Mixed Population Research Articles

Analog Serious Games for Medical Education: A Scoping Review

Abstract Purpose Serious games are increasingly used in medical education to actively engage learners. Analog serious games are a nondigital subset of serious games with specific purposes that go beyond entertainment. This scoping review describes the literature pertaining to analog serious games and provides recommendations regarding gaps and emerging directions for future research. Method The authors conducted a scoping review following the Arksey and O’Malley framework, searching 3 databases (MEDLINE, Embase, and CINAHL) for studies of analog serious games designed for physician-track learners published from January 2013 through December 2023. Two authors independently screened the titles and abstracts, whereas 1 of 5 authors screened each full text and extracted data from eligible records. The authors iteratively analyzed the data within numerous categories and coded the findings to examine how the field has evolved during the past decade. Results The searches retrieved 3,955 records with 865 duplicates. The authors reviewed 3,090 title and abstract records and 202 full-text records. Eighty-eight records met the inclusion criteria, including research reports, conference abstracts, descriptive reports, and short innovation reports. The peak years for publications were 2019 and 2023 (15 publications each). Fewer abstracts and articles were published during the beginning of the COVID-19 pandemic (i.e., 2020-2022). The most common scholarship type was description studies (63 [72%]), whereas the dominant game formats were board games (51 [58%]) and card games (33 [38%]). Most studies tested analog serious games with medical students (60 [68%]) and/or residents and fellows (39 [44%]), with numerous studies including mixed study populations. Conclusions This scoping review demonstrates moderate growth within the field of analog serious games, along with numerous opportunities for future research. Although analog game–based learning cannot entirely replace traditional pedagogical approaches, analog serious games have potential to meaningfully complement education for physician-track learners in all medical training stages.

The unappreciated centrality of ethnoracially mixed Americans to the nation’s demographic future

The ethnoracial future of the United States has been framed as a demographic binary: Whites vs. people of color. The argument here is that this binary distorts by failing to take into adequate account the rapidly growing group of Americans who have been raised in mixed minority and White families, the great majority of the total mixed population. The members of this group generally have distinctive social characteristics: socioeconomic advantages compared to minorities and social integration into milieus with many Whites, as revealed by relatively high rates of marriage to them. However, their identities often encompass their minority heritage. Accordingly, they straddle the society’s major ethnoracial fracture line, creating an in-between social space and connecting, through kinship and other close social relations, both of its sides. However, their numbers are distorted in public national population data, such as census data and population projections; and they are typically counted as part of the non-White population. The recently announced revision of the race/ethnic data standards for the census offers an opportunity to refashion public data in a way that illuminates the important role this mixed group is likely to play in the nation’s demographic future.

Long‐distance migrations, population mixing, and growth rate of lumpfish (Cyclopterus lumpus) revealed from tag‐recaptures

AbstractWe reveal that lumpfish (Cyclopterus lumpus) frequently migrate over long distances between their summer feeding area in the open ocean and their spring spawning sites in coastal areas, through applying tag‐recapture methodology. A total of 2750 C. lumpus were tagged in the Irminger Sea around Iceland and in the Norwegian Sea over 6 years, of which 17 C. lumpus were recaptured. Interestingly, four individuals were recaptured more than 1000 km distant from where they were tagged. C. lumpus tagged in the Irminger Sea and north of Iceland were recaptured around Iceland, whereas none of the fish tagged in other areas of the Norwegian Sea were recaptured in Iceland. This difference in recapture rate from different areas suggests that a higher proportion of C. lumpus from the Irminger Sea and north of Iceland spawns around Iceland in comparison with C. lumpus in other areas. Two fish tagged east of Iceland were recaptured on the coast of Denmark, with one fish having a displacement distance of 1612 km. The recapture of these two fish in Denmark demonstrates that part of the C. lumpus population spawning in Denmark utilizes the Norwegian Sea as a major feeding area and that the Norwegian Sea is a common feeding area for several distinct populations of C. lumpus. The growth rate of tagged fish varied from 1.2 to 11.1 cm year−1, indicating that males that are >20 cm and females that are >25 cm during the summer are capable of sufficient growth to achieve a suitable size for spawning (≥25 and ≥35 cm for males and females, respectively) the following spring.

