bluuebunny/crossref_metadata_2025 huggingface dataset:
Safety and performance of a novel synthetic biomimetic scaffold for iliac crest defect reconstruction during surgical treatment of pelvic girdle pain: a first-in-human trial
Authors: Giannoudis Peter V , Andrzejwski Paul , Chloros George , Hensor Elizabeth M A
Published: January 2025

Introduction

Surgical treatment of pelvic girdle pain (PGP) involves arthrodesis of sacroiliac (SI) and pubic symphysis joints. Fusion of pubic symphysis involves the implantation of an autologous iliac crest tricortical graft harvested from the iliac crest. The objective was to assess the safety of a novel synthetic graft substitute (b.Bone) for iliac crest reconstruction and to evaluate the results of PGP surgical treatment.

Sources of data

Consecutive participants undergoing pelvic fusion and requiring iliac crest reconstruction were enrolled and followed-up for 12 months in a prospective first-in-human clinical investigation. Adverse events were documented, and health-related quality of life was evaluated using EuroQol-5D-5L questionnaire. Iliac crest defect healing was evaluated by the Modified Lane and Sandhu radiological scoring system. In addition, relevant published peer-reviewed scientific articles identified from PubMed.

Areas of agreement

The EQ-5D-5L scores improved steadily reaching the highest point at 365 days. By 365 days complete healing of the bone defect was observed.

Areas of controversy

The management of PGP remains challenging with mixed results reported in the literature.

Growing points

While there is lack of consensus on how to manage PGP, the present study shows improved outcomes at one year following surgery. The synthetic b.Bone scaffold is a safe option with good healing outcomes for iliac crest defect reconstruction.

Areas timely for developing research

Although b.Bone synthetic scaffold found to be safe, further studies reporting on surgical treatment of PGP are required to confirm the findings in comparative trials.
Plastome sequences shed light on phylogenetic relationships, divergence time, and biogeography of the enigmatic endemism Eokochia saxicola (Amaranthaceae)
Authors: Galise Teresa Rosa , Strumia Sandro , Santangelo Annalisa , Cozzolino Salvatore , Cafasso Donata
Published: January 2025

Eokochia saxicola is one of the rarest plants in Europe and together with Spirobassia hirsuta they are the only Eurasian members of the Chenolea clade (Camphorosmeae, Amaranthaceae). This is a relict clade represented by only six species with a highly disjoint distribution in four continents. To investigate the phylogenetic origin and biogeographical history of E. saxicola we performed a plastome sequence analysis of E. saxicola and its related S. hirsuta and compared their plastomes with related Amaranthaceae plastomes. The investigation revealed a progressive plastid genome size reduction, from E. saxicola to S. hirsuta, ruling out a progenitor-derivative origin of the rare endemism from the widespread S. hirsuta. Plastome phylogenetic analysis also offered insights into the branching lineages of the Chenolea clade, revealing E. saxicola and S. hirsuta as sister taxa to Bassia. Camphorosmeae originated towards the end of the Oligocene, and Bassia emerged as a vicariant sister taxon to E. saxicola and S. hirsuta, with an estimated divergence time of 9.7 Mya. Ancestral area reconstruction and divergence time estimation suggest a vicariant origin for the endemic perennial E. saxicola and for the widespread annual S. hirsuta ~4 Mya in the European continent, a much more recent time than previously estimated.
Understanding the pathophysiology of Pseudomonas aeruginosa colonization as a guide for future treatment for chronic leg ulcers
Authors: Matheus Gabriela Gonzalez , Chamoun Michelle N , Khosrotehrani Kiarash , Sivakumaran Yogeesan , Wells Timothy J
Published: January 2025

Chronic leg wounds represent a major burden of disease worldwide, costing health care systems billions of dollars each year. Aside from the financial implications, they also impose a significant physical and psychosocial burden on the patient, their relatives and/or carers, and the community. Whilst measures such as maintenance of wound hygiene, debridement, dressings and compression are the current standard of care, complete healing is not always achievable and ulcer recurrence is common. Thus, there is still a gap to breach in terms of understanding the intricate pathophysiology of chronic wounds and the role this plays on treatment and management. Pseudomonas aeruginosa has been linked to poor wound healing, with the pathogen being frequently isolated from chronic leg ulcers. Characterized by its multi-drug resistance, targeting P. aeruginosa requires the development of novel therapeutic options. Thus, the aim of this literature review is to describe the pathophysiology of P. aeruginosa in chronic leg ulcers and discuss novel treatment strategies. Here, we describe the key molecular mechanisms driving the observed clinical effect of P. aeruginosa on wounds and discuss novel strategies of molecular targeting of this common bacteria, establishing new approaches that could benefit patients with chronic hard to heal wounds.
Lance Taylor (1940–2022) Retrospective: A Structuralist and Worldly Philosopher of Our Times
Authors: Dutt Amitava Krishna , Rada Codrina
Published: January 2025

Lance Jerome Taylor was a leading thinker in development economics and heterodox macroeconomics. He passed away at age 82, leaving behind a unique and rich legacy of seminal contributions to economics, and legions of scholars he mentored over more than five decades. This retrospective article is a tribute to his contributions to development economics and heterodox macroeconomics. We concentrate on certain aspects of his work to reflect both continuity and change during the different phases of his scholarship over time, and to allow us to focus on what, in our view, may well be his most influential and lasting contributions.
Measuring the size and severity of the integrated cyber attack surface across US county governments
Authors: Harry Charles , Sivan-Sevilla Ido , McDermott Mark
Published: January 2025

