bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Knee Osteoarthritis and Cardiovascular Disease in Type 2 Diabetes Mellitus: Impact of Exercise
Authors: Park Dojoon , Ko Seung-Hyun , Choi Youn-Ho , Koh Hae-Seok , Han Kyungdo
Published: October 2024

Knee osteoarthritis (OA), type 2 diabetes mellitus (T2DM), and cardiovascular disease (CVD) are major chronic conditions that frequently co-occur, posing substantial health burdens. This study aimed to investigate the association between knee OA and CVD outcomes in patients with T2DM, as well as the impact of exercise behavior on these associations. Utilizing data from the National Health Insurance Service (NHIS) in South Korea, we examined a cohort of 1,091,898 individuals diagnosed with T2DM between 2009 and 2012. The incidence rates of CVD, myocardial infarction (MI), stroke, heart failure (HF), and cardiovascular mortality were significantly higher in the knee OA group compared to those without knee OA (CVD: 23.25 vs. 18.23 per 1000 person-years; MI: 4.38 vs. 3.86; stroke: 11.70 vs. 8.97; HF: 10.62 vs. 8.19; CV mortality: 2.26 vs. 1.91). After adjusting for confounding factors, knee OA was associated with an increased risk of CVD (HR 1.13, 95% CI 1.11–1.16), MI (HR 1.07, 95% CI 1.02–1.13), stroke (HR 1.14, 95% CI 1.10–1.18), and HF (HR 1.13, 95% CI 1.09–1.17). Regular and intermittent exercise significantly reduced the risk of CVD, MI, stroke, HF, and cardiovascular mortality in T2DM patients with knee OA (e.g., regular exercise: HR 0.63, 95% CI 0.52–0.76; intermittent exercise: HR 0.69, 95% CI 0.61–0.78 for CV mortality). The association between knee OA and increased CVD risk was more pronounced in non-insulin users (HR 1.13, 95% CI 1.10-1.16) and those with a shorter duration of diabetes (HR 1.10, 95% CI 1.07-1.13). These results underscore the importance of promoting physical activity to mitigate cardiovascular risks in T2DM patients with knee OA. Incorporating exercise into care strategies is crucial for improving cardiovascular health in this population.
Adiponectin deficiency is a critical factor contributing to cognitive dysfunction in obese mice after sevoflurane exposure
Authors: Chu John Man Tak , Chiu Suki Pak Wing , Wang Jiaqi , Chang Raymond Chuen Chung , Wong Gordon Tin Chun
Published: October 2024

Background
The growing number of obese individuals is expected to create an increase in the number of major operations to be performed in those patients. Obesity is a risk factor for a range of postoperative complications including perioperative neurocognitive disorders. However, the neurotoxic effects of general anaesthesia in the obese subjects are not yet determined. We hypothesize that general anaesthesia such as sevoflurane induces neurotoxicity in obese animals while no significant impact is induced in lean mice. This vulnerability depends on the reduction of the adiponectin in the obese mice.
Methods
Obese mice were bred by subjecting C57BL/6 mice to a 60% high fat diet. Both obese mice lean mice were exposed to 2 hours of sevoflurane. To confirm the role of adiponectin deficiency in sevoflurane induced neurotoxicity, adiponectin knockout mice were established and exposed to the sevoflurane. Finally, the neuroprotective effects of adiponectin receptor agonist (AdipoRon) were examined. Cognitive functions, neuroinflammatory responses and neuronal degeneration were accessed.
Results
Sevoflurane triggered significant cognitive dysfunction, neuroinflammatory response and neuronal degeneration in obese mice while no significant impact was observed in lean mice. Similar cognitive dysfunction and neuronal degeneration were also observed in the adiponectin knockout mice after sevoflurane exposure. Administration of AdipoRon prevented the deleterious effects of sevoflurane in both obese and adiponectin knockout mice.
Conclusions
Our findings demonstrated that obese mice are more susceptible to sevoflurane triggered neurotoxicity and cognitive impairment compared with lean animals. Adiponectin deficiency in obese subjects is one of the underlying mechanisms and treatment with adiponectin receptor agonist ameliorates this vulnerability. These findings may have therapeutic implications to reduce the incidence of anaesthesia induced neurotoxicity in obese subjects.
Can dissociative amnesia be a residual symptom of prolonged complex post-traumatic stress disorder?
Authors: Metin İzzet Çağrı , Yıldırım Selman , Karahan Aykut
Published: October 2024

Background
Dissociative amnesia, a disorder characterized by impairments in multiple memory areas, is frequently associated with trauma. Complex post-traumatic stress disorder (CPTSD) is marked by mood dysregulation, negative self-concept, and impaired interpersonal relationships, in addition to the classic symptoms of post-traumatic stress disorder (PTSD). The relationship between CPTSD and dissociative amnesia, as well as whether CPTSD should be considered a dissociative subtype, remains uncertain in the literature. Individuals diagnosed with CPTSD tend to exhibit higher levels of dissociative symptoms than those diagnosed with PTSD.
Clinical presentation:
We present the clinical report of a 42-year-old male who, after a car accident, exhibited core symptoms of PTSD along with symptoms of self-organization disorders. While these symptoms persisted, the patient developed dissociative amnesia years after the trauma. Neuroimaging studies, psychometric tests, reviewed hospital records, and clinical interviews were conducted to speculate on the differential diagnosis of organic psychiatric conditions and potential diagnoses. The possible relationship between dissociative amnesia and complex post-traumatic stress disorder was examined.
Conclusion
This case demonstrates the complexity of differentiating dissociative amnesia from organic conditions. Discussing the possible shared mechanisms between CPTSD and dissociative amnesia could contribute to a better understanding of both conditions.
Analysis of the efficacy of different amounts of parathyroid grafts in the treatment of secondary hyperparathyroidism
Authors: chen Wentan , zhou Ge , chen Dong , cao Zhe
Published: October 2024

