Discovery of a new class of cell-penetrating peptides by novel phage display platform.

The primary hurdles for small interference RNA (siRNA) in clinical use are targeted and cytosolic delivery. To overcome both challenges, we have established a novel platform based on phage display, called NNJA. In this approach, a lysosomal cathepsin substrate is engineered within the flexible loops of PIII, that is displaying a unique random sequence at its N-terminus. NNJA library selection targeting cell-expressed targets should yield specific peptides localized in the cytoplasm. That is because phage internalization and subsequent localization to lysosome, upon peptide binding to the cell expressed target, will result in cleavage of PIII, rendering phage non-infective. Such phage will be eliminated from the selected pool and only peptide-phage that escapes lysosomes will advance to the next round. Proof of concept studies with the NNJA library demonstrated cytosolic localization of selected peptide-phage and peptide-siRNA, confirmed through confocal microscopy. More importantly, conjugation of siHPRT to monomeric or multimeric NNJA peptides resulted in significant reduction in HPRT mRNA in various cell types without significant cytotoxicity. Sequence similarity and clustering analysis from NGS dataset provide insights into sequence composition facilitating cell penetration. NNJA platform offers a highly efficient peptide discovery engine for targeted delivery of oligonucleotides to cytosol.

Performance of HER2 DAKO HercepTest and Ventana 4B5 immunohistochemical assays on detecting HER2 gene-amplification in uterine serous carcinomas.

We compared the performance of two commonly-used HER2 immunohistochemistry (IHC) assays in uterine serous carcinomas (USC), correlating with HER2 gene amplification by fluorescence in-situ hybridization (FISH). Sixty-five USCs were stained by both HercepTest™ and PATHWAY 4B5 assays. FISH was performed by HER2 IQFISH pharmDx. Consensus HER2 IHC scoring was performed, and HER2 testing results were evaluated using USC-specific criteria. Complete concordance between HercepTest and 4B5 assays was achieved in 44/65 tumors (68%). The overall HER2 IHC/FISH concordance was 94% (45/48) by HercepTest and 91% (42/46) by 4B5. All HER2 IHC 3+ cases with HercepTest (n = 6) and 4B5 (n = 4) were gene-amplified, corresponding to specificities of 100%. For cases with IHC 2+, 41% (7/17) by HercepTest and 42% (8/19) by 4B5 had HER2 gene amplification. The sensitivity for HercepTest and 4B5 were 38% and 25%, respectively, at a cut-off of IHC 3+ (P = 0.50), and were 81% and 75%, respectively, at a cut-off of IHC 2+ (P > 0.99). Among HER2 IHC 0-1+ cases, 3/42 cases by HercepTest and 4/42 cases by 4B5 showed amplified FISH results, corresponding to overall false negative rates of 19% for HercepTest and 25% for 4B5. By using USC-specific IHC scoring criteria, both HercepTest and 4B5 assays showed high specificities (100%) for HER2 gene amplification in IHC 3+ cases, high IHC/FISH concordance, and comparable sensitivity for detecting HER2 gene amplification. The notable false negative rates using IHC 2+ as a cut-off for reflexing FISH analysis may warrant consideration for performing FISH in IHC 1+ cases until more data become available.

Improving detection of carcinoma in situ in bladder cancer: urinary cytology vs the Xpert® BC Monitor.