Development and validation of the prediction score for augmented renal clearance in critically Ill Japanese adults.

Augmented renal clearance (ARC) decreases the therapeutic concentration of drugs excreted by the kidneys in critically ill patients. Several ARC prediction models have been developed and validated; however, their usefulness in Japan has not been comprehensively investigated. Thus, we developed a unique ARC prediction model for a Japanese mixed intensive care unit (ICU) population and compared it with existing models. This retrospective study enrolled a mixed ICU population in Japan from January 2019 and June 2022. The primary outcome was the development and validation of a model to predict ARC onset based on baseline information at ICU admission. Patients admitted until May 2021 were included in the training set, and external validation was performed on patients admitted thereafter. A multivariate logistic regression model was used to develop an integer-based predictive scoring system for ARC. The new model (the JPNARC score) was externally validated along with the ARC and Augmented Renal Clearance in Trauma Intensive Care (ARCTIC) scores. A total of 2,592 critically ill patients were enrolled initially, with 651 patients finally included after excluding 1,941 patients. The training and validation datasets comprised 456 and 195 patients, respectively. Multivariate analysis was performed to develop the JPNARC score, which incorporated age, sex, serum creatinine, and diagnosis upon ICU admission (trauma or central nervous system disease). The JPNARC score had a larger area under the receiver operating characteristic curve than the ARC and ARCTIC scores in the validation dataset (0.832, 0.633, and 0.740, respectively). An integer-based scoring system was developed to predict ARC onset in a critically ill Japanese population and showed high predictive performance. New models designed to predict the often-unrecognized ARC phenomenon may aid in the decision-making process for upward drug dosage modifications, especially in resource- and labor-limited settings.

Reply to Gatti and Pea, "Are the pharmacokinetic data of meropenem studied in CSF of a mixed population composed of patients with cerebral infections and patients with extracerebral infections really helpful for clinicians treating CNS infections?"

Reply to Gatti and Pea, "Are the pharmacokinetic data of meropenem studied in CSF of a mixed population composed of patients with cerebral infections and patients with extracerebral infections really helpful for clinicians treating CNS infections?"

Collaborative and side-by-side artmaking: reducing social isolation in refugee youth group art therapy

ABSTRACT Background Research on social isolation in refugee youth is important because it affects their sense of belonging, mental health and wellbeing; integration and acculturation into a new country; education; and future employment opportunities. There is limited art therapy research in Australia in this area, leaving a compelling gap in understanding the effectiveness of collaborative and side-by-side artmaking in group art therapy to connect refugee youth with their peers. Aims This study aimed to explore whether collaborative and side-by-side artmaking in group art therapy would connect youth more effectively; alleviate their social isolation from trauma, displacement and re-settlement experiences; provide a safe environment and platform to express themselves; and improve their mental health and wellbeing. Methods The triangular mixed-methods approach used standardised scales and semi-structured interviews to gather information from youth, teachers and art therapists. Mixed-method data analysis was applied using the Reliable Change Index, line graphs, descriptive statistics, and thematic analysis. Results Refugee youths’ self-esteem and confidence seemed to increase through collaborative and side-by-side artmaking. Results highlighted the importance of social connection, self-esteem, confidence and a sense of safety for making positive connections during artmaking. Conclusions Findings indicate potential benefits of pportunities for refugee youth to connect with their peers in the school environment and of group art therapy. Implications for practice and future research Opportunities could be achieved through collaborative and side-by-side artmaking in group art therapy. A larger study, longer programme and mixed populations in the school setting are recommended for future research. Plain-language summary The research aimed to examine if there was an effect of a six-week art therapy programme on social isolation for five 14–15-year-old female refugee youth. This research is important because social isolation affects youth’s mental health and wellbeing. Through creating art individually and next to each other (side-by-side artmaking), and creating artworks together (collaborative artmaking), the programme aimed to reduce social isolation and increase connections between youth during the sessions and in the school environment. The research was conducted in an early intervention creative therapies service onsite at a Queensland English-language transition secondary school. The service is provided by accredited art therapists and uses creative methods to support culturally diverse refugee youth in resettling, learning and recovering from trauma and stress. During the research, youth participants engaged in art activities, such as drawing and painting, while listening to music. Interventions were designed to establish group bonds, build self-esteem and resilience, and empower youth in a safe and supportive environment. Art therapists and teachers observed youth during the research period, completed standardised scales before and after the programme and participated in semi-structured interviews. The youth participants also completed standardised scales and were interviewed before and after the programme. The results showed that after the six-week programme, youths’ wellbeing and connections to each other increased. Three central themes were identified: (1) social connection is important within the school environment; (2) self-esteem and confidence are related to connecting to others and social isolation; and (3) there is a sense of safety in artmaking individually and collaboratively with peers. The study found that the art therapy programme positively affected youth mental health and wellbeing. This suggests the programme effectively reduced participants’ social isolation, potentially offering positive opportunities to connect other youth at risk of social isolation.

