bluuebunny/crossref_metadata_2025_split huggingface dataset:
Increased Cellular Expression of Interleukin-6 in Patients With Ossification of the Posterior Longitudinal Ligament
Authors: Saito Hideki , Yayama Takafumi , Mori Kanji , Kumagai Kosuke , Fujikawa Hitomi , Chosei Yuya , Imai Shinji 
Published: February 2023

Study Design.
We performed histologic, immunohistochemical, immunoblot examination and suspension array analyses of cytokine expression in cultured cells derived from human cervical ossification of the posterior longitudinal ligament (OPLL).

Objective.
To determine the roles of interleukin-6 (IL-6) during the maturation of osteoblasts and chondrocytes associated with the development of OPLL.

Summary of Background Data.
Ectopic OPLL affects ~3% of the general population, with a higher incidence in Asian ethnic groups. Alterations in cytokine profiles may influence osteoblast differentiation, but the mechanisms and signaling pathways associated with the ossification process remain unclear.

Methods.
Samples were collected from 14 patients with OPLL who had undergone spinal surgery and seven with cervical spondylotic myelopathy without OPLL. Tissue sections were used for histologic and immunohistochemical studies, and primary cells from ligamentum samples were used for cytokine array and immunoblotting. A suspension array was used to measure the concentrations of 27 inflammatory cytokines or growth factors.

Results.
Suspension array and immunoblot analyses revealed significantly elevated levels of IL-6 in OPLL patients. Alterations in IL-6 concentrations were found to alter the expression of the genes Sox9, Runx2, and SIRT1. In addition, immunohistochemical analysis revealed that these factors are present in mesenchymal cells within the degenerative portion of the ligament matrix that is adjacent to the ossification front.

Conclusions.
IL-6 plays a profound role in the osteoblast differentiation process along with the induction of chondrocyte hypertrophy and cell apoptosis in the early stages of ossification in OPLL. These changes in cytokine profiles are essential factors for regulation of the ectopic ossified plaque in OPLL.
Global Sagittal Spinal Compensation for Dropped Head Alignment
Authors: Nishimura Hirosuke , Endo Kenji , Sawaji Yasunobu , Suzuki Hidekazu , Aihara Takato , Murata Kazuma , Konishi Takamitsu , Yamauchi Hideya , Ueshima Tomoyuki , Yamamoto Kengo 
Published: February 2023

Study Design.
This is a retrospective radiographic study of a consecutive series of cases in patients with dropped head syndrome (DHS) at a single tertiary referral center.

Objective.
The aim was to clarify the compensation among parameters of spinal sagittal alignment in patients with DHS.

Summary of Background Data.
The treatment strategy for DHS should vary according to the types of global sagittal spinal alignment. However, theoretical evidence in consideration of spinal sagittal compensation against the dropped head condition is lacking.

Materials and Methods.
One hundred sixteen patients diagnosed with isolated neck extensor myopathy were enrolled. Radiographic measurements were made, including parameters of spinal sagittal alignment. The patients were divided into three groups according to sagittal spinal balance: C7SVA (sagittal vertical axis) ≥ +50 mm (P-DHS; positive imbalanced DHS), −50 mm ≤C7SVA <+50 mm (B-DHS; balanced DHS), and C7SVA <−50 mm (N-DHS; negative imbalanced DHS). Correlations among the various spinal parameters were analyzed.

Results.
Among all types of DHS, there was no correlation between C2-C7 angle (C2-C7A) and T1 slope. In B-DHS, other correlations among the adjacent spinal segments were maintained. In N-DHS, there was no correlation between C2-C7A and TK, and in P-DHS, there was also no correlation between TK and lumbar lordosis.

Conclusions.
The loss of compensation at the cervicothoracic junction was observed in all DHS types. B-DHS showed decompensation only at the cervicothoracic junction. N-DHS presented additional decompensation of the thoracic spine, and P-DHS showed decompensation between the thoracic and lumbar spine. Evaluation of global sagittal spinal balance is important for determining global spinal compensation associated with DHS and when considering treatment strategy.
Single-step assembly of lipid-gelatin-epigallocatechin-3-gallate hybrid nanoparticles for cancer therapy
Authors: Song Juan , Yu Xudong , Lv Chengzhi , Wang Dong 
Published: February 2023

Objective
Novel core-shell lipid-gelatin-epigallocatechin-3-gallate hybrid nanoparticles (LGE-N) were prepared to increase the stability and antitumor efficacy of epigallocatechin-3-gallate (EGCG).

