Standard behavioral weight loss interventions often set uniform physical activity (PA) goals and promote PA self-monitoring; however, adherence remains a challenge, and recommendations may not accommodate all individuals. Identifying patterns of PA goal attainment and self-monitoring behavior will offer a deeper understanding of how individuals adhere to different types of commonly prescribed PA recommendations  and guide future recommendations for improved intervention effectiveness.This study examined weekly patterns of adherence to step-based and minute-based PA goals and self-monitoring behavior during a 6-month online behavioral weight loss intervention.Participants were prescribed weekly PA goals for steps  and minutes of MVPA (50-200 minutes/week) as part of a lifestyle program. Goals gradually increased during the initial 2 months, followed by 4 months of fixed goals. PA was self-reported daily on the study website. For each week, participants were categorized as adherent if they self-monitored their PA and met the program PA goal, suboptimally adherent if they self-monitored but did not meet the program goal, or nonadherent if they did not self-monitor. The probability of transitioning into a less adherent status was examined using multinomial logistic regression.Participants (N=212) were predominantly middle-aged females with obesity, and 67 (31.6%) self-identified as a racial/ethnic minority. Initially, 73 (34.4%) participants were categorized as adherent to step-based goals, with 110 [51.9%] suboptimally adherent and 29 [13.7%] nonadherent, and there was a high probability of either remaining suboptimally adherent from week to week or transitioning to a nonadherent status. However, 149 (70.3%) participants started out adherent to minute-based goals , with suboptimally adherent seen as the most variable status. During the graded goal phase, participants were more likely to transition to a less adherent status for minute-based goals  compared to step-based goals ; however, no differences were seen during the fixed goal phase .States of vulnerability to poor PA adherence can emerge rapidly and early in obesity treatment. There is a window of opportunity within the initial 2 months to bring more people toward adherent behavior, especially those who fail to meet the prescribed goals but engage in self-monitoring. Although this study describes the probability of adhering to step- and minute-based targets, it will be prudent to determine how individual characteristics and contextual states relate to these behavioral patterns, which can inform how best to adapt interventions.ClinicalTrials.gov NCT02688621; https://clinicaltrials.gov/ct2/show/NCT02688621 Adherence to physical activity (PA) is a pervasive challenge in behavioral weight control programs. Many individuals fail to achieve program recommendations and adopt a physically active lifestyle ,2. As a Ordinarily, all individuals receive the same programmatic goals, which gradually progress to targeted PA levels -7. RecomSelf-monitoring, a key element of lifestyle programs intended to promote behavioral awareness and fulfillment of recommendations ,13, servOthers have examined transitions in levels of adherence to dietary self-monitoring and found that individuals who partially self-monitor in 1 week have a greater chance of improving to full self-monitoring during the first 2 months of treatment, whereas after the first 2 months, partial self-monitoring in 1 week foreshadows discontinuation of self-monitoring . Using aExamination of weekly adherence to the different types of PA goals offers insight into goal operationalization, progression, and timing, since lifestyle programs tend to prescribe goals on a weekly basis. Therefore, this study aims to describe weekly patterns of adherence to (1) step-based goals and self-monitoring steps and (2) minute-based goals and self-monitoring minutes of MVPA, as well as examine whether weekly transitional patterns differ between step-based goals versus minute-based goals, across 6 months of an online, group-based behavioral weight control program.2; were at least 18 years of age with access to a smartphone, computer, and the internet; had no medical contraindications to moderate-intensity PA ; and demonstrated the capacity to monitor their PA using their smartphone or personal fitness tracker prior to randomization. The study was approved by the institutional review boards at both clinical sites, and written informed consent was obtained from all participants. The investigation included only the control group (N=212) to avoid the potential of financial incentives obscuring PA adherence patterns  that evaluated the impact of financial incentives on weight loss in a group-based behavioral weight control program delivered online . Brieflyerns see .All participants received a goal-oriented behavioral weight control program delivered online, which has been shown effective in previous studies ,19. WeekParticipants were instructed to use their personal fitness tracker or a smartphone app to track their total steps and minutes of planned exercise of at least a moderate-to-vigorous intensity and then record both their total steps and minutes of MVPA on the study website daily. In other words, participants were asked to report both metrics for each day of the study period, as opposed to reporting only 1 metric, even if they did not perform any PA on that day. Self-monitoring records were reviewed by the facilitator, who provided tailored feedback via email on a weekly basis with positive reinforcement of healthy lifestyle choices, constructive guidance promoting potential areas for change, and reminders of the program recommendations.The total number of steps and minutes of MVPA both were self-reported by participants daily on the study website. Weekly totals for steps and for minutes of MVPA were calculated by summing the daily reported values, with each week beginning on the day of the scheduled group session.Adherence to the program step goals (yes/no) and the MVPA minute goal (yes/no) was separately determined for each participant and for each week of the program based on the proportion of the program goal achieved. For example, a participant could be categorized as nonadherent to the step goal and adherent to the MVPA goal. For steps, the average daily step count for a given week was divided by that week’s program step goal and multiplied by 100%. For minutes of MVPA, the total minutes reported in a given week were divided by the program MVPA goal and multiplied by 100%. Proportions of ≥100% indicated that the corresponding goal was met (yes), and proportions of <100% indicated that the goal was unmet (no). A value of 0 was assumed for missing and implausible entries, including daily step counts of <1000 or >30,000 ,22 and >Adherence to self-monitoring of steps (yes/no) and minutes of MVPA (yes/no) was based on whether an entry was submitted and calculated separately for each type of PA goal . For steps, a participant was considered to have self-monitored (yes) in a given week if ≥1 record of any step count was submitted, including a value of 0. Likewise, a participant was considered to have self-monitored minutes of MVPA (yes) for a given week if ≥1 record of any number of minutes, including 0, was submitted. If no entry was submitted for the corresponding PA goal on any of the 7 days, the participant was considered nonadherent to self-monitoring (no) for that week. The approach described here is consistent with previous work, which categorized a participant as adherent if ≥1 record of any value of exercise minutes was submitted for a given week and nonadherent if no records were submitted .adherence to PA goal and adherence to PA self-monitoring were used to categorize participants into 3 mutually exclusive categories each week for step-based goals and separately for minute-based goals. Participants were categorized as (1) adherent if they met the goal and self-monitored, (2) suboptimally adherent if they did not meet the goal but did self-monitor, and (3) nonadherent if they did not self-monitor  [The variables -monitor . It was nactive) , which anactive) . CategorDescriptive analyses were conducted to characterize the sample and determine frequencies for the number of participants meeting PA goals and self-monitoring their PA each week. Marginal proportions of weekly PA adherence categories were separately tabulated for each type of PA recommendation (steps and minutes of MVPA) beginning at week 3 and continuing through the end of the 6-month period. The weekly transition probabilities of adherence status were then independently summarized for step- and minute-based goals using separate models for the graded PA goal phase (weeks 3-8), fixed PA goal phase (weeks 9-24), and across all time points (weeks 3-24). Models were conditioned on the probability of maintaining the same adherence status from the preceding week or transitioning to another status within each type of goal prescription.P<.05.The likelihood of having an adherent, suboptimally adherent, or nonadherent status over time was examined for step- and minute-based goals, separately, using multinomial logistic regression for correlated data. The odds of having a less adherent status were modeled for each type of PA recommendation during the graded PA goal phase, fixed PA goal phase, and across all time points. Comparisons were then made between models for step- versus minute-based goals on the odds of transitioning into a less adherent status. All analyses were performed using SAS 9.4 , and the level of statistical significance was set at 2. The majority  were female, and approximately one-third  self-identified as a racial/ethnic minority. Most participants had at least a college degree  and were employed full-time . Retention was 81.1% (n=172) at the 6-month assessment visit.All participants randomized to the control group (N=212) in the larger RCT  were incOn average, of the 212 participants, 144 (67.7%) self-monitored their steps on ≥1 day/week during the 6-month period and 27 (12.4%) met the prescribed steps goal each week. Approximately one-third  of the participants started out adherent to the 7000-daily-step goal in week 3 . Rates dComparable to daily steps, 143 (67.4%) participants self-monitored their total minutes of MVPA on ≥1 day per week over the 6-month period ; howeverThe weekly transitional probabilities of adherence to prescribed PA goals and PA self-monitoring across successive weeks of the behavioral weight control program are summarized for steps and minutes of MVPA in During the initial 8 weeks, as the goals progressed from 7000 to 10,000 daily steps, the probability that a participant would remain adherent was 29%, while the probability of transitioning from adherent to suboptimally adherent was 67% , as well as for minute-based goals .Analyses examining adherence status over time indicated that participants were significantly more likely to be in a less adherent category relative to adherent as the program progressed . Thus, pFor steps, participants were 1.24 times more likely to be less adherent, relative to being adherent, each week during the graded goal phase, 1.07 times more likely to shift to a less adherent status during the fixed goal phase, and 1.09 times more likely to be in a less adherent category each week across the 6-month period. For minutes of MVPA, participants were 1.39 and 1.06 times more likely to be in a