Comparing the effect of FUAS and myomectomy on the elasticity of myometrium around targeted uterine fibroid.

BACKGROUND: Focused ultrasound ablation surgery (FUAS) has been widely employed to treat patients with uterine fibroid (UF). This study aimed to estimate myometrial stiffness changes in patients who received FUAS for UFs or myomectomy (ME) and compare the recovery of surrounding myometrium between FUAS and ME groups. Our results may provide more evidence for guiding the proper conception timing in patients with UF. METHODS: This study enrolled 173 patients from May 2022 to August 2023. Shear wave elastography (SWE) was used to dynamically monitor myometrial elasticity changes in patients before and after surgery. Moreover, our study monitored and analyzed the stiffness changes in the targeted fibroid after FUAS, as well as in the myometrium around after FUAS or ME. RESULTS: The stiffness of the myometrium around the resected fibroid was significantly higher than at the preoperative level until 6 months. Conversely, the stiffness of the surrounding myometrium was only temporarily increased 1 day after FUAS. The comparison between FUAS and ME groups regarding the stiffness of the surrounding myometrium showed that nonsignificant differences were detected between the two groups before the treatment. The stiffness of the surrounding myometrium in the ME group was statistically significantly higher than that of the FUAS group 1 day as well as 1, 3, and 6 months after the treatment, respectively. CONCLUSION: The FUAS had less impact on the surrounding myometrium than the ME, which may be more conducive to the recovery of myometrial elasticity in patients with UF.

Sensitivity and specificity of the uniform field electroretinogram in glaucoma detection in comparison to the pattern electroretinogram.

PURPOSE: To determine the ability of the photopic negative response (PhNR) of the uniform field electroretinogram (UF-ERG) to identify early glaucomatous changes in comparison to the checkerboard and bar stimuli of the pattern electroretinogram (PERG). METHODS: Forty-nine glaucoma patients were classified into two groups: glaucoma-suspect (23 eyes) and early to moderate glaucoma (30 eyes), based on their clinical examination and the results of standard automated perimetry. Thirty patients (30 eyes) with intraocular pressures (IOP) of 21 mmHg or less, with no history of reported high IOP, were included as controls. PERG and UF-ERG recordings were obtained on a Diagnosys D-341 Attaché-Envoy System. Visual field testing was done only for glaucoma-suspect and glaucoma patients. RESULTS: All three tests (PERG bar stimulus, PERG checkerboard stimulus and PhNR) displayed significantly prolonged peak times for glaucoma and glaucoma-suspect patients, with delays ranging from 7.8 to 14.8%, depending on the test. The PERG bar stimulus also showed a significantly lower N95 amplitude for both glaucoma groups (with reductions of 26.0% and 33.0% for glaucoma-suspect and glaucoma groups, respectively). The PERG checkerboard N95 amplitude component had high sensitivity for detecting glaucoma patients but a low specificity (97% and 37%, respectively; AUC = 0.61). Overall, the PhNR peak time showed the highest sensitivity and specificity (77% and 90%, respectively; AUC = 0.87). CONCLUSIONS: PERG bar stimuli and the PhNR of the UF-ERG can be used in the clinical setting to detect glaucoma-related changes in glaucoma-suspect and glaucoma patients. However, our data confirm that the PhNR peak time has the best combined sensitivity and specificity.

Efficient and fast screening and separation based on computer-aided screening and complex chromatography methods for lipoxygenase inhibitors from Ganoderma lucidum.

