bluuebunny/crossref_metadata_2025 huggingface dataset:
Supplementary Image from A Compound That Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer
Authors: Uo Takuma , Ojo Kayode K. , Sprenger Cynthia C.T. , Epilepsia Kathryn S. , Perera B. Gayani K. , Damodarasamy Mamatha , Sun Shihua , Kim Soojin , Hogan Hannah H. , Hulverson Matthew A. , Choi Ryan , Whitman Grant R. , Barrett Lynn K. , Michaels Samantha A. , Xu Linda H. , Sun Vicky L. , Arnold Samuel L.M. , Pang Haley J. , Nguyen Matthew M. , Vigil Anna-Lena B.G. , Kamat Varun , Sullivan Lucas B. , Sweet Ian R. , Vidadala Ram , Maly Dustin J. , Van Voorhis Wesley C. , Plymate Stephen R.
Published: July 2024

Supplementary Image shows uncropped Western blot images.
Figure S6 from A Compound That Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer
Authors: Uo Takuma , Ojo Kayode K. , Sprenger Cynthia C.T. , Epilepsia Kathryn S. , Perera B. Gayani K. , Damodarasamy Mamatha , Sun Shihua , Kim Soojin , Hogan Hannah H. , Hulverson Matthew A. , Choi Ryan , Whitman Grant R. , Barrett Lynn K. , Michaels Samantha A. , Xu Linda H. , Sun Vicky L. , Arnold Samuel L.M. , Pang Haley J. , Nguyen Matthew M. , Vigil Anna-Lena B.G. , Kamat Varun , Sullivan Lucas B. , Sweet Ian R. , Vidadala Ram , Maly Dustin J. , Van Voorhis Wesley C. , Plymate Stephen R.
Published: July 2024

Figure S6 shows RPPA Profiling.
Data from A Compound That Inhibits Glycolysis in Prostate Cancer Controls Growth of Advanced Prostate Cancer
Authors: Uo Takuma , Ojo Kayode K. , Sprenger Cynthia C.T. , Epilepsia Kathryn S. , Perera B. Gayani K. , Damodarasamy Mamatha , Sun Shihua , Kim Soojin , Hogan Hannah H. , Hulverson Matthew A. , Choi Ryan , Whitman Grant R. , Barrett Lynn K. , Michaels Samantha A. , Xu Linda H. , Sun Vicky L. , Arnold Samuel L.M. , Pang Haley J. , Nguyen Matthew M. , Vigil Anna-Lena B.G. , Kamat Varun , Sullivan Lucas B. , Sweet Ian R. , Vidadala Ram , Maly Dustin J. , Van Voorhis Wesley C. , Plymate Stephen R.
Published: July 2024

Abstract
Metastatic castration-resistant prostate cancer remains incurable regardless of recent therapeutic advances. Prostate cancer tumors display highly glycolytic phenotypes as the cancer progresses. Nonspecific inhibitors of glycolysis have not been utilized successfully for chemotherapy, because of their penchant to cause systemic toxicity. This study reports the preclinical activity, safety, and pharmacokinetics of a novel small-molecule preclinical candidate, BKIDC-1553, with antiglycolytic activity. We tested a large battery of prostate cancer cell lines for inhibition of cell proliferation, in vitro. Cell-cycle, metabolic, and enzymatic assays were used to demonstrate their mechanism of action. A human patient-derived xenograft model implanted in mice and a human organoid were studied for sensitivity to our BKIDC preclinical candidate. A battery of pharmacokinetic experiments, absorption, distribution, metabolism, and excretion experiments, and in vitro and in vivo toxicology experiments were carried out to assess readiness for clinical trials. We demonstrate a new class of small-molecule inhibitors where antiglycolytic activity in prostate cancer cell lines is mediated through inhibition of hexokinase 2. These compounds display selective growth inhibition across multiple prostate cancer models. We describe a lead BKIDC-1553 that demonstrates promising activity in a preclinical xenograft model of advanced prostate cancer, equivalent to that of enzalutamide. BKIDC-1553 demonstrates safety and pharmacologic properties consistent with a compound that can be taken into human studies with expectations of a good safety margin and predicted dosing for efficacy. This work supports testing BKIDC-1553 and its derivatives in clinical trials for patients with advanced prostate cancer.
Table S1 from Zinc-alpha-2-glycoprotein Secreted by Triple-Negative Breast Cancer Promotes Peritumoral Fibrosis
Authors: Verma Surbhi , Giagnocavo Stephanie D. , Curtin Meghan C. , Arumugam Menusha , Osburn-Staker Sandra M. , Wang Guoying , Atkinson Aaron , Nix David A. , Lum David H. , Cox James E. , Hilgendorf Keren I.
Published: July 2024

Supplemental Table 1: Primers used
A Case Report: Bilateral synchronous percutaneous nephrolithotomy
Authors: Satyagraha Paksi , Daryanto Besut , Nugroho Prasetyo
Published: July 2024

