bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Relationship between Socket Comfort, Pain, and Mobility Over Treatment Milestones for Individuals with Lower-Limb Loss
Authors: Pousett Brittany Mae , Harasym Charlene C. , Rapaport Malena Sofia , Moe David W. , Miller William C. 
Published: July 2024

ABSTRACT

Introduction
This study investigates the relationships among mobility, pain, and socket comfort for people with lower-limb amputations who use prostheses over specific treatment milestones.

Methods
This is a retrospective chart analysis from January 1, 2015, to July 15, 2021. Outcome measures included are the Socket Comfort Score, Pain Scale, 2-Minute Walk Test, and PLUS-M (Prosthetic Limb Users Survey of Mobility). Data were collected at 4 milestones: Baseline and Discharge from Rehabilitation for those receiving their first prosthesis in rehabilitation and Initial Evaluation and Definitive Fitting for experienced prosthesis users receiving a replacement socket. Demographic data were analyzed using descriptive statistics, and the strength of the correlations was determined using Pearson’s correlations.

Results
Measures were included from 59 individuals in rehabilitation and 165 individuals receiving a replacement socket. The sample was in general older males with transtibial amputations due to a variety of etiologies. The Pain Scale was negatively correlated with the Socket Comfort Score (−0.49 < r < −0.60), and the PLUS-M was correlated with the 2-minute walk test (0.41 < r < 0.61) at all milestones. Additionally, there were positive correlations between the PLUS-M and Socket Comfort Score (0.30 < r < 0.32), and negative correlations between the PLUS-M and Pain Scale (−0.46 < r < −0.32) for those receiving a replacement socket.

Conclusions
The relationship among comfort, pain, and mobility changes over the treatment timeline. There is evidence that, by addressing comfort and pain for those with experience using a prosthesis, clinicians can support the goal of increasing self-reported functional mobility.

Clinical Relevance
This study provides novel information about the relationships among pain, comfort, and mobility and the importance of considering the impact of treatment milestones when taking outcome measures and providing interpretative values as scores and relationships differ over the course of treatment.
Beyond diagnosis: exploring coeliac disease incidence alongside clinical and laboratory characteristics of newly diagnosed children in Slovenia
Authors: Rižnik Petra , Kamhi Trop Tina , Klemenak Martina , Krenčnik Tomaž , Milanič-Koron Tanja , Mojškerc Eva Miler , Pavlin Tatjana , Požek Šavs Tina , Zupančič Janez , Dolinšek Jernej 
Published: July 2024

Objective
Coeliac disease is characterized by a wide array of clinical presentations. The focus of our study was to comprehensively assess the clinical manifestations of coeliac disease in newly diagnosed children in Slovenia. Our objectives include estimating the incidence of the disease in children in 2022.

Methods
In this prospective study, Slovenian paediatric gastroenterologists were invited to provide patient data using medical records of children under 19 diagnosed with coeliac disease from March 2021 to October 2023. Patient data were collected through a dedicated web-based form adapted from the CD SKILLS project, including data on clinical manifestations and laboratory results. Furthermore, the study included an estimation of the incidence of coeliac disease in children and adolescents in Slovenia in 2022.

Results
Analysis involved data from 160 children and adolescents (median age: 8 years; 61.9% female). Overall, 16.9% were asymptomatic at diagnosis and 29.4% belonged to a high-risk group for coeliac disease. Among symptomatic cases (N = 133), abdominal pain was the leading symptom (44.4%), followed by anaemia (12.0%) and diarrhoea (10.5%). Malabsorption symptoms were more prevalent in very young children. Anaemia was found in 22.8 and 10.7% had abnormal alanine aminotransferase levels. The estimated incidence of coeliac disease in Slovene children in 2022 was 17.5/100 000.

Conclusion
Abdominal pain emerged as the primary symptom of coeliac disease in children and adolescents, except in very young children where malabsorption symptoms were predominant. Our observation of a lower prevalence of abnormal liver function tests suggests subclinical coeliac disease may be less common in children. Moreover, the calculated coeliac disease incidence in Slovenia aligns with existing data.
African Immigrant Women's Experiences of Maternity Care in the United States
Authors: Appiah-Kubi Ruth , Kim Yeong-Hyun , Attanasio Laura B. 
Published: July 2024

Abstract

Objective:
The purpose of this study was to explore maternity care experiences of African immigrant women during the perinatal period including factors affecting access to and use of care.

