bluuebunny/crossref_metadata_2025_split huggingface dataset:
Camonsertib in DNA damage response-deficient advanced solid tumors: phase 1 trial results
Authors: Yap Timothy A. , Fontana Elisa , Lee Elizabeth K. , Spigel David R. , Højgaard Martin , Lheureux Stephanie , Mettu Niharika B. , Carneiro Benedito A. , Carter Louise , Plummer Ruth , Cote Gregory M. , Meric-Bernstam Funda , O’Connell Joseph , Schonhoft Joseph D. , Wainszelbaum Marisa , Fretland Adrian J. , Manley Peter , Xu Yi , Ulanet Danielle , Rimkunas Victoria , Zinda Mike , Koehler Maria , Silverman Ian M. , Reis-Filho Jorge S. , Rosen Ezra 
Published: June 2023

AbstractPredictive biomarkers of response are essential to effectively guide targeted cancer treatment. Ataxia telangiectasia and Rad3-related kinase inhibitors (ATRi) have been shown to be synthetic lethal with loss of function (LOF) of ataxia telangiectasia-mutated (ATM) kinase, and preclinical studies have identified ATRi-sensitizing alterations in other DNA damage response (DDR) genes. Here we report the results from module 1 of an ongoing phase 1 trial of the ATRi camonsertib (RP-3500) in 120 patients with advanced solid tumors harboring LOF alterations in DDR genes, predicted by chemogenomic CRISPR screens to sensitize tumors to ATRi. Primary objectives were to determine safety and propose a recommended phase 2 dose (RP2D). Secondary objectives were to assess preliminary anti-tumor activity, to characterize camonsertib pharmacokinetics and relationship with pharmacodynamic biomarkers and to evaluate methods for detecting ATRi-sensitizing biomarkers. Camonsertib was well tolerated; anemia was the most common drug-related toxicity (32% grade 3). Preliminary RP2D was 160 mg weekly on days 1–3. Overall clinical response, clinical benefit and molecular response rates across tumor and molecular subtypes in patients who received biologically effective doses of camonsertib (>100 mg d−1) were 13% (13/99), 43% (43/99) and 43% (27/63), respectively. Clinical benefit was highest in ovarian cancer, in tumors with biallelic LOF alterations and in patients with molecular responses. ClinicalTrials.gov registration: NCT04497116.
Predicting U.S. county opioid poisoning mortality from multi-modal social media and psychological self-report data
Authors: Giorgi Salvatore , Yaden David B. , Eichstaedt Johannes C. , Ungar Lyle H. , Schwartz H. Andrew , Kwarteng Amy , Curtis Brenda 
Published: June 2023

AbstractOpioid poisoning mortality is a substantial public health crisis in the United States, with opioids involved in approximately 75% of the nearly 1 million drug related deaths since 1999. Research suggests that the epidemic is driven by both over-prescribing and social and psychological determinants such as economic stability, hopelessness, and isolation. Hindering this research is a lack of measurements of these social and psychological constructs at fine-grained spatial and temporal resolutions. To address this issue, we use a multi-modal data set consisting of natural language from Twitter, psychometric self-reports of depression and well-being, and traditional area-based measures of socio-demographics and health-related risk factors. Unlike previous work using social media data, we do not rely on opioid or substance related keywords to track community poisonings. Instead, we leverage a large, open vocabulary of thousands of words in order to fully characterize communities suffering from opioid poisoning, using a sample of 1.5 billion tweets from 6 million U.S. county mapped Twitter users. Results show that Twitter language predicted opioid poisoning mortality better than factors relating to socio-demographics, access to healthcare, physical pain, and psychological well-being. Additionally, risk factors revealed by the Twitter language analysis included negative emotions, discussions of long work hours, and boredom, whereas protective factors included resilience, travel/leisure, and positive emotions, dovetailing with results from the psychometric self-report data. The results show that natural language from public social media can be used as a surveillance tool for both predicting community opioid poisonings and understanding the dynamic social and psychological nature of the epidemic.
Biological 2,4,6-trinitrotoluene removal by extended aeration activated sludge: optimization using artificial neural network
Authors: Karimi Hossein , Mohammadi Farzaneh , Rajabi Saeed , Mahvi Amir Hossein , Ghanizadeh Ghader 
Published: June 2023

