bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel DNA methylome biomarkers associated with adalimumab response in rheumatoid arthritis patients
Authors: Hageman Ishtu , Mol Femke , Atiqi Sadaf , Joustra Vincent , Sengul Hilal , Henneman Peter , Visman Ingrid , Hakvoort Theodorus , Nurmohamed Mike , Wolbink Gertjan , Levin Evgeni , Li Yim Andrew Y.F. , D’Haens Geert , de Jonge Wouter J.
Published: December 2023

Background and aims

Rheumatoid arthritis (RA) patients are currently treated with biological agents mostly aimed at cytokine blockade, such as tumor necrosis factor-alpha (TNFα). Currently, there are no biomarkers to predict therapy response to these agents. Here, we aimed to predict response to adalimumab (ADA) treatment in RA patients using DNA methylation in peripheral blood (PBL).

Methods

DNA methylation profiling on whole peripheral blood from 92 RA patients before the start of ADA treatment was determined using Illumina HumanMethylationEPIC BeadChip array. After 6 months, treatment response was assessed according to the European Alliance of Associations for Rheumatology (EULAR) criteria for disease activity. Patients were classified as responders (Disease Activity Score in 28 Joints (DAS28) < 3.2 or decrease of 1.2 points) or as non-responders (DAS28 > 5.1 or decrease of less than 0.6 points). Machine learning models were built through stability-selected gradient boosting to predict response prior to ADA treatment with predictor DNA methylation markers.

Results

Of the 94 RA patients, we classified 49 and 43 patients as responders and non-responders, respectively. We were capable of differentiating responders from non-responders with a high performance (area under the curve (AUC) 0.76) using a panel of 27 CpGs. These classifier CpGs are annotated to genes involved in immunological and pathophysiological pathways related to RA such as T-cell signaling, B-cell pathology, and angiogenesis.

Conclusion

Our findings indicate that the DNA methylome of PBL provides discriminative capabilities in discerning responders and non-responders to ADA treatment and may therefore serve as a tool for therapy prediction.
Experimental analysis and biaxial biomechanical behaviour of ex-vivo sheep trachea
Authors: Pandelani Thanyani , Ngwangwa Harry , Nemavhola Fulufhelo
Published: December 2023

Besides surgery, there are currently no other established methods for routine treatment of tracheal pathologies such a tracheal stenosis or tracheal and airway tumors. Even with several attempts to repair the infected trachea with artificial and natural prostheses, there is a need for the fundamental understanding of the tissue’s mechanical behaviour. The purpose of this study was to investigate the mechanical behaviour of the tracheal tissue under biaxial tensile loading. Furthermore, the study examines the material properties of the tissue through a study of the model parameters for six constitutive models. Materials and methods: The fourteen (n = 14) specimens of sheep trachea (Vleis Merino) measured to be ∼30 × 20 mm where only the effective area of ∼25 × 16 mm was subjected to engineering strain. In this study, we assume that the tracheal tissue is anisotropic and incom-pressible, therefore we apply and study the material parameters from six different constitutive material models. Results: The results show that the tracheal tissue is twice as stiff along the circumferential direction as it is along the longitudinal direction. It is also observed that the material properties are different (non-homogeneous) along the trachea. Conclusion: The findings of this study will benefit computational models for the study of tracheal diseases or injuries. Furthermore, these findings will assist in the development of regenerative medicine for different tracheal pathologies and in the bioengineering of replacement tissue in cases of damage.
The role of repetitive transcranial magnetic stimulation therapy in functional bowel disease
Authors: Li Guangyao , Lv Tingcong , Jin Binghui , Fan Zhe
Published: December 2023

Objective

This study investigates the effectiveness of repetitive transcranial magnetic stimulation (rTMS) as a biophysical therapy for alleviating symptoms of functional bowel disorder (FBD) and associated psychological symptoms by targeting the brain-gut axis.

Methods

We conducted a comparative analysis involving 226 subjects, comprising the FBD group (n = 113) and a healthy control group (n = 113). Within the FBD group, participants were further divided into those who received rTMS therapy (FBD treatment group, n = 63) and those who did not (FBD control group, n = 50). The FBD treatment group was subcategorized based on the number of rTMS treatments received. We evaluated various factors, including gender, age, monthly household income, daily activity level, and sleep quality, as potential risk factors for FBD. Severity assessments of FBD and associated symptoms (constipation, anxiety, depression, and somatization disorders) were conducted using validated scales before and after treatment.

Results

Our findings revealed a higher incidence of FBD in women, with most cases emerging at age 50 or older. We identified lower monthly household income, reduced daily activity levels, and poorer sleep quality as factors associated with a higher likelihood of FBD. FBD patients exhibited higher scores for constipation, anxiety, depression, and somatization disorders compared to healthy controls. rTMS therapy was effective in reducing gastrointestinal symptoms, anxiety, depression, and somatization disorders among FBD patients. Notably, the extent of improvement was positively correlated with the number of rTMS sessions. No adverse effects were observed during the study.

