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In summer 2020, New York City (NYC) implemented a free air conditioner (AC) distribution program in response to the threats of extreme heat and COVID-19. The program distributed and installed ACs in the homes of nearly 73,000 older, low-income residents of public and private housing. To evaluate the program’s impact, survey data were collected from October 2020 to February 2021 via mail and online from 1447 program participants and 902 non-participating low-income NYC adults without AC as a comparison group. Data were examined by calculating frequencies, proportions, and logistic regression models. Participants were 3 times more likely to report staying home during hot weather in summer 2020 compared to non-participants (adjusted odds ratio [AOR] = 3.0, 95% confidence interval [CI] = 2.2, 4.1), with no difference between groups in summer 2019 (AOR = 1.0, CI = 0.8, 1.3). Participants were less likely to report that 2020 hot weather made them feel sick in their homes compared to non-participants (AOR = 0.2, CI = 0.2, 0.3). The program helped participants—low-income residents and primarily people of color—stay home safely during hot weather. These results are relevant for climate change health-adaptation efforts and heat-health interventions.

Digital educational games have evolved in recent years due to the need to support education and training focused on non-technical skills. Data gathered through interaction with the graphical user interface are explored and exploited to analyze the players' experience. Many researchers have pointed the importance of analysis of players’ in-game behavior, which can help to enhance the learning process, identify learners' strategies, and improve the effectiveness of the serious game. This study is devoted to the analysis of students' behavior in a simulation game called CLONE, which targets work scheduling, situation awareness, and decision-making. The students’ performance and their behavioral strategies are examined based on sequences analysis of players' in-game actions. Moreover, outlier detection is proposed as an instrument for obtaining information that might help better understand students’ behavior. The findings of the study show that such indicators as time spent on planning schedule, time spent on inspecting additional information, and intensity of delegation activity are significantly higher for successful games than for lost ones. The sequences analysis and clustering reveal students' prevailing in-game strategies, which mostly consist of inspection, reading medical records, delegation, and scheduling. Eventually, outlier detection discloses the game sessions with uncertain strategies and unstructured scheduling.

Walking, running, jumping, or even just standing up are habits that we all have to perform in our everyday lives. However, defects in tissues composing the knee joint can drastically alter our ability to complete those simple actions. The knee joint is made up of the interaction between bones (femur, tibia, and patella), tendons, ligaments, and the two menisci (lateral and medial) in order to ensure smooth body movements. The meniscus corresponds to a crescent-shaped fibrocartilaginous tissue, which is found in the knee joint between the femoral condyles and the tibial plateau. It plays a key role in the stability of the knee joint. However, it is quite vulnerable and therefore tears can occur within this tissue and compromise the proper function of the knee. Recently, numerous efforts have been made in order to find solutions to repair and regenerate the meniscus, supported by both bioengineering researchers and orthopedic surgeons. However, due to its poor healing capacity and its complex structure, the reconstruction of the meniscus remains particularly challenging. In this review, the current treatment options will be explained and the possibility of using organoids as building blocks for implant formation or as an in vitro three-dimensional model will be highlighted.

This study is a quantitative research and used a correlational research design to investigate the relationship between pre-service teachers’ prior mathematics achievement (PA) at the senior high school and mathematics self-efficacy (MSEF) on learning and achievement in geometry and trigonometry in colleges of education. A sample of 449 pre-service teachers (264 males and 185 females) randomly selected from the population was used for the study. The result revealed a strong positive relationship between PA (r = 0.543), MSEf (r = 0.542), and geometry and trigonometry score. The study then concludes that the factors (PA, MSEf) have a positive relationship with geometry and trigonometry achievement. The study recommended that colleges of education should place much emphasis on pre-service teachers’ entry grade in mathematics when considering the requirement for admission.

Porphyromonas gingivalis exacerbates tissue hypoxia and worsens periodontal inflammation. This study investigated the effect of a therapeutic oxygen carrier (M101), derived from Arenicola marina, on hypoxia and associated inflammation in the context of periodontitis.The effect of M101 on GLUT-1, GLUT-3, HIF-1α, and MMP-9 expression, hypoxia, and antioxidant status in oral epithelial cells (EC) exposed to CoClM101 downregulated GLUT-1, GLUT-3, HIF-1α, and MMP-9 levels in EC exposed to CoClM101 showed promise in resolving hypoxia and associated inflammation-mediated tissue degradation. Its potential in the clinical management of periodontitis must be further investigated.