INTRODUCTION: Accurate screening and targeted preparative isolation of active substances from natural medicines have long been technical challenges in natural medicine research. OBJECTIVES: This study outlines a new approach for improving the efficiency of natural product preparation, focusing on the rapid and accurate screening of potential active ingredients in Ganoderma lucidum and efficient preparation of lipoxidase inhibitors, with the aim of providing new ideas for the treatment of Alzheimer's disease with G. lucidum. METHODS: The medicinal plant G. lucidum was selected through ultrafiltration coupled with liquid chromatography and mass spectrometry (UF-LC-MS) and computer-assisted screening for lipoxygenase (LOX) inhibitors. In addition, the inhibitory effect of the active compounds on LOX was studied using enzymatic reaction kinetics, and the underlying mechanism is discussed. Finally, based on the earlier activity screening guidelines, the identified ligands were isolated and purified through complex chromatography (high-speed countercurrent chromatography and semi-preparative high-performance liquid chromatography). RESULTS: Five active ingredients, ganoderic acids A, B, C2, D2, and F, were identified and isolated from G. lucidum. We improved the efficiency and purity of active compound preparation using virtual computer screening and enzyme inhibition assays combined with complex chromatography. CONCLUSION: The innovative methods of UF-LC-MS, computer-aided screening, and complex chromatography provide powerful tools for screening and separating LOX inhibitors from complex matrices and provide a favourable platform for the large-scale production of bioactive substances and nutrients.

[Primary prevention of food allergy in children]. / Prévention primaire de l'allergie alimentaire de l'enfant.

Pediatricians and allergists have noted a recent increase in cases of food allergy and anaphylaxis to peanuts and nuts, affecting very young children with worrying consequences in terms of quality of life. Children suffering from persistent cow's milk protein allergies that do not heal spontaneously are at very high risk of a fatal accident. Based on the findings of these studies, recommendations for primary prevention are made.

Accurately quantified plasma free glycine concentration as a biomarker in patients with acute ischemic stroke.

We developed a hollow fiber centrifugal ultrafiltration (HFCF-UF) method to study the change of plasma levels of free glycine (Gly) in patients with acute ischemic stroke (AIS). Twenty-four patients with AIS confirmed by diffusion-weighted imaging (DWI) were enrolled. During the study period, the patients did not receive any supplemental amino acids therapy that could affect the obtained results. Our results showed that although AIS patients adopted different methods of treatment (thrombolytic and non-thrombolytic), the clinical NIHSS score of AIS showed a downward trend whereas Gly concentration showed increased trend. Moreover, plasma free Gly concentration was positively correlated with ASPECTS score. The correlation between Gly levels and infarct volume showed a statistical significance. That is to say, higher Gly level predicted smaller infarct size. Thus, the change of free Gly level in plasma could be considered as a potential biomarker of AIS.

Analysis of factors with low positive predictive value in the diagnosis of urinary tract infection by flow cytometry.

PURPOSE: Culture-negative urine specimens can be rapidly screened by urine flow cytometry (UFC), while low positive predictive value (PPV) limits the clinical application. We explored the factors associated with a low PPV. METHODS: A total of 5095 urine specimens were analyzed with UFC and culture. Diagnostic performance of leukocytes, bacteria, and BACT-info flags was evaluated by sensitivity, specificity, PPV, and negative predictive value (NPV). The association of contaminated culture and squamous epithelial cell count and BACT-info flag was performed by logistic regression analysis. RESULTS: The NPVs of parallel combination of bacteria and leucocytes were 98.9% in males and 97.9% in females, and PPVs of serial combination were 86.6% and 77.8% in men and women, respectively. The PPV of Gram-negative flag was higher than that of Gram-positive flag. The proportions of contamination in the urine culture results of false positive specimens were 86.9% in males and 98.5% in females at the cutoff points of the serial combination, and these parameters were 53.2% in males and 85.6% in females for the Gram-positive flag. There was a statistically significant association between contaminated cultures and squamous epithelial cells count in females, but not in males. Associations between contaminated cultures and Gram-positive flags or Gram-pos/-neg flags were statistically significant, but there was no association between contaminated cultures and Gram-negative flags. CONCLUSIONS: A serial combination of leukocytes and bacteria may maximize PPV in the diagnosis of bacterial urinary tract infection by urine flow cytometry, and contamination is the main reason for a low PPV.

Monitoring of ultra- and diafiltration processes by Kalman-filtered Raman measurements.

