bluuebunny/crossref_metadata_2025 huggingface dataset:
DFUCare: deep learning platform for diabetic foot ulcer detection, analysis, and monitoring
Authors: Sendilraj Varun , Pilcher William , Choi Dahim , Bhasin Aarav , Bhadada Avika , Bhadadaa Sanjay Kumar , Bhasin Manoj
Published: September 2024

Introduction

Diabetic foot ulcers (DFUs) are a severe complication among diabetic patients, often leading to amputation or even death. Early detection of infection and ischemia is essential for improving healing outcomes, but current diagnostic methods are invasive, time-consuming, and costly. There is a need for non-invasive, efficient, and affordable solutions in diabetic foot care.

Methods

We developed DFUCare, a platform that leverages computer vision and deep learning (DL) algorithms to localize, classify, and analyze DFUs non-invasively. The platform combines CIELAB and YCbCr color space segmentation with a pre-trained YOLOv5s algorithm for wound localization. Additionally, deep-learning models were implemented to classify infection and ischemia in DFUs. The preliminary performance of the platform was tested on wound images acquired using a cell phone.

Results

DFUCare achieved an F1-score of 0.80 and a mean Average Precision (mAP) of 0.861 for wound localization. For infection classification, we obtained a binary accuracy of 79.76%, while ischemic classification reached 94.81% on the validation set. The system successfully measured wound size and performed tissue color and textural analysis for a comparative assessment of macroscopic wound features. In clinical testing, DFUCare localized wounds and predicted infected and ischemic with an error rate of less than 10%, underscoring the strong performance of the platform.

Discussion

DFUCare presents an innovative approach to wound care, offering a cost-effective, remote, and convenient healthcare solution. By enabling non-invasive and accurate analysis of wounds using mobile devices, this platform has the potential to revolutionize diabetic foot care and improve clinical outcomes through early detection of infection and ischemia.
Factors affecting early red oak (Quercus rubra L.) regeneration near its northern distribution limit in Quebec
Authors: Lebel Desrosiers Simon , Collin Alexandre , Bélanger Nicolas
Published: September 2024

Red oak is an important species within the North American landscape, with climate change projections indicating a potential northward shift in its distribution. However, understanding the factors influencing its regeneration success at the northern limit remains limited. Site conditions and seed provenance adaptability may play critical roles. To bridge this knowledge gap, we conducted a seed transfer study in two northern red oak stands in Quebec. We firstly investigated stand regeneration history through dendrochronological characterization. Then, we monitored the survival and growth of saplings for four red oak provenances across a south-to-north gradient in field and greenhouse settings, with varying soil nutrient levels due to fertilization, and with or without protection from large herbivores. Results indicated that stands have similar age structures with red oak establishment coinciding with the last major fire disturbance in the early 1920s. However, tree species composition and density differed, suggesting differences in fire disturbance regime or ecological succession status prior to fire. Site had the largest influence on red oak regeneration, with the highest tree density and soil water availability site exhibiting a 29% higher survival rate. Protection against large herbivores also significantly impacted red oak seedling performance, leading to a 16% higher survival rate. Germination, survival and growth also significantly differed between provenances. The local (northernmost) provenance exhibited the poorest overall performance with 28 to 42% lower germination, survival and growth rates, while the two southernmost provenances exhibited superior germination and sprout survival. An increase in soil nutrient availability was beneficial to red oak in the greenhouse, but only marginally benefited survival and growth in the field, suggesting that this factor is of less importance than other factors (e.g., water and light availability) for red oak early regeneration. The findings of this study suggest that silvicultural efforts to favor red oak should focus on site and provenance selection, and that water availability is currently limiting red oak regeneration success at acorn and early seedling life stages (i.e., 1 year old seedlings) near its northern distribution limit.
Optimizing purebred selection to improve crossbred performance
Authors: Barani Somayeh , Miraie Ashtiani Sayed Reza , Nejati Javaremi Ardeshir , Khansefid Majid , Esfandyari Hadi
Published: September 2024

Crossbreeding is a widely adopted practice in the livestock industry, leveraging the advantages of heterosis and breed complementarity. The prediction of Crossbred Performance (CP) often relies on Purebred Performance (PB) due to limited crossbred data availability. However, the effective selection of purebred parents for enhancing CP depends on non-additive genetic effects and environmental factors. These factors are encapsulated in the genetic correlation between crossbred and purebred populations (rpc). In this study, a two-way crossbreeding simulation was employed to investigate various strategies for integrating data from purebred and crossbred populations. The goal was to identify optimal models that maximize CP across different levels of rpc. Different scenarios involving the selection of genotyped individuals from purebred and crossbred populations were explored using ssGBLUP (single-step Genomic Best Linear Unbiased Prediction) and ssGBLUP-MF (ssGBLUP with metafounders) models. The findings revealed an increase in prediction accuracy across all scenarios as rpc values increased. Notably, in the scenario incorporating genotypes from both purebred parent breeds and their crossbreds, both ssGBLUP and ssGBLUP-MF models exhibited nearly identical predictive accuracy. This scenario achieved maximum accuracy when rpc was less than 0.5. However, at rpc = 0.8, ssGBLUP, which exclusively included sire breed genotypes in the training set, achieved the highest overall prediction accuracy at 73.2%. In comparison, the BLUP-UPG (BLUP with unknown parent group) model demonstrated lower accuracy than ssGBLUP and ssGBLUP-MF across all rpc levels. Although ssGBLUP and ssGBLUP-MF did not demonstrate a definitive trend in their respective scenarios, the prediction ability for CP increased when incorporating both crossbred and purebred population genotypes at lower levels of  rpc. Furthermore, when rpc was high, utilizing paternal genotype for CP predictions emerged as the most effective strategy. Predicted dispersion remained relatively similar in all scenarios, indicating a slight underestimation of breeding values. Overall, the rpc value emerged as a critical factor in predicting CP based on purebred data. However, the optimal model to maximize CP depends on the factors influencing rpc. Consequently, ongoing research aims to develop models that optimize purebred selection, further enhancing CP.
Proficiency testing within Eurotransplant
Authors: Zoet Yvonne M. , Heidt Sebastiaan , van der Linden-van Oevelen Marissa J. H. , Haasnoot Geert W. , Claas Frans H. J.
Published: September 2024