Purpose This study compares the efficacy of two different ranges of parathyroid transplantation weights with the aim of determining a preferable range for transplantation weight.Methods From May 2018 to June 2023, 79 patients underwent total parathyroidectomy with autotransplantation. Demographic data, symptoms, and pre- or postoperative biochemical indicators were compared between two different ranges of parathyroid transplantation weights.Results All 79 surgeries were successful, with a total of 316 parathyroid glands reported among the patients. The patients were diagnosed with parathyroid hyperplasia. Postoperatively, itching, bone pain, and muscle weakness disappeared, while serum parathyroid hormone and phosphate levels significantly decreased. With an average follow-up of 12 months, no transplant-dependent recurrence was observed.Conclusion Parathyroid transplantation with a weight of 30–50 mg is a feasible, safe, and effective surgical approach.
Assessing the value for money, from a policy maker prospective, of 24 randomised controlled trial designs for an online weight maintenance guided self-help intervention: An expected value of sample information analysis.
Authors: Breeze Penny , Pidd Katharine , Pollard Daniel , Ren Shijie , Bates Sarah , Thomas Chloe , Ahern Amy , Griffin Simon , Brennan Alan
Published: October 2024

Objective:
To analyse whether conducting a randomised controlled trial (RCT) to evaluate an online weight maintenance guided self-help intervention (the SWiM intervention) would offer good value for money in the United Kingdom.
Method
We examined 24 RCT designs by varying inclusion criteria (participants completing behavioural weight management, specialist-led weight management, diabetes prevention programme, type 2 diabetes remission, digital weight management, all weight management services), trial duration (1-2 years), and sample size (n=500 or 2000). Trial benefits were estimated by the method of expected value of sample information analysis using a health economic model. The model examines how the proposed intervention affects weight maintenance over time (with uncertainty), and generates estimated lifetime Quality Adjusted Life Years (QALYs) and National Health Service (NHS) costs. Structured expert elicitation with 4 experts was undertaken to quantify pre-trial uncertainty in the effectiveness of SWiM compared with usual care. All trial designs were simulated to estimate trial benefits: the reduction in the costs of an inefficient decision for future populations over 10 years. Trial designs offer value for money if trial benefits exceed trial costs.
Results:
For three inclusion criteria options (groups recently completing ‘diabetes remission’, ‘digital weight management’ or ‘specialist weight management’), the cost of the proposed trials was estimated to exceed the estimated trial benefit (value of the reduction in decision uncertainty) over 10 years. For the other three inclusion criteria options (groups recently completed ‘behavioural weight management’, ‘diabetes prevention programme’, or ‘all weight loss programmes’), 12 trial designs produced greater benefits than costs. The optimal trial design option would include ‘all weight loss programmes’, with 2 years follow-up and sample size n=2000.
Conclusion:
Investment in an RCT to evaluate the SWiM intervention with two years of follow-up patients completing a range of weight loss interventions offers the greatest value to the NHS.
A Pilot Study of a Gratitude Journaling Intervention to Enhance Spiritual Well-Being and Exercise Self-Efficacy in Black Breast Cancer Survivors
Authors: Cousin Lakeshia , Braithwaite Dejana , Anton Stephen , Zhang Zhongyue , Lee Ji-Hyun , Leewenburgh Christiaan , Lyon Debra
Published: October 2024

Background
Breast cancer (BC) survivorship presents significant health disparities, particularly affecting Black women, who experience a 40% higher BC death rate compared to White women. These disparities are exacerbated by comorbidities, which contribute to poorer overall health outcomes. Additionally, Black BC survivors often face psychosocial challenges, including increased stress and lower well-being, which can lead to adverse physical health effects. This pilot study aims to assess the feasibility and efficacy of a culturally sensitive gratitude journaling intervention designed to enhance spiritual well-being, exercise self-efficacy, and reduce inflammation among Black BC survivors.
Methods
This pilot study employed a two-group, parallel random-assignment experimental design to compare a gratitude journaling intervention with a general memory journaling control group. Twenty-six Black women aged 40 to 70 years with a history of BC were randomly assigned to either the gratitude journaling intervention group (n = 13) or the control group (n = 13). The gratitude intervention group engaged in gratitude journaling twice weekly for eight weeks, while the control group documented daily memories. Outcomes measured included dispositional gratitude, spiritual well-being, perceived stress, exercise self-efficacy, and inflammatory biomarkers. Statistical analyses included the Wilcoxon rank sum test and Fisher's exact test.
Results
Twenty-six participants were enrolled, with 73% completing baseline and post-intervention assessments. The intervention group showed a significant improvement in spiritual well-being (p = 0.014) with a large effect size (ES = 0.57). Marginal improvements in exercise self-efficacy were also observed (ES = 0.39). Although there were no significant differences in dispositional gratitude and perceived stress between groups, the intervention group exhibited trends toward increased gratitude and reduced stress. Inflammatory biomarker analysis indicated non-significant changes, though IL-6 levels increased in the intervention group.
Conclusion
This study demonstrates the feasibility and acceptability of a gratitude journaling intervention among Black BC survivors. The intervention significantly enhanced spiritual well-being and showed promise in improving exercise self-efficacy, suggesting its potential for promoting holistic wellness in this population. These findings provide a foundation for future larger-scale randomized controlled trials to further evaluate the efficacy of gratitude-based interventions for Black BC survivors.
Trial registration:
This study was registered prospectively at ClinicalTrials.gov (NCT05473026) on 07-01-2022.
Clinical practice pattern of Pneumocystis pneumonia prophylaxis in systemic lupus erythematosus: a cross- sectional study from lupus registry of nationwide institutions (LUNA)
Authors: Onishi Takahisa , Sada Ken-ei , Hayashi Keigo , Miyawaki Yoshia , Yoshimi Ryusuke , Shimojima Yasuhiro , Ohno Shigeru , Kajiyama Hiroshi , Ichinose Kunihiro , Sato Shuzo , Fujiwara Michio , Yajima Nobuyuki , Kida Takashi , Matsuo Yusuke , Nishimura Keisuke , Yamane Takashi
Published: October 2024

