bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of adjuvant chemotherapy on survival for patients with completely resected high-risk stage IB NSCLC
Authors: Shen Zi-Qing , Feng Kun-Peng , Fang Zi-Yao , Xia Tian , Pan Shu , Ding Cheng , Xu Chun , Ju Sheng , Chen Jun , Li Chang , Zhao Jun
Published: January 2024

Background

The use of adjuvant chemotherapy (ACT) in completely resected stage IB NSCLC is still controversial. This study aims to investigate the efficacy of ACT in pathological stage IB non-small cell lung cancer (NSCLC) with high risk factors.

Methods

Patients with pT2aN0M0 stage IB NSCLC who underwent complete resection from 2013 to 2017 were retrospectively analyzed. Univariate and multivariable logistic regression analysis was used to assess potential independent risk factors associated with poor prognosis. To compare survival between patients who received ACT and those who did not.

Results

In univariate and multivariate analyses, adenocarcinomas with predominantly micropapillary (MIP) and solid patterns (SOL), poorly differentiated squamous cell carcinoma (SCC), number of lymph nodes dissected less than 16 and tumor size larger than 36 mm were identified as high-risk factors for recurrence. In patients with high risk factors for recurrence, ACT resulted in significantly longer DFS (HR, 0.4689, 95%CI, 1.193–3.818; p = 0.0108) and OS (HR, 0.4696, 95%CI, 0.6578–6.895; p = 0.2073), although OS failed to reach statistically significance. After propensity score matching (PSM), 67 pairs of patients were 1:1 matched in the two groups and all baseline characteristics were well balanced. The results also demonstrated that ACT was associated with improved DFS (HR, 0.4776, 95%CI, 0.9779–4.484; p = 0.0440) while OS was not significantly different (92.5% vs. 91.0%; HR, 0.6167, 95%CI, 0.1688–2.038; p = 0.7458). In patients with low-risk factors for recurrence, DFS (HR, 0.4831, 95%CI, 0.03025-7.715; p = 0.6068) and OS (HR, 0.969, 95%CI, 0.08364-11.21; p = 0.9794) was not significantly different between those who received ACT and those who did not.

Conclusion

In patients with completely resected stage IB NSCLC, ACT can improve survival in patients with high risk for recurrence. Further large multicenter studies are needed to confirm these findings.
In-vitro generation of follicle-like structures from human germ cell-like cells derived from theca stem cell combined with ovarian somatic cells
Authors: Mirbahari Seyedeh Nasim , Amorim Christiani A. , Hassani Fatemeh , Totonchi Mehdi , Haddadi Mahnaz , valojerdi Mojtaba Rezazadeh , Dalman Azam
Published: January 2024

Background

The objective of this study was to induce the differentiation of human theca stem cells (hTSCs) into germ cell-like cells (hGCLCs) and assess their developmental progression following in vitro 3D culture with ovarian somatic cells within the follicle-like structures. To achieve this, the hTSCs were isolated from small antral follicles of three patients of varying ages and were then seeded in a differentiation medium for 40 days. The differentiated hGCLCs were subsequently aggregated with somatic ovarian cells (cumulus cells and hTSCs) in a ratio of 1:10 and cultured in a growth medium in a suspension culture dish. In addition to examining the morphologies, sizes, and viabilities of the differentiated hGCLCs, this study also analyzed the expression of DAZL and GDF9 proteins within the follicle-like structures.

Results

After 12 days, the hTSCs began to differentiate into hGCLCs, with their shapes changing from spindle-shaped to spherical. The sizes of hGCLCs increased during the differentiation period (from 25 μm to 50 μm). The survival rate of the hGCLCs after differentiation and in vitro development in primordial follicle-like structures was 54%. Unlike hTSCs, which did not express the DAZL protein, the hGCLCs and follicle-like structures successfully expressed DAZL protein (P-value < 0.05). However, hGCLCs poorly expressed the GDF9 protein. Further, the culture of hGCLCs in primordial follicle-like structures significantly increased GDF9 expression (P-value < 0.05).

Conclusion

In conclusion, our study demonstrated that 3D cultures with ovarian somatic cells in follicle-like structures caused the successful differentiation of reproducible hGCLCs from hTSCs derived from three patients of different ages. Moreover, this method not only enhanced the in vitro development of hGCLCs but also presented a novel approach for co-culturing and developing in vitro oocyte like cells, ultimately leading to the production of artificial follicles.
Changes in type VI collagen degradation reflect clinical response to treatment in rheumatoid arthritis patients treated with tocilizumab
Authors: Thudium Christian S. , Frederiksen Peder , Karsdal Morten A. , Bay-Jensen Anne-Christine
Published: January 2024

Objectives

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation in multiple articular joints, causing pain, joint damage, and loss of joint function. Despite the successful development of disease-modifying therapies, the heterogeneity of RA means that a significant proportion of patients respond poorly to treatment. This highlights the need for personalized medicine and predictive biomarkers to optimize treatment efficacy, safety, and cost. This study aimed to explore the relationship between type VI collagen (Col VI) remodeling and clinical response to anti-IL-6 receptor treatment.

Methods

Type VI collagen degradation was quantified using the C6M biomarker, a fragment of type VI collagen degraded by MMPs. Longitudinal differences in average biomarker levels between placebo and treatment groups were estimated using linear mixed models. The predictive capacity of the marker based on change from baseline to 4 weeks was analyzed using logistic regression.

Results

Both 4 mg and 8 mg doses of Tocilizumab (TCZ) reduced serum C6M concentrations compared to the placebo. Furthermore, C6M levels were more reduced in patients responding to treatment compared to early non-responders. A lower early reduction in C6M was associated with reduced odds of ACR treatment response and lowered disease activity.

