhibited a negative association. This complementary application of satellite and street view imagery opens the pathway for high-resolution interpolation of entomological surveillance data and has the potential to optimize vector control strategies. Consequently it supports the mitigation of emerging infectious diseases transmitted by Aedes aegypti, such as dengue, chikungunya, and Zika, which cause thousands of deaths each year.

BackgroundMechanical thrombectomy is a cornerstone treatment for acute ischemic stroke (AIS) with large vessel occlusion (LVO), yet the optimal technique remains debated. The SOFIA/SOFIA PLUS catheter has emerged as a promising tool for direct aspiration thrombectomy.PurposeThis prospective multi-center study, adhering Good-Clinical-Practice guidelines, aimed to evaluate the safety and efficacy of the SOFIA/SOFIA PLUS catheter for direct aspiration as a first-line treatment technique in patients with acute anterior circulation LVO.Materials and methodsBetween 10/2017 and 12/2021, 246 consecutive patients presenting with AIS due to anterior circulation LVO were enrolled from 14 European centers. Primary treatment with SOFIA catheters was performed within 6 h of symptom onset. Clinical and radiological data were collected, and statistical analyses were conducted.ResultsThe mean age of the included patients was 71.6 ± 13.9 years, with 44.7% being male. Primary aspiration achieved complete recanalization in 72.8% of patients, with functional independence observed in 63.8% after 90 days. Secondary outcomes included a median NIHSS of 4 at 24 h post-procedure, median ASPECTS of 7 on follow-up imaging, and a mortality rate of 24.4% at 90 days. No device malfunctions were observed, and the rate of symptomatic intracranial hemorrhage was 4.4%.ConclusionPrimary aspiration with the SOFIA/SOFIA PLUS catheter demonstrates favorable safety and efficacy profiles in the treatment of anterior circulation LVO. These findings support the utilization of this technique as a first-line approach in mechanical thrombectomy for AIS, contributing to the growing body of evidence endorsing the effectiveness of direct aspiration thrombectomy in stroke management.

OBJECTIVES:. Anemia has been associated with an increased risk of both cardiac arrest and stroke, frequent complications of COVID-19. The effect of hemoglobin level at ICU admission on a composite outcome of cardiac arrest or stroke in an international cohort of COVID-19 patients was investigated. DESIGN:. Retrospective analysis of prospectively collected database. SETTING:. A registry of COVID-19 patients admitted to ICUs at over 370 international sites was reviewed for patients diagnosed with cardiac arrest or stroke up to 30 days after ICU admission. Anemia was defined as: normal (hemoglobin ≥ 12.0 g/dL for women, ≥ 13.5 g/dL for men), mild (hemoglobin 10.0–11.9 g/dL for women, 10.0–13.4 g/dL for men), moderate (hemoglobin ≥ 8.0 and < 10.0 g/dL for women and men), and severe (hemoglobin < 8.0 g/dL for women and men). PATIENTS:. Patients older than 18 years with acute COVID-19 infection in the ICU. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Of 6926 patients (median age = 59 yr, male = 65%), 760 patients (11.0%) experienced stroke (2.0%) and/or cardiac arrest (9.4%). Cardiac arrest or stroke was more common in patients with low hemoglobin, occurring in 12.8% of patients with normal hemoglobin, 13.3% of patients with mild anemia, and 16.7% of patients with moderate/severe anemia. Time to stroke or cardiac arrest by anemia status was analyzed using Cox proportional hazards regression with death as a competing risk. Covariates selected through clinical knowledge were age, sex, comorbidities (diabetes, hypertension, obesity, and cardiac or neurologic conditions), pandemic era, country income, mechanical ventilation, and extracorporeal membrane oxygenation. Moderate/severe anemia was associated with a higher risk of cardiac arrest or stroke (hazard ratio, 1.32; 95% CI, 1.05–1.67). CONCLUSIONS:. In an international registry of ICU patients with COVID-19, moderate/severe anemia was associated with increased hazard of cardiac arrest or stroke.

Gynecomastia in adolescence is a benign condition that mostly disappears spontaneously within approximately two years from onset. When it is associated with hypogonadism, it may suggest a disorder of sexual differentiation. We report the case of a young man (18 years old) with gynecomastia associated with azoospermia, small testes, hyperestrogenism and hypergonadotropic hypogonadism. A karyotype 46,XX was found, and searching for SRY (sex-determining region Y) by fluorescence in situ hybridization (FISH) highlighted the presence of the gene on the terminal region of the short arm, with breakpoints likely in Xp22.3 and Yp11.3. Implications of testosterone replacement therapy with respect to sex differentiation disorder and to physical performance are discussed.