Monitoring the protein concentration and buffer composition during the Ultrafiltration/Diafiltration (UF/DF) step enables the further automation of biopharmaceutical production and supports Real-time Release Testing (RTRT). Previously, in-line Ultraviolet (UV) and Infrared (IR) measurements have been used to successfully monitor the protein concentration over a large range. The progress of the diafiltration step has been monitored with density measurements and Infrared Spectroscopy (IR). Raman spectroscopy is capable of measuring both the protein and excipient concentration while being more robust and suitable for production measurements in comparison to Infrared Spectroscopy (IR). Regardless of the spectroscopic sensor used, the low concentration of excipients poses a challenge for the sensors. By combining sensor measurements with a semi-mechanistic model through an Extended Kalman Filter (EKF), the sensitivity to determine the progress of the diafiltration can be improved. In this study, Raman measurements are combined with an EKF for three case studies. The advantages of Kalman-filtered Raman measurements for excipient monitoring are shown in comparison to density measurements. Furthermore, Raman measurements showed a higher measurement speed in comparison to Variable Pathlength (VP) UV measurement at the trade-off of a slightly worse prediction accuracy for the protein concentration. However, the Raman-based protein concentration measurements relied mostly on an increase in the background signal during the process and not on proteinaceous features, which could pose a challenge due to the potential influence of batch variability on the background signal. Overall, the combination of Raman spectroscopy and EKF is a promising tool for monitoring the UF/DF step and enables process automation by using adaptive process control.

Performance evaluation of E-nose and E-tongue combined with machine learning for qualitative and quantitative assessment of bear bile powder.

Bear bile powder (BBP) is a valuable animal-derived product with a huge adulteration problem on market. It is a crucially important task to identify BBP and its counterfeit. Electronic sensory technologies are the inheritance and development of traditional empirical identification. Considering that each drug has its own specific odor and taste characteristics, electronic tongue (E-tongue), electronic nose (E-nose) and GC-MS were used to evaluate the aroma and taste of BBP and its common counterfeit. Two active components of BBP, namely tauroursodeoxycholic acid (TUDCA) and taurochenodeoxycholic acid (TCDCA) were measured and linked with the electronic sensory data. The results showed that bitterness was the main flavor of TUDCA in BBP, saltiness and umami were the main flavor of TCDCA. The volatiles detected by E-nose and GC-MS were mainly aldehydes, ketones, alcohols, hydrocarbons, carboxylic acids, heterocyclic, lipids, and amines, mainly earthy, musty, coffee, bitter almond, burnt, pungent odor descriptions. Four different machine learning algorithms (backpropagation neural network, support vector machine, K-nearest neighbor, and random forest) were used to identify BBP and its counterfeit, and the regression performance of these four algorithms was also evaluated. For qualitative identification, the algorithm of random forest has shown the best performance, with 100% accuracy, precision, recall and F1-score. Also, the random forest algorithm has the best R2 and the lowest RMSE in terms of quantitative prediction.

Combination of UC-3500 and UF-5000 as a quick and effective method to exclude bacterial urinary tract infection.

BACKGROUND: Our study aims to evaluate the performance of the combination of Sysmex urine dry chemistry analyzer UC-3500 and urine particle analyzer UF-5000 in screening bacterial urinary tract infection (UTI). METHODS: We analyzed 2000 urine specimens from patients with suspected UTI by using a urine dry chemistry analyzer (UC-3500) and a fully automated sediment analyzer (UF-5000). After being tested by the instrument, all specimens were sent to our clinical microbiology laboratory for culture. In addition, 600 urine specimens were selected to evaluate the accuracy of the six screening strategies established in this study. RESULTS: The consistency of UF-5000 bacterial classification and bacterial culture was fair (Kappa = 0.339). The counts of WBC and BACT elevated with sequential group designs (P < 0.001). The cut-off value of WBC was 32.20/µL for males (AUC, 0.942, 95%CI, 0.930-0.955) and 39.15/µL for females (AUC, 0.931, 95%CI, 0.914-0.948). The sensitivity and specificity of WBC were relatively higher than those of BACT. Strategy④ and Strategy⑥ in all six strategies had a good negative predictive value (NPV) which was 98.73%. CONCLUSION: UF-5000 bacterial classification cannot be used as a practical reference. 32.20/µL (male) and 39.15/µL (female) for WBC as well as 22.35/µL (male) and 127.25/µL (female) for BACT were used as cut-off values to effectively determine whether UTI occurs. WBC, BACT and LEU joint screening programs were suitable to rapidly and effectively exclude bacterial UTI.

