bluuebunny/crossref_metadata_2025 huggingface dataset:
Fractured sternal wire causing a cardiac laceration
Authors: Khouzam Matthew S. , Jacobsen Kristina , Boyer Joseph H. , Zeeshan Ahmad , Spurlock David , Karas Tomer Z. , Suarez-Cavelier Jorge E. , Rinewalt Daniel , Bogar Linda , Silvestry Scott , Palmer George J. , Accola Kevin D. , Khouzam Nayer
Published: December 2023

Background

Hemopericardium is a serious complication that can occur after cardiac surgery. While most post-operative causes are due to inflammation and bleeding, patients with broken sternal wires and an unstable sternum may develop hemopericardium from penetrating trauma.

Case presentation

We present the case of a 62-year-old male who underwent triple coronary bypass surgery and presented five months later with sudden anterior chest wall pain. Chest computed tomography revealed hemopericardium with an associated broken sternal wire that had penetrated into the pericardial space. The patient underwent a redo-sternotomy which revealed a 3.5 cm bleeding, jagged right ventricular laceration that correlated to the imaging findings of a fractured sternal wire projecting in the pericardial space. The laceration was repaired using interrupted 4 − 0 polypropylene sutures in horizontal mattress fashion between strips of bovine pericardium. The patient’s recovery was uneventful and he was discharged on post-operative day four without complications.

Conclusion

Patients with broken sternal wires and an unstable sternum require careful evaluation and management as these may have potentially life-threatening complications if left untreated.
Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7
Authors: Luo Hong , Fu Lingyun , Wang Xueting , Yini Xu  , Ling Tao  , Shen Xiangchun
Published: December 2023

Background

Salvianolic acid B (Sal B), a water-soluble phenolic compound derived from Salvia miltiorrhiza Bunge, is commonly used in Traditional Chinese Medicine to treat cardiovascular disease. In our previous study, Sal B protected against myocardial fibrosis induced by diabetic cardiomyopathy (DCM). This study aimed to investigate the ameliorative effects and potential mechanisms of Sal B in mitigating myocardial fibrosis induced by DCM.

Methods

Various methods were used to investigate the effects of Sal B on myocardial fibrosis induced by DCM in vivo and in vitro. These methods included blood glucose measurement, echocardiography, HE staining, Masson’s trichrome staining, Sirius red staining, cell proliferation assessment, determination of hydroxyproline levels, immunohistochemical staining, evaluation of fibrosis-related protein expression (Collagen-I, Collagen-III, TGF-β1, p-Smad3, Smad3, Smad7, and α-smooth muscle actin), analysis of Smad7 gene expression, and analysis of Smad7 ubiquitin modification.

Results

The animal test results indicated that Sal B significantly improved cardiac function, inhibited collagen deposition and phenotypic transformation, and ameliorated myocardial fibrosis in DCM by upregulating Smad7, thereby inhibiting the TGF-β1 signaling pathway. In addition, cell experiments demonstrated that Sal B significantly inhibited the proliferation, migration, phenotypic transformation, and collagen secretion of cardiac fibroblasts (CFs) induced by high glucose (HG). Sal B significantly decreased the ubiquitination of Smad7 and stabilized the protein expression of Smad7, thereby increasing the protein expression of Smad7 in CFs and inhibiting the TGF-β1 signaling pathway, which may be the potential mechanism by which Sal B mitigates myocardial fibrosis induced by DCM.

Conclusion

This study revealed that Sal B can improve myocardial fibrosis in DCM by deubiquitinating Smad7, stabilizing the protein expression of Smad7, and blocking the TGF-β1 signaling pathway.
Suspension syndrome: a scoping review and recommendations from the International Commission for Mountain Emergency Medicine (ICAR MEDCOM)
Authors: Rauch Simon , Lechner Raimund , Strapazzon Giacomo , Mortimer Roger B. , Ellerton John , Skaiaa Sven Christjar , Huber Tobias , Brugger Hermann , Pasquier Mathieu , Paal Peter
Published: December 2023

Background

Suspension syndrome describes a multifactorial cardio-circulatory collapse during passive hanging on a rope or in a harness system in a vertical or near-vertical position. The pathophysiology is still debated controversially.

Aims

The International Commission for Mountain Emergency Medicine (ICAR MedCom) performed a scoping review to identify all articles with original epidemiological and medical data to understand the pathophysiology of suspension syndrome and develop updated recommendations for the definition, prevention, and management of suspension syndrome.

Methods

A literature search was performed in PubMed, Embase, Web of Science and the Cochrane library. The bibliographies of the eligible articles for this review were additionally screened.

Results

The online literature search yielded 210 articles, scanning of the references yielded another 30 articles. Finally, 23 articles were included into this work.

