Search Results (312)

Background: Ankylosis of the temporomandibular joint (TMJ) is a rare developmental disorder that involves fibrous or bony fusion within the joint. It is a severe structural and functional disorder. Typically, the phenotype manifests as joint immobilization and results in facial deformity and trismus. To date, ankylosis is rarely diagnosed as congenital and its occurrence mechanism has not been thoroughly understood. We observed a female patient who as a newborn showed slight facial asymmetry and impaired mandibular retraction. In addition, non-uniform occlusal fissures were noted; the lower part of the left earlobe was slightly smaller than the right earlobe. The aim of the work was the identification of pathogenic variants in the genome related to ankylosis. Ankylosis has no known causative gene yet; thus, Whole Exome Sequencing (WES) was performed. Materials and Methods: We observed a female patient with facial asymmetry and impaired mandibular retraction from birth. No phenotypic abnormalities were noted on the head or elsewhere on the body. A diagnostic computed tomography (CT) scan of the head performed at five months of age led to the diagnosis of congenital zygomatic-coronoid ankylosis. Genomic DNA samples were subjected to WES. Library preparation was carried out using the Twist Library Preparation EF Kit 2.0, followed by target enrichment with the Twist Exome 2.0 Plus Comprehensive Exome. Sequencing reads were aligned to the human reference genome (GRCh38), and variant calling was performed using standard bioinformatics workflows. Variants were subsequently filtered, annotated, and interpreted using VariantStudio. Assessment of variant pathogenicity was primarily based on comparisons with public databases, including ClinVar and VarSome, and was supported by in silico prediction tools such as SIFT and PolyPhen-2. Results: In genes responsible for disorders of the I and II pharyngeal arches, three pathogenic variants were identified: in the genes TCOF1 and POLR1B, responsible for the development of Treacher Collins syndrome (TCS), and one in the DHODH gene, responsible for Miller syndrome. Additionally, in genes that have not been linked so far with rare facial disorders, 42 variants were identified, of which 8 are listed as pathogenic. We present the first described patient with congenital ankylosis, who, although showing no phenotypic features of these syndromes, has identified pathogenic variants in genes responsible for craniofacial dysostosis. Conclusions: Variants in TCOF1, POLR1B and DHODH may represent candidate genetic factors associated with susceptibility to ankylosis. WES analysis is an appropriate method in the case of patients with congenital diseases with unknown genetic origin. In this study we provide a comprehensive list of all identified pathogenic variants. This might be useful for scientists searching for the genetic background of skeletal system issues, one of which could be bone and fibrous tissue remodeling. Full article

With the increasing density of urban underground space development, the soil disturbance induced by large-section rectangular pipe jacking poses a significant threat to the safety of underlying subway tunnels. Taking the Lihe Road utility tunnel project in Wuhan, which crosses over Metro Line 4, as the engineering background, a three-dimensional finite element (FE) model was established using Midas GTS NX to simulate the entire pipe jacking process. Field monitoring data from caisson excavation, ground improvement, pipe jacking, and backfill grouting were introduced for validation, enabling a systematic investigation of the influence mechanism of pipe jacking on existing tunnels. In the numerical simulation, the modified Mohr–Coulomb constitutive model was adopted for the soil, and a “portal-type” reinforcement system was introduced. The pipe jacking process was simulated equivalently with a 1.2 m advance per cycle. The results indicate that the ground settlement induced by pipe jacking exhibits a stage-wise accumulation pattern and eventually develops into a stable settlement trough. The vertical settlement of the tunnel follows an evolutionary law of “early occurrence in the near field, delayed response in the far field, and final convergence,” with peak settlements of 2.44 mm and 2.53 mm for the left and right lines, respectively. Ground improvement significantly mitigates soil deformation, reducing the maximum surface settlement from 45.5 mm to 11.1 mm, decreasing the tunnel’s peak vertical settlement by 37%, and reducing horizontal displacement by 64%, thereby effectively suppressing lateral soil extrusion. The proposed closed-loop analysis method of “numerical simulation–monitoring validation–measure evaluation” reveals the spatiotemporal evolution law of soil–tunnel interaction during pipe jacking construction and provides valuable reference for risk control in similar engineering projects. Full article

