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Study Design: Retrospective cohort study., Objective: This study aimed to compare perioperative outcomes of Rett syndrome and Cerebral palsy patients undergoing posterior spinal fusion for neuromuscular scoliosis., Summary of Background Data: Surgical correction in the treatment of scoliosis for patients with Rett syndrome (RS) has been shown to increase survival rate. Cerebral palsy (CP) patients, like RS patients, are often nonverbal, nonambulatory, with frequent surgical complications., Methods: Retrospective review of 36 RS and 80 CP patients undergoing PSF from 2005-2023. Data and x-ray measurements were collected pre- and post-operatively. Sub-analysis was performed comparing non-ambulatory patients (GMFCS IV-V). Wilcoxon-Rank Sum, Fisher's Exact, and Chi-square tests were utilized., Results: The primary outcome measure, complication rates, was similar between the groups (P=0.09). Preoperative Cobb angle, levels fused, fixation points, and LOS were similar (P>0.05). EBL was significantly higher in CP patients as was rate of transfusion (P=0.001) and surgical time (P=0.001). Postoperative Cobb angle (P=0.002) was significantly higher for CP patients. There was no significant difference between CP and RS patients in both preoperative (P=0.383) and postoperative (P=0.051) coronal decompensation. Nonambulatory status was associated with increased odds of having a postoperative complication (OR=6.17, 95% C.I. 1.36 - 28.04). Sub-analysis of non-ambulatory RS and CP patients revealed significantly higher postoperative Cobb (P=0.008), EBL (P=0.019) and surgical time (P=0.017) in CP patients compared to RS patients. There were no significant differences in preoperative Cobb, levels fused, fixation points, hospital stay, or complication rate (P>0.05)., Conclusion: RS patients are shown to have better outcomes to CP patients in terms of surgical, perioperative, and radiographic variables. Ambulatory status was identified as an independent risk factor for complications., Competing Interests: Conflicts of Interest and Source of Funding: Dr. Sarwahi received personal fees and royalties from Precision Spine, INC. outside the submitted work and not relevant to the study. All other authors declare they have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Immunosuppressive medications play a crucial role in inflammatory bowel disease (IBD) but increase susceptibility to infections, underlining the importance of vaccination. Nevertheless, vaccination rates are often low., Aims: This study assessed the perspective of gastroenterologists (GEs) on vaccination of IBD patients., Methods: An online survey was applied to GEs worldwide, from 10/2022 to 06/2023., Results: The 271 respondents considered vaccination important, however, 26 % never/rarely prescribed vaccines and 60 % admitted having limited or no confidence on managing their side effects - GEs practicing in Europe, male and older more often felt capable of this. Female and younger participants were more aware of the need to alter the current workflow in vaccination. Some respondents proposed to delegate the responsibility of vaccination to general practitioners, nurses in gastroenterology units, or infectious diseases specialists, but 19 % considered that no change was needed., Conclusion: Overall, the importance of addressing vaccine hesitancy, providing flyers to patients, and implementing vaccine guidelines were consensually recognized. The data indicated that the vaccination process needs reformulation and that different opinions/attitudes toward vaccines are influenced by demographic factors, workplace characteristics, affiliation, and teaching activities. Delegating the responsibility of vaccination and adopting a multidisciplinary approach seem like effective strategies to increase vaccination coverage among IBD patients., Competing Interests: Conflicts of interest C.A. served as a speaker and received honoraria from Pfizer, Glaxo Smith Klein and Astra-Zeneca. F.M. served as a speaker and received honoraria from Merck Sharp & Dohme, Abbvie, Vifor, Falk, Laboratórios Vitória, Ferring, Hospira, and Biogen. For the remaining authors, there are no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Aims: To investigate the molecular events associated with acquiring macrolide resistance genes [mefE/mel (Mega) or ermB] in Streptococcus pneumoniae (Spn) during nasopharyngeal colonization., Methods and Results: Genomic analysis of 128 macrolide-resistant Spn isolates revealed recombination events in genes of the conjugation apparatus, or the competence system, in strains carrying Tn916-related elements. Studies using confocal and electron microscopy demonstrated that during the transfer of Tn916-related elements in nasopharyngeal cell biofilms, pneumococcal strains formed clusters facilitating their acquisition of resistance determinants at a high recombination frequency (rF). Remarkably, these aggregates comprise both encapsulated and nonencapsulated pneumococci that span extracellular and intracellular compartments. rF assessments showed similar rates regardless Mega was associated with large integrative and conjugative elements (ICEs) (>23 kb) or not (∼5.4 kb). The rF for Mega Class IV(c) insertion region (∼53 kb) was three orders of magnitude higher than the transformation of the capsule locus. Metabolomics studies of the microenvironment created by colonization of human nasopharyngeal cells revealed a link between the acquisition of ICEs and the pathways involving nicotinic acid and sucrose., Conclusions: Pneumococcal clusters, both extracellular and intracellular, facilitate macrolide resistance acquisition, and ICEs were acquired at a higher frequency than the capsule locus. Metabolic changes could serve as intervention targets., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

This study aimed to determine the protective role of the high release of C. albicans extracellular DNA (eDNA) in a polymicrobial biofilm formed by S. aureus and S. mutans in the course of DNase I treatment. A tube-flow biofilm bioreactor was developed to mimic biofilm formation in the oral cavity. eDNA release was quantified by real-time PCR (qPCR) and confocal microscopy analysis were used to determine the concentration and distribution of eDNA and intracellular DNA (iDNA). The mean amount of eDNA released by each species in the polymicrobial was higher than that in monospecies biofilms (S. aureus: 3.1 × 10 -2  ng/μl polymicrobial versus 5.1 × 10 -4  ng/μl monospecies; S. mutans: 3 × 10 -1  ng/μl polymicrobial versus 2.97 × 10 -2  ng/μl monospecies; C. albicans: 8.35 ng/μl polymicrobial versus 4.85 ng/μl monospecies). The large amounts of eDNA released by C. albicans (96%) in polymicrobial biofilms protects the S. aureus and S. mutans cells against the degradation by DNase I and dampens the effect of clindamycin., (© 2024. The Author(s) under exclusive licence to Sociedade Brasileira de Microbiologia.)

RTS,S/AS01 E , the first approved malaria vaccine, demonstrated moderate efficacy during the phase 3 pediatric trial. We previously investigated cell-mediated immune (CMI) responses following the primary 3-dose immunization and now report responses to the booster dose given 18 months later. Thirty CMI markers were measured by Luminex in supernatants of peripheral blood mononuclear cells from 709 children and infants after RTS,S/AS01 E antigen stimulation, and their associations with malaria risk and antibodies one month post-booster and one year later were assessed. IL-2, IFN-γ, IL-17, IL-5, and IL-13 were associated with RTS,S/AS01 E booster vaccination, and IL-2 responses to the circumsporozoite protein (CSP) remained higher after one year. IL-2 was associated with reduced malaria risk in one site, and IL-10 was associated with increased risk in infants. Anti-CSP IgG and IL-2 were moderately correlated one year after booster. This study highlights the moderate cell-mediated immunogenicity of the RTS,S/AS01 E booster dose that aligns with partial recovery of RTS,S/AS01 E vaccine efficacy., (© 2024. The Author(s).)