Conclusion

Our study underscores the efficacy of biophysical therapy, specifically repetitive transcranial magnetic stimulation, in mitigating FBD symptoms and associated psychological distress. The treatment’s effectiveness is positively linked to the frequency of rTMS sessions.
An artificial intelligence-assisted diagnostic system for the prediction of benignity and malignancy of pulmonary nodules and its practical value for patients with different clinical characteristics
Authors: Zhang Lichuan , Shao Yue , Chen Guangmei , Tian Simiao , Zhang Qing , Wu Jianlin , Bai Chunxue , Yang Dawei
Published: December 2023

Objectives

This study aimed to explore the value of an artificial intelligence (AI)-assisted diagnostic system in the prediction of pulmonary nodules.

Methods

The AI system was able to make predictions of benign or malignant nodules. 260 cases of solitary pulmonary nodules (SPNs) were divided into 173 malignant cases and 87 benign cases based on the surgical pathological diagnosis. A stratified data analysis was applied to compare the diagnostic effectiveness of the AI system to distinguish between the subgroups with different clinical characteristics.

Results

The accuracy of AI system in judging benignity and malignancy of the nodules was 75.77% (p < 0.05). We created an ROC curve by calculating the true positive rate (TPR) and the false positive rate (FPR) at different threshold values, and the AUC was 0.755. Results of the stratified analysis were as follows. (1) By nodule position: the AUC was 0.677, 0.758, 0.744, 0.982, and 0.725, respectively, for the nodules in the left upper lobe, left lower lobe, right upper lobe, right middle lobe, and right lower lobe. (2) By nodule size: the AUC was 0.778, 0.771, and 0.686, respectively, for the nodules measuring 5–10, 10–20, and 20–30 mm in diameter. (3) The predictive accuracy was higher for the subsolid pulmonary nodules than for the solid ones (80.54 vs. 66.67%).

Conclusion

The AI system can be applied to assist in the prediction of benign and malignant pulmonary nodules. It can provide a valuable reference, especially for the diagnosis of subsolid nodules and small nodules measuring 5–10 mm in diameter.
Factors associated with long COVID syndrome in a Colombian cohort
Authors: Martínez-Ayala María Camila , Proaños Nadia Juliana , Cala-Duran Julian , Lora-Mantilla Alvaro Jose , Cáceres-Ramírez Catalina , Villabona-Flórez Silvia Juliana , Camacho-López Paul Anthony
Published: December 2023

Introduction

After acute phase of SARS-CoV-2 infection, some patients persist with clinical symptoms, a phenomenon known as Long COVID syndrome. It is necessary to understand the factors associated with the persistence of these symptoms to develop individualized preventive approaches and effectively address this challenge.

Objective

To determine the factors associated with the persistence of symptoms six months after COVID-19 infection.

Materials and methods

A ambidirectional cohort, single-center study, that included individuals previously diagnosed with COVID-19 by real-time polymerase chain reaction (PCR) positive test, who were followed for a period of six months. Univariate, bivariate and a multivariate binomial regression model were performed to determine risk factors associated with the persistence of COVID-19 symptoms at the six months of follow-up.

Results

The prevalence of long COVID syndrome was 47%. Age demonstrated no significant association with Long COVID (RR 0.999 [95% CI 0.996–1.002]); however, female sex (RR 1.148 [95% CI 1.038–1.268]), requirement of mechanical ventilation (RR 1.278 [95% CI 1.050–1.555]), presence of Chronic Obstructive Pulmonary Disease (COPD) (RR 1.340 [95% CI 1.104–1.626]), Rheumatic Disease (RR 1.259 [95% CI 1.055–1.504]) and the Hospitalization Type: General Hospitalization (RR 1.247 [95% CI 1.090–1.427]) and ICU Hospitalization (RR 1.490 [95% CI 1.221–1.818]) were significantly associated with the persistence of symptoms at the six month of follow-up.

Conclusion

Female sex, presence of COPD, rheumatic disease, hospitalization type and requirement of mechanical ventilation during index infection were identified as significant risk factors for the diagnosis of Long COVID. These findings emphasize the importance of addressing Long COVID syndrome in terms of prevention and management, taking these risk factors into consideration.
DNase improves the efficacy of antimicrobial photodynamic therapy in the treatment of candidiasis induced with Candida albicans
Authors: Jordão Cláudia Carolina , Klein Marlise Inêz , Barbugli Paula Aboud , Mima Ewerton Garcia de Oliveira , de Sousa Tábata Viana , Ferrisse Túlio Morandin , Pavarina Ana Claudia
Published: December 2023

The study evaluated the association of DNase I enzyme with antimicrobial photodynamic therapy (aPDT) in the treatment of oral candidiasis in mice infected with fluconazole-susceptible (CaS) and -resistant (CaR) Candida albicans strains. Mice were inoculated with C. albicans, and after the infection had been established, the tongues were exposed to DNase for 5 min, followed by photosensitizer [Photodithazine®(PDZ)] and light (LED), either singly or combined. The treatments were performed for 5 consecutive days. Treatment efficacy was evaluated by assessing the tongues via fungal viable population, clinical evaluation, histopathological and fluorescence microscopy methods immediately after finishing treatments, and 7 days of follow-up. The combination of DNase with PDZ-aPDT reduced the fungal viability in mice tongues immediately after the treatments by around 4.26 and 2.89 log10 for CaS and CaR, respectively (versus animals only inoculated). In the fluorescence microscopy, the polysaccharides produced by C. albicans and fungal cells were less labeled in animals treated with the combination of DNase with PDZ-aPDT, similar to the healthy animals. After 7 days of the treatment, DNase associated with PDZ-aPDT maintained a lower count, but not as pronounced as immediately after the intervention. For both strains, mice treated with the combination of DNase with PDZ-aPDT showed remission of oral lesions and mild inflammatory infiltrate in both periods assessed, while animals treated only with PDZ-aPDT presented partial remission of oral lesions. DNase I enzyme improved the efficacy of photodynamic treatment.
The cause-and-effect relationship between gut microbiota abundance and carcinoid syndrome: a bidirectional Mendelian randomization study
Authors: Zhang Zexin , Li Dongting , Xie Fengxi , Muhetaer Gulizeba , Zhang Haibo
Published: December 2023

