bluuebunny/crossref_metadata_2025 huggingface dataset:
Spatial-temporal Characteristics and Driving Factors of the Coupling Coordination between Primary Health Care and Socioeconomic Development: A Case Study of Beijing, China
Authors: Liu Haopeng , Ma Chengyu , Lv Siyu , Tong Zirun
Published: March 2024

Background
Primary Health Care (PHC) plays a central role in achieving universal health coverage and is a key focus of China's healthcare reforms. It is important to balance PHC development across different regions and ensure its harmonious growth with economic and social factors. This balance is essential for equitable health access and overall societal well-being. This study aims to examine the spatial imbalance in PHC development and its coordination with socioeconomic factors, trying to explore the driving factors behind the imbalance.
Methods
This study focuses on the 16 districts of Beijing from 2012 to 2021, constructing a social, economic, and PHC evaluation indicator system. First, this study used the entropy weight method and coupling coordination model to analyze the Coupling Coordination Degree (CCD) of PHC, economic, and social development. Then, Moran's I was used to test the spatial association characteristics of PHC development and the CCD. Lastly, the Geodetector was used to explore the driving factors behind the dual imbalance in PHC.
Results
Between 2012 and 2021, Beijing's PHC resources significantly increased. The evaluation values for PHC in the central city, near suburbs, and far suburbs were 0.46, 0.23, and 0.06, respectively, with a Moran’s I of 0.22 (P = 0.02), signifying a spatial imbalance in PHC development. The CCD of these regions were 0.72, 0.57, and 0.35, respectively, with a Moran’s I of 0.48 (P = 0.002), signifying the CCD imbalance. Factors such as population (q = 0.90), physician (q = 0.87), and government financial spending (q = 0.82) emerged as principal drivers of this dual imbalance.
Conclusions
Over the last decade, Beijing's PHC resources have significantly increased, but spatial imbalance persists. Several districts exhibit a lag in primary health care relative to socio-economic advancements, with pronounced systemic imbalances in the far suburbs. Factors driving this dual imbalance include geographical features, resident economic status, demographics, medical resources, and government regulation ability. Enhanced governmental investment and policy support for primary health care in the far suburbs are recommended.
Study on the Correlation Between Job Happiness and Behavior Choices of Research Integrity of Teachers in Vocational Colleges
Authors: Zhou Wenqiang , Chen Shougen
Published: March 2024

This paper delves deeply into the relationship between teachers’ job happiness and research integrity behavioral choices in vocational colleges, aiming to provide new ideas for vocational colleges to reduce academic misconduct incidents. Based on the previous theoretical research, a preliminary fitting model is constructed, and through the method of empirical research, it is validated that increasing the job happiness of teachers in vocational colleges can improve their behavior choices of research integrity. Relevant strategies for improving vocational teachers’ research integrity behavior choices based on the sense of growth and sense of belonging are proposed, which open up a new management approach and a new focus for the management of research integrity in vocational colleges.
Distinct recognition of mutant huntingtin aggregates by autophagy receptor SQSTM1/p62 versus optineurin has differential effects on cell survival
Authors: Seong Jihye , Kim Heejung , Lee Hae Nim , Ryu Hoon , Inn Kyung-Soo
Published: March 2024

Huntington's disease (HD) is a neurodegenerative disease caused by a polyglutamine (polyQ) expansion in the N-terminus of huntingtin (HTT). Mutant HTT (mHTT) undergoes misfolding and tends to aggregate, yet these aggregates are not effectively cleared by autophagy thus contributing to neurotoxicity in HD. The polyQ length of HTT in patients with HD varies from 40 to > 90; however, the precise mechanisms of autophagy dysfunction for mHTT with varying polyQ lengths remain unclear. In this study, we developed new HTT-polyQ aggregation sensors based on bimolecular fluorescence complementation (BiFC) to monitor the real-time aggregation process of mHTT with varying polyQ lengths. Using BiFC-based aggregation sensors, we demonstrated that mHTT aggregation kinetics is faster with a longer polyQ length, suggesting a correlation between polyQ length and the onset age of HD. Interestingly, we discovered that the different aggregation kinetics of mHTT may determine the physical properties of the aggregates: mHTT-polyQ43 forms liquid-like protein condensates, whereas mHTT-polyQ103 generates tightly concentrated aggregates. Furthermore, mHTT aggregates with different physical states were selectively recognized by distinct autophagy receptors, which resulted in differential effects on cell viability. The liquid-like mHTT-polyQ43 condensates were recognized by SQSTM1/p62 but failed to proceed through autophagy thereby facilitating cytotoxicity. In contrast, mHTT-polyQ103 aggregates were selectively recognized by optineurin, which led to autophagic degradation and prolonged cell survival. Therefore, our results suggest that different therapeutic strategies should be considered for the HD patients with different polyQ lengths.
Transient Anterior Subcapsular Vacuolar Lens Opacities After Tanito Microhook Trabeculotomy: Report of Six Cases
Authors: Shimizu Hiroshi , Tanito Masaki
Published: March 2024