Aims: To investigate the risk factors for unsuccessful radial head reduction (RHR) in children with chronic Monteggia fractures (CMFs) treated surgically. Methods: A total of 209 children (mean age 6.84 years (SD 2.87)), who underwent surgical treatment for CMFs between March 2015 and March 2023 at six institutions, were retrospectively reviewed. Assessed risk factors included age, sex, laterality, dislocation direction and distance, preoperative proximal radial metaphysis width, time from injury to surgery, reduction method, annular ligament reconstruction, radiocapitellar joint fixation, ulnar osteotomy, site of ulnar osteotomy, preoperative and postoperative ulnar angulation, ulnar fixation method, progressive ulnar distraction, and postoperative cast immobilization. Independent-samples t-test, chi-squared test, and logistic regression analysis were used to identify the risk factors associated with unsuccessful RHR. Results: Redislocation occurred during surgery in 48 patients (23%), and during follow-up in 44 (21.1%). The mean follow-up of patients with successful RHR was 13.25 months (6 to 78). According to the univariable analysis, time from injury to surgery (p = 0.002) and preoperative dislocation distance (p = 0.042) were identified as potential risk factors for unsuccessful RHR. However, only time from injury to surgery (p = 0.007) was confirmed as a risk factor by logistic regression analysis. Receiver operating characteristic curve analysis and chi-squared test confirmed that a time from injury to surgery greater than 1.75 months increased the rate of unsuccessful RHR above the cutoff (p = 0.002). Conclusion: Time from injury to surgery is the primary independent risk factor for unsuccessful RHR in surgically treated children with CMFs, particularly in those with a time from injury to surgery of more than 1.75 months. No other factors were found to influence the incidence of unsuccessful RHR. Surgical reduction of paediatric CMFs should be performed within the first two months of injury whenever possible. Cite this article: Bone Jt Open 2024;5(7):581–591.

ROS1 rearrangements are considered rare in non-small-cell lung cancer (NSCLC). This retrospective real-world study aimed to evaluate first-line treatment with crizotinib, a tyrosine kinase inhibitor (TKI) standard of care vs. new generation ROS1 anti-cancer agents. Forty-nine ROS1-expressing NSCLC patients, diagnosed with advanced metastatic disease, were included. Molecular profiling using either FISH/CISH or NGS was performed on tissue samples. Twenty-eight patients were treated with crizotinib, while fourteen patients were administered newer drugs (entrectinib, repotrectinib) and seven patients received platinum-doublet chemotherapy in a first-line setting. Overall response rate and disease control rate for the crizotinib and entrectinb/repotrectinib cohort were 68% and 82% vs. 86% and 93%, respectively. Median progression free survival was 1.6 years (95% CI 1.15–2.215) for the crizotinib treatment vs. 2.35 years for the entrectinib/repotrectinib cohort (95% CI 1.19–3.52). Central nervous system progression was noted in 20% and 25% of the crizotinib and entrectinib/repotrectinib cohorts, respectively. This multi-center study presents real-world treatment patterns of ROS1 NSCLC population, indicating that crizotinib exhibited comparable results to entrectinib/repotrectinib in a first-line setting, although both response rate and survival was numerically longer with treatment with newer agents.

Abstract Background Biological invasions pose risks to the normal functioning of ecosystems by altering the structure and composition of several communities. Molluscs stand out as an extensively studied group given their long history of introduction by either natural or anthropogenic dispersal events. An alien population of the lymnaeid species Orientogalba viridis was first sighted in 2009 in southern Spain. In its native range (Australasian), this species is one of the main intermediate hosts of Fasciola hepatica, a major worldwide trematode parasite largely affecting humans, domestic animals and wildlife. Methods We collected field populations of O. viridis from its native (Malaysia) and invaded (Spain) ranges. We performed detailed morphoanatomical drawings of the species and screened for natural infection of parasites. Individuals were molecularly characterized using ITS2 for comparison with existing sequences in a fine phylogeography study. We founded experimental populations at two different conditions (tropical, 26 °C and temperate, 21 °C) to study the life-history traits of exposed and non-exposed individuals to different F. hepatica isolates. Results We found a 9% natural prevalence of trematode infection (98% similarity with a sequence of Hypoderaeum conoideum [Echinostomatidae]) in the Spanish field population. The haplotypes of O. viridis found in our study from Spain clustered with Australian haplotypes. Experimental infection with F. hepatica was successful in both experimental conditions but higher in tropical (87% prevalence) than in temperate (73%). Overall lifespan, however, was higher in temperate conditions (mean 32.5 ± 7.4 weeks versus 23.3 ± 6.5) and survivorship remained above 70% during the first 20 weeks. In parasite-exposed populations, life expectancy dropped from an overall 37.75 weeks to 11.35 weeks but still doubled the time for initial cercariae shedding. Cercariae shedding started at day 23 post-exposure and peaked between days 53 and 67 with an average of 106 metacercariae per snail. Conclusions Whether O. viridis will succeed in Europe is unknown, but the odds are for a scenario in which a major snail host of F. hepatica occupy all available habitats of potential transmission foci, ravelling the epidemiology of fasciolosis. This research provides a comprehensive understanding of O. viridis biology, interactions with parasites and potential implications for disease transmission dynamics, offering valuable insights for further research and surveillance. Graphical Abstract

