bluuebunny/crossref_metadata_2025 huggingface dataset:
Large-scale survival analysis with a cure fraction
Authors: Han Bo , Wang Xiaoguang , Sun Liuquan
Published: November 2024

With the advent of massive survival data with a cure fraction, large-scale regression for analyzing the effects of risk factors on a general population has become an emerging challenge. This article proposes a new probability-weighted method for estimation and inference for semiparametric cure regression models. We develop a flexible formulation of the mixture cure model consisting of the model-free incidence and the latency assumed by the semiparametric proportional hazards model. The susceptible probability assesses the concordance between the observations and the latency. With the susceptible probability as weight, we propose a weighted estimating equation method in a small-scale setting. Robust nonparametric estimation of the weight permits stable implementation of the estimation of regression parameters. A recursive probability-weighted estimation method based on data blocks with smaller sizes is further proposed, which achieves computational and memory efficiency in a large-scale or online setting. Asymptotic properties of the proposed estimators are established. We conduct simulation studies and a real data application to demonstrate the empirical performance of the proposed method.
Reversible electroporation for cancer therapy
Authors: Shiwani Taha , Singh Dhesi Simran , Wah Tze Min
Published: November 2024

Reversible electroporation (EP) refers to the use of high-voltage electrical pulses on tissues to increase cell membrane permeability. It allows targeted delivery of high concentrations of chemotherapeutic agents including cisplatin and bleomycin, a process known as electrochemotherapy (ECT). It can also be used to deliver toxic concentrations of calcium and gene therapies that stimulate an anti-tumour immune response. ECT was validated for palliative treatment of cutaneous tumours. Evidence to date shows a mean objective response rate of ∼80% in these patients. Regression of non-treated lesions has also been demonstrated, theorized to be from an in situ vaccination effect. Advances in electrode development have also allowed treatment of deep-seated metastatic lesions and primary tumours, with safety demonstrated in vivo. Calcium EP and combination immunotherapy or immunogene electrotransfer is also feasible, but research is limited. Adverse events of ECT are minimal; however, general anaesthesia is often necessary, and improvements in modelling capabilities and electrode design are required to enable sufficient electrical coverage. International collaboration between preclinical researchers, oncologists, and interventionalists is required to identify the most effective combination therapies, to optimize procedural factors, and to expand use, indications and assessment of reversible EP. Registries with standardized data collection methods may facilitate this.
Impact of genetic alterations on long-term outcomes in resectable intrahepatic cholangiocarcinoma: meta-analysis
Authors: Giannone Fabio , Del Zompo Fabio , Saviano Antonio , Pencreach Erwan , Schuster Catherine , Baumert Thomas F , Pessaux Patrick
Published: November 2024

Background

Intrahepatic cholangiocarcinoma is a public health threat because of its aggressiveness. Its genetic background differs from other biliary cancers. The aim of this study was to investigate the impact of genetic alterations on long-term outcomes.

Methods

PubMed, MEDLINE, Scopus, and Cochrane Library databases were systematically searched for studies assessing long-term outcomes after resection of intrahepatic cholangiocarcinoma according to genetic mutational profiling until 31 May 2022. The main outcome was the impact of genetic alterations on long-term outcomes in these patients. HR (95% c.i.) was used for effect size. Publication bias was investigated.

Results

A total of 24 retrospective studies were included. KRAS, IDH1/2, and TP53 were identified as the only three genes whose mutation correlated with survival (HR: 2.476, 95% c.i. 1.67–3.671, P < 0.01 for KRAS; HR: 0.624, 95% c.i. 0.450–0.867, P < 0.01 for IDH1/2; and HR: 2.771, 95% c.i. 2.034–3.775, P < 0.01 for TP53). The prevalence of KRAS and IDH1/2 mutations differed between western and eastern studies (P < 0.001 for both genes).

Conclusion

Determining the overall prevalence of the most common actionable and undruggable mutations may help to expand target therapy indications in the adjuvant setting. Inconsistent results have been found for some infrequent gene alterations; their rare involvement could potentially bias their prognostic meaning.
Divergent neurodegenerative patterns: Comparison of [18F] fluorodeoxyglucose-PET- and MRI-based Alzheimer’s disease subtypes
Authors: Wheatley Sophia H , Mohanty Rosaleena , Poulakis Konstantinos , Levin Fedor , Muehlboeck J Sebastian , Nordberg Agneta , Grothe Michel J , Ferreira Daniel , Westman Eric
Published: November 2024