Evaluation of the fully automated urine particle analyzer UF-1500.

BACKGROUND AND AIMS: This study primarily assessed the performance of the UF-1500, the novel and compact model of the fully automated urine particle analyzer and evaluated its performance against the existing UF-5000 instrument. MATERIALS AND METHODS: A total of 648 residual urine specimens were randomly collected and examined using both the UF-1500 and UF-5000 instruments as well as manual microscopy. For each parameter, the concordance rates and detection accuracy of the UF-1500 against manual microscopy were compared with the UF-5000. RESULTS: The concordance rates between the UF-1500 and manual microscopy were 75.3%-98.5%. The UF-1500 concordance rates within one group agreement were observed to be >90%, for all parameters except for YLCs. The differences within one group agreement between the UF-1500 and manual microscopy were insignificant, in comparison to the UF-5000, with exceptions noted for ECs and YLCs. The sensitivity and specificity of the UF-1500 for RBCs, WBCs, Squa.ECs, and BACT exceeded 80%, while the positive predictive values of ECs and CASTs were below 70%. CONCLUSION: The UF-1500 exhibited a performance that was comparable to the existing instrument, the UF-5000, and was suitable to be introduced in clinical practice. For the samples with suspected false-positive or false-negative results, a manual microscopic examination is required for accurate testing.

Therapeutic drug monitoring of free vancomycin concentration in practice: A new analytical technique based on the HFCF-UF sample separation method.

The aim of this study was to establish a method for free vancomycin concentration determination in human plasma and apply it to clinical therapeutic drug monitoring (TDM). The unbound vancomycin in plasma was separated by the hollow fiber centrifugal ultrafiltration (HFCF-UF) technique and analyzed by HPLC. Chromatographic conditions were optimized, the specificity, linearity, precision, recovery and stability of the method were examined, and plasma samples of patients were measured. The standard curve for free vancomycin is y = 0.0277x - 0.0080 with good linearity within 0.25-50 µg·mL-1 . The relative and absolute recovery rates for vancomycin were 98.63-101.0% and 88.41-101.2%, respectively. The intraday and interday precision RSDs were <10%. Plasma was stable under several conditions. The TDM value of the free vancomycin concentration of 20 patients was 0.99-38.51 µg·mL-1 , and the correlation between the free and total concentrations was not significant. The unbound fraction of vancomycin ranged from 25.5 to 84.8%, with large variation. The operation of free vancomycin separation by HFCF-UF was simple and suitable for TDM in practice. The unbound fraction of vancomycin in clinical samples varied significantly between individuals. It is recommended to perform free concentration TDM in critically ill patients.

Identification of Xanthine Oxidase Inhibitors from Celery Seeds Using Affinity Ultrafiltration-Liquid Chromatography-Mass Spectrometry.

