bluuebunny/crossref_metadata_2025 huggingface dataset:
Brazil’s Unified Health System: the fight for a universal right in an unequal country
Authors: Vieira-Machado Cristiani , Dias de Lima Luciana
Published: October 2024

This article analyzes Brazil's Unified Health System (SUS), established by the 1988 Constitution. The article initially presents the previous trajectory of national health policy and the context of democratization in the 1980s, which favored health reform and created a public, universal, and comprehensive health system. It then explores the advances and contradictions recorded in more than three decades of implementation of the SUS. The main advances observed were the creation of institutional mechanisms compatible with the federative arrangement and social participation, political and administrative decentralization, the national expansion of access to health, changes in the health care model, including strengthening primary care, and improvements in health indicators. On the other hand, the persistence of structural problems and disputes between different health agendas, with differences between governments, led to contradictions in financing and public-private relations in health. Despite the differences between countries, the analysis of the Brazilian case provides lessons on the challenges in building universal health systems in Latin America.
Moisture Barrier of Polylactic Acid/Graphene Nanocomposite Films
Authors: Tang Man Chio , Agarwal Sushant , Alsewailem Fares D. , Choi Hyoung J. , Gupta Rakesh K.
Published: October 2024

Moisture barrier properties of nanocomposite films of polylactic acid (PLA) and graphene nanoplatelets (GNP) were studied. Polylactic acid is a bioderived and biodegradable polymer which can be a substitute for conventional polymers as a packaging material if its barrier properties can be improved. Graphene nanoplatelets were dispersed in the PLA matrix via melt-blending to act as moisture barriers. Moisture permeability was measured as a function of graphene concentration using MOCON® water vapor transmission equipment. It was found that at a loading of only 1.2 vol% GNP, the water vapor permeability was reduced by 35% compared to neat PLA. This result is better than that observed with PLA/clay nanocomposites under identical conditions. Graphene nanoplatelets are severely agglomerated, and TEM pictures show large areas through which diffusion can occur without any hindrance. An explanation is presented to account for the observed behavior.
Access to oral healthcare for children during the COVID-19 pandemic: A mixed-methods study in the Aegean Region of Türkiye
Authors: Arabulan Sevgi , Önçağ Rüştü Özant , Öcek Zeliha Aslı
Published: October 2024

Background
The COVID-19 pandemic significantly disrupted healthcare systems, particularly affecting vulnerable populations such as children and individuals with special needs, causing delays and reductions in routine dental services. The aim of this study was to evaluate the accessibility of dental services and identify determinants of access to oral health care for children aged 0–13 years during the COVID-19 pandemic restriction period.
Methods
We used a mixed-method research design. This cross-sectional study included 270 children aged 0 to 13 years who visited Ege University Pediatric Dental Clinics between August 2021 and February 2022. Interviewer-administered questionnaires collected information about sociodemographic and economic characteristics, as well as dental service utilization during the pandemic. "Access" to receive oral health care to address existing dental problems is defined separately for each application to the institution. Qualitative data from 16 in-depth interviews were analysed using thematic analysis to explore the barriers to accessing oral healthcare during the COVID-19 pandemic.
Results
During the pandemic, 62.3% of dental institutions' applications failed to access care. Parental education, employment status, and household income significantly affected access (p < 0.005). Multiple logistic regression revealed that applying to university clinics (OR = 4.78; 95% CI 2.24–10.21) and private institutions (OR = 4.33; 95% CI 2.30–8.17) led to higher access rates when compared to public dental centres. The father's regular employment (OR = 3.39; 95% CI 1.37–8.34) and the child's previous dental contacts (OR = 2.37; 95% CI 1.21–4.62) increased the likelihood of accessing oral healthcare. The risk of contracting infections and income loss were pandemic related barriers. The most common barriers were those concerning the availability of services at public dental clinics. Children with disabilities faced further barriers due to the risk of infection, difficulty reaching institutions, and unmet dental needs for treatment under general anaesthesia.
Conclusion
Higher socioeconomic status and past contact with dentists had a positive effect on oral healthcare access. Dental services provided by public institutions had a lower level of access. The COVID-19 pandemic highlighted oral healthcare inequalities, particularly for those children with disabilities in Türkiye. Policymakers should strengthen public health crisis plans in order to improve children's oral healthcare access.
Therapeutic efficacy of galectin-1 inhibitor in treating malignant peripheral nerve sheath tumor
Authors: Shih Tsung-Chieh , Wang Hsiao-Chi , Torres Keila , Xia Roger , Malogolowkin Marcio , Hsu Ssu-Wei , Chen Ching-Hsien
Published: October 2024

Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas with limited treatment options. Galectin-1 (Gal-1) is crucial in Ras activation, which is crucial in MPNST pathology. We aimed to disrupt the Gal-1/Ras interaction as a therapeutic strategy. Targeting the Ras binding pocket on Gal-1, we designed LLS30, a Gal-1 inhibitor to bind where H-Ras(G12V) interacts with Gal-1. Here, we show that LLS30 disrupts Gal-1–Ras interactions, causing Ras delocalization and subsequent suppression of the Ras/ERK pathway in MPNST cells. In vivo, LLS30 significantly inhibited tumor growth and metastasis in human MPNST xenograft models. RNA-seq analysis revealed LLS30’s impact on key cellular pathways, including p53, interferon gamma, EMT, and proliferation. These findings highlight LLS30 as a potent, rationally designed Gal-1 inhibitor with promising therapeutic implications for MPNST and potentially other malignancies driven by Gal-1 and Ras.
The Influence of Weld Start Reentrant Angle on Fatigue Life Determined Through Analysis and Physical Testing
Authors: Cook David Bradley , Lee Christy , Stickel Donald
Published: October 2024