[18F] fluorodeoxyglucose (FDG)-PET and MRI are key imaging markers for neurodegeneration in Alzheimer’s disease. It has been well established that parieto-temporal hypometabolism on FDG-PET is closely associated with medial temporal atrophy on MRI in Alzheimer’s disease. Substantial biological heterogeneity, expressed as distinct subtypes of hypometabolism or atrophy patterns, has been previously described in Alzheimer’s disease using data-driven and hypothesis-driven methods. However, the link between these two imaging modalities has not yet been explored in the context of Alzheimer’s disease subtypes. To investigate this link, the current study utilized FDG-PET and MRI scans from 180 amyloid-beta positive Alzheimer’s disease dementia patients, 339 amyloid-beta positive mild cognitive impairment and 176 amyloid-beta negative cognitively normal controls from the Alzheimer’s Disease Neuroimaging Initiative. Random forest hierarchical clustering, a data-driven model for identifying subtypes, was implemented in the two modalities: one with standard uptake value ratios and the other with grey matter volumes. Five hypometabolism- and atrophy-based subtypes were identified, exhibiting both cortical-predominant and limbic-predominant patterns although with differing percentages and clinical presentations. Three cortical-predominant hypometabolism subtypes found were Cortical Predominant (32%), Cortical Predominant+ (11%) and Cortical Predominant posterior (8%), and two limbic-predominant hypometabolism subtypes found were Limbic Predominant (36%) and Limbic Predominant frontal (13%). In addition, little atrophy (minimal) and widespread (diffuse) neurodegeneration subtypes were observed from the MRI data. The five atrophy subtypes found were Cortical Predominant (19%), Limbic Predominant (27%), Diffuse (29%), Diffuse+ (6%) and Minimal (19%). Inter-modality comparisons showed that all FDG-PET subtypes displayed medial temporal atrophy, whereas the distinct MRI subtypes showed topographically similar hypometabolic patterns. Further, allocations of FDG-PET and MRI subtypes were not consistent when compared at an individual level. Additional analysis comparing the data-driven clustering model with prior hypothesis-driven methods showed only partial agreement between these subtyping methods. FDG-PET subtypes had greater differences between limbic-predominant and cortical-predominant patterns, and MRI subtypes had greater differences in severity of atrophy. In conclusion, this study highlighted that Alzheimer’s disease subtypes identified using both FDG-PET and MRI capture distinct pathways showing cortical versus limbic predominance of neurodegeneration. However, the subtypes do not share a bidirectional relationship between modalities and are thus not interchangeable.
Theoretical study on stacking distance dependence of one- and two-photon absorption properties of phenalenyl π-dimer models
Authors: Yokoyama Masako , Kishi Ryohei , Kitagawa Yasutaka
Published: November 2024

Stacking distance (d) dependence of the peak positions and intensities of one-photon absorption (OPA) and two-photon absorption (TPA) spectra of phenalenyl π-dimer models was investigated theoretically. Excitation energies and transition dipole moments required to simulate the OPA and TPA spectra were evaluated at the extended multiconfigurational quasi-degenerate second-order perturbation theory (XMC-QDPT2) level. The first TPA peak intensity for the model with d = 3.0 Å, related to the electronic transition along the stacking direction, was enhanced by a two-order magnitude compared with that for the model with d = 6.0 Å. We also obtained diradical character (y)-dependent behavior of the TPA property for the first TPA peak predicted from the valence-bond configuration interaction method based on the two-site model.
Counter-representations in an Australian web drama: trans-Pacific repertoire and diasporic contradictions in No Ordinary Love
Authors: Oh David C
Published: November 2024

No Ordinary Love is a web drama written by Esther Fwati, a Zambian Australian actor-writer, and her friend, Helen Kim, a Korean Australian writer-director. The five-episode web drama, which claims to be “inspired” by Korean television, positions a diasporic story of multiracial, inter-diasporic love between a Zambian Australian woman and a Korean Australian man. Despite its short length, the web drama’s counter-representational choices weave together global media flows and diasporic interpretations of race and family in multicultural Australia. I argue that the show’s explicit counter-representational centering of a Black woman and an Asian man subverts gendered racialization, and its assertion of diasporic communities as commonplace disrupts ideas of Australia as White and Anglophone. However, its representation of immigrant family conflict displaces racism onto the immigrant mother that stands in contrast to Australia as a multicultural nation that is progressive in its acceptance of difference.
Cardiac cycle modulates alpha and beta suppression during motor imagery
Authors: Lai Giuseppe , Landi David , Vidaurre Carmen , Bhattacharya Joydeep , Herrojo Ruiz Maria
Published: November 2024

Previous interoception research has demonstrated that sensory processing is reduced during cardiac systole, an effect associated with diminished cortical excitability, possibly due to heightened baroreceptor activity. This study aims to determine how phases of the cardiac cycle—systole and diastole—modulate neural sensorimotor activity during motor imagery (MI) and motor execution (ME). We hypothesised that MI performance, indexed by enhanced suppression of contralateral sensorimotor alpha (8–13 Hz) and beta (14–30 Hz) activity, would be modulated by the cardiac phases, with improved performance during diastole due to enhanced sensory processing of movement cues. Additionally, we investigated whether movement cues during systole or diastole enhance muscle activity. To test these hypotheses, 29 participants were instructed to perform or imagine thumb abductions, while we recorded their electroencephalography, electrocardiogram, and electromyogram (EMG) activity. We show that imaginary movements instructed during diastole lead to more pronounced suppression of alpha and beta activity in contralateral sensorimotor cortices, with no significant cardiac timing effects observed during ME as confirmed by circular statistics. Additionally, diastole was associated with significantly increased EMG on the side of actual and, to a lesser degree, imagined movements. Our study identifies optimal cardiac phases for MI performance, suggesting potential pathways to enhance MI-based assistive technologies.
When emotion and time meet from human and rodent perspectives: a central role for the amygdala?
Authors: Doyère Valérie , Droit-Volet Sylvie
Published: November 2024

