Co-dependent formation of the Toxoplasma gondii sub-pellicular microtubules and inner membrane skeleton.

One of the defining features of apicomplexan parasites is their cytoskeleton composed of alveolar vesicles, known as the inner membrane complex (IMC) undergirded by intermediate-like filament network and an array of subpellicular microtubules (SPMTs). In Toxoplasma gondii, this specialized cytoskeleton is involved in all aspects of the disease-causing lytic cycle, and notably acting as a scaffold for parasite offspring in the internal budding process. Despite advances in our understanding of the architecture and molecular composition, insights pertaining to the coordinated assembly of the scaffold are still largely elusive. Here, T. gondii tachyzoites were dissected by advanced, iterative expansion microscopy (pan-ExM) revealing new insights into the very early sequential formation steps of the tubulin scaffold. A comparative study of the related parasite Sarcocystis neurona revealed that different MT bundling organizations of the nascent SPMTs correlate with the number of central and basal alveolar vesicles. In absence of a so far identified MT nucleation mechanism, we genetically dissected T. gondii γ-tubulin and γ-tubulin complex protein 4 (GCP4). While γ-tubulin depletion abolished the formation of the tubulin scaffold, a set of MTs still formed that suggests SPMTs are nucleated at the outer core of the centrosome. Depletion of GCP4 interfered with the correct assembly of SPMTs into the forming daughter buds, further indicating that the parasite utilizes the γ-tubulin complex in tubulin scaffold formation .

Dietary Sugar and Anthropometrics among Young Children in the Guelph Family Health Study: Longitudinal Associations.

Purpose: Our understanding of the influence of sugar intake on anthropometrics among young children is limited. Most existing research is cross-sectional and has focused on sugar-sweetened beverages. The study objective was to investigate longitudinal associations between young children's total, free, and added sugar intake from all food sources at baseline with anthropometric measures at baseline and 18 months.Methods: The Guelph Family Health Study (GFHS) is an ongoing randomized controlled trial and a family-based health promotion study. Food records and anthropometric data were collected at baseline (n = 109, 55 males; 3.7 ± 1.1 y, mean ± SD) and 18 months (n = 109, 55 males; 5.1 ± 1.1 y) of the GFHS pilots. Associations between sugar intakes and anthropometrics were estimated using linear regression models with generalized estimating equations adjusted for age, sex, household income, and intervention status.Results: Total sugar intake was inversely associated with body weight at 18 months (P = 0.01). There was no effect of time on any other associations between total, free, and added sugar intakes and anthropometrics.Conclusions: Early life dietary sugar intakes may not relate to anthropometric measures in the short term. Further investigation into potential associations between dietary sugar intakes and anthropometric variables over longer time periods is warranted.

Improvement of PbSn Solder Reliability with Ge Microalloying-Induced Optimization of Intermetallic Compounds Growth.

PbSn solders are used in semiconductor devices for aerospace or military purposes with high levels of reliability requirements. Microalloying has been widely adopted to improve the reliability for Pb-free solders, but its application in PbSn solders is scarce. In this article, the optimization of PbSn solder reliability with Ge microalloying was investigated using both experimental and calculation methods. Intermetallic compounds (IMC) growth and morphologies evolution during reliability tests were considered to be the main factors of device failure. Through first-principle calculation, the growth mechanism of interfacial Ni3Sn4 was discussed, including the formation of vacancies, the Ni-vacancies exchange diffusion and the dominant Ni diffusion along the [1 0 0] direction. The doping of Ge in the cell increased the exchange energy barrier and thus inhibited the IMC development and coarsening trend. In three reliability tests, only 0.013 wt% Ge microalloying in Pb60Sn40 was able to reduce IMC thickness by an increment of 22.6~38.7%. The proposed Ge microalloying method in traditional PbSn solder could yield a prospective candidate for highly reliable applications.

Vegan grade medium component screening and concentration optimization for the fermentation of the probiotic strain Lactobacillus paracasei IMC 502® using Design of Experiments.

