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The recent acceleration of commercial, private and multi-national spaceflight has created an unprecedented level of activity in low Earth orbit, concomitant with the largest-ever number of crewed missions entering space and preparations for exploration-class (lasting longer than one year) missions. Such rapid advancement into space from many new companies, countries and space-related entities has enabled a ‘second space age’. This era is also poised to leverage, for the first time, modern tools and methods of molecular biology and precision medicine, thus enabling precision aerospace medicine for the crews. The applications of these biomedical technologies and algorithms are diverse, and encompass multi-omic, single-cell and spatial biology tools to investigate human and microbial responses to spaceflight. Additionally, they extend to the development of new imaging techniques, real-time cognitive assessments, physiological monitoring and personalized risk profiles tailored for astronauts. Furthermore, these technologies enable advancements in pharmacogenomics, as well as the identification of novel spaceflight biomarkers and the development of corresponding countermeasures. In this Perspective, we highlight some of the recent biomedical research from the National Aeronautics and Space Administration, Japan Aerospace Exploration Agency, European Space Agency and other space agencies, and detail the entrance of the commercial spaceflight sector (including SpaceX, Blue Origin, Axiom and Sierra Space) into aerospace medicine and space biology, the first aerospace medicine biobank, and various upcoming missions that will utilize these tools to ensure a permanent human presence beyond low Earth orbit, venturing out to other planets and moons.The current ‘second space age’ has enabled multiple studies on the effects of spaceflight on human physiology and health, which are contributing to the development of measures that will be needed to maintain astronaut health in future space missions. [ABSTRACT FROM AUTHOR]

Purpose: The construction industry is one of the major contributors of greenhouse gas emissions (UNEP, 2022), but it provides numerous valuable opportunities to contribute to the reduction of greenhouse gas emissions (IPPC, 2023). Innovation within the industry and the adoption of sustainable practices are key to achieve this. This is possible with the contribution of highly knowledgeable professionals and skilled workers. However, different countries, including Malta are facing skill gaps and resource shortages. The purpose of this paper is to define the existing skill gaps and mismatches in climate change adaptation in the built environment in Malta. The research focuses on the positionality of the professionals working in the sector as they operate within a legal framework guided through various policies, and through their role and responsibility, they are in contact with the other stakeholders in the sector. Design/methodology/approach: The data generation strategy used in this study involved a pragmatic approach through a mixed method research methodology, namely, interviews, a questionnaire and a focus group discussion. The three tier scaffolding approach in the data generation strategy allowed for a progressive validation of the data generated. Findings: The research indicates that the professionals in the sector are aware of their roles and responsibilities to address climate change in their practices, and they have the disposition to acknowledge the need of continuous professional training. Moreover, this study points out that the professionals in the built environment sector are concerned about other gaps within the industry and not solely by skill gaps. Their responsibility to address climate change through greener solutions is often hindered by fragmentation in the system including bureaucratic procedures, clients' demands, lack of enforcement and general education of the need to address and adapt climate change among the general public. The professionals appeal for an overhaul in the "culture" of the construction industry through a comprehensive rather than a piecemeal approach. This research puts in the limelight the need of a comprehensive strategy to address skill gaps and mismatches in accordance with the need for climate change adaptation as the ultimate challenge rather than addressing different issues separately within the sector. Originality/value: The paper is to define the existing skill gaps and mismatches in climate change adaptation in the built environment in Malta. By identifying these skill gaps and mismatches, it would be possible to devise an action plan to iron-out such hindrances as part of a broader climate action adaptation strategy. [ABSTRACT FROM AUTHOR]

Context: Competitive swimmers are at high risk of overuse musculoskeletal injuries due to their high training volumes. Spine injuries are the second most common musculoskeletal injury in swimmers and are often a result of the combination of improper technique, high loads on the spine in strokes that require hyperextension, and repetitive overuse leading to fatigue of the supporting trunk muscles. The purpose of this review is to summarize the current evidence regarding swimming biomechanics, stroke techniques, and common injuries in the lumbar spine to promote a discussion on the prevention and rehabilitation of lower back injuries in competitive swimmers. Evidence Acquisition: From a PUBMED/MEDLINE search, 16 articles were identified for inclusion using the search terms "swimming," "low back" or "lumbar," and "injury" or "injuries." Study Design: Narrative review. Level of Evidence: Levels 4 and 5. Results: The trunk muscles are integral to swimming stroke biomechanics. In freestyle and backstroke, the body roll generated by the paraspinal and abdominal muscles is integral to efficient stroke mechanics by allowing synergistic movements of the upper and lower extremities. In butterfly and breaststroke, the undulating wave like motion of the dolphin kick requires dynamic engagement of the core to generate repetitive flexion and extension of the spine and is a common mechanism for hyperextension injuries. The most common lower back injuries in swimming were determined to be lumbar strain, spondylolysis and spondylolisthesis, facet joint pain, and disc disease. Most overuse swimming injuries can be treated conservatively with physical therapy and training adjustments. Conclusion: Managing swimmers with low back pain requires a basic knowledge of swimming technique and a focus on prevention-based care. Since most swimming injuries are secondary to overuse, it is important for providers to understand the mechanisms underlying the swimming injury, including an understanding of the biomechanics involved in swimming and the role of spine involvement in the 4 strokes that assist in stabilization and force generation in the water. Knowledge of the biomechanics involved in swimming and the significant demands placed on the spinal musculoskeletal system will aid the clinician in the diagnosis and management of injuries and assist in the development of a proper rehabilitation program aimed at correction of any abnormal swimming mechanics, treatment of pain, and future injury prevention. Strength of Recommendations: B. Recommendation based on limited quality or inconsistent patient-oriented evidence. [ABSTRACT FROM AUTHOR]

The synthesis and characterization of a new paramagnetic ligand, 4-(N′-methyl-2′-benzimidazolyl)-1,2,3,5-dithiadiazolyl (MebimDTDA), is presented. MebimDTDA exhibits polymorphism in the solid state. The red microcrystalline form (Form I-red) is diamagnetic below T = 370 K, consistent with typical multi-center two-electron bonding interactions (i.e., pancake bonds) between planar π-radicals. By contrast, the green–black crystalline form (Form II-green) exhibits paramagnetic properties consistent with the observed unusual crystal packing in which some, but not all, of the radicals are arranged in a typical pancake-bonded geometry. Crystallographic analysis, magnetic data, and computational methods are employed to elucidate the structure-property relationship, with an emphasis on the role of crystal packing. [ABSTRACT FROM AUTHOR]

The invasive intra‐arterial approach is the gold standard for measuring blood pressure in intensive care units where accuracy is crucial. However, invasive procedures increase the risk of infections and mortality. This evidence‐based review aimed to determine whether continuous non‐invasive blood pressure (CNIBP) monitoring, using Radial Artery Applanation Tonometry (RAAT) devices, is as accurate as invasive methods. Six papers were included: three prospective cohort studies and three comparative studies. Most studies showed that mean arterial pressure is accurately recorded through RAAT monitoring; however, more research is needed to assess the accuracy of non‐invasive readings of systolic and diastolic blood pressures, as data are not always concordant. [ABSTRACT FROM AUTHOR]