Initiated by a long stay of Valérie Doyère in the laboratory of Joseph LeDoux, a Franco–American collaborative group was formed around the topic of emotion and time perception in a comparative perspective between humans and non-human animals. Here, we discuss results from our studies on the mechanisms underlying time distortion under 2 conditions, timing of a threatening stimulus and timing of a neutral stimulus in the context of fear, with insights from neurodevelopment. Although the type of temporal distortion depends on the experimental situations, in both humans and rodents a high-arousal emotion automatically triggers acceleration of an “internal clock” system, an effect that may rely on the early maturing amygdala. Our studies, particularly in humans, also point to the role of attention and self-awareness in regulating the effect of fear on timing, relying on the prefrontal cortex, a late maturing structure. Thus, in line with LeDoux, while the amygdala may process all characteristics of events (including time) necessary to quickly trigger appropriate survival behaviors, some type of time distortions may rely on higher-order processing, some specific to humans. The extent of the network underlying threat-related time distortions remains to be explored, with species comparisons being a promising means of investigation.
Individual differences in functional connectivity during suppression of imagined threat
Authors: Westhoff Marlon , Vogelbacher Christoph , Schuster Verena , Hofmann Stefan G
Published: November 2024

Functional magnetic resonance imaging studies typically rely on between-person analyses. To examine individual differences in functional connectivity, we used Group Iterative Multiple Model Estimation and its subgrouping function to analyze functional magnetic resonance imaging data of 54 participants who were suppressing imagined future threat. A two-stage random-effects meta-analytic approach was employed to examine individual differences. In addition to generalizable connections between brain regions, we identified individual differences in personalized models suggesting different pathways through which individuals suppress future threat. Two subgroups with distinct connectivity patterns emerged: One subgroup (n = 29; 53.70%), characterized by an additional lagged connection from the right to the left posterior cingulate cortex, exhibited comparatively higher anxiety and less brain connectivity, whereas the other subgroup (n = 25; 46.30%), showing an additional connection from the left posterior cingulate cortex to the ventromedial prefrontal cortex, was associated with lower anxiety levels and greater connectivity. This study points to individual differences in functional connectivity during emotion regulation.
Cabotegravir Maintains Protective Efficacy in the Setting of Bacterial STIs: A Secondary Analysis of HPTN 083
Authors: Clement Meredith E , Hanscom Brett , Haines Daniel , Bazan Jose A , Chotirosniramit Nuntisa , Kofron Ryan , Mannheimer Sharon , Mayer Kenneth H , Torres Silva Mayara Secco , Soto-Torres Lydia , Rinehart Alex R , Rooney James F , Jennings A , Gomez-Feliciano K , McCauley Marybeth , Grinsztejn Beatriz , Landovitz Raphael J ,   for HPTN 083 Study Team, Chariyalertsak Suwat , Dunne Eileen F , Phanuphak Nittaya , Viet Ha Tran , Sued Omar , Losso Marcelo H , Kailas Esper G , Valdez Ramalho Jose , Madruga  , Riegel Santos Breno , Grinsztejn Beatriz , Hinojosa Boyer Juan Carlos , Antonio Valencia Javier , Huamani  , Gallardo-Cartagena Jorge A , Gonzales Pedro , Cabello Robinson , Middelkoop Keren , Overton E Turner , Oyedele Temitope , Liu Albert , Justman Jessica , Hurt Christopher , Reirden Daniel , Fichtenbaum Carl , Hall Christopher , Mayer Kenneth , Magnus Manya , van Dam Cornelius , Franks Julie , Kelley Colleen , Arduino Roberto C , Rompalo Anne , Swaminathan Shobha , Ellen Abdalian Sue , Van Tieu Hong , Bazan Jose , Frank Ian , del Rio Carlos , Gaur Aditya , Landovitz Raphael J , Clark Jesse , Novak Richard , Presti Rachel , Gulick Roy (Trip)
Published: November 2024

Background

Sexually transmitted infections (STIs) have been shown to facilitate HIV transmission and acquisition. HPTN 083, a global clinical trial, demonstrated superiority of long-acting cabotegravir (CAB-LA) versus daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) for HIV prevention among transgender women and cisgender men who have sex with men. This analysis assessed whether CAB-LA maintained protective efficacy when bacterial STIs (syphilis, rectal/urethral gonorrhea and chlamydia) were present.

Methods

STI events per 100 person-years (PY) were calculated, including by subgroups (age, race/ethnicity, gender, education, treatment arm, drug use, alcohol use, region/country, condom usage, partner number, marital status, baseline STI). Association between baseline factors and STI incidence was modeled using Poisson regression. Cox proportional hazards modeling with STI status as a time-varying covariate was used to evaluate potential interactions between STI status and the relative efficacy of CAB-LA vs. TDF/FTC.

Findings

Among 3,859 participants, overall STI incidence rate was 50.7 infections/100PY. STIs were diagnosed in 1,562 (40.5%) participants; 79% of STIs occurred in 25% of the participants. STI incidence was not different by PrEP arm. In the final multivariable model, age, region, race, education level, marital status, and baseline STI were associated with incident STI (p<0.05). HIV incidence was lower with CAB-LA vs. TDF/FTC with or without STIs (hazard ratios 0.37 and 0.31, respectively), with no significant interaction between STIs and the HR for HIV incidence (p = 0.75).