Conclusions

Suspension Syndrome is a rare entity. A neurocardiogenic reflex may lead to bradycardia, arterial hypotension, loss of consciousness and cardiac arrest. Concomitant causes, such as pain from being suspended, traumatic injuries and accidental hypothermia may contribute to the development of the Suspension Syndrome. Preventive factors include using a well-fitting sit harness, which does not cause discomfort while being suspended, and activating the muscle pump of the legs. Expediting help to extricate the suspended person is key. In a peri-arrest situation, the person should be positioned supine and standard advanced life support should be initiated immediately. Reversible causes of cardiac arrest caused or aggravated by suspension syndrome, e.g., hyperkalaemia, pulmonary embolism, hypoxia, and hypothermia, should be considered. In the hospital, blood and further exams should assess organ injuries caused by suspension syndrome.
Determining rib fracture age from CT scans with a radiomics-based combined model: a multicenter retrospective study
Authors: Tang Yilin , Jin Liang , Ji Wenbin , Ma Zhuangxuan , Li Dechun , Hong Wei , Li Ming
Published: December 2023

Objectives

We aimed to develop a combined model based on clinical and radiomic features to classify fracture age.

Methods

We included 1219 rib fractures from 239 patients from our center between March 2016 and September 2022. We created an external dataset using 120 rib fractures from 32 patients from another center between October 2019 and August 2023. According to tasks (fracture age between < 3 and ≥ 3 weeks, 3–12, and > 12 weeks), the internal dataset was randomly divided into training and internal test sets. A radiomic model was built using radiomic features. A combined model was constructed using clinical features and radiomic signatures by multivariate logistic regression, visualized as a nomogram. Internal and external test sets were used to validate model performance.

Results

For classifying fracture age between < 3 and ≥ 3 weeks, the combined model had higher areas under the curve (AUCs) than the radiomic model in the training set (0.915 vs 0.900, p = 0.009), internal test (0.897 vs 0.854, p < 0.001), and external test sets (0.881 vs 0.811, p = 0.003). For classifying fracture age between 3–12 and > 12 weeks, the combined model had higher AUCs than the radiomic model in the training model (0.848 vs 0.837, p = 0.12) and internal test sets (0.818 vs 0.793, p < 0.003). In the external test set, the AUC of the nomogram-assisted radiologist was 0.966.

Conclusion

The combined radiomic and clinical model showed good performance and has the potential to assist in the classification of rib fracture age. This will be beneficial for clinical practice and forensic decision-making.

Critical relevance statement

This study describes the development of a combined radiomic and clinical model with good performance in the classification of the age of rib fractures, with potential clinical and forensic applications.

Key points

• Complex factors make it difficult to determine the age of a fracture.

• Our model based on radiomic features performed well in classifying fracture age.

• Associating the radiomic features with clinical features improved the model’s performance.

Graphical Abstract
Quantification and significance of extraprostatic findings on prostate MRI: a retrospective analysis and three-tier classification
Authors: Wagnerova Monika , Macova Iva , Hanus Petr , Jurka Martin , Capoun Otakar , Lambert Lukas , Burgetova Andrea
Published: December 2023

Objectives

To quantify extraprostatic findings (EPFs) on prostate MRI, estimate the proportion of reported and unreported EPFs, assess their clinical importance, and propose standardized reporting of EPFs.

Materials and methods

Prostate 3-T MRI studies, reports, and clinical data from 623 patients (age 67.9 ± 8.2 years) were retrospectively analyzed and re-evaluated for the presence of EPFs and their clinical significance: E1—no finding or findings that have no clinical significance; E2—potentially significant findings; and E3—significant findings.

Results

Secondary reading identified 1236 EPFs in 593 patients (1.98 ± 1.13 EPFs per patient, no EPFs in 30 patients), from which 468 (37.8%) were mentioned in the original report. The most common findings included diverticulosis (44% of patients), hydrocele (34%), inguinal fat hernia (16%), and bladder wall trabecular hypertrophy (15%). There were 80 (6.5%) E2 EPFs and 30 (2.4%) E3 EPFs. From E3 EPFs, 10 (33%) were not originally reported. A workup was suggested in 35 (52%) of the 67 originally reported E2 and E3 findings with follow-up and performed in 20 (30%). Fourteen (21%) EPFs in 11 patients influenced their management. Four experienced radiologists originally reported 1.8 to 2.5 findings per patient (p < 0.0001).

Conclusions

EPFs on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. Only 30% of E2 and E3 findings are further explored, and 21% influence patient management. We suggest that an “E” category should be attached to the PI-RADS system to identify the presence of EPFs that require further workup.

Critical relevance statement

Extraprostatic findings on prostate MRI are frequent, but only 2.4% are clinically significant (E3), and 33% of these are not reported. We advocate standardized reporting of extraprostatic findings indicating their clinical significance.

Key points

• Extraprostatic findings on prostate MRI are frequent with an average of two findings per patient.

• 2.4% of extraprostatic findings are significant, and 33% of these are not reported.

• There is a significant variability among experienced radiologists in reporting extraprostatic findings.

Graphical Abstract
Successful full-term pregnancy after preterm event in a liver transplant patient: a case report
Authors: Galsone Ramona , Vītiņa Sandra , Jansone Maira , Staka Aiga , Mohammadian Reza
Published: December 2023

Background

Pregnancy after liver transplantation poses a significant challenge to both the patient and the transplant team.

Case presentation

We present the case of a 19-year-old European patient who underwent liver transplantation 5 years previously owing to autoimmune hepatitis. Poor compliance with immunosuppressive therapy and missed follow-up visits during the patient’s first pregnancy likely contributed to her liver function deterioration, hospitalization, and failed pregnancy. Owing to the patient’s complex medical history, combined immunosuppressive treatment, and risks to the fetus, her second pregnancy was high risk. However, close outpatient monitoring and adherence to treatment led to a successful, uneventful, full-term pregnancy and healthy delivery.