Abstract Background In recent years, significant efforts have been directed towards the research and development of disease-modifying therapies for dementia. These drugs focus on prodromal (mild cognitive impairment, MCI) and/or early stages of Alzheimer’s disease (AD). Literature evidence indicates that a considerable proportion of individuals with MCI do not progress to dementia. Identifying individuals at higher risk of developing dementia is essential for appropriate management, including the prescription of new disease-modifying therapies expected to become available in clinical practice in the near future. Methods The ongoing INTERCEPTOR study is a multicenter, longitudinal, interventional, non-therapeutic cohort study designed to enroll 500 individuals with MCI aged 50–85 years. The primary aim is to identify a biomarker or a set of biomarkers able to accurately predict the conversion from MCI to AD dementia within 3 years of follow-up. The biomarkers investigated in this study are neuropsychological tests (mini-mental state examination (MMSE) and delayed free recall), brain glucose metabolism ([18F]FDG-PET), MRI volumetry of the hippocampus, EEG brain connectivity, cerebrospinal fluid (CSF) markers (p-tau, t-tau, Aβ1-42, Aβ1-42/1–40 ratio, Aβ1-42/p-Tau ratio) and APOE genotype. The baseline visit includes a full cognitive and neuropsychological evaluation, as well as the collection of clinical and socio-demographic information. Prognostic models will be developed using Cox regression, incorporating individual characteristics and biomarkers through stepwise selection. Model performance will be evaluated in terms of discrimination and calibration and subjected to internal validation using the bootstrapping procedure. The final model will be visually represented as a nomogram. Discussion This paper contains a detailed description of the statistical analysis plan to ensure the reproducibility and transparency of the analysis. The prognostic model developed in this study aims to identify the population with MCI at higher risk of developing AD dementia, potentially eligible for drug prescriptions. The nomogram could provide a valuable tool for clinicians for risk stratification and early treatment decisions. Trial registration ClinicalTrials.gov NCT03834402. Registered on February 8, 2019

Abstract In this paper we revisit the S 1 reduction of 4d N $$ \mathcal{N} $$ = 1 gauge theories, considering a double scaling on the radius of the circle and on the real masses arising from the global symmetries in the compactification. We discuss the implication of this double scaling for SQCD with gauge algebra of ABCD type. We then show how our prescription translates in the reduction of the 4d superconformal index to the 3d squashed three sphere partition function. This allows us to derive the expected integral identities for the 3d dualities directly from the four dimensional ones. This is relevant for the study of orthogonal SQCD, where the derivation from the 4d index is not possible in absence of the double scaling, because of a divergence due to a flat direction in the Coulomb branch of the effective theory on the circle. Furthermore, we obtain, for the even orthogonal case, a 3d duality with a quadratic fundamental monopole superpotential already discussed in the literature, that receives in this way an explanation from 4d.

Abstract Although Down syndrome (DS) is considered a risk factor for hemodynamic instabilities (mainly pulmonary hypertension–PH) following surgery for congenital cardiac communications, many DS patients do surprising well postoperatively. We prospectively analyzed perioperative factors for a possible correlation with post-cardiopulmonary bypass (CPB) inflammatory reaction and postoperative PH in pediatric subjects. Sixty patients were enrolled (age 3 to 35 months), 39 of them with DS. Clinical and echocardiographic parameters (anatomical and hemodynamic) were computed preoperatively. Pulmonary and systemic mean arterial pressures (PAP and SAP) were assessed invasively intra and postoperatively. Immediate postoperative PAP/SAP ratio (PAP/SAPIPO) and the behavior of pressure curves were selected as primary outcome. Serum levels of 36 inflammatory proteins were measured by chemiluminescence preoperatively and 4 h post CPB. Of all factors analyzed, peripheral oxygen saturation (O2Sat, bedside assessment) was the only preoperative predictor of PAP/SAPIPO at multivariate analysis (p = 0.007). Respective values in non-DS, DS/O2Sat ≥ 95% and DS/O2Sat

Abstract Background From the first steps of prostate cancer (PCa) initiation, tumours are in contact with the most-proximal adipose tissue called periprostatic adipose tissue (PPAT). Extracellular vesicles are important carriers of non-coding RNA such as miRNAs that are crucial for cellular communication. The secretion of extracellular vesicles by PPAT may play a key role in the interactions between adipocytes and tumour. Analysing the PPAT exovesicles (EVs) derived-miRNA content can be of great relevance for understanding tumour progression and aggressiveness. Methods A total of 24 samples of human PPAT and 17 samples of perivesical adipose tissue (PVAT) were used. EVs were characterized by western blot and transmission electron microscopy (TEM), and uptake by PCa cells was verified by confocal microscopy. PPAT and PVAT explants were cultured overnight, EVs were isolated, and miRNA content expression profile was analysed. Pathway and functional enrichment analyses were performed seeking potential miRNA targets. In vitro functional studies were evaluated using PCa cells lines, miRNA inhibitors and target gene silencers. Results Western blot and TEM revealed the characteristics of EVs derived from PPAT (PPAT-EVs) samples. The EVs were up taken and found in the cytoplasm of PCa cells. Nine miRNAs were differentially expressed between PPAT and PVAT samples. The RORA gene (RAR Related Orphan Receptor A) was identified as a common target of 9 miRNA-regulated pathways. In vitro functional analysis revealed that the RORA gene was regulated by PPAT-EVs-derived miRNAs and was found to be implicated in cell proliferation and inflammation. Conclusion Tumour periprostatic adipose tissue is linked to PCa tumour aggressiveness and could be envisaged for new therapeutic strategies.