Introduction. Bilateral synchronous Percutaneous Nephrolithotomy (PCNL) begins to be considered as an effective therapy as the staged PCNL for bilateral kidney stone treatment, but it remains to be an challenging procedure. Especially on bilateral obstruction patients that already developed severe hydronephrosis.Case. We present a case of a 49 years old male with flank pain on both sides continuously. From non- contrast abdominalCT-scan showed bilateral pyelum stone and bilateral severe hydronephrosis. From laboratory findings, the creatinine serum was 1,5 mg/dL and ureum serum was level 69,8 mg/dL. We performed bilateral synchronous PCNL in a prone position, and stone fragmentation with a pneumatic lithotripter. The operation lasted for about 2 hours with minimal amount of bleeding. After 5 months of follow-up, he already has no stone with normal ureum-creatinine level (0,77mg/dL; 43,7 mg/dL) and did not have any complaint.Conclusion. Bilateral synchronous PCNL is a safe choice to be done in order to treat bilateral pyelum stone, it can decrease length of stay, total cost therapy, and morbidity of the patient.
Characteristic of Urethral Stone Patients in Tertiary Hospital, East Java
Authors: Fawzi Akmal , Satyagraha Paksi , Daryanto Besut
Published: July 2024

Objectives. Urethral stone is uncommon with proportion < 2% of all urinary tract stones. The common symptom is urinary retention. Urethral stone therapy depends on the stone location and size. The aim from this research is to find out characteristic urethral stone patients.Methods. The study was conducted retrospectively by collecting data from Saiful Anwar General Hospital and urology medical records from January 2014-August 2017. There were a total of 59 patients with urethral stones.Results. Fifty nine patients were obtained with mean age 52±13.66 years old. The most common chief complaint is urinary retention in 47 patients (80%) with duration of retention between 1 hour and 3 days. Stone size is 1-2 cm in 36 patients (61%) and the largest stone is 6 cm. Anterior urethral stones were located in naviculare fossa in 24 patients (41%) and treated by dorsal meatotomy and meatoplasty. Posterior urethral stones were in 12 patients (20%) and treated by vesicolithotripsy. Anterior and posterior lubrication procedures have 33% and 60% successful rate. There were 27 patients who underwent vesicolithotripsy for further management. Urethrolitotomy and repair urethra was performed for 6 cm stone size.Conclusions. The most chief complaints are urinary retention in urethral stone patients. Most urethral stones were located in naviculare fossa with dorsal meatotomy and meatoplasty as the leading management of choice.
Efficacy and Safety of Combination therapy compared to Monotherapy for Overactive Bladder: A Meta-Analysis
Authors: Dhani Fauzan Kurniawan , Rachman Wendi
Published: July 2024

Introduction. Overactive Bladder (OAB) Syndrome is urinary urgency often accompanied by increased daytime frequency and nocturia, with or without urgency incontinence. Individuals with OAB report significant impairment to quality of life. Antimuscarinic become first line therapy of OAB patients with dose escalation or change of antimuscarinic if symptom improvement is inadequate. Increasing the antimuscarinic dose often exacerbates anticholinergic Adverse Events (AEs) that can lead to treatment discontinuation. The aim of this meta-analysis to find out the efficacy and safety of combination therapy compared to solifenacin alone.Methods . We searched for data’s of Randomized clinical trials in PUBMED, EMBASE, and the Cochrane Library. There was no year restriction and only English is allowed. The outcomes were Micturition Episode/24h , Incontinence Episode/24h , AEs and Discontinue medication due to AEs. The data’s were carried out using PRISMA guideline and statistically analysed by using RevMan 5.3.0.Result. Three RCTs studies, including 7007 patients were assessed for efficacy and safety of combination therapy compared solifenacin alone. It is revealed Micturation [HR -0.46; 95%CI: -0.63, -0.29; I2 13%; p<0.00], Incontinence [HR -0.27; 95%CI: -0.42, -0.13; I2 13%; p<0.00], Adverse Events [HR 1.09; 95%CI: 0.94, 1.27; I2 0%; p=0.27] and Discontinue Medication due to AEs [HR 1.26; 95%CI: 0.70, 2.24; I2 0%; p=0.44].Conclusion. The efficacy of combination therapy of mirabegron plus solifenacin significantly improved storage symptoms regarding micturition and incontinence episode, compared to solifenacin monotherapy. Combination therapy provides better therapeutic benefits for patients with overactive bladder syndrome.
Late management of traumatic complete penile amputation: A Case Report
Authors: Junaidi Mustafa V , Haris Nasrudin , Annisya Handini
Published: July 2024

Traumatic complete penile amputation is a rare condition. Despite the implementation and success of known repair strategies, rural hospitals nevertheless face limitations. Furthermore, the amputation of the penis is accompanied by significant challenges and complications in the later stages. We present a case of a 43-year-old man who had previously undergone complete amputation of his penis and is now experiencing urine retention. A suprapubic cystostomy procedure was performed on the patient to divert urine. The patient planned to have a reconstructive operation by seeking treatment at a specialized tertiary referral hospital with expertise in reconstructive urology. However, the patient displayed a hesitancy to interact with healthcare practitioners. The purpose of this case report is to illustrate the complexities of traumatic total penile amputation and the early care of a rare urology case that may arise in peripheral hospitals without urologists.
Edward Jenner e a origem da inoculação vacinal
Authors: Krizek João Pedro Ocanha
Published: July 2024

