bluuebunny/crossref_metadata_2025 huggingface dataset:
Trochanteric hip fractures treated surgically—outcome in a ten-year cohort of 46,121 patients from the Swedish National Hip Fracture Registry
Authors: Borg Tomas , Forssten Maximilian Peter , Mohammad Ismail Ahmad , Cao Yang , Mohseni Shahin
Published: January 2025

Objectives:

To compare postoperative mortality regarding 2 techniques in the treatment of trochanteric hip fractures (THFs).

Design:

Retrospective cohort study.

Setting:

National databases.

Patients:

All consecutive surgically treated THF cases between 2008 and 2017 were included. Pathological fractures or patients younger than 60 years were excluded.

Intervention:

Patients were grouped based on the surgical technique: sliding hip screw (SHS) or intramedullary (IM) nail. This data set was cross-referenced with a National Board of Health and Welfare's patient registry and a Cause of Death registry.

Main outcome measurements:

Mortality, comorbidities, and length of stay (LOS).

Results:

Forty-six thousand one hundred twenty-one cases were included. Twenty-five thousand eight hundred seventy-seven patients received a SHS, and 20,244 received an IM nail. Patients in the IM group were more often female (71.8% vs. 69.2%, P < 0.001), slightly less fit for surgery (American Society of Anesthesiologists score ≥3: 61.2% vs. 60.1%, P = 0.003), and more frail (Orthopedic Frailty Score ≥2: 54.2% vs. 52.8%, P = 0.005). Multifragment fractures were more prevalent in the IM nail group (66.6% vs. 32.0%, P < 0.001), which suffered from a higher comorbidity burden. After adjusting for potential confounders, no clinically significant differences in 7-day, 30-day, 90-day, or 1-year postoperative mortality were observed. Subgroup analyses focusing on 2-fragment and multifragment fractures could not detect any difference in mortality. LOS was 1 day shorter for the IM nail group as a whole.

Conclusions:

Based on 10 years of data including 46,121 patients with THF managed with SHS or IM nail, no difference was observed in mortality up to 1 year postoperatively, when comparing surgical technique. LOS was shorter for the IM nail group.
Assessment of a New CT Detector and Filtration Technology: Part 1 — X-ray Beam Characterization and Radiation Dosimetry
Authors: Barreto Izabella , Correa Nathalie , Moser Patricia , Tuna Ibrahim , Massini Tara , Rill Lynn , Arreola Manuel
Published: January 2025

Purpose:

This study evaluated beam quality and radiation dosimetry of a CT scanner equipped with a novel detector and filtration technology called PureVision Optics (PVO). PVO features miniaturized electronics, a detector cut with microblade technology, and increased filtration in order to increase x-ray detection and reduce image noise.

Methods:

We assessed the performance of two similar 320-detector CT scanners: one equipped with PVO and one without. Beam quality was measured by determining the half-value layer (HVL) and effective energy (E
eff) for both scanners using all tube voltages (80 kV, 100 kV, 120 kV, 135 kV) and bowtie filters (small, medium, large) available. Energy correction factors were identified for optically stimulated luminescent dosimeters (OSLDS) compared to a calibrated ionization chamber. Surface and internal doses were measured for an anthropomorphic CT angiography head phantom and a cadaver head scanned with CTDIvol matched as close as possible at the conventional (55.1 mGy) and PVO (55.4 mGy) CT scanners.

Results:

For all scan settings, the PVO scanner showed significantly higher HVL (range, 4.33–11.02 mm Al) and effective energy (range, 39.4–68.0 keV) values compared to the conventional scanner (HVL, 4.19–8.25 mm Al; effective energy, 38.4–55.2 keV). For equivalent CTDIvol values, the energy-corrected surface skin and lens doses were on average 6.7% lower with the PVO scanner than the conventional scanner (P < 0.01).

Conclusions:

PVO technology yielded higher HVL and effective energies and, for the same CTDIvol, resulted in lower surface organ doses, indicating a potential for reduced patient radiation exposure in clinical settings.
Assessment of a New CT Detector and Filtration Technology: Part 2—Image Quality in Phantoms, Cadavers, and Patients
Authors: Barreto Izabella , Stoddard Graham , Heshmat Anahita , Massini Tara , Tuna Ibrahim , Rill Lynn , Arreola Manuel
Published: January 2025

Purpose:

The purpose of this work was to evaluate the image quality of a commercial CT scanner equipped with a novel detector and filtration technology called PureVision Optics (PVO).

Methods:

CT number, noise, contrast-to-noise ratio (CNR), modulation transfer function (MTF), and noise power spectrum (NPS) were assessed using the ACR CT Accreditation phantom scanned with various acquisitions at 80 kV, 100 kV, 120 kV, and 135 kV, each with multiple CTDIvol values of 20 mGy, 40 mGy, and 65 mGy. Artifacts were evaluated in an anthropomorphic head phantom, a cadaver head, and in patient studies. Two neuroradiologists assessed image quality features in various patients who were examined with unenhanced brain CT on both scanners.

Results:

Compared with the conventional scanner, for the same CTDIvol, the PVO scanner produced 20.3% less image noise (P < 0.001), 18.9% higher CNR (P < 0.01), and 24.6% higher spatial resolution (P < 0.001). Streak artifacts were less severe with the PVO scanner for the phantom, cadaver, and patient scans (P < 0.05). Radiologists scored the PVO scanner as significantly better for visualization of the cerebrospinal fluid space over the cerebral sulci in high convexity, image noise in gray and white matter, and artifacts in the posterior fossa. They also significantly preferred the PVO scanner for visualization of the border between brain gray and white matter, cerebrospinal fluid space around the mesencephalon, and overall diagnostic acceptability.

