bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uplift modeling to predict individual treatment effects of renal replacement therapy in sepsis-associated acute kidney injury patients
Authors: Li Guanggang , Li Bo , Song Bin , Liu Dandan , Sun Yue , Ju Hongyan , Xu Xiuping , Mao Jingkun , Zhou Feihu 
Published: March 2024

AbstractRenal replacement therapy (RRT) is a crucial treatment for sepsis-associated acute kidney injury (S-AKI), but it is uncertain which S-AKI patients should receive immediate RRT. Identifying the characteristics of patients who may benefit the most from RRT is an important task. This retrospective study utilized a public database and enrolled S-AKI patients, who were divided into RRT and non-RRT groups. Uplift modeling was used to estimate the individual treatment effect (ITE) of RRT. The validity of different models was compared using a qini curve. After labeling the patients in the validation cohort, we characterized the patients who would benefit the most from RRT and created a nomogram. A total of 8289 patients were assessed, among whom 591 received RRT, and 7698 did not receive RRT. The RRT group had a higher severity of illness than the non-RRT group, with a Sequential Organ Failure Assessment (SOFA) score of 9 (IQR 6,11) vs. 5 (IQR 3,7). The 28-day mortality rate was higher in the RRT group than the non-RRT group (34.83% vs. 14.61%, p < 0.0001). Propensity score matching (PSM) was used to balance baseline characteristics, 458 RRT patients and an equal number of non-RRT patients were enrolled for further research. After PSM, 28-day mortality of RRT and non-RRT groups were 32.3% vs. 39.3%, P = 0.033. Using uplift modeling, we found that urine output, fluid input, mean blood pressure, body temperature, and lactate were the top 5 factors that had the most influence on RRT effect. The area under the uplift curve (AUUC) of the class transformation model was 0.068, the AUUC of SOFA was 0.018, and the AUUC of Kdigo-stage was 0.050. The class transformation model was more efficient in predicting individual treatment effect. A logistic regression model was developed, and a nomogram was drawn to predict whether an S-AKI patient can benefit from RRT. Six factors were taken into account (urine output, creatinine, lactate, white blood cell count, glucose, respiratory rate). Uplift modeling can better predict the ITE of RRT on S-AKI patients than conventional score systems such as Kdigo and SOFA. We also found that white blood cell count is related to the benefits of RRT, suggesting that changes in inflammation levels may be associated with the effects of RRT on S-AKI patients.
Phage-layer interferometry: a companion diagnostic for phage therapy and a bacterial testing platform
Authors: Needham Patrick , Page Richard C. , Yehl Kevin 
Published: March 2024

AbstractThe continuing and rapid emergence of antibiotic resistance (AMR) calls for innovations in antimicrobial therapies. A promising, ‘re-emerging’ approach is the application of bacteriophage viruses to selectively infect and kill pathogenic bacteria, referred to as phage therapy. In practice, phage therapy is personalized and requires companion diagnostics to identify efficacious phages, which are then formulated into a therapeutic cocktail. The predominant means for phage screening involves optical-based assays, but these methods cannot be carried out in complex media, such as colored solutions, inhomogeneous mixtures, or high-viscosity samples, which are often conditions encountered in vivo. Moreover, these assays cannot distinguish phage binding and lysis parameters, which are important for standardizing phage cocktail formulation. To address these challenges, we developed Phage-layer Interferometry (PLI) as a companion diagnostic. Herein, PLI is assessed as a quantitative phage screening method and prototyped as a bacterial detection platform. Importantly, PLI is amenable to automation and is functional in complex, opaque media, such as baby formula. Due to these newfound capabilities, we foresee immediate and broad impact of PLI for combating AMR and protecting against foodborne illnesses.
VpROM: a novel variational autoencoder-boosted reduced order model for the treatment of parametric dependencies in nonlinear systems
Authors: Simpson Thomas , Vlachas Konstantinos , Garland Anthony , Dervilis Nikolaos , Chatzi Eleni 
Published: March 2024

