Miracle-dz/UniFAR-FTUs huggingface dataset:
Genomic approaches to cancer and minimal residual disease detection using circulating tumor DNA

Liquid biopsies using cell-free circulating tumor DNA (ctDNA) are being used frequently in both research and clinical settings. ctDNA can be used to identify actionable mutations to personalize systemic therapy, detect post-treatment minimal residual disease (MRD), and predict responses to immunotherapy. ctDNA can also be isolated from a range of different biofluids, with the possibility of detecting locoregional MRD with increased sensitivity if sampling more proximally than blood plasma. However, ctDNA detection remains challenging in early-stage and post-treatment MRD settings where ctDNA levels are minuscule giving a high risk for false negative results, which is balanced with the risk of false positive results from clonal hematopoiesis. To address these challenges, researchers have developed ever-more elegant approaches to lower the limit of detection (LOD) of ctDNA assays toward the part-per-million range and boost assay sensitivity and specificity by reducing sources of low-level technical and biological noise, and by harnessing specific genomic and epigenomic features of ctDNA. In this review, we highlight a range of modern assays for ctDNA analysis, including advancements made to improve the signal-to-noise ratio. We further highlight the challenge of detecting ultra-rare tumor-associated variants, overcoming which will improve the sensitivity of post-treatment MRD detection and open a new frontier of personalized adjuvant treatment decision-making.
Pleural Empyema Caused by Streptococcus intermedius and Fusobacterium nucleatum: A Distinct Entity of Pleural Infections

Abstract Background Many community-acquired pleural infections are caused by facultative and anaerobic bacteria from the human oral microbiota. The epidemiology, clinical characteristics, pathogenesis, and etiology of such infections are little studied. The aim of the present prospective multicenter cohort study was to provide a thorough microbiological and clinical characterization of such oral-type pleural infections and to improve our understanding of the underlying etiology and associated risk factors. Methods Over a 2-year period, we included 77 patients with community-acquired pleural infection, whereof 63 (82%) represented oral-type pleural infections. Clinical and anamnestic data were systematically collected, and patients were offered a dental assessment by an oral surgeon. Microbial characterizations were done using next-generation sequencing. Obtained bacterial profiles were compared with microbiology data from previous investigations on odontogenic infections, bacteremia after extraction of infected teeth, and community-acquired brain abscesses. Results From the oral-type pleural infections, we made 267 bacterial identifications representing 89 different species. Streptococcus intermedius and/or Fusobacterium nucleatum were identified as a dominant component in all infections. We found a high prevalence of dental infections among patients with oral-type pleural infection and demonstrate substantial similarities between the microbiology of such pleural infections and that of odontogenic infections, odontogenic bacteremia, and community-acquired brain abscesses. Conclusions Oral-type pleural infection is the most common type of community-acquired pleural infection. Current evidence supports hematogenous seeding of bacteria from a dental focus as the most important underlying etiology. Streptococcus intermedius and Fusobacterium nucleatum most likely represent key pathogens necessary for establishing the infection.
Zinc protects against lead-induced testicular damage via modulation of steroidogenic and xanthine oxidase/uric acid/caspase 3-mediated apoptotic signaling in male Wistar rats

Abstract Aim This study evaluated the effect of lead, with or without zinc co-administration, on steroidogenic and xanthine oxidase (XO)/uric acid (UA)/caspase 3-mediated apoptotic signaling in the testis. Materials and methods Forty male Wistar rats were divided into four groups at random; vehicle-treated control, zinc-treated, lead-treated, and lead + zinc-treated groups. Results Lead exposure significantly lowered overall weight gain, testicular, epididymal, seminal vesicle, and prostate weights. Also, lead decreased sperm count, viability and motility but increased the fraction of sperm with aberrant morphology. In addition, lead caused a marked rise in the level of UA and XO activity but a decrease in nuclear factor erythroid 2-related factor 2 (Nrf2), reduced glutathione (GSH) as well as total antioxidant capacity (TAC) levels, and superoxide dismutase (SOD) and catalase activities. Furthermore, lead increased the testicular levels of nuclear factor kappa B (NFkB), interleukin-1beta (IL-1β), and tumour necrotic factor-alpha (TNF-α), which were associated with an increase in testicular caspase 3 activity and DNA fragmentation as well as a decline in circulating gonadotropin releasing hormone (GnRH), luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone, and testicular 3β-hydroxysteroid dehydrogenase (3β-HSD) and 17β-hydroxysteroid dehydrogenase (17β-HSD). These were associated with lead-induced degenerative changes in testicular tissues evidenced by shrunken seminiferous tubules, degeneration and sloughing of germ cells. Co-administration of zinc prevented lead-induced testicular injury by ameliorating oxidative stress, apoptosis, and inflammation through downregulation of XO/UA/caspase 3 pathway and upregulation of testicular 3β-HSD/17β-HSD. Conclusion This study demonstrated that zinc protected against lead-induced testicular toxicity via the downregulation of XO/UA/caspase 3 signaling.
Short-term load forecasting method based on support vector machine combined with wavelet transform