Conclusions:

For matched CTDIvol values, the scanner equipped with PVO technology produced better objective and subjective image quality metrics in brain CT imaging compared with a conventional CT scanner without PVO. In clinical settings, PVO may allow for lower doses while enhancing imaging through dense areas, improving visualization of subtle details, and offering more effective options for examining obese patients.

This research received financial support from Canon Medical Systems USA. The study design and data were fully controlled by the coauthors, of which none are employees or consultants of Canon Medical Systems USA.
High-resolution 0.25 mm Detector CT Has Limited Impact on Right Adrenal Vein Detectability in Preprocedural Contrast Enhanced CT for Adrenal Venous Sampling
Authors: Morisaka Hiroyuki , Imaizumi Akira , Wumu Tihan , Ii Takanori , Araki Takuji , Onishi Hiroshi
Published: January 2025

Objective:

This study aims to identify factors associated with the detectability of the right adrenal vein (RAV) on preoperative contrast-enhanced CT scans of adrenal venous sampling (AVS) in the era of high-resolution CT (HRCT).

Materials and Methods:

In this retrospective study, 36 patients (15 men and 21 women; mean age, 56 y) who underwent preoperative contrast-enhanced CT [11 patients in HRCT with 0.25 mm detector matrix (Cannon Medical Systems) and 25 patients in conventional multidetector CT with 0.5 mm matrix] were included. A contrast agent dose of 600 mgI/kg was injected, and CT images were acquired at a fixed scan delay of 50 and 80 seconds. Adrenal venography and venous sampling were performed for the diagnosis of suspected primary hyperaldosteronism. The qualitative detectability of RAV on preoperative CT was assessed with adrenal venography as a reference. Clinical and imaging factors associated with a good detectability of RAV were analyzed via regression analysis. Optimal acquisition timing was assessed by analyzing the time-intensity curve and contrast enhancement pattern of the inferior vena cava using CT data from a separate cohort (n=5).

Results:

The qualitative detectability of RAV was deemed good in 15 patients and poor in 21 patients. Regression analysis revealed that only heterogeneous enhancement of inferior vena cava with bolus high attenuation, corresponding to an optimal acquisition timing from time-intensity curve analysis, was associated with a good detectability of RAV (odds ratio, 5.06). The use of HRCT was not statistically significant.

Conclusions:

Optimal acquisition timing is a crucial factor for the detectability of RAV in preprocedural CT for AVS, while high-resolution 0.25 detector CT appears to have limited significance.
Triangular Margin: Reliable Imaging Feature of Fibrous Dysplasia in Long Bones?
Authors: El Kandoussi Amine , Staffa Steven J. , Ömeroğlu Emre , Hung Yin P. , Bauer Fabian , Lozano-Calderon Santiago , Chang Connie Y.
Published: January 2025

Objective:

To determine the utility of a triangular margin as an imaging diagnostic feature for fibrous dysplasia.

Materials and Methods:

We retrospectively reviewed all surgically biopsied or managed benign and malignant bone tumors by a single orthopedic oncologist over 19 years (2003 to 2022). A musculoskeletal radiologist and an orthopedic oncologist, both with >10 years of experience, retrospectively evaluated all imaging in consensus. Groups were compared using the χ2 test.

Results:

There were a total of 152 subjects [mean age 49±21 (range 7.8 to 91) years]; 80 (53%) females and 72 (47%) males. There were 52 subjects with fibrous dysplasia, 31 subjects with other benign bone tumors, and 69 subjects with malignant bone tumors. The sensitivity and specificity of a triangular margin for distinguishing fibrous dysplasia from other benign or malignant bone tumors were 74% and 96% on radiographs, 73% and 100% on CT, and 78% and 91% on MRI, respectively. The triangular margin was more prevalent in fibrous dysplasia (85%) versus benign (16%) and malignant (1.6%) primary bone tumors in all 3 modalities (P<0.001). Multivariate analysis of the aggregated imaging data suggests that if a lesion has a triangular margin, it is 14 times more likely to be a fibrous dysplasia than another benign bone tumor (P=0.012).

Conclusions:

The presence of a triangular margin could increase a radiologist’s confidence that a bone tumor is fibrous dysplasia.
Deep Learning–Based Precontrast CT Parcellation for MRI-Free Brain Amyloid PET Quantification
Authors: Choo Kyobin , Joo Jaehoon , Lee Sangwon , Kim Daesung , Lim Hyunkeong , Kim Dongwoo , Kang Seongjin , Hwang Seong Jae , Yun Mijin
Published: January 2025

Purpose

This study aimed to develop a deep learning (DL) model for brain region parcellation using CT data from PET/CT scans to enable accurate amyloid quantification in 18F-FBB PET/CT without relying on high-resolution MRI.

Patients and Methods

A retrospective dataset of PET/CT and T1-weighted MRI pairs from 226 individuals (157 with mild cognitive impairment or dementia and 69 healthy controls) was used. The dataset was split into training/validation (60%) and test (40%) sets. Utilizing auto-generated segmentation labels, 3 UNets were independently trained for multiplanar brain parcellation on CT and subsequently ensembled. Amyloid load was measured across 46 volumes of interest (VOIs), derived from the Desikan-Killiany-Tourville atlas. Dice similarity coefficient between the proposed CT-based DL model and MRI-based (FreeSurfer) method was calculated, with SUVR comparison using linear regression analysis and intraclass correlation coefficient. Global SUVRs were also compared within groups with clinical dementia ratings (CDRs) of 0, 0.5, and 1.

