Miracle-dz/UniFAR-FTUs huggingface dataset:
Proteoform-Resolved FcɤRIIIa Binding Assay for Fab Glycosylated Monoclonal Antibodies Achieved by Affinity Chromatography Mass Spectrometry of Fc Moieties

Fcɤ receptors (FcɤR) mediate key functions in immunological responses. For instance, FcɤRIIIa is involved in antibody-dependent cell-mediated cytotoxicity (ADCC). FcɤRIIIa interacts with the fragment crystallizable (Fc) of immunoglobulin G (IgG). This interaction is known to be highly dependent on IgG Fc glycosylation. Thus, the impact of glycosylation features on this interaction has been investigated in several studies by numerous analytical and biochemical techniques. FcɤRIIIa affinity chromatography (AC) hyphenated to mass spectrometry (MS) is a powerful tool to address co-occurring Fc glycosylation heterogeneity of monoclonal antibodies (mAbs). However, MS analysis of mAbs at the intact level may provide limited proteoform resolution, for example, when additional heterogeneity is present, such as antigen-binding fragment (Fab) glycosylation. Therefore, we investigated middle-up approaches to remove the Fab and performed AC-MS on the IgG Fc to evaluate its utility for FcɤRIIIa affinity assessment compared to intact IgG analysis. We found the protease Kgp to be particularly suitable for a middle-up FcɤRIIIa AC-MS workflow as demonstrated for the Fab glycosylated cetuximab. The complexity of the mass spectra of Kgp digested cetuximab was significantly reduced compared to the intact level while affinity was fully retained. This enabled a reliable assignment and relative quantitation of Fc glycoforms in FcɤRIIIa AC-MS. In conclusion, our workflow allows a functional separation of differentially glycosylated IgG Fc. Consequently, applicability of FcɤRIIIa AC-MS is extended to Fab glycosylated IgG, i.e., cetuximab, by significantly reducing ambiguities in glycoform assignment vs. intact analysis.
Assessing the Impact of Sample Heterogeneity on Transcriptome Analysis of Human Diseases Using MDP Webtool

Transcriptome analyses have increased our understanding of the molecular mechanisms underlying human diseases. Most approaches aim to identify significant genes by comparing their expression values between healthy subjects and a group of patients with a certain disease. Given that studies normally contain few samples, the heterogeneity among individuals caused by environmental factors or undetected illnesses can impact gene expression analyses. We present a systematic analysis of sample heterogeneity in a variety of gene expression studies relating to inflammatory and infectious diseases and show that novel immunological insights may arise once heterogeneity is addressed. The perturbation score of samples is quantified using nonperturbed subjects (i.e., healthy subjects) as a reference group. Such a score allows us to detect outlying samples and subgroups of diseased patients and even assess the molecular perturbation of single cells infected with viruses. We also show how removal of outlying samples can improve the “signal” of the disease and impact detection of differentially expressed genes. The method is made available via the mdp Bioconductor R package and as a user-friendly webtool, webMDP, available at http://mdp.sysbio. tools.
Targeted High Resolution LC/MS3 Adductomics Method for the Characterization of Endogenous DNA Damage

