bluuebunny/crossref_metadata_2025_split huggingface dataset:
Precision Delivery of Human Bone Marrow-Derived Mesenchymal Stem Cells Into the Pancreas Via Intra-arterial Injection Prevents the Onset of Diabetes
Authors: Primavera Rosita , Regmi Shobha , Yarani Reza , Levitte Steven , Wang Jing , Ganguly Abantika , Chetty Shashank , Guindani Michele , Ricordi Camillo , Meyer Everett , Thakor Avnesh S 
Published: March 2024

Abstract
Mesenchymal stem cells (MSCs) are a promising therapy to potentially treat diabetes given their potent anti-inflammatory and immune-modulatory properties. While these regenerative cells have shown considerable promise in cell culture, their clinical translation has been challenging. In part, this can be attributed to these cells not reaching the pancreas to exert their regenerative effects following conventional intravenous (IV) injection, with the majority of cells being trapped in the lungs in the pulmonary first-pass effect. In the present study, we will therefore examine whether direct delivery of MSCs to the pancreas via an intra-arterial (IA) injection can improve their therapeutic efficacy. Using a mouse model, in which repetitive low doses of STZ induced a gentle, but progressive, hyperglycemia, we tested bone marrow-derived MSCs (BM-MSCs) which we have shown are enriched with pro-angiogenic and immunomodulatory factors. In cell culture studies, BM-MSCs were shown to preserve islet viability and function following exposure to proinflammatory cytokines (IFN-γ, IL-1β, and TNF-α) through an increase in pAkt. When tested in our animal model, mice receiving IV BM-MSCs were not able to mitigate the effects of STZ, however those which received the same dose and batch of cells via IA injection were able to maintain basal and dynamic glycemic control, to similar levels as seen in healthy control animals, over 10 days. This study shows the importance of considering precision delivery approaches to ensure cell-based therapies reach their intended targets to enable them to exert their therapeutic effects.
Tolerogenic CD11c+dendritic cells regulate CD4+Tregs in replacing delayed ischemic preconditioning to alleviate ischemia–reperfusion acute kidney injury
Authors: Wang Pingping , Li Chunyao , Peng Tao , Ruan Longzhu , Wu Aijie , Zhu Jiaojiao , Shi Wenlu , Chen Menghua , Zhang Ting 
Published: March 2024

AbstractIschemia–reperfusion injury (IRI) is one of the primary clinical causes of acute kidney injury (AKI). The key to IRI lies in immune‐inflammatory damage, where dendritic cells (DCs) play a central role in eliciting immune responses within the context of inflammation induced by ischemia–reperfusion. Our previous study has confirmed that delayed ischemic preconditioning (DIPC) can reduce the kidney injury by mediating DCs to regulate T‐cells. However, the clinical feasibility of DIPC is limited, as pre‐clamping of the renal artery is not applicable for the prevention and treatment of ischemia–reperfusion acute kidney injury (I/R‐AKI) in clinical patients. Therefore, the infusion of DCs as a substitute for DIPC presents a more viable strategy for preventing renal IRI. In this study, we further evaluated the impact and mechanism of infused tolerogenic CD11c+DCs on the kidneys following IRI by isolating bone marrow‐derived dendritic cells and establishing an I/R‐AKI model after pre‐infusion of DCs. Renal function was significantly improved in the I/R‐AKI mouse model after pre‐infused with CD11c+DCs. The pro‐inflammatory response and oxidative damage were reduced, and the levels of T helper 2 (Th2) cells and related anti‐inflammatory cytokines were increased, which was associated with the reduction of autologous DCs maturation mediated by CD11c+DCs and the increase of regulatory T‐cells (Tregs). Next, knocking out CD11c+DCs, we found that the reduced immune protection of tolerogenic CD11c+DCs reinfusion was related to the absence of own DCs. Together, pre‐infusion of tolerogenic CD11c+DCs can replace the regulatory of DIPC on DCs and T‐cells to alleviate I/R‐AKI. DC vaccine is expected to be a novel avenue to prevent and treat I/R‐AKI.
Reducing falls among residents of retirement homes
Authors: Coleman Alanna 
Published: March 2024

