Large language models encode clinical knowledge.

Large language models (LLMs) have demonstrated impressive capabilities, but the bar for clinical applications is high. Attempts to assess the clinical knowledge of models typically rely on automated evaluations based on limited benchmarks. Here, to address these limitations, we present MultiMedQA, a benchmark combining six existing medical question answering datasets spanning professional medicine, research and consumer queries and a new dataset of medical questions searched online, HealthSearchQA. We propose a human evaluation framework for model answers along multiple axes including factuality, comprehension, reasoning, possible harm and bias. In addition, we evaluate Pathways Language Model1 (PaLM, a 540-billion parameter LLM) and its instruction-tuned variant, Flan-PaLM2 on MultiMedQA. Using a combination of prompting strategies, Flan-PaLM achieves state-of-the-art accuracy on every MultiMedQA multiple-choice dataset (MedQA3, MedMCQA4, PubMedQA5 and Measuring Massive Multitask Language Understanding (MMLU) clinical topics6), including 67.6% accuracy on MedQA (US Medical Licensing Exam-style questions), surpassing the prior state of the art by more than 17%. However, human evaluation reveals key gaps. To resolve this, we introduce instruction prompt tuning, a parameter-efficient approach for aligning LLMs to new domains using a few exemplars. The resulting model, Med-PaLM, performs encouragingly, but remains inferior to clinicians. We show that comprehension, knowledge recall and reasoning improve with model scale and instruction prompt tuning, suggesting the potential utility of LLMs in medicine. Our human evaluations reveal limitations of today's models, reinforcing the importance of both evaluation frameworks and method development in creating safe, helpful LLMs for clinical applications.

Multi-Frequency 3D Shear Wave Absolute Vibro-Elastography (S-WAVE) System for the Prostate.

This article describes a novel system for quantitative and volumetric measurement of tissue elasticity in the prostate using simultaneous multi-frequency tissue excitation. Elasticity is computed by using a local frequency estimator to measure the three-dimensional local wavelengths of steady-state shear waves within the prostate gland. The shear wave is created using a mechanical voice coil shaker which transmits simultaneous multi-frequency vibrations transperineally. Radio frequency data is streamed directly from a BK Medical 8848 transrectal ultrasound transducer to an external computer where tissue displacement due to the excitation is measured using a speckle tracking algorithm. Bandpass sampling is used that eliminates the need for an ultra-fast frame rate to track the tissue motion and allows for accurate reconstruction at a sampling frequency that is below the Nyquist rate. A roll motor with computer control is used to rotate the transducer and obtain 3D data. Two commercially available phantoms were used to validate both the accuracy of the elasticity measurements as well as the functional feasibility of using the system for in vivo prostate imaging. The phantom measurements were compared with 3D Magnetic Resonance Elastography (MRE), where a high correlation of 96% was achieved. In addition, the system has been used in two separate clinical studies as a method for cancer identification. Qualitative and quantitative results of 11 patients from these clinical studies are presented here. Furthermore, an AUC of 0.87±0.12 was achieved for malignant vs. benign classification using a binary support vector machine classifier trained with data from the latest clinical study with leave one patient out cross-validation.

Robust and data-efficient generalization of self-supervised machine learning for diagnostic imaging.

Machine-learning models for medical tasks can match or surpass the performance of clinical experts. However, in settings differing from those of the training dataset, the performance of a model can deteriorate substantially. Here we report a representation-learning strategy for machine-learning models applied to medical-imaging tasks that mitigates such 'out of distribution' performance problem and that improves model robustness and training efficiency. The strategy, which we named REMEDIS (for 'Robust and Efficient Medical Imaging with Self-supervision'), combines large-scale supervised transfer learning on natural images and intermediate contrastive self-supervised learning on medical images and requires minimal task-specific customization. We show the utility of REMEDIS in a range of diagnostic-imaging tasks covering six imaging domains and 15 test datasets, and by simulating three realistic out-of-distribution scenarios. REMEDIS improved in-distribution diagnostic accuracies up to 11.5% with respect to strong supervised baseline models, and in out-of-distribution settings required only 1-33% of the data for retraining to match the performance of supervised models retrained using all available data. REMEDIS may accelerate the development lifecycle of machine-learning models for medical imaging.

3-D Transducer Mounted Shear Wave Absolute Vibro-Elastography: Proof of Concept.