Supplementary Methods

Association between pre-treatment CD4+ T-cell density from available baseline tumor tissue (n=14) and the duration of time on treatment in days.

Trial Protocol

Waterfall plots demonstrating the percent change in sum of RECIST v1.1 target lesions compared to baseline. Twenty-five out of 26 patients were included; 1 patient withdrew consent and no follow-up imaging was available for review. The waterfall plots are color-coded by (A) best overall response (PR, SD, PD), (B) cohort (1-6), and (C) tumor type (melanoma, RCC, NSCLC). The majority of patients who experienced disease progression on the study had progression in non-target lesions, as denoted by as asterisk (*), and therefore the percent change in tumor from baseline by RECIST is less than the 20% disease progression threshold for multiple patients who had PD.

Current periodontal treatments aim to control bacterial infection and decrease inflammation. To optimize contemporary conventional treatments that present limitations owing to an inability to reach the lesion site, new methods are based on nanomedicine. Nanomedecine allows delivery of host-modulatory drugs or antibacterial molecules at the lesion site in an optimal concentration with decreased toxicity and risk of systemic side effects. Chitosan and polylactic-co-glycolic acid-loaded nanoparticles, carbon quantum dots, and mesoporous silicates open new perspectives in periodontitis management. The potential therapeutic impact of the main nanocarriers is discussed.

We here describe a prototype of a patient-derived tumoroid that prefigures the precision medicine approach by helping experimental assessment of response to current treatments. The introduction of microvessels to help forming a tumor-connected vasculature, and of peripheral blood immune cells was shown to be essential for the representativeness of the model. The study is based on a cohort of 11 patients at various stages of the disease. Noteworthy, this predictive vascularized, and immunocompetent micromodel can be obtained within 2 weeks, matching the constraints of the patient journey. Histological analyses confirmed that major features of the original tumor were conserved. Transcriptomic analysis confirmed the functionality of the tumoroid. The responses to either anti-angiogenic treatment or platinum-based chemotherapy regimen highlighted the role of immune mechanisms. We also discussed the possibility to apply this original experimental model to the analysis of response to immune checkpoint blockers, or oncolytic vector-based therapies.

Background The contribution of artefenomel to the clinical and parasiticidal activity of ferroquine and artefenomel in combination in uncomplicated Plasmodium falciparum malaria was investigated. Methods This Phase 2a, randomized, open-label, parallel-group study was conducted from 11th September 2018 to 6th November 2019 across seven centres in Benin, Burkina Faso, Gabon, Kenya, and Uganda. Patients aged ≥ 14–69 years with microscopically confirmed infection (≥ 3000 to ≤ 50,000 parasites/µL blood) were randomized 1:1:1:1 to 400 mg ferroquine, or 400 mg ferroquine plus artefenomel 300, 600, or 1000 mg, administered as a single oral dose. The primary efficacy analysis was a logistic regression evaluating the contribution of artefenomel exposure to Day 28 PCR-adjusted adequate clinical and parasitological response (ACPR). Safety was also evaluated. Results The randomized population included 140 patients. For the primary analysis in the pharmacokinetic/pharmacodynamic efficacy population (N = 121), the contribution of artefenomel AUC0–∞ to Day 28 PCR-adjusted ACPR was not demonstrated when accounting for ferroquine AUC0–d28, baseline parasitaemia, and other model covariates: odds ratio 1.1 (95% CI 0.98, 1.2; P = 0.245). In the per-protocol population, Day 28 PCR-adjusted ACPR was 80.8% (21/26; 95% CI 60.6, 93.4) with ferroquine alone and 90.3% (28/31; 95% CI 74.2, 98.0), 90.9% (30/33; 95% CI 75.7, 98.1) and 87.1% (27/31; 95% CI 70.2, 96.4) with 300, 600, and 1000 mg artefenomel, respectively. Median time to parasite clearance (Kaplan–Meier) was 56.1 h with ferroquine, more rapid with artefenomel, but similar for all doses (30.0 h). There were no deaths. Adverse events (AEs) of any cause occurred in 51.4% (18/35) of patients with ferroquine 400 mg alone, and 58.3% (21/36), 66.7% (24/36), and 72.7% (24/33) with 300, 600, and 1000 mg artefenomel, respectively. All AEs were of mild-to-moderate severity, and consistent with the known profiles of the compounds. Vomiting was the most reported AE. There were no cases of QTcF prolongation ≥ 500 ms or > 60 ms from baseline. Conclusion The contribution of artefenomel exposure to the clinical and parasitological activity of ferroquine/artefenomel could not be demonstrated in this study. Parasite clearance was faster with ferroquine/artefenomel versus ferroquine alone. All treatments were well tolerated. Trial registration: ClinicalTrials.gov, NCT03660839 (7 September, 2018).