Conclusion

In a large PrEP trial with high STI incidence, CAB-LA maintained robust protective efficacy relative to TDF/FTC in the setting of bacterial STIs.
Long-Term Effectiveness of Financial Incentives for Not Prescribing Unnecessary Antibiotics to Children With Acute Respiratory and Gastrointestinal Infections: Japan's Nationwide Quasi-Experimental Study
Authors: Okubo Yusuke , Uda Kazuhiro , Miyairi Isao
Published: November 2024

Background

To address antibiotic overuse, the Japanese government implemented a novel financial incentive policy in 2018. The policy enables eligible healthcare facilities to claim ¥800 (approximately $5.7) per case wherein a rationale to not prescribe antibiotics is offered for children aged <3 years with acute upper respiratory tract infections or gastroenteritis. Although the short-term effect of this policy was observed in our previous study, its long-term effects have not been evaluated nationwide.

Methods

We conducted a quasi-experimental study using a staggered difference-in-differences design with propensity score matching. Data from 165 113 children born between April 2017 and March 2019 were extracted from 2 nationwide administrative databases. The study tracked these children until May 2022, comparing those exposed to the policy with those who were not.

Results

The introduction of financial incentives led to a 44.9% reduction (95% confidence interval, 41.1%–47.7%) in total antibiotic prescriptions within the first month and 19.5% reduction (8.7%–29.1%) over 48 months. Broad-spectrum antibiotic use also decreased by 24.4% (95% confidence interval, 14.0%–33.6%) over the same period. The policy did not result in increased hospitalizations, after-hours visits, or healthcare costs, but it was associated with a slight increase in the number of office visits. A dose-response relationship was observed, with reductions in antibiotic use leveling off after approximately 5 incentives.

Conclusions

Financial incentives effectively reduced antibiotic prescriptions in children without adverse health outcomes, demonstrating sustained benefits over 4 years. This antimicrobial stewardship intervention offers a scalable model for other countries aiming to curb antibiotic overuse and combat antimicrobial resistance.
Inflation targeting and the real exchange rate trend: theoretical discussion and empirical evidence for developed and developing countries
Authors: Nassif André , Feijó Carmem , Araújo Eliane , Leão Rafael
Published: November 2024

Economic literature shows evidence that a competitive real exchange rate (RER), i.e., slightly undervalued, is key for development in developing countries. This paper discusses the connections between inflation targeting (IT) regimes and RER trends in economies highly open to capital flows. Following Rodrik’s (2008. The real exchange rate and economic growth, Brookings Papers on Economic Activity, Washington, 2008, vol. 39, no. 2 (Fall), 365–439), the RER trend is estimated for a sample of 31 out of the 38 developed and developing countries that, by the final year of the period covered in this study (2019), had already adopted IT. Covering the period 2000–2019, we showed that all developed and Latin American developing countries had an RER overvaluation trend, while the European, Asian and African (South Africa) developing countries registered an undervaluation trend in the same period. Through a dynamic panel data model, we tested and validated the following hypotheses, which, to the best of our knowledge, are a seminal contribution. We found in Latin American developing countries, whose ITs are centred on the main objective of pursuing price stability, the RER overvaluation trend (a by-product of this monetary policy regime) is driven by higher interest rate differentials to the USA and is harmful to their economic growth. In developed countries, this trend is not explained by their IT framework but by their high per capita income level, which reflects their high average labour productivity and development pattern. Yet, the trend of RER undervaluation in Asian and European developing countries and South Africa reflects their governments’ ability to combine a more flexible IT regime with a floating but managed exchange rate system aimed at preserving a competitive and stable RER in the long term.
Central bank balance sheets under foreign exchange accumulation: insights from endogenous money theory and monetary policy implementation
Authors: Bozhinovska Simona
Published: November 2024

This article proposes to draw on the recent experiences of many central banks of advanced economies and the evolution of their operational frameworks in the new context of increased domestic liquidity when analyzing the operations of central banks that engage in exchange rate management and increase their official foreign reserves as a result. It argues that the theoretical literature on endogenous money set within the context of an open economy with an exchange rate objective needs to be amended to account for such developments, as it would be entirely possible for a central bank that accumulates substantial foreign reserves to adopt a floor system and thus maintain a near-perfect control over its policy interest rate without the need for any compensating measure. On the grounds of the reverse causation argument, establishing a direct link between the foreign reserves and the monetary base should not entail any quantitative effect on other economic variables.
The utility of brief instruments for depression screening in dialysis patients
Authors: Vázquez Isabel , Figueiras Adolfo , Salgado-Barreira Ángel
Published: November 2024

Background

Depression is a frequent but often underdiagnosed comorbid disorder in dialysis patients. The Beck Depression Inventory–Second Edition (BDI-II) is a reliable and valid instrument for depression screening but is relatively long for repeated use in clinical practice. The aim of this study was to compare the BDI-II with the shorter questionnaires Beck Depression Inventory–FastScreen (BDI-FS), the depression subscale of the Hospital Anxiety Depression Scale (HADS-D), the Mental Health (MH) scale of the 36-item Short Form Health Survey (SF-36) and two items of the MH (‘So down in the dumps that nothing could cheer you up’ and ‘Downhearted and blue’) to determine the most efficient instruments for screening depressive symptoms in dialysis patients.