DNA can be damaged through covalent modifications of the nucleobases by endogenous processes. These modifications, commonly referred to as DNA adducts, can persist and may lead to mutations, and ultimately to the initiation of cancer. A screening methodology for the majority of known endogenous DNA adducts would be a powerful tool for investigating the etiology of cancer and for the identification of individuals at high-risk to the detrimental effects of DNA damage. This idea led to the development of a DNA adductomic approach using high resolution data-dependent scanning, an extensive MS2 fragmentation inclusion list of known endogenous adducts, and neutral loss MS3 triggering to profile all DNA modifications. In this method, the detection of endogenous DNA adducts is performed by observation of their corresponding MS3 neutral loss triggered events and their relative quantitation using the corresponding full scan extracted ion chromatograms. The method's inclusion list consists of the majority of known endogenous DNA adducts, compiled, and reported here, as well as adducts specific to tobacco exposure included to compare the performance of the method with previously developed targeted approaches. The sensitivity of the method was maximized by reduction of extraneous background signal through the purification and minimization of the amount of commercially obtained enzymes used for the DNA hydrolysis. In addition, post-hydrolysis sample purification was performed using off-line HPLC fraction collection to eliminate the highly abundant unmodified bases, and to avoid introduction of plasticizers found in solid-phase extraction cartridges. Also, several instrument parameters were evaluated to optimize the ion signal intensities and fragmentation spectra quality. The method was tested on an animal model of lung carcinogenesis where A/J mice were exposed to the tobacco specific lung carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK) with its effects enhanced by co-exposure to the pro-inflammatory agent lipopolysaccharide (LPS). Lung DNA were screened for endogenous DNA adducts known to result from oxidative stress and LPS-induced lipid peroxidation, as well as for adducts due to NNK exposure. The relative quantitation of the detected DNA adducts was performed using parallel reaction monitoring MS2 analysis, demonstrating a general workflow for analysis of endogenous DNA adducts.
Soft nanocomposite electroadhesives for digital micro- and nanotransfer printing

A soft nanocomposite surface with voltage-tunable adhesive strength manipulates nano- and microscale objects. Automated handling of microscale objects is essential for manufacturing of next-generation electronic systems. Yet, mechanical pick-and-place technologies cannot manipulate smaller objects whose surface forces dominate over gravity, and emerging microtransfer printing methods require multidirectional motion, heating, and/or chemical bonding to switch adhesion. We introduce soft nanocomposite electroadhesives (SNEs), comprising sparse forests of dielectric-coated carbon nanotubes (CNTs), which have electrostatically switchable dry adhesion. SNEs exhibit 40-fold lower nominal dry adhesion than typical solids, yet their adhesion is increased >100-fold by applying 30 V to the CNTs. We characterize the scaling of adhesion with surface morphology, dielectric thickness, and applied voltage and demonstrate digital transfer printing of films of Ag nanowires, polymer and metal microparticles, and unpackaged light-emitting diodes.
Cardiac Magnetic Resonance in Primary Prevention of Sudden Cardiac Death

Sudden death accounts for 400,000 deaths annually in the United States. Most sudden deaths are cardiac and are related to arrhythmias secondary to structural heart disease or primary electrical abnormalities of the heart. Implantable cardioverter defibrillator significantly improves survival in patients at increased risk of life-threatening arrhythmias, but better selection of eligible patients is required to avoid unnecessary implantation and identify those patients who may benefit most from this therapy. Left ventricular (LV) ejection fraction (EF) measured by echocardiography has been considered the most reliable parameter for long-term outcome in many cardiac diseases. However, LVEF is an inaccurate parameter for arrhythmic risk assessment as patients with normal or mildly reduced LV systolic function could experience sudden cardiac death (SCD). Among other tools for arrhythmic stratification, magnetic resonance (CMR) provides the most comprehensive cardiac evaluation including in vivo tissue characterization and significantly aids in the identification of patients at higher SCD risk. Most of the evidence are related to late gadolinium enhancement (LGE), which was proven to detect cardiac fibrosis. LGE has been reported to add incremental value for prognostic stratification and SCD prediction across a wide range of cardiac diseases, including both ischemic and nonischemic cardiomyopathies. In addition, T1, T2 mapping and extracellular volume assessment were reported to add incremental value for arrhythmic assessment despite suffering from several technical limitations. CMR should be part of a multiparametric approach for patients' evaluation, and it will play a pivotal role in prognostic stratification according to the current evidence.
En bloc kidney transplant from pediatric donor to an adult

