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We investigated thermal management challenges in semiconductor devices that use fusion bonding, with a focus on measuring the thermal resistance of the bonded interface. Starting with two fusion-bonded silicon wafers, we thinned the top wafer to below 100 μ m and used frequency domain thermoreflectance to measure the effective thermal boundary resistance of the fusion bond. We established the measurement uncertainty with a multilayer thermal diffusion model, considering the effects of the top Si layer thickness and laser spot size. The thermal boundary resistance was measured to be 0.2 and 0.5 m 2 K/MW for two types of bonded wafers, with total SiO 2 film thicknesses of 200 and 470 nm at the fusion bond layer, respectively. We also created defects at the interface and imaged these defects with the thermal phase response at specific frequencies chosen according to a thermal model. The method described can be applied to other types of wafer-to-wafer or die-to-die bonding including direct, polymeric, and metallic bonds. [ABSTRACT FROM AUTHOR]

Background: It is essential to better characterize the energetic profile of individuals during very low-intensity physical activity. The objectives of the present study were to determine whether the saver profile from sit-to-stand persists during light physical activity and characterize patterns in substrate utilization from sit-to-stand and during very low-intensity physical activity in healthy men and women. Methods: Sixty-two healthy adults (38 women) performed an experimental sequence that corresponded to 15-minute sitting (SIT1), followed by 15-minute standing (STAND), 15-minute sitting again (SIT2), and finally 15 minutes of light cycling. Continuous indirect calorimetry was allowed to calculate energy expenditure (EE) and respiratory quotient through the entire sequence. Savers and nonsavers (<5% and ≥ 5% increase in EE from sitting to standing, respectively) were determined. Results: There was an interaction effect in EE between savers and nonsavers through the whole sequence (P =.008). Only nonsavers (71%) exhibited a significant increase in EE from SIT1 to STAND (P <.001). Nonsavers and savers significantly increased EE during 15 minutes of light cycling relative to sitting or standing (P <.001), without any difference between groups. The percentage of change in respiratory quotient from SIT1 to STAND was significantly different between the 2 groups, with increased values in savers and decreased values in nonsavers (P =.03). Significantly lower values in respiratory quotient and EE were found during 15 minutes of light cycling in women compared with men (P <.001). Conclusions: It is essential to determine individuals' energetic phenotype to determine those who may benefit more from strategies such as standing or light physical activity. The sexual dimorphism in terms of substrate use during such exercise should be considered. [ABSTRACT FROM AUTHOR]

Background: Shunt failure is an undesirable but common occurrence following neurosurgical shunting for pediatric hydrocephalus. Little is known about the occurrence of failure in lower-middle income country (LMIC) settings in South America. The objective of this study was to evaluate shunt failure in the sole publicly funded pediatric hospital in La Paz, Bolivia, with limited resources. Methods: A retrospective review of all patients at the Children's Hospital of La Paz, Bolivia (Hospital del Niño "Dr. Ovidio Aliaga Uria"), was conducted to identify all patients whose index surgical shunting for hydrocephalus was performed between 2019 and 2023. Categorical, continuous, and shunt failure data were statistically summarized. Results: A total of 147 unique pediatric patients underwent index ventriculoperitoneal shunting for hydrocephalus in the study period. There were 90 (61%) male and 57 (39%) female patients, with a median age of 2.2 months at index shunting procedure. The most common surgical indications were congenital hydrocephalus (n = 95, 65%), followed by hydrocephalus secondary to congenital defect (n = 25, 17%) and tumor (n = 18, 12%). A total of 18 (12%) of patients experienced inpatient failure during index admission requiring surgical revision at a median time of 12.5 days after index shunting. Postoperative imaging (OR 2.97, P = 0.037) and postoperative infection (OR 3.26, P = 0.032) during index admission both independently and statistically predicted inpatient failure. Of the 96 patients (65%) with postoperative follow-up, 16 (n = 16/96, 17%) patients experienced outpatient failure requiring readmission to hospital and surgical revision at a median time of 3.7 months after discharge. Kaplan–Meier estimations of overall inpatient and outpatient failure in this cohort were 23% (95% CI 14–37) and 28% (95% CI 15–49), respectively. Conclusions: Both inpatient and outpatient shunt failures are significant complications in the management of pediatric hydrocephalus in La Paz, Bolivia. We identify multiple avenues to improve these outcomes which are institution-specific based on the review of these failures. Lessons learnt may be applicable to other similarly resourced institutions across South American LMICs. [ABSTRACT FROM AUTHOR]

Background: There is a lack of knowledge regarding siblings' experiences of being a brother or sister of a child with a life-threatening or life-limiting condition. Siblings' perspectives are often expressed through their parents and not by siblings themselves. Method: This study has a qualitative design within hermeneutic phenomenology. Thirteen siblings (ages 3–29) of children with cancer or genetic conditions participated in semi-structured interviews. Analyses followed a thematic analysis guided by van Manen's lifeexistentials. Results: One overall theme, "What about me?", illustrates that siblings of children with LT/LL conditions are dealing with their own challenges and needs in the situation while also struggling to receive attention from their parents. The overall theme derives from three subthemes: living with heavy strains, feeling disregarded, and having needs of one's own. Conclusion: The study revealed that siblings' own needs compete with the needs of the ill child, resulting in the risk of siblings taking a step back rather than expressing what they might actually need themselves. These findings can inform healthcare professionals on the importance of educating and supporting parents and the surrounding community close to the sibling, for example, by helping schoolteachers understand how to meet siblings' needs. [ABSTRACT FROM AUTHOR]

M-type stars are the most common stars in the Universe. They are ideal hosts for the search of exoplanets in the habitable zone (HZ), as their small size and low temperature make the HZ much closer-in than their solar twins. Harboring very deep convective layers, they also usually exhibit very intense magnetic fields. Understanding their environment, in particular their coronal and wind properties, is thus very important, as they might be very different from what is observed in the solar system. The mass-loss rate of M-type stars is poorly known observationally, and recent attempts to estimate it for some of them (e.g., TRAPPIST-1 and Proxima Centauri) can vary by an order of magnitude. In this work, we revisit the stellar wind properties of M dwarfs in the light of the latest estimates of M ̇ through Ly α absorption at the astropause and slingshot prominences. We outline a modeling strategy to estimate the mass-loss rate, radiative loss, and wind speed, with uncertainties, based on an Alfvén-wave-driven stellar wind model. We find that it is very likely that several TRAPPIST-1 planets lie within the Alfvén surface, which implies that these planets experience star–planet magnetic interactions (SPMIs). We also find that SPMIs between Proxima Cen b and its host star could be the reason for recently observed radio emissions. [ABSTRACT FROM AUTHOR]

This study developed an Occupational Personality Inventory (OPI). Specifically, it answered and accomplished the following objectives: (1) To construct items of the proposed Occupational Personality Inventory based on literature and studies. (2) To establish the validity of the proposed Occupational Personality Inventory by: (1.1) Face Validity and (2.2) Content Analysis. (3) To establish the reliability of the proposed Occupational Personality Inventory by Test Re-Test Design. (4) To establish a standardization process of the proposed Occupational Personality Inventory. Research and Development (R&D) was the research method used in the study. Most of the items were found valid after it underwent experts' face validation and Lawshe's content validity method. The items garnered an excellent reliability using test re-test method. A manual was made for the uniformity of administration of the test and consistent scoring of the inventory to guarantee the standardization process. The study's findings led to the conclusions that the items of the created Occupational Personality Inventory evaluated and represented various occupational personalities of the employees; employees were discriminated against based on their occupational personalities according to the items in the scale; every item in the inventory met statistical validity requirements; and the reliability index of the OPI is excellent. [ABSTRACT FROM AUTHOR]