A method based on wavelet decomposing and support vector machine was proposed. Load series was decomposed into different frequency sub-series. The series with high frequency was denoised using soft threshold. Denoised series was decomposed using different wavelet, each sub-series was modeled by using matching support vector machines. Results showed that db4 wavelet had high forecasting accuracy, its absolute percent forecasting error was 1.6692. The result obtained by using support vector machine directly and the above result were compared, simulation showed the effectiveness of the proposed method.
Designing and building OSCEBot ® for virtual OSCE – Performance evaluation

ABSTRACT With AI’s advancing technology and chatbots becoming more intertwined in our daily lives, pedagogical challenges are occurring. While chatbots can be used in various disciplines, they play a particularly significant role in medical education. We present the development process of OSCEBot ®, a chatbot to train medical students in the clinical interview approach. The SentenceTransformers, or SBERT, framework was used to develop this chatbot. To enable semantic search for various phrases, SBERT uses siamese and triplet networks to build sentence embeddings for each sentence that can then be compared using a cosine-similarity. Three clinical cases were developed using symptoms that followed the SOCRATES approach. The optimal cutoffs were determined, and each case’s performance metrics were calculated. Each question was divided into different categories based on their content. Regarding the performance between cases, case 3 presented higher average confidence values, explained by the continuous improvement of the cases following the feedback acquired after the sessions with the students. When evaluating performance between categories, it was found that the mean confidence values were highest for previous medical history. It is anticipated that the results can be improved upon since this study was conducted early in the chatbot deployment process. More clinical scenarios must be created to broaden the options available to students.
Global Measurements of the Radiation Exposure of Civil Air Crews from 1997 to 1999

The exposure of aircrew to the increased cosmic radiation at aviation flight altitudes will soon be treated in the European Union as an occupational risk, with the consequence that the radiation exposure of aircrew must be determined. This work describes about 200 h of in-flight measurements performed during a period of 22 months from 1997 to 1999 on cargo aircraft. Various monitors were used to measure different radiation field components and to investigate the spatial dose equivalent rate distribution and the spatial radiation field composition. The monitors were rem counters for neutrons, and a scintillator and an ionisation chamber for the directly ionising and photon components. One of the main goals was to calibrate the monitors in the cosmic radiation field at flight altitudes against a tissue-equivalent proportional counter (TEPC) used as a reference instrument for the quantity ambient dose equivalent. The sum of the readings of a neutron rem counter with its response extended to high energy neutrons and of an ionisation chamber was found to be a fair approximation of the total dose equivalent as measured by the TEPC. The 'field calibration factor determined is 1.0±0.1. The global dose equivalent distributions as a function of magnetic latitude and cut-off rigidity were obtained for the range of altitudes encountered in civil aviation and can be described by simple mathematical functions for use in rough dose-equivalent rate estimates. Surrounding the TEPC with an active shielding detector and the application of coincidence techniques allowed dose equivalent fractions of charged and uncharged particles in the cosmic radiation to be separated. The low-LET radiation component was found to consist of 90% charged particles and 10% photons while the high-LET component contains a fraction of 30% from protons (pions) and 70% from neutrons.
Chemokine receptor CXCR7 activates Aurora Kinase A and promotes neuroendocrine prostate cancer growth