Results

The DL-based CT parcellation achieved mean Dice similarity coefficients of 0.80 for all 46 VOIs, 0.72 for 16 cortical and limbic VOIs, and 0.83 for 30 subcortical VOIs. For regional and global SUVR comparisons, the linear regression yielded a slope, y-intercept, and R
2 of 1 ± 0.027, 0 ± 0.040, and ≧0.976, respectively (P < 0.001), and the intraclass correlation coefficient was ≧0.988 (P < 0.001). For global SUVRs in each CDR group, these values were 1 ± 0.020, 0 ± 0.026, ≧0.993, and ≧0.996, respectively (P < 0.001). Both MRI-based and CT-based global SUVR showed a consistent increase as the CDR score increased.

Conclusions

The DL-based CT parcellation agrees strongly with MRI-based methods for amyloid PET quantification.
Frontal Sinus Volume in Normocephalic Nonsyndromic Sagittal Craniosynostosis: A Comparative Study
Authors: Velazquez Alexander , Lebhar Michael S. , Roux Jeffrey , Tramel Sarah , Metildi Marisa , Nichols Todd , Humphries Laura S. , Hoppe Ian C.
Published: January 2025

Purpose:

This study aimed to investigate frontal sinus volume as a potential indicator of cranial compensatory growth in unoperated normocephalic nonsyndromic sagittal craniosynostosis (NNSC) patients compared with age-matched and sex-matched controls. Previous studies have suggested that frontal sinus volume is suppressed in unoperated craniosynostosis and may be an intracranial space conservation phenomenon.

Methods:

Head computed tomographies (CTs) from 22 unoperated NNSC patients at our institution were utilized in this study and matched with age-matched and sex-matched control subjects. Frontal sinus volumes were measured using Syngo.Via, and statistical analysis was performed. Inclusion criteria for patients included the presence of a frontal sinus with unoperated sagittal craniosynostosis, whereas inclusion criteria for controls included the presence of a frontal sinus and no craniofacial trauma. Pearson correlation coefficient and significance values were calculated to evaluate the relationship between frontal sinus volume and craniosynostosis.

Results:

Six of 22 patients with NNSC were found to have the presence of a frontal sinus volume, compared with controls where all patients had the presence of a frontal sinus. When compared with age-sex matched controls, our analysis revealed a Pearson correlation coefficient of 0.993 and a high significance of P < 0.001, indicating a strong association between decreased-to-absent frontal sinus volume in unoperated NNSC patients.

Conclusion:

The findings of this study demonstrate a correlation between decreased-to-absent frontal sinus volume in patients with NNSC in comparison to normal controls. These findings highlight the potential utility of frontal sinus volume as a diagnostic tool in identifying the degree of compensation that the skull has undergone in nonsyndromic sagittal craniosynostosis.
The Effects of Selenium Supplementation on Lipid Profile and the Inflammatory and Oxidative Stress Markers in Patients With Kidney Diseases
Authors: Sabet Hamid Reza , Jalali Maryam , Rezaei Hadi , Rezaei Tahereh , Motamed Mahsa , Keshavarzian Omid , Nematolahi Samane
Published: January 2025

This meta-analysis analyzed randomized controlled trials (RCTs) to determine the impact of selenium supplementation on lipid profiles, inflammatory markers, and oxidative stress in patients with chronic kidney disease (CKD). Data were combined using a fixed- or random-effects model. Results of 7 included RCTs showed a significant increase in high-density lipoprotein cholesterol (HDL-c) levels following selenium intake. However, circulating levels of triglycerides, total cholesterol, LDL-c, and malondialdehyde (MDA) were not significantly affected. Selenium intake also reduced high-sensitivity C-reactive protein (hs-CRP) levels compared to controls, suggesting that selenium supplementation might lower and elevate hs-CRP and HDL-c levels, respectively, indicating its potential therapeutic effect.
Robust undulatory locomotion through neuromechanical adjustments in a dissipative medium
Authors: Ishimoto Kenta , Moreau Clément , Herault Johann
Published: January 2025

Dissipative environments are ubiquitous in nature, from microscopic swimmers in low-Reynolds-number fluids to macroscopic animals in frictional media. In this study, we consider a mathematical model of a slender elastic locomotor with an internal rhythmic neural pattern generator to examine various undulatory locomotion such as
Caenorhabditis elegans
swimming and crawling behaviours. By using local mechanical load as mechanosensory feedback, we have found that undulatory locomotion robustly emerges in different rheological media. This progressive behaviour is then characterized as a global attractor through dynamical systems analysis with a Poincaré section. Furthermore, by controlling the mechanosensation, we were able to design the dynamical systems to manoeuvre with progressive, reverse and turning motions as well as apparently random, complex behaviours, reminiscent of those experimentally observed in
C. elegans
. The mechanisms found in this study, together with our dynamical systems methodology, are useful for deciphering complex animal adaptive behaviours and designing robots capable of locomotion in a wide range of dissipative environments.
Consistency and individuality of honeybee stinging behaviour across time and social contexts
Authors: Kannan Kavitha , Galizia C. Giovanni , Nouvian Morgane
Published: January 2025