Methods

A cross-sectional study was conducted involving patients from 14 health centres undergoing in-centre haemodialysis or peritoneal dialysis. All patients completed the BDI-II, HADS-D and MH scale. The sensitivity, specificity and positive and negative predictive values for each brief instrument were assessed relative to BDI-II ≥16.

Results

Of the 145 patients included in the study (mean age 62 years; 66% male), 24.8% had depressive symptoms (BDI ≥16). The cut-off points with the highest sensitivity and negative predictive value for BDI-FS were ≥3 (91.7% and 96.1%, respectively) and ≥4 (80.6% and 92.4%, respectively) and for the HADS-D these were ≥4 (91.7% and 95.8%, respectively) and ≥5 (83.3% and 92.6%, respectively). The cut-off points for the total MH and the two items (considered separately or together) resulted in lower sensitivity (<80%) and lower negative predictive values (<90%).

Conclusions

Both the BDI-FS and HADS-D are adequate screening tools for depression in the dialysis population. As the BDI-FS is easier to complete and score and enables identification of patients at risk of suicide, it may be the best alternative to the BDI-II for depression screening in dialysis patients in clinical settings.
Remote management of anaemia in patients with end-stage kidney disease using a wearable, non-invasive sensor
Authors: Steig Amy , Miller Forrest , Shreim Samir , Wilcox Jake , Sykes Carole , Whittaker David , Sivaprakasam Rajesh , Gupta Samit , Kuraguntla David
Published: November 2024

Anaemia is a prevalent complication in patients with end-stage kidney disease (ESKD) undergoing haemodialysis. This study evaluates the accuracy of the Alio SmartPatch™, a non-invasive remote monitoring device, in measuring haemoglobin (Hb) and haematocrit (Hct) levels in haemodialysis patients by comparing its results with standard blood-based laboratory methods. The results from 116 patients across multiple sites in the USA and the Kingdom of Jordan show that SmartPatch measurements align closely with standard blood-based laboratory methods, meeting clinically acceptable limits of agreement. The current standard methods of Hb and Hct measurements are invasive and require visits to clinical sites, whereas the FDA-cleared SmartPatch offers non-invasive measurement of these parameters up to 240 times per month, thereby enhancing personalized care and patient engagement. This study demonstrates the potential of remote monitoring technologies, such as the SmartPatch, to improve the management of ESKD-associated anaemia. Further research is warranted to evaluate the device's long-term outcomes and its impact across diverse patient populations.
The evaluation of kidney transplant candidates prior to waitlisting: a scoping review
Authors: Boerstra Brittany A , Pippias Maria , Kramer Anneke , Dirix Marie , Daams Joost , Jager Kitty J , Hellemans Rachel , Stel Vianda S
Published: November 2024

Before patients with kidney failure can undergo kidney transplantation, their suitability is assessed through a transplantation work-up. Variation in the transplantation work-up could contribute to inefficiency and inequality in accessing the transplant waiting list and kidney transplantation. We conducted a scoping review on the evaluation of kidney transplant candidates prior to waitlisting, investigating: (i) content of the transplantation work-up; (ii) contraindications to waitlisting; and (iii) organization of the transplantation work-up. A systematic search was conducted in Ovid Medline and Ovid EMBASE in collaboration with a medical information specialist. Studies investigating practice patterns since 2013 related to the evaluation of adults receiving their first kidney graft from a deceased donor were included. Results from 20 studies showed substantial variation in the evaluation of kidney transplant candidates. The content of the transplantation work-up differed between studied centers, yet common domains included screening for infections, heart disease, peripheral artery disease, and malignancy. Commonly reported contraindications to waitlisting were obesity and age-related factors. However, strict cut-off for BMI and age were used less. The organization of the transplantation work-up differed across studied centers with regard to referral and waitlisting decisions, screening and prioritization, and the setting of the transplantation work-up. Literature on the evaluation of kidney transplant candidates is limited, but our findings suggest substantial variation in pre-waitlisting practices among centers. This may contribute to differences in kidney transplantation access and outcomes between countries. Further research on pre-transplantation practices, specifically regarding the standardization of the transplantation work-up, is needed.
Testosterone variation in a semi-captive population of Asian elephants in Myanmar
Authors: Moullec Héloïse , Berger Vérane , Santos Diogo J , Ukonaho Susanna , Yon Lisa , Briga Michael , Nyein U Kyaw , Lummaa Virpi , Reichert Sophie
Published: November 2024