Lactobacillus paracasei IMC502® is a commercially successful probiotic strain. However, there are no reports that investigate growth medium composition in relation to improved biomass production for this strain. The major outcome of the present study is the design and optimization of a growth medium based on vegan components to be used in the cultivation of Lactobacillus paracasei IMC502®, by using Design of Experiments. Besides comparing different carbon sources, the use of plant-based peptones as nitrogen sources was considered. In particular, the use of guar peptone as the main nitrogen source, in the optimization of fermentation media for the production of probiotics, could replace other plant peptones (e.g. potato, rice, wheat, and soy) which are part of the human diet, thereby avoiding an increase in product and process prices. A model with R2 and adjusted R2 values higher than 95% was obtained. Model accuracy was equal to 94.11%. The vegan-optimized culture medium described in this study increased biomass production by about 65% compared to growth on De Man-Rogosa-Sharpe (MRS) medium. Moreover, this approach showed that most of the salts and trace elements generally present in MRS are not affecting biomass production, thus a simplified medium preparation can be proposed with higher probiotic biomass yield and titer. The possibility to obtain viable lactic acid bacteria at high density from vegetable derived nutrients will be of great interest to specific consumer communities, opening the way to follow this approach with other probiotics of impact for human health.

SpaceANOVA: Spatial Co-occurrence Analysis of Cell Types in Multiplex Imaging Data Using Point Process and Functional ANOVA.

Multiplex imaging platforms have enabled the identification of the spatial organization of different types of cells in complex tissue or the tumor microenvironment. Exploring the potential variations in the spatial co-occurrence or colocalization of different cell types across distinct tissue or disease classes can provide significant pathological insights, paving the way for intervention strategies. However, the existing methods in this context either rely on stringent statistical assumptions or suffer from a lack of generalizability. We present a highly powerful method to study differential spatial co-occurrence of cell types across multiple tissue or disease groups, based on the theories of the Poisson point process and functional analysis of variance. Notably, the method accommodates multiple images per subject and addresses the problem of missing tissue regions, commonly encountered due to data-collection complexities. We demonstrate the superior statistical power and robustness of the method in comparison with existing approaches through realistic simulation studies. Furthermore, we apply the method to three real data sets on different diseases collected using different imaging platforms. In particular, one of these data sets reveals novel insights into the spatial characteristics of various types of colorectal adenoma.

[First-line management of infertile couple. Guidelines for clinical practice of the French College of Obstetricians and Gynecologists 2022]. / Prise en charge de première intention du couple infertile : mise à jour des RPC 2010 du CNGOF.

OBJECTIVE: To update the 2010 CNGOF clinical practice guidelines for the first-line management of infertile couples. MATERIALS AND METHODS: Five major themes (first-line assessment of the infertile woman, first-line assessment of the infertile man, prevention of exposure to environmental factors, initial management using ovulation induction regimens, first-line reproductive surgery) were identified, enabling 28 questions to be formulated using the Patients, Intervention, Comparison, Outcome (PICO) format. Each question was addressed by a working group that had carried out a systematic review of the literature since 2010, and followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) methodology to assess the quality of the scientific data on which the recommendations were based. These recommendations were then validated during a national review by 40 national experts. RESULTS: The fertility work-up is recommended to be prescribed according to the woman's age: after one year of infertility before the age of 35 and after 6months after the age of 35. A couple's initial infertility work-up includes a single 3D ultrasound scan with antral follicle count, assessment of tubal permeability by hysterography or HyFOSy, anti-Mullerian hormone assay prior to assisted reproduction, and vaginal swabbing for vaginosis. If the 3D ultrasound is normal, hysterosonography and diagnostic hysteroscopy are not recommended as first-line procedures. Chlamydia trachomatis serology does not have the necessary performance to predict tubal patency. Post-coital testing is no longer recommended. In men, spermogram, spermocytogram and spermoculture are recommended as first-line tests. If the spermogram is normal, it is not recommended to check the spermogram. If the spermogram is abnormal, an examination by an andrologist, an ultrasound scan of the testicles and hormonal test are recommended. Based on the data in the literature, we are unable to recommend a BMI threshold for women that would contraindicate medical management of infertility. A well-balanced Mediterranean-style diet, physical activity and the cessation of smoking and cannabis are recommended for infertile couples. For fertility concern, it is recommended to limit alcohol consumption to less than 5 glasses a week. If the infertility work-up reveals no abnormalities, ovulation induction is not recommended for normo-ovulatory women. If intrauterine insemination is indicated based on an abnormal infertility work-up, gonadotropin stimulation and ovulation monitoring are recommended to avoid multiple pregnancies. If the infertility work-up reveals no abnormality, laparoscopy is probably recommended before the age of 30 to increase natural pregnancy rates. In the case of hydrosalpinx, surgical management is recommended prior to ART, with either salpingotomy or salpingectomy depending on the tubal score. It is recommended to operate on polyps>10mm, myomas 0, 1, 2 and synechiae prior to ART. The data in the literature do not allow us to systematically recommend asymptomatic uterine septa and isthmoceles as first-line surgery. CONCLUSION: Based on strong agreement between experts, we have been able to formulate updated recommendations in 28 areas concerning the initial management of infertile couples.

