bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and associated factors of locomotive syndrome in young Japanese adults: a cross-sectional study
Authors: Sawaya Yohei , Hirose Tamaki , Onuma Sora , Nakajima Rina , Fujita Seiya , Muroi Shiori , Sato Ryo , Yin Lu , Shiba Takahiro , Kobayashi Kaoru , Urano Tomohiko
Published: May 2024

Background

The onset of locomotive syndrome (LS) precedes that of frailty. Therefore, the first step in extending healthy life expectancy is to implement measures against LS in young adults. The aim of this study was to investigate the prevalence of LS and its associated factors in young adults for early detection and prevention of LS.

Methods

The participants of this study comprised 413 university students specializing in health sciences (192 males and 221 females) with an average age of 19.1 ± 1.2 years. All participants voluntarily participated in the study and reported no serious health problems. The presence or absence of LS was evaluated using the stand-up test, two-step test, and the 25-question Geriatric Locomotive Function Scale. Additionally, musculoskeletal assessment (one-leg standing, squatting, shoulder elevation, and standing forward bend), body composition analysis (weight, body mass index, body fat mass, body fat percentage, skeletal muscle mass index (SMI), and phase angle), handgrip strength test, physical activity assessment, and nutritional assessment were conducted. Sex-stratified analyses were performed, comparing groups with and without LS. Factors associated with LS were explored using binomial logistic regression.

Results

Of the 413 young adults studied, 86 individuals (20.8%) were found to have LS. When stratified by sex, LS was observed to have a considerably higher prevalence in females (55, 24.9%) than in males (31, 16.1%). In males, the notable differences between the groups with and without LS were observed in one-leg standing and phase angle, whereas in females, differences were identified in body fat mass, body fat percentage, SMI, musculoskeletal pain, and handgrip strength. Two types of binomial logistic regression analysis revealed that the inability to perform one-leg standing was associated with LS in males, while the presence of musculoskeletal pain and a high body fat percentage were identified as factors associated with LS in females.

Conclusions

One in five young adults were found to have LS in this study, underscoring the necessity for early intervention and LS health education. Furthermore, effective management of musculoskeletal pain is also crucial.
Machine learning-based prediction models affecting the recovery of postoperative bowel function for patients undergoing colorectal surgeries
Authors: Yang Shuguang , Zhao Huiying , An Youzhong , Guo Fuzheng , Zhang Hua , Gao Zhidong , Ye Yingjiang
Published: May 2024

Purpose

The debate surrounding factors influencing postoperative flatus and defecation in patients undergoing colorectal resection prompted this study. Our objective was to identify independent risk factors and develop prediction models for postoperative bowel function in patients undergoing colorectal surgeries.

Methods

A retrospective analysis of medical records was conducted for patients who undergoing colorectal surgeries at Peking University People’s Hospital from January 2015 to October 2021. Machine learning algorithms were employed to identify risk factors and construct prediction models for the time of the first postoperative flatus and defecation. The prediction models were evaluated using sensitivity, specificity, the Youden index, and the area under the receiver operating characteristic curve (AUC) through logistic regression, random forest, Naïve Bayes, and extreme gradient boosting algorithms.

Results

The study included 1358 patients for postoperative flatus timing analysis and 1430 patients for postoperative defecation timing analysis between January 2015 and December 2020 as part of the training phase. Additionally, a validation set comprised 200 patients who undergoing colorectal surgeries from January to October 2021. The logistic regression prediction model exhibited the highest AUC (0.78) for predicting the timing of the first postoperative flatus. Identified independent risk factors influencing the time of first postoperative flatus were Age (p < 0.01), oral laxatives for bowel preparation (p = 0.01), probiotics (p = 0.02), oral antibiotics for bowel preparation (p = 0.02), duration of operation (p = 0.02), postoperative fortified antibiotics (p = 0.02), and time of first postoperative feeding (p < 0.01). Furthermore, logistic regression achieved an AUC of 0.72 for predicting the time of first postoperative defecation, with age (p < 0.01), oral antibiotics for bowel preparation (p = 0.01), probiotics (p = 0.01), and time of first postoperative feeding (p < 0.01) identified as independent risk factors.

Conclusions

The study suggests that he use of probiotics and early recovery of diet may enhance the recovery of bowel function in patients undergoing colorectal surgeries. Among the various analytical methods used, logistic regression emerged as the most effective approach for predicting the timing of the first postoperative flatus and defecation in this patient population.
CircPRELID2 functions as a promoter of renal cell carcinoma through the miR-22-3p/ETV1 cascade
Authors: Lin Xi , Zhi Yi
Published: May 2024

Background

Emerging evidence has indicated that a number of circular RNAs (circRNAs) participate in renal cell carcinoma (RCC) carcinogenesis. Nevertheless, the activity and molecular process of circPRELID2 (hsa_circ_0006528) in RCC progression remain unknown.

Methods

CircPRELID2, miR-22-3p and ETS variant 1 (ETV1) levels were gauged by qRT-PCR. Effect of the circPRELID2/miR-22-3p/ETV1 axis was evaluated by detecting cell growth, motility, and invasion. Immunoblotting assessed related protein levels. The relationships of circPRELID2/miR-22-3p and miR-22-3p/ETV1 were confirmed by RNA immunoprecipitation (RIP), luciferase reporter or RNA pull-down assay.