Conclusion

These findings suggest that quantifying type VI collagen turnover may aid in identifying patients less likely to respond to treatment, indicating a new path towards optimizing patient care. Further studies are needed to validate these findings and explore the underlying mechanisms driving the observed relationships.
Decreased expression of NAT10 in peripheral blood mononuclear cells from new-onset ankylosing spondylitis and its clinical significance
Authors: Luo Qing , Zhu Juxiang , Wang Shiqian , fu Peng , Fu Biqi , Huang Zikun , Li Junming
Published: January 2024

Background

NAT10 is the firstly recognized RNA acetyltransferase that participates in multiple cellular biological processes and human disease. However, the role of N-acetyltransferase 10 (NAT10) in ankylosing spondylitis (AS) is still poorly elaborated.

Methods

Fifty-six patients with New-Onset AS, 52 healthy controls (HC), 20 patients with rheumatoid arthritis (RA) and 16 patients with systemic lupus erythematosus (SLE) were recruited from The First Afliated Hospital of Nanchang University, and their clinical characteristics were recorded. The expression level of NAT10 in peripheral blood mononuclear cell (PBMC) was examined using reverse transcription-quantitative PCR analysis. The correlations between the expression level of NAT10 in the New-Onset AS patients and disease activity of AS were examined, and receiver operating characteristic (ROC) curves were built to evaluate predictive value in AS. Univariate analysis and multivariate regression analysis were used to analyze the risk factors and construct predictive model.

Results

The mRNA expressions of NAT10 in PBMC from new-onset AS patients were significantly low and there were negative correlation between mRNA NAT10 and ASDAS-CRP, BASDIA in new-onset AS patients. ROC analysis suggested that mRNA NAT10 has value in distinguishing new-onset AS patients from HC, RA and SLE. Furthermore, a novel predictive model based on mRNA NAT10 and neutrophil percentages (N%) was constructed for distinguishing new-onset AS patients from HC (AUC = 0.880, sensitivity = 84.62%, specificity = 76.92%) and the predictive model correlated with the activity of new-onset AS. Furthermore, the predictive model could distinguish new-onset AS patients from RA and SLE (AUC = 0.661, sensitivity = 90.38%, specificity = 47.22%). Moreover, the potential predictive value of the combination of predictive model-HLA-B27 for AS vs. HC with a sensitivity of 92.86% (39/42), a specificity of 100.00% (52/52) and an accuracy of 96.81% (91/94) was superior to that of HLA-B27, which in turn had a sensitivity of 84.44% (38/45), a specificity of 100.00% (52/52) and an accuracy of 92.78% (90/97).

Conclusion

The present study suggested that the decreased mRNA NAT10 may play a role in AS pathogenesis and predictive model based on mRNA NAT10 and N% act as bioindicator for forecast and progression of diseases.
Genetic correction of induced pluripotent stem cells from a DFNA36 patient results in morphologic and functional recovery of derived hair cell-like cells
Authors: Luo Yi , Wu Kaiwen , Zhang Xiaolong , Wang Hongyang , Wang Qiuju
Published: January 2024

Background

TMC1 is one of the most common deafness genes causing DFNA36. Patient-derived human induced pluripotent stem cells (iPSCs) provide an opportunity to modelling diseases. TMC1 p.M418K mutation in human is orthologous to Beethoven mice. Here, we investigated the differentiation, morphology and electrophysiological properties of hair cell-like cells (HC-like cells) derived from DFNA36 patient.

Methods

Inner ear HC-like cells were induced from iPSCs derived from DFNA36 (TMC1 p.M418K) patient (M+/−), normal control (M+/+) and genetic corrected iPSCs (M+/C). Immunofluorescence, scanning electron microscopy and whole-cell patch-clamp were used to study the mechanism and influence of TMC1 p.M418K mutation.

Results

In this study we successfully generated HC-like cells from iPSCs with three different genotypes. HC-like cells from M+/− showed defected morphology of microvilli and physiological properties compared to M+/+. HC-like cells from M+/C showed recovery in morphology of microvilli and physiological properties.

Conclusions

Our results indicate that TMC1 p.M418K mutation didn’t influence inner ear hair cell differentiation but the morphology of microvilli and electrophysiological properties and gene correction induced recovery. CRISPR/Cas9 gene therapy is feasible in human patient with TMC1 p.M418K mutation.
Progress and application of adipose-derived stem cells in the treatment of diabetes and its complications
Authors: Yan Dongxu , Song Yujie , Zhang Bing , Cao Guojie , Zhou Haitao , Li Hong , Sun Hao , Deng Meng , Qiu Yufeng , Yi Wei , Sun Yang
Published: January 2024

Diabetes mellitus (DM) is a serious chronic metabolic disease that can lead to many serious complications, such as cardiovascular disease, retinopathy, neuropathy, and kidney disease. Once diagnosed with diabetes, patients need to take oral hypoglycemic drugs or use insulin to control blood sugar and slow down the progression of the disease. This has a significant impact on the daily life of patients, requiring constant monitoring of the side effects of medication. It also imposes a heavy financial burden on individuals, their families, and even society as a whole. Adipose-derived stem cells (ADSCs) have recently become an emerging therapeutic modality for DM and its complications. ADSCs can improve insulin sensitivity and enhance insulin secretion through various pathways, thereby alleviating diabetes and its complications. Additionally, ADSCs can promote tissue regeneration, inhibit inflammatory reactions, and reduce tissue damage and cell apoptosis. The potential mechanisms of ADSC therapy for DM and its complications are numerous, and its extensive regenerative and differentiation ability, as well as its role in regulating the immune system and metabolic function, make it a powerful tool in the treatment of DM. Although this technology is still in the early stages, many studies have already proven its safety and effectiveness, providing new treatment options for patients with DM or its complications. Although based on current research, ADSCs have achieved some results in animal experiments and clinical trials for the treatment of DM, further clinical trials are still needed before they can be applied in a clinical setting.
Non-coding RNAs regulating endothelial progenitor cells for venous thrombosis: promising therapy and innovation
Authors: Sun Li-Li , Liu Zhao , Ran Feng , Huang Dian , Zhang Ming , Li Xiao-Qiang , Li Wen-Dong
Published: January 2024