Dumbbell-like hetero nanostructures based on gold and iron oxides is a promising material for biomedical applications, useful as versatile theranostic agents due the synergistic effect of their optical and magnetic properties. However, achieving precise control on their morphology, size dispersion, colloidal stability, biocompatibility and cell targeting remains as a current challenge. In this study, we address this challenge by employing biomimetic routes, using ferritin protein nanocages as template for these nanoparticles' synthesis. We present the development of an opto-magnetic nanostructures using the ferritin protein, wherein gold and iron oxide nanostructures were produced within its cavity. Initially, we investigated the synthesis of gold nanostructures within the protein, generating clusters and plasmonic nanoparticles. Subsequently, we optimized the conditions for the superparamagnetic nanoparticles synthesis through controlled iron oxidation, thereby enhancing the magnetic properties of the resulting system. Finally, we produce magnetic nanoparticles in the protein with gold clusters, achieving the coexistence of both nanostructures within a single protein molecule, a novel material unprecedented to date. We observed that factors such as temperature, metal/protein ratios, pH, dialysis, and purification processes all have an impact on protein recovery, loading efficiency, morphology, and nanoparticle size. Our findings highlight the development of ferritin-based nanomaterials as versatile platforms for potential biomedical use as multifunctional theranostic agents., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background and Purpose: Fentanyls and nitazenes are μ-opioid receptor agonists responsible for a large number of opioid overdose deaths. Here, we determined the potency, dissociation kinetics and antagonism by naloxone at the μ receptor of several fentanyl and nitazene analogues, compared to morphine and DAMGO., Experimental Approach: In vitro assays of G protein activation and signalling and arrestin recruitment were performed. AtT20 cells expressing μ receptors were loaded with a membrane potential dye and changes in fluorescence used to determine agonist potency, dissociation kinetics and susceptibility to antagonism by naloxone. BRET experiments were undertaken in HEK293T cells expressing μ receptors to assess Gi protein activation and β-arrestin 2 recruitment., Key Results: The apparent rate of agonist dissociation from the μ receptor varied: morphine, DAMGO, alfentanil and fentanyl dissociated rapidly, whereas isotonitazene, etonitazene, ohmefentanyl and carfentanil dissociated slowly. Slowly dissociating agonists were more resistant to antagonism by naloxone. For carfentanil, the slow apparent rate of dissociation was not because of G protein receptor kinase-mediated arrestin recruitment as its apparent rate of dissociation was not increased by inhibition of G protein-coupled receptor kinases (GRKs) with Compound 101. The in vitro relative potencies of fentanyls and nitazenes compared to morphine were much lower than that previously observed in in vivo experiments., Conclusions and Implications: With fentanyls and nitazenes that slowly dissociate from the μ receptor, antagonism by naloxone is pseudo-competitive. In overdoses involving fentanyls and nitazenes, higher doses of naloxone may be required for reversal than those normally used to reverse heroin overdose., (© 2024 The Author(s). British Journal of Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society.)

Background: Evidence on long COVID symptom clustering patterns among patients with COVID-19 is limited. We summarized long COVID symptoms in clusters defined by number of symptoms co-occurring together, and we assessed Health-Related Quality of Life (HQRoL), Work Productivity and Activity Impairment (WPAI) outcomes across these clusters over time. We assessed associations between the clusters and BNT162b2 vaccination status., Methods: A prospective longitudinal patient-reported outcomes (PRO) study recruited laboratory-confirmed symptomatic COVID-19 patients seeking testing from a national retail pharmacy. Long COVID-19 symptoms were self-reported by participants at 4-week, 3-month and 6-month surveys. Patient classes identified via latent class analysis (LCA) with long COVID-19 symptoms were simplified into clusters based on number of symptoms. HRQoL and WPAI outcomes were collected using EQ-ED-5L and WPAI: GH questionnaires. Mixed models for repeated measures analyses were conducted to examine associations between exposure groups and outcomes., Results: The study included 328 participants that were segmented into three groups of long COVID-19 symptoms based on LCA and then simplified by the number of symptoms (Cluster 1 low, <2; Cluster 2 moderate, 2-6; and Cluster 3 high, >6 symptoms). The number of long COVID-19 symptoms was negatively associated with HRQoL and WPAI, whereby participants with high symptom burden (>6 symptoms) had the lowest HRQoL and WPAI scores assessed by absenteeism, presenteeism, work productivity loss, activity impairment, and hours worked metrics. Compared with those unvaccinated and not up-to-date with COVID-19 vaccination, subjects boosted with BNT162b2 consistently reported less symptom burden during the follow-up, regardless of their symptom-based cluster., Conclusion: Three distinct patient clusters based on frequency of long COVID symptoms experienced different HRQoL and WPAI outcomes over 6 months. The cluster with more concomitant symptoms experienced greater burden than the others. Participants up-to-date with BNT162b2 reported lower symptom burden across all clusters and timeframes., Clinical Trial Registration: Clinicaltrials.gov NCT05160636., (© 2024. The Author(s).)

Immunotherapy can lead to long-term survival for some cancer patients, yet generalized success has been hampered by insufficient antigen presentation and exclusion of immunogenic cells from the tumor microenvironment. Here, we developed an approach to reprogram tumor cells in vivo by adenoviral delivery of the transcription factors PU.1, IRF8, and BATF3, which enabled them to present antigens as type 1 conventional dendritic cells. Reprogrammed tumor cells remodeled their tumor microenvironment, recruited, and expanded polyclonal cytotoxic T cells; induced tumor regressions; and established long-term systemic immunity in multiple mouse melanoma models. In human tumor spheroids and xenografts, reprogramming to immunogenic dendritic-like cells progressed independently of immunosuppression, which usually limits immunotherapy. Our study paves the way for human clinical trials of in vivo immune cell reprogramming for cancer immunotherapy.

Gastrointestinal bleeding (GIB) is a serious complication following allogeneic hematopoietic stem cell transplantation (HSCT), with limited data on its incidence and characteristics, particularly for upper gastrointestinal bleeding (UGIB) of gastric origin. We aimed to evaluate the incidence, clinical, endoscopic, and histopathologic features, and outcomes of UGIB, with a focus on gastric vascular ectasias (GVEs) in patients undergoing HSCT with graft-versus-host disease (GVHD) prophylaxis using post-transplant cyclophosphamide (PTCY), sirolimus or calcineurin inhibitors, and mycophenolate mofetil. This retrospective, single-center study included all adult patients who underwent allogeneic HSCT at a single institution between January 2017 and December 2023. Data were collected on transplant procedures, complications, and GIB incidents, with UGIB cases undergoing endoscopic and histologic examination. Out of 559 patients, 38 (6.6%) experienced UGIB, with 27 cases (70%) attributed to GVE. GVE typically presented as melena or hematemesis at a median time of 68 d (range, 29 to 125) after transplant. Endoscopy revealed diffuse oozing from gastric antral mucosa without distinct lesions, while histology showed vascular congestion and mild foveolar hyperplasia. The 6-mo cumulative incidence of GVE was 5.1%. Older age (≥60 yr) and diagnosis of myelodysplastic/myeloproliferative neoplasm were significant risk factors. All cases resolved with no attributable mortality with supportive measures including transfusions, proton-pump inhibitors, and sirolimus withdrawal in some cases. GVE is a notable cause of UGIB in HSCT recipients on PTCY-based GVHD prophylaxis, presenting significant morbidity but favorable outcomes with appropriate management. The potential role of sirolimus and conditioning agents in GVE pathogenesis warrants further investigation., (Copyright © 2024. Published by Elsevier Inc.)