Quantitative tissue stiffness characterization using ultrasound (US) has been shown to improve prostate cancer (PCa) detection in multiple studies. Shear wave absolute vibro-elastography (SWAVE) allows quantitative and volumetric assessment of tissue stiffness using external multifrequency excitation. This article presents a proof of concept of a first-of-a-kind 3-D hand-operated endorectal SWAVE system designed to be used during systematic prostate biopsy. The system is developed with a clinical US machine, requiring only an external exciter that can be mounted directly to the transducer. Subsector acquisition of radio frequency (RF) data allows imaging of shear waves with a high effective frame rate (up to 250 Hz). The system was characterized using eight different quality assurance phantoms. Due to the invasive nature of prostate imaging, at this early stage of development, validation of in vivo human tissue was instead carried out by intercostally scanning the livers of n = 7 healthy volunteers. The results are compared with 3-D magnetic resonance elastography (MRE) and an existing 3-D SWAVE system with a matrix array transducer (M-SWAVE). High correlations were found with MRE (99% in phantoms, 94% in liver data) and with M-SWAVE (99% in phantoms, 98% in liver data).

Registration of trans-perineal template mapping biopsy cores to volumetric ultrasound.

PURPOSE: Pathology from trans-perineal template mapping biopsy (TTMB) can be used as labels to train prostate cancer classifiers. In this work, we propose a framework to register TTMB cores to advanced volumetric ultrasound data such as multi-parametric transrectal ultrasound (mpTRUS). METHODS: The framework has mainly two steps. First, needle trajectories are calculated with respect to the needle guiding template-considering deflections in their paths. In standard TTMB, a sparsely sampled ultrasound volume is taken prior to the procedure which contains the template overlaid on top of it. The position of this template is detected automatically, and the cores are mapped following the calculated needle trajectories. Second, the TTMB volume is aligned to the mpTRUS volume by a two-step registration method. Using the same transformations from the registration step, the cores are registered from the TTMB volume to the mpTRUS volume. RESULTS: TTMB and mpTRUS of 10 patients were available for this work. The target registration errors (TRE) of the volumes using landmarks picked by three research assistants (RA) and one radiation oncologist (RO) were on average 1.32 ± 0.7 mm and 1.03 ± 0.6 mm, respectively. Additionally, on average, our framework takes only 97 s to register the cores. CONCLUSION: Our proposed framework allows a quick way to find the spatial location of the cores with respect to volumetric ultrasound. Furthermore, knowing the correct location of the pathology will facilitate focal treatment and will aid in training imaging-based cancer classifiers.

Risk factors of severe COVID-19 in people with multiple sclerosis : A systematic review and meta-analysis.

OBJECTIVES: To gather, synthesize, and meta-analyze data regarding the risk factors associated with a severe course of COVID-19 among patients with multiple sclerosis (pwMS). METHODS: MEDLINE, Embase, Scopus, and WoS were searched in May 2021. Briefly, the eligibility criteria included: 1) studies assessing COVID-19 severity among adult pwMS; 2) definitive diagnoses or high clinical suspicion of COVID-19; 3) a categorization of COVID-19 severity into at least two categories; 4) quantitative effect size and precision measurements; and 5) English language; and 6) clear effect size/precision measures. internal validity of studies was assessed using the NIH Quality Assessment Tools. A list of possible risk factors was created based on the search results and was later used in extraction, synthesis, and meta-analysis of the data. RESULTS: Thirteen studies were included in the syntheses. Outcome measures were either extracted from the papers, obtained from the primary researchers or calculated manually. The meta-analyses showed a significantly (P<0.05) increased odds of a severe COVID-19 in pwMS with all of the assessed risk factors, except smoking and most DMTs. CONCLUSION: This study facilitates evidence-based risk/benefit assessments in practice. Older men with progressive MS on anti-CD20 therapies are more at risk of an unfortunate COVID-19 outcome.

Centre-specific autonomous treatment plans for prostate brachytherapy using cGANs.