We describe in this review the historical evidence leading up to the concept and design of Vigil and subsequent clinical applications including safety and efficacy in a randomized, controlled Phase IIB trial. Vigil (gemogenovatucel-T) is a unique triple function targeted immunotherapy that demonstrates preclinical and clinical systemic anticancer activity. Construction of Vigil involves harvest of autologous malignant tissue for neoantigen targeting (ideally containing clonal neoantigens) followed by a two-day process involving transfection with a plasmid to provide a permissive 'training environment' for the patient's immune system. Transfected plasmid components contain an expressive human GMCSF DNA segment to enhance anticancer immune functional response and a second component expressing bi-shRNAfurin which reduces TGFβ isomers (TGFβ1 and TGFβ2) thereby reducing cancer inhibition of the targeted immune response. Results generated to date justify advancement to confirmatory clinical trials supporting product regulatory approval. Plain Language Summary Vigil is an anticancer treatment that employs three methods of enhancing the body's immune system to identify and kill cancer cells. The construction of Vigil involves cancer cells from the same person being treated (personalized therapy) in combination with added anticancer genetic signals to enhance the number and function anti-anticancer immune cells and to guide the immune cells to the cancer and not to normal organs of the body. In this manner, an army of immune cells are created that can move to attacking the cancer using blood vessels to get to the cancer anywhere it tries to grow in the body. One study (Phase I) performed with this product to determine safety and dose range demonstrated an optimal dose and schedule. Another study (Phase IIA) showed initial clinical benefit. A third more complex study (Phase IIB) in patients treated with Vigil compared with standard of care without Vigil demonstrated the ability to prolong the patients life and time without their cancer getting worse without any significant side effects associated with the treatment in a unique subset of ovarian cancer patients, those with the ability to repair their DNA. Based on the composite of these results, Vigil is an attractive targeted immunotherapy justified for late-stage clinical testing. Article highlights Vigil is a novel triple function immunotherapy designed to deliver personalized clonal neoantigens. Historical background Expression of GMCSF has been extensively studied and demonstrates safety, efficacy and immune activation in various solid tumor malignancies. Modulation of both GMCSF and TGFβ impact anticancer immune response specifically related to clinical benefit in association with GMCSF up regulation and TGFβ down regulation. bi-shRNA mechanism bi-shRNA is designed to take advantage of both cleave-dependent and cleavage independent RISC loading thus decreasing mRNA and subsequent protein expression to block signals associated with cancer progression. Vigil: mechanism Vigil is constructed from autologous tumor cells transfected with a plasmid encoding a GMCSF expressive unit, bi-shRNA directed to furin and clonal neoantigens. Clonal neoantigens are associated with increased clinical benefit to immune therapies. Vigil plasmid Vigil plasmid is produced using GMP manufacturing. Vigil construction & product delivery Vigil is constructed via a 2 day manufacturing process consisting of tissue dissociation, electroporation and irradiation. Preparation of the drug product The drug substance is formulated to appropriate concentration using freeze media. Every Vigil batch/lot is tested for product release criteria which has been verified for regulatory suitability. Vigil clinical experience 230 patients have received 1433 doses over various clinical trials in solid tumors. Vigil Phase I testing in solid tumor cancer Phase I testing of Vigil demonstrated manufacturing optimization, appropriate dose, safety and immune response in advanced solid tumor patients. Vigil Phase I/II testing in Ewing's sarcoma Vigil has been tested as monotherapy and in combination with temozolomide/irinotecan in Ewings sarcoma and demonstrated safety and evidence of efficacy. Vigil Phase IIA/IIB evaluation in ovarian cancer In Phase IIA trial in newly diagnosed Stage IIIB/IV ovarian cancer patients, Vigil demonstrated immune activation via ELISpot assay which correlated with clinical benefit. In Phase IIB trial also in newly diagnosed Stage IIIB/IV ovarian cancer patients, Vigil demonstrated improved RFS and OS in BRCA-wt patients. This benefit was further enhanced in patients with HRP molecular profile. In both trials, Vigil demonstrated no ≥ Grade 3 adverse events. Vigil-related biomarkers Several biomarkers have been identified retrospectively including TP53 mutation, and high ENTPD1 expression. Conclusion Vigil demonstrates a strong safety profile combined with durable clinical benefit. [ABSTRACT FROM AUTHOR]

Human lice have long been parasites of humans and are responsible for several epidemics in human medical history. However, their morphology, particularly head and body lice, remains very similar. In this study, we discriminate human louse species based on the number, shape and size of aeropyles (respiratory pores) of the egg operculum as well as the size of the respiratory orifice in the aeropyles. For this purpose, lice and eggs were collected from infested patients referring to Parasitology Department of Avicenne Hospital (Bobigny, France) and analyzed morphologically. The microscopic examination of the aeropyles revealed a large variation in the number ranging from 5 to 12 for head lice, 10 to 16 for body lice and 13 to 18 for pubic lice with a statistically distinct average of 8.3, 12.9 and 15.7, respectively. Although the length of the head and body louse eggs were almost similar, the width of body louse eggs were bigger than those of head louse (412.9 μm and 363.5 μm, respectively), while pubic louse eggs had the smallest length (692.9 μm) and width (286.1 μm). In addition, pubic louse eggs had a greater operculum length and width (253.7 μm length and 220.7 μm width) than head (230.6 μm length and 210.2 μm width) and body lice (227.9 μm length and 199.9 μm width). Moreover, pubic lice had the smallest average aeropyle size (41.2 μm) compared to head (51.1 μm) and body lice (49.1 μm). The respiratory orifice on the aeropyles of head and body lice (9.9 μm) were almost twice as big as those of pubic lice (4.9 μm). There was an inverse correlation between the number of aeropyles and their size in head, body and pubic lice. These findings are helpful in accurate identification of human louse species using their eggs, which could be useful for control management strategies against these ectoparasites. [ABSTRACT FROM AUTHOR]

Active systems of self-propelled agents, e.g., birds, fish, and bacteria, can organize their collective motion into myriad autonomous behaviors. Ubiquitous in nature and across length scales, such phenomena are also amenable to artificial settings, e.g., where brainless self-propelled robots orchestrate their movements into spatialtemporal patterns via the application of external cues or when confined within flexible boundaries. Like their natural counterparts, these approaches typically require many units to initiate collective motion, so controlling the ensuing dynamics is challenging. Here, we demonstrate a simple mechanism that leverages nonlinear elasticity to tame near-diffusive motile particles in forming structures capable of directed motion and other emergent behaviors. Our elasto-active system comprises two centimeter-sized self-propelled microbots connected with elastic beams. These microbots exert forces that suffice to buckle the beam and set the structure in motion. We first rationalize the physics of the interaction between the beam and the microbots. Then we use reducedorder models to predict the interactions of our elasto-active structures with boundaries, e.g., walls and constrictions, and demonstrate how they can exhibit remarkable emergent behaviors such as maze navigation. These findings demonstrate that allowing and understanding changes in body morphology can enhance the capabilities of active matter systems and enable the design of robotic materials capable of space exploration, adaptation, and complex interactions with their surrounding environment. [ABSTRACT FROM AUTHOR]

Human lice have long been parasites of humans and are responsible for several epidemics in human medical history. However, their morphology, particularly head and body lice, remains very similar. In this study, we discriminate human louse species based on the number, shape and size of aeropyles (respiratory pores) of the egg operculum as well as the size of the respiratory orifice in the aeropyles. For this purpose, lice and eggs were collected from infested patients referring to Parasitology Department of Avicenne Hospital (Bobigny, France) and analyzed morphologically. The microscopic examination of the aeropyles revealed a large variation in the number ranging from 5 to 12 for head lice, 10 to 16 for body lice and 13 to 18 for pubic lice with a statistically distinct average of 8.3, 12.9 and 15.7, respectively. Although the length of the head and body louse eggs were almost similar, the width of body louse eggs were bigger than those of head louse (412.9 μm and 363.5 μm, respectively), while pubic louse eggs had the smallest length (692.9 μm) and width (286.1 μm). In addition, pubic louse eggs had a greater operculum length and width (253.7 μm length and 220.7 μm width) than head (230.6 μm length and 210.2 μm width) and body lice (227.9 μm length and 199.9 μm width). Moreover, pubic lice had the smallest average aeropyle size (41.2 μm) compared to head (51.1 μm) and body lice (49.1 μm). The respiratory orifice on the aeropyles of head and body lice (9.9 μm) were almost twice as big as those of pubic lice (4.9 μm). There was an inverse correlation between the number of aeropyles and their size in head, body and pubic lice. These findings are helpful in accurate identification of human louse species using their eggs, which could be useful for control management strategies against these ectoparasites. [ABSTRACT FROM AUTHOR]