Limited methodologies to measure, enumerate, aggregate, and evaluate the cyber attack surface of US county governments prevent the full estimation of the importance of local government cybersecurity to national resilience. Our study aims to address this gap. We further develop existing OSINT-based methodologies to measure the attack surface and assess the size and vulnerability of publicly accessible county infrastructures. By collecting data on 42 735 Internet-facing devices across 3095 US county governments (98% of all counties), we show, for the first time, variations in size, diversity, and vulnerability of exposed county government attack surfaces. We develop and compare service- and Common Vulnerability Exposure (CVE)-based measures for attack surface diversity and severity, each showing different correlation trends with county population. We also highlight the lack of correlation between density of CVEs and likelihood of exploitation and develop measures to quantify the risk, revealing the impact of county government vulnerability on national cyber resilience. Previously studied as islands of insecurity, our novel empirical approach holistically estimates potential county vulnerability to common attack vectors upon service misconfiguration and aggregates CVEs, their severity, and probability of exploitation across county infrastructures, shedding light on the integrated and aggregated attack surface exposed across US county governments.
Long-term pulse pressure trajectories and risk of incident atrial fibrillation: the Tromsø Study
Authors: Sharashova Ekaterina , Gerdts Eva , Ball Jocasta , Schnabel Renate B , Stylidis Michael , Tiwari Sweta , Mathiesen Ellisiv B , Wilsgaard Tom , Løchen Maja-Lisa
Published: January 2025

Background and Aims

Sex-based differences in the association of long-term trends in pulse pressure with future risk of atrial fibrillation (AF) have been explored using data from the population-based Tromsø Study 1986–2016.

Methods

Women (n = 8331) and men (n = 7638) aged ≥20 years who attended at least two of the three Tromsø Study surveys conducted between 1986 and 2001 (the exposure period) were followed up for incident AF throughout 2016 (the follow-up period). Pulse pressure ≥60 mmHg was considered elevated. Group-based trajectory modelling and Cox regression were used for statistical analyses.

Results

Three long-term trajectory groups for pulse pressure were identified: Group 1 had normal pulse pressure throughout the exposure period, Group 2 had normal pulse pressure at the beginning and elevated pulse pressure at the end of the exposure period, and Group 3 had elevated pulse pressure throughout. Over the follow-up period, 568 (6.8%) women and 798 (10.5%) men developed AF. After adjustment for potential confounders at baseline, the long-term trajectory groups for elevated pulse pressure were associated with increased risk of AF in women, but not in men. In women, the adjusted hazard ratios of AF were 1.60 (95% confidence interval: 1.23, 2.09) for trajectory Group 2 and 2.78 (1.93, 4.02) for trajectory Group 3, compared with Group 1.

Conclusions

Long-term elevated pulse pressure trajectories were independently associated with increased risk of AF in women, but not in men. Our findings call for further investigations to understand the mechanisms behind these sex-based differences.
First-in-human trial of atrial fibrillation ablation using real-time tissue optical assessment to predict pulsed field lesion durability
Authors: Martins Raphael P , Papiashvili Giorgi , Sabirov Askar , Sabirov Sherzod , Herranz David , Bailleul Christophe , Verma Atul
Published: January 2025

Aims

Loss of bipolar electrograms immediately after pulsed field ablation (PFA) makes lesion durability assessment challenging.

Objective

The aim of this trial (NCT 06700226) was to evaluate a novel ablation system that can optically predict lesion durability by detecting structural changes in the tissue during ablation.

Methods and results

Patients with paroxysmal atrial fibrillation underwent pulmonary vein isolation (PVI) using PFA (AblaView®, MedLumics). Using polarization-sensitive optical coherence reflectometry (PS-OCR), reflective characteristics of myocardial tissue and visualization of real-time contrast between healthy tissue and ablated tissue using a drop in tissue birefringence (BiR) was assessed. Wide antral PVI was performed using single point irrigated PFA (unipolar, 1800V, 3 trains, 21 s). Remapping was performed at 3 months. Primary efficacy outcome was the ability of PS-OCR to predict lesion durability at 3-month remapping. Serious adverse events were recorded. Ten patients were included. In total, 38/40 PVs could be isolated with the system. The mean drop of BiR was 17.3 ± 11.5%. Dragging across the ablation lines showed a persistent drop in BiR. During the remap procedures (8/10 patients ablated only with PFA), 12 PVs (37.5%) were found to be electrically reconnected. The mean loss of BiR during all PFA for durable lesions was 20.9%, while only 10.1% BiR loss was observed during the index ablation for reconnected areas (P < 0.001). None of the points with ≥17% loss of birefringence was found to be reconnected.

Conclusion

This first-in-human study supports the use of real-time drop in tissue BiR for lesion assessment and durability during PFA delivery, and its procedural safety.
Etiology and hemodynamic patterns of orthostatic hypotension in a tertiary syncope unit
Authors: Johansson Madeleine , Gagaouzova Boriana S , van Rossum Ineke A , Thijs Roland D , Hamrefors Viktor , van Dijk J Gert , Fedorowski Artur
Published: January 2025

Background

Orthostatic hypotension (OH) is an important differential diagnosis in unexplained syncope. Neurogenic OH (nOH) has been postulated to differ from non-neurogenic OH (non-nOH), yet pathophysiological differences are largely unexplored. We aimed to investigate etiology and tilt table test (TTT)-induced hemodynamic responses in symptomatic OH patients.