Eurotransplant is responsible for the international allocation of organs between eight countries in Europe. All HLA laboratories affiliated to Eurotransplant must be EFI or ASHI-accredited and must participate in the Eurotransplant external proficiency testing (EPT) program, organized by the Eurotransplant Reference Laboratory (ETRL). EPT within Eurotransplant has a long tradition, starting in 1978. The current EPT program consists of the following schemes: HLA typing including serology, CDC crossmatching, HLA-specific antibody detection, and identification. Participants enter the results of laboratory tests using a web-based application. Assessed results are visible on the website. An additional component called “patient-based cases” runs since 2016. Results are summarized and published on the EPT website. Furthermore, these results are discussed during the annual extramural tissue typers meeting, which is organized by the ETRL. Thanks to this EPT program, the performance of all HLA laboratories affiliated to Eurotransplant can be monitored and corrected, if necessary. Because all affiliated laboratories are assessed in the same EPT program, where these laboratories show to be consistent in most of their results, Eurotransplant EPT has proven to be an efficient tool to create a more uniform level of quality of histocompatibility testing within Eurotransplant.
Unveiling the role of IGF1R in autism spectrum disorder: a multi-omics approach to decipher common pathogenic mechanisms in the IGF signaling pathway
Authors: Yang Kang , Zhang Tian , Niu Ruize , Zhao Liyang , Cheng Zhonghe , Li Jun , Wang Lifang
Published: September 2024

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition marked by impairments in social interaction, communication, and repetitive behaviors. Emerging evidence suggests that the insulin-like growth factor (IGF) signaling pathway plays a critical role in ASD pathogenesis; however, the precise pathogenic mechanisms remain elusive. This study utilizes multi-omics approaches to investigate the pathogenic mechanisms of ASD susceptibility genes within the IGF pathway. Whole-exome sequencing (WES) revealed a significant enrichment of rare variants in key IGF signaling components, particularly the IGF receptor 1 (IGF1R), in a cohort of Chinese Han individuals diagnosed with ASD, as well as in ASD patients from the SFARI SPARK WES database. Subsequent single-cell RNA sequencing (scRNA-seq) of cortical tissues from children with ASD demonstrated elevated expression of IGF receptors in parvalbumin (PV) interneurons, suggesting a substantial impact on their development. Notably, IGF1R appears to mediate the effects of IGF2R on these neurons. Additionally, transcriptomic analysis of brain organoids derived from ASD patients indicated a significant association between IGF1R and ASD. Protein-protein interaction (PPI) and gene regulatory network (GRN) analyses further identified ASD susceptibility genes that interact with and regulate IGF1R expression. In conclusion, IGF1R emerges as a central node within the IGF signaling pathway, representing a potential common pathogenic mechanism and therapeutic target for ASD. These findings highlight the need for further investigation into the modulation of this pathway as a strategy for ASD intervention.
Neutrophil-to-lymphocyte ratio as a predictive biomarker for hyperprogressive disease mediated by immune checkpoint inhibitors: a systematic review and meta-analysis
Authors: Pei Bo , Zhang Jue , Lai Lin , Chen Hui
Published: September 2024

Background

Hyperprogressive disease (HPD) is a novel pattern of paradoxically rapid tumor progression, which often leads to early death, mostly in the first 2 months of treatment with immune checkpoint inhibitors (ICIs). Currently, there is no validated biomarker to assess patients at risk of HPD.

Aim

The aim of this study was to systematically evaluate the predictive value of the neutrophil-to-lymphocyte ratio (NLR) in HPD and establish a reliable variable to support clinicians in defining personalized treatment strategies.

Methods

PubMed, Embase, Web of Science, Scopus, and Cochrane Library databases were searched for studies published before 31 December 2023. The Newcastle–Ottawa Scale (NOS) was used to evaluate the quality of eligible studies. The pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using a random-effects or a fixed-effects model to evaluate the association between the NLR and the risk of HPD.

Results

A total of 17 studies with 2,964 patients were included for meta-analysis. The incidence of HPD across different types of tumors ranged from 6.3% to 35.6%. In the pooled analysis of the NLR and HPD, we identified that the NLR significantly associated with the risk of HPD (OR = 0.65; 95% CI: 0.46 to 0.91; p = 0.01) (I2 = 52%, p = 0.007).

