Search

This qualitative study explored the use of the terms high-, low-, and no-tech among preservice teachers during a sudden shift to virtual instruction. Focus areas included how preservice teachers and mentor teachers described the role and purpose of these varied levels of technology for their teaching in a virtual setting. The findings show that choices related to levels of technology use are nuanced and complicated and include a need for consideration of the context. We include a simplified framework to guide future instructional decisions for the integration of technology at various levels.

This paper reflects on the delivery of Professional Doctorate programmes from a sample of educational (EdD) and sustainable built environment (DSBE) practitioners at a Welsh University in the United Kingdom (UK). The paper explores the 'learner journey' of a sample of Professional Doctorate students as they navigate their studies during COVID-19 pandemic. A qualitative approach was adopted, and semi-structured questionnaires were used to collect data from students on the EdD and DSBE pathways. A thematic analysis was conducted, and the data presented explored how students have navigated their respective pathways and change projects across various modules, during their 'learning journey' and how successful they perceive that journey to be, in relation to a range of factors. The findings from this paper provide a unique insight into the experiences of Professional Doctorate students during a period of significant upheaval. Recommendations are provided for supervisors of Professional Doctorates, Higher Education Managers, as well as Policy Makers in supporting Professional Doctorate students during the studies. Best practice is highlighted with regard to practice-based approaches and demonstrates the differences across two academic disciplines. The use of agile digital and online learning in response to the COVID-19 pandemic further suggests an ongoing model for leadership in Higher Education.

School mascots, including the Confederate Rebel, have come under scrutiny with calls to adopt more inclusive and representative symbols for all school stakeholders. Using qualitative methodology, we interviewed six school-based helping professionals in a southeastern US school district to examine their perceptions and experiences with the educational, personal, social, and community impacts associated with the Rebel school mascot. Four unique themes were identified from the participants and will be discussed along with implications and future research.

This study was part of a larger three-year investigation of the effectiveness of a small-group, content-focused (science, social studies) preschool shared book reading vocabulary intervention implemented with Spanish-speaking emergent bilinguals enrolled in a one-way dual-language bilingual program. A subset of bilingual preschool teachers (N = 23), representing treatment teachers from each of the three intervention years, was observed to understand the sustainability of the curricular approach and materials one, two, and three years post-intervention when instructional guidance was no longer provided by the research team. Findings from post-intervention observations and teacher self-reports suggest that teachers continued to implement the intervention approach and materials on some level but the explicit rich vocabulary instruction during the book reading experience was observed less the further teachers were out of the intervention. Implications for research are discussed.

This paper describes an application providing decision support for generating a shortlist of promising electricity-saving options for households in South Africa. The decision problem is characterised by constraints on time and other resources, and by substantial uncertainty around the preferences for energy-related attributes and the performance of alternatives on those attributes. We use a stochastic multi-criteria acceptability analysis model to incorporate preferential uncertainties, and adapt this for use with quantiles and other "simplified" formats for representing uncertain attribute evaluations.

Trial registration ClinicalTrials.gov Identifier: NCT05821153, Registered April 20 2023, Retrospectively registered, https://classic.clinicaltrials.gov/ct2/show/NCT05821153

ABSTRACT: Chromosome X is often excluded from bovine genetic studies due to complications caused by the sex specific nature of the chromosome. As chromosome X is the second largest cattle chromosome and makes up approximately 6% of the female genome, finding ways to include chromosome X in dairy genetic studies is important. Using female animals and treating chromosome X as an autosome, we performed X chromosome inclusive genome-wide association studies in the selective breeding environment of the New Zealand dairy industry, aiming to identify chromosome X variants associated with milk production traits. We report on the findings of these genome-wide association studies and their potential effect within the dairy industry. We identify missense mutations in the MOSPD1 and CCDC160 genes that are associated with decreased milk volume and protein production and increased fat production. Both of these mutations are exonic SNP that are more prevalent in the Jersey breed than in Holstein-Friesians. Of the 2 candidates proposed it is likely that only one is causal, though we have not been able to identify which is more likely.