Abstract Background Despite a multimodal approach including surgery, chemo- and radiotherapy, the 5-year event-free survival rate for rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in childhood, remains very poor for metastatic patients, mainly due to the selection and proliferation of tumour cells driving resistance mechanisms. Personalised medicine-based protocols using new drugs or targeted therapies in combination with conventional treatments have the potential to enhance the therapeutic effects, while minimizing damage to healthy tissues in a wide range of human malignancies, with several clinical trials being started. In this study, we analysed, for the first time, the antitumour activity of SFX-01, a complex of synthetic d, l-sulforaphane stabilised in alpha-cyclodextrin (Evgen Pharma plc, UK), used as single agent and in combination with irradiation, in four preclinical models of alveolar and embryonal RMS. Indeed, SFX-01 has shown promise in preclinical studies for its ability to modulate cellular pathways involved in inflammation and oxidative stress that are essential to be controlled in cancer treatment. Methods RH30, RH4 (alveolar RMS), RD and JR1 (embryonal RMS) cell lines as well as mouse xenograft models of RMS were used to evaluate the biological and molecular effects induced by SFX-01 treatment. Flow cytometry and the modulation of key markers analysed by q-PCR and Western blot were used to assess cell proliferation, apoptosis, autophagy and production of intracellular reactive oxygen species (ROS) in RMS cells exposed to SFX-01. The ability to migrate and invade was also investigated with specific assays. The possible synergistic effects between SFX-01 and ionising radiation (IR) was studied in both the in vitro and in vivo studies. Student’s t-test or two-way ANOVA were used to test the statistical significance of two or more comparisons, respectively. Results SFX-01 treatment exhibited cytostatic and cytotoxic effects, mediated by G2 cell cycle arrest, apoptosis induction and suppression of autophagy. Moreover, SFX-01 was able to inhibit the formation and the proliferation of 3D tumorspheres as monotherapy and in combination with IR. Finally, SFX-01, when orally administered as single agent, displayed a pattern of efficacy at reducing the growth of tumour masses in RMS xenograft mouse models; when combined with a radiotherapy regime, it was observed to act synergistically, resulting in a more positive outcome than would be expected by adding each exposure alone. Conclusions In summary, our results provide evidence for the antitumour properties of SFX-01 in preclinical models of RMS tumours, both as a standalone treatment and in combination with irradiation. These forthcoming findings are crucial for deeper investigations of SFX-01 molecular mechanisms against RMS and for setting up clinical trials in RMS patients in order to use the SFX-01/IR co-treatment as a promising therapeutic approach, particularly in the clinical management of aggressive RMS disease.

Objective: The aim of this review was to summarize the process and results of the Region of Murcia's 2022 Report Card on Physical Activity for Children and Youth. Methods: Indicators from the Global Matrix initiative (Overall Physical Activity, Organized Sport & Physical Activity, Physical Fitness, Active Play, Active Transport, Sedentary Behaviors, Family & Peers, School, Community & Environment, and Government) were evaluated based on the best available data in the Region of Murcia. Results: Active play was the indicator with the highest grade (B+), followed by Organized Sport & Physical Activity (B) and Active Play (B). School and Family and Peers indicators obtained a C+ and C grade, respectively. Both Community and Environment and Sedentary Behaviors indicators received a D+ grade. The grade for Overall Physical Activity and Government indicators was D. Physical Fitness was the indicator with the lowest grade of this Report Card (D−). None of the indicators received an incomplete grade (INC) because of a lack of available information. Conclusions: The present Report Card offers evidence highlighting the low level of physical activity in Spanish children and adolescents living in the Region of Murcia. Further studies and surveillance efforts are urgently needed for most of the indicators analyzed, which should be addressed by researchers and the Region of Murcia's Government for this specific population. A strong commitment from the Government of the Region of Murcia is needed at all levels to promote a cultural change that will lead children and young people in this region to improve the current situation.

Abstract In this paper we propose a physical derivation of a 4d conjectural duality for USp(2N) with an anti-symmetric rank-two tensor and fundamental flavors, in presence of a non-trivial superpotential. This duality has been conjectured as a consequence of an exact identity between the superconformal indices of the two phases, proved in the mathematical literature. Here we show that the duality can be derived by a combined sequence of known dualities, deconfinement of tensor matter, RG flow and Higgsing. Furthermore, by following these steps on the superconformal index, we provide an alternative derivation of the integral identity as well.

