bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromophobe renal cell carcinoma with sarcomatoid and heterologous osteosarcoma-like differentiation: a case report and literature review
Authors: Abuorouq Saleh , Sahawneh Firas , Halalsheh Omar , Haddad Husam K , Mekail Raed , Alzoubi Hiba , Alrjoub Mo’ath , Serhan Hashem A 
Published: August 2023

Abstract
Chromophobe renal cell carcinoma (CRCC) is a subtype of renal cell carcinoma (RCC) with a favorable prognosis. Sarcomatoid differentiation in RCC is assumed to be the outcome of the parent tumor’s dedifferentiation and associated with poorer prognosis. Sarcomatoid differentiation can be detected in CRCC as well as other subtypes, but the occurrence of divergent osteosarcoma-like components in sarcomatoid CRCC is extremely unusual. Only six cases have been previously reported in the literature, we reviewed them and presented the seventh case in a 71-year-old male who had a left kidney heterogeneous mass. The resected tumor showed a sarcoma-like spindle cell area with an adjacent osteosarcoma area producing lacy bone material and bony trabeculae in a hard area mixed with a typical CRCC. In conclusion, sarcomatoid CRCC with osteosarcomatous differentiation is a very rare tumor and should be kept in mind especially when dealing with small or frozen sections biopsies.
Signs of an Augustinian Original Sin in Milan? The Origin and Nature of Human Sin According to Ambrose
Authors: Dupont Anthony 
Published: August 2023

Abstract
Ambrose’s conception of sin is seldom studied. When it is, scholars often regard Ambrose’s thinking as an imperfect preparation for that of his best-known pupil, Augustine of Hippo. The present article redresses this oversight by investigating Ambrose’s conception of sin in its own right. The starting point for Ambrose’s hamartiology is his belief in the personal choice of the will. On several occasions, he attributes the Fall in Eden entirely to human responsibility. Because of this first sin, Adam and Eve lost their potential for perfect virtue and immortality. Adam’s sin, moreover, had consequences for all humankind: mortality, the loss of godlikeness, and the dissemination of a tendency to sin being chief among them. Ambrose’s reflections on Christian baptism provide an important litmus test for his thinking about the impact of Adamic sin. What exactly does baptism erase? According to the Milanese catechist, baptism erases primarily individual sins. Though Ambrose accepts the pernicious impact of Adam’s sin, we argue that his doctrine of (original) sin may not be accurately considered proto-Augustinian. Unlike Augustine’s view, here it is not Adam’s sin per se that humankind has inherited, but rather a general tendency to sin. Ambrose also never speaks of inherited guilt, but of a contamination. Finally, Ambrose always tries to balance the negative influence of original sin with his belief in individual choice and his programme of moral improvement for all Christians.
Phosphate starvation: response mechanisms and solutions
Authors: Madison Imani , Gillan Lydia , Peace Jasmine , Gabrieli Flavio , Van den Broeck Lisa , Jones Jacob L , Sozzani Rosangela 
Published: August 2023

Abstract
Phosphorus is essential to plant growth and agricultural crop yields, yet the challenges associated with phosphorus fertilization in agriculture, such as aquatic runoff pollution and poor phosphorus bioavailability, are increasingly difficult to manage. Comprehensively understanding the dynamics of phosphorus uptake and signaling mechanisms will inform the development of strategies to address these issues. This review describes regulatory mechanisms used by specific tissues in the root apical meristem to sense and take up phosphate from the rhizosphere. The major regulatory mechanisms and related hormone crosstalk underpinning phosphate starvation responses, cellular phosphate homeostasis, and plant adaptations to phosphate starvation are also discussed, along with an overview of the major mechanism of plant systemic phosphate starvation responses. Finally, this review discusses recent promising genetic engineering strategies for improving crop phosphorus use and computational approaches that may help further design strategies for improved plant phosphate acquisition. The mechanisms and approaches presented include a wide variety of species including not only Arabidopsis but also crop species such as Oryza sativa (rice), Glycine max (soybean), and Triticum aestivum (wheat) to address both general and species-specific mechanisms and strategies. The aspects of phosphorus deficiency responses and recently employed strategies of improving phosphate acquisition that are detailed in this review may provide insights into the mechanisms or phenotypes that may be targeted in efforts to improve crop phosphorus content and plant growth in low phosphorus soils.
γ-ray detection from occasional flares in T Tauri stars of NGC 2071 – I. Observational connection
Authors: Filócomo A , Albacete-Colombo J F , Mestre E , Pellizza L J , Combi J A 
Published: August 2023