AbstractSerious health issues can result from exposure to the nitrogenous pollutant like 2,4,6-trinitrotoluene (TNT), which is emitted into the environment by the munitions and military industries, as well as from TNT-contaminated wastewater. The TNT removal by extended aeration activated sludge (EAAS) was optimized in the current study using artificial neural network modeling. In order to achieve the best removal efficiency, 500 mg/L of chemical oxygen demand (COD), 4 and 6 h of hydraulic retention time (HRT), and 1–30 mg/L of TNT were used in this study. The kinetics of TNT removal by the EAAS system were described by the calculation of the kinetic coefficients K, Ks, Kd, max, MLSS, MLVSS, F/M, and SVI. Adaptive neuro fuzzy inference system (ANFIS) and genetic algorithms (GA) were used to optimize the data obtained through TNT elimination. ANFIS approach was used to analyze and interpret the given data, and its accuracy was around 97.93%. The most effective removal efficiency was determined using the GA method. Under ideal circumstances (10 mg/L TNT concentration and 6 h), the TNT removal effectiveness of the EAAS system was 84.25%. Our findings demonstrated that the artificial neural network system (ANFIS)-based EAAS optimization could enhance the effectiveness of TNT removal. Additionally, it can be claimed that the enhanced EAAS system has the ability to extract wastewaters with larger concentrations of TNT as compared to earlier experiments.
Gold nanoparticle decorated post-synthesis modified UiO-66-NH2 for A3-coupling preparation of propargyl amines
Authors: Mohammadi Leila , Taghavi Reza , Hosseinifard Mojtaba , Vaezi Mohammad Reza , Rostamnia Sadegh 
Published: June 2023

AbstractIn this report, the novel UiO‑66‑NH2based-MOF(Zr) catalytic system which further modified with nitrogen-rich organic ligand (5-aminotetrazole) using post synthetic modification (PSM) approach has been prepared here as an efficient catalyst to promote the A3-coupling preparation of propargyl amines in green aquatic media. This newly highly efficient catalyst was synthesized upon Zr-based MOF (UiO‑66‑NH2) which successfully functionalized with 2,4,6‑trichloro‑1,3,5‑triazine (TCT) and 5‑aminotetrazole, following through stabilization of gold metal (Au) nanopartilces. The addition ofN-rich organic ligand through post-synthesis modification which can be assisted to stabilize the bister and stable gold nanoparticles caused to unique structure of the final composite in favor of the progress of the A3coupling reaction. Also several strategies comprising XRD, FT-IR, SEM, BET, TEM, TGA, ICP, EDS and elemental mapping analyzes, were used to indicate the successful preparation of the UiO-66-NH2@ Cyanuric Chloride@ 5-amino tetrazole/Au-NPs. The results of productivity catalyst are accomplished in good to excellent yields for all sort of reactions under mild conditions which is a proof of superior activity heterogeneous catalyst containing Au-nanoparticles. In addition, the suggested catalyst represented excellent reusability with no remarkable loss in activity up 9 sequential runs.
A mechanistic interpretation of relativistic rigid body rotation
Authors: Catheline Stefan 
Published: June 2023

AbstractThe starting point of this manuscript is classical rigid body rotation. As it is well known, it contradicts basis of relativity since infinite speed is reached at infinite distance from the rotation center O. In order to fix this problem, a phenomenological circle-based construction using Euclidian trigonometry is first described: the relativistic rigid body rotation. The physical Eulerian acceleration implied by this geometrical construction then sketches future links with Maxwell’s equation and Lense-Thirring effect. More importantly, relativistic rigid body rotation is shown to be compatible with Lorentz transformation and brings new geometrical interpretations of time and space intervals.
Overexpression of fatty acid synthase attenuates bleomycin induced lung fibrosis by restoring mitochondrial dysfunction in mice
Authors: Shin Hyesun , Park Shinhee , Hong Jisu , Baek Ae-Rin , Lee Junehyuk , Kim Do-Jin , Jang An-Soo , Chin Su Sie , Jeong Sung Hwan , Park Sung-Woo 
Published: June 2023