AbstractReduced Order Models (ROMs) are of considerable importance in many areas of engineering in which computational time presents difficulties. Established approaches employ projection-based reduction, such as Proper Orthogonal Decomposition. The limitation of the linear nature of such operators is typically tackled via a library of local reduction subspaces, which requires the assembly of numerous local ROMs to address parametric dependencies. Our work attempts to define a more generalisable mapping between parametric inputs and reduced bases for the purpose of generative modeling. We propose the use of Variational Autoencoders (VAEs) in place of the typically utilised clustering or interpolation operations, for inferring the fundamental vectors, termed as modes, which approximate the manifold of the model response for any and each parametric input state. The derived ROM still relies on projection bases, built on the basis of full-order model simulations, thus retaining the imprinted physical connotation. However, it additionally exploits a matrix of coefficients that relates each local sample response and dynamics to the global phenomena across the parametric input domain. The VAE scheme is utilised for approximating these coefficients for any input state. This coupling leads to a high-precision low-order representation, which is particularly suited for problems where model dependencies or excitation traits cause the dynamic behavior to span multiple response regimes. Moreover, the probabilistic treatment of the VAE representation allows for uncertainty quantification on the reduction bases, which may then be propagated to the ROM response. The performance of the proposed approach is validated on an open-source simulation benchmark featuring hysteresis and multi-parametric dependencies, and on a large-scale wind turbine tower characterised by nonlinear material behavior and model uncertainty.
Advanced age-related macular degeneration and risk factors in eyes with pachydrusen
Authors: Nam Seung Wan , Noh Hoon , Yoon Je Moon , Ham Don-Il 
Published: March 2024

AbstractThe risk of progression to advanced age-related macular degeneration (AMD) varies depending on the type of drusen. This retrospective longitudinal study included 248 eyes of 156 patients with pachydrusen without advanced AMD at baseline. Macular neovascularization (MNV) and geographic atrophy (GA) were evaluated. Risk factors for progression to advanced AMD were determined using multivariate Cox regression analysis. The mean age at baseline was 65.4 ± 9.1 years, and the mean follow-up duration was 6.40 ± 3.58 years. The mean total number of pachydrusen and macular pachydrusen were 4.10 ± 2.85 and 2.27 ± 1.81 per eye, respectively. Pachydrusen was accompanied by other types of drusen in 4.8% (12 eyes) of eyes at baseline. During follow-up, MNVs occurred in 2.8% (seven eyes), including polypoidal choroidal vasculopathy (PCV six eyes); however, no GA occurred. Regarding risk factors for progression to neovascular AMD, age (p = 0.023) and macular pigmentary changes (p = 0.014) were significantly associated with MNV development. The cumulative incidence of MNV was significantly higher in the group with macular pigmentary changes (17.39% vs. 0.57% at 10 years; p = 0.0005). The number of macular pachydrusen and the presence of MNV in the fellow eye did not show a statistically significant relationship with MNV development. Age and macular pigmentary changes are risk factors for MNV development in the eyes with pachydrusen. Eyes with pachydrusen appear to have a risk profile for advanced AMD that is different from that of AMD eyes with drusen or drusenoid deposits other than pachydrusen.
Nortriptyline hydrochloride, a potential candidate for drug repurposing, inhibits gastric cancer by inducing oxidative stress by triggering the Keap1-Nrf2 pathway
Authors: Zhu Chunyang , Lu Yangyang , Wang Shasha , Song Jialin , Ding Yixin , Wang Yan , Dong Chen , Liu Jiani , Qiu Wensheng , Qi Weiwei 
Published: March 2024

AbstractEffective drugs for the treatment of gastric cancer (GC) are still lacking. Nortriptyline Hydrochloride (NTP), a commonly used antidepressant medication, has been demonstrated by numerous studies to have antitumor effects. This study first validated the ability of NTP to inhibit GC and preliminarily explored its underlying mechanism. To begin with, NTP inhibits the activity of AGS and HGC27 cells (Human-derived GC cells) in a dose-dependent manner, as well as proliferation, cell cycle, and migration. Moreover, NTP induces cell apoptosis by upregulating BAX, BAD, and c-PARP and downregulating PARP and Bcl-2 expression. Furthermore, the mechanism of cell death caused by NTP is closely related to oxidative stress. NTP increases intracellular reactive oxygen species (ROS) and malondialdehyde (MDA) levels, decreasing the mitochondrial membrane potential (MMP) and inducing glucose (GSH) consumption. While the death of GC cells can be partially rescued by ROS inhibitor N-acetylcysteine (NAC). Mechanistically, NTP activates the Kelch-like ECH-associated protein (Keap1)—NF-E2-related factor 2 (Nrf2) pathway, which is an important pathway involved in oxidative stress. RNA sequencing and proteomics analysis further revealed molecular changes at the mRNA and protein levels and provided potential targets and pathways through differential gene expression analysis. In addition, NTP can inhibited tumor growth in nude mouse subcutaneous tumor models constructed respectively using AGS and MFC (mouse-derived GC cells), providing preliminary evidence of its effectiveness in vivo. In conclusion, our study demonstrated that NTP exhibits significant anti-GC activity and is anticipated to be a candidate for drug repurposing.
Friction injury of the central vein caused by catheter for hemodialysis: an in vitro study
Authors: Wang Zhaoxing , Wang Kunpeng , Xu Yan 
Published: March 2024