Mapping the single cell spatial immune landscapes of the melanoma microenvironment.

Melanoma is a highly immunogenic malignancy with an elevated mutational burden, diffuse lymphocytic infiltration, and one of the highest response rates to immune checkpoint inhibitors (ICIs). However, over half of all late-stage patients treated with ICIs will either not respond or develop progressive disease. Spatial imaging technologies are being increasingly used to study the melanoma tumor microenvironment (TME). The goal of such studies is to understand the complex interplay between the stroma, melanoma cells, and immune cell-types as well as their association with treatment response. Investigators seeking a better understanding of the role of cell location within the TME and the importance of spatial expression of biomarkers are increasingly turning to highly multiplexed imaging approaches to more accurately measure immune infiltration as well as to quantify receptor-ligand interactions (such as PD-1 and PD-L1) and cell-cell contacts. CyTOF-IMC (Cytometry by Time of Flight - Imaging Mass Cytometry) has enabled high-dimensional profiling of melanomas, allowing researchers to identify complex cellular subpopulations and immune cell interactions with unprecedented resolution. Other spatial imaging technologies, such as multiplexed immunofluorescence and spatial transcriptomics, have revealed distinct patterns of immune cell infiltration, highlighting the importance of spatial relationships, and their impact in modulating immunotherapy responses. Overall, spatial imaging technologies are just beginning to transform our understanding of melanoma biology, providing new avenues for biomarker discovery and therapeutic development. These technologies hold great promise for advancing personalized medicine to improve patient outcomes in melanoma and other solid malignancies.

The Influence of BMI in Asthma: Which Traits Are due to Obesity and Which to the Asthma and Obesity Phenotype?

Background: The characteristics of the asthma and obesity phenotype have been described in cluster studies but have not been subsequently confirmed. Specific characteristics of this phenotype have not been differentiated from those inherent to the patient’s body mass index (BMI). Objectives: This study aims to assess the effect of BMI on asthma in order to identify which traits could define the asthma and obesity phenotype and which are inherent to the patient's BMI. Methods: A real-life retrospective observational study was conducted based on data from 2514 patients with suspected asthma collected at the first visit to the allergy clinic between November 2014 and November 2017. All patients had to perform an appropriate spirometry maneuver. All BMI, sex, and age groups were represented. Results: The influence of BMI on asthma differed according to age group and sex. All spirometry results and FeNO were influenced by BMI. The only notable asthma characteristics were later onset of asthma with higher BMI values. No other differences were found between the BMI groups. Conclusions: The effect of BMI on asthma is age-dependent; therefore, it should be corrected for age. The most important variations are in FeNO and spirometry results. The specific characteristics of the asthma and obesity phenotype are a greater perception of symptoms with fewer alterations in respiratory function tests and a lower prevalence of atopy, rhinitis, and allergy, including allergic asthma. Other characteristics of this phenotype, such as a higher female prevalence or late-onset or noneosinophilic asthma, are nonspecific for this phenotype