Celery seeds have been used as an effective dietary supplement to manage hyperuricemia and diminish gout recurrence. Xanthine oxidase (XOD), the critical enzyme responsible for uric acid production, represents the most promising target for anti-hyperuricemia in clinical practice. In this study, we aimed to establish a method based on affinity ultrafiltration-liquid chromatography-mass spectrometry (UF-LC-MS) to directly and rapidly identify the bioactive compounds contributing to the XOD-inhibitory effects of celery seed crude extracts. Chemical profiling of celery seed extracts was performed using UPLC-TOF/MS. The structure was elucidated by matching the multistage fragment ion data to the database and publications of high-resolution natural product mass spectrometry. Thirty-two compounds, including fourteen flavonoids and six phenylpeptides, were identified from celery seed extracts. UF-LC-MS showed that luteolin-7-O-apinosyl glucoside, luteolin-7-O-glucoside, luteolin-7-O-malonyl apinoside, luteolin-7-O-6'-malonyl glucoside, luteolin, apigenin, and chrysoeriol were potential binding compounds of XOD. A further enzyme activity assay demonstrated that celery seed extract (IC50 = 1.98 mg/mL), luteolin-7-O-apinosyl glucoside (IC50 = 3140.51 µmol/L), luteolin-7-O-glucoside (IC50 = 975.83 µmol/L), luteolin-7-O-6'-malonyl glucoside (IC50 = 2018.37 µmol/L), luteolin (IC50 = 69.23 µmol/L), apigenin (IC50 = 92.56 µmol/L), and chrysoeriol (IC50 = 40.52 µmol/L) could dose-dependently inhibit XOD activities. This study highlighted UF-LC-MS as a useful platform for screening novel XOD inhibitors and revealed the chemical basis of celery seed as an anti-gout dietary supplement.

Consistency analysis of the Sysmex UF-5000 and Atellica UAS 800 urine sedimentation analyzers.

OBJECTIVE: To evaluate the consistency between the results of Sysmex UF-5000 system and Atellica® UAS 800 Urine Sediment Analyzer. METHODS: A total of 636 random urine samples were collected from inpatients and outpatients from March to September 2021. Urine was collected for analysis by the Sysmex UF-5000, Atellica UAS 800 systems, and manual microscopic examination. The results of manual microscopy as the gold standard, the coincidence rate and false-negative rate of Sysmex UF-5000 and Atellica UAS 800 systems in the detection of red blood cells, white blood cells, and casts were calculated. RESULTS: The coincidence rates of red blood cells, white blood cells, and cast, crystals, and other sediment components for the Sysmex UF-5000 system were 85.37%, 87.89%, 91.67%, 88.36%, and 71.86%. The false-negative rates were 28.47%, 3.75%, 68.97%, 37.25%, and 30.63%. The coincidence rates of red blood cells, white blood cells, and cast, crystals, and other sediment components for the Atellica UAS 800 system were 85.06%, 90.25%, 59.12%, 91.67%, and 67.45% and the false-negative rates were 60.42%, 21.25%, 36.21%, 19.64%, and 35.80%. CONCLUSION: Two instruments are superior in the detection of red blood cells and white blood cells. The Atellica UAS 800 system with image review has a good coincidence rate in the identification of crystals and casts. The identification of various sediment components in urine by both instruments meets the laboratory requirements. Two instruments with different methodologies have their own characteristics, and we should reasonably use them according to the conditions of the laboratory.

Screening and Capability Assessment of Tyrosinase Inhibitors in Isodon excisoides by Ultrafiltration Coupled with UHPLC-Q-TOF-MS and Molecular Docking Technology.

Tyrosinase inhibitors can alleviate the harm to the liver caused by tyrosinase. How to effectively screen out natural tyrosinase inhibitors becomes a focus. In this study, Isodon excisoides was first extracted with the ultrasound optimized by response surface methodology. Then, a method combined ultrafiltration with ultra-liquid chromatography mass spectrometry (UHPLC/MS) was built to screen and identify tyrosinase inhibitors. The binding energies of active ingredients to tyrosinase were calculated by molecular docking. The reliability of the results was validated by the IC50 of enzyme inhibition assay. As a result, the binding energies of 7 components including excisanin B, lasiokaurin, rabdophyllin G, rabdoserrin B, rabdosin D, rabdosinate and weisiensin were lower than that of resveratrol. It was indicated that these components had high tyrosinase inhibitory activity. The IC50 values of lasiokaurin and excisanin B were 177 and 142 µmol/mL, which were less than that of resveratrol (183 µmol/mL). It showed that this way was simple, rapid, reliable and effective, which provided a new strategy to screen natural bioactive compounds from plants.

Performance of Sysmex UF-5000 for candiduria screening.