Background and Aims: Gastrointestinal (GI) symptoms, common in type 2 diabetes (T2D), are typically bothersome, socially embarrassing, and impact negatively on quality of life. They may also contribute to diabetes distress (DD), but this has never been formally evaluated. We aimed to investigate the relationships between GI symptoms, DD and depressive symptoms in a large cohort of individuals with T2D in Bangladesh. Materials and Methods: 1406 unselected T2D individuals (female 58.8%; mean age 51.0 ± 12.5 years) from four diabetes clinics in Bangladesh completed validated questionnaires evaluating GI symptoms (PAGI‐SYM), DD (DDS‐17) and depressive symptoms (PHQ‐9). Results: 31.1% of participants reported GI symptoms (36.2% females, 23.7% males), while 51.1% had elevated DD and 37.8% depressive symptoms. GI symptoms exhibited independent relationships with both DD and depressive symptoms, and their likelihood was higher among those with DD (OR: 3.6 [2.2–5.6] and with depressive symptoms (OR: 5.9 [3.5–9.9]). Conclusions: GI symptoms are independently associated with both DD and depressive symptoms in people with T2D in Bangladesh. [ABSTRACT FROM AUTHOR]

Understanding enzyme catalysis as connected to protein motions is a major challenge. Here, based on temperature kinetic studies combined with isotope effect measurements, we obtain energetic description of C-H activation in NAD-dependent UDP-glucuronic acid C4 epimerase. Approach from the ensemble-averaged ground state (GS) to the transition state-like reactive conformation (TSRC) involves, alongside uptake of heat ( Δ H ‡ = 54 kJ mol−1), significant loss in entropy (− T Δ S ‡ = 20 kJ mol−1; 298 K) and negative activation heat capacity ( Δ C p ‡ = −0.64 kJ mol−1 K−1). Thermodynamic changes suggest the requirement for restricting configurational freedom at the GS to populate the TSRC. Enzyme variants affecting the electrostatic GS preorganization reveal active-site interactions important for precise TSRC sampling and H-transfer. Collectively, our study captures thermodynamic effects associated with TSRC sampling and establishes rigid positioning for C-H activation in an enzyme active site that requires conformational flexibility in fulfillment of its natural epimerase function. Enzymes involve structural flexibility in their function, but understanding enzyme catalysis as connected to protein motions is a major challenge. Here, the authors obtain energetic description of C-H activation in nicotinamide coenzyme-dependent UDP-glucuronic acid C4 epimerase based on temperature kinetic studies and isotope effect measurements. [ABSTRACT FROM AUTHOR]

Background: Colorectal cancer is a public health issue and was the third leading cause of cancer-related death worldwide in 2022. Early diagnosis can improve prognosis, making screening a central part of colorectal cancer management. Blood-based screening, diagnosis and follow-up of colorectal cancer patients are possible with the study of cell-free circulating tumor DNA. This study aimed to identify novel DNA methylation biomarkers of colorectal cancer that can be used for the follow-up of patients with colorectal cancer. Methods: A DNA methylation profile was established in the Gene Expression Omnibus (GEO) database (n = 507) using bioinformatics analysis and subsequently confirmed using The Cancer Genome Atlas (TCGA) database (n = 348). The in silico profile was then validated on local tissue and cell-free DNA samples using methylation-specific digital PCR in colorectal cancer patients (n = 35) and healthy donors (n = 35). Results: The DNA methylation of COL25A1 and METAP1D was predicted to be a colorectal cancer biomarker by bioinformatics analysis (ROC AUC = 1, 95% CI [0.999–1]). The two biomarkers were confirmed with tissue samples, and the combination of COL25A1 and METAP1D yielded 49% sensitivity and 100% specificity for cell-free DNA. Conclusion: Bioinformatics analysis of public databases revealed COL25A1 and METAP1D DNA methylation as clinically applicable liquid biopsies DNA methylation biomarkers. The specificity implies an excellent positive predictive value for follow-up, and the high sensitivity and relative noninvasiveness of a blood-based test make these biomarkers compatible with colorectal cancer screening. However, the clinical impact of these biomarkers in colorectal cancer screening and follow-up needs to be established in further prospective studies. [ABSTRACT FROM AUTHOR]

Group B Streptococcus (GBS) asymptomatically colonises the vagina of up to 40% of pregnant women and can transmit to neonates during birth, causing neonatal pneumonia, sepsis, meningitis, and significant mortality. Vaginal GBS colonisation can be attributed to a range of host and bacterial factors, which may include the composition of the vaginal microbial community. There are few studies that have examined the vaginal community composition in relation to GBS colonisation throughout pregnancy. Here, we performed 16S rRNA sequencing (V3-V4) on vaginal swabs from women at 24- and 36-weeks' gestation, who were GBS culture-negative or GBS culture-positive at either 24 weeks or 36 weeks' gestation or at both timepoints. Vaginal swabs from 93 women were analysed; 46 women were culture-negative, 11 women GBS culture-positive at 24 weeks only, 21 women GBS culture-positive at 36 weeks only and 15 women GBS culture-positive at both timepoints on Brilliance GBS agar. V3-V4 16S rRNA gene amplicon sequencing demonstrated that in women that were GBS culture-positive at 36 weeks gestation only, G. vaginalis was significantly more abundant at 24-weeks' gestation despite a lack of significant changes in community richness between the 24- and 36-week samples. The vaginal microbial communities of women persistently colonised with GBS, had a significantly higher abundance of Lactobacillus iners, compared to other groups where L. crispatus, L. gasseri or L. jensenii were dominant. We have characterised the vaginal microbial community composition during pregnancy in relation to GBS colonisation status, in a longitudinal study for the first time. The most interesting finding was that in women that were persistently colonised with GBS throughout pregnancy, there was a significant increase in L. iners and significant reduction in L. crispatus abundance. Given the lack of detail of the role that the vaginal microbial community plays in GBS colonisation in the literature, it is imperative that the relationship between L. iners and GBS in this unique environmental niche is further investigated. [ABSTRACT FROM AUTHOR]