Abstract Background Healthcare-Associated Infections (HAIs) are a global public health issue, representing a significant burden of disease that leads to prolonged hospital stays, inappropriate use of antimicrobial drugs, intricately linked to the development of resistant microorganisms, and higher costs for healthcare systems. The study aimed to measure the prevalence of HAIs, the use of antimicrobials, and assess healthcare- and patient-related risk factors, to help identify key intervention points for effectively reducing the burden of HAIs. Methods A total of 28 acute care hospitals in the Lombardy region, Northern Italy, participated in the third European Point Prevalence Survey (PPS-3) coordinated by ECDC for the surveillance of HAIs in acute care hospitals (Protocol 6.0). Results HAIs were detected in 1,259 (10.1%, 95% CI 9.6–10.7%) out of 12,412 enrolled patients. 1,385 HAIs were reported (1.1 HAIs per patient on average). The most common types of HAIs were bloodstream infections (262 cases, 18.9%), urinary tract infections (237, 17.1%), SARS-CoV-2 infections (236, 17.0%), pneumonia and lower respiratory tract infections (231, 16.7%), and surgical site infections (152, 11.0%). Excluding SARS-CoV-2 infections, the overall prevalence of HAIs was 8.4% (95% CI 7.9–8.9%). HAIs were significantly more frequent in patients hospitalized in smaller hospitals and in intensive care units (ICUs), among males, advanced age, severe clinical condition and in patients using invasive medical devices. Overall, 5,225 patients (42.1%, 95% CI 41.3–43.0%) received systemic antimicrobial therapy. According to the WHO’s AWaRe classification, the Access group accounted for 32.7% of total antibiotic consumption, while Watch and Reserve classes accounted for 57.0% and 5.9% respectively. From a microbiological perspective, investigations were conducted on only 64% of the HAIs, showing, however, a significant pattern of antibiotic resistance. Conclusions The PPS-3 in Lombardy, involving data collection on HAIs and antimicrobial use in acute care hospitals, highlights the crucial need for a structured framework serving both as a valuable benchmark for individual hospitals and as a foundation to effectively channel interventions to the most critical areas, prioritizing future regional health policies to reduce the burden of HAIs.

Abstract Understanding contemporary organizations hinges on the comprehension of rules and rule behavior. This scholarship explores the idea of employees rule-breaking for pro-social reasons. It challenges the belief that workplace rule violations are only motivated by personal gain and self-interest. Through two surveys conducted among grassroots civil servants working in public welfare programs, this research delves into the impact of social, relational, and bureaucratic factors on employees’ attitudes and behaviors toward pro-social rule-breaking. The study discovered that when individuals receive social support and witness co-workers’ rule-breaking, they are likelier to exhibit pro-social rule-breaking attitudes and behaviors. In contrast, organizational structure variables bureaucratic centralization and formalization and disciplinary control factors bureaucratic rule-breaking punishment and the certainty of detection diminish employees’ willingness to break the rules for pro-social reasons. The findings highlight the importance of recognizing social, relational, and bureaucratic organizational attributes to better understand pro-social rule-breaking among grassroots civil servants in public sector welfare agencies.

Abstract Detection of high glycated hemoglobin (A1c) is associated with worse postoperative outcomes, including predisposition to develop systemic and local infectious events. Diabetes and infectious Outcomes in Cardiac Surgery (DOCS) study is a retrospective case–control study aimed to assess in DM and non-DM cardiac surgery patients if a new screening and management model, consisting of systematic A1c evaluation followed by a specialized DM consult, could reduce perioperative infections and 30-days mortality. Effective July 2021, all patients admitted to the cardiac surgery of IRCCS ISMETT were tested for A1c. According to the new protocol, glucose values of patients with A1c ≥ 6% or with known diabetes were monitored. The diabetes team was activated to manage therapy daily until discharge or provide indications for the diagnostic-therapeutic process. Propensity score was used to match 573 patients managed according to the new protocol (the Screen+ Group) to 573 patients admitted before July 2021 and subjected to the traditional management (Screen−). Perioperative prevalence of infections from any cause, including surgical wound infections (SWI), was significantly lower in the Screen+ as compared with the Screen− matched patients (66 [11%] vs. 103 [18%] p = 0.003). No significant difference was observed in 30-day mortality. A1c analysis identified undiagnosed DM in 12% of patients without known metabolic conditions. In a population of patients undergoing cardiac surgery, systematic A1c evaluation at admission followed by specialist DM management reduces perioperative infectious complications, including SWI. Furthermore, A1c screening for patients undergoing cardiac surgery unmasks unknown DM and enhances risk stratification.