Objective

Carcinoid syndrome (CS) commonly results from neuroendocrine tumors. While active substances are recognized as the main causes of the typical symptoms such as diarrhea and skin flush, the cause-and-effect relationship between gut microbiota abundance and CS remains unclear.

Methods

The Single Nucleotide Polymorphisms (SNPs) related to gut microbiota abundance and CS were obtained from the GWAS summary data. The inverse variance weighted (IVW) method was used to assess the causal relationship between gut microbiota abundance and CS. Additionally, the MR-Egger, Weighted Median model, and Weighted model were employed as supplementary approaches. The heterogeneity function of the TwoSampleMR package was utilized to assess whether SNPs exhibit heterogeneity. The Egger intercept and Presso test were used to assess whether SNPs exhibit pleiotropy. The Leave-One-Out test was employed to evaluate the sensitivity of SNPs. The Steiger test was utilized to examine whether SNPs have a reverse causal relationship. A bidirectional mendelian randomization (MR) study was conducted to elucidate the inferred cause-and-effect relationship between gut microbiota abundance and CS.

Results

The IVW results indicated a causal relationship between 6 gut microbiota taxa and CS. Among the 6 gut microbiota taxa, the genus Anaerofilum (IVW OR: 0.3606, 95%CI: 0.1554–0.8367, p-value: 0.0175) exhibited a protective effect against CS. On the other hand, the family Coriobacteriaceae (IVW OR: 3.4572, 95%CI: 1.0571–11.3066, p-value: 0.0402), the genus Enterorhabdus (IVW OR: 4.2496, 95%CI: 1.3314–13.5640, p-value: 0.0146), the genus Ruminiclostridium6 (IVW OR: 4.0116, 95%CI: 1.2711–12.6604, p-value: 0.0178), the genus Veillonella (IVW OR: 3.7023, 95%CI: 1.0155–13.4980, p-value: 0.0473) and genus Holdemanella (IVW OR: 2.2400, 95%CI: 1.0376–4.8358, p-value: 0.0400) demonstrated a detrimental effect on CS. The CS was not found to have a reverse causal relationship with the above 6 gut microbiota taxa.

Conclusion

Six microbiota taxa were found to have a causal relationship with CS, and further randomized controlled trials are needed for verification.
Dehalococcoides mccartyi strain CBDB1 takes up protons from the cytoplasm to reductively dehalogenate organohalides indicating a new modus of proton motive force generation
Authors: Hellmold Nadine , Eberwein Marie , Phan My Hanh Thi , Kümmel Steffen , Einsle Oliver , Deobald Darja , Adrian Lorenz
Published: December 2023

Proton translocation across the cytoplasmic membrane is a vital process for all organisms. Dehalococcoides strains are strictly anaerobic organohalide respiring bacteria that lack quinones and cytochromes but express a large membrane-bound protein complex (OHR complex) proposed to generate a proton gradient. However, its functioning is unclear. By using a dehalogenase-based enzyme activity assay with deuterium-labelled water in various experimental designs, we obtained evidence that the halogen atom of the halogenated electron acceptor is substituted with a proton from the cytoplasm. This suggests that the protein complex couples exergonic electron flux through the periplasmic subunits of the OHR complex to the endergonic transport of protons from the cytoplasm across the cytoplasmic membrane against the proton gradient to the halogenated electron acceptor. Using computational tools, we located two proton-conducting half-channels in the AlphaFold2-predicted structure of the OmeB subunit of the OHR complex, converging in a highly conserved arginine residue that could play a proton gatekeeper role. The cytoplasmic proton half-channel in OmeB is connected to a putative proton-conducting path within the reductive dehalogenase subunit. Our results indicate that the reductive dehalogenase and its halogenated substrate serve as both electron and proton acceptors, providing insights into the proton translocation mechanism within the OHR complex and contributing to a better understanding of energy conservation in D. mccartyi strains. Our results reveal a very simple mode of energy conservation in anaerobic bacteria, showing that proton translocation coupled to periplasmic electron flow might have importance also in other microbial processes and biotechnological applications.
Effect of time delay in inter-hospital transfer on outcomes of endovascular treatment of acute ischemic stroke
Authors: Pardo Keshet , Naftali Jonathan , Barnea Rani , Findler Michael , Perlow Alain , Brauner Ran , Auriel Eitan , Raphaeli Guy
Published: December 2023

Background

Endovascular treatment (EVT) with mechanical thrombectomy is the standard of care for large vessel occlusion (LVO) in acute ischemic stroke (AIS). The most common approach today is to perform EVT in a comprehensive stroke center (CSC) and transfer relevant patients for EVT from a primary stroke center (PSC). Rapid and efficient treatment of LVO is a key factor in achieving a good clinical outcome.

