bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of anti-VEGF treatment on development of proliferative diabetic retinopathy in routine clinical practice
Authors: Moshfeghi Andrew A. , Khurana Rahul N. , Moini Hadi , Sherman Steven , Reed Kimberly , Boucher Nick , Rahimy Ehsan 
Published: May 2024

Abstract
Background
This study evaluated impact of anti–vascular endothelial growth factor (VEGF) treatment on proliferative diabetic retinopathy (PDR) development among patients with non-proliferative diabetic retinopathy (NPDR) in US real-world clinical practice.

Methods
This was a retrospective analysis of electronic medical records (Vestrum Health; January 2013 to June 2019) of eyes with baseline NPDR, without DME, and naïve to anti-VEGF treatment at index DR diagnosis. Eyes that received anti-VEGF and/or laser treatment over the course of study before development of PDR constituted the treated cohort while the remaining including those treated with laser constituted the anti-VEGF naïve cohort. Survival analysis via Kaplan–Meier method evaluated time to DME and PDR development by baseline NPDR severity, with anti-VEGF treatment as censoring variable. Baseline factors affecting PDR development were analyzed using Cox multivariable regression, censoring for anti-VEGF treatment.

Results
Among anti-VEGF–naive eyes, cumulative incidence of DME in eyes with mild (n = 70,050), moderate (n = 39,116), and severe NPDR (n = 10,692) at baseline was 27.1%, 51.2%, and 60.6%. Multivariable regression analysis identified baseline NPDR severity as the most significant predictor of PDR development over 48 months (hazard ratio [HR] [95% confidence interval {CI}] of 2.69 (2.65–2.72) for moderate vs mild NPDR and 6.51 (6.47–6.55) for severe vs mild NPDR). Cumulative incidence (95% CI) of PDR was 7.9% (7.4%–8.3%), 20.9%, (20.0%–21.7%) and 46.8% (44.4%–49.2%) over 48 months in eyes with mild, moderate, and severe NPDR at baseline, respectively. Among treated eyes with baseline severe NPDR, cumulative incidence of PDR at 48 months was 50.1% in eyes treated with laser (n = 546; HR [95% CI] vs no treatment: 0.8 [0.7–1.0]), 27.4% in eyes treated with anti-VEGF (n = 923; HR [95% CI]: 0.4 [0.4–0.5]), and 25.6% in eyes treated with anti-VEGF plus laser (n = 293; HR [95% CI]: 0.5 [0.4–0.7]) compared with 49.9% in eyes with no treatment (n = 8930).

Conclusions
DME and PDR development rates increased with increasing baseline NPDR severity. Approximately half of anti-VEGF‒naive eyes with severe NPDR progressed to PDR within 4 years in US clinical practice. The progression rate from severe NPDR to PDR was approximately halved with anti-VEGF versus no treatment.
Adolescent boys’ experiences of mental health and school health services - an interview study from Norway
Authors: Helland Lindborg Tonje , Kristensson Hallström Inger , Synnøve Litland Astrid , Åvik Persson Helene 
Published: May 2024

Abstract
Background
Mental health problems among adolescents is a global challenge. During the transition to adolescence, physiological, psychological, and social changes occur, leading to increased vulnerability. Thus, adolescent boys are less likely to seek help for mental health problems, which makes them an undetected group. The aim of this study was to gain a deeper understanding of adolescent boys’ experiences of mental health and school health service.

Methods
An inductive, qualitative design was chosen using three focus group interviews and three individual interviews. The study included 18 adolescent boys in 7th grade, in a school located in a medium-sized municipality in Norway. The interviews were analysed with qualitative content analysis. The consolidated criteria for reporting qualitative research (COREQ) were followed in this study.

Results
The overall theme “barriers towards seeking help”, and three categories— navigating stigma and privacy concerns; perceptions of self-responsibility; and lacking knowledge of mental health problems and help-seeking—described the adolescent boys experiences. The awareness and willingness to seek help were present, but there are barriers preventing the adolescent boys from acting on that willingness.