The promising results obtained in the PARADIGM-HF trial prompted the approval of sacubitril/valsartan (SAC/VAL) as a first-in-class treatment for heart failure with reduced ejection fraction (HFrEF) patients. The effect of SAC/VAL treatment was also studied in patients with heart failure with preserved ejection fraction (HFpEF) and, although improvements in New York Heart Association (NYHA) class, HF hospitalizations, and cardiovascular deaths were observed, these results were not so promising. However, the demand for HFpEF therapies led to the approval of SAC/VAL as an alternative treatment, although further studies are needed. We aimed to elucidate the effects of a 9-week SAC/VAL treatment in cardiac function and metabolism using a preclinical model of HFpEF, the Zucker Fatty and Spontaneously Hypertensive (ZSF1) rats. We found that SAC/VAL significantly improved diastolic function parameters and modulated respiratory quotient during exercise. Ex-vivo studies showed that SAC/VAL treatment significantly decreased heart, liver, spleen, and visceral fat weights; cardiac hypertrophy and percentage of fibrosis; lipid infiltration in liver and circulating levels of cholesterol and sodium. Moreover, SAC/VAL reduced glycerophospholipids, cholesterol, and cholesteryl esters while increasing triglyceride levels in cardiac tissue. In conclusion, SAC/VAL treatment improved diastolic and hepatic function, respiratory metabolism, reduced hypercholesterolemia and cardiac fibrosis and hypertrophy, and was able to modulate cardiac metabolic profile. Our findings might provide further insight into the therapeutic benefits of SAC/VAL treatment in obese patients with HFpEF., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Longstanding disease control in Crohn's disease (CD) is challenging and requires understanding treatment efficacy and outcomes assessment. With multiple novel therapeutic options, rigorous evaluation of outcomes in randomized controlled trials (RCTs) is crucial to inform clinical practice. This study systematically reviewed RCTs focusing on CD outcomes to elucidate the breadth and depth of reported outcomes and measurement instruments. A systematic search was conducted on MEDLINE and Scopus for RCTs published from 1 January 2000 to 31 January 2023. Eligible studies included full-text articles with at least 50 adult CD patients. Primary and secondary outcomes, along with their measurement instruments, were categorized according to the Outcome Measures in Rheumatology Filter 2.1 framework. From 88 included studies, 393 outcomes were analyzed. Clinical outcomes, such as clinical remission and response, were the most prevalent (50.6%); biomarkers (11.5%) and patient-reported outcomes (10.2%) were also assessed. Other outcomes included disease behavior and complications (2%), endoscopy (10.4%), histology (0.5%), radiology (1.3%), healthcare utilization (3.8%), and therapy-related safety (6.9%). Composite outcomes showed an increasing trend, reflecting a shift toward comprehensive evaluations. Coprimary endpoints, including clinical symptoms and mucosal inflammation, were reported in 21 of 88 studies. This review highlights the evolving landscape of outcome assessment in CD RCTs, emphasizing the increasing complexity of outcomes. The prominence of composite outcomes underscores efforts to capture the multidimensional nature of CD. These findings will inform the second stage of a two-round e-Delphi aimed at prioritizing key domains and outcomes for developing a multiple-component outcome for RCTs in CD research., (© 2024 The Author(s). United European Gastroenterology Journal published by Wiley Periodicals LLC on behalf of United European Gastroenterology.)

The mechanisms by which organisms recognize the 'self' from the 'non-self' remain poorly understood. Moreover, the capability of transplanted tissue to functionally integrate is unclear in many organisms. Here, we report that two injured Mnemiopsis leidyi individuals, a species of planktonic animals known as comb jellies or ctenophores, are capable of rapidly fusing into a single entity in which some physiological functions are integrated. Our results highlight two interesting phenomena. First, ctenophores may lack an allorecognition mechanism that prevents fusion events between conspecifics. Second, fused individuals rapidly integrate and share physiological functions and neurobehavioral outputs. Ctenophores are among the earliest-branching animal groups of extant metazoans 1 and possess a unique nervous system with enigmatic homology to other phyla 2. Our observations warrant further research into understanding the evolution of self-nonself recognition systems and the functional integration of neuronal structures in ctenophores., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: According to previous studies, a prolonged hospital stay, along with the patient's clinical features, can lead to the onset of disability., Objectives: This study aimed to identify predictive factors of moderate-to-severe disability following hospital discharge in rib fracture patients., Methods: We conducted a retrospective study with hospitalized adult patients with rib fractures who received conservative treatment. Patients' clinical profiles and characteristics were collected from their clinical histories and healthcare professional records., Results: Overall, patients exhibited a 44% rate of moderate-to-severe disability after a six-day hospital stay. The incidence of patients with a prolonged hospital stay who showed disabilities was associated with male sex (HR 0.73, p < 0.001), presence of first rib fracture (HR 1.78, p = 0.047), presence of flail chest (HR 1.29, p = 0.046), severity of lung injury (HR 1.65, p < 0.001), and functional status (HR 1.37, p < 0.001)., Conclusions: Moderate-to-severe disability in patients with rib fractures may depend on factors such as sex, functionality, severity of lung injury, and presence of first rib fracture and flail chest during a prolonged hospital stay.

Objectives: Preventive health care for children comprises routine well-child visits and immunizations. Women with physical, sensory, or intellectual or developmental disabilities tend to experience more barriers to preventive health care; yet it is unknown whether such barriers are observed among their young children., Methods: This population-based study in Ontario, Canada included children born between 2012 and 2019 whose mothers had a physical (n = 74 084), sensory (n = 26 532), or intellectual or developmental (n = 1391) disability, multiple disabilities (n = 5774), or no disability (n = 723 442). Primary outcomes were receipt of the recommended number of well-child visits and routine immunizations in the first 2 years. Secondary outcomes included receipt of the enhanced 18-month developmental assessment and any developmental screen. Relative risks (aRR) were generated using modified Poisson regression and adjusted for maternal sociodemographics and mental health and child sex., Results: Compared with children of mothers without disabilities, those whose mothers had intellectual or developmental disabilities were less likely to receive the recommended number of well-child visits (56.3% vs 63.2%; aRR 0.92, 95% confidence interval [CI] 0.88-0.97), routine immunizations (43.8% vs 53.7%; aRR 0.88, 95% CI 0.83-0.94), enhanced 18-month developmental assessment (52.3% vs 60.8%; aRR 0.92, 95% CI 0.88-0.97), or any developmental screen (54.9% vs 62.5%; aRR 0.94, 95% CI 0.90-0.99). Other disability groups did not experience such disparities., Conclusions: There is a need to develop resources to improve access to preventive health care for young children of women with intellectual or developmental disabilities., (Copyright © 2024 by the American Academy of Pediatrics.)

This 45-year study (1978-2022) at a single institution evaluated HSCT outcomes and complications, emphasizing recent advances, with to provide insights into HSCT's evolving field and ongoing efforts to enhance patient outcomes. Involving 1707 patients, the study revealed an initial phase (1978-1987) with a limited activity that yielded modest outcomes, a nearly three-decade span (1988-2016) with a substantial increase in transplant activity, emphasizing umbilical cord blood transplantation (UCBT) for patients lacking a suitable matched sibling donor. In addition to a gradual increase in recipient age, significant improvement in outcomes emerged in the recent period (2017-2022), marked by UCBT replacement with haploidentical transplants, introduction of PTCY-based GVHD prophylaxis for all type of transplants, and increased use of conditioning regimens with thiotepa, busulfan, and fludarabine. In this period, reductions in GVHD, non-relapse mortality, and relapse rates significantly contributed to improved overall survival, event-free survival, and GVHD-free/relapse-free survival. The study identified specific factors, including GVHD prophylaxis and donor selection changes, associated with these positive trends. This four-decade study provides a unique perspective on allogeneic HSCT, showcasing the dynamic evolution of transplantation practices and their impact on outcomes, offering valuable insights for personalized treatment approaches and emphasizing continual innovation in this critical therapeutic modality., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Takayasu's arteritis (TA) is a granulomatous vasculitis that involves the aortic artery and its branches, resulting in stenosis, occlusion, and aneurysmal dilatation. Cardiovascular involvement is one of the main complications and a major cause of mortality in these patients. Herein, we describe the case of a woman with TA who presented with severe acute heart failure secondary to myocarditis and responded well to immunosuppressive therapy.

Background: Studies evaluating the effects of natural disasters on cancer outcomes are scarce, especially among USA ethnic minority groups, and none have focused on the effects of concurrent natural disasters and the COVID-19 pandemic. The goal of this secondary data analysis is to explore the impact of concurrent exposure to COVID-19 and earthquakes on psychological distress and symptom burden among Puerto Rican cancer survivors., Methods: This secondary data analysis ( n = 101) was part of a longitudinal case-control cohort study ( n = 402) aimed at describing unmet psychological needs among Puerto Rican cancer patients and non-cancer subjects previously exposed to Hurricane María in 2017. The research team pooled data from participants (cancer survivors and non-cancer group) from their baseline assessments and from follow-up assessments conducted during January-July 2020 (earthquake and the lockdown period). A descriptive, paired t -test, non-parametric mean rank test, and two-sided Pearson correlation analyses were performed., Results: Psychological distress and cancer symptom burden diminished over time. Resilience was significantly correlated with all the psychological and symptom burden variables during both pre- and post-earthquake and COVID-19 assessment periods., Conclusions: The results support the role of resilience, social support, and post-traumatic growth as potential protective factors preventing psychological distress and diminishing cancer symptom burden among cancer survivors exposed to natural disasters and the COVID-19 pandemic.