Results

CircPRELID2 was up-regulated in RCC. CircPRELID2 silencing suppressed RCC cell growth, motility and invasion. Moreover, circPRELID2 silencing weakened M2-type macrophage polarization in THP1-induced macrophage cells. CircPRELID2 sequestered miR-22-3p, and circPRELID2 increased ETV1 expression through miR-22-3p. Moreover, the inhibitory impact of circPRELID2 silencing on RCC cell malignant behaviors was mediated by the miR-22-3p/ETV1 axis. Furthermore, circPRELID2 knockdown in vivo hampered growth of xenograft tumors.

Conclusion

Our study demonstrates that circPRELID2 silencing can mitigate RCC malignant development through the circPRELID2/miR-22-3p/ETV1 axis, highlighting new therapeutic targets for RCC treatment.
Serum stromal cell-derived factor-1 concentrations are increased and associated with nonalcoholic fatty liver disease in children with obesity
Authors: Liu Yuesheng , Hao Lijun , Wang Linhao , Lu Mengnan , Yin Chunyan , Xiao Yanfeng
Published: May 2024

Introduction

Stromal cell-derived factor-1 (SDF-1) is a newly discovered small molecule adipocytokine, and research has shown that it is closely related to the occurrence and development of obesity. However, there are currently few research reports on SDF-1 in childhood obesity and nonalcoholic fatty liver disease (NAFLD), and this study aims to explore the relationship between SDF-1 and obesity related indicators in obese children.

Methods

Serum SDF-1 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Clinical and biochemical data were collected, such as body mass index (BMI), waist and hip circumference, blood pressure, liver enzymes, cholesterol, and fasting insulin. Children with NAFLD or not were evaluated through Color Doppler Ultrasound.

Results

Serum SDF-1 concentrations were significantly higher in obese subjects than in non-obese subjects (P < 0.05), and were elevated in the NAFLD obese subjects than in the non-NAFLD obese subjects (P < 0.05). SDF-1 was positively correlated with BMI, waist-to-hip ratio, systolic blood pressure, body fat percentage (BFP), basal metabolic rate (BMR), alanine transaminase (ALT), aspartate transaminase (AST), glutyltranspeptidase (GT), and homoeostasis model of HOMA-IR, independent of their uric acid (UA), total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), very-low-density lipoprotein (VLDL), gender and age. BFP and BMR were associated with the serum SDF-1 concentrations in multivariable linear regression analysis.

Conclusion

These results suggest that SDF-1 levels are elevated in obese children and are associated with NAFLD, indicating that SDF-1 may play a role in the development of childhood obesity and metabolic disorders.
Comparison of dmft and behavior rating scores between children with systemic disease and healthy children at the first dental visit
Authors: Erbas Unverdi Gizem , Ozgur Beste , Gungor Hamdi Cem , Casamassimo Paul S.
Published: May 2024

Purpose

To evaluate and compare oral health and behavior scores at the first dental visit and dental treatment need using general anesthesia/sedation (GA/S) of children with systemic diseases (SD) and healthy children.

Methods

Data were obtained from healthy children (n = 87) and children with SD (n = 79), aged 4 to 6 years, presenting to a hospital dental clinic for a first dental examination. The total number of decayed, missing and filled teeth (dmft), dental behavior score using Frankl Scale, and dental treatment need using GA/S were recorded. Chi-square / Fisher’s exact test and Mann–Whitney U tests were used for statistical analyses.

Results

The patients with SD were diagnosed with cardiac disease (61%), renal disease (9%), and pediatric cancers (30%). The median dmft values of the SD group (3.00) were significantly lower than those of healthy children (5.00) (p = 0.02) and healthy children exhibited significantly more positive behavior (90.8%) than children with SD (73.4%) (p = 0.002). The number of patients needing GA/S for dental treatment did not differ significantly between the two groups (p = 0.185). There was no relationship between dental treatment need with GA/S and dental behavior scores of the patients (p = 0.05). A statistically significant relationship was found between the patients’ dmft scores and the need for dental treatment using GA/S; and the cut-off value was found to be dmft > 4 for the overall comparisons.

Conclusion

The presence of chronic disease in children appeared to affect the cooperation negatively at the first dental visit compared to healthy controls, however, it did not affect the oral health negatively. Having a negative behavior score or SD did not necessitate the use of GA/S for dental treatment.
Patients as teachers: a within-subjects randomized pilot experiment of patient-led online learning modules for health professionals
Authors: Ndjaboue Ruth , Beaudoin Caroline , Comeau Sandrine , Dagnault Anne , Dogba Maman Joyce , Numainville Sarah , Racine Charles , Straus Sharon , Tremblay Marie-Claude , Witteman Holly O.
Published: May 2024

Purpose

Many health professions education programs involve people with lived experience as expert speakers. Such presentations may help learners better understand the realities of living with chronic illness or experiencing an acute health problem. However, lectures from only one or a small number of people may not adequately illustrate the perspectives and experiences of a diverse patient cohort. Additionally, logistical constraints such as public health restrictions or travel barriers may impede in-person presentations, particularly among people who have more restrictions on their time. Health professions education programs may benefit from understanding the potential effects of online patient-led presentations with a diverse set of speakers. We aimed to explore whether patient-led online learning modules about diabetes care would influence learners’ responses to clinical scenarios and to collect learners’ feedback about the modules.