Conclusion

Liver transplant recipients who desire to become pregnant require careful planning and management to ensure optimal outcomes for both the mother and the fetus. A personalized strategy is necessary to balance the potential benefits of childbirth with the risks involved in pregnancy after liver transplantation.
Mesenchymal stromal cells secretome restores bioenergetic and redox homeostasis in human proximal tubule cells after ischemic injury
Authors: Faria João , Calcat-i-Cervera Sandra , Skovronova Renata , Broeksma Bonnie C. , Berends Alinda J. , Zaal Esther A. , Bussolati Benedetta , O’Brien Timothy , Mihăilă Silvia M. , Masereeuw Rosalinde
Published: December 2023

Background

Ischemia/reperfusion injury is the leading cause of acute kidney injury (AKI). The current standard of care focuses on supporting kidney function, stating the need for more efficient and targeted therapies to enhance repair. Mesenchymal stromal cells (MSCs) and their secretome, either as conditioned medium (CM) or extracellular vesicles (EVs), have emerged as promising options for regenerative therapy; however, their full potential in treating AKI remains unknown.

Methods

In this study, we employed an in vitro model of chemically induced ischemia using antimycin A combined with 2-deoxy-d-glucose to induce ischemic injury in proximal tubule epithelial cells. Afterwards we evaluated the effects of MSC secretome, CM or EVs obtained from adipose tissue, bone marrow, and umbilical cord, on ameliorating the detrimental effects of ischemia. To assess the damage and treatment outcomes, we analyzed cell morphology, mitochondrial health parameters (mitochondrial activity, ATP production, mass and membrane potential), and overall cell metabolism by metabolomics.

Results

Our findings show that ischemic injury caused cytoskeletal changes confirmed by disruption of the F-actin network, energetic imbalance as revealed by a 50% decrease in the oxygen consumption rate, increased oxidative stress, mitochondrial dysfunction, and reduced cell metabolism. Upon treatment with MSC secretome, the morphological derangements were partly restored and ATP production increased by 40–50%, with umbilical cord-derived EVs being most effective. Furthermore, MSC treatment led to phenotype restoration as indicated by an increase in cell bioenergetics, including increased levels of glycolysis intermediates, as well as an accumulation of antioxidant metabolites.

Conclusion

Our in vitro model effectively replicated the in vivo-like morphological and molecular changes observed during ischemic injury. Additionally, treatment with MSC secretome ameliorated proximal tubule damage, highlighting its potential as a viable therapeutic option for targeting AKI.
A new generation of mesenchymal stromal/stem cells differentially trained by immunoregulatory probiotics in a lupus microenvironment
Authors: Hoseinzadeh Akram , Mahmoudi Mahmoud , Rafatpanah Houshang , Rezaieyazdi Zahra , Tavakol Afshari Jalil , Hosseini Sara , Esmaeili Seyed-Alireza
Published: December 2023

Background

Increasing evidence suggests that multipotent mesenchymal stem/stromal cells (MSCs) are a promising intervention strategy in treating autoimmune inflammatory diseases. It should be stated that systemic immunoregulation is increasingly recognized among the beneficial effects of MSCs and probiotics in treating morbid autoimmune disorders such as lupus. This study aimed to determine if immunoregulatory probiotics L. rhamnosus or L. delbrueckii can change the immunomodulatory effects of MSCs in lupus-like disease.

Methods

Pristane-induced lupus (PIL) mice model was created via intraperitoneal injection of Pristane and then confirmed. Naïve MSCs (N-MSCs) were coincubated with two Lactobacillus strains, rhamnosus (R-MSCs) or delbrueckii (D-MSCs), and/or a combination of both (DR-MSCs) for 48 h, then administrated intravenously in separate groups. Negative (PBS-treated normal mice) and positive control groups (PBS-treated lupus mice) were also investigated. At the end of the study, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to determine the percentage of Th cell subpopulations in splenocytes and the level of their master cytokines in sera, respectively. Moreover, lupus nephritis was investigated and compared. Analysis of variance (ANOVA) was used for multiple comparisons.

Results

Abnormalities in serum levels of anti-dsDNA antibodies, creatinine, and urine proteinuria were significantly suppressed by MSCs transplantation, whereas engrafted MSCs coincubation with both L. strains did a lesser effect on anti-dsDNA antibodies. L. rhamnosus significantly escalated the ability of MSCs to scale down the inflammatory cytokines (IFN-ɣ, IL-17), while L. delbrueckii significantly elevated the capacity of MSCs to scale down the percentage of Th cell subpopulations. However, incubation with both strains induced MSCs with augmented capacity in introducing inflammatory cytokines (IFN-ɣ, IL-17). Strikingly, R-MSCs directly restored the serum level of TGF-β more effectively and showed more significant improvement in disease parameters than N-MSCs. These results suggest that R-MSCs significantly attenuate lupus disease by further skew the immune phenotype of MSCs toward increased immunoregulation.

