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Biomaterials induced host immune responses, and fibrotic overgrowth remains a major barrier to the long-term function of medical devices and biomaterial consisting of tissue grafts. Screening new biomaterials to identify anti-fibrotic formulation requires in vivo testing, which is challenging to multiplex and remains a significant obstacle to progress in this field. Herein, we synthesized a combinatorial chemically modified hydrogel library and developed a cellular barcoding method that enables high-throughput multiplexed in vivo screening of 20 formulations in a single mouse and 100 formulations in a single non-human primate. Our screening method consists of implanting a mixture of biomaterials and each barcoded with human umbilical vein epithelial cells (HUVEC) from different individual donors. Single nucleotide polymorphism (SNP) genotypes of the cells were utilized as readouts using next-generation sequencing (NGS) to pair the material identity with material performance. Screening of the library using a xenogeneic transplantation model identified three novel lead hydrogel formulations (Z4-A10, Z1-A3, and Z2-A19) with improved anti-fibrotic properties that enable long-term cell viability. Z4-A10 was used to encapsulate human islets and validated for long-term glycemic control in an STZ-induced C57BL/6J diabetic mouse model. Leads, Z1-A3 and B2-A17, were further validated as immunomodulating coatings for medical-grade catheters to prevent fibrosis and occlusion, highlighting the translation of our screening approach and findings to other medical devices. Our results suggest that the developed cellular barcoding method and in vivo multiplexed screening technique can be leveraged to identify biomaterials for a wide range of clinical applications. Significantly, our newly discovered leads can improve the long-term performance of medical devices and encapsulated cell-based therapeutics.

Code and data used in the theoretical model of intraperitoneal cytokine delivery used in the publication., Funding Sources: Cancer Prevention Research Institute of Texas grant RR160047 (OV) Avenge Bio Sponsored Research Agreement to Rice University (OV) and Cell Trans (JO) Emerson Collective (AJ, WP) Welch Foundation (OI, ADH) Rice University Academy Fellowship (MJ) National Science Foundation grant 1842494 (AN) National Institute of Health grant 1RO1DK120459-01 (AN, OV)

Pancreatic cancer is often diagnosed at advanced stages and responds poorly to chemotherapy. Because high tumor T cell infiltration corresponds with better clinical outcomes in pancreatic cancer patients, immunotherapy has gained significant interest over the last decade for the treatment of recurrent pancreatic cancer. IL-12 is a proinflammatory cytokine with pleiotropic effects including activation of CD8+ T cells and NK cells. Unfortunately, systemic high dose IL-12 administration led to severe toxicities in clinical trials which has limited further development of this cytokine as a cancer therapeutic. To address this limitation, we developed an implantable cytokine delivery platform to allow for local administration of IL-12. These cytokine factories, composed of genetically engineered epithelial cells encapsulated in biocompatible polymers, allow for safe and controlled dosing in vivo. Tumor adjacent administration of IL-12-based cytokine factories caused reduction of intraperitoneal pan02 tumor burden by 80% after only 1 week of treatment in mice with pancreatic cancer. Single cell RNAseq of the tumor adjacent immune cells at this time point showed 2x more T and NK cells present in the IL-12 treated mice than untreated mice suggesting modulation of the tumor microenvironment via immune cell infiltration. Importantly, the necessary IL-12 dose was well tolerated in all mice without signs of toxicity for 180 days. In efforts to evaluate the translatability of this platform, we further tested IL-12-based cytokine factories in a non-human primate. The cytokine factories produced a high local IL-12 concentration without substantial leakage into the systemic circulation and were well tolerated by the primates as shown by the lack of fever or weight loss, as well as the lack of renal or liver toxicity. Our findings highlight the therapeutic potential of IL-12 treatments when administered locally via cytokine factories in preclinical animal models. Further, these findings provide rationale for future development and clinical testing of cytokine factories for treatment of a wide range of metastatic peritoneal cancers in humans. Citation Format: Amanda Nash, Samira Aghlara-Fotovat, Bertha Castillo, Annie Nguyen, Andrew Cui, Andrea Hernandez, Peter Rios, Sofia Ghani, Ira Joshi, Chunyu Xu, Rahul Sheth, Weiyi Peng, Jose Oberholzer, Amir Jazaeri, Omid Veiseh. IL-12-based cytokine factories modulate tumor microenvironment to eradicate pancreatic tumors in mice and are well tolerated in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3547.