Background: Alzheimer’s disease (AD) is the most commonly occurring form of dementia. It is predominantly a disease of later life, affecting 5% of those over 65 in the UK. Objectives: Review and update guidance to the NHS in England and Wales on the clinical effectiveness and cost-effectiveness of donepezil, galantamine, rivastigmine [acetylcholinesterase inhibitors (AChEIs)] and memantine within their licensed indications for the treatment of AD, which was issued in November 2006 (amended September 2007 and August 2009). Data sources: Electronic databases were searched for systematic reviews and/or meta-analyses, randomised controlled trials (RCTs) and ongoing research in November 2009 and updated in March 2010; this updated search revealed no new includable studies. The databases searched included The Cochrane Library (2009 Issue 4, Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Trials), MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, PsycINFO, EconLit, ISI Web of Science Databases – Science Citation Index, Conference Proceedings Citation Index, and BIOSIS; the Centre for Reviews and Dissemination (CRD) databases – NHS Economic Evaluation Database, Health Technology Assessment, and Database of Abstracts of Reviews of Effects. Review methods: The clinical effectiveness systematic review was undertaken following the principles published by the NHS CRD. We included RCTs whose population was people with AD. The intervention and comparators depended on disease severity, measured by the Mini Mental State Examination (MMSE). Interventions: mild AD (MMSE 21–26) – donepezil, galantamine and rivastigmine; moderate AD (MMSE 10–20) – donepezil, galantamine, rivastigmine and memantine; severe AD (MMSE 99% probability that the AChEIs are more cost-effective than BSC. These analyses assume that the AChEIs have no effect on survival. For the AChEIs, in people with mild to moderate AD, the probabilistic sensitivity analyses suggested that donepezil is the most cost-effective, with a 28% probability of being the most cost-effective option at a WTP of £30,000 per QALY (27% at a WTP of £20,000 per QALY). In the deterministic results, donepezil dominates the other drugs and BSC, which, along with rivastigmine patches, are associated with greater costs and fewer QALYs. Thus, although galantamine has a slightly cheaper total cost than donepezil (£69,592 vs £69,624), the slightly greater QALY gains from donepezil (1.616 vs 1.617) are enough for donepezil to dominate galantamine.The probability that memantine is cost-effective in a moderate to severe cohort compared with BSC at a WTP of £30,000 per QALY is 38% (and 28% at a WTP of £20,000 per QALY). The deterministic ICER for memantine is £32,100 per/QALY and the probabilistic ICER is £36,700 per/QALY. Limitations: Trials were of 6 months maximum follow-up, lacked reporting of key outcomes, provided no subgroup analyses and used insensitive measures. Searches were limited to English language, The model does not include behavioural symptoms and there is uncertainty about the model structure and parameters. Conclusions: The additional clinical effectiveness evidence identified continues to suggest clinical benefit from the AChEIs in alleviating AD symptoms, although there is debate about the magnitude of the effect. Although there is also new evidence on the effectiveness of memantine, it remains less supportive of this drug’s use than the evidence for AChEIs. The conclusions concerning cost-effectiveness are quite different from the previous assessment. This is because both the changes in effectiveness and costs between drug use and non-drug use underlying the ICERs are very small. This leads to highly uncertain results, which are very sensitive to change. Research priorities: RCTs to include mortality, time to institutionalisation and quality of life, powered for subgroup analysis. Funding: The National Institute for Health Research Health Technology Assessment programme.

An application of building a system dynamics model of the way households might respond to interventions aimed at reducing energy consumption (specifically the use of electricity) is described in this paper. A literature review of past research is used to build an initial integrated model of household consumption, and this model is used to generate a small number of research hypotheses about how households possessing different characteristics might react to various types of interventions. These hypotheses are tested using data gathered from an efficiency intervention conducted in a town in the South African Western Cape in which households were able to exchange regular light bulbs for more efficient compact fluorescent lamp light bulbs. Our experiences are (a) that a system dynamics approach proved useful in advancing a non-traditional point of view for which, for historical and economic reasons, data were not abundantly available; (b) that, in areas where traditional models are heavily quantitative, some scepticism to a system dynamics model may be expected; and (c) that a statistical comparison of model results by means of empirical data may be an effective tool in reducing such scepticism.