AbstractProper lipid metabolism is crucial to maintain alveolar epithelial cell (AEC) function, and excessive AEC death plays a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). The mRNA expression of fatty acid synthase (FASN), a key enzyme in the production of palmitate and other fatty acids, is downregulated in the lungs of IPF patients. However, the precise role of FASN in IPF and its mechanism of action remain unclear. In this study, we showed that FASN expression is significantly reduced in the lungs of IPF patients and bleomycin (BLM)-treated mice. Overexpression of FASN significantly inhibited BLM-induced AEC death, which was significantly potentiated by FASN knockdown. Moreover, FASN overexpression reduced BLM-induced loss of mitochondrial membrane potential and the production of mitochondrial reactive oxygen species (ROS). Oleic acid, a fatty acid component increased by FASN overexpression, inhibited BLM-induced cell death in primary murine AECs and rescue BLM induced mouse lung injury/fibrosis. FASN transgenic mice exposed to BLM exhibited attenuated lung inflammation and collagen deposition compared to controls. Our findings suggest that defects in FASN production may be associated with the pathogenesis of IPF, especially mitochondrial dysfunction, and augmentation of FASN in the lung may have therapeutic potential in preventing lung fibrosis.
Robust-stein estimator for overcoming outliers and multicollinearity
Authors: Lukman Adewale F. , Farghali Rasha A. , Kibria B. M. Golam , Oluyemi Okunlola A. 
Published: June 2023

AbstractLinear regression models with correlated regressors can negatively impact the performance of ordinary least squares estimators. The Stein and ridge estimators have been proposed as alternative techniques to improve estimation accuracy. However, both methods are non-robust to outliers. In previous studies, the M-estimator has been used in combination with the ridge estimator to address both correlated regressors and outliers. In this paper, we introduce the robust Stein estimator to address both issues simultaneously. Our simulation and application results demonstrate that the proposed technique performs favorably compared to existing methods.
Salmonella T3SS effector SseK1 arginine-glycosylates the two-component response regulator OmpR to alter bile salt resistance
Authors: Hasan Md Kamrul , Scott Nichollas E. , Hays Michael P. , Hardwidge Philip R. , El Qaidi Samir 
Published: June 2023

AbstractType III secretion system (T3SS) effector proteins are primarily recognized for binding host proteins to subvert host immune response during infection. Besides their known host target proteins, several T3SS effectors also interact with endogenous bacterial proteins. Here we demonstrate that the Salmonella T3SS effector glycosyltransferase SseK1 glycosylates the bacterial two-component response regulator OmpR on two arginine residues, R15 and R122. Arg-glycosylation of OmpR results in reduced expression of ompF, a major outer membrane porin gene. Glycosylated OmpR has reduced affinity to the ompF promoter region, as compared to the unglycosylated form of OmpR. Additionally, the Salmonella ΔsseK1 mutant strain had higher bile salt resistance and increased capacity to form biofilms, as compared to WT Salmonella, thus linking OmpR glycosylation to several important aspects of bacterial physiology.
Establishment of cancer-associated fibroblasts-related subtypes and prognostic index for prostate cancer through single-cell and bulk RNA transcriptome
Authors: Qian Youliang , Feng Dechao , Wang Jie , Wei Wuran , Wei Qiang , Han Ping , Yang Lu 
Published: June 2023

AbstractCurrent evidence indicate that cancer-associated fibroblasts (CAFs) play an important role in prostate cancer (PCa) development and progression. In this study, we identified CAF-related molecular subtypes and prognostic index for PCa patients undergoing radical prostatectomy through integrating single-cell and bulk RNA sequencing data. We completed analyses using software R 3.6.3 and its suitable packages. Through single-cell and bulk RNA sequencing analysis, NDRG2, TSPAN1, PTN, APOE, OR51E2, P4HB, STEAP1 and ABCC4 were used to construct molecular subtypes and CAF-related gene prognostic index (CRGPI). These genes could clearly divide the PCa patients into two subtypes in TCGA database and the BCR risk of subtype 1 was 13.27 times higher than that of subtype 2 with statistical significance. Similar results were observed in MSKCC2010 and GSE46602 cohorts. In addtion, the molucular subtypes were the independent risk factor of PCa patients. We orchestrated CRGPI based on the above genes and divided 430 PCa patients in TCGA database into high- and low- risk groups according to the median value of this score. We found that high-risk group had significant higher risk of BCR than low-risk group (HR: 5.45). For functional analysis, protein secretion was highly enriched in subtype 2 while snare interactions in vesicular transport was highly enriched in subtype 1. In terms of tumor heterogeneity and stemness, subtype 1 showd higher levels of TMB than subtype 2. In addition, subtype 1 had significant higher activated dendritic cell score than subtype 2. Based on eight CAF-related genes, we developed two prognostic subtypes and constructed a gene prognostic index, which could predict the prognosis of PCa patients very well.
Asymmetric lung increases particle filtration by deposition
Authors: Kundu Debjit , Panchagnula Mahesh V. 
Published: June 2023