Methods

We present our retrospective cohort of patients who underwent EVT between 2018 and 2021, including direct admissions and patients transferred from PSC. Primary endpoints were time intervals (door-to-puncture, onset-to-puncture, door-to-door) and favorable outcome (mRS ≤ 2) at 90 days. Secondary outcomes were successful recanalization, mortality rate, and symptomatic intracranial hemorrhage (sICH). Additional analysis was performed for transferred patients not treated with EVT; endpoints were time intervals, favorable outcomes, and reason for exclusion of EVT.

Results

Among a total of 405 patients, 272 were admitted directly to our EVT center and 133 were transferred; there was no significant difference between groups in the occluded vascular territory, baseline NIHSS, wake-up strokes, or thrombolysis rate. Directly admitted patients had a shorter door-to-puncture time than transferred patients (190 min vs. 293 min, p < 0.001). The median door-to-door shift time was 204 min. We found no significant difference in functional independence, successful recanalization rates, or sICH rates. The most common reason to exclude transferred patients from EVT was clinical or angiographic improvement (55.6% of patients).

Conclusion

Our results show that transferring patients to the EVT center does not affect clinical outcomes, despite the expected delay in EVT. Reassessment of patients upon arrival at the CSC is crucial, and patient selection should be done based on both time and tissue window.
Flavonoids and fibrate modulate apoE4-induced processing of amyloid precursor protein in neuroblastoma cells
Authors: Davra Viralkumar , Benzeroual Kenza E.
Published: December 2023

Introduction

Apolipoprotein (apo) E4, being a major genetic risk factor for Alzheimer’s disease (AD), is actively involved in the proteolytic processing of amyloid precursor protein (APP) to amyloid β (Aβ) peptide, the principle constituent of amyloid plaques in Alzheimer Disease (AD) patients. ApoE4 is believed to affect APP processing through intracellular cholesterol homeostasis, whereas lowering the cholesterol level by pharmacological agents has been suggested to reduce Aβ production. This study has investigated the effects of hypolipidemic agents fenofibrate, and the flavonoids–naringenin and diosmetin–on apoE4-induced APP processing in rat neuroblastoma cells stably transfected with human wild-type APP 695 (B103-hAPP695wt).

Results

B103-hAPP695wt cells were pretreated with different doses of flavonoids and fenofibrate for 1 h prior to apoE4 exposure for 24 h. ApoE4-induced production of intra- and extracellular Aβ peptides has been reduced with fenofibrate, naringenin, and diosmetin treatments. Pretreatment with diosmetin has significantly reduced apoE4-induced full-length APP (fl- APP) expression, whereas naringenin and fenofibrate had no effect on it. In addition, the increase in the apoE4-induced secretion of sAPPtotal and sAPPα has been dose-dependently reduced with drug pretreatment. On the other hand, the decrease in the expression of both APP-carboxy terminal fragments (CTF)-α and –β (generated by the α- or β-secretase cleavage of APP) by apoE4 was dose-dependently increased in cells pretreated with fenofibrate and naringenin but not diosmetin.

Conclusion

Thus, we suggest that fenofibrate, naringenin, and diosmetin treatments can reduce apoE4- induced Aβ production by distinct mechanisms that may prove useful in developing drugs for AD patients.
Identifying barriers and facilitators to adopting healthier dietary choices in clinical care: a cross-sectional observational study
Authors: de Frel Daan L. , Wicks Hope , Bakk Zsuzsa , van Keulen Nicole , Atsma Douwe E. , Janssen Veronica R.
Published: December 2023

Background and aims

Adopting healthier diets can drastically improve societal health. Our environment plays a crucial role in daily dietary choices and hospitals in particular can stimulate patients to adopt healthier eating habits. Unfortunately, no robust clinically applicable cuing tools exist to help guide in-hospital dietary interventions. The purpose of this study was to identify patient-related barriers and facilitators to adopting healthier dietary choices.

Methods and results

This cross-sectional observational study was conducted on the cardiology ward of a university medical center between June 2020 and January 2021. Of the 594 patients asked and the 312 completed surveys on healthy eating intentions, 285 responses were considered for analysis. Notably, the majority of respondents were male (68.8%), with an average hospital stay of 3.3 days. The results indicate that cardiac patients attribute significantly greater influence on their dietary behavior to doctors compared to other caregivers, including dieticians (X2 = 37.09, df = 9, p < 0.001). Also, younger patients (below 70 years of age) were more inclined to plan changing dietary behavior than older patients. Most mentioned facilitators for adopting a healthier diet were more information/counseling, help in preparing food, support from family and friends, and more emphasis from a doctor.

