bluuebunny/crossref_metadata_2025 huggingface dataset:
Long‐Term Hemorrhagic Morbidity for Children With Moyamoya Treated With Revascularization Surgery in a Single Center Retrospective Cohort
Authors: See Alfred P. , Kocher Sophia D. , Piwowarczyk Paulina , Alexandrescu Sanda , Ligon Keith L. , Orbach Darren B. , Smith Edward R. , Lehman Laura L.
Published: July 2024

Background

Children with moyamoya arteriopathy have reduced subsequent ischemic risk after revascularization surgery and it is also suggested that hemorrhagic risk may also be reduced by minimizing hemodynamic stress on collateral vasculature recruited within the brain parenchyma, but this has been studied only in intermediate follow‐up or follow‐up for more than a decade in East Asian populations. We aimed to evaluate the incidence of hemorrhagic stroke in long‐term follow‐up and identify at‐risk subpopulations.

Methods

A single surgeon's personal case series with decades of follow‐up was reviewed for children (18 years or younger) treated with revascularization surgery. This included medical records and the surgeon's personal correspondence.

Results

Hemorrhagic stroke occurred in 2.6% of 302 children followed for a median of 21 years after surgery. Occurring at a median of 19 years (interquartile range 14–22.75) after surgery, these hemorrhages would not be recognized in series that discontinue follow‐up at transition from pediatric to adult neurosurgical care. There was a higher proportion (5.5‐fold hazard, 95% CI, 1.1–27.6) of patients who had prior radiation therapy in the group with hemorrhagic stroke compared with the overall group. Close retrospective evaluation of vascular imaging suggests aneurysms of the collateral periventricular vessels as a common culprit.

Conclusion

Children who have moyamoya treated with revascularization surgery remain at long‐term risk of hemorrhagic stroke during adulthood, even though their ischemic stroke risk is significantly mitigated. These patients would benefit from continued clinical and radiological follow‐up, potentially with advanced imaging modalities.
Exploring the Potential of Off-the-Shelf Tools as Digital Probes: Appropriation of a Mobile Diary App
Authors: Aytaç Aysun , Junginger Sabine , Rogers Jon
Published: July 2024

When cultural probes emerged in 1999, they were, for the most part, crafted from physical, non-digital, materials used to explore people's lives through playful co-creation and ambiguity. They have since become an important method for design researchers to generate insights into user behavior. Today, there is a growing need for user research to involve remote alternatives, something that was very much amplified during the global COVID-19 pandemic. The ubiquity of smartphones has given researchers the potential to have a remote window into people's lives like never before. This raises questions about the probe-like qualities of smartphone apps from a design research perspective. What options are available to design researchers? What are their strengths and weaknesses? What criteria matter? How can we improve on them? We share what we learned while using a mobile diary app for a remote in-home study with 31 households. We discuss the limitations of the app we ended up using and identify the need for an easy-to-adapt, off-the-shelf digital probe suitable for design researchers. The results and findings are intended to encourage designers to work toward digital probes and provide guidance for those who depend on commercially available mobile dairy apps in the meantime.
Multimode Design and Analysis of an Integrated Leg-Arm Quadruped Robot with Deployable Characteristics
Authors: Zhao Fuqun , Wu Yifan , Yang Xinhua , Ding Xilun , Xu Kun , Guo Sheng , Jin Xiaodong
Published: July 2024

To improve locomotion and operation integration, this paper presents an integrated leg-arm quadruped robot (ILQR) that has a reconfigurable joint. First, the reconfigurable joint is designed and assembled at the end of the leg-arm chain. When the robot performs a task, reconfigurable configuration and mode switching can be achieved using this joint. In contrast from traditional quadruped robots, this robot can stack in a designated area to optimize the occupied volume in a nonworking state. Kinematics modeling and dynamics modeling are established to evaluate the mechanical properties for multiple modes. All working modes of the robot are classified, which can be defined as deployable mode, locomotion mode and operation mode. Based on the stability margin and mechanical modeling, switching analysis and evaluation between each mode is carried out. Finally, the prototype experimental results verify the function realization and switching stability of multimode and provide a design method to integrate and perform multimode for quadruped robots with deployable characteristics.
Unsupervised modeling of mutational landscapes of adeno-associated viruses viability
Authors: De Leonardis Matteo , Fernandez-de-Cossio-Diaz Jorge , Uguzzoni Guido , Pagnani Andrea
Published: July 2024

Adeno-associated viruses 2 (AAV2) are minute viruses renowned for their capacity to infect human cells and akin organisms. They have recently emerged as prominent candidates in the field of gene therapy, primarily attributed to their inherent non-pathogenic nature in humans and the safety associated with their manipulation. The efficacy of AAV2 as gene therapy vectors hinges on their ability to infiltrate host cells, a phenomenon reliant on their competence to construct a capsid capable of breaching the nucleus of the target cell. To enhance their infection potential, researchers have extensively scrutinized various combinatorial libraries by introducing mutations into the capsid, aiming to boost their effectiveness. The emergence of high-throughput experimental techniques, like deep mutational scanning (DMS), has made it feasible to experimentally assess the fitness of these libraries for their intended purpose. Notably, machine learning is starting to demonstrate its potential in addressing predictions within the mutational landscape from sequence data. In this context, we introduce a biophysically-inspired model designed to predict the viability of genetic variants in DMS experiments. This model is tailored to a specific segment of the CAP region within AAV2’s capsid protein. To evaluate its effectiveness, we conduct model training with diverse datasets, each tailored to explore different aspects of the mutational landscape influenced by the selection process. Our assessment of the biophysical model centers on two primary objectives: (i) providing quantitative forecasts for the log-selectivity of variants and (ii) deploying it as a binary classifier to categorize sequences into viable and non-viable classes.
Concurrent of compound heterozygous variant of a novel in-frame deletion and the common hypomorphic haplotype in TBX6 and inherited 17q12 microdeletion in a fetus
Authors: Li Guoqiang , Chen Yiyao , Han Xu , Li Niu , Li Shuyuan
Published: July 2024