Methods
The LGE-N was prepared by a single-step double-emulsion method, in which EGCG-gelatin nanoparticles were formed and stabilized in the inner phase by gelatinization. The cytotoxicity of EGCG solution (EGCG-S) and LGE-N were assessed by a standard 3-(4, 5-dimethylthiazol- 2-yl)-2, 5-diphenyltetrazolium bromide assay.

Results
The obtained LGE-N had a spherical shape, with relatively high encapsulation efficiency (92.30 ± 1.63%), drug loading capacity (11.09 ± 0.62%) and controlled drug release. In-vitro cytotoxicity studies revealed that LGE-N exhibited a lower half maximal inhibitory concentration compared with EGCG-S in MCF-7 (a breast carcinoma cell line) cells. When labeled with a fluorescent probe, Dir, LGE-N was shown to accumulate much more in tumor. In addition, the LGE-N achieved potent antitumor efficacy at a dose of 5 mg/kg in 4T1-implanted mice.

Conclusion
Our study highlights the unique EGCG-entrapped lipid-gelatin hybrid nanoparticles, which may be a powerful strategy for further cancer therapy.
Association Between Length of Storage of Transfused Packed RBC Units and Outcome of Surgical Critically Ill Adults: A Subgroup Analysis of the Age of Blood Evaluation Randomized Trial*
Authors: Lehr Anab Rebecca , Hébert Paul , Fergusson Dean , Sabri Elham , Lacroix Jacques 
Published: February 2023

Objectives:
The Age of Blood Evaluation (ABLE) study reported no clinical benefit in fresher compared with standard delivery RBC units (length of storage: 6.9 ± 4.1 vs 22.0 ± 8.4 d, respectively). Perioperative patients are often anemic, at risk of blood loss, and more exposed to RBC transfusions. We address the question whether fresh RBC units are safer than standard delivery RBC units in perioperative ICU patients.

Design:
Subgroup analysis of surgical nontrauma adults enrolled in the ABLE randomized controlled trial.

Setting:
ICUs.

Patients:
Three hundred twenty surgical patients among the 2,510 ICU adults recruited in the ABLE study who had a request for a first RBC transfusion in the first week in ICU stay and an anticipated length of mechanical ventilation greater than or equal to 48 hours. We included perioperative patients but excluded elective cardiac surgery and trauma.

Interventions:
Surgical participants were allocated to receive either RBC units stored less than or equal to 7 days or standard issue RBC.

MEASUREMENTS AND MAIN RESULTS:
The primary outcome was 90-day all-cause mortality. One hundred seventy-two perioperative patients were allocated to the fresh and 148 to the standard group. Baseline data were similar. The length of storage was 7.2 ± 6.4 in fresh and 20.6 ± 8.4 days in standard group (p < 0.0001). The 90-day mortality was 29.7% and 28.4%, respectively (absolute risk difference: 0.01; 95% CI –0.09 to 0.11; p = 0.803). No significant differences were observed for all secondary outcomes, including 6-month mortality, even after adjustment for age, country, and Acute Physiology and Chronic Health Evaluation score.

Conclusions:
There was no evidence that fresh red cells improved outcomes as compared to standard issue red cells in critically ill surgical patients, consistent with other patients enrolled in the ABLE trial.
The Status Quo of Continuing Medical Education in South-East Asia and Eastern Mediterranean Regions: A Scoping Review of 33 Countries
Authors: Vakani Farhan Saeed , Uebel Kerry , Balasooriya Chinthaka , Demirkol Apo 
Published: February 2023

Introduction:
Continuing medical education is a process of continuous learning to maintain physicians' competence and professional performance. Efforts to make continuing medical education (CME) programs mandatory in the South-East Asia Region by linking credits to the renewal of registration have met with mixed success. However, there are no recent reviews on the CME status in regions with a large number of developing countries. This review aims to map the practices and regulation of the CME activities in the South-East Asia and Eastern Mediterranean regions.

Methods:
A scoping review was undertaken using a modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews checklist. A search was conducted within PubMed, Embase, Web of Science, Scopus databases, and national medical and health council websites.