Conclusion

The study highlights the importance of involving doctors in formulating dietary policies and patient-directed interventions within hospital settings. It also sheds light on the barriers and facilitators for promoting healthier dietary behaviors among patients during their hospitalization.
Phytochemical profile and anti-inflammatory activity of the hull of γ-irradiated wheat mutant lines (Triticum aestivum L.)
Authors: Park Jisu , Kil Yun-Seo , Ryoo Ga-Hee , Jin Chang Hyun , Hong Min Jeong , Kim Jin-Baek , Jung Chan-Hun , Nam Joo-Won , Han Ah-Reum
Published: December 2023

Wheat (Triticum aestivum Linn.; Poaceae) is the second most cultivated food crop among all global cereal crop production. The high carbohydrate content of its grains provides energy, multiple nutrients, and dietary fiber. After threshing, a substantial amount of wheat hull is produced, which serves as the non-food component of wheat. For the valorization of these by-products as a new resource from which functional components can be extracted, the hull from the seeds of cultivated wheat mutant lines bred after γ-irradiation were collected. Untargeted metabolite analysis of the hull of the original cultivar (a crossbreeding cultivar., Woori-mil × D-7) and its 983 mutant lines were conducted using ultra-performance liquid chromatography–electrospray ionization quadrupole time-of-flight mass spectrometry technique. A total of 55 molecules were tentatively identified, including 21 compounds found in the Triticum species for the first time and 13 compounds not previously described. Among them, seven flavonolignans with a diastereomeric structure, isolated as a single compound from the hull of T. aestivum in our previous study, were used as the standards in the metabolite analysis. The differences in their collision cross-section values were shown to contribute to the clear distinction between tricine-lignan stereoisomers. To select functionally active agents with anti-inflammatory activity among the identified compounds, the wheat hull samples were evaluated for their inhibitory effect on nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. As a result of multivariate analysis based on the results of chemical and biological profiles of the wheat hull samples, 10 metabolites were identified as key markers, contributing to the distinction between active and inactive mutant lines. Considering that one of the four key markers attributed to anti-inflammatory activity has been identified to be a flavonolignan, the wheat hull could be a valuable source of diverse tricin-lignan type compounds and used as a natural health-promoting product in food supplements.
Analysis of recurrence and metastasis patterns and prognosis after complete resection of retroperitoneal liposarcoma
Authors: Gao Xiaofeng , Ding Pingan , Zhang Zhidong , Li Yong , Zhao Qun , Wang Dong , Zhao Xuefeng , Liu Yu , Tan Bibo
Published: December 2023

Objective

To analyze the recurrence and metastasis patterns and prognosis after complete resection of retroperitoneal liposarcoma.

Methods

The clinical postoperative follow-up data and results of patients who underwent complete resection of retroperitoneal liposarcoma from September 10, 2014, to September 8, 2021, at Hebei Medical University hospital were collected retrospectively.

Results

A total of 60 patients with complete resection of retroperitoneal liposarcoma, including 33 cases of retroperitoneal liposarcoma recurrence, 2 cases of liver metastasis, and 1 case of lung metastasis, were included. The results showed that 100% of the recurrent sites were located in the primary region of the tumor, with most recurrences located near the kidney, paracolic sulci, and iliac vessels. Three patients had distant metastasis without obvious recurrence on imaging examination. The pathological type of retroperitoneal liposarcoma, Ki67 expression, and presence of serum albumin were risk factors for recurrence and metastasis after complete resection of retroperitoneal liposarcoma. The malignancy and Ki67 expression were independent risk factors for recurrence and metastasis as well as for overall survival of patients undergoing complete resection of retroperitoneal liposarcoma.

Conclusion

Complete resection remains the most effective method to treat retroperitoneal liposarcoma. Patients with pathological types of retroperitoneal liposarcoma showing dedifferentiation, pleomorphism, mixed type, and high Ki67 expression should be closely monitored and observed after complete resection, especially for imaging changes in the primary tumor area.
MRI T2 mapping assessment of T2 relaxation time in desmoid tumors as a quantitative imaging biomarker of tumor response: preliminary results
Authors: Souza Felipe F. , D’Amato Gina , Jonczak Emily Elizabeth , Costa Philippos , Trent Jonathan C. , Rosenberg Andrew E. , Yechieli Raphael , Temple H. Thomas , Pattany Pradip , Subhawong Ty K.
Published: December 2023

Objectives

Because size-based imaging criteria poorly capture biologic response in desmoid-type fibromatosis (DF), changes in MRI T2 signal intensity are frequently used as a response surrogate, but remain qualitative. We hypothesized that absolute quantification of DF T2 relaxation time derived from parametric T2 maps would be a feasible and effective imaging biomarker of disease activity.

Methods

This IRB-approved retrospective study included 11 patients with DF, managed by observation or systemic therapy, assessed by 3T MRI. Tumor maximum diameter, volume, and T2-weighted signal intensity were derived from manual tumor segmentations. Tumor:muscle T2 signal ratios were recorded. Two readers measured tumor T2 relaxation times using a commercial T2 scanning sequence, manual ROI delineation and commercial calculation software enabling estimation of reader reliability. Objective response rates based on RECIST1.1 and best responses were compared between size-based and signal-based parameters.

Results

Median patient age was 52.6 years; 8 subjects were female (73%). Nine patients with longitudinal assessments were followed for an average of 314 days. Median baseline tumor diameter was 7.2 cm (range 4.4 - 18.2 cm). Median baseline T2 was 65.1 ms (range 40.4 - 94.8 ms, n=11); median at last follow-up was 44.3 ms (-32% from baseline; range 29.3 - 94.7 ms, n=9). T2 relaxation times correlated with tumor:muscle T2 signal ratios, Spearman p=0.78 (p<0.001). T2 mapping showed high inter-reader reliability, ICC=0.84. The best response as a percentage change in T2 values was statistically significant (mean -17.9%, p=0.05, paired t-test) while change in diameter was not (mean -8.9%, p=0.12).