Background: In Sweden, surgical treatment of Hirschsprung's disease (HSCR) was centralized from four to two pediatric surgery centers 1st of July 2018. In adults, centralization of surgical care for complex or rare diseases seems to improve quality of care. There is little evidence supporting centralization of pediatric surgical care. The aim of this study was to assess surgical management and postoperative outcome in HSCR patients following centralization of care. Methods: This study retrospectively analyzed data of patients with HSCR that had undergone pull-through at a pediatric surgery center in Sweden from 1st of July 2013 to 30th of June 2023. Patients managed from 1st of July 2013 to 30th of June 2018 (before centralization) were compared with patients managed from 1st of July 2018 to 30th of June 2023 (after centralization) regarding surgical treatment, unplanned procedures under general anesthesia or readmissions up to 90 days after pull-through as well as complications classified according to Clavien–Madadi up to 30 days after pull-through. Results: In the 5-year period prior to centralization, 114 individuals from 4 treating centers were included and compared to 83 patients from 2 treating centers in the second period. There was no difference regarding age at pull-through or proportion of patients with a stoma prior to pull-through. An increase of laparoscopically assisted endorectal pull-through (8.8% to 39.8%) was observed (p < 0.001). No significant differences were seen in postoperative hospital stay, unplanned procedures under general anesthesia, or readmissions up to 90 days after pull-through. There was no difference in severe complications (Clavien–Madadi ≥ 3); however, HAEC treated with antibiotics increased following centralization (10.5–24.1%; p = 0.018). Conclusion: Centralization of care for HSCR does not seem to delay time to pull-through nor reduce severe complications, unplanned procedures under general anesthesia or readmissions up to 90 days after pull-through. The increased HAEC rate may be due to increased awareness of mild HAEC. Level of evidence: Level III. [ABSTRACT FROM AUTHOR]

Background: Decision-making is a highly complex process that depends on numerous cognitive functions, such as episodic memory. It is also influenced by aging. However, how changes in episodic memory with age contribute to changes in decision-making is not clear yet. Objective: This work aimed to examine the role of two memory processes, recollection and familiarity, in decision-making in ageing. Method: Thirty young adults and 30 older adults performed two episodic memory tasks: recognition, which allowed for the measurement of recollection and familiarity, and recall, which allowed for the measurement of recollection. In both tasks, they first viewed a series of pictures and then were asked to recognise or recall them respectively. They also performed an original scenario task based on situations inspired by everyday life, evaluating decision-making under conditions of either risk or ambiguity. In this task, participants were presented with short descriptions of situations requiring a decision and had to choose between two given options. Results: Lower performances was observed in recall and recognition tasks in older than in young adults. In the scenarios task, young adults sought significantly more risk and ambiguity than older adults. In both young and older adults, recollection and familiarity processes were involved differently in decision-making. The former is more involved in decision-making under ambiguity, and the latter in decision-making under risk. Conclusions: The results suggest that decision-making changes with age, but that the involvement of the episodic memory, familiarity and recollection processes, does not appear to vary with age. [ABSTRACT FROM AUTHOR]

Background and Objectives: Parkinson's disease (PD) is a pathological state characterized by a combined set of abnormal movements including slow motion, resting tremors, profound stiffness of skeletal muscles, or obvious abnormalities in posture and gait, together with significant behavioral changes. Until now, no single therapeutic modality was able to provide a complete cure for PD. This work was a trial to assess the immunomodulatory effects of canagliflozin with or without levodopa/carbidopa on rotenone-induced parkinsonism in Balb/c mice. Materials and Methods: In a mouse model of PD, the effect of canagliflozin with or without levodopa/carbidopa was assessed at the behavioral, biochemical, and histopathological levels. Results: The combination of levodopa/carbidopa and canagliflozin significantly mitigated the changes induced by rotenone administration regarding the behavioral tests, striatal dopamine, antioxidant status, Nrf2 content, SIRT–1/PPAR–gamma axis, RAGE/HMGB1/NF-κB signaling, and mitochondrial dysfunction; abrogated the neuroinflammatory responses, and alleviated the histomorphologic changes induced by rotenone administration relative to the groups that received either levodopa/carbidopa or canagliflozin alone. Conclusions: Canagliflozin may represent a new adjuvant therapeutic agent that may add value to the combatting effects of levodopa/carbidopa against the pathological effects of PD. [ABSTRACT FROM AUTHOR]

This paper introduces a novel design for a liquid-deployed Piezoelectric Micromachined Ultrasonic Transducer (PMUT). This design was specifically developed to resonate at a lower ultrasonic frequency than a PMUT with a circular, fully clamped diaphragm with the same diameter. Furthermore, the novel design was also optimised to enhance its ultrasonic radiation reception capabilities. These parametric enhancements were necessary to develop a PMUT device that could form part of an eventual microscale sensory device used for the Structural Health Monitoring (SHM) of reinforced concrete (RC) structures. Through these two enhancements, an eventual microscale sensor can be made smaller, thus taking up a smaller die footprint and also be able to be deployed further apart from each other. Eventually, this would reduce the developed distributed sensor system's cost. The innovative design employed a configuration where the diaphragm was only pinned at particular points along its circumference. This paper presents results from Finite Element Modelling (FEM), as well as experimental work that was conducted to develop and test this novel PMUT. The experimental work presented involved both laser vibrometry and ultrasonic radiation lab work. The results show that when compared to a clamped diaphragm design, the novel device managed to achieve the required reduction in resonant frequency and presented an enhanced sensitivity to incoming ultrasonic radiation. [ABSTRACT FROM AUTHOR]

Epidemiologic studies of birth defects often conduct separate analyses for cases that have isolated defects (e.g., spina bifida only) and cases that have multiple defects (e.g., spina bifida and a congenital heart defect). However, in some instances, cases with additional defects (e.g., spina bifida and clubfoot) may be more appropriately considered as isolated because the co‐occurring defect (clubfoot) is believed to be developmentally related to the defect of interest. Determining which combinations should be considered isolated can be challenging and potentially resource intensive for registries. Thus, we developed automated classification procedures for differentiating between isolated versus multiple defects, while accounting for developmentally related defects, and applied the approach to data from the Texas Birth Defects Registry (1999–2018 deliveries). Among 235,544 nonsyndromic cases in Texas, 89% of cases were classified as having isolated defects, with proportions ranging from 25% to 92% across 43 specific defects analyzed. A large proportion of isolated cases with spina bifida (44%), lower limb reduction defects (44%), and holoprosencephaly (32%) had developmentally related defects. Overall, our findings strongly support the need to account for isolated versus multiple defects in risk factor association analyses and to account for developmentally related defects when doing so, which has implications for interpreting prior studies. [ABSTRACT FROM AUTHOR]

As global demand for seafood increases, recirculating aquaculture systems (RAS) have gained prominence for sustainable fish rearing. The sustainability of RAS still requires improvement, particularly managing the fish waste. Here we investigated the growth and nutrient removal capabilities of three microalgal species (Isocrysis galbana, Phaeodactylum tricornutum and Skeletonema marinoi) in aquaculture wastewater (AWW) mixed at different concentrations with cultivation medium. All three microalgae showed growth in different concentrations of the AWW obtained from an Atlantic salmon RAS facility in Agder, Norway. The average growth rates for I. galbana, S. marinoi and P. tricornutum at 75% AWW concentration were 0.31± 0.00 day-1, 0.34 ± 0.00 day-1, 0.25 ± 0.02 day-1, respectively. All three species effectively contributed to nitrate, ammonium and phosphate removal. When cultivated in 75% AWW, the microalgae achieved nearly complete removal of nitrite, nitrate, and phosphate, while approximately 90% of ammonium was also removed. Our results confirm the viability of AWW for microalgal cultivation on a laboratory scale suggesting this presents a sustainable route to further develop a circular bioeconomy in aquaculture. [ABSTRACT FROM AUTHOR]