Antecedentes : las características del fenotipo del asma y la obesidad se han descrito en estudios grupales, pero no se han confirmado posteriormente. Las características específicas de este fenotipo no se han diferenciado de las inherentes al índice de masa corporal (IMC) del paciente. Objetivos : Este estudio tiene como objetivo evaluar el efecto del IMC sobre el asma para identificar qué rasgos podrían definir el fenotipo del asma y la obesidad y cuáles son inherentes al IMC del paciente. Métodos : Se realizó un estudio observacional retrospectivo de la vida real basado en datos de 2514 pacientes con sospecha de asma recopilados en la primera visita a la clínica de alergia entre noviembre de 2014 y noviembre de 2017. Todos los pacientes tuvieron que realizar una maniobra de espirometría adecuada. Estuvieron representados todos los grupos de IMC, sexo y edad. Resultados : La influencia del IMC sobre el asma difirió según grupo de edad y sexo. Todos los resultados de la espirometría y el FeNO estuvieron influenciados por el IMC. Las únicas características notables del asma fueron la aparición tardía del asma con valores de IMC más altos. No se encontraron otras diferencias entre los grupos de IMC. Conclusiones : El efecto del IMC sobre el asma depende de la edad; por lo tanto, debe corregirse según la edad. Las variaciones más importantes se encuentran en los resultados de FeNO y espirometría. Las características específicas del fenotipo de asma y obesidad son una mayor percepción de los síntomas con menos alteraciones en las pruebas de función respiratoria y una menor prevalencia de atopia, rinitis y alergia, incluido el asma alérgica. Otras características de este fenotipo, como una mayor prevalencia femenina o asma de aparición tardía o no eosinofílica, no son específicas de este fenotipo (AU)

Extremely Low Contact Resistivity of Bi2Te3-Based Modules Enabled by NiP-Based Alloy Barrier.

Electrode diffusion barrier plays an important role in thermoelectric cooling devices. Compared with p-type Bi0.5Sb1.5Te3, the compatibility between commercial Ni barrier and n-type Bi2Te2.7Se0.3 is a key bottleneck to enhance the performance of Bi2Te3-based cooling devices. This paper proposed a NiP alloy barrier to improve the compatibility with n-type Bi2Te2.7Se0.3, and systemically investigated the contact and interfacial dynamics properties. Due to the low diffusion rate of NiP alloy, the initial interfacial contact resistivity of Bi2Te2.7Se0.3/NiP is as low as 0.90 µΩ cm2, and it further can be depressed below 1.98 µΩ cm2 even after aging at 423 K for 35 days, indicating the superior thermal stability of the NiP barrier layer compared to the commercial Ni barrier layer. Based on the NiP barrier, a 15-pair bismuth telluride device is prepared and a high cooling temperature difference of 71.5 K at a hot-side temperature of 304 K is achieved, which proves the practical applications potential of NiP barrier for Bi2Te3-based modules.

A Method for Fast Au-Sn Bonding at Low Temperature Using Thermal Gradient.

Flip chip bonding technology on gold-tin (Au-Sn) microbumps for MEMS (Micro Electro Mechanical Systems) and 3D packaging is becoming increasingly important in the electronics industry. The main advantages of Au-Sn microbumps are a low electrical resistance, high electrical reliability, and fine pitch. However, the bonding temperature is relatively high, and the forming mechanism of an intermetallic compound (IMC) is complicated. In this study, Au-Sn solid-state diffusion (SSD) bonding is performed using the thermal gradient bonding (TGB) method, which lowers bonding temperature and gains high bonding strength in a short time. Firstly, Au-Sn microbumps with a low roughness are prepared by using an optimized process. Then, Au-Sn bonding parameters including bonding temperature, bonding time, and bonding pressure are optimized to obtain a higher bonding quality. The shear strength of 23.898 MPa is obtained when bonding in the HCOOH environment for 10 min at the gradient temperature of 150 °C/250 °C with a bonding pressure of more than 10 MPa. The IMC of Au-Sn is found to be Au-Sn and Au5Sn. The effect of annealing time on the IMC is also investigated. More and more Au5Sn is generated with an increase in annealing time, and Au5Sn is formed after Sn is depleted. Finally, the effect of annealing time on the IMC is verified by using finite element simulation, and the bonding strength of IMC was found to be higher when the bonding temperature is 150 °C at the cold side and 250 °C at the hot side. The temperature in the bonding area can reach 200 °C, which proves that the Au-Sn bonding process is solid-state diffusion because the temperature gradient reaches 2500 °C/cm.