ABSTRACT
NGC 2071 is a star-forming region that overlaps with three γ-ray sources detected by the Fermi Space Telescope. We propose that strong flare activity in T Tauri stars could produce γ-ray emission in a way that makes them a counterpart to some unidentified sources detected by the Large Area Telescope aboard the Fermi satellite. We have performed a spectral and temporal analysis for two Fermi data sets: the first 2 yr and the entire 14 yr of observations. We have found that the γ-ray source is detectable at 3.2σ above the background at energies above 100 GeV during the first 2 yr of observation. The analysis of the expected frequency of the highest energy flares occurring in T Tauri stars is consistent with our estimate. In addition, we have determined the minimum energy of the flare that would produce γ-ray emission, which is ∼5 × 1037 erg. This agreement becomes a hard observational constraint supporting previous hypotheses about rare flares as the origin of unidentified γ-ray sources in star-forming regions.
The Architecture of Metabolic Networks Constrains the Evolution of Microbial Resource Hierarchies
Authors: Takano Sotaro , Vila Jean C C , Miyazaki Ryo , Sánchez Álvaro , Bajić Djordje 
Published: August 2023

Abstract
Microbial strategies for resource use are an essential determinant of their fitness in complex habitats. When facing environments with multiple nutrients, microbes often use them sequentially according to a preference hierarchy, resulting in well-known patterns of diauxic growth. In theory, the evolutionary diversification of metabolic hierarchies could represent a mechanism supporting coexistence and biodiversity by enabling temporal segregation of niches. Despite this ecologically critical role, the extent to which substrate preference hierarchies can evolve and diversify remains largely unexplored. Here, we used genome-scale metabolic modeling to systematically explore the evolution of metabolic hierarchies across a vast space of metabolic network genotypes. We find that only a limited number of metabolic hierarchies can readily evolve, corresponding to the most commonly observed hierarchies in genome-derived models. We further show how the evolution of novel hierarchies is constrained by the architecture of central metabolism, which determines both the propensity to change ranks between pairs of substrates and the effect of specific reactions on hierarchy evolution. Our analysis sheds light on the genetic and mechanistic determinants of microbial metabolic hierarchies, opening new research avenues to understand their evolution, evolvability, and ecology.
Evaluation of the determinants for improved pluripotency induction and maintenance by engineered SOX17
Authors: Hu Haoqing , Ho Derek Hoi Hang , Tan Daisylyn Senna , MacCarthy Caitlin M , Yu Cheng-han , Weng Mingxi , Schöler Hans Robert , Jauch Ralf 
Published: August 2023

Abstract
An engineered SOX17 variant with point mutations within its DNA binding domain termed SOX17FNV is a more potent pluripotency inducer than SOX2, yet the underlying mechanism remains unclear. Although wild-type SOX17 was incapable of inducing pluripotency, SOX17FNV outperformed SOX2 in mouse and human pluripotency reprogramming. In embryonic stem cells, SOX17FNV could replace SOX2 to maintain pluripotency despite considerable sequence differences and upregulated genes expressed in cleavage-stage embryos. Mechanistically, SOX17FNV co-bound OCT4 more cooperatively than SOX2 in the context of the canonical SoxOct DNA element. SOX2, SOX17, and SOX17FNV were all able to bind nucleosome core particles in vitro, which is a prerequisite for pioneer transcription factors. Experiments using purified proteins and in cellular contexts showed that SOX17 variants phase-separated more efficiently than SOX2, suggesting an enhanced ability to self-organise. Systematic deletion analyses showed that the N-terminus of SOX17FNV was dispensable for its reprogramming activity. However, the C-terminus encodes essential domains indicating multivalent interactions that drive transactivation and reprogramming. We defined a minimal SOX17FNV (miniSOX) that can support reprogramming with high activity, reducing the payload of reprogramming cassettes. This study uncovers the mechanisms behind SOX17FNV-induced pluripotency and establishes engineered SOX factors as powerful cell engineering tools.
Circulating KIM-1 is a minimally invasive biomarker correlated with treatment response to nivolumab in patients with metastatic renal cell carcinoma
Authors: Xu Wenxin , Vemula Sai V , Niman Samuel M , Liu Xiaowen , Takakura Ayumi , Huang Zimo , Choueiri Toni K , Freedman Matthew L , Catalano Paul J , Bonventre Joseph V , Gupta Saurabh , McDermott David F , Bhatt Rupal S 
Published: August 2023