Edward Jenner (1749-1823) appears as one of the names related to vaccines. He performed a successful vaccination. He presented the vaccination procedures and results in several publications that made artificial immunization known in several countries. Initially, we present a brief introduction to the subject followed by the translation into Portuguese of one of these publications (Jenner, 1801). In very accessible language, he presented a brief account of the origins of vaccine injection and his investigations into cowpox. We hope that this translation can contribute to expanding knowledge about Jenner’s contributions to the field of immunology.
Transcriptomic and proteomic differences in BTK-WT and BTK-mutated CLL and their changes during therapy with pirtobrutinib
Authors: Aslan Burcu , Manyam Ganiraju , Iles Lakesla R. , Tantawy Shady I. , Desikan Sai Prasad , Wierda William G. , Gandhi Varsha
Published: July 2024

Covalent Bruton tyrosine kinase inhibitors (cBTKis), which bind to the BTK C481 residue, are now primary therapeutics for chronic lymphocytic leukemia (CLL). Alterations at C481, primarily C481S, prevent cBTKi binding and lead to the emergence of resistant clones. Pirtobrutinib is a noncovalent BTKi that binds to both wild-type (WT) and C481S-mutated BTK and has shown efficacy in BTK-WT and -mutated CLL patient groups. To compare baseline clinical, transcriptomic, and proteomic characteristics and their changes during treatment in these 2 groups, we used 67 longitudinal peripheral blood samples obtained during the first 3 cycles of treatment with pirtobrutinib from 18 patients with CLL (11 BTK-mutated, 7 BTK-WT) enrolled in the BRUIN (pirtobrutinib in relapsed or refractory B-cell malignancies) trial. Eastern Cooperative Oncology Group performance status, age, and Rai stage were similar in both groups. At baseline, lymph nodes were larger in the BTK-mutated cohort. All patients achieved partial remission within 4 cycles of pirtobrutinib. Lactate dehydrogenase and β2-microglobulin levels decreased in both cohorts after 1 treatment cycle. Expression analysis demonstrated upregulation of 35 genes and downregulation of 6 in the BTK-mutated group. Gene set enrichment analysis revealed that the primary pathways enriched in BTK-mutated cells were involved in cell proliferation, metabolism, and stress response. Pathways associated with metabolism and proliferation were downregulated in both groups during pirtobrutinib treatment. Proteomic data corroborated transcriptomic findings. Our data identified inherent differences between BTK-mutated and -WT CLL and demonstrated molecular normalization of plasma and omics parameters with pirtobrutinib treatment in both groups.
Multi-scale Modeling and Finite Element Analyses of Thermal Conductivity of 3D C/SiC Composites Fabricating by Flexible-Oriented Woven Process
Authors: Sun Zheng , Shan Zhongde , Huang Hao , Wang Dong , Wang Wang , Liu Jiale , Tan Chenchen , Chen Chaozhong
Published: July 2024

Thermal conductivity is one of the most significant criterion of three-dimensional carbon fiber-reinforced SiC matrix composites (3D C/SiC). Represent volume element (RVE) models of microscale, void/matrix and mesoscale proposed in this work are used to simulate the thermal conductivity behaviors of the 3D C/SiC composites. An entirely new process is introduced to weave the preform with three-dimensional orthogonal architecture. The 3D steady-state analysis step is created for assessing the thermal conductivity behaviors of the composites by applying periodic temperature boundary conditions. Three RVE models of cuboid, hexagonal and fiber random distribution are respectively developed to comparatively study the influence of fiber package pattern on the thermal conductivities at the microscale. Besides, the effect of void morphology on the thermal conductivity of the matrix is analyzed by the void/matrix models. The prediction results at the mesoscale correspond closely to the experimental values. The effect of the porosities and fiber volume fractions on the thermal conductivities is also taken into consideration. The multi-scale models mentioned in this paper can be used to predict the thermal conductivity behaviors of other composites with complex structures.
Binary classification with fuzzy logistic regression under class imbalance and complete separation in clinical studies
Authors: Charizanos Georgios , Demirhan Haydar , İçen Duygu
Published: July 2024

Background

In binary classification for clinical studies, an imbalanced distribution of cases to classes and an extreme association level between the binary dependent variable and a subset of independent variables can create significant classification problems. These crucial issues, namely class imbalance and complete separation, lead to classification inaccuracy and biased results in clinical studies.

Method

To deal with class imbalance and complete separation problems, we propose using a fuzzy logistic regression framework for binary classification. Fuzzy logistic regression incorporates combinations of triangular fuzzy numbers for the coefficients, inputs, and outputs and produces crisp classification results. The fuzzy logistic regression framework shows strong classification performance due to fuzzy logic’s better handling of imbalance and separation issues. Hence, classification accuracy is improved, mitigating the risk of misclassified conditions and biased insights for clinical study patients.

Results

The performance of the fuzzy logistic regression model is assessed on twelve binary classification problems with clinical datasets. The model has consistently high sensitivity, specificity, F1, precision, and Mathew’s correlation coefficient scores across all clinical datasets. There is no evidence of impact from the imbalance or separation that exists in the datasets. Furthermore, we compare the fuzzy logistic regression classification performance against two versions of classical logistic regression and six different benchmark sources in the literature. These six sources provide a total of ten different proposed methodologies, and the comparison occurs by calculating the same set of classification performance scores for each method. Either imbalance or separation impacts seven out of ten methodologies. The remaining three produce better classification performance in their respective clinical studies. However, these are all outperformed by the fuzzy logistic regression framework.