Whether individuals exhibit consistent behavioural variation is a central question in the field of animal behaviour. This question is particularly interesting in the case of social animals, as their behaviour may be strongly modulated by the collective. In this study, we ask whether honeybees exhibit individual differences in stinging behaviour. We demonstrate that bees are relatively stable in their decision to sting—or not—in a specific context and show temporal consistency suggestive of an internal state modulation. We also investigated how social factors such as the alarm pheromone or another bee modulated this behaviour. The presence of alarm pheromone increased the likelihood of a bee to sting but this response decayed over trials, while the presence of a conspecific decreased individual stinging likelihood. These factors, however, did not alter stinging consistency. We therefore propose that social modulation acts by shifting the stinging threshold of individuals. Finally, experimental manipulation of group composition with respect to the ratio of aggressive and gentle bees within a group did not affect the behaviour of focal bees. Overall, our results establish honeybee stinging behaviour as a promising model for studying mechanistically how collective and individual traits interact to regulate individual variability.
Does fast running limit numerical variability of the vertebral column in rabbits and hares (Leporidae: Lagomorpha)?
Authors: Gunji Megu , Taewcharoen Nuttakorn , Yamada Fumio , Sherratt Emma
Published: January 2025

In mammalian vertebral columns, locomotive ability is expected to be an evolutionary driver of variation in the number of vertebrae; in species evolved to run fast or have a flexible vertebral column, they generally have limited numerical variation and low occurrence of malformed vertebrae to maintain their running performance. Although this hypothesis is supported among species sharing similar locomotive constraints (e.g. dorsomobile versus dorsostable species), whether it applies at the within-species level is unknown. We test this hypothesis using species of Leporidae (rabbits and hares) with different locomotive abilities: we examined the number of presacral vertebrae and the frequency of abnormalities in 504 specimens from 4 species, representing cursorial, saltatorial and generalist modes. Our results show that the cursorial leporids had the lowest numerical variability and fewest abnormalities within species, although this was not statistically different from saltatorial or generalist species. We also identified 11 conditions of vertebral abnormality previously unexplored and theorize that each may pose different degrees of locomotive impairment and effects on species’ fitness. The lack of statistical support for the hypothesis at a finer phylogenetic level suggests further research is needed to understand whether numerical variability is under stabilizing selection or a developmental response to locomotive constraints in cursorial animals.
Covariant currents and a thermodynamic uncertainty relation on curved manifolds
Authors: Miller Harry J. D.
Published: January 2025

A framework for defining stochastic currents associated with diffusion processes on curved Riemannian manifolds is presented. This is achieved by introducing an overdamped Stratonovich–Langevin equation that remains fully covariant under nonlinear transformations of state variables. This approach leads to a covariant extension of the short-time thermodynamic uncertainty relation, describing a trade-off between the total entropy production rate and thermodynamic precision associated with short-time currents in curved spaces and arbitrary coordinate systems.
Population variability across geographical ranges: perspectives and challenges
Authors: Ten Caten Cleber , Dallas Tad
Published: January 2025

Populations fluctuate over time and across geographical space, and understanding how different factors contribute to population variability is a central goal in population ecology. There is a particular interest in identifying trends of population variability within geographical ranges as population densities of species can fluctuate substantially across geographical space. A common assumption is that populations vary more near species geographical range edges because of unsuitable environments and higher vulnerability to environmental variability in these areas. However, empirical data rarely support this expectation, suggesting that population variability is not related to its position within species geographical ranges. We propose that performance curves, which describe the relationship between population growth rates and environmental conditions, can be used to disentangle geographical patterns of population variability. Performance curves are important for understanding population variability because populations fluctuate more in locations where they have lower growth rates owing to unsuitable environmental conditions. This is important for the assessment of these geographical patterns in population variability because geographical edges often do not reflect environmental edges. Considering species performance curves when evaluating geographical patterns of population variability would also allow researchers to detect populations that are more susceptible to future changes in environmental conditions.
Kin discrimination causes plastic responses in floral and clonal allocation
Authors: Lewis Isabeau , Friedman Jannice
Published: January 2025

The composition of a plant’s neighbourhood shapes its competitive interactions. Neighbours may be related individuals due to limited seed dispersal or clonal growth, so that the ability to recognize and respond to the presence of kin is beneficial. Here, we ask whether plants plastically adjust their floral and clonal allocation in response to their neighbour’s identity. In a species that reproduces both sexually and clonally, we test the following predictions in response to neighbouring kin: (i) a reduction in floral display will occur to minimize costly floral structures and pollinator competition, as well as to mitigate inbreeding; and (ii) a decrease in clonality will occur to minimize resource competition and overcrowding among kin. We grew focal individuals of
Mimulus guttatus
(syn.
Erythranthe guttata
) surrounded by neighbours of varying relatedness (non-kin, outcross siblings or self siblings) and measured a suite of vegetative, floral and clonal traits. Consistent with our predictions, focal plants reduced floral and clonal allocation in the presence of kin. Moreover, focal plants increased their floral and clonal allocation when surrounded by non-kin neighbours that were high-performing. Together, we demonstrate a clear and predictable response to kin, which has general implications for the structure and function of plant neighbourhoods.
Concomitant motor responses facilitate the acquisition of multiple prior distributions in human coincidence timing
Authors: Natsume Shu , Roach Neil W. , Miyazaki Makoto
Published: January 2025