Clinical data: A nine-month-old female infant diagnosed with transposition of the great arteries with symptoms of heart failure associated with cyanosis and difficulty in gaining weight was referred to our center with late diagnosis (at nine months of age). Chest radiography: Cardiomegaly; attenuated peripheral vascular markings. Electrocardiography: Sinus rhythm with biventricular overload and aberrantly conducted supraventricular extra systoles. Echocardiography: Wide atrial septal defect, ventricular axis torsion with concordant atrioventricular connection and discordant ventriculoarterial connection. Computed tomography angiography: Concordant atrioventricular connection, right ventricle positioned superiorly and left ventricle positioned inferiorly; discordant ventriculoarterial connection with right ventricle connected to the aorta and left ventricle connected to pulmonary artery. Diagnosis: Crisscross heart is a rare congenital heart defect, accounting for 0.1% of congenital heart diseases. It consists of the 90° rotation of ventricles' axis in relation to their normal position; therefore, ventricles are positioned in the superior-inferior direction rather than anterior-posterior. Most cases have associated cardiac anomalies, and in this case, it is associated with transposition of the great arteries. The complexity and rarity of its occurrence make diagnosis and surgical treatment challenging. Operation: Modified Senning procedure using the pericardial sac in the construction of a tunnel from pulmonary veins to the right atrium. Cardiopulmonary bypass time of 147 minutes with nine minutes of total circulatory arrest. [ABSTRACT FROM AUTHOR]

Population aging, reduced economic capacity, and neglecting the treatments for oral pathologies, are the main causal factors for about 3 billion individuals who are suffering from partial/total edentulism or alveolar bone resorption: thus, the demand for dental implants is increasingly growing. To achieve a good prognosis for implant‐supported restorations, adequate peri‐implant bone volume is mandatory. The Guided Bone Regeneration (GBR) technique is one of the most applied methods for alveolar bone reconstruction and treatment of peri‐implant bone deficiencies. This technique involves the use of different types of membranes in association with some bone substitutes (autologous, homologous, or heterologous). However, time for bone regeneration is often too long and the bone quality is not simply predictable. This study aims at engineering and evaluating the efficacy of modified barrier membranes, enhancing their bioactivity for improved alveolar bone tissue regeneration. We investigated membranes functionalized with chitosan (CS) and chitosan combined with the peptide GBMP1α (CS + GBMP1α), to improve bone growth. OsseoGuard® membranes, derived from bovine Achilles tendon type I collagen crosslinked with formaldehyde, were modified using CS and CS + GBMP1α. The functionalization, carried out with 1‐ethyl‐3‐(3 dimethylaminopropyl)carbodiimide and sulfo‐N‐Hydroxysuccinimide (EDC/sulfo‐NHS), was assessed through FT‐IR and XPS analyses. Biological assays were performed by directly seeding human osteoblasts onto the materials to assess cell proliferation, mineralization, gene expression of Secreted Phosphoprotein 1 (SPP1) and Runt‐Related Transcription Factor 2 (Runx2), and antibacterial properties. Both CS and CS + GBMP1α functionalizations significantly enhanced human osteoblast proliferation, mineralization, gene expression, and antibacterial activity compared to commercial membranes. The CS + GBMP1α functionalization exhibited superior outcomes in all biological assays. Mechanical tests showed no significant alterations of membrane biomechanical properties post‐functionalization. The engineered membranes, especially those functionalized with CS + GBMP1α, are suitable for GBR applications thanks to their ability to enhance osteoblast activity and promote bone tissue regeneration. These findings suggest a potential advancement in the treatment of oral cavity problems requiring bone regeneration. [ABSTRACT FROM AUTHOR]

Type IV pili (T4P) produced by the pathogen Pseudomonas aeruginosa play a pivotal role in adhesion, surface motility, biofilm formation, and infection in humans. Despite the significance of T4P as a potential therapeutic target, key details of their dynamic assembly and underlying molecular mechanisms of pilus extension and retraction remain elusive, primarily due to challenges in isolating intact T4P machines from the bacterial cell envelope. Here, we combine cryo-electron tomography with subtomogram averaging and integrative modelling to resolve in-situ architectural details of the dynamic T4P machine in P. aeruginosa cells. The T4P machine forms 7-fold symmetric cage-like structures anchored in the cell envelope, providing a molecular framework for the rapid exchange of major pilin subunits during pilus extension and retraction. Our data suggest that the T4P adhesin PilY1 forms a champagne-cork-shaped structure, effectively blocking the secretin channel in the outer membrane whereas the minor-pilin complex in the periplasm appears to contact PilY1 via the central pore of the secretin gate. These findings point to a hypothetical model where the interplay between the secretin protein PilQ and the PilY1-minor-pilin priming complex is important for optimizing conformations of the T4P machine in P. aeruginosa, suggesting a gate-keeping mechanism that regulates pilus dynamics. Type IV pili (T4P) enable bacteria to sense, move, and adhere to surfaces. Here, the authors solve the structure of the T4P machine in Pseudomonas aeruginosa, revealing the localization and regulatory role of its tip adhesin, PilY1. [ABSTRACT FROM AUTHOR]

Topological defects are ubiquitous, they manifest in a wide variety of systems such as liquid crystals, magnets or superconductors. The recent quest for non‐abelian anyons in condensed matter physics stimulates the interest for topological defects since they can be hosted in vortices in quantum magnets or topological superconductors. In addition to these vortex defects, this study proposes to investigate edge dislocations in 2D magnets as new building blocks for topological physics since they can be described as vortices in the structural phase field. It demonstrates the existence of higher order topological dislocations within the higher order moiré pattern of the van der Waals 2D magnet CrCl3 deposited on Au(111). Surprisingly, these higher order dislocations arise from ordinary simple edge dislocations in the atomic lattice of CrCl3. This study provide a theoretical framework explaining the higher order dislocations as vortices with a winding Chern number of 2. It is expected that these original defects can stabilize some anyons either in a 2D quantum magnet or within a 2D superconductor coupled to it. [ABSTRACT FROM AUTHOR]

As we age, we lose muscle strength and power, a condition commonly referred to as sarcopenia (ICD-10-CM code (M62.84)). The prevalence of sarcopenia is about 5–10% of the elderly population, resulting in varying degrees of disability. In this review we emphasise that sarcopenia does not occur suddenly. It is an aging-induced deterioration that occurs over time and is only recognised as a disease when it manifests clinically in the 6th–7th decade of life. Evidence from animal studies, elite athletes and longitudinal population studies all confirms that the underlying process has been ongoing for decades once sarcopenia has manifested. We present hypotheses about the mechanism(s) underlying this process and their supporting evidence. We briefly review various proposals to impede sarcopenia, including cell therapy, reducing senescent cells and their secretome, utilising targets revealed by the skeletal muscle secretome, and muscle innervation. We conclude that although there are potential candidates and ongoing preclinical and clinical trials with drug treatments, the only evidence-based intervention today for humans is exercise. We present different exercise programmes and discuss to what extent the interindividual susceptibility to developing sarcopenia is due to our genetic predisposition or lifestyle factors. [ABSTRACT FROM AUTHOR]