AbstractVascular injury such as central venous stenosis (CVS) is a common complication in hemodialysis patients with central venous catheters (CVCs), yet the impact of the microstructure and partial physic characteristics of catheter surface on the chronic injury of central vein has not been elucidated. In this study, the microscopic morphology of tips and bodies of six different brands of polyurethane CVCs was observed and their roughness was assessed. Subsequently, an in vitro model was established to measure the coefficients of friction (COF) between CVCs (tips and bodies) and the vena cava intima of Japanese rabbits under the same condition in a linear reciprocating mode, and changes in the intima of vessels after friction were observed. The study found that there was a significant variation in surface roughness among different brands of CVCs (tips P < 0.001, bodies P = 0.02), and the COF was positively correlated with the catheter surface roughness (tips P = 0.005, R = 0.945, bodies P = 0.01, R = 0.909). Besides, the endovascular roughness increased after friction. These findings suggest that the high roughness surface of CVCs may cause chronic mechanical friction injury to the central venous intima, which is one of the potential factors leading to CVS or occlusion. This provides a breakthrough for reducing complications, improving patient prognosis, and advancing catheter surface lubrication technology.
A high-content screen reveals new regulators of nuclear membrane stability
Authors: Gunn Amanda L. , Yashchenko Artem I. , Dubrulle Julien , Johnson Jodiene , Hatch Emily M. 
Published: March 2024

AbstractNuclear membrane rupture is a physiological response to multiple in vivo processes, such as cell migration, that can cause extensive genome instability and upregulate invasive and inflammatory pathways. However, the underlying molecular mechanisms of rupture are unclear and few regulators have been identified. In this study, we developed a reporter that is size excluded from re-compartmentalization following nuclear rupture events. This allows for robust detection of factors influencing nuclear integrity in fixed cells. We combined this with an automated image analysis pipeline in a high-content siRNA screen to identify new proteins that both increase and decrease nuclear rupture frequency in cancer cells. Pathway analysis identified an enrichment of nuclear membrane and ER factors in our hits and we demonstrate that one of these, the protein phosphatase CTDNEP1, is required for nuclear stability. Analysis of known rupture determinants, including an automated quantitative analysis of nuclear lamina gaps, are consistent with CTDNEP1 acting independently of actin and nuclear lamina organization. Our findings provide new insights into the molecular mechanism of nuclear rupture and define a highly adaptable program for rupture analysis that removes a substantial barrier to new discoveries in the field.
Characteristics of resistivity variation in deep granite and in-situ detection applications
Authors: Fu Zhen , Zhang Yuezheng , Ji Hongguang , Zhang Chunrui , Chen Dongsheng , Qin Yuan 
Published: March 2024

AbstractDuring the construction of deep vertical shafts, water inrush and flooding accidents are prone to occur, which seriously affect construction safety. Accurately determining the groundwater conditions is a prerequisite for effectively controlling water hazards and conducting risk management. In order to ensure the accuracy of the resistivity method in deep vertical well water exploration construction, a combination of indoor rock physics, mechanical testing, and on-site engineering measurements was used to analyze the influencing factors of granite resistivity. The corresponding relationship between resistivity and formation integrity was revealed, and water exploration experiments were conducted in the working face of deep underground mines. The results show that: (1) Rock resistivity is influenced by metallic minerals, saturation, temperature, ion content of fracture water, and joints. Regarding deep subsurface detection issues, the main factors affecting the detection results are water content and rock integrity. (2) During the loading process, rock resistivity exhibits significant stage response characteristics, which are closely related to rock integrity and damage accumulation. (3) A degradation model for aquifer zoning based on resistivity benchmark line was established. When the formation resistivity is higher than the benchmark line, it indicates a well-integrated formation with low water content. (4) Resistivity cloud maps and zoning degradation models can be used to visually determine and evaluate the occurrence status of formations and the effectiveness of grouting.
Insights from Turkey's big data: unraveling the preventability, pathogenesis, and risk management of Alzheimer's disease (AD)
Authors: Yiğit Talip , Ata Naim , Dinçer Murat , Ülgü M. Mahir , Birinci Şuayip , Ayvalı M. Okan 
Published: March 2024