Method

This within-subjects randomized experiment involved 26 third-year medical students at Université Laval in Quebec, Canada. Participation in the experiment was an optional component within a required course. Prior to the intervention, participating learners responded to three clinical scenarios randomly selected from a set of six such scenarios. Each participant responded to the other three scenarios after the intervention. The intervention consisted of patient-led online learning modules incorporating segments of narratives from 21 patient partners (11 racialized or Indigenous) describing why and how clinicians could provide patient-centered care. Working with clinical teachers and psychometric experts, we developed a scoring grid based on the biopsychosocial model and set 0.6 as a passing score. Independent evaluators, blinded to whether each response was collected before or after the intervention, then scored learners’ responses to scenarios using the grid. We used Fisher’s Exact test to compare proportions of passing scores before and after the intervention.

Results

Learners’ overall percentage of passing scores prior to the intervention was 66%. Following the intervention, the percentage of passing scores was 76% (p = 0.002). Overall, learners expressed appreciation and other positive feedback regarding the patient-led online learning modules.

Discussion

Findings from this experiment suggest that learners can learn to provide better patient-centered care by watching patient-led online learning modules created in collaboration with a diversity of patient partners.
Importance of multimodal resident education curriculum for general surgeons: perspectives of trainers and trainees
Authors: Lee Jeeyeon , Kwon Hyung Jun , Park Soo Yeon , Jung Jin Hyang
Published: May 2024

Purpose

Satisfaction should be prioritized to maximize the value of education for trainees. This study was conducted with professors, fellows, and surgical residents in the Department of general surgery (GS) to evaluate the importance of various educational modules to surgical residents.

Methods

A questionnaire was administered to professors (n = 28), fellows (n = 8), and surgical residents (n = 14), and the responses of the three groups were compared. Four different categories of educational curricula were considered: instructor-led training, clinical education, self-paced learning, and hands-on training.

Results

The majority of surgeons regarded attending scrubs as the most important educational module in the training of surgical residents. However, while professors identified assisting operators by participating in surgery as the most important, residents assessed the laparoscopic training module with animal models as the most beneficial.

Conclusions

The best educational training course for surgical residents was hands-on training, which would provide them with several opportunities to operate and perform surgical procedures themselves.
An evaluation of written materials for supporting hypertensive patient education and counselling when performing a new medicine service in Poland
Authors: Jasińska-Stroschein Magdalena , Dymek Justyna , Drozd Mariola , Sierpniowska Olga , Jędra Artur , Stankiewicz Agnieszka , Stasiak Paulina , Cholewa Sylwia , Nowakowska Magdalena , Waszyk-Nowaczyk Magdalena
Published: May 2024

Background. The New Medicine Service (NMS) was developed in England more than ten years ago, as a three-stage consultation led by community pharmacists to support patients taking new medication for a chronic disease. In Poland, the scheme was officially introduced in January 2023. However, its implementation into common practice has been presented with various obstacles, including the need to develop relationships with general practitioners, resolve the payment structure, and provide training with adequate supporting materials. Hence, written materials have been designed for use as an optional tool for counselling patients receiving an NMS in community pharmacies. Methods. The present study evaluates the ability of these materials to inform patients about the need to adhere to anti-hypertensive medication. A group of 401 randomly-selected adult visitors to pharmacies and/or healthcare centres were surveyed; one third had hypertension in their history. Results. The structure, grammar and readability of the text achieved the required threshold of 40% according to the Plain Language Index. The designed materials effectively informed the patients about anti-hypertensive medication, reflected in an increased score in a knowledge test, and were rated positively regarding information level, comprehensibility and presentation. Conclusion. The proposed material may serve as an additional, “patient-friendly” educational tool for use as part of an NMS.
Numerical evaluation of internal femur osteosynthesis based on a biomechanical model of the loading in the proximal equine hindlimb
Authors: Lang Jan J. , Li Xinhao , Micheler Carina M. , Wilhelm Nikolas J. , Seidl Fritz , Schwaiger Benedikt J. , Barnewitz Dirk , von Eisenhart-Rothe Ruediger , Grosse Christian U. , Burgkart Rainer
Published: May 2024