Conclusions
Lack of knowledge and a non-permissive culture for mental health problems among adolescents contributes to decreased help-seeking behaviour among adolescent boys. The school health service is the most related health service for adolescents and should focus on being available and strengthening empowerment and mental health literacy through the development and implementation of interventions to promote mental health.
Association of frailty status with overall survival in elderly hypertensive patients: based on the Chinese Longitudinal Healthy Longevity Survey
Authors: Li Liying , Liang Yueting , Xin Dajun , Liu Lu , Tan Zhuomin , Wang Ziqiong , Zhang Muxin , Ruan Haiyan , Zhao Liming , Wang Kexin , Zheng Yi , Song Ningying , He Sen 
Published: May 2024

Abstract
Background
Hypertension and frailty often coexist in older people. The present study aimed to evaluate the association of frailty status with overall survival in elderly hypertensive patients, using data from the Chinese Longitudinal Healthy Longevity Survey.

Methods
A total of 10,493 elderly hypertensive patients were included in the present study (median age 87.0 years, 58.3% male). Frailty status was assessed according to a 36-item frailty index (FI), which divides elderly individuals into four groups: robustness (FI ≤ 0.10), pre-frailty (0.10 < FI ≤ 0.20), mild-frailty (0.20 < FI ≤ 0.30), and moderate-severe frailty (FI > 0.30). The study outcome was overall survival time. Accelerated failure time model was used to evaluate the association of frailty status with overall survival.

Results
During a period of 44,616.6 person-years of follow-up, 7327 (69.8%) participants died. The overall survival time was decreased with the deterioration of frailty status. With the robust group as reference, adjusted time ratios (TRs) were 0.84 (95% confidence interval [CI]: 0.80–0.87) for the pre-frailty group, 0.68 (95% CI: 0.64–0.72) for the mild frailty group, and 0.52 (95% CI: 0.48–0.56) for the moderate-severe frailty group, respectively. In addition, restricted cubic spline analysis revealed a nearly linear relationship between FI and overall survival (p for non-linearity = 0.041), which indicated the overall survival time decreased by 17% with per standard deviation increase in FI (TR = 0.83, 95% CI: 0.82–0.85). Stratified and sensitivity analyses suggested the robustness of the results.

Conclusions
The overall survival time of elderly hypertensive patients decreased with the deterioration of frailty status. Given that frailty is a dynamic and even reversible process, early identification of frailty and active intervention may improve the prognosis of elderly hypertensive patients.
Update on the practice of premarital screening for sickle cell traits in Africa: a systematic review and meta-analysis
Authors: Dilli Priscilla Peter , Obeagu Emmanuel , Tamale Andrew , Ajugwo Anselm , Pius Theophilus , Makeri Danladi 
Published: May 2024

Abstract
Background
Screening for sickle cell traits before marriage or producing children is one of the outstanding preventive measures for sickle cell disease (SCD).The disease is a collection of inherited blood disorders that impact millions globally, with a predominant 75% occurrence in the sub-Saharan region. With increasing burden of SCD on the continent amidst a cost effective prevention method, no study has systematically reviewed or presented meta-analytic uptake or practice of premarital sickle cell trait screening.

Methods
This review systematically explored the uptake or practice of premarital genotype screening in Africa. We searched PubMed and Scopus databases for African studies on premarital screening for sickle cell traits.

Results
Our results indicate that the pooled uptake of premarital sickle cell trait screening in Africa is 47.82% (95% CI: [46.53–49.11]; I2: 98.95% [98.74–99.13]). Our review observed, a significant relationship between the awareness of sickle cell disease and the uptake of genotype screening; F(1, 13) = 12.04, p = 0.004). The model explained approximately 48.08% of the variation in genotype screening (R² = 0.4808) and predicted a 0.729 increase in the likelihood of genotype screening uptake for every unit rise in sickle cell disease awareness (β = 0.729, p = 0.004). Additionally, Pearson correlation (r = 0.6934) indicated a moderately strong positive correlation between the two variables.

Conclusion
With over 75% of the global burden of sickle cell disease domiciled in Africa, the continent cannot overlook the cost of hemoglobinopathies. The uptake of sickle cell traits screening is suboptimal across the continent. To achieve the mandate of sustainable development goal number (3); to end preventable deaths of newborns and children under 5 years of age by 2030, there is need to intensify campaigns on premarital genetic screening through education and other health promotion tools.
The effect of artificial saliva on the control of dry mouth: a semi-experimental study on COVID-19 patients under Non-invasive mechanical ventilation
Authors: Sedighi Ladan , Khari Sorour , Hasheminik Morteza , Salimi Akinabadi Atefe , Alipour Haleh , Shafigh Elnaz , Shafigh Navid 
Published: May 2024

Abstract
Objectives
Since maintaining oral hygiene is essential in nursing care, the present study was conducted to determine the effect of oral care using Mucosamin artificial saliva spray to control dry mouth in ICU patients with COVID-19.