less adherent category each week during the graded and fixed goal phases, respectively, and 1.11 times more likely to shift to a less adherent category each week over the entire 6 months.P=.004). In other words, participants were more likely to become less adherent from week to week with respect to minute-based goals compared to step-based goals during weeks 3-8. No significant difference was seen in the propensity to be adherent between step- and minute-based goals during the fixed goal phase (P=.65). Although a trend was noted between models for steps and minutes of MVPA in the odds of being in a less adherent category when examining the full 6-month period (P=.07), the difference was not statistically significant.When steps and minutes of MVPA were compared during the graded PA goal phase, participants were significantly more likely to regress to a less adherent category the following week when examining minutes of MVPA relative to considering steps (To the best of our knowledge, this study is the first to describe the stability of adherence to weekly self-monitoring and attainment of PA goals prescribed in terms of daily steps and weekly minutes of MVPA during an online behavioral weight control program. Few participants met the initial step-based goals and subsequently either remained in a nonadherent or a suboptimally adherent status from one week to the next or transitioned from a suboptimally adherent to a nonadherent status over time. Conversely, most participants started out adherent to the minute-based goals but demonstrated greater variability between adherence statuses from week to week than was seen for step-based goals. Thus, participants with overweight and obesity enrolled in a behavioral weight control program were unlikely to achieve even the lowest step-based goals or to catch up with the goals as the step target progressively increased but had a greater chance of meeting the minute-based goals, particularly early in treatment.The weekly transitional probabilities identified in this study underscore the initial 2 months of a lifestyle program as a formative period that contributes to an individual’s chances of future PA adherence. Participants who met the earliest recommendations were most likely to be adherent at 6 months relative to those who started out suboptimally adherent or nonadherent. Intriguingly, the likelihood of long-term adherence increased 2-fold if a participant remained adherent through the graded goal phase. Our findings substantiate previous studies that demonstrate that the first 2 months of program initiation serve as a critical juncture associated with better long-term program adherence, weight loss, and health-related outcomes ,27-30. FFew participants achieved stability in adherent behavior, which is of concern. Indeed, nonadherence was the most consistent status and was increasingly more likely over time, regardless of the type of PA goal. Some adults with overweight may prefer monitoring minute-based activity rather than step counts ; howeverSuboptimally adherent behavior appeared to be the most vulnerable to transitions, particularly with respect to minute-based goals. It is striking that participants had the best chances of shifting from suboptimally adherent to fully adherent behavior during the graded goal phase, yet the likelihood of becoming nonadherent outweighed becoming adherent after 2 months. A similar pattern with weekly dietary self-monitoring was previously reported where individuals who demonstrated suboptimal adherence to dietary self-monitoring had the greatest potential for transitioning to adherent behavior during the first 2 months of a lifestyle program but not after that time . It is pTo capitalize on the early weeks of program initiation and move more individuals toward adherent behavior, reevaluating how PA recommendations are structured for behavioral weight control is warranted. It is apparent that providing everyone with the same incremental, linear progression of PA goals does not accommodate the dynamic process of lifestyle change for each individual. From a clinical perspective, it is imperative to appreciate that the continuation of conventional treatment likely will not help vulnerable subgroups transition to adherent behavior. Instead, it may be important to provide tailored goals that adapt based on the individual’s recent PA, thus providing more realistic, attainable PA targets ,41-43.Although this study took the formative step of describing behavioral patterns, more work is needed to identify precisely how best to adapt treatment to capitalize on these patterns and enhance outcomes. There are likely other factors, such as cognitive, affective, and motivational components, influencing whether individuals are adherent to PA, and these should be explored to guide treatment tailoring -48. For This research advances our understanding of the effects of different types of PA goals commonly prescribed in behavioral weight control interventions on goal attainment combined with self-monitoring among a large sample of adults with overweight and obesity. However, findings should be considered with the following limitations in mind. First, participants were predominantly women with obesity, and results may not generalize to other populations. Next, the influence of exercise history or the level of activity when entering the study on adherence patterns could not be determined. If program goal attainment differs between individuals who are inactive at study entry compared to those who are already engaging in some PA at baseline, recommendations may be tailored based on baseline activity levels. Although the goals offered in the program are similar to those provided by other behavioral weight control programs ,7, patteThis study begins to identify key transition points in the behavior change process as it relates to PA adherence for step- and minute-based goals in a behavioral weight loss program and provides a useful framework for detecting responsiveness to program recommendations. Moreover, it may assist in shaping more effective PA recommendations in lifestyle programs, particularly during the early period of program initiation. The initial 2 months provide a window of opportunity to assist people in transitioning to adherent behavior, especially those who fail to meet the PA goals but engage in self-monitoring. As a result, researchers and clinicians should consider PA self-monitoring and goal attainment concurrently as an indication of an individual’s adherence status. Emphasis should be placed on strategies that help people start and reach the 2-month mark with consistent self-monitoring and attainment of PA recommendations, since this appears to be a formative period for continued adherence. Future research should investigate how these transitional patterns in PA adherence status are influenced by individual characteristics and contextual factors, as well as how they relate to weight loss and other health-related outcomes, to inform optimization of treatment recommendations.


In sub-Saharan Africa, the efficacy of intermittent preventive therapy in pregnancy with sulphadoxine-pyrimethamine (IPTp-SP) for malaria in pregnancy is threatened by parasite resistance. We conducted an individual-participant data (IPD) meta-analysis to assess the efficacy of intermittent screening with malaria rapid diagnostic tests (RDTs) and treatment of RDT-positive women with artemisinin-based combination therapy (ISTp-ACT) compared to IPTp-SP, and understand the importance of subpatent infections.Plasmodium falciparum at delivery. The effects of subpatent  infections were assessed in both arms pooled using multi-variable fixed-effect models adjusting for the number of patent infections. PROSPERO registration: CRD42016043789.We searched MEDLINE and the Malaria-in-Pregnancy Library on May 6, 2021 for trials comparing ISTp-ACT and IPTp-SP. Generalised linear regression was used to compare adverse pregnancy outcomes , or preterm delivery) and peripheral or placental dhfr/dhps quintuple mutant parasites are saturated, but sextuple mutants are still rare , and three from low-resistance areas (West-Africa). Four trials contributed IPD data . At delivery, the prevalence of any malaria infection  and patent infection  were similar. Subpatent infections were more common in ISTp recipients . There was no difference in adverse pregnancy outcome . Subpatent infections were associated with LBW , lower mean birthweight , and preterm delivery .Five trials conducted between 2007 and 2014 contributed , two from high SP-resistance areas where ISTp-ACT was not superior to IPTp-SP and may result in more subpatent infections than the existing IPTp-SP policy. Subpatent infections were associated with increased LBW and preterm delivery. More sensitive diagnostic tests are needed to detect and treat low-grade infections.Centers for Disease Control and Prevention and Worldwide Antimalarial Resistance Network. The final search was conducted May 6, 2021. ISTp with artemisinin-based combination therapy was associated with a higher relative risk of malaria during pregnancy or at delivery and a non-significant increase in the risk of low birth weight. Modelling also suggested that screening with RDTs was less effective than IPTp-SP in the 2This pooled analysis of five trials provides further evidence that ISTp with the current generation of rapid diagnostic tests (RDTs) is not superior to the existing strategy of IPTp with SP, regardless of the level of SP resistance. In addition, this is the largest individual patient data (IPD) meta-analysis of the impact of low-density infections below the level of detection by RDTs on clinically relevant pregnancy outcomes. The study provides evidence that these subpatent infections are potentially harmful and associated with poor birth outcomes, providing a possible explanation for the inferior efficacy of the ISTp strategies that rely on the current generation of RDTs.This study suggests that ISTp with the current generation of RDTs is not a suitable alternative to IPTp-SP even in high SP resistance areas where the dihydrofolate reductase/dihydropteroate synthase (dhfr/dhps) quintuple mutant parasites are saturated or have reached near saturation, but where the sextuple mutants are still rare, as is the case in most of East and southern Africa. Scale up of IPTp with SP in these areas should continue while simultaneously pursuing further research on alternative strategies, including assessing the use of more sensitive diagnostic tests to detect and treat more low-grade infections, either as ISTp or as an adjunct to IPTp-SP.Alt-text: Unlabelled box1Approximately 11.6 million pregnancies in sub-Saharan Africa were exposed to malaria in 2019 One approach would be to use an alternative drug; however, poor tolerability undermines the effectiveness of amodiaquine, alone or combined with SP Another potential approach is to screen women with a rapid diagnostic test (RDT) at each scheduled antenatal care (ANC) visit and treat test-positive women with an effective drug. This approach is known as intermittent screening and treatment in pregnancy (ISTp). In two trials in West Africa, ISTp was non-inferior to IPTp-SP in reducing low birth weight (LBW) in areas with good parasite sensitivity to SP ,15. It wWe carried out a systematic review and meta-analysis of individual-participant data (IPD) to comprehensively evaluate the potential utility of ISTp