OBJECTIVE: To present six cases exhibiting transient anterior subcapsular vacuolar lens opacities following early postoperative Tanito microhook trabeculotomy (TMH) performed by the same surgeon.
METHODS: Six patients who underwent lens-sparing TMH at Meizankai Shimizu Eye Clinic from November 2021 to May 2023, and developed anterior subcapsular vacuolar lens opacities postoperatively were reviewed. Detailed records of surgeries, clinical findings, and outcomes were collected and reported.
RESULTS: In all six cases, anterior vacuolar subcapsular lens opacities were observed on the day after surgery, gradually decreasing without affecting visual acuity or contrast sensitivity. In all cases, without any specific interventions, the opacities disappeared by 21 months postoperatively.
CONCLUSION: Anterior subcapsular cataracts, characterized by a vacuolar appearance and transient existence, should be recognized as an early complication of ab interno glaucoma surgery, possibly linked to excessive anterior chamber irrigation leading to traumatic cataracts on the lens surface.
Analyzing Urban Space Resilience: Human Mobility Pulses in Auckland's Urban Hotspots through the lens of COVID-19
Authors: Chuang I-Ting , Chen Qing Qing
Published: March 2024

The COVID-19 pandemic has affected people's daily lives since its outbreak, which has taken the discussion about urban resilience to new heights. Locational data streaming provides opportunities to explore how individuals utilize different urban spaces while their daily routines are disrupted. In this paper, we built on the radical transformation of social behaviours imposed by the government's emergency policies to explore the impacts and recovery of the visiting patterns in urban hotspots under one of the most stringent settings in Auckland, New Zealand. The ‘urban hotspots’ here refer to vibrant urban places that attract both dense (high frequency) and diverse (visitors from different places) visitors. To quantify the impacts, we utilised mobile location data, which consists of 85.53 million data points collected from about 3 million users during 2020. Then, we analysed the signs of returning human activities in urban hotspots before and after the two most stringent COVID-19 lockdowns and evaluated the variation of visiting patterns bi-weekly. Our findings suggest that in addition to essential services (supermarkets and medical institutions), urban parks are notably resilient urban spaces providing significant support for people. This result provides empirical evidence of the added value of urban parks within the urban resilience framework, highlighting the novelty of our methodology that, without presumption, identifies the most resilient urban space as urban green. This also informs planning and rethinking of urban structural strategies as part of the city's recovery from crises and disasters.
Dynamic Changes in Extracellular Vesicle-Associated miRNAs Elicited by Ultrasound in Inflammatory Bowel Disease Patients
Authors: Tran Florian , Scharmacher Alena , Baran Nathan , Mishra Neha , Wozny Marek , Chavez Samuel Pineda , Bhardwaj Archana , Hinz Sophia , Juzenas Simonas , Bernardes Joana P. , Sievers Laura Katharina , Lessing Matthias , Aden Konrad , Lassen Arne , Bergfeld Arne , Weber Hauke Jann , Neas Lennart , Vetrano Stefania , Schreiber Stefan , Rosenstiel Philip
Published: March 2024

Background and Aims
Blood-based biomarkers that reliably indicate disease activity in the intestinal tract are an important unmet need in the management of patients with IBD. Extracellular vesicles (EVs) are cell-derived membranous microparticles, which reflect the cellular and functional state of their site of site of origin. As ultrasound waves may lead to molecular shifts of EV contents, we hypothesized that application of ultrasound waves on inflamed intestinal tissue in IBD may amplify the inflammation-specific molecular shifts in EVs like altered EV-miRNA expression, which in turn can be detected in the peripheral blood.
Methods
26 patients with IBD were included in the prospective clinical study. Serum samples were collected before and 30 minutes after diagnostic transabdominal ultrasound. Differential miRNA expression was analyzed by sequencing. Candidate inducible EV-miRNAs were functionally assessed in vitro by transfection of miRNA mimics and qPCR of predicted target genes.
Results
Serum EV-miRNA concentration at baseline correlated with disease severity, as determined by clinical activity scores and sonographic findings. Three miRNAs (miR-942-5p, mir-5588, mir-3195) were significantly induced by sonography. Among the significantly regulated EV-miRNAs, miR-942-5p was strongly induced in higher grade intestinal inflammation and correlated with clinical activity in Crohn’s disease. Prediction of target regulation and transfection of miRNA mimics inferred a role of this EV-miRNA in regulating barrier function in inflammation. Induction of mir-5588 and mir-3195 did not correlate with inflammation grade.
Conclusions
This proof-of-concept trial highlights the principle of induced molecular shifts in EVs from inflamed tissue through transabdominal ultrasound. These inducible EVs and their molecular cargo like miRNA could become novel biomarkers for intestinal inflammation in IBD.
Comparative Performance of Different Glucometers for Random Glucose Measurements in Diabetic Patients
Authors: Cosmas Febronia Nyamwiza , Mbugi Erasto Vitus
Published: March 2024