Results:
Evidence on the provision of CME is available for all but seven of the 33 countries in both regions. Fourteen countries of varying income levels have implemented mandatory CME linked to the renewal of registration. They have statutory bodies governing CME and allocating credits, with most requiring a large number of hourly based activities for the renewal of registration and evidence of a wide range of local providers.

Conclusions:
Financial resources, a thorough organizational structure and standards, and a wide range of local CME providers seem to promote the implementation of mandatory CME in most of these countries.
Fibroblast growth factor 5 overexpression ameliorated lipopolysaccharide-induced apoptosis of hepatocytes through regulation of the phosphoinositide-3-kinase/protein kinase B pathway
Authors: Cui Shengyu , Li Yuhua , Zhang Xutao , Wu Bing , Li Ming , Gao Jixian , Xu Lin , Xia Hao 
Published: February 2023

Abstract

Background:
Sepsis is a systemic inflammatory syndrome induced by several infectious agents. Multiple organs are affected by sepsis, including the liver, which plays an important role in metabolism and immune homeostasis. Fibroblast growth factors (FGFs) participate in several biological processes, although the role of FGF5 in sepsis is unclear.

Methods:
In this study, lipopolysaccharide (LPS) was administrated to mice to establish a sepsis-induced liver injury. A similar in vitro study was conducted using L-02 hepatocytes. Western blot and immunohistochemistry staining were performed to evaluate the FGF5 expression level in liver tissues and cells. Inflammatory cell infiltrations, cleaved-caspase-3 expressions, reactive oxygen species and levels of inflammatory cytokines were detected by immunofluorescence, dihydroethidium staining, and reverse transcription quantitative polymerase chain reaction analysis, respectively. Flow cytometry was used to detect the apoptosis level of cells. In addition, ribonucleic acid (RNA)-sequencing was applied to explore the possible mechanism by which FGF5 exerted effects.

Results:
LPS administration caused FGF5 down-regulation in the mouse liver as well as in L-02 hepatocytes. Additionally, with FGF5 overexpression, liver injury and the level of hepatocyte apoptosis were ameliorated. Further, RNA sequencing performed in hepatocytes revealed the phosphoinositide-3-kinase/protein kinase B (PI3K/AKT) pathway as a possible pathway regulated by FGF5. This was supported using an inhibitor of the PI3K/AKT pathway, which abrogated the protective effect of FGF5 in LPS-induced hepatocyte injury.

Conclusion:
The anti-apoptotic effect of FGF5 on hepatocytes suffering from LPS has been demonstrated and was dependent on the activation of the PI3K/AKT signaling pathway.
The Influence of Kinesiology Tape on Breathing Mechanics in College-Aged Individuals–A Randomized Trial
Authors: Lindenberg Kelly M. , Shipe Nancy K. , Kletzli Katelynn , Cannizzaro Rebecca , Timko Jonathan , Calhoun Kyla 
Published: February 2023

Purpose:Kinesiology Tape (KT) has been used to improve mobility and muscle activation. Limited research has studied its effect on respiratory function. The purpose of this study was to investigate the influence of KT on chest wall excursion (CWE) and magnitude of respiratory muscle activation.Methods:Ninety subjects were randomly assigned to receive KT, sham tape, or no tape around the lower thoracic region. Measures, including CWE, maximal inspiratory pressure (MIP), and surface electromyography (sEMG) of intercostal and scalene muscles, were taken during a maximal inspiratory effort before (T-B) and after (T-1) tape application. Subjects continued to wear the tape and returned 48 hours later for another set of measurements (T-2). Repeated measures Analysis of Variance and post-hoc paired t-tests were used to determine the influence of tape.Results:No significant differences were identified for sEMG amplitude or CWE. Maximal inspiratory pressure scores showed no significant between-group effect; however, a significant within-group effect was found. Post-hoc analyses revealed significant differences between T-B and T-2 and T-1 and T-2 for all groups.Conclusion:Kinesiology Tape application did not show increased muscle activation, CWE, or MIP compared with sham and control scenarios. A significant training effect for MIP was identified. Future research should investigate KT effects in other age groups or with the presence of pulmonary pathology.
Relevance of Guy's stone score in evaluation and outcome of percutaneous nephrolithotomy
Authors: Kapoor Rohit , Mane Deepak , Jai Singh Siddharth , Satav Vikram , Sabale Vilas , Ranjan Pratyush 
Published: February 2023

Abstract

Objectives
This study aimed to ascertain the relevance of the Guy's stone score in the evaluation and outcome of percutaneous nephrolithotomy (PCNL).