Abstract Liver cancer ranks as the fifth leading cause of cancer-related death globally. Direct intratumoral injections of anti-cancer therapeutics may improve therapeutic efficacy and mitigate adverse effects compared to intravenous injections. Some challenges of intratumoral injections are that the liquid drug formulation may not remain localized and have unpredictable volumetric distribution. Thus, drug delivery varies widely, highly-dependent upon technique. An X-ray imageable poloxamer 407 (POL)-based drug delivery gel was developed and characterized, enabling real-time feedback. Utilizing three needle devices, POL or a control iodinated contrast solution were injected into an ex vivo bovine liver. The 3D distribution was assessed with cone beam computed tomography (CBCT). The 3D distribution of POL gels demonstrated localized spherical morphologies regardless of the injection rate. In addition, the gel 3D conformal distribution could be intentionally altered, depending on the injection technique. When doxorubicin (DOX) was loaded into the POL and injected, DOX distribution on optical imaging matched iodine distribution on CBCT suggesting spatial alignment of DOX and iodine localization in tissue. The controllability and localized deposition of this formulation may ultimately reduce the dependence on operator technique, reduce systemic side effects, and facilitate reproducibility across treatments, through more predictable standardized delivery.

Abstract The aim of this study is to analyse the relationship between sport modalities practiced, physical fitness, body composition, and healthy habits in an active young population, using a statistical model for prediction. A total of 2255 (1528 boys and 727 girls) children and adolescents aged 6–17 years old who were involved in extracurricular sports from rural areas of Spain participated. Physical fitness was assessed through validated field test and, body composition was determinated using bioelectrical impedance analysis. Adherence to the Mediterranean diet was assessed by KIDMED questionnaire. The general sport variable was significant in VO2max when comparing the invasion and combat modalities to the reference level (court/net). The sex and age variables revealed significant differences in all physical fitness and body composition parameters. Health parameters, such as hours of additional practice, adherence to the Mediterranean diet, and previous experience, showed significant differences. The study concludes that the sport modality variables of training, sex, age, and maturational period have an impact on body composition and fitness parameters in this population. Therefore, by focusing on factors associated with lower values in health indicators, we can prevent health problems during adulthood, such as cardiorespiratory deficits.

Abstract Background Circulating total insulin-like growth factor-I (IGF-I) is an established risk factor for prostate cancer. However, only a small proportion of circulating IGF-I is free or readily dissociable from IGF-binding proteins (its bioavailable form), and few studies have investigated the association of circulating free IGF-I with prostate cancer risk. Methods We analyzed data from 767 prostate cancer cases and 767 matched controls nested within the European Prospective Investigation into Cancer and Nutrition cohort, with an average of 14-years (interquartile range = 2.9) follow-up. Matching variables were study center, length of follow-up, age, and time of day and fasting duration at blood collection. Circulating free IGF-I concentration was measured in serum samples collected at recruitment visit (mean age 55 years old; standard deviation = 7.1) using an enzyme-linked immunosorbent assay (ELISA). Conditional logistic regressions were performed to examine the associations of free IGF-I with risk of prostate cancer overall and subdivided by time to diagnosis (≤ 14 and > 14 years), and tumor characteristics. Results Circulating free IGF-I concentrations (in fourths and as a continuous variable) were not associated with prostate cancer risk overall (odds ratio [OR] = 1.00 per 0.1 nmol/L increment, 95% CI: 0.99, 1.02) or by time to diagnosis, or with prostate cancer subtypes, including tumor stage and histological grade. Conclusions Estimated circulating free IGF-I was not associated with prostate cancer risk. Further research may consider other assay methods that estimate bioavailable IGF-I to provide more insight into the well-substantiated association between circulating total IGF-I and subsequent prostate cancer risk.

Abstract Background Lung cancer is one of the most lethal cancers worldwide and patient clinical outcomes seem influenced by their socioeconomic position (SEP). Since little has been investigated on this topic in the Italian context, our aim was to investigate the role of SEP in the care pathway of lung cancer patients in terms of diagnosis, treatment and mortality. Methods This observational retrospective cohort study included patients discharged in the Lazio Region with a lung cancer diagnosis between 2014 and 2017. In the main analysis, educational level was used as SEP measure. Multivariate models, adjusted for demographic and clinical variables, were applied to evaluate the association between SEP and study outcomes, stratified for metastatic (M) and non-metastatic (NM) cancer. We defined a diagnosis as 'delayed' when patients received their initial cancer diagnosis after an emergency department admission. Access to advanced lung cancer treatments (high-cost, novel and innovative treatments) and mortality were investigated within the 24-month period post-diagnosis. Moreover, two additional indicators of SEP were examined in the sensitivity analysis: one focusing on area deprivation and the other on income-based exemption. Results A total of 13,251 patients were identified (37.3% with metastasis). The majority were males (> 60%) and over half were older than 70 years. The distribution of SEP levels among patients was as follow: 31% low, 29% medium–low, 32% medium–high and 7% high. As SEP increased, the risks of receiving a delayed diagnosis ((high vs low: M: OR = 0.29 (0.23–0.38), NM: OR = 0.20 (0.16–0.25)) and of mortality ((high vs low M: OR = 0.77 (0.68–0.88) and NM: 0.61 (0.54–0.69)) decreased. Access to advanced lung cancer treatments increased in accordance with SEP only in the M cohort (high vs low: M: OR = 1.57 (1.18–2.09)). The primary findings were corroborated by sensitivity analysis. Conclusions Our study highlighted the need of public health preventive and educational programs in Italy, a country where the care pathway of lung cancer patients, especially in terms of diagnosis and mortality, appears to be negatively affected by SEP level.