Conclusion

In the future, the NLR may serve as a remarkable biomarker for predicting the risk of HPD in clinical practice.
Construction of a novel model based on PVT1-MYC duet-related genes for predicting survival and characterization of the tumor microenvironment in pancreatic cancer
Authors: Ren Bo , Ren Jie , Gu Minzhi , Liu Xiaohong , You Lei , Zhao Yupei
Published: September 2024

Pancreatic cancer is an extremely malignant tumor. PVT1 and MYC signaling has been considered as a therapeutic target recently. Nonetheless, the prognostic values and critical regulatory networks of PVT1-MYC duet in pancreatic cancer remain unclear. Firstly, we identified PVT1-MYC duet-related genes using public databases. Then we analyzed our Hi-C and ChIP-seq data to confirm PVT1-MYC duet. We performed LASSO regression and multivariate Cox regression analysis to build a prognostic model whose effectiveness and robustness were validated by Cox regression, ROC analysis, calibration curve, and nomogram. Besides, we conducted functional enrichment analyses, mutation profiles analyses and the immune features analyses to compare low- and high-risk group. Functional enrichment analyses revealed that several terms associated with cancer progression were enriched in the high-risk group. Mutation profile analysis showed that high-risk group had higher tumor mutation burden, and immune analysis demonstrated high-risk group had more immunosuppressive tumor microenvironment. Finally, we detected PVT1 expression in pancreatic cancer and paracancer tissues from the PUMCH cohort, which showed that PVT1 was significantly upregulated in pancreatic cancer and associated with invasion, metastasis, and poor prognosis. We further performed transwell and proliferation assays and found that PVT1, CDC6, and COL17A1 could promote migration or proliferation of PDAC cells. This study constructed a prognostic model based on three PVT1-MYC duet-related genes, which had a significant potential in predicting the prognosis and tumor microenvironment of pancreatic cancer. These results suggested that targeting PVT1-MYC duet or its regulatory processes could be a therapeutic option with great interests.
Challenging cases in rheumatic disease pregnancy: management perspectives from reproductive rheumatologists
Authors: Mani Iswariya , Bermas Bonnie , Edens Cuoghi , Sammaritano Lisa , Zell JoAnn , Birru Talabi Mehret
Published: September 2024

Pregnant women with rheumatic and musculoskeletal diseases (RMDs) have a higher risk of adverse pregnancy and perinatal outcomes compared to those without RMDs. Although evidence-based guidelines have been developed for the reproductive health care and management of these individuals, multiple areas of uncertainty exist around the diagnosis and treatment of pregnant patients with confirmed or suspected RMDs. We present a series of outpatient cases that address areas of uncertainty in the field of reproductive rheumatology. Expert opinions were elicited from rheumatologists who have expertise in the reproductive health of individuals with RMDs to build new understanding around diagnosis or treatment approaches. The cases focused on the interpretation of antiphospholipid antibodies in various clinical scenarios, diagnosis and management of nephrotic-range proteinuria during pregnancy, and the use of tumor necrosis factor inhibitors during pregnancy. Our objective was not to replace existing guidelines and classification criteria but rather to provide a range of expert opinions that rheumatologists might consider when tailoring treatment and care for patients, particularly in challenging situations with limited data.
Assessing the clinical efficacy of phacoemulsification cataract extraction in treating acute primary angle closure and fellow primary angle closure suspect eyes using AS-OCT
Authors: Zhao Rumin , Geng Wenhui , Wu Yunlong , Zhang Zijian , Zhao Bojun
Published: September 2024

Purpose

This study aimed to compare anterior segment parameters pre-and postoperatively in acute primary angle closure (APAC) and fellow primary angle closure suspect (PACS) eyes using anterior segment optical coherence tomography (AS-OCT) and evaluate the clinical effectiveness of cataract extraction in the treatment of APAC and fellow PACS eyes.

Methods

Quantitative measurements of various parameters, including anterior chamber depth (ACD), anterior chamber volume (ACV), lens vault (LV), iridocorneal angle contact index (ITCI), iris thickness (IT), iris volume (IV), and iris curvature (IC), were obtained using Tomey CASIA2 AS-OCT on 60 eyes from 30 patients (APAC eyes and their fellow PACS eyes) before and after surgery. Simultaneous analysis of the differences between the APAC eyes and fellow PACS eyes in these parameters, visual acuity (VA), and intraocular pressure (IOP) were performed.

Results

After surgery, both the APAC eyes and fellow PACS eyes (a total of 60 eyes) showed a significant increase in ACD and ACV, compared to preoperative measurements. Furthermore, LV and ITCI significantly decreased postoperatively. In the PACS group, IC significantly decreased postoperatively, while there was no statistically significant difference in the APAC group. In the APAC group, there was a significant decrease in IOP and improvement in VA at 1 day, 1 week, and the final follow-up compared to preoperative levels. The IOP values in the PACS group were within the normal range across various time points. VA in the PACS group showed significant improvement at 1 week postoperatively and at the final follow-up compared to preoperative levels. Significant differences of VA were observed in the initial, preoperative, first postoperative day, first postoperative week, and final follow-up, with better outcomes observed in the PACS group compared to the APAC group.