Methods

We performed a retrospective study analyzing patients referred for unexplained syncope or highly symptomatic orthostatic intolerance with TTT-verified classical OH (cOH). Medical records were analyzed for the presumptive etiology of cOH. Fifty-two patients (mean age 73±9 years, 46% women) with good quality TTT recordings were divided into three groups on clinical grounds: nOH, non-nOH, and mixed OH. The log-ratio (LR) method was applied to compare the decrease in mean arterial pressure (MAPLR) and corresponding contributions of heart rate (HRLR), stroke volume (SVLR) and total peripheral resistance (TPRLR) during the upright phase of TTT.

Results

The prevalence of cOH was 12 (23%) nOH, 14 (27%) non-nOH and 26 (50%) mixed OH. No difference in MAPLR was observed among the three groups during the 4th upright minute of TTT (nOH: -0.10±0.04 vs. non-nOH: -0.07±0.05 and vs. mixed OH: -0.06±0.05, p=0.10). The contributions of HRLR, SVLR and TPRLR to the drop in MAPLR did not differ between groups (all p>0.05).

Conclusions

One-half of highly symptomatic OH patients had mixed OH, whereas one-quarter had either pure neurogenic, or non-neurogenic OH, respectively. Different forms of OH were indifferentiable based on hemodynamic responses during TTT, questioning the clinical utility of such classification. Larger studies are needed to confirm these findings.
Mammalian retinal specializations for high acuity vision evolve in response to both foraging strategies and morphological constraints
Authors: Kopania Emily E K , Clark Nathan L
Published: January 2025

Vision is a complex sensory system that requires coordination among cellular and morphological traits, and it remains unclear how functional relationships among traits interact with ecological selective pressures to shape the evolution of vision. Many species have specialized high visual acuity regions in the retina defined by patterns of ganglion cell density, which may evolve in response to ecological traits. For example, ganglion cell density can increase radially towards the center of the retina to form an area centralis, which is thought to improve acuity towards the center of the visual field in predators. Another example is the horizontal streak, where ganglion cells are dense in a horizontal pattern across the retina, which is thought to be beneficial in horizon-dominated habitats. At the morphological level, many have proposed that predation selects for high orbit convergence angles, or forward-facing eyes. We tested these hypotheses in a phylogenetic framework across eutherian mammals and found support for the association between the horizontal streak and horizon-dominated habitats. However, we did not find a significant association between orbit convergence and predation. We also tested if retinal specializations evolve in response to orbit convergence angles. We found that horizontal streaks were associated with side-facing eyes, potentially facilitating panoramic vision. Previous studies observed that some species with side-facing eyes have an area centralis shifted towards the temporal side of the retina, such that the high acuity region would project forward, but this relationship had not been tested quantitatively. We found that the temporal distance of the area centralis from the center of the retina was inversely correlated with orbit convergence, as predicted. Our work shows a strong relationship between orbit convergence and retinal specializations. We find support that both visual ecology and functional interactions among traits play important roles in the evolution of ocular traits across mammals.
A male-biased sex ratio increases the opportunity for precopulatory sexual selection but does not change the Bateman gradient
Authors: McDonald Grant C , Edmunds Danielle , Morimoto Juliano , Wigby Stuart , Perry Jennifer C
Published: January 2025

Theory predicts that the sex ratio within populations should influence the strength of sexual selection, and sex ratio is often used as a proxy for sexual selection. However, recent studies challenge this relationship. We manipulated adult sex ratios in Drosophila melanogaster to comprehensively investigate the relationship between sex ratio and sexual selection. Consistent with theory, we found stronger sexual selection in males than females and an increased variance in male reproductive success (the opportunity for selection) in male-biased sex ratios. In addition, males faced more intense sperm competition in male-biased sex ratios, although the structure of sexual networks was largely invariant to sex ratio. Despite this, we show that sex ratios did not influence sexual selection in males as measured by the Bateman gradient. We leverage randomized null models to reconcile these results and show that the higher male reproductive variance in male-biased sex ratios may be explained by random chance in mating, rather than competitive mechanisms. Our findings indicate that caution is warranted over the long-standing assumption that sex ratio bias is a good proxy for the strength of sexual selection.
Loneliness and biomarkers of Alzheimer’s disease, axonal damage, and astrogliosis: A coordinated analysis of two longitudinal cohorts
Authors: Terracciano Antonio , Walker Keenan A , An Yang , Bilgel Murat , Sutin Angelina R , Luchetti Martina , Karakose Selin , Stephan Yannick , Blennow Kaj , Zetterberg Henrik , Ashton Nicholas J , Karikari Thomas K , Kac Przemysław R , Moghekar Abhay R , Thambisetty Madhav , Ferrucci Luigi , Resnick Susan M
Published: January 2025

Objectives

Loneliness is associated with an elevated risk of dementia. There is mixed evidence from imaging studies on whether loneliness is associated with neuropathology in dementia-free adults. This study tests whether loneliness is associated with plasma neurobiomarkers of amyloid (Aβ42/Aβ40), phosphorylated tau 181 (pTau181), neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) and imaging measures of amyloid and tau.