Background: Radical cystectomy (RC) is a major surgery associated with a high morbidity rate. Perioperative fluid management according to enhanced recovery after surgery (ERAS) protocols aims to maintain patients in an optimal euvolemic state while exposing them to acute kidney injury (AKI) in the event of hypovolemia. Postoperative AKI is associated with severe morbidity and mortality. Our main objective was to determine the association between perioperative variables, including some component of ERAS protocols, and occurrence of postoperative AKI within the first 30 days following RC in patients presenting bladder cancer. Our secondary objective was to evaluate the association between a postoperative AKI and the occurrence or worsening of a chronic kidney disease (CKD) within the 2 years following RC. Methods: We conducted a retrospective observational study in a referral cancer center in France on 122 patients who underwent an elective RC for bladder cancer from 01/02/2015 to 30/09/2019. The primary endpoint was occurrence of AKI between surgery and day 30. The secondary endpoint was survival without occurrence or worsening of a postoperative CKD. AKI and CKD were defined by KDIGO (Kidney Disease: Improving Global Outcomes) classification. Logistic regression analyse was used to determine independent factors associated with postoperative AKI. Fine and Gray model was used to determine independent factors associated with postoperative CKD. Results: The incidence of postoperative AKI was 58,2% (n = 71). Multivariate analysis showed 5 factors independently associated with postoperative AKI: intraoperative restrictive vascular filling < 5ml/kg/h (OR = 4.39, 95%CI (1.05–18.39), p = 0.043), postoperative sepsis (OR = 4.61, 95%CI (1.05–20.28), p = 0.043), female sex (OR = 0.11, 95%CI (0.02–0.73), p = 0.022), score SOFA (Sequential Organ Failure Assessment) at day 1 (OR = 2.19, 95%CI (1.15–4.19), p = 0.018) and delta serum creatinine D1 (OR = 1.06, 95%CI (1.02–1.11), p = 0.006). During the entire follow-up, occurrence or worsening of CKD was diagnosed in 36 (29.5%). A postoperative, AKI was strongly associated with occurrence or worsening of a CKD within the 2 years following RC even after adjustment for confounding factors (sHR = 2.247, 95%CI [1.051–4.806, p = 0.037]). Conclusion: A restrictive intraoperative vascular filling < 5ml/kg/h was strongly and independently associated with the occurrence of postoperative AKI after RC in cancer bladder patients. In this context, postoperative AKI was strongly associated with the occurrence or worsening of CKD within the 2 years following RC. A personalized perioperative fluid management strategy needs to be evaluated in these high-risk patients. [ABSTRACT FROM AUTHOR]

Background: Fabry disease (FD) is a rare X-linked lysosomal storage disorder marked by alpha-galactosidase-A (α-Gal A) deficiency, caused by pathogenic mutations in the GLA gene, resulting in the accumulation of glycosphingolipids within lysosomes. The current screening test relies on measuring α-Gal A activity. However, this approach is limited to males. Infrared (IR) spectroscopy is a technique that can generate fingerprint spectra of a biofluid's molecular composition and has been successfully applied to screen numerous diseases. Herein, we investigate the discriminating vibration profile of plasma chemical bonds in patients with FD using attenuated total reflection Fourier-transform IR (ATR-FTIR) spectroscopy. Results: The Fabry disease group (n = 47) and the healthy control group (n = 52) recruited were age-matched (39.2 ± 16.9 and 36.7 ± 10.9 years, respectively), and females were predominant in both groups (59.6% and 65.4%, respectively). All patients had the classic phenotype (100%), and no late-onset phenotype was detected. A generated partial least squares discriminant analysis (PLS-DA) classification model, independent of gender, allowed differentiation of samples from FD vs. control groups, reaching 100% sensitivity, specificity and accuracy. Conclusion: ATR-FTIR spectroscopy harnessed to pattern recognition algorithms can distinguish between FD patients and healthy control participants, offering the potential of a fast and inexpensive screening test. [ABSTRACT FROM AUTHOR]

Due to the expanding oil-related activities, the arctic and sub-arctic marine environments are increasingly vulnerable to oil-related pollution such as accidental oil spills. These cold-water ecosystems harbor many fish species that are both ecologically and economically important such as the pelagic polar cod (Boreogadus saida), capelin (Mallotus villosus), and benthic long rough dab (Hippoglossoides platessoides). The latter two are much less studied and it is crucial to characterize their responses to oil-related contaminants and develop molecular biomarkers and genomic resources for future monitoring. In this study, liver slice preparation and culture methods were used to characterize the transcriptome responses (using RNA-seq) in capelin and long rough dab to exposures of the polycyclic aromatic hydrocarbon (PAH) compound benzo[a] pyrene (BaP). The liver slice culture and exposure experiments were performed onboard a research vessel in the Barents Sea. Strong up-regulation of genes involved in biotransformation, particularly the aryl hydrocarbon receptor signaling pathway was observed in both species. A comparison of the number of differentially expressed genes (DEGs) with previously published polar cod exposures indicates that the latter respondedmore strongly (higher number of genes), suggesting higher uptake and bioconcentration of BaP in the fatty liver tissue, although other factors such as differences in clearance rate could potentially affect the responses. This study provides new genomic resources and gene expression biomarkers in capelin and long rough dab, enhancing our understanding of their response mechanism to oil-related contaminants. [ABSTRACT FROM AUTHOR]

decade after the implementation of multimedia frameworks in the news media, it is necessary to determine which mechanisms have been incorporated into the daily routines of the news media. To accomplish this, we analysed the channels, forms and intertextual modalities employed by two leading international newspapers in their coverage of an unpredictable news event with global repercussions and a specific period: the UK government crisis of July 2022, which led to the resignation of the British Prime Minister Boris Johnson. We used a qualitative methodology of transmedia information analysis (Calvo & Serrano Tellería, 2021), adapted to assess the daily operations of online media in updating their content. Additionally, interviews were conducted with the teams responsible for this coverage. The coverage analysis revealed a transmedia depth of ten to eleven informative modalities. We found several residual differences in their audience participation policies. Certain generalist modalities, such as live streaming, video news, podcasts or social networks, were well established and used to attract readership. Furthermore, various models of newsletters and discussion forums with varying levels of access restriction were employed. However, neither of the studied media outlets offered an auditory transcription of their content. While a specific transmedia information model is emerging in digital media, further research should be undertaken to complement these findings. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to investigate if diurnal oscillation in maximal fat oxidation (MFO) and substrate oxidation rates during exercise exists in subjects with metabolic syndrome (MetS). Methods: In a randomized crossover design, 14 MetS patients were assigned to two graded exercise tests conditions performed in the morning (between 7:00 and 9:00 a.m) and in the afternoon (between 4:00 and 5:00 p.m). MFO was defined as the highest absolute value of fat oxidation obtained from the average of last 2-min stages during an indirect calorimetry test. Results: MFO increased by 20.6% from morning to afternoon (p = 0.0002, Cohen's d = 0.52). There was a significant time of day, (p < 0.0001, η2p = 0.76) and intensity effect (p = 0.002, η2p = 0.32) in fat oxidation (Fatox) rates indicating that Fatox was higher in the afternoon than in the morning. Conclusion: Our study extends previous findings on the existence of diurnal variation in maximal fat oxidation to MetS patients, highlighting the afternoon as a more favorable time for fat utilization during exercise. These findings have practical implications for optimizing training timing in MetS patients. Trial registration number: PACTR202306776991260. [ABSTRACT FROM AUTHOR]

Background: Histopathological analysis represents the gold standard in clinical practice for diagnosing skin neoplasms. While the current diagnostic workflow has specialized in producing robust and accurate results, interpreting tissue architecture and malignant cellular morphology correctly remains one of the greatest challenges for pathologists. This paper aims to explore the prospect of applying x‐ray virtual histology to human skin tumor excisions and correlating it with the histological validation. Materials and Methods: Seven skin biopsies containing intriguing melanoma types and pigmented skin lesions were scanned using x‐ray Computed micro‐Tomography (μCT) and then sectioned for conventional histology assessment. Results: The tissue microarchitecture reconstructed by μCT offers detailed insights into diagnosing the malignancy or benignity of the skin lesions. Three‐dimensional reconstruction via x‐ray virtual histology reveals infiltrative patterns in basal cell carcinoma and evaluated invasiveness in melanoma. The technology enables the identification of pagetoid distributions of neoplastic cells and the assessment of melanoma depth in three dimensions. Conclusion: Although the proposed approach is not intended to replace conventional histology, the non‐destructive nature of the sample and the clarity provided by virtual inspection demonstrate the promising impact of μCT as a valid support method prior to conventional histological sectioning. Indeed, μCT images can suggest the optimal sectioning position before using a microtome, as is commonly performed in histological practice. Moreover, the three‐dimensional nature of the proposed approach paves the way for a more accurate assessment of significant prognostic factors in melanoma, such as Breslow thickness, by considering the whole micro‐volume rather than a two‐dimensional observation. [ABSTRACT FROM AUTHOR]

