bluuebunny/crossref_metadata_2025_split huggingface dataset:
Advancements in the treatment of age-related macular degeneration: a comprehensive review
Authors: Papaioannou Christos 
Published: February 2024

Abstract
Age-related macular degeneration (AMD) stands as a leading cause of irreversible blindness, particularly affecting central vision and impeding daily tasks. This paper provides a thorough exploration of AMD, distinguishing between its two main subtypes—Wet and Dry AMD—while shedding light on the prevalence and risk factors, including age, genetics, and smoking.
The focus shifts to the current and future treatment landscape, examining both Dry and Wet AMD. Regarding Dry AMD, interventions such as antioxidant supplementation and ongoing clinical trials offer hope. Notable among these is Pegcetacoplan which is the only Food and Drug Administration (FDA)-approved medication, displaying promising results in reducing geographic atrophy lesions.
For Wet AMD, anti-Vascular Endothelial Growth Factor therapies like Ranibizumab (Lucentis®) have been instrumental, and newer drugs like Faricimab and OPT-302 show comparable efficacy with extended dosing intervals. Additionally, gene therapies such as RGX-314 present a potential paradigm shift, reducing or eliminating the need for frequent injections. Biosimilars offer cost-effective alternatives.
The paper also delves into the integration of technology and artificial intelligence in AMD management, highlighting the role of smartphone apps for patient monitoring and artificial intelligence algorithms for diagnosis and surveillance. Furthermore, patient perspectives on artificial intelligence demonstrate a positive correlation between understanding and trust.
The narrative concludes with a glimpse into ground-breaking technologies, including retinal implants and bionic chips, offering hope for vision restoration. Overall, this paper underscores the multifaceted approach in addressing AMD, combining traditional and innovative strategies, paving the way for a more promising future in AMD treatment.
A systematic review of patient-reported outcome measures in patients with anti-neutrophil cytoplasmic antibody associated vasculitis
Authors: Floyd Lauren , Ahmed Muhammad , Morris Adam D , Nixon Andrew C , Mitra Sandip , Dhaygude Ajay , Rowland Christine 
Published: February 2024

Abstract

Objectives
ANCA-associated vasculitis (AAV) is associated with significant morbidity, fatigue, pain and poor health-related quality of life (HRQoL). This review aims to assess the comprehensiveness of existing patient reported outcome measures (PROMs) used in AAV and identify associations with poorer HRQoL outcomes.

Methods
A literature review of studies using PROMs, including those labelled HRQoL in people with AAV as a primary or secondary study outcome were screened and reviewed up to July 2023. Quality was assessed using the Critical Appraisal Skills Programme.

Results
A total of 30 articles were included which utilised 22 different PROM tools, 76.7% (n = 23) used the SF-36 or a variation as a generic measure of health status and or HRQoL. Two studies developed a disease-specific PROM. The AAV-PRO showed good psychometric properties but potential limitations in capturing all relevant aspects of the disease experience for AAV patients. Factors associated with poorer HRQoL included: neurological and sinonasal involvement, women and younger patients. A total of 86.6% of studies showed no meaningful relationships between the SF-36 and BVAS, VDI or disease duration. Depression and anxiety were common and socioeconomic factors such as unemployment were significantly associated with poorer mental health outcomes. Glucocorticoids were found to be independently associated with worse SF-36 scores.

Conclusion
Generic PROMs are useful in measuring significant changes but lack sensitivity to specific symptoms and unique AAV-related issues, while existing disease-specific PROMs have some limitations and may not fully capture the AAV patient’s perspective on disease and treatment burden.
Associations between plasma metabolism-associated proteins and future development of giant cell arteritis: results from a prospective study
Authors: Wadström Karin , Jacobsson Lennart T H , Mohammad Aladdin J , Warrington Kenneth J , Matteson Eric L , Jakobsson Magnus E , Turesson Carl 
Published: February 2024

Abstract

Objective
The aim of this study was to investigate the relationship between biomarkers associated with metabolism and subsequent development of GCA.

Method
Participants in the population-based Malmö Diet Cancer Study (MDCS; N = 30 447) who were subsequently diagnosed with GCA were identified in a structured process. Matched GCA-free controls were selected from the study cohort. Baseline plasma samples were analysed using the antibody-based OLINK proteomics metabolism panel (92 metabolic proteins). Analyses were pre-designated as hypothesis-driven or hypothesis-generating. In the latter, principal component analysis was used to identify groups of proteins that explained the variance in the proteome.

