Evolution of protective SARS-CoV-2-specific B and T cell responses upon vaccination and Omicron breakthrough infection.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron breakthrough infection (BTI) induced better protection than triple vaccination. To address the underlying immunological mechanisms, we studied antibody and T cell response dynamics during vaccination and after BTI. Each vaccination significantly increased peak neutralization titers with simultaneous increases in circulating spike-specific T cell frequencies. Neutralization titers significantly associated with a reduced hazard rate for SARS-CoV-2 infection. Yet, 97% of triple vaccinees became SARS-CoV-2 infected. BTI further boosted neutralization magnitude and breadth, broadened virus-specific T cell responses to non-vaccine-encoded antigens, and protected with an efficiency of 88% from further infections by December 2022. This effect was then assessed by utilizing mathematical modeling, which accounted for time-dependent infection risk, the antibody, and T cell concentration at any time point after BTI. Our findings suggest that cross-variant protective hybrid immunity induced by vaccination and BTI was an important contributor to the reduced virus transmission observed in Bavaria in late 2022 and thereafter.

The clinical signature of genetic variants and serum levels of macrophage migration inhibitory factor in Egyptian breast cancer patients.

PURPOSE: Macrophage migration inhibitory factor (MIF) is an integral cytokine for the modulation of both innate and adaptive immunity and is involved in the pathogenesis of various cancers. However, conflicting findings on the relationship between MIF polymorphisms and breast cancer (BC) have been reported in earlier research. We investigated the clinical value of serum MIF levels and the association between MIF rs1049829 and rs755622 variants with their serum levels and propensity to develop BC. METHODS: A total of 133 treatment-naïve Egyptian BC females and 126 apparently healthy controls were matriculated in this case-control study. The serum MIF protein levels were quantified by ELISA, whereas the genotyping was executed utilizing the TaqMan® allelic discrimination assay. RESULTS: A significant increase in the serum MIF level in BC cases was observed in comparison to control subjects (P < 0.0001), with a diagnostic potential to discriminate BC with 92.5% sensitivity and 73.7% specificity at a cut-off value > 9.47 ng/mL. Besides, a significant difference in serum MIF level was observed in BC cases with progesterone receptor (PR) negativity compared to those with PR positivity (P = 0.046). Moreover, a significant association was depicted between the rs1049829 variant of MIF gene and the protective effect against BC meanwhile the rs755622 variant demonstrated no significant link with BC risk. CONCLUSIONS: This study revealed that serum MIF levels may be regarded as a promising serum tumor marker for BC. Also, the rs1049829 variant of the MIF gene is considered a protective candidate against BC.

Clinical Pharmacology of Glucagon.

Glucagon was discovered about a hundred years ago and its role in health and disease is under continuous investigation. Glucagon is a counter regulatory hormone secreted by alpha cells of the pancreas in response to multiple stimuli. Although some of glucagon's actions and its clinical application have been described, clinical experience with glucagon has been historically overshadowed by that of insulin. To date, the role of glucagon's actions in pharmacotherapy has been under explored. Glucagon plays a considerable role as a hormonal regulator via its known actions on the liver. The rise in obesity and diabetes mellitus prevalence is bringing focus to glucagon's known physiological roles and possible clinical applications. Six glucagon products and a glucagon analog are approved for use in the United States. Clinical pharmacology studies provide crucial support of glucagon's actions as evident from comprehensive pharmacokinetics and pharmacodynamics evaluations in humans. Here, we briefly describe the established physiological role of glucagon in humans and its known relationship with disease. We later summarize the clinical pharmacology of available glucagon products with different routes of administration.

Allostatic load as a predictor of postoperative complications in patients with breast cancer.