Background: Proper management of diabetic patients is dependent on accuracy in patient self-monitoring of blood glucose levels at home and during health care visits are key. Several glucometers are currently available in the market with variability in technical and clinical accuracies. The aimed at assessing the performance of various glucometers and their reliability as tools worth relying upon for patient blood sugar management.
Methods:This cross-sectional study involved 125 aged 39-59 years old (47% males, 55.2% females) diabetic patients recruited from November 2022 to January 2023 at Muhimbili National Hospital Emergency Medicine Department. Patients’ demographic and other relevant information were recorded using questionnaires along with glucometer readings and the laboratory values of glucose. Bland Altman graphs, ISO 15197:2013, Consensus Grid Reference, were used to assess the technical and clinical accuracies.
Results: An estimate of 62.4% of participants did not have glucometers at home. The results als showed five glucometers namely, Accu Chek, Gluco Plus, Gluco navii, One Touch Plus and Care sense, to have relatively stable mean glucose levels between glucometers and known laboratory glucose readings. There was likelihood for Care sense not meeting the ISO 15179:2013 criteria while both Accu Chek and Care sense glucometers had higher CV values of 77% and 56.5%, respectively.
Conclusions: This study highlights the variability in readings among glucometers with GlucoPlus, Gluco navii and One Touch Plus showing a degree of reliability for patients self-monitoring of random blood glucose levels. Thus regular evaluation of glucometers remains key for their accuracy and patient management.
Multi-centric validation of Truenat MTB Rif Dx for Diagnosis of Extrapulmonary Tuberculosis
Authors: Singh Urvashi B. , Singh Manjula , Rodrigues Camilla , Christopher D J , Mahajan Neeraj , Srivas Abhinav , Singh Kh Jitenkumar , Kanswal Sunita , Rao M. V. V. , kazi Mubin , Sawant Damini , Thangakunam Balamugesh , Vijay Coelho Victor , Shankar Deepa , Bhatnagar Anuj , Mohan Anant , Ahuja Vineet
Published: March 2024

Extra-pulmonary TB (EPTB) is difficult to diagnose due to paucibacillary nature of disease. Current study evaluated accuracy of Truenat MTB-Rif Dx (TN), for detection of Mycobacterium tuberculosis and resistance to rifampicin. Samples were collected from 2103 treatment naive adults with presumptive EPTB, and tested by smear microscopy, liquid culture (LC) (MGIT-960) and GeneXpert MTB/RIF (GX) (Microbiological Reference Standards, MRS). TN results were compared to MRS and Composite Reference Standards (CRS, Microbiology, histopathology, radiology, clinical features prompting decision to treat, response to treatment). TN and GX results were further compared to Clinical Reference Standards (CRS). CRS grouped patients into 551 confirmed, 1096 unconfirmed, and 409 as unlikely TB. TN sensitivity and specificity was 73.7% and 90.4% against GX. Against LC, TN sensitivity and specificity was 62.3% and 84.9%; highest sensitivity (89%) in pus samples and specificity (92%) in CSF was similar to GX. TN sensitivity was better in fluid and biopsy samples, slightly inferior for lymph node aspirates. TN sensitivity for RIF resistance detection was slightly superior to GX. TN detected 169 TB patients initiated on treatment, which were missed by GX. The study establishes TN at par with GX and can be utilized for quick and accurate diagnosis of EPTB.
Targeting ZAKα Interactions and Ribosomes with Novel peptides: The role of ZAKα in Mitochondrial Function and Cancer Cell Proliferation
Authors: Yang Jaw-Ji , Hsu Ying-Chang , Yeh Yang-Shan
Published: March 2024

Phage display was used to identify high-affinity and high-specificity peptides that might inhibit ZAKα, a kinase implicated in cellular proliferation, differentiation, and stress response and implicated in both malignant tumor growth and metastasis as well as the pathogenesis of cardiac hypertrophy and fibrotic heart disease. Two peptides were found to specifically bind to ZAKα, PhD30 and PhD35. Their introduction into cancer cells led to the dissociation of ZAKα from RPS20 and the ubiquitination of RPS20 protein resulting in a reduction of essential mitochondria proteins and mitochondria activity impeding the translation of mitochondrial-associated eukaryotic ribosomes, a process we believe to be crucial for tumor growth. This mechanism of action suggests that the primary effect of PhD30 and PhD35 is to lower mitochondrial activity by causing a shortage of essential proteins in mitochondria without changing the number of apoptotic and necrotic cancer cells. Thus, these findings may prove pivotal to the development of a novel approach utilizing these peptides to inhibit cancer cell growth by targeting mitochondrial function, rather than the conventional method of inducing apoptosis.
Bedside Teaching – Insights Into the Medical Student Experience and Likely Impact on Future Role as Clinical Teacher
Authors: Uhomoibhi Catherine , Kearns Angela
Published: March 2024

Background
Medical students and doctors are rarely taught how to be educators but are expected to perform the role of clinical teacher once qualified (Cheesman, 2009). Evidence suggests that clinical teaching has declined in recent years for a variety of reasons (Alpert, 2009), while clear benefits exist when it is done well, particularly concerning history-taking and communication skills. Qureshi (2014) suggests that development of teaching skills should be incorporated into the undergraduate medical curriculum, while Charnell et al (2018) advocate providing training after graduation and as an integrated part of an induction programme. No such strategies currently exist for our graduates, and there is a lack of opinion regarding their expectations and ability to deliver bedside teaching.
Methods
This qualitative study sought to explore the varied experiences of doctors with regards to bedside teaching, and the influence such encounters may have on their future potential role as educator. In-depth interviews were conducted with fourteen final year medical students to gain a detailed understanding. An interpretative phenomenological approach was used for data analysis to organise the data into themes and sub-themes.
Results
Medical students identified a range of affirmative and challenging aspects regarding their undergraduate experiences. All recognized important practices necessary to meet individual learning needs and highlighted the positive impact such experiences would have on their future role as educators. Students preferred receiving constructive feedback as opposed to positive or no feedback at all, and all acknowledged a sense of responsibility towards being a future educator.
Conclusion
The findings of this study suggest that while medical students recognise the role of doctors as clinical educators and strive to fulfil this responsibility based on their own undergraduate experiences, training in the art of clinical teaching would be of benefit to all.
Is a definitive trial of Take-Home Naloxone in emergency settings indicated? Results of a cluster randomised feasibility study
Authors: Snooks Helen A , Jones Jenna K , Bell Fiona B , Benger Jonathon R , Black Sarah L , Dixon Simon , Edwards Adrian , Emery Helena , Evans Bridie A , Fuller Gordon W , Goodacre Steve , Hoskins Rebecca , John Ann , MClinRes Sasha Johnston , Jones Matthew B , Moore Chris R , Parab Rakshita , Pilbery Richard , Sampson Fiona C , Watkins Alan
Published: March 2024