The use of pediatric kidney donors is not a common practice. Transplant physicians and surgeons are concerned with technical issues as well as inadequate nephrons mass. We reported a case of en bloc kidney transplant from a pediatric donor to serve as a teaching case. The donor is a 3-year-old infant who died as a result of influenza. Due to the age and size discrepancy with an adult, it was decided to transplant the kidneys en bloc into an adult with successful outcome. En bloc technique renders the kidneys transplantable which would have been otherwise discarded and theoretically protect against hyperfiltration injury. Small pediatric donors are excellent resources and should be considered for donation whenever option is available.
Deep Learning-Based Deep Brain Stimulation Targeting and Clinical Applications

Background The purpose of the present study was to evaluate deep learning-based image-guided surgical planning for deep brain stimulation (DBS). We developed deep learning semantic segmentation-based DBS targeting and prospectively applied the method clinically. Methods T2∗ fast gradient-echo images from 102 patients were used for training and validation. Manually drawn ground truth information was prepared for the subthalamic and red nuclei with an axial cut ∼4 mm below the anterior–posterior commissure line. A fully convolutional neural network (FCN-VGG-16) was used to ensure margin identification by semantic segmentation. Image contrast augmentation was performed nine times. Up to 102 original images and 918 augmented images were used for training and validation. The accuracy of semantic segmentation was measured in terms of mean accuracy and mean intersection over the union. Targets were calculated based on their relative distance from these segmented anatomical structures considering the Bejjani target. Results Mean accuracies and mean intersection over the union values were high: 0.904 and 0.813, respectively, for the 62 training images, and 0.911 and 0.821, respectively, for the 558 augmented training images when 360 augmented validation images were used. The Dice coefficient converted from the intersection over the union was 0.902 when 720 training and 198 validation images were used. Semantic segmentation was adaptive to high anatomical variations in size, shape, and asymmetry. For clinical application, two patients were assessed: one with essential tremor and another with bradykinesia and gait disturbance due to Parkinson’s disease. Both improved without complications after surgery, and microelectrode recordings showed subthalamic nuclei signals in the latter patient. Conclusion The accuracy of deep learning-based semantic segmentation may surpass that of previous methods. DBS targeting and its clinical application were made possible using accurate deep learning-based semantic segmentation, which is adaptive to anatomical variations.
Analysis of Cricket Ball Type and Innings on State Level Cricket Batter’s Performance

Background: The aim of this investigation was to compare the type of cricket balls utilized and innings on cricket batting performance in the First-Class Australian competition. Methods: Batting performance measures of 43 state level cricket batters were collected from two seasons of the Sheffield shield tournament (N = 60 games) that incorporated both Kookaburra™ (n = 30 games) and Duke™ (n = 30 games) cricket balls. Results: First-innings batting performances were significantly greater for the average number of runs scored (37.5 ± 13.4 vs. 31.2 ± 11.3), balls faced (60.7 ± 26.2 vs. 49.9 ± 23.6), boundary 4s (3.8 ± 1.9 vs. 2.9 ± 1.4), and boundary 6s (0.2 ± 0.3 vs. 0.1 ± 0.3) scored per game (p < 0.05), as well as centuries scored (5.74 ± 8.56 vs. 1.49 ± 5.14%) compared to second innings performances (p < 0.05). There were no differences for any batting performance measures as a result of ball type (p > 0.05). However, significantly more wickets were taken by pace bowlers during Duke™ ball games (85.0 ± 12.8 vs. 76.4 ± 13.9%), while relatively more wickets were taken by spin bowlers during Kookaburra™ ball games (14.2 ± 12.5 vs. 22.0 ± 14.1%; p < 0.05). Conclusions: Cricket batting performance was comparable in games involving the Kookaburra™ or Duke™ ball. However, pace bowlers were more successful transferring their skill to the Duke™ ball, while spin bowlers were more successful with the KB™ ball. Subsequently, batters may be able to effectively adapt their movement technique, and transfer their skill to the Duke™ ball conditions. Future research is suggested to examine the influence of the cricket playing surface’s deterioration on cricket batter’s interceptive performance.
Electrochemical Generation and Detection of Transient Concentration Gradients in Microfluidic Channels. Theoretical and Experimental Investigations