Allostatic load (AL) is a biological measure of cumulative exposure to socioenvironmental stressors (e.g., poverty). This study aims to examine the association between allostatic load (AL) and postoperative complications (POC) among patients with breast cancer. Females ages 18+ with stage I-III breast cancer who received surgical management between 01/01/2012-12/31/2020 were identified in the Ohio State Cancer registry. The composite AL measure included biomarkers from the cardiovascular, metabolic, immune, and renal systems. High AL was defined as composite scores greater than the cohort's median (2.0). POC within 30 days of surgery were examined. Univariable and multivariable regression analysis examined the association between AL and POC. Among 4459 patients, 8.2% had POC. A higher percentage of patients with POC were unpartnered (POC 44.7% vs no POC 35.5%), government-insured (POC 48.2% vs no POC 38.3%) and had multiple comorbidities (POC 32% vs no POC 20%). Patients who developed POC were more likely to have undergone sentinel lymph node biopsy followed by axillary lymph node dissection (POC 51.2% vs no POC 44.6%). High AL was associated with 29% higher odds of POC (aOR 1.29, 95% CI 1.01-1.63). A one-point increase in AL was associated with 8% higher odds of POC (aOR 1.08, 95% CI 1.02-1.16) and a quartile increase in AL was associated with 13% increased odds of POC (aOR 1.13, 95% CI 1.01-1.26). Among patients undergoing breast cancer surgery, increased exposure to adverse socioenvironmental stressors, operationalized as AL, was associated with higher odds of postoperative complications.

Dissecting Acute Drug-Induced Hepatotoxicity and Therapeutic Responses of Steatotic Liver Disease Using Primary Mouse Liver and Blood Cells in a Liver-On-A-Chip Model.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is hallmarked by hepatic steatosis, cell injury, inflammation, and fibrosis. This study elaborates on a multicellular biochip-based liver sinusoid model to mimic MASLD pathomechanisms and investigate the therapeutic effects of drug candidates lanifibranor and resmetirom. Mouse liver primary hepatocytes, hepatic stellate cells, Kupffer cells, and endothelial cells are seeded in a dual-chamber biocompatible liver-on-a-chip (LoC). The LoC is then perfused with circulating immune cells (CICs). Acetaminophen (APAP) and free fatty acids (FFAs) treatment recapitulate acute drug-induced liver injury and MASLD, respectively. As a benchmark for the LoC, multiplex immunofluorescence on livers from APAP-injected and dietary MASLD-induced mice reveals characteristic changes on parenchymal and immune cell populations. APAP exposure induces cell death in the LoC, and increased inflammatory cytokine levels in the circulating perfusate. Under FFA stimulation, lipid accumulation, cellular damage, inflammatory secretome, and fibrogenesis are increased in the LoC, reflecting MASLD. Both injury conditions potentiate CIC migration from the perfusate to the LoC cellular layers. Lanifibranor prevents the onset of inflammation, while resmetirom decreases lipid accumulation in hepatocytes and increases the generation of FFA metabolites in the LoC. This study demonstrates the LoC potential for functional and molecular evaluation of liver disease drug candidates.

Identifying and Treating Those at Risk: Disparities in Rapid Relapse Among TNBC Patients in the National Cancer Database.

PURPOSE: This study was designed to characterize features of rapid relapse TNBC (rrTNBC), an aggressive, poor prognosis breast cancer subset using the National Cancer Database (NCDB). METHODS: Patients diagnosed with TNBC between 2010 and 2019 within NCDB were included in analyses. rrTNBC was defined as all-cause mortality ≤24 months from diagnosis. Patient demographic, tumor, and treatment association with rrTNBC were evaluated in univariate, bivariate analyses, and multiple logistic regression models. Two-part models are used to compare receipt of treatment (i.e., receipt of both chemotherapy and breast surgery) versus not in its relationship with rrTNBC. RESULTS: Overall, 14.5% of patients were categorized as rrTNBC. Age older than 75 years (-41.3%), Black race (-1.4%), Medicare (-2.6%), and Charlson-Deyo score ≥2 (-4.9%) were associated with a lower probability of receiving both chemotherapy and breast surgery. Not receiving both treatments (vs. receiving both chemotherapy and breast surgery) was associated with a two-to-three-fold higher probability of rrTNBC among patients aged older than 75 years (16.6% vs. 6%), having Medicare (3.6% vs. 1.6%), and Charlson-Deyo score ≥2 (16.6% vs. 5.9%). CONCLUSIONS: Age, insurance, and comorbidity were related to a lower likelihood of treatment; yet receiving treatment reduced the risk of rrTNBC threefold for each. These findings might be valuable to inform clinical care delivery, as well as future research that examines treatment protocols among diverse patients.