AbstractExtensive research into dementia has more recently honed in on several key areas. These areas include the advancement of techniques such as the accumulation of amyloid-β and tau proteins, the monitoring of cerebral hypometabolism rates etc. The primary objective of this study is to explore the intricate interplay between Alzheimer's disease (AD)—other dementias (D) and various chronic illnesses in terms of time, intensity, and connectivity. In this context, we retrospectively examined data of 149,786 individuals aged 65 and above who received diagnoses of AD and D in the year 2020. At first, logistic regression (LR) analysis has been made with “sex”, “age” and “foreigner” (citizenship status) independent variables for AD and D. The LR models shows that while “sex” and “age” variables have a small rate on the risk of developing AD/D, it is detected that being a foreigner increase the risk of AD and D as 69.8% and 88.5% respectively. Besides, the LR models have middle-level success prediction rate for both of the two dependent variables. Additionally, we used the parallel coordinates graphs method within the R Studio to visualize their relationships and connections. The findings of this investigation strongly suggest that AD/D don’t stand as isolated conditions, but rather stem from intricate interactions and progressive processes involving diverse chronic diseases over time. Notably, ailments including hypertension, coronary artery disease, diabetes, hyperlipidemia, and psychological disorders, contribute substantially to the emergence of both AD and D. This study highlights that the fight against AD/D can only be possible with next-generation prophylactic interventions that can predict and manage risks. Such an approach holds the potential to potentially lower AD and dementia to levels that are amenable to treatment.
Strengthened impact of boreal winter North Pacific Oscillation on ENSO development in warming climate
Authors: Chen Shangfeng , Chen Wen , Xie Shang-Ping , Yu Bin , Wu Renguang , Wang Zhibiao , Lan Xiaoqing , Graf Hans-F 
Published: March 2024

AbstractThe North Pacific Oscillation (NPO), an important mode of atmospheric variability, is a crucial trigger for the development of El Niño-Southern Oscillation (ENSO) via the seasonal footprinting mechanism. How the NPO effect on ENSO changes in response to greenhouse warming remains unclear, however. Here, using climate model simulations under high-emission scenarios, we show that greenhouse warming leads to an enhanced influence of NPO on ENSO as is manifested by enhanced responses of winter sea surface temperature (SST), precipitation and wind anomalies in the equatorial Pacific to the preceding winter NPO. The strengthened NPO impact is also reflected in an increased frequency of NPO events that are followed by ENSO events. Warmer background SST enhances the wind-evaporation-SST feedback over the subtropical North Pacific due to a nonlinear SST-evaporation relationship. This strengthens the NPO-generated surface zonal wind anomalies over the equatorial western-central Pacific, which trigger ENSO. Increased impact of winter NPO on ENSO could enable prediction of interannual variability at longer leads.
Antiviral drugs prolong survival in murine recessive dystrophic epidermolysis bullosa
Authors: Tartaglia Grace , Fuentes Ignacia , Patel Neil , Varughese Abigail , Israel Lauren E , Park Pyung Hun , Alexander Michael H , Poojan Shiv , Cao Qingqing , Solomon Brenda , Padron Zachary M , Dyer Jonathan A , Mellerio Jemima E , McGrath John A , Palisson Francis , Salas-Alanis Julio , Han Lin , South Andrew P 
Published: March 2024

AbstractRecessive dystrophic epidermolysis bullosa (RDEB) is a rare inherited skin disease characterized by defects in type VII collagen leading to a range of fibrotic pathologies resulting from skin fragility, aberrant wound healing, and altered dermal fibroblast physiology. Using a novel in vitro model of fibrosis based on endogenously produced extracellular matrix, we screened an FDA-approved compound library and identified antivirals as a class of drug not previously associated with anti-fibrotic action. Preclinical validation of our lead hit, daclatasvir, in a mouse model of RDEB demonstrated significant improvement in fibrosis as well as overall quality of life with increased survival, weight gain and activity, and a decrease in pruritus-induced hair loss. Immunohistochemical assessment of daclatasvir-treated RDEB mouse skin showed a reduction in fibrotic markers, which was supported by in vitro data demonstrating TGFβ pathway targeting and a reduction of total collagen retained in the extracellular matrix. Our data support the clinical development of antivirals for the treatment of patients with RDEB and potentially other fibrotic diseases.
Medikamentöse Therapie der portalen Hypertension
Authors: Martin Anna , Goeser Tobias , Kasper Philipp 
Published: March 2024