OBJECTIVE: To investigate and compare the performance of urinary cytology and the Xpert BC Monitor test in the detection of bladder cancer in various clinically significant patient cohorts, including patients with carcinoma in situ (CIS), in a prospective multicentre setting, aiming to identify potential applications in clinical practice. PATIENTS AND METHODS: A total of 756 patients scheduled for transurethral resection of bladder tumour (TURBT) were prospectively screened between July 2018 and December 2020 at six German University Centres. Central urinary cytology and Xpert BC Monitor tests were performed prior to TURBT. The diagnostic performance of urinary cytology and the Xpert BC Monitor was evaluated according to sensitivity (SN), specificity (SC), negative predictive value (NPV) and positive predictive value (PPV). Statistical comparison of urinary cytology and the Xpert BC Monitor was conducted using the McNemar test. RESULTS: Of 756 screened patients, 733 (568 male [78%]; median [interquartile range] age 72 [62-79] years) were included. Bladder cancer was present in 482 patients (65.8%) with 258 (53.5%) high-grade tumours. Overall SN, SC, NPV and PPV were 39%, 93%, 44% and 92% for urinary cytology, and 75%, 69%, 59% and 82% for the Xpert BC Monitor. In patients with CIS (concomitant or solitary), SN, SC, NPV and PPV were 59%, 93%, 87% and 50% for urinary cytology, and 90%, 69%, 95% and 50% for the Xpert BC Monitor. The Xpert BC Monitor missed four tumours (NPV = 98%) in patients with solitary CIS, while potentially avoiding 63.3% of TURBTs in inconclusive or negative cystoscopy and a negative Xpert result. CONCLUSION: Positive urinary cytology may indicate bladder cancer and should be taken seriously. The Xpert BC Monitor may represent a useful diagnostic tool for correctly identifying patients with solitary CIS and unsuspicious or inconclusive cystoscopy.

Prevalence of SARS-CoV-2 in newborns born to SARS-CoV-2-positive mothers at 2 weeks of life.

Introduction: Limited evidence exists on management recommendations for neonates born to SARS-CoV-2-positive mothers. This study looked at transmission risk of neonates presenting for primary care in a large regional health system within New York during the early months of the COVID-19 pandemic. Methods: This was a prospective, observational study of newborns born to SARS-CoV-2-positive mothers presenting at any of the 19 Northwell Health-Cohen Children's Medical Center primary care practices who underwent another oropharyngeal/nasopharyngeal swab for detection of SARS-CoV-2 by day of life (DOL) 14. Results: Among 293 newborns born to SARS-CoV-2-positive mothers who were negative at birth, 222 were retested at DOL 14, corresponding to times with different predominant strains. Of these, seven tested positive but had no symptoms. Conclusion: The overall low transmission rates and absence of symptomatic infection support the safety of direct breastfeeding after hospital discharge with appropriate hand and breast hygiene.

Utilization and Patient-Reported Outcomes of Direct-to-Consumer Telemedicine During the First 6 Weeks of the COVID-19 Pandemic in the Largest Pediatric Ambulatory Network in New York State.

Objective: We aimed to (1) describe telemedicine utilization and usability during the first 6 weeks of the pandemic and (2) determine if usability varied by individual- or visit-level characteristics. Methods: We conducted a retrospective cohort study of ambulatory pediatric telemedicine visits occurring between March 10, 2020, and April 18, 2020, across a large academic health system. We performed manual chart review to assess individual- and visit-level characteristics and invited caregivers to respond to an adapted Telehealth Usability Questionnaire (TUQ). We used multiple logistic regression to determine predictors of high usability. Results: There were 3,197 ambulatory pediatric telemedicine visits, representing 2,967 unique patients. Patients were racially/ethnically diverse (42.5% non-Hispanic White) and primarily English-speaking (89.2%). Surveys were completed by 441 (17%) of those invited. Every item of the TUQ had agreement or strong agreement from the majority of respondents. Compared with non-Hispanic White, non-Hispanic Asian identity was associated with lower usability in three domains and overall, and non-Hispanic Black identity was associated with higher satisfaction and future use. As compared with caregivers of infants younger than 1 year, caregivers of older patients reported lower usability in the three domains. Conclusions: Telemedicine was successfully implemented across 18 ambulatory pediatric specialties in the largest health system in New York State at the onset of COVID-19, and caregivers found it usable and acceptable. Usability scores did not vary by visit-level characteristics but did vary by race/ethnicity and age. Further research is necessary to identify modifiable drivers of the patient experience, particularly in non-Hispanic Asian communities and older adolescents.

Sociodemographic Disparities in Ambulatory Pediatric Telemedicine Utilization During COVID-19.