Methods:
We used Sandelowski's (2010) qualitative descriptive approach to examine how African immigrant women from various countries of origin and with diverse ethnic backgrounds experienced and navigated the maternity care system in the United States during pregnancy and childbirth. We conducted semi-structured interviews with 15 African immigrant women living in the Columbus, Ohio area. Participants were recruited using purposive and snowball sampling between February 2021 and May 2021. Interviews were recorded, transcribed, and analyzed using a reflexive thematic analysis approach.

Findings:
Four major themes defined the experiences of our study participants: access to information, patient–clinician relationships, experiences of discrimination, and costs of maternity care.

Clinical Implications:
Findings highlight key barriers to providing quality and acceptable maternity care to African immigrant women at multiple levels. This group's unique barriers underlie the importance of incorporating their diverse experiences into maternity care models and clinical practice. Further research is needed to evaluate and improve maternity care for African immigrant women.
Survey of the Barriers, Enablers, and Preferences to Swimming for People With Chronic Low Back Pain
Authors: Oakes Helen , De Vivo Marlize , Stephensen David , Mills Hayley 
Published: July 2024

Background and Purpose:
It is common practice for health professionals to recommend swimming to people with chronic low back pain (CLBP) for rehabilitation and pain management and to improve levels of physical activity. Uptake and engagement in swimming involve a change in behavior, influenced by various factors including barriers, enablers, and preferences. The aim of this study was to identify the most common barriers, enablers, and preferences to swimming for people with CLBP and map them onto the Capability Opportunity Motivation-Behavior (COM-B) model.

Methods:
People with CLBP were invited to complete a survey collecting data regarding the barriers, enablers, and preferences in relation to swimming. The questions were scored on a 5-point Likert scale and mapped onto the COM-B model.

Results:
Eighty-two people completed the survey. More than 50% of participants agreed with the following barriers: I am not sure which swimming stroke is best for my back pain and I lack motivation to go swimming. These barriers mapped to the psychological capability and reflective motivation dimensions on the COM-B model. At least 50% of participants agreed with the following enablers: I would like to use swimming to improve my strength, flexibility, weight, fitness, health, mood, and well-being; setting goals and making an action plan could help me swim regularly, I am more likely to go swimming if a health professional advised me and I believe that swimming is good for my back. These enablers were also mapped to the reflective motivation and physical and social opportunity dimensions on the COM-B model.

Discussion and Conclusions:
The findings from this survey suggest that when recommending swimming, health professionals should discuss the wider health benefits of swimming, discuss specific swimming strokes and why swimming could be beneficial for back pain, and consider using motivational tools to encourage reflective motivation such as goal setting and action planning.
Basophils drive the resolution and promote wound healing in adult and aged mice
Authors: Bex Julie , Peter Victoria , Saji Chaimae , Chapart Léa , Jin Suoqin , Gautier Gregory , Thibaudeau Olivier , Thaminy Morgane K. , Tchen John , Simon Quentin , Dai Xing , Miyake Kensuke , Karasuyama Hajime , Jiang Jean X. , Naidoo Karmella , Benhamou Marc , Blank Ulrich , Monteiro Renato , Gros Graham Le , Charles Nicolas , Pellefigues Christophe 
Published: July 2024

