Abstract: Female pelvic floor dysfunction (FPFD) is a series of conditions caused by the displacement or dysfunction of the patient's pelvic organs due to defects, injuries, and deterioration of the pelvic floor supportive structures, with stress urinary incontinence and pelvic organ prolapse being the most common. The mechanism of pelvic floor dysfunction is complex and not yet fully understood, and is often related to one or more functional abnormalities of muscles, connective tissues, fascia, nerves and blood vessels. Specialized clinicians are often unable to cover the comprehensive medical professional information of various specialties such as gynecology and obstetrics, urology, anus and intestines, imaging, etc., and the systematic and comprehensive diagnosis and treatment of the disease will be limited. The application of artificial intelligence concepts in the medical field not only improves the diagnostic efficiency of physicians, but also provides reference and basis for the development of comprehensive treatment programs. This article follows and draws on the diagnosis and treatment process of pelvic floor dysfunction recommended in various guidelines, incorporates physical therapy techniques into the conventional non-surgical treatment of pelvic floor dysfunction, provides guidance for the diagnosis and treatment of pelvic floor dysfunction, and briefly introduces the clinical application and value of pelvic floor intelligent diagnosis and treatment in pelvic floor dysfunction.

Due to the still large number of patients diagnosed with pelvic neoplasms (colorectal, gynecological, and urological) in advanced stages right from the initial diagnosis, surgery represents the mainstay of treatment, often implying wide, eventually multi-organ resections in order to achieve negative surgical margins. Perineal wound morbidity, particularly in extralevator abominoperineal excision, leads to complications and local infection rates of up to 40%. Strategies to reduce postoperative wound complications are pursued to address this issue.The VRAM flap remains the gold standard for autologous reconstruction after pelvic oncological resection; it was initially designed for abdominal wall defects and later expanded for large pelvic tissue defects.The flap's application is based on its physical characteristics, including abundant tissue and a generous skin paddle, which effectively obliterates dead space after exenterations. The generous skin paddle offers good cosmetic and functional outcomes at the recipient site.This article describes the case of a patient histopathologically diagnosed with stage IIIA squamous cell carcinoma of the uterine cervix who received multimodal onco-surgical treatment. The surgical mainstay of this treatment is pelvic exenteration. Pelvic reconstruction after this major surgery was performed using a vertical flap with the rectus abdominis.

Background: Parity and vaginal delivery may contribute to female urinary incontinence prev-alence. The aim of this study was to evaluate the impact of parity and type of child delivery on pelvic floor muscle strength (PFMS). Material and Methods: 140 healthy women were prospectively evaluated and distributed into 4 groups: G1 (n=34) 30-40 years old; G2 (n=38) 41-50; G3 (n=35) 51-60 and G4 (n=33) over 60. De-mographic data, and body mass index (BMI) were obtained using a clinical questionnaire. Sub-jective PFMS assessments were performed using transvaginal digital palpation (TDP), and ob-jective evaluation was obtained using a portable perineometer. Results: BMI was significantly higher in G4 compared to G1. There was a positive linear rela-tionship between age and BMI. The number of pregnancies was higher in G4 compared to G2 and vaginal delivery was more frequent in G4 compared to G1 and G3. There was no statistical correlation among different groups in PFMS assessed either by TDP and perineometer. Like-wise, we did not observe any negative linear relationship between PFMS and parity or number of vaginal deliveries. Conclusion: Our data demonstrates that both the number of pregnancies and of vaginal deliv-eries had no impact on PFMS in continent women.

Stress urinary incontinence (SUI) influences the quality of life of women. The research applied ICIQ LUTS qol (The International Consultation Incontinence Questionnaire Lower Urinary Tract Symptoms quality of life) as a tool to measure the quality of life (QOL) of patients with stage 1 SUI in many areas. 140 perimenopausal women who participated in a urodynamic test at Department of Gynecology, Endocrinology and Gynecologic Oncology, Pomeranian Medical University, Police, Poland in the years 2013-2015 were enrolled in the study. Patients were divided into two groups: A and B. Two questionnaires were applied: the author’s original questionnaire and the standardized ICIQ LUTS qol. Gymnastic plans were recommended 4 times per week for the period of 3 months. The plan for group A included the exercises of pelvic floor muscles (PFM) with the simultaneous tension of the transverse abdominal muscle (TrA) and for group B included the exercises of PMF without TrA. The evaluation of the quality of life of patients with stage 1 SUI with the use of ICIQ LUTS qol among patients from groups A and B after therapy showed a significant improvement in most areas. More impact is observed in the physiotherapy of both PFM with TrA.

Background/Objectives Bowel endometriosis (BE) is defined as the presence of endometrial-like tissue in the muscular layer of the bowel wall. When BE does not cause severe obstruction to fecal transit, not leading to (sub)occlusive symptoms, the decision to operate becomes challenging as intestinal surgery is associated with higher complication rates and long-term bowel dysfunction. The aim of this cross-sectional study is to evaluate the quality of life (QoL) in patients with BE undergoing medical therapy or expectant management, investigating the impact of characteristics of BE nodules on QoL and intestinal function. Methods A retrospective cross-sectional analysis was conducted on 580 patients with BE who did not undergo surgery but were treated conservatively by medical therapy or expectant management between January 2017 and August 2022. The diagnosis of BE was done by transvaginal ultrasound and confirmed at double contrast barium enema. After at least one year of follow-up, QoL and intestinal function of patients were evaluated by the Endometriosis Health Profile-5 (EHP-5) questionnaire and Bowel Endometriosis Symptom score (BENS), whereas pain symptoms were assessed by the Visual Analogic Scale (VAS 0-10). Statistical analysis was performed to investigate possible associations between QoL and characteristics of bowel nodules (dimension, location, and evidence of stenosis) as well as type and length of eventual medical therapy. Results Patients with BE had a satisfying overall QoL with a mean EHP-5 score of 105.42 ± 99.98 points and VAS lower than 3 for all pain domains; additionally, they did not show a significant impartment of bowel function with mean BENS score of 4.89 ± 5.28 points. Notably, patients under medical therapy had a better QoL than patients without therapy (p

This study investigates the application of frequency augmentation techniques to improve condition-based maintenance (CBM+) systems for airborne weapon systems, focusing on the predictive accuracy of velocity and acceleration parameters. Utilizing MIL-STD-1553B MUX data from 138 sorties of fixed-wing aircraft, we explored six augmentation methods, including traditional interpolations (linear, quadratic, cubic spline) and advanced machine learning models (K-Nearest Neighbor, LSTM, and Bi-LSTM). Our findings indicate that while traditional methods like linear interpolation are more effective for velocity parameters, advanced ML techniques, particularly Bi-LSTM, provide better results for acceleration parameters, which exhibit more complex and rapid variability. The study underscores the necessity of tailoring augmentation approaches to specific parameter characteristics and highlights the potential of ML models in capturing intricate patterns within time-series data. These insights are critical for advancing CBM+ systems in military avionics, enhancing reliability and operational efficiency through improved data processing strategies. Future work should explore more performant augmentation techniques, such as by integrating multi-dimensional datasets, and explore ways to develop automated tools for a more powerful predictive maintenance framework.

Quantitative analysis of human gait is critical for early discovery, progressive tracking, and rehabilitation of neurological and musculoskeletal disorders, such as Parkinson’s Disease, stroke, and Cerebral Palsy. Gait analysis typically involves estimating gait characteristics, such as spatio-temporal gait parameters and gait health indicators (e.g., step time, length, symmetry, and balance). Traditional methods of gait analysis involve the use of cameras, wearables, and force plates, but are limited in operational requirements when applied in daily life - such as direct line-of-sight, carrying devices, and dense deployment. This paper introduces a novel approach for gait analysis by passively sensing footstep-induced floor vibrations during walking using vibration sensors mounted on the floor surface. Our approach is non-intrusive, scalable, and perceived as more privacy-friendly, making it suitable for continuous gait health monitoring in daily life. We developed a floor vibration-based gait analysis framework to estimate various gait parameters that are used as standard metrics in medical practices, including temporal parameters (step, stride, stance, swing, double-support, single-support time) and spatial parameters (step length, width, angle, stride length), and extracts gait health indicators (cadence/walking speed, left-right symmetry, gait balance, initial contact types). The main challenge is that floor vibrations are distinct across different floor types. To address this challenge, our approach develops floor-adaptive algorithms to extract floor-specific features and is designed to be generalizable to various settings, including homes, hospitals, and eldercare facilities. We evaluate our approach through real-world walking experiments with 20 adults with 12,231 labeled gait cycles across concrete and wooden floors. Our results show 90.5% (RMSE 0.08s), 71.3% (RMSE 0.38m), and 92.3% (RMSPE 7.7%) accuracy in estimating temporal, spatial parameters, and gait health indicators, respectively.

Background/aims: Prior research identified a significant association between heart disease and metabolic dysfunction-associated liver steatohepatitis (MASLD), but the mechanisms are unclear. This study aims to search predictive biomarkers for grade I left ventricular diastolic dysfunction (LVDD), an early stage of heart failure (HF), in type 2 diabetes mellitus (T2DM) patients. Methods: This single-center, prospective observational study screened 73 T2DM patients for grade 1 LVDD and MASLD using 2D echocardiography, tissue analysis, spectral color Doppler, and Fibromax. Results: The study analyzed 50 patients (mean age 58±11.3 years) with a median diabetes duration of 7 years, abdominal obesity (mean BMI 34.4±5.9 kg/m2), and a mean HbA1c of 7.9±1.5%. The prevalence of grade I LVDD, fibrosis, mild steatosis, moderate to severe liver steatosis, mild MASLD, and moderate MASLD was 54%, 44%, 14%, 80%, 43%, and 34%, respectively. Regression analysis revealed that grade 1 LVDD was positively associated with age, Fibrotest, ɑ2-macroglobulin, epicardiac adipose tissue (EAT), and negatively associated with lateral s`, E wave, E/e`, E/A, medium E`, and septal e` (p< 0.05 for all). ɑ2-macroglobulin > 1.92 g/L (AUROC= 0.782, sensitivity 70.4%, specificity 81.2%) and fibrotest score > 0.11 (AUROC 0.766, sensitivity 92.6%, specificity 56.2%) were significant predictors of grade I LVDD. Conclusion: HF is a multifaceted disorder associated with multisystem organ damage, including nonalcoholic MASLD. Although the underlying mechanisms remain unclear, innovative non-invasive biomarkers, such as ɑ2-macroglobulin or fibrotest, could concurrently indicate liver stiffness and the likelihood of grade I LVDD, an early, asymptomatic HF stage in T2DM patients.

Introduction Total pelvic exenteration (TPE) is a highly complex surgery associated with a high morbidity rate of 40% in reference units. It is performed for advanced or recurrences tumors in the pelvis with infiltration of multiple organs. Sometimes TPE is indicated in situations of palliation due to the side effects of radiotherapy or tumor progression. The aim of our study is to evaluate a single center experience in TPEs using a minimally invasive approach (LTPE) and compare the perioperative outcomes with the open technique (OTPE). Material and methods A prospective study of the TPE carried out in our unit between 2013-2023 was used. All anterior and posterior exenterations were discarded. Perioperative outcomes were evaluated. Results A total of 19 TPEs were analyzed, 9 LTPEs and 10 OTPEs. Most tumors originated from the colon and cervix. Hyperthermic intraperitoneal chemotherapy (HIPEC) was applied in one case of LTPE and intraoperative radiotherapy (IORT) in one case of OTPE. Cases with palliative intent were one in each group. Surgery time was 407 minutes for LTPE and 367 min for OPTE (p=0.38). Length of hospital stay was longer in the OPTE group at 21.6 days vs LTPE with 10.1 days, (p=0.23). The R0 rate excluding palliative cases was 88.9% for LTPE vs. 70% for OPTE (p=0.33). Major morbidity (grade III) was 45% in the LTPE group with no mortality and 40% (grade III/IV) in the OPTE group with one patient dying on admission. Survival was similar in both groups. Conclusion LTPE is a feasible and safe approach with similar perioperative outcomes and a trend toward shorter hospital stay.

Peritoneal fluid is an ovarian exudate from the growing follicle or corpus luteum. Therefore, the free concentrations of estrogens and progesterone are always much higher than in plasma, especially after ovulation. The peritoneum is not vascularised, and peritoneal implants and the superficial portion of deep endometriosis are likely influenced mainly by peritoneal fluid. Follicular phase progesterone concentrations are as high as during the luteal phase in plasma. This explains that most peritoneal implants are rarely proliferative and out of phase with the endometrium. From some 5 mm of depth onwards, endometriosis is rather influenced by plasma hormone concentra-tions, and the deeper parts can be proliferative as the endometrium. Because of these progesterone concentrations, progesterone resistance has to be postulated, permitting endometriosis lesions to initiate and develop. This opens the discussion of whether endometriosis is similar to the basal endometrium. These peritoneal fluid concentrations are important to understand the natural history and medical therapy of endometriosis. Most medical therapies decrease ovarian function and affect peritoneal fluid steroid hormone concentrations. It is suggested that the efficacy of medical therapy for endometriosis-associated pain is a consequence of the decreased estrogen concentrations in the peritoneal cavity and that the local effect of progestins may not be determinant for pain relief. If this is true, a history of endometriosis should not be considered a contraindication for hormone re-placement therapy.

Transport systems are essential in the path towards sustainable urbanisation and the transition to more sustainable living. Recently, European cities have undergone substantial changes, owing to which suburbanisation is posing new challenges. Suburban areas are often more affordable in terms of housing, but their neighbourhoods tend to be car-oriented. This leads to higher commuter costs, immobility, transport and time poverty, pollution, and accident rates and a lack of social interaction. To offer sustainable mobility options to citizens, we must comprehensively understand their specific mobility practices, together with their personal characteristics, and the built environment. This study centred on the Barcelona Metropolitan Region, which has a public transport network that covers the entire area. The aim of this study was to examine the relationship between travel behaviour, transport mode use, individual characteristics, and place of residence, using detailed information sources. Herein, we used data from the annual travel survey conducted in the Barcelona region from 2018 to 2021, together with land-use and other information sources. Our findings suggest that transport policies have encouraged sustainable mobility practices, particularly in the centre of Barcelona. Despite the positive results, considerable disparities exist between the inner and outer city, with notably decreased sustainable mobility practices in the latter. Our results indicate that promoting sustainable mobility policies requires further changes in transport, city, and land-use planning that consider equity, the socioeconomic profile of citizens, and mixed urban planning.