The brain optimizes timing behaviour by acquiring a prior distribution of target timing and integrating it with sensory inputs. Real events have distinct temporal statistics (e.g. fastball/slowball in ball sports), making it vital to acquire multiple prior distributions. In previous studies, participants acquired two prior distributions by assigning different types of motor responses or motor effectors to each prior. However, in daily tasks, different types of motor responses or effectors cannot always be selected for each target state. Here, we demonstrate that concomitant motor responses (CMRs) can facilitate multiple-prior acquisition. The non-CMR group made timing responses using only their dominant hand, irrespective of the prior distributions (short/long interval), whereas the CMR group selectively added a non-dominant hand response concomitantly to the dominant hand response for one of the priors. The CMR group acquired the two independent priors more quickly, and the divergence between the acquired priors was greater. Facilitation of multiple-prior acquisition was also observed with concomitant vocalization, indicating that this effect is not limited to bimanual interactions. These results demonstrate behavioural contexts that facilitate multiple-prior acquisition while using an identical type of motor response and effector, which can be effective in utilizing Bayesian estimation in daily life.
Social learning preserves both useful and useless theories by canalizing learners’ exploration
Authors: Derex Maxime , Bonnefon Jean-François , Boyd Robert , McElreath Richard , Mesoudi Alex
Published: January 2025

In many domains, learning from others is crucial for leveraging cumulative cultural knowledge, which encapsulates the efforts of successive generations of innovators. However, anecdotal and experimental evidence suggests that reliance on social information can reduce the exploration of the problem space. Here, we experimentally investigate the extent to which cultural transmission fosters the persistence of arbitrary solutions in a context where participants are incentivized to improve a physical system across multiple trials. Participants were exposed to various theories about the system, ranging from accurate to misleading. Our findings indicate that even under conditions conducive to exploration, the transmission of cultural knowledge canalizes learners’ focus, limiting their consideration of alternative solutions. This effect was observed in both the theories produced and the solutions attempted by participants, irrespective of the accuracy of the provided theories. These results challenge the notion that arbitrary solutions persist only when they are efficient or intuitive and underscore the significant role of cultural transmission in shaping human knowledge and technologies.
The release of sexual conflict after sex loss is associated with evolutionary changes in gene expression
Authors: Defendini Hélène , Prunier-Leterme Nathalie , Robin Stéphanie , Lameiras Sonia , Baulande Sylvain , Simon Jean-Christophe , Jaquiéry Julie
Published: January 2025

Sexual conflict can arise because males and females, while sharing most of their genome, can have different phenotypic optima. Sexually dimorphic gene expression may help reduce conflict, but the expression of many genes may remain sub-optimal owing to unresolved tensions between the sexes. Asexual lineages lack such conflict, making them relevant models for understanding the extent to which sexual conflict influences gene expression. We investigate the evolution of sexual conflict subsequent to sex loss by contrasting the gene expression patterns of sexual and asexual lineages in the pea aphid
Acyrthosiphon pisum
. Although asexual lineages of this aphid produce a small number of males in autumn, their mating opportunities are limited because of geographic isolation between sexual and asexual lineages. Therefore, gene expression in parthenogenetic females of asexual lineages is no longer constrained by that of other morphs. We found that the expression of genes in males from asexual lineages tended towards the parthenogenetic female optimum, in agreement with theoretical predictions. Surprisingly, males and parthenogenetic females of asexual lineages overexpressed genes normally found in the ovaries and testes of sexual morphs. These changes in gene expression in asexual lineages may arise from the relaxation of selection or the dysregulation of gene networks otherwise used in sexual lineages.
From iRBD to Parkinson’s disease: Tracking Glymphatic Dysfunction Using Automated DTI-ALPS Analysis
Authors: Marecek S , Rottova V , Nepozitek J , Krajca T , Krupicka R , Keller J , Zogala D , Trnka J , Sonka K , Ruzicka E , Dusek P
Published: January 2025

Diffusion tensor image analysis along the perivascular space (DTI-ALPS) is a non-invasive marker of glymphatic function that typically relies on manual region of interest (ROI) placement. This study compared glymphatic function in treatment-naïve, de novo diagnosed patients with Parkinson’s disease (PD), patients with isolated REM behavior disorder (iRBD), and healthy controls using both manual and automatic DTI-ALPS methods. ALPS scores were analyzed bilaterally and correlated with clinical severity (MDS-UPDRS) and nigrostriatal denervation (DAT-SPECT). The study included 79 PD patients (60±12 years), 57 iRBD patients (67±7 years), and 48 controls (62±10 years). ANCOVA revealed significant inter-group differences using both manual (p=0.018) and automatic (p=0.002) methods. Automatic analysis showed significantly lower ALPS scores in PD compared to controls (p=0.001) and iRBD (p=0.009). ALPS scores correlated with symptom severity and nigrostriatal degeneration. These findings highlight early glymphatic dysfunction in PD and demonstrate the reliability of the automatic DTI-ALPS method.
Effect of moderate altitude with and without nocturnal oxygen therapy on the next-day cerebrovascular function in patients with chronic obstructive pulmonary disease – A randomized, cross-over trial at 2048 m
Authors: Gilliand Dominic , Latshang Tsogyal D. , Aeschbacher Sayaka S. , Huber Fabienne , Flueck Deborah , Lichtblau Mona , Ulrich Stefanie , Hasler Elisabeth D. , Scheiwiller Philipp M. , Müller Julian , Ulrich Silvia , Bloch Konrad E. , Furian Michael
Published: January 2025

Background

This study investigated whether nocturnal oxygen therapy (NOT) improves next-day cerebrovascular function in lowlanders with COPD staying at moderate altitude.