Background and Aims: Acute porphyria is a chronic recurrent disease with late diagnosis, heterogeneous clinical presentations and potentially devastating complications. The study aimed at providing real‐world evidence on the natural course of acute porphyria, patient characteristics, disease burden, and healthcare utilization before diagnosis. Methods: This observational study used anonymized claims data covering 8 365 867 persons from German statutory health insurance, spanning 6 years (2015–2020). Patients with at least one diagnosis of acute porphyria during the index period (2019–2020) were classified into three groups by attack frequency. These findings were compared with two age‐ and sex‐adjusted reference groups: the general population and fibromyalgia patients. Prevalence over the index period was calculated for all porphyria patients and those with active acute porphyria. Results: We revealed a prevalence of 79.8 per 1 000 000 for acute porphyria, with 12.9 per 1 000 000 being active cases. Acute porphyria patients, particularly with frequent attacks, demonstrated a higher comorbidity burden compared to the general population. Within the year before the recorded diagnosis, patients with acute porphyria required a median of 23.0 physician visits, significantly higher than the general population's 16.0. Additionally, 33.8% were hospitalized at least once during this period, a notably higher proportion than the general population (19.3%). Conclusions: This study's findings, collected before the introduction of givosiran, as the first approved preventive therapy for acute porphyria in Europe, highlight the need for healthcare strategies and policies tailored to the complex needs of acute porphyria patients. The significant healthcare demands, heightened comorbidity burden, and increased healthcare system utilization emphasize the urgency of developing a comprehensive support infrastructure for these patients. Also, these acute porphyria real‐world findings provide additional insights on disease characteristics in Germany. [ABSTRACT FROM AUTHOR]

Candidemia and invasive candidiasis (IC) are causes of morbidity and mortality in healthcare settings, with notable differences between children and adults. Understanding the species distribution and antimicrobial susceptibility profiles of clinical isolates can guide empiric therapy in patients at risk of IC. This study investigated the incidence and antifungal susceptibility patterns of yeasts involved in IC in pediatric and adult patients from 2019 to 2023. The average incidence of IC was 0.715 per 1000 patients, increasing over the study period; infants had the highest incidence rates. Over half of the IC episodes occurred in intensive care units (ICUs). Non-albicans Candida (NAC) species represented the most frequently isolated species in adults and children (55.96% and 50.0%, respectively), with the prevalence of C. parapsilosis (26.45% and 14.7%, respectively), N. glabratus (14.97% and 8.82%, respectively) and C. tropicalis (4.36% and 2.94%, respectively). C. lusitaniae was identified in 14.7% of pediatric IC cases. In NAC species, antifungal resistance has also increased over the five years of the study: 69.12% were resistant to azoles and 7.35% were resistant to micafungin. Resistance was higher in pediatric patients. Our study highlights differences in IC characteristics between pediatric and adult populations and emphasizes the importance of targeted antifungal stewardship in ICU patients with NAC invasive infections. [ABSTRACT FROM AUTHOR]

Cellular processes are controlled by the thermodynamics of the underlying biomolecular interactions. Frequently, structural investigations use one monomeric binding partner, while ensemble measurements of binding affinities generally yield one affinity representative of a 1:1 interaction, despite the majority of the proteome consisting of oligomeric proteins. For example, viral entry and inhibition in SARS-CoV-2 involve a trimeric spike surface protein, a dimeric angiotensin-converting enzyme 2 (ACE2) cell-surface receptor and dimeric antibodies. Here, we reveal that cooperativity correlates with infectivity and inhibition as opposed to 1:1 binding strength. We show that ACE2 oligomerizes spike more strongly for more infectious variants, while exhibiting weaker 1:1 affinity. Furthermore, we find that antibodies use induced oligomerization both as a primary inhibition mechanism and to enhance the effects of receptor-site blocking. Our results suggest that naive affinity measurements are poor predictors of potency, and introduce an antibody-based inhibition mechanism for oligomeric targets. More generally, they point toward a much broader role of induced oligomerization in controlling biomolecular interactions. [ABSTRACT FROM AUTHOR]

Polymers are versatile materials widely used in various industries, with significant applications in biomedicine where biofouling on polymer surfaces presents major health and economic challenges. Biofouling, initiated by bacterial adhesion, can be mitigated by modifying surface properties through laser micro- and nano-texturing, an approach that offers advantages over chemical treatments. This study introduces an economical mass production process for textured polymeric components using injection molding to replicate hierarchical textures. Testing revealed that all textured samples significantly reduced bacterial adhesion compared to untextured surfaces across different designs and bacteria types after 24 h of culture. The study examined factors like wettability, nanoscale roughness, and pattern dimensions to explain these outcomes, comparing them with existing studies. Despite all textured samples showing decreased wettability and roughness, these factors alone did not ensure reduced bacterial adhesion. The most effective anti-adhesive performance was observed in surfaces with parallel ridge patterns, which segmented the surface into isolated areas that limited bacterial interaction and hindered micro-colony formation, highlighting the importance of specific surface patterning in combating biofouling. [ABSTRACT FROM AUTHOR]

Objective: To retrospectively evaluate the long-term outcomes after percutaneous cryoablation of abdominal wall endometriosis (AWE). Method: The Institutional Review Board approved this retrospective observational review of 40 consecutive patients, of a median age of 37 years (interquartile range [IQR] 32–40 years), presenting with a total of 52 symptomatic AWE nodules. All patients underwent cryoablation between January 2013 and May 2022 with a minimum follow-up period of 12 months. Outcomes were assessed using a visual analog scale (VAS) that measured pain, as well as by magnetic resonance imaging (MRI). The pain-free survival rates were derived using the Kaplan–Meier estimator. Adverse events were analyzed and graded using the classification system of the Cardiovascular and Interventional Radiological Society of Europe. Results: The median follow-up time was 40.5 months (IQR 26.5–47.2 months). The median VAS score before cryoablation was 8 (IQR 7–9). Complete relief of symptoms was documented in 80% (32/40) of patients at 3 months after initial cryoablation and correlated with the absence of residual endometriosis nodules on MRI. The median pain-free survival rates were 89.2% [95% CI, 70.1–96.4%] at 36 months and 76.8% [95% CI, 55.3–83.8%] after 60 months. No patient or lesion characteristics were found to be prognostic of failure. No major adverse events or side effects were reported in long term. Conclusion: Cryoablation safely and effectively afforded long-term pain relief for patients with AWE nodules. Clinical relevance statement: AWE cryoablation was found to be safe and effective in the long-term. Key Points: • Cryoablation is highly effective with 80% of patients experiencing complete relief of AWE symptoms after a single procedure. • Cryoablation is safe without long-term adverse events or side effects. • The median pain-free survival rates are 89.2% at 36 months and 76.8% at 60 months. [ABSTRACT FROM AUTHOR]