AbstractHuman lung is known to be an asymmetric dichotomously branched network of bronchioles. Existing literature on the relation between anatomy and air-flow physics in the tracheobronchial trees has discussed the results of asymmetry. We discuss a secondary (but an important) lung function to seek asymmetry: to protect the acinus from a high pathogen load. We build morphometric parameter-based mathematical models of realistic bronchial trees to explore the structure-function relationship. We observe that maximum surface area for gas exchange, minimum resistance and minimum volume are obtained near the symmetry condition. In contrast, we show that deposition of inhaled foreign particles in the non-terminal airways is enhanced by asymmetry. We show from our model, that the optimal value of asymmetry for maximum particle filtration is within 10% of the experimentally measured value in human lungs. This structural trait of the lung aids in self-defence of the host against pathogen laden aerosols. We explain how natural asymmetric design of typical human lungs makes a sacrifice away from gas exchange optimality to gain this protection. In a typical human lung, when compared to most optimal condition (which is associated with symmetric branching), the fluidic resistance is 14% greater, the gas exchange surface area is about 11% lower, the lung volume is about 13% greater to gain an increase of 4.4% protection against foreign particles. This afforded protection is also robust to minor variations in branching ratio or variation in ventilation, which are both crucial to survival.
Origin, genetic structure and evolutionary potential of the natural hybrid Ranunculus circinatus × R. fluitans
Authors: Zalewska-Gałosz J. , Kwiatkowska M. , Prančl J. , Skubała K. , Lučanová M. , Gebler D. , Szoszkiewicz K. 
Published: June 2023

AbstractUnderstanding the genetic variability of hybrids provides information on their current and future evolutionary role. In this paper, we focus on the interspecific hybridRanunculus circinatus × R. fluitansthat forms spontaneously within the groupRanuculusL. sect.BatrachiumDC. (Ranunculaceae Juss.). Genome-wide DNA fingerprinting using amplified fragment length polymorphisms (AFLP) was employed to determine the genetic variation among 36 riverine populations of the hybrid and their parental species. The results demonstrate a strong genetic structure ofR. circinatus × R. fluitanswithin Poland (Central Europe), which is attributed to independent hybridization events, sterility of hybrid individuals, vegetative propagation, and isolation through geographical distance within populations. The hybridR. circinatus × R. fluitansis a sterile triploid, but, as we have shown in this study, it may participate in subsequent hybridization events, resulting in a ploidy change that can lead to spontaneous fertility recovery. The ability to produce unreduced female gametes of the hybridR. circinatus × R. fluitansand the parental speciesR. fluitansis an important evolutionary mechanism inRanunculussect.Batrachiumthat could give rise to new taxa.
Personal sustained cooperation based on networked evolutionary game theory
Authors: Yan Jun 
Published: June 2023

AbstractEvolutionary game theory on complex networks provides an effective theoretical tool to explain the emergence of sustained cooperative behavior. Human society has formed various organizational networks. The network structure and individual behavior take on a variety of forms. This diversity provides the basis for choice, so it is crucial for the emergence of cooperation. This article provides a dynamic algorithm for individual network evolution, and calculates the importance of different nodes in the network evolution process. In the dynamic evolution simulation, the probability of the cooperation strategy and betrayal strategy is described. In the individual interaction network, cooperative behavior will promote the continuous evolution of individual relationships and form a better aggregative interpersonal network. The interpersonal network of betrayal has been in a relatively loose state, and its continuity must rely on the participation of new nodes, but there will be certain "weak links" in the existing nodes of the network.
Development and application of random forest regression soft sensor model for treating domestic wastewater in a sequencing batch reactor
Authors: Cheng Qiu , Chunhong Zhan , Qianglin Li 
Published: June 2023