Single-unit red blood cell (1-RBC) transfusion policy has shown to effectively reduce transfusion burden while maintaining comparable clinical outcomes in hematological patients compared to the classical double-unit policy. However, its effects specifically after autologous stem cell transplantation (ASCT) have not been previously studied. We aimed to evaluate the impact of the 1-RBC policy on transfusion burden in a homogeneous cohort of patients undergoing ASCT. We retrospectively compared the transfusion requirements and the clinical outcomes of 187 patients transplanted from May 2019 to December 2022 under a 1-RBC policy, with a historical cohort of 153 patients transplanted from January 2016 to April 2019 under a double-unit policy. The 1-RBC policy was associated with a 32% reduction in RBC utilization and lower number of RBC transfusions at day 30 after transplantation (median 2 versus 3 units; P < .0001), with an odds ratio of 0.49 in multivariate analysis (P = .03). However, the number of transfusion episodes remained similar (median of 2 in both arms; P = .34). No significant differences in length of stay, hemoglobin levels at discharge or 30-day mortality were observed. In conclusion, transitioning to the 1-RBC represents a straightforward action in current practice that significantly reduces blood transfusions in patients undergoing ASCT, without negatively impacting clinical outcomes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

To evaluate the antibacterial, antibiofilm and antivirulence potential of the main diterpenes from Copaifera spp. oleoresins against multidrug-resistant (MDR) bacteria. Antimicrobial assays included determination of the Minimum Inhibitory Concentration (MIC), Minimum Bactericidal Concentration (MBC), Minimum Inhibitory Concentration of Biofilm (MICB 50 ), as well as synergistic and antivirulence assays for eight diterpenes against MDR. The tests revealed that two diterpenes (named 1 and 5) showed the best results, with MIC and MBC between 12.5 and 50 μg/mL against most MDR bacteria. These diterpenes exhibited promising MICB 50 in concentration between 3.12-25 μg/mL but showed no synergistic antimicrobial activity. In the assessment of antivirulence activity, diterpenes 1 and 5 inhibited only one of the virulence factors evaluated (Dnase) produced by some strains of S. aureus at subinhibitory concentration (6.25 μg/mL). Results obtained indicated that diterpenes isolated from Copaifera oleoresin plays an important part in the search of new antibacterial and antibiofilm agents that can act against MDR bacteria., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Childhood interstitial and diffuse lung disease (chILD) encompasses a broad spectrum of rare disorders. The Children's Interstitial and Diffuse Lung Disease Research Network (chILDRN) established a prospective registry to advance knowledge regarding etiology, phenotype, natural history, and management of these disorders., Methods: This longitudinal, observational, multicenter registry utilizes single-IRB reliance agreements, with participation from 25 chILDRN centers across the U.S. Clinical data are collected and managed using the Research Electronic Data Capture (REDCap) electronic data platform., Results: We report the study design and selected elements of the initial Registry enrollment cohort, which includes 683 subjects with a broad range of chILD diagnoses. The most common diagnosis reported was neuroendocrine cell hyperplasia of infancy, with 155 (23%) subjects. Components of underlying disease biology were identified by enrolling sites, with cohorts of interstitial fibrosis, immune dysregulation, and airway disease being most commonly reported. Prominent morbidities affecting enrolled children included home supplemental oxygen use (63%) and failure to thrive (46%)., Conclusion: This Registry is the largest longitudinal chILD cohort in the United States to date, providing a powerful framework for collaborating centers committed to improving the understanding and treatment of these rare disorders., (© 2023 Wiley Periodicals LLC.)

Parkinson's Disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons in the Substantia nigra pars compacta (SNpc). Apoptosis is thought to play a critical role in the progression of PD, and thus understanding the effects of antiapoptotic strategies is crucial for developing potential therapies. In this study, we developed a unique genetic model to selectively delete Casp3, the gene encoding the apoptotic protein caspase-3, in dopaminergic neurons (TH-C3KO) and investigated its effects in response to a subacute regime of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration, which is known to trigger apoptotic loss of SNpc dopaminergic neurons. We found that Casp3 deletion did not protect the dopaminergic system in the long term. Instead, we observed a switch in the cell death pathway from apoptosis in wild-type mice to necrosis in TH-C3KO mice. Notably, we did not find any evidence of necroptosis in our model or in in vitro experiments using primary dopaminergic cultures exposed to 1-methyl-4-phenylpyridinium in the presence of pan-caspase/caspase-8 inhibitors. Furthermore, we detected an exacerbated microglial response in the ventral mesencephalon of TH-C3KO mice in response to MPTP, which mimicked the microglia neurodegenerative phenotype (MGnD). Under these conditions, it was evident the presence of numerous microglial phagocytic cups wrapping around apparently viable dopaminergic cell bodies that were inherently associated with galectin-3 expression. We provide evidence that microglia exhibit phagocytic activity towards both dead and stressed viable dopaminergic neurons through a galectin-3-dependent mechanism. Overall, our findings suggest that inhibiting apoptosis is not a beneficial strategy for treating PD. Instead, targeting galectin-3 and modulating microglial response may be more promising approaches for slowing PD progression., (© 2024. The Author(s).)

Introduction: Cannabichromene (CBC) is a minor constituent of cannabis that is a selective cannabinoid CB2 receptor agonist and activator of TRPA1. To date, it has not been shown whether (-)-CBC, (+)-CBC, or both can mediate these effects. In this study, we investigate the activity of the CBC enantiomers at CB1, CB2, and Transient receptor potential ankyrin 1 (TRPA1) receptors in vitro . Materials and Methods: CBC enantiomers were purified from synthetic CBC by chiral chromatography, and their optical activity was confirmed by spectroscopy. Human CB1 and CB2 receptor activity was measured using a fluorescent assay of membrane potential in stably transfected AtT20 cells. TRPA1 activation was measured using a fluorescent assay of intracellular calcium in stably transfected HEK293 cells. Results: The (-)-CBC activated CB2 with an EC 50 of 1.5 µM, to a maximum of 60% of (-)CP55940. (+)-CBC did not activate CB2 at concentrations up to 30 µM. Only 30 µM (-)-CBC produced detectable activation of CB1, (+)-CBC was inactive. Both (-)-CBC and (+)-CBC activated TRPA1; at 30 µM (-)-CBC produced an activation 50% of that of the reference agonist cinnamaldehyde (300 µM), 30 µM (+)-CBC activated TRPA1 to 38% of the cinnamaldehyde maximum. Discussion: It is unclear whether (-)-CBC is the sole or even the predominant enantiomer of CBC enzymatically synthesized in cannabis. This study shows that (-)-CBC is the active isomer at CB2 receptors, while both isomers activate TRPA1. The results suggest that medicinal preparations of CBC that target cannabinoid receptors would be most effective when (-)-CBC is the dominant isomer.

Background and Aims: Effective management of inflammatory bowel disease (IBD) relies on a comprehensive understanding of infliximab (IFX) pharmacokinetics (PK). This study's primary goal was to develop a robust PK model, identifying key covariates influencing IFX clearance (CL), while concurrently evaluating the risk of disease progression during the maintenance phase of IBD treatment., Methods: The multicenter, prospective, real-world DIRECT study was conducted in several care centers, which included 369 IBD patients in the maintenance phase of IFX therapy. A two-compartment population PK model was used to determine IFX CL and covariates. Logistic and Cox regressions were applied to elucidate the associations between disease progression and covariates embedded in the PK model., Results: The PK model included the contributions of weight, albumin, antidrug antibody (ADA), and fecal calprotectin (FC). On average, higher ADA, FC concentration and weight, and lower albumin concentration resulted in higher IFX CL. In the multivariate regression analyses, FC levels influenced the odds of disease progression in the majority of its definitions, when adjusted for several confounding factors. Additionally, alongside FC, both IFX and CL demonstrated a significant impact on the temporal aspect of disease progression., Conclusion: In this 2-year real-world study, readily available clinical covariates, notably FC, significantly impacted IFX availability in IBD patients. We demonstrated that subclinical active inflammation, as mirrored by FC or CRP, substantially influenced IFX clearance. Importantly, FC emerged as a pivotal determinant, not only of IFX pharmacokinetics but also of disease progression. These findings underscore the need to integrate FC into forthcoming IFX pharmacokinetic models, amplifying its clinical significance., (© The Author(s) 2024. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