Clinical Effectiveness and Safety of Midazolam Compared With Lorazepam for Control of Seizures in Adults

What Is the Issue? The emergency treatment of prolonged seizures or status epilepticus is required to be rapid and efficient to prevent permanent brain damage or death. Benzodiazepines, such as midazolam, lorazepam, diazepam, and clonazepam, are established as first-line treatment medications for acute treatments of seizures. Various administration routes of delivery for these drugs have become available, but the comparative clinical effectiveness and safety among administration routes are still unclear. Decision-makers are interested in whether the current use of intramuscular (IM) midazolam for treatment of seizures by paramedics in a prehospital environment can be switched to IV lorazepam as normally used by nurses and physicians in clinic settings. What Did We Do? We identified and summarized the literature on the evidence of the clinical effectiveness and safety of midazolam compared to lorazepam in adults to control seizures. We searched key resources, including journal citation databases, and conducted a focused internet search for relevant evidence published since 2019. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings. What Did We Find? We identified 1 systematic review (SR) that included 4 randomized controlled trials (RCTs), only 1 was relevant to this review. This double-blind RCT determined the efficacy of IM midazolam as noninferior to IV lorazepam for treatment of seizures by paramedics in a mixed population of adults (89%) and children (11%). The authors of the SR conducted a subanalysis of a dataset of participant-level data and showed that IM midazolam was as effective and safe as IV lorazepam in adult patients for prehospital seizure cessation. The findings of the adult population were similar to those of the whole randomized population of both adults and children. What Does This Mean? With the shorter time required to administration of midazolam by the IM route compared to administration of lorazepam by the IV route, and the comparable efficacy and safety between the 2 active treatments, the use of IM midazolam may be a better option in the prehospital environment when IV access in patients with seizures is not readily established. Switching of IM midazolam to IV lorazepam for treatment of seizures by paramedics may not be practical.

Spinocerebellar ataxia type 10 and Huntington disease-like 2 in Venezuela: Further evidence of two different ancestral founder effects.

The American continent populations have a wide genetic diversity, as a product of the admixture of three ethnic groups: Amerindian, European, and African Sub-Saharan. Spinocerebellar ataxia type 10 (SCA10) and Huntington disease-like 2 (HDL2) have very ancient ancestral origins but are restricted to two populations: Amerindian and African Sub-Saharan, respectively. This study aimed to investigate the genetic epidemiological features of these diseases in Venezuela. In-phase haplotypes with the expanded alleles were established in seven unrelated index cases diagnosed with SCA10 and in 11 unrelated index cases diagnosed with HDL2. The origins of remote ancestors were recorded. The geographic origin of the ancestors showed grouping in clusters. SCA10 had a minimal general prevalence of 1:256,174 families in the country, but within the identified geographic clusters, the prevalence ranged from 5 per 100,000 to 43 per 100,000 families. HDL2 had a general prevalence of 1:163,016 families, however, within the clusters, the prevalence ranged from 31 per 100,000 to 60 per 100,000 families. The locus-specific haplotype shared by all families worldwide, including the Venezuelans, supports a single old ancestral origin in each case. Knowing the genetic ancestry and geographic origins of patients in Ibero-American mixed populations could have significant diagnostic implications; thus, both diseases in Venezuela should always be first explored in patients with a suggestive phenotype and ancestors coming from the same known geographic clusters.