Background
Opioids kill more people than any other class of drug. Naloxone is an opioid antagonist which can be distributed in kits for peer administration. We aimed to determine feasibility of undertaking a definitive randomised controlled trial (RCT) of Take-home Naloxone (THN) in emergency settings.
Methods
Using individual-level-routine health records (2015-21) we tested feasibility of developing a discriminant function to identify people at high-risk of fatal opioid poisoning for outcome comparisons.
We undertook a clustered RCT on paired UK Emergency Department (ED) and ambulance service sites. At intervention sites, we recruited practitioners to administer THN to patients presenting with opioid overdose or related condition during ta 1year recruitment period, 2019 – 21.
We assessed feasibility of intervention and trial methods against predetermined progression criteria.
Results
Within routine health records on the population of Wales (~3,200,000), we identified 1,105 adult deaths from opioid poisoning, of whom 307 (27.8%) had no ED or drugs service contacts in the year before death. At a predicted probability threshold of 0.0003, a discriminant function based on demographics and recent healthcare contacts identified 809 opioid related deaths within 1 year (sensitivity 74.7%) in 989,151 people, missing 274 cases. Lowering the threshold to 0.0002 increased sensitivity to 86.1% but included a further 608,191 non-cases; raising it to 0.0004 reduced sensitivity to 65.4% and inclusion of non-cases to 646,750.
At two intervention sites, randomly selected from 4: 299/687 (43.5%) clinical staff were trained; 60/277 eligible patients (21.7%) were supplied with a THN kit and no adverse events were reported.
Conclusion
With a low incidence of opioid-related death and significant proportion with no contact with ED or drug services in the year before death, the numbers needed to reach a reasonable sensitivity was very high. This study did not meet progression criteria, a fully powered trial is not planned.
Trial Registration
ISRCTN13232859 (Registered 16/02/2018)
Single-cell genotyping and transcriptomic profiling in focal cortical dysplasia
Authors: Baulac Stephanie , Baldassari Sara , Klingler Esther , Teijeiro Lucia Gomez , Doladilhe Marion , Raoux Corentin , Roig-Puiggros Sergi , Bizzotto Sara , Sami Lina , Ribierre Theo , Aronica Eleonora , Adle-Biassette Homa , Chipaux Mathilde , Jabaudon Denis
Published: March 2024

Focal cortical dysplasia type II (FCDII) is a cortical malformation causing refractory epilepsy. FCDII arises from developmental somatic mutations in mTOR pathway genes, leading to focal cortical dyslamination and abnormal cytomegalic cells. Which cell types carry pathogenic mutations and how they affect cell-type-specific transcriptional programs remains unknown. To address this question, here we combined single-nucleus genotyping and transcriptomics in morphologically-identified cells using surgical cortical samples from genetically-characterized FCDII patients. Mutations were predominantly detected in glutamatergic neurons and astrocytes and only a small fraction of mutated cells exhibited cytomegalic features, revealing incomplete penetrance of FCDII-causing mutations. Moreover, we identified cell-type-specific transcriptional dysregulations in both mutated and non-mutated FCDII cells, including synapse and neurodevelopment-related pathways, that may account for epilepsy, and dysregulation of mitochondrial metabolism pathways in cytomegalic cells. Together, these findings reveal cell-autonomous and non-cell-autonomous mechanisms at play in FCDII, towards the development of precision therapies for this disorder.
The role of preconditioning with photobiomodulation in preventing oral mucositis and xerostomia and improving quality of life in cancer patients undergoing chemotherapy: a randomized clinical trial
Authors: khalil marwa , hamadah omar , saifo maher
Published: March 2024

Background
Given the suffering experienced by cancer patients, effective solutions must be found to prevent painful and debilitating side effects of anticancer treatment. This trial aims to study the effect of preconditioning with photobiomodulation in preventing oral mucositis and xerostomia in cancer patients undergoing chemotherapy alone for the first time, and to examine its role in affecting patients' quality of life.
Materials and Methods
This is a prospective, randomized, double-blind clinical trial including 45 patients divided into three age- and sex-matched groups. Group 1: received basic oral care instructions before undergoing chemotherapy. Group 2: received basic oral care instructions plus photobiomodulation using an intraoral 650 nm diode laser. Group 3: received basic oral care instructions plus photobiomodulation using 650 nm diode laser intraorally and 980 nm extraoral.
Results
In Group 2 and Group 3, 73.3% and 80% of patients did not develop mucositis, respectively, while the remaining patients in both groups had only mild erythema. In contrast, all patients in Group 1 had oral mucositis that ranged from mild erythema to ulceration > 3 cm2. There were statistically significant differences between the three groups in oral mucositis assessment scale after a week and after 2 weeks (p = .000). Regarding LENT SOMA scale, there was a statistically significant difference between the three groups studied (P = .037). There was also a statistically significant difference in the Oral Health Impact Profile (OHIP-14) between the three groups studied (P = .003 after a week, P = .023 after 2 weeks).
conclusions
Preconditioning before starting chemotherapy, whether with the intraoral red laser alone or in combination with the extraoral infrared laser, has shown significant results in preventing oral mucositis and dry mouth, and it has also played a major role in improving the quality of life of patients.
Trial registration
This trial was registered in ISRCTN registry under no ISRCTN70634383 (https://doi.org/10.1186/ISRCTN70634383) on 24/07/2023.
The DCN-BiFPN Object Detection Algorithm based on YOLOv8
Authors: Yu Bo , Li Shun , Wang Wei , Meng Yuanze , Liu Dongying
Published: March 2024