Conclusions

Results demonstrated that Lactobacillus strains showed different capabilities in training/inducing new abilities in MSCs, in such a way that pretreated MSCs with L. rhamnosus might benefit the treatment of lupus-like symptoms, given their desirable properties.

Graphical abstract
Identifying secreted biomarkers of dopaminergic ventral midbrain progenitor cells
Authors: Rifes Pedro , Isaksson Marc , Rusimbi Charlotte , Ramón Santonja Adrián , Nelander Jenny , Laurell Thomas , Kirkeby Agnete
Published: December 2023

Background

Ventral midbrain (VM) dopaminergic progenitor cells derived from human pluripotent stem cells have the potential to replace endogenously lost dopamine neurons and are currently in preclinical and clinical development for treatment of Parkinson’s Disease (PD). However, one main challenge in the quality control of the cells is that rostral and caudal VM progenitors are extremely similar transcriptionally though only the caudal VM cells give rise to dopaminergic (DA) neurons with functionality relevant for cell replacement in PD. Therefore, it is critical to develop assays which can rapidly and reliably discriminate rostral from caudal VM cells during clinical manufacturing.

Methods

We performed shotgun proteomics on cell culture supernatants from rostral and caudal VM progenitor cells to search for novel secreted biomarkers specific to DA progenitors from the caudal VM. Key hits were validated by qRT-PCR and ELISA.

Results

We identified and validated novel secreted markers enriched in caudal VM progenitor cultures (CPE, LGI1 and PDGFC), and found these markers to correlate strongly with the expression ofEN1, which is a predictive marker for successful graft outcome in DA cell transplantation products. Other markers (CNTN2 and CORIN) were found to conversely be enriched in the non-dopaminergic rostral VM cultures. Key novel ELISA markers were further validated on supernatant samples from GMP-manufactured caudal VM batches.

Conclusion

As a non-invasive in-process quality control test for predicting correctly patterned batches of caudal VM DA cells during clinical manufacturing, we propose a dual ELISA panel measuring LGI1/CORIN ratios around day 16 of differentiation.
A 3D “sandwich” co-culture system with vascular niche supports mouse embryo development from E3.5 to E7.5 in vitro
Authors: Xu Junjun , Zhang Linye , Ye Zihui , Chang Binwen , Tu Zheng , Du Xuguang , Wen Xi , Teng Yili
Published: December 2023

Background

Various methods for ex utero culture systems have been explored. However, limitations remain regarding the in vitro culture platforms used before implanting mouse embryos and the normal development of mouse blastocysts in vitro. Furthermore, vascular niche support during mouse embryo development from embryonic day (E) 3.5 to E7.5 is unknown in vitro.

Methods

This study established a three-dimensional (3D) “sandwich” vascular niche culture system with in vitro culture medium (IVCM) using human placenta perivascular stem cells (hPPSCs) and human umbilical vein endothelial cells (hUVECs) as supportive cells (which were seeded into the bottom layer of Matrigel) to test mouse embryos from E3.5 to E7.5 in vitro. The development rates and greatest diameters of mouse embryos from E3.5 to E7.5 were quantitatively determined using SPSS software statistics. Pluripotent markers and embryo transplantation were used to monitor mouse embryo quality and function in vivo.

Results

Embryos in the IVCM + Cells (hPPSCs + hUVECs) group showed higher development rates and greater diameters at each stage than those in the IVCM group. Embryos in the IVCM + Cells group cultured to E5.5 morphologically resembled natural egg cylinders and expressed specific embryonic cell markers, including Oct4 and Nanog. These features were similar to those of embryos developed in vivo. After transplantation, the embryos were re-implanted in the internal uterus and continued to develop to a particular stage.

Conclusions

The 3D in vitro culture system enabled embryo development from E3.5 to E7.5, and the vascularization microenvironment constructed by Matrigel, hPPSCs, and hUVECs significantly promoted the development of implanted embryos. This system allowed us to further study the physical and molecular mechanisms of embryo implantation in vitro.
The application of nanoparticles in theranostic systems targeting breast cancer stem cells: current progress and future challenges
Authors: Lin Xinyu , Wang Ying , Fang Kai , Guo Zijian , Lin Nan , Li Lihua
Published: December 2023

Breast cancer (BC) is one of the diseases with the highest female mortality rates in the world and is closely related to breast cancer stem cells (BCSCs). Conventional breast cancer chemotherapy drugs target noncancer stem cells (non-CSCs), while cancer stem cells (CSCs) can still survive, which is an important reason for breast cancer drug resistance and local recurrence or distant metastasis. How to eradicate BCSCs while killing BCs is the key factor to improve the effect, and it is also an important scientific problem to be solved urgently. Therefore, targeted BCSC therapy has become a research hotspot. Interestingly, the emergence of nanotechnology provides a new idea for targeting BCSCs. This study summarizes the current application status of nanomaterials in targeting BCSCs, and attempts to construct a new type of lipid nanoparticle (LNP) that can target BCSCs through mRNA, providing a new idea for the treatment of BC.
COX6A2 deficiency leads to cardiac remodeling in human pluripotent stem cell-derived cardiomyocytes
Authors: Jiang Mengqi , Song Yuanxiu , Chen Xi , Lu Wenjing , Zhu Min , Wei Mingyu , Lan Feng , Cui Ming , Bai Yun
Published: December 2023

Background

Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism.