Background: The pancreas is a complex abdominal organ with many anatomical variations, and therefore automated pancreas segmentation from medical images is a challenging application. Purpose: In this paper, we present a framework for segmenting individual pancreatic subregions and the pancreatic duct from three‐dimensional (3D) computed tomography (CT) images. Methods: A multiagent reinforcement learning (RL) network was used to detect landmarks of the head, neck, body, and tail of the pancreas, and landmarks along the pancreatic duct in a selected target CT image. Using the landmark detection results, an atlas of pancreases was nonrigidly registered to the target image, resulting in anatomical probability maps for the pancreatic subregions and duct. The probability maps were augmented with multilabel 3D U‐Net architectures to obtain the final segmentation results. Results: To evaluate the performance of our proposed framework, we computed the Dice similarity coefficient (DSC) between the predicted and ground truth manual segmentations on a database of 82 CT images with manually segmented pancreatic subregions and 37 CT images with manually segmented pancreatic ducts. For the four pancreatic subregions, the mean DSC improved from 0.38, 0.44, and 0.39 with standard 3D U‐Net, Attention U‐Net, and shifted windowing (Swin) U‐Net architectures, to 0.51, 0.47, and 0.49, respectively, when utilizing the proposed RL‐based framework. For the pancreatic duct, the RL‐based framework achieved a mean DSC of 0.70, significantly outperforming the standard approaches and existing methods on different datasets. Conclusions: The resulting accuracy of the proposed RL‐based segmentation framework demonstrates an improvement against segmentation with standard U‐Net architectures. [ABSTRACT FROM AUTHOR]

The main objective of this study is to assess and contrast the efficacy of distinct spatial prediction methods in a simulation aimed at optimizing the embodied energy during the construction of prestressed slab bridge decks. A literature review and cross-sectional analysis have identified crucial design parameters that directly affect the design and construction of bridge decks. This analysis determines the critical design variables to improve the deck's energy efficiency, providing practical guidance for engineers and professionals in the field. The methods analyzed in this study are ordinary Kriging and a multilayer perceptron neural network. The methodology involves analyzing the predictive performance of both models through error analysis and assessing their ability to identify local optima on the response surface. The results show that both models generally overestimate the observed values. The Kriging model with second-order polynomials yields a 4% relative error at the local optimum, while the neural network achieves lower root mean square errors (RMSEs). Neither the Kriging model nor the neural network provides precise predictions but point to promising solution regions. Optimizing the response surface to find a local minimum is crucial. High slenderness ratios (around 1/28) and 40 MPa concrete grade are recommended to improve energy efficiency. [ABSTRACT FROM AUTHOR]

Cervical relaxation (CR) was performed in ewes during diestrus, to prospect a feasible protocol for non-surgical embryo transfer (NSET). In Trial 1, naturally mated ewes (n=13) received CR protocols with estradiol benzoate (EB, 1 mg on D6) and oxytocin (OT, 50 IU on D7) only (G-EB+OT) or associated with human chorionic gonadotropin (hCG, 300 IU on D7, G-EB+OT+hCG) and were compared to non-hormonally treated (G-control) ewes. Estradiol concentration increased (P<0.05) from D6 to D7 in G-EB+OT and G-EB+OT+hCG, then decreased (P<0.05) on D8. The G-EB+OT had reduced (P<0.05) progesterone on D8, and 0% (0/5) pregnancy, while G-control had 100% (3/3) conception rate. The treatment with hCG mitigated the progesterone drop on D8 and resulted in 50% (2/4) conception rate. In Trial 2, cervical transposing success after treatment with EB, OT, and hCG on D6 and D7 was assessed in nulliparous (n=25) and multiparous (n=30) ewes. The EB+OT+hCG protocol allowed efficient cervical transposition (~78% of cervical transposition success into ~5 min) in nulliparous and multiparous females and did not alter total and blood perfusion areas of corpora lutea (CL). The use of EB+OT+hCG was efficient to ensure effective cervical transposing in nulliparous and multiparous ewes, with no apparent deleterious effect on CL function, and may contribute to animal welfare, allowing a less invasive NSET procedure. [ABSTRACT FROM AUTHOR]

Background: How pediatric medulloblastoma patients fare in Lower Middle-Income Country (LMICs) in South America is not well understood. Correspondingly, the aim of this study was to summarize the pediatric neurosurgical experience of an institution in La Paz, and compare outcomes to that of a generalized High Income Country (HIC) United States (US) experience. Methods: A retrospective review of all pediatric neurosurgical medulloblastoma patients at the Children's Hospital of La Paz, Bolivia (Hospital del Niño "Dr. Ovidio Aliaga Uria") between 2014 and 2023 was conducted and compared to a generalized US experience abstracted from the US National Cancer Database (NCDB) and National Inpatient Sample (NIS) databases. Categorical, continuous and survival data were statistically summarized and compared. Results: A total of 24 pediatric medulloblastoma patients underwent neurosurgical treatment at the Hospital del Niño. In this La Paz cohort, there were 15 (63%) males and 9 (38%) females, with a mean age of 5.6 years old at diagnosis. The majority of patients underwent subtotal resection (STR, 79%), while the remaining patients underwent biopsy only. Ten (42%) patients expired during their hospitalization, and mean length of stay overall was 39 days. Only 8 (33%) patients received adjuvant treatment after surgery. Median overall survival from diagnosis in the La Paz cohort was 1.9 months. Compared to the US databases, the La Paz cohort experienced significantly more emergency room admissions for surgery, less gross total resection, more STR, more return to operating room for ventriculoperitoneal shunting, more bacteremia, more tracheostomy procedures, more percutaneous gastrostomy placements, longer lengths of stay, less adjuvant chemotherapy, less radiation therapy, shorter follow-up, and ultimately, significantly shorter overall survival (all P < 0.050). Conclusions: Pediatric neurosurgical medulloblastoma outcomes at the Children's Hospital of La Paz, Bolivia are significantly inferior to that of a generalized US experience. Future research is required to identify institution- and country-specific initiatives to improve discrepancies between institutions in LMICs in South America compared to HICs. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to critically examine previous studies' claims about the magnitude of gender differences and gender inequality in physical education (PE) in Sweden. Method: The data were based on students' (N = 39,980) perceptions of PE and were gathered from four large research projects in Sweden. Three effect size measures (Cramer's V, r squared, and Cohen's d) were calculated for gender differences. Results: In general, there are small gender differences; and after controlling for students' grade, "sports capital," and parents' "educational capital," the differences are practically irrelevant. Conclusion: This study provides compelling evidence that there are small, or even irrelevant, gender differences in students' perceptions of PE in Sweden. Moreover, given that previous research asserts that large gender differences can be used as an indicator of inequality, this study suggests that gender inequality issues related to students' perceptions of PE are relatively small. [ABSTRACT FROM AUTHOR]

Given the pressing climate and sustainability challenges, shifting industrial processes towards environmentally friendly practices is imperative. Among various strategies, the generation of green, flexible materials combined with efficient reutilization of biomass stands out. This review provides a comprehensive analysis of the hydrothermal carbonization (HTC) process as a sustainable approach for developing carbonaceous materials from biomass. Key parameters influencing hydrochar preparation are examined, along with the mechanisms governing hydrochar formation and pore development. Then, this review explores the application of hydrochars in supercapacitors, offering a novel comparative analysis of the electrochemical performance of various biomass-based electrodes, considering parameters such as capacitance, stability, and textural properties. Biomass-based hydrochars emerge as a promising alternative to traditional carbonaceous materials, with potential for further enhancement through the incorporation of extrinsic nanoparticles like graphene, carbon nanotubes, nanodiamonds and metal oxides. Of particular interest is the relatively unexplored use of transition metal dichalcogenides (TMDCs), with preliminary findings demonstrating highly competitive capacitances of up to 360 F/g when combined with hydrochars. This exceptional electrochemical performance, coupled with unique material properties, positions these biomass-based hydrochars interesting candidates to advance the energy industry towards a greener and more sustainable future. [ABSTRACT FROM AUTHOR]