Results
There were 95 cases with a confirmed incident diagnosis of GCA (median 12.0 years after inclusion). Among biomarkers with a priori hypotheses, adhesion G protein-coupled receptor E2 (ADGRE2) was positively associated [odds ratio (OR) per S.D. 1.67; 95% CI 1.08–2.57], and fructose-1,6-bisphosphatase 1 (FBP1) was negatively associated (OR per S.D. 0.59; 95% CI 0.35–0.99) with GCA. In particular, ADGRE2 levels were associated with subsequent GCA in the subset sampled &lt;8.5 years before diagnosis. For meteorin-like protein (Metrnl), the highest impact on the risk of GCA was observed in those patients sampled closest to diagnosis, with a decreasing trend with longer time to GCA (P = 0.03). In the hypothesis-generating analyses, elevated levels of receptor tyrosine-like orphan receptor 1 (ROR1) were associated with subsequent GCA.

Conclusion
Biomarkers identified years before clinical diagnosis indicated a protective role of gluconeogenesis (FBP1) and an association with macrophage activation (ADGRE2 and Metrnl) and proinflammatory signals (ROR1) for development of GCA.
The natural history of insomnia: evaluating illness severity from acute to chronic insomnia; is the first the worst?
Authors: Boyle Julia T , Morales Knashawn H , Muench Alexandria , Ellis Jason , Vargas Ivan , Grandner Michael A , Posner Donn , Perlis Michael L 
Published: February 2024

Abstract

Study Objectives
The 3P and 4P models represent illness severity over the course of insomnia disorder. The 3P model suggests that illness severity is worst during acute onset. The 4P model suggests that illness severity crescendos with chronicity. The present analysis from an archival dataset assesses illness severity with new onset illness (i.e. from good sleep [GS] to acute insomnia [AI] to chronic insomnia [CI]). Illness severity is quantified in terms of total wake time (TWT).

Methods
GSs (N = 934) were followed up to 1 year with digital sleep diaries, and classified as GS, AI, or CI. Data for CIs were anchored to the first of 14 days with insomnia so that day-to-day TWT was represented prior to and following AI onset. A similar graphic (+/−acute onset) was constructed for number of days per week with insomnia. GS data were temporally matched to CI data. Segmented linear mixed regression models were applied to examine the change in slopes in the AI-to-CI period compared to GS-to-AI period.

Results
Twenty-three individuals transitioned to AI and then CI. Average TWT rose during the first 2 weeks of AI onset (b = 1.8, SE = 0.57, p = 0.001) and was then stable for 3 months (b = −0.02, SE = 0.04, p = 0.53). Average number of affected days was stable from AI to CI (b = 0.0005, SE = 0.002, p = 0.81). That is, while there was week-to-week variability in the number of days affected, no linear trend was evident.

Conclusions
In our sample of CIs, primarily with middle insomnia, the average severity and number of affected days were worst with the onset of AI (worst is first) and stable thereafter.
The Effect of Copy Number Hemiplasy on Gene Family Evolution
Authors: Li Qiuyi , Chan Yao-ban , Galtier Nicolas , Scornavacca Celine 
Published: February 2024

Abstract
The evolution of gene families is complex, involving gene-level evolutionary events such as gene duplication, horizontal gene transfer, and gene loss, and other processes such as incomplete lineage sorting (ILS). Because of this, topological differences often exist between gene trees and species trees. A number of models have been recently developed to explain these discrepancies, the most realistic of which attempts to consider both gene-level events and ILS. When unified in a single model, the interaction between ILS and gene-level events can cause polymorphism in gene copy number, which we refer to as copy number hemiplasy (CNH). In this paper, we extend the Wright–Fisher process to include duplications and losses over several species, and show that the probability of CNH for this process can be significant. We study how well two unified models—multilocus multispecies coalescent (MLMSC), which models CNH, and duplication, loss, and coalescence (DLCoal), which does not—approximate the Wright–Fisher process with duplication and loss. We then study the effect of CNH on gene family evolution by comparing MLMSC and DLCoal. We generate comparable gene trees under both models, showing significant differences in various summary statistics; most importantly, CNH reduces the number of gene copies greatly. If this is not taken into account, the traditional method of estimating duplication rates (by counting the number of gene copies) becomes inaccurate. The simulated gene trees are also used for species tree inference with the summary methods ASTRAL and ASTRAL-Pro, demonstrating that their accuracy, based on CNH-unaware simulations calibrated on real data, may have been overestimated.
Sex‐dependent expression of galectin‐1, a cardioprotective β‐galactoside‐binding lectin, in human calcific aortic stenosis
Authors: Jover Eva , Martín‐Núñez Ernesto , Garaikoetxea Mattie , Matilla Lara , Blanco‐Colio Luis M. , Pérez‐Sáez Juan M. , Navarro Adela , Fernández‐Celis Amaya , Gainza Alicia , Álvarez Virginia , Sádaba Rafael , Tamayo Ibai , Rabinovich Gabriel A. , Martín‐Ventura José L. , López‐Andrés Natalia 
Published: February 2024