Abstract Background Poor sleep quality occurs in patients with psoriasis at rates nearly twice that of the general population. Chronic sleep impairment is an independent risk factor for the development of cardiovascular disease. Here, we examine the association between sleep quantity and history of myocardial infarction in patients with psoriasis. Methods This observational, cross-sectional study utilized data from the 2020 National Psoriasis Foundation Annual Survey. Effect estimates were obtained using a multivariate logistic regression model, which controlled for prespecified covariates. Results Based on data from 1405 individuals with psoriasis, our analysis demonstrated a significant association between sleep quantity and history of myocardial infarction: odds ratio (OR) 0.67 [95% confidence interval (CI) 0.49–0.92], p = 0.012. The association was not significantly influenced by psoriasis severity (OR 1.01, [95% CI 0.99–1.03], p = 0.38), comorbid psoriatic arthritis (OR 1.06, [95% CI 0.48–2.38], p = 0.88), sleep apnea, or other traditional risk factors for myocardial infarction. Conclusion Our analyses indicate an association between sleep quantity and history of myocardial infarction in patients with psoriasis. For each hour increase in average nightly sleep, patients with psoriasis have a 33% decrease in the odds of having a history of myocardial infarction. The chief limitation of this study is its cross-sectional design limiting ascertainment of causality.

Bisphenol A (BPA) is an endocrine-disrupting compound, used as the key monomer of polycarbonate plastics and epoxy resins. BPA has been detected in both humans and farm animals and has been correlated with decreased sperm counts and motility. BPS and BPF are structural analogs of BPA and are increasingly being used in manufacturing as BPA substitutes. In this study, we aim to assess the direct outcomes of BPA, bisphenol S (BPS), and bisphenol F (BPF) exposure on bovine sperm parameters in vitro to elucidate how they affect sperm quality and fertilization potential, and to assess whether BPS and/or BPF are less harmful than BPA. Sperm from three or more bulls was obtained from either fresh samples or cryopreserved straws and exposed to 0.05 mg/mL of BPA, BPS, and BPF in vitro. After 4 h incubation, motility, capacitation, apoptosis/necrosis, and mitochondrial membrane potential levels were measured by computer-assisted sperm analysis or computational flow cytometry. Results showed that BPA exposure significantly reduced both fresh and cryopreserved sperm motility, capacitation, viability and mitochondrial membrane potential levels. Furthermore, BPF significantly decreased motility, capacitation and mitochondrial membrane potential in cryopreserved sperm only. BPS did not have any significant effects on any of the parameters measured. Our results suggest that BPA is the most harmful to sperm, while BPF is toxic under certain conditions, and BPS seems to be the least detrimental. Overall, this study provides an understanding of how the ubiquitous environmental chemicals, bisphenols, may impact male fertility even after ejaculation.

Abstract Culturally dependent human social behaviours involving artificial light usage can potentially affect light pollution patterns and thereby impact the night‐time ecology in populated areas, although to date this has not been examined globally. By analysing continuous (monthly), highly resolved, spatially explicit data on global night lights (Visible and Infrared Imaging Radiometer Suite–Day/Night Band‐VIIRS‐DNB; 2014–2019) with circular statistical techniques, we evaluated whether macro‐cultural activities involving social aggregations and the use of artificial lights shape annual lighting patterns globally. Scheduled routines associated with cultural‐specific festivities appear to be important drivers of observed seasonal patterns in urban night‐time lights. For instance, the display of Christmas lights between Christmas and Epiphany Day celebrations (December–January) coincides with the annual peak in urban night‐time light intensity in Christian countries. Analogously, night celebrations during the Holy Month of Ramadam (from May to July) or the month‐long period of Karthika Masam (from October to November) fits with annual night light peaks in Muslim and Hindu countries. Annual peaks of urban light intensity in China and Vietnam also match with Chinese and Vietnamese (Tê't) New Year celebrations (January–February). In contrast, predominantly Buddhist countries, which do not have such prominent and prolonged celebrations involving artificial lights, show a relatively uniform distribution of night light peaks throughout the annual cycle. Social behaviour and sociocultural contexts help explain how people modify the global nightscape and contribute to light pollution globally. Understanding the cultural contexts responsible for peaks in artificial light usage is an important first step if humans are to mitigate any deleterious effects associated with global increases in night‐time light pollution. Read the free Plain Language Summary for this article on the Journal blog.