Abstract:
Falls among older adults (OAs) living in retirement homes (RHs) in Canada are a major public health concern due to high morbidity and mortality as well as significant healthcare expenditures. This quality improvement (QI) initiative, conducted for the author's Doctor of Nursing Practice (DNP) project, aimed to decrease fall rates and ED transfers related to falls among OAs in six RHs across the Greater Toronto Area in Ontario, Canada through a multipart intervention with two primary goals. First, the project aimed to facilitate RH NPs' implementation of a comprehensive fall risk assessment and fall prevention strategy in their practice by incorporating the Stopping Elderly Accidents, Deaths & Injuries (STEADI) toolkit into their armamentarium. Second, it sought to enhance the knowledge of the RHs' registered practical nurses (RPNs), personal support workers (PSWs), and unregulated care providers (UCPs) in assessing fall risk and incorporating fall prevention strategies in their daily practice. By improving NP, RPN, PSW, and UCP knowledge and increasing (by 20%) RPN, PSW, and UCP use of fall prevention strategies, this QI initiative successfully reduced fall rates in the RHs by 40.4%, with no falls requiring transfer to the ED, in the postintervention period. The results of this project highlight the need for an interdisciplinary approach to fall risk reduction in RHs that includes implementation of multifactorial intervention strategies as well as effective organizational policies and procedures for maximum impact.
Postmenopausal endometriosis: a challenging condition beyond menopause
Authors: Vallée Alexandre , Carbonnel Marie , Ceccaldi Pierre-François , Feki Anis , Ayoubi Jean-Marc 
Published: March 2024

Abstract

Importance and Objective
Postmenopausal endometriosis is a complex condition that challenges the conventional belief that endometriosis resolves with menopause. Despite the cessation of menstruation, a subset of women continues to experience or develop endometriosis-related symptoms during the postmenopausal period. Thus, this review aimed to shed light on postmenopausal endometriosis, exploring its clinical features, diagnostic considerations, management approaches, and the potential impact on women's health.

Methods
PubMed/Medline, Scopus, and Web of Science databases were used for the research, with only articles in English language, using the following terms: “postmenopausal endometriosis,” “menopause,” “management,” “treatment,” and “quality of life,” from inception to 2023.

Discussion and Conclusion
The clinical features of postmenopausal endometriosis include persistent or recurrent pelvic pain, dyspareunia, bowel, or urinary symptoms and, occasionally, abnormal vaginal bleeding. The absence of menstrual cycles presents a diagnostic challenge, as the traditional diagnostic criteria for endometriosis rely on menstrual patterns. Visual cues may be less evident, and the symptoms often overlap with other gynecological conditions, necessitating a thorough evaluation to differentiate postmenopausal endometriosis from other potential causes. Management approaches for postmenopausal endometriosis encompass surgical intervention, hormonal therapies, pain management, and individualized care. Postmenopausal endometriosis significantly impacts the quality of life, sexual health, and long-term well-being of women. Understanding the clinical features, diagnostic challenges, and management approaches of postmenopausal endometriosis is crucial for healthcare professionals to provide effective care and to improve the quality of life of women affected by this condition.
“Not feeling like myself” in perimenopause — what does it mean? Observations from the Women Living Better survey
Authors: Coslov Nina , Richardson Marcie K. , Woods Nancy Fugate 
Published: March 2024

Abstract

Objective
This study aimed to understand the meaning of the phrase “not feeling like myself” (NFLM) when used by those on the path to menopause by exploring the relationship of symptoms reported to ratings of NFLM.

Methods
Participants responded to the item “Many women report just not feeling like themselves during this phase of life. How often was this true for you over the past 3 months?” choosing from “none of the time” to “all of the time.” They rated bother associated with 61 symptoms and provided demographic information. Individual symptoms and the symptom bother scale scores were correlated with NFLM. Symptom scale scores were then entered in a two-stage multiple regression model to identify symptoms associated significantly with NFLM.