DNA-protein crosslinks (DPCs) are toxic lesions that inhibit DNA related processes. Post-translational modifications (PTMs), including SUMOylation and ubiquitylation, play a central role in DPC resolution, but whether other PTMs are also involved remains elusive. Here, we identify a DPC repair pathway orchestrated by poly-ADP-ribosylation (PARylation). Using Xenopus egg extracts, we show that DPCs on single-stranded DNA gaps can be targeted for degradation via a replication-independent mechanism. During this process, DPCs are initially PARylated by PARP1 and subsequently ubiquitylated and degraded by the proteasome. Notably, PARP1-mediated DPC resolution is required for resolving topoisomerase 1-DNA cleavage complexes (TOP1ccs) induced by camptothecin. Using the Flp-nick system, we further reveal that in the absence of PARP1 activity, the TOP1cc-like lesion persists and induces replisome disassembly when encountered by a DNA replication fork. In summary, our work uncovers a PARP1-mediated DPC repair pathway that may underlie the synergistic toxicity between TOP1 poisons and PARP inhibitors., (© 2024. The Author(s).)

The need to transition to more sustainable agriculture that is adaptable to environmental challenges, reducing dependence on chemical fertilizers and minimizing environmental impact, represents the new paradigm of the moment. In this scenario, studies with the adoption of bioinputs in corn cultivation emerge as a viable option for the sustainability of agricultural activity. Therefore, the objective was to evaluate the effect of doses of neem vegetable cake on the yield components of corn crops. An experimental design was used of randomized blocks was used, consisting of four doses of neem vegetable rendering (3 kg ha-1, 6 kg ha-1, 9 kg ha-1 and 12 kg ha-1) and a treatment control without the presence of organic fertilizer. The result indicates the presence of a significant effect of treatments with the application of neem cake on the main components of corn yield, including grain productivity, suggesting that the high carbon content present in the organic product can induce phytochemical effects and biological changes. in the soil, making it more productive. It was found that, when administering the maximum experimental dose, compared to the control group, there was a significant effect (p≤0.01) of 21.3% on grain productivity, jumping from 2,140 kg ha -1, when did not apply organic fertilizer, to 2,596 kg ha-1 with the application of 12 kg of neem cake per hectare. It is noted that the increase in grain productivity was in the proportion of 38 kg ha-1 of corn for each kilo of neem cake applied. To facilitate interpretation and decision-making, an analysis of the economic viability of neem cake for rainfed corn was also determined, also identifying the maximum experimental dose of 12 kg ha-1, as the most economically viable, providing an increase in profit of around R$ 119.92 per hectare, in relation to the control.

Patients aged 50 or above diagnosed with myeloid neoplasms (MNs) are typically not candidates for germline testing. However, approximately 8% carry pathogenic germline variants. Allogeneic haematopoietic stem cell transplantation (alloHSCT) remains an option for those aged over 50; neglecting germline testing could mask the risk for relative donor cell-derived MN. We propose a germline-augmented somatic panel (GASP), combining MN predisposition genes with a myeloid somatic panel for timely germline variant identification when initial testing is not indicated. Out of our 133 whole-exome-sequenced MN cases aged over 50 years, 9% had pathogenic/likely variants. GASP detected 92%, compared to 50% with somatic-only panel. Our study highlights the relevance of germline screening in MN, particularly for alloHSCT candidates without established germline-testing recommendations., (© 2024 British Society for Haematology and John Wiley & Sons Ltd.)

Obstructive sleep apnea (OSA) is a sleep disorder that has been associated with the incidence of other pathologies. Diagnosis is mainly based on the apnea-hypopnea index (AHI) obviating other repercussions such as intermittent hypoxemia, which has been found to be associated to cardiovascular complications. Blood-based samples and urine have been the most utilised biofluids in metabolomics studies related to OSA, while sweat could be an alternative due to its non-invasive and accessible sampling, its reduced complexity, and comparability with other biofluids. Therefore, this research aimed to evaluate metabolic overnight changes in sweat collected from patients with OSA classified according to the AHI and oxygen desaturation index (ODI), looking for potential cardiovascular repercussions. Pre- and post-sleeping sweat samples from all individuals (n = 61) were analysed by gas chromatography coupled to high-resolution mass spectrometry after appropriate sample preparation to detect as many metabolites as possible. Permanent significant alterations in the sweat were reported for pyruvate, serine, lactose, and hydroxybutyrate. The most relevant overnight metabolic alterations in sweat were reported for lactose, succinate, urea, and oxoproline, which presented significantly different effects on factors such as the AHI and ODI for OSA severity classification. Overall metabolic alterations mainly affected energy production-related processes, nitrogen metabolism, and oxidative stress. In conclusion, this research demonstrated the applicability of sweat for evaluation of OSA diagnosis and severity supported by the detected metabolic changes during sleep., (© 2023 The Authors. Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Background and Aims: Diversity in pappus shapes and size in Asteraceae suggests an adaptive response to dispersion challenges adjusting diaspore to optimal phenotypic configurations. Here, by analysing the relationship among pappus-cypsela size relationships, flight performance and pappus types in an evolutionary context, we evaluate the role of natural selection acting on the evolution of diaspore configuration at a macro-ecological scale in the daisy family., Methods: To link pappus-cypsela size relationships with flight performance we collected published data on these traits from 82 species. This allowed us to translate morphometric traits in flight performance for 150 species represented in a fully resolved backbone phylogeny of the daisy family. Through ancestral reconstructions and evolutionary model selection we assessed whether flight performance was associated with and constrained by different pappus types. Additionally, we evaluated, through phylogenetic regressions, whether species with different pappus types exhibited evolutionary allometric pappus-cypsela size relationships., Results: The setose pappus type had the highest flight performances and represented the most probable ancestral state in the family. Stepwise changes in pappus types independently led from setose to multiple instances of pappus loss with associated reduction in flight performance. Flight performance evolution was best modelled as constrained by five adaptive regimes represented by specific pappus types which correspond with specific optimal diaspore configurations that are distinct in pappus-cypsela allometric relationships., Conclusions: Evolutionary modelling suggests natural selection as the main factor of diaspore configuration changes which proceeded towards five optima, often overcoming constraints imposed by allometric relationships and favouring evolution in certain directions. With the perspective that natural selection is the main process driving the observed patterns, various biotic and abiotic are suggested as principal drivers of transitions in diaspore configurations along space and time in the daisy family history. Results also allow discussion of evolutionary changes in a historical context., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Annals of Botany Company. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

The aim of this study is to evaluate the relationship between clinical severity and functionality, occupational performance, and health-related quality of life in patients hospitalized with pulmonary embolism. Pulmonary embolism patients were grouped by clinical severity using the Pulmonary Embolism Severity Index. Those scoring ≥160 were in the high-severity group (HSG); those scoring < 160 in the low-moderate group (LMSG). The main variables were functionality assessed by the World Health Organization Disability Assessment Schedule (WHODAS), self-perception of occupational performance assessed by the Canadian Occupational Performance Measure (COPM), pain and fatigue assessed by a Visual Analogue Scale (VAS), and health-related quality of life assessed by the EuroQol-5Dimensions (EQ-5D). Patients were evaluated at hospital admission and at 1-month and 3-month follow-up. At admission, there were significant differences between groups in the WHODAS and health-related quality of life in favor of the LMSG. At 1-month and at 3-month follow-up, there were significant differences between the LMSG and HSG in WHODAS, COMP, NRS pain, fatigue and EQ-5D scores in favor of the LMSG. An association exists between clinical severity and mid-term functionality, self-perception of occupational performance, pain, fatigue, and health-related quality of life in PE patients.