The influence of acute toe reentrant angle on fatigue life at a robotic weld start location was investigated both analytically using Linear Elastic Fracture Mechanics (LEFM) and through physical testing. 2D LEFM results show no significant change in Stress Intensity Factor (SIF) within a toe reentrant angle range of 60 degrees (acute) to 120 degrees (obtuse). 3D LEFM was used to compare crack growth rates for idealized 60 and 90 degree weld start geometry. Crack propagation was identical for these two cases. Physical fatigue test specimens were created with two distinct toe reentrant angle groups averaging 68 and 103 degrees at the weld start locations. Fatigue failure cycles at three stress ranges for the two groups produced similar stress-life trends. The study concludes that local weld start acute toe reentrant angle change between 60 and 90 degrees does not significantly influence the joint fatigue life under axial loading.
What is the influence on adjacent segment lordosis after single-level PELD? – an observational study of radiological alignment changes
Authors: Shiwen Li , Quan Qi , Wenyu Wang , Yang Liu , Xiaoyan Wang
Published: October 2024

Study Design:
Retrospective cohort study.
Purpose
To investigate the change in lumbar lordosis angle after single-level percutaneous endoscopic lumbar discectomy (PELD) and the difference in lordosis angle between L4/5 and L5/S1.
Methods
All patients were divided into L4/5 and L5/S1 groups according to surgical level. Lateral radiographs before and one year after surgery were collected to assess changes in lordotic angulation at all lumbar segments who underwent PELD at L4/5 and L5/S1.
Results
In total, 92 lumbar disc herniation patients (44 males and 48 females) treated with single-level PELD (52 at L4/5 and 40 at L5/S1) were enrolled. Fifty-two patients received the transforaminal approach (L4/5 21.7%, L5/S1 34.8%), and 40 patients received the interlaminar approach (L4/5 34.8%, L5/S1 8.7%). The L4/5 group had a mean 2° increase in operated segment lordosis (SL) (P < 0.001), the L5/L1 group had a mean − 1° change in the operated SL (P < 0.001), and the segmental lordosis gain was associated with lordosis changes at adjacent segments of -1° at L5/S1 (< 0.001) in the L4/5 group and 1° at L4/5 (< 0.001) in the L4/5 group. Modest gains in global lordosis (LL) angle were 2° (< 0.001) in the L4/5 group and 1° (< 0.001) in the L5/S1 group. The preoperative mean value of PI-LL was 15° in the L4/5 group and 18° in the L5/S1 group, and the postoperative mean value of PI-LL was 14° (P = 0.257) in the L4/5 group and 12° (P = 0.728) in the L5/S1 group.
Conclusion
There are subtle changes in lordosis at the operated segment and adjacent segments after single-level PELD surgery. The impact of surgery on LL is greater at the L4/5 segment than at the L5/S1 segment; additionally, the impact of surgery on lordosis is greater when the interlaminar approach is used than when the transforaminal approach is used.
Cord Blood Neuroglobin: First Discovery Opens New Perspectives in Perinatal Medicine
Authors: Filonzi Laura , Ardenghi Alessia , Ponzi Davide , Bolchi Angelo , Ciummo Ylenia , Paterlini Silvia , Beretta Virginia , Dell'orto Valentina , Bruno Maria Teresa , Palanza Paola , Marzano Francesco Nonnis , Perrone Serafina
Published: October 2024

To assess whether Neuroglobin could play a functional role during fetal development and birth, it was analyzed in 83 umbilical cord blood samples where its concentration ranged between 1.65 and 45.18 ng/ml, mean 18.49 ng/ml. Although resembling concentrations previously detected in many pathologic conditions in adults, none of newborns displayed altered Apgar score and were regularly discharged in healthy status. Surprisingly, 83.13% of babies had Ngb concentrations higher than the putative 8.4 ng/ml value, recently hypothesized as a prognostic cut-off between good and bad recovery from cerebral ischemia in adults. Significant Pearson correlations were observed between Ngb and Hb (r = 0.368, p = 0.001), and Htc (r = 0.372, p = 0.001) confirming its physiological role in oxygen-regulated metabolic information within the child-mother dyad. Besides the direct action in regulating blood flow and gas exchange, the first Ngb discovery in cord blood is discussed in relation to new perspectives in perinatal medicine.
Personalized Prediction of Glycemic Responses to Food in Women with Gestational Diabetes: Gut Microbiota Matters
Authors: Popova Polina V. , Isakov Artem O. , Rusanova Anastasia N. , Sitkin Stanislav I. , Anopova Anna D. , Vasukova Elena A. , Tkachuk Alexandra S. , Nemikina Irina S. , Stepanova Elizaveta A. , Eriskovskaya Angelina I. , Stepanova Ekaterina A. , Pustozerov Evgenii A. , Kokina Maria A. , Vasilieva Elena Y. , Vasilyeva Lyudmila B. , Zgairy Soha , Rubin Elad , Even Carmel , Turjeman Sondra , Pervunina Tatiana M. , Grineva Elena N. , Koren Omry , Shlyakhto Evgeny V.
Published: October 2024