Objective: Few studies have examined sociodemographic disparities in ambulatory pediatric telemedicine utilization during the coronavirus disease 2019 pandemic. We aimed to (1) assess disparities in telemedicine visit completion during the first 6 weeks of the pandemic in 2020 and (2) determine if these disparities were significantly different from those present in 2019, when all visits occurred in person. Methods: We compared sociodemographic characteristics of patients with successful versus unsuccessful telemedicine visits from March 10, 2020 to April 18, 2020, using generalized linear mixed models. We performed the same analysis for in-person visits from the same period in 2019. We tested for differences across years using interaction terms in a combined 2019-2020 model. Results: Of 3,639 telemedicine visits scheduled, 3,033 (83.3%) were successful. In 2020, Black/African American race was significantly associated with lower odds of telemedicine visit success (odds ratio 0.65 [95% confidence interval 0.49-0.87]) compared with White race, after adjusting for age, gender, ethnicity, insurance type, visit timing, visit specialty, social vulnerability index, and internet access. In 2019, racial identity other than White was significantly associated with lower odds of in-person visit success than White, as was public insurance compared with private. In the full 2019-2020 model, in-person visits (2019) had lower odds of success than telemedicine visits (2020), and neither race, insurance type, nor any other sociodemographic characteristic had significant interactions with year. Conclusions: Racial disparities were evident in telemedicine utilization early in the pandemic; however, these disparities were not significantly different from those seen in 2019, when all visits were in person. Furthermore, telemedicine may improve access to care overall, despite having no significant impact on inequity. Efforts to eliminate racial disparities in ambulatory pediatric health care utilization are necessary across visit modalities.

Quality of Web-Based Sickle Cell Disease Resources for Health Care Transition: Website Content Analysis.

Background: Adolescents and young adults with sickle cell disease (SCD) transitioning from pediatric to adult health care face a high-risk period associated with increased use of acute health care services and mortality. Although 59% of American citizens report using the internet for health care information, the quality of web-based, patient-facing resources regarding transition in SCD care has not been evaluated. Objective: This study aimed to evaluate the quality and readability of web-based health information on SCD, especially as it pertains to the transition to adulthood for inidividuals with SCD. The study also compared the readability and content scores of websites identified in 2018 to those from 2021 to assess any change in quality over time. Methods: Keywords representing phrases adolescents may use while searching for information on the internet regarding transition in SCD care, including "hydroxyurea" and "SCD transition," were identified. A web-based search using the keywords was conducted in July 2021 using Google, Yahoo, and Bing. The top 20 links from each search were collected. Duplicate websites, academic journals, and websites not related to SCD health care transition were excluded. Websites were categorized based on the source: health department, hospital or private clinician, professional society, and other websites. Websites were assessed using Health On the Net Foundation code of conduct (HONcode), Flesch Reading Ease (FRE), Flesch-Kincaid Grade Level (FGL), Ensuring Quality Information for Patients (EQIP), and a novel SCD content checklist (SCDCC). EQIP and SCDCC scores range from 0- to 100. Each website was reviewed by 2 research assistants and assessed for interrater reliability. Descriptive statistics were calculated. Results: Of the 900 websites collected, 67 (7.4%) met the inclusion criteria: 13 health department, 7 hospital or private clinician, 33 professional society, and 14 other websites. A total of 15 (22%) out of 67 websites had HONcode certification. Websites with HONcode certification had higher FRE and EQIP scores and lower FGL scores than those without HONcode certification, reflecting greater readability. Websites without HONcode certification had higher SCDCC scores, reflecting greater clinical content. Only 7 (10%) websites met the National Institutes of Health recommendation of a seventh-grade or lower reading level. Based on EQIP scores, 6 (9%) websites were of high quality. The mean SCDCC score was 20.60 (SD 22.14) out of 100. The interrater reliability for EQIP and SCDCC ratings was good (intraclass correlation: 0.718 and 0.897, respectively). No source of website scored significantly higher mean EQIP, FRE, FGL, or SCDCC scores than the others (all P<.05). Conclusions: Although seeking health care information on the web is very common, the overall quality of information about transition in SCD care on the internet is poor. Changes to current web-based health care information regarding SCD care transitions would benefit transitioning youth by providing expectations, knowledge, skills, and tools to increase self-efficacy.