Hormones are known to be involved in life-history trade-offs as systemic signals that establish functional links among traits and regulate key behavioural and physiological transitions between states in organisms. Although major functions of many steroid hormones such as testosterone are conserved among vertebrates, circulating concentrations vary widely both within and across species, and the degree to which observed hormone concentrations mediate life-history responses to environmental variation is less understood. In this study, we investigated how faecal testosterone metabolite (FTM) concentrations varied with extrinsic and intrinsic factors. To do so, we took advantage of a 6-year period of longitudinal sampling of FTM, indicators of stress and oxidative status in a semi-captive population of Asian elephants (n = 3163 samples from 173 individuals) in Myanmar. We determined how the variation in FTM is associated with age, sex, origin (captive-born or wild-caught), seasonality of the environment, individual stress level [measured by faecal glucocorticoid metabolite (FGM) and heterophil to lymphocyte ratio (H/L)] and oxidative status (reactive oxygen metabolite concentrations and superoxide dismutase activity). We reported that FTM increased with age from juvenile to adulthood for both sexes, with higher FTM concentrations in males than females. Moreover, elephants showed significantly higher FTM concentrations during the hot season and monsoon than in the cold season. However, for the physiological indicators, we found contrasting results. While FTM concentrations were strongly positively correlated with FGM concentrations, FTM concentrations were not related to H/L ratios. Finally, we found no relationship between FTM and the oxidative status of individuals. Our study provides new insights on the factors associated with variation in testosterone concentrations—a key hormone for reproduction and fitness of individuals—in Asian elephants living in their natural environment, which has relevance for effective conservation measures of this endangered species.
Image-guided percutaneous revascularization of the coronary arteries
Authors: Alasnag Mirvat , Bardooli Fawaz , Johnson Tom , Truesdell Alexander G
Published: November 2024

The European Society of Cardiology recently updated guidelines on the management of chronic coronary syndromes upgrading the use of intracoronary imaging for complex percutaneous coronary interventions (PCI) to a class 1A recommendation. It is essential that the interventional community appreciate the additive value of intracoronary imaging over angiography alone—not only to obtain optimal acute PCI results but also to improve longer-term cardiovascular outcomes. The purpose of this manuscript is to review the latest evidence that informed the recent guideline recommendations and expand on the specific role of the different imaging modalities before, during, and after PCI.
External validation of EuroSCORE I and II in patients with infective endocarditis: results from a nationwide prospective registry
Authors: Heinen Floris J , Peijster Annelot J L , Fu Edouard L , Kamp Otto , Chamuleau Steven A J , Post Marco C , van der Stoel Michelle D , Keyhan-Falsafi Mohammed-Ali , van Nieuwkoop Cees , Klautz Robert J M , Tanis Wilco ,   the Cardiothoracic Surgery Registration Committee of the Netherlands Heart Registration, Bramer S , van Boven W J P , Vonk A B A , Koene B M J A , Bekkers J A , Hoohenkerk G J F , Markou A L P , de Weger A , Segers P , Porta F , Speekenbrink R G H , Stooker W , Li W W L , Daeter E J , van der Kaaij N P , Douglas Y L
Published: November 2024

OBJECTIVES

The primary objective was to externally validate EuroSCORE I and II in surgically treated endocarditis patients. The secondary objective was to assess the predictive performance of both models across sex, redo surgery, age, and urgency.

METHODS

Data were retrieved from the Netherlands Heart Registration. All patients with infective endocarditis who underwent cardiac surgery between 2013 and 2021 were included. Predictive performance was assessed by discrimination (area under the curve), calibration (calibration-in-the-large and calibration plots), and a decision curve analysis.

RESULTS

Two thousand five hundred and sixty-nine cases were included. Overall postoperative 30-day mortality was 10.2%. The area under the curve was 0.73 for EuroSCORE I and 0.72 for EuroSCORE II. Both models overpredict postoperative 30-day mortality, with observed-to-expected ratios of 0.37 and 0.69. EuroSCORE I overpredicts mortality across the full range, whereas EuroSCORE II overpredicts mortality only above a 20% predicted probability. We observed no significant differences in predictive performance across sex, redo surgery, or age. Discriminative capacity of EuroSCORE II was poor in emergency surgeries.

CONCLUSIONS

Both EuroSCORE models demonstrate acceptable discriminative capacity in IE patients. EuroSCORE I consistently overestimates mortality and should not be utilized in endocarditis patients. EuroSCORE II can be used in IE patients up to a predicted probability of approximately 20%, regardless of sex, redo surgery, or age. Beyond this point, the predicted mortality risk should be halved to approach the true mortality risk. EuroSCORE II should not be used for risk prediction in emergency endocarditis surgeries and patients should not be withheld from indicated surgical treatment solely based on high EuroSCOREs.
Access points to different levels of health care over 13 years. Utilization behaviour in a changing health care system. Results of a three-wave cross-sectional series in Austria
Authors: Kraxner Roland , Dorner Thomas E , Roth Dominik , Hoffmann Kathryn
Published: November 2024

Providing health care is a balancing act among human resources, financial pressures and system-intrinsic factors. Understanding the utilization behaviour of primary and secondary care facilities [general practitioners (GPs) vs. specialists, as well as in- and outpatient hospital care] is crucial for a country like Austria, which has free access to all levels of care. The aim of this study was to reassess access point consultations in relation to sociodemographic variables over time. The databases used for this cross-sectional analysis were the Austrian Health Interview Surveys 2006/07, 2014, and 2019, with sample sizes of 15 474, 15 770, and 15 461 persons, respectively. Analyses included patterns of utilization behaviour, multivariable logistic regression models, and diff-in-diff analyses highlighting differences between the observation periods. GP and secondary care consultations increased from 2014 to 2019. While there were fewer GP visits in 2014 than in 2006/07, GP consultation rates grew by 3.2% between 2014 and 2019. Secondary care utilization increased by 5.4%–8.2% between 2006/07 and 2019, with the highest growth in older and less-educated persons. Secondary-level utilization without prior GP visits decreased again in 2019 after peaking in 2014. Utilization of all access points increased over the entire observation period, especially regarding secondary-level care. Higher GP visit rates do not seem to result in a drop in secondary-level consultations. These results emphasize the coordinator role of primary care in ongoing structural health reforms in European countries, such as Austria.
De Novo Long-Read Genome Assembly and Annotation of the Mosquito Gut-Dwelling Fungus, Smittium minutisporum
Authors: Prakash Anusha , Wang Yan
Published: November 2024