Venous thromboembolism, which includes deep venous thrombosis (DVT) and pulmonary embolism, is the third most common vascular disease in the world and seriously threatens the lives of patients. Currently, the effect of conventional treatments on DVT is limited. Endothelial progenitor cells (EPCs) play an important role in the resolution and recanalization of DVT, but an unfavorable microenvironment reduces EPC function. Non-coding RNAs, especially long non-coding RNAs and microRNAs, play a crucial role in improving the biological function of EPCs. Non-coding RNAs have become clinical biomarkers of diseases and are expected to serve as new targets for disease intervention. A theoretical and experimental basis for the development of new methods for preventing and treating DVT in the clinic will be provided by studies on the role and molecular mechanism of non-coding RNAs regulating EPC function in the occurrence and development of DVT. To summarize, the characteristics of venous thrombosis, the regulatory role of EPCs in venous thrombosis, and the effect of non-coding RNAs regulating EPCs on venous thrombosis are reviewed. This summary serves as a useful reference and theoretical basis for research into the diagnosis, prevention, treatment, and prognosis of venous thrombosis.
Identifying optimal candidates for autologous peripheral blood stem cell therapy in patients with decompensated liver cirrhosis: a prognostic scoring system
Authors: Tian Siyuan , Guo Guanya , Zhou Xia , Liu Yansheng , Jia Gui , Zheng Linhua , Cui Lina , Wang Kemei , Zhang Miao , Sun Keshuai , Ma Shuoyi , Yang Chunmei , Zhou Xinmin , Guo Changcun , Shang Yulong , Han Ying
Published: January 2024

Background

Stem cell transplantation shows great potential to improve the long-term survival of cirrhosis patients. However, therapeutic effects may not be homogeneous across the whole study population. This study constructed an easy-to-use nomogram to improve prognostic prediction and aid in treatment decision making for cirrhotic patients.

Methods

From August 2005 to April 2019, 315 patients with decompensated cirrhosis receiving autologous peripheral blood stem cell (PBSC) transplantation were enrolled in this study. They were randomly classified into training (2/3) and validation (1/3) groups. A predictive model was developed using Cox proportional hazard models and subsequently validated. The predictive performance of the model was evaluated and also compared with other prognostic models.

Results

Age, creatinine, neutrophil-to-lymphocyte ratio, and Child–Turcotte–Pugh class were included in the nomogram as prognostic variables. The nomogram showed high discrimination power concerning the area under receiver operating characteristic curves (3/5-year AUC: 0.742/0.698) and good consistency suggested by calibration plots. Patients could be accurately stratified into poor- and good-outcome groups regarding liver-transplantation free survival after receiving PBSC therapy (P < 0.001). Compared with poor-outcome group, the liver function of patients listed for liver transplantation in the good-outcome group was significantly improved (P < 0.001). Besides, our nomogram achieved a higher C-index (0.685, 95% CI 0.633–0.738) and better clinical utility compared with other conventional prognostic models.

Conclusions

The proposed nomogram facilitated an accurate prognostic prediction for patients with decompensated cirrhosis receiving PBSC transplantation. Moreover, it also held the promise to stratify patients in clinical trials or practice to implement optimal treatment regimens for individuals.
Genetic algorithm-based secure cooperative control for high-order nonlinear multi-agent systems with unknown dynamics
Authors: Wang Xin , Yang Dongsheng , Dolly D Raveena Judie , Chen Shuang , Alassafi Madini O. , Alsaadi Fawaz E. , Lyu Jianhui
Published: January 2024

Research has recently grown on multi-agent systems (MAS) and their coordination and secure cooperative control, for example in the field of edge-cloud computing. MAS offers robustness and flexibility compared to centralized systems by distributing control across decentralized agents, allowing the system to adapt and scale without overhaul. The collective behavior emerging from agent interactions can solve complex tasks beyond individual capabilities. However, controlling high-order nonlinear MAS with unknown dynamics raises challenges. This paper proposes an enhanced genetic algorithm strategy to enhance secure cooperative control performance. An efficient encoding method, adaptive decoding schemes, and heuristic initialization are introduced. These innovations enable compelling exploration of the solution space and accelerate convergence. Individual enhancement via load balancing, communication avoidance, and iterative refinement intensifies local search. Simulations demonstrate superior performance over conventional algorithms for complex control problems with uncertainty. The proposed method promises robust, efficient, and consistent solutions by adapting to find optimal points and exploiting promising areas in the space. This has implications for securely controlling real-world MAS across domains like robotics, power systems, and autonomous vehicles.
Transcriptomic analysis identifies diagnostic genes in polycystic ovary syndrome and periodontitis
Authors: Liu Xiaodan , Zhang Jingran , Wang Xiao , Zhang Zhihui
Published: January 2024

Purpose

To investigate underlying co-mechanisms of PCOS and periodontitis through transcriptomic approach.