Xpert bladder cancer monitor to predict the need for a second TURB (MoniTURB trial).

To determine whether Xpert bladder cancer monitor, a noninvasive PCR-based biomarker test, can predict the need for 2nd transurethral resection of the bladder (TURB) better than clinical assessment. Patients scheduled for TURB were prospectively screened. After initial TURB, patients were assigned to 2nd TURB or follow-up cystoscopy at 3 months (FU) by clinicians' discretion. Central urine cytology and Xpert monitor tests were performed prior to the 1st TURB and 2nd TURB or FU, respectively. Statistical analysis to compare clinical assessment and Xpert monitor comprised sensitivity (SENS), specificity (SPEC), NPV and PPV. Of 756 screened patients, 171 were included (114 with 2nd TURB, 57 with FU). Residual tumors were detected in 34 patients who underwent 2nd TURB, and recurrent tumors were detected in 2 patients with FU. SENS and SPEC of Xpert monitor were 83.3% and 53.0%, respectively, PPV was 32.6% and NPV was 92.1%. Clinical risk assessment outperformed Xpert monitor. In patients with pTa disease at initial TURB, Xpert monitor revealed a NPV of 96%. Xpert monitor was not superior than clinical assessment in predicting the need for 2nd TURB. It might be an option to omit 2nd TURB for selected patients with pTa disease.

The locus coeruleus contributes to the anorectic, nausea, and autonomic physiological effects of glucagon-like peptide-1.

Increasing the therapeutic potential and reducing the side effects of U.S. Food and Drug Administration-approved glucagon-like peptide-1 receptor (GLP-1R) agonists used to treat obesity require complete characterization of the central mechanisms that mediate both the food intake-suppressive and illness-like effects of GLP-1R signaling. Our studies, in the rat, demonstrate that GLP-1Rs in the locus coeruleus (LC) are pharmacologically and physiologically relevant for food intake control. Furthermore, agonism of LC GLP-1Rs induces illness-like behaviors, and antagonism of LC GLP-1Rs can attenuate GLP-1R-mediated nausea. Electrophysiological and behavioral pharmacology data support a role for LC GLP-1Rs expressed on presynaptic glutamatergic terminals in the control of feeding and malaise. Collectively, our work establishes the LC as a site of action for GLP-1 signaling and extends our understanding of the GLP-1 signaling mechanism necessary for the development of improved obesity pharmacotherapies.

Caregiver support, burden, and long-term planning among caregivers of individuals with intellectual and developmental disabilities: A cross-sectional study.

BACKGROUND: Long-term care planning (LTCP) is critical for individuals with intellectual/developmental disabilities. Objectives of this study were to investigate progression through LTCP, and associations between social support and: (1) LTCP and (2) burden among family caregivers. METHODS: A cross-sectional survey was distributed to caregivers of individuals with intellectual/developmental disabilities in NY, OH, PA, and TX, exploring demographics, supports, burden, and LTCP behaviours. Bivariate and linear multiple regression analyses were used to investigate study objectives. RESULTS: Caregivers (n = 405) were predominantly parents, female, non-Hispanic, and in the 'learning to plan' stage of LTCP. Caregiver-identified social support was associated with further progression in LTCP (p = .020) and lower caregiver burden (p < .001). CONCLUSION: Social support was associated with further progression in LTCP, and associated with less burden, however fewer than 40% of caregivers reported having social support. Ongoing exploration of emotional/social needs of caregivers is necessary to better support these families.

Consensus Statements on Precision Oncology in the China Greater Bay Area.