Methods

Participants were cognitively unimpaired older adults from the Baltimore Longitudinal Study on Aging (BLSA; N=1,028 individuals and up to 2,277 neurobiomarker measurements; Baseline mean age=66, SD=15 years) and the UK Biobank (N=1,263 individuals and up to 2,526 neurobiomarker measurements; Baseline mean age=60, SD=7 years). Single-item measures of loneliness and the Quanterix Single Molecule Array assays were used in both samples. In a subset of BLSA participants, positron emission tomography (PET) was used to assess cerebral amyloid burden (n=220) and tau in the entorhinal cortex (n=102).

Results

In both samples and meta-analyses, loneliness was unrelated to plasma measures of Aβ42/Aβ40, pTau181, NfL, and GFAP. Changes in loneliness were also unrelated to changes in the plasma neurobiomarkers, and no consistent evidence of moderation by age, sex, or APOE ε4 allele was found. Loneliness was also unrelated to PET based measures of amyloid and tau.

Discussion

This study found no associations between loneliness and measures of Alzheimer’s disease pathology, axonal damage, or astrogliosis.
The outcome of diabetic retinopathy health education program in patients with type 2 diabetes mellitus: a quasi-experimental study
Authors: Rif’atunnailah Mat Isa , Mei-Chan Chong , Wan Ling Lee , Tajunisah Iqbal , Mohd Iman Saiful Suhardi , Thandar Soe Sumaiyah Jamaludin , Nurul Afieda Roslim
Published: January 2025

Diabetic retinopathy (DR) may develop into sight-threatening DR and vision loss if early intervention is not carried out. This study was aimed to assess the effectiveness of DR health education program for patients with type 2 diabetes mellitus (T2DM). The quasi-experimental research design was applied. The intervention group underwent a web-based DR health education program while the control group was followed up the usual way at an ophthalmology clinic for 1 year. Data were analysed using descriptive statistics, repeated measures ANOVA and general linear model to evaluate the mean difference between groups. A total of 180 patients with T2DM were enrolled in the study, with equal number in the control and intervention groups, respectively, with 28% of dropout rate. There was a significant mean difference in knowledge score [F (1178)  = 116.57, P = 0.001], diabetes self-care [F (1178)  = 116.57, P = 0.001] and visual-related quality of life [F (1178)  = 12.70), P = 0.001] between the control and the intervention groups. The intervention group scored the highest in all three categories. Educational interventions positively affected adherence to self-care and visual-related quality of life in type 2 diabetic patients as shown in this study. DRHEP should be considered an added benefit in T2DM management, starting with comprehensive care enrollment.
A Mean Value Theorem for Dirichlet Polynomials Associated With Primitive Dirichlet L-Functions
Authors: Baluyot Siegfred , Turnage-Butterbaugh Caroline L
Published: January 2025

Consider the family of Dirichlet $L$-functions of all even primitive characters of conductor at most $Q$, where $Q$ is a parameter tending to infinity. For $X=Q^{\eta }$ with $1<\eta <2$, we examine Dirichlet polynomials of length $X$ with coefficients those of the Dirichlet series of a product of an arbitrary (finite) number of shifted $L$-functions from the family. Assuming the Generalized Lindelöf Hypothesis for Dirichlet $L$-functions, we prove an asymptotic formula for averages of these Dirichlet polynomials. Our result agrees with the prediction of the recipe of Conrey, Farmer, Keating, Rubinstein, and Snaith for these averages. One may view our result as evidence for the “one-swap” terms in the recipe prediction for the general $2k$th moment of the family of Dirichlet $L$-functions.
One-year monitorization of the gut colonization by multidrug resistant bacteria in elderly of a single long-term care facility
Authors: Colmenarejo Cristina , Rodríguez-Jiménez Concepción , Navarro Francisco Javier , Mateo Ana Belén , Pellejero Eva María , Belda-Moreno Rosa María , Ureña-Méndez Roberto , Pérez-Serrano Raúl , Illescas Soledad , Ramón Muñoz-Rodríguez José , del Campo Rosa
Published: January 2025

Objective

To monitor the gut colonization by multidrug resistant (MDR) bacteria in residents of a single long-term care facility (LTCF) in relation to their clinical evolution, antibiotic consumption and mortality risk.

Methods

In a total of 187 voluntarily enrolled residents, five rectal swabs samples were recovered over 1 year. Selective media were used to isolate MDR bacteria. Clinical data related to infections, antibiotic consumption and mortality were recovered. Mortality risk among residents who were MDR colonized and non-colonized was compared by Kaplan–Meier curves.

Results

Globally, 25% of residents have gut colonization by ESBL-producing Escherichia coli with a lack of other pathogens such as Acinetobacter baumannii or Clostridioides difficile. Monitoring of ESBL-producing E. coli colonization for 1 year allowed to us to establish three categories among residents: 48.6% never colonized, 15.5% had a persistent colonization, and the remaining 35.8% presented intermittent colonization. The rates of mortality, infections and antibiotic exposure were comparable among ESBL-producing E. coli colonized and non-colonized residents, except for the intermittent colonization group in which a higher and statistically significant mortality rate was observed. As expected, urinary and respiratory tract infections were the most prevalent infectious pathologies in the LTCF, with amoxicillin/clavulanate and fluoroquinolones being the most prescribed antibiotics. A high percentage of ESBL-producing E. coli (28%), and fluoroquinolone resistance were detected in clinical samples.