Background: Handheld cameras may increase access to teleretinal diabetic retinopathy screenings (TDRS), as they are more economical and nimbler than traditional desktop cameras. However, their use in safety-net clinical settings is less understood. Methods: The Los Angeles County Department of Public Health collaborated with the Los Angeles County Department of Health Services (DHS) to pilot the use of handheld cameras in DHS’s TDRS program. This study assessed screening metrics and interviewed TDRS coordinators and photographers about their experiences using these cameras. Results: Handheld cameras are harder to operate and performed less optimally on key screening metrics (e.g., image quality) compared to desktop cameras. However, this challenge appeared to be linked to the selected model, rather than to all handheld cameras. The adoption of handheld cameras in DHS was aided by their integration into an existing agency infrastructure that already supports the use of desktop cameras; these operational supports include an established workflow, a data platform, and experienced photographers. Conclusions: The use of handheld cameras for TDRS is a promising practice for assuring equitable access to screenings. Handheld cameras are portable, smaller in size, and lower in cost than desktop cameras. Future projects should invest in and assess the performance of higher-quality models of these cameras, especially their use in safety-net clinical settings.

Background: Amyloid beta peptides (Aβ) have been identified as the main pathogenic agents in Alzheimer’s disease (AD). Soluble Aβ oligomers, rather than monomer or insoluble amyloid fibrils, show membrane-binding capacity to red blood cells (RBCs) and trigger several morphological and functional alterations in RBCs that can result in impaired oxygen transport and delivery. Since bioactive lipids have been recently proposed as potent protective agents against Aβ toxicity, we investigated the role of sphingosine-1-phosphate (S1P) in signaling pathways involved in the mechanism underlying ATP release in Aβ-treated RBCs. Methods: In RBCs following different treatments, ATP, 2,3 DPG, cAMP levels, and caspase 3 activity were determined by spectrophotometric and immunoassay. Results: S1P rescued the inhibition of ATP release from RBCs triggered by Aβ through a mechanism involving caspase-3 and restoring 2,3 DPG and cAMP levels within the cell. Conclusions: These findings reveal the molecular basis of S1P protection against Aβ in RBCs and suggest new therapeutic avenues in AD.

Background: We aimed to evaluate the effect of early pelvic binder use in emergency management of suspected pelvic trauma, compared with the conventional stepwise approach. Methods: We enrolled trauma patients with initial stabilization using a pelvic binder for suspecting pelvic injury. Inclusion criteria were traumatic injury requiring a trauma team and at least one of the following: loss of consciousness or Glasgow coma score (GCS) < 13; systolic blood pressure < 90 mmHg; falling from ≥6 m; injury to multiple vital organs; and suspected pelvic injury. Various parameters, including gender, age, mechanism of injury, GCS, mortality, hospital stay, initial vital sign, revised trauma score, injury severity score, and outcome, were assessed and compared with historical controls. Results: A total of 204 patients with high-energy multiple-trauma from single level I trauma center in North Taiwan were enrolled in the study from August 2013 to July 2014. The two group baseline patient characteristics were all collected and compared. The trauma patients with suspected pelvic fractures initially stabilized with a pelvic binder had shorter hospital and ICU stays. The study group achieved statistically significantly improved survival and lower mean blood transfusion volume and mortality rate although they were more severe in the trauma score. Conclusions: We recommend prompt pelvic binder use for suspected pelvic injury before definitive imaging is available, as a cervical spine collar is used to protect the cervical spine from further injury prior to definitive identification and characterization of an injury.

Bamboo engineering materials are green, high-strength, tough, durable, and structurally safe, and have promising application prospects in various modern green and low-carbon buildings. To invest the vibration behavior of new bamboo bundle veneer -laminated lumber (BLVL) for use in floor slabs, this study designed two kinds of full-scale vibration tests under a pedestrian load: an extraction hammer impact test, and a static concentrated load test, it is expected to provide theoretical and data support for the application of bamboo bundle veneer laminated composite materials in the construction field. The results showed that the self-oscillation frequency and mid-span deflection of the BLVL composite met the requirements of multiple relevant regulations when used as the structural material of floor slabs. The BLVL floor slab had a higher flexural stiffness and better vibration-damping performance than the OSB floor slab. The first-order self-oscillation frequency of the BLVL composite floor slab was 13.769 Hz, the damping ratio of the first three orders of modalities was 1.262–2.728%, and the maximum static deflection in the span of the joist was 0.932 mm under a 1 kN concentrated load. The 1 kN static deflection of the BLVL was reduced by 22.33%, and the root mean square (RMS) acceleration of the walking load response was significantly lower than that of the OSB floor slab. The preparation of BLVL composite materials by homogeneous lamination of bamboo bundle veneer and wood veneer may help improve the vibration behavior of bamboo-wood structures such as floor slabs and walls.

Feeling pain means feeling oneself, as the body feels discomfort as a kind of "disturbance experi-ence". Endometriosis is a disease in which the predominant symptom is pain felt by women pri-marily within the pelvis, but also outside of the body. The clinical biomarker used in the diagnosis of this disease is microRNAs. Treatment of endometriosis is complex and is based mainly on phar-macotherapy. Physiotherapy can complement pharmacological treatment in reducing pain using non-invasive treatments for the body. Therefore, databases have been searched to find the most effective forms of physiotherapy for the treatment of endometriosis. The literature review conducted here suggests that it is necessary to perform multicentre studies in order to establish which forms of physical therapy may be most effective in reducing pain and improving the quality of life of women suffering from endometriosis. Certainly, this type of research in conjunction with the assessment of pain and endometriosis markers would be of great clinical value in order to develop an interdisci-plinary treatment model.

The human landscape transforming activity contributes to the global change of vegetation in different forms. Hunting is one of the most ancient human landscape-shaping activities. Feeders for hunting are particularly disruptive to vegetation. In the present study, we conducted a vegetation survey in these highly disturbed places. We are investigating the vegetation dynamics over several years in in the turkey oak–sessile oak zone, in two areas with different moisture and shade conditions (forest and clearing). One important background factor is changes in precipitation and temperature. The novelty of our present study lies in the fact that the observation takes place with continuous disturbance, where the human influence is very large. Our results confirm that the weed infestation be detectable at bait sites over a long period, and the interannual changes were typical in every year, according to the fact that in August, more weed species are usually present with a greater cover at the bait sites. The main meteorological factors played a role in the degree of weed infestation in each year. There was a higher proportion of vegetation regeneration in wetter years, while dry periods do not favor successional processes. With the drying of the climate, the disturbed areas are constantly losing their natural value, but wetter weather is not an automatic solution either. A more precise understanding of vulnerable systems and careful planning of treatment interventions is necessary.

In the past thirty years, childhood obesity rates have risen significantly worldwide, affecting over 340 million children in affluent nations. This surge is intricately tied to metabolic disorders, notably insulin resistance, type 2 diabetes mellitus (T2DM), and the continually evolving spectrum of metabolic-associated (dysfunction) steatotic liver disease (MASLD). This review underscores the alarming escalation of childhood obesity and delves comprehensively into the evolving and dynamic changes of nomenclature surrounding diverse conditions of hepatic steatosis, from the initial recognition of non-alcoholic fatty liver disease (NAFLD) to the progressive evolution into MASLD. Moreover, it emphasizes the crucial role of pediatric endocrinologists in thoroughly and accurately investigating MASLD onset in children with T2DM where each condition influences and exacerbates the progression of the other. The review critically highlights the inadequacies of current screening strategies and diagnosis, stressing the need for a paradigm shift. A proposed solution involves the integration of hepatic magnetic resonance imaging assessment in the diagnostic arsenal for children showing insufficient glycaemic control and weight loss post-T2DM diagnosis, thereby complementing conventional liver enzyme testing. This holistic approach aims to significantly enhance diagnostic precision, fostering improved outcomes in this vulnerable high-risk pediatric population.

Digital gait monitoring is increasingly used to assess locomotion and fall risk. The aim of this work is analyzing the changes in the foot-floor contact sequences of Parkinson’s Disease (PD) patients in the year following the implant for deep brain stimulation (DBS). During their best-ON condition, 30 PD patients underwent gait analysis at baseline (T0), at 3 months (T1), and 12 months (T2) after the DBS neurosurgery for bilateral high-frequency subthalamic nucleus stimulation. Thirty age-matched controls underwent gait analysis once. Each subject was equipped with bilateral foot-switches and a 5-minute walk was recorded, including both straight-line and turnings. The walking speed, turning time, stride time variability, percentage of atypical gait cycles, stance, swing, and double support duration were estimated. Overall, the gait performance of PD patients improved after DBS, as also confirmed by the decrease in the UPDRS-III score from 19.4±1.8 to 10.2±1.0 points (T0 vs. T2) (p < 0.001). In particular, the percentage change of atypical gait cycles of PD more affected side decreased at T1 (Straigh-line: -72%; Turnings: -43%) and at T2 (Straigh-line: -54%; Turnings: -20%). The percentage of atypical gait cycles proved an informative digital biomarker for quantifying PD gait changes after DBS, both in straight-line paths and turnings.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive impairment and memory loss. Oxidative stress (OS) has emerged as a central element in the pathophysiology of AD, linking various pathological features including amyloid-β (Aβ) plaque formation, tau hyperphosphorylation, and synaptic dysfunction. This review comprehensively examines the role of OS in AD, focusing on the mechanisms of reactive oxygen species (ROS) production, mitochondrial dysfunction, and their impact on neuronal integrity. Additionally, the review highlights recent advances in antioxidant therapy. Elevated ROS levels in the aging brain exacerbate oxidative damage to lipids, proteins, and DNA, contributing to neuronal atrophy and synaptic loss. Mitochondrial dysfunction further amplifies OS, disrupting cellular energy metabolism and promoting neurodegeneration. Despite the strong association between OS and AD, antioxidant therapies have shown inconsistent clinical outcomes. Emerging strategies targeting offer promising avenues for therapeutic intervention. This review highlights the need for a multifaceted approach in understanding and mitigating OS-related damage in AD, aiming to pave the way for more effective treatments and improved patient outcomes.

5-(4-aminophenyl )-2-amino -1,3,4-thiadiazole was prepared by reaction of Thiosemicarbazide with 4-amino benzoic acid under reflux condition for 7 hours. The compound which has been synthesized successfully was subjected to addition reaction with 4-(Dimethylamino) benzaldehyde under reflux condition for 6 hours to synthesize Schiff bases. These compounds was characterized by using FTIR) and evaluated for their anticancer activity. The effect of (1, 3, 4-thiadiazole derivative) on the activity of malignant cells was studied by using different types of cell lines [Breast cancer, and human prostate cancer]. And was used the Electron microscope to show that the effect of the derivative on the cancer cells before and after 3 days of the injection time. It was found that the Schiff base of thiadiazole-1,3,4-(Dimethylamino)benzylidineamino]- [4-2-phenyl]amino was effective in reducing the size and density of malignant cells. That of 46.7 while in breast ) 145(DUprostate for growth inhibition produce of equal 85.9 µg/ml.

With the renewed interest for lunar surface exploration, the European Space Agency envisions to stimulate the creation of lunar communications and navigation services (LCNS) to enable, among others, autonomous navigation capabilities for lunar rovers. As the number of satellites foreseen in such a service is much smaller compared to Earth based global navigation satellite systems (GNSS), different complementary technologies are pursued to improve the attainable navigation accuracy for lunar rovers. One way to improve the position accuracy provided by the LCNS satellites is to constrain the vertical position using a high resolution digital elevation model (DEM). This article presents the results of a variance covariance analysis of an extended Kalman filter (EKF) implementation in which the LCNS ranging measurements are used together with DEM from the LRO LOLA instrument. Assuming a realistic orbit determination and time synchronization (ODTS) accuracy of the LCNS satellites, the usage of a navigation grade IMU and an oven controlled crystal oscillator (OCXO), a 3-sigma position accuracy of less than 10 meters can be obtained. Furthermore, the availability is substantially improved as the DEM aided solution enables a position solution in case of only 3 visible satellites.

In this part of the series of two papers, we extend the theorems discussed in part I for infinite series. We then use these theorems to develop distinct novel results involving the Hurwitz zeta function, Riemann zeta function, Polylogarithm and Fibonacci numbers. In continuation, we obtain some zeros of the newly developed zeta functions and explain their behaviour using plots in complex plane. Furthermore, we provide particular cases for the theorems and corollaries which show that our results generalise the currently available functions and series such as the Riemann zeta function and the geometric series. Finally, we provide four miscellaneous examples to showcase the vast scope of the developed theorems.

Background and Objectives: High job strain is worsening the outcome in coronary artery disease, CAD. Severe dissatisfaction on workplace, imbalance between high demands , and low rewards, are affecting the quality of life, and diminishing the duration of life, especially in CAD patients. Our study included two samples : CAD patients (experimental group), and without CAD patients, but with traditional risk factors (control group). The main objective of the study was the role played by high sensitivity C reactive protein, hs CRP, and microalbuminuria, as mediators of job strain and CAD relationship. Secondary objectives were the following: identification of the most vulnerable patients( with significant job strain) and intervention towards this category, for cardiovascular events prevention (primary or secondary). Materials and Methods: The utilized methods were the following : clinical exam; electrocardiogram; echocardiogram; non contrast enhanced computed chest tomography; laboratory findings ( lipid profile, glycemia, hs CRP, microalbuminuria); type D scale, DS 14; depression questionnaire, PHQ-9; and satisfaction with work scale, SWWS. Results: The highest values for hs CRP and microalbuminuria were noticed in patients with the lowest Likert score, for both samples CAD, and without CAD patients. The highest job strain was noticed in females. More than half of CAD patients ,with low Likert scores, revealed myocardial infarction. Conclusions: Microalbuminuria and hs CRP were statistical significant in the study as intercessors, in job strain and CAD relationship. The most vulnerable patients for vascular events were females, in both groups : CAD and “CAD waiting desk”. In CAD sample, the vascular vulnerability was also increased by high job strain.

Diastolic dysfunction, a prevalent condition characterized by impaired relaxation and filling of the left ventricle, significantly contributes to heart failure with preserved ejection fraction (HFpEF). Galectin-3, a β-galactoside-binding lectin, has garnered attention as a potential biomarker and mediator of fibrosis and inflammation in cardiovascular diseases. This comprehensive review investigates the impact of galectin-3 on diastolic dysfunction. We explore its molecular mechanisms, including its involvement in cellular signaling pathways and interaction with components of the extracellular matrix. Evidence from both animal models and clinical studies elucidates galectin-3's role in cardiac remodeling, inflammation, and fibrosis, shedding light on the underlying pathophysiology of diastolic dysfunction. Additionally, we examine the diagnostic and therapeutic implications of galectin-3 in diastolic dysfunction, emphasizing its potential as both a biomarker and a therapeutic target. This review underscores the significance of comprehending galectin-3's role in diastolic dysfunction and its promise in enhancing diagnosis and treatment approaches for HFpEF patients.