BACKGROUND: Next-generation sequencing comprehensive genomic panels (NGS CGPs) have enabled the delivery of tailor-made therapeutic approaches to improve survival outcomes in patients with cancer. Within the China Greater Bay Area (GBA), territorial differences in clinical practices and health care systems and strengthening collaboration warrant a regional consensus to consolidate the development and integration of precision oncology (PO). Therefore, the Precision Oncology Working Group (POWG) formulated standardized principles for the clinical application of molecular profiling, interpretation of genomic alterations, and alignment of actionable mutations with sequence-directed therapy to deliver clinical services of excellence and evidence-based care to patients with cancer in the China GBA. METHODS: Thirty experts used a modified Delphi method. The evidence extracted to support the statements was graded according to the GRADE system and reported according to the Revised Standards for Quality Improvement Reporting Excellence guidelines, version 2.0. RESULTS: The POWG reached consensus in six key statements: harmonization of reporting and quality assurance of NGS; molecular tumor board and clinical decision support systems for PO; education and training; research and real-world data collection, patient engagement, regulations, and financial reimbursement of PO treatment strategies; and clinical recommendations and implementation of PO in clinical practice. CONCLUSION: POWG consensus statements standardize the clinical application of NGS CGPs, streamline the interpretation of clinically significant genomic alterations, and align actionable mutations with sequence-directed therapies. The POWG consensus statements may harmonize the utility and delivery of PO in China's GBA.

Stabilization and improved functionality of three-dimensional perfusable microvascular networks in microfluidic devices under macromolecular crowding.

BACKGROUND: There is great interest to engineer in vitro models that allow the study of complex biological processes of the microvasculature with high spatiotemporal resolution. Microfluidic systems are currently used to engineer microvasculature in vitro, which consists of perfusable microvascular networks (MVNs). These are formed through spontaneous vasculogenesis and exhibit the closest resemblance to physiological microvasculature. Unfortunately, under standard culture conditions and in the absence of co-culture with auxiliary cells as well as protease inhibitors, pure MVNs suffer from a short-lived stability. METHODS: Herein, we introduce a strategy for stabilization of MVNs through macromolecular crowding (MMC) based on a previously established mixture of Ficoll macromolecules. The biophysical principle of MMC is based on macromolecules occupying space, thus increasing the effective concentration of other components and thereby accelerating various biological processes, such as extracellular matrix deposition. We thus hypothesized that MMC will promote the accumulation of vascular ECM (basement membrane) components and lead to a stabilization of MVN with improved functionality. RESULTS: MMC promoted the enrichment of cellular junctions and basement membrane components, while reducing cellular contractility. The resulting advantageous balance of adhesive forces over cellular tension resulted in a significant stabilization of MVNs over time, as well as improved vascular barrier function, closely resembling that of in vivo microvasculature. CONCLUSION: Application of MMC to MVNs in microfluidic devices provides a reliable, flexible and versatile approach to stabilize engineered microvessels under simulated physiological conditions.

Autocatalytic base editing for RNA-responsive translational control.

Genetic circuits that control transgene expression in response to pre-defined transcriptional cues would enable the development of smart therapeutics. To this end, here we engineer programmable single-transcript RNA sensors in which adenosine deaminases acting on RNA (ADARs) autocatalytically convert target hybridization into a translational output. Dubbed DART VADAR (Detection and Amplification of RNA Triggers via ADAR), our system amplifies the signal from editing by endogenous ADAR through a positive feedback loop. Amplification is mediated by the expression of a hyperactive, minimal ADAR variant and its recruitment to the edit site via an orthogonal RNA targeting mechanism. This topology confers high dynamic range, low background, minimal off-target effects, and a small genetic footprint. We leverage DART VADAR to detect single nucleotide polymorphisms and modulate translation in response to endogenous transcript levels in mammalian cells.

Maternal Anti-Ro Antibody Titers Obtained With Commercially Available Immunoassays Are Strongly Associated With Immune-Mediated Fetal Heart Disease.