Resting energy expenditure changes after antineoplastic treatment in gynecological cancer: a prospective pilot study.

Introduction: Introduction: energy metabolism in cancer patients is influenced by different factors. However, the effect of antineoplastic treatment is not clear, especially in women. Objective: to evaluate resting energy expenditure (REE) by indirect calorimetry (IC) before (T0) and after (T1) first cycle period of antineoplastic therapy: radiotherapy (RT), chemotherapy (CT), and concomitant chemoradiation therapy (CRT), quality of life (QoL) and accuracy of REE were compared with international guidelines recommendations per kilogram (European Society for Clinical Nutrition and Metabolism [ESPEN]). Methods: an observational, longitudinal study was conducted in women with gynecological cancer diagnosis undergoing antineoplastic treatment: RT, CT and CRT. Weight loss, actual body weight and height were measured. REE was evaluated in T0-T1 and compared with ESPEN recommendations. Kruskal-Wallis test and Bland-Alman analysis were used to determine the agreement (± 10 % of energy predicted) of REE adjusted by physical activity (TEE) compared with ESPEN recommendations, respectively. Results: fifty-four women with cancer were included: 31.5 % (n = 17) for RT group, 31.5 % (n = 17) for CT group and 37 % (n = 20) for CRT group. REE showed statistical differences between T0 and T1 in the total population (p = 0.018), but these were not associated with anticancer therapy groups (p > 0.05). QoL had no significant changes after treatment (p > 0.05). Accuracy of 25 and 30 kcal/kg compared to TEE was less than 30 %. Conclusion: REE in women with gynecological cancer decreased after antineoplastic treatments but this is not associated with a particular antineoplastic therapy. It is needed to develop research to determine the accuracy of ESPEN recommendations with TEE estimated by IC and clinical factors in women with cancer.

Introducción: Antecedentes: el metabolismo energético en pacientes con cáncer está influenciado por diferentes factores. Sin embargo, el efecto sobre el tratamiento antineoplásico no es claro, especialmente en mujeres. Objetivo: evaluar el gasto energético en reposo (GER) mediante calorimetría indirecta (CI) antes (T0) y después (T1) del primer ciclo del tratamiento antineoplásico: radioterapia (RT), quimioterapia (QT) y quimio-radioterapia concomitante (QRT), calidad de vida (CdV) y precisión del GER con las con las recomendaciones internacionales por kilogramo de peso (European Society for Clinical Nutrition and Metabolism [ESPEN]). Métodos: se realizó un estudio longitudinal, observacional en mujeres con diagnóstico de cáncer ginecológico en tratamiento antineoplásico. Se evaluó el GER en T0 y T1. Se midieron la pérdida de peso, el peso corporal y la talla. Se usaron las pruebas de Kruskal-Wallis y el análisis Bland-Altman para determinar la concordancia (± 10 % de GER) del REE ajustado por actividad física (TEE) en comparación con las recomendaciones de ESPEN. Resultados: se incluyeron 54 mujeres con cáncer; 31,5 % (n = 17) en el grupo RT, 31,5 % (n = 17) en el de QT y 37 % (n = 20) en el de QRT. GER mostró diferencias estadísticas entre T0 y T1 en la población total (p = 0,018); no se asoció con la terapia contra el cáncer (p > 0,05). La calidad de vida no tuvo cambios significativos después del tratamiento (p > 0,05). La precisión de 25 y 30 kcal/kg en comparación con TEE fue inferior al 30 %. Conclusión: el GER en mujeres con cáncer ginecológico disminuyó después del tratamiento antineoplásico, pero no se asoció a una terapia antineoplásica en particular. Es fundamental desarrollar más investigaciones que compare las recomendaciones de ESPEN y con los valores de la CI comparando más factores clínicos para ofrecer una intervención nutricional precisa.