Transient concentration gradients generated and detected electrochemically in continuous flow microchannels were investigated by numerical simulations and amperometric measurements. Operating conditions including device geometry and hydrodynamic regime were theoretically delineated for producing gradients of various profiles with tunable characteristics. Experiments were carried out with microfluidic devices incorporating a dual-channel-electrode configuration. Under these conditions, high electrochemical performance was achieved both to generate concentration gradients and to monitor their dynamics along linear microchannels. Good agreement was observed between simulated and experimental data validating predictions between gradient properties and generation conditions. These results demonstrated the capability of electrochemical microdevices to produce in situ tunable concentration gradients with real-time monitoring. This approach is versatile for the active control in microfluidics of microenvironments or chemical gradients with high spatiotemporal resolution.
Nanonetwork of Coordination Polymer AHMT-Ag for the Effective and Broad Spectrum Detection of 6-Mercaptopurine in Urine and Blood Serum

Nanocrystalline coordination polymers (NCCPs) have been considered as an incredible electrochemical sensor for the effective detection of biologically dynamic drug 6-mercaptopurine (6-MP). In the present report, a significantly stable infinite arrayed coordination polymeric network was self-assembled via metal with efficient organic tecton 4-amino-3-hydrazino-5-mercapto-1,2,4,-triazole (AHMT) in which silver(I) ions are coordinated by AHMT via hydrazino and exocyclic thiol linkage to form AHMT-Ag NCCP. An efficient and highly sensitive detection of 6-MP is attained owing to eminent electron channeling via polymeric nanocrystallite pores. An effective charge transfer leads to an interface of the AHMT-Ag nano-pores and electrolyte anchored electrode via π–π electron coupling and hydrophobic interaction. The voltammogram exposes acute redox behavior of 6-MP and discloses an impeccable illustration for the AHMT-Ag facilitated oxidation of 6-MP. This unique signature was applied in voltammetric detection of 6-MP in blood serum, human urine, and pharmaceutical formulation (tablet) by a considerable high sensitivity of 0.074, 0.058, and 0.036 μA/μM and a detection limit of 87, 97, and 37 nM, respectively. Thus, the prepared AHMT-Ag NCCP can provide a valuable platform for fabrication of highly sensitive electrochemical devices to assay biologically essential drug molecules.
UMOTMA: Underwater multiple object tracking with memory aggregation

Underwater multi-object tracking (UMOT) is an important technology in marine animal ethology. It is affected by complex factors such as scattering, background interference, and occlusion, which makes it a challenging computer vision task. As a result, the stable continuation of trajectories among different targets has been the key to the tracking performance of UMOT tasks. To solve such challenges, we propose an underwater multi-object tracking algorithm based on memory aggregation (UMOTMA) to effectively associate multiple frames with targets. First, we propose a long short-term memory (LSTM)-based memory aggregation module (LSMAM) to enhance memory utilization between multiple frames. Next, LSMAM embeds LSTM into the transformer structure to save and aggregate features between multiple frames. Then, an underwater image enhancement module ME is introduced to process the original underwater images, which improves the quality and visibility of the underwater images so that the model can extract better features from the images. Finally, LSMAM and ME are integrated with a backbone network to implement the entire algorithm framework, which can fully utilize the historical information of the tracked targets. Experiments on the UMOT datasets and the underwater fish school datasets show that UMOTMA generally outperforms existing models and can maintain the stability of the target trajectory while ensuring high-quality detection. The code is available via Github.
Non-invasive Ventilation in Cancer Patients: a historically matched controlled study