Abstract Background Context Pelvic ring fractures are becoming more common in the aging population and can prove to be fatal, having mortality rates between 10% and 16%. Stabilization of these fractures is challenging and often require immediate internal fixation. Therefore, it is necessary to have a biomechanical understanding of the different fixation techniques for pelvic ring fractures. Methods A previously validated three-dimensional finite element model of the lumbar spine, pelvis, and femur was used for this study. A unilateral pelvic ring fracture was simulated by resecting the left side of the sacrum and pelvis. Five different fixation techniques were used to stabilize the fracture. A compressive follower load and pure moment was applied to compare different biomechanical parameters including range of motion (contralateral sacroiliac joint, L1-S1 segment, L5-S1 segment), and stresses (L5-S1 nucleus stresses, instrument stresses) between different fixation techniques. Results Transiliac -trans sacral screw fixation at S1 and S2 showed the highest stabilization for horizontal and vertical displacement at the sacral fracture site and reduction of contralateral sacroiliac joint for bending and flexion range of motion by 165% and 121%, respectively. DTSF (Double transiliac rod and screw fixation) model showed highest stabilization in horizontal displacement at the pubic rami fracture site, while the L5_PF_W_CC (L5-Ilium posterior screw fixation with cross connectors) and L5_PF_WO_CC ( L5-Ilium posterior screw fixation without cross connectors) showed higher rod stresses, reduced L1-S1 (approximately 28%), and L5-S1 (approximately 90%) range of motion. Conclusions Longer sacral screw fixations were superior in stabilizing sacral and contralateral sacroiliac joint range of motion. Lumbopelvic fixations displayed a higher degree of stabilization in the horizontal displacement compared to vertical displacement of pubic rami fracture, while also indicating the highest rod stresses. When determining the surgical approach for pelvic ring fractures, patient-specific factors should be accounted for to weigh the advantages and disadvantages for each technique.

Background and Objectives: The existing recommendations for female pelvic magnetic susceptibility weighted imaging MRI (FP-SWI) have not been optimized to capture the disease characteristics of the female pelvis. Therefore, it is imperative to explore acquisition parameters before conducting larger-scale studies. To establish optimized flip angle (FA) for acquiring FP-SWI to improve the image quality of female pelvic lesion sites. Materials and Methods: To evaluate signal quality and lesion conspicuity, regions of interest (ROIs) were manually drawn within the lesion on SWI sequences. Signal intensity was measured within the ROIs. Additionally, signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were calculated for SWI sequences acquired at three FA: 10°, 15°, and 20°. Finally, a qualitative assessment of anatomical detail visualization, geometric distortion extent, artifacts, and lesion clarity was performed using a four-point scale. The Wilcoxon rank sum test was employed to compare the qualitative evaluation parameters. The intra-class correlation coefficient (ICC) was calculated to determine the consistency of subjective ratings between two observers. Results: FA=10° showed significantly higher SNR than FA=15° and 20° in most anatomical regions (P&lt;0.05), while the CNR was significantly higher than FA=15° and 20° (P&lt;0.05). Compared with FA=15° and 20°, the image quality of FA=10° was significantly higher, with less distortion and ghosting, and better image contrast (P&lt;0.05). Lesions with FA=10° exhibited higher clarity compared to FA=15° and 20° (P&lt;0.05). Conclusions: The image quality of FP-SWI images at FA=10° exceeds that at FA=15° and 20°. We recommend that when conducting SWI examination of the female pelvic cavity, the FA value should be set at 10° to stabilize the SWI sequence and improve image quality.

Background and objectivesː Physical examination is the predominant method for evaluating pelvic floor defects. Magnetic Resonance Imaging (MRI) is a radiological technique useful to identify the underlying defects of pelvic floor structures that require surgery. The primary aim was to find correspondence between the clinical and radiological staging of pelvic organ prolapse (POP) before and after vaginal surgery. A secondary endpoint was to investigate, through clinical and MRI findings if surgery influences continence mechanisms. Finally, we reported changes in the quality of life in women who underwent surgery for prolapse. Materials and methodsː Twenty-five women with prolapse stage ≥ 2 POP-Q were recruited in this prospective study. They underwent preoperative clinical examination, MRI at rest and under the Valsalva maneuver, and quality of life questionnaires. Three months after vaginal surgery they repeated clinical and radiological evaluation. Resultsː Twenty women completed the study. Both clinical and MRI evaluations showed an improvement in prolapse and symptoms after surgery. There were some discrepancies between clinical and radiological staging. MRI parameters did not show differences between pre and postoperative at rest; under the Valsalva maneuver instead, the measurements changed after surgery. Continence was not worsening by the widening of the vesicourethral angle. Patients reported improvement in quality of life. Conclusionsː MRI is an accurate and objective method to define the stage of prolapse but the clinical evaluation alone is sufficient to stage prolapse before surgery and evaluate the result at follow-up. It is an accurate method to visualize some pelvic structures that can be compromised because of pelvic organ prolapse. MRI showed that vaginal surgery doesn’t affect continence mechanisms.

This review provides a comprehensive analysis of the pelvic plexus and its regulation across various mammalian species, including rats, cats, dogs, and pigs. The pelvic and hypogastric nerves play crucial roles in regulating pelvic functions such as micturition, defecation, and erection. The anatomical organization of these nerves varies, forming either well-defined ganglia or complex plexuses. Despite these variations, the neurons within these structures are consistently regulated by key neurotransmitters—norepinephrine and acetylcholine. These neurons also possess receptors for testosterone and prolactin, particularly in rats, indicating the significant role of these hormones in neuronal function and development. Moreover, neuropeptides such as vasoactive intestinal peptide (VIP), substance P, neuropeptide Y (NPY), somatostatin (SOM), galanin (GAL), and calcitonin gene-related peptide (CGRP) are co-released with neurotransmitters to modulate pelvic functions. This review highlights the complex interplay between neurotransmitters, neuropeptides, and hormones in regulating pelvic physiology and emphasizes the importance of hormonal regulation in maintaining the functionality and health of the pelvic plexus across different species.

Background: Symptomatic Pelvic Congestion Syndrome (PCS) is often underdiagnosed and undertreated. We investigate a symptoms-based screening algorithm and treatment algorithm focused on position and location of pain for each type of PCS. Methods: This study is a retrospective, single-institution, multi-site review of 343 female patients who presented with pelvic pain. Results: Following a symptoms-based algorithm, 302 patients fulfilled criteria for inclusion; 299 patients had positional symptoms with a positive predictive value (PPV) of 97.99%, sensitivity of 98.99% and Odds Ratio (OR) of 48.83 (p=0.0003) while duplex ultrasonography (DUS) had a PPV of 98.84%, sensitivity of 86.49%, and OR of 6.4 (p=0.0396) confirmed by contrast venography. Patients with Type I PCS were treated with embolization and 87.5% reported total relief of anterior symptoms. Patients with Type II PCS were treated with embolization and/or vascular stenting based on their associated lesion, May-Thurner syndrome or Nutcracker syndrome, and 88.54% reported ≥50% symptom relief and 59.03% reported ≥80% symptom relief. Full treatment resulted in a mean “overall satisfaction” score of 96.07%. Conclusions: Algorithmic approaches are essential for PCS evaluation, diagnosis, and treatment. Patients with positional pelvic symptoms consistent with PCS should undergo diagnostic venography. Distinguishing between the types of PCS and using symptoms as a guide may be beneficial over a “one-size-fits-all” approach.

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly termed nonalcoholic fatty liver disease (NAFLD), is a widespread global health concern that affects around 25% of the global population. Its influence is expanding, and it is anticipated to overtake alcohol as the leading cause of liver failure and liver-related death worldwide. Unfortunately, there are no approved therapies for MASLD; as such, national and international regulatory health agencies undertook strategies and action plans designed to expedite the development of drugs for treatment of MASLD. A sedentary lifestyle and an unhealthy diet intake are important risk factors. Western countries have a greater estimated prevalence of MASLD partly due to lifestyle habits. Mitochondrial dysfunction is strongly linked to the development of MASLD. Further, it has been speculated that mitophagy, a type of mitochondrial quality control, may be impaired in MASLD. Thyroid hormone (TH) coordinates signals from the nuclear and mitochondrial genomes to control mitochondrial biogenesis and function in hepatocytes. Mitochondria are known TH targets and preclinical and clinical studies suggest that TH, thyroid receptor β (TR-β) analogs, and synthetic analogs specific to liver could be of therapeutic benefit in treating MASLD. In this review, we highlight how mitochondrial dysfunction contributes to development of MASLD, and how understanding the role of TH in improving mitochondrial function paved the way for innovative drug development programs of TH-based therapies targeting MASLD.

Introduction: The COVID-19 pandemic highlighted the necessity for rapid, efficient testing at large-scale events. Developing rapid and efficient testing methods was critical, especially for events with a high risk of virus spread. The queueing theory offers a powerful tool to manage the flow of people through testing centers. This study uses the M/M/c model to examine how different floor plan configurations impact the efficiency of RADT testing centers. Aim of the study: This research applies queueing theory to optimize the Rapid Antigen Diagnostic Test (RADT) processes at mass gatherings. The study uses the M/M/c queueing model to evaluate the dynamics of RADT centers configured in U-shaped and straight-line layouts. The primary goal is to assess the feasibility of using RADTs efficiently at events and mass gathering entrances, aiming to enhance throughput and minimize wait times. Methodology: The study involved 500 healthy participants, managed by medical staff across a U-shaped and a straight floor plans. Agile management techniques were employed to enhance operational efficiency. The process stages included queue number issuance, registration, sample collection, sample mixing, and results dissemination. Results: Both floor plans enabled the completion of RADT screening in approximately 2 minutes per participant. The U-shaped layout slightly outperformed the straight-line setup in efficiency, demonstrating its effectiveness in optimizing the testing process. Conclusion: This study confirms the feasibility of implementing Rapid Antigen Diagnostic Test (RADT) processes at mass gatherings. It was found that the U-shaped floor plan configuration is particularly effective, indicating its potential suitability for future mass testing scenarios.

To estimate the progressive collapse resistance capacity of a multi-column frame tube structure with the assembled truss beam composite floor (ATBCF), the pushdown analysis, and the nonlinear dynamic analysis as well, are conducted for such a structure by using the alternate load path (ALP) method. The bearing capacities of the remaining structures at three different work conditions, which are the side middle column failure, the edge middle column failure, and the corner column failure, are individually studied, and the collapse mechanism for the remaining structures is analyzed from the aspects of the internal force redistribution and the failure mode of the second defense line. Simultaneously, the influence of the column failure time on the dynamic response of the remaining structure and the dynamic amplification coefficient are discussed. The results show that the residual bearing capacity of the remaining structure with the bottom corner column failure is higher than that of the one with the side or edge middle column failure, while the latter has a stronger plastic deformation capacity. When the ALP method is adopted to operate the progressive collapse analysis, it is reasonable to take the column failure time as 0.1 times of the first-order vertical vibration period of the remaining structure, and it is suitable to set the dynamic amplification coefficient as of 2.0, which is the ratio of the maximum dynamic displacement to the static displacement of the remaining structure under the transient loading condition.

This study explores the significance of active suspension systems for vehicles with lower chassis compared to conventional ones, aiming at the development of future automobiles. Conventional linear MR (Magneto-Rheological) dampers were found inadequate in ensuring sufficient vibration control because the vehicle's chassis becomes lowered in the unmanned vehicles or purposed based vehicles. As an alternative, a rotary type of MR damper is proposed in this work. The proposed damper is designed based on pre-specified design parameters through mathematical modeling and magnetic field analyses. Subsequently, a prototype of the rotary MR damper identical to the design is fabricated, and effectiveness is shown through experimental investigations. In configuring the experiments, a proportional-integral (PI) controller is employed for current control to reduce the response time of the damper. The results presented in this work provides useful guidelines to develop a new type of MR damper applicable to various types of future vehicles’ suspension systems with low distance from the tire to the body floor.

Proper blood-brain barrier (BBB) function is essential to maintain homeostasis keeping the central nervous system healthy. Disruption of the BBB has been described in nearly all neurological disease and injury contexts. Given the various physical and metabolic roles of the BBB and gliovascular unit (GVU), dysfunction should be assessed across multiple levels to pinpoint the exact nature of the impairment. Here we describe imaging techniques for evaluating various aspects of BBB and GVU integrity and function, tailored for use in mouse models with protocols for quantitative image analysis. These imaging techniques complement classical dye tracer experiments and reveal underlying molecular causes of BBB dysfunction.

Research has been growing on object detection using semi-supervised methods in past few years. We examine the intersection of these two areas for floor-plan objects to promote the research objective of detecting more accurate objects with less labelled data. The floor-plan objects include different furniture items with multiple types of the same class, and this high inter-class similarity impacts the performance of prior methods. In this paper, we present Mask R-CNN based semi-supervised approach that provides pixel-to-pixel alignment to generate individual annotation masks for each class to mine the inter-class similarity. The semi-supervised approach has a student-teacher network that pulls information from the teacher network and feeds it to the student network. The teacher network uses unlabeled data to form pseudo-boxes, and the student network uses both unlabeled data with the pseudo boxes and labelled data as ground truth for training. It learns representations of furniture items by combining labelled and unlabeled data. On the Mask R-CNN detector with ResNet-101 backbone network, the proposed approach achieves mAP of 98.8%, 99.7%, and 99.8% with only 1%, 5% and 10% labelled data, respectively. Our experiment affirms the efficiency of the proposed approach as it outperforms the fully supervised counterpart using only 10% of the labels.

This paper presents technical solutions to increase Industry 4.0 maturity. Within the “5G-Enabled Manufacturing” project, a 5G network has been deployed at the shop floor to enable fast and scalable connectivity. This network was used to connect a grinding machine to a private cloud to enable visibility and transparency of the production data, which is the basis for Industry 4.0 and smart manufacturing. Results indicate a present lack of commercially available product independent solutions for interconnection and data transfer despite the availability of open standards and well-documented demonstrator projects. The solution is described and discussed regarding technical interoperability, focusing on the system layout, communication standards, and open systems. From the discussion, it is derived that manufacturing end-users are in need to expand and further internalize knowledge on future information and communication technologies to reduce their dependency on equipment and technology providers.

Our hypothesis that controlled ozone applications interfere into the redox balance of the biological organism (first published in 1998 with a preclinical trial on protecting the liver from CCl4 intoxication), has been verified over the last 2 decades in reactive oxygen species (ROS)-induced mitochondrial pathologies, such as rheumatoid arthritis, osteoarthritis, aging processes, diabetes-2 and in prevention of intoxications. Low-dose ozone acts as a redox bioregulator: The restoration of the disturbed redox balance is comprehensible in a number of preclinical and clinical studies by a remarkable increase of the antioxidant repair markers, here mainly shown as glutathione increase and a reduction in oxidative stress markers, mainly malondialdehyde. The mechanism of action is shown, relevant data are displayed, evaluated and comprehensively discussed: The repair side of the equilibrium increases by 21% up to 140% compared to the non-ozone treated groups and depending on the indication; the stress markers are simultaneously reduced, the redox system regains its balance.