Background
Pneumocystis jirovecii pneumonia (PCP) is an opportunistic infection in patients undergoing immunosuppressive therapy, such as glucocorticoid (GC) medication, for systemic autoimmune diseases like systemic lupus erythematosus (SLE). Despite the confirmed effectiveness of PCP prophylaxis, its clinical administration, especially in conjunction with GC dosage, remains unclear. We aimed to describe the clinical practice of PCP prophylaxis in association with SLE in Japan, evaluate the relationship between GC dosage and PCP prophylaxis, and explore the practice patterns associated with PCP prophylaxis.
Methods
This cross-sectional study used data from the Lupus Registry of Nationwide Institutions in Japan from 2016 to 2021 and included patients diagnosed with SLE. Using descriptive statistics, multivariate analysis, and decision tree analysis, we examined the prevalence of PCP prophylaxis and its association with the GC dosage.
Results
Out of 1,460 patients, 21% underwent PCP prophylaxis. The frequency of prophylaxis decreased with a decrease in GC dosage. After adjusting for confounders, logistic regression revealed the odds ratio of PCP prophylaxis increased with higher prednisolone (PSL) doses: 3.7 for 5 ≤ PSL < 7.5 mg, 5.2 for 7.5 ≤ PSL < 10 mg, 9.0 for 10 ≤ PSL < 20 mg, and 43.1 for PSL ≥ 20 mg, using PSL < 5 mg as the reference. Decision tree analysis indicated that a PSL dosage of < 11 mg/day and immunosuppressant use were key determinants of PCP prophylaxis.
Conclusion
This study provides valuable insights into PCP prophylaxis practices in patients with SLE in Japan, underscoring the importance of GC dosage and concomitant immunosuppressant use.
Combined microsurgical and endovascular approach in the hybrid operating angiosuite: A case series on blood-blister intracranial aneurysms
Authors: Ahn Hong Suk , Choi Jai Ho , Kim So Yeon , Jeon Hong Jun , Cho Byung Moon
Published: October 2024

Purpose: Blood blister-like aneurysms (BBAs) are small, fragile vascular lesions that develop on the walls of the supraclinoid internal carotid artery. This absence of a neck complicates surgical and endovascular treatment options. The hybrid operating angiosuite (HOA), which integrates traditional surgical techniques with endovascular interventions, provides an innovative approach to managing BBAs. This study aims to evaluate a series of clinical cases focused on treating BBAs using a combination of microsurgical extracranial-intracranial bypass and endovascular trapping within the HOA.
Methods:We analyzed a series of patients with BBAs treated from 2014 to 2022. Skilled bimanual neurovascular surgeons implemented treatment plans using both microsurgical and neurointerventional techniques across four distinguished neurosurgery centers: Kangdong Sacred Heart Hospital, Seoul St. Mary’s Hospital, Yongin Severance Hospital, and International St. Mary’s Hospital. Clinical outcomes were measured using the Glasgow Outcome Scale (GOS) at discharge and the modified Rankin Score (mRS) during follow-up, with scores of 0–2 indicating favorable outcomes. Follow-up imaging via computed tomography angiography or magnetic resonance angiography was conducted on average 6–12 months post-procedure to assess BBA recurrence and graft vessel patency.
Results: Seven patients (average age, 45 years) were treated at the HOA. The surgical approach included high-flow bypass in five patients and superficial temporal artery double-barrel bypass in two. Follow-up imaging revealed no BBA recurrences and maintained patency of bypass flow.
Conclusion: Our findings suggest that a hybrid approach offers a safer and more effective strategy for managing BBAs, potentially improving patient outcomes.
Choroidal Blood Flow Changes in Central Serous Chorioretinopathy: Impact on Pigment Epithelial Detachment and Subretinal Fluid
Authors: Xu Amin , Lai Qiaoling , Sun Gongpeng , Chen Zhen , Chen Changzheng
Published: October 2024

Purpose
Investigate how choroidal blood flow affacts pigment epithelial detachment (PED) and subretinal fluid (SRF) in central serous chorioretinopathy (CSC) .
Methods
We collected CSC patients, dividing into group with PED and without PED, as well as healthy individuals. Using SS-OCT to measure three-dimensional choroidal vascular index (CVI), choroidal vascular volume (CVV), SRF and PED area and volume, subfoveal choroidal thickness (SFCT), and the choroid thickness beneath the highest point of PED(PED-ct). Image-J was used to analyze and calculated flow void area (FVa) and flow void area percentage (FV%) of choriocapillary.
Results
The SFCT, three-dimensional CVI, CVV, FVa and FV% of CSC patients were higher than normal group, compared to CSC without PED, three-dimensional CVI in CSC with PED is higher, both difference was significant (P < 0.05). Among CSC patients, the FV% and SRF area, the CVV and SFCT all showed positive correlation. In CSC with PED, the CVV and PED-ct, the FVa, FV% and PED, SRF area were both positively correlated.
Conclusions
The occurrence of PED and SRF in CSC is not only related to the low blood flow of choriocapillary, but also related to the increase in the vascular density and the expansion of Sattler and Haller.
Analysis of Vertical Loading Forces on three different sagittal split ramus osteotomy modifications
Authors: Nascimento Frederico Felipe Antonio Oliveira , Stella John Paul , Klüppel Leandro Eduardo , de Moraes Márcio
Published: October 2024