Phase Equilibria of the Ag-Al-Au Ternary System and Interfacial Reactions in the Au-xAg/Al Couples at 450 °C.

The phase equilibria of the Ag-Al-Au ternary system and the solid-state reaction couple for the Au-xAg/Al system were investigated isothermally at 450 °C. By investigating the Ag-Al-Au ternary system and its isothermal section, this study aims to provide a clearer understanding of the phase stability and interfacial reactions between different phases. This information is crucial for designing materials and processes in electronic packaging, with the potential to reduce costs and improve reliability. There were seven single-phase regions, thirteen two-phase regions, and six three-phase regions, with no ternary intermetallic compound (IMC) formed in the isothermal section of the Ag-Al-Au ternary system. When the Au-25 wt.% Ag/Al couple was aged at 450 °C for 240-1500 h, the AuAl2, Au2Al, and Au4Al phases formed at the interface. When the Ag contents increased to 50 and 75 wt.%, the Ag2Al, AuAl2, and Au4Al phases formed at the interface. When the aging time increased from 240 h to 1500 h, the total IMC thickness in all Au-xAg/Al couples became thicker, but the types of IMCs formed at the interface did not change. The total IMC thickness also increased with the increase in the Ag content. When the Ag content was greater than 25 wt.%, the Au2Al phase was converted into the Ag2Al phase. The IMC growth mechanism in all of the couples followed a reaction-controlled process.

Dual-modality imaging of immunofluorescence and imaging mass cytometry for whole-slide imaging and accurate segmentation.

Imaging mass cytometry (IMC) is a powerful technique capable of detecting over 30 markers on a single slide. It has been increasingly used for single-cell-based spatial phenotyping in a wide range of samples. However, it only acquires a rectangle field of view (FOV) with a relatively small size and low image resolution, which hinders downstream analysis. Here, we reported a highly practical dual-modality imaging method that combines high-resolution immunofluorescence (IF) and high-dimensional IMC on the same tissue slide. Our computational pipeline uses the whole-slide image (WSI) of IF as a spatial reference and integrates small-FOV IMC into a WSI of IMC. The high-resolution IF images enable accurate single-cell segmentation to extract robust high-dimensional IMC features for downstream analysis. We applied this method in esophageal adenocarcinoma of different stages, identified the single-cell pathology landscape via reconstruction of WSI IMC images, and demonstrated the advantage of the dual-modality imaging strategy.

Characterization of papillary and clear cell renal cell carcinoma through imaging mass cytometry reveals distinct immunologic profiles.

Objective: To characterize and further compare the immune cell populations of the tumor microenvironment (TME) in both clear cell and papillary renal cell carcinoma (RCC) using heavy metal-labeled antibodies in a multiplexed imaging approach (imaging mass cytometry). Materials and methods: Formalin-fixed paraffin-embedded (FFPE) baseline tumor tissues from metastatic patients with clear cell renal cell carcinoma (ccRCC) and papillary renal cell carcinoma (pRCC) were retrospectively requisitioned from an institutional biorepository. Pretreated FFPE samples from 33 RCC patients (10 ccRCC, 23 pRCC) were accessioned and stained for imaging mass cytometry (IMC) analysis. Clinical characteristics were curated from an institutional RCC database. FFPE samples were prepared and stained with heavy metal-conjugated antibodies for IMC. An 11-marker panel of tumor stromal and immune markers was used to assess and quantify cellular relationships in TME compartments. To validate our time-of-flight (CyTOF) analysis, we cross-validated findings with The Cancer Genome Atlas Program (TCGA) analysis and utilized the CIBERSORTx tool to examine the abundance of main immune cell types in pRCC and ccRCC patients. Results: Patients with ccRCC had a longer median overall survival than did those with pRCC (67.7 vs 26.8 mo, respectively). Significant differences were identified in the proportion of CD4+ T cells between disease subtypes (ccRCC 14.1%, pRCC 7.0%, p<0.01). Further, the pRCC cohort had significantly more PanCK+ tumor cells than did the ccRCC cohort (24.3% vs 9.5%, respectively, p<0.01). There were no significant differences in macrophage composition (CD68+) between cohorts. Our results demonstrated a significant correlation between the CyTOF and TCGA analyses, specifically validating that ccRCC patients exhibit higher levels of CD4+ T cells (ccRCC 17.60%, pRCC 15.7%, p<0.01) and CD8+ T cells (ccRCC 17.83%, pRCC 11.15%, p<0.01). The limitation of our CyTOF analysis was the large proportion of cells that were deemed non-characterizable. Conclusions: Our findings emphasize the need to investigate the TME in distinct RCC histological subtypes. We observed a more immune infiltrative phenotype in the TME of the ccRCC cohort than in the pRCC cohort, where a tumor-rich phenotype was noted. As practical predictive biomarkers remain elusive across all subtypes of RCC, further studies are warranted to analyze the biomarker potential of such TME classifications.