We aimed to develop a prediction model for postprandial glycemic response (PPGR) in pregnant women with gestational diabetes mellitus (GDM) and to explore the influence of gut microbial data on prediction accuracy. We enrolled 105 pregnant women (70 GDM and 35 healthy). Participants underwent continuous glucose monitoring (CGM) for 7 days and provided detailed food diaries. Stool samples were collected at 28.8 ± 3.6 gestational weeks, followed by 16S rRNA gene sequence analysis. We developed machine learning algorithms for predicting PPGR, incorporating CGM measurements, meal content, lifestyle factors, biochemical parameters, anthropometrics, and gut microbiota data. The accuracy of the models with and without gut microbiota were compared. PPGR prediction models were created based on 2,706 meals with measured PPGRs. The integration of microbiome data in models increased the explained variance in peak glycemic levels (GLUmax) from 34–42% and the explained variance in the incremental area under the glycemic curve 120 minutes after meal start (iAUC120) from 50–52%. The final model performed better than the model based solely on carbohydrate count in terms of correlation between predicted and measured PPGRs (r = 0.72 vs r = 0.51 for iAUC120 and r = 0.66 vs r = 0.35 for GLUmax). After summing the SHAP values of associated features, the microbiome emerged as the fourth most impactful parameter for GLUmax and iAUC120 prediction, following meal composition, CGM measurements, and meal context. Microbiome features rank among the top 5 most impactful parameters in predicting PPGR in women with GDM.
Development and Validation of a Nomogram for Predicting Poor Prognosis in Spontaneous Cervical Artery Dissection
Authors: Yang Zhicheng , Lu Hongzhang , Yang Lijuan
Published: October 2024

Objective
To propose a nomogram for individual risk assessment of poor prognosis of spontaneous cervical artery dissection.
Methods
We included 75 patients with spontaneous cervical artery dissection from November 2013 to April 2024. The nomogram was formulated and validated by receiver operator charcateristis curve (AUC) and calibration curves.
Results
The Nomogram prediction model consisted of four variables,including male(OR = 2.56, 95% CI 0.85 to 7.70), eCAD-type(OR = 13.41, 95% CI 2.89 to 62.17), hypertension(OR = 2.86, 95% CI 0.97 to 8.50), hyperhomocysteinemia(OR = 3.15, 95% CI 0.93 to 10.70). AUC was 0.788,95%CI was 0.686 to 0.891 in the training set, and 0.763 and 0.662 to 0.863 in the validation set, respectively.
Conclusions
A nomogram and risk evaluation table were created with strong predictive capabilities for identifying poor prognosis in cases of cervical artery dissection, offering a valuable tool for personalized risk assessment.
Beyond the Screen: Quality, Reliability, And Accuracy of YouTube Videos on Physiotherapy in Down Syndrome
Authors: Yıkılmaz Seval Kutlutürk , Öztürk Fatma , Utlu Defne Kaya
Published: October 2024

People use social media applications such as YouTube as a source of information because of the opportunities they provide, even though the accuracy of the content has not been verified. This study aims to evaluate the characteristics, quality, reliability, and transparency of YouTube content on physiotherapy interventions for Down's syndrome. In the study, the YouTube application was searched using six keywords. Video quality was determined by the Global Quality Scale (GQS), reliability by the modified DISCERN (mDISCERN), and reliability/transparency by the Journal of American Medical Association (JAMA) benchmark criteria. Of the 362 reviewed videos, 17 were included in the study, with 5 uploaded by patients and their relatives, and 12 by physiotherapists. The videos uploaded by physiotherapists were of higher quality and reliability than those uploaded by patients and their relatives. Statistically significant relationships were found between number of views and likes (p = 0.001), between video duration and mDISCERN score (p = 0.003), and between GQS and mDISCERN score (p = 0.007). The mDISCERN score was found to be effective on the GSQ (p = 0.006). Physiotherapists' YouTube content on Down syndrome was suitable for patients and health professionals but lacked transparency, which needs improvement.
Nanoparticle-mediated mRNA delivery to TNBC PDX tumors
Authors: El-Sahli Sara , Manturthi Shireesha , Durocher Emma , Bo Yuxia , Akman Alexandra , Sannan Christina , Kirkby Melanie , Iroakazi Chiamaka Divine , Deyell Hannah , Kaczmarek Shelby , Lee Seung-Hwan , Iqbal Umar , Cote Marceline , Wang Lisheng , Gadde Suresh
Published: October 2024

mRNA-based therapies can overcome several challenges faced by traditional therapies in treating a variety of diseases by selectively modulating genes/proteins without genomic integration. However, due to mRNA’s poor stability and inherent limitations, nanoparticle (NP) platforms have been developed to deliver functional mRNA into cells. In cancer treatment, mRNA technology has multiple applications, such as restoration of tumor suppressors and activating anti-tumor immunity. Most of these applications have been evaluated using simple cell line-based tumor models, which failed to represent the complexity, heterogeneity, and 3D architecture of patient tumors. This discrepancy has led to inconsistencies and failures in clinical translation. Compared to cell line models, Patient-derived xenograft (PDX) models more accurately represent patient tumors and are better suitable for modeling. Therefore, for the first time, this study employed two different TNBC PDX tumors to examine the effects of mRNA-NPs. mRNA-NPs are developed using EGFP-mRNA as a model and studied in TNBC cell lines, ex vivo TNBC PDX organotypic slice cultures, and in vivoTNBC PDX tumors. Our findings show that NPs can effectively accumulate in tumors after intravenous administration, protecting and delivering mRNA to PDX tumors with different genetic and chemosensitivity backgrounds. These studies offer more clinically relevant modeling systems for mRNA nanotherapies for cancer applications.
Immunogenomic Landscape of B cells in Patients with Septic Shock
Authors: Wu Xun-Yao , Li Yuan-Yuan , Zhong Qing , Li Shan , Chen Yan , Peng Jin-Min , Hu Xiao-Yun , Jiang Wei , Wang Chun-Yao , Dong Run , Weng Li , Du Bin
Published: October 2024