Methods

PCOS and periodontitis gene expression data were downloaded from the GEO database to identify differentially expressed genes. GO and KEGG pathway enrichment analysis and random forest algorithm were used to screen hub genes. GSEA analyzed the functions of hub genes. Correlations between hub genes and immune infiltration in two diseases were examined, constructing a TF-ceRNA regulatory network. Clinical samples were gathered from PCOS and periodontitis patients and RT-qPCR was performed to verify the connection.

Results

There were 1661 DEGs in PCOS and 701 DEGs in periodontitis. 66 intersected genes were involved and were enriched in immune and inflammation-related biological pathways. 40 common genes were selected from the PPI network. RF algorithm demonstrated that ACSL5, NLRP12, CCRL2, and CEACAM3 were hub genes, and GSEA results revealed their close relationship with antigen processing and presentation, and chemokine signaling pathway. RT-qPCR results confirmed the upregulated gene expression in both PCOS and periodontitis.

Conclusion

The 4 hub genes ACSL5, NLRP12, CCRL2, and CEACAM3 may be diagnostic genes for PCOS and periodontitis. The created ceRNA network could provide a molecular basis for future studies on the association between PCOS and periodontitis.
COVID-19-related cardiovascular disease risk due to weight gain: a nationwide cohort study
Authors: Lee Su Kyoung , Lim Yohwan , Jeong Seogsong , Han Hyun Wook
Published: January 2024

Background

Cardiovascular disease (CVD) is a significant contributor to morbidity and mortality worldwide, with CVD and post-acute COVID-19 associated CVD increasing. It remains unknown whether COVID-19 patients with weight gain are at a high risk for CVD events. Therefore, the primary objective of this study is to investigate the association between weight control and the risk of CVD following COVID-19.

Methods

The study included 2,024,728 adults who participated in two rounds of health screening between 2017 and 2020. The final cohort, which included 70,996 participants in the COVID-19 group and 212,869 participants in the control group. The adjusted hazard ratio of BMI change to CVD risk was calculated using Cox proportional hazards regression.

Results

We identified a total of 2869 cases of CVD (861 events for COVID-19 group and 2,008 events for the control group). Compared to individuals with a stable BMI, COVID-19 patients without obesity had an increased risk of CVD (adjusted hazard ratio [aHR] = 2.28; 95% confidence interval [CI], 1.15–4.53; p-value = 0.018). Additionally, non-COVID-19 patients with obesity also exhibited a higher risk of CVD (aHR = 1.58; 95% CI, 1.01–2.47; p-value = 0.046).

Conclusion

In conclusion, people who gained weight during the pandemic, regardless of their weight category, had a significantly higher risk of CVD associated with COVID-19 compared to those who maintained their weight before the pandemic.
Facile fabrication and characterization of MXene/cellulose composites for electrical properties, electric heating performance
Authors: Kang Chan Sol , Kim Jong Kyu , Lee Chae-Seok , Chang HoJong , Cho Yeong Heon , Prasad Cheera , Choi Hyeong Yeol
Published: January 2024

Developing energy-efficient and multifunctional wearable electronic textiles (E-textiles) is a significant challenge. This study investigates MXene-coated cellulose hybrid fibers, focusing on their electrical properties, heating performance, and thermal stability. The fabrication process involves continuous dipping of cellulose fibers into an aqueous MXene solution, resulting in the creation of MXene-coated cellulose hybrid fibers. We confirm the uniform coating of MXene sheets on the cellulose fiber surfaces, with increasing content throughout the dip coating cycle, as evidenced by X-ray diffraction and scanning electron microscopy analysis. The high thermal conductivity of MXene acts as a heat source, impacting the thermal stability of cellulose fibers at lower temperatures. Additionally, the electrical properties of MXene/cellulose hybrid fiber composites are influenced at elevated temperatures. Remarkably, the longitudinal electrical conductivity of the MXene-coated cellulose fiber composites exhibits a notable increase of 0.06 S/cm after the final coating cycle, demonstrating the effective and conductive nature of the layer-by-layer MXene network formed on the cellulose fibers.
Intestinal Behçet's and suspected intestinal Behçet’s disease: a report of four surgical cases
Authors: Ono Rika , Tominaga Tetsuro , Nonaka Takashi , Takamura Yuma , Oishi Kaido , Shiraishi Toshio , Hashimoto Shintaro , Noda Keisuke , Sawai Terumitsu , Okano Shinji , Nagayasu Takeshi
Published: January 2024

Background

Intestinal Behçet's disease (BD) is often associated with ulceration that requires surgery, including perforation and abscess formation. However, no consensus has been reached on the optimal extent of resection or treatment strategy. This study reviewed four cases of intestinal or suspected intestinal BD.

