bluuebunny/crossref_metadata_2025 huggingface dataset:
Maternal investment and early thermal conditions affect performance and antipredator responses
Authors: Iglesias-Carrasco Maider , Zhang Jiayu , Noble Daniel W A
Published: April 2024

Exposure to increased temperatures during early development can lead to phenotypic plasticity in morphology, physiology, and behavior across a range of ectothermic animals. In addition, maternal effects are known to be important contributors to phenotypic variation in offspring. Whether the 2 factors interact to shape offspring morphology and behavior is rarely explored. This is critical because climate change is expected to impact both incubation temperature and maternal stress and resource allocation. Using a fully factorial design, and Bayesian multivariate mixed models, we explored how the manipulation of early thermal environment and yolk-quantity in eggs affected the morphology, performance, and antipredator behavior of 2 sympatric Australian skink species (Lampropholis delicata and L. guichenoti). We found that juveniles from the hot treatment were larger than those on the cold treatment in L. guichenoti but not L. delicata. Using repeated behavioral measures for individual lizards, we found an interaction between incubation temperature and maternal investment in performance, with running speed being affected in a species-specific way by the treatment. We predicted that changes in performance should influence antipredator responses. In support of this prediction, we found that maternal investment impacted antipredator behavior, with animals from the yolk-reduced and cold treatment resuming activity faster after a simulated predatory attack in L. delicata. However, the prediction was not supported in L. guichenoti. Our results highlight the importance of exploring the multifaceted role that environments play across generations to understand how different anthropogenic factors will impact wildlife in the future.
Short-homology-mediated PCR-based method for gene introduction in the fission yeast Schizosaccharomyces pombe
Authors: Zhang Cai-Xia , Hou Ying-Chun
Published: April 2024

Schizosaccharomyces pombe is a commonly utilized model organism for studying various aspects of eukaryotic cell physiology. One reason for its widespread use as an experimental system is the ease of genetic manipulations, leveraging the natural homology-targeted repair mechanism to accurately modify the genome. We conducted a study to assess the feasibility and efficiency of directly introducing exogenous genes into the fission yeast S. pombe using Polymerase Chain Reaction (PCR) with short-homology flanking sequences. Specifically, we amplified the NatMX6 gene (which provides resistance to nourseothricin) using PCR with oligonucleotides that had short flanking regions of 20 bp, 40 bp, 60 bp and 80 bp to the target gene. By using this purified PCR product, we successfully introduced the NatMX6 gene at position 171 385 on chromosome III in S. pombe. We have made a simple modification to the transformation procedure, resulting in a significant increase in transformation efficiency by at least 5-fold. The success rate of gene integration at the target position varied between 20% and 50% depending on the length of the flanking regions. Additionally, we discovered that the addition of dimethyl sulfoxide and boiled carrier DNA increased the number of transformants by ~60- and 3-fold, respectively. Furthermore, we found that the removal of the pku70+ gene improved the transformation efficiency to ~5% and reduced the formation of small background colonies. Overall, our results demonstrate that with this modified method, even very short stretches of homologous regions (as short as 20 bp) can be used to effectively target genes at a high frequency in S. pombe. This finding greatly facilitates the introduction of exogenous genes in this organism.
High intratumoral 5-hydroxymethylcytosine levels protect against disease relapse in patients with atypical fibroxanthoma and pleomorphic dermal sarcoma
Authors: Gambichler Thilo , Razeghpour Fahimeh , Sorescu Emilia , Stücker Markus , Abu Rached Nessr , Becker Jürgen C , Susok Laura
Published: April 2024

Hydroxymethylation plays a significant role in cancer development and progression. We hypothesized that hydroxymethylation markers may have prognostic potential in AFX/PDS (atypical fibroxanthoma/pleomorphic dermal sarcoma) as also observed in other tumours. Moreover, we wanted to find out whether hydroxymethylation markers might aid differentiation between AFX and PDS.
Long-term consequences on stigmatization and disease burden during adulthood among patients with childhood or adolescence-onset atopic dermatitis
Authors: Halioua Bruno , Skayem Charbel , Merhand Stéphanie , Hayoun Yaron Ben , Taieb Charles
Published: April 2024

The World Health Organization is calling on governments to take action to reduce the stigmatization of patients with skin diseases, highlighting the significant psychosocial burden experienced by patients with atopic dermatitis (AD) from childhood onwards. This cross-sectional study reveals that stigma experienced in childhood or adolescence increases the risk of disease burden, stress and stigma in adulthood, underlining the importance of reinforced psychological support. It highlights the need for dermatologists to target these patients, in order to improve their quality of life.
Surgeon age in relation to patients’ long-term survival after gastrectomy for gastric adenocarcinoma: nationwide population-based cohort study
Authors: Leijonmarck Wilhelm , Mattsson Fredrik , Asplund Johannes , Markar Sheraz , Lagergren Jesper
Published: April 2024

Background

Increasing surgeon age may influence patient outcomes after complex procedures due to gained experience but also decreased technical and cognitive abilities. This study aimed to clarify whether surgeon age influences patients’ long-term survival after gastrectomy for gastric adenocarcinoma.

Methods

Population-based cohort study including all patients who underwent open and curatively intended gastrectomy for gastric adenocarcinoma between 2006 and 2015 in Sweden, with follow-up throughout 2020. Surgeon age, categorized into three equal-sized groups (tertiles), was assessed in relation to 5-year all-cause mortality rate (main outcome) and 5-year disease-specific death (secondary outcome) using multivariable Cox regression adjusted for patient age, sex, education, co-morbidity, pathological tumour stage, tumour sublocation and neoadjuvant therapy. Lymph node yield, resection margin status, in-hospital complications and annual surgeon volume of gastrectomy were considered potential mediators.