Objective: The study aimed to compare and analyze the in vitro mechanical behavior of vertical load on three different sagittal split osteotomy designs proposed by Epker, Wolford, and Wyatt, focusing on the implications of each design on mandibular stability.
Study Design: Synthetic polyurethane hemi-mandibular models were used to replicate the osteotomies according to the designs suggested by Epker, Wolford, and Wyatt. Each model group was subjected to linear vertical loading until system failure, with peak load and deformation recorded. The study utilized a controlled sample preparation and loading test to ensure standardization across all groups. Analysis of variance (ANOVA) and the Tukey test were applied to compare the mechanical responses among the different osteotomy designs.
Results: The findings indicated no significant difference in displacement and vertical loading resistance between Groups 1 and 2; however, differences were found in Group 3 (Wyatt), where increased mandibular fragility was observed when screws were placed in thinner bone areas. Statistical analysis showed that the modifications in the osteotomy design led to significant differences in mechanical behavior, particularly in Group 3, highlighting the importance of bone thickness and osteotomy technique on postoperative early stability and mechanical stress distribution.
Conclusions: The study concludes that the choice of sagittal split osteotomy design significantly impacts the mechanical behavior under vertical loading, with particular emphasis on the importance of bone thickness at fixation points and the technique used. The findings suggest a preference for the modification proposed in group 1 and 2 in cases where increased mandibular stability and minimized postoperative complications are desired.
High seroprevalence of yellow fever, dengue, and chikungunya viruses in the Greater Darfur region of Sudan: Implications for national health policy and surveillance
Authors: Mohamed Nouh Saad , Siddig Emmanuel Edwar , Musa Abdualmoniem Omer , Elduma Adel , Ahmed Ayman
Published: October 2024

Objectives
Arboviruses pose a significant global health challenge. This study investigated the seroprevalence of major human arboviral infections, including yellow fever (YFV), dengue (DENV), Crimean-Congo hemorrhagic fever (CCHF), Rift Valley fever (RVFV), West Nile virus (WNV), and chikungunya (CHIKV), in the Darfur region from September to December 2018. ELISA-IgM was used to detect antibodies. RT‒PCR was used to confirm YFV infection in positive IgM samples.
Results
A total of 152 blood samples were collected, with 123 (80.9%) from males and 29 (19.1%) from females. The participants were grouped by age: 50 (32.9%) were under 20 years, 96 (63.2%) were aged 20–45 years, and 6 (3.9%) were over 45 years. The seroprevalence rates for YFV, DENV, and CHIKV were 68 (44.7%), 23 (15.1%), and 5 (3.3%), respectively. There were 11 confirmed YFV cases (7.2%) using RT-PCR. Among these, 3/11 were positive for DENV-IgM, and 1/11 was positive for CHIKV-IgM. Among the 68 YFV-positive individuals, 15 (22.1%) had been exposed to DENV, and 2 (2.9%) had been exposed to CHIKV. Coexposure to DENV and CHIKV was detected in 3 (1.9%) patients, while 2 (1.3%) patients had triple exposure to YFV, CHIKV, or DENV. No exposure to CCHF, RVFV, or WNV was detected.
Hydrocephalus Surgery 2.0: A Systematic Review of the Robotic Effectiveness in Neurosurgical Interventions
Authors: Łajczak Paweł , Łajczak Anna
Published: October 2024

Background: Hydrocephalus is a neurological condition characterizing the accumulation of cerebrospinal fluid in the ventricles of the brain, causing an increased intracranial pressure that may injure the neurological tissue. Traditional surgical treatment, with ventriculoperitoneal (VP) shunt and endoscopic third ventriculostomy (ETV), may lead to complications such as shunt obstruction and inaccurate catheter placement. Robotics-assisted (RA) surgery is promising for enhanced precision with improved outcomes. The objective of this systematic review is to assess the clinical effectiveness, complications, and benefits of robotic-assisted surgical interventions in the case of hydrocephalus.
Methods: PRISMA-guided literature search was done in databases including PubMed, Web of Science, Cochrane Reviews, Scopus, and Embase. Inclusion criteria encompassed English language, original, peer-reviewed journal articles in robotic-assisted surgical interventions in hydrocephalus. Patient demographics, robotic systems used, procedural results, and complication details were extracted.
Results: In total, 12 of the articles discussed robotic-assisted interventions for hydrocephalus. The robotic systems used included ROSA, NaoTrac, Remebot, and more. The findings established that the robotic systems are very accurate. Almost all the studies showed successful outcomes with minimum robot-related complications like minor bleeding or conversion to manual surgery. As researchers get more experience, robotic systems are improving surgical efficiency and precision after the learning curve.
Conclusions: Robotic assistance in hydrocephalus offers potential for advancement in achieving surgical precision and, thereby, reducing complications associated with conventional methods. Their high costs act as a limitation; however, their potential to enhance patient outcomes makes robotic systems an integral asset to neurosurgery practice. Future research should focus on large scale trials, long term outcomes, and cost-effectiveness analysis to optimize the integration of robotic systems in hydrocephalus management.
Desensitization reduces some COVID-19-associated symptoms in minors with allergic rhinitis
Authors: Zhang Mengni , Liu QiQi , Zhang Shipeng , Wang Xiaocui , Zhang Qinxiu
Published: October 2024