Conclusions

Analysis of T2 relaxation time maps of DF may offer a feasible quantitative biomarker for assessing the extent of response to treatment. This approach may have high inter-reader reliability.
Evaluating the bioequivalence and safety of liraglutide injection versus Victoza® in healthy Chinese subjects: a randomized, open, two-cycle, self-crossover phase I clinical trial
Authors: Liu Chao , Xu Hongrong , Yuan Fei , Chen Hanjing , Sheng Lei , Chen Weili , Xie Haisong , Xu Hongmei , Li Xuening
Published: December 2023

Background: Liraglutide is an acylated glucagon-like peptide-1 (GLP-1) analog, and its pharmacokinetic and pharmacodynamic properties as a GLP-1 receptor (GLP-1R) agonist make it an important therapeutic option for many patients with type 2 diabetes mellitus. This study compared the bioequivalence and safety of liraglutide with the originator product in healthy Chinese adult subjects.

Methods: Subjects (N = 36, both sexes) were randomized in a 1:1 ratio into two groups (18 cases each) for a two-cycle, self-crossover trial. Each cycle involved a single subcutaneous injection of the test and reference drugs, with a washout period of 14 days. The plasma drug concentration was quantified by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The main pharmacokinetic parameters were statistically analyzed to assess drug bioequivalence. Furthermore, the safety of the drugs was assessed throughout the trial.

Results: The geometric mean ratios of Cmax, AUC0-t, and AUC0-∞ were 103.73%, 103.01%, and 103.03%, respectively, and their 90% confidence intervals (CIs) were consistent with the range of 80.00%–125.00%, indicating that the two formulations had similar pharmacokinetics. Meanwhile, safety results showed that both drugs were well tolerated.

Conclusion: Studies have shown that the test drug has similar bioequivalence and safety to the reference drug.

Clinical trial registration: (http://www.chinadrugtrials.org.cn/index.html), identifier (CTR20171303).
Gut microbiota dynamics in a 1-year follow-up after adult liver transplantation in Northeast China
Authors: Zhang Ruoyan , Qiu Wei , Sun Xiaodong , Li Jing , Geng Xiaochen , Yu Shichao , Liu Ying , Huang Heyu , Li Mingyue , Fan Zhongqi , Li Mingqian , Lv Guoyue
Published: December 2023

Background: Liver transplantation (LTx) is the most effective treatment for end-stage liver diseases. Gut microorganisms influence the host physiology. We aim to profile the dynamics of gut microbiota in the perioperative period and a 1-year follow-up of LTx recipients in Northeast China.

Methods: A total of 257 fecal samples were longitudinally collected from 85 LTx patients using anal swabs from pre-LTx to 1-year post-LTx. A total of 48 fecal samples from end-stage liver disease patients without LTx served as the control. 16S rRNA sequencing was used to analyze gut microbiota diversity, bacterial genera, phenotype classification, and metabolic pathways.

Results: The diversity of gut microbiota decreased significantly after transplantation, accompanied by a profound change in the microbial structure, which is characterized by increased abundance of facultative anaerobic bacteria dominated by g_Enterococcus and reduced anaerobic bacteria composition. Predicted functional analysis also revealed disturbances in the metabolic pathway of the gut microbiota. After LTx, the diversity of microbiota gradually recovered but to a less preoperative level after 1 year of recovery. Compared with pre-transplantation, the microbiome structure was characterized by an increase in Acidaminococcus and Acidithiobacillus after 1 year of transplantation.

Conclusion: LTx and perioperative treatment triggered gut microbial dysbiosis. The gut microbiota was restructured after LTx to near to but significantly differed from that of pre-LTx.
Optogenetic demonstration of the involvement of SMA-negative mural cells in the regulation of cerebral blood flow
Authors: Iba Chisato , Abe Yoshifumi , Tanaka Kenji F.
Published: December 2023

Mural cells are critical components of the cerebral vasculature. They are categorized into three primary subsets: arteriole smooth muscle cells (aSMCs), pericytes (PCs) and venule smooth muscle cells (vSMCs). It is well known that aSMCs can directly regulate cerebral blood flow (CBF) with their own contraction and dilation mechanisms. On the other hand, the direct involvement of PCs or vSMCs in CBF regulation is controversial. This ambiguity is largely due to the lack of specifically manipulable tools to isolate their function. To address this issue, we employed a set-subtraction approach by using a combination of tTA-mediated gene induction and Cre-mediated gene excision. We developed transgenic mice expressing optical actuators, channelrhodopsin-2 (ChR2) and photoactivated adenylyl cyclase (PAC) in smooth muscle actin (SMA)-negative mural cells that lack the machinery for SMA-mediated vasoregulation. Using these mouse models, we assessed CBF alterations in response to optical stimulation using laser Doppler techniques. Our results showed that optical stimulation induced notable CBF changes in both models. This study provides evidence for the potential regulatory role of PCs and vSMCs in cerebral hemodynamics and introduces powerful tools to specifically manipulate these cell types in vascular neurobiology.
The influence of psychological needs and motivation on game cheating: insights from self-determination theory
Authors: Lee Sung Je , Jeong Eui Jun , Kim Dan J. , Kong Jeonyoung
Published: December 2023

Introduction

Game cheating (i.e., behavior of violating rules in games by using unregulated Software or assistive devices to gain advantage) poses a fatal problem as it destroys fair competition systems and negatively impacts the game ecosystem. Game cheating is reported to be common in competitive online games because they stimulate strongly a user’s motivation and psychological needs. However, there is still in lack of academic research which focused on the issue from the psycho-social perspective.