ABSTRACTAn active resolution is critical to control the duration of inflammation and limit its pathological consequences. Defects in resolution during wound healing allow the emergence of chronic wounds, a common complication in the elderly. Here, we show that basophils infiltrate the periphery of mouse skin wounds for at least three weeks, during both the inflammation and resolution phases of wound healing. Depletion of basophils induces an increased secretion of inflammatory molecules, accumulation and activation of pro-inflammatory leukocytes, and delays the wound healing response. Basophils particularly promote epidermal differentiation towards homeostasis in the wounds. Basophil-derived IL-4 and M-CSF drive partly their immunoregulatory and healing properties. Unexpectedly, aged mice basophils infiltrate more potently the wounds to promote inflammation resolution, showing a transcriptomic signature biased towards tissue remodeling. Thus, basophils are not pro-inflammatory but pro-resolution cells during an essential biological process such as skin wound healing. Unraveling basophil pro-resolution properties may reveal new strategies to fight chronic wounds in the elderly.SUMMARYThe resolution of inflammation is essential for homeostasis and becomes defective with age. Here we show basophil immunoregulatory properties promote resolution during skin wound healing, in both adult and aged mice.
Large language models management of complex medication regimens: a case-based evaluation
Authors: Xu Steven , Most Amoreena , Chase Aaron , Hedrick Tanner , Murray Brian , Keats Kelli , Smith Susan , Barreto Erin , Liu Tianming , Sikora Andrea 
Published: July 2024

AbstractBackgroundLarge language models (LLMs) have shown capability in diagnosing complex medical cases and passing medical licensing exams, but to date, only limited evaluations have studied how LLMs interpret, analyze, and optimize complex medication regimens. The purpose of this evaluation was to test four LLMs ability to identify medication errors and appropriate medication interventions on complex patient cases from the intensive care unit (ICU).MethodsA series of eight patient cases were developed by critical care pharmacists including history of present illness, laboratory values, vital signs, and medication regimens. Then, four LLMs (ChatGPT (GPT-3.5), ChatGPT (GPT-4), Claude2, and Llama2-7b) were prompted to develop a medication regimen for the patient. LLM generated medication regimens were then reviewed by a panel of seven critical care pharmacists to assess for presence of medication errors and clinical relevance. For each medication regimen recommended by the LLM, clinicians were asked to assess for if they would continue a medication, identify perceived medication errors in the medications recommended, identify the presence of life-threatening medication choices, and rank overall agreement on a 5-point Likert scale.ResultsThe clinician panel rated to continue therapies recommended by the LLMs between 55.8-67.9% of the time. Clinicians perceived between 1.57-4.29 medication errors per recommended regimen, and life-threatening recommendations were present between 15.0-55.3% of the time. Level agreement was between 1.85-2.67 for the four LLMs.ConclusionsLLMs demonstrated potential to serve as clinical decision support for the management of complex medication regimens with further domain specific training; however, caution should be used when employing LLMs for medication management given the present capabilities.
Calcium-triggered (de)ubiquitination events in synapses
Authors: Ainatzi Sofia , Kaufmann Svenja V. , Silbern Ivan , Georgiev Svilen V. , Lorenz Sonja , Rizzoli Silvio O. , Urlaub Henning 
Published: July 2024

AbstractNeuronal communication relies on neurotransmitter release from synaptic vesicles (SVs), whose dynamics are controlled by calcium-dependent pathways, as many thoroughly studied phosphorylation cascades. However, little is known about other post-translational modifications, as ubiquitination. To address this, we analysed resting and stimulated synaptosomes (isolated synapses) by quantitative mass spectrometry. We identified more than 5,000 ubiquitination sites on ∼2,000 proteins, the majority of which participate in SV recycling processes. Several proteins showed significant changes in ubiquitination in response to calcium influx, with the most pronounced changes in CaMKIIα and the clathrin adaptor protein AP180. To validate this finding, we generated a CaMKIIα mutant lacking the ubiquitination target site (K291) and analysed it both in neurons and non-neuronal cells. K291 ubiquitination influences CaMKIIα activity and synaptic function by modulating its autophosphorylation at a functionally important site (T286). We suggest that ubiquitination in response to synaptic activity is an important regulator of synaptic function.
Transcriptional landscapes underlying Notch-induced lineage conversion and plasticity of mammary basal cells
Authors: Merle Candice , Rodrigues Calvin , Langeroudi Atefeh Pourkhalili , Journot Robin , Rost Fabian , Dang Yiteng , Rulands Steffen , Fre Silvia 
Published: July 2024