CXCR7 is an atypical chemokine receptor that recruits β-arrestin (ARRB2) and internalizes into clathrin-coated intracellular vesicles where the complex acts as a scaffold for cytoplasmic kinase assembly and signal transduction. Here, we report that CXCR7 was elevated in the majority of prostate cancer (PCa) cases with neuroendocrine features (NEPC). CXCR7 markedly induced mitotic spindle and cell cycle gene expression. Mechanistically, we identified Aurora Kinase A (AURKA), a key regulator of mitosis, as a novel target that was bound and activated by the CXCR7-ARRB2 complex. CXCR7 interacted with proteins associated with microtubules and golgi, and, as such, the CXCR7-ARRB2-containing vesicles trafficked along the microtubules to the pericentrosomal golgi apparatus, where the complex interacted with AURKA. Accordingly, CXCR7 promoted PCa cell proliferation and tumor growth, which was mitigated by AURKA inhibition. In summary, our study reveals a critical role of CXCR7-ARRB2 in interacting and activating AURKA, which can be targeted by AURKA inhibitors to benefit a subset of patients with NEPC.
Specific Cryptosporidium antigens associate with reinfection immunity and protection from cryptosporidiosis

There is no vaccine to protect from cryptosporidiosis, a leading cause of diarrhea in infants in low- and middle-income countries. Here, we comprehensively identified parasite antigens associated with protection from reinfection. A Cryptosporidium protein microarray was constructed by in vitro transcription and translation of 1,761 C. parvum, C. hominis, or C. meleagridis antigens, including proteins with a signal peptide and/or a transmembrane domain. Plasma IgG and/or IgA from Bangladeshi children longitudinally followed for cryptosporidiosis from birth to 3 years of age allowed for identification of 233 seroreactive proteins. Seven of these were associated with protection from reinfection. These included Cp23, Cp17, Gp900, and 4 additional antigens — CpSMP1, CpMuc8, CpCorA and CpCCDC1. Infection in the first year of life, however, often resulted in no detectable antigen-specific antibody response, and antibody responses, when detected, were specific to the infecting parasite genotype and decayed in the months after infection. In conclusion, humoral immune responses against specific parasite antigens were associated with acquired immunity. While antibody decay over time and parasite genotype-specificity may limit natural immunity, this work serves as a foundation for antigen selection for vaccine design.
Biomechanical Evaluation of Posterior Shoulder Instability With a Clinically Relevant Posterior Glenoid Bone Loss Model

Background: Existing biomechanical studies of posterior glenoid bone loss and labral pathology are limited by their use of anterior instability models, which differ in both orientation and morphology and have been performed in only a single, neutral arm position. Purpose: To evaluate the biomechanical effectiveness of a posterior labral repair in the setting of a clinically relevant posterior bone loss model in various at-risk arm positions. Study Design: Controlled laboratory study. Methods: Ten fresh-frozen cadaveric shoulders were tested in 7 consecutive states using a 6 degrees of freedom robotic arm: (1) native, (2) posterior labral tear (6-9 o’clock), (3) posterior labral repair, (4) mean posterior glenoid bone loss (7%) with labral tear, (5) mean posterior glenoid bone loss with labral repair, (6) large posterior glenoid bone loss (28%) with labral tear, and (7) large posterior glenoid bone loss with labral repair. Bone loss was created using 3-dimensional printed computed tomography model templates. Biomechanical testing consisted of 75 N of posterior-inferior force and 75 N of compression at 60° and 90° of flexion and scaption. Posterior-inferior translation, lateral translation, and peak dislocation force were measured for each condition. Results: Labral repair significantly increased dislocation force independent of bone loss state between 10.1 and 14.8 N depending on arm position. Dislocation force significantly decreased between no bone loss and small bone loss (11.9-13.5 N), small bone loss and large bone loss (9.4-14.3 N), and no bone loss and large bone loss (21.2-26.5 N). Labral repair significantly decreased posterior-inferior translation compared with labral tear states by a range of 1.0 to 2.3 mm. In the native state, the shoulder was most unstable in 60° of scaption, with 29.9 ± 6.1-mm posterior-inferior translation. Conclusion: Posterior labral repair improved stability of the glenohumeral joint, and even in smaller to medium amounts of posterior glenoid bone loss the glenohumeral stability was maintained with labral repair in this cadaveric model. However, a labral repair with large bone loss could not improve stability to the native state. Clinical Relevance: This study shows that larger amounts of posterior glenoid bone loss (>25%) may require bony augmentation for adequate stability.
A new metal resistor bolometer for measuring vacuum ultraviolet and soft x radiation