In this study, we tested the performance of the Sysmex UF-5000 system to detect yeast-like cell (YLC) counting to screen for candiduria. Urine samples were screened for leukocyte and yeast amount by flow cytometry and results were compared with fungal culture results. A total of 56,749 urine samples were enrolled in this study. Urine culture and urinalysis of YLC data were used to evaluate the performance of YLC in diagnosing candiduria. Different cut-off values (YLC. 5, 10, 20, 50, 100/µl) were evaluated. Youden index was used to determine the ideal cut-off value, and the highest was 0.95 with 5 YLC/µl. When the cut-off value for YLC is 5 cells/µl, 95.15% of the samples were "negative" with flow cytometry and culture (NPV:100%). In conclusion, detection of YLC by flow cytometer (Sysmex UF-5000) can be a rapid alternative method to exclude candiduria prior to urine culture.

Screening and characterisation of potential antioxidant, hypoglycemic and hypolipidemic components revealed in Portulaca oleracea via multi-target affinity ultrafiltration LC-MS and molecular docking.

INTRODUCTION: Portulaca oleracea is a commonly used nutritional vegetable and traditional herbal medicine with plenty of nutrients and manifold pharmacological activities. However, the potential active ingredients for its remarkable antioxidant, hypoglycemic and hypolipidemic activities remain unexplored. OBJECTIVES: The present study aims to systematically evaluate the antioxidant activities of different extracts of P. oleracea and screen bioactive ligands that can interact with α-glucosidase, pancreatic lipase, and superoxide dismutase (SOD). METHODS: In this research, the antioxidant activities of different parts of P. oleracea and their corresponding total phenolic content (TPC) and total flavonoid content (TFC) were systematically determined. Subsequently, a multi-target affinity ultrafiltration method was developed using affinity ultrafiltration with SOD, α-glucosidase, and pancreatic lipase coupled to liquid chromatography-mass spectrometry (UF-LC-MS). Later, molecular docking was used to further investigate the possible interaction mechanism between these ligands and target enzymes. RESULTS: Among them, the ethyl acetate (EA) fraction showed the highest antioxidant activity along with the highest TPC and TFC, and four compounds in the EA fraction were quickly retrieved as potential SOD, α-glucosidase, and pancreatic lipase ligands, respectively. Molecular docking revealed that these potential ligands exhibited strong binding ability and inhibitory activities on SOD, α-glucosidase, and pancreatic lipase. CONCLUSION: The present study revealed that P. oleracea can be used as a functional food with excellent antioxidant, hypoglycemic and hypolipidemic effects. Meanwhile, the integrated strategy based on multi-target UF-LC-MS and molecular docking also provided a powerful tool and a multidimensional perspective for further exploration of active ingredients in P. oleracea responsible for the antioxidant, hypoglycemic and hypolipidemic activities.

A Review on Current Strategies for Extraction and Purification of Hyaluronic Acid.

Since it is known that hyaluronic acid contributes to soft tissue growth, elasticity, and scar reduction, different strategies of producing HA have been explored in order to satisfy the current demand of HA in pharmaceutical products and formulations. The current interest deals with production via bacterial and yeast fermentation and extraction from animal sources; however, the main challenge is the right extraction technique and strategy since the original sources (e.g., fermentation broth) represent a complex system containing a number of components and solutes, which complicates the achievement of high extraction rates and purity. This review sheds light on the main pathways for the production of HA, advantages, and disadvantages, along with the current efforts in extracting and purifying this high-added-value molecule from different sources. Particular emphasis has been placed on specific case studies attempting production and successful recovery. For such works, full details are given together with their relevant outcomes.

Fabrication of Sulfated Heterosaccharide/Poly (Vinyl Alcohol) Hydrogel Nanocomposite for Application as Wound Healing Dressing.