Femoral fractures are often considered lethal for adult horses because femur osteosynthesis is still a surgical challenge. For equine femur osteosynthesis, primary stability is essential, but the detailed physiological forces occurring in the hindlimb are largely unknown. The objective of this study was to create a numerical testing environment to evaluate equine femur osteosynthesis based on physiological conditions. The study was designed as a finite element analysis (FEA) of the femur using a musculoskeletal model of the loading situation in stance. Relevant forces were determined in the musculoskeletal model via optimization. The treatment of four different fracture types with an intramedullary nail was investigated in FEA with loading conditions derived from the model. The analyzed diaphyseal fracture types were a transverse (TR) fracture, two oblique fractures in different orientations (OB-ML: medial-lateral and OB-AP: anterior-posterior) and a ”gap” fracture (GAP) without contact between the fragments. For the native femur, the most relevant areas of increased stress were located distally to the femoral head and proximally to the caudal side of the condyles. For all fracture types, the highest stresses in the implant material were present in the fracture-adjacent screws. Maximum compressive (-348 MPa) and tensile stress (197 MPa) were found for the GAP fracture, but material strength was not exceeded. The mathematical model was able to predict a load distribution in the femur of the standing horse and was used to assess the performance of internal fixation devices via FEA. The analyzed intramedullary nail and screws showed sufficient stability for all fracture types.
DLL3-guided therapies in small-cell lung cancer: from antibody-drug conjugate to precision immunotherapy and radioimmunotherapy
Authors: Su Po-Lan , Chakravarthy Karthik , Furuya Naoki , Brownstein Jeremy , Yu Jianhua , Long Meixiao , Carbone David , Li Zihai , He Kai
Published: May 2024

DLL3 acts as an inhibitory ligand that downregulates Notch signaling and is upregulated by ASCL1, a transcription factor prevalent in the small-cell lung cancer (SCLC) subtype SCLC-A. Currently, the therapeutic strategies targeting DLL3 are varied, including antibody-drug conjugates (ADCs), bispecific T-cell engagers (BiTEs), and chimeric antigen receptor (CAR) T-cell therapies. Although rovalpituzumab tesirine (Rova-T) showed promise in a phase II study, it failed to produce favorable results in subsequent phase III trials, leading to the cessation of its development. Conversely, DLL3-targeted BiTEs have garnered significant clinical interest. Tarlatamab, for instance, demonstrated enhanced response rates and progression-free survival compared to the standard of care in a phase II trial; its biologics license application (BLA) is currently under US Food and Drug Administration (FDA) review. Numerous ongoing phase III studies aim to further evaluate tarlatamab’s clinical efficacy, alongside the development of novel DLL3-targeted T-cell engagers, both bispecific and trispecific. CAR-T cell therapies targeting DLL3 have recently emerged and are undergoing various preclinical and early-phase clinical studies. Additionally, preclinical studies have shown promising efficacy for DLL3-targeted radiotherapy, which employs β-particle-emitting therapeutic radioisotopes conjugated to DLL3-targeting antibodies. DLL3-targeted therapies hold substantial potential for SCLC management. Future clinical trials will be crucial for comparing treatment outcomes among various approaches and exploring combination therapies to improve patient survival outcomes.
METTL14 regulates CD8+T-cell activation and immune responses to anti‐PD‐1 therapy in lung cancer
Authors: Sun Chongqi , Wang Jian , Li Huixing , Liu Luyao , Lin Yu , Zhang Ling , Zu Xianglong , Zhu Yizhi , Shu Yongqian , Shen Dong , Wang Qiong , Liu Yiqian
Published: May 2024

Background

N6-methyladenosine (m6A) modification plays an important role in lung cancer. However, methyltransferase-like 14 (METTL14), which serves as the main component of the m6A complex, has been less reported to be involved in the immune microenvironment of lung cancer. This study aimed to analyze the relationship between METTL14 and the immune checkpoint inhibitor programmed death receptor 1 (PD-1) in lung cancer.

Methods

CCK-8, colony formation, transwell, wound healing, and flow cytometry assays were performed to explore the role of METTL14 in lung cancer progression in vitro. Furthermore, syngeneic model mice were treated with sh-METTL14 andan anti-PD-1 antibody to observe the effect of METTL14 on immunotherapy. Flow cytometry and immunohistochemical (IHC) staining were used to detect CD8 expression. RIP and MeRIP were performed to assess the relationship between METTL14 and HSD17B6. LLC cells and activated mouse PBMCs were cocultured in vitro to mimic immune cell infiltration in the tumor microenvironment. ELISA was used to detect IFN-γ and TNF-α levels.

Results

The online database GEPIA showed that high METTL14 expression indicated a poor prognosis in patients with lung cancer. In vitro assays suggested that METTL14 knockdown suppressed lung cancer progression. In vivo assays revealed that METTL14 knockdown inhibited tumor growth and enhanced the response to PD-1 immunotherapy. Furthermore, METTL14 knockdown enhanced CD8+T-cell activation and infiltration. More importantly, METTL14 knockdown increased the stability of HSD17B6 mRNA by reducing its m6A methylation. In addition, HSD17B6 overexpression promoted the activation of CD8+ T cells.

Conclusion

The disruption of METTL14 contributed to CD8+T-cell activation and the immunotherapy response to PD-1 via m6A modification of HSD17B6, thereby suppressing lung cancer progression.
Helicobacter pylori disrupts gastric mucosal homeostasis by stimulating macrophages to secrete CCL3
Authors: Wei Yan-Fei , Li Xue , Zhao Meng-Ran , Liu Si , Min Li , Zhu Sheng-Tao , Zhang Shu-Tian , Xie Si-An
Published: May 2024

Background

Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis.

Methods

The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry.

Results

After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased.