Background

TBX6, a member of the T-box gene family, encodes the transcription factor box 6 that is critical for somite segmentation in vertebrates. It is known that the compound heterozygosity of disruptive variants in trans with a common hypomorphic risk haplotype (T-C-A) in the TBX6 gene contribute to 10% of congenital scoliosis (CS) cases. The deletion of chromosome 17q12 is a rare cytogenetic abnormality, which often leads to renal cysts and diabetes mellitus. However, the affected individuals often exhibit clinical heterogeneity and incomplete penetrance.

Methods

We here present a Chinese fetus who was shown to have CS by ultrasound examination at 17 weeks of gestation. Trio whole-exome sequencing (WES) was performed to investigate the underlying genetic defects of the fetus. In vitro functional experiments, including western-blotting and luciferase transactivation assay, were performed to determine the pathogenicity of the novel variant of TBX6.

Results

WES revealed the fetus harbored a compound heterozygous variant of c.338_340del (p.Ile113del) and the common hypomorphic risk haplotype of the TBX6 gene. In vitro functional study showed the p.Ile113del variant had no impact on TBX6 expression, but almost led to complete loss of its transcriptional activity. In addition, we identified a 1.85 Mb deletion on 17q12 region in the fetus and the mother. Though there is currently no clinical phenotype associated with this copy number variation in the fetus, it can explain multiple renal cysts in the pregnant woman.

Conclusions

This study is the first to report a Chinese fetus with a single amino acid deletion variant and a T-C-A haplotype of TBX6. The clinical heterogeneity of 17q12 microdeletion poses significant challenges for prenatal genetic counseling. Our results once again suggest the complexity of prenatal genetic diagnosis.
Relationship between plasma TNF-α levels and agitation symptoms in first episode patients with schizophrenia
Authors: Wang Xiaoying , Chen Wenjin , Gou Mengzhuang , Li Wei , Li Na , Tong Jinghui , Zhou Yanfang , Xie Ting , Yu Ting , Feng Wei , Li Yanli , Chen Song , Tian Baopeng , Tan Shuping , Wang Zhiren , Pan Shujuan , Luo Xingguang , Zhang Ping , Huang Junchao , Tian Li , Li Chiang-Shan R. , Tan Yunlong
Published: July 2024

Background

Increasing evidence suggested that immune abnormalities involved in the pathophysiology of schizophrenia. However, the relationship between immunity and clinical features has not been clarified. The aim of this study was to measure the plasma levels of tumor necrosis factor alpha (TNF-α) and soluble TNF-α receptor 1 (sTNF-α R1) and to investigate their association with agitation in first episode patients with schizophrenia (FEPS).

Methods

The plasma TNF-α and sTNF-α R1 levels were measured using sandwich enzyme-linked immunosorbent assay (ELISA) in the FEPS with (n = 36) and without agitation (n = 49) symptoms, and healthy controls (HCs, n = 54). The psychopathology was assessed by the Positive and Negative Syndrome Scale (PANSS), and the agitation symptoms were evaluated by the PANSS excitatory component (PANSS-EC).

Results

The plasma TNF-α levels in patients with and without agitation symptoms were significantly higher than those in HCs. The patients with agitation had significantly higher plasma TNF-α levels compared to the patients without agitation. There were no significant differences in the sTNF-α R1 levels among the three groups. Furthermore, the plasma TNF-α levels were positively correlated with the PANSS total score, Positive and General psychopathological subscores, and PANSS-EC score in the FEPS, but the relationships were not found for the plasma sTNF-α R1 levels.

Conclusions

These results suggested that TNF-α might play an important role in the onset and development of agitation symptoms of schizophrenia.
Case Series: Hyperbilirubinemia under elexacaftor/tezacaftor/ivacaftor in the presence of Gilbert’s syndrome
Authors: Weitzel Julia , Welsner Matthias , Taube Christian , Ballmann Manfred , Sutharsan Sivagurunathan
Published: July 2024

Liver-related side effects are a known complication of treatment with elexacaftor/tezacaftor/ivacaftor (ETI) for cystic fibrosis (CF). Gilbert’s syndrome is caused by a genetic mutation that reduces activity of the enzyme UDP glucuronosyltransferase 1 polypeptide A1 (UGT1A1), causing elevated levels of unconjugated bilirubin in the blood and duodenal bile. The presence of Gilbert’s syndrome and CF might represent additive risk factors for liver-related adverse events during ETI treatment. This case series describes six people with CF (pwCF) in whom previously unknown Gilbert’s syndrome was unmasked after initiation of treatment with ETI. Although all patients had some level of hepatic dysfunction and/or elevated levels of bilirubin after initiation of ETI, the clinical course varied. Only one patient had to stop ETI therapy altogether, while the others were able to continue treatment (some at a reduced dosage and others at the full recommended daily dosage). All patients, even those using a lower dosage, experienced clinical benefit during ETI therapy. Gilbert’s syndrome is not a contraindication for ETI therapy but may be mistaken for a risk factor for liver-related adverse events in pwCF. This is something that physicians need to be aware of in pwCF who show liver adverse events during ETI therapy.
Predicting risk of the subsequent early pregnancy loss in women with recurrent pregnancy loss based on preconception data
Authors: Yang Xin , Wang Ruifang , Zhang Wei , Yang Yanting , Wang Fang
Published: July 2024

Background

For women who have experienced recurrent pregnancy loss (RPL), it is crucial not only to treat them but also to evaluate the risk of recurrence. The study aimed to develop a risk predictive model to predict the subsequent early pregnancy loss (EPL) in women with RPL based on preconception data.