Use of the Micro-Agar Larval Development Test to Differentiate Resistant and Susceptible Cooperia spp. Isolates in Cattle Within the Context of Parasite Population Replacement

Gastrointestinal nematode infections are a global concern in grazing cattle production systems, even more so due to the widespread problem of anthelmintic resistance. In response, early anthelmintic resistance detection methods, such as the micro-agar larval development test (MALDT), and parasite management strategies, such as the replacement of resistant parasite populations with susceptible ones, have been developed. This study aimed to characterize ivermectin-susceptible and -resistant isolates of Cooperia spp. using MALDT in the context of a parasite population replacement strategy. Three Cooperia spp. field isolates were evaluated: a susceptible one (Coop-S), a resistant one (Coop-R), and a post-replacement one (Coop-PR). The MALDT was performed in 96-well plates with 12 known concentrations of eprinomectin (EPR) on an agar base. Each test was performed in quadruplicate. Data analysis included nonlinear regression to determine EC50, EC90, and EC99 values, resistance ratios (RRs), and R2. The results showed clear differentiation between the isolates, with RR values of 5.78 and 1.28 for Coop-R and Coop-PR, respectively, compared to Coop-S. The MALDT proved to be a reliable tool for differentiating ivermectin-susceptible from ivermectin-resistant isolates of Cooperia spp., and future evaluations of this test in mixed nematode populations are recommended for routine diagnosis of anthelmintic resistance.

New evidence on patella resurfacing in modern total knee arthroplasty for all inflammatory arthritis in a mixed Asian population

BackgroundTraditional teaching advocates for routine patella resurfacing (PR) during total knee arthroplasty (TKA) in patients with inflammatory arthritis. However, evidence on this topic remains limited in the Asian population. This study aims to evaluate the postoperative outcomes and complication of patella resurfacing (PR) during primary total knee arthroplasty (TKA) in Asian patients with inflammatory arthritis. MethodsA retrospective analysis was conducted using registry data from our institution. Patients with inflammatory arthritis who underwent primary TKA from August 2017 to December 2021 were included in the study. Patients were divided into two groups - patella resurfaced (PR, n = 25) and non-resurfaced patella (PNR, n = 31) groups. Demographics, operative data, patient reported outcome measures, and complications were compared. ResultsPreoperative range of motion (ROM) (PR:95.3 ± 23.6° vs PNR:105 ± 19.5°, p = 0.106), Knee Society Scoring System Knee score (KS-KS) (PR:44.6 ± 17.4 vs PNR:49.3 ± 17.7, p = 0.331) and Knee Society Function Score (KS-FS) (PR:40.9 ± 27.3 vs PNR:47.7 ± 27.0, p = 0.325) and Oxford Knee Score (OKS) (PR:25.0 ± 7.8 vs PNR:23.3 ± 10.3, p = 0.525) were similar in both groups. Outcomes between PR and PNR groups at the one-year mark in terms of ROM (PR:112.7 ± 18.1 vs PNR:114.6 ± 16.5, p = 0.455), OKS (PR:41.5 ± 3.9 vs PNR:41 ± 4.7, p = 0.954), KS-KS (PR:84.5 ± 13.2 vs PNR:89.2 ± 9.3, p = 0.095) and KS-FS (PR:73.6 ± 18.3 vs PNR:78.7 ± 19.3, p = 0.173) were also similar. Intraoperative complication (PR:0/25 vs PNR: 3/31 (9.6 %), p = 0.245) and re-operation rates (PR: 1/25 (4 %) vs PNR: 1/31 (3.2 %), p = 0.877) were also similar in both groups. ConclusionThis study conducted on a mixed Asian population with inflammatory arthritis demonstrated that the one-year postoperative ROM and functional outcomes, complication, and re-operation rates between PR and PNR groups were similar. Hence, routine patella resurfacing on all Asian patients with inflammatory arthritis undergoing TKA may not be necessary.