with a conventional RDT and an artemisinin combination therapy (ISTp-ACT) and define factors that determine the efficacy of ISTp-ACT relative to IPTp-SP in different settings. We also examined the effect of subpatent malaria infections missed by rapid diagnostic tests but detected by nucleic acid amplification tests like polymerase chain reaction (PCR) on adverse pregnancy outcomes in these trials.22.1An electronic literature search, using the search terms: ((intermittent AND screening) AND malaria) AND pregnan* AND Clinical Trial[ptyp] AND Humans[Mesh]) was conducted on August 8, 2016, and updated on May 6, 2021, following PRISMA guidelines 2.2a priori defined statistical analysis plan. Reviewers were unblinded to the authors of the source study. Two reviewers (JRG and CK) independently assessed the risk of bias for the included trials using the Cochrane risk-of-bias tool for randomised trials version 2 (RoB2) Two independent reviewers (JRG and MM or CK) screened titles, abstracts, and full texts of all citations. For eligible studies, authors were contacted to request de-identified individual-level data. Three attempts were made to contact authors. Data were analysed using STATA/MP2 16.0 (StataCorp LP), according to an 2.3Plasmodium infection detected in peripheral or placental blood by PCR, microscopy, RDT, or histopathology (acute and/or chronic infection) and 2) adverse live-birth, defined as the composite of LBW (<2500 grams), small-for-gestational-age  The co-primary outcomes for the comparison of the effect of ISTp-ACT vs IPTp-SP were 1) maternal malaria infection at delivery, defined as any Secondary outcome definitions are provided in Supplement 3, page 2. The analyses of the impact of ISTp-ACT versus IPTp-SP during pregnancy excluded enrolment and delivery time points from incidence data. Analysis of the impact of patent and subpatent  infection on adverse pregnancy outcomes included enrolment and delivery time points.2.42.4.1Log-binomial generalised linear regression models were used to obtain risk ratios (RR) and 95% confidence intervals (CI). When convergence was not achieved, we followed suggestions from Cummings.a priori as covariates in all unadjusted models because the randomisation was stratified by study site in all IPD studies and by gravidity in Malawi I2 statistic Plasmodium falciparum dihydropteroate synthase (Pfdhps) K540E mutation) and high (>90% PfdhpsK540E) resistance The primary analyses of the primary and secondary outcomes used two-stage IPD meta-analysis. Because the number of studies was small, fixed-effect models were used ,26. BecaSupportive secondary analyses using covariate adjusted and subgroup analyses were performed using the 2-stage model. Potential effect modifiers and confounding variables were pre-specified. In addition to the stratification factors study site and gravidity, these included the baseline factors maternal haemoglobin concentration, bed net use, and gestational age. Maternal socioeconomic status, maternal education, and malaria status at enrolment were excluded because they were missing in a large proportion of participants in at least one of the studies.Further sensitivity analyses to assess the robustness of the primary analysis were conducted using 1-stage models, with site and gravidity included as covariates, and random-effect models.2.4.2The effect of exposure to subpatent malaria on pregnancy outcomes was examined using fixed-effect models with robust Poisson regression for binary outcomes and linear regression for continuous outcomes, accounting for study and the total number of malaria tests conducted, including the number of patent infections detected. In the binary models, risk ratios (RR) correspond to the change in the risk of the adverse outcome associated with one additional positive test  during pregnancy. In models with continuous outcomes, the mean difference in the outcome measure associated with each additional patent or subpatent infection was estimated. Both types of models included a robust estimator of variance. Crude models included study arm and the number of patent and subpatent infections as the two exposure variables of interest. Adjusted models  also included gestational age at enrolment, maternal age, gravidity (paucigravidae [G1-G2]/multigravidae), and the number of sick visits . A sensitivity analysis was conducted to determine if the method used to assess gestational age influenced the conclusions for outcomes requiring gestational age at delivery  .Details of the performance of the RDTs to detect PCR-positive infections have been described previously 2.5The five original studies were approved by the relevant local and international partner ethical committees and institutional review boards. The protocol for the meta-analysis was reviewed by the US Centers for Disease Control and Prevention (CDC) Human Research Protection Office and deemed exempt from further review. Written consent was required from each patient for participation in each individual study.2.6WWARN had no role in study design, data collection, data analysis, data interpretation, or writing of the report. CDC staff were involved in study design, data collection, data analysis, data interpretation, and writing of the report. The corresponding author had full access to all the data in the study and had final responsibility for the decision to submit for publication.33.1PfdhpsK540E and >10% PfdhpsA581G A total of 141 studies were reviewed , and a 40% increased risk of patent infection , but not subpatent infection . At delivery, women in the ISTp arm had an 18% increased risk of any peripheral-blood malaria infection , reflecting 31% more subpatent infections , but not more patent infections  , maternal anaemia (haemoglobin <11 g/dL [p=0.97] and <9 g/dL [p=0.14])  . There wp=0.14]) , or mean3.3.22=7.5%), but the mean birthweight was 28g lower in IST recipients . None of the other neonatal outcomes were significantly different between arms , and 1,632 (22.4%) had at least one subpatent infection. About three-quarters (74.7%) of the 1,632 women with subpatent infections did not have evidence of any patent infection during pregnancy or delivery. Similarly, 29.8% of the 2,352 women with patent infections did not have additional subpatent infections identified.Data on patent and subpatent infection were available from three of the five trials ,15,18. OEach patent infection during pregnancy was associated with an 11% increase in the risk of the composite adverse pregnancy outcome . A smaller, non-significant increase was seen with subpatent infections  . Each pa4This meta-analysis of five trials confirmed that ISTp with ACTs was not superior to the current IPTp-SP strategy in the situations where it was tested. These included areas in West Africa where the prevalence of SP resistance was low and in Kenya and Malawi where it was high. Babies born to mothers in the ISTp arm weighed slightly less than those in the IPTp-SP, though the risk of LBW was not significantly different. Women randomised to ISTp had a 21% increased risk of clinical malaria during pregnancy and an 18% increased risk of peripheral blood malaria infection at delivery, reflecting 31% more subpatent infections. There was no difference in the prevalence of placental malaria or anaemia between the two study arms. Further analysis to assess the impact of subpatent infections on newborn outcomes, while controlling for the effect of patent infections, showed that each antenatal subpatent infection was associated with a 26 gram decrease in mean birth weight and a 13% increased risk of LBW. This association with birthweight reflected an increased risk of preterm delivery rather than fetal growth retardation. Overall, these results suggest ISTp with the current generation of RDTs is not a suitable alternative to the existing IPTp-SP strategy, even in areas with high SP resistance in East and southern Africa. Our observation that subpatent infections are associated with an increased risk of LBW suggests that, compared with conventional RDT use for ISTp, the detection and treatment of more low-density infections with more sensitive diagnostic point-of-care tests may enhance birth outcomes. Further, the high proportion of women with evidence of malaria at delivery, including those in the IPTp-SP arm, highlights that better adherence to ITN usage and improved strategies to prevent malaria in pregnancy remain urgently needed to address the serious adverse effects of malaria in pregnancy on the developing fetus, newborn and infant development ,33.One reason for the modest efficacy of ISTp compared to IPTp-SP likely reflects a three- to six-fold difference  between the study arms in the duration of pregnancy spent under prophylaxis. Approximately one-quarter of women in the ISTp arms (26.4%) had at least one patent infection detected by RDTs during pregnancy. This proportion is a function of both malaria transmission intensity and the sensitivity of the diagnostic test, which is affected by parasite density and immunity. In the ISTp arm, only RDT-positive women received treatment and benefitted from the post-treatment prophylactic effect of the long-acting component of the ACT, estimated to be about two weeks with a 3-day treatment dose of artemether-lumefantrine and four weeks with dihydroartemisinin-piperaquine dhfr/dhps mutant haplotype that includes the dhps-A581G substitution The failure of ISTp to show incremental effectiveness compared to IPTp-SP is consistent with a recent mathematical model based on these trials The observed difference in birthweight may also reflect a non-malaria effect of SP A limitation of this study is that the effect of subpatent infection on birth outcome could only be adjusted for the number of patent infections, but not for their parasite density or duration. Furthermore, women were enrolled in the second or third trimester. Many women are already infected by their first antenatal visit, including from carriage of infections acquired prior to conception. Malaria infection early in pregnancy is associated with dysregulation of essential regulators of angiogenesis, metabolism, and inflammation resulting in placental insufficiency and an increased risk of maternal anaemia later in pregnancy, preterm birth, fetal growth restriction As described in the primary study reports, ISTp was well tolerated. Although requiring more steps and more time, ISTp was also generally well received by providers and pregnant women . Most wo32it is also critical to further explore IPT with more effective antimalarials such as dihydroartemisinin-piperaquine.This analysis of data from five trials found no evidence that ISTp with the current generation of RDTs improves maternal or neonatal outcomes compared to the current strategy IPTp with SP, and should not replace IPTp-SP even in areas with a high prevalence of parasites with the SP-resistant quintuple mutation. Further studies should be considered with highly sensitive diagnostic tests, as ISTp or as part of hybrid strategies that combine screening and treatment with IPTp-SP in high SP resistance areas. It remains possible that ISTp, ideally starting as early in pregnancy as possible, would perform more favourably in settings with a higher prevalence of the sextuple mutant resistant parasites or could be a potential strategy where the risk of malaria in pregnancy is low but its consequences still severe All authors declare no competing interests.