Methods

A prospective, dynamic population cohort study was carried out at the Second Hospital of Lanzhou University. From September 2019 to December 2022, a total of 1050 non-pregnant women with RPL were participated. By December 2023, 605 women had subsequent pregnancy outcomes and were randomly divided into training and validation group by 3:1 ratio. In the training group, univariable screening was performed on RPL patients with subsequent EPL outcome. The least absolute shrinkage and selection operator (LASSO) regression and multivariate logistic regression were utilized to select variables, respectively. Subsequent EPL prediction model was constructed using generalize linear model (GLM), gradient boosting machine (GBM), random forest (RF), and deep learning (DP). The variables selected by LASSO regression and multivariate logistic regression were then established and compared using the best prediction model. The AUC, calibration curve, and decision curve (DCA) were performed to assess the prediction performances of the best model. The best model was validated using the validation group. Finally, a nomogram was established based on the best predictive features.

Results

In the training group, the GBM model achieved the best performance with the highest AUC (0.805). The AUC between the variables screened by the LASSO regression (16-variables) and logistic regression (9-variables) models showed no significant difference (AUC: 0.805 vs. 0.777, P = 0.1498). Meanwhile, the 9-variable model displayed a well discrimination performance in the validation group, with an AUC value of 0.781 (95%CI 0.702, 0.843). The DCA showed the model performed well and was feasible for making beneficial clinical decisions. Calibration curves revealed the goodness of fit between the predicted values by the model and the actual values, the Hosmer–Lemeshow test was 7.427, and P = 0.505.

Conclusions

Predicting subsequent EPL in RPL patients using the GBM model has important clinical implications. Future prospective studies are needed to verify the clinical applicability.

Trial registration

This study was registered in the Chinese Clinical Trial Registry with the registration number of ChiCTR2000039414 (27/10/2020).
What is the state of the art on traditional medicine interventions for zoonotic diseases in the Indian subcontinent? A scoping review of the peer-reviewed evidence base
Authors: Asaaga Festus A. , Tomude Emmanuel S. , Rahman Mujeeb , Shakeer Irfan , Ghotge Nitya S. , Burthe Sarah J. , Schäfer Stefanie M. , Vanak Abi T. , Purse Bethan V. , Hoti Subhash L.
Published: July 2024

Background

Traditional medicine (TM) interventions are plausible therapeutic alternatives to conventional medical interventions against emerging and endemic zoonotic diseases, particularly in low-and middle-income countries that may lack resources and infrastructure. Despite the growing popularity in the usage of TM interventions, their clinical safety and effectiveness are still contested within conventional healthcare in many countries.

Methods

We conducted a scoping review of the peer-reviewed literature that synthesises and maps the evidence on TM interventions for the treatment and prevention of zoonoses on the Indian subcontinent. The region, a global hotspot of biodiversity and emerging infections, is characterised by high prevalence of TM use. Based on the scientific literature (mostly case study research, n=l06 studies), our review (1) maps the scope of the literature, (2) synthesises the evidence on the application of TM interventions for zoonoses, and (3) critically reflects on the state of TM and identifies areas for future research focus.

Results

The evidence synthesis confirmed widespread usage of TM interventions for zoonoses on the subcontinent, with the majority of research reported from India (n=99 studies, 93.4%), followed by Pakistan (n=3 studies, 2.8%), Bangladesh (n=2 studies, 1.9%), and Sri Lanka (n=1, 0.9%). Most of the reviewed studies reported on ethno-medicinal uses of plant species, primarily for treating dengue (n=20 studies), tuberculosis (n=18 studies), Escherichia coli infection (n=16 studies), lymphatic filariasis and cholera (n=9 apiece). However, the evidence on the safety and effectiveness of these reported TM interventions is limited, indicating that these data are rarely collected and/or shared within the peer-reviewed literature.

Conclusion

This review thus highlights that, whilst TMs are already being used and could offer more widely accessible interventions against emerging and endemic zoonoses and ectoparasites, there is an urgent need for rigorous clinical testing and validation of the safety and effectiveness of these interventions.
Online-to-offline combined with problem-based learning is an effective teaching modality in the standardized residency training of nephrology
Authors: Wu Junxia , Ke You , Chen Zhida , Alhendi Mhd Alaa , Zhu Lina , Ma Kunling
Published: July 2024

Background

The online-to-offline (O2O) teaching method is recognized as a new educational model that integrates network learning into offline classroom education, while problem-based learning (PBL) is a teaching modality that guides students to apply acquired theoretical knowledge to solve practical problems. However, implementing O2O combined with PBL has not been extensively explored in nephrology residency training. This study aims to explore the efficacy of O2O combined with PBL in the standardized residency training of nephrology by comparing it with the traditional lecture-based teaching (LBT).