Results

Among 1647 patients, the 5-year all-cause mortality rate was increased for surgeon age ≥55 years (adjusted HR 1.21, 95% c.i. 1.04 to 1.41) and borderline elevated for age 47–54 years (HR 1.16, 95% c.i. 0.99 to 1.36), compared with age ≤46 years. Five-year disease-specific death was increased for surgeon age ≥55 years (HR 1.25, 95% c.i. 1.06 to 1.48) and 47–54 years (HR 1.22, 95% c.i. 1.02 to 1.44), compared with age ≤46 years. The associations attenuated and became statistically non-significant after adjustment for lymph node yield, resection margin status and complications.

Conclusion

Surgeon age ≥47 years might be associated with worse long-term survival in patients who undergo gastrectomy for gastric adenocarcinoma, possibly mediated in part by differences in lymph node yield, resection margin status and complications.
Characterizing brain tau and cognitive decline along the amyloid timeline in Alzheimer’s disease
Authors: Cody Karly A , Langhough Rebecca E , Zammit Matthew D , Clark Lindsay , Chin Nathaniel , Christian Bradley T , Betthauser Tobey J , Johnson Sterling C
Published: April 2024

Recent longitudinal PET imaging studies have established methods to estimate the age at which amyloid becomes abnormal at the level of the individual. Here we recontextualized amyloid levels into the temporal domain to better understand the downstream Alzheimer’s disease processes of tau neurofibrillary tangle (NFT) accumulation and cognitive decline.

This cohort study included a total of 601 individuals from the Wisconsin Registry for Alzheimer’s Prevention and Wisconsin Alzheimer’s Disease Research Center that underwent amyloid and tau PET, longitudinal neuropsychological assessments and met clinical criteria for three clinical diagnosis groups: cognitively unimpaired (n = 537); mild cognitive impairment (n = 48); or dementia (n = 16). Cortical 11C-Pittsburgh compound B (PiB) distribution volume ratio (DVR) and sampled iterative local approximation were used to estimate amyloid positive (A+; global PiB DVR > 1.16 equivalent to 17.1 centiloids) onset age and years of A+ duration at tau PET (i.e. amyloid chronicity). Tau PET burden was quantified using 18F-MK-6240 standardized uptake value ratios (70–90 min, inferior cerebellar grey matter reference region). Whole-brain and region-specific approaches were used to examine tau PET binding along the amyloid timeline and across the Alzheimer’s disease clinical continuum.

Voxel-wise 18F-MK-6240 analyses revealed that with each decade of A+, the spatial extent of measurable tau spread (i.e. progressed) from regions associated with early to late NFT tau stages. Regional analyses indicated that tau burden in the entorhinal cortex was detectable, on average, within 10 years of A+ onset. Additionally, the entorhinal cortex was the region most sensitive to early amyloid pathology and clinical impairment in this predominantly preclinical sample. Among initially cognitively unimpaired (n = 472) individuals with longitudinal cognitive follow-up, mixed effects models showed significant linear and non-linear interactions of A+ duration and entorhinal tau on cognitive decline, suggesting a synergistic effect whereby greater A+ duration, together with a higher entorhinal tau burden, increases the likelihood of cognitive decline beyond their separable effects.

Overall, the amyloid time framework enabled a spatiotemporal characterization of tau deposition patterns across the Alzheimer’s disease continuum. This approach, which examined cross-sectional tau PET data along the amyloid timeline to make longitudinal disease course inferences, demonstrated that A+ duration explains a considerable amount of variability in the magnitude and topography of tau spread, which largely recapitulated NFT staging observed in human neuropathological studies. By anchoring disease progression to the onset of amyloid, this study provides a temporal disease context, which may help inform disease prognosis and timing windows for anti-amyloid therapies.
Effective treatment of solar facial porokeratosis in one patient with topical atorvastatin/cholesterol cream
Authors: Peng Kexin , Wong Wenghong , Yan Kexiang , Zhang Zhenghua
Published: April 2024

We report a rare case of solar facial porokeratosis (SFP) treated topically with atorvastatin/cholesterol or cholesterol alone for 48 weeks. The patient reported no obvious skin irritation and was delighted with the outcome. This study supported the effectiveness of a pathogenesis-directed treatment for SFP. Moreover, we point out that topical statins combined with cholesterol might have a long-term benefit in the treatment of SFP.
Strength and resilience of developing brain circuits predict adolescent emotional and stress responses during the COVID-19 pandemic
Authors: Hu Linfeng , Stamoulis Catherine
Published: April 2024

The COVID-19 pandemic has had profound but incompletely understood adverse effects on youth. To elucidate the role of brain circuits in how adolescents responded to the pandemic’s stressors, we investigated their prepandemic organization as a predictor of mental/emotional health in the first ~15 months of the pandemic. We analyzed resting-state networks from n = 2,641 adolescents [median age (interquartile range) = 144.0 (13.0) months, 47.7% females] in the Adolescent Brain Cognitive Development study, and longitudinal assessments of mental health, stress, sadness, and positive affect, collected every 2 to 3 months from May 2020 to May 2021. Topological resilience and/or network strength predicted overall mental health, stress and sadness (but not positive affect), at multiple time points, but primarily in December 2020 and May 2021. Higher resilience of the salience network predicted better mental health in December 2020 (β = 0.19, 95% CI = [0.06, 0.31], P = 0.01). Lower connectivity of left salience, reward, limbic, and prefrontal cortex and its thalamic, striatal, amygdala connections, predicted higher stress (β = −0.46 to −0.20, CI = [−0.72, −0.07], P < 0.03). Lower bilateral robustness (higher fragility) and/or connectivity of these networks predicted higher sadness in December 2020 and May 2021 (β = −0.514 to −0.19, CI = [−0.81, −0.05], P < 0.04). These findings suggest that the organization of brain circuits may have played a critical role in adolescent stress and mental/emotional health during the pandemic.
An executive-functions-based reading training enhances sensory-motor systems integration during reading fluency in children with dyslexia
Authors: Farah Rola , Dworetsky Ally , Coalson Rebecca S , Petersen Steven E , Schlaggar Bradley L , Rosch Keri S , Horowitz-Kraus Tzipi
Published: April 2024