This cross-sectional study evaluates the association of a cap on monthly out-of-pocket spending on high-cost drugs with use of these drugs and out-of-pocket spending in California in 2015 and 2016. High prescription drug costs are a substantial problem for many patients who cannot afford their medications, even with health insurance. Capping monthly out-of-pocket (OOP) costs for high-cost drugs may increase the affordability of these medications. In January 2016, Covered California implemented a monthly cap on OOP costs for high-cost drugs to increase patient access. We evaluated the association of this cap with high-cost drug use and OOP spending.STROBE) reporting guideline.This cross-sectional study used pharmacy claims data from private insurers offering coverage in Covered California  from 2015 to 2016. These data represent 9 of the 11 participating insurers, covering 91% (2016) to 93% (2015) of enrollees with drug coverage. We defined cap-eligible drugs as those with a proxy price (imputed price for insurers not reporting cost information) greater than the 30-day supply threshold cost for each metal tier in 2015 or 2016 . Results are stratified by metal tier, which is the marketplace indication of plan generosity, with Bronze being the least generous and Platinum being the most generous. Metal tiers have different cost-sharing caps, and sicker patients may enroll in metal tiers with more generous coverage. Data were analyzed using Microsoft Excel and Access. Analyses were performed from May 1, 2019, through June 30, 2020.The number of patients who filled at least 1 cap-eligible drug increased from 2015 to 2016, with 1442 and 1927 Silver enrollees filling a cap-eligible drug in 2015 and 2016, respectively. We found no change in the total days supplied for patients in Bronze plans but small increases in the mean days supplied for the other metal tiers .Fewer patients reached the maximum OOP spending in each month in 2016 than in 2015 . Of the The findings of this cross-sectional study suggest that Covered California’s drug cap policy was associated with modest changes in high-cost drug use and adherence and with making expenses more consistent throughout the year. Although these results were found for Silver, Gold, and Platinum plans, they were not found for Bronze plans. Fewer enrollees reached the annual maximum OOP spending after implementation of the policy.This study has limitations. This was a descriptive study; more detailed statistical analyses will be needed to establish causation. The proxy costs used to identify cap-eligible drugs are estimates and may not reflect actual spending. Similar to proxy costs, plan sponsors varied in the extent they reported cost-sharing amounts, although not over time. Thus, our results likely represent an undercount of the number of patients reaching the annual maximum OOP spending.1 which have slightly lowered OOP costs for patients.2 Other states have implemented or are considering similar policies for other drugs,4 such as insulin.6 Our findings suggest that cost-sharing caps for high-cost drugs may be associated with increased adherence and increased consistency of OOP spending for patients.Caps on prescription drug OOP spending are relatively new. Most states that have enacted caps have focused on chemotherapy medications,


No differences were observed in relation to tumor type, grade and stage. BCa neovasculature-related PSMA overexpression may be useful in defining the degree of extension of the neoplasm. In addition, testing PSMA expression by immunohistochemistry may hold theranostic implications both considering anti-angiogenesis agents and radio-labelled PSMA ligands for intracavitary radionuclide therapy. In our opinion, BCa neovasculature-related PSMA overexpression may be considered an apt target for anti-angiogenesis and radionuclide treatment in BCa, once the evaluation of tumor-retention time for the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment will be performed.Bladder cancer (BCa) patients are diagnosed by cytology and cystoscopy. However, these diagnostic tests bear some limitations. We sought for reliable biomarkers to better determine BCa extension. Prostate-specific membrane antigen (PSMA) appears to fulfill this requirement in prostate cancer but its role in BCa has not been established yet. We then analyzed 87 bladder tissue samples from 74 patients assessing PSMA expression by immunohistochemistry. The median PSMA expression, exclusively found in tumor neovasculature, in terms of H-score significantly differed between non-tumor samples and tumor samples ( Despite urothelial BCa has been reported to be 3 times more common in men, many studies conclude that women have poorer prognosis2.Bladder cancer (BCa) is the 10th most common form of cancer worldwide, with 549,000 new cases estimated and 200,000 deaths2.The excess risk in men has been hypothesized to be driven by higher exposure to carcinogens , whereas the reasons for poorer survival in women is not clear3. Cytology and cystoscopy are the conventionally used techniques for BCa diagnosis and monitoring but these have some limitations. The former has low sensitivity for low grade and low stage tumors, the latter has high specificity but it is invasive, therefore new diagnostic biomarkers would be desirable.The most common type of BCa is urothelial carcinoma, and approximately 75% of cases are non–muscle invasive (NMIBC) at diagnosis. Generally, NMIBC has a favorable prognosis and is diagnosed and treated with trans-urethral endoscopic resection, followed by intravesical therapy if the risk of recurrence of NMIBC or progression to muscle-invasive bladder cancer (MIBC) is high4. The presence of nodal metastases, found in 20% to 25% of patients at the time of RC, is an important indicator for poor outcome along with pathologic tumor stage5. However, up to 37% of patients with locally-advanced BCa and absent nodal involvement (i.e. T stage > pT2 and pN0) develop distant metastases6. Thus, biological markers able to predict prognosis in this subset are still needed.MIBC is found in about 25% of patients at the time of diagnosis, and these are conventionally treated by means of radical cystectomy (RC) and lymph node dissection9. It is known that PSMA plays a functional role in prostate cancer progression10, but its role in BCa progression is not well established yet.Prostate-specific membrane antigen (PSMA) is a non-soluble type 2 integral membrane protein with carboxypeptidase activity, expressed on the apical surface of endothelial cells. The expression of this antigen is not fully prostate-specific as it is also expressed in tumor-associated neovasculature of several solid malignancies12. For human the most frequent used PET imaging PSMA ligand is the low-weight urea-based PSMA inhibitor Glu-NH-CO–NH-Lys(Ahx)-HBED-CC labelled with 68Gallium (68 Ga-PSMA-11). Like the PSMA monoclonal antibody used for immunostaining in our study (i.e. SP29), 68 Ga-PSMA-11 binds to a C-terminal epitope of the large extra-membrane domain of PSMA. How much the degree of uptake of 68 Ga-PSMA-11 uptake in BCa significantly correlates with PSMA expression in the different BCa lesions and stage of the disease has to be demonstrated yet.PSMA has been validated as a target for PET imaging of prostate cancer, at primary staging and biochemical recurrenceThe aim of the present study was to assess whether PSMA expression could represent a useful marker for BCa diagnosis and to establish whether its expression could be an apt target for anti- angiogenesis and/or radionuclide treatment in BCa.The analysis of PSMA expression was feasible in the overall series of tumor and non tumor samples . We observed PSMA expression only in the tumor neovasculature; in particular PSMA positivity in the tumors was observed in the tumor neovasculature, while in the non tumor tissue it was expressed in the neovasculature of dysplastic area and in some cases it was observed in ulcerated area. Eighteen samples (20.7%) were classified as non tumor samples of whom 11 (12.6%) were healthy bladder tissue, 3 (3.4%) were hyperplasia and 4 (4.6%) were dysplastic tissue. Sixty-nine (79.3%) were tumor samples , 1 sarcomatoid carcinoma, 2 poorly differentiated urothelial carcinomas, 1 urothelial carcinoma with glandular differentiation, 10 conventional urothelial carcinomas and 3 large nested urothelial carcinomas.The median PSMA expression in terms of H-score in the overall series was 210 (range 0–300) (Table p = 0.00288) (Table The median PSMA expression in terms of H-score significantly differed between non tumor and tumor samples (8) Table , that sh8) Table . No diff68 Ga-PSMA-11 PET/CT of this patient.In Fig. 13. However, its use requires specialized personnel for the analysis and appropriate laboratory equipment. For these reasons, it is not feasible in all the laboratories and the search of new biomarkers is still ongoing.The clinical management of patients with BCa is normally based on cytology and cystoscopy. These techniques are not 100% accurate in the diagnosis, localization and discriminating between low- and high-risk patients, indicating the need for companion biomarkers to be used in BCa clinical practice, even more they could serve as therapeutic target. Several molecular tests have been proposed and among them Fluorescence in situ hybridization  obtained FDA approval for the diagnosis and monitoring of BCa patients15. In fact, several studies reported that differences in PSMA expression in terms of cellular or tissue localization may depend on the type of antibody and platform used and sample analyzed. It has also been reported that other healthy and benign tissues different from prostate cancers display PSMA apical and cytoplasmic positivity, and PSMA expression is also observed in the neovasculature17. In the bladder, we demonstrated that PSMA is expressed exclusively in the neoformed vessels of carcinoma, even in in situ tumors, and it showed a weak expression in the vasculature of inflammatory/erosive benign lesions (chronic and erosive cystitis). These results are in accordance with literature data showing that PSMA is a marker of tumor associated neo-angiogenesis. These data could be useful in BCa diagnosis and could acquire even more importance in considering new therapeutic strategies, such as anti-angiogenesis agents and radio-labelled PSMA ligands.Despite in vitro and in vivo studies have demonstrated PSMA expression in various malignant and benign tumors as promising biomarker, its role in BCa diagnosis and evolution has yet to be confirmed19.Despite no differences have been observed on PSMA expression exclusively found in tumor neovasculature, in relation to tumor type, grade and stage, we found that PSMA expression, in terms of H-score was different between non tumor samples and tumor samples, reflecting the presence of a neoplasm. In addition, the high PSMA expression observed in the papillary tumors is in accordance with the fact that they are frequently accompanied by abundant fibrovascular supporting stroma. Moreover, the exuberant PSMA-positive neovascularization could be explained