Methods

This randomized, placebo-controlled crossover trial was performed in stable patients with moderate to severe COPD (FEV1/FVC <0.7 and FEV130-80%predicted), living <800m and pulse oximetry (SpO2) ≥92%. Patients underwent assessments at 490m and during 2 stays of 2 days at 2048m while NOT or placebo (each at 3L min−1through nasal cannula) were applied according to a randomized cross-over design. At both altitudes, SpO2, cerebral tissue oxygenation (CTO, near-infrared spectroscopy), mean arterial blood pressure (MAP, finger plethysmography) and middle cerebral artery systolic peak blood flow velocity (sMCAv, transcranial Doppler ultrasound) were assessed while patients were(0)quietly breathing FiO20.21;(i)quietly breathing FiO21.0,(ii)voluntarily hyperventilating,(iii)voluntarily hyperventilating under FiO21.0, and(iv)during head-up tilting. Indices of cerebrovascular responsiveness to changes in blood gases and blood pressure were computed.

Results

A total of 18 patients (8 women aged mean±SD 65±5y, FEV154.7±13.9%predicted) were analyzed. At 2048m under placebo, patients became hypoxemic, mean±SE SpO290.3±0.4% vs. 93.7±0.4% at 490m, while MAP, CTO and sMCAv remained unchanged compared to 490m. All ventilatory maneuvers at 2048 m induced greater increases in SpO2compared to 490m while changes in MAP, CTO and sMCAv were similar. Head-up tilting induced a similar blood pressure fall at 2048m compared to 490m, whereas cerebral blood flow velocity changed less in response to systemic hypotension (mean±SE ΔsMCAv/ΔMAP 0.9±0.3 vs. 2.3±0.4cm s−1mmHg−1) at 2048m. No alteration in cerebrovascular function as a treatment effect of NOT was observed in either maneuver.

Conclusion

This randomized clinical trial in moderate-to-severe COPD patients ascending to 2048m showed that moderate daytime systemic hypoxemia does not translate to cerebral hypoxia nor cerebrovascular autoregulatory impairments while at rest or under ventilatory or orthostatic challenges.
Integrating transcriptomic data with metabolic model unravels the electron transfer mechanisms ofMethanosarcina barkeri
Authors: Tang Wentao , Lin Sen , Deng Yangfan , Guo Gang , Chen Guanghao , Hao Tianwei
Published: January 2025

Methanogenic archaea, particularlyMethanosarcina, are pivotal to the global carbon cycle and renewable energy production due to their versatile metabolic capabilities. Although transcriptomic analysis is widely employed to identify key genes and pathways inMethanosarcinaunder various methanogenic conditions—including the emerging direct interspecies electron transfer (DIET)-based methanogenesis—the weak correlation between gene expression levels and protein abundances poses challenges for interpreting transcriptomic data. To address this, we integrated transcriptomic data into a metabolic model ofMethanosarcina barkerifor the first time, enabling more refined predictions and enhancing the interpretability of transcriptomic insights. This novel integrated model was subsequently utilized to simulate aceticlastic, hydrogenotrophic, and DIET-based methanogenesis. The results revealed that previous assumptions failed to account for the role of the CO₂ reduction pathway in aceticlastic methanogenesis. The model also successfully captured key transcriptomic features of DIET-based methanogenesis, clarifying the functional roles of crucial enzymes like the F420H2dehydrogenase Fpo and the transmembrane hydrogenase Vht in electron transfer. This integrative approach provided a deeper understanding of electron transfer mechanisms inM. barkeriand offered valuable insights for advancing methanogen-based biotechnologies. Moreover, the study critically evaluated the relationship between gene expression and metabolic flux, establishing a practical framework for deriving meaningful insights from the growing volume of transcriptomic data.
Perilysosomal Ca2+ overload impairs autophagic degradation in β-cell lipotoxicity
Authors: Nguyen Ha Thu , Ly Luong Dai , Ngo Thuy Thi Thanh , Lee Soo Kyung , Noriega Polo Carlos , Lee Subo , Lee Taesic , Cha Seung-Kuy , Lee Myung-Shik , Wiederkehr Andreas , Wollheim Claes B , Park Kyu-Sang
Published: January 2025

Saturated fatty acids impose lipotoxic stress on pancreatic β-cells, leading to β-cell failure and diabetes. In this study, we investigate the critical role of organellar Ca2+ disturbance on defective autophagy and β-cell lipotoxicity. Palmitate, a saturated fatty acid, induced perilysosomal Ca2+ elevation, sustained mTORC1 activation on the lysosomal membrane, suppression of the lysosomal transient receptor potential mucolipin 1 (TRPML1) channel, and accumulation of undigested autophagosomes in β-cells. These Ca2+ aberrations with autophagy defects by palmitate were prevented by a mTORC1 inhibitor or a mitochondrial superoxide scavenger. To alleviate perilysosomal Ca2+ overload, strategies such as lowering extracellular Ca2+, employing voltage-gated Ca2+ channel blocker or ATP-sensitive K+ channel opener effectively abrogated mTORC1 activation and preserved autophagy. Furthermore, redirecting perilysosomal Ca2+ into the endoplasmic reticulum (ER) with an ER Ca2+ ATPase activator, restores TRPML1 activity, promotes autophagic flux, and improves survival of β-cells exposed to palmitate-induced lipotoxicity. Our findings suggest oxidative stress-Ca2+ overload-mTORC1 pathway involves in TRPML1 suppression and defective autophagy during β-cell lipotoxicity. Restoring perilysosomal Ca2+ homeostasis emerges as a promising therapeutic strategy for metabolic diseases.
Insights into global antimicrobial resistance dynamics through the sequencing of enteric bacteria from U.S. international travelers
Authors: Sridhar Sushmita , Worby Colin , Bronson Ryan A , Turbett Sarah E , Oliver Elizabeth , Shea Terrance , Rao Sowmya R , Sanchez Vanessa , Becker Margaret , Kogut Lucyna , Slater Damien M , Harris Jason B. , Walters Maroya S , Walker Allison Taylor , Knouse Mark C , Leung Daniel T , Kelly Paul , Ryan Edward T. , LaRocque Regina C , Earl Ashlee M.
Published: January 2025