Materials and methods
The current semi-experimental research was conducted on eighty patients with COVID-19 selected using the available sampling method. The study tool was a Beck oral assessment scale (BOAS). The case and control groups were selected from two hospitals with relatively similar conditions and treatment procedures. For patients in the intervention group, mucosamin artificial saliva spray was used in addition to the common care, while control group patients received only common care.

Results
Eighty patients were randomly assigned to two groups named control and intervention (40 patients in each group). The intervention was very effective in reducing the BOAS score after four days in comparison with the control group (9.23 vs. 12.05, respectively; p-value < 0.001). Based on the adjusted model, the application of artificial saliva reduced the BOAS score, indicating improvement in mouth dryness. While the BOAS score was increased in the control group, it had a declining trend in the intervention one.

Conclusion
The study’s results showed that using artificial saliva spray could effectively reduce the symptoms of dry mouth in patients with COVID-19 treated with non-invasive mechanical ventilation.

Clinical relevance
The present study introduced an applicable solution (artificial saliva) to treat mouth dryness in ICU patients under mechanical ventilation.
M1 macrophage-derived exosomes promote intervertebral disc degeneration by enhancing nucleus pulposus cell senescence through LCN2/NF-κB signaling axis
Authors: Fan Chunyang , Wang Wei , Yu Zilin , Wang Jiale , Xu Wei , Ji Zhongwei , He Wei , Hua Di , Wang Wentao , Yao Linye , Deng Yongkang , Geng Dechun , Wu Xiexing , Mao Haiqing 
Published: May 2024

AbstractIntervertebral disc degeneration (IVDD) is the primary factor contributing to low back pain (LBP). Unlike elderly patients, many young IVDD patients usually have a history of trauma or long-term abnormal stress, which may lead to local inflammatory reaction causing by immune cells, and ultimately accelerates degeneration. Research has shown the significance of M1-type macrophages in IVDD; nevertheless, the precise mechanism and the route by which it influences the function of nucleus pulposus cell (NPC) remain unknown. Utilizing a rat acupuncture IVDD model and an NPC degeneration model induced by lipopolysaccharide (LPS), we investigated the function of M1 macrophage-derived exosomes (M1-Exos) in IVDD both in vivo and in vitro in this study. We found that M1-Exos enhanced LPS-induced NPC senescence, increased the number of SA-β-gal-positive cells, blocked the cell cycle, and promoted the activation of P21 and P53. M1-Exos derived from supernatant pretreated with the exosome inhibitor GW4869 reversed this result in vivo and in vitro. RNA-seq showed that Lipocalin2 (LCN2) was enriched in M1-Exos and targeted the NF-κB pathway. The quantity of SA-β-gal-positive cells was significantly reduced with the inhibition of LCN2, and the expression of P21 and P53 in NPCs was decreased. The same results were obtained in the acupuncture-induced IVDD model. In addition, inhibition of LCN2 promotes the expression of type II collagen (Col-2) and inhibits the expression of matrix metalloproteinase 13 (MMP13), thereby restoring the equilibrium of metabolism inside the extracellular matrix (ECM) in vitro and in vivo. In addition, the NF-κB pathway is crucial for regulating M1-Exo-mediated NPC senescence. After the addition of M1-Exos to LPS-treated NPCs, p-p65 activity was significantly activated, while si-LCN2 treatment significantly inhibited p-p65 activity. Therefore, this paper demonstrates that M1 macrophage-derived exosomes have the ability to deliver LCN2, which activates the NF-κB signaling pathway, and exacerbates IVDD by accelerating NPC senescence. This may shed new light on the mechanism of IVDD and bring a fresh approach to IVDD therapy.
Graphical Abstract
Impact of extracorporeal membrane oxygenation treatments on acquired von Willebrand syndrome in patients with out-of-hospital cardiac arrest: a retrospective observational study
Authors: Chiba Yuki , Goto Kota , Suzuki Misako , Horiuchi Hisanori , Hayakawa Mineji 
Published: May 2024