Some of neurodegenerative diseases may be characterized by continuing behavioral and cognitive dysfunction that contains memory loss and/or apathy. Alzheimer's disease is the most typical type of such neurodegenerative disease characterized by deficit of cognition and alteration of behavior. Despite the huge efforts against Alzheimer's disease, there has been yet no successful treatment for this disease. Interestingly, several possible risk genes to cognitive dysfunction are frequently expressed within brain cells, which may also be linked to cholesterol metabolism, lipid transport, exosomes and/or caveolae formation, suggesting that caveolae may be a therapeutic target to consider cognitive dysfunctions. Interestingly, modulation of autophagy/mitophagy with the alteration of glucagon-like peptide-1 (GLP-1) and N-methyl-d-aspartate (NMDA) receptors signaling may offer a novel approach to prevent and alleviate the cognitive dysfunction. A paradigm that both GLP-1 and NMDA receptors at caveolae sites is promising and crucial for the treatment of cognitive dysfunctions has been presented here, which might also be able to modify the progression of Alzheimer's disease. This research direction may open the potential to move a clinical care toward disease-modifying treatment strategies with maximal benefits for patients without detrimental adverse events for neurodegenerative diseases.

Objective: Subclinical left ventricular disfunction (LVD) is common in asymptomatic patients with type 2 diabetes (T2D). Many patients with diabetes have an impaired diastolic and systolic function. With preserved ejection fraction LV (EFLV), the latter is defined as reduced global longitudinal strain (GLS), detected using the speckle-tracking echocardiography. This study is aimed to define the long-term structural and functional disorders of the LV myocardium in patients with T2D without CVD. Methods: Of the 120 patients with and without T2D of both sexes aged from 45 to 75 years (57.11±7.9 years), included in the study in 2012-2013, only 57 responded to the follow-up study. The patients were divided into two groups: one with T2D (n=29), the other without it, control (n=28). All patients underwent transthoracic two-dimensional echocardiography with assessment of standard indicators of systolic and diastolic cardiac function, as well as GLS. In addition, all participants underwent laboratory diagnostics of carbohydrate metabolism disorders markers, NT-proBNP and CRP. The median follow-up duration was 7.2 [7.0-7.8] years. Results: During the follow-up, a statistically significant increase in the incidence of diastolic dysfunction (DD) in the type 2 diabetes group was found from 53% to 61% (p = 0.004); no significant dynamics were noted in the control group (p = 0.48). The presence of T2D significantly increases the risk of developing DD (p=0.04). The presence of T2D, increased fasting glucose levels, and an increased HOMA index were independent predictors of the development of DD. Impairment of LVEF was not observed in both groups. At the same time, the proportion of patients with reduced GLS (< -18%) increased in the T2D group (p = 0.036). A significant difference in the frequency of decreased GLS depending on T2D was demonstrated. The presence of obesity, an increase in the HOMA index and an increase in CRP levels are independent predictors of impaired GLS. Conclusions: T2D is an independent risk factor for the worsening of subclinical left ventricular dysfunction in asymptomatic patients with T2D without CVD over 7-year follow-up. Diastolic dysfunction is represented by delayed relaxation of the LV myocardium; with preserved LVEF, reduced 2D GLS identifies systolic dysfunction. The tight control of glycemia, lipidemia, blood pressure and body weight is associated with the absence of poor clinical outcomes.

Market crises pose significant challenges for businesses, emphasizing the importance of effective crisis management strategies. Central to these strategies is the ability to identify and retain loyal customers, who often serve as the bedrock of stability during tumultuous times. This paper investigates the application of deep meta-learning analysis to predict loyal customers as a cornerstone of market crisis management. Drawing upon an extensive literature review, the study explores previous research on market crises, customer loyalty, and the evolution of deep learning and meta-learning in crisis management contexts. Methodologically, the paper outlines data collection, model development, and evaluation procedures tailored for deep meta-learning-based customer prediction. In results, the overall accuracy of model 85%, a precision 0.88, recall 0.82, and F1-score 0.85 were obtained. The analysis demonstrates the effectiveness of deep meta-learning models in accurately identifying loyal customers during market crises, offering insights into their performance and applicability compared to traditional methods. Practical implications include potential applications in crisis management for businesses and considerations for real-world implementation.

Various symptoms have been reported to persist beyond acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, which is referred as long coronavirus disease 19 (long COVID-19). Over 65 million individuals suffer from long COVID-19. However, the causes of long COVID-19 have been largely unknown. Since long COVID-19 symptoms are observed throughout the body, vascular endothelial dysfunction may be a strong candidate to induce long COVID-19. The angioten-sin-converting enzyme 2 (ACE2), the entry receptor of SARS-CoV-2, is ubiquitously expressed in endothelial cells. We previously found that the risk factors for athero-sclerotic cardiovascular disease (ASCVD) and the history of ASCVD can be the risk for severe COVID-19, suggesting a contribution of pre-existing endothelial dysfunction to severe COVID-19. Here, we show a significant association of endothelial dysfunction with development of long COVID-19 and show that biomarkers for endothelial dysfunction in patients with long COVID-19 are also crucial players in development of ASCVD. We consider the influence of long COVID-19 on development of chronic kidney disease (CKD) and ASCVD. Furthermore, we suggest the therapeutic interventions for long COVID-19 by considering endothelial dysfunction as the treatment tar-gets for long COVID-19. Such interventions may prevent pandemic of CKD and ASCVD in post COVID-19 era.

Progress in understanding the pathogenesis and treatment of Alzheimer's disease (AD) is based on the recognition of the primary causes of the disease, which can be deduced from the knowledge of risk factors and biomarkers measurable in the early stages of the disease. Insights into risk factors and the time course of biomarker abnormalities point to a role for mitochondrial dysfunction and oxidative stress in the onset and development of AD. Coenzyme Q10 (CoQ10) is a lipid antioxidant and electron transporter in the mitochondrial electron transport system. The availability and activity of CoQ10 is crucial for proper mitochondrial function and cellular bioenergetics. Based on the mitochondrial hypothesis of AD and the hypothesis of oxidative stress, the regulation of the efficiency of the oxidative phosphorylation system by means of CoQ10 can be considered promising in restoring the mitochondrial function impaired in AD, or in preventing the onset of mitochondrial dysfunction and the development of amyloid and tau pathology in AD.

The placenta is a vital organ of pregnancy, regulating adaptation to pregnancy, gestational-parent/fetal exchange and ultimately fetal development and growth. Not surprisingly, in cases of placental dysfunction - where aspects of placental development or function become compromised - adverse pregnancy outcomes can result. One common placenta-mediated disorder of pregnancy is preeclampsia (PE), a hypertensive disorder of pregnancy with a highly heterogeneous clinical presentation. The wide array of clinical characteristics observed in pregnant individuals and neonates of a PE pregnancy are likely the result of distinct forms of placental pathology underlying the PE diagnosis, explaining why no one common intervention has proven effective in the prevention or treatment of PE. The historical paradigm of placental pathology in PE highlights an important role for utero-placental malperfusion, placental hypoxia and oxidative stress, and a critical role for placental mitochondrial dysfunction in the pathogenesis and progression of the disease. In the current review, the evidence of placental mitochondrial dysfunction in the context of PE will be summarized, highlighting how altered mitochondrial function may be a common feature across distinct PE subtypes. Further, advances in this field of study and therapeutic targeting of mitochondria as a promising intervention for PE will be discussed.

The thyroid gland secretes essential hormones for the growth regulation and the metabolic activity of the body. Thyroid dysfunction includes many conditions that can indirectly affect dental treatments. Therefore, the practitioner must be aware of these pathologies and their signs and symptoms in order to elaborate specific dental treatment plans, thus avoiding any per- and/or postoperative complications. Moreover, the dentist can help in the screening of undiagnosed thyroid dysfunction among patients.

Acute Respiratory Distress Syndrome (ARDS) is a severe lung condition with a high mortality rate for which there are no effective therapeutics. The failure of the alveolar-capillary barrier, composed of lung endothelial (EC) and alveolar epithelial (AEC) cells, is a critical factor leading to excessive inflammation and edema characteristics of acute lung injury (ALI). Phosphodiesterases (PDE) are enzymes well-recognized for their roles in regulating endothelial permeability and inflammation. Although PDE inhibitors are used as therapeutics for inflammatory diseases like COPD (chronic obstructive pulmonary disease), their efficacy in treating ARDS has not yet been established. In this study, we investigate the effects of ensifentrine, an FDA-approved novel dual PDE 3/4 inhibitor, on lung endothelial and epithelial dysfunction caused by methicillin-resistant S. aureus (MRSA), a pathogen involved in bacterial ARDS. Human primary lung endothelial cells and alveolar epithelial cell lines (A549 and immortalized AEC) were treated with heat-killed MRSA, and their responses were assessed in the presence or absence of ensifentrine. Ensifentrine given either pre- or post exposure attenuated MRSA-induced increased lung endothelial permeability. VE-cadherin junctions, which serve to stabilize the EC barrier, were disrupted by MRSA; however, ensifentrine effectively prevented this disruption. Pre-treatment with ensifentrine protected against MRSA-induced EC pro-inflammatory signaling by inhibiting the expression of VCAM-1, ICAM-1, and by reducing the IL-6 release. In AEC, MRSA caused upregulation of ICAM-1, activation of NF-kB and production of IL-8, all of which were inhibited by ensifentrine. These results indicate that dual inhibition of phosphodiesterases 3 and 4 by ensifentrine is barrier protective and attenuates MRSA-induced inflammation in both lung endothelial and epithelial cells. The PDE3/4 inhibitor ensifentrine may represent a promising novel strategy for the treatment of ALI.

The introduction of innovative digital tools for supporting manufacturing processes has far-reaching effects on an organizational and an individual level due to the development of Industry 4.0. The FACTS4WORKERS project funded by H2020, i.e. Worker-Centric Workplaces in Smart Factories, aims to develop user-centered assistance systems in order to demonstrate their impact and applicability at the shop floor. To do so it is important to understand how to develop such tools and how to assess if advantages can be derived from the created ICT system. This study introduces the technology of a workplace solution that is linked to a specific industrial challenge. Subsequently, a 2-stepped approach to evaluate the presented system is discussed. Heuristics, which are an output of project “Heuristics for Industry 4.0”, are used to test if the developed solution covers critical aspects of socio-technical system design. Insights into the design, development and holistic evaluation of digital tools at the shop floor should be shown.

In municipal waterworks large amounts of waste in the form of sludge have to be discarded. This investigation focuses on the processing of ceramic floor tiles incorporated with a municipal waterworks sludge. Four floor tile formulations containing up to 10 wt. % of the municipal waterworks sludge in replacement of kaolin were prepared. The floor tile processing route consisted of dry powder granulation, uniaxial pressing, and firing between 1190 and 1250 °C using a fast-firing cycle (<60 min). The densification behavior and technological properties of the floor tile pieces as function of the sludge addition and firing temperature were determined. The development of the microstructure was followed by XRD and SEM/EDS. The results show that the replacement of kaolin with municipal waterworks sludge, in the range up to 10 wt. %, allows the production of ceramic floor tiles (group BIb and group BIIa, ISO 13006 Standard) at lower firing temperatures. These results suggest a new possibility for valorization of municipal waterworks sludge with many economical and environmental benefits.

The recent rise of deep learning (DL) and its promising capabilities in capturing non-explicit detail from large datasets have attracted substantial research attention in the field of medical image processing. DL provides ground for technology development for computer-aided diagnosis and segmentation in radiology and radiation oncology. Amongst the anatomical locations where recent auto-segmentation algorithms have been employed, the pelvis remains one of the most challenging due to large intra- and inter-patient soft-tissue variabilities. This review provides a comprehensive and clinically-oriented overview of DL-based segmentation studies for bladder, prostate, cervical and rectal cancers, highlighting the key findings, challenges and limitations.

Background: Chronic pelvic pain is a debilitating condition affecting quality of life. Endometriosis is one of the leading causes of CPP, but recent studies highlighted the role of interstitial cystitis/bladder pain syndrome (IC/PBS) in causing CPP. Only some studies addressed the coexistence between these two conditions, which seems more frequent than what is supposed, leading to diagnostic delays and unnecessary surgeries. This systematic review aimed to evaluate the estimate of the coexistence of endometriosis and IC/PBS. Methods: We performed a systematic review of the literature indexed on PubMed, Scopus, ISI Web of Science, and Cochrane using a combination of keywords and text words represented by “painful bladder syndrome”, “endometriosis”, “interstitial cystitis”, “bladder pain syndrome”. We performed a meta-analysis of the results. Results: Meta-analysis shows that the coexistence of endometriosis and IC/PBS in women with CPP ranges between 15,5-78,3%, which is higher than the prevalence of IC/PBS in the general population. Conclusions: Women with CPP need a multidisciplinary approach and a referral to centers with specific expertise. In cases of endometriosis unresponsive to treatment, other reasons for CPP need to be ruled out, above all in women not responsive to treatment.

Coupled Delft3D-object model has been developed to predict object’s mobility and burial on sandy seafloor. The Delft3D model is used to predict seabed environment such as currents, waves (peak period, significant wave height, wave direction), water level, sediment transport, and seabed change, which are taken as the forcing term to the object model consisting of three components: (a) object‘s physical parameters such as diameter, length, mass, and rolling moment, (b) dynamics of rolling cylinder around its major axis, and (c) empirical sediment scour model with re-exposure parameterization. The model is compared with the observational data collected from a field experiment from 21 April to 23 May 2013 off the coast of Panama City, Florida funded by the Department of Defense Strategic Environmental Research and Development Program. The experimental data contain both objects’ mobility using sector scanning and pencil beam sonars and simultaneous environmental time series data of the boundary layer hydrodynamics and sediment transport conditions. Comparison between modeled and observed data clearly show the model capability.

