Hasil untuk "Internal medicine"

Ozge Ece Gunaydin, Sercan Onal Aykar, Esin Ergin et al.

Abstract Objective Thoracic mobility significantly enhances athletic ability and performance. The objective of this study was to examine the impact of thoracic mobility exercises on the physical attributes of strength, endurance, flexibility, and the speed of serve and spike in female adolescent volleyball players. Method In this study, 36 adolescent female adolescent volleyball players participated. Participants were divided into 2 groups as mobility added training and only training program. In the mobility group, thoracic mobility exercises were applied in addition to the training program for 4 weeks. The athletes were evaluated in terms of internal and external rotation strength, endurance, thoracic mobility, spike and serve speeds. A 2 × 2 ANOVA was used to compare the differences between the groups. Results In this study, significant increases were observed in strength, scapular endurance, thoracic rotation angles, smash and serve speed in both the thoracic mobility group and the control group (p < 0.05). However, it was determined that changes in some parameters differed between groups; right internal rotation strength increased only in the control group, while hyperextension increased only in the thoracic mobility group (p < 0.05). However, no group was found to be superior to the other in terms of any parameter in the intergroup comparisons (p > 0.05). Conclusion The results indicate that thoracic mobility exercises added to training programs yield similar results to the control group in terms of strength, endurance, flexibility, spike and serve speed. Future studies with longer-term interventions, dose-response design, and different sports disciplines may further contribute to the literature. Trial registration ClinicalTrials.gov NCT07203209, 24.09.2025. Retrospectively registered.

Alexander Barzykin, Robert Boyce, Eyal Neuman

As the FX markets continue to evolve, many institutions have started offering passive access to their internal liquidity pools. Market makers act as principal and have the opportunity to fill those orders as part of their risk management, or they may choose to adjust pricing to their external OTC franchise to facilitate the matching flow. It is, a priori, unclear how the strategies managing internal liquidity should depend on market condions, the market maker's risk appetite, and the placement algorithms deployed by participating clients. The market maker's actions in the presence of passive orders are relevant not only for their own objectives, but also for those liquidity providers who have certain expectations of the execution speed. In this work, we investigate the optimal multi-objective strategy of a market maker with an option to take liquidity on an internal exchange, and draw important qualitative insights for real-world trading.

Charlotte Stix, Matteo Pistillo, Girish Sastry et al.

The most advanced future AI systems will first be deployed inside the frontier AI companies developing them. According to these companies and independent experts, AI systems may reach or even surpass human intelligence and capabilities by 2030. Internal deployment is, therefore, a key source of benefits and risks from frontier AI systems. Despite this, the governance of the internal deployment of highly advanced frontier AI systems appears absent. This report aims to address this absence by priming a conversation around the governance of internal deployment. It presents a conceptualization of internal deployment, learnings from other sectors, reviews of existing legal frameworks and their applicability, and illustrative examples of the type of scenarios we are most concerned about. Specifically, it discusses the risks correlated to the loss of control via the internal application of a misaligned AI system to the AI research and development pipeline, and unconstrained and undetected power concentration behind closed doors. The report culminates with a small number of targeted recommendations that provide a first blueprint for the governance of internal deployment.

Hanan Hendawy, Ahmed Farag, Asmaa Elhaieg et al.