A new metal resistor bolometer has been developed by applying thin‐film technology. It is composed of three layers, a 4‐μm‐thick radiation absorber made of gold, a 7.5‐μm‐thick kapton dielectric, and a 0.1‐μm‐thick 5‐kΩ gold resistor. This detector with the appropriate electronics shows a linear response to radiation power, including both neutral‐particle emission and electromagnetic radiation from the soft x‐ray part of the spectrum to the infrared. The bolometer has a very high operating reliability and sufficient suppression of ambient interference under extreme environmental conditions, such as high neutron and gamma radiation fluxes, high temperatures, mechanical vibrations, and strong electromagnetic fields. In plasma discharges in the ASDEX tokamak a radiation detection limit of 100 μW/cm2 was obtained at a time resolution of 10 ms. The bolometers of an array can be calibrated in situ; the calibration data are reproducible and stable in time within ±10%. Measurements in ASDEX which demonstrate the .
Temperature-dependent carrier state mediated by H-NS promotes the long-term coexistence of Y. pestis and a phage in soil

The study of carrier state phages challenged the canonical lytic-lysogenic binary, and carrier state appears to be ubiquitous and ecologically important. However, the mechanisms of the carrier state are not well elucidated due to the limited phage models. Herein, we reported phage HQ103, similar to Escherichia coli phage P2. In contrast to the temperate P2 phage, the HQ103 phage does not insert its genome into the bacterial chromosome and displays a dual behavior depending on the temperature. At 37°C, HQ103 lyses the host and forms clear plaques due to the truncation of repressor CI and mutation of promoter Pc. In contrast, HQ103 maintains a carrier state lifestyle with Y. pestis at an environmental temperature (21°C). Mechanistically, we found that the host-encoded histone-like nucleoid-structuring protein H-NS, which is highly expressed at 21°C to silence the Cox promoter Pe and inhibits the phage lytic cycle. Subsequently, the HQ103 carrier state Y. pestis could grow and co-exist with the phage in the soil at 21°C for one month. Thus, this study reveals a novel carrier state lifestyle of phage HQ103 due to the H-NS mediated xenogeneic silencing and demonstrates that the carrier state lifestyle could promote long-term phage-host coexist in nature.
Daily Precipitation Forecasting in Dakar Using the NCEP–NCAR Reanalyses

Abstract In order to predict the daily rain amount at Dakar at 1–5-day lead times, 65 thermodynamical and dynamical indices are computed at each grid point for the area 15°S–30°N, 30°W–30°E. The data used are NCEP–NCAR reanalyses and daily rainfall obtained by averaging over 21 rain gauges near Dakar, for 23 Augusts (1968–90). At each lead time and each grid point, a Pearson product–moment correlation coefficient r is computed between each index and the rainfall over 17 Augusts (1968–84). Predictive regression equations are developed including the 65 indices taken at the grid points where their r value is at a maximum. The prediction skill is tested over six Augusts (1985–90). The variance (R2) explained is 42% for the 1-day lead time, it decreases slowly up to the 4-day lead time (35%), and it is 28% at the 5-day lead time. The skill is better than when climatological data are used to predict rain amount. Among the predictors that appear most frequently in the predicting equations are lifting condensatio.
Some two-sided bounding inequalities for the Butzer-Flocke-Hauss omega function

A new integral representation is obtained for the Butzer-Flocke-Hauss complete real-argument Omega function $\Omega(x), $ which is closely associated with the complex-index Bernoulli function $B_\alpha(z)$ and with the complex-index Euler function $E_\alpha(z). $ Three two-sided bounding inequalities are given for this Omega function and their efficiency is also discussed.
Evaluation of blood pressure response during dobutamine stress echocardiography in patients without cardiovascular diseases