AbstractWe aimed to analyze sex‐related differences in galectin‐1 (Gal‐1), a β‐galactoside‐binding lectin, in aortic stenosis (AS) and its association with the inflammatory and fibrocalcific progression of AS. Gal‐1 was determined in serum and aortic valves (AVs) from control and AS donors by western blot and immunohistochemistry. Differences were validated by ELISA and qPCR in AS samples. In vitro experiments were conducted in primary cultured valve interstitial cells (VICs). Serum Gal‐1 was not different neither between control and AS nor between men and women. There was no association between circulating and valvular Gal‐1 levels. The expression of Gal‐1 in stenotic AVs was higher in men than women, even after adjusting for confounding factors, and was associated with inflammation, oxidative stress, extracellular matrix remodeling, fibrosis, and osteogenesis. Gal‐1 (LGALS1) mRNA was enhanced within fibrocalcific areas of stenotic AVs, especially in men. Secretion of Gal‐1 was up‐regulated over a time course of 2, 4, and 8 days in men's calcifying VICs, only peaking at day 4 in women's VICs. In vitro, Gal‐1 was associated with similar mechanisms to those in our clinical cohort. β‐estradiol significantly up‐regulated the activity of an LGALS1 promoter vector and the secretion of Gal‐1, only in women's VICs. Supplementation with rGal‐1 prevented the effects elicited by calcific challenge including the metabolic shift to glycolysis. In conclusion, Gal‐1 is up‐regulated in stenotic AVs and VICs from men in association with inflammation, oxidative stress, matrix remodeling, and osteogenesis. Estrogens can regulate Gal‐1 expression with potential implications in post‐menopause women. Exogenous rGal‐1 can diminish calcific phenotypes in both women and men.
MicroRNA‐409‐3p/BTG2 signaling axis improves impaired angiogenesis and wound healing in obese mice
Authors: Bestepe Furkan , Ghanem George F. , Fritsche Colette M. , Weston James , Sahay Sumedha , Mauro Amanda K. , Sahu Parul , Tas Sude M. , Ruemmele Brooke , Persing Sarah , Good Miranda E. , Chatterjee Abhishek , Huggins Gordon S. , Salehi Payam , Icli Basak 
Published: February 2024

AbstractWound healing is facilitated by neoangiogenesis, a complex process that is essential to tissue repair in response to injury. MicroRNAs are small, noncoding RNAs that can regulate the wound healing process including stimulation of impaired angiogenesis that is associated with type‐2 diabetes (T2D). Expression of miR‐409‐3p was significantly increased in the nonhealing skin wounds of patients with T2D compared to the non‐wounded normal skin, and in the skin of a murine model with T2D. In response to high glucose, neutralization of miR‐409‐3p markedly improved EC growth and migration in human umbilical vein endothelial cells (HUVECs), promoted wound closure and angiogenesis as measured by increased CD31 in human skin organoids, while overexpression attenuated EC angiogenic responses. Bulk mRNA‐Seq transcriptomic profiling revealed BTG2 as a target of miR‐409‐3p, where overexpression of miR‐409‐3p significantly decreased BTG2 mRNA and protein expression. A 3′ untranslated region (3′‐UTR) luciferase assay of BTG2 revealed decreased luciferase activity with overexpression of miR‐409‐3p, while inhibition had opposite effects. Mechanistically, in response to high glucose, miR‐409‐3p deficiency in ECs resulted in increased mTOR phosphorylation, meanwhile BTG‐anti‐proliferation factor 2 (BTG2) silencing significantly decreased mTOR phosphorylation. Endothelial‐specific and tamoxifen‐inducible miR‐409‐3p knockout mice (MiR‐409IndECKO) with hyperglycemia that underwent dorsal skin wounding showed significant improvement of wound closure, increased blood flow, granulation tissue thickness (GTT), and CD31 that correlated with increased BTG2 expression. Taken together, our results show that miR‐409‐3p is a critical mediator of impaired angiogenesis in diabetic skin wound healing.
Use of Intraoperative Neuromonitoring: A Review
Authors: Vucicevic Rajko S. , Salazar Luis M. , Federico Vincent P. , Sayari Arash J. 
Published: February 2024