Ribosomal A site binding pattern differs between Arm methyltransferases from clinical pathogens and a natural producer of aminoglycosides

The extensive use of aminoglycosides to treat bacterial infections has led to significant resistance, posing a global health threat. Recent clinical reports highlight high levels of aminoglycoside resistance due to Arm/Kam methyltransferases, which methylate specific nucleotides in 16S rRNA, preventing antibiotic binding to the ribosome. This study compared the ribosomal A site binding patterns of Arm methyltransferases from clinical pathogens (ArmA, RmtB, RmtC, and RmtD) with those of the Sgm methyltransferase from a natural aminoglycoside producer. We introduced single mutations near the G1405 nucleotide in helix 44 of 16S rRNA to assess their impact on the methylation ability of Arm methyltransferases in E. coli cells with homogeneous mutant ribosomes. We evaluated how these mutations affected bacterial viability in cells with mixed and homogeneous ribosome populations and determined the minimal inhibitory concentration of kanamycin to assess their impact on Arm enzyme activity. Notably, Sgm methyltransferase exhibited a distinct methylation pattern compared to Arm methyltransferases from clinical strains. Structural comparisons of Sgm, RmtB, and RmtC revealed different spatial orientations of key amino acids involved in ribosomal binding, highlighting evolutionary differences. This research enhances understanding of Arm methyltransferases and lays the groundwork for designing inhibitors to combat this potent form of antibiotic resistance.

Circulating levels of amyloid-beta (1-40) peptide associate with cardiometabolic traits and risk for metabolic dysfunction-associated steatotic liver disease

Abstract Background and Aims The ageing-associated amyloid-beta 1-40 peptide (Αbeta40) has recently emerged as a blood-based biomarker of cardiovascular disease (CVD). Its levels predict future cardiovascular death and MACE in patients with established CVD. The clinical value of Abeta40 in patients with metabolic syndrome who do not concomitantly have clinically overt CVD or other end-organ damage remains poorly understood. At the present study we investigated the clinical value of plasma Αbeta40 in patients with pre- or established metabolic syndrome who are at risk for metabolic dysfunction-associated steatotic liver disease (MASLD). Methods Αbeta40 was measured in plasma by enzyme-linked immunosorbent assay and cardiometabolic traits were determined in a mixed population (n=888) of patients with established (n=243) and pre- or without metabolic syndrome (n=645) who did not have clinical signs of established cardiometabolic disease (heart failure, coronary artery disease, MASLD, chronic kidney disease). The endpoint of the study was the association of Abeta40 with cardiometabolic indices and risk (BARD score) for MASLD. Odds ratio (OR) was calculated by ordinal regression analysis for the increasing incidence of metabolic syndrome components per increasing Abeta40 (1-SD) after adjustment for age, sex, smoking status and hyperlipidemia. Results Abeta40 levels are associated with the presence of metabolic syndrome and with higher odds for increasing incidence of metabolic syndrome components after adjustment for sex, age, smoking status, hypertension and dyslipidemia. Increased Abeta40 plasma levels were associated with decreased HDL-C levels (OR: 1.004, 95% CI:1.000-1.009, P=0.049) and increased triglyceride levels (OR: 1.007, 95%CI: 1.001-1.012, P=0.033) after adjustment for traditional cardiovascular risk factors (age, sex, smoking status, hypertension and hyperlipidemia). Among the total population (n=888), we identified n=473 subjects with increased MASLD risk if any of the following was present: hepatic steatosis index≥36 or fatty liver index≥60 or Fib-4 index≥2.67 or NAFLD score≥0.675. Among patients with high-risk for MASLD, patients with increased BARD score had significantly higher Abeta40 levels (median Abeta40 concentration in patients with BARD score≥2 vs. patients with BARD score<2: 54.9 pg/ml (IQR=38.25) vs. 41.9 pg/m (IQR=30.35), P=0.012). Increased Abeta40 levels were associated with increased odds for AST/ALT≥0.8 ratio and increased odds for BARD score≥2 after adjustment for age, sex, smoking status, hypertension and hyperlipidemia. Conclusion Our findings suggest that Abeta40 peptide is associated with cardiometabolic traits and risk for MASLD. Whether Abeta40 may emerge as an early cardiometabolic prognostic biomarker, future longitudinal studies are warranted to determine the prognostic value of Abeta40 for the development of cardiometabolic diseases in patients with metabolic syndrome.