Promoting the sensitive detection of ethamsylate via a colorimetric sensing platform based on the enhanced oxidase-mimicking activity of ultrathin MnO2 nanosheets.

In this work, we present a novel colorimetric sensing platform for the sensitive detection of ethamsylate (ETM) usingultrathin MnO2 nanosheets with enhancedoxidase-mimicking activity. A facile template-free hydrothermal process was applied to synthesize the MnO2 nanosheets under mild conditions. The nanosheets exhibited oxidase-mimicking activity, facilitating the conversion of TMB into the blue-colored oxTMB in the absence of H2O2. However, the presence of ETM inhibited this activity, resulting in the conversion of oxTMB back to colorless TMB and a substantial decrease in the blue color intensity. The colorimetric response exhibited a linear relationship with ETM concentration over the range of 0.5 to 10.0 µg/mL and a detection limit of 0.156 µg/mL. To further elucidate the underlying mechanism, we performed extensive characterization and kinetic experiments. The findings demonstrated that this unique property is attributed to the remarkable capacity of the MnO2 nanosheets to absorb oxygen, producing superoxide radicals (O2-). The oxidase-mimicking activity of the nanosheets was further confirmed by the reaction kinetics, following Michaelis-Menten's behavior. Moreover, the applicability of the sensing platform was assessed by determining ETM concentrations in various real samples (different pharmaceuticals, human plasma, and environmental water). The well-established platform demonstrates the prospective role that nanomaterials-based sensing platforms may play in clinical diagnostics, pharmaceutical analysis, and other relevant fields.

Benefit and potential risk: Effects of in ovo copper oxide nanoparticles supplementation on hatchability traits, organ weights and histological features of newly hatched chicks.

This investigation was directed to examine the influence of copper oxide nanoparticles (CuO-NPs) on the hatchability traits, and chick quality of newly hatched broiler chicks. A total of 480 eggs were randomly divided into four treatment groups, each consisting of three duplicates. As a negative control (NC), the first group was not injected; the second group was injected with saline and served as a positive control (PC), the third and fourth groups were injected with 30 and 60 ppm of (CuO-NPs)/egg. Eggs were injected into the amniotic fluid on the eighteenth day of the incubation period. Results showed that the hatchability, chick yield %, yolk free-body mass (YFBM), chick length, shank length (SL), and relative weight of the heart, gizzard and intestine of day-old broiler chicks were all unaffected by the in ovo injection of CuO-NPs. The Pasgar Score was slightly improved compared to the NC and PC groups. Also, the in ovo administration of CuO-NPs (60 ppm/egg) significantly increased the intestine length. Both levels of CuO-NPs significantly increased the concentration of Cu ions in the hepatic tissue. Additionally, different levels of tissue damage were seen in the liver of the birds that were given low or high dosages of CuO-NPs. Conclusively, the in ovo injection of CuO-NPs has a good result on the appearance of the chicks (Pasgar score). However, negative effect of CuO-NPs on liver tissue may raise concerns about the potential risks of applying CuO-NPs in ovo administration.

The "foothill" entry for cephalomedullary nailing in unstable proximal femoral fractures: a technical note with a review of the literature.

Cephalomedullary nailing for unstable proximal femoral fractures is widely utilized, especially for geriatric osteoporotic fractures. There are two starting points for entry, namely trochanteric tip entry and pyriformis fossa entry, both have advantages and disadvantages, the tip of the greater trochanter seems that it is not the ideal starting point for trochanteric entry nails, the study presents the foothill entry point as a reproducible, technically feasible entry point to overcome the shortcoming of both standard starting points, and it could be easy executed with clear intraoperative fluoroscopic landmarks and lead to appropriate nail position without intraoperative complications.