Aiming at the problems of traditional target detection algorithms such as high demand for model equipment, low detection accuracy, high leakage rate of overlapping targets, and repeated detection of the same target, we propose an improved multilayer deformable convolution as well as a method for fusing attention mechanisms, and use improved BiFPN feature pyramid feature fusion in the network constructed using this method. First, the improved deformable convolution is used to replace part of the ordinary convolution in the original network to enhance the ability of the modified network to extract feature targets from irregular targets; second, the improved cascade feature fusion module is used to enhance the ability of the neural network to represent features at different scales and semantic levels, and by using the improved cascade feature module, it makes the network able to extract features from feature maps at different levels or scales. features, followed by using the weighted bidirectional feature pyramid network connectivity module to stitch the feature maps of different layers along the channel dimension, which is used to enrich the network's representation capability of the target, and finally, the hybrid attention mechanism is added to the network, which reduces the interference of the background as well as non-target objects on the target, and improves the network's accuracy of target detection. The experimental results show that the improved model in this paper improves over the original model by 3.3\% and 4.7\% in mAP50 and mAP50-95.
Effects of MBP under the ERAS Concept on Electrolyte Disturbances and Functional Recovery after Robotic Surgery for Urologic Tumors in Older Adults
Authors: Liu Hongze
Published: March 2024

Background
Mechanical bowel preparation (MBP) involves the cleansing of bowel excreta and secretions using methods such as preoperative oral laxatives, retrograde enemas, and dietary adjustments. When combined with oral antibiotics, preoperative MBP can effectively lower the risk of anastomotic leakage, minimize the occurrence of postoperative infections, and reduce the likelihood of other complications. To study the effects of MBP under the Enhanced Recovery After Surgery (ERAS) concept on postoperative electrolyte disorders and functional recovery in older people with urological tumors undergoing robot-assisted surgery.
Methods
Older people with urological tumors undergoing robot-assisted surgery were randomly divided into two groups. The experimental group underwent preoperative MBP, while the control group did not. The differences in electrolyte levels and functional recovery between the two groups after radical surgery for urological tumors were observed.
Results
The incidence of postoperative electrolyte disorders in the experimental group was significantly higher than that in the control group (P < 0.05). Subgroup analysis showed that the electrolyte disorder was age-related (P < 0.05). There were no significant differences between the two groups in terms of postoperative complications, gastrointestinal function recovery, laboratory indicators of infection, body temperature, and length of hospital stay (P > 0.05).
Conclusion
Under the accelerated recovery background, preoperative MBP increases the risk of postoperative electrolyte disorders in older people with urological tumors and does not reduce the incidence of postoperative complications or promote postoperative functional recovery.
Obesity prevalence and obesity prediction model among Korean men in their 30s and 40s: a 2022 Community Health Survey
Authors: Han Myeunghee
Published: March 2024

Purpose
This study aimed to explore general and health-related characteristics according to body mass index (BMI). This study aimed to build a predictive model for BMI in Korean men in their 30s and 40s.
Methods
Data from 28,388 men aged 30-40 years from the 2022 Community Health Survey wereused. The participants were divided into underweight / normal weight groups (n=14,296, 50.4%) and overweight / obese groups (n=14,092, 49.6%) based on their BMI. Chi-square tests and independent t-tests were used to compare general and health-related characteristics. A prediction model was constructed using decision tree analysis. A split-sample test was conducted to verify the validity of the prediction model.
Results
The proportions of participants in the underweight / normal and overweight / obese groups were 50.4% and 49.6%, respectively. From the decision tree, the variable of amount of alcohol consumed was the primary factor predicting BMI (chi-square=228.477, p<.001). The characteristics of the group with the highest overweight or obesity rate of 60.6% were that they drank more than seven cups of alcohol at a time, were married, and were sleep-deprived. In contrast, the characteristics of the group with the lowest overweight or obesity rate (38.7%) were that they drank less than six cups of alcohol at a time, got enough or extra sleep time, and smoked less than 15 cigarettes.
Conclusions
The proportions of participants in the underweight / normal and overweight / obese groups were 50.4% and 49.6%, respectively. From the decision tree, the variable of amount of alcohol consumption was the primary factor predicting BMI. The characteristics of the group with the highest overweight or obesity rate of 60.6% were that they drank more than seven cups of alcohol at a time, were married, and were sleep-deprived. In contrast, the characteristics of the group with the lowest overweight or obesity rate (38.7%) were that they drank less than six cups of alcohol at a time, got enough or over sleep time, and smoked less than 15 cigarettes.
CasRx-Based Kras G12D Silencing for In Vivo Tumor Inhibition in Spontaneous Lung Adenocarcinoma
Authors: Wang Xiaojing , Liu Fei , Xu Lingling , Shi Yan , Zhang Linxiang , Chen Fuliang , Gu Shihui , Jin Zhixin , Zhou Hangtian , Li Tianwen , Gong Huiyuan , Li Wei , Zhang Yongyan , Huang Yinlong , Chen Sixieyang , Liu Yueguang , Li Xiang
Published: March 2024