Results
Sixty-three percent (63.3%) of participants reported NFLM 50% of the time or more over the previous 3 months. Individual symptom ratings correlated with NFLM (r > 0.300) included the following: fatigue (r = 0.491); feeling overwhelmed/less able to cope (r = 0.463); low feelings (r = 0.440); anxiety, more nervousness (r = 0.398); being irritable (r = 0.380); harder time concentrating (r = 0.378); difficulty making decisions (r = 0.357); feeling like “I can't calm down on the inside” (r = 0.333); being more forgetful (r = 0.332); tearfulness/crying (r = 0.306); and worrying more (r = 0.302). A two-stage regression analysis revealed less education completed and greater overall stress ratings as significant predictors in stage 1. In stage 2, five symptom groups met the P < 0.001 criterion: anxiety/vigilance, fatigue/pain, brain fog, sexual symptoms, and volatile mood symptoms.

Conclusions
NFLM was associated with anxiety/vigilance, fatigue/pain, brain fog, sexual symptoms, and volatile mood symptoms. Recognizing symptoms associated with NFLM may allow for more accurate expectations and improve perimenopause care.
Current challenges in xenotransplantation
Authors: Vadori Marta , Cozzi Emanuele 
Published: March 2024

Purpose of review
In recent years, the xenotransplantation science has advanced tremendously, with significant strides in both preclinical and clinical research. This review intends to describe the latest cutting-edge progress in knowledge and methodologies developed to overcome potential obstacles that may preclude the translation and successful application of clinical xenotransplantation.

Recent findings
Preclinical studies have demonstrated that it is now possible to extend beyond two years survival of primate recipients of life saving xenografts. This has been accomplished thanks to the utilization of genetic engineering methodologies that have allowed the generation of specifically designed gene-edited pigs, a careful donor and recipient selection, and appropriate immunosuppressive strategies.
In this light, the compassionate use of genetically modified pig hearts has been authorized in two human recipients and xenotransplants have also been achieved in human decedents. Although encouraging the preliminary results suggest that several challenges have yet to be fully addressed for a successful clinical translation of xenotransplantation. These challenges include immunologic, physiologic and biosafety aspects.

Summary
Recent progress has paved the way for the initial compassionate use of pig organs in humans and sets the scene for a wider application of clinical xenotransplantation.
A Case Series of Choroidal and Orbital Neuroendocrine Tumors: Metastasis
Authors: Zhuang Tony Zibo , Bergstrom Chris , El-Rayes Bassel F. , Shaib Walid L. 
Published: March 2024

Abstract
Neuroendocrine tumors (NETs) are rare cancers with heterogeneous histologies, response to treatments, and prognoses. Majority of these cancers originate in the gastrointestinal tract and metastasize to the liver. We report the cases of 5 patients with low-grade NET disease with rare metastases to the choroids. Two of the patients were treated with peptide receptor radionuclide therapy (lutetium 177 [177Lu]). This is the first report confirming peptide radionuclide therapy safety in patients with low-grade NET with ocular metastases.
Translating knowledge on placebo and nocebo effects into clinical practice
Authors: Caliskan Elif Buse , Bingel Ulrike , Kunkel Angelika 
Published: March 2024

Abstract

Introduction:
Positive and negative treatment expectations are powerful modulators of health and treatment outcomes. A substantial part of treatment success is due to contextual factors modulating patient's expectations towards a treatment. Consequently, treatment expectations should be a target of therapeutic interventions themselves.

Objectives:
This article highlights the neurobiological underpinnings of treatment expectations as well as strategies to modulate contextual factors to optimize treatment outcomes in daily clinical settings.

Methods:
This clinical update aligns with the 2022 IASP Global Year Translating Pain Knowledge into Practice and selectively reviews the best available evidence and practice.

Results:
The effects of treatment expectations, also known as placebo and nocebo effects, are observed in various clinical conditions and physiological systems. However, most of our knowledge comes from the field of pain, where expectation effects substantially contribute to overall analgesic treatment outcomes. Experimental placebo analgesia paradigms provide the best illustration of how analgesic effects can be attributed not only to a pharmacological or specific treatment, but instead are the result of the expectation towards the treatment. The impact of expectations on treatment outcome is highly variable between individuals, and the identification of factors predicting an individual's response has proven to be challenging. Further research is required to provide personalized treatment strategies for the daily clinical practice.