Introduction: The existence of primary adrenal gland lymphoma (PAGL) has been debated due to lack of lymphoid tissue in the adrenal glands. PAGL is extremely rare, accounting for less than 1% of all types of lymphomas. The aim of this study was to analyze patients with PAGL in Polish population. Material and Methods: We retrospectively reviewed 13 adult patients with PAGL diagnosed in Polish Hematological Centers. Results: A total of 13 patients (5 women and 8 men) with PAGL were included into the study. The median age at the diagnosis was 69.1 years (range: 31–85). The most common histological type was diffuse large B-cell lymphoma (DLBCL)-12 patients, the remaining one was diagnosed with Hodgkin lymphoma (HL). In 7 patients (54%), the left adrenal gland was involved; in 3 patients (23.5%), the right adrenal gland was involved; and 3 patients (23.5%) had bilateral lymphoma. Systemic symptoms (B symptoms) were observed in 11 out of 13 patients (85%). Two patients (15%) were treated with chemotherapy alone and the remaining eleven patients (85%) with immune and chemotherapy together (85%). During the follow-up period, 11 patients died, 8 had relapsed or refractory disease (62%), and 3 patients (23%) had relapse in central nervous system (CNS). The median progression-free survival (PFS) was 14.63 months, while the median overall survival (OS) was 20.30 months. Adrenalectomy of the involved adrenal gland was associated with shorter PFS (p = 0.0165), with trend of shorter OS. Achieving complete remission (CR) after front line treatment was associated with significantly longer OS (p = 0.0239) and PFS (p = 0.0152). Conclusions: Adrenal glands are extremely rare as primary locations of extranodal lymphoma. The prognosis of PAGL is generally poor. In this study, we described demographic, clinical, and pathological characteristics as well as factors that may affect survival among these groups. So far, it is the largest polish multicenter experience describing patients with PAGL. Full article

Background and Clinical Significance: SLIPPERS syndrome (Supratentorial Lymphocytic Inflammation with Parenchymal Perivascular Enhancement Responsive to Steroids) was first described in 2015 as a variant of CLIPPERS restricted to supratentorial regions. Only a few cases have been reported so far, and its distinction from primary angiitis of the central nervous system (PACNS) remains challenging, as both may present with overlapping clinical, radiological, and histopathological features. We report two patients initially diagnosed with SLIPPERS but finally fulfilling the diagnostic criteria for PACNS, highlighting the complexity of the differential diagnosis. Case Presentation: The first patient was a 49-year-old woman who presented with seizures, memory impairment, and facial neuralgia. MRI showed multiple cortico-subcortical and deep nodular lesions in the left hemisphere with gadolinium enhancement. Brain biopsy revealed a T-cell-predominant lymphocytic vascular infiltrate. She responded to corticosteroids but later relapsed, requiring methotrexate for long-term immunosuppression, with no further recurrences during seven years of follow-up. The second patient was a 64-year-old man with hypertension, dyslipidemia, and alcohol use who developed repeated focal-to-generalized seizures. MRI disclosed multifocal nodular gadolinium-enhancing right hemispheric lesions, with SWI microhemorrhages. Biopsy demonstrated transmural T-cell vasculitic infiltrates. He responded to corticosteroids and methotrexate, but radiological progression at 14 months prompted replacement with cyclophosphamide. Conclusions: There is a considerable clinical, radiological, and histological overlap between SLIPPERS and PACNS. Careful analysis of advanced MRI sequences, particularly angiographic and vessel-wall imaging studies, combined with meticulous histopathological analysis, is essential to avoid misdiagnosis. These similarities suggest that some cases attributed to SLIPPERS may, in fact, correspond to variants of PACNS. Full article