Methods

Sixty residency trainees who participated in the standardized training of internal medicine in the nephrology department of the Second Affiliated Hospital of Zhejiang University School of Medicine were equally allocated into O2O combined with PBL (O2O/PBL) or the LBT group demographically matched. Examinations of theory, practice skills, clinical thinking and teaching satisfaction surveys were utilized to assess the teaching effects of the two groups.

Results

Participants from the O2O/PBL group outperformed those from the LBT group in the examination of theory (81.233 ± 9.156 vs. 75.800 ± 7.009, mean ± SEM), practice skills (104.433 ± 3.569 vs.100.316 ± 4.628, mean ± SEM) and clinical thinking (88.933 ± 4.473 vs. 86.667 ± 3.844, mean ± SEM). There was no significant difference in the teaching satisfaction between the two groups.

Conclusion

The current study shows the positive impact of O2O combined with PBL approach on standardized residency training in nephrology without reducing teaching satisfaction.
Does an instructional video as a stand-alone tool promote the acquisition of practical clinical skills? A randomised simulation research trial of skills acquisition and short-term retention
Authors: Ott Thomas , Demare Tim , Möhrke Julia , Silber Saskia , Schwab Johannes , Reuter Lukas , Westhphal Ruben , Schmidtmann Irene , Dietz Sven-Oliver , Pirlich Nina , Ziebart Alexander , Engelhard Kristin
Published: July 2024

Background

The effectiveness of instructional videos as a stand-alone tool for the acquisition of practical skills is yet unknown because instructional videos are usually didactically embedded. Therefore, we evaluated the acquisition of the skill of a humeral intraosseous access via video in comparison to that of a self-study with an additional retention test.

Methods

After ethical approval, we conducted two consecutive studies. Both were designed as randomised controlled two-armed trials with last-year medical students as independent samples at our institutional simulation centre of a tertiary university hospital centre. In Study 1, we randomly assigned 78 participants to two groups: Vid-Self participants watched an instructional video as an intervention, followed by a test, and after seven days did a self-study as a control, followed by a test. Self-Vid ran through the trial in reverse order.

In Study 2, we investigated the influence of the sequence of the two teaching methods on learning success in a new sample of 60 participants: Vid-Self watched an instructional video and directly afterward did the self-study followed by a test, whereas Self-Vid ran through that trial in reverse order.

In Studies 1 and 2, the primary outcome was the score (worst score = 0, best score = 20) of the test after intervention and control. The secondary outcome in Study 1 was the change in score after seven days.

Results

Study 1: The Vid-Self (Participants n = 42) was superior to the Self-Vid (n = 36) (mean score 14.8 vs. 7.7, p < 0.001). After seven days, Self-vid outperformed Vid-Self (mean score 15.9 vs. 12.5, p < 0.001).

Study 2: The Vid-Self (n = 30) and Self-Vid (n = 30) scores did not significantly differ (mean 16.5 vs. mean 16.5, p = 0.97).

Conclusion

An instructional video as a stand-alone tool effectively promotes the acquisition of practical skills. The best results are yielded by a combination of an instructional video and self-study right after each other, irrespective of sequence.

Trial registrations

ClinicalTrials.gov: NCT05066204 (13/04/2021) (Study 1) and NCT04842357 (04/10/2021) (Study 2).
Language confidence and job satisfaction among foreign-born nurses in Japan: mediating effect of workplace discrimination and moderating effect of immigration duration
Authors: Hua Jing , Kondo Akiko , Wang Congcong , Ganchulun Sambuu
Published: July 2024

Aim

This study explored the relationship between language confidence and job satisfaction, the mediating role of workplace discrimination, and the moderating role of immigration duration among foreign-born nurses in Japan.

Introduction

Job satisfaction is an important factor in preventing migrant nurses’ turnover intentions; however, the relationships among language confidence, immigration duration, workplace discrimination, and job satisfaction among foreign-born nurses remain unclear.

Methods

A cross-sectional study was conducted. Data were collected between June and August 2022 through an online survey of nurses who were born outside of Japan but were currently working as registered nurses in Japan. PROCESS v4.0 Macro for SPSS 28.0 was applied to analyze the effect of language confidence on job satisfaction, the mediator effect of workplace discrimination (model 4), and the moderator effect of immigration duration (model 15).

Results

Data from 187 participants were analyzed. The results showed that 1) foreign-born nurses’ language confidence was negatively correlated with workplace discrimination and positively correlated with job satisfaction; 2) workplace discrimination played a partially mediating role between language confidence and job satisfaction; and 3) immigration duration positively moderated the relationship between language confidence and job satisfaction.

Conclusion

Foreign-born nurses with stronger confidence in their proficiency in Japanese perceived less workplace discrimination and higher job satisfaction. Workplace discrimination acted as a mediator in the relationship between language confidence and job satisfaction, and this relationship was strengthened with longer migration periods. Managers and policymakers should implement policies and strategies to combat workplace discrimination and provide tailored support to improve foreign-born nurses’ job satisfaction, which may contribute to their retention in Japan.
Prognostic significance of hemoglobin, albumin, lymphocyte, and platelet (HALP) score in breast cancer: a propensity score-matching study
Authors: Jiang Tongchao , Sun Haishuang , Xue Shuyu , Xu Tiankai , Xia Wen , Wang Ying , Guo Ling , Lin Huanxin
Published: July 2024

Background

The hemoglobin-albumin-lymphocyte-platelet (HALP) score functions as a comprehensive index that assesses the systemic inflammatory response, nutritional, and immune status. This study aimed to explore the relationship between preoperative HALP score and the prognosis of BC patients and to develop predictive nomograms.