Conclusions

The monitoring of gut colonization by MDR microorganisms in a single LTCF for 1 year demonstrated the predominance of ESBL-producing E. coli. Almost half of the residents were resistant to its colonization, whereas in 15.5% of them gut colonization was stable. Incidence of infectious episodes and antibiotic exposure were comparable between colonized and non-colonized subjects, but the group with the highest risk of mortality was that with intermittent colonization by ESBL-producing E. coli.
Principles and implementation strategies for equitable and representative academic partnerships in global health informatics research
Authors: Campbell Elizabeth , Bear Don’t Walk Oliver J , Fraser Hamish , Gichoya Judy , Wagholikar Kavishwar B , Kanter Andrew S , Holl Felix , Craig Sansanee
Published: January 2025

Objective

Developing equitable, sustainable informatics solutions is key to scalability and long-term success for projects in the global health informatics (GHI) domain. This paper presents key strategies for incorporating principles of health equity in the GHI project lifecycle.

Materials and Methods

The American Medical Informatics Association (AMIA) GHI Working Group organized a collaborative workshop at the 2023 AMIA Annual Symposium that included the presentation of five case studies of how principles of health equity have been incorporated into projects situated in low-and-middle-income countries and with Indigenous communities in the U.S. and best practices for operationalizing these principles into other informatics projects.

Results

We present five principles: (1) Inclusion and Participation in Ethical, Sustainable Collaborations; (2) Engaging Community-Based Participatory Research Approaches; (3) Stakeholder Engagement; (4) Scalability and Sustainability; (5) Representation in Knowledge Creation, along with strategies that informatics researchers may use to incorporate these principles into their work.

Discussion

Presented case studies and subsequent focus groups yielded key concepts and strategies to promote health equity that may be operationalized across GHI projects.

Conclusion

Equitable, sustainable, and scalable GHI projects require intentional integration of community and stakeholder perspectives in project development, implementation, and knowledge creation processes.
Whole stillage inclusion level influences in vitro fiber digestibility and ruminal fermentation of tall fescue hay
Authors: Ajayi Happiness J , Davis Brittany E , Lehmkuhler Jeffrey W , Harmon David L , Jiang Yun , Trotta Ronald J
Published: January 2025

With the growing bourbon industry in the southeastern U.S. leading to increased production of liquid distillery byproducts, there is a pressing need to explore sustainable uses for whole stillage [containing residual grain (corn, rye, malted barley) and liquid after ethanol separation] in livestock nutrition. The objectives of this study were to evaluate the effects of increasing whole stillage inclusion on the in vitro fiber digestibility and ruminal fermentation of tall fescue hay. Ruminal contents were obtained from 2 ruminally cannulated Angus × Holstein steers (390 ± 4.49 kg BW) fed a basal diet consisting of 90% tall fescue hay and 10% cracked corn. Whole stillage was obtained from a local distillery, homogenized, and replaced water in the Goering and Van Soest buffer preparation at 0.00%, 9.06%, 18.1%, or 36.3% on a v/v basis to simulate ruminal fill of whole stillage under practical conditions. Tall fescue hay was used as the substrate and vessels were incubated for 48 h. Results were analyzed with the GLM procedure of SAS using polynomial contrast statements for statistical comparison. Increasing whole stillage inclusion linearly decreased (P = 0.002) apparent dry matter (DM) digestibility, with the lowest (quadratic: P = 0.03) coefficients for true DM and neutral detergent fiber (NDF) digestibility occurring at 36.3% whole stillage inclusion. The rate and extent of gas production, methane production, and total volatile fatty acid (VFA) concentration increased (P < 0.05) with increasing whole stillage inclusion. The final pH of the fermentation media linearly decreased (P < 0.001) with increasing whole stillage inclusion. The molar acetate, valerate, isovalerate, and isobutyrate proportions decreased (P < 0.05) with increasing whole stillage inclusion. The molar propionate proportion responded quadratically (P < 0.01), with the peak proportion occurring at 36.3% whole stillage inclusion. Increasing whole stillage inclusion linearly decreased (P < 0.001) the viable number of cellulolytic and 2-deoxyglucose-resistant cellulolytic bacteria in the fermentation media. Peptide- and amino acid-utilizing bacteria increased linearly (P < 0.001) and hyper-ammonia-producing bacterial concentration peaked (quadratic: P = 0.05) at 36.3% whole stillage inclusion. Increasing whole stillage inclusion in the in vitro ruminal media demonstrated negative effects on the fermentation of tall fescue hay, as indicated by decreased NDF digestibility, cellulolytic bacteria, pH, and branched-chain VFA proportions.
Nutrient use and methane emissions in growing beef fed different protein sources and a pasture-based diet
Authors: Christodoulou Christos , Kliem Kirsty E , Auffret Marc D , Humphries David J , Kirton Paul , Jalal Hassan , Newbold John R , Davison Nicholas , Smith Laurence G , Stergiadis Sokratis
Published: January 2025