Abstract Background Literature suggests colonic resection and primary anastomosis (RPA) instead of Hartmann’s procedure (HP) for the treatment of left-sided colonic emergencies. We aim to evaluate the surgical options globally used to treat patients with acute left-sided colonic emergencies and the factors that leading to the choice of treatment, comparing HP and RPA. Methods This is a prospective, international, multicenter, observational study registered on ClinicalTrials.gov. A total 1215 patients with left-sided colonic emergencies who required surgery were included from 204 centers during the period of March 1, 2020, to May 31, 2020. with a 1-year follow-up. Results 564 patients (43.1%) were females. The mean age was 65.9 ± 15.6 years. HP was performed in 697 (57.3%) patients and RPA in 384 (31.6%) cases. Complicated acute diverticulitis was the most common cause of left-sided colonic emergencies (40.2%), followed by colorectal malignancy (36.6%). Severe complications (Clavien-Dindo ≥ 3b) were higher in the HP group (P

Safeners protect crops by enhancing their ability to metabolize various compounds, including herbicides. They increase a crop’s tolerance to herbicide damage, activating herbicide-metabolizing proteins, and aiding in their detoxification. This study aimed to investigate the chemical effects of safeners in tomato cultivation and focus on injury reduction and tissue protection. The experiment followed a randomized factorial design (5 × 4) with four replications repeated twice. We evaluated the effects of herbicides dicamba, 2,4-D, metribuzin, and sulfentrazone (diluted to 1% of the recommended field rate) and safeners benoxacor, fenclorim, melatonin, 2,4,6-T, and an untreated control. Safeners were applied to the seeds before sowing, and herbicides were applied as a foliar spray 25 days after sowing. Visual injury was evaluated 7, 14, and 21 days after application (DAA). Biomass measurements were taken 21 DAA. Results showed that preconditioning tomato seeds with 2,4,6-T, melatonin, and fenclorim 7 DAA significantly decreased injury by 25, 25, and 23%, respectively. Moreover, applying melatonin, benoxacor, and 2,4,6-T 21 DAA led to significantly greater dry biomass, which increased by 1.5, 1.42, and 1.44 times, respectively, compared with the control. This research provides valuable insights into the chemical effects of benoxacor, fenclorim, 2,4,6-T, and melatonin safeners in tomato cultivation. The findings demonstrate the potential for preconditioning tomato plants with 2,4,6-T, melatonin, and fenclorim to reduce herbicide injury. Additionally, melatonin, benoxacor, and 2,4,6-T stimulated growth, increasing tomato dry biomass. Understanding plant defense mechanisms and the protective effects of safeners against herbicide damage contributes to developing effective weed management strategies.

Objectives To investigate the use of maintenance immunosuppressive treatments following liver transplantation and to compare their risk–benefit profiles in clinical practice.Design Retrospective multicentrer cohort study.Setting Four Italian regions (Lombardy, Veneto, Lazio, Sardinia).Methods Data were integrated from the national transplant information system and administrative claims data from four Italian regions. All adults who underwent incident liver transplantation between 2009 and 2019 were identified and categorised into two groups: cirrhosis or hepatocellular carcinoma (HCC). The trend of immunosuppressive treatment over years was analysed, and their effectiveness/safety profiles were compared using multivariate Cox models (HR; 95% CI).Main outcome measures Mortality, transplant reject/graft failure, incidence of severe infections, cancer, diabetes, major adverse cardiovascular events and lipid-modifying agents use.Results The study comprised 750 subjects in the cirrhosis cohort and 1159 in the HCC cohort. Over the study years, there was a decline in the use of cyclosporine-CsA, while combination therapy involving tacrolimus with other drugs increased compared with monotherapy. Overall, tacrolimus monotherapy use was slightly over 40% in both groups, followed by tacrolimus+mycophenolate (39.5%-cirrhosis; 30.6%-HCC) and tacrolimus+molecular target of rapamycin inhibitors (mTORi) (8.5%-cirrhosis; 13.3%-HCC). No significant differences emerged in risk–benefit profile of different tacrolimus-based therapies, except for a higher risk of mortality in cirrhosis subjects under tacrolimus monotherapy compared with tacrolimus+mycophenolate (HR: 2.07; 1.17 to 3.65).Conclusions The study highlights a shift over time in postliver transplant therapeutic patterns, favouring the use of tacrolimus in combination with mycophenolate or mTORi, rather than monotherapy. Moreover, a potential association between tacrolimus monotherapy and increased mortality in the cirrhosis cohort was identified. Further research is warranted to investigate these findings more deeply and to optimise treatment strategies for liver transplant recipients.