Effective bladder reconstruction remains a significant challenge in urology, particularly for conditions requiring partial or complete bladder replacement. In this study, the efficacy is evaluated of two types of scaffolds, silk fibroin (SF) and adipose-derived stem cells (ADSCs-SF), in promoting bladder regeneration and their associated outcomes. A rat model was used to compare the surgical outcomes and morphological recovery of bladder tissues implanted with SF and ADSCs-SF scaffolds. Post-operative recovery, including voiding ability and complication rates, was assessed. The morphological and histological changes of the regenerated bladder tissue were evaluated at multiple time points (2, 4, 8, and 12 weeks) using gross tissue analysis, histometric assessments, and immunohistochemical staining. Both scaffold types demonstrated successful integration into the bladder wall with no significant differences in body weight or voiding issues. The SF scaffold group exhibited graft shrinkage and a 41.6% incidence of bladder calculus formation. In contrast, the ADSCs-SF scaffold facilitated superior morphological restoration, with bladder tissue progressively adopting a more normal shape and no incidence of bladder calculus. Histological analysis revealed that the ADSCs-SF scaffold significantly promoted the regeneration of a more organized urothelium layer and smooth muscle tissue. It also resulted in higher vessel density and reduced infiltration of inflammatory cells when compared to the SF scaffold alone. Additionally, the ADSCs-SF group exhibited enhanced expression of key markers, including uroplakin III, a urothelial marker, and α-SMA, a smooth muscle cell marker. These findings suggest that the ADSCs-SF scaffold not only supports the structural integrity of the bladder but also improves tissue regeneration and reduces adverse inflammatory responses, offering a promising approach for bladder repair and reconstruction.

Claire Delehouzé, Melodie Mallais, Arnaud Comte et al.

Abstract In the past two decades, various non-apoptotic pathways of regulated cell death have been identified; a small subset of these, including necroptosis and ferroptosis, manifests the phenotypic features of necrotic death. These two regulated necroses are being extensively studied because of their putative roles in severe acute and chronic pathologies. Moreover, as these regulated necrotic pathways are coactivated in a number of common pathologies, the development of multi-target directed ligands (that is, the use of a polypharmacological strategy) is a path-breaking avenue of research. In this study, we determined that the 7-azaindole derivative, sibiriline, inhibited both RIPK1-driven necroptosis (induced by Tumor Necrosis Factor-α) and ferroptosis (triggered by various classes of ferroptosis inducers), with EC50s against each in the µM range. We next performed a combined large-scale transcriptomic study in order to determine the molecular mechanisms of action of sibiriline. We identified the stress response protein heme oxygenase-1 (HMOX1) as the main biomarker of ferroptosis inhibition by sibiriline. We hypothesized that this compound reacts as an antioxidant to block ferroptosis; indeed, we found that sibiriline inhibits lipid peroxidation by trapping phospholipid-derived peroxyl radicals as a radical-trapping antioxidant (RTA). Taken together, these results show that sibiriline is a new dual inhibitor of necroptosis and ferroptosis cell death pathways; it works by inhibition of both RIPK1 kinase and (phospho)lipid peroxidation. We also demonstrate the in vitro efficacy of sibiriline to inhibit cell death in cell-based models of Parkinson’s disease and cystic fibrosis. These findings shed light on the high therapeutic potency of RIPK1 inhibitors with RTA activity.

Antonino Mazzone, Nicola Montano

Lan Li, Lan Li, Qingyuan Tan et al.

Coagulopathy is a critical pathophysiological mechanism of acute pancreatitis (AP), arising from the complex interplay between innate immune, endothelial cells and platelets. Although initially beneficial for the host, uncontrolled and systemic activation of coagulation cascade in AP can lead to thrombotic and hemorrhagic complications, ranging from subclinical abnormalities in coagulation tests to severe clinical manifestations, such as disseminated intravascular coagulation. Initiation of coagulation activation and consequent thrombin generation is caused by expression of tissue factor on activated monocytes and is ineffectually offset by tissue factor pathway inhibitor. At the same time, endothelial-associated anticoagulant pathways, in particular the protein C system, is impaired by pro-inflammatory cytokines. Also, fibrin removal is severely obstructed by inactivation of the endogenous fibrinolytic system, mainly as a result of upregulation of its principal inhibitor, plasminogen activator inhibitor type 1. Finally, increased fibrin generation and impaired break down lead to deposition of (micro) vascular clots, which may contribute to tissue ischemia and ensuing organ dysfunction. Despite the high burden of coagulopathy that have a negative impact on AP patients’ prognosis, there is no effective treatment yet. Although a variety of anticoagulants drugs have been evaluated in clinical trials, their beneficial effects are inconsistent, and they are also characterized by hemorrhagic complications. Future studies are called to unravel the pathophysiologic mechanisms involved in coagulopathy in AP, and to test novel therapeutics block coagulopathy in AP.