Methods

A human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes.

Results

COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model.

Conclusions

We have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.
Healthcare workers’ compliance with the catheter associated urinary tract infection prevention guidelines: an observational study in Yemen
Authors: Al-Sayaghi Khaled Mohammed , Alqalah Talal Ali Hussein , Alkubati Sameer Abdulmalik , Alshoabi Sultan Abdulwadoud , Alsabri Mohammed , Alrubaiee Gamil Ghaleb , Almoliky Mokhtar Abdo , Saleh Khalil A. , Al-Sayaghi Anas Khaled , Elshatarat Rami A. , Saleh Zyad T. , Saleh Ahmad Mahmoud , Abdel-Aziz Hassanat Ramadan
Published: December 2023

Background

Catheter-associated urinary tract infection is a global problem but it can be prevented with the appropriate implementation of evidence-based guidelines. This study was conducted to assess the level of compliance of healthcare workers with the catheter-associated urinary tract infection prevention guidelines during the insertion of a urinary catheter.

Methods

An observational study using a descriptive cross-sectional design was conducted at Sana’a City hospitals, Yemen. All the nurses and physicians from the governmental, teaching, and private hospitals were eligible to participate in the study. The data collection was performed through convenience sampling from March 2020 to December 2020, using a structured observational checklist prepared specifically for this study.

Results

The majority of the urinary catheter insertions were performed by nurses. There were no written policy or procedures for an urinary catheter insertion and no in-service education or training departments in the majority of the hospitals. The overall mean score of compliance was 7.31 of 10. About 71% of the healthcare workers had a high or acceptable level of compliance and 29% had an unsafe level of compliance. Compliance was low for maintaining aseptic technique throughout the insertion procedure, using a single use packet of lubricant jelly, performing hand hygiene immediately before insertion, and securing the urinary catheter once inserted. Factors affecting the healthcare workers compliance were gender, the working ward/unit of the healthcare workers, the availability of a written policy/procedure and a department or unit for in-service education.

Conclusion

Yemeni healthcare workers’ overall compliance was acceptable but it was unsafe in several critical measures. There is an urgent need for developing, implementing, and monitoring national guidelines and institutional policy and procedures for catheter-associated urinary tract infection prevention. Periodical in-service education and training programs and adequate access to the necessary materials and supplies are paramount.
Causal associations between genetically determined common psychiatric disorders and the risk of falls: evidence from Mendelian randomization
Authors: Zhang Haitao , Xu Chuanglong , Yuan Chunchun , Shi Binhao , Zhu Wenhao , Wang Hongyu , Fu Furui , Tang Dezhi , Wang Yongjun
Published: December 2023

Background

The causal associations between psychiatric disorders and falls risk remains uncertain. Consequently, this study aimed to explore the causal relationship between genetically determined three common psychiatric disorders and the risk of falls based on Mendelian randomization (MR).

Methods

The genome-wide association study (GWAS) data for schizophrenia (SCZ) (N = 320,404), major depressive disorder (MDD) (N = 480,359), and Alzheimer's disease (AD) (N = 63,926) were obtained as exposures. The GWAS data for falls risk (N = 451,179) was obtained as outcome. Univariate Mendelian randomization (UVMR) was used to evaluate the direct causal relationship between SCZ, MDD, AD, and risk of falls. Inverse variance weighting (IVW) was used as the primary analysis method. Sensitivity analysis was performed to assess the validity of the casualty. Multivariate Mendelian randomization (MVMR) analysis was conducted after adjusting body mass index and smoking initiation. Mediating MR was conducted to calculate the mediating effects of potential intermediaries.

Results

UVMR analysis showed that SCZ (OR 1.02, 95% CI 1.01–1.04, p = 8.03E−03) and MDD (OR 1.15, 95% CI 1.08–1.22, p = 1.38E−05) were positively associated with the risk of falls. Sensitivity analysis results were reliable and robust. MVMR results indicated that the relationship between MDD and SCZ and falls risk remained significant. Mediating MR results demonstrated that smoking initiation mediated partial causal effect of SCZ (0.65%, P = 0.03) and MDD (14.82%, P = 2.02E−03) on risk of falls.

Conclusions

This study provides genetic evidence for a causal relationship of individuals with SCZ and MDD on an increased risk of falls. Healthcare providers should be aware of the risk of falls in MDD and SCZ patients and develop strategies accordingly.
Systemic immune-inflammation index (SII) and the risk of all-cause, cardiovascular, and cardio-cerebrovascular mortality in the general population
Authors: Wang Huan , Nie Huiyong , Bu Gang , Tong Xiaoning , Bai Xiaofang
Published: December 2023

Background

An elevated systemic immune-inflammation index (SII) is associated with higher mortality in patients with coronary artery disease and other diseases. However, the potential of SII for predicting mortality in the general population has been underexplored. Therefore, this study aimed to analyze the relationship between the SII and all-cause, cardiovascular disease, and cardiocerebrovascular disease mortality in the general population.