The Simple View of Reading model suggests that intact language processing and word decoding lead to proficient reading comprehension, with recent studies pointing at executive functions as an important component contributing to reading proficiency. Here, we aimed to determine the underlying mechanism(s) for these changes. Participants include 120 8- to 12-year-old children (n = 55 with dyslexia, n = 65 typical readers) trained on an executive functions–based reading program, including pre/postfunctional MRI and behavioral data collection. Across groups, improved word reading was related to stronger functional connections within executive functions and sensory networks. In children with dyslexia, faster and more accurate word reading was related to stronger functional connections within and between sensory networks. These results suggest greater synchronization of brain systems after the intervention, consistent with the “neural noise” hypothesis in children with dyslexia and support the consideration of including executive functions as part of the Simple View of Reading model.
Hyaluronic acid microresonators for memorable humidity sensing
Authors: Liao Hsin-Yen , Heah Wey Yih , Suharman  , Yamagishi Hiroshi , Yamamoto Yohei
Published: April 2024

Self-assembled hyaluronic acid (HA) microspheres are utilized for memorable optical humidity sensing. Because of the extremely high hygroscopic property of HA, the microsphere deforms in a highly humid atmosphere and the shape change is irreversible, thereby memorizing the history of the humidity change. The optically memorable humidity sensor can notify whether the humidity exceeds the upper limit of 50%.
Origin of Antimicrobial Therapy
Authors: Kazanjian Powel
Published: April 2024

Medical historians typically situate the origins of the antimicrobial era during the early germ period at the turn of the 20th century. They have regarded the development of chemical compounds designed to treat infectious diseases by killing their causative germ as the beginning of the antimicrobial era. Scholars, however, had been speculating about the causal relationship between germs and diseases for centuries beforehand. One of them also addressed the practical applications of this theory. The Italian physician Fracastoro proposed in 1546 that infectious diseases could be treated by administering substances to antagonize disease causing germs. He claimed that health could be restored to people who became ill with infections by nullifying the responsible germs at a time when investigators could not see germs or investigate their ability to cause disease. The long genealogy of antimicrobial therapy from its conception to its fruition took place over the span of several centuries.
The Impact of Pretransplant Respiratory Virus Detection on Posttransplant Outcomes in Children Undergoing Hematopoietic Cell Transplantation
Authors: Kim Sara Ruth , Nordlander Anna , Xie Hu , Kim Yae-Jean , Ogimi Chikara , Thakar Monica S , Leisenring Wendy , Englund Janet A , Boeckh Michael , Waghmare Alpana
Published: April 2024

Background

Pretransplant respiratory virus (RV) infections have been associated with negative transplant outcomes in adult hematopoietic cell transplantation (HCT) recipients. In the era of HCT delay because of high-risk RVs, we examined the impact of pretransplant RV detection on transplant outcomes in pediatric HCT recipients.

Methods

This retrospective cohort study included pediatric myeloablative allogeneic HCT recipients from 2010 to 2019. All patients were screened for RV at least once within 90 days before HCT using reverse transcriptase polymerase chain reaction (PCR), regardless of symptoms. Posttransplant outcomes included days alive and out of hospital and progression to lower respiratory tract infection (LRTI).

Results

Among 310 patients, 134 had an RV detected in the 90 days before HCT. In univariable analysis, transplant factors including younger age, total body irradiation, umbilical cord blood transplantation, lymphocyte count <100/mm3, HCT comorbidity index score ≥3, and viral factors including symptomatic infection, human rhinovirus as a virus type, and symptomatic pretransplant upper respiratory tract infection were associated with fewer days alive and out of hospital. In multivariable analysis, transplant factors remained significant, but not viral factors. There was a higher incidence of progression to posttransplant LRTI with the same pretransplant RV if the last positive PCR before HCT was ≤30 days compared with >30 days (P = .007).

Conclusions

In the setting of recommending HCT delay for high-risk RVs, symptomatic upper respiratory tract infection, including human rhinovirus infections, may lead to increased duration of hospitalization and early progression to LRTI when transplantation is performed within 30 days of the last positive PCR test.
Tofacitinib for the treatment of refractory immune checkpoint inhibitor-associated immune nephritis
Authors: Shivaraj Kiran , Tchakarov Amanda , Dong Yanlan , Lin Jamie S
Published: April 2024

Immune checkpoint inhibitor (ICI)-associated immune nephritis or acute interstitial nephritis (AIN) is one of the rare but known complication of ICI therapy. Guidelines recommend treatment of ICI-associated AIN with steroids, then TNF-alpha inhibitor infliximab. However, some cases are refractory to these therapies, potentially due to insufficient cytokine blockade. This is the first case where a 65-year-old female with metastatic lung adenocarcinoma, requiring high maintenance doses of steroids for immune nephritis was treated with tofacitinib, an oral Janus kinase (JAK) inhibitor. Tofacitinib enabled successful steroid tapering and might be a therapy option for refractory immune nephritis.
Biomarkers in clinical epidemiology studies
Authors: Zoccali Carmine , Tripepi Giovanni , Stel Vianda , Fu Edouard L , Mallamaci Francesca , Dekker Friedo , Jager Kitty J
Published: April 2024