Background: Despite the tremendous effort in hamstring injury prevention, injury rates in soccer remain elevated. Hypothesis: Hamstring and hip/pelvic isometric strength imbalances may increase the likelihood of hamstring strain injury (HSI) occurrence amongst soccer players.Study design: Case-control study.Methods: In 120 male soccer players (mean age: 20.0 +/- 6.96 years) pre-season maximum isometric strength of the hip adductors, abductors, flexors, and knee flexors were measured, and strength ratios were calculated. Previous injury and anthropometric data were registered. Injury data were collected following the FIFA/UEFA consensus. A multivariate and Machine learning-based Logistic Regression model was employed to estimate the likelihood of players sustaining a hamstring injury.Results: 21 players sustained 32 hamstring injuries. Players with higher abduction strength in the dominant leg had an 18.5% lower risk of sustaining a hamstring injury (OR = 0.818, CI 95% = [(0.695-0.964]). No other significant contributor variables were found to be significant predictors of hamstring injury in the player group (p> 0.05).Conclusion: Isometric strength of the abductor muscles in the dominant limb had a significant association with hamstring injury.Clinical relevance: Our findings indicate the utilization of hip strength measurements as an integral component of the pre-season screening assessment, thereby affirming prior research on the correlation between lumbo-pelvic stability and incidence of hamstring injuries. Consequently, clinicians should contemplate incorporating hip strengthening exercises into regular training sessions, rehabilitation programs, and injury prevention protocols especially indicated when lower hip strength levels are observed.

The occurrence rate of occupational accidents caused by slipping and falling is 50% worldwide. Determining the slip safety risk is necessary to minimize the accidents caused by slipping in pedestrian walking areas. By on-site testing, this study aims to determine the slip risks of floor coverings used in walking areas with many pedestrians in public service buildings (PSB). For this purpose, on-site measurements were performed in two environments and six locations in PSB using portable GMG 200 and pendulum testers operating according to DIN 51131 and TS EN 14231 standards. These tests were performed on four-floor coverings with polished surface treatment in PSB. Since the floor coverings measured have a polished surface, it can be seen that the dynamic friction coefficients (DCOF) values are very low, and the slip risks are high. By statistically analyzing the slip test data using the K-means method, a new safety classification was made according to the usage areas of floor coverings. To minimize the risk of slip safety, especially for students, patients, and employees in PSB, it is recommended to use floor coverings with high DCOF values and low slip risk.

This study investigated the effects of fish oil (FO) treatment, particularly enriched with eicosapentaenoic acid (EPA), on obesity induced by a high-fat diet (HFD) in mice. The investigation focused on elucidating the impact of FO on epigenetic modifications in white adipose tissue (WAT) and the involvement of adipose-derived stem cells (ASCs). C57BL/6j mice were submitted to a control diet or a HFD for 16 weeks, treated (or not) with FO for the last 8 weeks. WAT was removed for RNA and protein extraction, while ASCs were isolated, cultured, and treated with Leptin. All samples were analyzed using functional genomics tools, including PCR-array, RT-PCR and Western Blot assays. Mice receiving HFD displayed increased body mass, fat accumulation, and altered gene expression associated with WAT inflammation and dysfunction. FO supplementation attenuated these effects, a potential protective role against HFD-induced obesity. Analysis of H3K27 revealed HFD-induced changes in histone, which were partially reversed by FO treatment. The study further explored leptin signaling in ASCs, suggesting a potential mechanism for ASC dysfunction in the leptin-rich environment of obese WAT. Overall, FO supplementation demonstrated efficacy in mitigating HFD-induced obesity, influencing epigenetic and molecular pathways, and shedding light on the role of ASCs and leptin signaling in WAT dysfunction associated with obesity.

Background: The incidence of metabolic dysfunction-associated steatohepatitis (MASH)-related hepatocellular carcinoma (HCC) is increasing annually with a rise in the incidence of obesity and metabolic syndrome. Based on preliminary reports regarding the potential association of HCC and periodontitis, this study aimed to analyze the involvement of periodontal bacteria as well as the oral and intestinal bacterial flora in MASH-related HCC (MASH-HCC). Methods: Forty-one patients with MASH and 19 with MASH-HCC who completed survey questionnaires, underwent periodontal examinations, and subjected to sample collection (saliva, mouth-rinsed water, feces, and peripheral blood) participated in the study. Bayesian network analysis was used to analyze the causation between various factors, including MASH-HCC, examinations, and bacteria. Results: The occupancy rate of the genus Fusobacterium in the intestinal bacterial flora was significantly higher in in the MASH-HCC group than in the MASH group (p = 0.002), whereas that of Butyricicoccus (p = 0.022) and Roseburia (p &lt; 0.05) was significantly lower. Bayesian network analysis revealed the absence of periodontal pathogenic bacteria and enteric bacteria affecting HCC. However, HCC directly affected the periodontal bacterial species Porphyromonas gingivalis, Tannerella forsythia, Fusobacterium nucleatum, and Prevotella intermedia in the saliva, as well as the genera Lactobacillus, Roseburia, Fusobacterium, Prevotella, Clostridium, Ruminococcus, Trabulsiella, and SMB53 in the intestine. Furthermore, P. gingivalis in the oral cavity directly affected the genera Lactobacillus and Streptococcus in the intestine. Conclusion: MASH-HCC directly affects periodontal pathogenic and intestinal bacteria, and P. gingivalis may affect the intestinal bacteria associated with gastrointestinal cancer.

Reducing waiting times is crucial for ports to be efficient and competitive. Important causes of waiting times are cascading interactions between realistic hydrodynamics, accessibility policies, vessel-priority rules, and detailed berth availability. The main challenges are determining the cause of waiting and finding rational solutions to reduce waiting time. In this study, we focus on the role of the design depth of a channel on the waiting times. We quantify the performance of channel depth for a representative fleet rather than the common approach of a single normative design vessel. It relies on a mesoscale agent-based discrete-event model that can take processed Automatic Identification System and hydrodynamic data as its main input. The presented method’s validity is assessed by hindcasting one year of observed anchorage area laytimes for a liquid bulk terminal in the Port of Rotterdam. The hindcast demonstrates that the method predicts the causes of 73.4% of the non-excessive laytimes of vessels, thereby correctly modelling 60.7% of the vessels-of-call. Following a recent deepening of the access channel, cascading waiting times due to tidal restrictions were found to be limited. Nonetheless, the importance of our approach is demonstrated by testing alternative maintained bed level designs, revealing the method’s potential to support rational decision-making in coastal zones.

Introduction: Lymph-nodal prostate cancer oligometastases are differently treated according to their site: pelvic are locoregional lymph-nodes, instead para-aortic lymph-nodes are considered as distant metastases. Aim of the study was a comparison between para-aortic and pelvic oligometastases treated with stereotactic body radiation therapy (SBRT). Material/methods: This is a retrospective analysis. De-novo metastatic or extra-nodal disease were excluded. Univariate and multivariate analyses were performed; pattern of recurrence was evaluated too. A propensity score matching (PSM) was applied to create comparable cohorts. Primary end-point was the progression-free survival (PFS). Secondary end-points were biochemical relapse-free survival (BRFS), ADT-free survival (ADTFS), polymetastases-free survival (PMFS), local progression-free survival (LPFS) and pattern of relapse. Results: 240 lymph-nodal oligometastases in 164 patients (127 pelvic and 37 para-aortic) were treated. Median PFS was 20 and 11 months in pelvic and para-aortic patients respectively (p=0.042). The difference was not confirmed at the multivariate analysis (p=0.06). Median BRFS was 16 and 9 months respectively in pelvic and para-aortic group (p=0.07). No statistically significant differences for ADTFS or PMFS were detected. The cumulative 5-years LPFS was 90.5%. At PSM no statistically significant differences for all the study end-points were detected. Conclusions: Patients affected by para-aortic disease might have PFS comparable to pelvic disease; local control is high in both cohorts. Our results support the use of SBRT also to para-aortic metastases.

Heavy load carrying of water, firewood, and sand/stones is a ubiquitous activity for women living in developing countries. Although the intra-abdominal pressure associated with heavy load carrying is hypothesized to increase the risk of pelvic organ prolapse (POP) among women, relevant epidemiologic data are lacking. We conducted a comparative study involving two exploratory cross-sectional studies among convenience samples of women carrying heavy loads, with different characteristics: (1) as part of their activities for daily living, in Shinyanga region, Tanzania; and (2) working as sand miners in Pokhara, Nepal. Women were categorized has having “low” or “high” load-carrying exposures based on the measured weights of the loads being carried at the time of the survey, as well as on self-reported duration and frequency of load carrying. A summary score for lower abdominal discomfort suggestive of POP was generated using questions from the Pelvic Organ Prolapse Distress Inventory (POPDI-6). Women with higher load carrying exposures had on average higher discomfort scores in both Tanzania (adjusted prevalence difference (PDa)=3.7; 95% CI: -3.8-11.3; p=0.33) and Nepal (PDa=9.3; 95% CI: -4.9-23.6; p=0.18). We identified trends suggestive of an association between increasing heavy load carrying exposures and symptoms of lower abdominal discomfort. Our findings underscore the need for larger epidemiologic studies of the potential adverse reproductive health effects of heavy load carrying activities on women in developing countries.

Increased soluble endoglin (sENG) were observed in human brain arteriovenous malformations (bAVMs), and overexpression of sENG with vascular endothelial growth factor (VEGF)-A induced dysplastic vessel formation in mouse brain. However, the underlying mechanism of sENG-induced vascular malformations is not clear. While evidence suggests the role of sENG as a pro-inflammatory modulator, increased microglial accumulation and inflammations were observed in bAVMs. Therefore, we hypothesized that microglia mediate sENG-induced inflammation and endothelial cell (EC) dysfunction in bAVMs. In this study, we confirmed that sENG with VEGF-A overexpression induced dysplastic vessel formation. Remarkably, there were increased microglial activation around dysplastic vessels with expression of NLRP3, inflammasome marker. We found that sENG increased the gene expression of VEGF-A, pro-inflammatory cytokines/inflammasome mediators (TNF-α, IL-6, NLRP3, ASC, Caspase-1, and IL-1β), and proteolytic enzyme (MMP-9) in BV2 microglia. The conditioned media from sENG-treated BV2 (BV2-sENG-CM) significantly increased angiogenic factors (Notch-1 and TGFβ) and pERK1/2 in ECs while it decreased IL-17RD, an anti-angiogenic mediator. Finally, the BV2-sENG-CM significantly increased EC migration and tube formation. Together, our study demonstrates that sENG provokes microglia to release angiogenic/inflammatory responses which may be involved in EC dysfunction. Our study suggests the contribution of microglia in the pathology of sENG-associated vascular malformations.

Modified mRNAs (modRNAs) are an emerging delivery method for gene therapy. In particular, the modRNA-based COVID-19 vaccines have proven that modRNA is a safe and effective therapeutic tool. Moreover, modRNA has the potential to treat various human diseases including cardiac dysfunction. Acute myocardial infarction (MI) is a major cardiac disorder that currently lacks curative treatment options. MI is commonly accompanied by fibrosis and impaired cardiac function. Our group previously demonstrated that the matricellular protein CCN5 inhibits cardiac fibrosis (CF) and improves cardiac dysfunction. However, it remains elusive whether the early intervention of CF under stress conditions is beneficial or more detrimental due to potential adverse effects such as left ventricular (LV) rupture. To obtain acute CCN5 expression, we used modRNA-mediated gene transfer in a mouse MI model. To evaluate CCN5 activity, we established two independent experimental schemes: 1) preventive intervention and 2) therapeutic intervention. Cardiac function and structural changes were measured by echocardiography and magnetic resonance imaging. Finally, fibrosis and the underlying molecular pathway were analyzed by western blotting, quantitative real-time polymerase chain reaction, and immunohistochemistry. The modRNA-CCN5 gene transfer successfully ameliorated CF and enhanced cardiac function in both preventive and therapeutic interventions without LV rupture or any adverse cardiac remodeling. Conclusively, early intervention in CF by modRNA-CCN5 gene transfer is an efficient and safe therapeutic modality for treating MI-induced heart failure without adverse structural remodeling.

The coexistence of SAH with T2DM is a common comorbidity. In this present study, we investigated the link between altered plasma antioxidant trace elements (ATE: Manganese, Selenium, Zinc and Copper) and fatty acids ratio (FAR: polyunsaturated/saturated) imbalance as transition biomarkers between vascular pathology (SAH) to metabolic pathology (T2DM). Our data revealed strong correlation between plasma ATE and FAR profile which is modified during SAH-T2DM association compared to healthy group. This relationship is mediated by lipotoxicity (simultaneously prominent visceral adipose tissue lipolysis, significant flow of non-esterified free fatty acids release, TG-Chol-dyslipidemia, high association of Total SFA, Palmitic acid, Arachidonic acid and PUFA 6/ PUFA 3; drop in tandem of PUFA / SFA and EPA+DHA); oxidative stress (lipid peroxidation confirmed by TAS depletion and MDA raise, concurrently drop of Zn/Cu-SOD, GPx, GSH, Se, Zn, Se/Mn, Zn/Cu; concomitantly enhance Cu, Mn and Fe); endothelial dysfunction (endotheline-1 increase); athero-thrombogenesis risk (concomitantly raise of ApoB100/ApoA1, Ox-LDL, tHcy and Lp(a)) and inflammation (higher of Hs-CRP, Fibrinogen and Ferritin). Our study open to new therapeutic targets and to better dietary management, such as to establish dietary ATE and PUFA 6 / PUFA 3 or PUFA / SFA reference values for atherosclerotic risk prevention in hypertensive-diabetics patients.

This study presents the development of a number of finite element (FE) models of the pelvis using different continuum and structural modelling approaches. Four FE models were developed using different modelling approaches: continuum isotropic, continuum orthotropic, hybrid isotropic and hybrid orthotropic. The models were subjected to an iterative adaptation process based on the Mechanostat principle. Each model was adapted to a number of common daily living activities (walking, stair ascent, stair descent, sit-to-stand and stand-to-sit) by applying onto it joint and muscle loads derived using a musculoskeletal modelling framework. The resulting models, along with a structural model previously developed by the authors, were compared visually in terms of bone architecture, and their response to a single load case was compared to a continuum FE model derived from CT imaging data. The main findings of this study were that the continuum orthotropic model was the closest to the CT derived model in terms of load response albeit having less total bone volume, suggesting that the role of material directionality in influencing the maximum orthotropic Young's modulus should be included in continuum bone adaptation models. In addition, the hybrid models, where trabecular and cortical bone were distinguished, had similar outcomes, suggesting that the approach to modelling trabecular bone is less influential when the cortex is modelled separately.

Muscle mass at admission is important to survive stroke, and stroke-induced sarcopenia is a serious problem because of its poor prognosis. Muscle mass measurement and monitoring are essential for appropriate re-habilitation and nutrition management. Several methods are used to assess skeletal muscle mass in stroke, such as computed tomography (CT), ultrasonography, bioelectrical impedance analysis, dual-energy X-ray absorptiometry, biomarkers, and anthropometrics. In stroke, a head CT is used to estimate muscle mass by measuring the temporal muscle. However, it is mostly retrospectively conducted due to radiation exposure. After stroke, limb muscle atrophy and diaphragm dysfunction are observed using ultrasound. However, ultrasound requires an understanding of the methods and skill. A bioelectrical impedance analysis can be used to assess muscle mass in patients after a stroke unless they have dynamic fluid changes. Dual-energy X-ray absorptiometry is used for follow-up after hospital discharge. Urinary titin N-fragment and serum C-terminal agrin fragment reflect muscle atrophy after stroke. Anthropometrics may be useful with limited resources. We summarized the features of each measurement and proved the recent evidence to properly measure and monitor skeletal muscle mass after stroke.