Abstract
The purpose of this review is to provide an updated overview of intraoperative neuromonitoring (IONM), including its applications in cervical, thoracic, lumbar, and spinal deformity surgical procedures, and its cost-effectiveness, serving as a reference for education and clinical decision-making.
Higher CCR5 density on CD4+ T-cells in mothers and infants is associated with increased risk of in-utero HIV-1 transmission
Authors: Shalekoff Sharon , Dias Bianca Da Costa , Loubser Shayne , Strehlau Renate , Kuhn Louise , Tiemessen Caroline T. 
Published: February 2024

Objective:
CCR5-tropic viruses are preferentially transmitted during perinatal HIV-1 infection. CCR5 density on CD4+ T-cells likely impacts susceptibility to HIV-1 infection.

Design:
Fifty-two mother–infant dyads were enrolled. All mothers were living with HIV-1, 27 of the infants acquired HIV-1 in utero and 25 infants remained uninfected.

Methods:
CCR5 density, together with frequencies of CD4+ and CD8+ T-cells expressing immune activation (CCR5, ICOS and HLA-DR) and immune checkpoint (TIGIT and PD-1) markers, were measured in whole blood from the dyads close to delivery.

Results:
Compared with mothers who did not transmit, mothers who transmitted HIV-1 had less exposure to ART during pregnancy (P = 0.015) and higher plasma viral load close to delivery (P = 0.0005). These mothers, additionally, had higher CCR5 density on CD4+ and CD8+ T-cells and higher frequencies of CCR5, ICOS and TIGIT-expressing CD8+ T-cells. Similarly, compared with infants without HIV-1, infants with HIV-1 had higher CCR5 density on CD4+ and CD8+ T-cells and higher frequencies of CCR5, TIGIT, and PD-1-expressing CD4+ and CD8+ T-cells as well as higher frequencies of HLA-DR-expressing CD8+ T-cells. CCR5 density on maternal CD4+ T-cells remained significantly associated with transmission after adjusting for maternal viral load and CD4+ T cell counts. Mother–infant dyads with shared high CCR5 density phenotypes had the highest risk of transmission/acquisition of infection compared with dyads with shared low-CCR5 density phenotypes.

Conclusion:
This study provides strong evidence of a protective role for a combined mother–infant low CD4+ T-cell CCR5 density phenotype in in-utero transmission/acquisition of HIV-1.
Immunization Simulation Using Actual-Size Infant Manikins for Medical Students in Indonesia
Authors: Gunardi Hartono , Wirahmadi Angga , Medise Bernie Endyarni , Sekartini Rini , Muktiarti Dina , Findyartini Ardi , Nadhif Muhammad Hanif , Sirait Agaprita E. , Soedjatmiko Soedjatmiko , Tengkawan Jeslyn 
Published: February 2024

Introduction
Manikins are tools used in simulation training for medical students to develop important skills, one of which is immunization. However, conventional manikins often do not resemble the actual size of an infant's arm or leg. This study aimed to determine the impact of using actual-size manikins on students' knowledge and practical skills, evaluate their confidence in immunization practice, and assess students' responses and feedback regarding the practice using actual-size manikins.

Methods
This was a quasi-experimental study involving medical students at the Faculty of Medicine, Universitas Indonesia, from October 2020 to April 2021. Students in the intervention group used newly developed actual-size infant arm and leg manikins, while the control group used conventional manikins. All students underwent the objective structured clinical examination (OSCE) and the scores were compared between the 2 groups. Within the intervention group, data on pretest and posttest scores, feedback questionnaires, and self-confidence assessments were also obtained and analyzed.

Results
A total of 205 students were included. Statistically significant difference was found in the OSCE scores between the intervention and control groups (P < 0.01). Students in the intervention group (n = 108) showed significant improvement in knowledge scores after the workshop (P < 0.01). Most students (81.7%) expressed confidence in administering vaccines to live patients after practicing with manikins. In addition, 98.2% of students (n = 107) acknowledged the benefits of practicing with actual-size manikins in accurately determining the injection sites.