AbstractIn western industrialized nations, liver cirrhosis is the most common cause of portal hypertension. Portal hypertension is defined by a persistent increase in portal pressure >7mmHg. An HVPG >10mmHg defines the presence of clinically significant portal hypertension. The presence of clinically significant portal hypertension (CSPH) in patients with liver cirrhosis is a key risk factor for the transition from a compensated to a decompensated stage of the disease. CPSH can be determined invasively by measuring HPVG or noninvasively by measuring liver stiffness, platelet count and spleen stiffness. If acute decompensation manifests itself (e.g. ascites, esophageal variceal bleeding), this is associated with a significant increase in patient morbidity and mortality. Non-selective beta blockers (NSBB) are the standard medical therapy for portal hypertension in the presence of CSPH. Due to the additional α1-antiadrenergic effects, carvedilol leads to a greater reduction in portal pressure compared to traditional NSBB (e.g. Propanolol). In patients with compensated liver cirrhosis, carvedilol is better than traditional NSBB at reducing the risk of variceal bleeding and the occurrence of hepatic decompensation. The early identification of CSPH and evaluation of drug therapy to reduce portal hypertension is therefore crucial to improve the prognosis of patients.
Suiziddrohungen bei Entlassung aus stationär-psychiatrischer Behandlung
Authors: Koban Christoph , Teismann Tobias 
Published: March 2024

ZUSAMMENFASSUNGSuiziddrohungen vor einer geplanten Entlassung stellen Behandler im stationären Setting vor erhebliche Schwierigkeiten; insbesondere, da sich nicht sicher differenzieren lässt zwischen sogenannten Suizidgesten und genuiner Suizidalität. Es empfiehlt sich, frühzeitig während eines stationären Aufenthalts suizidales Erleben und Verhalten explizit zum Thema zu machen. Die therapeutische Auseinandersetzung sollte dabei auf einem fundierten Fallkonzept aufbauen und muss die motivationale Ausgangslage von Patienten berücksichtigen. Motivations- und beziehungsfördernde Therapiestrategien sind veränderungsorientierten Therapieinterventionen dabei immer voranzustellen. Strukturierte Therapieprogramme während und nach dem stationären Aufenthalt können für die weitergehende Aufarbeitung genutzt werden.
Classification of Male Athletes Based on Critical
Power
Authors: Olaya-Cuartero Javier , Pueo Basilio , Penichet-Tomas Alfonso , Jimenez-Olmedo Jose M. 
Published: March 2024

AbstractThis study aimed to classify male athletes based on their performance levels
derived from running critical power (CP) using the 9/3-minute Stryd CP test,
enabling customized training strategies and goal setting. Twenty-four trained
athletes underwent the 9/3-minute running CP test on a certified 400-m athletics
track. Hierarchical cluster analysis using Ward's method categorized
athletes based on CP into distinct performance tiers. Three clusters were
identified with centroids of 3.87±0.12, 4.45±0.17, and 5.14±0.29 W/kg. Five
performance tiers were defined through ordinary least square linear regression
based on power (W/kg): Tier 1: Fair (2.9 to 3.6 W/kg), Tier 2: Tourist (3.6 to
4.2 W/kg), Tier 3: Regional (4.2 to 4.8 W/kg), Tier 4: National (4.8 to
5.5 W/kg), Tier 5: International (5.5 to 6.1 W/kg). Low semi-partial R-squared
(SpR
2) values (0.02 to 0.05) indicated minimal homogeneity
loss when merging clusters. R-squared (R
2) explained 89% to
96% of CP variance, emphasizing cluster analysis effectiveness. The linear
regression model demonstrated a strong fit (r
2+=+0.997) with a
significant intercept (3.22 W/kg), slope (0.63 W/kg/tier), and a low standard
error of estimate (0.045 W/kg). This classification offers insights into male
athlete performance levels based on CP, facilitating targeted training programs
for varying performance levels.