Conclusion

Lens extraction surgery can significantly improve anterior segment crowding in APAC and PACS eyes. For APAC eyes, combined cataract extraction with intraocular lens implantation and gonioscopy-assisted goniosynechialysis under direct visualization is feasible and safe. Further, in the fellow PACS eye of APAC patients with either significant or mild cataracts, phacoemulsification can maintain or improve preoperative visual acuity to varying degrees and stabilize IOP.
Enhanced understanding of cinnamaldehyde’s therapeutic potential in osteoarthritis through bioinformatics and mechanistic validation of its anti-apoptotic effect
Authors: Sheng Yueyang , Zhai Ruiqing , Li Shan , Wang Xinyu , Wang Ying , Cui Zhengguo , Wang Chao , Wang Qianqian , Zhang Yanzhuo , Wu Chengai
Published: September 2024

Introduction

Osteoarthritis (OA) is a globally prevalent joint disorder affecting approximately 240 million individuals worldwide. Cinnamaldehyde, known for its broad anti-inflammatory and anti-aging effects across various cell types, has not been investigated for its potential impact on apoptosis in OA chondrocytes.

Methods

To explore the effectiveness of cinnamaldehyde in mitigating knee osteoarthritis by reducing chondrocyte apoptosis, bioinformatics analysis was first conducted to identify apoptosis-associated differentially expressed genes (APDEGs). Gene expression datasets GSE55235 and GSE114007 were analyzed using weighted gene co-expression network analysis (WGCNA). Gene modules of interest were cross-referenced with APDEGs to identify those specific to OA. LASSO regression analysis was employed to build a risk model, and this model, along with datasets GSE114007, GSE55457, and GSE12021, was validated using ROC analysis. Cellular experiments and blood analyses from OA patients were performed to evaluate the effects of cinnamaldehyde on apoptosis-related gene expression.

Results

Cinnamaldehyde administration was found to rectify the abnormal expression of key apoptosis-related genes in OA patients. Specifically, cinnamaldehyde may affect knee osteoarthritis by regulating apoptosis-related genes such as ZFAND5, BCL6, ELL2, FOSL2, MARCKS, and SGCD. Additionally, three novel apoptotic targets in OA chondrocytes—ZFAND5, ELL2, and SGCD—were identified.

Discussion

These findings provide significant theoretical support for the clinical use of cinnamaldehyde in OA treatment. The discovery of novel apoptotic targets presents new therapeutic possibilities for future OA interventions.
Therapeutic effects of Kangxian Yanshen formula on patients with chronic kidney disease stages 3–4: a retrospective cohort study
Authors: Chu Aojiao , Wei Wenqian , Liu Ni , Zhang Fan , Zhang Xianwen , Li Xueling , Zheng Rong , Ma Zhifang , Li Yi , Rong Shu , Zhong Yifei
Published: September 2024

Background

This study retrospectively evaluated the actual efficacy of Kangxian Yanshen Formula Chinese medicine on renal function-related indicators in chronic kidney disease (CKD) stage 3–4 patients.

Methods

In this retrospective cohort study, we collected 212 adult CKD patients with baseline estimated glomerular filtration rate (eGFR) of 15–60 ml/min/1.73 m2. All participants received usual care (i.e., Western medications), and participants in the exposure group (n = 109) were additionally prescribed Kangxian Yanshen Formula Chinese medicine. The primary outcome was an adjusted hazard risk and 95% confidence interval (95% CI) of a 30% decrease in eGFR at month 36 from baseline.

Results

In terms of eGFR, among participants treated with additional Kangxian Yanshen Formula, after adjusting for covariates, there was a 57.1% reduction in the risk of a 30% decline from baseline in eGFR among participants in the Kangxian Yanshen Formula group compared with the Western medicine group (adjusted hazard risk: 0.429; 95% CI 0.269–0.682). In addition, participants in the Kangxian Yanshen Formula group had a significantly higher change in eGFR from baseline to month 12 than those in the western medicine group (3.40 ± 11.62 versus −3.87 ± 8.39; between-group difference Δ5.61 [± 2.26 standard deviation] mL/min/1.73 m2; P = 0.014). Participants in both groups showed a decreasing trend in eGFR at months 24 and 36.

Conclusion

In patients with stage 3–4 CKD, Kangxian Yanshen Formula Chinese medicine therapy may help delay eGFR decline, but high-quality randomized controlled trials are needed to validate the results further.
Fluid resuscitation strategy in patients with placenta previa accreta: a retrospective study
Authors: Zhou Fan , Liu Na , Huang Guiqiong , Yu Haiyan , Wang Xiaodong
Published: September 2024

Objectives

Obstetric hemorrhage is the leading cause of maternal death worldwide. Placenta previa accreta is one of the major direct causes of postpartum hemorrhage, accounting for two-thirds of obstetric hemorrhage cases. Fluid resuscitation is a life-saving procedure for patients suffering from massive hemorrhage. This study aims at evaluating the risk factors of massive hemorrhage and appropriate fluid resuscitation strategy in patients with placenta previa accreta.

Methods

This study retrospectively analyzed the risk factors for massive hemorrhage, clinical characteristics, and perinatal outcomes of patients with placenta previa accreta. Maternal noninvasively evaluated hemodynamic indicators, including maternal heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and shock index, were collected and analyzed at nine time points, from the administration of anesthesia until the end of procedures, in patients diagnosed with placenta previa accreta and receiving different fluid supply volumes.