Case presentations

In Case 1, a 74-year-old woman diagnosed with BD 2 years earlier was treated with anti-tumor necrosis factor α antibody (Infliximab) and steroids. She had oral and pubic ulcers. After close investigation of abdominal pain, perforation of the gastrointestinal tract was suspected and surgery was performed. Multiple perforating ulcers and abscesses were found in the distal ileum, and the small intestine was resected. Postoperatively, the patient was treated with an increased steroid dose and symptoms have remained stable. Case 2 involved a 69-year-old woman with oral and pubic ulcers, ocular ulcer, and skin lesions. She experienced sudden onset of abdominal pain during treatment for lymphoma. She showed multiple perforating ulcers throughout the ileum and underwent resection of the small intestine and ileostomy. Upper abdominal pain appeared during postoperative treatment for high-output syndrome. The patient underwent omentoplasty after perforation of the upper gastrointestinal tract was diagnosed. Postoperatively, anti-interleukin-1 beta antibodies (canakinumab) was administered to control the disease. Case 3 involved an 81-year-old, previously healthy woman. She presented to her previous physician with complaints of pubic ulcer, hemorrhage and abdominal pain. Colonoscopy showed multiple ulcers throughout the entire colon. Steroid therapy was started, but bleeding proved difficult to control and total proctocolectomy was performed. Histopathology revealed multiple perforating ulcers and BD was diagnosed. Postoperatively, the patient remains under steroid control. Case 4 involved a 43-year-old man with abdominal pain who showed abscess formation in the ileocecal region. After excision of the ileocecal area, multiple ulcers were diagnosed. Two years later, abdominal pain recurred and free air was found in the abdomen on close imaging. Emergency anastomotic resection was performed due to ulceration and perforation of the anastomosis.

Conclusions

Intestinal BD may flare up after surgical treatment and require multiple surgeries. Introducing pharmacotherapy as soon as possible after surgical treatment is important to control the disease.
Retinal neurovascular alteration in type 2 diabetes with renal impairment in association with systemic arterial stiffness
Authors: Ari Widjaja Sauli , Mieler William F. , Sasono Wimbo , Soelistijo Soebagijo A. , Kartasasmita Arief S. , Murakami Akira , Nakao Shintaro
Published: January 2024

Background

Diabetic retinopathy (DR) patients should be alert for subclinical macroangiopathy. We aimed to investigate the association between retinal neurovascular alteration and systemic arterial stiffness in type 2 diabetes mellitus (type 2 DM) patients with varying degrees of renal impairment.

Methods

The study included 170 patients with confirmed diagnosis of type 2 DM aged ≥18 years old. Renal function was assessed by estimated glomerular filtration rate (eGFR). Arterial stiffness was measured by brachial-ankle pulse wave velocity (baPWV) and ankle brachial index (ABI). Retinal neurovascular parameters were derived from Optical Coherence Tomography (OCT)/OCT-Angiography, represented by vessel density (VD Central, Inner, Outer, Full), foveal avascular zone (FAZ area and FAZ perimeter) of the superficial capillary plexus, the average of macular ganglion cell-inner plexiform layer thickness (ave mGC-IPLt) and the average of retinal nerve fiber layer thickness (aveRNFLt). The association between variables among the groups (according to renal function, diabetic retinopathy (DR) severity, and arterial stiffness categories) were analyzed by regression analysis with multiple hypothesis testing commands.

Results

Out of the 265 eyes, the mean DM duration and HbA1c were 6.21 ± 6.37 years and 8.44 ± 2.06% respectively. While the mean of eGFR, baPWV and ABI were 66.78 ± 32.80 ml/min/1.73m2, 15.49 ± 3.07 m/s, and 1.05 ± 0.12, respectively. Patients with more severe renal impairment demonstrated longer DM duration (p < 0.001), higher baPWV (p < 0.0001), and retinal vascular alteration. Proliverative DR group showed the lowest eGFR (p < 0.0001), highest baPWV (p < 0.0001), and retinal neurovascular changes. Significantly lower eGFR and retinal vascular alteration were found in the baPWV > 14 group. Some neurovascular parameters were significantly negatively correlated with baPWV; moreover, retinal neurovascular changes were also noted in the abnormal ABI group.

Conclusions

The strong association between changes in the retinal neurovascular system, DR severity, renal impairment, and arterial stiffness in type 2 DM was confirmed. Patients with more severe renal impairment had higher levels of arterial stiffness, more severe DR and retinal neurovascular alteration. Retinal neurovascular changes seen in OCT/OCTA might mimic renal microvascular alteration and systemic arterial stiffness. Therefore, assessment of baPWV and OCT/OCTA should be integrated in DR screening to enhance cardiovascular risk stratification and prognosis as well as to provide clinically useful early identification of subclinical micro- and macrovascular alterations.
Fully endoscopic far-lateral supracerebellar infratentorial approach for trigeminal neuralgia: illustrative case reports
Authors: Yao Hong , Yang Wenlei , Tang Hao , Cheng Yijun , Lin Shaojian , Wu Zhe Bao
Published: January 2024

Background

Trigeminal neuralgia (TN) is a common cause of craniofacial pain. The retrosigmoid approach is usually used to treat TN, but no cases of endoscopic far-lateral supracerebellar infratentorial approach (EF-SCITA) were used to undergo operation for TN.

Case presentation

Two patients were presented with severe facial pain and preliminary diagnosis was TN. Preoperative magnetic resonance imaging revealed that a superior cerebellar artery (SCA) compressed the trigeminal nerve in case 1, and a tumor located in the petrous apex extending into the Meckel’s cave compressed the trigeminal nerve in case 2. Operations were achieved through the EF-SCITA. The pain was totally relieved with no postsurgical complications in both cases.

