Miracle-dz/UniFAR-FTUs huggingface dataset:
Development of a Standardized Semantic Feature-Based Reporting Proforma for Intraoperative Ultrasound Findings in Brain Tumors and Application in High-Grade Gliomas – A Preliminary Study

Abstract Purpose A semantic feature-based reporting proforma for intraoperative ultrasound findings in brain tumors was devised to standardize reporting. It was applied as a pilot study on a cohort of histologically confirmed high-grade supratentorial gliomas (Grade 3 and 4) for internal validation. Materials and Methods This intraoperative semantic ultrasound proforma was used to evaluate 3D ultrasound volumes using Radiant DICOM software by 3 surgeons. The ultrasound semantic features were correlated with histological features like tumor grade, IDH status, and MIB index. Results 68 patients were analyzed using the semantic proforma. Irregular crenated was the most common margin (63.2%) and lesions were heterogeneously hyperechoic (95.6%). Necrosis was commonly seen and noted as single (67.6%) or multiple (13.2%) in over 80% cases. A separate perilesional zone, which was predominantly hyperechoic in 41.8% and both hypo and hyperechoic in 12.7%, could be identified in 54.5% of cases. Grade 4 tumors were more likely to have an irregular crenated margin (71.2%) with a single large area of necrosis, while Grade 3 tumors were likely to have smooth (31.3%) or non-characterizable margins (31.2%) with no or multiple areas of necrosis. IDH-negative tumors were more likely to have a single large focus of necrosis. Among the GBMs (52 cases), MIB labelling index of>15% was associated with poorly delineated, uncharacterizable margins, when compared with MIB labelling index<15% (23.5 vs. 0%), (p=0.046). Conclusion A detailed semantic proforma was developed for brain tumors and was internally validated. A few ultrasound sematic features were identified correlating with histological features in high-grade gliomas. It will require further external validation for refinement and acceptability.
Osteoblast-specific inactivation of p53 results in locally increased bone formation

Inactivation of the tumor suppressor p53 (encoded by the Trp53 gene) is relevant for development and growth of different cancers, including osteosarcoma, a primary bone tumor mostly affecting children and young adolescents. We have previously shown that deficiency of the ribosomal S6 kinase 2 (Rsk2) limits osteosarcoma growth in a transgenic mouse model overexpressing the proto-oncogene c-Fos. Our initial aim for the present study was to address the question, if Rsk2 deficiency would also influence osteosarcoma growth in another mouse model. For that purpose, we took advantage of Trp53fl/fl mice, which were crossed with Runx2Cre transgenic mice in order to inactivate p53 specifically in osteoblast lineage cells. However, since we unexpectedly identified Runx2Cre-mediated recombination also in the thymus, the majority of 6-month-old Trp53fl/fl;Runx2-Cre (thereafter termed Trp53Cre) animals displayed thymic lymphomas, similar to what has been described for Trp53-deficient mice. Since we did not detect osteosarcoma formation at that age, we could not follow our initial aim, but we studied the skeletal phenotype of Trp53Cre mice, with or without additional Rsk2 deficiency. Here we unexpectedly observed that Trp53Cre mice display a unique accumulation of trabecular bone in the midshaft region of the femur and the humerus, consistent with its previously established role as a negative regulator of osteoblastogenesis. Since this local bone mass increase in Trp53Cre mice was significantly reduced by Rsk2 deficiency, we isolated bone marrow cells from the different groups of mice and analyzed their behavior ex vivo. Here we observed a remarkable increase of colony formation, osteogenic differentiation and proliferation in Trp53Cre cultures, which was unaffected by Rsk2 deficiency. Our data thereby confirm a critical and tumorigenesis-independent function of p53 as a key regulator of mesenchymal cell differentiation.
Using whole-genome sequence data to examine the epidemiology of Salmonella, Escherichia coli and associated antimicrobial resistance in raccoons (Procyon lotor), swine manure pits, and soil samples on swine farms in southern Ontario, Canada