Purpose: To study the association between the use of drugs for hypertension or heart failure, particularly diuretics, and risk of death in COVID-19. Methods: We conducted a cohort study, based on record linked individual-based data from national registers, of all Swedish inhabitants 50 years and older (n = 3,909,321) at the start of the first SARS-CoV-2 wave in Sweden. The association between use of angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB), thiazides, loop diuretics, aldosterone antagonists, beta blocking agents and calcium channel blockers at the index date 6 March 2020, and death in COVID-19 during 7 March to 31 July 2020, was analysed using Cox-proportional hazards regression, adjusted for a wide range of possible confounders. Results: Use of loop diuretics was associated with higher risk [adjusted hazard ratio (HR) 1.26; 95% confidence interval (95% CI) 1.17–1.35] and thiazides with reduced risk (0.78; 0.69–0.88) of death in COVID-19. In addition, lower risk was observed for ACEI and higher risk for beta-blocking agents, although both associations were weak. For ARB, aldosterone antagonists and calcium channel blockers no significant associations were found. Conclusion: In this nationwide cohort of nearly 4 million persons 50 years and older, the use of loop diuretics was associated with increased risk of death in COVID-19 during the first SARS-CoV-2 wave in Sweden. This contrasted to the decreased risk observed for thiazides. As treatment with loop diuretics is common, particularly in the elderly, the group most affected by severe COVID-19, this finding merit further investigation. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus is the most common medical condition in pregnancy, disproportionately affecting overweight or obese women and those from non-White populations. The lack of standardised screening and diagnostic consensus contributes to varying prevalence. Conventional risk factor-based screening can leave women undiagnosed, leading to increased risk of harm. If diet and lifestyle modifications fail to achieve glycaemic targets, prompt treatment should be initiated to manage glucose levels. A planned birth is crucial to ensure the best outcomes. Postpartum, women need screening for type 2 diabetes and other cardiometabolic risk factors, enrollment in diabetes prevention programmes, and counselling on the increased risk of future cardiometabolic disease for themselves and their offspring, highlighting the importance of ongoing prevention and management strategies. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that indirect verbal exposure to traumatic events can be sufficient to cause intrusions and other posttraumatic stress symptoms. In this study, we used a verbal trauma report to experimentally induce intrusions and a tactile task to manipulate the putative processes underlying intrusion development. Our findings indicate that the verbal report indeed induced intrusive recall. Moreover, the verbal report induced negative mood, state anxiety, and state dissociation, with mood and state dissociation predicting intrusion development. Additionally, the tactile task interfered with intrusion formation as indicated by the primary diary measure, but not the retrospective self-report. However, these results await further replication as this and previous trials suffered from limited statistical power. The findings support the reports by trauma therapists who experience secondary traumatization. They also challenge the assumption that all intrusions develop bottom-up from low-level sensory input via sensory representations. Future studies should explore differential processes for intrusion development based on their modality. [ABSTRACT FROM AUTHOR]

Research Integrity Advisors are used in Australia to provide impartial guidance to researchers who have questions about any aspect of responsible research practice. Every Australian institution conducting research must provide access to trained advisors. This national policy could be an important part of creating a safe environment for discussing research integrity issues and thus resolving issues. We conducted the first formal study of advisors, using a census of every Australian advisor to discover their workload and attitudes to their role. We estimated there are 739 advisors nationally. We received responses to our questions from 192. Most advisors had a very light workload, with an median of just 0.5 days per month. Thirteen percent of advisors had not received any training, and some advisors only discovered they were an advisor after our approach. Most advisors were positive about their ability to help colleagues deal with integrity issues. The main desired changes were for greater advertising of their role and a desire to promote good practice rather than just supporting potential issues. Advisors might be a useful policy for supporting research integrity, but some advisors need better institutional support in terms of training and raising awareness. [ABSTRACT FROM AUTHOR]

The pathophysiology behind neurological and cognitive sequelae of COVID-19 may be related to dysfunction of the blood-brain barrier (BBB) and previous research indicate transient neuronal injury and glial activation. The aim of this study was to investigate if COVID-19 is related to increased BBB permeability by analyzing leakage of biomarkers such as astrocyte-derived extracellular vesicles (EVs) and S100B. We also investigated whether levels of these biomarkers correlated with self-reported symptoms that persisted > 2 months. The samples in this 1-year follow-up study came from an ongoing longitudinal study of unvaccinated patients hospitalized for COVID-19 at Danderyd University Hospital, Stockholm, Sweden, between April and June 2020. Blood samples were collected at baseline and 4, 8, and 12 months after hospitalization. Information on self-reported clinical symptoms was collected at follow-up visits. A total of 102 patients were enrolled, and 47 completed all follow-up measurements. Peak levels of both biomarkers were observed at 4 months in the subset of 55 patients who were measured at this timepoint. At 12 months, the biomarkers had returned to baseline levels. The biomarkers were not correlated with any of the long-term self-reported symptoms. COVID-19 is associated with transient increased BBB permeability, shown by elevated levels of astrocyte biomarkers in plasma. However, these levels return to baseline 12 months post-infection and do not correlate with long-term symptoms. Further research is needed to unravel the underlying mechanisms causing long-term symptoms in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Stroke survivors commonly face challenges such as reduced physical activity and cardiorespiratory fitness (CRF) as well as balance and gait impairments, exacerbating their disability. While high-intensity exercise interventions have demonstrated some potential, their effects on these items remain uncertain. Therefore, our study aimed to investigate the impact of high-intensity training protocols on CRF, gait ability, and balance in stroke survivor populations. Two independent investigators systematically searched five databases for relevant RCTs following the PICO model. Through a systematic review of 25 RCTs published up to 31 May 2023, including adult first-stroke survivors, comparing high-intensity exercise training versus low-to-mild or no exercises, we evaluated outcomes such as the Six-Minute Walking Test (6 MWT), peak oxygen uptake (VO2peak), Ten-Meter Walk Test (10 MWT), Berg Balance Scale (BBS), and Timed Up and Go test (TUG). The protocol was registered in PROSPERO (registration number CRD42023456773). Meta-analyses indicated significant enhancements in CRF, as measured by 6 MWT and VO2peak, following high-intensity exercise interventions. However, no significant differences were observed in BBS, 10 MWT, and TUG. Our findings underscore the potential of high-intensity exercise interventions in ameliorating CRF among stroke survivors, although further research involving standardized protocols and long-term follow-ups is imperative to optimize rehabilitation outcomes. [ABSTRACT FROM AUTHOR]

