bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exosomes secreted from Amniotic mesenchymal stem cells modify trophoblast activities by delivering miR-18a-5p and regulating HRK-p53 interaction
Authors: Zhao Wendi , Li Wenting , Zuo Jianxin , Zhou Huansheng , Gao Guoqiang , Ye Yuanhua , Chu Yijing 
Published: December 2024

Abstract

BACKGROUND
Amniotic mesenchymal stem cells (AMSCs) have been demonstrated as effective in tissue repair and regeneration. Trophoblast dysfunction is associated with several types of pregnancy complications. The aim of this study is to investigate the effects of AMSCs on the biological activities of human trophoblasts, as well as their molecular mechanisms.

METHODS
Exosomes were isolated from AMSC supernatants, and characterized and quantified by transmission electron microscopy (TEM) , nanoparticle tracking analysis (NTA) and Western blotting assay. Immunofluorescence assay was performed to detect the uptake of AMSCs-derived exomes (AMSC-Exos) by human trophoblasts. Human trophoblasts were subjected to transcriptome analysis after being co-cultured with AMSC-Exos. Lentiviral transfection was performed to construct the human trophoblast cell lines with stable HRK knockdown or overexpression. Immunohistochemistry was used to detect the HRK expression in preeclampsia (PE) patients. CCK8 and Transwell assays were respectively used to detect the trophoblast proliferation and migration. TUNEL flow cytometry assay was used to detect the apoptosis in trophoblasts. qRT-PCR and Western blotting assays were used to detect the mRNA and protein levels of the genes. Dual luciferase reporter assays were used to detect the changes in gene-transcript levels.

RESULTS
AMSC-Exos could be absorbed by human trophoblasts. Transcriptome analysis showed that HRK was significantly reduced in human trophoblasts co-cultured with AMSC-Exos. HRK inhibited cell proliferation and migration in human trophoblasts and promoted their apoptosis via p53 upregulation. miR-18a-5p, present at high levels in AMSC-Exos, improved trophoblast proliferation and migration, and inhibited their apoptosis by inhibiting the HRK expression.

CONCLUSION
miR-18a-5p present in AMSC-Exos could be absorbed by trophoblasts, and in turn, improved their proliferation and migration and inhibited their apoptosis by HRK down-regulation.
The Whites-Only Immigration Regime
Authors: Hernandez Kelly Lytle 
Published: December 2024

Abstract
After the U.S. Civil War, federal authorities began building the framework for our modern immigration regime. By the 1930s, they had adopted a variety of laws, rules, and tactics designed to target non-White immigrants for exclusion, punishment, and removal, imposing a Whites-only immigration regime in all but name. To date, federal authorities have revised but have yet to repeal this regime. This essay is a written version of the author’s 2024 Western History Association presidential address.
Lessons Learned: Preventing Faculty Burnout
Authors: Hoffmann Chelsey 
Published: December 2024

Introduction
Physician Assistant/Associate (PA) clinicians face a major learning curve when transitioning from patient provider to PA educator. Furthermore, PA educators juggle multiple responsibilities including teaching, grading, advising, mentoring, interviewing, researching, writing, and more. Recently published research has indicated that 52.4% of PA educators thought about leaving their faculty roles within the past year. To assist in the effort to prioritize faculty retention, a personal story of faculty burnout and lessons learned is shared.

Methods
Burnout and its three associated subscales are defined, while symptoms of burnout are outlined in a manner specific to the role of a PA faculty member.

Results
Drawing from the existing evidence base, suggestions are made to improve the well-being of PA educators and prevent faculty burnout or turnover.