Conclusions
Simulation with the actual-size manikins significantly improved students' knowledge and practical immunization skills, leading to increased confidence and competence in their immunization skills.
Changes to an intensive care unitAcinetobacter baumanniipopulation following COVID-19 disruptions and targeted infection prevention interventions
Authors: Liu Haiyang , Moran Robert A. , Doughty Emma L. , Hua Xiaoting , Snaith Ann E. , Zhang Linghong , Chen Xiangping , Guo Feng , van Schaik Willem , McNally Alan , Yu Yunsong 
Published: February 2024

AbstractCarbapenem-resistantAcinetobacter baumannii(CRAB) is a persistent nosocomial pathogen that poses a significant threat to global public health. A three-month cross-sectional observational study was conducted in a 28-bed ICU in Hangzhou, China. The same ICU was sampled for the same duration and with a similar methodology in 2019, 20 months prior to the outset of this study. Following COVID-19-associated delays, a series of IPC measures targeting patients, staff and the ICU environment were implemented for 8 months prior to and throughout this study. A total of 5,341 samples were collected from the ICU environment (n = 4450) and patients (n = 891).A. baumanniiisolates were obtained from 9·5% of these samples (n = 505). MostA. baumanniiisolated in this ICU were CRAB (419/518; 80·9%). Fewer CRAB were isolated here (407 from 363 sampling occasions) than in 2019 (502 from 336 sampling occasions). However, MIC50/MIC90values for imipenem increased from 32/64 mg/L in the 2019 study to 64/128 mg/L here. This was accompanied by the proportion of global clone 2 (GC2) isolates falling from 99·5% in 2019 to 50·8% (213/419) in 2021. The phylogenetic diversity of GC2 increased, apparently driven by regular introductions of distinct clusters in association with patients. The remaining CRAB (40·2%; 206/419) were a highly clonal population of ST164, which appears to have persisted in the ICU since an introduction in mid-2020. We found clusters of GC2 and ST164 isolates with identical core genomes in different room or bed unit environments, and in multiple patients, indicative of transmission in the ICU.Changes to IPC procedures in this ICU were associated with a reduction in the total prevalence of CRAB, and in the number of CRAB isolated from clinical specimens. At the phenotypic level, the CRAB population exhibited increased resistance to carbapenems, and this may be the result of increased antibiotic prescribing over the COVID-19 period. The increased diversity of this CRAB population appears to have been the result of repeated introductions to the ICU with patients, which have continued despite interventions.
The process of developing and piloting a tool in the Maldives and Zimbabwe for assessing disability inclusion in health systems performance
Authors: Kuper Hannah , Heydt Phyllis , Hameed Shaffa , Smythe Tracey , Kujinga Tapiwanashe 
Published: February 2024

AbstractThere are 1.3 billion people with disabilities globally. On average, they experience greater healthcare needs and more barriers accessing healthcare. Yet, health systems have failed to adequately include people with disabilities. The purpose of this study was to develop and pilot-test a tool for assessing disability inclusion in health system performance. We presented the “Missing Billion” disability-inclusive health system framework, which includes 4 system-level components and 5 service delivery components, and outputs and outcomes. We developed a tool, consisting of 48 indicators related to the framework components. We consulted international experts, who considered the framework and indicator set to be logical and comprehensive. The tool was pilot-tested in the Maldives (2020) and Zimbabwe (2021), working with local researchers to collect relevant data through document review and key informant interviews. The pilot data demonstrated that collecting data on the indicators was feasible. The tool highlighted areas where the health systems were performing well in terms of disability inclusion (e.g. governance) and other areas where there were large gaps (e.g. leadership) or lack of data (e.g. accessibility, outputs and outcomes). The indicators were updated and refined. We established a process for undertaking the assessment, highlighting the importance of leadership and ownership by the Ministry of Health, to facilitate data collection and implementation of recommendations. In conclusion, this new tool for assessing disability inclusion in health systems performance can help to identify key issues and guide and monitor action.Highlights–There are 1.3 billion people with disabilities globally, and they often have poorer health and worse healthcare access than others in the population.–There is currently no comprehensive tool to assess how inclusive the healthcare system is for people with disabilities. The “Missing Billion” disability inclusive health system conceptual framework was proposed, together with 48 corresponding indicators. The indicator set allows description of the level of disability-inclusion in health systems.–The indicators were pilot-tested in the Maldives and Zimbabwe and were able to highlight areas of good practice, and identify where further improvements are needed. Some modifications were needed to the indicator set.–This new assessment approach can help policy makers, in particular at Ministries of Health, to identify key issues and guide action, and thereby may ultimately improve health systems for all.