The management of blunt abdominopelvic trauma with combined hemoperitoneum and pelvic fractures is challenging for trauma surgeons. Although angioembolization can achieve hemostasis in most visceral organ injuries and pelvic fractures after blunt abdominal trauma, it cannot effectively control hemorrhage in patients with blunt bowel mesenteric injury (BBMI). This study aimed to determine the risk factors associated with hemodynamically unstable patients with BBMI and to test the hypothesis that pelvic fracture is an independent risk factor for patients with unstable BBMI and concomitant pelvic fracture to guide the therapeutic sequence for difficult-to-manage patients. This retrospective study reviewed the data of hospitalized patients with trauma between 2009 and 2021 and included 158 adult patients with surgically proven BBMI. The patients were divided on the basis of the presence of a shock episode before emergency laparotomy. The shock group included 44.3% of all patients in the study (n = 70). Clinical injury severity and prognosis for patients in the shock group were poorer than those for patients in the non-shock group, and more invasive treatments and transfusions were performed for patients in the shock group than for those in the non-shock group. Pelvic fractures were more frequently associated in the shock group than in the non-shock group (21.4% vs. 5.7%; p = 0.003). In multivariate analysis, the presence of intracerebral hemorrhage (odds ratio [OR] = 10.87, 95% confidence intervals [CIs]: 1.70–69.75) and rib fracture (OR = 5.94, 95% CIs = 1.06–33.45) were identified as independent predictors of shock, whereas the effect of pelvic fracture did not achieve statistical significance (OR = 2.94, 95% CIs = 0.66–13.13) after adjusting for confounding factors. For patients with BBMI, outcomes need to be improved during early diagnosis and treatments should be expeditiously performed on the basis of the rapid identification of unstable hemodynamic status. In unstable patients with concomitant pelvic fractures, we support the current management algorithm that recommends performing laparotomy first.

To achieve rapid post-earthquake repair of self-centering ribbed floor flat beam frame structures, a ductile hybrid joint consisting of dog bone weakened energy dissipating steel bars connected to the upper and lower column sections through high-strength threads based on the damage control design concept is proposed. By moving the ductile energy dissipating zone out to the locally weakened section of the energy dissipating steel bars and the locally unbonded prestressed steel bars in the core area, the residual deformation was limited and the seismic performance was improved. Based on the working principle of hybrid joints, low cycle loading tests were conducted on two joint specimens to analyze the influence of lateral prestress on the seismic performance of the hybrid joints. Numerical modeling methods were used to compare the position of the energy-consuming steel bars in the composite layer and the friction performance of joints. The research results indicated that the hybrid joint had stable load-bearing, deformation, and energy dissipation capabilities, with damage primarily concentrated on the energy-consuming steel bars. Even at an inter-story displacement angle of 5.5%, the upper and lower column segments remained elastic. After unloading, the connection seam at the joint was closed, and the self-centering performance was good. When the inter-story displacement angle reached 5.5%, the lateral prestress increased from 150 kN to 250 kN, the ultimate bearing capacity of the joint increased by 16.3%, and the cumulative energy consumption increased by 30.0%. The influence of the friction coefficient of the joint surface on the structural performance was set at a threshold of 0.7. When it was less than the threshold, the ultimate bearing capacity and initial stiffness of the joint increased with an increase in the friction coefficient. After reaching the threshold, the increase in the ultimate bearing capacity of the joint slowed down, and the rate of stiffness degradation gradually accelerated. This joint had excellent seismic performance and can also achieve post-earthquake repair of structures.

A sustainable matrix based on eucalyptol essential oil/sawdust was developed and applied on one-sided laminated plywood. This finish aims to serve as a eucalyptol odor slow release. Eucalyptol odor release was monitored with gas chromatography coupled with a flame ionization detector (GC – FID: Limits of Detection and Quantification of 0.70 g/m3 and 2.11 g/m3, respectively, and with linearity up to 18.6 g/m3). Measurement of the eucalyptol odor released was performed during a six-month period and it was found that the release followed a first-order exponential decay with a decay rate constant of 0.0169 per day. The half-life was determined to be of 48 days. The granulometry and particle size porosity of sawdust were analyzed by Scanning Electron Microscopy. Sawdust size fraction between 112 – 200 μm showed best eucalyptol absorption capacity with 1:3 masses ratio (sawdust:eucalyptol). The time capacity of eucalyptol release depends of composite eucalyptol – sawdust quantity. Where this relation was determined: 15.0 grams of composite eucalyptol-sawdust by 0.8 mm diameter aperture gave 6 months of eucalyptol release, that was considered very positive, understanding high volatility of eucalyptol and a small quantity of composite for further products. The new product is characterized by a carbon footprint (considering the industry frontiers) of 5.94 kg CO2eq/m2 of plywood floor.

Object detection is one of the most critical tasks in the field of Computer vision. This task comprises identifying and localizing an object in the image. Architectural floor plans represent the layout of buildings and apartments. The floor plans consist of walls, windows, stairs, and other furniture objects. While recognizing floor plan objects is straightforward for humans, automatically processing floor plans and recognizing objects is a challenging problem. In this work, we investigate the performance of the recently introduced Cascade Mask R-CNN network to solve object detection in floor plan images. Furthermore, we experimentally establish that deformable convolution works better than conventional convolutions in the proposed framework. Identifying objects in floor plan images is also challenging due to the variety of floor plans and different objects. We faced a problem in training our network because of the lack of publicly available datasets. Currently, available public datasets do not have enough images to train deep neural networks efficiently. We introduce SFPI, a novel synthetic floor plan dataset consisting of 10000 images to address this issue. Our proposed method conveniently surpasses the previous state-of-the-art results on the SESYD dataset and sets impressive baseline results on the proposed SFPI dataset. The dataset can be downloaded from SFPI Dataset Link. We believe that the novel dataset enables the researcher to enhance the research in this domain further.

This paper presents a new framework to classify floor plan elements and represent them in a vector format. Unlike existing approaches using image-based learning frameworks as the first step to segment the image pixels, we first convert the input floor plan image into vector data and utilize graph neural network. Our framework consists of three steps. (1) image pre-processing and vectorization of the floor plan image. (2) region adjacency graph conversion. (3) graph neural network on converted floor plan graphs. Our approach is able to capture different types of indoor elements including basic elements such as walls, doors, and symbols as well as spatial elements such as rooms and corridors. In addition, the proposed method can also detect element shapes. Experimental results show that our framework can classify indoor elements with an F1 score of 95%, with scale and rotation invariance. Furthermore, we propose a new graph neural network model that takes the distance between nodes into account, which is a valuable feature of spatial network data.

The paper highlights the problems associated with the application of daylight and integral lighting in industrial facilities. In the case study of a multi-storey textile plant, we show how combined lighting (daylight and integral illumination) can be evaluated in production halls labelled F and G. These halls have large areas 54 x 54 metres, and are more than 5 meters high. There is daylight only on side through connected windows in a vertical position. In this paper we want to present case studies of these two production halls in the textile factory located in Kosice (Slovakia). These are halls that are lit through by daylight from two sides through external walls that are opposite or next to each other. The results of the case studies can be applied in similar production halls illuminated by a “bilateral” —a double-side daylight system and natural illumination through windows on two sides in a vertical position. Such a situation is typical of multi-storey buildings in light industry. The proposed approach of daylight factor calculation can also be applied to floor space in other similar buildings.

Portal myofibroblasts (PMF) are known to be critical in bile duct injury, but their role in liver fibrogenesis remains underexplored. Thy-1, an adhesion molecule integral to fibroblasts, relevant in fibrogenesis and detectable in serum as soluble Thy-1 (sThy-1), is expressed by PMF but not hepatic stellate cells in vitro. This study aimed to elucidate the correlation between Thy-1 expression in liver histology and sThy-1 levels in serum with the degree of liver fibrosis in patients with primary biliary cholangitis (PBC) and metabolic dysfunction associated steatotic liver disease (MASLD). Liver histology samples were stained for Thy-1 and sThy-1 was measured using an enzyme-linked immunosorbent assay (ELISA). In patients with PBC and MASLD, portal Thy-1 expression significantly correlated with increased fibrosis. The sinusoidal Thy-1 expression also significantly correlated with increased fibrosis in patients with PBC (p

Metabolic dysfunction associated fatty liver disease (MAFLD), a globally prevalent chronic liver disease, has only limited pharmacological options. Both metformin and Ganwei, a botanical supplement containing a potent inducer for glycine N-methyltransferase (GNMT), have shown great promise for MAFLD. We conducted a 4-arm, randomized, placebo-controlled trial to investigate the safety and efficacy of metformin and Ganwei for MAFLD. Between September 2021 and March 2023, 64 patients with MAFLD were received metformin alone, Ganwei alone, combination of metformin and Ganwei, and placebo for 6 months. The primary MAFLD outcome was assessed by control attenuation parameter (CAP) and kilopascal (kPa) scores for liver steatosis and fibrosis, utilizing FibroScan. At 6 months after treatment, significant MAFLD improvements were observed in patients treated with Ganwei alone (repeated measures ANOVA test, p = 0.048 for both CAP and kPa scores). By employing a 6-point steatosis grade scale, the Ganwei alone arm exhibited a statistically better improvement than the placebo-controlled arm (mean score 1.1±1.9 vs. 0.1±0.7, p &lt; 0.01). In addition, patients in the Ganwei alone arm showed significant quality-of-life improvements. There was no serious adverse events observed. Our study demonstrated that Ganwei can be an effective treatment option for MAFLD patients. Clinical trial registration: NCT06244550.

Introduction: To compare the results of patient-specific absolute dosimetry using homogeneous slab phantom and anthropomorphic heterogeneous female pelvic phantom in cervical cancer patients. Materials and method: Thirty RapidArc plans already planned on treatment planning system (TPS) for cervical cancer patients were exported on both the phantoms viz. RW3 slab phantom and AHFP and dose were calculated using an anisotropic analytic algorithm (AAA). All the plans were delivered by linear accelerator (LA) and the dose for each plan was measured by a 0.6cc ion chamber. The percentage (%) variation between planned and measured doses were calculated and analyzed.Results: In the case of slab phantom, the mean percentage variations between planned and measured doses of all rapid arc QA plans were as 1.4299 and standard deviation 0.768 (t=0.00508, ρ= 0.497982) The result is not significant at p < .05. For the AHFP phantom, the mean percentage variations between planned and measured doses of all rapid arc QA plans were as 6.890 and standard deviation 2.565 (t= 3.21604, ρ= 0.001063 <0.05), the outcome is significant. Discussion: In the case of homogenous slab phantom, there is less than a 3% difference in percentage between planned and measured doses with a standard deviation of 0.7682 (t=0.00508, p= .497982. The result is not significant at p< 0.05). The deviations of planned and measured value of dose in the AHFP phantom were found as 10.67% (maximum value), 2.31% (minimum value) and 6.89% (average value) with standard deviation 2.565 (t=3.21604, p=0.001063. The result is significant at p<0.05). Also, the percentage of variation between homogeneous slab phantoms with AHFP phantom, the t-value is -11.17016. The p-value is < .00001. The result is significant at p<0.05. We can see that the outcomes differ significantly due to the influence of heterogeneous media.Conclusion: AHFP phantom results showed more dose variability than slab homogenous phantom outcomes. Therefore, patient-specific absolute dosimetry should be performed using a heterogeneous phantom that closely resembles the actual human body in terms of both density and design.

Because most of the recognized causes of superior gluteal nerve (SGN) injury are iatrogenic, detailed knowledge of the anatomy of the SGN is crucial to prevent its injury associated with surgical procedures. This study aims to describe the precise location of SGN or its branches at the greater sciatic foramen, measure the distances of these nervous structures to palpable bony landmarks, and evaluate the possible correlation between these parameters and pelvis size. Twenty human cadaveric hemipelvises were studied. After dissection to expose the SGN or its branches at the greater sciatic foramen, the distances from these nervous structures to the greater trochanter (GT), to the anterior superior iliac spine (ASIS), to the posterior superior iliac spine (PSIS), to the ischial tuberosity (IT), and to the greater sciatic notch were measured. We found that at the greater sciatic foramen the SGN emerges as a common trunk in 75% of hemipelvises, and already divided in its superior and inferior branches in 25% of hemipelvises. When the SGN exits the pelvis as a common trunk, it does so, in most cases, in contact with the bone at the apex of the greater sciatic notch or superior to it. The median distance from the SGN at the greater sciatic notch to the PSIS, ASIS, GT and IT is 7.6 cm, 10.9 cm, 7.5 cm and 10.8 cm, respectively. We found a positive correlation between some of the analyzed parameters and the size of the pelvis. The anatomical data of this study may serve as pivotal guides during orthopedic pelvic surgery, contributing to minimize SNG iatrogenic lesions with significant implications in the patient's quality of life.

Enophthalmos is a severe complication of primary reconstruction following orbital floor frac-tures, oncological resections or maxillo-facial syndromes. The goal of secondary reconstruction is to re-store symmetrical globe positions to recover function and aesthetics. In this article we pre-sent a method of computer-assisted orbital floor reconstruction using a mirroring technique and a customized titanium or high-density polyethylene mesh, printed using computer aided manufac-turing techniques. This reconstructive protocol involves 4 steps: mirroring of the healthy orbit at the affected site, vir-tual design of a patient specific orbital floor mesh, computer-assisted manufacturing (CAD) of the implant, and surgical insertion of the device. Using a computed tomography data set, the un-injured side of the craniofacial skeleton was reflected onto the contralateral injured side, and a reconstructive orbital floor prosthesis was virtually designed on the mirrored orbital bone sur-face. The solid-to-layer (.STL) files of the prosthesis were then manufactured using Direct Metal Laser Sintering (DMLS) or Computer Numerical Control (CNC) methods, leading to the produc-tion of 10 titanium meshes and 2 high density polyethylene (HDPE) implants. Clinical outcomes were assessed using 3dMD photogrammetry and computed tomography measures in 14 treated patients. The technique described here appears to be a viable method to correct complex orbital floor de-fects needing delayed reconstruction. This article represents the prosecution of a previous study, which is part of a wider experimental protocol for orbital floor reconstruction using comput-er-assisted design-computer-assisted manufacturing (CAD-CAM) technology

Cardiovascular disease (CVD), a group of disorders affecting the heart or blood vessels, are the primary cause of death worldwide, with an immense impact on patient quality of life and disa-bility. According to the World Health Organization, CVD takes an estimated 17.9 million lives each year, where more than four out of five CVD deaths are due to heart attacks and strokes. In the decades to come, increased prevalence of age-related CVD, such as atherosclerosis, coronary artery stenosis, myocardial infarction (MI), valvular heart disease, and heart failure (HF) will contribute to even greater health and economic burden as the global average life expectancy increases and consequently the world’s population continues to age. Considering this, it is important to focus our research efforts on understanding the fundamental mechanisms underlying CVD. In this review, we focus on cellular senescence and mitochondrial dysfunction, which have long been established to contribute to CVD. We also assess the recent advances in targeting mitochondrial dysfunction and senescence with a focus on therapies that influence both and therefore perhaps represent strategies with the most clinical potential, range, and utility.