This study investigated the effects of different protein sources on feed intake, nutrient, and energy utilization, growth performance, and enteric methane (CH4) emissions in growing beef cattle, also evaluated against a pasture-based diet. Thirty-two Holstein × Angus growing beef were allocated to four dietary treatments: a total mixed ration (TMR) including solvent-extracted soybean meal as the main protein source (n = 8), TMR with local brewers’ spent grains (n = 8), TMR with local field beans (n = 8), and a diet consisting solely of fresh-cut Italian ryegrass (GRA; n = 8). Every 4 wk, animals were moved to digestibility stalls within respiration chambers to measure nutrient intakes, energy and nitrogen (N) utilization, and enteric CH4 emissions. Feed intake (Calan gates), nutrient intakes, and CH4 emissions (GreenFeed) were also measured when animals were group-housed. In respiratory chambers, enteric CH4 yield per kg of dry matter intake (DMI), per kg of organic matter intake (OMI), and per kg body weight were lower (P < 0.05) for GRA. Feces and urine energy outputs were higher (P = 0.007 and P < 0.001, respectively) for GRA steers than concentrate-fed steers. Urinary nitrogen output (UNO, P = 0.026), manure (feces + urine) nitrogen output (MNO, P = 0.034), UNO/nitrogen intake (P = 0.002), and MNO/nitrogen intake (P = 0.006) were higher for GRA. During group-housing periods, CH4 emissions, measured by GreenFeed, were similar to those measured in chambers. Similar CH4 yield between treatments, expressed per kg digestible DMI and digestible OMI, may indicate that the lower diet digestibility was likely the reason for the reduced enteric CH4 emissions in pasture-based diets. The higher energy output and nitrogen losses, and the reduced nitrogen utilization for steers fed the fresh-cut ryegrass diet indicate less efficient energy and nitrogen utilization, which can be considered environmentally undesirable. The lower growth rates in the pasture-based system should also be accounted for when this is adopted for reducing production costs.
Comparative cardiovascular safety of romosozumab versus bisphosphonates in Japanese patients with osteoporosis: a new-user, active comparator design with instrumental variable analyses
Authors: Tominaga Ryoji , Ikenoue Tatsuyoshi , Ishii Ryosuke , Niihata Kakuya , Aita Tetsuro , Okuda Tadahisa , Shimizu Sayaka , Taguri Masataka , Kurita Noriaki
Published: January 2025

This study analyzed the association of romosozumab, a human monoclonal antibody with bone-forming and bone resorption-inhibiting effects, and bisphosphonates with the development of cardiovascular disease among patients with osteoporosis. A new-user design was employed to address selection bias, and instrumental variable analysis was used to address confounding by indication. Japanese patients aged ≥40 years, diagnosed with osteoporosis or experienced a fragility fracture, were admitted to medical facilities covered by a commercial administrative claims database, and newly prescribed romosozumab or bisphosphonates after the commercialization of romosozumab in Japan (March 4, 2019) were included based on verification of a 180-day washout period. Cardiovascular disease (myocardial infarction or stroke) was identified based on information regarding diagnosis, medical procedures, and drug codes. Facility-level prescription preference for romosozumab was used as an instrumental variable, defined as the proportion of romosozumab prescribed at the patient’s facility within 90 days prior to the index date. Of the 59 694 included prescriptions, 8808 were for romosozumab and 50 886 were for bisphosphonates. The mean age in the romosozumab group was higher than that in the bisphosphonates group (80.5 vs. 78.2 years, respectively), and most patients were females (85.3 vs. 80.2%, respectively). The incidence of cardiovascular disease within 1 year of prescription was 12.3 per 100 person-years for romosozumab versus 11.4 for bisphosphonates (unadjusted incidence rate ratio: 1.08, 95% confidence interval: 1.00–1.18). An instrumental variable analysis using the two-stage residual inclusion method yielded a hazard ratio of 1.30 (95% confidence interval: 0.88–1.90) for romosozumab compared with bisphosphonates over 1 year. Although possibly underpowered, this study showed that no definitive evidence of increased cardiovascular risk associated with romosozumab use compared with bisphosphonates was observed in patients with osteoporosis. These findings should be further validated by larger pharmacoepidemiological studies to alleviate clinicians’ concerns about romosozumab’s safety.
The Present and Future of the International Criminal Court
Authors: Hofmański Piotr
Published: January 2025

The author focuses on issues of key importance from the point of view of the future of international criminal justice. One of these is the desire to make the system of the Rome Statute more universal. Another issue is the scope of the jurisdiction of the International Criminal Court and the faulty triggering mechanism. The author postulates a return to the discussion on equipping the Court with universal jurisdiction and unification of the triggering mechanism in such a way that investigations into the crime of aggression are initiated in the same way as remaining investigations concerning other crimes are covered by the Court’s jurisdiction. The author considers the weakening of the readiness to cooperate with the Court, resulting from the tense political situation, to be a serious threat to the future of the Court.
Impact of nanostructured formulations for schistosomiasis treatment: a systematic review of in vivo preclinical evidence
Authors: de Castro Carvalho Silva Laís , Cunha dos Reis Luís Felipe , Malaquias Luiz Cosme Cotta , Carvalho Flávia Chiva , Novaes Rômulo Dias , Marques Marcos José
Published: January 2025

Background

Schistosomiasis is a neglected tropical disease caused by Schistosoma sp., and praziquantel (PZQ) is the first-line treatment. However, traditional PZQ formulations have low solubility and fast metabolism, limiting its effectiveness. Thus, nanoparticles have been proposed to improve the bioavailability and efficacy of poorly soluble antischistosomal drugs.

Aims

This systematic review used in vivo preclinical studies to map the available evidence and compare the efficacy of free PZQ and PZQ-based nanostructured formulations (N-PZQ) for schistosomiasis treatment.