This paper discusses the use of biomarkers in clinical practice and biomedical research. Biomarkers are measurable characteristics that can be used to indicate the presence or absence of a disease or to track the progression of a disease. They can also be used to predict how a patient will respond to a particular treatment. Biomarkers have enriched clinical practice and disease prognosis by providing measurable characteristics that indicate biological processes. They offer valuable insights into disease susceptibility, progression, and treatment response, aiding drug development and personalized medicine. However, developing and implementing biomarkers come with challenges that must be addressed. Rigorous testing, standardization of assays, and consideration of ethical factors are crucial in ensuring the reliability and validity of biomarkers.

Reliability is vital in biomarker research. It ensures accurate measurements by preventing biases and facilitating robust correlations with outcomes. Conversely, validation examines which and how many biomarkers correspond to theoretical constructs and external criteria, establishing their predictive value. Multiple biomarkers are sometimes necessary to represent the complex relationship between exposure and disease outcomes accurately.

Susceptibility factors are pivotal in disease states' complex interaction among genetic and environmental factors. Gaining a comprehensive understanding of these factors is essential for effectively interpreting biomarker data and maximizing their clinical usefulness. Using well-validated biomarkers can improve diagnoses, more effective treatment evaluations, and enhanced disease prediction. This, in turn, will contribute to better patient outcomes and drive progress in medicine.
Economics of Emergency Department Visits by Patients With Inflammatory Bowel Disease: A Real-World Analysis
Authors: Clarke Kofi , Momin Arsh , Rosario Michelle , Stuart August , Dalessio Shannon , Tinsley Andrew , Williams Emmanuelle , Coates Matthew
Published: April 2024

Background

Inflammatory bowel disease (IBD) is associated with significant psychosocial, economic, and physical burden on patients. IBD care in the United States results in significant healthcare expenditure with recurring emergency department (ED) care and hospital admissions. Despite advances in therapy and improved access to specialty care, there is still room for improvement in cost-efficient care. Specialty medical homes and interdisciplinary care models have emerged as ways to improve medical care, patient outcomes, and quality of life, as well as improve the impact of healthcare costs. There is limited real-world data on cost in the United States, with many articles citing cost estimates from models.

Methods

We analyzed real-world data from our tertiary care center with a focus on recurrent ED visits by IBD patients. Descriptive statistics were used for a cost analysis of multiple ED visits by IBD patients. Patients with ≥4 visits to the ED in a 6-month period were described as SuperUsers and were included in a separate analysis. The cost of hospitalization was also included.

Results

Total cost associated with all ED visits from SuperUsers were $72 999.57 with an average of $6636.32 per patient. When the patients were admitted, the total cost of ED visits and hospitalizations was $721 461.52, with an average of $65 587.41 per patient.

Conclusions

ED utilization by IBD patients with or without hospitalization is expensive and is typically driven by a cohort of SuperUsers. More work needs to be done to improve cost-effectiveness in IBD care, including reducing the frequency of ED visits.
Serine protease inhibitor, SerpinA3n, regulates cardiac remodelling after myocardial infarction
Authors: Sun Qihao , Chen Wei , Wu Rimao , Tao Bo , Wang Ping , Sun Baiming , Alvarez Juan F , Ma Feiyang , Galindo David Ceja , Maroney Sean P , Saviola Anthony J , Hansen Kirk C , Li Shen , Deb Arjun
Published: April 2024

Aims

Following myocardial infarction (MI), the heart repairs itself via a fibrotic repair response. The degree of fibrosis is determined by the balance between deposition of extracellular matrix (ECM) by activated fibroblasts and breakdown of nascent scar tissue by proteases that are secreted predominantly by inflammatory cells. Excessive proteolytic activity and matrix turnover has been observed in human heart failure, and protease inhibitors in the injured heart regulate matrix breakdown. Serine protease inhibitors (Serpins) represent the largest and the most functionally diverse family of evolutionary conserved protease inhibitors, and levels of the specific Serpin, SerpinA3, have been strongly associated with clinical outcomes in human MI as well as non-ischaemic cardiomyopathies. Yet, the role of Serpins in regulating cardiac remodelling is poorly understood. The aim of this study was to understand the role of Serpins in regulating scar formation after MI.

Methods and results

Using a SerpinA3n conditional knockout mice model, we observed the robust expression of Serpins in the infarcted murine heart and demonstrate that genetic deletion of SerpinA3n (mouse homologue of SerpinA3) leads to increased activity of substrate proteases, poorly compacted matrix, and significantly worse post-infarct cardiac function. Single-cell transcriptomics complemented with histology in SerpinA3n-deficient animals demonstrated increased inflammation, adverse myocyte hypertrophy, and expression of pro-hypertrophic genes. Proteomic analysis of scar tissue demonstrated decreased cross-linking of ECM peptides consistent with increased proteolysis in SerpinA3n-deficient animals.