Antimicrobial resistance (AMR) is an urgent threat to public health, but gaps in surveillance limit the detection of emergent novel threats and knowledge about the global distribution of AMR genes. International travelers frequently acquire AMR organisms, and thus may provide a window into AMR dynamics in otherwise poorly monitored regions and environments. To assess the utility of travelers as global AMR sentinels, we collected pre- and post-travel stool samples from 608 travelers, which were screened for the presence of extended-spectrum beta-lactamase producing Enterobacterales, carbapenem-resistant Enterobacterales, and mcr-mediated colistin-resistant Enterobacterales. A total of 307 distinct AMR organisms were sequenced in order to determine genotypic patterns and their association with travel region and behavior. Travel-associated AMR organisms were overwhelmingly E. coli, which exhibited considerable phylogenetic diversity regardless of travel region. However, the prevalence of resistance genes varied by region, with blaCTX-M-55and blaCTX-M-27significantly more common in travelers returning from South America and South-Eastern Asia, respectively. Hybrid assembly and plasmid reconstruction revealed the genomic neighborhood of blaCTX-M-55frequently matched a motif previously linked to animal populations. Contact with animals was also associated with virulence factors in acquired AMR organisms, including carriage of the ColV plasmid, a driver of avian pathogenic E. coli. We identified novel variants of the mcr-1 gene in strains acquired from Western Africa, highlighting the potential for traveler surveillance to detect emerging clinical threats. Ongoing efforts to track travel-acquired organisms could complement existing global AMR surveillance frameworks.
Drug treatment alters performance in a neural microphysiological system of information processing
Authors: Watmuff Bradley , Habibollahi Forough , Desouza Candice , Khajehnejad Moein , Loeffler Alon , Baranes Koby , Poulin Noah , Kotter Mark , Kagan Brett
Published: January 2025

Assessment of pharmacological intervention on in vitro neural systems often emphasizes molecular and structural changes. However, neural systems fundamentally process and act on information. For preclinical assays to predict drug efficacy, they must model these physiological functions. DishBrain, an in vitro assay embodying a neural system in a simulated game-world, enables quantification of information-processing capacity and dose-response profiling. Hyperactive glutamatergic dysregulation is linked to many neurological disorders. Inducible overexpression of neurogenin 2 (NGN2) in hiPSCs generated glutamatergic cultures with dysregulated hyperactivity. Anti-seizure medications (ASMs) were trialed on this model within a game-world using closed-loop electrophysiological stimulation and recordings. MEA data from day 21 of differentiation revealed significant electrophysiological development. Treatments included dimethyl sulfoxide (DMSO), phenytoin, perampanel, or carbamazepine. Carbamazepine 200 μM significantly reduced firing rates and improved gameplay metrics, such as hit/miss ratio and rally length. This marks the first demonstration of altered synthetic biological intelligence (SBI) in a neural model after drug treatment. Notably, only inhibitory compounds enhanced goal-directed activity, linking glutamatergic attenuation to performance. Neurocomputational analysis revealed nuanced pharmacological responses during closed-loop stimulation, highlighting insights beyond spontaneous activity metrics.
The influence of fetal sex on maternal blood pressure in pregnancy
Authors: Decina Caitlin S. , Beaumont Robin N. , Juodakis Julius , Warrington Nicole M. , Patel Kashyap A. , Njølstad Pål R. , Johansson Stefan , Hattersley Andrew T. , Jacobsson Bo , Lowe William L. , Evans David M. , Freathy Rachel M.
Published: January 2025

Background

Pregnancy with a male fetus carries a higher risk of term pre-eclampsia than pregnancy with a female fetus. Based on evidence that maternal blood pressure (BP) may be raised in pregnancies with Beckwith-Wiedemann syndrome (fetal overgrowth), a possible contributing factor to the association between male sex and term pre-eclampsia is that males grow faster, reaching ∼130 g higher birth weight, on average, than females. The association between fetal sex and maternal BP in healthy pregnancies is not known. We hypothesized that male sex would be associated with higher maternal BP in healthy pregnancies, and that this association would be explained by birth weight differences between males and females.