Abstract

Background
There are currently no circulating biomarkers used for clinical monitoring of clear cell renal cell carcinoma (ccRCC). Such a biomarker could facilitate individualized treatment decisions and minimize exposure to ineffective therapies. Prior studies have suggested that circulating KIM-1 is a potential minimally invasive biomarker for ccRCC, but the utility of KIM-1 for identifying early response to nivolumab therapy is not known.

Methods
CheckMate-009 was a prospective trial investigating nivolumab (every 3 weeks at 0.3, 2, or 10 mg/kg) in patients with metastatic clear cell RCC. We measured serum KIM-1 at baseline and after 3 weeks of treatment (prior to cycle 2) using a custom sandwich immunoassay using the R-PLEX platform. Human KIM-1 antibody (R&D systems, #AF1750) was used to prepare biotin conjugated antibodies and detection antibodies. The assay lowest limit of detection for KIM-1 was 4.88 pg/mL. We assessed the association between early changes in serum KIM-1 and treatment related clinical outcomes.

Results
Clinical data and serum KIM-1 was analyzed in 54 patients. KIM-1 was high in all patients at baseline (median serum KIM-1 5913 pg/mL, IQR 2137-25101 pg/mL). 25 patients (48%) had a decrease in KIM-1 at 3 weeks after a single dose of nivolumab. Decrease in KIM-1 at 3 weeks was associated with improved PFS (univariable HR 0.26, 95% CI 0.13-0.52; multivariable HR 0.22, 95% CI 0.097-0.50 after adjustment for sex, prior nephrectomy, nivolumab dose, and IMDC risk factors).

Conclusions
Serum KIM-1 is elevated in patients with metastatic ccRCC and is associated with clinical outcomes. Among patients treated with nivolumab in the CheckMate-009 trial, early decrease in KIM-1 from baseline to 3 weeks was predictive for PFS.
CDMRP DOD Funding: yes
Spatial proteomics enables identification of prognostic biomarkers in papillary renal cell carcinoma
Authors: Haake Scott , Brewer Jared , Nesta Alex , Vento Joseph , Beckermann Kathryn , Reddy Anupama 
Published: August 2023

Abstract

Background
Papillary renal cell carcinoma (PRCC) is the second most common adult kidney cancer histology, constituting 15-20% of cases. While some patients may have indolent PRCC tumors that grow slowly, other tumors rapidly metastasize. Some PRCC tumors respond to immune checkpoint inhibitors. Thus, understanding the immune tumor microenvironment and how it correlates with patient outcomes in this relatively rare disease is a critical need. Spatial interrogation of patient samples has the potential to offer novel insights into the tumor-immune axis and provide avenues for enhanced diagnosis and treatment. Addressing questions of spatial arrangement within tumors has remained a technical and biological challenge, but emerging spatial biology technologies provide molecular data at single cell resolution. We hypothesized that the spatial interaction of immune, stromal and tumor cells would be prognostic for PRCC patients.

Methods
A tissue microarray was assembled from an archive of ~100 patients presenting with PRCC. This dataset was assayed with PhenoCycler/CODEX (Akoya Biosciences) using a 31-antibody panel with immune- and cancer-related proteins. We have developed methodology and novel algorithms to perform signal normalization, cell segmentation, and cell typing. We computed neighborhoods for each of 2.5 million cells and performed network analysis to identify spatial clusters. This method allowed us to identify clusters consistently present across multiple TMA spots from the same patient and across multiple patients.

Results
Using spatial neighborhood analysis, we have identified diverse spatial clusters of potential clinical relevance, including five distinct M2 macrophage spatial clusters. We have described one of the clusters as being physically associated with helper T cells, which is visualized on a PRCC spot and shows co-occurence of M2-macrophages (CD163) and helper T cells (CD4). This pattern was replicated in additional TMA spots from the same patient. In contrast, other clusters of M2-macrophages (M2-M2 spatial cluster and M2-M1 macrophages) are visualized to show vastly different cellular neighborhoods. Clinical associations show that the patients with presence of the M2-T helper cluster have a poor cancer-associated survival (p=0.005). In comparison, the total proportion of M2 macrophages is not associated with survival (p=0.4), highlighting the importance of characterizing spatial interactions beyond cell type quantitation.