Simple Summary: The way animals are housed and cared for in research is vital for both ethical reasons and the quality of research produced. One important aspect of mouse housing is air quality. In this study, we measured levels of two potentially harmful compounds, ammonia and carbon dioxide, as well as humidity and temperature, in mouse cages. This study followed the mice from adulthood (100 days old) to middle age (322 days old) as they gained 35–50% body weight. The mice were divided by sex, and their cages were cleaned either weekly (7 d) or bi-weekly (14 d). Our findings show that air quality remains within the safe levels for younger, lighter mice, but changes throughout the day, with higher levels of carbon dioxide, ammonia, and humidity when the mice are active at night. However, as the mice aged and gained weight, the ammonia and humidity levels increased, potentially reaching harmful levels. Carbon dioxide and temperature were less affected by these changes. Our study suggests that it is important to consider mice's activity patterns and body mass when determining the frequency of cage cleaning and housing density. Housing conditions are essential for ensuring animal welfare and high-quality research outcomes. In this study, we continuously monitored air quality—specifically ammonia, carbon dioxide, relative humidity, and temperature—in Individually Ventilated Cages (IVCs) housing five female or male C57BL/6N mice. The cages were cleaned either weekly or bi-weekly, and the data were collected as the mice aged from 100 to 348 days. The survival rate remained above 96%, with body weight increasing by 35–52% during the study period. The ammonia levels rose throughout the cleaning cycle, but averaged below 25 ppm. However, in the older, heavier mice with bi-weekly cage cleaning, the ammonia levels reached between 25 and 75 ppm, particularly in the males. While circadian rhythms influenced the ammonia concentration only to a small extent, the carbon dioxide levels varied between 800 and 3000 ppm, increasing by 30–50% at night and by 1000 ppm with body weight. Humidity also correlated primarily with the circadian rhythms (10% higher at night) and, to a lesser extent, with body weight, reaching ≥70% in the middle-aged mice. The temperature variations remained minimal, within a 1 °C range. We conclude that air quality assessments in IVCs should be conducted during animals' active periods, and both housing density and biomass must be considered to optimise welfare. [ABSTRACT FROM AUTHOR]

Current adeno-associated virus (AAV) gene therapy using nature-derived AAVs is limited by non-optimal tissue targeting. In the treatment of muscular diseases (MD), high doses are often required but can lead to severe adverse effects. Here, we rationally design an AAV capsid that specifically targets skeletal muscle to lower treatment doses. We computationally integrate binding motifs of human integrin alphaV beta6, a skeletal muscle receptor, into a liver-detargeting capsid. Designed AAVs show higher productivity and superior muscle transduction compared to their parent. One variant, LICA1, demonstrates comparable muscle transduction to other myotropic AAVs with reduced liver targeting. LICA1's myotropic properties are observed across species, including non-human primate. Consequently, LICA1, but not AAV9, effectively delivers therapeutic transgenes and improved muscle functionality in two mouse MD models (male mice) at a low dose (5E12 vg/kg). These results underline the potential of our design method for AAV engineering and LICA1 variant for MD gene therapy. Gene therapy using adeno-associated virus (AAV) has shown promise for treating genetic diseases yet limited by inefficient delivery. Here, the authors develop an AAV variant targeting specifically the skeletal muscle and enabling effective gene therapy for muscle diseases at significantly lower doses. [ABSTRACT FROM AUTHOR]

Background: The primary aim of specialised palliative care (SPC) is to improve the quality of life (QoL) for patients with a high symptom burden from a life-threatening disease. This randomised study aimed to assess the QoL impact of early integration of SPC alongside tumour-specific palliative treatment in patients with gastrointestinal (GI) cancers. Methods: We randomly assigned ambulatory patients with advanced GI cancer to early integration of SPC and palliative tumour-specific treatment or tumour-specific treatment alone. The primary endpoint was QoL assessed at baseline and every sixth week using the Functional Assessment of Cancer Therapy—General (FACT-G) questionnaire. Results: A total of 118 patients were randomised. The difference in total FACT-G score between patients assigned to early integration with SPC and controls was 5.2 points (95% CI: −0.1 to 10.5, p = 0.216), 6.7 points (95% CI: 0.2 to 13.3, p = 0.172), and 13 points (95% CI: 5.7 to 20.2, p = 0.004) at weeks 6, 12, and 24, respectively. Conclusions: This prospective randomised trial strengthens the argument for early integration of SPC with tumour-specific treatment in patients with advanced GI cancers. We found an improved QoL for patients with advanced GI cancer 24 weeks after randomisation to early integration of home-based SPC. Clinical trial registration: ClinicalTrials.gov (ref: NCT02246725). [ABSTRACT FROM AUTHOR]

Accumulation processes, where many potentially coupled features are acquired over time, occur throughout the sciences, from evolutionary biology to disease progression, and particularly in the study of cancer progression. Existing methods for learning the dynamics of such systems typically assume limited (often pairwise) relationships between feature subsets, cross-sectional or untimed observations, small feature sets, or discrete orderings of events. Here we introduce HyperTraPS-CT (Hypercubic Transition Path Sampling in Continuous Time) to compute posterior distributions on continuous-time dynamics of many, arbitrarily coupled, traits in unrestricted state spaces, accounting for uncertainty in observations and their timings. We demonstrate the capacity of HyperTraPS-CT to deal with cross-sectional, longitudinal, and phylogenetic data, which may have no, uncertain, or precisely specified sampling times. HyperTraPS-CT allows positive and negative interactions between arbitrary subsets of features (not limited to pairwise interactions), supporting Bayesian and maximum-likelihood inference approaches to identify these interactions, consequent pathways, and predictions of future and unobserved features. We also introduce a range of visualisations for the inferred outputs of these processes and demonstrate model selection and regularisation for feature interactions. We apply this approach to case studies on the accumulation of mutations in cancer progression and the acquisition of anti-microbial resistance genes in tuberculosis, demonstrating its flexibility and capacity to produce predictions aligned with applied priorities. Author summary: Many important processes in biology and medicine involve a progressive buildup of features over time. These might be, for example, the accumulation of different mutations as cancer progresses, or the evolution of bacteria to be resistant to more and more drugs. Here we introduce an algorithm called HyperTraPS-CT that allows us to use data to learn the details of how these features build up over time. The algorithm provides information on which features affect each other, which come early and which come late, and what might happen in the future. It is more flexible than several existing approaches, and can be used across many different scentific situations; we demonstrate its use in learning about leukemia progression and tuberculosis drug resistance. This approach has the potential to help make useful predictions about how new instances of these processes will evolve, about data which can't be observed due to technological limitations, and about possible mechanisms that determine how features interact. [ABSTRACT FROM AUTHOR]

Ghrelin is an appetite-stimulating hormone secreted from the gastric mucosa in the fasting state, and secretion decreases in response to food intake. After sleeve gastrectomy (SG), plasma concentrations of ghrelin decrease markedly. Whether this affects appetite and glucose tolerance postoperatively is unknown. We investigated the effects of ghrelin infusion on appetite and glucose tolerance in individuals with obesity before and 3 mo after SG. Twelve participants scheduled for SG were included. Before and 3 mo after surgery, a mixed-meal test followed by an ad libitum meal test was performed with concomitant infusions of acyl-ghrelin (1 pmol/kg/min) or placebo. Infusions began 60 min before meal intake to reach a steady state before the mixed-meal and were continued throughout the study day. Two additional experimental days with 0.25 pmol/kg/min and 10 pmol/kg/min of acyl-ghrelin infusions were conducted 3 mo after surgery. Both before and after SG, postprandial glucose concentrations increased dose dependently during ghrelin infusions compared with placebo. Ghrelin infusions inhibited basal and postprandial insulin secretion rates, resulting in lowered measures of β-cell function, but no effect on insulin sensitivity was seen. Ad libitum meal intake was unaffected by the administration of ghrelin. In conclusion, ghrelin infusion increases postprandial plasma glucose concentrations and impairs β-cell function before and after SG but has no effect on ad libitum meal intake. We speculate that the lower concentration of ghrelin after SG may impact glucose metabolism following this procedure. NEW & NOTEWORTHY: Ghrelin's effect on glucose tolerance and food intake following sleeve gastrectomy (SG) was evaluated. Acyl-ghrelin was infused during a mixed-meal and ad libitum meals before and 3 mo after surgery. Postprandial glucose concentrations increased during ghrelin infusions, both before and after surgery, while insulin production was inhibited. However, ad libitum meal intake did not differ during ghrelin administration compared with placebo. The decreased ghrelin concentration following SG may contribute to the glycemic control after surgery. [ABSTRACT FROM AUTHOR]