To better understand the contribution of wildlife to the dissemination of Salmonella and antimicrobial resistance in Salmonella and Escherichia coli, we examined whole-genome sequence data from Salmonella and E. coli isolates collected from raccoons (Procyon lotor) and environmental sources on farms in southern Ontario. All Salmonella and phenotypically resistant E. coli collected from raccoons, soil, and manure pits on five swine farms as part of a previous study were included. We assessed for evidence of potential transmission of these organisms between different sources and farms utilizing a combination of population structure assessments (using core-genome multi-locus sequence typing), direct comparisons of multi-drug resistant isolates, and epidemiological modeling of antimicrobial resistance (AMR) genes and plasmid incompatibility (Inc) types. Univariable logistic regression models were fit to assess the impact of source type, farm location, and sampling year on the occurrence of select resistance genes and Inc types. A total of 159 Salmonella and 96 resistant E. coli isolates were included. A diversity of Salmonella serovars and sequence types were identified, and, in some cases, we found similar or identical Salmonella isolates and resistance genes between raccoons, soil, and swine manure pits. Certain Inc types and resistance genes associated with source type were consistently more likely to be identified in isolates from raccoons than swine manure pits, suggesting that manure pits are not likely a primary source of those particular resistance determinants for raccoons. Overall, our data suggest that transmission of Salmonella and AMR determinants between raccoons and swine manure pits is uncommon, but soil-raccoon transmission appears to be occurring frequently. More comprehensive sampling of farms, and assessment of farms with other livestock species, as well as additional environmental sources (e.g., rivers) may help to further elucidate the movement of resistance genes between these various sources.
Dependence of optical receiver sensitivity, in a 147-Mbit/s heterodyne DPSK system, as a function of optical and electrical parameter variations

Measurements of the changes in optical receiver sensitivity are described. They are caused by (a) the effect of bandpass and low-pass filtering, (b) the dependence on integer and noninteger values of the intermediate-frequency-to-bit-rate ratio, (c) the influence of the local oscillator power, and (d) the impact of deviation from ideal pi phase-shift modulation. The studies were conducted at lambda =1.523 mu m and at a bit rate of 147.75 Mb/s, using external-cavity lasers with negligible phase noise. The results demonstrate the conditions for optimum DPSK system performance in the absence of laser phase noise. The receiver degradation observed for deviations from optimal electrical and optical conditions have been measured and found to be in good agreement with earlier theoretical calculations of microwave phase modulated schemes. >
Systematic Ground Motion Observations in the Canterbury Earthquakes and Region-Specific Non-Ergodic Empirical Ground Motion Modeling

This paper presents an examination of ground motion observations from 20 near-source strong motion stations during the most significant ten events in the 2010–2011 Canterbury earthquake sequence to examine region-specific systematic effects based on relaxing the conventional ergodic assumption. On the basis of similar site-to-site residuals, surfical geology, and geographical proximity, 15 of the 20 stations are grouped into four sub-regions: the Central Business District; and Western, Eastern, and Northern suburbs. Mean site-to-site residuals for these sub-regions then allows for the possibility of non-ergodic ground motion prediction over these sub-regions of Canterbury, rather than only at strong motion station locations. The ratio of the total non-ergodic vs. ergodic standard deviation is found to be, on average, consistent with previous studies, however it is emphasized that on a site-by-site basis the non-ergodic standard deviation can easily vary by ±20%.
The Influence of Expertise upon the Designer's Approach to Studio Practice and Tool Use

ABSTRACT Industrial design is characterized by the embodiment of design intentions. From conceptualization through to design specification, the designer employs a variety of design tools to externalize and develop design solutions to often ill-defined design problems. Surveys of student and practicing designers synthesise existing theoretical and empirical studies of design practice to analyse designer attitudes towards tool use and effectiveness. The survey studies illustrate the influence of expertise upon the designer's attitudes towards tool use during studio practice. Results indicate a relationship between limited experience and the designer's perceptions of and approaches to iterative exploration and design divergence. The use of certain designerly tools appear to compound a tendency for design convergence and fixation.
A Study of a Simple PDP Driver Architecture using the Transformer Network