Results

Complicated with placenta increta/percreta and gestational age of delivery later than 37 weeks are two independent risk factors of massive hemorrhage in patients with placenta previa accreta. A total of 62.27% (170/273) patients diagnosed with placenta increta/percreta had massive hemorrhage, significantly higher than those diagnosed with placenta previa accreta (5.88%, 6/102). Patients delivered after 37 weeks of gestation had significantly higher ratios (86.84%, 99/114) of massive hemorrhage compared with those delivered between 36 and 36+6 weeks of gestation (35.39%, 63/178). Maternal SBP, DBP, and MAP started to decrease immediately after the baby was delivered and reached a relatively stable trough state at 15–30 min after delivery. No statistical differences were found in hemodynamic indicators, the occurrence of hypotension, or in-hospital days after the procedure among the transfusion volumes < 30 ml/kg, 30–80 ml/kg, and ≥ 80 ml/kg groups.

Conclusion

Patients with a suspected diagnosis of placenta previa accreta should plan to deliver before 37 weeks of gestation. The ability to identify concurrent placenta increta/percreta should be improved to schedule a reasonably rapid perioperative plan. Restrictive fluid resuscitation could achieve good effects in maintaining hemodynamic stability in patients with placenta previa accreta. A time period of 15–30 min after delivery is the critical stage for fluid resuscitation.
Advanced age woman with diminished ovarian reserve obtained live birth following a zero pronuclei-derived four-cell frozen-thawed embryo transfer on day 4: a case report
Authors: Zhang Xiao-lei , Chen Yong-qian , Zhang Ya-juan
Published: September 2024

Objective

Advanced maternal age and diminished ovarian reserve (DOR) are challenges in infertile patients for in vitro fertilization-embryo transfer (IVF-ET). This study aimed to investigate the pregnancy outcomes of women with advanced age and DOR undergoing low-quality embryo transfers.

Case report

We report a rare case of successful pregnancy resulting from a zero pronuclei (0PN)-derived four-cell embryo transfer on day 4 (D4). An advanced age patient with DOR underwent five unsuccessful embryo transfers. A successful outcome was achieved when the patient underwent a hormone replacement FET cycle and received 0PN-derived four-cell frozen-thawed cleavage embryo transfer on D4. Fourteen days after the transfer, her serum β-human chorionic gonadotropin level was 575.3 mIU/mL. Subsequent prenatal examinations were normal, and the patient delivered a full-term healthy baby girl by caesarean section. Achieving a successful pregnancy after 0PN-derived four-cell frozen-thawed embryo transfer on D4 is rare. This increasingly exhibits significance for advanced age patients with DOR.

Conclusion

Selectively transferring embryos with slow growth but low fragments and no evident damage is beneficial for advanced age patients with DOR. For these individuals, obtaining embryos is challenging. Therefore, a personalized embryo transfer strategy should be considered to increase the possibility of pregnancy.
99mTc-FAPI-04 SPECT/CT outperforms contrast-enhanced CT in detecting metastasis in postoperative patients with colorectal cancer
Authors: Sun Donghua , Ma Li , Liu Yan , Bao Caili , Jia Guorong , Wang Tao , Wang Yingqiu
Published: September 2024

Purpose

To compare the performance of 99mTc-FAPI-04 SPECT/CT and contrast-enhanced CT (CECT) in the detection of postoperative metastasis in patients with colorectal cancer (CRC).

Methods

The postoperative patients with CRC were consecutively recruited from January 2023 to June 2023, and the enrolled patients completed 99mTc-FAPI-04 SPECT/CT imaging and CECT examination within two weeks. Histopathological analysis and the follow-up results were used as the reference criteria. The location and number of metastatic sites and the detection accuracy between the two imaging methods were compared. The tumor-to-background ratio (TBR) of liver metastasis and lymph node metastasis in 99mTc-FAPI-04 SPECT/CT imaging were also calculated for comparison.

Results

In total, 19 postoperative CRC patients, including 15 patients with metastasis, were included in this study. In the patient-based analysis, 99mTc-FAPI-04 SPECT/CT showed a significantly higher sensitivity for the detection of metastasis than CECT (93.3% vs. 80.0%, p = 0.038), but both techniques had the same specificity (100%, 4/4). For the lesion-based analysis, the detection rates of metastatic sites were 92.2% (47/51) and 72.5% (37/51) for 99mTc-FAPI-04 SPECT/CT and CECT, respectively, and the difference between them was statistically significant. In the diagnosis of liver metastasis and lymph node metastasis, 99mTc-FAPI-04 SPECT/CT both exceeded CECT. Additionally, the TBR in lymph node metastasis was higher than that in liver metastasis.

Conclusion

The findings suggested that 99mTc-FAPI-04 SPECT/CT could detect metastasis more effectively than CECT, especially liver and lymph node metastases, in postoperative CRC patients.
Dopaminergic neurodegeneration in Gerstmann–Sträussler–Scheinker (P102L) disease: insights from imaging and pathological examination
Authors: Irie Ken-Ichi , Honda Hiroyuki , Tateishi Takahisa , Mori Shinichiro , Yamamoto Akifumi , Morimitsu Makoto , Shinsuke Kikuchi , Moritaka Taiga , Kurata Seiji , Kumazoe Hiroyuki , Shijo Masahiro , Sasagasako Naokazu , Taniwaki Takayuki
Published: September 2024