by the role of the gene FGFR3 and its mutations at the level of BCa cells, an indirect marker of tumor aggression implicated in the neo-angiogenesis processWe are aware of the retrospective nature of the study and of the limited number of analyzed cases, but this explorative work could thus form the basis for future research to assess the real diagnostic and prognostic value of PSMA on enlarged case series of samples of BCa.68 Ga-PSMA-11PET/CT19. Both 18F-FDG and 68 Ga-PSMA-11 PET/CT were performed in a single patient, which showed PSMA expression both at the site of the primary BCa and in metastatic lymph nodes20. Similarly, in a 78-year-old patient with high-grade urothelial carcinoma  could be investigated in BCa with future studies both as an alternative to maintenance endovesical treatments of superficial BCa and as a supplementary therapeutic option for metastatic BCa patients. We demonstrated by immunohistochemistry the presence of PSMA in the neovasculature of BCa and demonstrated positive targeting of PET-labeled PSMA ligand. In future the evaluation of tumor-retention time is needed to assess the appropriateness of long half-life therapeutic PSMA ligands as radionuclide treatment for BCa.In the clinical scenario of metastatic BCa patients, the verification of PSMA-expressing BCa lesions by either This retrospective study included BCa patients followed up at the Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori  between 2009 and 2020.21.Seventy-four patients were enrolled in the study and 87 BCa samples were analyzed. The study protocol was reviewed and approved by the Area Vasta Romagna Ethics Committee. Patients’ median age was 73 years (range 40–93). All diagnostic procedures and pathology analyses were carried out in accordance with the relevant guidelines and regulations, and written informed consent was obtained from all study participants. The histology and grading of 87 lesions were established by an expert pathologist at our hospital in accordance with the International Society of Urological Pathology (ISUP) Consensus Conference guidelines 410, using the Ventana Benchmark Ultra staining system  with Optiview DAB Detection Kit . Tissue sections were incubated for 32 min with ready-to-use anti-PSMA antibody . Sections were automatically counterstained with hematoxylin II . PCa and breast cancer tissues were used as positive and negative controls, respectively, in all of the experiments. Biomarker expression was quantified as the percentage of immunopositive tumor cells with membrane staining. Non-malignant tissue around the tumor, when present, was also evaluated for PSMA expression. Staining intensity  was assessed to calculate the H-score, defined as the product of the percentage of the immunopositive tumor cells and the staining intensity. All samples were evaluated by 2 independent observers. Disagreement of > 10% positive cells was resolved by consensus after joint review using a multihead microscope.Immunostaining for PSMA expression was performed, as already described in our previous paperp-values were based on two-sided testing and values lower than 0.05 were considered statistically significant. Statistical analyses were performed using SAS statistical software version 14 .Descriptive statistics are reported as median values and ranges. The normality of data distribution was assessed by Shapiro Wilk test. Since the data were not distributed in a normal way, the relationship between median PSMA expression values and pathology-based categories was evaluated by Mann–Whitney nonparametric test. All


ATP channels, the GLP-1 receptor antagonist, exendin-(9-39), increases fasting plasma glucose and prevents protein-induced hypoglycemia. Studies in human and mouse islets lacking functional KATP channels have demonstrated that the effect on plasma glucose is at least in part mediated by inhibition of insulin secretion resulting from lower cytoplasmic cAMP levels. The understanding of the role of incretin hormones in the pathophysiology of hyperinsulinemic hypoglycemia is important for the exploration of the GLP-1 receptor as a therapeutic target for these conditions. In this article, we will review incretin physiology and evidence supporting a role of the incretin hormones in the pathophysiology of hyperinsulinemic hypoglycemia, as well as results from proof-of concept studies exploring a therapeutic approach targeting the GLP-1 receptor to treat hyperinsulinemic hypoglycemia.Incretin hormones play an important role in the regulation of glucose homeostasis through their actions on the beta cells and other tissues. Glucagon-like peptide-1 (GLP-1) and glucose dependent insulinotropic polypeptide (GIP) are the two main incretins and are secreted by enteroendocrine L- and K-cells, respectively. New evidence suggests that incretin hormones, particularly GLP-1, play a role in the pathophysiology of hyperinsulinemic hypoglycemia. In individuals with acquired hyperinsulinemic hypoglycemia after gastrointestinal surgery, including Nissen fundoplication and gastric bypass surgery, the incretin response to a meal is markedly increased and antagonism of the GLP-1 receptor prevents the hyperinsulinemic response. In individuals with congenital hyperinsulinism due to inactivating mutations in the genes encoding the beta cell K Incretins are hormones secreted by intestinal cells in response to ingested nutrients that play a role in the regulation of glucose homeostasis. Glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are the two main incretins. Incretins effects on glucose homeostasis are mediated by several mechanisms, the most prominent being potentiation of insulin secretion. Effects of endogenous GLP-1 have been better characterized using the receptor antagonist exendin-(9-39). In this article, we will review incretin physiology and evidence supporting a role of GLP-1 in the pathophysiology of hyperinsulinemic hypoglycemia, as well as results from proof-of concept studies exploring a therapeutic approach targeting the GLP-1 receptor to treat hyperinsulinemic hypoglycemia.via both neural and endocrine mediated factors  significantly increases fasting plasma glucose and decreases the insulin to glucose ratio on the fasting state, effectively reversing the hyperinsulinemic hypoglycemia phenotype. These effects were mediated by reduction in islet cAMP concentration, as demonstrated by experiments in vitro in isolated -/-Sur1 mouse islets  effectively inhibited amino acid-stimulated insulin secretion from these islets. Furthermore, in adolescents and adults with KATP hyperinsulinism, a continuous intravenous infusion of exendin-(9-39) resulted in higher fasting plasma glucose concentrations and lower insulin to glucose ratio; plasma glucagon concentration was unaffected by exendin-(9-39) in this study. These studies suggest that GLP-1 and its receptor play a role in the pathophysiology of congenital hyperinsulinism and that targeting the GLP-1 receptor may be an effective treatment approach for this condition  or vehicle through a continuous intravenous infusion. This study found that the insulin surge following the meal was blunted with the administration of the GLP-1 antagonist, suggesting that GLP-1 plays an important role in the exaggerated insulin response seen in post-prandial hypoglycemia in children who had undergone a fundoplication . Glucagovia the stomach (using a gastrostomy tube into the remnant stomach), rather than via the bypassed gastrointestinal tract. Post-prandial levels of insulin and GLP-1 normalized with nutrient administration into the stomach rather than the gastric bypass route, suggesting that altered nutrient delivery to the intestines contributes to dumping syndrome  given as an intravenous infusion to adult individuals with post-prandial hypoglycemia after gastric bypass surgery led to a blunted insulin response, suggesting that GLP-1 is responsible for the exaggerated insulin secretion in dumping syndrome . ExendinThe importance of incretin hormones on the regulation of glucose homeostasis through pancreatic and extra-pancreatic actions is well established. Because of their glucose lowering effects, therapies that enhance incretin actions through inhibiting degradation of endogenous incretins or through activation of the GLP-1 receptor are now in use for the treatment of type 2 diabetes. The recognition of a role for GLP-1 in the pathophysiology of congenital and acquired hyperinsulinemic hypoglycemia has brought forward the possibility of targeting the GLP-1 receptor for the treatment of this condition and promising progress has been made to this end.MD performed literature review and wrote the manuscript. DDDL reviewed literature and edited the manuscript. All authors contributed to the article and approved the submitted version.MD receives fellowship funding from training grant 5T32DK063688-18.DDDL is named as an inventor in patent USA Patent Number 9,616,108, 2017; USA Patent Number 9,821,031, 2017; Europe Patent Number EP 2120994, 2018; and Europe Patent Number EP2818181, 2019; which cover the use of exendin-(9-39) for treating hyperinsulinism and postprandial hypoglycemia. DL has donated all financial proceeds from these patents to the Children’s Hospital of Philadelphia. DL has served as a consultant for Zealand Pharma A/S, Crinetics Pharmaceuticals, Hanmi Pharmaceutical, Heptares Therapeutics, Poxel Pharma, Ultragenyx, and Eiger Pharma. She has received research funding unrelated to this project from Tiburio Therapeutics, Crinetics Pharmaceuticals, and Twist Pharma. DL owns stock options from Merck & Co.The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Coronavirus disease 2019 (COVID-19) is an infectious disease caused by the novel coronavirus. The role of environmental factors in COVID-19 transmission is unclear. This study aimed to analyze the correlation between meteorological conditions  and dynamics of the COVID-19 pandemic in Poland. Data on a daily number of laboratory-confirmed COVID-19 cases and the number of COVID-19-related deaths were gatheredfrom the official governmental website. Meteorological observations from 55 synoptic stations in Poland were used. Moreover, reports on the movement of people across different categories of places were collected. A cross-correlation function, principal component analysis and random forest were applied. Maximum temperature, sunshine duration, relative humidity and variability of mean daily temperature affected the dynamics of the COVID-19 pandemic. An increase intemperature and sunshine hours decreased the number of confirmed COVID-19 cases. The occurrence of high humidity caused an increase in the number of COVID-19 cases 14 days later. Decreased sunshine duration and increased air humidity had a negative impact on the number of COVID-19-related deaths. Our study provides information that may be used by policymakers to support the decision-making process in nonpharmaceutical interventions against COVID-19. Coronavirus disease 2019 (COVID-19) is an infectious disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) . COVID-1On 11 March 2020, the World Health Organization announced