Methods

This study involved 26,855 participants (≥ 18 years) from the National Health and Nutrition Examination Survey 1999–2014 who were grouped according to the SII tertiles. Survival differences between the groups were analyzed using log-rank tests and Kaplan–Meier plots. Furthermore, multivariate Cox regression and restricted cubic spline analyses were used to examine the relationship between the SII and all-cause, cardiovascular, and cardio-cerebrovascular mortality.

Results

Overall, 1947 (7.425%) participants died following an average follow-up of 87.99 ± 54.04 months. Among these, 325 (1.210%) deaths were related to cardiovascular diseases and 392 (1.459%) to cardio-cerebrovascular mortality. Kaplan–Meier analysis revealed statistically significant differences in all-cause, cardiovascular, and cerebrovascular mortality between the SII tertiles (log-rank test: all P < 0.001). Multi-adjusted models showed that participants in the highest tertile of SII had a higher risk of death from all-cause (hazard ratio [HR] = 1.48, 95% confidence interval [CI] 1.48–1.48) and cardiovascular mortality (HR = 1.60, 95% CI 1.60–1.61) compared with those in the lowest tertile. In addition, the restricted cubic spline curve indicated a nonlinear association between SII and all-cause mortality (P < 0.001), with threshold value of SII at 18.284. There was a 15% decrease in the risk of all-cause mortality for each twofold change in SII on the left flank (HR = 0.85, 95% CI 0.69–1.05) and a 42% increase (HR = 1.42, 95% CI 1.23–1.64) on the right flank of the inflection point. In addition, the risk of cardiovascular mortality increased nonlinearly by 39% per twofold change in SII (HR = 1.39, 95% CI 1.07–1.81). There was also a nonlinear increase in the risk of cardio-cerebrovascular mortality per twofold change in SII (HR = 1.29, 95% CI 1.00–1.66).

Conclusions

In the general population, the SII was significantly associated with all-cause, cardiovascular, and cardio-cerebrovascular mortality, regardless of the established risk factors.
Differentiation between cerebral alveolar echinococcosis and brain metastases with radiomics combined machine learning approach
Authors: Yimit Yasen , Yasin Parhat , Tuersun Abuduresuli , Abulizi Abudoukeyoumujiang , Jia Wenxiao , Wang Yunling , Nijiati Mayidili
Published: December 2023

Background

Cerebral alveolar echinococcosis (CAE) and brain metastases (BM) share similar in locations and imaging appearance. However, they require distinct treatment approaches, with CAE typically treated with chemotherapy and surgery, while BM is managed with radiotherapy and targeted therapy for the primary malignancy. Accurate diagnosis is crucial due to the divergent treatment strategies.

Purpose

This study aims to evaluate the effectiveness of radiomics and machine learning techniques based on magnetic resonance imaging (MRI) to differentiate between CAE and BM.

Methods

We retrospectively analyzed MRI images of 130 patients (30 CAE and 100 BM) from Xinjiang Medical University First Affiliated Hospital and The First People's Hospital of Kashi Prefecture, between January 2014 and December 2022. The dataset was divided into training (91 cases) and testing (39 cases) sets. Three dimensional tumors were segmented by radiologists from contrast-enhanced T1WI images on open resources software 3D Slicer. Features were extracted on Pyradiomics, further feature reduction was carried out using univariate analysis, correlation analysis, and least absolute shrinkage and selection operator (LASSO). Finally, we built five machine learning models, support vector machine, logistic regression, linear discrimination analysis, k-nearest neighbors classifier, and Gaussian naïve bias and evaluated their performance via several metrics including sensitivity (recall), specificity, positive predictive value (precision), negative predictive value, accuracy and the area under the curve (AUC).

Results

The area under curve (AUC) of support vector classifier (SVC), linear discrimination analysis (LDA), k-nearest neighbors (KNN), and gaussian naïve bias (NB) algorithms in training (testing) sets are 0.99 (0.94), 1.00 (0.87), 0.98 (0.92), 0.97 (0.97), and 0.98 (0.93), respectively. Nested cross-validation demonstrated the robustness and generalizability of the models. Additionally, the calibration plot and decision curve analysis demonstrated the practical usefulness of these models in clinical practice, with lower bias toward different subgroups during decision-making.

Conclusion

The combination of radiomics and machine learning approach based on contrast enhanced T1WI images could well distinguish CAE and BM. This approach holds promise in assisting doctors with accurate diagnosis and clinical decision-making.
Amino acid and mineral digestibility, bone ash, and plasma inositol is increased by including microbial phytase in diets for growing pigs
Authors: Lagos Liz Vanessa , Bedford Mike Richard , Stein Hans Henrik
Published: December 2023

Background

The effect of microbial phytase on amino acid and energy digestibility is not consistent in pigs, which may be related to the phytase dosage or the adaptation length to the diet. Therefore, an experiment was conducted to test the hypotheses that increasing dietary phytase after an 18-day adaptation period: 1) increases nutrient and energy digestibility; 2) increases plasma P, plasma inositol, and bone ash of young pigs; and 3) demonstrates that maximum phytate degradation requires more phytase than maximum P digestibility.