Conclusion

Our study demonstrates a hitherto unappreciated causal role of Serpins in regulating matrix function and post-infarct cardiac remodelling.
Disproportionately high aortic valve calcium scores in atrial fibrillation: implications for transcatheter aortic valve replacement
Authors: Masson Rajeev , Nkomo Vuyisile T , Holmes David R , Pislaru Sorin V , Arsanjani Reza , Chao Chieh-Ju , Klanderman Molly , Abraham Bishoy , Morsy Mahmoud , Fortuin F David , Sweeney John P , Sell-Dotten Kristen , Alsidawi Said
Published: April 2024

Aims

Doppler mean gradient (MG) can underestimate aortic stenosis (AS) severity in patients with atrial fibrillation (AF) compared with patients with sinus rhythm (SR), potentially delaying intervention in AF. This study compared outcomes in patients with AF and SR following transcatheter aortic valve replacement (TAVR) and investigated delay in TAVR based on computed tomography aortic valve calcium score (AVCS).

Methods and results

Patients who underwent TAVR from 2013 to 2017 for native valve severe AS were identified from an institutional database. Baseline characteristics and overall survival were compared between those with SR and AF. There were 820 patients (mean age 81 years; 41.6% females) included in this study. AF was present in 356 patients. Patients with AF were older (82.2 vs. 80.5, P = 0.003) and had a lower MG compared with patients with SR (42.0 vs. 44.9, P = 0.002) with similar indexed aortic valve area (0.4 vs. 0.4, P = 0.17). Median AVCS was higher in AF (males: AF 2850.0 vs. SR 2561.0, P = 0.044; females: AF 1942.0 vs. SR 1610.5, P = 0.025). Projected AVCS, assuming the same age of diagnosis, was similar between AF and SR. Median survival post-TAVR was worse in AF compared with SR (3.2 vs. 5.4 years, log rank P < 0.001). AF, lower MG, higher right ventricular systolic pressure, dialysis, diabetes, and significant tricuspid regurgitation were associated with higher mortality (P < 0.05 for all).

Conclusion

Older age and higher AVCS in patients with AF compared with those with SR suggest that AS was both underestimated and more advanced at TAVR referral.
Steeper at the top: cognitive ability and earnings in Finland and Norway
Authors: Bratsberg Bernt , Rogeberg Ole , Terviö Marko
Published: April 2024

We document a convex relationship between earnings rank and cognitive ability for men in Finland and Norway using administrative data on over 350,000 men in each country: the top earnings percentile score on average 1 standard deviation higher than median earners, while median earners score about 0.5 standard deviation higher than the bottom percentile of earners. Top earners also have substantially less variation in cognitive test scores. While some high-scoring men are observed to have very low earnings, the lowest cognitive scores are almost absent among the top earners. Overall, the joint distribution of earnings rank and ability is very similar in Finland and Norway. We find that the slope of the ability curve across earnings ranks is steepest in the upper tail, as is the slope of the earnings curve across cognitive ability. The steep slope of the ability curve across the top earnings percentiles differs markedly from the flat or declining slope recently reported for Sweden.
Diabetes and coronary artery disease as risk factors for dementia
Authors: Olesen Kevin K W , Thrane Pernille G , Gyldenkerne Christine , Thomsen Reimar W , Mortensen Janne K , Kristensen Steen D , Maeng Michael
Published: April 2024

Aims

Diabetes is associated with an increased risk of dementia, but it is still debated to which degree this risk depends on the presence of atherosclerotic cardiovascular disease (CVD). In this study, we hypothesize that patients with diabetes and coexisting coronary artery disease (CAD), as a marker of systemic atherosclerotic CVD, have a substantially higher risk of developing dementia.

Methods and results

Patients ≥65 years, who underwent coronary angiography, were stratified by diabetes and CAD. Outcomes were all-cause dementia, Alzheimer’s dementia, and vascular dementia. We estimated adjusted hazard ratios (aHRs) using patients with neither diabetes nor CAD as a reference. A total of 103 859 patients were included. Of these, 23 189 (22%) had neither diabetes nor CAD, 3876 (4%) had diabetes, 61 020 (59%) had CAD, and 15 774 (15%) had diabetes and CAD. During a median follow-up of 6.3 years, 5592 (5.5%) patients were diagnosed with all-cause dementia. Patients with diabetes and CAD had the highest HR of all-cause dementia [aHR 1.37, 95% confidence interval (CI) 1.24–1.51], including Alzheimer’s dementia (aHR 1.41, 95% CI 1.23–1.62) and vascular dementia (aHR 2.03, 95% CI 1.69–2.45). Patients with diabetes alone (aHR 1.14, 95% CI 0.97–1.33) or CAD alone (aHR 1.11, 95% CI 1.03–1.20) had a modestly increased rate of all-cause dementia.

Conclusion

The combination of diabetes and CAD is associated with an increased rate of dementia, in particular vascular dementia, suggesting that the diabetes-related risk of dementia is partly mediated through concomitant atherosclerotic CVD. This underscores the importance of atherosclerotic CVD prevention in diabetic patients to reduce cognitive decline.
Stereotactic arrhythmia radioablation and its implications for modern cardiac electrophysiology: results of an EHRA survey
Authors: Kovacs Boldizsar , Lehmann Helge Immo , Manninger Martin , Saguner Ardan Muammer , Futyma Piotr , Duncker David , Chun Julian
Published: April 2024