PURPOSE: In low-dose-rate prostate brachytherapy (LDR-PB), treatment planning is the process of determining the arrangement of implantable radioactive sources that radiates the prostate while sparing healthy surrounding tissues. Currently, these plans are prepared manually by experts incorporating the centre's planning style and guidelines. In this article, we develop a novel framework that can learn a centre's planning strategy and automatically reproduce rapid clinically acceptable plans. METHODS: The proposed framework is based on conditional generative adversarial networks that learn our centre's planning style using a pool of 931 historical LDR-PB planning data. Two additional losses that help constrain prohibited needle patterns and produce similar-looking plans are also proposed. Once trained, this model generates an initial distribution of needles which is passed to a planner. The planner then initializes the sources based on the predicted needles and uses a simulated annealing algorithm to optimize their locations further. RESULTS: Quantitative analysis was carried out on 170 cases which showed the generated plans having similar dosimetry to that of the manual plans but with significantly lower planning durations. Indeed, on the test cases, the clinical target volumes achieving [Formula: see text] of the prescribed dose for the generated plans was on average [Formula: see text] ([Formula: see text] for manual plans) with an average planning time of [Formula: see text] min ([Formula: see text] min for manual plans). Further qualitative analysis was conducted by an expert planner who accepted [Formula: see text] of the plans with some changes ([Formula: see text] requiring minor changes & [Formula: see text] requiring major changes). CONCLUSION: The proposed framework demonstrated the ability to rapidly generate quality treatment plans that not only fulfil the dosimetric requirements but also takes into account the centre's planning style. Adoption of such a framework would save significant amount of time and resources spent on every patient; boosting the overall operational efficiency of this treatment.

A hybrid scaffold of gelatin glycosaminoglycan matrix and fibrin as a carrier of human corneal fibroblast cells.

A hybrid scaffold of gelatin-glycosaminoglycan matrix and fibrin (FGG) has been synthesized to improve the mechanical properties, degradation time and cell response of fibrin-like scaffolds. The FGG scaffold was fabricated by optimizing some properties of fibrin-only gel and gelatin-glycosaminoglycan (GG) scaffolds. Mechanical analysis of optimized fibrin-only gel showed the Young module and tensile strength of up to 72 and 121 KPa, respectively. Significantly, the nine-fold increase in the Young modulus and a seven-fold increase in tensile strength was observed when fibrin reinforced with GG scaffold. Additionally, the results demonstrated that the degradation time of fibrin was enhanced successfully up to 7 days which was much longer time compared to fibrin-only gel with 38 h of degradation time. More than 45% of FGG initial mass was preserved on day 7 in the presence of aprotinin. Human corneal fibroblast cells (HCFCs) were seeded on the FGG, fibrin-only gel and GG scaffolds for 5 days. The FGG scaffold showed excellent cell viability over 5 days, and the proliferation of HCFCs also increased significantly in comparison with fibrin-only gel and GG scaffolds. The FGG scaffold illustrates the great potential to use in which appropriate stability and mechanical properties are essential to tissue functionality.

Bioengineering Approaches for Corneal Regenerative Medicine.

BACKGROUND: Since the cornea is responsible for transmitting and focusing light into the eye, injury or pathology affecting any layer of the cornea can cause a detrimental effect on visual acuity. Aging is also a reason for corneal degeneration. Depending on the level of the injury, conservative therapies and donor tissue transplantation are the most common treatments for corneal diseases. Not only is there a lack of donor tissue and risk of infection/rejection, but the inherent ability of corneal cells and layers to regenerate has led to research in regenerative approaches and treatments. METHODS: In this review, we first discussed the anatomy of the cornea and the required properties for reconstructing layers of the cornea. Regenerative approaches are divided into two main categories; using direct cell/growth factor delivery or using scaffold-based cell delivery. It is expected delivered cells migrate and integrate into the host tissue and restore its structure and function to restore vision. Growth factor delivery also has shown promising results for corneal surface regeneration. Scaffold-based approaches are categorized based on the type of scaffold, since it has a significant impact on the efficiency of regeneration, into the hydrogel and non-hydrogel based scaffolds. Various types of cells, biomaterials, and techniques are well covered. RESULTS: The most important characteristics to be considered for biomaterials in corneal regeneration are suitable mechanical properties, biocompatibility, biodegradability, and transparency. Moreover, a curved shape structure and spatial arrangement of the fibrils have been shown to mimic the corneal extracellular matrix for cells and enhance cell differentiation. CONCLUSION: Tissue engineering and regenerative medicine approaches showed to have promising outcomes for corneal regeneration. However, besides proper mechanical and optical properties, other factors such as appropriate sterilization method, storage, shelf life and etc. should be taken into account in order to develop an engineered cornea for clinical trials.

Prostate brachytherapy intraoperative dosimetry using a combination of radiographic seed localization with a C-arm and deformed ultrasound prostate contours.