Conclusions

In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.
Exploring the changing association between parental and adolescent fruit and vegetable intakes, from age 10 to 30 years
Authors: Braune Tanya , Adams Jean , Winpenny Eleanor M.
Published: May 2024

Background

Adolescence is a pivotal developmental stage, where escalating rates of overweight and obesity have raised concerns about diet quality and its association with adverse health outcomes. Parents are known to have considerable influence on childhood diet, but how this influence changes as adolescents mature is unknown. This study investigates the association between parental fruit and vegetable (FV) intake and adolescent FV consumption, exploring how this changes across adolescence and when adolescents leave home.

Methods

Adolescents aged 10–30 years (n = 12,805) from the UK Household Longitudinal Study (UKHLS), and their parents, reported FV intakes every 2 years. Multilevel linear regression models were fitted to assess associations between parental and adolescent FV intakes, investigating interactions with age and living arrangement, and adjusting for sociodemographic covariates.

Results

Parental FV intake was positively associated with adolescent FV intake (β = 0.20 [95%CI:0.19,0.22] portions/day), with the strength of this association lowest during early adolescence (10–14 years) and peaking at 17–18 years (β = 0.30 [95%CI: 0.27,0.33] portions/day). When adolescents no longer lived in the parental home, the association of parental FV intake with adolescent FV consumption decreased, but a positive association was maintained up to age 30 years.

Conclusions

Our findings emphasise the enduring effect of parental FV consumption on adolescent FV consumption, highlighting the potential for interventions to promote increased FV intake, acknowledging the lasting influence of parental diet, even beyond the confines of the parental home.
Choline metabolism reprogramming mediates an immunosuppressive microenvironment in non-small cell lung cancer (NSCLC) by promoting tumor-associated macrophage functional polarization and endothelial cell proliferation
Authors: Xiao Bijing , Li Guanjun , Gulizeba Haimiti , Liu Hong , Sima Xiaoxian , Zhou Ting , Huang Yan
Published: May 2024

Introduction

Lung cancer is a prevalent malignancy globally, and immunotherapy has revolutionized its treatment. However, resistance to immunotherapy remains a challenge. Abnormal cholinesterase (ChE) activity and choline metabolism are associated with tumor oncogenesis, progression, and poor prognosis in multiple cancers. Yet, the precise mechanism underlying the relationship between ChE, choline metabolism and tumor immune microenvironment in lung cancer, and the response and resistance of immunotherapy still unclear.

Methods

Firstly, 277 advanced non-small cell lung cancer (NSCLC) patients receiving first-line immunotherapy in Sun Yat-sen University Cancer Center were enrolled in the study. Pretreatment and the alteration of ChE after 2 courses of immunotherapy and survival outcomes were collected. Kaplan–Meier survival and cox regression analysis were performed, and nomogram was conducted to identify the prognostic and predicted values. Secondly, choline metabolism-related genes were screened using Cox regression, and a prognostic model was constructed. Functional enrichment analysis and immune microenvironment analysis were also conducted. Lastly, to gain further insights into potential mechanisms, single-cell analysis was performed.

Results

Firstly, baseline high level ChE and the elevation of ChE after immunotherapy were significantly associated with better survival outcomes for advanced NSCLC. Constructed nomogram based on the significant variables from the multivariate Cox analysis performed well in discrimination and calibration. Secondly, 4 choline metabolism-related genes (MTHFD1, PDGFB, PIK3R3, CHKB) were screened and developed a risk signature that was found to be related to a poorer prognosis. Further analysis revealed that the choline metabolism-related genes signature was associated with immunosuppressive tumor microenvironment, immune escape and metabolic reprogramming. scRNA-seq showed that MTHFD1 was specifically distributed in tumor-associated macrophages (TAMs), mediating the differentiation and immunosuppressive functions of macrophages, which may potentially impact endothelial cell proliferation and tumor angiogenesis.

Conclusion

Our study highlights the discovery of ChE as a prognostic marker in advanced NSCLC, suggesting its potential for identifying patients who may benefit from immunotherapy. Additionally, we developed a prognostic signature based on choline metabolism-related genes, revealing the correlation with the immunosuppressive microenvironment and uncovering the role of MTHFD1 in macrophage differentiation and endothelial cell proliferation, providing insights into the intricate workings of choline metabolism in NSCLC pathogenesis.
Increasing the etanercept dose in a treat-to-target approach in juvenile idiopathic arthritis: does it help to reach the target? A post-hoc analysis of the BeSt for Kids randomised clinical trial
Authors: van Dijk Bastiaan T. , Bergstra Sytske Anne , van den Berg J. Merlijn , Schonenberg-Meinema Dieneke , van Suijlekom-Smit Lisette W.A. , van Rossum Marion A.J. , Koopman-Keemink Yvonne , ten Cate Rebecca , Allaart Cornelia F. , Brinkman Daniëlle M.C. , Hissink Muller Petra C.E.
Published: May 2024

Background

Etanercept has been studied in doses up to 0.8 mg/kg/week (max 50 mg/week) in juvenile idiopathic arthritis (JIA) patients. In clinical practice higher doses are used off-label, but evidence regarding the relation with outcomes is lacking. We describe the clinical course of JIA-patients receiving high-dose etanercept (1.6 mg/kg/week; max 50 mg/week) in the BeSt for Kids trial.