Cardiovascular diseases (CVD) account for about 17.3 million annual deaths worldwide. 85% of these deaths occurred as a result of myocardial infarction (MI) and stroke. Chronic heart diseases, such as arterial hypertension (AH), coronary heart disease, various cerebrovascular diseases, dilated and hypertrophic cardiomyopathies are widespread, with a fairly high incidence of mortality and disability. Most of these diseases are characterized by cardiac arrhythmias, conduction and contractility disorders. Additionally, interruption of the electrical activity of the heart, the appearance of extensive ectopic foci and heart failure are all symptoms of a number of severe hereditary diseases. The molecular mechanisms leading to the development of CVD are associated with impaired permeability and excitability of cell membranes and mainly caused by dysfunction of cardiac Ca2+ channels. Acquired channelopathies are caused by metabolic disorders, increased tone of the sympathetic nervous system, age-related changes that lead to deterioration of coronary blood flow and hemodynamics. Currently known channelopathies, such as the long or short QT syndromes, Brugada and Lenegre syndromes, catecholaminergic polymorphic ventricular tachycardia, etc., are congenital and genetic disorders caused by mutations of genes "responsible" for the conductive properties of certain channel-forming proteins, including pore-forming subunits of Ca2+ channels. Over the past 50 years, more than 100 varieties of ion channels have been found in the cardiovascular system cells. The relationship between the activity of these channels and cardiac pathology, as well as the general cellular biological function, has been intensively studied on several cell types and experimental animal models in vivo и in situ. In this review, we discuss the origin of Ca2+ channelopathies and the role of Ca2+ channels of various types: L- R-, T-types voltage-gated calcium channels, RyR2, non-selective hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, transient receptor potential (TRPC, TRPM7, TRPA1) channels in the development of cardio-vascular pathology.

Over the last decades, cellular immunotherapy has revealed its curative potential. However, the inherent physiological characteristics of immune cells can limit the potency of this approach. Best defined in T cells, dysfunction associated with terminal differentiation, exhaustion, senescence, and activation-induced cell death undermine adoptive cell therapies. In this review, we concentrate on how the multiple mechanisms that articulate the various forms of immune dysfunction impact cellular therapies primarily involving conventional T cells, but also other lymphoid subtypes, in addition to the various strategies put in place to circumvent these effects. The repercussions of immune cell dysfunction across the full life cycle of cell therapy, from the source material, during manufacturing, and after adoptive transfer are discussed. Applicable to cellular products prepared from native and unmodified immune cells, as well as genetically engineered therapeutics, the understanding and potential modulation of dysfunctional features is key to the development of improved cellular immunotherapies.

Rheumatoid arthritis (RA) is a chronic systemic inflammatory autoimmune disease that affects about 1% of the global population, with a female-male ratio of 3:1. To date, genetic predisposition, the involvement of a deficient immune system and lifestyle are known to be the major responsible for the onset of the disease. RA preferably affects the joints, with consequent joint swelling and deformities followed by ankylosis. Patients suffering from rheumatoid arthritis can also develop extra-articular manifestations, which mainly affect the cardiovascular system, the nervous system, the skin, the eye, the respiratory system, the kidney and the gastrointestinal system. It has been shown that about 20% of RA patients can develop neuropathies, multiple mononeuritis, distal sensory neuropathies and sense motor neuropathies. Neurological involvement occurs as a consequence of vasculitis of the nerve vessels leading to vascular ischaemia, axonal degeneration and neuronal demyelination. In RA, the risk of developing cardiovascular disease is very high and depends, most probably, on vascular damage resulting from endothelial dysfunction. Hence, it is reasonable to assume that the integrity of the endothelium is also involved in the neurological disorders resulting from RA. This review aims to highlight the main characteristics of the extra-articular manifestations at the nervous level resulting from rheumatoid arthritis. To this end, the literature main results on these pathological manifestations have been collected with particular focus on the involvement of endothelial dysfunction. In fact, the endothelium could be considered a valuable target for minimizing the incidence of extra-articular neurological manifestations in RA.

A pump station is a very important flood control facility for mitigating inundation of urban lowland areas. It is not easy to secure a site to increase the capacity of a pump station in an urban area because of various limitations or to maximize the discharge capacity of the pump sump. Adding a facility to improve the pump capacity of a pump station may affect the flow characteristics, such as unexpected increases in the flow velocity and vorticity, and cause severe problems with operating the pump station. To solve those problems, anti-vortex devices (AVDs) have been developed and adopted for appropriate design standards. The Korean design criteria for AVDs are based on experience and foreign standards because not enough data on the AVD are available. In this study, the flow in the sump was numerically simulated at various AVD heights to collect information on improving the design and efficiency of a pump station. Consequently, an appropriate height for the AVD and changes in the flow pattern and vortex in the pump sump were determined and compared with 12 cases of inflow conditions with respect to the vertical location.

Exposure to cadmium sulfate (CdSO4) can lead to neurotoxicity. Nevertheless, the precise molec-ular mechanisms underlying this phenomenon remain unclear, and effective treatment strategies are scarce. This study explored the protective effects of ellagic acid (EA), a natural polyphenolic compound, against CdSO4 exposure-induced neurotoxicity in HT22 cells. Additionally, the inves-tigation sought to elucidate the molecular mechanisms underlying this phenomenon. Our findings demonstrated that exposure of HT22 cells to CdSO4 resulted in apoptosis, which was effectively reversed by EA supplementation. EA supplementation also decreased reactive oxygen species (ROS) and mitochondrial ROS productions, reduced malondialdehyde (MDA) levels, and restored the activities of superoxide dismutase (SOD) and catalase (CAT). Additionally, EA supplementation at 5–20 μM significantly counteracted Cd-induced mitochondrial membrane potential and ATP losses and reduced the ratio of Bax/Bcl-2 and cleaved-caspase-3 protein expression. Furthermore, EA supplementation upregulated Nrf2 and HO-1 protein expression while downregulating the phosphorylation of JNK and p38 proteins. Pharmacological inhibition of JNK partially inhibited CdSO4-induced Nrf2/HO-1 activation and exacerbated its cytotoxicity. In conclusion, our results indicate that EA supplementation provides protection against CdSO4-induced cell apoptosis in HT22 cells by inhibiting oxidative stress and activating the Nrf2 pathway. Activation of the JNK pathway plays a protective role in CdSO4-induced cell apoptosis in HT22 cells.

Background/Objectives: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing at an alarming rate. Cardiovascular disease (CVD) is the leading cause of mortality in MASLD patients, therefore, the therapeutic interventions for MASLD should improve coronary risk factors such as obesity, diabetes and dyslipidemia, in addition to improving liver function. The evidence on effect of sodium-glucose cotransporter 2 inhibitors (SGLT2is) which have beneficial pharmacological properties for MASLD, especially the long-term effects, on the progression of MASLD in Asian population is very limited. Methods: The retrospective longitudinal study was performed by using the medical records at the National Center for Global Health and Medicine, Kohnodai Hospital, Japan. We picked up patients with type 2 diabetes who had taken SGLT2is for at least 3 years or longer between April 1, 2014 and March 31, 2018. We collected the data on metabolic parameters, including blood tests and anthropometric parameters, and compared the data before and after the initiation of SGLT2is treatment. Results: During the observation period, 324 patients had taken SGLT2is for 3 years. The 3-year-SGLT2is treatment significantly reduced body weight, hemoglobin A1c, low-density lipoprotein-cholesterol, triglyceride and non-high-density lipoprotein-cholesterol (HDL-C) and significantly increased HDL-C. Furthermore, this treatment significantly improved liver function and the markers for hepatic steatosis and hepatic fibrosis. Conclusions: Considering that the development of CVD determines the prognosis of MASLD patients, the long-term SGLT2is treatment may be an ideal therapy for MASLD patients.

Glycogen storage disorders (GSDs) are a group of inherited metabolic disorders characterized by defects in enzymes involved in glycogen metabolism. Deficiencies in enzymes responsible for glycogen breakdown and synthesis can impair mitochondrial function. For instance, in GSD type II (Pompe disease), acid alpha-glucosidase deficiency leads to lysosomal glycogen accumulation, which secondarily impacts mitochondrial function through dysfunctional mitophagy, which disrupts mitochondrial quality control generating oxidative stress. In GSD type III (Cori disease), the lack of the debranching enzyme causes glycogen accumulation and affects mitochondrial dynamics and biogenesis by disrupting the integrity of muscle fibers. Malfunctional glycogen metabolism can disrupt various cascades thus causing mitochondrial and cell metabolic dysfunction through various mechanisms. These dysfunctions include altered mitochondrial morphology, impaired oxidative phosphorylation, increased production of reactive oxygen species (ROS), and defective mitophagy. The oxidative burden typical of GSDs compromises mitochondrial integrity and exacerbates the metabolic derangements observed in GSDs. The intertwining of mitochondrial dysfunction and GSDs underscores the complexity of these disorders and has significant clinical implications. GSD patients often present with multisystem manifestations, including hepatomegaly, hypoglycemia, and muscle weakness, which can be exacerbated by mitochondrial impairment. Moreover, mitochondrial dysfunction may contribute to the progression of GSD-related complications, such as cardiomyopathy and neurocognitive deficits. Targeting mitochondrial dysfunction thus represents a promising therapeutic avenue in GSDs. Potential strategies include antioxidants to mitigate oxidative stress, compounds that enhance mitochondrial biogenesis, and gene therapy to correct the underlying mitochondrial enzyme deficiencies. Mitochondrial dysfunction plays a critical role in the pathophysiology of GSDs. Recognizing and addressing this aspect can lead to more comprehensive and effective treatments, improving the quality of life of GSD patients. This review aims to elaborate on the intricate relationship between mitochondrial dysfunction and various types of GSDs. The review presents challenges and treatment options for several GSD

One of the hallmarks of the SARS-CoV-2 infection has been the inflammatory process that played a role in its pathogenesis, resulting in mortality within susceptible individuals. This uncontrolled inflammatory process leads to severe systemic symptoms via multiple pathways, however, the role of endothelial dysfunction and thrombosis have not been truly explored. This review aims to highlight the pathogenic mechanisms of these inflammatory triggers leading to thrombogenic complications. There are direct and indirect pathogenic pathways of the infection that are examined in detail. We also describe the case of carotid artery thrombosis in a patient following the SARS-CoV-2 infection, while reviewing the literature on the role of ACE2, the endothelium, and the different mechanisms by which SARS-CoV-2 may manifest both acutely and chronically. We also highlight differences from the other coronaviruses that have made this infection pandemic with similarities to the influenza virus.

This paper shows the usage of a numerical analysis model which enables the calculation of the life of a railway wheels used for low-floor freight wagons as a function of its primary operating factors, which allows carrying out sensitivity analyses. Low-floor wagons are being increasingly used for combined transport applications and many types of bogies have been proposed in order to constitute the wagons. Due to the uniqueness of this type of wagons, the bogie configurations in terms of wheelbase and axle load have hardly been analyzed so far. The numerical analysis model used addresses the primary challenges that arise in the vehicle – track interaction and establish the relations among them. The main aspects of this model have been described in the paper, which has been later used to calculate the life of an ordinary-diameter wheel for several wheelbase and axle load values. This study has been replicated with reduced-diameter wheels, which are commonly used for low-floor wagons. In this way, it is possible to know the evolution of the life depending on the wheelbase and the axle load. The root causes underlying the observed behaviors can be explained by the entire understanding of the rolling phenomenon provided by the full analytical work.

T cells follow a triphasic distinct pathway of activation, proliferation and differentiation before becoming functionally and phenotypically ‘exhausted’ in settings of chronic infection, autoimmunity and in cancer. Exhausted T cells progressively lose canonical effector functions, exhibit altered transcriptional networks and epigenetic signatures and gain constitutive expression of a broad coinhibitory receptor suite. This review outlines recent advances in our understanding of exhausted T cell biology and examines cellular and molecular mechanisms by which a state of dysfunction or exhaustion is established, and mechanisms by which exhausted T cells may still contribute to pathogen or tumour control. Further, this review describes our understanding of exhausted T cell heterogeneity and outlines the mechanisms by which checkpoint blockade differentially engages exhausted T cell subsets to overcome exhaustion and recover T cell function.

Gastric-type endocervical adenocarcinoma (GAS) is a rare non-human papillomavirus associated mucinous adenocarcinoma of the cervix. Its clinical manifestations are extremely atypical, with hidden lesions and difficulty in obtaining materials, resulting in a low positive rate of screening and biopsy. The pathological morphological features are similar to benign lesions, but the biological characteristics are highly malignant, posing great challenges to diagnosis. The preoperative diag-nostic rate is low, which is prone to misdiagnosis and missed diagnosis, leading to delayed treatment and seriously affecting the prognosis of patients. Here，we reported a case of ovarian endometriosis cyst combined with GAS confirmed by surgery and postoperative pathology, with "pelvic mass" as the initial symptom. Through case report and literature review, the characteristics and current re-search progress of GAS were summarized, in order to provide references for diagnosis of GAS, and provide theoretical guidance for formulating reasonable treatment strategy and improving patient prognosis.

Background and Objectives: Angioembolization has emerged as an effective therapeutic approach for pelvic hemorrhages; however, its exact effect size remains uncertain. Therefore, we conducted this systematic review and meta-analysis to investigate the effect size of embolization-related pelvic complications after nonselective angioembolization compared to that after selective angioembolization in patients with pelvic injury accompanying hemorrhage. Materials and Methods Relevant articles were collected by searching the PubMed, EMBASE, and Cochrane databases until June 24, 2023. Meta-analyses were conducted using odds ratios (ORs) for binary outcomes. Quality assessment was conducted using the risk of bias tool in non-randomized studies of interventions. Results: Five studies examining 357 patients were included in the meta-analysis. Embolization-related pelvic complications did not significantly differ between patients with nonselective and selective angioembolization (OR 1.581, 95% confidence interval [CI] 0.592 to 4.225, I2 = 0%). However, in-hospital mortality was more likely to be higher in the nonselective group (OR 2.232, 95% CI 1.014 to 4.913, I2 = 0%) than in the selective group. In the quality assessment, two studies were found to have a moderate risk of bias, whereas two studies exhibited a serious risk of bias. Conclusions: Despite the favorable outcomes observed with nonselective angioembolization concerning embolization-related pelvic complications, determining the exact effect sizes was limited owing to the significant risk of bias and heterogeneity. Nonetheless, the low incidence of ischemic pelvic complications appears to be a promising result.