Uplift pressure is a major contributor to seismic instability in arch dam abutments, particularly where jointed rock masses form wedge-shaped failure blocks. This study develops an integrated numerical framework combining nonlinear finite element analysis, the Londe limit-equilibrium method, and Incremental Dynamic Analysis (IDA) to quantify the seismic stability of multiple abutment wedges in the Bakhtiari Arch Dam. A three-dimensional finite element model is used to compute dam–abutment thrust forces, while sixteen far-field ground motions are scaled to capture the progression of wedge instability with increasing spectral acceleration. Uplift pressures on joint planes are varied to represent different levels of grout curtain performance. The results indicate that uplift pressure is the dominant factor controlling wedge stability, substantially reducing effective normal stresses and shifting IDA and fragility curves toward lower acceleration demands. Deep wedges (WL4, WL5, WL6 located in the left abutment of the dam) exhibit the highest vulnerability, with instability probabilities exceeding 50% at spectral accelerations as low as 0.34 g under 50% uplift conditions, compared with values greater than 0.65 g for upper wedges. Parametric analyses further show that increasing the joint friction angle significantly enhances seismic resistance, whereas cohesion has a comparatively minor effect. The findings emphasize the necessity of accurate uplift characterization and wedge-specific seismic assessment, and they highlight the crucial role of grout-curtain effectiveness in ensuring the seismic safety of arch dam abutments. Full article

Diabetes mellitus (DM) is a chronic disease characterised by chronic hyperglycaemia due to a defect in the production of or cell insensitivity to insulin. If left untreated, it might result in severe side effects such retinal, nephropathy, neuropathy, and cardiovascular disease. Extensive research has been made to develop more effective and less expensive alternatives to existing treatment regimes. This review aims to evaluate research done thus far to test the effect of Saccharomyces boulardii (S. boulardii or Sb) in treating DM and its complications. Searches were conducted using Scopus, Web of Science, PubMed and Google Scholar on 26 July 2025. Overall, 227 articles were identified, and 5 fulfilled the inclusion criteria. Results extracted were from two models of diabetes (type 1 and 2) and two strains of Sb. In type 1 diabetes models, a significant reduction in glycaemia was observed, while in type 2 diabetes models, a non-significant effect was noted, depending on the strain used. Furthermore, an improvement in cardiac function was observed through reduced heart rate variability, a decrease in blood pressure, an increase in C-peptide and hepatic glycogen stores, enhanced liver healing, a nephroprotective effect, as well as a reduction in oxidative stress, blood triglyceride levels, and the inflammatory response. Administration of Sb induced positive modulation of the intestinal microbiota, with a decrease in pathobionts in the stools. Overall, the few studies evaluated indicate that the use of Sb appears to be a promising approach to improve the management of diabetes and its associated metabolic and related complications. The protocol of this review is registered in PROSPERO under ID CRD420251012919. Full article

Total Coronary Revascularization via left Anterior Thoracotomy (TCRAT) represents a modern evolution of sternum-sparing, on-pump multivessel coronary artery bypass grafting. In this review, we will summarize the historical development, detail the surgical principles, and provide a comprehensive overview of the clinical outcomes of TCRAT. The technique combines cardiopulmonary bypass using peripheral arterial as well as venous cannulation and cardioplegic cardiac arrest using transthoracic aortic cross-clamping with surgical access through a left anterior minithoracotomy. By applying special slinging and rotational maneuvers, both a stable exposition of all coronary territories—in particular those of the right and the circumflex coronary artery—and a quiet, bloodless operating field enable complete anatomical revascularization and complex coronary surgery procedures, including all variations in multiarterial grafting in unselected patients. Data from all published clinical series were integrated, and a weighted analysis of a total of 2282 patients was performed. TCRAT proved to be very effective with regard to complete anatomical revascularization and modern grafting strategies, and it showed excellent perioperative safety in an all-comers population. Both the 30-day mortality and perioperative stroke incidence were distinctly below 1.0%. Data from mid-term follow-up, although rare so far, are promising and compare well to those of the important RCTs. The TCRAT approach eliminates sternal complications completely and accelerates recovery. As an on-pump arrested-heart surgery, TCRAT inherently permits the combination of minimally invasive multivessel CABG with a variety of other cardiac operations, mainly the combination with valve procedures. The integration of robotic and endoscopic assistance represents the next evolutionary step. With its reproducibility and broad applicability, TCRAT holds strong potential to become a standard routine technique in the field of minimally invasive cardiac surgery. Full article