Results

Data indicated that increasing inclusion of phytase [0, 250, 500, 1,000, 2,000, and 4,000 phytase units (FTU)/kg feed] in corn-soybean meal-based diets increased apparent ileal digestibility (AID) of Trp (quadratic; P < 0.05), and of Lys and Thr (linear; P < 0.05), and tended to increase AID of Met (linear; P < 0.10). Increasing dietary phytase also increased AID and apparent total tract digestibility (ATTD) of Ca and P (quadratic; P < 0.05) and increased ATTD of K and Na (linear; P < 0.05), but phytase did not influence the ATTD of Mg or gross energy. Concentrations of plasma P and bone ash increased (quadratic; P < 0.05), and plasma inositol also increased (linear; P < 0.05) with increasing inclusion of phytase. Reduced concentrations of inositol phosphate (IP)6 and IP5 (quadratic; P < 0.05), reduced IP4 and IP3 (linear; P < 0.05), but increased inositol concentrations (linear; P < 0.05) were observed in ileal digesta as dietary phytase increased. The ATTD of P was maximized if at least 1,200 FTU/kg were used, whereas more than 4,000 FTU/kg were needed to maximize inositol release.

Conclusions

Increasing dietary levels of phytase after an 18-day adaptation period increased phytate and IP ester degradation and inositol release in the small intestine. Consequently, increasing dietary phytase resulted in improved digestibility of Ca, P, K, Na, and the first 4 limiting amino acids, and in increased concentrations of bone ash and plasma P and inositol. In a corn-soybean meal diet, maximum inositol release requires approximately 3,200 FTU/kg more phytase than that required for maximum P digestibility.
Comparison of the efficacy of anti-diabetic medications as add-on to metformin in type 2 diabetes mellitus from a real-world database
Authors: Ono Ryosuke , Ogami Chika , Hasegawa Chihiro , To Hideto , Matsumoto Yoshiaki , Tsuji Yasuhiro
Published: December 2023

Background

Metformin is recommended as a first-line drug in the guidelines of the treatment for type 2 diabetes mellitus. However, high-quality evidence from clinical trials directly comparing the degree of hypoglycemic effect of combination therapy of metformin and a hypoglycemic agent with a different mechanism of action with that of monotherapy of a hypoglycemic drug is lacking. We aimed to examine whether combination therapy of hypoglycemic agents with metformin showed antagonism, addition, or synergism compared to monotherapy with hypoglycemic agents other than metformin regarding hemoglobin A1c levels.

Methods

This retrospective cohort study used a medical information database in Japan. Non-insulin anti-hyperglycemic agents with different mechanisms of action were classified into eight drug classes. A monotherapy cohort and a combination therapy added to the metformin cohort were defined. The change in hemoglobin A1c levels was evaluated to compare the treatment effect between the cohorts.

Results

A total of 13,359 patients with type 2 diabetes mellitus in the monotherapy cohort and 1,064 in the metformin combination therapy cohort were identified. A comparison of the change from baseline HbA1c level by drug class between the two cohorts showed a similar trend. Among those treated with dipeptidyl peptidase-4 inhibitor and sodium-glucose co-transporter-2 inhibitor, no clinically significant difference was observed between the two cohorts (0.00% and -0.07% for unadjusted, 0.15% and -0.03% for propensity score matching-adjusted, and 0.09% and -0.01% for inverse probability treatment weighting-adjusted analysis).

Conclusions

According to the results of this study, the effect of dipeptidyl peptidase-4 inhibitor or sodium-glucose co-transporter-2 inhibitor added to metformin seems to be additive with respect to the reduction in hemoglobin A1c.
Geo-temperature response to reinjection in sandstone geothermal reservoirs
Authors: Li Jialong , Kang Fengxin , Bai Tong , Li Zhenhan , Zhao Qiang , Zhang Pingping , Zheng Tingting , Sui Haibo
Published: December 2023

To study the evolution rules and behaviors of heat transport in a sandstone geothermal reservoir caused by cooled water reinjection, this research focuses on the quantitative relationship among reinjection parameters and the thermal breakthrough time of production wells. The permeation, tracer, and reinjection tests were conducted in a simulation model using a large sand tank in conjunction with the numerical simulation method based on COMSOL Multiphysics. Subsequently, sensitivity analysis and nonlinear fitting were performed to investigate the effects of fluid viscosity and density on the reinjection process, and to analyze the impact of reinjection parameters on the thermal breakthrough time of production wells, along with their underlying mechanisms and law. The results indicate that the migration velocity of reinjection water is greater in coarse sand layer compared to that in medium sand layer, and the thermal breakthrough time t is linearly correlated with reinjection rate (Q) raised to the power of − 0.85, temperature difference (ΔT) raised to the power of − 0.21, and spacing between the production and reinjection wells (R) raised to the power of 1.4. The correlation equation and analysis show that when the temperature difference between production and reinjection ΔT is more than 30 ℃, the influence of ΔT on the thermal breakthrough time of production well becomes weak, because ΔT exerts an effect on the thermal breakthrough time of production well t by influencing the relative position of the 18.5 ℃ isotherm in the temperature transition region. The error in reinjecting high-temperature fluid into low-temperature fluid may be corrected by introducing a viscosity correction coefficient αμ.
Relationship between antihypertensive drug use and number of people with high blood pressure in FY 2018: a descriptive epidemiological study based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan open data
Authors: Mizuno Kanako , Inose Ryo , Yoshimura Yukina , Muraki Yuichi
Published: December 2023

Background

In most countries barring Japan, antihypertensive drug use has been reported using the defined daily doses/1000 inhabitants/day (DID). Although DID has been shown to allow for the assessment of the number of patients treated with a particular drug, the relationship between DID and the number of patients with hypertension has not been clarified. This study aimed to clarify the relationship between antihypertensive drug use and the number of people with high blood pressure based on the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) open data.