Conclusion:
Patient's previous experiences and expectations are powerful modulators of treatment efficacy, tolerability, and adherence. By providing a comprehensive overview of recent advances in this field, this review offers valuable insights for clinicians and researchers seeking to improve patient–clinician interaction.
Synaptic weight dynamics underlying memory consolidation: implications for learning rules, circuit organization, and circuit function
Authors: Bhasin Brandon J , Raymond Jennifer L , Goldman Mark S 
Published: March 2024

AbstractSystems consolidation is a common feature of learning and memory systems, in which a long-term memory initially stored in one brain region becomes persistently stored in another region. We studied the dynamics of systems consolidation in simple circuit architectures with two sites of plasticity, one in an early-learning and one in a late-learning brain area. We show that the synaptic dynamics of the circuit during consolidation of an analog memory can be understood as a temporal integration process, by which transient changes in activity driven by plasticity in the early-learning area are accumulated into persistent synaptic changes at the late-learning site. This simple principle naturally leads to a speed-accuracy tradeoff in systems consolidation and provides insight into how the circuit mitigates the stability-plasticity dilemma of storing new memories while preserving core features of older ones. Furthermore, it imposes two constraints on the circuit. First, the plasticity rule at the late-learning site must stably support a continuum of possible outputs for a given input. We show that this is readily achieved by heterosynaptic but not standard Hebbian rules. Second, to turn off the consolidation process and prevent erroneous changes at the late-learning site, neural activity in the early-learning area must be reset to its baseline activity. We propose two biologically plausible implementations for this reset that suggest novel roles for core elements of the cerebellar circuit.Significance StatementHow are memories transformed over time? We propose a simple organizing principle for how long term memories are moved from an initial to a final site of storage. We show that successful transfer occurs when the late site of memory storage is endowed with synaptic plasticity rules that stably accumulate changes in activity occurring at the early site of memory storage. We instantiate this principle in a simple computational model that is representative of brain circuits underlying a variety of behaviors. The model suggests how a neural circuit can store new memories while preserving core features of older ones, and suggests novel roles for core elements of the cerebellar circuit.
Treatment Heterogeneity of Water, Sanitation, Hygiene, and Nutrition Interventions on Child Growth by Environmental Enteric Dysfunction and Pathogen Status for Young Children in Bangladesh
Authors: Butzin-Dozier Zachary , Ji Yunwen , Coyle Jeremy , Malenica Ivana , Rogawski McQuade Elizabeth T. , Grembi Jessica Anne , Platts-Mills James A. , Houpt Eric R. , Graham Jay P. , Ali Shahjahan , Rahman Md Ziaur , Alauddin Mohammad , Famida Syeda L. , Akther Salma , Hossen Md. Saheen , Mutsuddi Palash , Shoab Abul K. , Rahman Mahbubur , Islam Md. Ohedul , Miah Rana , Taniuchi Mami , Liu Jie , Alauddin Sarah , Stewart Christine P. , Luby Stephen P. , Colford John M. , Hubbard Alan E. , Mertens Andrew N. , Lin Audrie 
Published: March 2024