This study evaluated the effects of a passive upper-limb exoskeleton in agricultural work using a repeated-measures design with 24 adult males across three exoskeleton conditions (No Exo, Prototype, and Airframe), three work directions (left, front, and right), and two work distances (near and far). Outcomes included muscle activity, center of pressure travel, task completion time, perceived exertion, body part discomfort, and usability. Airframe use significantly reduced shoulder and upper-arm muscle activity by about 25–35 percent, consistent with the mechanical sharing of shoulder elevation torque. Erector spinae activity showed a compensatory increase trend, suggesting heightened trunk stabilization demands. Center of pressure varied by direction and distance, with greater excursion for leftward and far tasks, but did not differ among exoskeleton conditions, indicating preserved postural stability. Task time was unaffected by exoskeleton and distance but was longest for leftward tasks. Perceived exertion and discomfort varied by direction and distance and tended to be lower on average with Airframe. Usability differed only in the effectiveness factor, which favored Airframe. An integrated evaluation emphasizing EMG, center of pressure, and perceived fatigue, with usability as needed, is recommended for field validation. Full article

Angiography-derived physiology (ADP) has emerged as a validated, wire-free method for the functional assessment of coronary artery disease (CAD). By avoiding pressure-wire instrumentation and hyperemic agents, ADP reduces procedure time, radiation exposure, and cost, while maintaining strong diagnostic performance with invasive physiology. These platforms include FFRangio (CathWorks), QFR (Medis Medical Imaging), and vFFR (Pie Medical Imaging), which have undergone extensive validation and are FDA approved for use. Randomized trials, predominantly with QFR, thus far demonstrate improved outcomes of ADP-guided strategies compared with angiography alone, whereas non-inferiority to wire-based FFR guidance has not yet been established. As clinical trials continue, thoughtful integration into routine practice requires careful image acquisition, platform-specific training, and awareness of limitations. In particular, validation remains incomplete in complex subsets such as left main disease, bifurcations, and bypass grafts, though evidence is growing in the application in acute coronary syndromes, post-PCI prognostication, and surgical planning. As ongoing studies mature and ADP technology evolves, these tools are poised to reshape physiologic assessment, streamline catheterization laboratory workflow, and become integral to contemporary PCI planning and optimization. This review summarizes current evidence, clinical applications, limitations, integration into the catheterization lab, and future directions of ADP. Full article

Integrating IoT devices into smart grids raises some hard problems related to safe data sharing, the ability to grow, and energy use. Blockchain provides a safe way to check identities without a central authority. Typical ways to confirm transactions, like Proof-of-Work (PoW), use a lot of power, making them bad for devices that cannot use much energy. This study introduces a safe authentication system using Blockchain, a Deep Neural Network (DNN), and a power-saving way to confirm transactions (EACM). The system picks validators based on how much power they have left and their trust scores to save power during confirmation. Using the IoT-Enabled Smart Grid Dataset, simulations showed a transaction speed of 372 TPS, which is 32% better than normal methods. The system correctly authenticates 98.69% of the time, with a confirmation delay of 5.9 milliseconds and an 18% drop in validator node energy use. Also, the system spots 98.4% of unauthorized access tries, with a false acceptance rate (FAR) of 1.7% and a false rejection rate (FRR) of 0.31%. These outcomes prove the system’s ability to offer safe, fast, and energy-saving authentication for big, real-time Smart Grid IoT setups. Full article

In the present work, we investigate the post-glacial aggradation of three tributary valleys draining the left hydrographic basin of the Tiber River in central Rome: the Murcia, Caffarella, and Grottaperfetta valleys. We describe the Upper Pleistocene–Holocene stratigraphic record of the alluvial successions occurring in the Caffarella Valley through the core data collected in a dedicatedly performed 35 m deep borehole. We provide seven ¹⁴C age constraints to the sediment aggradation which allow us to make a comparison with the Grottaperfetta and Murcia valleys, for which we present previously unpublished borehole data, and with the Tiber River Valley investigated in the previous literature. In particular, we highlight the effects of a mid-Holocene (5200–3800 yr BP) erosional phase, partially overlapping with the global 4.2 ka cooling/drying event, and we discuss the possible occurrence of a sea level fluctuation linked with this paleoclimatic event which has not been detected so far by other sedimentary records. Finally, we provide evidence for the widespread occurrence of a 6th century BCE (2550–2450 yr BP) overflooding phase that was previously observed only in the eastern portion of the Tiber River Valley in central Rome, which we suggest may be originated by concurrent intensive deforestation activity in central Italy. Full article