Gerstmann–Sträussler–Scheinker (GSS) disease is an inherited prion disease characterized by dementia, cerebellar ataxia, and painful sensory disturbances. GSS is pathologically defined by the presence of amyloid plaques comprised of prion protein predominantly localized in the cerebral cortex, cerebellar cortex, and basal ganglia, resulting from mutations in the prion protein gene. This study investigated five cases of GSS P102L [GSS caused by a leucine (L) substitution of proline (P) at position 102 of the prion protein gene] with L-dopa-resistant extrapyramidal symptoms and reduced dopamine transporter single-photon emission computed tomography (DAT-SPECT) uptake. Clinical findings revealed diverse manifestations, with all cases exhibiting parkinsonism, and four patients had a vertical gaze palsy. Notably, all patients showed reduced striatal DAT-SPECT uptake, indicating neurodegeneration of the nigrostriatal system. Autopsy findings in one case confirmed prion protein plaques and dopaminergic neuron loss in the substantia nigra of a patient with GSS P102L. Additionally, reduced DAT immunostaining was observed in the putamen compared with a control. While previous studies have identified reduced DAT-SPECT and positron emission tomography uptake in Creutzfeldt-Jakob disease and fatal familial insomnia owing to nigrostriatal neurodegeneration induced by abnormal prion protein deposition, similar phenomena in GSS P102L have not been reported. This study provides support for a correlation between abnormal prion protein deposition and nigrostriatal system degeneration in GSS P102L. Our results reveal the importance of considering GSS P102L in cases of atypical Parkinsonism and abnormal DAT-SPECT results, which would serve as a valuable indicator for subsequent prion genetic testing.
Microbiome-metabolome analysis insight into the effects of high-salt diet on hemorheological functions in SD rats
Authors: Qi Luming , Li Yao , Chen Zhixuan , Wei Changhong , Wen Xue , Hu Shuangyan , Wu Hang , Lv Zhuoheng , Xu Zhangmeng , Xia Lina
Published: September 2024

The present study examined the effect of two dietary regimens with elevated salt concentrations (4% and 8% salt) on hemorheological functions of SD rats, and explored the underlying mechanisms mainly through microbiome-metabolome analysis. An 8% HSD substantially altered the hemorheological parameters, and compromised intestinal barrier integrity and reduced the short-chain fatty acid levels. The microbiome-metabolome analysis revealed that 49 genus-specific microorganisms and 156 metabolites showed a consistent trend after exposure to both 4% and 8% HSDs. Pathway analysis identified significant alterations in key metabolites within bile acid and arachidonic acid metabolism pathways. A two-sample Mendelian randomization (MR) analysis verified the link between high dietary salt intake and hemorheology. It also suggested that some key microbes and metabolites (such as Ruminococcaceae_UCG-005, Lachnospiraceae_NK4A136, Ruminiclostridium_6, and Ruminococcaceae_UCG-010, TXB-2, 11,12-diHETrE, glycochenodeoxycholate) may involve in abnormalities in blood rheology caused by high salt intake. Collectively, our findings underscored the adverse effects of high dietary salt on hemorheological functions and provide new insight into the underlying mechanism based on microbiome-metabolome analysis.
FGF21 inhibits ferroptosis caused by mitochondrial damage to promote the repair of peripheral nerve injury
Authors: Yan Yao , Ran Xinyu , Zhou Zihan , Gu Yuting , Wang Rendu , Qiu Chuanqi , Sun Yinuo , Wang Jifeng , Xiao Jian , Lu Yingfeng , Wang Jian
Published: September 2024

Introduction

Ferroptosis is a new type of cell death characterized by lipid peroxidation and iron dependency, representing an emerging disease regulation mechanism. The limited understanding of ferroptosis in peripheral nerve injury (PNI) complicates the management of such injuries. Mitochondrial dysfunction, which contributes to ferroptosis, further exacerbates the challenges of peripheral nerve repair

Methods

In this study, we established an in vitro model of Schwann cells model treated with TBHP and an in vivo sciatic nerve crush injury model in rats. These models were used to investigate the effects of fibroblast growth factor 21 (FGF21) on PNI, both in vitro and in vivo, and to explore the potential mechanisms linking injury-induced ferroptosis and mitochondrial dysfunction.

Results

Our findings reveal that PNI triggers abnormal accumulation of lipid reactive oxygen species (ROS) and inactivates mitochondrial respiratory chain complex III, leading to mitochondrial dysfunction. This dysfunction catalyzes the oxidation of excessive polyunsaturated fatty acids, resulting in antioxidant imbalance and loss of ferroptosis suppressor protein 1 (FSP1), which drives lipid peroxidation. Additionally, irregular iron metabolism, defective mitophagy, and other factors contribute to the induction of ferroptosis. Importantly, we found that FGF21 attenuates the abnormal accumulation of lipid ROS, restores mitochondrial function, and suppresses ferroptosis, thus promoting PNI repair. Notably, glutathione peroxidase 4 (GPX4), a downstream target of nuclear factor E2-related factor 2 (Nrf2), and the ERK/Nrf2 pathway are involved in the regulation of ferroptosis by FGF21.

Conclusion

FGF21 promotes peripheral nerve repair by inhibiting ferroptosis caused by mitochondrial dysfunction. Therefore, targeting mitochondria and ferroptosis represents a promising therapeutic strategy for effective PNI repair.
Advancing pharmacogenomic research in US Hmong populations: prevalence of key single nucleotide variations in California Hmong
Authors: Sun Boguang , Thao Tou , Culhane-Pera Kathleen , Yang Eric , Thor Mai Yang , Yang Pao , Xiong Metta , Vang Zoua , Straka Robert J.
Published: September 2024

Introduction

In collaboration with the Minnesota Hmong community, we have previously discovered significant differences in allele frequencies for key Single Nucleotide Variations (SNVs) within Very Important Pharmacogenes (VIPs) between Hmong and East Asians. Recognizing the potential clinical implications of these observed differences, we sought to validate these observations in a Hmong cohort residing in California, the state with the largest Hmong population in the US. Robust validation of these differences would affect motivation for clinicians treating individuals who identify as Hmong to consider pharmacogenomic (PGx) testing as a means to improve clinical decision making when using therapeutic agents in this unique population.