Stereotactic arrhythmia radioablation (STAR) is a treatment option for recurrent ventricular tachycardia/fibrillation (VT/VF) in patients with structural heart disease (SHD). The current and future role of STAR as viewed by cardiologists is unknown. The study aimed to assess the current role, barriers to application, and expected future role of STAR. An online survey consisting of 20 questions on baseline demographics, awareness/access, current use, and the future role of STAR was conducted. A total of 129 international participants completed the survey [mean age 43 ± 11 years, 25 (16.4%) female]. Ninety-one (59.9%) participants were electrophysiologists. Nine participants (7%) were unaware of STAR as a therapeutic option. Sixty-four (49.6%) had access to STAR, while 62 (48.1%) had treated/referred a patient for treatment. Common primary indications for STAR were recurrent VT/VF in SHD (45%), recurrent VT/VF without SHD (7.8%), or premature ventricular contraction (3.9%). Reported main advantages of STAR were efficacy in the treatment of arrhythmias not amenable to conventional treatment (49%) and non-invasive treatment approach with overall low expected acute and short-term procedural risk (23%). Most respondents have foreseen a future clinical role of STAR in the treatment of VT/VF with or without underlying SHD (72% and 75%, respectively), although only a minority expected a first-line indication for it (7% and 5%, respectively). Stereotactic arrhythmia radioablation as a novel treatment option of recurrent VT appears to gain acceptance within the cardiology community. Further trials are critical to further define efficacy, patient populations, as well as the appropriate clinical use for the treatment of VT.
Technological Development and Advances for Constructing and Analyzing Plant Pangenomes
Authors: Hu Haifei , Li Risheng , Zhao Junliang , Batley Jacqueline , Edwards David
Published: April 2024

A pangenome captures the genomic diversity for a species, derived from a collection of genetic sequences of diverse populations. Advances in sequencing technologies have given rise to three primary methods for pangenome construction and analysis: de novo assembly and comparison, reference genome-based iterative assembly, and graph-based pangenome construction. Each method presents advantages and challenges in processing varying amounts and structures of DNA sequencing data. With the emergence of high-quality genome assemblies and advanced bioinformatic tools, the graph-based pangenome is emerging as an advanced reference for exploring the biological and functional implications of genetic variations.
Agents of Change: Geriatrics Workforce Programs Addressing Systemic Racism and Health Equity
Authors: Gordon Barbara A , Azer Lilian , Bennett Katherine , Edelman Linda S , Long Monica , Goroncy Anna , Alexander Charles , Lee Jung-Ah , Rosich Rosellen , Severance Jennifer J
Published: April 2024

Many factors affect how individuals and populations age, including race, ethnicity, and diversity, which can contribute to increased disease risk, less access to quality healthcare, and increased morbidity and mortality. Systemic racism—a set of institutional policies and practices within a society or organization that perpetuate racial inequalities and discrimination—contributes to health inequities of vulnerable populations, particularly older adults. The National Association for Geriatrics Education (NAGE) recognizes the need to address and eliminate racial disparities in healthcare access and outcomes for older adults who are marginalized due to the intersection of race and age. In this paper, we discuss an anti-racist framework that can be used to identify where an organization is on a continuum to becoming anti-racist and to address organizational change. Examples of NAGE member Geriatric Workforce Enhancement Programs (GWEPs) and Geriatrics Academic Career Awards (GACAs) activities to become anti-racist are provided to illustrate the framework and to guide other workforce development programs and healthcare institutions as they embark on the continuum to become anti-racist and improve the care and health of vulnerable older adults.
Medicaid spending and utilization of gene and RNA therapies for rare inherited conditions
Authors: Odouard Ilina C , Ballreich Jeromie , Socal Mariana P
Published: April 2024

Gene and RNA therapies are promising treatments for many rare diseases. Pediatric populations that could benefit from these drugs are overrepresented among state Medicaid programs. Using Medicaid State Drug Utilization Data, we examined Medicaid spending and utilization of rare disease gene and RNA therapies. Between 2017 and 2022, the number of available gene and RNA therapies increased from 3 to 13, yearly Medicaid spending increased from $148.3 million to $879.7 million, and the number of yearly treatments (a proxy for number of patients) increased from 327 to 1638. Nearly all spending was attributed to spinal muscular atrophy (SMA) and Duchenne muscular dystrophy drugs. States participating in Medicaid pooled purchasing initiatives had 39% higher treatments per 100 000 enrollees with no differences in spending. Compared to states without a carve-out, states that carved SMA drugs out of managed Medicaid contracts had higher utilization (54%). Spending among carve-out states varied according to managed care enrollment, being higher for those with <80% of enrollees in managed care as compared with those with ≥80% of enrollees in managed care. This suggests that multi-state purchasing initiatives and managed care carve-outs can help increase access to gene and RNA therapies among Medicaid beneficiaries, but it is unclear if these strategies are effective at managing spending.
Can sugar taxes be used for financing surgical systems in Nigeria? A mixed-methods political economy analysis
Authors: Ifeanyichi Martilord , Dim Cyril , Bognini Maeve , Kebede Meskerem , Singh Darshita , Onwujekwe Obinna , Hargest Rachel , Friebel Rocco
Published: April 2024