Materials and methods
This 2-year hospital-based, prospective clinical study enrolled 100 patients who were indicated for PCNL. All patients were allocated into groups according to the Guy's stone score and were compared for factors associated with stone-free rate (SFR) and complication risk. The data were statistically analyzed using SPSS version 20.

Results
The median patient age was 40 years (range, 5–70 years). A greater portion of the patients were aged 31–40 years. A majority of the stones were solitary, found in 83% of the kidneys. Overall, 49% were grouped as Guy's stone score 1, 26% as 2, 11% as 3, and 14% as 4. The overall SFR was 97%. Furthermore, SFR was found to be 100% for Guy's stone score 1, 100% for 2, 90.91% for 3, and 85.7% for 4. Intraoperative and postoperative complication rates were found in 6% and 38% of the patients, respectively. Among postoperative complications, pain (26%) was the most frequent, followed by fever (8%), bleeding (3%), and puncture site abscess (1%).

Conclusions
Based on the study findings, Guy's stone score was efficient in predicting PCNL outcomes.
Clinical and prostate multiparametric magnetic resonance imaging findings as predictors of general and clinically significant prostate cancer risk: A retrospective single-center study
Authors: Massanova Matteo , Vere Rebecca , Robertson Sophie , Crocetto Felice , Barone Biagio , Dutto Lorenzo , Ahmad Imran , Underwood Mark , Salmond Jonathan , Patel Amit , Celentano Giuseppe , Bhatt Jaimin R. 
Published: February 2023

Abstract

Background
To evaluate the predictive values of Prostate Imaging Reporting and Data System version 2 (PI-RADS v2), prostate-specific antigen (PSA) level, PSA density (PSAD), digital rectal examination findings, and prostate volume, individually and in combination, for the detection of prostate cancer (PCa) in biopsy-naive patients.

Methods
We retrospectively analyzed 630 patients who underwent transrectal systematic prostate biopsy following prostate multiparametric magnetic resonance imaging. A standard 12-core biopsy procedure was performed. Univariate and multivariate analyses were performed to determine the significant predictors of clinically significant cancer but not PCa.

Results
The median age, PSA level, and PSAD were 70 years, 8.6 ng/mL, and 0.18 ng/mL/mL, respectively. A total of 374 (59.4%) of 630 patients were biopsy-positive for PCa, and 241 (64.4%) of 374 were diagnosed with clinically significant PCa (csPCa). The PI-RADS v2 score and PSAD were independent predictors of PCa and csPCa. The PI-RADS v2 score of 5 regardless of the PSAD value, or PI-RADS v2 score of 4 plus a PSAD of <0.3 ng/mL/mL, was associated with the highest csPCa detection rate (36.1%–82.1%). Instead, the PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL yielded the lowest risk of csPCa.

Conclusion
The combination of the PI-RADS v2 score and PSAD could prove to be a helpful and reliable diagnostic tool before performing prostate biopsies. Patients with a PI-RADS v2 score of <3 and PSAD of <0.3 ng/mL/mL could potentially avoid a prostate biopsy.
Field Therapy for Actinic Keratosis: A Structured Review of the Literature on Efficacy, Cost, and Adherence
Authors: Lampley Nathaniel , Rigo Rachel , Schlesinger Todd , Rossi Anthony M. 
Published: February 2023

BACKGROUND
Although there are evidence-based guidelines for actinic keratosis management, selecting a cost-effective field therapy is challenging because of limited studies comparing cost, efficacy, and adherence among treatments.

OBJECTIVE
To review the literature on field-directed therapies for actinic keratosis, comparing efficacy, cost, and adherence data for topical and in-office treatments.

MATERIALS AND METHODS
PubMed, Embase, Web of Science, and Google Scholar databases were searched from October 2020 to March 2021 for articles on field therapy for actinic keratosis. Total cost per regimen was estimated using wholesale acquisition cost package prices and Medicare coverage rates for May 2021. Effective cost was approximated by dividing total cost by complete response rate.

RESULTS
Efficacy data for various field therapies range widely, and long-term follow-up is limited. Cross-study comparisons are challenging because of heterogeneity of studies. Field-directed therapy with topical 5-fluorouracil and photodynamic therapy have similar effective cost. Adherence may significantly affect real-world efficacy and long-term clearance; this would favor shorter duration topical regimens or in-office procedures.