Background.
B cells play a critical role in protecting against infections. Decreased cell number, altered phenotype and function were found in B cells from patients with sepsis/septic shock, however, the underlying molecular mechanisms were not elucidated. In the present study, we aimed to explore the B cells composition, gene expressions and B cell receptor (BCR) characterization in patients with septic shock.
Methods.
B cells were isolated from peripheral blood of patients with septic shock and healthy controls (HCs). Bulk RNA sequencing, single-cell RNA and BCR sequencing were performed. Subsequent cellular and molecular experiments were conducted to verify the analysis.
Results.
We found expansion of plasmablast population in patients with septic shock. However, both the BCR clonotype diversity and clonality were decreased. The CA8 expression was higher in B cells and promoted plasmablast proliferation through Akt signaling pathway. We further discovered that adrenomedullin (ADM) expression was up-regulated in septic shock-derived B cells compared with HCs. Moreover, B cells from patients displayed abnormal mitochondria structure and stimulation of ADM in vitro promoted B cell apoptosis through ribonucleotide reductase regulatory subunit M2 (RRM2)-related cell death.
Conclusion.
Our study provides a comprehensive genomic picture of B cells from patients with septic shock. We explored the underlying molecular mechanism involved in abnormal B cell compartment and function, which would be promising targets for lymphopenia and immunosuppression in sepsis/septic shock patients.
Application of metagenomic next-generation sequencing in the diagnosis of pneumonia in patients with cancer
Authors: Qin Rong , Wang Chao , Cong Minghua , Tian Le , Li Ning
Published: October 2024

Background
With the development of new sequencing technologies, metagenomic next-generation sequencing (mNGS) has become a diagnostic tool for respiratory tract infections. Patients with cancer may develop pneumonia caused by infections or antitumor therapy. Therefore, pneumonia in patients with cancer is more complex than that in healthy individuals. Currently, few reports are available on the use of mNGS for diagnosing pneumonia in patients with cancer.
Methods
In this retrospective study, 14 patients with cancer diagnosed with pneumonia in March 2023 were enrolled from the Emergency Department of the Chinese Academy of Medical Sciences Cancer Hospital. Sputum samples from the patients were examined using conventional tests and mNGS to identify pathogens. The mNGS and conventional test results were compared to assess the diagnostic yield and value of mNGS in improving the prognosis of pneumonia in patients with cancer.
Results
mNGS was more sensitive than conventional tests (sputum culture [SC] and polymerase chain reaction [PCR]) for detecting pathogens. The results were positive in 12/14 samples (86%) using mNGS compared with 8/14 samples (57%) using conventional testing. Compared with conventional tests, mNGS detected additional pathogens in 8 specimens. In 9/14 samples (64%), mNGS detected more pathogens than conventional testing. In nine patients (64%), the diagnosis was changed, and the antimicrobial regimen was adjusted based on the mNGS results. mNGS detected antibiotic resistance genes in five patients, which provided guidance for antibiotic selection.
Conclusions
mNGS is a promising technology for detecting pneumonia pathogens in patients with cancer and improves the diagnostic yield and prognosis. mNGS can be used to aid in early diagnosis and guide treatment of pneumonia in patients with cancer.
Association between Oral Frailty and Intrinsic Capacity among Older Patients
Authors: huang chunyan , Zhu Lingzhi , Shi Xiaolan , Zhu Haiqiong , Shen Xiaoxing , Ouyang xiaojun
Published: October 2024

OBJECTIVES: Oral and systemic health are interrelated and interact with each other. However, the relationship between intrinsic capacity (IC) and oral frailty (OF) has not been studied. Hence, the purpose of this research was to clarify the correlation between OF and IC in older patients.
DESIGN: Cross-sectional study.
SETTING: Hospital-based.
PARTICIPANTS: This investigation included 303 patients aged ≥60 years (149 women and 154 men).
MEASUREMENTS: IC was evaluated in five dimensions, including cognition (Mini-Mental State Examination), vitality (Short-Form Mini Nutritional Assessment), locomotion (Short Physical Performance Battery test), psychological (15-item Geriatric Depression Scale), and sensory (self-reported hearing and vision) capacities. On the basis of thefive domains, an IC composite score (0–5) was created, with lower scores denoting worse IC. The Oral Frailty Index-8 (OFI-8) is a questionnaire that can be usedto screen for oral frailty simply. Eight factors were considered to determine the OF classification. Multiple linear and logistic regressions were carried out to investigate the relationships between OF and its items with the IC composite score and IC domains.
RESULTS: A total of 303 patients were enrolled, with an average age of 75.77±8.18 years. Overall, 44.2% and 61.1% of the participants had OF and IC impairment, respectively. Multiple linear and logistic regressions revealedthat OF was an independent predictor of IC decline. Additionally, multiple linear regression analyses revealedthat the OF group had lower scores in the IC domains (vitality and locomotion) and higher scores in the psychological domain than the non-OF group. OF items (inability to chew hard food [β=-0.172, p=0.002], less frequently going out [β=-0.125, p=0.018], and brushing teeth less than twice a day [β=-0.151, p=0.004]) were the most susceptible to the impact of IC decline. Among the three OF items above, the inability to chew hard food was correlated with worse locomotion (β=-0.122, p=0.028) and psychological capacity (β=0.151, p=0.018), brushing teeth less than twice a day was related to worse cognitive (β=-0.168, p=0.006) and sensory capacity (β=-0.126, p=0.029), and less frequently going out was associated with worse locomotion function (β=-0.202, p<0.001).
CONCLUSION: The present findings suggest that patients with OF may have more severe IC deficits. Among OF items, the inability to chew hard food, brushing teeth less than twice a day, and less frequently going out are important indicators related to the development of IC decline. OF may be employed to detect and manage IC decline.
Prevalence of drug-drug interactions in pediatrics with cardiac disorders receiving off label drugs- a cross-sectional study
Authors: Aamir Muhammad , Fatima Anam , Shahbaz Naila , Akbar Shehla , Aslam Adeel , Barkat Kashif , Afaq Samia
Published: October 2024