This study determined the feasibility of investing revenues raised through Nigeria’s sugar-sweetened beverage (SSB) tax of 10 Naira/l to support the implementation of the National, Surgical, Obstetrics, Anaesthesia and Nursing Plan, which aims to strengthen access to surgical care in the country. We conducted a mixed-methods political economy analysis. This included a modelling exercise to predict the revenues from Nigeria’s SSB tax based on its current tax rate over a period of 5 years, and for several scenarios such as a 20% ad valorem tax recommended by the World Health Organization. We performed a gap analysis to explore the differences between fiscal space provided by the tax and the implementation cost of the surgical plan. We conducted qualitative interviews with key stakeholders and performed thematic analyses to identify opportunities and barriers for financing surgery through tax revenues. At its current rate, the SSB tax policy has the potential to generate 35 914 111 USD in year 1, and 189 992 739 USD over 5 years. Compared with the 5-year adjusted surgical plan cost of 20 billion USD, the tax accounts for ∼1% of the investment required. There is a substantial scope for further increases in the tax rate in Nigeria, yielding potential revenues of up to 107 663 315 USD, annually. Despite an existing momentum to improve surgical care, there is no impetus to earmark sugar tax revenues for surgery. Primary healthcare and the prevention and treatment of non-communicable diseases present as the most favoured investment areas. Consensus within the medical community on importance of primary healthcare, along the recent government transition in Nigeria, offers a policy window for promoting a higher SSB tax rate and an adoption of other sin taxes to generate earmarked funds for the healthcare system. Evidence-based advocacy is necessary to promote the benefits from investing into surgery.
Genetic correlation between circulating cytokines and risk of three ophthalmic diseases: a bidirectional two-sample Mendelian randomization study
Authors: Zhang Xin , Fu Qiangqiang , Cai Yuying , Li Xianglian , Chen Li , Jiang Yaping , Chen Yihui
Published: April 2024

Purpose

Pathogenesis and the associated risk factors of cataracts, glaucoma, and age-related macular degeneration (AMD) remain unclear. We aimed to investigate causal relationships between circulating cytokine levels and the development of these diseases.

Patients and methods

Genetic instrumental variables for circulating cytokines were derived from a genome-wide association study of 8293 European participants. Summary-level data for AMD, glaucoma, and senile cataract were obtained from the FinnGen database. The inverse variance weighted (IVW) was the main Mendelian randomization (MR) analysis method. The Cochran’s Q, MR-Egger regression, and MR pleiotropy residual sum and outlier test were used for sensitivity analysis.

Results

Based on the IVW method, MR analysis demonstrated five circulating cytokines suggestively associated with AMD (SCGF-β, 1.099 [95%CI, 1.037–1.166], P = 0.002; SCF, 1.155 [95%CI, 1.015–1.315], P = 0.029; MCP-1, 1.103 [95%CI, 1.012–1.202], P = 0.026; IL-10, 1.102 [95%CI, 1.012–1.200], P = 0.025; eotaxin, 1.086 [95%CI, 1.002–1.176], P = 0.044), five suggestively linked with glaucoma (MCP-1, 0.945 [95%CI, 0.894–0.999], P = 0.047; IL1ra, 0.886 [95%CI, 0.809–0.969], P = 0.008; IL-1β, 0.866 [95%CI, 0.762–0.983], P = 0.027; IL-9, 0.908 [95%CI, 0.841–0.980], P = 0.014; IL2ra, 1.065 [95%CI, 1.004–1.130], P = 0.035), and four suggestively associated with senile cataract (TRAIL, 1.043 [95%CI, 1.009–1.077], P = 0.011; IL-16, 1.032 [95%CI, 1.001–1.064], P = 0.046; IL1ra, 0.942 [95%CI, 0.887–0.999], P = 0.047; FGF-basic, 1.144 [95%CI, 1.052–1.244], P = 0.002). Furthermore, sensitivity analysis results supported the above associations.

Conclusion

This study highlights the involvement of several circulating cytokines in the development ophthalmic diseases and holds potential as viable pharmacological targets for these diseases.
A challenging case of severe bilateral septic arthritis with osteomyelitis of the sternoclavicular joint in a patient with end-stage renal disease
Authors: Khoo Chun Yuet , Chia Cynthia Ming Li
Published: April 2024

Septic arthritis of the sternoclavicular joint (SCJ) is a rare condition that comprises <1% of all joint infections. We report a case of severe bilateral septic arthritis of the SCJ in a patient with end-stage renal disease on peritoneal dialysis. A 44-year-old female presented with right SCJ infection 1 month after recovering from a tenckhoff catheter exit-site infection. She completed 6 weeks of antibiotics however this progressed to bilateral SCJ septic arthritis with osteomyelitis necessitating multiple surgical debridement and excision of bilateral clavicular heads. Further imaging showed signs of renal osteodystrophy and degenerative joint changes resembling calcium pyrophosphate deposition. Patients with end-stage renal disease have multiple risk factors including immune system dysfunction, renal osteodystrophy and dialysis access sites that increase susceptibility to bacteraemia and seeding. Therefore in such patients, prompt assessment is necessary to ensure expeditious diagnosis and treatment of this potentially debilitating condition. A multidisciplinary team involving various specialties is crucial for the holistic care for such patients and to reduce the risk of recurrence.
Dietary intake of copper and gastric cancer: a pooled analysis within the Stomach cancer Pooling (StoP) Project
Authors: Sassano Michele , Collatuzzo Giulia , Seyyedsalehi Monireh Sadat , Pelucchi Claudio , Bonzi Rossella , Palli Domenico , Ferraroni Monica , Lunet Nuno , Morais Samantha , López-Carrillo Lizbeth , Malekzadeh Reza , Pakseresht Mohammadreza , López-Cervantes Malaquias , Ward Mary H , Camargo Maria Constanza , Curado Maria Paula , Vioque Jesùs , Zhang Zuo-Feng , Boccia Stefania , Negri Eva , La Vecchia Carlo , Boffetta Paolo
Published: April 2024

Background

Evidence on the potential association between dietary copper intake and gastric cancer (GC) is lacking. Thus, we aimed to evaluate this association within the Stomach cancer Pooling (StoP) Project—an international consortium of epidemiological studies on GC.

Methods

Data from five case–control studies within the StoP Project were included (2448 cases, 4350 controls). We estimated adjusted odds ratios (ORs) and 95% CIs for the association between dietary copper intake and GC using multivariable mixed-effects logistic regression models. We also modelled the dose–response relationship between copper intake and GC using a logistic mixed-effects model with fractional polynomial.