PURPOSE: The purpose of the study was to assess the feasibility of performing intraoperative dosimetry for permanent prostate brachytherapy by combining transrectal ultrasound (TRUS) and fluoroscopy/cone beam CT [CBCT] images and accounting for the effect of prostate deformation. METHODS AND MATERIALS: 13 patients underwent TRUS and multiview two-dimensional fluoroscopic imaging partway through the implant, as well as repeat fluoroscopic imaging with the TRUS probe inserted and retracted, and finally three-dimensional CBCT imaging at the end of the implant. The locations of all the implanted seeds were obtained from the fluoroscopy/CBCT images and were registered to prostate contours delineated on the TRUS images based on a common subset of seeds identified on both image sets. Prostate contours were also deformed, using a finite-element model, to take into account the effect of the TRUS probe pressure. Prostate dosimetry parameters were obtained for fluoroscopic and CBCT-dosimetry approaches and compared with the standard-of-care Day-0 postimplant CT dosimetry. RESULTS: High linear correlation (R2 > 0.8) was observed in the measured values of prostate D90%, V100%, and V150%, between the two intraoperative dosimetry approaches. The prostate D90% and V100% obtained from intraoperative dosimetry methods were in agreement with the postimplant CT dosimetry. Only the prostate V150% was on average 4.1% (p-value <0.05) higher in the CBCT-dosimetry approach and 6.7% (p-value <0.05) higher in postimplant CT dosimetry compared with the fluoroscopic dosimetry approach. Deformation of the prostate by the ultrasound probe appeared to have a minimal effect on prostate dosimetry. CONCLUSIONS: The results of this study have shown that both of the proposed dosimetric evaluation approaches have potential for real-time intraoperative dosimetry.

Stereolithography 3D Bioprinting Method for Fabrication of Human Corneal Stroma Equivalent.

3D bioprinting technology is a promising approach for corneal stromal tissue regeneration. In this study, gelatin methacrylate (GelMA) mixed with corneal stromal cells was used as a bioink. The visible light-based stereolithography (SLA) 3D bioprinting method was utilized to print the anatomically similar dome-shaped structure of the human corneal stroma. Two different concentrations of GelMA macromer (7.5 and 12.5%) were tested for corneal stroma bioprinting. Due to high macromer concentrations, 12.5% GelMA was stiffer than 7.5% GelMA, which made it easier to handle. In terms of water content and optical transmittance of the bioprinted scaffolds, we observed that scaffold with 12.5% GelMA concentration was closer to the native corneal stroma tissue. Subsequently, cell proliferation, gene and protein expression of human corneal stromal cells encapsulated in the bioprinted scaffolds were investigated. Cytocompatibility in 12.5% GelMA scaffolds was observed to be 81.86 and 156.11% at day 1 and 7, respectively, which were significantly higher than those in 7.5% GelMA scaffolds. Elongated corneal stromal cells were observed in 12.5% GelMA samples after 7 days, indicating the cell attachment, growth, and integration within the scaffold. The gene expression of collagen type I, lumican and keratan sulfate increased over time for the cells cultured in 12.5% GelMA scaffolds as compared to those cultured on the plastic tissue culture plate. The expression of collagen type I and lumican were also visualized using immunohistochemistry after 28 days. These findings imply that the SLA 3D bioprinting method with GelMA hydrogel bioinks is a promising approach for corneal stroma tissue biofabrication.

Biobleaching of mechanical paper pulp using Streptomyces rutgersensis UTMC 2445 isolated from a lignocellulose-rich soil.

AIMS: The utilization of micro-organisms in pulp and paper industries has proved biobleaching technology as an environmentally friendly alternative to the conventional approach. In this paper, the effect of actinobacterial fermentation broth on pulp biobleaching has been investigated. METHODS AND RESULTS: Actinobacterial colonies were isolated from lignocellulose-rich soil samples and screened for xylanase production and bleaching activity. The most efficient isolate in bleaching activity showed 100% similarity to Streptomyces rutgersensis. Pulp treatment with 5-day fermentation broth of this strain showed up to 7% increase in brightness (30°C for 6 h, pH (5-7)) compared to untreated (control) pulp. Also, after 60 min biotreatment, significant reduction (12·5%) in consumption of bleaching chemicals was achieved to obtain final brightness of 55%. CONCLUSION: Actinobacterial fermentation broth can be considered as a rich source of effective biobleaching agents which may be considered as environmental friendly and cost-effective technique in comparison with traditional method. SIGNIFICANCE AND IMPACT OF THE STUDY: Our findings showed ability of S. rutgersensis UTMC 2445 in bleaching chemomechanical paper pulp. Also, two strains of Saccharothrix, a rare actinobacterium, with biobleaching activity were introduced. In the proposed method, there is no need to use purified enzymes, and biobleaching process can be done using the fermentation broth.