Novel insight into mitochondrial dynamin-related protein-1 as a new chemo-sensitizing target in resistant cancer cells.

Mitochondrial dynamics have pillar roles in several diseases including cancer. Cancer cell survival is monitored by mitochondria which impacts several cellular functions such as cell metabolism, calcium signaling, and ROS production. The equilibrium of death and survival rate of mitochondria is important for healthy cellular processes. Whereas inhibition of mitochondrial metabolism and dynamics can have crucial regulatory decisions between cell survival and death. The steady rate of physiological flux of both mitochondrial fission and fusion is strongly related to the preservation of cellular bioenergetics. Dysregulation of mitochondrial dynamics including fission and fusion is a critical machinery in cells accompanied by crosstalk in cancer progression and resistance. Many cancer cells express high levels of Drp-1 to induce cancer cell invasion, metastasis and chemoresistance including breast cancer, liver cancer, pancreatic cancer, and colon cancer. Targeting Drp-1 by inhibitors such as Midivi-1 helps to enhance the responsiveness of cancer cells towards chemotherapy. The review showed Drp-1 linked processes such as mitochondrial dynamics and relationship with cancer, invasion, and chemoresistance along with computational assessing of all publicly available Drp-1 inhibitors. Drp1-IN-1, Dynole 34-2, trimethyloctadecylammonium bromide, and Schaftoside showed potential inhibitory effects on Drp-1 as compared to standard Mdivi- 1. This emerging approach may have extensive strength in the context of cancer development and chemoresistance and further work is needed to aid in more effective cancer management.

Bariatric surgery in inflammatory bowel disease: a comparative analysis of 450,000 patients.

BACKGROUND: Studies were conducted to investigate the outcomes of bariatric surgery (BS) among inflammatory bowel disease (IBD) patients. OBJECTIVES: We aimed to analyze previous literature, comparing the outcomes of BS between IBD and non-IBD patients. SETTING: Not applicable. METHODS: PubMed, Scopus, and Web of Science were searched on 25/9/2023 for comparative studies on outcomes of BS in IBD patients. RevMan Software v5.4 was used to conduct the analysis. RESULTS: Our analysis revealed an insignificant difference in the change of body mass index (BMI) at 1-year post-BS between IBD and non-IBD patients. IBD patients had a higher risk of acute renal failure, hemorrhage, and readmission following BS (RR: 2.16, 95% CI: 1.55-3, RR: 1.57, 95% CI: 1.22-2.04, RR: 1.56, 95% CI: 1.17-2.08, respectively). No significant difference was observed between both groups regarding wounds, leak/intra-abdominal infection, thromboembolic complications, and bowel obstruction. A higher incidence of postoperative complications was seen among IBD patients undergoing RYGB compared with SG (RR: 2.21, 95% CI: 1.43-3.41). There was a significant decline in steroid use following BS in IBD patients (RR: .67, 95% CI: .53-.84). Comparison between UC and Crohn's disease (CD) revealed insignificant differences in treatment escalation or de-escalation. Both IBD and non-IBD patients had similar lengths of hospitalization. CONCLUSIONS: BS is equally effective in IBD and non-IBD patients in terms of weight loss at 1-year follow-up. Nevertheless, IBD patients are at a higher risk of postoperative complications, micronutrient deficiency, and readmission. Both UC and CD reported a decline in steroid use following surgery without a preferential advantage to a particular IBD sub-type.

Garlic bioactive substances and their therapeutic applications for improving human health: a comprehensive review.