Mosquito guts host a variety of microbes, yet fungi are often overlooked. Smittium (Harpellales, Zoopagomycota) comprises numerous species that are obligate symbionts residing in the hindgut of mosquito larvae. Despite their association with pathogen-bearing vectors, these fungal symbionts remain understudied, largely due to the lack of high-quality genome resources. This limitation has impeded a deeper understanding of their genome biology and adaptive strategies in relation to their mosquito hosts, which may hold significant epidemiological implications. To address this gap, we generated the first reference-quality genome assembly for this group of fungi, using PacBio HiFi long-reads for an axenic culture of Smittium minutisporum, originally isolated from the eastern treehole mosquito, Aedes triseriatus. The genome assembly consists of 53 contigs, spanning a total length of 32.5 Mb, and is predicted to encode 8,254 protein-coding genes, with repetitive regions constituting 25.22% of the genome. Notably, despite being highly contiguous and gap free, the Benchmarking Universal Single-Copy Ortholog analysis suggests a completeness score of 71.8%, implying unusual genome features, possibly shaped by adaptation and specialization within the mosquito gut. This high-quality genome resource will be invaluable for advancing our understanding of mosquito gut-dwelling fungi, their natural history, and their cryptic symbiosis with insect hosts.
Developing structures to support researchers studying health-harming industries
Authors: Pitt Hannah , Thomas Samantha , McCarthy Simone , van Schalkwyk May C I , Petticrew Mark , Randle Melanie , Daube Mike
Published: November 2024

It is well-documented that health-harming industries and the groups they fund use a range of tactics that seek to interfere with academic research. With the development of scholarship relating to the Commercial Determinants of Health (CDoH), an increasing number of public health researchers are working to examine the activities of health-harming industries and the impacts they have on health and equity. However, there has been limited research investigating the experiences of these researchers and the range of strategies that could be used to support them. This qualitative interpretivist study involved 10 online focus groups with 28 public health researchers (ranging from PhD students to emeritus professors) in Australia and the UK. The researchers worked on issues related to the alcohol, gambling, tobacco or ultra-processed food industries. Participants outlined a range of personal and professional risks relating to their research, including social media attacks, complaints to university personnel and funders, attempts to discredit their research, legal threats and freedom of information requests. Some described the impacts this had on their overall well-being, and even on their family life. They commented that current university systems and structures to support them were variable and could differ between individuals within institutions. This often left researchers feeling isolated and unsupported. Universities should recognize the risks to researchers working on issues relating to health-harming industries. They should proactively develop strategies and resources to inform and support researchers to conduct research that is important for public health and equity.
Iron Deficiency Anemia in Patients with Inflammatory Bowel Disease: A Call to Action to Improve Patient Care
Authors: Maness Sarah B
Published: November 2024

Lay Summary

There is an urgent need for gastroenterologists and other clinicians involved in inflammatory bowel disease patient care to emphasize the screening and treatment of iron deficiency anemia.
Forecasting and seasonal variability of the foot of the Shelfbreak Front in the Northern Middle Atlantic Bight
Authors: Silver Adrienne , Oliver Hilde , Gawarkiewicz Glen , Fratantoni Paula , Salois Sarah L
Published: November 2024

The Shelfbreak Front in the Northern Middle Atlantic Bight delineates the boundary between colder, fresher shelf water and warmer, saltier slope water. The location of the foot of the Shelfbreak Front, where the frontal isohalines and isopycnals intersect the bottom, is highly dynamic, impacting several commercial fisheries. In this work, we present new indices to quantify seasonal and interannual variability in the movement of the foot of the Shelfbreak Front. One index is generated from over three decades of observational Conductivity, Temperature, and Depth (CTD) data, and the other from GLORYS reanalysis fields. After detrending and removing seasonality, both indices capture similar variability and were found to be statistically significantly correlated with upstream along-shelf geostrophic velocities derived using satellite altimetry data. Using the lag correlation between the along-shelf geostrophic velocities from the Scotian Shelf to Georges Bank, skillful forecasts for the frontal indices were obtained up to three seasons in advance. This work provides a useful methodology for including variability of the foot of the Northern Middle Atlantic Bight Shelfbreak Front into ecosystem and stock assessment models using readily available near-real-time satellite altimetry data.
‘Market’ definition in ecosystems
Authors: Stylianou Konstantinos , Carballa-Smichowski Bruno
Published: November 2024