Conclusion

Fuzzy logistic regression showcases strong performance against imbalance and separation, providing accurate predictions and, hence, informative insights for classifying patients in clinical studies.
Strategic use of resources to enhance colorectal cancer screening for patients with diabetes (SURE: CRC4D) in federally qualified health centers: a protocol for hybrid type ii effectiveness-implementation trial
Authors: O’Malley Denalee M. , Crabtree Benjamin F. , Kaloth Srivarsha , Ohman-Strickland Pamela , Ferrante Jeanne , Hudson Shawna V. , Kinney Anita Y.
Published: July 2024

Background

Persons with diabetes have 27% elevated risk of developing colorectal cancer (CRC) and are disproportionately from priority health disparities populations. Federally qualified health centers (FQHCs) struggle to implement CRC screening programs for average risk patients. Strategies to effectively prioritize and optimize CRC screening for patients with diabetes in the primary care safety-net are needed.

Methods

Guided by the Exploration, Preparation, Implementation and Sustainment Framework, we conducted a stakeholder-engaged process to identify multi-level change objectives for implementing optimized CRC screening for patients with diabetes in FQHCs. To identify change objectives, an implementation planning group of stakeholders from FQHCs, safety-net screening programs, and policy implementers were assembled and met over a 7-month period. Depth interviews (n = 18–20) with key implementation actors were conducted to identify and refine the materials, methods and strategies needed to support an implementation plan across different FQHC contexts. The planning group endorsed the following multi-component implementation strategies: identifying clinic champions, development/distribution of patient educational materials, developing and implementing quality monitoring systems, and convening clinical meetings. To support clinic champions during the initial implementation phase, two learning collaboratives and bi-weekly virtual facilitation will be provided. In single group, hybrid type 2 effectiveness-implementation trial, we will implement and evaluate these strategies in a in six safety net clinics (n = 30 patients with diabetes per site). The primary clinical outcomes are: (1) clinic-level colonoscopy uptake and (2) overall CRC screening rates for patients with diabetes assessed at baseline and 12-months post-implementation. Implementation outcomes include provider and staff fidelity to the implementation plan, patient acceptability, and feasibility will be assessed at baseline and 12-months post-implementation.

Discussion

Study findings are poised to inform development of evidence-based implementation strategies to be tested for scalability and sustainability in a future hybrid 2 effectiveness-implementation clinical trial. The research protocol can be adapted as a model to investigate the development of targeted cancer prevention strategies in additional chronically ill priority populations.

Trial registration

This study was registered in ClinicalTrials.gov (NCT05785780) on March 27, 2023 (last updated October 21, 2023).
Multiparametric mri-based radiomics nomogram for predicting lymph-vascular space invasion in cervical cancer
Authors: Liu Feng-Hai , Zhao Xin-Ru , Zhang Xiao-Ling , Zhao Meng , Lu Shan
Published: July 2024

Purpose

To develop and validate a multiparametric magnetic resonance imaging (mpMRI)-based radiomics model for predicting lymph-vascular space invasion (LVSI) of cervical cancer (CC).

Methods

The data of 177 CC patients were retrospectively collected and randomly divided into the training cohort (n=123) and testing cohort (n = 54). All patients received preoperative MRI. Feature selection and radiomics model construction were performed using max-relevance and min-redundancy (mRMR) and the least absolute shrinkage and selection operator (LASSO) on the training cohort. The models were established based on the extracted features. The optimal model was selected and combined with clinical independent risk factors to establish the radiomics fusion model and the nomogram. The diagnostic performance of the model was assessed by the area under the curve.

Results

Feature selection extracted the thirteen most important features for model construction. These radiomics features and one clinical characteristic were selected showed favorable discrimination between LVSI and non-LVSI groups. The AUCs of the radiomics nomogram and the mpMRI radiomics model were 0.838 and 0.835 in the training cohort, and 0.837 and 0.817 in the testing cohort.

Conclusion

The nomogram model based on mpMRI radiomics has high diagnostic performance for preoperative prediction of LVSI in patients with CC.
An improved 3D-UNet-based brain hippocampus segmentation model based on MR images
Authors: Yang Qian , Wang Chengfeng , Pan Kaicheng , Xia Bing , Xie Ruifei , Shi Jiankai
Published: July 2024