Abstract Background The Aboriginal health workforce provide responsive, culturally safe health care. We aimed to co-design a culturally safe course with and for the Aboriginal health workforce. We describe the factors which led to the successful co-design, delivery, and evaluation of the “Managing hepatitis B” course for the Aboriginal health workforce. Methods A Participatory Action Research approach was used, involving ongoing consultation to iteratively co-design and then develop course content, materials, and evaluation tools. An Aboriginal and Torres Strait Islander research and teaching team received education in chronic hepatitis B and teaching methodologies. Pilot courses were held, in remote communities of the Northern Territory, using two-way learning and teach-back methods to further develop the course and assess acceptability and learnings. Data collection involved focus group discussions, in-class observations, reflective analysis, and use of co-designed and assessed evaluation tools. Results Twenty-six participants attended the pilot courses. Aboriginal and Torres Strait Islander facilitators delivered a high proportion of the course. Evaluations demonstrated high course acceptability, cultural safety, and learnings. Key elements contributing to success and acceptability were acknowledging, respecting, and integrating cultural differences into education, delivering messaging and key concepts through an Aboriginal and Torres Strait Islander lens, using culturally appropriate approaches to learning including storytelling and visual teaching methodologies. Evaluation of culturally safe frameworks and findings from the co-design process led to the creation of a conceptual framework, underpinned by meeting people’s basic needs, and offering a safe and comfortable environment to enable productive learning with attention to the following: sustenance, financial security, cultural obligations, and gender and kinship relationships. Conclusions Co-designed education for the Aboriginal health workforce must embed principles of cultural safety and meaningful community consultation to enable an increase in knowledge and empowerment. The findings of this research can be used to guide the design of future health education for First Nations health professionals and to other non-dominant cultures. The course model has been successfully transferred to other health issues in the Northern Territory.

The Mesoscale to Microscale Coupling team, part of the U.S. Department of Energy Atmosphere to Electrons (A2e) initiative, has studied various important challenges related to coupling mesoscale models to microscale models for the use case of wind energy development and operation. Several coupling methods and techniques for generating turbulence at the microscale that is subgrid to the mesoscale have been evaluated for a variety of cases. Case studies included flat-terrain, complex-terrain, and offshore environments. Methods were developed to bridge the terra incognita, which scales from about 100 m through the depth of the boundary layer. The team used wind-relevant metrics and archived code, case information, and assessment tools and is making those widely available. Lessons learned and discerned best practices are described in the context of the cases studied for the purpose of enabling further deployment of wind energy.

Abstract Nuclear compartments are prominent features of 3D chromatin organization, but sequencing depth limitations have impeded investigation at ultra fine-scale. CTCF loops are generally studied at a finer scale, but the impact of looping on proximal interactions remains enigmatic. Here, we critically examine nuclear compartments and CTCF loop-proximal interactions using a combination of in situ Hi-C at unparalleled depth, algorithm development, and biophysical modeling. Producing a large Hi-C map with 33 billion contacts in conjunction with an algorithm for performing principal component analysis on sparse, super massive matrices (POSSUMM), we resolve compartments to 500 bp. Our results demonstrate that essentially all active promoters and distal enhancers localize in the A compartment, even when flanking sequences do not. Furthermore, we find that the TSS and TTS of paused genes are often segregated into separate compartments. We then identify diffuse interactions that radiate from CTCF loop anchors, which correlate with strong enhancer-promoter interactions and proximal transcription. We also find that these diffuse interactions depend on CTCF’s RNA binding domains. In this work, we demonstrate features of fine-scale chromatin organization consistent with a revised model in which compartments are more precise than commonly thought while CTCF loops are more protracted.