Methods

PubMed, Embase, Scopus, and Web of Science were searched, and 1186 experimental studies published between 1974 and 2024 were screened. Parasitological, histopathological, pharmacokinetic, and toxicological outcomes were evaluated.

Results

Twelve relevant studies were identified exploring N-PZQ formulations based on liposomes, nanoliposomes, and nanocrystals. N-PZQ demonstrated better therapeutic efficacy than free PZQ, reducing parasite load, modifying oogram profiles, and down-regulating liver granuloma development (number and size). N-PZQ also exhibited improved pharmacokinetic profile, with enhanced bioavailability and longer half-life, as well as reduced toxicity (cytotoxicity, genotoxicity, and hepatotoxicity) compared to free PZQ.

Conclusion

PZQ-based nanostructured formulations represent a promising strategy to enhance schistosomiasis treatment by improving chemotherapy efficacy, optimizing antiparasitic responses, pharmacokinetics, and reducing drug toxicity.
Mid-quantile mixed graphical models with an application to mass public shootings in the U.S.
Authors: Merlo Luca , Geraci Marco , Petrella Lea
Published: January 2025

Mass public shootings in the U.S. have become a major public health hazard, impacting the safety and well-being of individuals and communities. Motivated by this pressing issue, we propose a mid-quantile mixed graphical model for investigating the intricacies of inter- and infra-domain relationships of this complex phenomenon, where conditional relations between discrete and continuous variables are modelled without stringent distributional assumptions using Parzen’s definition of mid-quantile. To retrieve the graph structure and recover only the most relevant connections, we consider the neighbourhood selection approach in which conditional mid-quantiles of each variable in the network are modelled as a sparse function of all others. We propose a two-step procedure to estimate the graph where, in the first step, conditional mid-probabilities are obtained semi-parametrically and, in the second step, the model parameters are estimated by solving an implicit equation with a LASSO penalty.
Performance of ChatGPT-4o in the diagnostic workup of fever among returning travellers requiring hospitalization: a validation study
Authors: Yelin Dana , Shirin Neta , Harris Itai , Peretz Yovel , Yahav Dafna , Schwartz Eli , Leshem Eyal , Margalit Ili
Published: January 2025

Background

Febrile illness in returned travellers presents a diagnostic challenge in non-endemic settings. Chat generative pretrained transformer (ChatGPT) has the potential to assist in medical tasks, yet its diagnostic performance in clinical settings has rarely been evaluated. We conducted a validation assessment of ChatGPT-4o’s performance in the workup of fever in returning travellers.

Methods

We retrieved the medical records of returning travellers hospitalized with fever during 2009–2024. Their clinical scenarios at time of presentation to the emergency department were prompted to ChatGPT-4o, using a detailed uniform format. The model was further prompted with four consistent questions concerning the differential diagnosis and recommended workup. To avoid training, we kept the model blinded to the final diagnosis. Our primary outcome was ChatGPT-4o’s success rates in predicting the final diagnosis when requested to specify the top three differential diagnoses. Secondary outcomes were success rates when prompted to specify the single most likely diagnosis, and all necessary diagnostics. We also assessed ChatGPT-4o as a predicting tool for malaria and qualitatively evaluated its failures.

Results

ChatGPT-4o predicted the final diagnosis in 68% [95% confidence interval (CI) 59–77%], 78% (95% CI 69–85%) and 83% (95% CI 74–89%) of the 114 cases, when prompted to specify the most likely diagnosis, top three diagnoses and all possible diagnoses, respectively. ChatGPT-4o showed a sensitivity of 100% (95% CI 93–100%) and a specificity of 94% (95% CI 85–98%) for predicting malaria. The model failed to provide the final diagnosis in 18% (20/114) of cases, primarily by failing to predict globally endemic infections (16/21, 76%).

Conclusions

ChatGPT-4o demonstrated high diagnostic accuracy when prompted with real-life scenarios of febrile returning travellers presenting to the emergency department, especially for malaria. Model training is expected to yield an improved performance and facilitate diagnostic decision-making in the field.
Velocity dispersion function evolution from strong lensing statistics
Authors: Ferrami G , Wyithe J Stuart B
Published: January 2025

The redshift and size distributions of galaxy-scale strong lenses depend on the evolution of early-type galaxies. We use this dependence to constrain the velocity dispersion function (VDF) evolution from the Strong Lensing Legacy Survey sample of lenses in the redshift range $0.25\lesssim z \lesssim 0.75$. Our modelling of the lens population includes lens identifiability given survey parameters, and constrains the evolution of the VDF based on the redshift distributions of sources and lenses as well as the distribution of Einstein radii. We consider five different assumptions for the reference VDF at redshift zero and two sets of scaling relations for the VDF. We find that in all cases the observed lens sample favours a slow evolution of both the VDF normalization factor and the VDF characteristic velocity with redshift which is consistent with a VDF that is constant in redshift for $z\lesssim 0.75$.
Real-world analysis of treatment patterns and survival outcome of glioblastoma patients in a German single-center study: Can survival rates of randomized controlled trials be achieved?
Authors: Paus Samuel , Hoffmann Johannes , Roeper Julia , Griesinger Frank
Published: January 2025

Background

The reported survival data for glioblastoma patients vary strongly between different studies. In our study, we therefore examined which data are applicable in a real-world population in a German center and how these real-world data perform in comparison to survival data presented in randomized controlled trials (RCTs).