CONCLUSION
Standardization of future studies examining efficacy of field treatments for actinic keratosis will allow comparison across treatments. In-office treatments such as photodynamic therapy represent a cost-effective alternative to topical therapies with comparable efficacy.
A lifetime economic research of universal HLA-B*58:01 genotyping or febuxostat initiation therapy in Chinese gout patients with mild to moderate chronic kidney disease
Authors: Hong Yuan , Chen Xichuang , Li Zhiping , Zhang Xiaoyan , Zhou Cong , Wang Yan , Wang Guangfei , Wu Wei , Zhou Danli , feng Li Hai 
Published: February 2023

Objective
To evaluate Chinese long-term economic impact of universal human leukocyte antigen B (HLA-B)*58:01 genotyping-guided urate-lowering therapy or febuxostat initiation therapy for gout patients with mild to moderate chronic kidney disease (CKD) from perspective of healthcare system.

Methods
A Markov model embedded in a decision tree was structured including four mutually exclusive health states (uncontrolled-on-therapy, controlled-on-therapy, uncontrolled-off-therapy, and death). Mainly based on Chinese real-world data, the incremental costs per quality-adjusted life years (QALYs) gained were evaluated from three groups (universal HLA-B*58:01 testing strategy, and no genotyping prior to allopurinol or febuxostat initiation therapy) at 25-year time horizon. All costs were adjusted to 2021 levels based on Chinese Consumer Price Index and were discounted by 5% annually. One-way and probability sensitivity analysis were performed.

Results
Among these three groups, universal HLA-B*58:01 genotyping was the most cost-effective strategy in base-case analysis according to Chinese average willingness-to-pay threshold of $37 654.50 per QALY. The based incremental cost-effectiveness ratio was $31784.55 per QALY, associated with 0.046 additional QALYs and $1463.81 increment costs per patient at a 25-year time horizon compared with no genotyping prior to allopurinol initiation strategy. Sensitivity analysis showed 64.3% robustness of these results.

Conclusion
From Chinese perspective of healthcare system, HLA-B*58:01 genotyping strategy was cost-effective for gout patients with mild to moderate CKD in mainland China, especially in the most developed area, such as Beijing and Shanghai. Therefore, we suggest China’s health authorities choose the genotyping strategy and make different recommendations according to the differences of local conditions.
Impact of pulmonary hypertension hemodynamic presentation on perioperative outcomes in patients undergoing elective cardiac surgery: An observational study
Authors: Wang Yi-Chia , Chen Yih-Sharng , Lin Pei-Lin , Huang Chi-Hsiang 
Published: February 2023

Abstract

Background
Pulmonary hypertension (PH) is classified by hemodynamic presentation into precapillary, isolated postcapillary, and combined postcapillary and precapillary PH. Whether PH type influences risk stratification in cardiac surgery remains undetermined. We aimed to evaluate the incidence of perioperative (≤30 days) morbidity and mortality in different PH population.

Methods
This was a retrospective observational study. All patients who underwent right heart catheterization between August 2015 and July 2020 were divided into the noncapillary, precapillary, isolated postcapillary, and combined postcapillary and pre capillary PH groups based on their mean pulmonary arterial pressure, pulmonary artery wedge pressure, and diastolic pressure difference preoperatively.

Results
Of the 500 patients who underwent elective cardiac surgeries, 487 were analyzed. Overall, 236 patients (48.7%) had PH, and isolated postcapillary PH was the most common presentation. Mild PH proportion was highest in the precapillary PH type (70.8%), followed by isolated postcapillary PH (46.2%), and finally combined postcapillary and precapillary PH (10.7%). Patients with PH had a greater frequency of renal insufficiency and wound infection within 30 days postoperatively. Mean pulmonary arterial pressure >25 mm Hg after cardiopulmonary bypass (CPB) was a risk factor for short-term complications. New York Heart Association Functional Class ≥II, long CPB duration, and isolated postcapillary PH or combined postcapillary and precapillary PH type are independent risk factors for short-term morbidity and mortality after elective cardiac surgery.

Conclusions
Isolated postcapillary PH and combined postcapillary and precapillary PH patients had a higher complication rate 30 days postoperatively among elective cardiac surgery patients. After CPB, mean pulmonary arterial pressure >25 mm Hg was associated with greater complication frequency.