Methods

92 patients with oligoarticular JIA, RF-negative polyarticular JIA or juvenile psoriatic arthritis were randomised across three treat-to-target arms: (1) sequential DMARD-monotherapy (sulfasalazine or methotrexate (MTX)), (2) combination-therapy MTX + 6 weeks prednisolone and (3) combination therapy MTX + etanercept. In any treatment-arm, patients could eventually escalate to high-dose etanercept alongside MTX 10mg/m2/week.

Results

32 patients received high-dose etanercept (69% female, median age 6 years (IQR 4–10), median 10 months (7–16) from baseline). Median follow-up was 24.6 months. Most clinical parameters improved within 3 months after dose-increase: median JADAS10 from 7.2 to 2.8 (p = 0.008), VAS-physician from 12 to 4 (p = 0.022), VAS-patient/parent from 38.5 to 13 (p = 0.003), number of active joints from 2 to 0.5 (p = 0.12) and VAS-pain from 35.5 to 15 (p = 0.030). Functional impairments (CHAQ-score) improved more gradually and ESR remained stable. A comparable pattern was observed in 11 patients (73% girls, median age 8 (IQR 6–9)) who did not receive high-dose etanercept despite eligibility (comparison group). In both groups, 56% reached inactive disease at 6 months. No severe adverse events (SAEs) occurred after etanercept dose-increase. In the comparison group, 2 SAEs consisting of hospital admission occurred. Rates of non-severe AEs per subsequent patient year follow-up were 2.27 in the high-dose and 1.43 in the comparison group.

Conclusions

Escalation to high-dose etanercept in JIA-patients who were treated to target was generally followed by meaningful clinical improvement. However, similar improvements were observed in a smaller comparison group who did not escalate to high-dose etanercept. No SAEs were seen after escalation to high-dose etanercept. The division into the high-dose and comparison groups was not randomised, which is a potential source of bias. We advocate larger, randomised studies of high versus regular dose etanercept to provide high level evidence on efficacy and safety.

Trial registration

Dutch Trial Register; NTR1574; 3 December 2008; https://onderzoekmetmensen.nl/en/trial/26585.
Monocytes release cystatin F dimer to associate with Aβ and aggravate amyloid pathology and cognitive deficits in Alzheimer’s disease
Authors: Li Qiang , Li Bing , Liu Li , Wang Kang-Ji , Liu Ming-Yue , Deng Yu , Li Ze , Zhao Wei-Dong , Wu Li-Yong , Chen Yu-Hua , Zhang Ke
Published: May 2024

Background

Understanding the molecular mechanisms of Alzheimer’s disease (AD) has important clinical implications for guiding therapy. Impaired amyloid beta (Aβ) clearance is critical in the pathogenesis of sporadic AD, and blood monocytes play an important role in Aβ clearance in the periphery. However, the mechanism underlying the defective phagocytosis of Aβ by monocytes in AD remains unclear.

Methods

Initially, we collected whole blood samples from sporadic AD patients and isolated the monocytes for RNA sequencing analysis. By establishing APP/PS1 transgenic model mice with monocyte-specific cystatin F overexpression, we assessed the influence of monocyte-derived cystatin F on AD development. We further used a nondenaturing gel to identify the structure of the secreted cystatin F in plasma. Flow cytometry, enzyme-linked immunosorbent assays and laser scanning confocal microscopy were used to analyse the internalization of Aβ by monocytes. Pull down assays, bimolecular fluorescence complementation assays and total internal reflection fluorescence microscopy were used to determine the interactions and potential interactional amino acids between the cystatin F protein and Aβ. Finally, the cystatin F protein was purified and injected via the tail vein into 5XFAD mice to assess AD pathology.

Results

Our results demonstrated that the expression of the cystatin F protein was specifically increased in the monocytes of AD patients. Monocyte-derived cystatin F increased Aβ deposition and exacerbated cognitive deficits in APP/PS1 mice. Furthermore, secreted cystatin F in the plasma of AD patients has a dimeric structure that is closely related to clinical signs of AD. Moreover, we noted that the cystatin F dimer blocks the phagocytosis of Aβ by monocytes. Mechanistically, the cystatin F dimer physically interacts with Aβ to inhibit its recognition and internalization by monocytes through certain amino acid interactions between the cystatin F dimer and Aβ. We found that high levels of the cystatin F dimer protein in blood contributed to amyloid pathology and cognitive deficits as a risk factor in 5XFAD mice.

Conclusions

Our findings highlight that the cystatin F dimer plays a crucial role in regulating Aβ metabolism via its peripheral clearance pathway, providing us with a potential biomarker for diagnosis and potential target for therapeutic intervention.
Third molar eruption in dental panoramic radiographs as a feature for forensic age assessment – new reference data from a German population
Authors: Timme Maximilian , Viktorov Jan , Steffens Laurin , Streeter Adam , Karch André , Schmeling Andreas
Published: May 2024