KRAS mutation represents a formidable challenge in cancer treatment. Here, we explored the CasRx-editing approach on lung adenocarcinoma driven by KRAS activation and Tp53 loss in vivo, a scenario closely resembling clinical conditions. We screened seven sgRNAs in vitro and identified CasRx + sgRNA5 effectively suppressed Kras-G12D transcript levels, leading to attenuation of cell growth. Subsequently, we administered CasRx + sgRNA5 via in vivo Adeno-associated viruses (AAV) delivery at the early tumorigenesis stage, resulting in inhibition of tumor initiation and progression, ultimately enhancing the survival of the mice. Mechanistically, the treatment directly inhibited KRAS signal pathways and regulated a potential protein network comprising KRAS, DUSP8, NR4A1, DUSP1, and EGR1. Encouragingly, the CasRx + sgRNA5 treatment in mice bearing the induced adenocarcinoma demonstrated a positive therapeutic outcome, characterized by seemingly reduced mutation burden, diminished tumor size, and trend of improved overall survival. Remarkably, no obvious off-target events were detected, highlighting the specificity and safety of CasRx therapy. This study establishes the feasibility of CasRx-based-Kras-G12D editing for in vivo tumor inhibition and provides insights into the potential role of the KRAS-associated protein network in early development of lung cancer. These findings hold promise for development of CasRx therapies for this aggressive malignancy.
Desmin Phosphorylation in human skeletal muscle can be modified by Resistance Exercise rendering the protein less vulnerable to protease-dependent cleavage
Authors: Jacko Daniel , Schaaf Kirill , Aussieker Thorben , Masur Lukas , Zacher Jonas , Bersiner Käthe , Bloch Wilhelm , gehlert Sebastian
Published: March 2024

The desmin intermediate filament (IF) system plays a crucial role in stress transmission, mechano-protection, and the regulation of signaling in skeletal muscle. Loss of IF integrity is considered a triggering factor for myofibril breakdown and muscle atrophy. Phosphorylation of desmin (pDes) has been identified as a priming factor leading to an organized process provoking muscle atrophy. Intervening in pDes has been suggested as a promising method to counteract the loss of muscle mass. Physical exercise stands out as a prominent and non-pharmacological option for purposefully modifying cellular signaling to promote muscle health and function.
To investigate whether resistance exercise (RE) specifically influences the regulation of pDes, 10 healthy young men (n=7) and women (n=3) performed 7 weeks of RE training (14 sessions; 2 per week). Muscle biopsies were collected in both untrained and trained conditions at rest (pre 1, pre 14) and one hour after RE (post 1, post 14). Desmin content and phosphorylation at serine 31 and 60 (pDesS31, pDesS60) as well as threonine 17 and 76/77 (pDesT17, pDesT76/77) were analyzed.
In untrained condition (pre 1, post 1), acute RE resulted in the dephosphorylation of S31 (p < 0.001) and S60 (p < 0.05). This was accompanied by reduced susceptibility of desmin in the exercised muscle to protease-induced cleavage compared to the resting state (p < 0.05). In the trained condition (pre 14, post 14), acute RE led to an augmented dephosphorylation of S31 (p < 0.01) as compared to the untrained condition (p < 0.05). Furthermore, training affected baseline phosphorylation, upregulating S31 and attenuating S60 as well as T17 while increasing total desmin content.
We conclude that RE is a potent stimulus for modifying desmin phosphorylation, making the protein less prone to cleavage. Because repeated resistance training changes the phosphorylation pattern of Desmin, we introduce pDes as an adaptive mechanism of skeletal muscle, contributing to the proteostatic regulation in response to recurring stress. Focusing on underlying mechanisms and determining the most effective loading in RE-dependent induction of pDes-modification might be a promising strategy to challenge muscle atrophy in health and disease.
Design, Implementation and Evaluation of an AI-based Tutor for Persian Learners of English Language
Authors: Vahid Mirzaeian
Published: March 2024

This paper endeavors to delineate the development and deployment of an AI-based intelligent feedback generator tailored to assist Persian learners of the English language. With a primary focus on efficacious system design, the approach involved compiling comprehensive data to pinpoint the most challenging aspects for such learners. Leveraging two AI-based engines for Persian and English, a feedback generator was devised. The framework fulfilled expectations by juxtaposing the logical forms of English and Persian sentences, thereby facilitating error detection. Most of the errors diagnosed were related to misused prepositions, determiners, tenses, and subjects. The results indicated its effectiveness to teach the English language to such learners. With minor adjustments, the system can also be adapted to aid English learners of Persian as it is capable of parsing input from both languages.
Investigating the role of GDF-15 in diabetes and obesity: A comprehensive analysis of a cohort from the KEDP-study
Authors: Abubaker Jehad , Abu-Farha Mohamed , Abdalla Mohammed , Albatineh Ahmed N , Al-Khairi Irina , Cherian Preethi , Qaddoumi Mohammad , Abdul-Ghani Muhammad , Al-Mulla Fahd
Published: March 2024