AbstractThe mammary epithelium derives from multipotent mammary stem cells (MaSCs) that progressively restrict their potency and engage into lineage commitment during embryonic development. Although postnatal mammary progenitors are lineage-restricted and unipotent, several lines of evidence have documented their extensive plasticity and ability to reactivate multipotency in several non-physiological contexts. We have previously shown that ectopic Notch1 activation in committed mammary basal cells, which never experience Notch activity in homeostatic conditions, triggers a progressive cell fate switch from basal to luminal cell identity in both the pubertal and adult mouse mammary gland. Here, we tested the conservation of this mechanism in other glandular epithelia and found that constitutive Notch1 signaling also induces a basal-to-luminal cell fate switch in adult cells of the lacrimal gland, the salivary gland, and the prostate. Since cells do not undergo lineage transition synchronously and this switch is progressive in time, we performed single cell transcriptomic analysis by SMART-Seq on index-sorted mutant mammary cells at different stages of lineage conversion, to reveal the molecular pathways underlying the fate transition. Combining single cell transcriptomics analyses with assays in organoid cultures, we demonstrate that proliferation of basal mutant cells is indispensable to convert them into luminal progenitors. We thus reveal the molecular mechanisms and individual transcriptional landscapes controlling lineage conversion and cellular plasticity of unipotent committed mammary cellsin vivowith spatial and temporal resolution. Given the strong implications of Notch signaling in cancer, these results also provide important insights into the mechanisms that drive cellular transformation.
Modelling the spatiotemporal dynamics of senescent cells in wound healing, chronic wounds, and fibrosis
Authors: Chandrasegaran Sharmilla , Sluka James P. , Shanley Daryl 
Published: July 2024

AbstractCellular senescence is known to drive age-related pathology through the senescence-associated secretory phenotype (SASP). However, it also plays important physiological roles such as cancer suppression, embryogenesis and wound healing. Wound healing is a tightly regulated process which when disrupted results in conditions such as fibrosis and chronic wounds. Senescent cells appear during the proliferation phase of the healing process where the SASP is involved in maintaining tissue homeostasis after damage. Interestingly, SASP composition and functionality was recently found to be temporally regulated, with distinct SASP profiles involved: a fibrogenic, followed by a fibrolytic SASP, which could have important implications for the role of senescent cells in wound healing. Given the number of factors at play a full understanding requires addressing the multiple levels of complexity, pertaining to the various cell behaviours, individually followed by investigating the interactions and influence each of these elements have on each other and the system as a whole. Here, a systems biology approach was adopted whereby a multi-scale model of wound healing that includes the dynamics of senescent cell behaviour and corresponding SASP composition within the wound microenvironment was developed. The model was built using the software CompuCell3D, which is based on a Cellular Potts modelling framework. We used an existing body of data on healthy wound healing to calibrate the model and validation was done on known disease conditions. The model provides understanding of the spatiotemporal dynamics of different senescent cell phenotypes and the roles they play within the wound healing process. The model also shows how an overall disruption of tissue-level coordination due to age-related changes results in different disease states including fibrosis and chronic wounds. Further specific data to increase model confidence could be used to explore senolytic treatments in wound disorders.
Multivariate analysis of multimodal brain structure predicts individual differences in risk and intertemporal preference
Authors: Bergström Fredrik , Schu Guilherme , Lee Sangil , Lerman Caryn , Kable Joseph W. 
Published: July 2024

AbstractLarge changes to brain structure (e.g., from damage or disease) can explain alterations in behavior. It is therefore plausible that smaller structural differences in healthy samples can be used to better understand and predict individual differences in behavior. Despite the brain’s multivariate and distributed structure-to-function mapping, most studies have used univariate analyses of individual structural brain measures. Here we used a multivariate approach in a multimodal data set composed of volumetric, surface-based, diffusion-based, and functional resting-state MRI measures to predict reliable individual differences in risk and intertemporal preferences. We show that combining twelve brain structure measures led to better predictions across tasks than using any individual measure, and by examining model coefficients, we visualize the relative contribution of different brain measures from different brain regions. Using a multivariate approach to brain structure-to-function mapping that combines across many brain structure properties, along with reliably measured behavior phenotypes, may increase out-of-sample prediction accuracies and insight into neural underpinnings. Furthermore, this methodological approach may be useful to improve predictions and neural insight across basic, translational, and clinical research fields.
Quantitative Analysis of Miniature Synaptic Calcium Transients Using Positive Unlabeled Deep Learning
Authors: Beaupré Frédéric , Bilodeau Anthony , Wiesner Theresa , Leclerc Gabriel , Lemieux Mado , Nadeau Gabriel , Castonguay Katrine , Fan Bolin , Labrecque Simon , Hložek Renée , De Koninck Paul , Gagné Christian , Lavoie-Cardinal Flavie 
Published: July 2024