Discussion
While being a PA faculty member is extremely rewarding, it can also be challenging, particularly for early-career PAs or those transitioning from clinical practice with no prior work experience as an educator. Strategic implementation of good habits may aid faculty members in preventing burnout and improving work-life balance.
“A good socket fit can make you or break you”: A multimethod study to explore the perceptions and experiences of socket fitting among people with lower-limb loss in Australia
Authors: Armitage Lucy , Kark Lauren , McDonald Kirsty A. , Sparke Darrel , Ford Belinda 
Published: December 2024

Background:
Iterative design and modification are used to manufacture lower limb prosthetic sockets that meet users' needs while also fulfilling safety and mobility criteria. Greater understanding of the expectations of prosthesis users regarding prosthetic fit as well as their experiences at the time of socket fitting is needed.

Objectives:
Describe lower limb prosthesis user perceptions and experiences of socket comfort and discomfort during their last fitting and compare this to their expectations for a perfectly fitting socket and their satisfaction with the socket they had fitted.

Study Design:
Mixed methods (quantitative and qualitative).

Methods:
A questionnaire was designed and administered in consultation with Amputees NSW (an amputee advocacy group) and distributed through their membership database. Qualitative responses were analyzed to explore prosthesis user experiences of socket fitting, general wear, as well as socket comfort, discomfort, and satisfaction. Quantitative responses were analyzed using descriptive, nonparametric methods.

Results:
Thirty participants with a range of lived experiences completed the questionnaire. Reported comfort and discomfort varied across participants and indicated that expectations and experiences of fit varied and changed over time, with some participants anticipating adjustment over time would be necessary. Qualitative analysis found experiences of prosthesis socket comfort/discomfort on the day of fitting and general experiences of socket comfort related to 2 key factors—the prosthesis itself and the individual prosthesis user.

Conclusions:
Understanding the experiences and expectations of prosthesis users for comfort and intended activities is central to ensure success of the socket fitting approach. Investigation into fit changes over time could provide insights into follow-up requirements, user education, and funding mechanisms.
Functional electrical stimulation in adult patients with cerebral palsy and foot drop—outcome in gait
Authors: Gather Katharina S. , Bleichner Niklas , Block Julia , Heitzmann Daniel W. W. , Weichold Claudia , Wolf Sebastian I. , Alimusaj Merkur , Putz Cornelia 
Published: December 2024

Background:
Foot drop is a common condition for patients with upper motor neuron syndrome such as cerebral palsy (CP). This study aimed to investigate the effects of functional electrical stimulation (FES) on gait function, quality of life, and FES satisfaction in adults with CP and foot drop. To analyze effects over time, an observational, longitudinal study was performed.

Methods:
In this observational prospective cohort study, 8 adults with CP (median age of 22 years; range: 18.5–33.25) received a FES system for 12 weeks. 3D gait analysis was performed at beginning (T1) and end of the study period (T2). To detect effects of FES, ankle kinematics, kinetics, and spatiotemporal parameters were monitored for the conditions FES-OFF and -ON at each examination.

Results:
Over time, walking speed increased significantly from T1ON (1.08 m/s) to T2OFF (1.21 m/s) with further improvement at T2ON. The ON-OFF difference of maximum dorsiflexion during swing tended to increase at T2 (2.49 degrees) compared with T1 (1.73 degrees) but with a more plantarflexed ankle position at T2 (range: −7.1 to 1.31 degrees) than T1 (range: −1.53 to 4.51 degrees) resulting in a significant decrease between T1ON and T2OFF. With FES, push-off energy tended to decrease for both examinations and lead to lower values over time.

Conclusion:
Positive therapeutic effects are represented in walking speed over time regardless of FES being OFF or ON even with a reduction in push-off energy. Despite no significant increase in maximum dorsiflexion in swing, over time, participants showed the tendency of an improvement in foot lift with FES-ON.
Structured light projection using image guide fibers for in situ photo-biofabrication
Authors: Chansoria Parth , Winkelbauer Michael , Zhang Shipin , Janiak Jakub , Liu Hao , Zenobi-Wong Marcy 
Published: December 2024