OBJECTIVE: Anti-Ro antibody-positive mothers are frequently referred for serial echocardiography due to the fetal risk of developing heart block and endocardial fibroelastosis. Little is known why only some and not all offspring develop these cardiac manifestations of neonatal lupus (CNL). This prospective study examined associations between anti-Ro antibody titers and fetal CNL. METHODS: Antibody-positive mothers referred since 2018 for fetal echocardiography at risk of CNL (group 1; n = 240) or with CNL (group 2; n = 18) were included. Maternal antibody titers were measured with a chemiluminescent immunoassay (CIA). Additional testing on diluted serum samples was used to quantify anti-Ro 60 antibody titers above the analytical measuring range (AMR) of the standard CIA (≥1,375 chemiluminescent units [CU]). RESULTS: Among 27 total mothers with a fetal diagnosis of CNL, all displayed anti-Ro 60 antibody titers that exceeded the AMR of the CIA at least 10-fold. Of 122 mothers in group 1 who underwent additional anti-Ro 60 antibody testing, event rates of CNL (n = 9) were 0% (0 of 45) among mothers with anti-Ro 60 antibody titers from 1,375-10,000 CU, 5% (3 of 56) among mothers with titers from 10,000-50,000 CU, but 29% (6 of 21) among mothers with titers >50,000 CU (odds ratio 13.1, P = 0.0008). Of mothers in group 2 with a primary diagnosis of CNL, 0% (0 of 18 mothers) had anti-Ro 60 antibody titers <10,000 CU, 44% (8 of 18 mothers) had titers from 10,000-50,000 CU, and 56% (10 of 18 mothers) had titers >50,000 CU. CONCLUSION: CNL is associated with substantially higher anti-Ro antibody titers than are obtained using a standard CIA. Enhancing the assay measuring range allows an improved specificity of identifying pregnancies at risk of CNL.

A Repeat Pattern of Founder Events for SARS-CoV-2 Variants in Alaska.

Alaska is a unique US state because of its large size, geographically disparate population density, and physical distance from the contiguous United States. Here, we describe a pattern of SARS-CoV-2 variant emergence across Alaska reflective of these differences. Using genomic data, we found that in Alaska, the Omicron sublineage BA.2.3 overtook BA.1.1 by the week of 27 February 2022, reaching 48.5% of sequenced cases. On the contrary, in the contiguous United States, BA.1.1 dominated cases for longer, eventually being displaced by BA.2 sublineages other than BA.2.3. BA.2.3 only reached a prevalence of 10.9% in the contiguous United States. Using phylogenetics, we found evidence of potential origins of the two major clades of BA.2.3 in Alaska and with logistic regression estimated how it emerged and spread throughout the state. The combined evidence is suggestive of founder events in Alaska and is reflective of how Alaska's unique dynamics influence the emergence of SARS-CoV-2 variants.

In Vivo Mechanism of Action of Sodium Caprate for Improving the Intestinal Absorption of a GLP1/GIP Coagonist Peptide.

Sodium caprate (C10) has been widely evaluated as an intestinal permeation enhancer for the oral delivery of macromolecules. However, the effect of C10 on the intestinal absorption of peptides with different physicochemical properties and its permeation-enhancing effect in vivo remains to be understood. Here, we evaluated the effects of C10 on intestinal absorption in rats with a glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GIP-GLP1) dual agonist peptide (LY) and semaglutide with different enzymatic stabilities and self-association behaviors as well as the oral exposure of the LY peptide in minipigs. Furthermore, we investigated the mechanism of action (MoA) of C10 for improving the intestinal absorption of the LY peptide in vivo via live imaging of the rat intestinal epithelium and tissue distribution of the LY peptide in minipigs. The LY peptide showed higher proteolytic stability in pancreatin and was a monomer in solution compared to that in semaglutide. C10 increased in vitro permeability in the minipig intestinal organoid monolayer to a greater extent for the LY peptide than for semaglutide. In the rat jejunal closed-loop model, C10 increased the absorption of LY peptide better than that of semaglutide, which might be attributed to higher in vitro proteolytic stability and permeability of the LY peptide. Using confocal live imaging, we observed that C10 enabled the rapid oral absorption of a model macromolecule (FD4) in the rat intestine. In the duodenum tissues of minipigs, C10 was found to qualitatively reduce the tight junction protein level and allow peptide uptake to the intestinal cells. C10 decreased the transition temperature of the artificial lipid membrane, indicating an increase in membrane fluidity, which is consistent with the above in vivo imaging results. These data indicated that the LY's favorable physicochemical properties combined with the effects of C10 on the intestinal mucosa resulted in an ∼2% relative bioavailability in minipigs.

Converting avocado seeds into a ready to eat snack and analysing for persin and amygdalin.