Biliary tract cancer incidence is increasing and the prognostic remains dismal. The development of personalized medicine is a pivotal issue in proposing therapeutic options for biliary tract cancer patients. Whole exome sequencing identifies approximately 15% of IDH1 mutations and 15% of FGFR2 fusions in intrahepatic cholangiocarcinoma. Other patients are not currently eligible for targeted therapy. Here, we present a patient treated for a metastatic cholangiocarcinoma with an unexpected response to a mammalian target of rapamycin (mTOR) targeting agent. Whole exome sequencing enabled the identification of TSC1 and ARID1A mutations. Reintroduction of mTOR inhibitors with similar results sustains the main role of these targeted agents in the control of the disease. These results suggest the existence of an mTOR oncogenic addiction in biliary tract cancer. Our results support the interest in performing exome sequencing in liver cancers and the potential to identify actionable mutations with important therapeutic issues. [ABSTRACT FROM AUTHOR]

Here, the generation of dynamic vortices across microscale barriers using the tube oscillation mechanism is demonstrated. Using a combination of high‐speed imaging and computational flow dynamics, the cyclic formation, expansion, and collapse of vortices are studied. The dynamics of vortices across circular , triangular, and blade‐shape barriers are investigated at different tube oscillation frequencies. The formation of an array of synchronous vortices across parallel blade‐shaped barriers is demonstrated. The transient flows caused by these dynamic vortex arrays are harnessed for the rapid and efficient mixing of blood samples. A circular barrier scribed with a narrow orifice on its shoulder is used to facilitate the injection of liquid into the microfluidic channel, and its rapid mixing with the main flow through the dynamic vortices generated across the barrier. This approach facilitates the generation of vortices with desirable configurations, sizes, and dynamics in a highly controllable, programmable, and predictable manner while operating at low static flow rates. [ABSTRACT FROM AUTHOR]

This article provides information on the emergency care of patients who have undergone metabolic bariatric surgery. It emphasizes that patients may present with few symptoms and little pain, but still be critically unwell. The article discusses common clinical signs of surgical complications and the importance of transferring patients to specialist bariatric centers when necessary. It also provides information on side effects and complications of different bariatric procedures, highlighting the need for prompt diagnosis and appropriate management to minimize morbidity and mortality. The document emphasizes the importance of specialized care in bariatric centers and collaboration with bariatric surgeons for optimal outcomes. [Extracted from the article]

Despite the availability of COVID-19 vaccines for youth since 2021, vaccine hesitancy has resulted in suboptimal uptake. Public health campaigns that empower local youth ambassadors as trusted messengers who share their personal narratives related to getting vaccinated hold promise for promoting COVID-19 vaccination. We used a seven-step approach to develop, implement, and evaluate a youth-led ambassador campaign to promote COVID-19 vaccine uptake in communities experiencing COVID-19 disparities in Worcester, MA. The seven steps included (1) engaging with key partners, (2) determining a community of focus, (3) identifying trusted sources, (4) determining campaign components, (5) training the vaccine ambassadors, (6) disseminating the campaign, and (7) evaluating the campaign. We trained nine youth as vaccine ambassadors. Ambassadors were guided through self-reflection of motivations for COVID-19 vaccination and the resulting personal narratives became the campaign messaging. English/Spanish vaccine messages developed by youth ambassadors were disseminated through social media platforms (n = 3), radio (n = 2), local TV (n = 2), flyers (n = 2,086), posters (n = 386), billboards (n = 10), and local bus ads (n = 40). Qualitative youth feedback indicate participation in the campaign was a positive and empowering experience which reinforces the importance of engaging youth in public health messaging. Youth empowerment through personal narratives (and storytelling) holds promise for future public health campaigns. [ABSTRACT FROM AUTHOR]

Previous research has lacked a comprehensive, longitudinal analysis of characteristics of solitude and sociability, and how they are associated with changes in psychosocial adjustment before and during the pandemic. The current study surveyed 1071 adolescents (Mage = 10.6, SD = 1.69, 49.86% female, age range = 8–14 years at Year 1) over six years (three years before pandemic, three years during pandemic). Piecewise linear mixed-effects analysis showed that adolescents with higher solitude and lower sociability reported improvements in adjustment during the pandemic, whereas adolescents with lower solitude and higher sociability reported declines in adjustment. The findings highlight the importance of considering multiple characteristics of solitude and sociability, as well as contextual factors (e.g., pandemic), to better understand the implications of solitude on adolescent adjustment. [ABSTRACT FROM AUTHOR]

Donald Trump's capture of the Republican Party enabled a radical questioning of received wisdom within the broader conservative intellectual movement. In particular, it enabled the emergence of a post-Trump, distinctly American New Right. This policy paper examines the American New Right and its visions for United States foreign policy. In the context of contemporary American politics, the New Right is best understood as a rejection of the 'fusionism' that has characterized US conservatism since the early decades after the Second World War. The paper argues that there are three major identifiable parts of the New Right: the Claremonters, the post-liberals and the national conservatives. In part because of their 'big-tent' character, as well as deft intellectual leadership by Yoram Hazony, the national conservatives have become the most influential group within the contemporary New Right. The article also examines how the New Right has attempted to create an alternative ideational infrastructure, with a clear focus on entrenching itself through large-scale credentialing of personnel deemed to be loyal to the New Right's agenda. There is reason to speak of a 'natcon takeover' of traditional conservative institutions. This is particularly the case with the Heritage Foundation, the largest and most influential conservative think tank. While all segments of the New Right ostensibly embrace some notion of grand strategic restraint, the policy paper argues that the rise of national conservatism is likely to accelerate the US pivot from Europe to Asia rather than lead to neo-isolationism, as is sometimes suggested. [ABSTRACT FROM AUTHOR]

Aim: Prediction intervals are a useful measure of uncertainty for meta‐analyses that capture the likely effect size of a new (similar) study based on the included studies. In comparison, confidence intervals reflect the uncertainty around the point estimate but provide an incomplete summary of the underlying heterogeneity in the meta‐analysis. This study aimed to estimate (i) the proportion of meta‐analysis studies that report a prediction interval in sports medicine; and (ii) the proportion of studies with a discrepancy between the reported confidence interval and a calculated prediction interval. Methods: We screened, at random, 1500 meta‐analysis studies published between 2012 and 2022 in highly ranked sports medicine and medical journals. Articles that used a random effect meta‐analysis model were included in the study. We randomly selected one meta‐analysis from each article to extract data from, which included the number of estimates, the pooled effect, and the confidence and prediction interval. Results: Of the 1500 articles screened, 866 (514 from sports medicine) used a random effect model. The probability of a prediction interval being reported in sports medicine was 1.7% (95% CI = 0.9%, 3.3%). In medicine the probability was 3.9% (95% CI = 2.4%, 6.6%). A prediction interval was able to be calculated for 220 sports medicine studies. For 60% of these studies, there was a discrepancy in study findings between the reported confidence interval and the calculated prediction interval. Prediction intervals were 3.4 times wider than confidence intervals. Conclusion: Very few meta‐analyses report prediction intervals and hence are prone to missing the impact of between‐study heterogeneity on the overall conclusions. The widespread misinterpretation of random effect meta‐analyses could mean that potentially harmful treatments, or those lacking a sufficient evidence base, are being used in practice. Authors, reviewers, and editors should be aware of the importance of prediction intervals. [ABSTRACT FROM AUTHOR]