the COVID-19 outbreak as a pandemic . HoweverBy the end of 2020, control measures to contain the spread of the COVID-19 pandemic based on social distancing, isolation of confirmed cases, contact tracing and quarantining were introduced . In JanuSeasonality is a long-recognized attribute of virus infection of humans ,18,19,20Some meteorological factors, e.g., temperature or sunlight, may facilitate SARS-CoV-2 destructions and impair the stability of the virus on different types of surfaces . MoreoveThis study aimed to analyze the correlation between meteorological conditions  and dynamics of the COVID-19 pandemic in Poland (daily number of laboratory-confirmed COVID-19 cases and the number of COVID-19-related deaths).2, of which 98.5% is dry land and 1.5% is water. As of 30 June 2020, the population of Poland amounted to 38,354,000 [Poland’s territory covers 312,696 km,354,000 . The couThe country’s location determines distinct seasonal variations of thermal variables used in the study but other meteorological predictors also reveal a clear annual cycle in Poland. The largest seasonal differences are found for moisture over Eastern Europe , and winThe greatest population concentration is in the south and central part of Poland.Data on daily number of laboratory-confirmed COVID-19 cases and the number of COVID-19-related deaths were gatheredfrom the official governmental website of the Polish Ministry of Health . In PolaIn order to assess the influence of meteorological conditions on pandemic dynamics, the meteorological observations from 55 synoptic stations in Poland were used . On theiTo perform detailed analyses and discussion of obtained results, we also used the COVID-19 Community Mobility Reports provided by Google . These rFirstly, the cross-correlation function (CCF) was applied to investigate if any of the meteorological parameters are correlated with new COVID-19 cases or new deaths. CCF is a function of similarity of two time series which give information about the degree of similarity and displacement of one relative to the other . It takeWe can assume that a series of new cases and new deaths are dependent on many variables—e.g., meteorological ones. Such an assumption means that all information included in these series can be described by them. However, with many variables we are not able to easily determine which ones carry information and how significant it is in relation to the whole signal. The solution is to use one of the common techniques of multivariate analysis-principal component analysis (PCA). This approach is also used in different areas of human health—e.g., clinical studies , schizopAnother technique used in this study was random forest, which is an ensemble machine learning method based on constructing many decision trees. This method combinesa large number of small decision trees into new predictors and therefore is able to make abetter prediction. It also performs better in terms of overfitting to training dataset compared to asingle decision tree method . It is wIn this section, the results obtained from all described statistical methods are presented. Each of them was written in a separate subsection. Along with a description of the results obtained, we also presented their interpretation.CCF was used to find correlation between daily meteorology parameters and epidemiological statistics and to find the time lag of when these signals were most similar. We used averaged daily data from synoptic stations, mobility data and confirmed COVID-19 cases and deaths. In Results of CCF between meteorological parameters and new deaths caused by COVID-19 are presented in The results of the cross-correlation between meteorological conditions and mobility data are presented in PCA was computed for sevenvariables: maximum temperature, minimum temperature, sunshine duration, relative humidity, wind speed and new deaths.Eigenvector elements are dimensionless numbers; therefore, to allow the analysis of the results in a more intuitive way, each eigenvector was divided by its maximum  element. Having above in mind, one eigenvector element giving maximal response to the associated Principal Component (PC) is always 100%. This operation results in obtaining “normalized eigenvectors”, whoseelements may reach values between −100 and +100%. Avalue of −100% means the strongest negative correlation of each variable to the estimated PC (variable response to associated PC is high but negative), 100% means direct proportionality (variable response to PC is high and positive) and 0% means absence of statistical dependence (variable not responding to PC). Each individual eigenvector element cannot be interpreted arbitrarily , but only in relation to the other eigenvalues related to analyzed PC. Each eigenvalue is proportional to the portion of the all input data “variance” that is associated with each eigenvector.Based on the data presented in By arranging all the series of metrological data listed above together with the series of daily numbers of COVID-19-related deaths in one observation matrix and employing PCA algorithm working on such an input matrix, we obtained results confirming some statistical dependence of the variables. A series of daily number of COVID-19-related deaths respond maximally to the 1st PC, which in turn represents the most significant proportion of the data variance (85.3%). These results allow us to conclude that the most statistically dependent meteorological variable with the number of deaths is relative humidity. Maximum temperature, as well as sunshine duration, ischaracterized by inverse proportionality to the number of COVID-19-related deaths, whichmeans that some effects (occurring over the entire observed time range) seen byincreasing the value of one variable are parallel to decreasing the value of the other variable. Second and 3rd PCs and the next ones are not worth analyzing as the percentage of variance indicates their low statistical significance.Results with random forest methods are presented in In this study, we presented results from three methods which gave us information about similarities between series of meteorological parameters and new COVID-19 cases and new deaths  or their importance in prediction (random forest). For all methods, we found potential influences on pandemic dynamics were maximum temperature, sunshine duration, relative humidity and variability of mean daily temperature. In the case of new COVID-19 cases, the maximum temperature and sunshine duration had the highest correlation and importance. Increases in temperature and sunshine hours decreased the number of confirmed cases. However, these two parameters are positively correlated each other (0.43), so, based only on these analyses, it is hard to clearly state which factor is dominant: high air temperature or amount of ultraviolent radiation (UV) reaching the Earth’s surface. Relative humidity is also a parameter which had an influence on spread, leading to the pandemic. The occurrence of high humidity caused an increase in the number of COVID-19 cases 14 days later. It is worth notingthat this parameter is weakly correlated with maximum temperature but highly correlated with sunshine duration. This correlation is negative (−0.63), which means that high humidity is when there is a low number of hours of sunshine. Against this background, it is clear that low UV levels and high relative humidity have increase the rate of new COVID-19 cases. We obtained very similar results when analyzing the relationship with new deaths. The statistics look a little different  but the general conclusions are the same. Decreased sunshine duration and increased air humidity had a negative impact on the number of deaths. Our results support the hypothesis of seasonality of SARS-CoV-2 coronavirus infections.One of the consequences of the pandemic is a drop in mobility, mainly due to the restrictions imposed by national governments. These restrictions are intended to reduce contact between people which should help fight against the pandemic. In this study we also assessedhow meteorological parameters impact on people’s mobility and whether this had an impact on the pandemic dynamic. In We observed that the time lag between meteorological parameters and epidemiological statistics was 10 to 14 days. This is in line with the data on the incubation period of SARS-CoV-2 that vary from 2 to 14 days—on average 5–6 days .In line with previous studies, we observed that increase in temperature and high UV levels mitigates the transmission of COVID-19 ,15,16. TA study on meteorological factors and the COVID-19 transmission carried out in four cities in China showed that temperature and relative humidity were the main driving factors ofCOVID-19 transmission (with the season and geographic location) . MoreoveThe data from this study reveal several practical implications. Data from weather forecast models can be used by governments to support the decision-making process to maintain or lift nonpharmaceutical interventions against COVID-19. Moreover, meteorological parameters should be applied in COVID-19 projection and forecasting models. The inclusion of meteorological parameters in COVID-19 projections models can improve the reliability of the obtained data concerning the predicted number of COVID-19 cases and deaths. Moreover, the knowledge of the correlation between the meteorological parameters and the risk of COVID-19 transmission can be used to formulate warning alerts for the local community—e.g., implementation of selected protective behaviors in response to changing meteorological conditions. This is the first study on meteorological parameters and dynamics of the COVID-19 pandemic in Central-European Countries. Further studies are needed to investigate the seasonality of SARS-CoV-2 coronavirus infections, especially in different geographical regions.This study has several limitations. First, only laboratory-confirmed COVID-19 cases were included in this analysis. We can hypothesize that due to the asymptomatic course of COVID-19, the real number of COVID-19 cases couldbe higher than the laboratory detected figure. Nevertheless, we used data from official governmental announcements that are only available data on the COVID-19 pandemic in Poland. Some authors suggest that all-cause mortality can be used as a reliable estimator of the real COVID-19 death toll ,49. It iWe observed a correlation between meteorological parameters and dynamics of the COVID-19 pandemic in Poland. Low temperature, limited sunshine duration as well as high relative humidity increase COVID-19 transmission. Moreover, relative humidity was identified as the most statistically dependent meteorological variable with the number of COVID-19-related deaths. Our study provides important information that may be used by policymakers to support the decision-making process innonpharmaceutical interventions against COVID-19 implemented atlocal and global health levels. Further studies on the meteorological parameters and dynamics of COVID-19 in Central and Eastern Europe are needed to verify the COVID-19 seasonality hypothesis.