Time- and space-resolved radiation emitted by the plasma produced by a 0.8 ns duration at full width half maximum, ~600 MW maximum power microwave (~9.6 GHz) pulse traversing a hydrogen-, helium-, or air-filled circular waveguide, is studied. Gas ionization by microwaves is an old subject but the regime investigated in the present experimental research, of very high-power microwaves and very short pulses using modern diagnostic tools, is new and follows a series of new studies performed so far only in our laboratory, revealing non-linear phenomena never observed before. In the present research, plasma radiation is observed along a slit made in a circular waveguide wall by either an intensified fast frame camera or a streak camera. Using calibrated input and output couplers, the transmission and reflection coefficients of the high-power microwaves were determined over a broad range of gas pressures, 0.1 kPa < P < 90 kPa. It was found that the intensity of the plasma light emission increases significantly after the high-power microwave pulse has left the waveguide. Depending on pressure, the radiation is either uniform along the slit, while the front of the emitted light follows the microwave pulse at a velocity close to its group velocity, or it remains in the vicinity of the input window, indicating that the plasma density is above critical density. It was also found that the radial distribution of radiation depends on pressure. At pressures <10 kPa, when the electron oscillatory energy reaches 20 keV close to the waveguide axis, light emission forms faster near the waveguide walls, where the ionization rate is maximal. Otherwise, when pressure is >80 kPa, light emission is most intense on the axis where the electron oscillatory energy is ~100 eV and the ionization rate is maximal. We also studied the UV radiation from the plasma, the duration of which was found to be longer than the duration of visible light emission. This indicates the existence of energetic electrons for tens of ns after the high-power microwave pulse has left the observation region. Considering that the emitted light intensity depends on the plasma density and temperature, the observed data may be used for a comparison with the results of collisional radiative models if the electron time and spatial energy distribution is known. Full article

Invasive fungal infections (IFIs) are one of the most significant public health challenges worldwide. Yet, research and communication thereof were left behind for a long time, until the WHO published a priority pathogens list to guide research, development, and public health action in October 2022. Indeed, due to the rising number of immunocompromised patients at risk and the high level of morbidity, mortality, and economic burden they entail, especially in low- and middle-income countries, IFIs are a serious public health threat. Fungal infections due to dimorphic fungi face additional challenges such as limited knowledge outside of endemic areas and restricted availability of antifungal molecules in areas affected by these infections. The number of related deaths per year is estimated at 2.5 million, but non-governmental organisations make a wider estimation, due to the difficulties in early in vitro diagnostic and troublesome collection and analysis of epidemiological data. Despite this fact, the therapeutic toolbox addressing these infections remains limited, with only four main families of molecules available so far. The antifungal therapeutic supply is composed of very toxic polyenes, the weakly selective and nearly unused 5-fluorocytosine, and azoles, some of which are becoming increasingly inefficient against IFIs. In the 2000–2020s, the fourth arising family consisted of safer semisynthetic echinocandins. Unfortunately, nowadays, more and more fungal isolates encountered in intensive care units exhibit a low susceptibility to echinocandins or are even multiresistant. In this review, we expose the current treatments available to fight against invasive fungal infections. We recall the discovery and physico-chemical aspects of these substances leading to structure/activity and structure/properties relationships. We particularly focus on the to-date resistances and their molecular mechanisms. We finally list some of the most relevant antifungal drug candidates, as they were freshly overviewed by the World Health Organization in April 2025, highlighting the importance of the molecular dimension of this pursuit toward the expansion of the antifungal therapeutic toolbox. Full article