Methods and findings

We tested the association between fetal sex and maternal systolic (SBP) and diastolic blood pressure (DBP), measured at ∼28 weeks of gestation, in a meta-analysis of five different cohorts of mother-child pairs (n up to 109,842). Maternal BP was analyzed as both a continuous and dichotomized (high BP: yes or no) outcome. Linear regression models were constructed with and without adjustment for birth weight to assess whether any difference in maternal BP was explained by the difference in birth weight between male and female babies. Lastly, we constructed a fetal genetic score for birth weight using 186 own-birth-weight-associated single-nucleotide polymorphisms (SNPs) to test whether birth-weight-raising-alleles in the fetus were associated with maternal BP in pregnancy (n up to 32,232). Both maternal SBP and DBP were higher in pregnancy when carrying a male fetus compared to a female fetus (mean difference 0.35 mmHg [95%CI: 0.15-0.55] and 0.35 mmHg [95%CI: 0.21-0.49], for SBP and DBP, respectively). An independent effect of fetal sex remained when including birth weight but attenuated slightly (0.22 mmHg [95%CI: 0.02-0.42] and 0.31 mmHg [95%CI: 0.17-0.45], for SBP and DBP respectively). A positive effect estimate was found for odds of experiencing high maternal BP given pregnancy with a male fetus, but confidence intervals were wide (OR 1.05 [95%CI: 0.98-1.12]). No evidence for an association was found between a fetal birth weight genetic score and SBP or DBP when conditioned on maternal genotype.

Conclusions

We found strong evidence to support a small effect of male fetal sex on higher maternal BP in pregnancy and that larger fetal size at birth does not contribute to a substantial part of this association. Our findings do not indicate a difference in maternal BP that would warrant changes to routine monitoring in clinical practice but do suggest that male sex may be a contributing risk factor for BP-related complications.
Receptor Allostery Promotes Context-Dependent Sonic Hedgehog Signaling During Embryonic Development
Authors: Ansari Shariq S. , Dillard Miriam E. , Ghonim Mohamed , Zhang Yan , Stewart Daniel P. , Canac Robin , Moskowitz Ivan P. , Wright William C. , Daly Christina A. , Pruett-Miller Shondra M. , Steinberg Jeffrey , Wang Yong-Dong , Chen Taosheng , Thomas Paul G. , Bridges James P. , Ogden Stacey K.
Published: January 2025

Sonic Hedgehog (SHH) signaling functions in temporal- and context-dependent manners to pattern diverse tissues during embryogenesis. The signal transducer Smoothened (SMO) is activated by sterols, oxysterols, and arachidonic acid (AA) through binding pockets in its extracellular cysteine-rich domain (CRD) and 7-transmembrane (7TM) bundle.In vitroanalyses suggest SMO signaling is allosterically enhanced by combinatorial ligand binding to these pockets butin vivoevidence of SMO allostery is lacking. Herein, we map an AA binding pocket at the top of the 7TM bundle and show that its disruption attenuates SHH and sterol-stimulated SMO induction. A knockin mouse model of compromised AA binding reveals that homozygous mutant mice are cyanotic, exhibit high perinatal lethality, and show congenital heart disease. Surviving mutants demonstrate pulmonary maldevelopment and fail to thrive. Neurodevelopment is unaltered in these mice, suggesting that context-dependent allosteric regulation of SMO signaling allows for precise tuning of pathway activity during cardiopulmonary development.
RNA modifications on Adenosine Regulate Macrophage Function
Authors: Griesche Valerie , Di Giorgio Salvatore , Brettschneider Julia , Tellioglu Irem , Kao Chih-Yuan , Lorenzo Jose Paulo , Pezzella Laura , Stoecklin Georg , Papavasiliou F. Nina
Published: January 2025

Macrophages are important innate immune cells that respond rapidly to inflammatory cues and fulfill diverse functions in the activation, execution and resolution of immune and inflammatory responses. Currently, there is no comprehensive understanding of the combinatorial effect of mRNA modifications in a single cell type, the consequences for mRNA processing and metabolism, and how these changes affect cell physiology. We use the mouse macrophage line RAW264.7 (RAW) to systematically address the combinatorial effect of two major mRNA modifications during macrophage stimulation: adenosine to inosine deamination (A-to-I), and adenosine N6 methylation (m6A). At the functional level we found that both METTL3 (the m6A writer) and ADAR1 (the adenosine deaminase) are required for full activation of RAW macrophages (as determined by expression of surface markers) and for optimal phagocytosis (a key macrophage function). Using both short read and single molecule sequencing on RAW cells with genetic deletions of the m6A writer METTL3 and the A deaminase ADAR1, we found that loss of m6A affected A-to-I levels while m6A levels remained relatively stable. A detailed investigation of potential interactions between m6A and A-to-I at the single transcript level is ongoing.
Practice what you preach: the effects of mission alignment on organizational performance
Authors: MacKenzie William I. , Colazo Jorge A. , Scherer Robert F.
Published: January 2025

Purpose

Association to Advance Collegiate Schools of Business (AACSB) accreditation encourages business schools to exhibit alignment within their mission, strategies and outcomes to achieve success. The present study aims to explore the idea of mission alignment and how it may serve as an important moderator to the relationship between organizational resources and school performance as measured through business school rank.

Design/methodology/approach

Our study utilizes the AACSB International business school survey (BSQ) data to analyze the mission statements of accredited business schools and capture data on organizational resources. We also created an index of mission alignment to gauge congruency between the stated mission and strategic focus. Our performance measure was the U.S. News and World Report undergraduate business school programs ranking value.

Findings

Our results show mission alignment on its own has little direct impact on organizational performance. However, when mission statement alignment and resource allocations are combined, they interact to influence organizational performance.

Originality/value

Our research demonstrates that resource allocation decisions and mission alignment are two important attributes of an organization and that mission alignment has the potential to leverage an organization’s resources and capabilities to improve performance.