Background: Evidence based medical interventions have improved outcomes of cardiovascular diseases, however, pediatric therapy is still based on clinical experience and extrapolation of adult data. Lack of evidence-based therapy increases the exposure of children to off-label (OL) drugs and clinically significant drug-drug interactions (CSDDIs) ultimately leading to adverse drug reactions. This study evaluated the prevalence of CSDDIs, OL drug use and the associated predictors.
Methodology: A cross-sectional study was designed to assess prevalence of CSDDIs and OL prescriptions in 250 patients admitted to pediatric cardiology ward of Hayatabad Medical Complex, Pakistan. DDIs of major severity were categorized as CSDDI. Association of various predictors including OL drug use with CSDDIs was evaluated using logistic regression.
Result: Of the total 250 pediatric patients, 28.6% patients were exposed to at least one clinically significant DDI, while 228 (91.20%) patients received at least one OL prescription. Furosemide was the most frequently prescribed drug involved in CSDDIs, while it was also one of the highly prescribed OL drug. Multivariate analysis revealed that, adolescent age group (OR 12.795; CI 3.077-53.198) and patients prescribed > 5 drugs (OR 3.544; CI 1.906-6.589) were significantly 12.7 and 3.5 times more likely to experience CSDDIs in reference to their corresponding categories. Conclusion: A high prevalence of CSDDIs and OL prescriptions was observed. OL drug presence was also observed to be a significant predictor associated with an increased risk of CSDDIs. Thus, to improve pediatric pharmacotherapy suitable medical interventions are required to decrease OL drug use and CSDDIs.
Evaluation of factors related to longitudinal CD4 count and the risk of death among HIV-infected patients using Bayesian joint models
Authors: Pilangorgi Sahar Souri , khodakarim Soheila , Nejat Mehdi
Published: October 2024

Background
In many epidemiological HIV studies, patients are frequently monitored over time to predict their survival by examining their CD4 levels repeatedly. This study aims to evaluate factors related to longitudinal CD4 count and the risk of death among HIV-infected patients using Bayesian joint models.
Methods
The information of patients who were infected with HIV in Fars Province, from 2011–2016 and followed up until 2022 was used in this study. A joint model of count longitudinal outcome and time to death is used to model information of HIV patients.
Results
The majority of patients were male (64.8%) with a median age of 35 years. During the follow-up, 123 patients (19%) died. The age-standardized mortality and incidence rates from 2011 to 2016 were 0.496 and 2.49 per 100000 person-years respectively. The 1-year and 5-year survival rates are 98% (95%CI: 97%, 99%) and 88% (95%CI: 85%, 91%) respectively. There is a significant association in this model between the CD4 cell count and the risk of death. Age, addiction, and unemployment were all significantly linked to a lower CD4 cell count. Age was positively correlated with the risk of death. Men, unemployed individuals, and those with hepatitis B had a higher risk of death.
Conclusion
In this study, we used the Bayesian joint model to investigate the association between the risk of death and the change in CD4 biomarkers that is repeatedly measured over time to determine the factors associated with the survival of HIV-infected persons. The joint model finds a strong association between the CD4 cell count and the risk of death. The joint model allows for a more comprehensive understanding of the factors influencing the CD4 cell count and survival time, compared to using separate models.
Characteristics, risk factors and a risk prediction model of tocilizumab-induced hypofibrinogenemia: a retrospective real-world study of inpatients
Authors: Cai Le , Wen Xiao , Qiu Zihan , Fu An , Guo Daihong , Zhu Man
Published: October 2024

Objective
The occurrence of hypofibrinogenemia after tocilizumab treatment has attracted increasing attention, which may cause bleeding and even life-threatening. This study aims to explore the risk factors for tocilizumab-induced hypofibrinogenemia (T-HFIB) and construct a risk prediction model.
Methods
A total of 221 inpatients that received tocilizumab from 2015 to 2023 were retrospectively collected and divided into T-HFIB group or control group. The risk factors for T-HFIB were obtained by logistic regression equation and used to establish the nomogram.
Results
T-HFIB was observed in 121 of 221 patients (54.75%). Multifactorial logistic regression analysis revealed that infection (OR = 2.002, 95%CI:1.018 ~ 3.935), COVID-19 (OR = 3.752, 95%CI:1.264 ~ 11.139), CAR-T therapy (OR = 4.409, 95%CI:2.017 ~ 0.894), and concomitant glucocorticoids (OR = 5.303, 95%CI:0.227 ~ 0.894) were identified as independent risk factors for T-HFIB, while high baseline fibrinogen level (OR = 0.813, 95%CI:0.670 ~ 0.988) and concomitant antirheumatic drugs (OR = 0.451, 95%CI:0.227 ~ 0.894) were identified as protective factors. A nomogram was established, and area under the curve (AUC) of prediction model was 0.772 (95%CI:0.709 ~ 0.836). Calibration curve showed a good prediction accuracy for the occurrence of T-HFIB.
Conclusion
The infection, COVID-19, CAR-T therapy, and concomitant glucocorticoids were independent risk factors for T-HFIB, while high baseline fibrinogen and concomitant antirheumatic drugs were protective factors. This nomogram can help early identify the patients at potential high risk of developing T-HFIB.
Factors influencing health information-seeking behavior in patients with periodontitis: A cross-sectional study
Authors: Xu Yuxin , Wang Mengli , Bao Li , Cheng Zijian , Li Xiaojun
Published: October 2024