Background/Objectives: Acute kidney injury (AKI) is a common and severe complication in patients with acute myocardial infarction (AMI). Very elderly patients are at a heightened risk of developing AKI. Fibrinogen and albumin are well-known biomarkers of inflammation and nutrition, which are highly related to AKI. We aim to explore the predictive value of the fibrinogen-to-albumin ratio (FAR) for AKI in very elderly patients with AMI. Methods: A retrospective cohort of AMI patients ≥ 75 years old hospitalized at the First Affiliated Hospital of Xi’an Jiaotong University between January 2018 and December 2022 was established. Clinical data and medication information were collected through the biospecimen information resource center at the hospital. Univariate and multivariable logistic regression models were used to analyze the association between FAR and the risk of AKI in patients with AMI. FAR was calculated as the ratio of fibrinogen (FIB) to serum albumin (ALB) level (FAR = FIB/ALB). The primary outcome is acute kidney injury, which was diagnosed based on KDIGO 2012 criteria. Results: Among 1236 patients enrolled, 66.8% of them were male, the median age was 80.00 years (77.00–83.00), and acute kidney injury occurred in 18.8% (n = 232) of the cohort. Comparative analysis revealed significant disparities in clinical characteristics between patients with or without AKI. Patients with AKI exhibited a markedly higher prevalence of arrhythmia (51.9% vs. 28.1%, p < 0.001) and lower average systolic blood pressure (115.77 ± 25.96 vs. 122.64 ± 22.65 mmHg, p = 0.013). In addition, after adjusting for age, sex, history of hypertension, left ventricular ejection fraction (LVEF), and other factors, FAR remained an independent risk factor for acute kidney injury (OR = 1.47, 95%CI: 1.36–1.58). ROC analysis shows that FAR predicted stage 2–3 AKI with superior accuracy (AUC 0.94, NPV 98.6%) versus any AKI (AUC 0.79, NPV 93.0%), enabling risk-stratified management. Conclusions: FAR serves as both a high-sensitivity screening tool for any AKI and a high-specificity sentinel for severe AKI, with NPV-driven thresholds guiding resource allocation in the fragile elderly. Full article

Background/Objectives: Posterior inferior cerebellar artery (PICA) aneurysms are one of the most difficult cerebrovascular lesions to treat and account for 0.5–3% of all intracranial aneurysms. They have deep anatomical locations, broad-neck configurations, high perforator density, and a close association with the brainstem, which creates considerable technical challenges for either microsurgical or endovascular treatment. Despite its acceptance as the standard of care for most posterior circulation aneurysms, PICA aneurysms are often associated with flow diversion using a coil or flow diversion due to incomplete occlusions, parent vessel compromise and high rate of recurrence. This case aims to describe the utility of microsurgical clipping as a durable and definitive option demonstrating the value of tailored surgical planning, preservation of anatomy and ancillary technologies for protecting a genuine outcome in ruptured PICA aneurysms. Methods: A 66-year-old male was evaluated for an acute subarachnoid hemorrhage from a ruptured and broad-necked fusiform left PICA aneurysm at the vertebra–PICA junction. Endovascular therapy was not an option due to morphology and the center of the recurrence; therefore, a microsurgical approach was essential. A far-lateral craniotomy with a partial C1 laminectomy was carried out for proximal vascular control, with careful dissection of the perforating arteries and precise clip application for the complete exclusion of the aneurysm whilst preserving distal PICA flow. Results: Post-operative imaging demonstrated the complete obliteration of the aneurysm with unchanged cerebrovascular flow dynamics. The patient had progressive neurological recovery with no new cranial nerve deficits or ischemic complications. Long-term follow-up demonstrated stable aneurysm exclusion and full functional independence emphasizing the sustainability of microsurgical intervention in challenging PICA aneurysms. Conclusions: This case intends to highlight the current and evolving role of microsurgical practice for treating posterior circulation aneurysms, particularly at a time when endovascular alternatives are limited by anatomy and hemodynamics. Advances in artificial intelligence cerebral aneurysm rupture prediction, high-resolution vessel wall imaging, robotic-assisted microsurgery and new generation flow-modifying implants have the potential to revolutionize treatment paradigms by embedding precision medicine principles into aneurysm management. While the discipline of cerebrovascular surgery is expanding, it can be combined together with microsurgery, endovascular technologies and computational knowledge to ensure individualized, durable, and minimally invasive treatment options for high-risk PICA aneurysms. Full article