Conclusions

We present the first two case reports of EF-SCITA to relieve classical and secondary TN successfully. The EF-SCITA can be a promising approach for treating TN.
4400 TEU cargo ship dynamic analysis by Gaidai reliability method
Authors: Gaidai Oleg , Wang Fang , Cao Yu , Liu Zirui
Published: January 2024

Modern cargo vessel transport constitutes an important part of global economy; hence it is of paramount importance to develop novel, more efficient reliability methods for cargo ships, especially if onboard recorded data is available. Classic reliability methods, dealing with timeseries, do not have the advantage of dealing efficiently with system high dimensionality and cross-correlation between different dimensions. This study validates novel structural reliability method suitable for multi-dimensional structural systems versus a well-established bivariate statistical method. An example of this reliability study was a chosen container ship subjected to large deck panel stresses during sailing. Risk of losing containers, due to extreme motions is the primary concern for ship cargo transport. Due to non-stationarity and complicated nonlinearities of both waves and ship motions, it is challenging to model such a phenomenon. In the case of extreme motions, the role of nonlinearities dramatically increases, activating effects of second and higher order. Moreover, laboratory tests may also be questioned. Therefore, data measured on actual ships during their voyages in harsh weather provides a unique insight into statistics of ship motions. This study aimed at benchmarking and validation of the state-of-the-art method, which enables extraction of the necessary information about the extreme system dynamics from onboard measured time histories. The method proposed in this study opens up broad possibilities of predicting simply, yet efficiently potential failure or structural damage risks for the nonlinear multi-dimensional cargo vessel dynamic systems as a whole. Note that advocated novel reliability method can be used for a wide range of complex engineering systems, thus not limited to cargo ship only.
Simulated cardiopulmonary bypass: a high fidelity model for developing and accessing clinical perfusion skills
Authors: Searles Bruce E. , Riley Jeffrey B. , Darling Edward M. , Wiles Jason R.
Published: January 2024

Background

Traditionally, novice perfusionists learn and practice clinical skills, during live surgical procedures. The profession’s accrediting body is directing schools to implement simulated cardiopulmonary bypass (CPB) into the curriculum. Unfortunately, no CPB simulation models have been validated. Here we describe the design and application of a CPB simulation model.

Methods

A CPB patient simulator was integrated into a representative operative theater and interfaced with a simple manikin, a heart-lung machine (HLM), clinical perfusion circuitry, and equipment. Participants completed a simulation scenario designed to represent a typical CPB procedure before completing an exit survey to assess the fidelity and validity of the experience. Questions were scored using a 5-point Likert scale.

Results

Participants (n = 81) contributed 953 opinions on 40 questions. The participants reported that the model of simulated CPB (1) realistically presented both the physiologic and technical parameters seen during CPB (n = 347, mean 4.37, SD 0.86), (2) accurately represented the psychological constructs and cognitive mechanisms of the clinical CPB (n = 139, mean 4.24, SD 1.08), (3) requires real clinical skills and reproduces realistic surgical case progression (n = 167, mean 4.38, SD 0.86), and (4) would be effective for teaching, practicing, and assessing the fundamental skills of CPB (n = 300, mean 4.54, SD 0.9). Participants agreed that their performance in the simulation scenario accurately predicted their performance in a real clinical setting (n = 43, mean 4.07, SD 1.03)

Conclusion

This novel simulation model of CPB reproduces the salient aspects of clinical CPB and may be useful for teaching, practicing, and assessing fundamental skills.
Preclinical evaluation of an 18F-labeled Nε-acryloyllysine piperazide for covalent targeting of transglutaminase 2
Authors: Wodtke Robert , Laube Markus , Hauser Sandra , Meister Sebastian , Ludwig Friedrich-Alexander , Fischer Steffen , Kopka Klaus , Pietzsch Jens , Löser Reik
Published: January 2024

Background

Transglutaminase 2 (TGase 2) is a multifunctional protein and has a prominent role in various (patho)physiological processes. In particular, its transamidase activity, which is rather latent under physiological conditions, gains importance in malignant cells. Thus, there is a great need of theranostic probes for targeting tumor-associated TGase 2, and targeted covalent inhibitors appear to be particularly attractive as vector molecules. Such an inhibitor, equipped with a radionuclide suitable for noninvasive imaging, would be supportive for answering the general question on the possibility for functional characterization of tumor-associated TGase 2. For this purpose, the recently developed 18F-labeled Nε-acryloyllysine piperazide [18F]7b, which is a potent and selective irreversible inhibitor of TGase 2, was subject to a detailed radiopharmacological characterization herein.

Results

An alternative radiosynthesis of [18F]7b is presented, which demands less than 300 µg of the respective trimethylammonio precursor per synthesis and provides [18F]7b in good radiochemical yields (17 ± 7%) and high (radio)chemical purities (≥ 99%). Ex vivo biodistribution studies in healthy mice at 5 and 60 min p.i. revealed no permanent enrichment of 18F-activity in tissues with the exception of the bone tissue. In vivo pretreatment with ketoconazole and in vitro murine liver microsome studies complemented by mass spectrometric analysis demonstrated that bone uptake originates from metabolically released [18F]fluoride. Further metabolic transformations of [18F]7b include mono-hydroxylation and glucuronidation. Based on blood sampling data and liver microsome experiments, pharmacokinetic parameters such as plasma and intrinsic clearance were derived, which substantiated the apparently rapid distribution of [18F]7b in and elimination from the organisms. A TGase 2-mediated uptake of [18F]7b in different tumor cell lines could not be proven. Moreover, evaluation of [18F]7b in melanoma tumor xenograft models based on A375-hS100A4 (TGase 2 +) and MeWo (TGase 2 −) cells by ex vivo biodistribution and PET imaging studies were not indicative for a specific targeting.