AbstractBackgroundWater, sanitation, hygiene (WSH), nutrition (N), and combined (N+WSH) interventions are often implemented by global health organizations, but WSH interventions may insufficiently reduce pathogen exposure, and nutrition interventions may be modified by environmental enteric dysfunction (EED), a condition of increased intestinal permeability and inflammation. This study investigated the heterogeneity of these treatments’ effects based on individual pathogen and EED biomarker status with respect to child linear growth.MethodsWe applied cross-validated targeted maximum likelihood estimation and super learner ensemble machine learning to assess the conditional treatment effects in subgroups defined by biomarker and pathogen status. We analyzed treatment (N+WSH, WSH, N, or control) randomly assigned in-utero, child pathogen and EED data at 14 months of age, and child LAZ at 28 months of age. We estimated the difference in mean child length for age Z-score (LAZ) under the treatment rule and the difference in stratified treatment effect (treatment effect difference) comparing children with high versus low pathogen/biomarker status while controlling for baseline covariates.ResultsWe analyzed data from 1,522 children, who had median LAZ of -1.56. We found that myeloperoxidase (N+WSH treatment effect difference 0.0007 LAZ, WSH treatment effect difference 0.1032 LAZ, N treatment effect difference 0.0037 LAZ) andCampylobacterinfection (N+WSH treatment effect difference 0.0011 LAZ, WSH difference 0.0119 LAZ, N difference 0.0255 LAZ) were associated with greater effect of all interventions on growth. In other words, children with high myeloperoxidase orCampylobacterinfection experienced a greater impact of the interventions on growth. We found that a treatment rule that assigned the N+WSH (LAZ difference 0.23, 95% CI (0.05, 0.41)) and WSH (LAZ difference 0.17, 95% CI (0.04, 0.30)) interventions based on EED biomarkers and pathogens increased predicted child growth compared to the randomly allocated intervention.ConclusionsThese findings indicate that EED biomarker and pathogen status, particularlyCampylobacterand myeloperoxidase (a measure of gut inflammation), may be related to impact of N+WSH, WSH, and N interventions on child linear growth.
Multi-species co-circulation of adenoviruses identified by next generation sequencing during an outbreak in coastal Kenya in 2023
Authors: Lambisia Arnold W. , Mutunga Martin , Katama Esther N. , Agoti Charles N. , Houldcroft Charlotte J. 
Published: March 2024

AbstractBackgroundAlthough seven human adenovirus (HAdV) species are known to exist,only F (types 40 and 41) and G, are identified as diarrhoeal disease agents. The role of other HAdV species in diarrhoeal disease remains unclear and data of their prevalence is limited. We describe HAdV species and types in hospitalised children with diarrhoea in coastal Kenya.Methods329 stool samples collected between June 2022 and August 2023 from children aged <13-years were screened for HAdV using quantitative polymerase chain reaction (qPCR). Positive HAdV cases were genotyped by adenovirus primers from the RespiCoV panel by amplification, next generation sequencing followed by phylogenetic analysis.Results65 samples (20%) tested HadV positive from which five HAdV species were identified. Other than HAdV F, other species included A, B, C and D; these were detected as either mono-detections or coinfections. Six HAdV F identified by NGS had been missed by our q PCR typing method. This appeared to be as a result of a 133-nucleotide deletion in the long fiber protein which abrogated a primer and probe binding site. Based on VESIKARI scores grading of diarrheal disease severity, 93% of the HAdV cases presented with severe disease. One child with an HAdV F infection died.ConclusionOur study shows the enormous diversity and clinical characteristics of HAdV species in children with diarrhoea in coastal Kenya. These data offers an opportunity to improve current diagnostic assays, increase knowledge of HAdV in Africa for control of outbreaks in the future.
Cancer-cell derived S100A11 promotes macrophage recruitment in ER+ breast cancer
Authors: Lee Sanghoon , Cho Youngbin , Li Yiting , Li Ruxuan , Brown Daniel , McAuliffe Priscilla , Lee Adrian V , Oesterreich Steffi , Zervantonakis Ioannis K. , Osmanbeyoglu Hatice Ulku 
Published: March 2024

AbstractMacrophages are pivotal in driving breast tumor development, progression, and resistance to treatment, particularly in estrogen receptor-positive (ER+) tumors, where they infiltrate the tumor microenvironment (TME) influenced by cancer cell-secreted factors. By analyzing single-cell RNA-sequencing data from 25 ER+ tumors, we elucidated interactions between cancer cells and macrophages, correlating macrophage density with epithelial cancer cell density. We identified that S100A11, a previously unexplored factor in macrophage-cancer crosstalk, predicts high macrophage density and poor outcomes in ER+ tumors. We found that recombinant S100A11 enhances macrophage infiltration and migration in a dose-dependent manner. Additionally, in 3D models, we showed that S100A11 expression levels in ER+ cancer cells predict macrophage infiltration patterns. Neutralizing S100A11 decreased macrophage recruitment, both in cancer cell lines and in a clinically relevant patient-derived organoid model, underscoring its role as a paracrine regulator of cancer-macrophage interactions in the pro-tumorigenic TME. This study offers novel insights into the interplay between macrophages and cancer cells in ER+ breast tumors, highlighting S100A11 as a potential therapeutic target to modulate the macrophage-rich tumor microenvironment.