Objective
The aim of this study was to observe the symptoms after infection with coronavirus disease 19 (COVID-19) in minor and adult allergic rhinitis (AR) patients receiving different treatment therapies [Sublingual immunotherapy (SLIT) and conventional therapy].
Methods
We recruited a total of 398 patients diagnosed with AR from the clinical system and divided them into AR-S, with AR-S1 representing individuals aged < 18 years of age, and AR-S2 those ≥ 18 years of age, and AR-C groups based on their treatment modalities. Between December 2022 and February 2023, we documented the respiratory symptoms and common manifestations of AR patients infected with the novel coronavirus.
Results
The AR-S1 group may be associated with a reduced risk of symptoms after infection including dry and itchy (OR = 0.373, 95%Cl:0.184–0.755), headache (OR = 0.385, 95%Cl:0.196–0.758), fatigue (OR = 0.376, 95%Cl:0.188–0.751), chest tightness (OR = 0.160, 95%Cl:0.049–0.522), and some symptoms after improvement of infection (cough, fatigue).
Conclusion
Minor AR patients with SLIT can reduce some of the symptoms in COVID-19-infected patients.
Level of Evidence: 3
Protocol Development: Effectivity and Safety evaluation between topical L-ascorbic acid 15% serum compared to Retinol 0.1% serum in Anti Aging Therapy: A double blinded, randomized controlled trial, split face study in Indonesia
Authors: Yolanda Keiko , Novianto Endi , Agustin Triana , Friska Dewi
Published: October 2024

Background
The process of aging in which a progressive decrease in both the function and capacity of the body, which includes the skin may cause the skin surface to appear pale, fine wrinkles and atrophy of the epidermis and dermis layer which leads to a thinner, transparent and fragile appearance of the skin. A variety of methods have been developed to prevent and treat skin aging, including the use of vitamin C as an potent antioxidant which is found to be beneficial skin aging therapy.
Objective
This study aims to investigate the effectivity and safety of topical L-ascorbic acid 15% serum towards skin aging using the parameters such as wrinkle, spots, ultraviolet spots, pores and skin moisture.
Methods
The study is a randomized clinical trial with double disguise and split-face carried out at the Dermatology and Venereology outpatient clinic, Dr. Cipto Mangkunkusumo Hospital in January – February 2024. Subjects includes woman and man aged 35–65 years outpatient clinic. Vitamin C serum containing L-ascorbic acid 15% and retinol 0.1% serum, were given to the patients to apply, and skin analysis profile measuring instrument using the JANUS III, examining eight skin parameters: age, hyperpigmentation, UV spots, wrinkles, pores, elasticity, porphyrin, sebum, and moisture before and after application of the vitamin C serum and retinol.
Discussion
Ascorbic Acid is expected to attenuate photoaging and the natural aging of the skin by reducing oxidative stress caused by external and internal factors and by promoting collagen gene expression and maturation. The data acquired from this study will be used to make recommendations for anti-aging therapy that has superior results than standard therapies but produces minimal side effects.
Joint Association of Systemic Inflammatory Response Index and Sarcopenia with Mortality Among Cancer Survivors
Authors: Huang Zhifei , Peng Wenjia , Zhao Mengdie , Gao Bo , Qian Jing , Zhu Shuangqiu , Ren Mingdong , Jiang Tao , Yusuf Sulaiman Abdulahi Yusuf , He Zelai , jiang hao
Published: October 2024

Purpose
The aim of this study was to investigate the joint association of systemic inflammatory response index (SIRI) and sarcopenia with cancer-specific and all-cause mortality in cancer survivors.
Methods
The study cohort comprised US cancer survivors from the NHANES database, with data collected between 1999–2006 and 2011–2018. The researchers tracked deaths up to 31 December 2019 by linking the relevant records to those held by the (NDI). A weighted sampling design was employed, with participants stratified according to the median value of the SIRI. Cox regression models were employed to assess the association between SIRI, sarcopenia, all-cause mortality, and cancer-specific mortality.
Results
The study cohort comprised 1316 cancer survivors. Over a median follow-up period of 9.21 years, 523 all-cause deaths were recorded, including 163 cancer-specific and 360 non-cancer deaths. Adjusting for multiple confounders, elevated SIRI levels were significantly associated with increased risks of all-cause (HR = 1.90 [1.58–2.28], P < 0.001), cancer (HR = 1.88 [1.26–2.78], P = 0.002), and non-cancer mortality (HR = 1.93 [1.54–2.41], P < 0.001). Sarcopenia also emerged as a significant predictor of mortality. Individuals with sarcopenia faced a 50% higher risk of all-cause mortality (HR = 1.50 [1.18–1.91], P < 0.001) and a 54% higher risk of non-cancer mortality (HR = 1.54 [1.11–2.12], P = 0.009). However, the association with cancer mortality was not significant in the fully adjusted model. When both sarcopenia and elevated SIRI were present, the risk was the highest for all-cause (HR = 2.54 [1.92–3.37], P < 0.001), cancer (HR = 2.29 [1.19–4.40], P = 0.014), and non-cancer mortality (HR = 2.63 [1.78–3.89], P < 0.001). Elevated SIRI alone was linked to significant risks for all-cause (HR = 1.91 [1.51–2.42], P < 0.001), cancer (HR = 1.95 [1.28–2.97], P = 0.002), and non-cancer mortality (HR = 1.92 [1.46–2.53], P < 0.001). Sarcopenia alone significantly increased the risk of all-cause mortality (HR = 1.63 [1.01–2.56], P = 0.043) but not cancer mortality.
Conclusion
Our study is the first to demonstrate the joint association between the SIRI and sarcopenia with mortality among cancer survivors. These findings underscore the importance of assessing and managing these two factors in cancer survivors to reduce the risk of death and improve survival outcomes.
Identification of a GII.P21-GII.13 recombinant norovirus strain, mutations shift its binding spectra to host receptor glycans
Authors: Yu yongxin , Chen Yunfei , Zhou Zexian , Dong Lei , Jin Miao , Wang Yongjie
Published: October 2024