Additional file 1: Study protocol.

Additional file 2: Clinical trial simulation to determine the dose and sample sizes.

Additional file 5. Supplementary tables and figures.

Additional file 4: Exposure–response pharmacokinetic/pharmacodynamic analysis.

Treatment with immune checkpoint inhibitors has altered the course of malignant melanoma, with approximately half of the patients with advanced disease surviving for more than 5 years after diagnosis. Currently, there are no biomarker methods for predicting outcome from immunotherapy. Here, we obtained transcriptomic information from a total of 105 baseline tumor samples comprising two cohorts of patients with advanced melanoma treated with programmed cell death protein 1 (PD-1)-based immunotherapies. Gene expression profiles were correlated with progression-free survival (PFS) within consecutive clinical benefit intervals (i.e., 6, 12, 18, and 24 months). Elastic net binomial regression models with cross validation were utilized to compare the predictive value of distinct genes across time. Lasso regression was used to generate a signature predicting long-term benefit (LTB), defined as patients who remain alive and free of disease progression at 24 months post treatment initiation. We show that baseline gene expression profiles were consistently able to predict long-term immunotherapy outcomes with high accuracy. The predictive value of different genes fluctuated across consecutive clinical benefit intervals, with a distinct set of genes defining benefit at 24 months compared to earlier outcomes. A 12-gene signature was able to predict LTB following anti-PD-1 therapy with an area under the curve (AUC) equal to 0.92 and 0.74 in the training and validation set, respectively. Evaluation of LTB, via a unique signature may complement objective response classification and characterize the logistics of sustained antitumor immune responses.

Primary segmental intestinal volvulus is a rare condition that may affect neonates. This condition occurs when a loop of bowel torses around the axis of its mesentery without any other abnormality or malrotation. In the earlier stages, the diagnosis can be challenging due to the lack of specific clinical and radiographic signs. Prompt surgical management is critical as a delay in diagnosis may result in bowel loss or death. We present a series of three cases of extremely low birth weight infants with primary segmental volvulus. A sentinel bowel loop was critical in guiding each patient’s surgical management as there were no other clinical markers concerning a pending intra-abdominal catastrophe. This case series suggests that a sentinel bowel loop may be a radiographic marker for primary segmental intestinal volvulus in extremely low birth weight infants.

Jessel et al. (Behavior Analysis & Practice, 13(1), 205–216, 2020a) conducted a review of the functional analysis literature between the years 1965 and 2016. The authors found an increasing trend in analyses replicating the components of Iwata et al. (Journal of Applied Behavior Analysis, 27, 197–209, 1982/1994a) and determined that those components have come to represent a standard format. Since the inception of the standard, other functional analysis formats (e.g., brief, latency-based, trial-based) have been developed to improve analysis efficiency and control, with most retaining fundamental components of the standard and some omitting all (e.g., interview-informed, synthesized contingency analysis; IISCA). We conducted a review of functional analyses in this two-part evaluation to determine the levels of efficiency and control afforded by functional analysis variations and formats.