Objective

Accurate delineation of the hippocampal region via magnetic resonance imaging (MRI) is crucial for the prevention and early diagnosis of neurosystemic diseases. Determining how to accurately and quickly delineate the hippocampus from MRI results has become a serious issue. In this study, a pixel-level semantic segmentation method using 3D-UNet is proposed to realize the automatic segmentation of the brain hippocampus from MRI results. Methods: Two hundred three-dimensional T1-weighted (3D-T1) nongadolinium contrast-enhanced magnetic resonance (MR) images were acquired at Hangzhou Cancer Hospital from June 2020 to December 2022. These samples were divided into two groups, containing 175 and 25 samples. In the first group, 145 cases were used to train the hippocampus segmentation model, and the remaining 30 cases were used to fine-tune the hyperparameters of the model. Images for twenty-five patients in the second group were used as the test set to evaluate the performance of the model. The training set of images was processed via rotation, scaling, grey value augmentation and transformation with a smooth dense deformation field for both image data and ground truth labels. A filling technique was introduced into the segmentation network to establish the hippocampus segmentation model. In addition, the performance of models established with the original network, such as VNet, SegResNet, UNetR and 3D-UNet, was compared with that of models constructed by combining the filling technique with the original segmentation network. Results: The results showed that the performance of the segmentation model improved after the filling technique was introduced. Specifically, when the filling technique was introduced into VNet, SegResNet, 3D-UNet and UNetR, the segmentation performance of the models trained with an input image size of 48 × 48 × 48 improved. Among them, the 3D-UNet-based model with the filling technique achieved the best performance, with a Dice score (Dice score) of 0.7989 ± 0.0398 and a mean intersection over union (mIoU) of 0.6669 ± 0.0540, which were greater than those of the original 3D-UNet-based model. In addition, the oversegmentation ratio (OSR), average surface distance (ASD) and Hausdorff distance (HD) were 0.0666 ± 0.0351, 0.5733 ± 0.1018 and 5.1235 ± 1.4397, respectively, which were better than those of the other models. In addition, when the size of the input image was set to 48 × 48 × 48, 64 × 64 × 64 and 96 × 96 × 96, the model performance gradually improved, and the Dice scores of the proposed model reached 0.7989 ± 0.0398, 0.8371 ± 0.0254 and 0.8674 ± 0.0257, respectively. In addition, the mIoUs reached 0.6669 ± 0.0540, 0.7207 ± 0.0370 and 0.7668 ± 0.0392, respectively. Conclusion: The proposed hippocampus segmentation model constructed by introducing the filling technique into a segmentation network performed better than models built solely on the original network and can improve the efficiency of diagnostic analysis.
Rate of abnormalities in quantitative MR neuroimaging of persons with chronic traumatic brain injury
Authors: Rahmani Farzaneh , Batson Richard D. , Zimmerman Alexandra , Reddigari Samir , Bigler Erin D. , Lanning Shawn C. , Ilasa Eveline , Grafman Jordan H. , Lu Hanzhang , Lin Alexander P. , Raji Cyrus A.
Published: July 2024

Background

Mild traumatic brain injury (mTBI) can result in lasting brain damage that is often too subtle to detect by qualitative visual inspection on conventional MR imaging. Although a number of FDA-cleared MR neuroimaging tools have demonstrated changes associated with mTBI, they are still under-utilized in clinical practice.

Methods

We investigated a group of 65 individuals with predominantly mTBI (60 mTBI, 48 due to motor-vehicle collision, mean age 47 ± 13 years, 27 men and 38 women) with MR neuroimaging performed in a median of 37 months post-injury. We evaluated abnormalities in brain volumetry including analysis of left-right asymmetry by quantitative volumetric analysis, cerebral perfusion by pseudo-continuous arterial spin labeling (PCASL), white matter microstructure by diffusion tensor imaging (DTI), and neurometabolites via magnetic resonance spectroscopy (MRS).

Results

All participants demonstrated atrophy in at least one lobar structure or increased lateral ventricular volume. The globus pallidi and cerebellar grey matter were most likely to demonstrate atrophy and asymmetry. Perfusion imaging revealed significant reductions of cerebral blood flow in both occipital and right frontoparietal regions. Diffusion abnormalities were relatively less common though a subset analysis of participants with higher resolution DTI demonstrated additional abnormalities. All participants showed abnormal levels on at least one brain metabolite, most commonly in choline and N-acetylaspartate.

Conclusion

We demonstrate the presence of coup-contrecoup perfusion injury patterns, widespread atrophy, regional brain volume asymmetry, and metabolic aberrations as sensitive markers of chronic mTBI sequelae. Our findings expand the historic focus on quantitative imaging of mTBI with DTI by highlighting the complementary importance of volumetry, arterial spin labeling perfusion and magnetic resonance spectroscopy neurometabolite analyses in the evaluation of chronic mTBI.
Exploring the causal association between uric acid and lung cancer in east Asian and European populations: a mendelian randomization study
Authors: Lin Ping , Zhang Linxiang , Tang Xiaohui , Wang Jihuang
Published: July 2024

Background

Lung cancer still ranks first in the mortality rate of cancer. Uric acid is a product of purine metabolism in humans. Its presence in the serum is controversial; some say that its high levels have a protective effect against tumors, others say the opposite, that is, high levels increase the risk of cancer. Therefore, the aim of this study was to investigate the potential causal association between serum uric acid levels and lung cancer.

Methods

Mendelian randomization was used to achieve our aim. Sensitivity analyses was performed to validate the reliability of the results, followed by reverse Mendelian analyses to determine a potential reverse causal association.

Results

A significant causal association was found between serum uric acid levels and lung cancer in East Asian and European populations. Further sublayer analysis revealed a significant causal association between uric acid and small cell lung cancer, while no potential association was observed between uric acid and non-small cell lung cancer, squamous lung cancer, and lung adenocarcinoma. The sensitivity analyses confirmed the reliability of the results. Reverse Mendelian analysis showed no reverse causal association between uric acid and lung cancer.

Conclusions

The results of this study suggested that serum uric acid levels were negatively associated with lung cancer, with uric acid being a potential protective factor for lung cancer. In addition, uric acid level monitoring was simple and inexpensive. Therefore, it might be used as a biomarker for lung cancer, promoting its wide use clinical practice.
Receiving home care forms and the risk for emergency department visits in community-dwelling Dutch older adults, a retrospective cohort study using national data
Authors: Smeekes Oscar S , De Boer Tim R , Van Der Mei Robert D , Buurman Bianca M , Willems Hanna C
Published: July 2024

Background

Older adults receiving home care have a higher risk of visiting the emergency department (ED) than community-dwelling older adults not receiving home care. This may result from a higher incidence of comorbidities and reduced functional autonomy in home care recipients. Since people receive different types of home care because of their different comorbidities and autonomy profiles, it is possible that distinguishing between the form of home care can help identify subpopulations with different risks for ED visits and help develop targeted interventions. This study aimed to compare the risk of visiting the ED in older adults receiving different forms of home care with those living at home without receiving home care in a national cohort in one year.