Introduction:
Growth differentiation factor 15 (GDF-15), a member of the transforming growth factor-β (TGF-β) superfamily, is expressed in various tissues and is produced during stressful conditions such as inflammation and oxidative stress. It has recently gained attention as a potential diagnostic and prognostic marker for metabolic disorders. However, little is known about the GDF-15 protein expression in diabetes and obesity, particularly across various ethnicities, age groups, and genders. This study investigated the association between GDF-15 plasma levels, diabetes mellitus, and obesity in individuals of various ages, ethnic groups, and genders.
Methods
We measured plasma GDF-15 concentrations in 2,083 participants from the Kuwait Diabetes Epidemiology Programme (KDEP) study cohort. The cohort included information on a anthropometric clinical, biochemical, and glycemic markers. The phenotype data were analyzed using multivariate regression analysis.
Results
The average plasma GDF-15 concentration across the study cohort was significantly higher in males than in females (580.6 ng/L vs. 519.3 ng/L, p < 0.001) and in those who were > 50 years old than those < 50 years of age (781.4 ng/L vs. 563.4 ng/L, p < 0.001). Participants from Arab ethnic backgrounds had higher GDF-15 levels than South Asians and Southeast Asians (597.0 vs 514.9 and 509.9 ng/L, p < 0.001). Furthermore, GDF-15 levels were significantly higher in obese individuals, in diabetic individuals, and in insulin resistant individuals. GDF-15 levels were positively corrrelated with BMI, hip and waist circumferences, blood pressure readings, and glycemic indices, including insulin and triglyceride levels, while they were negatively correlated with HDL.
Conclusion
The observed findings on the associations between higher levels of GDF-15 and increased age, diabetes, obesity, and insulin resistance suggest that GDF-15 may have particular utility as a valuable biomarker for metabolic disorders, especially in older age groups, among males, and within specific ethnic groups.
Amentoflavone maintaining extracellular matrix homeostasis and inhibiting subchondral bone loss in Osteoarthritis by Inhibiting ERK, JNK and NF-κB Signaling Pathways
Authors: Liang Jianhui , Hu Jiawei , Hong Xin , Zhou Ming , Xia Guoming , Hu Liangshen , Luo Song , Quan Kun , Yan Jianbin , Wang Song , Fan Shaoyong
Published: March 2024

Amentoflavone (AF), a plant biflavone isolated from Selaginella sinensis ethanol extract, is characterized by anti-inflammatory and anti-oxidant properties. According to previous studies, inflammation and oxidative stress are closely related to the pathophysiology of osteoarthritis (OA). However, the effects and mechanisms of AF on OA have not been elucidated.To investigate the inhibitory effects and its molecular mechanism of AF on extracellular matrix (ECM) degradation stimulated by IL-1β as well as subchondral bone loss induced by RANKL in mice chondrocytes. Quantitative PCR was used to detect the mRNA expression of genes related to inflammation, ECM, and osteoclast differentiation. Protein expression level of iNOS, COX-2, MMP13, ADAMTS5, COL2A1, SOX9, NFATc1, c-fos, JNK, ERK, P65, IκBα was measured by western blotting. The levels of TNF-α and IL-6 in the supernatants were measured by ELISA. The amount of ECM in chondrocytes was measured using toluidine blue staining. The levels of Aggrecan and Col2a1 in chondrocytes were measured using immunofluorescence. Tartrate-resistant acid phosphatase (TRAP) staining, F-actin staining and immunofluorescence were used to detect the effect of AF on osteoclast differentiation and bone resorption. The effect of AF on destabilization of the medial meniscus (DMM)-induced OA mice can be detected in hematoxylin-eosin (H&E) staining，Safranin O green staining and immunohistochemistry.AF might drastically attenuated IL-1β-stimulated inflammation and reduction of ECM formation by blocking ERK and NF-κB signaling pathways in chondrocytes. Meanwhile, AF suppressed the formation of osteoclasts and the resorption of bone function induced by RANKL. In vivo, AF played a protective role by stabilizing cartilage ECM and inhibiting subchondral bone loss in destabilization of the medial meniscus (DMM)-induced OA mice, further proving its protective effect in the development of OA. Our study show that AF alleviated OA by suppressing ERK, JNK and NF-κB signaling pathways in OA models in vitro and DMM-induced OA mice, suggesting that AF might be a potential therapeutic agent in the treatment of OA.
Performance Analysis of Rdx Mechanism in Data Transmission Using Ibm Web Sphere, Ai and Tandem Queue
Authors: NIRANJAN S. P. , LATHA S.DEVI
Published: March 2024

In this paper we have discussed tandem queue with two service nodes. In this system, the customer require services at both nodes elaborated RDX mechanism and IBM web sphere in artificial intelligence (AI). The first essential service (FES) starts in data search and initiating the data to be required in using the RDX mechanism then the second essential service (SES) starts from validating the information in IBM web sphere and insight with the use of AI. After the completion of a service at node1 if the minimum number of customer is less than ‘a’ then the server leaves for secondary job. The service started once the vacation reaches the threshold value. When the service ends at node 1, it departs from here to proceed node 2 and receive the second service from there. We have to find PGF of a queue size at an arbitrary time epoch by using supplementary variable technique. Various characteristics of the queueing system are also obtained with a numerical solution.
A practical trial example in flood susceptibility studies: Determination of flood susceptibility in Bozburun Peninsula (Marmaris/Türkiye) basins
Authors: ÖZKAN Efekan , EGE İsmail , POLAT Selahattin
Published: March 2024