Ilker Şengül, Esra Candar, Ibrahim Demirçubuk et al.

Carley Mitchell, Leyla Bayat, Wadad Mneimneh et al.

Large cell neuroendocrine carcinoma of the lung is a rare and aggressive pulmonary malignancy. Given its peripheral location, patients are frequently asymptomatic at the time of diagnosis or present with non-specific complaints. Moreover, its association with paraneoplastic syndromes or structural intrathoracic complications are highly atypical. Here, we report a case involving a 57-year-old female who presented with two simultaneous paraneoplastic syndromes, including hypertrophic pulmonary osteoarthropathy and secretory diarrhea, prior to the diagnosis of an early-stage large cell neuroendocrine carcinoma of the lung. Both syndromes showcased rapid symptomatic resolution following tumor resection. Upon disease recurrence, the patient developed a presentation consistent with Pancoast syndrome, with gradual improvement following the initiation of chemoradiotherapy. Individually, these conditions are rarely reported in association with large cell neuroendocrine carcinoma of the lung making their combination highly unusual. Furthermore, related symptoms were present both before and at the time of diagnosis, and upon disease recurrence. This highlights the importance of maintaining a high clinical suspicion for atypical manifestations of malignancy.

Masahito Hasegawa

We argue that operads provide a general framework for dealing with polynomials and combinatory completeness of combinatory algebras, including the classical $\mathbf{SK}$-algebras, linear $\mathbf{BCI}$-algebras, planar $\mathbf{BI}(\_)^\bullet$-algebras as well as the braided $\mathbf{BC^\pm I}$-algebras. We show that every extensional combinatory algebra gives rise to a canonical closed operad, which we shall call the internal operad of the combinatory algebra. The internal operad construction gives a left adjoint to the forgetful functor from closed operads to extensional combinatory algebras. As a by-product, we derive extensionality axioms for the classes of combinatory algebras mentioned above.

Moshe Kamensky

We define and study a higher-dimensional version of model theoretic internality, and relate it to higher-dimensional definable groupoids in the base theory.

Jonathan Weinberger

We give structural results about bifibrations of (internal) $(\infty,1)$-categories with internal sums. This includes a higher version of Moens' Theorem, characterizing cartesian bifibrations with extensive aka stable and disjoint internal sums over lex bases as Artin gluings of lex functors. We also treat a generalized version of Moens' Theorem due to Streicher which does not require the Beck--Chevalley condition. Furthermore, we show that also in this setting the Moens fibrations can be characterized via a condition due to Zawadowski. Our account overall follows Streicher's presentation of fibered category theory à la Bénabou, generalizing the results to the internal, higher-categorical case, formulated in a synthetic setting. Namely, we work inside simplicial homotopy type theory, which has been introduced by Riehl and Shulman as a logical system to reason about internal $(\infty,1)$-categories, interpreted as Rezk objects in any given Grothendieck--Rezk--Lurie $(\infty,1)$-topos.

Angus T Stock, Sarah Parsons, Varun J Sharma et al.

Abstract Objective Vasculitis is characterised by inflammation of the blood vessels. While all layers of the vessel can be affected, inflammation within the intimal layer can trigger thrombosis and arterial occlusion and is therefore of particular clinical concern. Given this pathological role, we have examined how intimal inflammation develops by exploring which (and how) macrophages come to populate this normally immune‐privileged site during vasculitis. Methods We have addressed this question for Kawasaki disease (KD), which is a type of vasculitis in children that typically involves the coronary arteries. We used confocal microscopy and flow cytometry to characterise the macrophages that populate the coronary artery intima in KD patient samples and in a mouse model of KD, and furthermore, have applied an adoptive transfer system to trace how these intimal macrophages develop. Results In KD patients, intimal hyperplasia coincided with marked macrophage infiltration of the coronary artery intima. Phenotypic analysis revealed that these ‘intimal macrophages’ did not express markers of resident cardiac macrophages, such as Lyve‐1, and instead, were uniformly positive for the chemokine receptor Ccr2, suggesting a monocytic lineage. In support of this origin, we show that circulating monocytes directly invade the intima via transluminal migration during established disease, coinciding with the activation of endothelial cells lining the coronary arteries. Conclusions During KD, intimal macrophages develop from circulating monocytes that infiltrate the inflamed coronary artery intima by transluminal migration.