Nowadays, natural polysaccharides-based hydrogels have achieved promising results as dressings to promote skin healing. In the present study, we prepared a novel hydrogel nanocomposite with poly(vinyl alcohol) (PVA) and sulfated heterosaccharide (UF), named UPH. The SEM results showed that the UPH had dense porous structures with a high porosity and a specific surface area. The UPH had a good swelling property, which can effectively adsorb exudate and keep the wound moist. The in vitro experiments results showed that the UPH was non-cytotoxic and could regulate the inflammatory response and promote the migration of fibroblasts significantly. The phenotypic, histochemistry, and Western blot analyses showed UPH treatment accelerated the wound healing and recovery of skin tissue at wound sites in a C57BL/6 mouse model. Furthermore, the UPH could promote the inflammation process to onset earlier and last shorter than that in a normal process. Given its migration-promoting ability and physicochemical properties, the UPH may provide an effective application for the treatment and management of skin wounds.

The ventral pathway of the human brain: A continuous association tract system.

The brain hemispheres can be divided into an upper dorsal and a lower ventral system. Each system consists of distinct cortical regions connected via long association tracts. The tracts cross the central sulcus or the limen insulae to connect the frontal lobe with the posterior brain. The dorsal stream is associated with sensorimotor mapping. The ventral stream serves structural analysis and semantics in different domains, as visual, acoustic or space processing. How does the prefrontal cortex, regarded as the platform for the highest level of integration, incorporate information from these different domains? In the current view, the ventral pathway consists of several separate tracts, related to different modalities. Originally the assumption was that the ventral path is a continuum, covering all modalities. The latter would imply a very different anatomical basis for cognitive and clinical models of processing. To further define the ventral connections, we used cutting-edge in vivo global tractography on high-resolution diffusion tensor imaging (DTI) data from 100 normal subjects from the human connectome project and ex vivo preparation of fiber bundles in the extreme capsule of 8 humans using the Klingler technique. Our data showed that ventral stream tracts, traversing through the extreme capsule, form a continuous band of fibers that fan out anteriorly to the prefrontal cortex, and posteriorly to temporal, occipital and parietal cortical regions. Introduction of additional volumes of interest in temporal and occipital lobes differentiated between the inferior fronto-occipital fascicle (IFOF) and uncinate fascicle (UF). Unequivocally, in both experiments, in all subjects a connection between the inferior frontal and middle-to-posterior temporal cortical region, otherwise known as the temporo-frontal extreme capsule fascicle (ECF) from nonhuman primate brain-tracing experiments was identified. In the human brain, this tract connects the language domains of "Broca's area" and "Wernicke's area". The differentiation in the three tracts, IFOF, UF and ECF seems arbitrary, all three pass through the extreme capsule. Our data show that the ventral pathway represents a continuum. The three tracts merge seamlessly and streamlines showed considerable overlap in their anterior and posterior course. Terminal maps identified prefrontal cortex in the frontal lobe and association cortex in temporal, occipital and parietal lobes as streamline endings. This anatomical substrate potentially facilitates the prefrontal cortex to integrate information across different domains and modalities.

Designing scalable ultrafiltration/diafiltration process of monoclonal antibodies via mathematical modeling by coupling mass balances and Poisson-Boltzmann equation.

Ultrafiltration/diafiltration (UF/DF) operations are employed for achieving the desired therapeutic monoclonal antibody (mAb) formulations. Due to electrostatic interactions between the charged proteins, solute ions, and uncharged excipients, the final pH and concentration values are not always equal to those in the DF buffer. At high protein concentrations, typical for industrial formulations, this effect becomes predominant. To account for challenges occurring in industrial environments, a robust mathematical framework enabling the prediction of pH and concentration profiles throughout the UF/DF process is provided. The proposed mechanistic model combines a macroscopic mass balance approach with a molecular approach based on a Poisson-Boltzmann equation dealing with electrostatic interactions and accounting for protein exclusion volume effect. The mathematical model was validated with experimental data of two commercially relevant mAbs obtained from an industrial UF/DF process using scalable laboratory equipment. The robustness and flexibility of the model were tested by using proteins with different isoelectric points and net charges. The latter was determined via a titration curve, enabling realistic protein charge-pH evaluation. In addition, the model was tested for different DF buffer types containing both monovalent and polyvalent ions, with various types of uncharged excipients. The model generality enables its implementation for the UF/DF processes of other protein varieties.