Methods

A retrospective cohort study using claims data collected in 2019 on the Dutch population aged ≥ 65 years (N = 3,314,440) was conducted. Participants were classified as follows: no claimed home care (NO), household help (HH), personal care (PC), HH + PC, and nursing home care at home (NHH). The primary outcome was the number of individuals that visited the ED. Secondary outcomes were the number of individuals whose home care changed, who were institutionalized, or who died. Exploratory logistic regression was applied.

Results

There were 2,758,093 adults in the NO group, 131,260 in the HH group, 154,462 in the PC group, 96,526 in the HH + PC group, and 34,612 in the NHH group. More ED visits were observed in the home care groups than in the NO group, and this risk increased to more than two-fold for the PC groups. There was a significant change to a more intensive form of home care, institutionalization, or death in all groups.

Conclusions

Distinguishing between the form of home care older adults receive identifies subpopulations with different risks for ED visits compared with community-dwelling older adults not receiving home care on a population level. Home care transitions are frequent and mostly involve more intensive care or death. Although older adults not receiving home care have a lower risk of ED visits, they contribute most to the absolute volume of ED visits.
Potential association of rheumatic diseases with bone mineral density and fractures: a bi-directional mendelian randomization study
Authors: Hong Chen-xuan , Pan Yan-zheng , Dai Feng-bo
Published: July 2024

Background

Previous studies have implicated rheumatoid arthritis as an independent risk factor for bone density loss. However, whether there is a causal relationship between rheumatic diseases and bone mineral density (BMD) and fractures is still controversial. We employed a bidirectional Mendelian analysis to explore the causal relationship between rheumatic diseases and BMD or fractures.

Methods

The rheumatic diseases instrumental variables (IVs) were obtained from a large Genome-wide association study (GWAS) meta-analysis dataset of European descent. Analyses were performed for the three rheumatic diseases: ankylosing spondylitis (AS) (n = 22,647 cases, 99,962 single nucleotide polymorphisms [SNPs]), rheumatoid arthritis (RA) (n = 58,284 cases, 13,108,512 SNPs), and systemic lupus erythematosus (SLE) (n = 14,267 cases, 7,071,163 SNPs). Two-sample Mendelian randomization (MR) analyses were carried out by using R language TwoSampleMR version 0.5.7. The inverse-variance weighted (IVW), MR-Egger, and weighted median methods were used to analyze the causal relationship between rheumatic diseases and BMD or fracture.

Results

The MR results revealed that there was absence of evidence for causal effect of AS on BMD or fracture. However, there is a positive causal relationship of RA with fracture of femur (95% CI = 1.0001 to 1.077, p = 0.046), and RA and fracture of forearm (95% CI = 1.015 to 1.064, p = 0.001). SLE had positive causal links for fracture of forearm (95% CI = 1.004 to 1.051, p = 0.020). Additionally, increasing in heel bone mineral density (Heel-BMD) and total bone mineral density (Total-BMD) can lead to a reduced risk of AS without heterogeneity or pleiotropic effects. The results were stable and reliable. There was absence of evidence for causal effect of fracture on RA (95% CI = 0.929 to 1.106, p = 0.759), and fracture on SLE (95% CI = 0.793 to 1.589, p = 0.516).

Conclusions

RA and SLE are risk factors for fractures. On the other hand, BMD increasing can reduce risk of AS. Our results indicate that rheumatic diseases may lead to an increased risk of fractures, while increased BMD may lead to a reduced risk of rheumatic diseases. These findings provide insight into the risk of BMD and AS, identifying a potential predictor of AS risk as a reduction in BMD.
Highly extensile approach for comminuted ulna coronoid process fractures with mini-plate fixation: a case series of 31 patients
Authors: Zhou Shi-Cheng , Jin Sheng-Yu , Wang Qing-Yu , Ren Guang-Kai , Peng Chuan-Gang , Wang Yan-Bing , Wu Dan-Kai
Published: July 2024

Background

For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up.

Methods

Thirty-one patients diagnosed with coronoid fractures accompanied with a “terrible triad” or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded.

Results

The mean follow-up time was 26.7 months (range, 14–60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey’s criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification.

Conclusion

An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.
Mentoring as a complex adaptive system – a systematic scoping review of prevailing mentoring theories in medical education
Authors: Teo Mac Yu Kai , Ibrahim Halah , Lin Casper Keegan Ronggui , Hamid Nur Amira Binte Abdul , Govindasamy Ranitha , Somasundaram Nagavalli , Lim Crystal , Goh Jia Ling , Zhou Yi , Tay Kuang Teck , Ong Ryan Rui Song , Tan Vanessa , Toh Youru , Pisupati Anushka , Raveendran Vijayprasanth , Chua Keith Zi Yuan , Quah Elaine Li Ying , Sivakumar Jeevasuba , Senthilkumar Samyuktha Dhanalakshmi , Suresh Keerthana , Loo Wesley Teck Wee , Wong Ruth Si Man , Pei Yiying , Sng Julia Huina , Quek Simone Qian Min , Owyong Jasmine Lerk Juan , Yeoh Ting Ting , Ong Eng Koon , Phua Gillian Li Gek , Mason Stephen , Hill Ruaraidh , Chowdhury Anupama Roy , Ong Simon Yew Kuang , Krishna Lalit Kumar Radha
Published: July 2024