Developing new cultivars, particularly in perennial species like Coffea arabica, can be a time-consuming process. Employing molecular markers in genome-wide selection (GWS) for predicting genetic values offers an alternative to accelerate this process. However, implementing GWS typically involves genotyping many markers for both training and candidate individuals, which can increase the total genotyping cost for the breeding program. Therefore, this study aimed to assess the feasibility of using low-density marker panels to predict the genetic merit of C. arabica for a range of desirable agronomic traits. For this purpose, GWS analyses were performed using the G-BLUP method with panels of varying marker densities, selected based on marker effect magnitude. The results indicate that employing lower-density panels might be advantageous for this species' improvement. Models based on these panels yielded accurate predictions for various traits and demonstrated high agreement in terms of selected individuals compared to more complex models.

Pancreatic ductal adenocarcinoma (PDAC) is the most aggressive and invasive type of pancreatic cancer and is expected to soon become the second leading cause of cancer-associated death. The high mortality rate is due to the clinical features that allow asymptomatic progression to advanced stages, a period when current therapeutic treatments have limited efficacy. To address these challenges, researchers are focused on identifying new molecular and circulating markers for early PDAC detection and precision medicine. In this mini-review, we report the most well-known and recently identified molecular and circulating biomarkers. This study aimed to emphasize the need for continued innovative research to develop diagnostic algorithms and therapies to improve the management of patients with PDAC.

Summary: Background: Nutri-Score is a scientifically validated 5-color front-of-pack nutrition label reflecting the nutrient profile of foods. It has been implemented in several European countries on a voluntary basis, pending the revision of the European labeling regulation. Hence, scientific evidence is needed regarding the ability of the nutrient profile underlying the Nutri-Score (uNS-NPS, 2023-updated version) to characterize healthier foods. Our objective was therefore to study the prospective association between the nutritional quality of diet characterized by the uNS-NPS and the risk of cardiovascular diseases in a large European population. Methods: Our analyses included 345,533 participants from the European Prospective Investigation into Cancer and Nutrition study (EPIC, 1992–2010, 7 European countries). Food intakes were assessed at baseline using country-specific dietary questionnaires. The uNS-NPS was calculated as a continuous scale for each food, based on its 100 g content of energy, sugars, saturated fatty acids, salt, fibre, and protein and percentage content of fruit, vegetables, and pulses. A dietary index was derived at the individual level (uNS-NPS DI: energy-weighted mean of uNS-NPS scores of all foods consumed by a participant). Cardiovascular events during follow-up were retrieved using country-specific methods (self-report, registry data). Multi-adjusted Cox models were computed. Findings: Overall, 16,214 first cardiovascular events were reported (median follow-up: 12.3 years; 4,103,133 person-years). The consumption of foods with a higher uNS-NPS score (reflecting a lower overall nutritional quality of diet) was associated with higher risks of total cardiovascular events (Hazards Ratio (HR) for an increment of 1 standard deviation: 1.03 (95% Confidence Interval 1.01–1.05)), especially myocardial infarction (HR = 1.03 (1.01–1.07)), and stroke (HR = 1.04 (1.01–1.07)). Interpretation: In this large prospective study among European adults, a higher risk of cardiovascular diseases (total and several subtypes) was observed in individuals consuming a diet with a lower nutritional value, as graded by the uNS-NPS score. This brings new evidence on the relevance of the updated nutrient profile underlying the Nutri-Score to characterize foods with a healthier nutrient profile. Funding: EPIC-CVD was supported by EU FP7, ERC, UK MRC, British Heart Foundation, and UK NIHR.

Ultrafast fiber lasers (UFLs) have become an attractive alternative to solid‐state lasers (SSL) due to their excellent beam quality, compactness, environmental stability, and easy thermal management. In the last decade, a significant research effort is spent to identify UFL architectures providing pulse energy, duration, and peak power comparable to those of complex and expensive, Ti:sapphire laser systems and semiconductor saturable absorber mirrors mode‐locked, Yb‐doped SSL. Lately, Mamyshev oscillators (MOs), relying on offset spectral filtering combined with nonlinear spectral broadening by self‐phase modulation, emerge as a promising solution and are rapidly becoming the state of the art for high energy/peak power UFLs based on large‐mode‐area (LMA) fibers. The focus of this work is the first demonstration of starting of the mode‐locking regime in an LMA MO with an affordable passively Q‐switched microchip laser. This solution was previously demonstrated only in low‐power MO based on single‐mode fibers, which are intrinsically easier to seed, if compared to high‐gain LMA UFLs, because of the lower amplified spontaneous emission noise floor. This starting technique in an easy‐to‐implement ring LMA MO at 1 μm is tested. The oscillator provides ≈50 nJ pulses at 12 MHz repetition rate with a minimum pulse duration of ≈50 fs after compression, resulting in MW peak power.