Conclusion

[18F]7b is a valuable radiometric tool to study TGase 2 in vitro under various conditions. However, its suitability for targeting tumor-associated TGase 2 is strongly limited due its unfavorable pharmacokinetic properties as demonstrated in rodents. Consequently, from a radiochemical perspective [18F]7b requires appropriate structural modifications to overcome these limitations.
Plasma galectin-9 levels correlate with blood monocyte turnover and predict simian/human immunodeficiency virus disease progression
Authors: Zablocki-Thomas Laurent , Ardeshir Amir , Takahashi Naofumi , White Kevin S. , Sumer Cinar Efe , Wallis Zoey K. , Didier Elizabeth S. , Kim Woong-Ki , Williams Kenneth C. , Kuroda Marcelo J.
Published: January 2024

Background

Late-stage human immunodeficiency virus (HIV) infection is typically characterized by low CD4 + T-cell count. We previously showed that profound changes in the monocyte turnover (MTO) rate in rhesus macaques infected by the simian immunodeficiency virus (SIV) outperforms declining CD4 + T-cell counts in predicting rapid health decline associated with progression to terminal disease. High MTO is associated with increased tissue macrophage death. However, MTO analysis is complex and not directly applicable to humans.

Methods

We explored blood-available biomarkers associated with MTO using comprehensive immune cell profiling via flow cytometry, blood cell count and chemistry, and ELISA.

Results

Plasma galectin-9 was identified as the most highly correlated marker with MTO. This correlation remained statistically significant during acute, chronic, and late-stage infections caused by three different SIV strains tested. In addition, the galectin-9 level also predicted decline in animal health, requiring medical cull. The correlation between MTO and galectin-9 was maintained even in uninfected animals showing variable MTO.

Conclusions

These findings support the exploration of galectin-9 as a surrogate biomarker of MTO for non-invasive monitoring of disease progression (e.g. HIV) that may also be applicable in humans and as a potential indicator of tissue macrophages apoptosis.
Translation, transcultural adaptation into Brazilian Portuguese and concurrent validity of the rheumatoid arthritis assessment scale (RAKAS–13/Brazil)
Authors: Mineiro Lindomar , Gallo da Silva Tamires Terezinha , Valderramas Silvia Regina , Kowalski Sergio Candido , dos Santos Paiva Eduardo , Gomes Anna Raquel Silveira
Published: January 2024

Background

Knowledge of patients about Rheumatoid Arthritis (RA) is a necessary aspect to better approach self-management support in a patient-centered manner. The research instrument known as the Rheumatoid Arthritis Knowledge Assessment Scale (RAKAS), consisting of 13 items, is simple, reliable and reproducible, and can be applied in both clinical practice and research protocols.

Objective

This study aimed to translate and culturally adapt the RAKAS vocabulary into Brazilian Portuguese and to evaluate its concurrent validity.

Methods

The RAKAS was translated into Brazilian Portuguese and administered to 52 elderly women with RA recruited between May 2021 and May 2022. Concurrent validity was assessed using the Spearman’s correlation coefficient between RAKAS and Patient Knowledge Questionnaire (PKQ).

Results

The participants considered RAKAS-13/BRAZIL easy to understand and did not report any doubts in answering the final version. Concurrent validity of the RAKAS–13/BRAZIL was low compared to the PKQ (ρ = 0.283, p = 0.038). Conclusion: The Brazilian Portuguese version of the RAKAS (RAKAS–13/BRASIL) proved to be a questionnaire that was easy and quick to administer to assess patient knowledge about Rheumatoid Arthritis, despite its low correlation with the PKQ in the present study.
The impact of hospitalization on mortality in patients with connective tissue disease-associated interstitial lung disease: a medical records review study
Authors: Korogodina Anna , Kaur Navneet , Xie Xianhong , Mehta Adhya , Cleven Krystal L. , Ayesha Bibi , Kumthekar Anand
Published: January 2024

Background

Interstitial lung disease (ILD) remains one of the most important causes of morbidity and mortality in patients with Connective Tissue Diseases (CTD). This study evaluated the impact of hospitalization on mortality in an ethnically and racially diverse cohort of CTD-ILD patients.

Methods

We conducted a medical records review study at Montefiore Medical Center, Bronx, NY. We included 96 patients and collected data on demographic characteristics, reasons for hospitalization, length of stay, immunosuppressant therapy use, and mortality. We stratified our patients into two cohorts: hospitalized and non-hospitalized. The hospitalized cohort was further subdivided into cardiopulmonary and non-cardiopulmonary admissions. Two-sample tests or Wilcoxon’s rank sum tests for continuous variables and Chi-square or Fisher’s exact tests for categorical variables were used for analyses as deemed appropriate.

Results

We identified 213 patients with CTD-ILD. Out of them, 96 patients met the study’s inclusion criteria. The majority of patients were females (79%), and self-identified as Hispanic (54%) and Black (40%). The most common CTDs were rheumatoid arthritis (RA) (29%), inflammatory myositis (22%), and systemic sclerosis (15%). The majority (76%) of patients required at least one hospitalization. In the non-hospitalized group, no deaths were observed, however we noted significant increase of mortality risk in hospitalized group (p = 0.02). We also observed that prolonged hospital stay (> 7 days) as well as older age and male sex were associated with increased mortality.

Conclusions

Prolonged (> 7 days) hospital stay and hospitalization for cardiopulmonary causes, as well as older age and male sex were associated with an increased mortality risk in our cohort of CTD-ILD patients.
Evaluation of core decompression outcome in systemic lupus erythematosus with hip osteonecrosis: a retrospective cohort study
Authors: Hadighi Pouya , Faezi Seyedeh Tahereh , Mortazavi Seyed Mohammad Javad , Rokni Mohsen , Aghaghazvini Leila , Kasaeian Amir , Nejadhosseinian Mohammad , Haerian Hoda , Fateh Hamid Reza
Published: January 2024

Background

Osteonecrosis is a major cause of morbidity for patients with systemic lupus erythematosus (SLE). Although core decompression is an approved and trusted technique to prevent further joint deterioration, this surgical method seems to be less beneficial for SLE patients. We aimed to evaluate the outcomes of core decompression in SLE patients with primary stages of femoral head osteonecrosis.