Garlic (Allium sativum L.) is a widely abundant spice, known for its aroma and pungent flavor. It contains several bioactive compounds and offers a wide range of health benefits to humans, including those pertaining to nutrition, physiology, and medicine. Therefore, garlic is considered as one of the most effective disease-preventive diets. Many in vitro and in vivo studies have reported the sulfur-containing compounds, allicin and ajoene, for their effective anticancer, anti-diabetic, anti-inflammatory, antioxidant, antimicrobial, immune-boosting, and cardioprotective properties. As a rich natural source of bioactive compounds, including polysaccharides, saponins, tannins, linalool, geraniol, phellandrene, ß-phellandrene, ajoene, alliin, S-allyl-mercapto cysteine, and ß-phellandrene, garlic has many therapeutic applications and may play a role in drug development against various human diseases. In the current review, garlic and its major bioactive components along with their biological function and mechanisms of action for their role in disease prevention and therapy are discussed.

Heterogeneous integration of spin-photon interfaces with a CMOS platform.

Colour centres in diamond have emerged as a leading solid-state platform for advancing quantum technologies, satisfying the DiVincenzo criteria1 and recently achieving quantum advantage in secret key distribution2. Blueprint studies3-5 indicate that general-purpose quantum computing using local quantum communication networks will require millions of physical qubits to encode thousands of logical qubits, presenting an open scalability challenge. Here we introduce a modular quantum system-on-chip (QSoC) architecture that integrates thousands of individually addressable tin-vacancy spin qubits in two-dimensional arrays of quantum microchiplets into an application-specific integrated circuit designed for cryogenic control. We demonstrate crucial fabrication steps and architectural subcomponents, including QSoC transfer by means of a 'lock-and-release' method for large-scale heterogeneous integration, high-throughput spin-qubit calibration and spectral tuning, and efficient spin state preparation and measurement. This QSoC architecture supports full connectivity for quantum memory arrays by spectral tuning across spin-photon frequency channels. Design studies building on these measurements indicate further scaling potential by means of increased qubit density, larger QSoC active regions and optical networking across QSoC modules.

Courtyard geometry's effect on energy consumption of AlKharga city residential buildings, Egypt.

The research aim is to clarify the effect of courtyard placement, the ratio between length and width, and courtyard orientation on energy consumption in residential buildings in hot and dry climates, to seek planning and designing alternatives for new cities and new residential complexes that are consistent with the environment and climate and save the consumption of energy used in the buildings. The research method was conducted through Design Builder software for simulation purposes. The reference model with the 157.25 m2 which accommodates a central square courtyard measuring 5 m × 5 m, on a residential building model in the New Valley Governorate of Kharga City, Egypt. The courtyard simulation is aimed to determine Less energy consumption inside the different case studies, in 9 courtyard placements The studied alternatives for Courtyard Placement, are (the center of the building, sub facades, and main facades). The different ratios are (1:1, 1.25:1, 1.5:1-1.75:1, 2:1, 2.25:1, 2.5-1). The longitudinal axis of the Courtyard has been oriented to the east-west direction for all placements, and north-south direction for all placements. Also, (orientation angle is Zero), it offered the percentages of better and worst cases in each position of the courtyard. The research findings suggest that the best Placement of the Courtyard that achieved the highest rate of saving of energy consumed inside the used building model was at the southwestern façade, with a saving rate of 18.73%. Then, the Placement of the Courtyard at the northwestern and southeastern facades with a saving rate of 17.91%, with a length-to-width ratio (2.5:1) if the longitudinal axis of the Courtyard is oriented in the north-south direction, Through the study, we conclude that the placement and orientation of the courtyard and its regular formation have contributed to rationalizing energy consumption in residential buildings, the study reached some important standards that could represent a methodological framework for designing contemporary residential buildings with an energy-efficient inner courtyard.

Innovative Therapeutic Approaches in Congenital Myasthenic Syndromes.