Methods

Clinicopathological data were collected for BC patients who underwent mastectomy between December 2010 and April 2014 from Sun Yat-sen University Cancer Center. The optimal cutoff value for HALP was determined by maximally selected rank statistics for overall survival data. Propensity score matching (PSM) was applied to develop comparable cohorts of high-HALP group and low-HALP group. Kaplan–Meier curves and Cox regression analyses were performed to determine the impact of HALP on BC patients. Prognostic nomograms were developed based on the multivariate Cox regression method. Then, the concordance index (C-index), calibration plots, and decision curves analysis (DCA) were applied to evaluate the prognostic performance of the nomograms.

Results

A total of 1,856 patients were included as the primary cohort, and 1,470 patients were matched and considered as the PSM cohort. In the primary cohort, the 5-year overall survival (OS) and progression-free survival (PFS) rates for high-HALP group (≥ 47.89) and low-HALP group (< 47.89) were 94.4% vs. 91.0% (P = 0.005) and 87.8% vs. 82.1% (P = 0.005), respectively. Similar results were observed in PSM cohort (5-year OS, 94.3% vs. 90.8%, P = 0.015; 5-year PFS, 87.5% vs. 83.2%, P = 0.036). Notably, multivariate Cox regression analysis in the PSM cohort showed that HALP could independently predict BC patient prognosis in both OS (HR: 0.596, 95%CI [0.405–0.875], P = 0.008) and PFS (HR: 0.707, 95%CI [0.538–0.930], P = 0.013). OS and PFS nomograms showed excellent predictive performance with the C-indexes of 0.783 and 0.720, respectively. The calibration plots and DCA also indicated the good predictability of the nomograms. Finally, subgroup analysis further demonstrated a favorable impact of HALP on both OS and PFS.

Conclusion

Preoperative HALP score can be used as a reliable independent predictor of OS and PFS in BC patients, and the nomograms may provide a personalized treatment strategy.
Evaluation of the ability of insulin resistance and lipid-related indices to predict the presence of NAFLD in obese adolescents
Authors: Yetim Aylin , Şahin Memduh , Kandemir İbrahim , Bulakçı Betül , Aksakal Melike Tuğrul , Karapınar Edanur , Sever Hayrettin , Baş Firdevs
Published: July 2024

Background

Nonalcoholic fatty liver disease (NAFLD) has become an important health issue in adolescents. Although several parameters and indices have been investigated for the evaluation of NAFLD in adults, these indices are limited in adolescents. In this study, body mass index, waist circumference, triponderal mass index, HbA1c, homeostatic model assessment insulin resistance (HOMA-IR), triglyceride/high-density lipoprotein (Tg/HDL), the lipid accumulation product (LAP) index, the triglyceride-glucose (TyG) index and the aminotransferase (AT) index were examined together, and their diagnostic values in the clinical treatment of NAFLD were compared.

Materials and methods

Seventynine adolescents (10–19 years old) with obesity who were admitted to a pediatric clinic between January and August 2022 and who were diagnosed with exogenous obesity without any comorbidities were included in the study. The presence of NAFLD was evaluated by liver magnetic resonance imaging. The laboratory findings were obtained retrospectively from system records. Parameters were compared between the NAFLD (+) and NAFLD (-) groups. Logistic regression analysis was used to determine the most effective factors for NAFLD treatment. Receiver operating characteristic (ROC) analysis was performed with significant indices. Sex, HOMA-IR, TyG and AT indices were evaluated together with multivariate analysis to design a diagnostic scale.

Results

HbA1c, HOMA-IR, AT indices and TyG indices were greater in the NAFLD (+) group (P = 0.012; P = 0.001; P = 0.012; P = 0.002, respectively). There was a positive correlation between liver fat percentage and HOMA-IR, the TyG index, the AT index, and Tg/HDL. According to the regression analysis, male sex and elevated HOMA-IR were determined to be significant risk factors for the presence of NAFLD. A probability scale with 4 parameters [sex, HOMA-IR, the TyG index, and alanine aminotransferase (ALT)] was designed with 82.5% specificity and 80% sensitivity.

Conclusion

Evaluation of the HOMA-IR and TyG indices, especially in high-risk patients, will support the diagnosis of NAFLD via ultrasonography. A probability scale with ALT, HOMA-IR, TyG, and sex data with a diagnostic accuracy of 80% may aid in the diagnosis of NAFLD in adolescents with obesity.
Net costs of breast cancer in Colombia: a cost-of-illness study based on administrative claims databases
Authors: Torres Gabriel Fernando , Alarcón Brigitte Alejandra , Reyes-Sanchez Juan Manuel , Castaño-Gamboa Natalia , Buitrago Giancarlo
Published: July 2024

Background

Breast Cancer (BC) is associated with substantial costs of healthcare; however, real-world data regarding these costs in Colombia is scarce. The contributory regime provides healthcare services to formal workers and their dependents and covers almost half of the population in Colombia. This study aims to describe the net costs of healthcare in women with BC covered by the contributory regime in Colombia in 2019 from the perspective of the Colombian Health System.