Pro-inflammatory cytokines have been approved as a cancer immunotherapy for treatment of metastatic melanoma and renal carcinoma for over 30 years. However, widespread use of cytokine therapy in the clinic is limited by its short half-life in circulation and the associated toxicities that emerge as a result of high systemic exposure. To overcome these limitations, we developed a clinically translatable cytokine delivery platform, called cytokine factories, composed of genetically engineered epithelial cells encapsulated in biocompatible polymers. These cells are able to produce a wide range of natural cytokines (IL2, IL7, IL10, or IL12) and allow for controlled and predictable dosing in vivo. In vivo administration of cytokine factories created a high local cytokine concentration (IP space) without substantial leakage into the systemic circulation. Local, or tumor adjacent, administration of pro-inflammatory (IL-2-based) cytokine factories caused reduction of tumor burden by 70% after only 1 week of treatment when delivered as a monotherapy to mice with malignant pleural mesothelioma (MPM). Importantly, when administered in combination with local anti-PD1 injections, these cytokine factories lead to eradication of these highly aggressive tumors in 7/7 treated mice. To validate the translatability of this platform, we evaluated the safety profile in non-human primates. Significantly, this platform produced local and systemic T cell biomarker profiles that predict efficacy without renal, liver, or general toxicity in non-human primates. Our findings demonstrate the safety and efficacy of cytokine factories in preclinical animal models and provide rationale for future clinical testing for the treatment of metastatic peritoneal cancers in humans. Citation Format: Amanda Nash, Samira Aghlara-Fotovat, Andrea Hernandez, Bertha Castillo, Alexander Lu, Aarthi Pugazenthi, Peter Rios, Sofia Ghani, Ira Joshi, Douglas Isa, Chunyu Xu, Rahul Sheth, Weiyi Peng, Jose Oberholzer, Amir Jazaeri, Hee-Jin Jang, Bryan Burt, Hyun-Sung Lee, Ravi Ghanta, Omid Veiseh. Evaluation of implantable cytokine factories in combination with checkpoint inhibitors for eradication of malignant pleural mesothelioma (MPM) tumors in mice with safe and predictable dosing in non-human primates [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4189.

In this study, we explore the effects of an educational intervention in the form of digital games targeted towards improving the learning outcomes in mathematics and Hindi language among first, second and third graders in four government schools in southern New Delhi. In addition to administering these games in the classroom, we randomly recruited 40 households from a low-income community, where children play the games as an extra-curricular activity. We measure the improvement in aptitude in math and Hindi pre- and post-intervention, using various demographic controls and find that the community intervention had some impact in boosting aptitude. In contrast, the school intervention did not show the desired results though it did register some improvement in children’s knowledge. Using qualitative observation coupled with the quantitative assessment of impact, we attempt to deconstruct the various infrastructural challenges and sampling issues posed in our school intervention, and identify key features that need to be adhered to for future researchers who may want to assess the impact of educational interventions on young children from underprivileged backgrounds in India.

Continuous glucose monitors (CGMs), used by patients with diabetes mellitus, can autonomously track fluctuations in blood glucose over time. However, the signal produced by CGMs during the initial recording period following sensor implantation contains substantial noise, requiring frequent recalibration via fingerprick tests. Here, we show that coating the sensor with a zwitterionic polymer, found via a combinatorial-chemistry approach, significantly reduces signal noise and improves CGM performance. We evaluated the polymer-coated sensors in mice as well as in healthy and diabetic non-human primates, and show that the sensors accurately record glucose levels without the need for recalibration. We also show that the polymer-coated sensors significantly abrogated immune responses to the sensor, as indicated by histology, fluorescent whole-body imaging of inflammation-associated protease activity, and gene expression of inflammation markers. The polymer coating may allow CGMs to become standalone measuring devices.