Methods

In this study, 23 patients (39 affected hip joints) with osteonecrosis of the femoral head with stage II of the disease, based on the Ficat-Arlet classification system, underwent core decompression. Also, patients demographic characteristics, clinical data, medication history, comorbidities, immunological findings, hip plain radiographs, history of total hip arthroplasty after core decompression, and patients satisfaction with joint function according to the Oxford hip score questionnaire were obtained.

Results

In the study, 53.8% of affected joints showed signs of radiographic deterioration in follow-up imaging. Sixty-one and a half percent (61.5%) of patients had unsatisfactory joint performance. A third (33.3%) of affected hip joints underwent total hip arthroplasty up to 5 years from core decompression. SLE patients with a history of receiving bisphosphonate were 83.2% less dissatisfied with their joint function than patients without a history of bisphosphonate use (P < 0.02). Of the 23 studied cases, the mean cumulative dose of prednisolone before and after core decompression surgery was 46.41 mg and 14.74 mg respectively. Besides, one case (2.6%) that had a high anti-phospholipid antibodies level during follow-up did not have any radiographic deterioration, and 9 cases (23.1%) had some degrees of radiographic deterioration.

Conclusions

The patients group that used bis-phosphonate, had a higher level of satisfaction with joint function after core decompression. Patients with high-level anti-phospholipid antibodies are related to a poor prognosis after core decompression.
Prognostic significance of right ventricular dysfunction in patients presenting with acute left-sided heart failure
Authors: Shaker Mirna M. , Taha Hesham S. , Kandil Hossam I. , Kamal Heba M. , Mahrous Hossam A. , Elamragy Ahmed A.
Published: January 2024

Background

The prognostic value of right ventricular (RV) function in chronic heart failure (HF) has lately been well established. However, research on its role in acute heart failure (AHF) is sparse.

Results

This study comprised 195 patients, aged between 18 and 80 years, with acute left-sided heart failure (HF) and a left ventricular ejection fraction (LVEF) < 50%. Patients with LVEF ≥ 50%, mechanical ventilatory or circulatory support, poor echocardiographic windows, prosthetic valves, congenital heart diseases, infective endocarditis, and/or life expectancy < 1 year due to non-cardiac causes were excluded. The study participants’ mean age was 57.7 ± 10.9 years, and 74.9% were males. Coronary artery disease was present in 80.5% of patients. The mean LVEF was 31% ± 8.7. RV dysfunction (RVD), defined as tricuspid annular plane systolic excursion (TAPSE) < 17 mm, RV S' < 9.5 cm/s and/or RV fractional area change (FAC) < 35%, was identified in 48.7% of patients. The RV was dilated in 67.7% of the patients. RVD was significantly associated with a longer HF duration, atrial fibrillation, and idiopathic dilated cardiomyopathy. The primary outcome, a 6-month composite of cardiovascular death or hospitalization for worsening HF (HHF), occurred in 42% of the participants. Cardiovascular mortality and HHF occurred in 30.5% and 23.9% of the patients, respectively. The primary endpoint and longer CCU stays were significantly more common in patients with RVD than in those with normal RV function. RV dilatation was significantly associated with the primary outcome, whether alone or in combination with RVD. Multivariate regression analysis showed that only RV global longitudinal strain (GLS) independently predicted poor outcomes.

Conclusions

RVD and RV dilatation strongly predict CV death and HHF in patients with AHF and LVEF < 50%. Multivariate analysis showed that RV GLS was the only predictor of a composite of CV death and HHF.
Ecdysone receptor strongly influences larval–pupal–adult transition and melanization in
Tuta absoluta
Authors: Wang Xiaodi , Wu Jiajia , Guo Jianyang , Yang Nianwan , Wan Fanghao , Lü Zhichuang , Liu Wanxue
Published: January 2024

Background

Tomato leaf miner (
Tuta absoluta
) is a quarantined pest that damages Solanaceae crops worldwide. The overuse of traditional pesticides negatively affects both human health and the environment. RNA interference (RNAi), based on double-stranded RNA (dsRNA) induction, can be beneficial in the control of
Tuta absoluta
; one of the key points of using this technique is the selection of target genes. Exploring the ecdysone receptors (EcR) associated with the growth and development of tomato leaf miners is an important research topic and the primary aim of this study.

Methods

In this study, RNA extraction, cDNA synthesis, gene cloning, bioinformatics analysis, and quantitative real-time polymerase chain reaction were used to obtain the full length, conserved domain, and relative expression levels of the
EcR
. RNAi was used to explore the effects of
EcR
on larval growth and development, pupal weight, and emergence rate.

Results

The full-length cDNA of
T. absoluta TaEcR
was 1859 bp, and the coding region including the ZnF_C4 and HOLI domains was relatively conserved. The relative expression of
EcR
in the early pupal stage was substantially higher than that in the other instars. Approximately 70% of
TaEcR
RNAi larvae died or pupated abnormally. In the few successful pupations, the pupa weights were substantially lower (36.44%) than those of the control group. The color of the pupae was abnormal, and they did not enter their normal black state; the emergence rate of pupae was reduced by 43.45% compared to that of the control group.

Conclusion

These results indicate that
TaEcR
inhibition can affect larval metamorphosis, pupation, melanism, eclosion abnormalities, and, ultimately, lead to death. The results of this study suggest that
TaEcR
may be a candidate factor for developing environmentally-friendly RNAi pesticides that have practical value in field control.