This study, carried out in the Bozburun Peninsula (Marmaris-Türkiye), which constantly faces the reality of flood disasters, aimed to determine the torrent and flood susceptibility levels on the basis of sub-basins. For this purpose, some hydrological analyses frequently used in geomorphology and hydrology studies were used. An important part of these analyses consists of the calculation of some morphometric indices. The indices preferred and calculated in our study are; bifurcation ratio (Br), texture ratio (T), drainage density (Dd), basin shape ratio (Bs), relief ratio (Rr), roughness value (Rn), stream accumulation time (Tc), hypsometric integral (Hi) and harmonic slope averages (Hsl) of the first series of streams in each sub-basin. Arc GIS 10.5 package program was used to create and process morphometric indices. While determining the torrent and flood susceptibility of the basins in question, the ranking and scoring of each parametric value on a sub-basin basis was done using a colouring scale in the Microsoft Excel 2010 program. First, the sub-basins were ranked according to their flood generation potential, and then, as 10 sub-basins were selected, susceptibility scores from 1 to 10 were assigned. However, only detecting and scoring the parameters in question may not be sufficient in some cases. Because each parameter will not contribute equally to flood susceptibility. In addition, relying only on expert opinion may lead to a subjective evaluation. The main difference of this study stems from the search for ways to eliminate this problem. In order to overcome these limitations and subjective evaluations, the AHP method, which is a decision-making matrix, was used in the study. In this way, it is thought that a stronger and more objective ranking can be achieved in a quantitative sense. For this purpose, the weight percentage results obtained in AHP were added to the previous scoring as a multiplier. Ultimately, these rankings were reduced to five susceptibility categories -simplified- and mapped. As a result of the analysis, it was determined that the sub-basins in the peninsula, which have a significant population, have high/very high flood susceptibility. Historical floods and field works were used as references to check the results obtained, and it was seen that the results pointed to basins that constantly face floods. Only the selection of these parameters and the extent to which prioritization with AHP will benefit need to be controlled in different regions. However, despite all this, it is thought that this study will be able to provide practical benefit and guidance to relevant researchers and decision makers.
Outcomes of laparoscopic, robotic and open nephroureterectomy with bladder cuff excision in patients with T3T4 upper urinary tract urothelial carcinoma: a multi-center retrospective study
Authors: Fang Jen-Kai , Yeh Hsin-Chih , Lee Hsiang-Ying , Weng Han-Yu , Tai Ta-Yao , Huang Chao-Yuan , Hong Jian-Hua , Yu Chih-Chin , Wu Shu-Yu , Chung Shiu-Dong , Tsai Chung-You , Hsueh Thomas Y. , Chiu Allen W. , Jiang Yuan-Hong , Lee Yu Khun , Chen I-Hsuan Alan , Lin Jen-Tai , Chen Yung-Tai , Lin Chang-Min , Cheong Ian-Seng , Huang Hsu-Che , Lo Shih-Hsiu , Lin Wei-Yu , Tseng Jen-Shu , Wu Chia-Chang , Wang Shian-Shiang , Chang Yi-Huei , Chang Chao-Hsiang
Published: March 2024

Background
Nephroureterectomy with bladder cuff excision is the standard treatment for high-risk upper urinary tract urothelial carcinoma (UTUC). Minimally invasive surgery is the most common procedure in our experience, however previous prospective studies have reported inferior oncological outcomes of laparoscopic nephroureterectomy for locally advanced UTUC. The aim of this study was to compare the outcomes of open, laparoscopic and robotic surgery.
Methods
We retrospectively reviewed 705 patients with locally advanced UTUC from multiple institutions throughout Taiwan. Perioperative outcomes and oncological outcomes were compared between the open, laparoscopic and robotic groups.
Results
The minimally invasive group had better overall and cancer-specific survival (CSS) rates. The 5-year CSS rates of the open, laparoscopic and robotic groups were 51%, 69%, and 77% respectively (p < 0.001). The robotic group had similar outcomes to the laparoscopic group. More lymph node dissections were performed and more lymph nodes were harvested in the robotic group.
Conclusions
Laparoscopic or robotic surgery can lead to better perioperative and oncological results in patients with locally advanced UTUC.
Dynamic Prospective Average and Marginal Impact Factors from a Scenario-Based Method for the German Power System until 2070
Authors: Blanke Tobias , Döring Bernd , Göttsche Joachim , Frisch Jérôme , Treeck Christoph van
Published: March 2024

Background: Rising greenhouse gas concentrations, primarily carbon dioxide, are raising global temperatures. Germany aims to reduce emissions by 95 \% by 2045 compared to 1990 under the Climate Change Act 2021. This paper introduces two methodologies to determine hourly German electricity system values for this decarbonization period: crucial for life cycle assessment (LCA) and carbon accounting (CA). It examines methodologies, including a new electricity impact calculation model which accounts for storage construction's environmental impact.
Methods: To achieve the study's objectives, an electricity dataset with hourly resolution will be explained. Subsequently, the two methodologies will be elucidated and applied to this dataset for multiple LCA impact categories.
Results: According to the results, the new model, which considers the emissions from storage construction, produces higher emissions than the existing model. This increase is more pronounced in future scenarios where storages have a higher share of electricity and during hours when storage discharge is high. This trend is observed for most of the considered LCA impacts. The newly calculated emissions match the literature values.
Conclusions: Based on the analysis, the obtained outcomes can be inferred to be reasonable. Moreover, comparing the two electricity impact models revealed significant variations in the results as the electric grid storage capacity increased. Therefore, the newly proposed model is beneficial in scenarios with high storage system capacity.