Norovirus is a pervasive pathogen that causes global outbreaks of viral gastroenteritis. Previous studies suggest that histo-blood group antigens (HBGAs) can interact with norovirus, facilitating its entry of host cells and significantly impacting its evolution. In this study, a complete genome of recombinant GII.13[GII.P21] norovirus from fecal samples was analyzed, revealing a weak effect of genomic recombination on the replication efficiency of GII.13[GII.P21]. Molecular dynamics simulations of GII.13 norovirus P proteins from 1978 to 2019 showed changes in binding capacity with HBGAs. Initially, GII.13 proteins bound A or B/H-type HBGAs, but subsequent residue mutations resulted in a loss of this binding capacity, favoring binding to the HBGA type I precursor (Lec) over A or B/H and Lewis antigens.
Single-Cell Analysis Reveals Ide-cel and Cilta-cel Characteristics That Influence Efficacy
Authors: Freeman Ciara , Noble Jerald , Song Xiaofei , Menges Meghan , Abraham-Miranda Julieta , Corallo Salvatore , De Avila Gabriel , Castaneda Omar , Liu Hien , Alsina Melissa , Nishihori Taiga , Shain Kenneth , Baz Rachid , Blue Brandon , Cruz Ariel Grajales , Hansen Doris , Atkins Reginald , Locke Frederick
Published: October 2024

Chimeric antigen receptor T-cells targeting BCMA have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM) with two approved products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). To explore biological differences, we analyzed pre-infusion products (IP) and CAR-enriched peripheral blood mononuclear cells (PBMCs) at expansion using single-cell RNA sequencing (scRNAseq) from 52 samples. Post-quality control 247,500 cells (117,530 CD4, 80,939 CD8) were analyzed. We found that ide-cel IPs from durable responders (DR) had higher construct expression, enhanced NFKB signaling, and anti-apoptotic signatures, correlating with improved progression free survival. CAR + ide-cel PBMCs in DRs showed upregulated ribosomal genes and higher CD27, KLF2, TCF7 expression. Relative to ide-cel, cilta-cel CAR + cells showed higher expression of CD27, GZMK, TCF7, and a 4-fold increase in CAR expression. In addition, the TCR repertoire was less clonal and more diverse. This study elucidates the distinct characteristics of ide-cel and cilta-cel, offering insights into their differing clinical efficacy.
Stabilization of cyclo-N6 by insertion into [18]-annulene: a DFT study
Authors: Pichierri Fabio
Published: October 2024

The elusiveness of hexazine (a.k.a. hexaazabenzene) and its perhydrogenated derivative, hexazinane, prompted the author to investigate the possibility of stabilizing the six-membered nitrogen ring by inserting it into [18]-annulene. The resulting compound is made of a central N6 ring surrounded by an outer ring of 18 carbon atoms that prevents its decomposition into dinitrogen. The N6 ring is non-planar and with a chair-like conformation that does not undergo conformational isomerization. The designed molecule can be stabilized either by oxidation to a hexa-oxide derivative or by coordination of ZnCl+. Furthermore, a triangle-shaped macrocyclic isomer made of three pyridazine moieties connected to each other by ethylene bridges represents a possible precursor in the synthesis of the N6-embedded hydrocarbon. By employing an alkali or alkaline-earth metal cation that coordinates the three pyridazine monomers it becomes possible to bring their nitrogen atoms in close proximity so that a subsequent aromatic fusion reaction could be attempted.
Mechanical properties and damage characterization of cracked granite after cyclic temperature action
Authors: Bao Xiankai , Wang Lingyu , Cui Guangqin , Qiao Jianlong , Tian Baolong , Huang Shunjia , Wang Lizhi
Published: October 2024

To study investigates the mechanical properties and damage characteristics of granite under the influence of cyclic temperature and crack inclination, uniaxial compression tests were conducted on granite with prefabricated cracks at cyclic temperatures of 30 °C, 50 °C, 70 °C, 100 °C, and 130 °C. The mechanical properties and damage characteristics of the granite were analyzed using characteristic stress, acoustic emission parameters, damage variables, fractal dimensions, and SEM. The results indicate that: (1) At the same cyclic temperature, the granite with a 45 ° prefabricated crack exhibits the lowest peak stress, elastic modulus, and σci/σm, resulting in a significant reduction in the specimen's load-bearing capacity. At the same crack inclination, the granite at 70 °C shows the highest peak stress, elastic modulus, σcc/σm, and σci/σm, with a noticeable reduction in internal microcracks. (2) At the same cyclic temperature, the b-value drop point of acoustic emissions in the 45 ° prefabricated crack specimen occurs earlier, indicating the earlier formation of the main crack inside the specimen. At the same crack inclination, the cumulative ring count and total energy of acoustic emissions are the lowest at 70 °C, indicating the least thermal damage to the specimen. (3) At the same cyclic temperature, the damage in the 45 ° prefabricated crack granite specimen develops more rapidly, with the damage variable reaching above 0.8 at the damage stress point, and the fluctuation in fractal dimension is minimal, indicating strong orderliness in the development of internal microcracks. At the same crack inclination, the fractal dimension of the granite specimen significantly increases at 70 °C, and the dispersion of damage proportion increases significantly after 70 °C. (4) At a cyclic temperature of 70 °C, the changes in cracks and pores in the granite uniaxial compression specimen are evident, with relatively mild damage; the final failure modes of specimens under various cyclic temperatures and crack inclinations differ significantly, transitioning from tensile-shear failure to shear failure and tensile failure as the crack inclination increases. The research results can provide theoretical references for understanding the mesoscopic damage and failure mechanisms of granite under different cyclic temperatures and crack inclinations.
Skew-pair fusion theory: An interpretable multimodal fusion framework
Authors: Hu Zhiwen , Hong HaiBo , Cai Xuqiang , Li Linxiang , Ren Zichu , Ma Xi-Ao , Jiang Haihua , Wang Xun
Published: October 2024