In this paper, a cost-effective PDP driving circuit using the transformer network is proposed. Compared with the previous works, the half-bridge type energy recovery circuit recovers the reactive energy not to the capacitor but to the source. A single sustain board architecture removes the blocking switches which are placed on the discharge path in parallel, thus reducing the number of devices. A simple reset circuit generates the same waveform as the previous approaches. The circuit configuration and modified driving waveforms are compared with the previous works. The validity of the proposed simplified driver is verified through tests using a 6-inch panel
Inpatient Case-mix Cost Vs Average Cost for Health Care Services in King Fahd Central Hospital, Saudi Arabia: A Comparative Study

Health care systems aim to deliver high-quality medical care while considering efficient resource usage and cost-effective forms of interventions. Such purposes require scientific tools or mechanisms which aid in cost assessment before the efforts of cost reduction are considered. Diagnosis-related groups based costing methodology (Case-mix) is considered one of the preferred costing approaches in the health care sector. King Fahd Central hospital Jazan, the only tertiary hospital in the Jazan region, was selected for case-mix system-based patient-level costing of health services. The study’s objective was to estimate the cost per Diagnosis-Related Group (DRG) per inpatient admission and compare it with the already established average cost of health care services for inpatients. We applied a cross-sectional retrospective approach to categorize the inpatients based on their diagnosis and procedures and then estimate the actual cost of health care services provided to inpatients during 2018 and compared it with the average cost of the health services. There was a considerable difference between DRG-based costing (SAR 269,663,897) and average costing (SAR 247,035,938). The Diagnosis Related Group costing was found to be more reliable and representative of the services provided to the patients and is recommended to be used for reimbursement purposes.
Targeting hypoxia and hypoxia‐inducible factor‐1 in the tumor microenvironment for optimal cancer immunotherapy

The development of new strategies of anticancer immunotherapies has provided promising approaches in the treatment of solid tumors. However, despite the improved survival in responders, most of the patients show incomplete responses with a lack of remarkable clinical improvement. Hypoxia has been identified as a common characteristic of solid tumors contributing to different aspects of tumor progression, including invasion, metastasis, and the creation of the immunosuppressive tumor microenvironment. Hypoxia, through its main mediator, hypoxia‐inducible factor‐1 (HIF‐1) is also associated with the limited efficacy of immunotherapies. Therefore, designing new strategies for immunotherapy implicating therapeutic targeting of HIF‐1 molecules may enhance the clinical effectiveness of immunotherapy. Here, we discuss the contribution of hypoxia to the development of the immunosuppressive tumor microenvironment. We will also outline different strategies for targeting hypoxia to provide insight into the therapeutic potential of the application of such strategies to improve the clinical benefit of cancer immunotherapy.
Offshore Wind Power Assessment on the East Coast of Saudi Arabia

This paper, to the best of author's knowledge, presents the first wind resource assessment for offshore-wind energy off the mainland coasts of Saudi Arabia, despite the onshore wind resource being known. The study utilized wind speed data from, in effect, an offshore meteorological station to study the annual and seasonal variation of wind speed, wind speed frequency distribution, energy yield and consequent opportunity for reduction in green house gases (GHG) emissions. These results were compared with contemporaneous data from a mainland location ∼ 10 km inland at the same longitude Energy yields were calculated using HOMER and RetScreen models. The annual mean wind measured at Abu Ali Island, the offshore location, was 5.43 m/s. This is larger than the 4.9 m/s measured over the same period at Abu Kharuf, the nearby inland location. Larger wind speeds were found in winter months than in summer months at both locations. At Abu Ali Island, the power of the wind could be extracted for 75% of the time at hub-height of 60 meters using modern wind machines of cut-in-speed 4 m/s, in comparison with 60% of time at Abu Kharuf. The prevailing wind direction was found to be North (N), North West (NNW) and North East (NNE).
Influence of SARS-CoV-2 on airway mucus production: A review and proposed model