AbstractSmall-scale distributed water treatment equipment such as sequencing batch reactor (SBR) is widely used in the field of rural domestic sewage treatment because of its advantages of rapid installation and construction, low operation cost and strong adaptability. However, due to the characteristics of non-linearity and hysteresis in SBR process, it is difficult to construct the simulation model of wastewater treatment. In this study, a methodology was developed using artificial intelligence and automatic control system that can save energy corresponding to reduce carbon emissions. The methodology leverages random forest model to determine a suitable soft sensor for the prediction of COD trends. This study uses pH and temperature sensors as premises for COD sensors. In the proposed method, data were pre-processed into 12 input variables and top 7 variables were selected as the variables of the optimized model. Cycle ended by the artificial intelligence and automatic control system instead of by fixed time control that was an uncontrolled scenario. In 12 test cases, percentage of COD removal is about 91. 075% while 24. 25% time or energy was saved from an average perspective. This proposed soft sensor selection methodology can be applied in field of rural domestic sewage treatment with advantages of time and energy saving. Time-saving results in increasing treatment capacity and energy-saving represents low carbon technology. The proposed methodology provides a framework for investigating ways to reduce costs associated with data collection by replacing costly and unreliable sensors with affordable and reliable alternatives. By adopting this approach, energy conservation can be maintained while meeting emission standards.
Raw water biofiltration for surface water manganese control
Authors: Earle Martin R. , Stoddart Amina K. , Gagnon Graham A. 
Published: June 2023

AbstractManganese (Mn) control in surface water systems is a challenge for the drinking water industry, especially through a sustainability framework. Current methods for removing manganese from surface water use strong oxidants that embed carbon and can be expensive and harmful to human health and the environment. In this study, we used a simple biofilter design to remove manganese from lake water, without conventional surface water pre-treatments. Biofilters with aerated influent removed manganese to concentrations below 10 µg/L when receiving influent water containing > 120 µg/L of dissolved manganese. Manganese removal was not inhibited by high iron loadings or poor ammonia removal, suggesting that removal mechanisms may differ from groundwater biofilters. Experimental biofilters also achieved lower effluent manganese concentrations than the full-scale conventional treatment process, while receiving higher manganese concentrations. This biological approach could help achieve sustainable development goals.
Assessing hypothalamic pituitary gonadal function in reproductive disorders
Authors: Koysombat Kanyada , Dhillo Waljit S. , Abbara Ali 
Published: June 2023

Abstract
Reproductive conditions secondary to disorders of the hypothalamic–pituitary–gonadal (HPG) axis are common and are associated with important health implications and considerable psychosocial impact. Basal and dynamic tests enable interrogation of individual components of the HPG axis, facilitating diagnosis and understanding of the pathophysiology of reproductive disorders. Onset of puberty is controlled by hypothalamic gonadotrophin-releasing hormone (GnRH) neuronal function. To date, a dynamic test of hypothalamic function is not yet available. Therefore, accurate differentiation of pubertal disorders such as constitutional delay of growth and puberty (CDGP) and congenital hypogonadotrophic hypogonadism (CHH) as causes of delayed puberty is challenging due to similar clinical presentations and hormonal profiles. Likewise, although the two commonest reproductive disorders in women, polycystic ovary syndrome (PCOS) and functional hypothalamic amenorrhoea (FHA) have disparate hypothalamic function, oligo/amenorrhoea frequently poses a diagnostic conundrum owing to the overlap in the criteria used to define both conditions. This review aims to describe pubertal and reproductive disorders secondary to pathologies affecting the HPG axis. Challenges encountered in clinical practice in differentiating pubertal and reproductive conditions are reviewed in conjunction with the utility of baseline and dynamic endocrine tests to interrogate specific components of the HPG axis. We also highlight putative hypothalamic, pituitary, and gonadal markers in development that could improve the diagnosis of patients presenting with disorders of puberty or reproduction.