Results

The OR for the highest quartile of copper intake compared with the lowest one was 0.78 (95% CI: 0.63–0.95; P for trend = 0.013). Results were similar for non-cardia-type (OR: 0.72; 95% CI: 0.57–0.91), intestinal-type (OR: 0.75; 95% CI: 0.56–0.99) and other histological-type GC (OR: 0.65; 95% CI: 0.44–0.96). The dose–response analysis showed a steep decrease in ORs for modest intakes (<1 mg/day), which were subsequently steady for ≤3 mg/day (OR: 0.09; 95% CI: 0.02–0.41) and slowly increased for higher intakes.

Conclusions

The findings of our large study suggest that copper intake might be inversely associated with GC, although their confirmation by prospective studies is required.
Efficacy and Safety of a Tetravalent Dengue Vaccine (TAK-003) in Children With Prior Japanese Encephalitis or Yellow Fever Vaccination
Authors: Sirivichayakul Chukiat , Biswal Shibadas , Saez-Llorens Xavier , López-Medina Eduardo , Borja-Tabora Charissa , Bravo Lulu , Kosalaraksa Pope , Alera Maria Theresa , Reynales Humberto , Rivera Luis , Watanaveeradej Veerachai , Yu Delia , Espinoza Felix , Dietze Reynaldo , Fernando LakKumar , Wickramasinghe V Pujitha , Moreira Edson Duarte , Fernando Asvini D , Gunasekera Dulanie , Luz Kleber , Venâncio da Cunha Rivaldo , Oliveira Ana Lucia , Rauscher Martina , Fan Huihao , Borkowski Astrid , Escudero Ian , Tuboi Suely , Lloyd Eric , Tricou Vianney , Folschweiller Nicolas , LeFevre Inge , Vargas Luis Martinez , Wallace Derek ,   for the TIDES Study Group, Fernando Asvini , Borja-Tabora Charissa , Sirivichayakul Chukiat , Yu Delia , Gunasekera Dulanie , López-Medina Eduardo , Rodriguez-Arenales Edith Johanna , Moreira Edson Duarte , Espinoza Felix , Velásquez Hector , Reynales Humberto , Luz Kleber , Jimeno Jose , Fernando LakKumar , Bravo Lulu , Vargas Luis Martinez , Rivera Luis , Alera Maria Theresa , Manacharoen Onanong , Lopez Pio , Kosalaraksa Pope , Pujitha Wickramasinghe V , Dietze Reynaldo , da Cunha Rivaldo Venâncio , Watanaveeradej Veerachai , Saez-Llorens Xavier , Brose Manja , Biswal Shibadas , Hutagalung Yanee , Tuboi Suely
Published: April 2024

Background

We explored the impact of prior yellow fever (YF) or Japanese encephalitis (JE) vaccination on the efficacy of Takeda's dengue vaccine candidate, TAK-003.

Methods

Children 4–16 years of age were randomized 2:1 to receive TAK-003 or placebo and were under active febrile surveillance. Symptomatic dengue was confirmed by serotype-specific reverse-transcription polymerase chain reaction. YF and JE vaccination history was recorded.

Results

Of the 20 071 children who received TAK-003 or placebo, 21.1% had a YF and 23.9% had a JE vaccination history at randomization. Fifty-seven months after vaccination, vaccine efficacy (95% confidence interval) was 55.7% (39.7%–67.5%) in those with YF vaccination, 77.8% (70.8%–83.1%) for JE vaccination, and 53.5% (45.4%–60.4%) for no prior YF/JE vaccination. Regional differences in serotype distribution confound these results. The apparent higher vaccine efficacy in the JE vaccination subgroup could be largely explained by serotype-specific efficacy of TAK-003. Within 28 days of any vaccination, the proportions of participants with serious adverse events in the YF/JE prior vaccination population were comparable between the TAK-003 and placebo groups.

Conclusions

The available data do not suggest a clinically relevant impact of prior JE or YF vaccination on TAK-003 performance. Overall, TAK-003 was well-tolerated and efficacious in different epidemiological settings.

Clinical Trials Registration.  NCT02747927.
A Qualitative Descriptive Exploration of the Experiences of Burn Therapists
Authors: Yelvington Miranda L , Wood Rachel E , Corson Tyler , Hu Jiale , Reynolds Stacey
Published: April 2024

Exposure to patients who have experienced major traumatic events places burn therapists at risk of developing high levels of anxiety and stress, directly impacting their quality of life. Poor professional quality of life has been associated with negative physical and emotional characteristics in healthcare professionals and may subsequently influence patient safety and satisfaction, job retention, and productivity. The purpose of this study was to understand and describe the experiences of occupational and physical therapists who provide acute therapy to people who have sustained burn injuries. Semistructured interviews were completed with 10 participants (8 females and 7 physical therapists) for this qualitative descriptive study. Conventional content analysis was used to analyze the data collected from semistructured interviews. Six themes emerged after content analysis: (1) the importance of therapeutic relationships to patient successes and therapists’ retention; (2) the autonomy and flexibility of burn therapists; (3) the impact of career longevity on compassion; (4) the uniqueness of burn team relationships and camaraderie; (5) the challenges of operating within the business of a healthcare system; and (6) the physical, mental, and emotional challenges to the burn therapists’ resiliency. This research brings to light the physical, mental, and emotional challenges that impact burn therapists’ resiliency, and which should be considered when creating programs to increase retention and professional quality of life in this professional population.