Objective: This systematic review aimed to evaluate the effects of Tai Chi on the health-related quality of life (HRQoL) of people with neurodegenerative diseases., Data Source: This review followed the guidelines of the updated PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020. A systematic search in five electronic databases (Medline via PubMed, Web of Science, Scopus, PEDro, and OTseeker) was performed., Study Inclusion and Exclusion Criteria: Randomized control trials (RCTs) examining Tai Chi interventions to improve HRQoL in patients with neurodegenerative diseases published through March 2023 were included., Data Extraction: Data were extracted from each study by two independent researchers into a data extraction form based on the Cochrane recommendations. Methodological quality and risk of bias were assessed., Data Synthesis: A meta-analysis was performed using Review Manager 5.3 software., Results: Of the 439 records that were screened, eight RCTs met the eligibility criteria. They assessed cognitive decline (n = 2) or Parkinson's disease (n = 6). RCT comparison groups included active interventions or usual care. The duration of Tai Chi therapy ranged from 8 to 24 weeks. A sensitivity analysis using a fixed effect model indicated that Tai Chi therapy significantly increased HRQoL [ P < 001, SMD (95% CI) = .41 [.21, .60], I 2 = 4%]., Conclusion: Tai Chi can effectively improve the HRQoL of people with neurodegenerative diseases, but the heterogeneity across intervention was relatively high. Further studies are needed as research into the benefits of Tai Chi in neurodegenerative disease rehabilitation is still limited., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Dynamic changes in neuronal activity and in noradrenergic locus coeruleus (LC) projections have been proposed during the transition from acute to chronic pain. Thus, the authors explored the cellular cFos activity of the LC and its projections in conjunction with spontaneous pain-like behavior in neuropathic rats., Methods: Tyrosine hydroxylase:Cre and wild-type Long-Evans rats, males and females, were subjected to chronic constriction injury (CCI) for 2 (short-term, CCI-ST) or 30 days (long-term, CCI-LT), evaluating cFos and Fluoro-Gold expression in the LC, and its projections to the spinal cord (SC) and rostral anterior cingulate cortex (rACC). These tests were carried out under basal conditions (unstimulated) and after noxious mechanical stimulation. LC activity was evaluated through chemogenetic and pharmacologic approaches, as were its projections, in association with spontaneous pain-like behaviors., Results: CCI-ST enhanced basal cFos expression in the LC and in its projection to the SC, which increased further after noxious stimulation. Similar basal activation was found in the neurons projecting to the rACC, although this was not modified by stimulation. Strong basal cFos expression was found in CCI-LT, specifically in the projection to the rACC, which was again not modified by stimulation. No cFos expression was found in the CCI-LT LCipsilateral (ipsi)/contralateral (contra)→SC. Chemogenetics showed that CCI-ST is associated with greater spontaneous pain-like behavior when the LCipsi is blocked, or by selectively blocking the LCipsi→SC projection. Activation of the LCipsi or LCipsi/contra→SC dampened pain-like behavior. Moreover, Designer Receptor Exclusively Activated by Designer Drugs (DREADDs)-mediated inactivation of the CCI-ST LCipsi→rACC or CCI-LT LCipsi/contra→rACC pathway, or intra-rACC antagonism of α-adrenoreceptors, also dampens pain-like behavior., Conclusions: In the short term, activation of the LC after CCI attenuates spontaneous pain-like behaviors via projections to the SC while increasing nociception via projections to the rACC. In the long term, only the projections from the LC to the rACC contribute to modulate pain-like behaviors in this model., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc., on behalf of the American Society of Anesthesiologists.)

This study aimed to investigate the kinetics of immune recovery following umbilical cord blood transplantation (UCBT) in adults who received a myeloablative conditioning (MAC) regimen and antithymocyte globulin (ATG). While the immune recovery kinetics has been extensively studied in pediatric UCBT recipients, limited data exist for adults. We conducted a comprehensive analysis of 221 consecutive adult patients who underwent UCBT with MAC and ATG at a single institution. Our objective was to evaluate the influence of patient, disease, and transplant factors, along with acute graft-versus-host disease (aGVHD), on immune reconstitution and overall survival. Our findings confirm a delayed recovery of T cells, while B and NK cell reconstitution exhibited rapid progress, with NK cell counts reaching normal levels within 3 months post-transplantation and B cells within 6 months. Within CD3 + T cells, CD8 + T cells also experienced a delayed recovery (12 months), but to a lesser extent compared to CD4 + T cells (18 months). Delayed immune recovery of T-cell subsets was associated with the development of aGVHD grade II-IV, older age, CMV negativity, and a female donor. Patients with lymphoproliferative diseases showed slower NK cell recovery. Our study demonstrates that adult patients undergoing MAC with ATG and receiving a single unit UCBT for hematologic malignancies experienced rapid reconstitution of NK and B cells. However, T cell recovery, particularly CD4 + T cells, was significantly delayed. To enhance T cell recovery, it may be crucial to consider UCB units with higher cellularity and optimize ATG doses in conditioning., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: The COVID-19 pandemic has disproportionately affected marginalized groups in the United States. Although most children have mild or asymptomatic COVID-19, some experience severe disease and long-term complications. However, few studies have examined health disparities in severe COVID-19 outcomes among US children., Objective: To examine disparities in the clinical outcomes of infants and children aged <5 years hospitalized with COVID-19 by race/ethnicity and payer status., Methods: Children aged <5 years hospitalized with an admission diagnosis of COVID-19 (April 2021-February 2023) were selected from the PINC AI™ Healthcare Database. Hospital outcomes included length of stay (LOS), intensive care unit (ICU) admission, oxygen supplementation, invasive mechanical ventilation (IMV), and prolonged duration of each outcome. Multivariable logistic regression models compared hospitalization outcomes by race/ethnicity and payer status., Results: Among 10,190 children (mean age: 0.9 years, 56.5% male, 66.7% Medicaid-insured), race/ethnicity was distributed as follows: White non-Hispanic (35.1%), Hispanic (any or Unknown race; 28.3%), Black non-Hispanic (15.2%), Other race/ethnicity (8.9%) and Unknown (12.5%). Payer status varied by race/ethnicity. White non-Hispanic children had the highest proportion with commercial insurance (42.9%) while other racial/ethnic groups ranged between 13.8% to 26.1%. Black non-Hispanic children had the highest proportion with Medicaid (82.3%) followed by Hispanic children (76.9%). Black non-Hispanic children had higher odds of prolonged outcomes: LOS (adjusted odds ratio [aOR] = 1.20, 95% confidence interval [CI]:1.05-1.38), ICU days (aOR = 1.44, 95% CI: 1.07-1.93), and IMV days (aOR = 1.80, 95% CI: 1.09-2.97) compared to White non-Hispanic children. Similar patterns were observed for Hispanic and children of Other race/ethnicity. Medicaid-insured and children with other insurance had higher odds of prolonged LOS and oxygen days than commercially insured patients., Conclusion: There were disparities in clinical outcomes of COVID-19 by race/ethnicity and insurance type, particularly for prolonged-duration outcomes. Further research is required to fully comprehend the causes and consequences of these disparities and develop strategies to reduce them while ensuring equitable healthcare delivery., Competing Interests: This study was sponsored by Pfizer, which had a role in the collection, analysis, and interpretation of data, the writing of the article, and the decision to submit the manuscript for publication. All authors are employees and shareholders of Pfizer Inc. The author(s) declare that this study received funding from Pfizer. The funder had the following involvement with the study: a role in the collection, analysis, and interpretation of data, the writing of the article, and the decision to submit the manuscript for publication., (© 2024 Ochapa, McGrath, Alfred, Lopez and Nepal.)

Blazed gratings are periodic surface structures of great interest for applications such as friction control, light trapping, and spectrometry. While different laser processing methods have been explored to produce these elements, they have not yet surpassed conventional surface manufacturing techniques, often based on lithography processes or mechanical ruling. This work introduces a new approach based on the combination of ultrashort pulses and triangular beam shaping, which enables the generation of asymmetrical grooves in a single step. The main advantage of this strategy is that by simply changing the laser processing direction we can induce a significant modification in the ratio of asymmetry between the sidewall angles of the machined channels. The paper includes a comprehensive study, which has been supported by statistical tools, of the effect of this and other experimental parameters on the morphology of grooves machined on stainless steel. As a result, we achieved a wide range of geometries, with asymmetry ratios spanning from 1 to 5 and channel depths between 3 and 15 µm. Furthermore, we demonstrate the validity of the approach through the successful manufacture of blazed gratings of various slopes. The results reflect the versatility and cost-efficiency of the proposed fabrication strategy, and thus its potential to streamline the production of sawtooth gratings and other devices that are based on asymmetrical features.