Background
To investigate the current status of health information-seeking behavior (HISB) of periodontitis patients, and to identity its main influencing factors using the Comprehensive Model of Information Seeking (CMIS).
Methods
In total, 274 periodontitis patients were recruited from a specialized dental hospital in Hangzhou by purposive sampling method for a cross-sectional study. Data were collected from the patients by using the general information questionnaire, the Health Information Seeking Behavior Scale, the Self-Efficacy Scale for Self-care (SESS), the Short Form of Health Literacy Dental Scale (HeLD⁃14), and the Brief Illness Perception Questionnaire (BIPQ). Univariate analysis and regression analysis were utilized to determine the factors influencing the HISB.
Results
The HISB score of periodontitis patients in this study was 3.68 ± 0.40. The low level of HISB was negatively associated with age of 40 ~ 59 (odds ratio [OR] 0.041, 95% confidence interval [CI] 0.006–0.299), age of 18 ~ 39 (OR 0.053, 95%CI 0.008–0.364), better understandability of information carriers (characteristic) [OR 0.317, 95%CI 0.119–0.840], better satisfaction of information carriers (utility) [OR 0.027, 95%CI 0.008–0.089] and high self-efficacy level [OR 0.124, 95% CI 0.030–0.505].
Conclusions
Elderly patients and those with lower self-efficacy require more attention. In terms of health information, it is important to make the information more understandable and to assess patients' expectations and needs for information in a timely matter, with a goal of improving the recent HISB of Chinese periodontitis patients.
Simulation of optical coherence tomography to determine refractive indices of retinal layers in different organisms
Authors: Pakarzadeh Hassan , Gharibshahi Masoumeh
Published: October 2024

Optical coherence tomography (OCT) is a non-invasive imaging technique capable to produce two-dimensional (2D) images or three-dimensional (3D) reconstructions of inhomogeneous samples. OCT is mainly used in ophthalmology as a powerful tool for early diagnosis of eye diseases. The main goal of this article is to simulate the interferogram of OCT images and obtain the refractive index related to each retina layers in different organisms, including human, monkey, cow and dog. To achieve this goal, by simulating the interferogram of OCT images in the time and frequency domains for a supergaussian light source, different retinal samples are studied and for the given layer thicknesses, the refractive indices of different retina layers are determined.
Evaluation of 3D-printed Porous titanium alloy versus Polyetheretherketone (PEEK) cages in the surgical treatment of multilevel cervical degenerative disease
Authors: Khalilullah Taha , Singhal Anupam , Nayak Pratibha , Amrhein Shannon , Panchal Ripul Rajen
Published: October 2024

Study Design
- Single-center retrospective cohort study.
Purpose
- To compare the long-term clinical and radiographic outcomes of patients who have undergone multilevel anterior cervical discectomy and fusion (ACDF) with either 3D-printed titanium (TTN) or polyetheretherketone (PEEK) cages.
Overview of Literature
- ACDF with 3D-printed TTN or polyetheretherketone (PEEK) cages is an effective surgery for patients with cervical radiculopathy/myelopathy. The advent of 3D-printed porous TTN cages and its microporous structure has contributed to diminished subsidence and improved osseointegration compared to PEEK. This study compares the long-term outcomes of both implants among patients who underwent a multi-level ACDF procedure.
Methods
– 96 patients underwent multilevel (2, 3, 4) ACDF surgery, of whom 66 and 30 received a PEEK and 3D-printed TTN interbody cage, respectively. Radiographic outcomes for fusion, cage migration, and subsidence were determined with cervical x-rays and analyzed with independent 2-sample T-test and χ2 test. Visual analog score (VAS) and Neck Disability Index (NDI) score were examined with repeated measure analysis of variance.
Results
- The TTN group reported diminished NDI scores compared to the PEEK group (6.74 ± 5.58 vs 11.29 ± 8.67, p = 0.017) 2 years postoperatively. Furthermore, patients with 3D-printed TTN implants had a significantly shorter duration to fusion at the distal operated level in 3-level ACDF procedures (12.0 ± 5.20 vs 19.1 ± 5.91) (p = .011). The two cohorts reported no statistically significant difference in fusion rates.
Conclusions
– 3D-printed TTN implants enhanced the time to bony fusion at distal levels relative to PEEK cages. Clinically, patients with 3D-printed TTN implants reported diminished NDI scores at 2 years postoperatively. Such findings highlight the difference in outcomes clinically and radiographically for PEEK and 3D-printed TTN implants that need to be considered in optimizing multilevel ACDF procedures.
18F-FDG PET/CT metabolic parameters are correlated with clinical features and valuable in clinical stratification management in patients of castleman disease
Authors: Wang Guolin , Xu Qianhe , Liu Yinuo , Wang Huatao , Yang Fei , Liu Zhenfeng , Su Xinhui
Published: October 2024