AbstractCa2+imaging methods are widely used for studying cellular activity in the brain, allowing detailed analysis of dynamic processes across various scales. Enhanced by high-contrast optical microscopy and fluorescent Ca2+sensors, this technique can be used to reveal localized Ca2+fluctuations within neurons, including in sub-cellular compartments, such as the dendritic shaft or spines. Despite advances in Ca2+sensors, the analysis of miniature Synaptic Calcium Transients (mSCTs), characterized by variability in morphology and low signal-to-noise ratios, remains challenging. Traditional threshold-based methods struggle with the detection and segmentation of these small, dynamic events. Deep learning (DL) approaches offer promising solutions but are limited by the need for large annotated datasets. Positive Unlabeled (PU) learning addresses this limitation by leveraging unlabeled instances to increase dataset size and enhance performance. This approach is particularly useful in the case of mSCTs that are scarce and small, associated with a very small proportion of the foreground pixels. PU learning significantly increases the effective size of the training dataset, improving model performance. Here, we present a PU learning-based strategy for detecting and segmenting mSCTs. We evaluate the performance of two 3D deep learning models, StarDist-3D and 3D U-Net, which are well established for the segmentation of small volumetric structures in microscopy datasets. By integrating PU learning, we enhance the 3D U-Net’s performance, demonstrating significant gains over traditional methods. This work pioneers the application of PU learning in Ca2+imaging analysis, offering a robust framework for mSCT detection and segmentation. We also demonstrate how this quantitative analysis pipeline can be used for subsequent mSCTs feature analysis. We characterize morphological and kinetic changes of mSCTs associated with the application of chemical long-term potentiation (cLTP) stimulation in cultured rat hippocampal neurons. Our data-driven approach shows that a cLTP-inducing stimulus leads to the emergence of new active dendritic regions and differently affects mSCTs subtypes.
Azole resistance: Patterns of amino acid substitutions inCandidasterol 14α-demethylase
Authors: Prasad Rao R. Shyama , Pinto Larina , Shastry Rajesh P. , Dakal Tikam Chand , Suravajhala Prashanth N. , Sashindran V. K. , Ghate Sudeep D. 
Published: July 2024

AbstractThe emergence of azole-resistantCandidainfections is a major concern. A key mechanism is the gain of resistance through amino acid substitutions in the sterol 14α-demethylase, the main target of azole drugs. While numerous resistant substitutions are known, the pattern of such substitutions is unclear. We hypothesized that the resistant substitutions occur disproportionately at the azole-binding sites. We compiled 2,222 instances of azole-resistant substitutions from the literature and performed extensive computational sequence analyses. Altogether there were 169 known substitutions at 133 sites in sterol 14α-demethylases of sevenCandidaspecies, whereasC. albicansalone had 120 substitutions at 97 sites. Just 10 sites and 18 substitutions (such as Y132F/H, K143R, D116E, and G464S) accounted for 75% of the total instances. Only about 48% of the sites were present within the previously recognized hotspot regions, while just 33% of the known azole-interacting residues had known resistant substitutions, most of them with only a few instances. The literature data on azole-resistant substitutions inCandidaappear to be highly biased as a few substitutions such as Y132F/H and K143R were preferentially sought and reported with over 1000 instances, while there were also numerous reports of “resistant” substitutions in azole-susceptibleCandidaisolates. Our study provides interesting perspectives into azole resistance.