Forensic age assessment in the living can provide legal certainty when an individual’s chronological age is unknown or when age-related information is questionable. An established method involves assessing the eruption of mandibular third molars through dental panoramic radiographs (PAN). In age assessment procedures, the respective findings are compared to reference data. The objective of this study was to generate new reference data in line with the required standards for mandibular third molar eruption within a German population. For this purpose, 605 PANs from 302 females and 303 males aged 15.04 to 25.99 years were examined. The PANs were acquired between 2013 and 2020, and the development of the mandibular third molars was rated independently by two experienced examiners using the Olze et al. staging scale from 2012. In case of disagreement in the assigned ratings, a consensus was reached through arbitration. While the mean, median and minimum ages were observed to increase with each stage of mandibular third molar eruption according to the Olze method, there was considerable overlap in the distribution of age between the stages. The minimum age for stage D, which corresponds to complete tooth eruption, was 16.1 years for females and 17.1 years for males. Thus, the completion of mandibular third molar eruption was found in both sexes before reaching the age of 18. In all individuals who had at least one tooth with completed eruption and who were younger than 17.4 years of age (n = 10), mineralization of the teeth in question was not complete. Based on our findings, the feature of assessing mandibular third molar eruption in PAN cannot be relied upon for determining age of majority.
Pressure injury treatment by intermittent electrical stimulation (PROTECT-2): protocol for a multicenter randomized clinical trial
Authors: Donaldson Chase , de Abreu Marcelo Gama , Mascha Edward J. , Rowbottom James , Harvester Eric , Khanna Ashish , Sura Tanmay , Sessler Daniel I. , Patarroyo Fabio Rodriguez , Gulluoglu Alper , Zajic Paul , Chauhan Utkarsh , Essber Hani , Kurz Andrea
Published: May 2024

Background

Pressure ulcers account for a substantial fraction of hospital-acquired pathology, with consequent morbidity and economic cost. Treatments are largely focused on preventing further injury, whereas interventions that facilitate healing remain limited. Intermittent electrical stimulation (IES) increases local blood flow and redistributes pressure from muscle-bone interfaces, thus potentially reducing ulcer progression and facilitating healing.

Methods

The Pressure Injury Treatment by Intermittent Electrical Stimulation (PROTECT-2) trial will be a parallel-arm multicenter randomized trial to test the hypothesis that IES combined with routine care reduces sacral and ischial pressure injury over time compared to routine care alone. We plan to enroll 548 patients across various centers. Hospitalized patients with stage 1 or stage 2 sacral or ischial pressure injuries will be randomized to IES and routine care or routine care alone. Wound stage will be followed until death, discharge, or the development of an exclusion criteria for up to 3 months. The primary endpoint will be pressure injury score measured over time.

Discussion

Sacral and ischial pressure injuries present a burden to hospitalized patients with both clinical and economic consequences. The PROTECT-2 trial will evaluate whether IES is an effective intervention and thus reduces progression of stage 1 and stage 2 sacral and ischial pressure injuries.

Trial registration

ClinicalTrials.gov NCT05085288 Registered October 20, 2021.
A bioprocess engineering approach for the production of hydrocarbons and fatty acids from green microalga under high cobalt concentration as the feedstock of high-grade biofuels
Authors: Patel Alok , Rantzos Chloe , Krikigianni Eleni , Rova Ulrika , Christakopoulos Paul , Matsakas Leonidas
Published: May 2024

Botryococcus braunii, a colonial green microalga which is well-known for its capacity to synthesize hydrocarbons, has significant promise as a long-term source of feedstock for the generation of biofuels. However, cultivating and scaling up B. braunii using conventional aqua-suspended cultivation systems remains a challenge. In this study, we optimized medium components and light intensity to enhance lipid and hydrocarbon production in a multi-cultivator airlift photobioreactor. BBM 3N medium with 200 μmol/m2/s light intensity and a 16 h light–8 h dark regimen yielded the highest biomass productivity (110.00 ± 2.88 mg/L/day), as well as the highest lipid and hydrocarbon content. Cultivation in a flat-panel bioreactor resulted in significantly higher biomass productivity (129.11 ± 2.74 mg/L/day), lipid productivity (32.21 ± 1.31 mg/L/day), and hydrocarbon productivity (28.98 ± 2.08 mg/L/day) compared to cultivation in Erlenmeyer flasks and open 20-L raceway pond. It also exhibited 20.15 ± 1.03% of protein content including elevated levels of chlorophyll a, chlorophyll b, and carotenoids. This work is noteworthy since it is the first to describe fatty acid and hydrocarbon profiles of B. braunii during cobalt treatment. The study demonstrated that high cobalt concentrations (up to 5 mg/L of cobalt nitrate) during Botryococcus culture affected hydrocarbon synthesis, resulting in high amounts of n-alkadienes and trienes as well as lipids with elevated monounsaturated fatty acids concentration. Furthermore, pyrolysis experiments on microalgal green biomass and de-oiled biomass revealed the lipid and hydrocarbon compounds generated by the thermal degradation of B. braunii that facilitate extra economical value to this system.
Retraction Note: Improved RFID mutual authentication protocol against exhaustive attack in the context of big data
Authors: Li Kongze
Published: May 2024

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13635-024-00151-w.
Low ankle–brachial index is associated with higher cardiovascular mortality in individuals with nonalcoholic fatty liver disease
Authors: Xiong Guang , Guo Liuqing , Li Liwei , Liang Min
Published: May 2024

Background and aims

Ankle brachial index (ABI) is a risk factor for cardiovascular mortality, but it is unclear whether ABI is associated with cardiovascular mortality in patients with nonalcoholic fatty liver disease (NAFLD). The current study aimed to evaluate the association between ABI with cardiovascular and all-cause mortality in patients with NAFLD.