Background and Objectives: To provide real-word clinical follow-up data on patients carrying variations of congenital myasthenic syndromes (CMS) and who respond to some innovative drugs. Methods: Patients recruited from the Neurology Department of the Mustapha Bacha university hospital in Algiers. Treated with innovative drugs, they were monitored and their clinical progress was evaluated on the basis of clinical arguments suggestive of CMSs, but also para clinical arguments (electromyography and genetic study). Results: Six patients carrying different mutations in different genes of CMSs were studied. They had different pathophysiologic profiles (slow or fast channel syndromes, low expressor of receptor). Their therapeutic management was based on innovative drugs, normally indicated in other, non-neurological pathologies. Their outcome was toward a clear clinical improvement. Discussion: This work relates the interest of proposing treatments (outside of Pyridostigmine) in the management of CMSs. These therapies can greatly modify the prognosis of patients suffering from this orphan disease. Classification of Evidence: This study provides Class IV evidence that for patients with congenital myasthenic syndromes, some innovative treatments are effective.

Measuring uterine cavity volume with sonohysterography: A new objective method.

Introduction: The uterine cavity is a potential space with limited methods for evaluating its volume, limiting the evaluation of interventions' effectiveness in various uterine conditions. This study aims to objectively measure the uterine cavity volume using sonohysterography coupled with a Foley catheter to provide a normative model of age and parity-related uterine cavity volume. Methods: The research included 35 women (group 1) with a total abdominal hysterectomy and 150 women (group 2) who underwent sonohysterography for various gynecologic indications. Saline infusion sonography was administered to all patients. The most common shape obtained after the saline infusion was taken to measure the uterine cavity's dimensions and volume. The uterine cavity volumes, as measured by sonohysterography, and the volumes of saline injected after the hysterectomy were compared. Results: A significant association exists between uterine cavity volumes measured by sonohysterography and true volumes measured immediately after hysterectomy (p = 0.001). The association between uterine cavity volume measured by sonohysterography and using only a Foley catheter balloon was statistically insignificant (p = 0.13). A statistically significant positive association was observed between the uterine cavity volume and the patient's age and parity (p ⩽ 0.05). Conclusion: Measuring the uterine cavity volume using a paediatric Foley catheter balloon coupled with sonohysterography offers an objective approach to measuring a normal (without gross pathologies) uterus volume. This technique would improve the diagnostic accuracy and the management of women with distinct uterine cavity morphologies.

Optimization of Phloretin-loaded Nanospanlastics for Targeting of FAS/SREBP1c/AMPK/ OB-Rb Signaling Pathway in HFD-induced Obesity.

OBJECTIVES: Obese patients are at increased risk for CVD, which is the main cause of premature death and has been a major cause of disability and ill health in recent years. PTN, a natural dihydrochalcone flavonoid, has a variety of pharmacological characteristics. This article aimed to prepare PTN-NSLs to evaluate their anti-obesity activity. METHODS: Morphology, Particle size, zeta potential, UV-vis, entrapment efficiency, FT-IR spectra, and an in vitro release study of PTN-NSLs were described. PTN-NSLs were also tested for their anti-obesity properties in obese rats. The LD50 of PTN-NSLs was calculated, as was the 1/20 LD50 prepared for the treatment of obese rats. Also, the level of glycemic, oxidative stress and inflammatory biomarkers were estimated in the obese rat's model. RESULTS: The synthesized PTN-NSLs were uniform, spherically shaped, and well dispersed with no aggregation noted, with a size range of 114.06 ± 8.35 nm. The measured zeta potential value of PTN-NSLs was -32.50.8 mv. Also, the UV spectra of PTN and PTN-NSLs have strong absorption at 225 and 285 nm. Also, the LD50 of PTN-NSLs was found to be 2750 mg/kg.b.w. Moreover, administrating obese rats with PTN-NSLs resulted in improved glycemic features as well as GSH, SOD, GPx, GR, IL10, TBARs, and IL-6 levels, as well as attenuated FAS, SREBP1c, AMPK, ACO, CPT1, and OB-Rb gene expression. CONCLUSIONS: Administration of PTN-NSLs significantly attenuated the levels of glycemic, oxidative stress, and inflammatory biomarkers. The biochemical and PCR findings are aided by histological investigations. Also, the present findings imply that PTN-NSLs might be a promising pharmacological tool for the treatment of obesity-related diseases.