Methods

The main data source was the Capitation Sufficiency Database, an administrative database that contains patient-level data on consumption of services included in the National Formulary (PBS, in Spanish Plan de Beneficios en Salud). Data on consumption of services not included in the PBS (non-PBS) were calculated using aggregated data from MIPRES database. All direct costs incurred by prevalent cases of BC, from January 1 to December 31, 2019, were included in the analysis. The net costs of the disease were estimated by multiplying the marginal cost and the expected number of cases with BC by region and age group. Marginal costs were defined as the costs of services delivered to patients with BC after subtracting the expected costs of health services due to age, comorbidity burden or region of residence. To calculate these costs, we used Propensity Score Matching in the main analysis. All costs were expressed in 2019 international dollars. Productivity losses, transportation expenses, and caregiving costs were not included.

Results

A total of 46,148 patients with BC were identified. Total net costs were $387 million (95% CI $377 to $396 million), 60% associated with non-PBS services. Marginal costs were $8,366 (95% Confidence Interval $8,170 to $8,573), with substantial variations between regions age groups (from $3,919 for older patients in the Amazonia region to $10,070 for younger patients in the Pacific region). The costs for PBS services were higher for ambulatory services and for patients who died during 2020.

Conclusions

BC imposes a substantial economic burden for the Colombian Health System with important variations in net costs between regions and age groups. Patients near death and ambulatory services were associated with higher costs of healthcare.
Leveraging a neutrophil-derived PCD signature to predict and stratify patients with acute myocardial infarction: from AI prediction to biological interpretation
Authors: Zhu Yihao , Chen Yuxi , Zu Yao
Published: July 2024

Background

Programmed cell death (PCD) has recently been implicated in modulating the removal of neutrophils recruited in acute myocardial infarction (AMI). Nonetheless, the clinical significance and biological mechanism of neutrophil-related PCD remain unexplored.

Methods

We employed an integrative machine learning-based computational framework to generate a predictive neutrophil-derived PCD signature (NPCDS) within five independent microarray cohorts from the peripheral blood of AMI patients. Non-negative matrix factorization was leveraged to develop an NPCDS-based AMI subtype. To elucidate the biological mechanism underlying NPCDS, we implemented single-cell transcriptomics on Cd45+ cells isolated from the murine heart of experimental AMI. We finally conducted a Mendelian randomization (MR) study and molecular docking to investigate the therapeutic value of NPCDS on AMI.

Results

We reported the robust and superior performance of NPCDS in AMI prediction, which contributed to an optimal combination of random forest and stepwise regression fitted on nine neutrophil-related PCD genes (MDM2, PTK2B, MYH9, IVNS1ABP, MAPK14, GNS, MYD88, TLR2, CFLAR). Two divergent NPCDS-based subtypes of AMI were revealed, in which subtype 1 was characterized as inflammation-activated with more vibrant neutrophil activities, whereas subtype 2 demonstrated the opposite. Mechanically, we unveiled the expression dynamics of NPCDS to regulate neutrophil transformation from a pro-inflammatory phase to an anti-inflammatory phase in AMI. We uncovered a significant causal association between genetic predisposition towards MDM2 expression and the risk of AMI. We also found that lidoflazine, isotetrandrine, and cepharanthine could stably target MDM2.

Conclusion

Altogether, NPCDS offers significant implications for prediction, stratification, and therapeutic management for AMI.
Finite element analysis of mechanical stress in a cementless tapered-wedge short stem in the varus position
Authors: Maeda Takahiro , Obayashi Osamu , Ishijima Muneaki , Sato Taichi , Musha Yoshiro , Ikegami Hiroyasu
Published: July 2024

Background

In recent years, the use of tapered-wedge short stems has increased due to their ability to preserve bones and tendons. Surgical techniques occasionally result in a varus position of the stem, which is particularly pronounced in short stems. Although the varus position is not clinically problematic, there are reports of an increased incidence of stress shielding and cortical hypertrophy. Thus, we evaluated and examined the acceptable range of varus angles using finite element analysis.

Methods

Patients diagnosed with osteoarthritis of the hip joint who had undergone arthroplasty were selected and classified into three types [champagne-flute (type A), intermediate (type B), and stovepipe (type C)]. Finite element analysis was performed using Mechanical Finder. The model was created using a Taperloc microplasty stem with the varus angle increased by 1° from 0° to 5° from the bone axis and classified into seven zones based on Gruen’s zone classification under loading conditions in a one-leg standing position. The volume of interest was set, the mean equivalent stress for each zone was calculated.

Results

A significant decrease in stress was observed in zone 2, and increased stress was observed in zones 3 and 4, suggesting the emergence of a distal periosteal reaction, similar to the results of previous studies. In zone 2, there was a significant decrease in stress in all groups at a varus angle ≥ 3°. In zone 3, stress increased from ≥ 3° in type B and ≥ 4° in type C. In zone 4, there was a significant increase in stress at varus angles of ≥ 2° in types A and B and at ≥ 3° in type C.

Conclusion

In zone 2, the varus angle at which stress shielding above Engh classification grade 3 may appear is expected to be ≥ 3°. Distal cortical hypertrophy may appear in zones 3 and 4; the narrower the medullary cavity shape, the smaller the allowable angle of internal recession, and the wider the medullary cavity shape, the wider the allowable range. Long-term follow-up is required in patients with varus angles > 3°.
Shear wave elastography of transverse carpal ligament increased with simulated carpal tunnel pressure
Authors: Zhang Hui , Elfar John C. , Kwoh C. Kent , Li Zong-Ming
Published: July 2024

Background

Elevation of carpal tunnel pressure is known to be associated with carpal tunnel syndrome. This study aimed to correlate the shear wave elastography in the transverse carpal ligament (TCL) with carpal tunnel pressures using a cadaveric model.