Background: Autism spectrum disorder (ASD) manifests in early childhood and significantly impairs social and communicative functions. Parents of children with ASD typically experience higher levels of stress compared to parents of children with other disabilities or health issues. This study investigates how a home-based early intervention known as the Portage program influences parenting stress and improves family awareness by using the Parental Stress Scale (PSS), and Family Awareness Scale. We enrolled 41 children diagnosed with ASD and their parents in this study. The median age of the children was 4 years, with a predominance of males (80%). We measured changes in parenting stress and family awareness as primary outcomes, with the children's behavior as a secondary outcome. Results: Post-intervention assessments showed statistically significant improvements in parenting stress and family awareness (P < 0.001). Additionally, notable improvements were observed in the children's social, language, self-help, cognitive, and motor skills, as well as general developmental age and ratio. Conclusions: A 3-month engagement with the Portage program markedly reduced stress among parents and increased family awareness regarding ASD. Significant advancements were also noted in multiple developmental domains of the children involved. [ABSTRACT FROM AUTHOR]

In the realm of immune response, pro‐inflammatory cytokines play a crucial role in regulating various physiological functions. Accurate measurement of these low‐molecular‐weight proteins is essential for understanding immune function, predicting diseases, and monitoring treatment effects. Optical aptasensors with advanced nanostructures, which utilize aptamers as bio‐probes, have emerged as a promising technology for cytokine detection, offering advantages over traditional antibody‐based nanobiosensors. Aptamers, single‐stranded nucleic acids with high specificity and affinity, enable cost‐effective mass production and consistent quality. Optical biosensors incorporating aptamers exhibit stability, resistance to environmental factors, and prolonged functionality. This review explores the current methodologies and advancements in optical aptasensors for cytokine detection, highlighting their potential as robust tools in diagnostics and therapeutics. Specifically, the applications of surface plasmon resonance and fluorescence techniques in aptasensors are discussed, focusing on the innovative approaches used to enhance sensitivity and specificity in cytokine detection. Notable examples of aptasensor designs utilizing nanoparticles, Förster resonance energy transfer, and amplification strategies are presented. These designs demonstrate high affinity, specificity, and improved sensitivity in detecting pro‐inflammatory cytokines such as interferon gamma. Overall, optical aptasensors show great promise in advancing the understanding of cytokine‐related disorders and enabling effective interventions. [ABSTRACT FROM AUTHOR]

Background: Magnetic resonance imaging (MRI) is the gold standard for delineating cancerous lesions in soft tissue. Catheter‐based interventions require the accurate placement of multiple long, flexible catheters at the target site. The manual segmentation of catheters in MR images is a challenging and time‐consuming task. There is a need for automated catheter segmentation to improve the efficiency of MR‐guided procedures. Purpose: To develop and assess a machine learning algorithm for the detection of multiple catheters in magnetic resonance images used during catheter‐based interventions. Methods: In this work, a 3D U‐Net was trained to retrospectively segment catheters in scans acquired during clinical MR‐guided high dose rate (HDR) prostate brachytherapy cases. To assess confidence in segmentation, multiple AI models were trained. On clinical test cases, average segmentation results were used to plan the brachytherapy delivery. Dosimetric parameters were compared to the original clinical plan. Data was obtained from 35 patients who underwent HDR prostate brachytherapy for focal disease with a total of 214 image volumes. 185 image volumes from 30 patients were used for training using a five‐fold cross validation split to divide the data for training and validation. To generate confidence measures of segmentation accuracy, five trained models were generated. The remaining five patients (29 volumes) were used to test the performance of the trained model by comparison to manual segmentations of three independent observers and assessment of dosimetric impact on the final clinical brachytherapy plans. Results: The network successfully identified 95% of catheters in the test set at a rate of 0.89 s per volume. The multi‐model method identified the small number of cases where AI segmentation of individual catheters was poor, flagging the need for user input. AI‐based segmentation performed as well as segmentations by independent observers. Plan dosimetry using AI‐segmented catheters was comparable to the original plan. Conclusion: The vast majority of catheters were accurately identified by AI segmentation, with minimal impact on plan outcomes. The use of multiple AI models provided confidence in the segmentation accuracy and identified catheter segmentations that required further manual assessment. Real‐time AI catheter segmentation can be used during MR‐guided insertions to assess deflections and for rapid planning of prostate brachytherapy. [ABSTRACT FROM AUTHOR]

We conducted a multicentre test‐negative case–control study covering the period from October 2023 to January 2024 among adult patients aged ≥ 18 years hospitalised with severe acute respiratory infection in Europe. We provide early estimates of the effectiveness of the newly adapted XBB.1.5 COVID‐19 vaccines against PCR‐confirmed SARS‐CoV‐2 hospitalisation. Vaccine effectiveness was 49% overall, ranging between 69% at 14–29 days and 40% at 60–105 days post vaccination. The adapted XBB.1.5 COVID‐19 vaccines conferred protection against COVID‐19 hospitalisation in the first 3.5 months post vaccination, with VE > 70% in older adults (≥ 65 years) up to 1 month post vaccination. [ABSTRACT FROM AUTHOR]

Given a set F of graphs, we call a copy of a graph in F an F -graph. The F -isolation number of a graph G, denoted by ι (G , F) , is the size of a smallest set D of vertices of G such that the closed neighborhood of D intersects the vertex sets of the F -graphs contained by G (equivalently, G - N [ D ] contains no F -graph). Thus, ι (G , { K 1 }) is the domination number of G. For any integer k ≥ 1 , let F 1 , k be the set of regular graphs of degree at least k - 1 , let F 2 , k be the set of graphs whose chromatic number is at least k, and let F 3 , k be the union of F 1 , k and F 2 , k . Thus, k-cliques are members of both F 1 , k and F 2 , k . We prove that for each i ∈ { 1 , 2 , 3 } , m + 1 k 2 + 2 is a best possible upper bound on ι (G , F i , k ) for connected m-edge graphs G that are not k-cliques. The bound is attained by infinitely many (non-isomorphic) graphs. The proof of the bound depends on determining the graphs attaining the bound. This appears to be a new feature in the literature on isolation. Among the result's consequences are a sharp bound of Fenech, Kaemawichanurat, and the present author on the k-clique isolation number and a sharp bound on the cycle isolation number. [ABSTRACT FROM AUTHOR]