Conclusions
In summary, we highlight the utility of spatial biology to explain the heterogeneity in patients’ tumors and to uncover novel correlates of clinical phenotypes, establishing a platform for future discovery in this field and the identification of additional spatial correlates of patient outcome and clinical response.
CDMRP DOD Funding: yes
A High-δ18O Mantle Source for the 2.06 Ga Phalaborwa Igneous Complex, South Africa?
Authors: Munro Joshua , Harris Chris 
Published: August 2023

ABSTRACTThe 2060 ± 2 Ma Phalaborwa Complex is a pipe-like, ultramafic to carbonatite intrusion formed from multiple magma pulses. The complex is made up of a main pipe consisting of clinopyroxenites, ultramafic pegmatoids, carbonatites and foskorite (olivine-apatite-magnetite-calcite assemblage), surrounded by many smaller syenite plugs. The range in mineral δ18O values for all rock types and minerals analysed in the Phalaborwa Complex is 2.24 to 18.3‰. However, 24 analyses of the most abundant and robust mineral, diopside, all have δ18O values between 6.5 and 8.1‰. The δ18O values of baddeleyite, olivine, diopside, magnetite, apatite and aegirine are thought to be magmatic. Most mineral pairs have differences in δ18O values that are consistent with magmatic equilibrium at high temperatures down to closure temperature. Alkali feldspar and phlogopite have more variable δ18O values, and both minerals may have undergone subsolidus O exchange. The δD values for petrographically fresh Phalaborwa Complex phlogopite range from −79 to −48‰ with a mean of −64 ± 9‰ (1σ, n = 19). The phlogopite δD values are consistent with subduction-related magmatic water. Despite petrographic evidence for fluid–rock interaction in the carbonatite–foskorite rocks, the carbonatite δ13C and δ18O range (δ18O, 8.13 to 12.00‰; δ13C, −3.19 to −5.60‰) overlaps with the unaltered, primary igneous carbonatite field.Magma δ18O values estimated from silicate and oxide minerals are mostly higher than normal mantle magmas (pyroxenites, ~7.6‰; foskorite, 7.2‰). The δ18O value of syenite magma estimated from aegirine is 7.8 ± 0.9‰ (1σ, n = 8), in equilibrium with whole-rock syenite δ18O values (8.7 ± 0.4‰, 1σ, n = 5). Local basement rocks have average bulk δ18O values of 8.6‰, and realistic proportions of assimilation by a mantle-derived magma (δ18O, 5.7‰) could not have produced the δ18O values in the pyroxenites or foskorites. Instead, it is proposed that the high-δ18O values of Phalaborwa Complex magmas reflect that of the mantle source. High δ18O values are also a feature of the Rustenburg Layered Suite of the Bushveld Complex (2060 to 2055 Ma), which may have had a similar high-δ18O mantle source. The higher δ18O values of the satellite syenites are consistent with an origin by partial melting of metasomatised country rock.
Ultrasonographic Evaluation of Diaphragmatic Thickness versus Excursion as a Predictor of Weaning in Mechanically Ventilated Patients
Authors: Elsharnouby Noha Mohamed , Ali Rania Mahrous , Eldeeb Abdallah Omar Abdelrazeg 
Published: August 2023

Abstract

Background
Best predictor of successful extubation after mechanical ventilation is a matter of debate.

Objective
The aim of this study was to assess the efficiency of diaphragm thickness and/or diaphragm excursion as measured by means of ultrasound as a predictor of extubation in mechanically ventilated patients in ICU.