Method

Guided by California Hmong community leaders and utilizing the basic approach of community-based participatory research, demographic, clinical information and a buccal swab was obtained from Hmong adults residing in California. A commercial PGx testing panel was performed on these samples and specific allele frequencies of interest were compared between California and Minnesota Hmong. Allele frequency differences between California Hmong, East Asians and Europeans, were also compared. Return-of-PGx-results and presentations of group data were made to members of the Hmong along with PGx educational sessions to help interpret the observations.

Results

In 118 California Hmong who completed the study, the allele frequencies for SNV’s were similar to previous Minnesota Hmong results. Furthermore, out of the 18 SNVs that were not previously reported in Hmong, allele frequencies were statistically different in 38% (7/18) of SNVs comparing California Hmong to East Asians, and in 77.8% (14/18) SNVs comparing California Hmong to Europeans.

Conclusion

These results validate the original study’s findings that Hmong people living in different US locations have similar allele frequencies for key PGx genes. Further, for many of these PGx genes, their allele frequencies are significantly different compared to either East Asians or Europeans. Clinicians should consider these important differences when prescribing medications for people who identify as Hmong.
Development and validation of a clinical prediction model for osteonecrosis of the jaw in patients receiving zoledronic acid using FAERS and canadian databases
Authors: Wei Zhen , Hong Chuan , Tu Chunhui , Ge Wukun , Hu Yaoyao , Lin Shuainan
Published: September 2024

Background

Osteonecrosis of the jaw (ONJ) stands as a severe complication linked to the use of bisphosphonates, particularly zoledronic acid, which is widely prescribed for managing conditions like osteoporosis and bone metastasis. This study is geared towards the development and validation of a clinical prediction model for ONJ in patients undergoing zoledronic acid treatment.

Methods

We harnessed data from the FDA Adverse Event Reporting System (FAERS) as our training dataset, while the Canada Vigilance Adverse Reaction (CVAR) database served as the testing dataset. The study encompassed patients treated with zoledronic acid and subsequently diagnosed with ONJ. We analysed a range of predictive factors, including breast cancer, bone metastasis, osteoporosis, vitamin D and calcium levels, comorbidities, the number of concomitant medications, dosage, age, weight, and gender. Logistic regression and nomogram analysis were the chosen methodologies for constructing the predictive model. To evaluate the model’s performance, we utilized receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis (DCA).

Results

The study encompassed a total of 2,126 patients in the training cohort, 911 patients in the internal test cohort from the FAERS database, and 121 patients in the external test cohort from the CVAR database. Notable predictors for ONJ included bone metastasis (OR: 1.65, 95% CI: 1.22–2.24), osteoporosis (OR: 0.33, 95% CI: 0.21–0.52), the number of concomitant medications (OR: 1.07, 95% CI: 1.05–1.09), and the dosage of zoledronic acid (OR: 1.24, 95% CI: 1.10–1.39). The nomogram exhibited robust discriminatory power, evidenced by an area under the curve (AUC) of 0.77 in the training cohort, 0.76 in the internal test cohort, and 0.90 in the external test cohort. Calibration plots demonstrated a strong alignment between observed and predicted probabilities. Furthermore, DCA highlighted the prediction model’s significant net benefit across various threshold probabilities.

Conclusion

By leveraging data from both the FAERS and Canadian databases, this study has successfully developed and validated a clinical prediction model for ONJ in patients receiving zoledronic acid. This model stands as a valuable tool for clinicians, enabling them to pinpoint high-risk patients and make evidence-based treatment decisions to minimize the risk of ONJ.
Mangiferin ameliorates polycystic ovary syndrome in rats by modulating insulin resistance, gut microbiota, and ovarian cell apoptosis
Authors: Yong Zhang , Mimi Chen , Yingjie Li , Yichen Guo , Yansu Yu , Zhi Zhou , Hui Lu , Si Yao , Chongming Wu , Xiaopo Zhang , Ning Ma , Weiying Lu
Published: September 2024