The cancer epigenome has been studied in cells cultured in two-dimensional (2D) monolayers, but recent studies highlight the impact of the extracellular matrix and the three-dimensional (3D) environment on multiple cellular functions. Here, we report the physical, biochemical, and genomic differences between T47D breast cancer cells cultured in 2D and as 3D spheroids. Cells within 3D spheroids exhibit a rounder nucleus with less accessible, more compacted chromatin, as well as altered expression of ~2000 genes, the majority of which become repressed. Hi-C analysis reveals that cells in 3D are enriched for regions belonging to the B compartment, have decreased chromatin-bound CTCF and increased fusion of topologically associating domains (TADs). Upregulation of the Hippo pathway in 3D spheroids results in the activation of the LATS1 kinase, which promotes phosphorylation and displacement of CTCF from DNA, thereby likely causing the observed TAD fusions. 3D cells show higher chromatin binding of progesterone receptor (PR), leading to an increase in the number of hormone-regulated genes. This effect is in part mediated by LATS1 activation, which favors cytoplasmic retention of YAP and CTCF removal., (© 2024. The Author(s).)

Cytomegalovirus (CMV) reactivations cause significant morbidity in allogeneic hematopoietic stem cell transplantation (HSCT) recipients. Graft-versus-host disease (GVHD) prophylaxis with post-transplantation cyclophosphamide (PTCy) is associated with an increased risk of CMV infections. Data are limited comparing HSCT with PTCy performed from matched sibling donors (MSDs), matched unrelated donors (MUDs), and haploidentical (Haplo) donors. In the present study, we aimed to characterize CMV reactivation and recurrence in patients with hematologic malignancies undergoing HSCT from MSD, MUD, and Haplo donors using PTCy as GVHD prophylaxis in the pre-letermovir era. We also analyzed risk factors of CMV reactivation, including GVHD as a time-dependent variable, on the incidence and mortality associated with CMV infections. We analyzed CMV reactivation in patients undergoing HSCT from 160 MSDs, 124 MUDs, and 82 Haplo donors from a single institution. Uniform GVHD prophylaxis with PTCy, sirolimus, and mycophenolate mofetil was given irrespective of donor type. Overall, 46% of patients had at least 1 CMV reactivation. The 1-year cumulative incidence of CMV infection was 39% for MSD, 44% for MUD, and 62% for Haplo donors (P < .001), with 96% of reactivations occurring before day +100. Multivariate analysis identified factors associated with the first CMV reactivation, including Haplo donor, positive recipient CMV serology, older patient age, and grade II-IV acute GVHD. The 1-year cumulative incidence of second reactivation from HSCT was 13%. Recipient CMV seropositivity, older patient age, and grade II-IV acute GVHD, but not type of donor, were identified as adverse factors for second CMV reactivation in multivariate analysis. The 1-year cumulative incidence of a third reactivation post HSCT was 4.4%. Ten cases of CMV disease were recorded, with no attributable deaths. Nevertheless, the risk for nonrelapse mortality was greater for patients who experienced CMV reactivation in multivariate time-dependent Cox model analysis. CMV reactivation is frequent in HSCT with PTCy in patients not receiving letermovir prophylaxis. Identified risk factors include the use of a Haplo donor, recipient CMV seropositivity, and grade II-IV acute GVHD. The prevalence of recurrent CMV reactivations is a noteworthy issue, especially after acute GVHD, warranting trials of secondary prophylaxis strategies., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Background: The emergence of new treatments the inflammatory bowel diseases (IBD) raised questions regarding the role of older agents, namely thiopurines., Aims: To clarify the benefits of combination treatment with thiopurines on Crohn's disease (CD) patients in the maintenance phase of infliximab., Methods: In this analysis of the 2-year prospective multicentric DIRECT study, patients were assessed in terms of clinical activity, faecal calprotectin (FC), C-reactive protein (CRP), and infliximab pharmacokinetics. A composite outcome based on clinical- and drug-related items was used to define treatment failure., Results: The study included 172 patients; of these, 35.5 % were treated with combination treatment. Overall, 18 % of patients achieved the composite outcome, without statistically significant differences between patients on monotherapy and on combination treatment (21.6% vs 11.5 %, p = 0.098). Median CRP, FC, and infliximab pharmacokinetic parameters were similar in both groups. However, in the sub-analysis by infliximab treatment duration, in patients treated for less than 12 months, the composite outcome was reached in fewer patients in the combination group than in the monotherapy group (7.1% vs 47.1 %, p = 0.021)., Conclusion: In CD patients in maintenance treatment with infliximab, combination treatment does not seem to have benefits over infliximab monotherapy beyond 12 months of treatment duration., Competing Interests: Conflict of interest PS served as speaker for Janssen and received Congress support from Janssen, Abbvie, Dr. Falk, Norgine and Pfizer. IR reports personal fees and/or non-financial support from Faes Pharma, Ferring, Pharmakern, Janssen and Takeda, outside the submitted work. She also reports research grants from Abbvie and Ferring, outside the submitted work. HTS served as speaker for Janssen and received Congress support from Abbvie, Ferring, Janssen, Pfizer, Takeda, Tillots, Dr. Falk and Biogen. FM served as a speaker and received honoraria from Abbvie, Biogen, Falk, Ferring, Hospira, Janssen, Laboratórios Vitória, Lilly, Pfizer, Merck Sharp & Dohme, Sandoz, Takeda, UCB and Vifor. All other authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Age-related macular degeneration (AMD) is one of the main causes of visual acuity (VA) loss in people over 50 years of age worldwide, with neovascular AMD (nAMD) accounting for 80% of cases of severe vision loss due to this disease. Anti-vascular endothelial growth factor (anti-VEGF) drugs have been used for the treatment of this disease for more than a decade, changing drastically the visual prognosis of these patients. However, initial studies reporting data on outcomes were short term. Currently, there are different series published on the long-term results of AMD after treatment with anti-VEGF, and the aim of this review is to synthesize these results. The mean follow-up of the included studies was 8.2 years (range 5-12 years). The mean initial VA was 55.3 letters in the Early Treatment Diabetic Retinopathy Study (ETDRS) (range 45.6-65) and the mean final VA was 50.1 letters (range 33.0-64.3), with a mean loss of 5.2 letters. At the end of follow-up, 29.4% of the patients maintained a VA > 70 letters. The 67.9% of patients remained stable at the end of follow-up (< 15 letter loss), with a severe loss (≥ 15 letters) of 30.1%. Fibrosis and atrophy were the main causes of long-term VA loss, occurring at the end of follow-up in 52.5% and 60.5%, respectively., (Copyright © 2023 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

(1) Background : This systematic review and meta-analysis explores the effectiveness of telerehabilitation in patients suffering from chronic neck pain, specifically on pain and disability. The research delves into an area of growing significance within the realm of healthcare, aiming to understand the impact of digital interventions on the rehabilitation process for individuals with prolonged neck pain. (2) Methods : The comprehensive review encompasses a wide array of studies evaluating the collective outcomes of numerous trials focused on telerehabilitation strategies. In this systematic review, PubMed/MEDLINE, Scopus, and Web of Science databases were systematically searched to identify studies on telerehabilitation's impact on pain. (3) Results : Eight studies met the inclusion criteria. Using the Downs and Black quality assessment, three studies were classified as good and five as fair. The authors identify specific modalities within telerehabilitation, such as remote exercise programs and virtual consultations, that contribute significantly to positive patient outcomes. Meta-analysis indicated a significant overall effect of telerehabilitation on pain reduction (MD = -1.27; 95% CI = -2.06; -0.47; p = 0.002). These findings support telerehabilitation's efficacy in pain management. (4) Conclusions : The synthesis of evidence presented in this systematic review and meta-analysis underscores the potential of telerehabilitation as an effective and accessible means of managing chronic neck pain, offering valuable insights for both healthcare practitioners and policymakers in advancing patient-centered care.