Background: Bone stress injuries (BSIs) are common in female runners, and recurrent BSI rates are high. Previous work suggests an association between higher impact loading during running and tibial BSI. However, it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs. This study compared impact variables at the beginning of a treadmill run to exertion and the changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs. Methods: We enrolled 45 female runners (aged 18–40 years) for this cross-sectional study: having no history of diagnosed lower extremity BSI (N-BSI, n = 14); a history of 1 lower extremity BSI (1-BSI, n = 16); and diagnosed by imaging, or a history of multiple (≥3) lower extremity BSIs (M-BSI, n = 15). Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit. The vertical average loading rate (VALR), vertical instantaneous loading rate (VILR), vertical stiffness during impact via instrumented treadmill, and tibial shock determined as the peak positive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run. Results: There were no differences between groups in VALR, VILR, vertical stiffness, or tibial shock in a fresh or exerted condition. However, compared to N-BSI, women with M-BSI had greater increase with exertion in VALR (–1.8% vs. 6.1%, p = 0.01) and VILR (1.5% vs. 4.8%, p = 0.03). Similarly, compared to N-BSI, vertical stiffness increased more with exertion among women with M-BSI (–0.9% vs. 7.3%, p = 0.006) and 1-BSI (–0.9% vs. 1.8%, p = 0.05). Finally, compared to N-BSI, the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI (0.9% vs. 5.5%, p = 0.03) and 1-BSI (0.9% vs. 11.2%, p = 0.02). Conclusion: Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI. These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.

Abstract Invasive species pose a major threat to biodiversity and inflict massive economic costs. Effective management of bio-invasions depends on reliable predictions of areas at risk of invasion, as they allow early invader detection and rapid responses. Yet, considerable uncertainty remains as to how to predict best potential invasive distribution ranges. Using a set of mainly (sub)tropical birds introduced to Europe, we show that the true extent of the geographical area at risk of invasion can accurately be determined by using ecophysiological mechanistic models that quantify species’ fundamental thermal niches. Potential invasive ranges are primarily constrained by functional traits related to body allometry and body temperature, metabolic rates, and feather insulation. Given their capacity to identify tolerable climates outside of contemporary realized species niches, mechanistic predictions are well suited for informing effective policy and management aimed at preventing the escalating impacts of invasive species.

Abstract Most African wild dog (Lycaon pictus) populations are in decline and, due to habitat fragmentation and conflict rates in areas of higher anthropogenic land‐use, are primarily restricted to protected areas. As a species that occurs at low densities, with a strict reproductive social structure, wild dogs rely on long‐range dispersal to facilitate colonization, reproduction, and pack formation. In Malawi, large carnivores have been subject to widespread population decline and several protected areas have a reduced large carnivore guild, including the loss of resident wild dog populations. Here, during a biodiversity monitoring camera trap survey, we captured a novel record of wild dogs in Vwaza Marsh Wildlife Reserve (Vwaza), Malawi. The 11 photographic captures of potentially three individual wild dogs represent the first documented evidence of the species in Vwaza and the first record since an unconfirmed report in 2011. We hypothesize that this group of wild dogs moved into Vwaza through the Malawi‐Zambia Transfrontier Conservation Area (MZTFCA), with the MZTFCA linking protected areas in Malawi with the Luangwa Valley, Zambia. The evidence provided here, and similar documentation in Kasungu National Park, Malawi, show that large carnivores can potentially move through the MZTFCA into protected areas in Malawi. We argue that the MZTFCA provides an important dispersal corridor that could help facilitate the recolonization of wild dogs, and other large carnivores, in Malawian protected areas. However, further research is needed to assess the permeability and status of the MZTFCA corridor into Malawi. We show that camera traps can be useful to document novel records of rare species and can be used to inform conservation management planning.