Methods

Eight human cadaveric hands were dissected to evacuate the tunnels. A medical balloon was inserted into each tunnel and connected to a pressure regulator to simulate tunnel pressure in the range of 0-210 mmHg with an increment of 30 mmHg. Shear wave velocity and modulus was measure in the middle of TCL.

Results

SWV and SWE were significantly dependent on the pressure levels (p < 0.001), and positively correlated to the tunnel pressure (SWV: R = 0.997, p < 0.001; SWE: R = 0.996, p < 0.001). Regression analyses showed linear relationship SWV and pressure (SWV = 4.359 + 0.0263 * Pressure, R2 = 0.994) and between SWE and pressure (SWE = 48.927 + 1.248 * Pressure, R2 = 0.996).

Conclusion

The study indicated that SWV and SWE in the TCL increased linearly as the tunnel pressure increased within the current pressure range. The findings suggested that SWV/SWE in the TCL has the potential for prediction of tunnel pressure and diagnosis of carpal tunnel syndrome.
Prevalence and quantity of lymph nodes at mediastinal stations in patients with lung cancer: lessons from 181 bilateral mediastinal lymphadenectomies
Authors: Trybalski Łukasz , Szadurski Jakub , Zhang Lanjun , Kużdżał Jarosław , Turna Akif , Wang Wei-dong , Warmus Janusz , Isık Gizem Ozcibik , Żanowska Katarzyna , Kocoń Piotr
Published: July 2024

Background

This study evaluated the prevalence and quantity of lymph nodes at particular stations of the mediastinum in patients with lung cancer. These data are important to radiologists, pathologists, and thoracic surgeons because they can serve as a benchmark when assessing the completeness of lymph node dissection. However, relevant data in the literature are scarce.

Methods

Data regarding the number of lymph nodes derived from two randomised trials of bilateral mediastinal lymph node dissection, the BML-1 and BML-2 study, were included in this analysis. Detectable nodes at particular stations of the mediastinum and the number of nodes at these stations were analysed.

Results

The mean number of removed nodes was 28.67 (range, 4–88). Detectable lymph nodes were present at stations 2R, 4R, and 7 in 93%, 98%, and 99% of patients, respectively. Nodes were rarely present at stations 9 L (33%), and 3 (35%). The largest number of nodes was observed at stations 7 and 4R (mean, 5 nodes).

Conclusion

The number of mediastinal lymph nodes in patients with lung cancer may be greater than that in healthy individuals. Lymph nodes were observed at stations 2R, 4R, and 7 in more than 90% of patients with lung cancer. The largest number of nodes was observed at stations 4R and 7. Detectable nodes were rarely observed at stations 3 and 9 L.

Trial registration

ISRCTN 86,637,908.
G protein-coupled receptors and traditional Chinese medicine: new thinks for the development of traditional Chinese medicine
Authors: Zhang Ting , An Wenqiao , You Shengjie , Chen Shilin , Zhang Sanyin
Published: July 2024

G protein-coupled receptors (GPCRs) widely exist in vivo and participate in many physiological processes, thus emerging as important targets for drug development. Approximately 30% of the Food and Drug Administration (FDA)-approved drugs target GPCRs. To date, the ‘one disease, one target, one molecule’ strategy no longer meets the demands of drug development. Meanwhile, small-molecule drugs account for 60% of FDA-approved drugs. Traditional Chinese medicine (TCM) has garnered widespread attention for its unique theoretical system and treatment methods. TCM involves multiple components, targets and pathways. Centered on GPCRs and TCM, this paper discusses the similarities and differences between TCM and GPCRs from the perspectives of syndrome of TCM, the consistency of TCM’s multi-component and multi-target approaches and the potential of GPCRs and TCM in the development of novel drugs. A novel strategy, ‘simultaneous screening of drugs and targets’, was proposed and applied to the study of GPCRs. We combine GPCRs with TCM to facilitate the modernisation of TCM, provide valuable insights into the rational application of TCM and facilitate the research and development of novel drugs. This study offers theoretical support for the modernisation of TCM and introduces novel ideas for development of safe and effective drugs.
Emerging paradigms: unmasking the role of oxidative stress in HPV-induced carcinogenesis
Authors: Letafati Arash , Taghiabadi Zahra , Zafarian Negar , Tajdini Roxana , Mondeali Mozhgan , Aboofazeli Amir , Chichiarelli Silvia , Saso Luciano , Jazayeri Seyed Mohammad
Published: July 2024

The contribution of the human papillomavirus (HPV) to cancer is significant but not exclusive, as carcinogenesis involves complex mechanisms, notably oxidative stress. Oxidative stress and HPV can independently cause genome instability and DNA damage, contributing to tumorigenesis. Oxidative stress-induced DNA damage, especially double-strand breaks, aids in the integration of HPV into the host genome and promotes the overexpression of two viral proteins, E6 and E7. Lifestyle factors, including diet, smoking, alcohol, and psychological stress, along with genetic and epigenetic modifications, and viral oncoproteins may influence oxidative stress, impacting the progression of HPV-related cancers. This review highlights various mechanisms in oxidative-induced HPV-mediated carcinogenesis, including altered mitochondrial morphology and function leading to elevated ROS levels, modulation of antioxidant enzymes like Superoxide Dismutase (SOD), Glutathione (GSH), and Glutathione Peroxidase (GPx), induction of chronic inflammatory environments, and activation of specific cell signaling pathways like the Phosphoinositide 3-kinase, Protein kinase B, Mammalian target of rapamycin (PI3K/AKT/mTOR) and the Extracellular signal-regulated kinase (ERK) signaling pathway. The study highlights the significance of comprehending and controlling oxidative stress in preventing and treating cancer. We suggested that incorporating dietary antioxidants and targeting cancer cells through mechanisms involving ROS could be potential interventions to mitigate the impact of oxidative stress on HPV-related malignancies.
Integrative multi-omics analysis unravels the host response landscape and reveals a serum protein panel for early prognosis prediction for ARDS
Authors: Lin Mengna , Xu Feixiang , Sun Jian , Song Jianfeng , Shen Yao , Lu Su , Ding Hailin , Lan Lulu , Chen Chen , Ma Wen , Wu Xueling , Song Zhenju , Wang Weibing
Published: July 2024