Multimodal fusion models have the potential to harness the homogeneity and heterogeneity of multimodal data as a performance turbocharger in multifaceted domains. Nonetheless, a formal fusion theory for fusion-pair alignment and sparsity assignment in latent representation spaces remain underdeveloped. Here we disentangle a dual cross-modal heterogeneity paradigm ingrained within the fabric of the involved models and present a universal skew-pair fusion theory. This holistic framework formalizes a dual interpretable mechanism—universal skew-layer alignment and bootstrapping sparsity—to bolster fusion gain in hybrid neural networks. Our comprehensive validation experiments across text-audio, audio-video, image-text, and text-text fusion tasks, demonstrating its empirical advantages over conventional late- and pairwise-fusion strategies. Inspired by multisensory integration, we further curate a sparsest skew-pair fusion network (SSFN) that outperforms late- and pairwise-fusion counterparts, even in seemingly “unimodal” fusion scenarios such as text-text fusion. Our findings suggest that this bioinspired framework could serve as a benchmark for reframing the multidisciplinary perspective on multimodal fusion and multisensory integration.
N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis
Authors: Ribeiro Mariana O. , Oliveira Mafalda , Nogueira Verónica , Costa Vítor , Teixeira Vitor
Published: October 2024

Background
Seipin is a protein encoded by the BSCL2 gene in humans and SEI1 gene in yeast, forming an Endoplasmic Reticulum (ER)-bound homo-oligomer. This oligomer is crucial in targeting ER-lipid droplet (LD) contact sites, facilitating the delivery of triacylglycerol (TG) to nascent LDs. Mutations in BSCL2, particularly N88S and S90L, lead to seipinopathies, which correspond to a cohort of motor neuron diseases (MNDs) characterized by the accumulation of misfolded N88S seipin into inclusion bodies (IBs) and cellular dysfunctions.
Methods
Quantitative untargeted mass spectrometric proteomic and lipidomic analyses were conducted to examine changes in protein and lipid abundance in wild-type (WT) versus N88S seipin-expressing mutant cells. Differentially expressed proteins were categorized into functional networks to highlight altered protein functions and signaling pathways. Statistical comparisons were made using unpaired, two-tailed Student's t-tests or two-way ANOVA. P-values < 0.05 are considered significant.
Results
In a well-established yeast model of N88S seipinopathy, misfolded N88S seipin forms IBs and exhibits higher levels of ER stress, leading to decreased cell viability due to increased reactive oxygen species (ROS), oxidative damage, lipid peroxidation, and reduced antioxidant activity. Proteomic and lipidomic analyses revealed alterations in phosphatidic acid (PA) levels, associated with disrupted inositol metabolism and decreased flux towards phospholipid biosynthesis. Importantly, deregulation of lipid metabolism contributed to ER stress beyond N88S seipin misfolding and IB formation. Additionally, the model exhibited deregulated iron (Fe) homeostasis during lifespan. N88S seipin-expressing cells showed impaired ability to cope with iron deficiency. This was linked to changes in the expression of Aft1p-controlled iron regulon genes, including the mRNA-binding protein CTH2 and the high-affinity iron transport system member FET3, in a p38/Hog1p- and Msn2p/Msn4p-dependent manner. Importantly, we unraveled a novel link between inositol metabolism and activation of the iron regulon in cells expressing the N88S seipin mutation. Despite iron accumulation, this was not associated with oxidative stress.
Conclusions
The study highlights that the effects of N88S seipin mutation extend beyond protein misfolding, with significant disruptions in lipid metabolism and iron homeostasis. This research marks a significant advance in understanding and defining the roles of proteins and signaling pathways that contribute to human seipinopathy. Altered cellular processes, as well as potential therapeutic targets and biomarkers, were identified and can be explored in translational studies using human cell models.
Transcriptomic Analyses and Novel Organoid and Xenograft Modeling Reveals Potential Drug Sensitivities in a KRAS G12V-Mutant Colorectal Cancer Brain Metastasis
Authors: Panovska Dena , Nasajpour Emon , Xing Yao Lulu , Gwyn Alexa , Morales Daniella , Chaudhary Suhani , Sathe Anuja , Tran Caitlynn To-Duyen , Feng Zhi-Ping , Rada Cara Coleen , Nakano Michitaka , Habib Pardes , Rabin Leif , Chang Steven D. , Kuo Calvin J. , Gui Chloe , Zadeh Gelareh , Nirschl Jeffrey J. , Vogel Hannes , Gephart Melanie Hayden , Ji Hanlee P. , Petritsch Claudia K.
Published: October 2024