Background

Effective mentorship is an important component of medical education with benefits to all stakeholders. In recent years, conceptualization of mentorship has gone beyond the traditional dyadic experienced mentor-novice mentee relationship to include group and peer mentoring. Existing theories of mentorship do not recognize mentoring’s personalized, evolving, goal-driven, and context-specific nature. Evidencing the limitations of traditional cause-and-effect concepts, the purpose of this review was to systematically search the literature to determine if mentoring can be viewed as a complex adaptive system (CAS).

Methods

A systematic scoping review using Krishna’s Systematic Evidence-Based Approach was employed to study medical student and resident accounts of mentoring and CAS in general internal medicine and related subspecialties in articles published between 1 January 2000 and 31 December 2023 in PubMed, Embase, PsycINFO, ERIC, Google Scholar, and Scopus databases. The included articles underwent thematic and content analysis, with the themes identified and combined to create domains, which framed the discussion.

Results

Of 5,704 abstracts reviewed, 134 full-text articles were evaluated, and 216 articles were included. The domains described how mentoring relationships and mentoring approaches embody characteristics of CAS and that mentorship often behaves as a community of practice (CoP). Mentoring’s CAS-like features are displayed through CoPs, with distinct boundaries, a spiral mentoring trajectory, and longitudinal mentoring support and assessment processes.

Conclusion

Recognizing mentorship as a CAS demands the rethinking of the design, support, assessment, and oversight of mentorship and the role of mentors. Further study is required to better assess the mentoring process and to provide optimal training and support to mentors.
Effectiveness of virtual and augmented reality for cardiopulmonary resuscitation training: a systematic review and meta-analysis
Authors: Sun Rao , Wang Yixuan , Wu Qingya , Wang Shuo , Liu Xuan , Wang Pei , He Yuqin , Zheng Hua
Published: July 2024

Background

Virtual reality (VR) and augmented reality (AR) are emerging technologies that can be used for cardiopulmonary resuscitation (CPR) training. Compared to traditional face-to-face training, VR/AR-based training has the potential to reach a wider audience, but there is debate regarding its effectiveness in improving CPR quality. Therefore, we conducted a meta-analysis to assess the effectiveness of VR/AR training compared with face-to-face training.

Methods

We searched PubMed, Embase, Cochrane Library, Web of Science, CINAHL, China National Knowledge Infrastructure, and Wanfang databases from the inception of these databases up until December 1, 2023, for randomized controlled trials (RCTs) comparing VR- and AR-based CPR training to traditional face-to-face training. Cochrane's tool for assessing bias in RCTs was used to assess the methodological quality of the included studies. We pooled the data using a random-effects model with Review Manager 5.4, and assessed publication bias with Stata 11.0.

Results

Nine RCTs (involving 855 participants) were included, of which three were of low risk of bias. Meta-analyses showed no significant differences between VR/AR-based CPR training and face-to-face CPR training in terms of chest compression depth (mean difference [MD], -0.66 mm; 95% confidence interval [CI], -6.34 to 5.02 mm; P = 0.82), chest compression rate (MD, 3.60 compressions per minute; 95% CI, -1.21 to 8.41 compressions per minute; P = 0.14), overall CPR performance score (standardized mean difference, -0.05; 95% CI, -0.93 to 0.83; P = 0.91), as well as the proportion of participants meeting CPR depth criteria (risk ratio [RR], 0.79; 95% CI, 0.53 to 1.18; P = 0.26) and rate criteria (RR, 0.99; 95% CI, 0.72 to 1.35; P = 0.93). The Egger regression test showed no evidence of publication bias.

Conclusions

Our study showed evidence that VR/AR-based training was as effective as traditional face-to-face CPR training. Nevertheless, there was substantial heterogeneity among the included studies, which reduced confidence in the findings. Future studies need to establish standardized VR/AR-based CPR training protocols, evaluate the cost-effectiveness of this approach, and assess its impact on actual CPR performance in real-life scenarios and patient outcomes.

Trial registration

CRD42023482286.
Identifying communication barriers between nurses and patients from the perspective of Iranian nurses: a Q-methodology-based study
Authors: Gheshlagh Reza Ghanei , Nemati Syede Mona , Negarandeh Reza , Bahramnezhad Fatemeh , Saqqezi Pershang Sharifi , Mahmoodi Hassan
Published: July 2024

Background

Effective communication is essential for high-quality healthcare, yet barriers often impede meaningful connection between nurses and patients. This study aimed to prioritize communication barriers between nurses and patients in Iranian hospitals, exploring nurses’ perspectives.

Methods

Thirty-one nurses participated in a six-step Q methodology study to identify different perspectives on communication barriers. Participants sorted a set of statements based on their own experiences and beliefs.

Results

The average age of participants was 38.07 (SD = 6.49), with 70% being women. Four distinct factors emerged, explaining 47% of the total variance in perspectives: Organizational factors and work conditions (20%), Emotional distress and psychological barriers (11%), Lack of mutual understanding and awareness (7%), and declining professional motivation and engagement among nurses (9%).