IMC based modified Smith predictor for second order delay dominated processes with RHP.

A modified Smith predictor (MSP) with IMC based tuning is proposed for second order delay dominated processes. These processes often exhibit unstable behaviour due to right half poles (RHP) with positive or negative zeros. The control scheme incorporates forward path PI/PID controller with a lead-lag filter and a PD controller in the feedback path. IMC technique having single tuning parameter is utilized to design the forward path controller, while the feedback path controller is tuned by Routh stability criterion. The proposed scheme ascertains quick set point following without overshoot and smooth disturbance rejection, resulting superior closed-loop performance compared to recent MSP schemes. Validation is made based on performance indices and stability margins.

Multimodal Mass Spectrometry Imaging of an Aggregated 3D Cell Culture Model.

Multimodal mass spectrometry imaging (MSI) is a leading approach for investigating the molecular processes within biological samples. The parallel detection of compounds including metabolites, lipids, proteins, and metal isotopes allows for a more holistic understanding of tissue microenvironments. Universal sample preparation is a primary enabler for samples of the same set to be run across multiple modalities. Using the same method and materials for a cohort of samples reduces any potential variability during sample preparation and allows for comparable analysis across analytical imaging techniques. Here, the MSI workflow is describing a sample preparation protocol for the analysis of three-dimensional (3D) cell culture models. The analysis of biologically relevant cultures by multimodal MSI offers a method in which models of cancer and disease can be studied for the use in early-stage drug development.

Molecular architecture of proliferative lupus nephritis as elucidated using 50-plex imaging mass cytometry proteomics.

Due to unique advantages that allow high-dimensional tissue profiling, we postulated imaging mass cytometry (IMC) may shed novel insights on the molecular makeup of proliferative lupus nephritis (LN). This study interrogates the spatial expression profiles of 50 target proteins in LN and control kidneys. Proliferative LN glomeruli are marked by podocyte loss with immune infiltration dominated by CD45RO+, HLA-DR+ memory CD4 and CD8 T-cells, and CD163+ macrophages, with similar changes in tubulointerstitial regions. Macrophages are the predominant HLA-DR expressing antigen presenting cells with little expression elsewhere, while macrophages and T-cells predominate cellular crescents. End-stage sclerotic glomeruli are encircled by an acellular fibro-epithelial Bowman's space surrounded by immune infiltrates, all enmeshed in fibronectin. Proliferative LN also shows signs indicative of epithelial to mesenchymal plasticity of tubular cells and parietal epithelial cells. IMC enabled proteomics is a powerful tool to delineate the spatial architecture of LN at the protein level.

High-precision dynamic torque control of high stiffness actuator for humanoids.

The high stiffness actuator (HSA), applied to each joint of an electrical driven humanoid robot, can directly affect the motion performance of the torque-controlled humanoid robots. For high control performance of HSA, a high-precision dynamic torque control (HDTC) is proposed. The HDTC consists of two phases: (1) A novel dynamic current control is used to linearize high stiffness actuator torque control system, which can estimate and compensate the nonlinear coupling parts; (2) An enhanced internal model control is designed to ensure high tracking accuracy in the system containing noisy torque signal and even numerical differentiation signals. Benefitting from dynamic current control and the enhanced internal model control, the proposed HDTC is accurate and adaptable. Finally, the superiority of the HDTC is verified with comparative experiments.