Methods
We performed a prospective study on fifty patients who successfully passed spontaneous breathing trial (SBT). During T-tube spontaneous breathing trial (SBT) we evaluated the right hemidiaphragm excursion by using the M mode and diaphragmatic thickness fraction (DTF%) using B mode, and they were classified in to the successful extubation group and the failure group. Primary outcome: defined as weaning failure and requirement of either noninvasive ventilation or mechanical ventilation. Secondary outcome: To investigate possible factors related to weaning failure

Results
Of the 50 patients in the study, 35 patients were successfully weaned and 15 failed weaning. The mean diaphragmatic thickness fraction with respect to cut-off value was higher in the failure group during SBT whereas the diaphragmatic excursion with respect to cut off value was less in the failure group during SBT while there was increase in both DTF and diaphragmatic excursion with respect to cut off value in the success group. The diaphragmatic excursion cut-off value predictive of weaning was 10 mm with a specificity 78% and sensitivity 82% respectively and the diaphragmatic thickness cut-off value predictive of weaning was 21.5% with a specificity of 71% and sensitivity of 76% respectively. There was negative correlation between diaphragmatic function and duration of mechanical ventilation.

Conclusion
The diaphragmatic ultrasonography was found to be a promising tool for predicting the extubation outcome for mechanically ventilated patients.
Risk Factors of Postoperative Atrial Fibrillation after On-Pump CABG Surgery
Authors: Sayed Amr Mohammed Abd-Elfattah , Gomaa Gehan Abd-Elhalim Ali , Abd-Elaziz Farouk kamal Eldin , Ibrahim Ahmed Abd-Elnasser Ibrahim 
Published: August 2023

Abstract

Background
Atrial fibrillation is the most common arrhythmia seen following CABG

Aim of the Work
We sought to determine the preoperative and intraoperative risk factors for occurrence of postoperative atrial fibrillation (AF) following on- pump coronary artery bypass grafting surgery (CABG).

Patients and Methods
We conducted an observational prospective study on 85 patients who underwent isolated on-pump CABG divided in two groups group A POAF group and group B non AF group. Personal history, Clinical, laboratory and procedure characters were noticed and recorded.

Results
Atrial fibrillation was diagnosed in 15.3% of the population postoperatively and many factors watched were not associated with statistically significant prediction of development of postoperative AF like age, sex, body mass index (BMI), smoking, Hypertension, Diabetes mellitus, history of epilepsy and chronic kidney disease. Regarding the pathology of ischemic heart disease we classified the patients into two categories: multivessel disease and left main disease, 3 patients were emergency revascularization due to acute MI with 92% of AF patients were with multivessel disease pathology.

Conclusion
The occurrence of AF following CABG is multifactorial but defining specific risk factor for development of new onset AF postoperatively is matter of conflict among studies.
Predictive Value of Doppler Renal Resistive Index for Prediction of Acute Kidney Injury in Septic Patients in Intensive Care Unit
Authors: Saeed Abdelaziz Mohammed , Hosney Mona Refaat , Ahmed Mohamed Saleh , Abuelmajd Ahmed Abdelsattar 
Published: August 2023

Abstract

Background
Acute kidney injury (AKI) occurs as a serious complication in septic patients. In its severe form, AKI requires renal replacement therapy, which is applied in 5–13% of intensive care units (ICU) patients. AKI is common in patients confined in ICU and remains to be associated with poor outcomes. According to the current diagnostic criteria, serum creatinine (SCr) and urine volume are used as diagnostic and staging criteria for AKI.

Aim of the Work
To evaluate predictive value of renal resistive index in detection of acute kidney injury. Measuring flow resistance in the renal circulation, Renal Resistive Index (RRI) could become part of vital organ function assessment using Doppler ultrasound.

Patients and Methods
This was a prospective descriptive study conducted on 150 ICU patients with sepsis; to evaluate prediction value of renal resistive index in detection of acute kidney injury. Measuring flow resistance in the renal circulation, RRI could become part of vital organ function assessment using Doppler ultrasound.

Results
We found that; the mean age of all patients was (38.4 ± 13.5) years. Regarding gender of the patients, the majority (62.7%) of patients were males; while (37.3%) were females. Regarding basic clinical data; the average MAP was (57.6 ± 14.8) mmHg, the average APACHE score was (14.6 ± 3.7), and the average SOFA score was (4.2 ± 0.92). Regarding comorbidities; (24.7%) of patients had septic shock, (20%) had DM, (34%) had HTN, and (14.7%) had IHD.

Conclusion
High RRI on ICU admission was a significant predictor for development of AKI stage 2 ± 3 during the first week. High RRI can be used as an early warning signal RRI, because of its high specificity. A combined score including RRI, APACHE III and fluid balance improved AKI prediction, suggesting that vasoconstriction or poor vascular compliance, severity of disease and positive fluid balance independently contribute to AKI development.