AbstractLight-based biofabrication techniques have revolutionized the field of tissue engineering and regenerative medicine. Specifically, the projection of structured light, where the spatial distribution of light is controlled at both macro- and micro-scale, has enabled precise fabrication of complex three-dimensional structures with high resolution and speed. However, despite almost two decades of progress, biofabrication processes have been mostly limited to benchtop devices which limit the flexibility in terms of where the fabrication can occur. Here, we demonstrate a Fiber-assisted Structured Light (FaSt-Light) projection apparatus for rapid in situ crosslinking of photoresins. This approach uses image-guide fiber bundles which can project bespoke images at multiple wavelengths, enabling flexibility and spatial control of different photoinitiation systems and crosslinking chemistries and also the location of fabrication. We demonstrate coupling of different sizes of fibers and different lenses attached to the fibers to be able to project small (several mm) or large (several cm) images for material crosslinking. FaSt-Light allows control over the cross-section of the crosslinked resins and enables the introduction of microfilaments which can further guide cellular infiltration, differentiation and anisotropic matrix production. The proposed approach could lead to a new range of in situ biofabrication techniques which improve the translational potential of photo-fabricated tissues and grafts.
Evolutionary dynamics at the leading edge of biological invasions
Authors: Poloni Silas , Lutscher Frithjof , Lewis Mark A. 
Published: December 2024

AbstractEmpirical evidence shows that evolution may take place during species’ range expansion. Indeed, dispersal ability tends to be selected for at the leading edge of invasions, ultimately increasing a species’ spreading speed. However, for organisms across many different taxa, higher dispersal comes at the cost of fitness, producing evolutionary trade-offs at the leading edge. Using reaction-diffusion equations and adaptive dynamics, we provide new insights on how such evolutionary processes take place. We show how evolution may drive phenotypes at the leading edge to maximize the asymptotic spreading speed, and conditions under which phenotypic plasticity in dispersal is selected for under different dispersal-reproduction trade-off scenarios. We provide some possible future research directions and other systems where the framework can be applied.
Virtual reality mediated brain-computer interface training improves sensorimotor neuromodulation in unimpaired and post spinal cord injury individuals
Authors: Mannan Malik Muhammad Naeem , Palipana Dinesh B. , Mulholland Kyle , Jurd Evan , Lloyd Ewan C.R. , Quinn Alastair R. J. , Crossley Claire B. , Rabbi Muhammad Fazle , Lloyd David G. , Teng Yang D. , Pizzolato Claudio 
Published: December 2024

AbstractReal-time brain-computer interfaces (BCIs) that decode electroencephalograms (EEG) during motor imagery (MI) are a powerful adjunct to rehabilitation therapy after neurotrauma. Immersive virtual reality (VR) could complement BCIs by delivering multisensory feedback congruent to the user’s MI, enabling therapies that engage users in task-oriented scenarios. Yet, therapeutic outcomes rely on the user’s proficiency in evoking MI to attain volitional BCI-commanded VR interaction. While previous studies suggested that users could improve BCI-evoked MI within a single session, the effects of multiple training sessions on sensorimotor neuromodulation remain unknown. Here, we present a longitudinal study assessing the impact of VR-mediated BCI training on lower-limb sensorimotor neuromodulation, wherein an EEG-based BCI was coupled with congruent real-time multisensory feedback in immersive VR. We show that unimpaired individuals could learn to modulate their sensorimotor activations during MI virtual walking over multiple training sessions, also resulting in increased BCI control accuracy. Additionally, when extending the system to immersive VR cycling, four individuals with chronic complete spinal cord injury (SCI) showed similar improvements. This is the first study demonstrating that individuals could learn modulating sensorimotor activity associated with MI using BCI integrated with immersive VR over multiple training sessions, even after SCI-induced motor and sensory decline. These results suggest that VR-BCI training may facilitate neuroplasticity, potentially strengthening sensorimotor pathways and functional connectivity relevant to motor control and recovery.
Sativex (Nabiximols) for the treatment of Agitation & Aggression in Alzheimer’s Dementia in UK nursing homes (STAND): a randomised, double-blind, placebo-controlled feasibility trial
Authors: Albertyn Christopher P , Guu Ta-Wei , Chu Petrina , Creese Byron , Young Allan H , Velayudhan Latha , Bhattacharyya Sagnik , Jafari Hassan , Kaur Simrat , Kandangwa Pooja , Carter Ben , Aarsland Dag 
Published: December 2024