There are various types of microstrip antenna that can be used for number of applications in wireless communication. In this paper, the design of Sierpienski fractal Slotted Hexagonal Microstrip Patch Antenna with FR4 glass epoxy substrate having dielectric constant, Er of 4.4, and thickness 1.6mm has been presented. It is instigated using stripline feeding. These antennas are compact, conformal to both the surfaces- planaramp; non-planar, simple, inexpensive, rugged, compatible with MMIC designs. Microstrip antenna is made up of a very thin metallic strip (patch) i.e, placed over a small fraction of a wavelength above a ground plane. The simulated results indicate that the antenna is suitable for RADAR (all types), GPS carriers, WLANs, Wimax, Satellite communication, navigation. The design is simulated using IE3D software and result is obtained in terms of smith chart, VSWR, return loss.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease that results from the destruction of insulin-producing pancreatic β cells in the islets of Langerhans. Islet cell transplantation has become a successful therapy for specific patients with T1DM with hypoglycemic unawareness. The reversal of T1DM by islet transplantation is now performed at many major medical facilities throughout the world. However, many challenges must still be overcome in order to achieve continuous, long-term successful transplant outcomes. Two major obstacles to this therapy are a lack of islet cells for transplantation and the need for life-long immunosuppressive treatment. Microencapsulation is seen as a technology that can overcome both these limitations of islet cell transplantation. This review depicts the present state of microencapsulated islet transplantation. Microencapsulation can play a significant role in overcoming the need for immunosuppression and lack of donor islet cells. This review focuses on microencapsulation and the clinical status of the technology in combating T1DM.

This paper presents a simple rectangular microstrip patch antenna for 5.25 GHz IEEE 802.11. The proposed antenna is designed on Roger TMM 3 substrate with dielectric constant 3.25 and thickness of 2.4 mm. The size of antenna is compact with patch dimension 14 × 16 mm2. The antenna parameters such as return loss, VSWR, gain, and directivity are simulated and optimized using commercial computer simulation technology microwave studio (CST MWS). The return loss is about −17 dB, gain is 7.9 dB, directivity is 6.3 dBi, and VSWR is 1.27 at the operating frequency 5.25 GHz. The main advantage of this antenna is that the designed structure is very simple compared to other proposed WLAN antennas and the cost for making this antenna is also low.

This paper documents Sesame Workshop India Trust’s work in impoverished communities in Mumbai with regard to the provision of Early Childhood Care and Education (ECCE) services. The model works with children aged birth to six who are served by the Integrated Child Development Scheme (ICDS), sponsored by the ministry of Women and Child Development (WCD), India. The model focuses on augmenting the capacities of the anganwadi (child care center) worker vis-à-vis pedagogy and access to material, and also works with caregivers advocating for a better ECCE environment. Integrating innovative technology as well as traditional Teaching Learning Materials (TLM) and operating at a scale of five thousand plus centers, the model demonstrates how programmes can be designed from ground-up, to be inclusive, scalable and successful in improving children’s learning outcomes.

The effects of corticosterone (1 mg/kg per day for 7 days) on serotonin 5-HT 1A 5-HT 2A 5-HT uptake sites, and α 2 -adrenergic receptor sites were measured. Corticosterone treatment significantly decreased the number of 5-HT 1A receptor sites ( B max = 108 ± 8.20fmol/mg protein and 152.31 ± 13.36 fmol/mg protein in corticosterone- and vehicle-treated rats, respectively). No significant differences were found in other measures. It is possible that corticosteroids exert some of their behavioral effects via regulation of 5-HT 1A sites in frontal cortex.