Methods

We performed a cohort study using the data of the1999–2004 National Health and Nutrition Examination Survey data of adults. Mortality data were followed up to December 2015. NAFLD was defined by the hepatic steatosis index or the US fatty liver index. ABI was classified into three groups: ABI ≤ 0.9 (low value); 0.9 < ABI ≤ 1.1 (borderline value); ABI greater than 1.1 (normal value).

Results

We found that low ABI was associated with an increased risk of cardiovascular mortality in patients with NAFLD (HR: 2.42, 95% CI 1.10–5.33 for low value ABI vs normal value ABI, P for trend = 0.04), and the relationship was linearly and negatively correlated in the range of ABI < 1.4. However, low ABI was not associated with all-cause mortality in patients with NAFLD. Stratified by cardiovascular disease, ABI remains inversely correlated with cardiovascular mortality in NAFLD patients without cardiovascular disease. Stratified by diabetes, ABI is inversely correlated with cardiovascular mortality in NAFLD patients regardless of diabetes status.

Conclusions

Low ABI is independently associated with higher cardiovascular mortality in NAFLD cases. This correlation remains significant even in the absence of pre-existing cardiovascular disease or diabetes.
Screening for eating disorders in adolescents with chronic pain: the Eating Attitudes Test–16–Chronic Pain
Authors: Sim Leslie , Fahrenkamp Amy , Geske Jennifer R. , Lebow Jocelyn , Thilges Hope , Peterson Carol B. , Matthews Abigail , Harbeck-Weber Cynthia
Published: May 2024

Background

Few measures have been validated to screen for eating disorders (ED) in youth with chronic pain. We conducted confirmatory (CFA) of two established factor structures of the Eating Attitudes Test-26 (EAT-26) in a sample of youth with chronic pain attending an intensive interdisciplinary pain treatment (IIPT) program and examined the validity of the best-fitting model in predicting ED diagnoses in this sample.

Methods

Participants were 880 adolescents (M age = 16.1, SD = 2.1) consecutively admitted into an IIPT program who completed the EAT-26 upon admission. CFA was conducted and in the case of inadequate fit, EFA was planned to identify alternative models. Factors of the best-fitting model were included in a logistic regression analysis to predict ED diagnoses.

Results

The TLIs (0.70; 0.90), RMSEAs (0.09; 0.07) and CFIs (0.73; 0.92) suggested poor fit of one model and adequate of the second model. Goodness of fit indices from EFA (TLI:0.85, RMSEA:0.06) did not outperform the fit of the second CFA. As such, the second model was retained with the exception of one factor. The items loaded onto a 16-item, five factor model: Fear of Getting Fat, Social Pressure to Gain Weight, Eating-Related Control, Eating-Related Guilt and Food Preoccupation. Based on chart review, 19.1% of the participants were diagnosed with an eating disorder. Logistic regression analyses indicated the new 16-item measure and Fear of Getting Fat, significantly predicted an ED diagnosis that did not include avoidant restrictive food intake disorder (ARFID) and Social Pressure to Gain Weight significantly predicted a diagnosis of ARFID.

Conclusions

An alternative 16-item, 5-factor structure of the EAT-26 should be considered in screening for EDs with youth with chronic pain.
Exergoeconomic evaluation and multi-objective optimization of a novel geothermal-driven zero-emission system for cooling, electricity, and hydrogen production: capable of working with low-temperature resources
Authors: Bahrami Hamid-Reza , Rosen Marc A.
Published: May 2024

Geothermal energy is an abundant natural resource in many regions around the world. However, in some areas, the temperature of the geothermal energy resource is too low to be efficiently harvested. Organic Rankine cycles (ORCs) are known for recovering heat from low-temperature resources and generating electricity. Furthermore, half-effect absorption chillers (HEACs) are designed to produce cooling with low-temperature resources. This study proposes a novel configuration that utilizes an ORC for electricity generation, a HEAC for cooling production, and a PEM electrolysis system to produce hydrogen. The power section consists of two turbines, one driven by the vapor produced from the geothermal flow expansion, which powers the PEM section, while the other turbine in the ORC is used to drive pumps and electricity production. First, the system is thermoeconomically analyzed for an initial set of inputs. Then, various parameters are analyzed to determine their influences on system performance. The analyses reveal that the system can work with geothermal source temperatures as low as 80 °C, but the exergy and energy (thermal) efficiencies decrease to around 17% under the base settings. Furthermore, the system is capable of working with resource temperatures up to 170 °C. Ten parameters are found to affect the system’s efficiency and effectiveness. To optimize the system, the Non-dominated Sorting Genetic Algorithm II (NSGA-II) is implemented to find the optimum conditions. The objective functions are exergy efficiency and unit polygeneration cost (UPGC), which can conflict. The optimization shows that the exergy efficiency of the system can reach 48% in the optimal conditions (for a heat source temperature of 112 °C and a mass flow rate of geothermal fluid of 44 kg/s), with a hydrogen production rate of 1.1 kg/h.