The fundamental goal of modern medicine is to increase human life expectancy. Currently, most of the patients in hospitals with different clinical profiles are elderly and senile subjects, with a high incidence of comorbidities, as well as concomitant age-related changes in peripheral tissues. One such change is sarcopenia, a progressive loss of muscle mass, strength, and muscle function that is associated with a high risk of adverse outcomes, leading to an increased risk of disability and death among older adults. The mechanisms of development of sarcopenia are currently being actively studied. This narrative review presents the issues of epidemiology, pathophysiology, and diagnostic criteria for sarcopenia. The relationships between sarcopenia and metabolic dysfunction-associated steatotic liver disease (MASLD) with possible promising directions for the treatment of this comorbid pathology are considered.

Erectile dysfunction (ED) is the inability to achieve or maintain an erection during sexual performance. ED is one of the most common and neglected complications of diabetes. Almost 35-75% of diabetic men around the world suffer from ED. Although the exact mechanism by which diabetes causes ED is not well understood. However, several studies suggested it may be related to damage to the nerve and vessels that supply the penis.

Hepatocellular carcinoma (HCC) is currently the third leading cause of malignancy-related mortalities worldwide. Natural killer (NK) cells are involved in the critical role of first line immunological defense against cancer development. Defects in NK cell functions are recognized as important mechanisms for immune evasion of tumor cells. NK cell function appears to be attenuated in HCC, and many previous reports suggested that NK cells play a critical role in controlling HCC, suggesting that boosting the activity of dysfunctional NK cells can enhance tumor cell killing. However, the detailed mechanisms of NK cell dysfunction in tumor microenvironment of HCC remain largely unknown. A better understanding of the mechanisms of NK cell dysfunction in HCC will help in the NK cell-mediated eradication of cancer cells and prolong patient survival. In this review, we describe the various mechanisms underlying NK cell dysfunction in HCC. Further, we summarize current advances in the approaches to enhance endogenous NK cell function and in adoptive NK cell therapies, to cure this difficult-to-treat cancer.

Iron deficiency in the fetal and neonatal period (perinatal iron deficiency) bodes poorly to neuro-development. Given its common occurrence and the negative impact on brain development, a screening and treatment strategy that is focused on optimizing brain development in perinatal iron deficiency is necessary. Pediatric societies currently recommend a universal iron supple-mentation strategy for full-term and preterm infants that does not consider individual variation in the body iron status and could lead to under-treatment or over-treatment. Moreover, the focus is on hematological normalcy and not optimal brain development. Several serum iron indices and hematological parameters in the perinatal period are associated with risk of abnormal neurodevelopment, suggesting their potential use as biomarkers for screening and monitoring treatment in infants at risk for perinatal iron deficiency. A biomarker-based screening and treatment strategy that is focused on optimizing brain development will likely improve outcome in perinatal iron deficiency.

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disorder affecting 1 in 500 people in the general population. Although characterized by asymmetric left ventricular hypertrophy, cardiomyocyte disarray and cardiac fibrosis, HCM is in fact a highly complex disease with heterogenous clinical presentation, onset and complications. While HCM is generally accepted as a disease of the sarcomere, variable penetrance in families with identical genetic mutations challenges the monogenic origin of HCM and instead implies a multifactorial cause. Furthermore, large scale genome sequencing studies revealed that many genes previously reported as causative of HCM in fact have little or no evidence of disease association. These findings thus call for a re-evaluation of the sarcomere-centered view of HCM pathogenesis. Here, we summarize our current understanding of sarcomere-independent mechanisms of cardiomyocyte hypertrophy, highlight the role of extracellular signals in cardiac fibrosis, and propose an alternative but integrated model of HCM pathogenesis.

As in glaucoma and other optic neuropathies cellular dysfunction often precedes cell death, sensitive assessment of retinal ganglion cell (RGC) function represents a key outcome measure for neuroprotective strategies aimed at targeting distressed but still viable cells. Here we offer a conceptual framework to identify progressive stages of RGC dysfunction leading to cell death in mouse models of glaucoma and other optic neuropathies based on non-invasive pattern electroretinogram (PERG), to differentiate phenotypic and altered RGC response dynamics, to assess susceptibility to stressors and to assess reversible dysfunction.

Failure characteristics induced by unloading disturbance and the corresponding mechanical mechanism of the coal seam floor are important theoretical bases for water-bursting prevention from the floor of the coal seam and rock burst alarm in deep mining. However, the existing two-dimensional ground-pressure-control theory based on shallow mining cannot sufficiently guide deep-mining practices. In this study, the redistribution of mining-induced stress field in rocks surrounding the longwall face and mechanical behaviors of strata in deep mining are investigated through a combination of numerical simulation, physical simulation, and field measurement. Results demonstrate that mining-induced stress fields in the floor of the longwall face differ in space and time. Vertical stress unloading from top to bottom of the floor and horizontal stress unloading are relatively low. A concentration zone of high horizontal stress exists at stope boundaries. The critical yield load of rock stratum in the floor is determined through thin plate yield theory. Under the combined effect of concentrated high horizontal and vertical resilience stresses, strata in the floor fracture from seam to seam if the load increases to the minimum critical buckling value. Fractured strata slide along the fracture surface, which leads to floor heave. The stope floor shows evident time-delay progressive failure characteristics. The stress shell in the stope floor in deep mining is found to be a sensitive mechanical parameter that produces three-dimensional ground-pressure behavior in the floor. This ground-pressure behavior in the stope floor is controlled by the existence of the corresponding stress shell and effects induced by its space–time evolution. This study provides theoretical basis for the dynamic control of a hazard-inducing environment in engineering and minimizing or altering disaster-occurrence conditions during the construction engineering of the coal seam floor.

Metabolic dysfunction associated fatty liver disease (MAFLD) has gained worldwide attention as a public health problem. Nonetheless, lack of enough mechanistic knowledge restrains effective treatments. It is known that T3 regulate hepatic lipid metabolism, and mitochondrial function. Liver dysfunction of T3 contributes to MAFLD, but its role is not fully understood. Objective: To evaluate the role of T3 dysfunction in the progression of MAFLD in an animal model. Method-ology: Male/adult Sprague Dawley rats (n=20) were allocated to a control group (standard di-et–2.93kcal/g) and diet group (CDHF–4.3kcal/g). Euthanasia took place in the 28th week. D3 ac-tivity and expression, UCP2 and D1 expression, REDOX status, mitochondrial, Krebs cycle and endoplasmic reticulum homeostasis in liver tissue were measured. Results: We observed an in-crease in D3 activity/expression (P<0.001) related to increased TBARS and carbonyls and GSH reduction in the MAFLD group (P<0.05). There was a T3-dependent decrease in UCP2 expression (P=0.01), mitochondrial capacity, respiratory activity with increased endoplasmic reticulum stress in the MAFLD group (P < 0.001). Surprisingly, in and environment with lower T3 levels we observed an augmented alpha-ketoglutarate dehydrogenase (KGDH) and glutamate dehydro-genase (GDH) enzymes activity (P<0.05). Conclusion: Induced D3, triggered by changes in the REDOX state, decreases T3 availability, and hepatic mitochondrial capacity. The Krebs cycle en-zymes were altered as well as reticulum stress. Taken together, these results shed new light on the role of T3 metabolism in MAFLD and new treatment opportunities.

Coronary microvascular dysfunction (CMD) is a clinical entity linked with various risk factors that significantly affect cardiac morbidity and mortality. Hypertension, one of the most important, causes both functional and structural alterations in the microvasculature, promoting the occurrence and progression of microvascular angina. Endothelial dysfunction and capillary rarefaction play the most significant role in the development of CMD among patients with hypertension. CMD is also related to several hypertension-related morphological and functional changes in the myocardium in the subclinical and early clinical stages, including left ventricular hypertrophy, interstitial myocardial fibrosis, and diastolic dysfunction. This indicates the fact that CMD, especially if associated with hypertension, is a subclinical marker of end-organ damage and heart failure, particularly the one with preserved ejection fraction. This is why it is important to search for microvascular angina in every patient with hypertension and chest pain not associated with obstructive coronary artery disease. Several highly sensitive and specific non-invasive and invasive diagnostic modalities have been developed to evaluate the presence and severity of CMD, but also to investigate additional complications that can affect further prognosis, especially among those with hypertensive heart disease. Although various pharmacological and interventional treatments demonstrated certain clinical effects, integrated diagnostic and therapeutic algorithms are necessary to reduce the burden of this emerging condition.

Metabolic dysfunction-associated fatty liver disease (MAFLD) has now affected nearly one third of global population and became the number one cause of chronic liver disease in the world because of the obesity pandemic. Chronic hepatitis resulting from hepatitis B virus (HBV) and hepatitis C virus (HCV) also remain significant challenges to liver health even in the 21st century. The coexistence of MAFLD and chronic viral hepatitis can markedly alter the disease course of individual diseases and can complicate the management of each of these disorders. Thorough understanding of the pathobiological interlink and interactions between MAFLD and these two chronic viral hepatitis infections are crucial for appropriate management of patients. We update these interlinks in this comprehensive clinical review.

Oligodendrocytes are myelinating cells of the central nervous system, which are generated by progenitor oligodendrocytes as a result of maturation processes. The main function of mature oligodendrocytes is to produce myelin, a lipid-rich multi-lamellar membrane that wraps tightly around neuronal axons, isolating them and facilitating nerve conduction through saltatory propagation. The myelination process requires the consumption of a lot of energy and a high metabolic turnover. Mitochondria are essential organelles which regulate many cellular functions including the energy production through oxidative phosphorylation. Any mitochondrial dysfunction impacts cellular metabolism and negatively affects the health of the organism. If the functioning of the mitochondria is unbalanced the myelination process is impaired. At the end of myelination, oligodendrocytes synthesize about 40% of the total lipids present in the brain. Since lipid synthesis occurs in the cellular endoplasmic reticulum, the alteration of this organelle can lead to partial or deficient myelination, triggering numerous neurodegenerative diseases. In this review the main dysfunctions of oligodendrocytes caused by exogenous or endogenous stimuli will be investigated. Furthermore, the oligodendrocyte reactions to excessive mitochondrial oxidative stress and an altered regulation of the functioning of the endoplasmic reticulum will be discussed.

Introduction: The disease caused by Coronavirus-2019 (COVID-19) was initially described in December 2019. Severe acute respiratory syndrome type 2 (Sars-Cov-2) is responsible for an important multisystem inflammatory spectrum. Cardiovascular conditions have been reported with an estimated frequency of 8-28%. In this context, transthoracic echocardiography associated with the analysis of the two-dimensional Global Longitudinal Strain (GLS) of the left ventricle derived from Speckle Tracking emerges as a promising modality. Objective: This study aims to evaluate the applicability of GLS and segmental deformity assessment in detecting subclinical myocardial dysfunction in patients that recovered from COVID-19 infection. Methods: The observational study involved 18 patients (mean age 52 years) with recent evidence of COVID-19 infection that underwent detailed echocardiographic evaluation with GLS, and cardiac magnetic resonance (CMR) according to segmental assessment results. The degree of correlation between the methods was analyzed and a systematic literature review was also conducted. Results: The mean left ventricular ejection fraction (LVEF) was 57.50 ± 9.98%. Only 16.6% of patients had reduced LVEF. The average GLS was – 18.70 ± 3.54% and in 44% of cases only one myocardial segment was affected, particularly the inferolateral basal. CMR revealed inflammatory cardiomyopathy. Discussion: Subclinical myocardial involvement is associated with major adverse cardiac events. Literature review supports the use of GLS for detecting early cardiac involvement. Conclusion: Speckle-tracking echocardiography has been shown to have clinical utility in a variety of settings and to offer superior prognostic value with a potential to enhance subclinical detection of myocardial changes in patients after COVID-19 infection.

Oil-Gan, also known as emblica, is the fruit of the genus Phyllanthus emblica L. The fruits of these trees are high in nutrients and have excellent effects on health care and development values. There are many methods for the management of diabetic nephropathy (DN). However, there is a lack of effective drugs for treating DN from throughout the disease course. The primary aim of this study was to examine the protective effects (including urine analyses, the measurement of inflammatory cytokine levels, and histological examination) and mechanisms of action of an ethyl acetate extract of P. emblica (EPE) on db/db mice, an animal model of diabetic nephropathy, as well as a secondary aim of examining the expression levels of protein kinase Cα (PKCα) in the kidney and its downregulation of vascular endothelial growth factor (VEGF) and fibrosis gene transforming growth factor-β1 (TGF-β1) by Western blot analyses. Eight db/m C57BLKS/J mice were used as the control group. Forty db/db mice were randomly divided into five groups. Treatments included vehicle, EPE1, EPE2, EPE3 (at doses of 100, 200, or 400 mg/kg EPE), or the comparative drug aminoguanidine for 8 weeks. After 8 weeks of treatment, blood samples were collected for analyses of blood glucose, insulin, and HbA1c levels, and pancreatic and kidney tissues were dissected for histological analyses. The present study indicated that the administration of EPE to db/db mice effectively controlled hyperglycemia and hyperinsulinemia by markedly lowering blood glucose, insulin, and glycosylated HbA1c levels. Administration of EPE to db/db mice decreased the levels of BUN and creatinine both in blood and urine and reduced urinary albumin excretion and the albumin creatine ratio (UACR) in urine. Moreover, EPE treatment decreased the blood levels of inflammatory cytokines, including kidney injury molecule-1 (KIM-1), C-reactive protein (CRP), and NLR family pyrin domain containing (NLRP3). Our findings showed that EPE not only had antihyperglycemic effects but also improved renal function in db/db mice. Histological examination of the kidney by immunohistochemistry indicated that EPE can improve kidney function by ameliorating glomerular morphological damage following glomerular injury; alleviating proteinuria by upregulating the expression of nephrin, a biomarker of early glomerular damage; and inhibiting glomerular expansion and tubular fibrosis. Moreover, the administration of EPE to db/db mice increased the expression levels of p- PKCα/t-PKCα but decreased the expression levels of VEGF and renal fibrosis biomarkers (TGF-β1, collagen IV, p-Smad2, p-Smad3, and Smad4), as shown by Western blot analyses. These results implied that EPE as a supplement has a protective effect against renal dysfunction through the amelioration of insulin resistance as well as the suppression of nephritis and fibrosis in a DN model.