Effect of beam configuration with inaccurate or incomplete small field output factors on the accuracy of treatment planning dose calculation.

PURPOSE: To evaluate the effect of beam configuration with inaccurate or incomplete small field output factors on the accuracy of dose calculations in treatment planning systems. METHODS: Output factors were measured using various detectors and for a range of field sizes. Three types of treatment machines were configured in two treatment planning systems. In the first (corrected) machine, the Exradin W1 scintillator was used to determine output factors. In the second (uncorrected) machine, the measured output factors by the A1SL ion chamber without considering output correction factors for small field sizes were utilized. In the third (clinical) machine, measured output factors by the Exradin W1 were used but not for field sizes smaller than 2 × 2 cm2 . The dose computed by the anisotropic analytical algorithm (AAA), Acuros XB (AXB) and collapsed cone convolution/superposition (CCC) algorithms in the three machines were delivered using static (jaw-, MLC-, and jaw/MLC-defined), and composite [intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT)] fields. The differences between measured and calculated dose values were analyzed. RESULTS: For static fields, the percentage differences between measured and calculated doses by the three algorithms in three configured machines were <2% for field sizes larger than 2 × 2 cm2 . In jaw- and jaw/MLC-defined fields smaller than 2 × 2 cm2 , the corrected machine presented better agreement with measurement. Considering output correction factors in MLC-defined fields, among the three configured machines, the accuracy of calculation improved to within ±0.5%. For MLC-defined field size of 1 × 1 cm2 , AXB showed the smallest percentage difference (1%). In IMRT and VMAT plans, the percentage differences between measured and calculated doses at the isocenter, as well as the gamma analysis of different plans, which include field sizes larger than 3 × 3 cm2 , did not vary noticeably. For smaller field sizes, using the corrected machine influences dose calculation accuracy. CONCLUSION: Configuration with corrected output factors improves accuracy of dose calculation for static field sizes smaller than 2 × 2 cm2 . For very small fields, the robustness of the dose calculation algorithm affects the accuracy of dose as well. In IMRT and VMAT plans, which include small subfields, the size of the jaw-defined field is an important factor and using corrected output factors increases dose calculation accuracy.

The association between low birth weight and mothers diseases in Iran: A case-control study.

BACKGROUND: Neonates are too vulnerable that low birth weight (LBW) and preterm birth can easily threaten their lives. Demographic, social and environmental factors as well as health care are contributing factors for LBW. The study was conducted in 10 provinces of Iran to investigate the association between LBW and mother's diseases. METHODS: A case-control study was conducted in 10 provinces of Iran on 2580 mothers (712 cases and 1868 controls) referred to public health care centers. We used a questionnaire to collect data. For univariate analysis we used chi-square test and for multivariable analysis we used logistic regression model. RESULTS: LBW was significantly associated with living in rural area (OR = 1.4 CI: 1.14-1.71), having body mass index (BMI)<18 (OR = 1.48 CI: 1.14-1.92), being a housewife (OR = 1.65 CI: 1.07-2.53), having high blood pressure (OR = 1.91 CI: 1.26-2.88), and having pregnancy without testing for diabetes (OR = 1.91 CI: 1.44-2.54). Minor thalassemia, hypothyroidism, oral health care and headache were not significant predictors for LBW. CONCLUSION: In this study, we observed that place of residence, BMI before pregnancy, mother's occupation and gestational diabetes were significant predictors of LBW. It is necessary to improve women's awareness about prenatal health care before pregnancy to avoid LBW.

Estimation of Dosimetric Parameters based on KNR and KNCSF Correction Factors for Small Field Radiation Therapy at 6 and 18 MV Linac Energies using Monte Carlo Simulation Methods.