Aim: To investigate the decisional needs in Denmark of people with kidney failure, relatives, and health professionals when planning end‐of‐life care. Design: A qualitative interview study. Methods: Individual semi‐structured interviews were carried out with people with kidney failure, relatives and health professionals from November 2021 to June 2022. Malterud's systematic text condensation was used to analyse transcripts. Results: A total of 13 patients, 10 relatives, and 12 health professionals were interviewed. Overall, four concepts were agreed on: (1) Talking about end of life is difficult, (2) Patients and relatives need more knowledge and information, (3) Health professionals need more tools and training, and (4) Experiencing busyness as a barrier to conversations about end of life. Conclusion: People with kidney failure, relatives, and health professionals shared certain decisional needs while also having some different decisional needs about end‐of‐life care. To meet these various needs, end‐of‐life conversations should be systematic and organized according to the patients' needs and wishes. Impact: Non‐systematic end‐of‐life care decision‐making processes limit patients' involvement. Patients and relatives need more knowledge about end‐of‐life care, and health professionals need more competences and time to discuss decisional needs. A shared decision‐making intervention for people with kidney failure when making end‐of‐life care decisions will be developed. Reporting Method: This empirical qualitative research is reported according to the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist. Patient or Public Contribution: Patients, relatives, and health professionals have been involved throughout the research process as part of the research team and advisory board. The patients are people with kidney failure and the relatives are relatives of a person with kidney failure. For this study, the advisory board has particularly contributed to the validation of the invitation letter for participation, the interview guides and the preparation of the manuscript. [ABSTRACT FROM AUTHOR]

Background This study validates the application of Systematized Nomenclature of Medicine second edition (SNOMED II) codes used to describe medical kidney biopsies in Denmark in encoded form, aiming to support robust epidemiological research on the causes, treatments and prognosis of kidney diseases. Methods Kidney biopsy reports from 1 January 1998 to 31 December 2018 were randomly extracted from the Danish National Patobank, using SNOMED codes. A 5% sample was selected, and nephrologists assessed the corresponding medical records, assigning each case the applied clinical diagnoses. Sensitivity, specificity, positive predictive values (PPV), negative predictive values and Cohen's kappa coefficient for the retrieved SNOMED codes were calculated. Results A total of 613 kidney biopsies were included. The primary clinical disease groups were glomerular disease (n  = 368), tubulointerstitial disease (n  = 67), renal vascular disease (n  = 51), diabetic nephropathy (n  = 51) and various renal disorders (n  = 40). Several SNOMED codes were used to describe each clinical disease group and PPV for the combined SNOMED codes were high for glomerular disease (94%), diabetic nephropathy (85%) and systemic diseases affecting the kidney (96%). Conversely, tubulointerstitial disease (62%), renal vascular disease (60%) and other renal disorders (17%) showed lower PPV. Conclusions SNOMED codes have a high PPV for glomerular diseases, diabetic nephropathy and systemic diseases affecting the kidney, in which they could be applied for future epidemiological research. [ABSTRACT FROM AUTHOR]

Delayed graft function (DGF) after kidney transplantation heralds a worse prognosis. In patients with hyperoxaluria, the incidence of DGF is high. Oxalic acid is a waste product that accumulates when kidney function decreases. We hypothesize that residual diuresis and accumulated waste products influence the DGF incidence. Patients transplanted between 2018-2022 participated in the prospective cohort study. Pre-transplant concentrations of oxalic acid and its precursors were determined. Data on residual diuresis and other recipient, donor or transplant related variables were collected. 496 patients were included, 154 were not on dialysis. Oxalic acid, and glyoxylic acid, were above upper normal concentrations in 98.8%, and 100% of patients. Residual diuresis was ≤150 mL/min in 24% of patients. DGF occurred in 157 patients. Multivariable binary logistic regression analysis demonstrated a significant influence of dialysis type, recipient BMI, donor type, age, and serum creatinine on the DGF risk. Residual diuresis and glycolic acid concentration were inversely proportionally related to this risk, glyoxylic acid directly proportionally. Results in the dialysis population showed the same results, but glyoxylic acid lacked significance. In conclusion, low residual diuresis is associated with increased DGF incidence. Possibly accumulated waste products also play a role. Pre-emptive transplantation may decrease the incidence of DGF. [ABSTRACT FROM AUTHOR]

The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its second Global Multi-Stakeholders’ Summit, an annual stimulating and forward-thinking meeting uniting experts to anticipate pivotal upcoming challenges and opportunities in the field of primary immunodeficiency (PID). The 2023 summit focused on three key identified discussion points: (i) How can immunoglobulin (Ig) therapy meet future personalized patient needs? (ii) Pandemic preparedness: what’s next for public health and potential challenges for the PID community? (iii) Diagnosing PIDs in 2030: what needs to happen to diagnose better and to diagnose more? Clinician-Scientists, patient representatives and other stakeholders explored avenues to improve Ig therapy through mechanistic insights and tailored Ig preparations/products according to patient-specific needs and local exposure to infectious agents, amongst others. Urgency for pandemic preparedness was discussed, as was the threat of shortage of antibiotics and increasing antimicrobial resistance, emphasizing the need for representation of PID patients and other vulnerable populations throughout crisis and care management. Discussion also covered the complexities of PID diagnosis, addressing issues such as global diagnostic disparities, the integration of patient-reported outcome measures, and the potential of artificial intelligence to increase PID diagnosis rates and to enhance diagnostic precision. These proceedings outline the outcomes and recommendations arising from the 2023 IPOPI Global Multi-Stakeholders’ Summit, offering valuable insights to inform future strategies in PID management and care. Integral to this initiative is its role in fostering collaborative efforts among stakeholders to prepare for the multiple challenges facing the global PID community. [ABSTRACT FROM AUTHOR]

Awards can propel academic careers. They also reflect the culture and values of the scientific community. But do awards incentivize greater transparency, inclusivity, and openness in science? Our cross-disciplinary survey of 222 awards for the "best" journal articles across all 27 SCImago subject areas revealed that journals and learned societies administering such awards generally publish little detail on their procedures and criteria. Award descriptions were brief, rarely including contact details or information on the nominations pool. Nominations of underrepresented groups were not explicitly encouraged, and concepts that align with Open Science were almost absent from the assessment criteria. At the same time, 10% of awards, especially the recently established ones, tended to use article-level impact metrics. USA-affiliated researchers dominated the winner's pool (48%), while researchers from the Global South were uncommon (11%). Sixty-one percent of individual winners were men. Overall, Best Paper awards miss the global calls for greater transparency and equitable access to academic recognition. We provide concrete and implementable recommendations for scientific awards to improve the scientific recognition system and incentives for better scientific practice. Research awards are an integral part of the universal "prestige economy" in science, but do they incentivize greater transparency, inclusivity, and openness? This study uses cross-disciplinary data to explore the level of transparency of publicly available award descriptions and assessment criteria, asking whether such awards contribute to or propagate existing reproducibility crises and inequities in science. [ABSTRACT FROM AUTHOR]