Background
Castleman disease (CD) is a rare lymphoproliferative disorder. This study is to evaluate the correlation between 18F-FDG PET/CT and clinical features in CD patients, and exploring its value in distinguishing disease severity and assisting in risk stratification.
Methods
We retrospectively enrolled 93 patients with newly diagnosed CD. Traditional semi-quantitative 18F-FDG PET/CT parameters including the maximum standardized uptake value (SUVmax), total metabolic lesion volume (MLV), total lesion glycolysis (TLG) were measured, and the lymph node to liver ratio of SUVmax (LLR), lymph node to mediastinal blood pool of SUVmax (LMR), spleen to liver ratio of SUVmax (SLR) and No. of involved lymph node stations (LNS) were calculated. The correlation between these metabolic parameters and clinical features were studyed using a univariate analysis. The influencing factors of CD severity were determined by univariate and multivariate analysis. The optimal cut-off values for metabolic parameters were obtained by receiver operating characteristic (ROC) curve .
Results
A total of 20 unicentric CD (UCD) and 73 multicentric CD (MCD) cases were included, with the highest SUVmax of Lymph nodes ranged 1.40 ~ 28.18 (median, 4.86). The metabolic parameters (SUVmax, MLV, TLG, LLR, LMR, SLR) in MCD were significantly higher than those in UCD (p < 0.05). There were significant differences in MLV, TLG, LLR and SLR among different histological subtypes (p < 0.05). The No. of involved lymph node stations (LNS) and spleen-to-liver ratio (SLR) were significantly correlated with laboratory findings. In univariate and multivariate analyses, SLR (p = 0.011; OR value = 14.806) and HGB (p = 0.004; OR value = 0.044) exhibited an independent correlation with disease severity. The ROC curve revealed that SLR had a sensitivity of 77.4%, specificity of 69.4% and AUC of 0.761 (cut-off value = 1.04; p < 0.001) in discriminating severity of CD. SLR also showed significant statistical differences between severe and non-severe iMCD (p = 0.016).
Conclusions
SLR is closely related to clinical features of CD, and can relatively effectively differentiate the severity of CD and assist in the clinical risk stratification of iMCD.
Association of clinical correlates, metabolic parameters, and thyroid hormones with suicide attempts in first-episode and drug-naïve adolescent depression comorbid with anxiety: a large-scale cross-sectional study
Authors: Fan Xiwang , Liu Xingyu , Zhou Rong , Zhang Chenqian , Lin Jing , Zhong Yiwen , Zhang Xiangyang
Published: October 2024

Background
The prevalence of youth depression is rising, making the identification of reliable biomarkers for early detection increasingly challenging. This study explores potential biomarkers in youth experiencing their first depressive episode, with comorbid anxiety, and metabolic or thyroid imbalances.
Methods
We recruited 399 participants and measured thyroid stimulating hormone (TSH), triiodothyronine (FT3), free thyroxine (FT4), fasting blood glucose (FBG), cholesterol levels, body mass index (BMI), and blood pressure.
Results
Participants with abnormal TSH levels exhibited longer durations of depression, higher rates of suicidal behavior, increased anxiety, and more severe psychotic symptoms. Significant differences were observed in FBG, cholesterol levels, blood pressure, and BMI. Suicidal behavior was associated with higher TSH levels, anti-thyroglobulin antibodies (A-TG), and total cholesterol (TC), as well as lower high-density lipoprotein cholesterol (HDL-C) and BMI.
Conclusions
Our findings indicate a higher incidence of suicidal behaviors in youth with major depressive disorder (MDD) and comorbid anxiety symptoms. Elevated TSH levels, abnormal TC and HDL-C levels, and metabolic dysfunctions are significant risk factors. These findings underscore the importance of monitoring these biomarkers in managing youth with MDD.
Prognostic implications of quantitative flow ratio and optical coherence tomography-guided neointimal characteristics in drug-coated balloon treatment for in-stent restenosis
Authors: Lu Shiwan , Pan Li , Gu Ning , Deng Yi , Deng Chancui , Li Xiushi , Wang Feng , Zhao Yongchao , Wang Zhenglong , Shi Bei
Published: October 2024

The aim of this study was to investigate the relationship between quantitative flow ratio (QFR) after drug-coated balloon (DCB) treatment for in-stent restenosis (ISR) and between neointimal characteristics assessed by optical coherence tomography (OCT) and clinical outcomes. This single-center, retrospective, observational cohort study included ISR patients who underwent DCB angioplasty under OCT guidance. The primary outcome of the study was a patient-oriented composite endpoint (POCE), defined as a composite endpoint of all-cause mortality, any stroke, any myocardial infarction, or any revascularization.During a median follow-up of 630 (IQR: 397–886) days, 147 ISR patients underwent OCT-guided DCB angioplasty, resulting in POCE development in 20 patients. At the post-procedural DCB angioplasty, the vessel-level QFR was significantly lower in the POCE group(0.88 [IQR:0.87, 0.90] vs 0.93 [IQR: 0.91, 0.95]; P < 0.001) than in the non-POCE group. Analysis of the qualitative characteristics of ISR lesions showed a significantly higher incidence of heterogeneous neointima in the POCE group compared with the non-POCE group (10 [50.00%] vs 12 [9.45%]; P < 0.001). In the multivariable Cox regression analysis, low vessel-level QFR (HR per 0.1 increase: 0.11; 95% CI: 0.03–0.39;P < 0.001) and heterogeneous neointima were independently associated with POCE. The POCE rate of vessels with the 2 features was 17.94 times higher than that of all other vessels (95%CI [2.91–110.6]; log-rank P < 0.001). Vessel-level QFR and heterogeneous neointima were independent factors associated with POCE in ISR patients after DCB angioplasty. Adding the QFR measure-ment to OCT findings may enable better discrimination of patients with subsequent POCE post-DCB angioplasty for ISR.
Intraoral Perfusion Assessment Using Endoscopic Hyperspectral Imaging (EHSI) – First Description of a Novel Approach
Authors: Römer Paul , Blatt Sebastian , Siegberg Fabia , Vinayahalingam Shankeeth , Al-Nawas Bilal , Kämmerer Peer W. , Thiem Daniel G. E.
Published: October 2024