Dobutamine stress echocardiography (DSE) is a diagnostic tool for determining coronary artery disease. Considering hypotension and hypertension as important complications of DSE, we aimed to evaluate the blood pressure (BP) responses during DSE. Patients without known cardiovascular diseases who underwent DSE were included. We excluded patients who had hypertension, diabetes mellitus, a known history of cardiovascular diseases, and those taking vasoactive medications. Systolic (SBP) and diastolic (DBP) blood pressure were recorded at baseline and peak stress. We included 688 patients with an age of 57.9 ± 12.01 years. During DSE, SBP (+19.72 ± 26.51 mm Hg, p < 0.001), DBP (+5.52 ± 17.35 mm Hg, p < 0.001), and HR (+54.05 ± 22.45 bpm, p < 0.001) significantly increased from baseline to peak stress. The normal cut‐off value was measured between 101–210 mm Hg for SBP and 50–121 mm Hg for DBP. According to this normal cutoff, 11 (1.3%) and 30 (4.4%) patients had hypotensive and hypertensive SBP and 15 (2.2%) and 21 (3.1%) patients had hypotensive and hypertensive DBP, respectively. The hypotensive response was correlated with baseline SBP (r = 0.6, p = 0.001) and atropine (r = −2.18, p = 0.043), and the hypertensive response was correlated with baseline SBP (r = 0.048, p < 0.001). Baseline BP and atropine consumption were the independent variables associated with the outside‐the‐normal range of blood pressure responses.
The claim of primacy of human gut Bacteroides ovatus in dietary cellobiose degradation

ABSTRACT A demonstration of cellulose degrading bacterium from human gut changed our view that human cannot degrade the cellulose. However, investigation of cellulose degradation by human gut microbiota on molecular level has not been completed so far. We showed here, using cellobiose as a model that promoted the growth of human gut key members, such as Bacteroides ovatus (BO), to clarify the molecular mechanism. Our results showed that a new polysaccharide utilization locus (PUL) from BO was involved in the cellobiose capturing and degradation. Further, two new cellulases BACOVA_02626GH5 and BACOVA_02630GH5 on the cell surface performed the degradation of cellobiose into glucose were determined. The predicted structures of BACOVA_02626GH5 and BACOVA_02630GH5 were highly homologous with the cellulase from soil bacteria, and the catalytic residues were highly conservative with two glutamate residues. In murine experiment, we observed cellobiose reshaped the composition of gut microbiota and probably modified the metabolic function of bacteria. Taken together, our findings further highlight the evidence of cellulose can be degraded by human gut microbes and provide new insight in the field of investigation on cellulose.
SerpinB1 is required for Rev‐erbα‐mediated protection against acute lung injury induced by lipopolysaccharide‐in mice

Acute lung injury (ALI) is a serious, life‐threatening inflammation of the lungs that still lacks effective treatment. We previously showed that serine protease inhibitor B1 (SerpinB1) protects against ALI induced by orthotopic autologous liver transplantation. However, the role of SerpinB1 in lipopolysaccharide (LPS)‐induced ALI and its regulatory mechanisms are not known.
Quasi-Newton methods for solving maximum eigenvalue and its corresponding eigenvector of high order matrix

This paper is aimed to solve the maximum eigenvalue of high order matrix and its corresponding eigenvector through the method which transfers the equations into a higher order nonlinear equations. At the same time,this paper puts forward the Quasi-Newton method which can solve the maximum eigenvalue and its corresponding eigenvector, the rearranging formula and algorithm of Broyden methods are given to solve the maximum eigenvalue and the corresponding eigenvector; the rearranging formula and algorithm of BFS methods; the rearranging formula and algorithm of DFP methods. The judgment matrix of analytic hierarchy process is used as an example. The results show that the idea is feasible and the convergence speed is higher.
Entropy Optimization Model on Bimatrix Game

This paper presents an entropy optimization model on bimatrix game (two-person non-zero-sum game). According to the Maximum Entropy Principle the entropy function of the players of bimatrix game has been considered as an objective and using it we formulate the model. This model is a non-linear programming model due to entropy function. The solution concept is based on Kuhn-Tucker optimality conditions. A numerical example is illustrated the results in this paper.