Methods

DID was calculated by extracting the use of oral antihypertensive drugs from outpatient prescriptions in the NDB Open Data in FY 2018. The number of people with high blood pressure was calculated using the number of enrollees in each sex–age group for systolic and diastolic blood pressure in the 40–74 years age group. The correlation between the DID of antihypertensive drugs and the number of people with high blood pressure by sex and age class was evaluated using Spearman’s rank correlation coefficient.

Results

The use of antihypertensive drugs increased with age in both men and women. Furthermore, in both sexes, dihydropyridine derivatives, calcium antagonists, and angiotensin II receptor blockers were the main drugs used from the age of 20 years onward. In addition, a very strong positive correlation was found between the number of people with high systolic blood pressure and DID in both sexes (men: r = 1, P < 0.05; women: r = 1, P < 0.05). In contrast, there was no significant correlation between the number of people with high diastolic blood pressure and DID in both sexes (men: r = − 0.214, P > 0.05; women: r = 0.393, P > 0.05).

Conclusions

To our knowledge, this study is the first to investigate the use of oral antihypertensive drugs in outpatient settings in Japan. In addition, the DID of antihypertensive drugs can be used as an alternative indicator of the number of people with high systolic blood pressure.
A Comparison of Neuropathic Pain Experiences Among Paralympic Versus Recreational Athletes with Spinal Cord Injury
Authors: Todd Kendra R. , Olsen Kenedy , Hamamoto Gail , Hirschfield Trevor J. , Kramer John L. K. , Martin Ginis Kathleen A.
Published: December 2023

Background

Individuals with spinal cord injury (SCI) report high levels of neuropathic pain. Current treatment options are primarily pharmaceutical, despite their limited effectiveness. Exercise may reduce neuropathic pain among persons with SCI; however, the optimal dose of exercise required to elicit analgesic effects remains unknown. The purpose of this study was to compare neuropathic pain intensity, pain catastrophizing, use of coping strategies, and positive affect and well-being among Paralympic versus recreational athletes with SCI who experience chronic neuropathic pain. Forty-seven athletes with SCI (25 Paralympic, 27 recreational) completed the International SCI Pain Basic Data Set, Douleur Neuropathique-4, coping strategies questionnaire, pain catastrophizing scale, and SCI-quality of life assessment.

Results

Paralympic athletes reported significantly greater neuropathic pain (p = 0.032) and positive affect and well-being (p = 0.047) than recreational athletes. No other comparisons were significant (ps > 0.09). Significant, medium-sized positive correlations were observed between neuropathic pain and total minutes of moderate-intensity exercise (r = 0.335, p = 0.023) and average minutes per day of moderate-intensity exercise (r = 0.375, p = 0.010) over the past week.

Conclusions

The results suggest that frequent moderate- to high-intensity exercise may exacerbate neuropathic pain sensations for persons with SCI. Research should investigate psychosocial and physiological mechanisms by which exercise may influence neuropathic pain to explain how Paralympic athletes with SCI are able to continue exercising while maintaining positive affect despite neuropathic pain.
The effect of parental diabetes prevention program participation on weight loss in dependent children: a prospective cohort study
Authors: Atluri Namratha , Thariath Joshua , McEwen Laura N. , Ye Wen , Song MinKyoung , Herman William H.
Published: December 2023

Introduction

Obesity has reached epidemic proportions in children and adolescents in the United States. Children’s behaviors are strongly influenced by parental behaviors, and weight loss in parents is positively associated with weight changes in their overweight/obese children. Research is limited on how parents’ National Diabetes Prevention Program (DPP) participation affects the health outcomes of their dependent children. Analyzing the impact of parental DPP participation on weight loss in their dependent children may provide valuable insight into an important secondary benefit of DPP participation.

Methods

In this study, we identified 128 adults with prediabetes who were offered the opportunity to participate in a DPP (n = 54 DPP participants and n = 74 DPP non-participants) and who had at least one child 3 to 17 years of age living with them. Age and BMI percentile for dependent children were collected from insurance claims data for 203 children (n = 90 children of DPP participants and n = 113 children of DPP non-participants). Parental practices related to diet and physical activity were assessed by surveys.

Results

There were no significant changes in BMI percentiles of overweight or obese children (i.e. BMI percentile ≥ 50%) of DPP participants vs DPP non-participants with prediabetes over one-year. Parents who enrolled and did not enroll in the DPP did not report differences in their parenting practices related to diet and physical activity.

Discussion

These results are not consistent with the literature that suggests parent-based interventions may influence their children’s weight trajectories. Limitations include small sample size, short time span of intervention, and limited availability of additional health/biographic data on dependent children. Future studies should collect primary outcome data on children, investigate whether there is a minimum duration of parental involvement and level of parental adherence, and assess the effect of parent–child dynamics on child weight trajectories.