Triple-negative breast cancers (TNBCs) display poor prognosis, have a high risk of tumour recurrence, and exhibit high resistance to drug treatments. Based on their gene expression profiles, the majority of TNBCs are classified as basal-like breast cancers. Currently, there are not available widely-accepted prognostic markers to predict outcomes in basal-like subtype, so the selection of new prognostic indicators for this BC phenotype represents an unmet clinical challenge.Here, we attempted to address this challenging issue by exploiting a bioinformatics pipeline able to integrate transcriptomic, genomic, epigenomic, and clinical data freely accessible from public repositories. This pipeline starts from the application of the well-established network-based SWIM methodology on the transcriptomic data to unveil important (switch) genes in relation with a complex disease of interest. Then, survival and linear regression analyses are performed to associate the gene expression profiles of the switch genes with both the patients’ clinical outcome and the disease aggressiveness. This allows us to identify a prognostic gene signature that in turn is fed to the last step of the pipeline consisting of an analysis at DNA level, to investigate whether variations in the expression of identified prognostic switch genes could be related to genetic (copy number variations) or epigenetic (DNA methylation differences) alterations in their gene loci, or to the activities of transcription factors binding to their promoter regions. Finally, changes in the protein expression levels corresponding to the so far identified prognostic switch genes are evaluated by immunohistochemical staining results taking advantage of the Human Protein Atlas.in silico recognition of a basal-like specific gene signature composed of 11 potential prognostic biomarkers to be further investigated.The application of the proposed pipeline on the dataset of The Cancer Genome Atlas (TCGA)-Breast Invasive Carcinoma (BRCA) patients affected by basal-like subtype led to an  Triple-In our recent paper , we analIn order to study the clinical relevance of the basal-like specific switch genes with respect to the patients’ survival, we exploited their expression profiles to perform the Kaplan-Meier analysis. We used the RNA-sequencing data available on the TCGA to stratify BC patients in two groups according to the expression levels of the 108 basal-like specific switch genes. Thus, for each switch genes, low (high)-expression groups refer to patients with the expression level of that gene lower (greater) than the median of its expression values across all BC patients. Then, a log-rank test was performed to assess a statistical significance  to each gene: the lower the p-value, the better the separation between the two prognosis groups. Switch genes with log-rank p-values less than 0.05 were candidate as potential biomarkers for predicting the survival rate of breast cancer patients. We found a total of 15 basal-like specific switch genes that were significantly associated  with BC patients’ prognosis. Among them, 11 switch genes  appeared to be an unfavourable prognostic gene , suggestA differential expression analysis showed that the 11 basal-like specific switch genes, whose unfavourable prognostic value was statistically significant from the previous survival analysis, were all up-regulated in the basal-like cancer condition compared to the normal condition . Yet, byTo statistically quantify the increasing trend of the median expression values of these 11 switch genes as the phenotype varies from physiological to pathological condition passing across the different BC subtypes, we exploited a linear regression model, where the index R-squared estimates the goodness-of-fit. We found that all but one showed a very strong straight-line relationship (R-squared ≥ 0.7) between their median expression and the tumour subtypes  that provided representative immunohistochemistry images in BC tissues and normal breast tissues. As expected, we found that six of these proteins were overexpressed in BC tissues compared to normal breast tissues (To provide some hints on which transcription factors (TFs) could regulate the expression of the 11 switch genes proposed as prognostic biomarkers for basal-like subtype, we built a gene regulatory network by combining information on both computationally predicted and experimentally validated TF-target relationships. In particular, we firstly exploited Pscan web tool  to prediNext, we investigated if the overexpression of the 11 basal-like prognostic biomarkers may depend on basal-like specific genomic alterations, such as Copy Number Variations (CNVs) and/or epigenomic alteration such as DNA methylation changes. In particular, we compared the CNVs and DNA methylation status of these 11 genes in basal-like subtype with respect to the less aggressive BC subtype, i.e., luminal A.The CNVs analysis was performed on a total of 317 TCGA-BRCA patients  for which CNVs data were available. Hierarchical clustering analysis on this data identified three main clusters and showed a different pattern of amplification and deletion in the selected genes between basal-like and luminal A patients . InteresAberrant DNA methylation is another epigenetic alteration that plays a fundamental role in precipitating the development of a large and diverse number of human cancers . For thiWe compared the frequency of amplification and deletion events between basal-like and luminal A, using Fisher’s exact test  and we aBC is the neoplasia with the highest incidence and mortality affecting women worldwide  and is rin vitro and ex vivo experiments to highlight molecular signatures shared among all BC subtypes. However, we believe that the in-depth investigation of the subtype-specific switch genes can allow us to find novel putative associations between gene functionality and subtype-specific aggressiveness especially for more aggressive BC subtypes. So, the goal of this study was to identify among the switch genes specific for basal-like subtype, those linked to a poor prognosis. In the wake of our recent study [http://kmplot.com/analysis/). Interestingly, these 11 switch genes showed their highest mRNA overexpression in the basal-like compared to the other BC subtypes, and this data further strengthens the hypothesis that these switch genes could be poor prognostic biomarkers in basal-like subtype affected patients   and the nt study , the 108patients . After tin vitro experiments performed on BC cell lines demonstrated that CTP depletion results in a senescence-like growth arrest through activation of p53, whereas cells with mutated p53 undergo differentiation or apoptotic cell death [CTPS1 (CTP synthase 1) gene, encodes an enzyme responsible for the catalytic conversion of UTP (uridine triphosphate) to CTP (cytidine triphosphate). This reaction is an important step in the biosynthesis of phospholipids and nucleic acids. Increased levels of the protein have been linked to several mammalian cancer types such as sarcoma , hepatomll death .in vivo xenograft model. Moreover, inhibition of LRP8 was found to attenuate Wnt/β-catenin signalling to suppress breast cancer stem cells (BCSCs) enriched in TNBC and responsible for chemoresistance and metastasis [LRP8 (LDL receptor-related protein 8) gene, encodes a member of the low-density lipoprotein receptor (LDLR) family. A recent study demonstrated that LRP8 was more strongly expressed in BC without hormone receptor expression (TNBC and HER2 positive) than in luminal tumours  . Authorstastasis , 36.Tubulin alpha-1C chain is a protein that in humans is encoded by the TUBA1C gene. TUBA1C is a member of the tubulin families and several studies demonstrated that its upregulation promotes oncogenesis and predicts poor prognosis in different tumour types , 38. TUBRecently, overexpression of DSCC1 (DNA replication and sister chromatid cohesion 1) was found to increase proliferation, invasion and migration of breast carcinoma cells, as well as its knockdown showed opposite outcomes , 44. BesPRAME nuclear receptor transcriptional regulator gene encodes an antigen that is preferentially expressed in human melanomas. The approved mutual link between BC and melanoma conditions emphasized the idea of utilizing this marker for targeting BC progression as well. Indeed, this protein was found to be involved in BC growth and metastasis and promote epithelial-to-mesenchymal transition in TNBC –47, suggCancer cell requires excess nutrients to meet their biosynthetic and bioenergetics needs and to maintain appropriate redox balance. Glucose and glutamine are important nutrients supporting cancer cell survival. SLC7A11 (solute carrier family 7 member 11) gene encodes a member of a heteromeric, sodium-independent, anionic amino acid transport system that is highly specific for cysteine and glutamate; imports extracellular cystine coupled to the efflux of intracellular glutamate. SLC7A11 expression can be induced under various stress conditions, likely as an adaptive response to enable cells to restore redox homeostasis and maintain survival under stress conditions . The uprThe gasdermin (GSDM) superfamily consist of several molecules involved in cell pyroptosis. Recently, various studies have revealed the dysfunction and abnormal expression of the GSDM family in multiple human cancers, implying the potential roles in tumorigenesis. GSDMC (gasdermin C), a member of GSDM superfamily was found to promote cell proliferation in colorectal cancer , and higCDCA7 (cell division cycle associated 7), was found to be elevated in various types of human cancer, including colon, lung, prostate and breast cancers , suggestCentromere proteins (CENPs), which comprise 18 subtypes, are related dynamically to association and dissociation during mitosis with microtubule regulation. Among the CNPs, the protein encoded by CENPN (centromere protein N) gene, binds directly to the centromere-targeting domain of CENP-A. CENP-N depletion causes down-regulation of several CENPs and is considered essential for making a new centromere. Other functions of CENP-N, including its deregulation in BC are unclear, except the study that associated elevated expression of this protein with significantly increased mortality and risk of recurrence in BC smokers in contrast with non-smokers BC subjects .RCOR2 (REST corepressor 2) is a protein-coding gene. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription corepressor activity. To date, its involvement in the growth and progression of BC was not yet bee investigated.in vitro as well as inhibits tumorigenesis in vivo [GINS4 is a subunit of the GINS complex  involved in the initiation and progression of DNA replication . GINS4 w in vivo , 59. As Based on these findings, we felt compelled to understand which regulatory events might be responsible for their upregulation in basal-like subtype. So, we investigated whether the deregulated expression of the selected switch genes could be related to the activity of known transcription factors, copy number variation and DNA methylation. The construction of a gene regulatory network showed how these switch genes interact with several TFs known to be altered in cancer condition , including in TNBC –62. NeveThe first limitation of this study is that it is based on gene expression data and, it would need further deepening at the protein level as soon as proteomic data will be available on large scale for the disease covered in this analysis. However, even if the cause-effect relationship cannot be directly inferred by expression data, correlation networks may highlight disease co-modulated genes that are functionally coordinated in response to an external stimulus, implying that they may be part of the same complexes or pathways, and may influence each other or maybe influenced by the same underlying mechanism(s).A further limitation of this study is that our entire results should be validated by using another independent dataset. However, the proposed bioinformatics pipeline requires a huge quantity of transcriptomic, genomic, epigenomic, and clinical data related to patients affected by different breast cancer subtypes and, currently, TCGA is the only free repository providing simultaneously all this information for the same patient cohort.Lastly, it would have been very interesting to correlate the expression of the 11 genes constituting the basal-like gene signature with the Ki-67 labeling index (Ki-67LI), defined as the percentage of Ki-67 antigen positive cells. Indeed, Ki-67LI is commonly used as proliferation marker and it has frequently been associated with the clinical outcome of TNBC patients , 64. UnfIn conclusion, our study showed that 11 basal-like specific switch genes are overexpressed in BC tissues compared to normal counterpart and associated with BC patients prognosis acting as unfavourable prognostic markers. Also, their highest expression was found in the basal-like subtype and this overexpression could be