Monoclonal antibodies targeting IgE, interleukin-4 and -13, and interleukin-5 are effective in treating severe type 2 asthma, but new targets are needed. Itepekimab is a new monoclonal antibody against the upstream alarmin interleukin-33. The efficacy and safety of itepekimab as monotherapy, as well as in combination with dupilumab, in patients with asthma are unclear.In a phase 2 trial, we randomly assigned, in a 1:1:1:1 ratio, adults with moderate-to-severe asthma receiving inhaled glucocorticoids plus long-acting beta-agonists (LABAs) to receive subcutaneous itepekimab (at a dose of 300 mg), itepekimab plus dupilumab (both at 300 mg; combination therapy), dupilumab (300 mg), or placebo every 2 weeks for 12 weeks. After randomization, LABA was discontinued at week 4, and inhaled glucocorticoids were tapered over weeks 6 through 9. The primary end point was an event indicating a loss of asthma control, assessed in the itepekimab group and the combination group, as compared with the placebo group. Secondary and other end points included lung function, asthma control, quality of life, type 2 biomarkers, and safety.A total of 296 patients underwent randomization. By 12 weeks, an event indicating a loss of asthma control occurred in 22% of the patients in the itepekimab group, 27% of those in the combination group, and 19% of those in the dupilumab group, as compared with 41% of those in the placebo group; the corresponding odds ratios as compared with placebo were as follows: in the itepekimab group, 0.42 (95% confidence interval [CI], 0.20 to 0.88; P = 0.02); in the combination group, 0.52 (95% CI, 0.26 to 1.06; P = 0.07); and in the dupilumab group, 0.33 (95% CI, 0.15 to 0.70). As compared with placebo, the forced expiratory volume in 1 second before bronchodilator use increased with the itepekimab and dupilumab monotherapies but not with the combination therapy. Itepekimab treatment improved asthma control and quality of life, as compared with placebo, and led to a greater reduction in the mean blood eosinophil count. The incidence of adverse events was similar in all four trial groups.Interleukin-33 blockade with itepekimab led to a lower incidence of events indicating a loss of asthma control than placebo and improved lung function in patients with moderate-to-severe asthma. (Funded by Sanofi and Regeneron Pharmaceuticals; ClinicalTrials.gov number, NCT03387852.).

Tumours use various strategies to evade immune surveillance1,2. Immunotherapies targeting tumour immune evasion such as immune checkpoint blockade have shown considerable efficacy on multiple cancers3,4 but are ineffective for most patients due to primary or acquired resistance5–7. Recent studies showed that some epigenetic regulators suppress anti-tumour immunity2,8–12, suggesting that epigenetic therapies could boost anti-tumour immune responses and overcome resistance to current immunotherapies. Here we show that, in mouse melanoma models, depletion of KDM5B—an H3K4 demethylase that is critical for melanoma maintenance and drug resistance13–15—induces robust adaptive immune responses and enhances responses to immune checkpoint blockade. Mechanistically, KDM5B recruits the H3K9 methyltransferase SETDB1 to repress endogenous retroelements such as MMVL30 in a demethylase-independent manner. Derepression of these retroelements activates cytosolic RNA-sensing and DNA-sensing pathways and the subsequent type-I interferon response, leading to tumour rejection and induction of immune memory. Our results demonstrate that KDM5B suppresses anti-tumour immunity by epigenetic silencing of retroelements. We therefore reveal roles of KDM5B in heterochromatin regulation and immune evasion in melanoma, opening new paths for the development of KDM5B-targeting and SETDB1-targeting therapies to enhance tumour immunogenicity and overcome immunotherapy resistance. KDM5B recruits SETDB1 to repress endogenous retroelements such as MMVL30, suppressing anti-tumour immunity, and the depletion of KDM5B induces a robust adaptive immune response and enhances the response to immune checkpoint blockade.

With the increasing use of magnetic resonance imaging in the assessment of acute intracerebral hemorrhage, diffusion-weighted imaging hyperintense lesions have been recognized to occur at sites remote to the hematoma in up to 40% of patients. We investigated whether blood pressure reduction was associated with diffusion-weighted imaging hyperintense lesions in acute intracerebral hemorrhage and whether such lesions are associated with worse clinical outcomes by analyzing imaging data from a randomized trial. We performed exploratory subgroup analyses in an open-label randomized trial that investigated acute blood pressure lowering in 1000 patients with intracerebral hemorrhage between May 2011 and September 2015. Eligible participants were assigned to an intensive systolic blood pressure target of 110–139 mm Hg versus 140–179 mm Hg with the use of intravenous nicardipine. Of these, 171 patients had requisite magnetic resonance imaging sequences for inclusion in these subgroup analyses. The primary outcome was the presence of diffusion-weighted imaging hyperintense lesions. Secondary outcomes included death or disability and serious adverse event at 90 days. Diffusion-weighted imaging hyperintense lesions were present in 25% of patients (mean age 62 years). Hematoma volume > 30 cm3 was an adjusted predictor (adjusted relative risk 2.41, 95% confidence interval 1.00–5.80) of lesion presence. Lesions occurred in 25% of intensively treated patients and 24% of standard treatment patients (relative risk 1.01, 95% confidence interval 0.71–1.43, p = 0.97). Patients with diffusion-weighted imaging hyperintense lesions had similar frequencies of death or disability at 90 days, compared with patients without lesions. Randomized assignment to intensive acute blood pressure lowering did not result in a greater frequency of diffusion-weighted imaging hyperintense lesion. Alternative mechanisms of diffusion-weighted imaging hyperintense lesion formation other than hemodynamic fluctuations need to be explored. Clinical trial registration ClinicalTrials.gov (Ref. NCT01176565; https://clinicaltrials.gov/ct2/show/NCT01176565 ).