Avocado seeds account for 13% of the waste from industrial production of cold-pressed avocado oil (CPAO). Therefore, the aim of this study was to valorise avocado seeds by converting it into an extruded snack product using a friction cooker and comparing their textural and physical characteristics to extruded brown rice and malted barley ready to eat (RTE) snacks. Concentration of toxins; amygdalin and persin were compared in extruded avocado seed and fresh avocado seeds. Avocado seed extrudates were significantly lower in lateral expansion, apparent density, porosity, hardness, and crispiness compared to brown rice extrudates. Antioxidant capacity and total phenolic content (TPC) was highest in freeze-dried avocado seeds. Antioxidant capacity and TPC of avocado seed extrudates were significantly higher than brown rice and malted barley. The concentrations of both amygdalin and persin in the RTE avocado seed snack were present at non-toxic levels (2.6 × 10-6 mg/g and 0.68 mg/g respectively).

Light-Switchable Membrane Permeability in Giant Unilamellar Vesicles.

In this work, giant unilamellar vesicles (GUVs) were synthesized by blending the natural phospholipid 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) with a photoswitchable amphiphile (1) that undergoes photoisomerization upon irradiation with UV-A (E to Z) and blue (Z to E) light. The mixed vesicles showed marked changes in behavior in response to UV light, including changes in morphology and the opening of pores. The fine control of membrane permeability with consequent cargo release could be attained by modulating either the UV irradiation intensity or the membrane composition. As a proof of concept, the photocontrolled release of sucrose from mixed GUVs is demonstrated using microscopy (phase contrast) and confocal studies. The permeability of the GUVs to sucrose could be increased to ~4 × 10-2 µm/s when the system was illuminated by UV light. With respect to previously reported systems (entirely composed of synthetic amphiphiles), our findings demonstrate the potential of photosensitive GUVs that are mainly composed of natural lipids to be used in medical and biomedical applications, such as targeted drug delivery and localized topical treatments.

Cost-Effective Solution of Remote Photoplethysmography Capable of Real-Time, Multi-Subject Monitoring with Social Distancing.

Recent advances in remote-photoplethysmography (rPPG) have enabled the measurement of heart rate (HR), oxygen saturation (SpO2), and blood pressure (BP) in a fully contactless manner. These techniques are increasingly applied clinically given a desire to minimize exposure to individuals with infectious symptoms. However, accurate rPPG estimation often leads to heavy loading in computation that either limits its real-time capacity or results in a costly setup. Additionally, acquiring rPPG while maintaining protective distance would require high resolution cameras to ensure adequate pixels coverage for the region of interest, increasing computational burden. Here, we propose a cost-effective platform capable of the real-time, continuous, multi-subject monitoring while maintaining social distancing. The platform is composed of a centralized computing unit and multiple low-cost wireless cameras. We demonstrate that the central computing unit is able to simultaneously handle continuous rPPG monitoring of five subjects with social distancing without compromising the frame rate and rPPG accuracy.

Pattern of SARS-CoV-2 variant B.1.1.519 emergence in Alaska.

Alaska has the lowest population density in the United States (US) with a mix of urban centers and isolated rural communities. Alaska's distinct population dynamics compared to the contiguous US may have contributed to unique patterns of SARS-CoV-2 variants observed in early 2021. Here we examined 2323 SARS-CoV-2 genomes from Alaska and 278,635 from the contiguous US collected from December 2020 through June 2021 because of the notable emergence and spread of lineage B.1.1.519 in Alaska. We found that B.1.1.519 was consistently detected from late January through June of 2021 in Alaska with a peak prevalence in April of 77.9% unlike the rest of the US at 4.6%. The earlier emergence of B.1.1.519 coincided with a later peak of Alpha (B.1.1.7) compared to the contiguous US. We also observed differences in variant composition over time between the two most populated regions of Alaska and a modest increase in COVID-19 cases during the peak incidence of B.1.1.519. However, it is difficult to disentangle how social dynamics conflated changes in COVID-19 during this time. We suggest that the viral characteristics, such as amino acid substitutions in the spike protein, likely contributed to the unique spread of B.1.1.519 in Alaska.