putatively related to genetic and epigenetic alterations as well as the action of important transcription factors. Taken together, these results turn on a beam of light on CTPS, CDCA7, GSDMC, LRP8, TUBA1C, CENPN, PRAME, SLC7A11, GINS4, DSCC1 and RCOR2 that can constituite a gene signature to evaluate the prognosis of basal-like breast cancer patients independently from the therapeutic intervention. It is worth to stress that our study has a purely computational nature and experimental validations would be necessary to investigate the actual role of the identified genes in the framework of basal-like breast cancer. However, we belive that our findings could provide advancements in the ongoing effort to identify specific prognostic biomarkers for basal-like subtype in order to improve the clinical management of this disease.The Cancer Genome Atlas (TCGA) is a comprehensive project born in 2006 from the joint effort between the National Cancer Institute and the National Human Genome Research Institute to improve diagnosis methods and treatments against cancers . This prhttps://www.proteinatlas.org) was leveraged to identify tumour-type specific proteins expression patterns and to perform immunohistochemistry image a direct comparison of the protein expression of selected prognostic indicators between normal and tumour breast tissues.The Human Protein Atlas is a research program initiated in 2003 to map all the human proteins in cells, tissues and organs using an integration of various omics technologies, including antibody-based imaging, mass spectrometry-based proteomics, transcriptomics and systems biology . All theSWIM (SWitchMiner) is a new methodology that considers differentially expressed genes within the co-expression network framework to predict important genes affected by a disease of interest, and combines this information with a structured network of correlated patterns. Considering the topological properties of the nodes and assessing their functional roles according to their ability to convey information within and between modules in the network, SWIM identifies a small pool of genes (known as switch genes) that are associated with intriguing patterns of molecular co-abundance and play a crucial role in the observed phenotype (transitions) . SWIM isTo analyze the correlation between the expression level of the 108 basal-like specific switch genes and patient overall survival (OS) and therefore to evaluate their prognostic value, we used the RNA-sequencing data from TCGA to split the entire cohort of BC patients (1049 samples) into two groups  according to the upper and lower expression quartile. In particular, low- and high-expression groups refer to patients with expression levels of the given switch gene lower and greater than the 50th percentile , respectively. For each patient cohort, the cumulative survival rates were computed for each switch gene according to the Kaplan-Meier (KM) method  on the chttp://kmplot.com/analysis/), which integrates gene expression data and OS information downloaded from GEO, EGA and TCGA for several types of cancer [To confirm the prognostic value of the basal-like specific switch genes points out from the KM survival analysis on the TCGA breast invasive carcinoma patients, we performed the KM analysis on different breast cancer dataset. To do this, we exploited the Kaplan-Meier plotter website  is an extension of independent two-samples t-test for comparing means in a situation where there are more than two groups. In one-way ANOVA, the data is organized into several groups based on one single grouping variable . In this study, the one-way ANOVA test was used to compare the means of selected genes in patients grouped based on the PAM50 breast cancer subtypes. A p-value ≤ 0.05 indicated that at least two groups significantly differ from each other and multiple pairwise-comparisons exploiting the t-test method were performed to identify which ones.The gene regulatory network of the selected switch genes was constructed by integrating information from Pscan , TRRUST Pscan is a web tool designed to computationally predict TF-target regulatory relationships . In partTRRUST is a freely available and manually curated database containing 8,444 TF-target regulatory relationships of 800 human transcription factors. These relationships have been derived from PubMed articles describing small-scale experimental studies of transcriptional regulations by using a sentence-based text mining approach .The human interactome, also called protein-protein interaction (PPI) network, was downloaded from Cheng and coauthors , where tCopy Number Variations (CNVs) data of TCGA-BRCA project were retrieved from TCGA repository and reported contiguous chromosome regions with log2 ratio segment means in a tab-delimited format. To obtain segment means values of CNVs of the selected genes for the enrolled patients, we employed GISTIC 2.0 software . Gistic’b “path file; -seg “filename”; -refgene refgenefiles/hg19.UCSC.add_miR.140312.refgene.mat; -mk genome.info.6.0_hg19.na31_minus_frequent_nan_probes_sorted_2.1.txt; -maxspace 2000; -ta 0.3; -td 0.3; -js 4;-qvt 0.01; -conf 0.99; -genegistic 1; -armpeel 1; -savegene 1.-The hierarchical clustering analysis was performed by using “Canberra” as clustering distance and “ward.D2” as clustering method. The association between the CNVs status of the selected genes and the BC subtypes was evaluated using Fisher’s exact test.https://gdac.broadinstitute.org/). The methylation data were acquired by the Illumina 450K array, which measures the level of methylation as a beta value for more than 450 000 CpG sites on the Illumina chip. The data contained information for about 485 578 CpG sites. To make available and pre-process methylation data in R environment, we used minfi package [DNA methylation data of TCGA-BRCA project were retrieved by Firehorse TCGA GDAC browser Click here for additional data file.S2 FigGene expression levels of the 11 basal-like specific switch genes point out from the Kaplan-Meier survival analysis in basal-like and normal samples available from TCGA repository. T-test was used to compare the means of the selected genes between the two sample groups  and statistical significance was indicated by the star symbols .(PNG)Click here for additional data file.S1 TableThe table is composed of two separated sheets. The first sheet reports the complete list of 108 switch genes found to be specific for basal-like breast cancer subtype. The second sheet reports the complete list of 11 switch gene whose activation was found to be associated with the worst prognosis from the KM survival analysis on the TCGA breast invasive carcinoma patients.(XLSX)Click here for additional data file.S2 TableThe table reports the results of the CNVs data analysis for the 11 basal-like prognostic biomarkers.(XLSX)Click here for additional data file.


Designed micro-nano structures on the surface of aluminum alloy provide excellent light trapping properties that can be used extensively in thermal photovoltaics, sensors, etc. However, the fabrication of high-performance antireflective micro-nano structures on aluminum alloy is challenging because aluminum has shallow intrinsic losses and weak absorption. A two-step strategy is proposed for fabricating broadband antireflection structures by superimposing nanostructures onto microscale structures. By optimizing the processing parameters of femtosecond laser, the average reflectances of 2.6% within the visible spectral region (400–800 nm) and 5.14% within the Vis-NIR spectral region (400–2500 nm) are obtained. Surface morphology is crucial in controlling the optical, chemical, biological, and other properties of solid surfaces . SpecialFemtosecond laser as a direct writing technology is a versatile fabrication method for micro/nanostructures that offers the following advantages: the capability to process almost all materials; the capability to induce nanostructures during ablating microstructures ; the capAluminum is the only material with high reflectivity from the UV to IR region . It is cThe experimental material is aluminum alloy (2A12), and its chemical composition is provided in Surface micro-nano structures on aluminum alloy surfaces were fabricated by an HR-Femto 50 femtosecond laser system , which can generate 350 fs pulses at a central wavelength of 1035 nm and a repetition rate of 1 MHz. The maximum average power is 60 W. An x-y galvo is used to scan the laser beam on the aluminum alloy surface in an atmospheric environment.Several laser processing parameters . A white light interferometer  was used to obtain the three-dimensional (3D) topography of the sample surface. A UV-Vis-NIR spectrophotometer with an integrating sphere  was utilized in order to investigate their absorption behaviors in Vis-NIR regions. An energy spectrum analyzer  was used to analyze the elements contained in the sample.The reflectance depends on the structures’ depth, shape, and period related to the processing parameters . The ant(1) Microscale light-trapping structureWhen the size of the cavity or the interval between the microstructures  is much larger than the wavelength of the incident light, the microcavity has excellent light-trapping property. The electromagnetic waves are trapped in the microcavity and reflected multiple times ,25; thus(2) Subwavelength structureSubwavelength structures  promote grating coupling and cavity-trapping mechanisms by exciting surface plasmon polaritons (SPPs) . Surface(3) NanoparticleMetallic nanoparticles  are excellent structures for exciting plasmon resonance and tuning the optical response of the surface . Metal n(4) Metal oxides layerMetal was oxidized on the surface of the microstructure as well as nanoparticles. The impedance mismatch caused by the vast refractive index difference between metal and air causes high reflectivity on the interface. Metal oxides as the transition layer can reduce impedance mismatch on the interface . As obseeff = fnmetal + (1−f)nair, and f is a filling factor of metal in the range 0–1. The more porous and rougher surfaces have smaller filling factors, and as f becomes smaller, surface reflectance is reduced gradually [Microscale light-trapping structures, subwavelength structures, and nanoparticles are visible on SEM images with scales of 100 μm, 5 μm, and 1 μm. The blackened aluminum alloy was made via a sizeable defocusing laser beam with high power. As observed in radually . StructuIt is necessary to have microscale light-trapping structures, subwavelength structures, and abundant nanoparticles simultaneously in order to achieve high-performance antireflection effects in a wide wavelength range. Thus, the laser processing parameters were improved based on the S series, as shown in The speed of a laser scan when processing structure B was selected according to the previous experimental experience. During the experiment, it was observed that the laser power and scanning intervals have a significant impact on the microscale frame structures. Thus, the single variable experiments of power and scanning intervals were performed, respectively. The processing target of the microscale frame structure is conical. It is defined that the regular topography conforming to the ideal structure  is of good quality. The processing effect we expect is shown in As shown in The femtosecond laser is used to fabricate micro/nanostructures for antireflection on the surface of 2A12 aluminum alloy. Different micro-nano structures and antireflection properties can be obtained by adjusting laser processing parameters. A slow laser scan with high power and sizeable defocusing can prepare blackened aluminum alloy. The blackened parameters of the polished surface are also applicable for samples with specific microscale frame structures. Subwavelength structures and nanoparticles can reduce the reflectance of aluminum alloy in the visible light band by exciting plasmon resonance and tuning the optical response of the surface. Microscale light-trapping structures, subwavelength structures, and nanoparticles can reduce the reflectance of aluminum alloy in the Vis-NIR spectral region by enhancing the light-trapping effect, exciting plasmon resonance, and tuning the optical response of the surface. The light-trapping effect of microscale frame structures can effectively inhibit the increase in reflectance of the antireflection micro/nanostructures on the aluminum alloy surface as the wavelength increases. The hierarchical structures formed by the microscale structures, subwavelength structures, and the rich nanoparticles obtained by the processing with blackened parameters can yield excellent antireflective properties in a broad spectrum. About 97.4% absorptivity in the visible spectral region (400–800 nm) and 94.8% absorptivity over the Vis-NIR spectral region (400–2500 nm) can be achieved. The method of processing micro-nano structures described in this article has the advantages of low cost, high efficiency, and strong adaptability.