Conclusion

These findings highlight the multi-faceted nature of communication barriers between nurses and patients in this context. Interventions should address organizational factors, emotional well-being of nurses, cultural awareness, and professional motivation to improve communication and ultimately, patient care. This study provides valuable insights for Iran and other developing countries that are facing similar challenges.
Investigation of coagulation and proteomics profiles in symptomatic feline hypertrophic cardiomyopathy and healthy control cats
Authors: Jiwaganont Palin , Roytrakul Sittiruk , Thaisakun Siriwan , Sukumolanan Pratch , Petchdee Soontaree
Published: July 2024

Background

Hypertrophic cardiomyopathy (HCM) is a crucial heart disease in cats. The clinical manifestations of HCM comprise pulmonary edema, dyspnea, syncope, arterial thromboembolism (ATE), and sudden cardiac death. D-dimer and prothrombin time (PT) are powerful biomarkers used to assess coagulation function. Dysregulation in these two biomarkers may be associated with HCM in cats. This study aims to assess D-dimer levels, PT, and proteomic profiling in healthy cats in comparison to cats with symptomatic HCM.

Results

Twenty-nine client-owned cats with HCM were enrolled, including 15 healthy control and 14 symptomatic HCM cats. The D-dimer concentration and PT were examined. Proteomic analysis was conducted by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry and liquid chromatography-tandem mass spectrometry (LC-MS/MS). In symptomatic cats, D-dimer levels were statistically significantly higher (mean ± SEM: 372.19 ng/ml ± 58.28) than in healthy cats (mean ± SEM: 208.54 ng/ml ± 10.92) with P-value of less than 0.01, while PT was statistically significantly lower in symptomatic cats (mean ± SEM: 9.8 s ± 0.15) compared to healthy cats (mean ± SEM: 11.08 s ± 0.23) with P-value of less than 0.0001. The proteomics analysis revealed upregulation of integrin subunit alpha M (ITGAM), elongin B (ELOB), and fibrillin 2 (FBN2) and downregulation of zinc finger protein 316 (ZNF316) and ectonucleoside triphosphate diphosphohydrolase 8 (ENTPD8) in symptomatic HCM cats. In addition, protein-drug interaction analysis identified the Ras signaling pathway and PI3K-Akt signaling pathway.

Conclusions

Cats with symptomatic HCM have higher D-dimer and lower PT than healthy cats. Proteomic profiles may be used as potential biomarkers for the detection and management of HCM in cats. The use of D-dimer as a biomarker for HCM detection and the use of proteomic profiling for a better understanding of disease mechanisms remain to be further studied in cats.
Construction of lignan glycosides biosynthetic network in Escherichia coli using mutltienzyme modules
Authors: Qiao Yuqi , Huang Doudou , Li Yajing , Jiang Songfan , Chen Xiao , Chen Junfeng , Xiao Ying , Chen Wansheng
Published: July 2024

Background

Due to the complexity of the metabolic pathway network of active ingredients, precise targeted synthesis of any active ingredient on a synthetic network is a huge challenge. Based on a complete analysis of the active ingredient pathway in a species, this goal can be achieved by elucidating the functional differences of each enzyme in the pathway and achieving this goal through different combinations. Lignans are a class of phytoestrogens that are present abundantly in plants and play a role in various physiological activities of plants due to their structural diversity. In addition, lignans offer various medicinal benefits to humans. Despite their value, the low concentration of lignans in plants limits their extraction and utilization. Recently, synthetic biology approaches have been explored for lignan production, but achieving the synthesis of most lignans, especially the more valuable lignan glycosides, across the entire synthetic network remains incomplete.

Results

By evaluating various gene construction methods and sequences, we determined that the pCDF-Duet-Prx02-PsVAO gene construction was the most effective for the production of (+)-pinoresinol, yielding up to 698.9 mg/L after shake-flask fermentation. Based on the stable production of (+)-pinoresinol, we synthesized downstream metabolites in vivo. By comparing different fermentation methods, including “one-cell, one-pot” and “multicellular one-pot”, we determined that the “multicellular one-pot” method was more effective for producing (+)-lariciresinol, (-)-secoisolariciresinol, (-)-matairesinol, and their glycoside products. The “multicellular one-pot” fermentation yielded 434.08 mg/L of (+)-lariciresinol, 96.81 mg/L of (-)-secoisolariciresinol, and 45.14 mg/L of (-)-matairesinol. Subsequently, ultilizing the strict substrate recognition pecificities of UDP-glycosyltransferase (UGT) incorporating the native uridine diphosphate glucose (UDPG) Module for in vivo synthesis of glycoside products resulted in the following yields: (+)-pinoresinol glucoside: 1.71 mg/L, (+)-lariciresinol-4-O-d-glucopyranoside: 1.3 mg/L, (+)-lariciresinol-4’-O-d-glucopyranoside: 836 µg/L, (-)-secoisolariciresinol monoglucoside: 103.77 µg/L, (-)-matairesinol-4-O-d-glucopyranoside: 86.79 µg/L, and (-)-matairesinol-4’-O-d-glucopyranoside: 74.5 µg/L.

Conclusions

By using various construction and fermentation methods, we successfully synthesized 10 products of the lignan pathway in Isatis indigotica Fort in Escherichia coli, with eugenol as substrate. Additionally, we obtained a diverse range of lignan products by combining different modules, setting a foundation for future high-yield lignan production.