Abstract Female subfertility is an increasing reproductive issue worldwide, which is partially related to abnormal ovarian follicular development. Granulosa cells (GCs), by providing the necessary physical support and microenvironment for follicular development, play critical roles in maintaining female fertility. We previously showed that ectopic expression of four and a half LIM domains 2 (FHL2) promoted ovarian granulosa cell tumor progression. However, its function in follicular development and fertility remains unknown. Here, we confirmed that FHL2 is highly expressed in human and mouse ovaries. FHL2 immunosignals were predominantly expressed in ovarian GCs. A Fhl2 knockout (KO) mouse model was generated to examine its roles in follicular development and fertility. Compared with wildtype, knockout of Fhl2 significantly decreased female litter size and offspring number. Furthermore, Fhl2 deficiency reduced ovarian size and impaired follicular development. RNA-sequencing analysis of GCs isolated from either KO or WT mice revealed that, Fhl2 deletion impaired multiple biological functions and signaling pathways, such as Ovarian Putative Early Atresia Granulosa Cell, ErbB, Hippo/YAP, etc. In vitro studies confirmed that FHL2 silencing suppressed GCs growth and EGF-induced GCs proliferation, while its overexpression promoted GC proliferation and decreased apoptosis. Mechanistic studies indicated that FHL2, via forming complexes with transcriptional factors AP-1 or NF-κB, regulated Egf and Egfr expression, respectively. Besides, FHL2 depletion decreased YAP1 expression, especially the active form of YAP1 (nuclear YAP1) in GCs of growing follicles. EGF, serving as an autocrine/paracrine factor, not only induced FHL2 expression and nuclear accumulation, but also stimulated YAP1 expression and activation. Collectively, our study suggests that FHL2 interacts with EGFR and Hippo/YAP signaling to regulate follicular development and maintain fertility. This study illuminates a novel mechanism for follicular development and a potential therapeutic target to address subfertility.

Abstract Psoriasis vulgaris is a systemic, chronic inflammatory disease affecting 2–3% of the population. Recent advances in the understanding of the pathophysiology of psoriatic disease have facilitated the development of novel therapeutic options with improved safety and efficacy. This article is coauthored by a patient with a lifelong history of psoriasis who experienced multiple treatment failures. He details his diagnosis and treatment experiences, as well as the physical, mental, and social ramifications of his skin condition. He then goes on to elaborate how evolutions in the treatment of psoriatic disease have impacted his life. This case is then discussed from the perspective of a dermatologist specializing in inflammatory skin disorders. We highlight the clinical features of psoriasis, its medical and psychosocial comorbidities, and the current landscape of psoriatic disease treatments.

Abstract Background Delta-9-tetrahydrocannabinol (THC) is the primary phytocannabinoid responsible for the psychoactive properties of cannabis and is known to interact with the endocannabinoid system, which is functionally present in the male reproductive system. Since cannabis consumption is the highest among reproductive aged males, the current study aimed to further investigate the effects of THC exposure to phenotypical, physiological, and molecular parameters in sperm. Bull sperm of known fertility were used as a translational model for human sperm and subjected to in vitro treatment with physiologically relevant experimental doses of THC. Sperm parameters, capacitation, apoptosis, and transcript levels were evaluated following treatment. Results Motility, morphology, and viability of bovine sperm was unaltered from THC exposure. However, 0.32µM of THC caused an increased proportion of capacitating sperm (p