Objectives: The present study systematically reviewed and provided a meta-analysis on early childhood caries (ECC) global prevalence and its association with socioeconomic indicators, both geographical and regarding unemployment rate, national income as well as income inequalities. Methods: Only cross-sectional or cohort studies covering ECC prevalence and experience in children younger than 71 months, reporting sample size, diagnostic criteria and conducted in urban and rural communities were considered. No language restriction was selected. Studies published from 2011 to 2022 available in PubMed, Web of Science, Embase and Open Grey literature were retrieved by ad hoc prepared search strings. The meta-analyses were conducted for both overall ECC prevalence and experience stratified by country of publication as well as measures of socioeconomic indicators using a random effects model using STATA 18®. Results: One hundred publications reporting ECC data from 49 countries (published from 2011 to 2022) were included and summarized by meta-analysis. The lowest prevalence was reported in Japan (20.6%) and Greece (19.3%). The global estimated random-effect pooled prevalence of ECC was 49% (95%CI: 0.44–0.55). The random-effect pooled caries prevalence (ECC) was 34% (95%CI: 02.20–0.48) (Central/South America), 36% (95%CI: 0.25–0.47) (Europe), 42% (95%CI: 0.32–0.53) (Africa), 52% (95%CI: 0.45–0.60) (Asia-Oceania), 57% (95%CI: 0.36–0.77) (North America) and 72% (95%CI: 0.58–0.85) (Middle East). When stratified by gross national income (GNI) the ECC prevalence ranged from 30% ($20,000-$39,999) to 57% in countries with the lowest GNI (<$5000). Stratification by inequality index (Gini index) resulted in an ECC prevalence range of 39% (low inequality) to 62% (no inequality), while for life expectancy the ECC prevalence ranged from 28% in countries with the highest life expectancy (< 80 years) to 62% in countries with 71–75 years life expectancy. Discussion: Within the limitations of this study (lack of certainty about the results as many countries are not represented and lack of uniformity in prevalence and experience data represented), results from 49 different countries reported a wide range of ECC prevalence. These reports indicated persisting high worldwide distribution of the disease. Both ECC prevalence and experience were associated with geographical areas and GNI. Registration: PROSPERO: CRD-42,022,290,418. [ABSTRACT FROM AUTHOR]

Background: The planification of radiation therapy (RT) for pancreatic cancer (PC) requires a dosimetric computed tomography (CT) scan to define the gross tumor volume (GTV). The main objective of this study was to compare the inter-observer variability in RT planning between the arterial and the venous phases following intravenous contrast. Methods: PANCRINJ was a prospective monocentric study that included twenty patients with non-metastatic PC. Patients underwent a pre-therapeutic CT scan at the arterial and venous phases. The delineation of the GTV was performed by one radiologist (gold standard) and two senior radiation oncologists (operators). The primary objective was to compare the Jaccard conformity index (JCI) for the GTVs computed between the GS (gold standard) and the operators between the arterial and the venous phases with a Wilcoxon signed rank test for paired samples. The secondary endpoints were the geographical miss index (GMI), the kappa index, the intra-operator variability, and the dose-volume histograms between the arterial and venous phases. Results: The median JCI for the arterial and venous phases were 0.50 (range, 0.17–0.64) and 0.41 (range, 0.23–0.61) (p = 0.10) respectively. The median GS-GTV was statistically significantly smaller compared to the operators at the arterial (p < 0.0001) and venous phases (p < 0.001), respectively. The GMI were low with few tumors missed for all patients with a median GMI of 0.07 (range, 0-0.79) and 0.05 (range, 0-0.39) at the arterial and venous phases, respectively (p = 0.15). There was a moderate agreement between the radiation oncologists with a median kappa index of 0.52 (range 0.38–0.57) on the arterial phase, and 0.52 (range 0.36–0.57) on the venous phase (p = 0.08). The intra-observer variability for GTV delineation was lower at the venous phase than at the arterial phase for the two operators. There was no significant difference between the arterial and the venous phases regarding the dose-volume histogram for the operators. Conclusions: Our results showed inter- and intra-observer variability in delineating GTV for PC without significant differences between the arterial and the venous phases. The use of both phases should be encouraged. Our findings suggest the need to provide training for radiation oncologists in pancreatic imaging and to collaborate within a multidisciplinary team. [ABSTRACT FROM AUTHOR]

The International Patient Organisation for Primary Immunodeficiencies (IPOPI) held its second Global Multi-Stakeholders’ Summit, an annual stimulating and forward-thinking meeting uniting experts to anticipate pivotal upcoming challenges and opportunities in the field of primary immunodeficiency (PID). The 2023 summit focused on three key identified discussion points: (i) How can immunoglobulin (Ig) therapy meet future personalized patient needs? (ii) Pandemic preparedness: what’s next for public health and potential challenges for the PID community? (iii) Diagnosing PIDs in 2030: what needs to happen to diagnose better and to diagnose more? Clinician-Scientists, patient representatives and other stakeholders explored avenues to improve Ig therapy through mechanistic insights and tailored Ig preparations/products according to patient-specific needs and local exposure to infectious agents, amongst others. Urgency for pandemic preparedness was discussed, as was the threat of shortage of antibiotics and increasing antimicrobial resistance, emphasizing the need for representation of PID patients and other vulnerable populations throughout crisis and care management. Discussion also covered the complexities of PID diagnosis, addressing issues such as global diagnostic disparities, the integration of patient-reported outcome measures, and the potential of artificial intelligence to increase PID diagnosis rates and to enhance diagnostic precision. These proceedings outline the outcomes and recommendations arising from the 2023 IPOPI Global Multi-Stakeholders’ Summit, offering valuable insights to inform future strategies in PID management and care. Integral to this initiative is its role in fostering collaborative efforts among stakeholders to prepare for the multiple challenges facing the global PID community. [ABSTRACT FROM AUTHOR]

Background: Emerging evidence suggests newborn screening analytes may yield insights into the etiologies of birth defects, yet no effort has evaluated associations between a range of newborn screening analytes and birth defects. Methods: This population-based study pooled statewide data on birth defects, birth certificates, and newborn screening analytes from Texas occurring between January 1, 2007 and December 31, 2009. Associations between a panel of thirty-six newborn screening analytes, collected by the statewide Texas Newborn Screening Program, and the presence of a birth defect, defined as at least one of 39 birth defects diagnoses recorded by the Texas Birth Defects Registry, were assessed using regression analysis. Findings: Of the 27,643 births identified, 20,205 had at least one of the 39 birth defects of interest (cases) as identified by the Texas Birth Defects Registry, while 7,438 did not have a birth defect (controls). Among 1,404 analyte-birth defect associations evaluated, 377 were significant in replication analysis. Analytes most consistently associated with birth defects included the phenylalanine/tyrosine ratio (N = 29 birth defects), tyrosine (N = 28 birth defects), and thyroxine (N = 25 birth defects). Birth defects most frequently associated with a range of analytes included gastroschisis (N = 29 analytes), several cardiovascular defects (N = 26 analytes), and spina bifida (N = 23 analytes). Conclusions: Several significant and novel associations were observed between newborn screening analytes and birth defects. While some findings could be consequences of the defects themselves or to the care provided to infants with these defects, these findings could help to elucidate mechanisms underlying the etiology of some birth defects. [ABSTRACT FROM AUTHOR]