Maines LW, Green CL, Keller SN et al.

Lynn W Maines, Cecelia L Green, Staci N Keller, Leo R Fitzpatrick, Charles D Smith Apogee Biotechnology Corporation, Hummelstown, PA, USACorrespondence: Charles D Smith, Apogee Biotechnology Corporation, 1214 Research Blvd, Suite 2015, Hummelstown, PA, 17036, USA, Email cdsmith@apogee-biotech.comIntroduction: Acute kidney injury (AKI) is a common multifactorial adverse effect of surgery, circulatory obstruction, sepsis or drug/toxin exposure that often results in morbidity and mortality. Sphingolipid metabolism is a critical regulator of cell survival and pathologic inflammation processes involved in AKI. Opaganib (also known as ABC294640) is a first-in-class experimental drug targeting sphingolipid metabolism that reduces the production and activity of inflammatory cytokines and, therefore, may be effective to prevent and treat AKI.Methods: Murine models of AKI were used to assess the in vivo efficacy of opaganib including ischemia-reperfusion (IR) injury induced by either transient bilateral occlusion of renal blood flow (a moderate model) or nephrectomy followed immediately by occlusion of the contralateral kidney (a severe model) and lipopolysaccharide (LPS)-induced sepsis. Biochemical and histologic assays were used to quantify the effects of oral opaganib treatment on renal damage in these models.Results: Opaganib suppressed the elevations of creatinine and blood urea nitrogen (BUN), as well as granulocyte infiltration into the kidneys, of mice that experienced moderate IR from transient bilateral ligation. Opaganib also markedly decreased these parameters and completely prevented mortality in the severe renal IR model. Additionally, opaganib blunted the elevations of BUN, creatinine and inflammatory cytokines following exposure to LPS.Conclusion: The data support the hypotheses that sphingolipid metabolism is a key mediator of renal inflammatory damage following IR injury and sepsis, and that this can be suppressed by opaganib. Because opaganib has already undergone clinical testing in other diseases (cancer and Covid-19), the present studies support conducting clinical trials with this drug with surgical or septic patients at risk for AKI.Keywords: opaganib, sphingosine kinase, sphingolipid, acute kidney injury, ischemia-reperfusion injury, lipopolysaccharide, sepsis

Ejaz Ahmed, Reza Arabi Belaghi, Yasin Asar et al.

Beta regression model is useful in the analysis of bounded continuous outcomes such as proportions. It is well known that for any regression model, the presence of multicollinearity leads to poor performance of the maximum likelihood estimators. The ridge type estimators have been proposed to alleviate the adverse effects of the multicollinearity. Furthermore, when some of the predictors have insignificant or weak effects on the outcomes, it is desired to recover as much information as possible from these predictors instead of discarding them all together. In this paper we proposed ridge type shrinkage estimators for the low and high dimensional beta regression model, which address the above two issues simultaneously. We compute the biases and variances of the proposed estimators in closed forms and use Monte Carlo simulations to evaluate their performances. The results show that, both in low and high dimensional data, the performance of the proposed estimators are superior to ridge estimators that discard weak or insignificant predictors. We conclude this paper by applying the proposed methods for two real data from econometric and medicine.

Mirko Signorelli, Pietro Spitali, Cristina Al-Khalili Szigyarto et al.