Despite the popularization of the concept of ‘ecosystems’ among academics and practitioners, ecosystems have so far failed to become a coherent unit of analysis in competition law. One of the reasons is that it is not yet apparent when ecosystem analysis should be preferred over standard market-based analysis, and we also lack empirical methodologies to define their boundaries. In this article we first describe contexts where formal definition of ecosystem boundaries (similar to market definition) is necessary or at least desirable to achieve quality analysis, and then describe methodologies on how to achieve that (hierarchical clustering, K-means clustering, network of complementarities, factor analysis, and snowball selection). Furthermore, we provide guidance on when each of the methodologies is pertinent. We describe the limitations of the substitutability, aftermarkets, and connected markets approaches in cases in which ecosystems are the main unit of analysis. Finally, we provide four examples of how, in such cases, these methodologies presented can be useful to practitioners: i) market inquiries, investigations, and pro-competition interventions; ii) designation of undertakings as having strategic market status; iii) conglomerate mergers and iv) calculation of fines and quantification of harm/effects.
Occurrence of Salmonella enterica in faecal sludge from Nigeria and genetic relatedness with strains associated with human infections in Africa
Authors: Jibril Abdurrahman Hassan , Dalsgaard Anders , Okeke Iruka N , Ibrahim Aliyu Musawa , Olsen John Elmerdahl
Published: November 2024

Aims

This study investigated occurrence of Salmonella in faecal sludge from public toilets in Nigeria and genetic relatedness of strains that have been reported to cause human infection across Africa.

Methods and results

The study collected 150 human sludge from public toilets and identified Salmonella through culture and PCR. Isolates were tested for antimicrobial susceptibility and sequenced using Illumina MiSeq. Draft sequences were compared with sequence data from Enterobase and GenBank. Twenty-four (16.0%) of sewage samples were positive for Salmonella [CI95 (10.2–21.8)]. Salmonella serotype Give [sequence type (ST) 516], Salmonella serotype Seftenberg (ST-14), and Salmonella serotype Chester (ST-411) were the most prevalent serovars found in 45.8%, 16.7%, and 16.7% of samples, respectively. Most of the isolates were sensitive to the antimicrobials tested, only one isolate of Salmonella serotype Derby showed resistance to ampicillin and cefazolin. Notably, 91.7% of the strains had the aac (6)-Iaa gene and point mutations in parC, gyrA, and acrB. Salmonella serotype Chester showed genetic relatedness with strains from Benin Republic and South Africa.

Conclusions

There is genetic relatedness of present strains and those associated with human infections in Africa.
Morphological variations in relation to sex and habitat in southern Mexico populations of the longarm river prawn Macrobrachium tenellum (Smith, 1871) (Decapoda: Caridea: Palaemonidae)
Authors: Julián-Caballero César Camilo , De los Santos-Romero Rodolfo , Ramírez-Ponce Andrés , García-Guerrero Marcelo U
Published: November 2024

The longarm river prawn, Macrobrachium tenellum (Smith, 1871), is an amphidromous species inhabiting rivers, estuaries, and coastal lagoons along the Pacific slope of the Western Hemisphere, having morphological differences depending on habitat. The species has an important ecological role, playing a crucial position in coastal-river equilibrium. There is nevertheless scarce information on morphological variations among specimens, which are influenced by factors such as sex and habitat. We investigated whether it is possible to detect such differences in the carapace and second pleonal pleuron between sexes and among three habitats (river, estuary, and lagoon) by using geometric morphometrics. Our results suggest that the size and shape of the carapace and pleura can effectively be distinguished between sexes based on morphological criteria. Significant differences in carapace size and shape were also detected across habitats, with less evident variations in the pleura. The findings suggest that rivers provide a suitable habitat for adult females, having a significantly larger carapace and second pleonal pleuron in this habitat. We identified three distinct ecophenotypes in females corresponding to the varying habitats: 1) river specimens possessing a robust carapace with a short, marked upcurved rostrum; 2) estuarine specimens exhibiting broader dorsal and antero-inferior regions with a thicker rostrum; 3) lagoon specimens having a slender carapace with a long, thin, upward-sloping rostrum. These variations are likely a result of indeterminate growth and adaptations to the specific hydrodynamics and substrates present in each habitat. This information is useful to understand how the environment has a significant effect on the shape and size of M. tenellum and provide useful insights for future research on the species of Macrobrachium.
When Diversity Backfires: The Asymmetric Role of Multicultural Diversity on Brand Perception
Authors: Uduehi Esther , Saint Clair Julian K , Hamilton Mitchell , Reed Americus
Published: November 2024

Brands are expanding their market to new consumers by displaying cultural diversity in marketing campaigns—but the risks are unclear. This article explores the role of the brand’s characteristics in multicultural diversity. Our findings suggest that when brands launch a new multicultural diversity campaign, it may be well-received if the brand’s original focus was on the needs of nonmarginalized consumers. However, for brands with a focus on the needs of marginalized consumers (i.e., marginalized-focused brands), such a campaign may be perceived as selling out, thereby negatively impacting consumers’ reactions. Six studies with Black and White U.S. consumers explore this novel “sellout effect” across various product categories and for consequential behaviors. Inclusion is identified as a key mechanism, mitigation strategies are explored, and implications for theory and practice are discussed. Findings highlight the importance of diversity marketing, understanding marginalization for consumers and brands, and the need for research that considers race and ethnicity.