Summary: Background: While vaccines have established utility against COVID-19, phase 3 efficacy studies have generally not comprehensively evaluated protection provided by previous infection or hybrid immunity (previous infection plus vaccination). Individual patient data from US government-supported harmonized vaccine trials provide an unprecedented sample population to address this issue. We characterized the protective efficacy of previous SARS-CoV-2 infection and hybrid immunity against COVID-19 early in the pandemic over three-to six-month follow-up and compared with vaccine-associated protection. Methods: In this post-hoc cross-protocol analysis of the Moderna, AstraZeneca, Janssen, and Novavax COVID-19 vaccine clinical trials, we allocated participants into four groups based on previous-infection status at enrolment and treatment: no previous infection/placebo; previous infection/placebo; no previous infection/vaccine; and previous infection/vaccine. The main outcome was RT-PCR-confirmed COVID-19 >7–15 days (per original protocols) after final study injection. We calculated crude and adjusted efficacy measures. Findings: Previous infection/placebo participants had a 92% decreased risk of future COVID-19 compared to no previous infection/placebo participants (overall hazard ratio [HR] ratio: 0.08; 95% CI: 0.05–0.13). Among single-dose Janssen participants, hybrid immunity conferred greater protection than vaccine alone (HR: 0.03; 95% CI: 0.01–0.10). Too few infections were observed to draw statistical inferences comparing hybrid immunity to vaccine alone for other trials. Vaccination, previous infection, and hybrid immunity all provided near-complete protection against severe disease. Interpretation: Previous infection, any hybrid immunity, and two-dose vaccination all provided substantial protection against symptomatic and severe COVID-19 through the early Delta period. Thus, as a surrogate for natural infection, vaccination remains the safest approach to protection. Funding: National Institutes of Health.

The corpus luteum is a transient ovarian endocrine gland that produces the progesterone necessary for the establishment and maintenance of pregnancy. The formation and function of this gland involves angiogenesis, establishing the tissue with a robust blood flow and vast microvasculature required to support production of progesterone. Every steroidogenic cell within the corpus luteum is in direct contact with a capillary, and disruption of angiogenesis impairs luteal development and function. At the end of a reproductive cycle, the corpus luteum ceases progesterone production and undergoes rapid structural regression into a nonfunctional corpus albicans in a process initiated and exacerbated by the luteolysin prostaglandin F2α (PGF2α). Structural regression is accompanied by complete regression of the luteal microvasculature in which endothelial cells die and are sloughed off into capillaries and lymphatic vessels. During luteal regression, changes in nitric oxide transiently increase blood flow, followed by a reduction in blood flow and progesterone secretion. Early luteal regression is marked by an increased production of cytokines and chemokines and influx of immune cells. Microvascular endothelial cells are sensitive to released factors during luteolysis, including thrombospondin, endothelin, and cytokines like tumor necrosis factor alpha (TNF) and transforming growth factor β 1 (TGFB1). Although PGF2α is known to be a vasoconstrictor, endothelial cells do not express receptors for PGF2α, therefore it is believed that the angioregression occurring during luteolysis is mediated by factors downstream of PGF2α signaling. Yet, the exact mechanisms responsible for angioregression in the corpus luteum remain unknown. This review describes the current knowledge on angioregression of the corpus luteum and the roles of vasoactive factors released during luteolysis on luteal vasculature and endothelial cells of the microvasculature.

Immunotherapeutic targeting of surface regulatory proteins and pharmacologic inhibition of critical signaling pathways has dramatically shifted our approach to the care of individuals with B cell malignancies. This evolution in therapy reflects the central role of the B cell receptor (BCR) signaling complex and its co-receptors in the pathogenesis of B lineage leukemias and lymphomas. Members of the Fc receptor-like gene family (FCRL1-6) encode cell surface receptors with complex tyrosine-based regulation that are preferentially expressed by B cells. Among them, FCRL1 expression peaks on naïve and memory B cells and is unique in terms of its intracellular co-activation potential. Recent studies in human and mouse models indicate that FCRL1 contributes to the formation of the BCR signalosome, modulates B cell signaling, and promotes humoral responses. Progress in understanding its regulatory properties, along with evidence for its over-expression by mature B cell leukemias and lymphomas, collectively imply important yet unmet opportunities for FCRL1 in B cell development and transformation. Here we review recent advances in FCRL1 biology and highlight its emerging significance as a promising biomarker and therapeutic target in B cell lymphoproliferative disorders.