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, prolonged anovulation and polycystic ovaries. However, there are no effective interventions to treat this disorder. As previously shown, mangiferin modulated the AMPK and NLRP3 signal pathways to alleviate nonalcoholic fatty liver disease (NAFLD). In recent years, mangiferin has emerged as a promising drug candidate for treating metabolic diseases. In this study, we evaluated the effects of mangiferin on a letrozole (LET) combined with high-fat diet (HFD)-induced PCOS rat model through estrous cycle detection, serum/tissue biochemical analysis, and hematoxylin and eosin (HE) staining of ovarian tissue. The mechanisms of mangiferin’s effects on PCOS rats were analyzed using 16S rRNA sequencing, RNA-seq, western blotting (WB), and immunohistochemical (IHC) staining. Our results displayed that mangiferin showed a promising effect in PCOS rats. It improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, ovarian dysfunction, and adipocyte abnormalities. RNA-seq analysis indicated that mangiferin may be involved in several signal pathways, including apoptosis, necrosis, and inflammation. Furthermore, western blot and immunohistochemical staining demonstrated that mangiferin regulates Caspase-3 and Cytc, exhibiting anti-apoptotic activity in the ovaries. Additionally, mangiferin significantly altered the gut microbiota community of PCOS rats, changing the abundance of firmicutes, bacteroidota, proteobacteria, and actinobacteria at the phylum level and the abundance of Blautia, Coprococcus, Roseburia, and Pseudomonas at the genus level. In conclusion, mangiferin is a promising and novel therapeutic agent for PCOS as it ameliorates insulin resistance, gut microbiota and ovarian cell apoptosis.
Taravana syndrome and posterior reversible encephalopathy syndrome: a microbubble hypothesis for neurological accidents in breath-hold divers
Authors: Druelle Arnaud , Castagna Olivier , Roffi Romain , Louge Pierre , Faivre Anthony , Blatteau Jean-Eric
Published: September 2024

Breath-hold diving is a challenging activity that can lead to serious and dangerous complications, such as the “Taravana” syndrome. This syndrome is characterized by the onset of neurological symptoms after deep or repeated dives. The main clinical manifestations are cerebral, including stroke and cognitive impairment. The pathophysiology of Taravana syndrome is still widely debated, but the most accepted theory is that it is a specific form of decompression sickness. We have reviewed the main theories explaining the onset of Taravana syndrome and, through the description of a particularly illustrative case of a freediver using an underwater scooter, we have formulated a hypothesis according to which micro-bubbles formed directly in cerebral structures would be at the origin of this syndrome. MRI showed diffuse encephalopathy with vasogenic edema. Analysis of the radiological sequences did not suggest an ischemic or embolic mechanism. This finding is likely to be associated with the diagnosis of posterior reversible encephalopathy syndrome. The rapid ascent speeds associated with underwater scooter use could potentially result in the formation of nitrogen micro-bubbles in the capillaries of brain tissue. The emergence of scooters in freediving can be a hazard because of their ability to facilitate very rapid ascents. It is therefore essential to take preventive measures to ensure the safety of users of these devices.
Transcriptome analysis of high- and low-selenium genotypes identifies genes responsible for selenium absorption, translocation, and accumulation
Authors: Li Ling , Ahsan Muhammad Zahir , Li Zhe , Panhwar Faiz Hussain , Zhang Yue , Luo Dan , Su Yang , Jia Xiaomei , Ye Xiaoying , Shen Caihong , Wang Songtao , Zhu Jianqing
Published: September 2024

Introduction

Selenium is an essential micronutrient the human body requires, which is closely linked to health. Rice, a primary staple food globally, is a major source of human selenium intake. To develop selenium-enriched rice varieties, it is imperative to understand the mechanisms behind selenium’s absorption and transport within rice, alongside identifying the key genes involved in selenium uptake, transport, and transformation within the plant.

Methods

This study conducted transcriptome sequencing on four types of rice materials (two with low-selenium and two with high-selenium contents) across roots, stems, leaves, and panicles to analyze the gene expression differences.

Results and discussion

Differential gene expression was observed in the various tissues, identifying 5,815, 6,169, 7,609, and 10,223 distinct genes in roots, stems, leaves, and panicles, respectively. To delve into these differentially expressed genes and identify the hub genes linked to selenium contents, weighted gene co-expression network analysis (WGCNA) was performed. Ultimately, 10, 8, 7, and 6 hub genes in the roots, stems, leaves, and panicles, respectively, were identified. The identification of these hub genes substantially aids in advancing our understanding of the molecular mechanisms involved in selenium absorption and transport during the growth of rice.
Exploring rice tolerance to salinity and drought stresses through Piriformospora indica inoculation: understanding physiological and metabolic adaptations
Authors: Raeisi Vanani Ali , Sheikhi Shahrivar Fatemeh , Nouri Amin , Sepehri Mozhgan
Published: September 2024

Drought and salinity are significant challenges to global food security. This study investigated the interactive impacts of Piriformospora indica inoculation with salinity and drought stresses on rice. Two greenhouse experiments were conducted. The first experiment evaluated two P. indica inoculation levels and three salinity levels (0-, 50-, and 100-mM sodium chloride), while the subsequent experiment assessed two inoculation levels under three drought intensities (25%, 50%, and 100% of available water content). P. indica spores were inoculated following optimized seed disinfection and germination processes. The shoot and root biomass under salinity stress were consistently higher in inoculated plants compared to controls. Sodium concentrations in shoots and roots exhibited an overall upward trend, with the trend being less pronounced in inoculated plants due to increased potassium uptake. Under salinity stress, nitrogen, magnesium, and calcium concentrations significantly increased in inoculated plants. With increasing salinity, there was a significant increase in catalase enzyme activity and soluble carbohydrate concentrations across all treatments, with a greater increase in inoculated plants. Plants under drought stress experienced reduced root and shoot biomass, but inoculated plants maintained higher biomass. Increasing drought stress led to decreased nitrogen, magnesium, and calcium concentrations in all treatments, with the reduction being less severe in inoculated plants. Catalase enzyme activity and carbohydrate increased with rising drought stress, with the increase being more pronounced in inoculated plants compared to non-inoculated ones. By promoting plant growth, nutrient uptake, and stress tolerance, P. indica inoculation has a significant potential to enhance crop productivity in extreme climate conditions.