BACKGROUND: Estimating dosimetric parameters for small fields under non-reference conditions leads to significant errors if done based on conventional protocols used for large fields in reference conditions. Hence, further correction factors have been introduced to take into account the influence of spectral quality changes when various detectors are used in non-reference conditions at different depths and field sizes. OBJECTIVE: Determining correction factors (KNR and KNCSF) recommended recently for small field dosimetry formalism by American Association of Physicists in Medicine (AAPM) for different detectors at 6 and 18 MV photon beams. METHODS: EGSnrc Monte Carlo code was used to calculate the doses measured with different detectors located in a slab phantom and the recommended KNR and KNCSF correction factors for various circular small field sizes ranging from 5-30 mm diameters. KNR and KNCSF correction factors were determined for different active detectors (a pinpoint chamber, EDP-20 and EDP-10 diodes) in a homogeneous phantom irradiated to 6 and 18 MV photon beams of a Varian linac (2100C/D). RESULTS: KNR correction factor estimated for the highest small circular field size of 30 mm diameter for the pinpoint chamber, EDP-20 and EDP-10 diodes were 0.993, 1.020 and 1.054; and 0.992, 1.054 and 1.005 for the 6 and 18 MV beams, respectively. The KNCSF correction factor estimated for the lowest circular field size of 5 mm for the pinpoint chamber, EDP-20 and EDP-10 diodes were 0.994, 1.023, and 1.040; and 1.000, 1.014, and 1.022 for the 6 and 18 MV photon beams, respectively. CONCLUSION: Comparing the results obtained for the detectors used in this study reveals that the unshielded diodes (EDP-20 and EDP-10) can confidently be recommended for small field dosimetry as their correction factors (KNR and KNCSF) was close to 1.0 for all small field sizes investigated and are mainly independent from the electron beam spot size.

Physical and Dosimetric Aspect of Euromechanics Add-on Multileaf Collimator on Varian Clinac 2100 C/D.

BACKGROUND: Before treatment planning and dose delivery, quality assurance of multi-leaf collimator (MLC) has an important role in intensity-modulated radiation therapy (IMRT) due to the creation of multiple segments from optimization process. OBJECTIVE: The purpose of this study is to assess the quality control of MLC leaves using EBT3 Gafchromic films. MATERIAL AND METHODS: Leaf Position accuracy and leaf gap reproducibility were checked with Garden fence test. The garden fence test consists of 5 thin bands A) 0.2 Cm width spaced at 2 Cm intervals and B) 1 Cm width spaced at 1 Cm intervals. Each leaf accuracy was analyzed with measuring the full-width half-maximum (FWHM). Maximum and average leaf transmission were measured with gafchromic EBT3 films from Ashland for both 6 MV and 18 MV beams. RESULTS: Leaf positions were found to be in a range between 1.78 - 2.53 mm, instead of nominal 2 mm for the test A and between 9.09 - 10.36 mm, instead of nominal 10 mm for the test B. The Average radiation transmission of the MLC was noted 1.79% and 1.98% of the open 10x10 Cm2 field at isocenter for 6 MV and 18 MV beams, respectively. Maximum radiation transmission was noted 4.1% and 4.4% for 6 MV and 18 MV beams, respectively. CONCLUSION: In this study, application of gafchromic EBT3 films for the quality assurance of Euromechanics multileaf collimator was studied. Our results showed that the average leaf leakage and positional accuracy of this type of MLC were in the acceptance level based on the Protocols.

3D simulation of solutes concentration in urinary concentration mechanism in rat renal medulla.

In this work, a mathematical model was developed to simulate the urinary concentration mechanism. A 3-D geometry was derived based on the detail physiological pictures of rat kidney. The approximate region of each tubule was obtained from the volume distribution of structures based on Walter Pfaller's monograph and Layton's region-based model. Mass and momentum balances were applied to solve for the change in solutes concentration and osmolality. The osmolality of short and long descending nephrons at the end of the outer medulla was obtained to be 530 mOsmol/kgH2O and 802 mOsmol/kgH2O, respectively, which were in acceptable agreement with experimental data. The fluid osmolality of the short and long ascending nephrons was also compatible with experimental data. The osmolality of CD fluid at the end of the inner medulla was determined to be 1198 mOsmol/kgH2O which was close the experimental data (1216 ±â€¯118). Finally, the impact of the position of each tubule on the fluid osmolality and solutes concentration were obvious in the results; for example, short descending limb a1, which is the closest tubule to the collecting duct, had the highest urea concentration in all tubules. This reflects the important effect of the 3D modeling on the precise analysis of urinary concentration mechanism.

New physical approaches to treat cancer stem cells: a review.

Cancer stem cells (CSCs) have been identified as the main center of tumor therapeutic resistance. They are highly resistant against current cancer therapy approaches particularly radiation therapy (RT). Recently, a wide spectrum of physical methods has been proposed to treat CSCs, including high energetic particles, hyperthermia (HT), nanoparticles (NPs) and combination of these approaches. In this review article, the importance and benefits of the physical CSCs therapy methods such as nanomaterial-based heat treatments and particle therapy will be highlighted.