Objectives
This study aimed to establish a method to detect and quantify mucosal malperfusion intraorally using state-of-the-art Endoscopic Hyperspectral Imaging (EHSI). For this purpose, mucosal ischemia was selectively induced by intraligamentary anesthesia (ILA) with and without + epinephrine using a standardized protocol.
Material and Methods
EHSI was performed using a novel endoscopic hyperspectral imaging system. Parameters assessed were Tissue Oxygen Saturation (StO2 [%]), Tissue Hemoglobin Index (THI), Near Infrared Perfusion Index (NPI) and Tissue Water Index (TWI). Fifty-seven healthy subjects received ILA using Articaine 4% with (ILA+) and without (ILA-) epinephrine at a dosage of 1:200,000 administered mesially and distally to the target tooth 42 (Universal No. 26). Mucosal perfusion was assessed using EHSI for 45 minutes post-injection.
Results
After ILA+, a distinct ischemia of the mucosa was already clinically apparent after 30 sec with significant reduction of THI and StO2 by an average of 57% (p < 0.001) and 7% (p < 0.040) compared to baseline values. Persistent hypoperfusion of the oral mucosa was observed throughout the monitoring period, exhibiting a gradual resolution at the 30-minute mark, and nearing baseline perfusion approximately 45 minutes post-injection. There was no papillary necrosis after ILA + injection.
Conclusion
EHSI is suitable to adequately detect and visualize actual perfusion of the intraoral mucosa. The study revealed that LA with epinephrine (1:200,000) induce temporary hypoxia in the dental papilla but without causing severe ischemia.
Clinical Relevance:
EHSI will enable promising applications in the future, i.a. success monitoring of periodontal therapies, intraoral free flap monitoring and the assessment of cancer margins.
Clinicopathological Characteristics of Mucinous Breast Cancer: a Retrospective Analysis of a 6-year Study From National Cancer Center in Vietnam
Authors: Phung Thi Huyen , Pham Thanh Tung , Nguyen Huu Thang , Nguyen Dinh Thach , Nguyen Thanh Long , Hoang Thi Hoai
Published: October 2024

Purpose: To evaluate clinicopathological features in women with mucinous breast cancer (MBC), distinguishing between pure (PMC) and mixed (MMC) subtype.
Methods: A retrospective analysis of all 358 women with MBC treated at Vietnam National Cancer hospital from June 2015 to December 2020. PMC was defined by ≥ 90% mucinous components.
Results: We identified 358 women with MBC (245 PMC and 113 MMC) representing 2.7% of all 13,254 BC patients. The proportion of stage I, II, III and IV were 34.9%, 50.8%, 10.4% and 3.9% respectively. The rate of HER2 overexpression is 12%, in which only 1.4% of patients was treated with anti-HER2. 193 patients (53.9%) had chemotherapy, including 55 patients (15.4%) treated in neoadjuvant setting. Only 3 patients (5.5%) achieved pCR.
PMC patients were older (54.4±13.3 vs 51.1±13.1 years), had lower Ki67 expression, lower incidence of nodal metastasis (N+) (p values <0.05). At median follow-up of 58 months, the 5-year overall survival rate of non-metastatic patients was 86.6%. Multivariate analysis showed N+ to be the most significant prognostic factor (HR=3.3; 95%CI 1.5-7.1), followed by T (HR=2.9; 95%CI 1.4-6.3), HER2+ (HR=2.5; 95%CI 1.2-5.3) and MMC subtype (HR=1.9; 95%CI 1.0-3.9). Amongs 245 patients with stage T1-2N0M0, 40.8% of those treated with CT related to worse overall survival (5-year OS 88.0% vs 95.6%, p=0.04)
Conclusion: Poor prognostic factors of MBC include high T, N stage, HER2 overexpression and MMC subtype. CT in stage T1-2N0M0 brings worse survival outcome. Given the low response rate to neoadjuvant CT, upfront surgery is appropriate for MBC patients.
ULK1 is required for autophagy and promotes metastatic progression in epithelial ovarian cancer
Authors: Shepherd Trevor , Webb Jack , Buensuceso Adrian , Tomas Emily , Borrelli Matthew , Viola Lauren , Hovey Owen , Valdes Yudith Ramos , Singha Bipradeb , Li Shawn
Published: October 2024

Epithelial ovarian cancer (EOC) is a leading cause of gynecological cancer mortality, driven largely by late diagnosis and chemo-resistant disease. While autophagy plays a critical role in the survival of EOC spheroids during metastasis, the role of ULK1, a key regulator of autophagy, in EOC progression remains unclear. To investigate this, we utilized CRISPR/Cas9 technology to delete ULK1 in EOC cell lines OVCAR8 and HEYA8, and the immortalized fallopian tube epithelial cell line FT190. Immunoblotting confirmed ULK1 deletion, which disrupted autophagy by blocking LC3 processing, causing p62 accumulation, and decreasing Beclin-1 phosphorylation. Culture-based assays revealed that ULK1 knockout decreased EOC spheroid cell viability due to increased apoptosis, and its loss impaired organoid growth. In vivo xenograft models demonstrated that ULK1 loss significantly reduced tumor burden and metastatic potential. These in vivo findings were supported by results from mesothelial clearance assays, which showed reduced spheroid invasion by ULK1 knockout cells. Proteomic analyses of OVCAR8 spheroids revealed dysregulation due to ULK1 loss in key signaling pathways, including MAPK, mTOR-PI3K-AKT, and apoptosis regulation. Overall, this study highlights ULK1 as a critical regulator of multiple steps of EOC growth and metastasis, underscoring its potential as a novel therapeutic target in advanced ovarian cancer.