Coronavirus disease 2019 (COVID-19) is a worldwide pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that has affected millions of lives. Individuals who survive severe COVID-19 can experience sustained respiratory symptoms that persist for months after initial infection. In other airway diseases, abnormal airway mucus contributes to sustained airway symptoms. However, the impact of SARS-CoV-2 on airway mucus has received limited attention. In the current review, we assess literature describing the impact of SARS-CoV-2 on airway pathophysiology with specific emphasis on mucus production. Accumulating evidence suggests that the 2 major secreted airway mucin glycoproteins, MUC5AC and MUC5B, are abnormal in some patients with COVID-19. Aberrations in MUC5AC or MUC5B in response to SARS-CoV-2 infection are likely due to inflammation, though the responsible mechanisms have yet to be determined. Thus, we also provide a proposed model highlighting mechanisms that can contribute to acute and sustained mucus abnormalities in SARS-CoV-2, with an emphasis on inflammatory cells and mediators, including mast cells and histamine. Last, we bring to light the challenges of studying abnormal mucus production in SARS-CoV-2 infections and discuss the strengths and limitations of model systems commonly used to study COVID-19. The evidence to date suggests that ferrets, nonhuman primates, and cats may have advantages over other models to investigate mucus in COVID-19.
Molecular characterization of Barrett’s esophagus at single-cell resolution

Significance Barrett’s esophagus (BE), the premalignant condition of esophageal adenocarcinoma, is categorized into different stages which correlate with the risk of developing carcinoma. We performed single-cell DNA-sequencing experiments with fresh biopsies, which revealed the appearance of a specific T > C and T > G mutational signature, known as COSMIC signature SBS17, in BE cells that are chromosomally unstable. The SBS17-specific mutations were, however, not detected in chromosomally stable BE cells. Additionally, we performed single-cell RNA sequencing experiments which identified seven genes that facilitate the distinction between different BE stages on histological sections. Barrett’s esophagus (BE) is categorized, based on morphological appearance, into different stages, which correlate with the risk of developing esophageal adenocarcinoma. More advanced stages are more likely to acquire chromosomal instabilities, but stage-specific markers remain elusive. Here, we performed single-cell DNA-sequencing experiments (scDNAseq) with fresh BE biopsies. Dysplastic BE cells frequently contained chromosomal instability (CIN) regions, and these CIN cells carried mutations corresponding to the COSMIC mutational signature SBS17, which were not present in biopsy-matched chromosomally stable (CS) cells or patient-matched nondiseased control cells. CS cells were predominantly found in nondysplastic BE biopsies. The single-base substitution (SBS) signatures of all CS BE cells analyzed were indistinguishable from those of nondiseased esophageal or gastric cells. Single-cell RNA-sequencing (scRNAseq) experiments with BE biopsies identified two sets of marker genes which facilitate the distinction between columnar BE epithelium and nondysplastic/dysplastic stages. Moreover, histological validation confirmed a correlation between increased CLDN2 expression and the presence of dysplastic BE stages. Our scDNAseq and scRNAseq datasets, which are a useful resource for the community, provide insight into the mutational landscape and gene expression pattern at different stages of BE development.
Pain in the Ehlers–Danlos syndromes: Mechanisms, models, and challenges

Chronic pain is one of the most common, yet poorly studied, complaints in people suffering from Ehlers–Danlos syndromes (EDS). This heterogeneous group of heritable connective tissue disorders is typically characterized by skin hyperextensibility, joint hypermobility, and generalized connective tissue fragility. Most EDS types are caused by genetic defects that affect connective tissue biosynthesis, thereby compromising collagen biosynthesis or fibrillogenesis and resulting in a disorganized extracellular matrix. Even though chronic pain is a major source of disability, functional impairment, and psychosocial suffering in EDS, currently used analgesics and other treatment strategies provide inadequate pain relief and thus represents an important unmet medical need. An important contributor to this is the lack of knowledge about the underlying mechanisms. In this narrative review, we summarize the current understanding of pain and the associated mechanisms in EDS based on clinical studies focusing on questionnaires and experimental pain testing as well as studies in animal models of EDS. In addition, we highlight the challenges, gaps, and opportunities in EDS‐pain research.
Genomic Stratification of Resectable Colorectal Liver Metastasis Patients and Implications for Adjuvant Therapy and Survival