Abstract
Background
Von Willebrand factor (vWF) plays a crucial role in hemostasis, acting as a key factor for platelet adhesion/aggregation and as a transport protein for coagulation factor VIII. vWF is secreted as a giant multimer, and it undergoes shear stress-dependent cleavage by a specific metalloproteinase in plasma. Among vWF multimers, high-molecular-weight (large) multimers are essential for hemostasis. Acquired von Willebrand syndrome, linked to various conditions, is a hemostatic disorder due to reduced vWF activity. Extracorporeal membrane oxygenation (ECMO), utilized recently for out-of-hospital cardiac arrest patients, generates high shear stress inside the pump. This stress may induce a conformational change in vWF, enhancing cleavage by a specific metalloproteinase and thereby reducing vWF activity. However, no study has investigated the effects of ECMO on vWF-related factors in patients receiving or not receiving ECMO. This study aimed to elucidate the relationship between ECMO treatment and acquired von Willebrand syndrome-related factors in patients with out-of-hospital cardiac arrest.

Methods
This study included patients with cardiogenic out-of-hospital cardiac arrest admitted to our hospital. The patients were categorized into two groups (ECMO and non-ECMO) based on the presence or absence of ECMO treatment. Plasma samples were collected from patients admitted to the emergency department (days 0–4). The vWF antigen (vWF: Ag), vWF ristocetin cofactor activity (vWF: RCo), and factor VIII activity were measured. Additionally, a large multimer of vWF was evaluated through vWF multimer analysis, utilizing western blotting to probe vWF under non-reducing conditions.

Results
The ECMO and non-ECMO groups included 10 and 22 patients, respectively. The median ECMO treatment in the ECMO group was 64.6 h. No differences in vWF: Ag or factor VIII activity were observed between the two groups during the observation period. However, the ECMO group exhibited a decrease in large vWF multimers and vWF: RCo during ECMO. Strong correlations were observed between vWF: RCo and vWF: Ag in both groups, although the relationships were significantly different between the two groups.

Conclusions
ECMO treatment in patients with out-of-hospital cardiac arrest resulted in the loss of large vWF multimers and decreased vWF activity. Hence, decreased vWF activity should be considered as a cause of bleeding during ECMO management.
The associations of adherence to the Mediterranean diet with chronic dizziness and imbalance in community-dwelling adults: KNHANES 2019–2021
Authors: Jeong Seong-Hae , Kim Eun Ji , Kwon Eunjin , Kim Ji-Soo , Jung Sukyoung 
Published: May 2024

Abstract
Background
Dizziness and vertigo rank among the top 10 reasons for emergency and clinical referrals to neurologists. Chronic dizziness and imbalance not only reduce quality of life, but also increase mortality. While the Mediterranean diet has long been considered beneficial for human and planetary health, its effects on chronic dizziness or imbalance are understudied. We investigated the associations of adherence to the Mediterranean diet with chronic dizziness and imbalance.

Methods
This study used data from the Korea National Health and Nutrition Examination Survey 2019–2021 and included 4,183 adults aged 40 years and older with complete information from diet, dizziness, and neurotology questionnaires. The alternate Mediterranean diet score (aMed) for nine food groups was calculated from 24-hour dietary recall data. Based on questionnaire responses, chronic dizziness was categorized as either isolated or chronic dizziness with imbalance, characterized by a cluster of difficulties maintaining a standing position, walking, or falling.

Results
In a multivariable-adjusted model, the prevalence of chronic imbalance was lower in the top aMed tertile than in the bottom tertile (OR 0.37; 95% CI, 0.18–0.74; p-trend = 0.01). Among the individual aMed components, the intake of whole grains and nuts exhibited an inverse relationship with chronic imbalance (OR 0.50; 95% CI, 0.27–0.93 for whole grains; OR 0.55; 95% CI, 0.31–1.01 for nuts). The aMed score was not associated with isolated chronic dizziness.

Conclusions
Greater adherence to the Mediterranean diet may reduce chronic imbalance, particularly with an adequate intake of whole grains and nuts.
Development and validation of a simple and practical model for early detection of diabetic macular edema in patients with type 2 diabetes mellitus using easily accessible systemic variables
Authors: Wu Guanrong , Hu Yijun , Zhu Qibo , Liang Anyi , Du Zijing , Zheng Chunwen , Liang Yanhua , Zheng Yuxiang , Hu Yunyan , Kong Lingcong , Liang Yingying , Amadou Maman Lawali Dan Jouma , Fang Ying , Liu Yuejuan , Feng Songfu , Yuan Ling , Cao Dan , Lin Jinxin , Yu Honghua 
Published: May 2024

Abstract
Objective
Diabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus (DM). The goal of early detection has not yet achieved due to a lack of fast and convenient methods. Therefore, we aim to develop and validate a prediction model to identify DME in patients with type 2 diabetes mellitus (T2DM) using easily accessible systemic variables, which can be applied to an ophthalmologist-independent scenario.