Effect of storage conditions on the quality of equine and canine mesenchymal stem cell derived nanoparticles including extracellular vesicles for research and therapy.

Nanoparticles including extracellular vesicles derived from mesenchymal stem cells are of increasing interest for research and clinical use in regenerative medicine. Extracellular vesicles (EVs), including also previously named exosomes, provide a promising cell-free tool for therapeutic applications, which is probably a safer approach to achieve sufficient healing. Storage of EVs may be necessary for clinical applications as well as for further experiments, as the preparation is sometimes laborious and larger quantities tend to be gained. For this purpose, nanoparticles were obtained from mesenchymal stem cells from adipose tissue (AdMSC) of horses and dogs. The EVs were then stored for 7 days under different conditions (- 20 °C, 4 °C, 37 °C) and with the addition of various additives (5 mM EDTA, 25-250 µM trehalose). Afterwards, the size and number of EVs was determined using the nano tracking analyzing method. With our investigations, we were able to show that storage of EVs for up to 7 days at 4 °C does not require the addition of supplements. For the other storage conditions, in particular freezing and storage at room temperature, the addition of EDTA was found to be suitable for preventing aggregation of the particles. Contrary to previous publications, trehalose seems not to be a suitable cryoprotectant for AdMSC-derived EVs. The data are useful for processing and storage of isolated EVs for further experiments or clinical approaches in veterinary medicine.

Reversal of diabetes by an oral Salmonella-based vaccine in acute and progressive diabetes in NOD mice.

Type 1 diabetes (T1D)-associated hyperglycemia develops, in part, from loss of insulin-secreting beta cells. The degree of glycemic dysregulation and the age at onset of disease can serve as indicators of the aggressiveness of the disease. Tracking blood glucose levels in prediabetic mice may demonstrate the onset of diabetes and, along with animal age, also presage disease severity. In this study, an analysis of blood glucose levels obtained from female NOD mice starting at 4 weeks until diabetes onset was undertaken. New onset diabetic mice were orally vaccinated with a Salmonella-based vaccine towards T1D-associated preproinsulin combined with TGFß and IL10 along with anti-CD3 antibody. Blood glucose levels were obtained before and after development of disease and vaccination. Animals were classified as acute disease if hyperglycemia was confirmed at a young age, while other animals were classified as progressive disease. The effectiveness of the oral T1D vaccine was greater in mice with progressive disease that had less glucose excursion compared to acute disease mice. Overall, the Salmonella-based vaccine reversed disease in 60% of the diabetic mice due, in part, to lessening of islet inflammation, improving residual beta cell health, and promoting tolerance. In summary, the age of disease onset and severity of glucose dysregulation in NOD mice predicted response to vaccine therapy. This suggests a similar disease categorization in the clinic may predict therapeutic response.

Integrated segmented IQ-modulator for orthogonal sampling and multi-level high-bandwidth signal generation.

Photonic-assisted signal processing of high-bandwidth signals emerges as a solution for challenges encountered in electronic-based processing. Here we present a concept for a compact, photonic-assisted digital-to-analog converter (DAC) and optical IQ-modulator in one single integrated device based on two innovative concepts: a segmented Mach-Zehnder modulator and orthogonal sampling. For electrically driving the modulator, only a single radio frequency oscillator and no pulse source or electrical DAC are required. The presented and simulated proof-of-concept device with six segments can generate a multi-level and high-bandwidth signal from low-bandwidth electronic drivers; e.g., we show the generation of a 120 Gbps data rate, 16-quadrature amplitude modulation (16-QAM, 30 Gbaud) signal solely based on low-bandwidth (5 GHz) non-return-to-zero (NRZ) signals. Integrated on a silicon photonic platform, the device provides fixable speed and bandwidth operations, positioning it as a viable solution for diverse communication systems.