AbstractBackgroundAlzheimer’s Disease (AD) patients often experience clinically significant agitation, leading to distress, increased healthcare costs, and earlier institutionalisation. Current treatments have limited efficacy and significant side effects. Cannabinoid-based therapies, such as the nabiximols oral spray (brand name: Sativex®; 1:1 delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD)), offer potential alternatives.MethodsThe ‘Sativex® for Agitation & Aggression in Alzheimer’s Dementia’ (STAND) trial was a randomised, double-blind, placebo-controlled, feasibility study conducted in UK care homes. Participants with probable AD and significant agitation were randomised to receive placebo or nabiximols for 4 weeks on an up-titrated schedule, followed by a 4-week observation period. This trial is registered withISRCTN 7163562.FindingsBetween October 2021 and June 2022, 53 candidates were assessed; 29 met eligibility criteria and were randomised. No participants withdrew, and adherence was high, and was generally feasible to deliver. The intervention was well tolerated, with no safety concerns reported.InterpretationDespite significant COVID-19 pandemic related challenges, administering nabiximols to advanced AD patients with agitation demonstrated feasibility and safety. Although no statistically significant treatment effects were observed, indications of positive clinical effects were noted. These findings support further investigation into cannabinoid-based therapies for agitation in AD.
Sprint interval exercise disrupts mitochondrial ultrastructure driving a unique mitochondrial stress response and remodelling in humans
Authors: Botella J. , Perri E. , Caruana N. J. , López-Calcerrada S. , Brischigliaro M. , Jamnick N. A. , Oorschot V. , Saner N. J. , Diaz-Lara J. , Taylor D. F. , Garnham A. , Fernández-Vizarra E. , Ugalde C. , Ramm G. , Stroud D. A. , Lazarou M. , Bishop D. J. 
Published: December 2024

SummaryExercise remains the most effective lifestyle intervention to remodel the mitochondrial network and to prevent most non-communicable diseases. Despite this, the molecular mechanisms by which different exercise prescriptions dictate mitochondrial remodelling are poorly understood in humans. Here, we show that, compared to moderate-intensity continuous exercise (MICE), sprint-interval exercise (SIE) – a known time-efficient high-intensity exercise – leads to mitochondrial stress and activates the mitochondrial unfolded protein response (UPRmt). The SIE-specific signature is characterized by a morphological and ultrastructural mitochondrial disturbance, concurrent with the activation of the integrated stress response (ISR) and mitochondrial quality control (MQC) pathways. When the respective exercises are repeated over time (8 weeks), our results demonstrate that moderate-intensity continuous training (MICT) and sprint-interval training (SIT) lead to a divergent mitochondrial remodelling. MICT elicits a mitochondrial adaptation characterized by an increase in markers of mitochondrial content, complex I activity, and enrichment of proteins involved in tricarboxylic acid (TCA) cycle and oxidative phosphorylation (OXPHOS) system. On the other hand, SIT leads to proteomic enrichment of pathways involved in mitochondrial 1-Carbon metabolism and protein quality control, concurrently with improvements in mitochondrial respiratory function. Lastly, we have identified COX7A2L as a divergently regulated protein across groups, significantly accumulating in III2+IV1respiratory supercomplexes only following SIT. In conclusion, our study provides mechanistic insights on how SIE and MICE divergently impact the post-exercise mitochondrial signalling, and subsequent long-term mitochondrial remodelling following training. These findings provide a strong basis for targeted exercise prescription to modulate specific mitochondrial adaptations in human skeletal muscle.
Impact of spatial aggregation on detection of spatiotemporal disease clusters: analysis of SARS-CoV-2 infections in 3-D high-density settings
Authors: Allison Keith , Lover Andrew A. 
Published: December 2024