Methods
In this four-center, observational study, a total of 1994 T2DM patients who underwent routine diabetic retinopathy screening were enrolled, and their information on ophthalmic and systemic conditions was collected. Forward stepwise multivariable logistic regression was performed to identify risk factors of DME. Machine learning and MLR (multivariable logistic regression) were both used to establish prediction models. The prediction models were trained with 1300 patients and prospectively validated with 104 patients from Guangdong Provincial People’s Hospital (GDPH). A total of 175 patients from Zhujiang Hospital (ZJH), 115 patients from the First Affiliated Hospital of Kunming Medical University (FAHKMU), and 100 patients from People’s Hospital of JiangMen (PHJM) were used as external validation sets. Area under the receiver operating characteristic curve (AUC), accuracy (ACC), sensitivity, and specificity were used to evaluate the performance in DME prediction.

Results
The risk of DME was significantly associated with duration of DM, diastolic blood pressure, hematocrit, glycosylated hemoglobin, and urine albumin-to-creatinine ratio stage. The MLR model using these five risk factors was selected as the final prediction model due to its better performance than the machine learning models using all variables. The AUC, ACC, sensitivity, and specificity were 0.80, 0.69, 0.80, and 0.67 in the internal validation, and 0.82, 0.54, 1.00, and 0.48 in prospective validation, respectively. In external validation, the AUC, ACC, sensitivity and specificity were 0.84, 0.68, 0.90 and 0.60 in ZJH, 0.89, 0.77, 1.00 and 0.72 in FAHKMU, and 0.80, 0.67, 0.75, and 0.65 in PHJM, respectively.

Conclusion
The MLR model is a simple, rapid, and reliable tool for early detection of DME in individuals with T2DM without the needs of specialized ophthalmologic examinations.
Augmentation of tumor expression of HLA-DR, CXCL9, and CXCL10 may improve olfactory neuroblastoma immunotherapeutic responses
Authors: Larkin Riley M. , Lopez Diana C. , Robbins Yvette L. , Lassoued Wiem , Canubas Kenneth , Warner Andrew , Karim Baktiar , Vulikh Ksenia , Hodge James W. , Floudas Charalampos S. , Gulley James L. , Gallia Gary L. , Allen Clint T. , London Nyall R. 
Published: May 2024

Abstract
Background
Olfactory neuroblastoma is a rare malignancy of the anterior skull base typically treated with surgery and adjuvant radiation. Although outcomes are fair for low-grade disease, patients with high-grade, recurrent, or metastatic disease oftentimes respond poorly to standard treatment methods. We hypothesized that an in-depth evaluation of the olfactory neuroblastoma tumor immune microenvironment would identify mechanisms of immune evasion in high-grade olfactory neuroblastoma as well as rational targetable mechanisms for future translational immunotherapeutic approaches.

Methods
Multispectral immunofluorescence and RNAScope evaluation of the tumor immune microenvironment was performed on forty-seven clinically annotated olfactory neuroblastoma samples. A retrospective chart review was performed and clinical correlations assessed.

Results
A significant T cell infiltration was noted in olfactory neuroblastoma samples with a stromal predilection, presence of myeloid-derived suppressor cells, and sparse natural killer cells. A striking decrease was observed in MHC-I expression in high-grade olfactory neuroblastoma compared to low-grade disease, representing a mechanism of immune evasion in high-grade disease. Mechanistically, the immune effector stromal predilection appears driven by low tumor cell MHC class II (HLA-DR), CXCL9, and CXCL10 expression as those tumors with increased tumor cell expression of each of these mediators correlated with significant increases in T cell infiltration.

Conclusion
These data suggest that immunotherapeutic strategies that augment tumor cell expression of MHC class II, CXCL9, and CXCL10 may improve parenchymal trafficking of immune effector cells in olfactory neuroblastoma and augment immunotherapeutic responses.