This article reports the first measurements of high-energy photons produced with the high-intensity PETawatt Aquitaine Laser (PETAL) laser. The experiments were performed during the commissioning of the laser. The laser had an energy of about 400 J, an intensity of 8 × 1018 W cm−2, and a pulse duration of 660 fs (FWHM). It was shot at a 2 mm-thick solid tungsten target. The high-energy photons were produced mainly from the bremsstrahlung process for relativistic electrons accelerated inside a plasma generated on the front side of the target. This paper reports measurements of electrons, protons and photons. Hot electrons up to ≈35 MeV with a few-MeV temperature were recorded by a spectrometer, called SESAME (Spectre ÉlectronS Angulaire Moyenne Énergie). K- and L-shells were clearly detected by a photon spectrometer called SPECTIX (Spectromètre Petal à Cristal en TransmIssion pour le rayonnnement X). High-energy photons were diagnosed by CRACC-X (Cassette de RAdiographie Centre Chambre-rayonnement X), a bremsstrahlung cannon. Bremsstrahlung cannon analysis is strongly dependent on the hypothesis adopted for the spectral shape. Different shapes can exhibit similar reproductions of the experimental data. To eliminate dependence on the shape hypothesis and to facilitate analysis of the data, simulations of the interaction were performed. To model the mechanisms involved, a simulation chain including hydrodynamic, particle-in-cell, and Monte Carlo simulations was used. The simulations model the preplasma generated at the front of the target by the PETAL laser prepulse, the acceleration of electrons inside the plasma, the generation of MeV-range photons from these electrons, and the response of the detector impacted by the energetic photon beam. All this work enabled reproduction of the experimental data. The high-energy photons produced have a large emission angle and an exponential distribution shape. In addition to the analysis of the photon spectra, positron production was also investigated. Indeed, if high-energy photons are generated inside the solid target, some positron/electron pairs may be produced by the Bethe–Heitler process. Therefore, the positron production achievable within the PETAL laser facility was quantified. To conclude the study, the possibility of creating electron/positron pairs through the linear Breit–Wheeler process with PETAL was investigated. [ABSTRACT FROM AUTHOR]

The EuPRAXIA EU project is at the forefront of advancing particle accelerator research and the development of photon sources through innovative plasma acceleration approaches. Within this framework, the EuAPS project aims to exploit laser wakefield acceleration to build and operate a betatron radiation source at the INFN Frascati National Laboratory. The EuAPS source will provide femtosecond X-ray pulses in the spectral region between about 1 and 10 keV, unlocking a realm of experimental ultrafast methodologies encompassing diverse imaging and X-ray spectroscopy techniques. This paper presents a description of the EuAPS betatron source, including simulations of the photon beam parameters, outlines the preliminary design of the dedicated photon beamline, and provides an insightful overview of its photon science applications. [ABSTRACT FROM AUTHOR]

Waardenburg syndrome (WS) is a common genetic cause of syndromic hearing loss, accounting for 2–5% of congenital cases. It is characterized by hearing impairment and pigmentation abnormalities in the skin, hair, and eyes. Seven genes are associated with WS: PAX3, MITF, EDNRB, EDN3, SOX10, KITLG, and SNAI2. This study investigates the genetic causes of WS in three familial cases. Whole-exome sequencing (WES) was performed to identify single nucleotide variants (SNVs). Copy number variants (CNVs) were analyzed from the WES raw data and through multiplex ligation-dependent probe amplification (MLPA). The study identified one pathogenic SNV and two novel CNVs, corresponding to type I and type II WS patterns in the three families. The SNV, a nonsense variant (c.1198C>T p.Arg400*), was found in MITF and segregated in the affected father. The two CNVs were a deletion of exon 5 in PAX3 in a family with two affected members and a large novel deletion comprising seven genes, including SOX10, in a family with three affected members. These findings confirmed a WS diagnosis through genetic testing. The study emphasizes the importance of integrating multiple genetic testing approaches for accurate and reliable diagnosis, highlighting their role in improving patient management and providing tailored genetic counseling. [ABSTRACT FROM AUTHOR]

Introduction: Our objective was to assess non‐inferiority of the unique approach used in our institution of combined 10 IU IM (intramyometrial) and 10 IU IV (intravenous) oxytocin to carbetocin IV in preventing severe postpartum blood loss in elective cesarean sections. The design was a prospective controlled phase IV non‐inferiority interventional trial. The setting was a tertiary center at University Hospital, Zurich, Switzerland. Material and Methods: The population consisted of 550 women undergoing elective cesarean section after 36 completed weeks of gestation at low risk for postpartum hemorrhage (PPH). Participants were assigned to either combined oxytocin regimen (10 IU IM and 10 IU IV) or carbetocin (100 μg IV). Non‐inferiority for oxytocin for severe PPH was assessed with a 0.05 margin using the Newcombe–Wilson score method. The main outcome measures were severe postpartum blood loss defined as delta hemoglobin (∆Hb, Hb prepartum—Hb postpartum) ≥30 g/L. Results: Non‐inferiority of combined oxytocin (IM/IV) in preventing severe postpartum blood loss was not shown (17 women in the oxytocin group vs. 7 in the carbetocin group). The number needed to treat when using carbetocin was 28. The risk difference for ∆Hb ≥30 g/L was 0.04 (oxytocin 0.06 vs. 0.03), 95% confidence interval (CI) (0.00–0.08). No significant difference was observed for ∆Hb (median 12 [IQR 7.0–19.0] vs. 11 [5.0–17.0], p = 0.07), estimated blood loss (median 500 [IQR 400–600] vs. 500 [400–575], p = 0.38), or the PPH rate defined as estimated blood loss ≥1000 mL (12[4.5] vs. 5 [2.0], risk difference 0.03, 95% CI (−0.01 to 0.06), p = 0.16). More additional uterotonics were administered in the oxytocin group compared to the carbetocin group (15.2% vs. 5.9%, p = 0.001). Total case costs were non‐significantly different in the oxytocin group (US $ 10 146 vs. 9621, mean difference 471.4, CI (−476.5 to 1419.3), p = 0.33). Conclusions: Combined (IM/IV) oxytocin is not non‐inferior to carbetocin regarding severe postpartum blood loss defined as postpartum Hb decrease ≥30 g/L in elective cesarean sections. We recommend carbetocin for use in clinical practice for elective cesarean sections. [ABSTRACT FROM AUTHOR]

The aging heart is characterized by a number of structural changes leading to ventricular stiffness, impaired resistance to stress and increased risk of developing heart failure (HF). Genetic or pharmacological removal of senescent cells has recently demonstrated the possibility to relieve some cardiac aging features such as hypertrophy and fibrosis. However, the contribution of the different cell types in cardiac aging remains fragmentary due to a lack of cell‐specific markers. Cardiomyocytes undergo post‐mitotic senescence in response to telomere damage, characterized by persistent DNA damage response and expression of the classical senescence markers p21 and p16, which are shared by many other cell types. In the present study, we used transcriptomic approaches to discover new markers specific for cardiomyocyte senescence. We identified Prominin2 (Prom2), encoding a transmembrane glycoprotein, as the most upregulated gene in cardiomyocytes of aged mice compared to young mice. We showed that Prom2 was upregulated by a p53‐dependent pathway in stress‐induced premature senescence. Prom2 expression correlated with cardiomyocyte hypertrophy in the hearts of aged mice and was increased in atrial samples of patients with HF with preserved ejection fraction. Consistently, Prom2 overexpression was sufficient to drive senescence, hypertrophy and resistance to cytotoxic stress while Prom2 shRNA silencing inhibited these features in doxorubicin‐treated cardiac cells. In conclusion, we identified Prom2 as a new player of cardiac aging, linking cardiomyocyte hypertrophy to senescence. These results could provide a better understanding and targeting of cell‐type specific senescence in age‐associated cardiac diseases. [ABSTRACT FROM AUTHOR]