Visual analysis is the primary method used to interpret single-case experimental design (SCED) data in applied behavior analysis. Research shows that agreement between visual analysts can be suboptimal at times. To address the inconsistent interpretations of SCED data, recent structured visual analysis technological advancements have been developed. To assess the extent to which structured visual analysis is used to guide or supplement applied behavior analyst’s interpretation of SCED graphs, a systematic review between the years of 2015 to 2020 in the Journal of Applied Behavior Analysis was conducted. Findings showed that despite recent efforts to develop structured visual analysis tools and criteria, these methods are rarely used to analyze SCED data. Here, an overview of structured visual analysis tools is shared, their utility is delineated, common characteristics are brought to light, and future directions for both their research and clinical use are highlighted.

There is myriad of strategies that can be employed in the classroom. One of these is the Cooperative Learning. Because cooperative learning is a common strategy, it will just be used in different topics without considering its effectiveness in a particular topic. Thus, little attention is given to test how effective this strategy is. This study endeavored to assess if cooperative learning can make the discussion of pie chart an engaging one. The study used Quasi-Experimental research design in fulfilling its objectives. The respondents are grade 6 learners studying at Langin Elementary School in Ronda, Cebu, Philippines. There are 30 respondents in total in both control (15) and experimental (15). The experimental group garnered the mean of 11.47 and the control group mean with 9 in the pretest. While in the posttest, the experimental group garnered 19.33 and the control group landed on 17.60. With the 0.05 significance level, the results between the pretest and posttest of the two groups were found to be significant (p-value= 0.00). This is a realization that strategies can possibly constitute a significant difference. In this study, both the traditional way of teaching the topic and the one that is being introduced marked significantly. Thus, it is recommended to have this strategy tested in different topics in Mathematics and other subjects wherein the findings of this study can be verified.

The lived experiences of the freshmen students be continue to ignored and not been heard by most institutions in the Philippines. This problem motivated the researcher to conduct the study to give a voice to those freshmen students who experience the phenomenon in their fresh start in college. This study utilized the Ryan & Deci’s Self-determination theory. Further, Heideggerian phenomenological design, and Interpretative Phenomenological Analysis popularized by Moustakas modified by Van Kaam with a 7-step analysis. To avoid researchers' bias, the researchers conducted bracketing and used purposive sampling technique before collecting the data. Utilizing a semi-structured instrument, the gather was done via online interviews with ten (10) participants from the Moalboal Campus of Cebu Technological University during the academic year 2021-2022. Based from the data analysis, themes that follows are derived: (1) Exciting Experiences, (2) Downside, (3) Support System, and (4) Adaptation. It is recommended that freshmen should undergo saturation through series of webinars or google meet ups to critically meet the desired information regarding the growing phenomenology around freshmen students.

Functional analyses are often conducted by behavior analysts to understand the environmental variables contributing to an individual’s problem behavior to better inform treatment implementation. While functional analyses are integral for designing function-based interventions, they often arrange contingencies to evoke and reinforce dangerous problem behavior. In Study 1 we reviewed 22 functional analyses with open-contingency classes including non-dangerous topographies of problem behavior and we found that participants were more likely to exhibit the non-dangerous behavior in 82% of the applications. We then conducted a single-subject comparison of closed and open-contingency classes with four additional participants in Study 2. Our results suggest that the functional analyses with the open-contingency class reduced the likelihood of observing dangerous problem behavior.