Background

The multidimensional biological mechanisms underpinning acute respiratory distress syndrome (ARDS) continue to be elucidated, and early biomarkers for predicting ARDS prognosis are yet to be identified.

Methods

We conducted a multicenter observational study, profiling the 4D-DIA proteomics and global metabolomics of serum samples collected from patients at the initial stage of ARDS, alongside samples from both disease control and healthy control groups. We identified 28-day prognosis biomarkers of ARDS in the discovery cohort using the LASSO method, fold change analysis, and the Boruta algorithm. The candidate biomarkers were validated through parallel reaction monitoring (PRM) targeted mass spectrometry in an external validation cohort. Machine learning models were applied to explore the biomarkers of ARDS prognosis.

Results

In the discovery cohort, comprising 130 adult ARDS patients (mean age 72.5, 74.6% male), 33 disease controls, and 33 healthy controls, distinct proteomic and metabolic signatures were identified to differentiate ARDS from both control groups. Pathway analysis highlighted the upregulated sphingolipid signaling pathway as a key contributor to the pathological mechanisms underlying ARDS. MAP2K1 emerged as the hub protein, facilitating interactions with various biological functions within this pathway. Additionally, the metabolite sphingosine 1-phosphate (S1P) was closely associated with ARDS and its prognosis. Our research further highlights essential pathways contributing to the deceased ARDS, such as the downregulation of hematopoietic cell lineage and calcium signaling pathways, contrasted with the upregulation of the unfolded protein response and glycolysis. In particular, GAPDH and ENO1, critical enzymes in glycolysis, showed the highest interaction degree in the protein–protein interaction network of ARDS. In the discovery cohort, a panel of 36 proteins was identified as candidate biomarkers, with 8 proteins (VCAM1, LDHB, MSN, FLG2, TAGLN2, LMNA, MBL2, and LBP) demonstrating significant consistency in an independent validation cohort of 183 patients (mean age 72.6 years, 73.2% male), confirmed by PRM assay. The protein-based model exhibited superior predictive accuracy compared to the clinical model in both the discovery cohort (AUC: 0.893 vs. 0.784; Delong test, P < 0.001) and the validation cohort (AUC: 0.802 vs. 0.738; Delong test, P  = 0.008).

Interpretation

Our multi-omics study demonstrated the potential biological mechanism and therapy targets in ARDS. This study unveiled several novel predictive biomarkers and established a validated prediction model for the poor prognosis of ARDS, offering valuable insights into the prognosis of individuals with ARDS.
Tagging large CNV blocks in wheat boosts digitalization of germplasm resources by ultra-low-coverage sequencing
Authors: Niu Jianxia , Wang Wenxi , Wang Zihao , Chen Zhe , Zhang Xiaoyu , Qin Zhen , Miao Lingfeng , Yang Zhengzhao , Xie Chaojie , Xin Mingming , Peng Huiru , Yao Yingyin , Liu Jie , Ni Zhongfu , Sun Qixin , Guo Weilong
Published: July 2024

Background

The massive structural variations and frequent introgression highly contribute to the genetic diversity of wheat, while the huge and complex genome of polyploid wheat hinders efficient genotyping of abundant varieties towards accurate identification, management, and exploitation of germplasm resources.

Results

We develop a novel workflow that identifies 1240 high-quality large copy number variation blocks (CNVb) in wheat at the pan-genome level, demonstrating that CNVb can serve as an ideal DNA fingerprinting marker for discriminating massive varieties, with the accuracy validated by PCR assay. We then construct a digitalized genotyping CNVb map across 1599 global wheat accessions. Key CNVb markers are linked with trait-associated introgressions, such as the 1RS·1BL translocation and 2NvS translocation, and the beneficial alleles, such as the end-use quality allele Glu-D1d (Dx5 + Dy10) and the semi-dwarf r-e-z allele. Furthermore, we demonstrate that these tagged CNVb markers promote a stable and cost-effective strategy for evaluating wheat germplasm resources with ultra-low-coverage sequencing data, competing with SNP array for applications such as evaluating new varieties, efficient management of collections in gene banks, and describing wheat germplasm resources in a digitalized manner. We also develop a user-friendly interactive platform, WheatCNVb (http://wheat.cau.edu.cn/WheatCNVb/), for exploring the CNVb profiles over ever-increasing wheat accessions, and also propose a QR-code-like representation of individual digital CNVb fingerprint. This platform also allows uploading new CNVb profiles for comparison with stored varieties.

Conclusions

The CNVb-based approach provides a low-cost and high-throughput genotyping strategy for enabling digitalized wheat germplasm management and modern breeding with precise and practical decision-making.