Trends and Challenges in AIoT/IIoT/IoT Implementation.

For the next coming years, metaverse, digital twin and autonomous vehicle applications are the leading technologies for many complex applications hitherto inaccessible such as health and life sciences, smart home, smart agriculture, smart city, smart car and logistics, Industry 4.0, entertainment (video game) and social media applications, due to recent tremendous developments in process modeling, supercomputing, cloud data analytics (deep learning, etc.), communication network and AIoT/IIoT/IoT technologies. AIoT/IIoT/IoT is a crucial research field because it provides the essential data to fuel metaverse, digital twin, real-time Industry 4.0 and autonomous vehicle applications. However, the science of AIoT is inherently multidisciplinary, and therefore, it is difficult for readers to understand its evolution and impacts. Our main contribution in this article is to analyze and highlight the trends and challenges of the AIoT technology ecosystem including core hardware (MCU, MEMS/NEMS sensors and wireless access medium), core software (operating system and protocol communication stack) and middleware (deep learning on a microcontroller: TinyML). Two low-powered AI technologies emerge: TinyML and neuromorphic computing, but only one AIoT/IIoT/IoT device implementation using TinyML dedicated to strawberry disease detection as a case study. So far, despite the very rapid progress of AIoT/IIoT/IoT technologies, several challenges remain to be overcome such as safety, security, latency, interoperability and reliability of sensor data, which are essential characteristics to meet the requirements of metaverse, digital twin, autonomous vehicle and Industry 4.0. applications.

Role of weight lost in breast cancer-related lymph / Importancia de la pérdida de peso en el linfedema secundario a cáncer de mama

Objective: Analysis of data collected in routine clinical practice of the combined impact of both physical activity and decrease in body mass index (BMI) on a minor prevalence of lymphedema in post-breast cancer patients. Methods: Analysis of data obtained by the specialized rehabilitation unit, from 99 female patients for 18 months, after a specific diet, sports program and complete decongestive therapy (CDT) was indicated. Personal data, affected organ volume, weight, physical activity level and Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer (FACT-B+4) were collected in follow-up visits. Results: Although the average of body-mass index showed no change during the assessment period, about 13% of patients in the second follow-up visit and 30% in the third one had lost weight. Women experiencing weight-loss in the third follow-up visit presented a reduced volume of the affected organ [−50 (−248 to 141) ml vs. 130 (−148 to 355) ml, p<0.05] as compared to weight-gaining patients. No relationship was established between physical activity and lymphedema volume changes. Conclusions: Apart from the conventional treatment with orthotics and manual lymph drainage, BCRL prevention and treatment needs to focus – right from the start – on weight management or weight-loss in obese patients.(AU)

Objetivo: Analizar los datos recopilados en la práctica clínica rutinaria sobre el impacto combinado de la actividad física y la reducción del índice de masa corporal (IMC) en la reducción de la prevalencia de linfedema secundario a cáncer de mama (BCRL). Métodos: Análisis de los datos obtenidos por la unidad de rehabilitación especializada, de 99 pacientes durante 18 meses, tras prescribirse una dieta específica, un programa deportivo y una terapia descongestiva completa (TDC). En las visitas de seguimiento se recopilaron datos personales, volumen del órgano afectado, peso, nivel de actividad física y FACT-B+4 (Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer). Resultados: Aunque el índice de masa corporal medio no reflejó cambios durante el periodo de evaluación, cerca del 13% de las pacientes habían perdido peso en la segunda semana de seguimiento, incrementándose este porcentaje al 30% en la tercera semana. Las mujeres que experimentaron pérdida de peso durante la tercera visita de seguimiento presentaron una reducción del volumen del órgano afectado [-50 (-248-141)ml vs. 130 (-148-355)ml, p<0,05] en comparación con las pacientes que habían ganado peso. No se estableció relación alguna entre la actividad física y los cambios de volumen de linfedema. Conclusiones: Aparte del tratamiento convencional con ortésicos y drenaje linfático manual, la prevención y tratamiento de BCRL debe centrarse, desde el inicio, en la gestión del peso o la pérdida de peso en las pacientes obesas.(AU)