Methods

Data of all patients treated with newly diagnosed glioblastoma in a single German center between 2010 and 2019 were analyzed and treatment patterns plus survival rates were matched to existing real-world data and results of RCTs.

Results

Two hundred thirty-three patients were analyzed. Median age was 63 years, f/m ratio was 1:162, and 73% of patients underwent surgery, while 27% had biopsy only. The extent of resection had a significant impact on overall survival (OS; P <.001), as well as age (P <.001), methylguanine methyltransferase methylation status (P <.001), and eastern cooperative oncology group performance status (P <.001). The median OS of our whole study population was 10.55 months. While a fictitious Stupp study cohort (built by using eligibility criteria of the EORTC-22981-26981 trial) with an OS of 14.3 months nearly achieved the survival results of the presented data from the EORTC-22981-26981 trial, the OS of the patients who did not fulfill the eligibility criteria was only 6.9 months.

Conclusion

Survival of patients with unfavorable prognostic factors is still poor and these patients are not represented in recent RCTs. Outcome data of RCTs can be transferred to real world cohorts, if in- and exclusion criteria are fulfilled, while outcome is significantly inferior in cohorts that do not fulfill these criteria.
Assessing the Impact of Messages About Reduced Nicotine Cigar Products Among People Who Use Little Cigars and Cigarillos: Insights From a Discrete Choice Experiment
Authors: Ntansah Charity A , Popova Lucy , Hardin James W , Kim Minji , Sterling Kymberle L , Reynolds Reed M , Hackworth Emily E , Ashley David L , Henderson Katherine C , Yang Bo , Thrasher James F
Published: January 2025

Introduction

The US Food and Drug Administration’s (FDA) pursuit of a low nicotine standard for cigarettes raises concerns that a focus on cigarettes may encourage people to use other combusted tobacco products, undermining the policy’s effectiveness. The FDA is considering expanding the policy to include cigar products, which will require effective messages for people who use those products.

Aims and Methods

In 2022, a discrete choice experiment was conducted with African American males and females and White males and females. Participants (n = 1722), aged 18–44 years and who had smoked little cigars and cigarillos (LCCs) in the past 30 days, evaluated seven message attributes about reduced nicotine content (RNC) LCCs (presence or absence of information on source, chemicals, harm, nicotine, addiction, quitting efficacy, and enjoyment) across 20 choice sets. Participants assessed two of three outcomes: affect toward the policy, perceived harm of RNC LCCs, and motivation to quit smoking LCCs.

Results

Messages listing the FDA as the source were selected as eliciting more positive affect toward the policy, increasing perceived harm and motivation to quit smoking LCCs. Source was the most influential attribute for selecting messages in terms of positive affect toward the policy and motivation to quit. Chemicals and harm attributes had the most substantial effect on selecting messages as increasing perceived harm.

Conclusions

Citing the FDA as a source may improve the perceived effectiveness of RNC communications for people who use LCCs. Misperceptions about presumed lower harms of RNC products can be corrected with information about their harm and chemical properties.

Implications

Our findings among people who use LCCs suggest that source information shown as the FDA logo can increase message effectiveness while also influencing risk perceptions and motivation to quit smoking LCCs. To address misperceptions about RNC LCC harms, educational messages should particularly consider incorporating information about chemicals and harms.
Co-occurring Change in Electronic Nicotine Delivery System (ENDS) and Cigarette Harm Perceptions and Use in Young Adults
Authors: Caouette Justin D , Epstein Marina , Halvorson Max A , Danzo Sarah , Kuklinski Margaret R , Oesterle Sabrina
Published: January 2025

Introduction

The use of electronic nicotine delivery systems (ENDS) may contribute to cigarette use and nicotine addiction by shifting perceptions and norms around tobacco, but little is known about whether or how ENDS use and norms are related to cigarette use and norms, particularly among young adults. This study tested two potential mechanisms by which END use may facilitate cigarette use: decreasing tobacco harm perceptions (desensitization) and increasing favorability of tobacco use (renormalization).

Aims and Method

Analyses included data from 2187 young adults in a longitudinal panel who reported any ENDS or combustible cigarette use at ages 21, 23, or 26. The sample was 53.6% male, 19.3% Hispanic, and 68.0% White. Parallel process latent growth models were fitted to test how change in ENDS use and harm perceptions about ENDS use co-occurred with change in cigarette use and harm perceptions about cigarette use across a 6-year period from ages 21, 23, and 26 (years 2014–2019).

Results

When ENDS harm perceptions decreased and ENDS use increased, cigarette harm perceptions decreased and the favorability of cigarettes increased. Decreases in ENDS harm perception were differentially associated with the likelihood of transition to cigarette use (an increase) and frequency of use when it occurred (a decrease).

Conclusions

Changing tobacco harm perceptions and favorability are two processes by which ENDS use may underlie transitions to cigarette use. Tobacco prevention messaging should emphasize the potential harms of ENDS use that could occur through shifting tobacco perceptions, especially among young adults who are not already frequent cigarette smokers.

Implications

Increasing favorability of ENDS (and increased ENDS use) may generalize to combustible cigarettes. Continued use of ENDS can increase risk of cigarette use when this exposure desensitizes nonsmoking young adults from the dangers of smoking and renormalizes pro-tobacco attitudes. Findings suggest that prevention messaging around tobacco products should emphasize the potential harms of ENDS use (including the increased likelihood of cigarette use after initiating ENDS), especially among young adults who are not already frequent cigarette smokers.