Methods

This study investigated the relationships between basic psychological needs (i.e., autonomy, competence, and relatedness) and motivation (i.e., intrinsic and extrinsic) based on self-determination theory, and examined their effects on the degree of game cheating with survey data of 322 gamers in a competitive online gaming community.

Results

The results showed the opposite associations between the two forms of motivation (intrinsic and extrinsic) and game cheating. On one hand, extrinsic motivation decreased by autonomy enhanced the degree of game cheating. On the other hand, intrinsic motivation increased by both autonomy and relatedness finally abated game cheating. Competence did not influence any form of motivation. The results indicated that people motivated by interest or enjoyment (i.e., intrinsic motivation) of the game tend to view game cheating negatively while those motivated by game victory and rewards are likely to have positive attitudes toward game cheating. Increasing the degree of user autonomy and social relations in the game could decrease game cheating through the enhancement of intrinsic motivation.

Discussion

Digital game cheating is a crucial problem threatening the spread of game culture and the growth of the eSports industry. The findings of this study reveal the influence of psychological needs and intrinsic motivation related to ‘game cheating,’ providing valuable guidelines in educational and policy aspects.
The mechanisms of nature-based therapy on depression, anxiety, stress, and life satisfaction: examining mindfulness in a two-wave mediation model
Authors: Kang Minjung , Yang Yeji , Kim Hyunjin , Jung Songhie , Jin Hye-Young , Choi Kee-Hong
Published: December 2023

Background

Nature-based therapy (NBT), which centers around engaging in activities within natural surroundings, has consistently demonstrated therapeutic benefits for mental health. While NBT highlights the potential of nature as a therapeutic resource for promoting mental health, there is limited knowledge regarding its underlying mechanisms.

Methods

Two hundred seventy-six Korean participants (204 women, mean age = 54.99 ± 23.25 years) participated in a 30-session gardening program held twice weekly for 15 weeks. Structural equation modeling with a two-wave autoregressive cross-lagged model was used to investigate the mediating effects of mindfulness.

Results

NBT significantly improved the mean scores of all psychological variables. The mediation model was partially confirmed, with mindfulness at post-intervention (T2) mediating the relationship between baseline (T1) depression and anxiety and post-intervention (T2) life satisfaction. However, no significant indirect effect was observed between the path from stress (T1) to life satisfaction (T2).

Conclusion

Mindfulness is a crucial component for improving mental health outcomes. This study underscores the need to prioritize and emphasize mindfulness practices in NBT.
Where I am from matters: factors influencing behavioral and emotional changes in autistic individuals during COVID-19 in Latin America
Authors: Montenegro María Cecilia , Ramírez Ana C. , Hernandez Rodriguez Juventino , Villalobos Bianca T. , Garrido Gabriela , Amigo Cecilia , Valdez Daniel , Barrios Natalia , Cukier Sebastián , Rattazzi Alexia , Rosoli Analía , García Ricardo , Paula Cristiane S. , Liz Georgina Pérez , Montiel-Nava Cecilia
Published: December 2023

Background

The COVID-19 pandemic brought an increased incidence of disease and mortality in the world at large, making it a particularly salient and stressful life event. For those individuals residing in Latin America, the pandemic was met with fragmented healthcare systems, economic downturn, and sociopolitical crisis which puts autistic individuals at risk for more detrimental outcomes. Behavioral and emotional challenges experienced by autistic individuals at the beginning of the pandemic could later develop into more severe symptomatology as the pandemic progresses. The present study aimed to explore changes in dysregulated (overt and internalizing) behaviors and preoccupation with getting sick during the COVID-19 pandemic among autistic children in 7 Latin American countries.

Method

Sample consisted of 1,743 caregivers, residing in: Argentina (n = 677, 38.8%) Brazil (n = 156, 9%), Chile (n = 251, 14.4%), Dominican Republic (n = 171, 9.8%), Mexico (n = 126, 7.2%), Uruguay (n = 259, 14.9%) and Venezuela (n = 103, 5.9%). The majority of caregivers who completed the questionnaire were mothers (85.1%), and most had a male autistic child (81.6%). A series of independent sample t-tests were conducted to assess country differences in dysregulated behaviors and preoccupation with getting sick. Linear regressions were conducted to identify which demographic characteristics and micro-level contextual factors predicted dysregulated overt behaviors and psychological changes.

Results

Contextual factors, such as country of residence, were related to preoccupation with getting sick and dysregulated behavior. Particularly, residing in Mexico and Brazil were related to changes in preoccupation with getting sick and mental health concerns. Coexistence predicted dysregulated internalizing behaviors, while being older significantly predicted preoccupation with getting sick. Increased screen time only predicted anxiety.