ABSTRACTIntroductionHigh-density congregate housing, including cruise ships, hotels, residence halls and correctional facilities are epidemiologically important, and key aspects of pathogen transmission have been elucidated in these environments. A range of methods have been developed to detect unusual clusters of infections in these settings; however use of explicitly 3-D (x,y,z) spatial data has received little attention. In this study, we use data collected during the COVID-19 pandemic to assess the fine-scale spatial epidemiology and the clustering of confirmed cases to better understand impacts of spatial resolution and aggregation on spatio-temporal cluster detection.MethodsData for this analysis combined the results from mandatory weekly viral testing during the 2020-2021 academic year with high-resolution spatial data from university students residing in high-rise residence halls at the University of Massachusetts, Amherst campus.These data were analyzed for statistically-significant clustering of SARS-CoV-2 cases in three-dimensional space as well as time, within and between the high-density buildings on campus. Two sets of analyses were conducted. The first used a Space-Time Permutation Model, which scans for areas with a greater than expected number of cases (SaTScan). To assess the impact of data aggregation, analysis was done at several levels of spatial resolution. Additionally, we performed sensitivity analyses using a purely temporal surveillance algorithm, CDC’s Early Aberration Reporting System-EARS.Results and conclusionsAnalysis with SaTScan at the room- and floor-level identified multiple statistically significant clusters within one residence hall. Analyses with these same cases aggregated at the floor-level were found to be as sensitive, but far less computationally intensive, than room-level analysis. Analysis at both of these spatial scales was more sensitive than analysis aggregated at the street address-level. Two events exceeding alert thresholds were detected in the purely temporal analysis; one of which was also detected in spatio-temporal analyses.These results expand our understanding of spatio-temporal scan metrics to include 3-D analysis, and optimizing choice of spatial scales. These results have broad applicability in epidemiology in assessing the ability of spatio-temporal methods for public health surveillance, with potential expansion to ecological studies incorporating vertical movement.
Large-scale analysis demonstrates the influence of CYP2C19 genotype on specific SSRI side effects
Authors: Eijsbouts Chris , Jiang Yunxuan , Ashenhurst James , Granka Julie M. ,   23andMe Research Team, Pitts Steven , Auton Adam , Abul-Husn Noura S. , Chubb Alison , Wu R. Ryanne 
Published: December 2024

AbstractThe majority of individuals receiving treatment for major depressive disorder (MDD) do not achieve remission from the first medication they try, and over 80% subsequently discontinue pharmacotherapy or switch to a different medication. SSRI discontinuation due to side effects is common.We evaluated the effect of CYP2C19 genotype on SSRI response using self-reported data from 114,627 direct-to-consumer genetics research participants who were prescribed an SSRI primarily metabolized by CYP2C19 (citalopram, escitalopram, or sertraline).Among participants taking citalopram or escitalopram, slower metabolizers experienced side effects significantly more often than faster metabolizers (OR=1.04 per grade, from 0 for poor metabolizers to 5 for ultrarapid metabolizers, 95%CI=[1.02-1.06] and OR=1.05 per grade, 95%CI=[1.02-1.07]) and were more likely to discontinue treatment due to side effects (OR=1.05, 95%CI=[1.03-1.08], e.g. 29.7% of poor vs. 21.6% of ultrarapid metabolizers, and OR=1.07, 95%CI=[1.04-1.11], e.g. 25.7% vs. 20.2%). Slower metabolizers taking escitalopram were more likely to suffer from sleep problems and sexual problems than faster metabolizers. Slower metabolizers taking sertraline reported tremor more often than faster metabolizers.Overall, we find substantial differences in side effect risk between individuals with different CYP2C19 genotypes in a large sample, supporting the notion that individuals seeking treatment for MDD may benefit from preemptive pharmacogenetic testing and genotype-guided dosing recommendations to minimize side effects and reduce discontinuations.