Longitudinal and high-dimensional measurements have become increasingly common in biomedical research. However, methods to predict survival outcomes using covariates that are both longitudinal and high-dimensional are currently missing. In this article, we propose penalized regression calibration (PRC), a method that can be employed to predict survival in such situations. PRC comprises three modeling steps: First, the trajectories described by the longitudinal predictors are flexibly modeled through the specification of multivariate mixed effects models. Second, subject-specific summaries of the longitudinal trajectories are derived from the fitted mixed models. Third, the time to event outcome is predicted using the subject-specific summaries as covariates in a penalized Cox model. To ensure a proper internal validation of the fitted PRC models, we furthermore develop a cluster bootstrap optimism correction procedure that allows to correct for the optimistic bias of apparent measures of predictiveness. PRC and the CBOCP are implemented in the R package pencal, available from CRAN. After studying the behavior of PRC via simulations, we conclude by illustrating an application of PRC to data from an observational study that involved patients affected by Duchenne muscular dystrophy, where the goal is predict time to loss of ambulation using longitudinal blood biomarkers.

K P Suraj, Arjun Chandran

Sepsis is a life-threatening organ dysfunction caused by dysregulated host response to infection. Even with advancement in understanding the pathophysiology and various monitoring tools and treatment measures, sepsis still remains a major cause of mortality and morbidity in critically ill patients. Over the last three decades, significant changes were seen regarding understanding the pathophysiology of sepsis. The management of sepsis has evolved over the last two decades by the advent of the Surviving Sepsis Campaign Guidelines which recommends early recognition and prompt treatment without delay.

Maria Grazia Puxeddu, Maria Grazia Puxeddu, Manuela Petti et al.

Modular organization is an emergent property of brain networks, responsible for shaping communication processes and underpinning brain functioning. Moreover, brain networks are intrinsically multilayer since their attributes can vary across time, subjects, frequency, or other domains. Identifying the modular structure in multilayer brain networks represents a gateway toward a deeper understanding of neural processes underlying cognition. Electroencephalographic (EEG) signals, thanks to their high temporal resolution, can give rise to multilayer networks able to follow the dynamics of brain activity. Despite this potential, the community organization has not yet been thoroughly investigated in brain networks estimated from EEG. Furthermore, at the state of the art, there is still no agreement about which algorithm is the most suitable to detect communities in multilayer brain networks, and a way to test and compare them all under a variety of conditions is lacking. In this work, we perform a comprehensive analysis of three algorithms at the state of the art for multilayer community detection (namely, genLouvain, DynMoga, and FacetNet) as compared with an approach based on the application of a single-layer clustering algorithm to each slice of the multilayer network. We test their ability to identify both steady and dynamic modular structures. We statistically evaluate their performances by means of ad hoc benchmark graphs characterized by properties covering a broad range of conditions in terms of graph density, number of clusters, noise level, and number of layers. The results of this simulation study aim to provide guidelines about the choice of the more appropriate algorithm according to the different properties of the brain network under examination. Finally, as a proof of concept, we show an application of the algorithms to real functional brain networks derived from EEG signals collected at rest with closed and open eyes. The test on real data provided results in agreement with the conclusions of the simulation study and confirmed the feasibility of multilayer analysis of EEG-based brain networks in both steady and dynamic conditions.

H. Sami Ullah, S. Aslam

Blockchain technology is one of the most contemporary and disruptive technologies in the world. It has gained considerable attention in numerous applications such as financial services, cybersecurity applications, Internet of Things (IoT), network data management. Now its range of applications is beyond the financial services as the healthcare industry has also adopted blockchain technology in its various subdomains such as Electronic Health Records (EHR), medical supply chain management system, genomic market, neuroscience technology, clinical research, and pharmaceutical medicine. Blockchain is considered a secure and viable solution for storing and accessing patients medical records and the patients can diagnosed and treated with safe and secure data sharing. Blockchain technology will revolutionize the healthcare systems with personalized, authentic, and secure access to the clinical data of patients and that data can be used for further health improvements and clinical researches. In this paper, we conduct a contemporary research on existing applications and developments in healthcare industry with the use of blockchain technology. We also discuss some robust applications and various existing companies that are using blockchain solutions for securing their data along with some current challenges and future perspectives.