Prognosis of cancer patients requiring Invasive Mechanical Ventilation (IMV) is poor. Various studies conducted mainly in patients with haematological malignancies have shown that Non-Invasive Ventilation (NIV) is associated with improved results OBJECTIVE: To compare NIV with IMV in patients with various malignancies. An assessment was also made of the possible bias in our results due to recent improvements in IMV. MATERIAL AND METHODS: A historically matched controlled study of NIV versus IMV. Forty seven patients treated by NIV were matched with 47 historical controls treated by IMV. Matching was performed according to 5 variables: type of cancer, leucopenia, allogeneic bone marrow transplantation, SAPS II score and reason for ventilation. RESULTS: Duration of ventilation and of hospitalisation were significantly (p=0.001) shorter in the NIV group; 48% of patients treated with NIV were discharged from the hospital versus 23% of those treated by IMV (p=0.08). NIV was statistically more effective than IMV in solid tumours, non transplanted and non leucopenic patients. Contrary to the period before 1996, when the analysis was restricted to the IMV matched cases, in the period since 1996, no difference in terms of mortality between IMV and NIV was found. CONCLUSIONS: In comparison with IMV, NIV in cancer patients: is associated with two significant advantages: reduction in ventilation duration and reduction in hospitalisation stay.
Vertical‐jump Tests: A Critical Review

THE DEVELOPMENT OF EXPLOsive power in the legs is important for success in a variety of athletic pursuits, from attacking in volleyball to rebounding in basketball. But even for activities that do not rely specifically on the vertical jump per se, such as blocking in football, vertical-jump tests provide an effective measurement of power as an indirect measure of performance. Such tests have been used for assessing weightlifters and powerlifters (11, 12), football and basketball players (6, 8), volleyball players (19), swimmers (2), and college students (7). Coaches and strength and conditioning professionals have long used performance tests such as the vertical jump to assess athletic ability, which helps them identify athletes’ strengths and weaknesses, chart and document progress, or assign positions and ranking to individuals (13). Since most athletes and coaches strive for an improvement in performance, vertical-jump testing is being used to measure the effectiveness of various training programs in the development of explosive power, including strengthtraining programs (14), plyometrics (18), and periodization training (8). The vertical jump has also been used for talent identification and the prediction of future success in specific athletic disciplines, including weightlifting (11, 22) and swimming (1). Clearly, vertical-jump testing has numerous sport applications, but there are many protocols being used to assess vertical-jump ability and explosive power in athletes. Depending on the equipment used, the vertical jump can be considered a field or laboratory test. Although laboratory tests using devices such as force platforms generally allow for a greater level of precision and accuracy in testing vertical jump, these measures also tend to be more expensive and less feasible for the average sports participant. Fortunately, many vertical-jump field tests exist that are very practical in terms of time, effort, and equipment.
N-Acetylcysteine Attenuates the Increasing Severity of Distant Organ Liver Dysfunction after Acute Kidney Injury in Rats Exposed to Bisphenol A

Distant organ liver damage after acute kidney injury (AKI) remains a serious clinical setting with high mortality. This undesirable outcome may be due to some hidden factors that can intensify the consequences of AKI. Exposure to bisphenol A (BPA), a universal chemical used in plastics industry, is currently unavoidable and can be harmful to the liver. This study explored whether BPA exposure could be a causative factor that increase severity of remote liver injury after AKI and examined the preventive benefit by N-acetylcysteine (NAC) in this complex condition. Male Wistar rats were given vehicle, BPA, or BPA + NAC for 5 weeks then underwent 45 min renal ischemia followed by 24 h reperfusion (RIR), a group of vehicle-sham-control was also included. RIR not only induced AKI but produced liver injury, triggered systemic oxidative stress as well as inflammation, which increasing severity upon exposure to BPA. Given NAC to BPA-exposed rats diminished the added-on effects of BPA on liver functional impairment, oxidative stress, inflammation, and apoptosis caused by AKI. NAC also mitigated the abnormalities in mitochondrial functions, dynamics, mitophagy, and ultrastructure of the liver by improving the mitochondrial homeostasis regulatory signaling AMPK-PGC-1α-SIRT3. The study demonstrates that NAC is an effective adjunct for preserving mitochondrial homeostasis and reducing remote effects of AKI in environments where BPA exposure is vulnerable.