Conclusion

Our findings highlight differences and predictions of behavioral challenges and psychological changes based on certain contextual factors and individual characteristics while experiencing severe life stressors such as a worldwide pandemic. This knowledge could help inform policies and decrees aimed at protecting those most vulnerable due to their increased difficulty adapting to change.
Quality of life for people with psychiatric disabilities employed in extended employment programs in two Arab towns in Israel: an exploratory study
Authors: Badran Leena , Rosenbaum Stephen , Rimmerman Arik
Published: December 2023

Introduction

This study aims to examine the quality of life (QOL) for people with psychiatric disabilities who are engaged in extended employment programs (homogeneous versus heterogeneous) in the Arab-populated Triangle Area of Israel. The homogeneous program participants are exclusively Arab while the heterogeneous program includes both Arabs and Jews.

Methods

Quantitative research study of 104 adults with psychiatric disabilities engaged in two communal extended employment programs. Participants completed demographic (age (years), gender, marital status (married, widowed/separated, married, single), religion (Muslim, Jewish, Christian), dichotomous nationality variable (Jewish/Arab), and years of education) and employment questionnaires (length of time in the employment program, number of working days/h and salary satisfaction); SF 12 Scale; and The Personal Wellbeing Index questionnaire. Two-sample T-Test, exploratory factor analysis and multiple linear regressions were conducted for tracking the differences between participants in homogeneous and heterogeneous programs.

Results

A significant difference was found between the programs in two QOL components, insofar as satisfaction with the standard of living, together with health satisfaction were rated higher for participants in the heterogeneous program than for their homogeneous program counterparts. Furthermore, the results indicate that physical health and gender were the most important variables in explaining QOL in both programs, while the employment variables were not significant.

Discussion

Since the research findings show that the employment-related-items aren’t significant in predicting the employees’ QOL, the definition and suitability of extended employment environments as a mental health service must be reexamined. Cultural elements may also have an impact on QOL when the programs are located in a traditional town, with gender playing a key role. The family’s role is pivotal in traditional societies, influencing an individual’s ability to participate in employment programs and the support they receive. In patriarchal societies, there can be added pressure on men with psychiatric disabilities to conform to societal expectations. Given the general lack of health awareness in Arab communities, there is a need to develop additional projects or incorporate physical health improvement as a rehabilitation goal when working with individuals with psychiatric disabilities, regardless of the type of community rehabilitation program.
Medical insurance, health risks, and household financial asset allocation: evidence from China household finance survey
Authors: Li Chengming , Li Jiashan , Zhai Chenchen , Dong Xiaoqi , Jiang Zhengyu , Jiang Shaoxiang
Published: December 2023

There is a lack of micro evidence on whether medical insurance may optimize the household financial asset allocation by transferring health risk, despite the fact that health risk is a significant component driving families’ precautionary savings. This article empirically examines the impact of health risk and social medical insurance on household risky financial asset allocation using a Probit model, based on data from the 2015–2019 China Household Finance Survey (CHFS). The findings indicate that social medical insurance, with its lower level of security, reduces the likelihood, but it can alter households’ preferences for risk by lowering marginal effect of health risk. According to the findings of the heterogeneity analysis, people who live in rural and less developed areas are more likely to experience the risk-inhibiting effects of social medical insurance and health risk. The eroding and risk-suppressing impacts of social medical insurance are likewise less pronounced for households headed by women and older people, as is the health risk’s suppressive influence on household involvement in risky financial markets. Compared with social medical insurance, commercial medical insurance with a higher level of coverage can dramatically increase household participation in riskier financial markets. This article provides micro-empirical evidence for the household asset allocation effect of medical insurance.
Specific analysis of PM2.5-attributed disease burden in typical areas of Northwest China
Authors: Liao Qin , Li Zhenglei , Li Yong , Dai Xuan , Kang Ning , Niu Yibo , Tao Yan
Published: December 2023

Background

Frequent air pollution events in Northwest China pose a serious threat to human health. However, there is a lack of specific differences assessment in PM2.5-related disease burden. Therefore, we aimed to estimate the PM2.5-related premature deaths and health economic losses in this typical northwest region, taking into account disease-specific, age-specific, and region-specific factors.

Methods

We utilized the WRF-Chem model to simulate and analyze the characteristics and exposure levels of PM2.5 pollution in Gansu Province, a typical region of Northwest China. Subsequently, we estimated the premature mortality and health economic losses associated with PM2.5 by combining the Global Exposure Mortality Model (GEMM) and the Value of a Statistical Life (VSL).

Results

The results suggested that the PM2.5 concentrations in Gansu Province in 2019 varied spatially, with a decrease from north to south. The number of non-accidental deaths attributable to PM2.5 pollution was estimated to be 14,224 (95% CI: 11,716–16,689), accounting for 8.6% of the total number of deaths. The PM2.5-related health economic loss amounted to 28.66 (95% CI: 23.61–33.63) billion yuan, equivalent to 3.3% of the regional gross domestic product (GDP) in 2019. Ischemic heart disease (IHD) and stroke were the leading causes of PM2.5-attributed deaths, contributing to 50.6% of the total. Older adult individuals aged 60 and above accounted for over 80% of all age-related disease deaths. Lanzhou had a higher number of attributable deaths and health economic losses compared to other regions. Although the number of PM2.5-attributed deaths was lower in the Hexi Corridor region, the per capita health economic loss was higher.

Conclusion

Gansu Province exhibits distinct regional characteristics in terms of PM2.5 pollution as well as disease- and age-specific health burdens. This highlights the significance of implementing tailored measures that are specific to local conditions to mitigate the health risks and economic ramifications associated with PM2.5 pollution.