IntroductionIn-person dermatology clinical research studies often face recruitment and participation challenges due to travel-, time-, and cost-associated barriers. Studies incorporating virtual/asynchronous formats can potentially enhance research subject participation and satisfaction, but few mobile health tools are available to enable remote study conduct. We developed SkinTracker, a patient-facing mobile app and researcher-facing web platform, that enables longitudinal collection of skin photos, patient reported outcomes, and biometric health and environmental data.MethodsEight design thinking sessions including dermatologists, clinical research staff, software engineers, and graphic designers were held to create the components of SkinTracker. Following iterative prototyping, SkinTracker was piloted across six adult and four pediatric subjects with atopic dermatitis (AD) of varying severity levels to test and provide feedback on SkinTracker for six months.ResultsThe SkinTracker app enables collection of informed consent for study participation, baseline medical history, standardized skin photographs, patient-reported outcomes (e.g., Patient Oriented Eczema Measure (POEM), Pruritus Numerical Rating Scale (NRS), Dermatology Life Quality Index (DLQI)), medication use, adverse events, voice diary to document qualitative experiences, chat function for communication with research team, environmental and biometric data such as exercise and sleep metrics through integration with an Apple Watch. The researcher web portal allows for management and visualization of subject enrollment, skin photographs for examination and severity scoring, survey completion, and other patient modules. The pilot study requested that subjects complete surveys and photographs on a weekly to monthly basis via the SkinTracker app. Afterwards, participants rated their experience in a 7-item user experience survey covering app function, design, and desire for participation in future studies using SkinTracker. Almost all subjects agreed or strongly agreed that SkinTracker enabled more convenient participation in skin research studies compared to an in-person format.DiscussionTo our knowledge, SkinTracker is one of the first integrated app- and web-based platforms allowing collection and management of data commonly obtained in clinical research studies. SkinTracker enables detailed, frequent capture of data that may better reflect the fluctuating course of conditions such as AD, and can be modularly customized for different skin conditions to improve dermatologic research participation and patient access.

Recent advances in biomaterials and 3D printing/culture methods enable various tissue-engineered tumor models. However, it is still challenging to achieve native tumor-like characteristics due to lower cell density than native tissues and prolonged culture duration for maturation. Here, we report a new method to create tumoroids with a mechanically active tumor-stroma interface at extremely high cell density. This method, named “inkjet-printed morphogenesis” (iPM) of the tumor-stroma interface, is based on a hypothesis that cellular contractile force can significantly remodel the cell-laden polymer matrix to form densely-packed tissue-like constructs. Thus, differential cell-derived compaction of tumor cells and cancer-associated fibroblasts (CAFs) can be used to build a mechanically active tumor-stroma interface. In this methods, two kinds of bioinks are prepared, in which tumor cells and CAFs are suspended respectively in the mixture of collagen and poly (N-isopropyl acrylamide-co-methyl methacrylate) solution. These two cellular inks are inkjet-printed in multi-line or multi-layer patterns. As a result of cell-derived compaction, the resulting structure forms tumoroids with mechanically active tumor-stroma interface at extremely high cell density. We further test our working hypothesis that the morphogenesis can be controlled by manipulating the force balance between cellular contractile force and matrix stiffness. Furthermore, this new concept of “morphogenetic printing” is demonstrated to create more complex structures beyond current 3D bioprinting techniques.

This study presents preliminary results from recent bathymetric LiDAR-guided surveys of submerged archaeological landscapes in the Apalachee Bay off the coast of Florida. We show how bathymetric LiDAR can re-identify previously recorded archaeological sites and identify new cultural deposits at shallow depths and help aid SCUBA surveys of submerged environments. While most prior archaeological applications of bathymetric LiDAR have focused on shipwrecks and historic era sites, our case study demonstrates that bathymetric LiDAR is capable of detecting Holocene and Pleistocene era archaeological sites as well. Detecting and eventually characterizing these ancient deposits will greatly expand our understanding of settlement trends when sea levels were lower and may provide insights into how some of the earliest coastal populations adapted to this novel and changing environment. Our SCUBA surveys also elucidate the impact of local environmental conditions of the applicability of deploying bathymetric LiDAR; specifically, eel grass cover does not hinder LiDAR capabilities, while high rates of sedimentation greatly reduce success in identifying archaeological deposits. Overall, our results show promise in the future of applying remote sensing to study shallow submerged archaeological landscapes, which can help improve our understanding of human–environment dynamics prior to and during periods of sea level change.