Objective: The present study aims to provide norms and age-, education-, and sex-adjusted data for the Wisconsin Card Sorting Test (WCST), the Modified Taylor Complex Figure (MTCF), and the Ruff-Light Trail Learning Test (RULIT) as part of the NEURONORMA-Plus project., Methods: We recruited 308 cognitively healthy individuals aged between 18 and 92 years. Tables are provided to convert raw scores to age-adjusted scaled scores, as well as adjustments for education and sex after applying independent regression models in 2 age groups (< 50 and ≥ 50 years)., Results: Older age had a negative effect on performance in both age groups. We observed a positive effect of education on WCST performance in the younger group (< 50 years), and on all MTCF measures (with the exception of the recognition task) in the older group (≥ 50 years). Education had no impact on performance in the RULIT, although sex did, with a small but significant effect whereby young men showed higher performance for one variable., Conclusion: The normative data provided can contribute to the clinical interpretation of performance in these tests in the Spanish population., (Copyright © 2023. Published by Elsevier España, S.L.U.)

Additive Manufacturing (AM) has revolutionized the production of complex three-dimensional (3D) structures; however, the efficient and precise fabrication of thin profiles remains a challenge. This study explores the application of femtosecond-laser-based additive manufacturing techniques for the production of thin profiles with micron-scale features, reaching profile thicknesses below 100 µm. The study investigates the effects of scanning strategy, with optimized processing parameters, on the fabrication of thin profiles; wall thickness measurements were carried out using various technologies to analyse the influence of each on the resulting values. The quality of the walls was quantified by means of a visual characterization of the melted volumes, analysing the evolution of the measured thickness with regard to the processing conditions and in relation to the theoretical thicknesses of the walls.

This article summarises some of the outstanding sessions that were (co)organised by the Allied Respiratory Professionals Assembly during the 2023 European Respiratory Society International Congress. Two sessions from each Assembly group are outlined, covering the following topics: Group 9.01 focuses on respiratory physiology techniques, specifically on predicted values and reference equations, device development and novel applications of cardiopulmonary exercise tests; Group 9.02 presents an overview of the talks given at the mini-symposium on exercise training, physical activity and self-management at home and outlines some of the best abstracts in respiratory physiotherapy; Group 9.03 highlights the nursing role in global respiratory health and presents nursing interventions and outcomes; and Group 9.04 provides an overview of the best abstracts and recent advances in behavioural science and health psychology. This Highlights article provides valuable insight into the latest scientific data and emerging areas affecting the clinical practice of Allied Respiratory Professionals., Competing Interests: Conflict of interest: E. Smith reports an unpaid leadership role as board director for Australia and New Zealand Society for Respiratory Science. Conflict of interest: N.S. Diciolla received a Fellowship for Research Training from the Department of Nursing and Physiotherapy, Faculty of Medicine and Health Sciences, University of Alcalá, Madrid, Spain (FPI-UAH-20) and has been awarded a Santander travel grant, from the University of Alcalá for a stay at the University of Aveiro (Aveiro, Portugal) from 1 June 2022 to 30 September 2022. Conflict of interest: M. Verkleij reports travel support from Stichting Astmabestrijding, the Netherlands; and unpaid leadership roles as a board member for the ECFS Mental Health Working Group and for the Cystic Fibrosis Foundation Advisory Committee (USA). Conflict of interest: D. Inal-Ince reports grants from Turkish Scientific and Technological Research Council of Turkey; grants and travel support from Hacettepe University, Scientific Research Coordination Unit; and travel support from the Turkish Thoracic Society. Conflict of interest: J.M. Padilha reports a leadership role as Nurse Group chair at Sociedade Portuguesa de Pneumologia. Conflict of interest: J. Cruz reports support to attend the ERS Congress 2023 as the outgoing ECM Representative of Assembly 9 of the ERS, and is an associate editor of this journal. Conflict of interest: All other authors have nothing to disclose., (Copyright ©The authors 2024.)

Adult-onset xanthogranuloma (AOX) and immunoglobulin G4-related disease (IgG4-RD) are uncommon fibrosing conditions that may exhibit localized ocular manifestations and occasionally systemic symptoms. These conditions exhibit overlapping clinical and histological features, suggesting a potential correlation between them, although their exact relationship remains unclear. This paper presents the case of a black male patient exhibiting typical histological indications of both AOX and IgG4-RD. The patient responded positively to corticosteroid treatment.

Genomic advancements have yielded pivotal insights into hematological neoplasms, particularly concerning germline predisposition mutations. Following the WHO 2016 revisions, dedicated segments were proposed to address these aspects. Current WHO 2022, ICC 2022, and ELN 2022 classifications recognize their significance, introducing more mutations and prompting integration into clinical practice. Approximately 5-10% of hematological neoplasm patients show germline predisposition gene mutations, rising with risk factors such as personal cancer history and familial antecedents, even in older adults. Nevertheless, technical challenges persist. Optimal DNA samples are skin fibroblast-extracted, although not universally applicable. Alternatives such as hair follicle use are explored. Moreover, the scrutiny of germline genomics mandates judicious test selection to ensure precise and accurate interpretation. Given the significant influence of genetic counseling on patient care and post-assessment procedures, there arises a demand for dedicated centers offering specialized services., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Selecting an attractive mate can involve trade-offs related to investment in sampling effort. Glucocorticoids like corticosterone (CORT) are involved in resolving energetic trade-offs. However, CORT is rarely studied in the context of mate choice, despite its elevated levels during reproductive readiness and the energetic transitions that characterize reproduction. Few systems are as well suited as anuran amphibians to evaluate how females resolve energetic trade-offs during mate choice. Phonotaxis tests provide a robust bioassay of mate choice that permit the precise measurement of inter-individual variation in traits such as choosiness-the willingness to pursue the most attractive mate despite costs. In Cope's gray treefrogs (Hyla chrysoscelis), females exhibit remarkable variation in circulating CORT as well as choosiness during mate choice, and a moderate dose of exogenous CORT rapidly (<1 h) and reliably induce large increases in choosiness. Here we measured the expression of glucocorticoid (GR) and mineralocorticoid (MR) receptors in the brains of females previously treated with exogenous CORT and tested for mate choosiness. We report a large decrease in GR expression in the hindbrain and midbrain of females that were treated with the moderate dosage of CORT-the same treatment group that exhibited a dramatic increase in choosiness following CORT treatment. This association, however, does not appear to be causal, as only forebrain GR levels, which are not affected by CORT injection, are positively associated with variation in choosiness. No strong effects were found for MR. We discuss these findings and suggest future studies to test the influence of glucocorticoids on mate choice., Competing Interests: Declaration of competing interest We have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Various studies have suggested interleukin 6 (IL-6) as a potential biomarker for detecting disease activity in Takayasu arteritis., Methods: A systematic review and meta-analysis was performed to assess differences in IL-6 levels in patients with active (aTA) and inactive Takayasu arteritis (iTA), as well as healthy controls (HCs), using validated activity scores. Study quality and the risk of bias were assessed using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) and the Newcastle-Ottawa and Joanna Briggs checklist, respectively. For the meta-analysis, we pooled the raw mean IL-6 levels in each group and then estimated and pooled the crude mean differences between the groups. We applied a random-effects model in all analyses., Results: Of the 93 eligible articles, 10 were included after removing duplicates and studies that met the exclusion criteria. Overall, 1825 patients with a mean age ranging from 24 to 40.6 years were included. The pooled levels of IL-6 increased depending on disease activity as follows: HCs: 3.08 (95% confidence interval [CI], 0.88-5.28), iTA: 7.21 (3.61-10.82), and aTA: 22.67 (12.44-32.91) pg/mL. Patients with aTA had higher IL-6 levels than HCs (21.52 [95% CI, -0.43 to 43.47]) and those with iTA (16.69 [95% CI, 5.32-28.06]), whereas IL-6 levels were not different between HCs and patients with iTA (3.62 [95% CI, -13.18 to 20.42])., Conclusions: Interleukin 6 levels are significantly increased in patients with aTA compared with those with iTA and HCs but not in patients with iTA compared with HCs. More studies are needed to establish the IL-6 cutoff value for assessing disease activity., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)