Supplemental Digital Content is available in the text Objective: To determine whether genomic risk groups identified by somatic mutation testing of colorectal liver metastasis (CRLM) can be used for “molecularly-guided” selection for adjuvant systemic chemotherapy and hepatic artery infusion of FUDR (SYS+HAI-FUDR). Background: Several genomic biomarkers have been associated with clinical phenotype and survival for patients with resectable CRLM. It is unknown whether prognostication afforded by genomic stratification translates into enhanced patient selection for adjuvant hepatic artery infusion therapy. Methods: Consecutive patients with resected CRLM and available mutational characterization via Memorial Sloan Kettering–Integrated Mutation Profiling of Actionable Cancer Targets were reviewed from a prospective institutional database. Patients were stratified into three genomic risk groups based on previously defined alterations in SMAD4, EGFR and the RAS/RAF pathway. The association between SYS+HAI-FUDR and overall survival, relative to adjuvant chemotherapy alone (SYS), was evaluated in each genomic risk group by Cox proportional hazard regression and propensity score matched analyses. Results: A total of 334 patients (SYS+HAI-FUDR 204; SYS 130) were identified; the rates of RAS/RAF alterations and SMAD4 inactivation were 47.4% and 11.7%, respectively. After a median follow-up of 58 months, adjuvant SYS+HAI-FUDR was independently associated with a reduced risk of death (HR 0.50, 95%CI 0.26–0.98, P = 0.045) in the low-risk genomic group, but not in the moderate-risk (HR 1.07, 95%CI 0.5–2.07, P = 0.749) or high-risk (HR 1.62, 95%CI 0.29–9.12, P = 0.537) cohorts. Following propensity score matching, adjuvant SYS+HAI-FUDR remained associated with significant improvements in long-term survival selectively in the low-risk genomic cohort (5-year actuarial survival: 89% vs. 68%, P = 0.019). Conclusions: Genomic alterations in RAS/RAF, SMAD4, and EGFR may be useful to guide treatment selection in resectable CRLM patients and warrant external validation and integration in future clinical trial design.
Metronomic Chemotherapy for Metastatic Breast Cancer

Background: As disease control and quality of life play a leading role in metastatic breast cancer (MBC), metronomic chemotherapy (MCT) is gaining popularity alongside conventional chemotherapy (CCT) and targeted therapies. Summary: MCT, defined as continuous administration of low-dose chemotherapeutic agents, is accepted as a therapy that exerts its effects via immunomodulation, anti-angiogenesis and direct cytotoxic effects. Oral administration of MCT is safe, easy to handle, and allows for flexible drug dosing. Dose accumulations associated with non-tolerable side effects are rare, so the medication can be administered for longer periods of time. Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic disease resistant to endocrine-based therapy and not requiring rapid tumor response are generally suitable for MCT. However, MCT may also be promising in patients with triple-negative and HER2-positive tumors without aggressive disease who prefer a lower toxicity profile compared to CCT. The most commonly used agents are cyclophosphamide (CTX), methotrexate (MTX), capecitabine (CAPE), and vinorelbine (VRL), whereby a combination of agents is frequently applied. Key Messages: Based on the growing body of evidence, MCT can be considered as a suitable treatment option in selected MBC patients. Nevertheless, there is an urgent need for randomized controlled trials comparing MCT with CCT, but also with best supportive care. Due to the multimodal mechanisms of action, the combination with targeted and immunological therapies may represent a new promising approach for the treatment of MBC.