Brain metastases (BM) occur in 2.3% of patients with colorectal cancer (CRC), which is the second leading cause of cancer deaths globally. Despite aggressive treatment like surgery and chemo-irradiation, median survival for patients with BM originating from CRC (CRC-BM) remains poor at 5.3 months, highlighting the need for improved therapies. Next-generation sequencing has identified KRAS mutations in approximately 40% of metastatic CRC cases. Therapies targeting mutant KRAS and downstream MAPK pathway components exist, but their effectiveness is often limited by therapy resistance, underscoring the need for novel drug targets beyond the MAPK pathway. Additionally, there is a lack of accurate preclinical models for CRC-BM. In this study, we generated a patient-derived organoid model (PDO) from a KRAS G12V mutant CRC-BM surgical sample. PDO consistently formed intracranial tumors in both male and female mice, indicative of their stable malignant potential. Both the PDO and PDO-derived xenografts (PDoX) retained the KRAS G12Vmutation and key epithelial and mesenchymal markers, closely resembling the original BM. Spatial transcriptome analysis of the patient BM revealed six distinct functional tumor epithelial cells, with features such as enhanced MAPK signaling and upregulated ER-stress. Bulk RNA sequencing analyses showed differences between PDO and PDoX, which reflected in vitro growth conditions. PDO, PDoX, and patient BM shared pathways including ER-stress and unfolded protein response (UPR) pathway. DNA methylation profiling revealed a varying number of differentially methylated regions between samples derived from primary CRC and BM, and comparable numbers of these regions between PDO and PDoX. Proof-of-concept was demonstrated by pharmacologically inhibiting RAS-RAF-MAPK signaling, and more effectively key molecules in the ER-stress sensor/UPR pathways. In conclusion, we developed a patient-derived organoid (PDO) model from a KRAS G12V mutant CRC-BM, closely mirroring the tumor’s clinical characteristics. Targeting the MAPK and ER/UPR pathways significantly reduced PDO viability, revealing key therapeutic vulnerabilities.
The Relations between Ethical Reasoning, Moral Intuitions, and Foreign Language among Engineering Students in the US, Netherlands, and China
Authors: Clancy Rockwell , Zhu Qin , Streiner Scott , Gammon Andrea , Thorpe Ryan
Published: October 2024

Background: Ethical knowledge and reasoning have been adopted as the goals of engineering ethics education, and measures of ethical reasoning have been developed by researchers and with participants in mostly the US. But US participants are global outliers on various psychological and social characteristics, and engineering is increasingly global. Further, it is also unclear whether ethical reasoning results in more ethical judgments or behaviors. To address these issues, this study sought to better understand the natures of and relations between ethical reasoning, moral intuitions, and foreign language among engineering students across multiple countries. Students at universities in the US, Netherlands, and China completed the ESIT (Engineering and Science Issues Test), MFQ (Moral Foundations Questionnaire), and demographics items online. Statistical hypothesis testing and correlation analysis were used to examine relations between study variables.
Results: (1) Students in the US evidenced higher rates of ethical reasoning than those in the Netherlands or China. (2) Ethics education was associated with lower rates of self-based reasoning. (3) Ethical reasoning was positively related to intuitions about care and fairness, and negatively relations to intuitions about loyalty, authority, and sanctity. (4) Students in China care more about loyalty, authority, and sanctity, and less about care and fairness, than those in the US or Netherlands. (5) Foreign language was associated with higher rates of ethical reasoning and less concern with sanctity.
Conclusions: Rather than ethical reasoning, education should aim at reducing self-based reasoning, and researchers must study a broader range of national groups to better understand how language affect ethics education.
A combined method for the evaluation of contributing factors to maritime dangerous goods transport accidents
Authors:   Zonguldak Bulent Ecevit University, Maritime Faculty, Department of Maritime Transportation and Management Engineering, Kdz. Eregli, Zonguldak, Türkiye., Eski Özge , Tavacioglu Leyla ,   Istanbul Technical University, Maritime Faculty, Department of Basic Sciences, Tuzla, Istanbul, Türkiye.
Published: October 2024

This paper evaluates the contributing factors to maritime dangerous goods (DG) transport accidents by integrating the Entropy Weight (EW) and Grey Relational Analysis (GRA) methods. For this purpose, investigation reports of maritime DG transport accidents that occurred worldwide between 2000 and 2023 are derived from the International Maritime Organization’s Integrated Shipping Information System (IMO GISIS) database’s Marine Casualties and Incidents (MCI) module. Eleven main ship operations and thirteen primary causes were selected by analysing accident investigation reports. The weights of main ship operations are calculated utilizing the EW method. The correlational degrees of the primary causes are then calculated using the GRA method. Most maritime DG transport accidents occur during unberthing, bunkering, and pilotage operations. The most common contributing factors of maritime DG transport accidents are collisions and occupational accidents. Specifically, maritime DG transport accidents are most likely to be caused by collisions during sailing, passage, maneuvering, and bunkering operations, as well as occupational accidents during cargo loading, anchoring, berthing, and mooring operations. The results of this paper can support stakeholders in developing the needed policies to guarantee the safety of maritime DG transport.
Metamodernismi. Kirjallisuuden ja kulttuurin muutos 2000-luvun Suomessa
Authors: Anttonen Salli , Hallila Mika , Helle Anna , Marttinen Heta , Sandbacka Kasimir
Published: October 2024

Metamodernism. The Change in Literature and Culture in 21st Century Finland maps the state and transformation of contemporary Finnish literature and culture since the postmodern era. The work highlights, from different perspectives, how this change and the metamodernism it represents are manifested in contemporary Finnish literature and culture. The collection aims to offer a broad understanding of how metamodernism is seen and implemented in Finnish culture. Metamodernism outlines the framework theoretically, conceptualizing the new phase as a nascent metamodernity that is taking shape on a global scale in different societies and cultures, especially in the Western world. The book’s 15 chapters, although the majority focus on literature, explore a wide range of genres including rap poetry, experimental poetry and prose, speculative fiction and children’s literature.