Routes of importation and spatial dynamics of SARS-CoV-2 variants during localised interventions in Chile

Abstract Human mobility is strongly associated with the spread of SARS-CoV-2 via air travel on an international scale, and with population mixing and the number of people moving between locations on a local scale. However, these conclusions are drawn mostly from observations in the context of the global north where international and domestic connectivity is heavily influenced by the air travel network; scenarios where land-based mobility can also dominate viral spread remain understudied. Furthermore, research on the effects of non-pharmaceutical interventions (NPIs) has mostly focused on national- or regional-scale implementations, leaving gaps in our understanding of the potential benefits of implementing NPIs at higher granularity. Here, we use Chile as a model to explore the role of human mobility on disease spread within the global south; the country implemented a systematic genomic surveillance program and NPIs at a very high spatial granularity. We combine viral genomic data, anonymised human mobility data from mobile phones and official records of international travellers entering the country to characterise the routes of importation of different variants, the relative contributions of airport and land border importations and the real-time impact of the country’s mobility network on the diffusion of SARS-CoV-2. The introduction of variants which are dominant in neighbouring countries (and not detected through airport genomic surveillance) is predicted by land border crossings and not by air travellers, and the strength of connectivity between comunas (Chile’s lowest administrative divisions) predicts the time of arrival of imported lineages to new locations. A higher stringency of local NPIs was also associated with fewer domestic viral importations. Our analysis sheds light on the drivers of emerging respiratory infectious disease spread outside of air travel, and on the consequences of disrupting regular movement patterns at lower spatial scales.

Validation of an artificial intelligence system for holter ECG analysis

Abstract Introduction Holter ECG is a commonly used tool to identify heart rhythm disorders. As physician-based analysis of such Holter ECG is time consuming, various approaches using computerized interpretation have been developed. However, accuracy of these tools remains inferior to physician-based analysis. Thus, this study assesses the diagnostic performance of an artificial intelligence (AI)-powered Holter ECG service in comparison to results from reference databases as well as with physician-based evaluation. Methods 231 ECG recordings, covering 2,261 hours of ECG with annotations for 10,024,315 heartbeats from the following reference databases were used: MIT-BIH Arrhythmia (MITDB), American Heart Association ECG (AHDB), MIT-BIH Atrial Fibrillation (AFDB), Long Term Atrial Fibrillation (LTAFDB). Those recordings were originally collected from a mixed population of inpatients and outpatients between 1975 and 2008. Analysis of these recordings regarding the detection of QRS complexes, QRS classification and detection of Atrial Fibrillation (AF) was performed using a novel service for AI-based ECG analysis. Results were compared to the diagnosis stated within the database. QRS complex detection accuracy was performed on recordings from MITDB and AHADB by checking if time positions are within 150 ms to reference annotations. The QRS classification in three classes (normal, supraventricular, ventricular) was then compared for each detected heartbeat. Mismatches were adjudicated manually by three experts. Episodes of Atrial Fibrillation were detected in recordings from MITDB, AFDB and LTAFDB and compared to the reference episodes from the databases. The accuracy was evaluated based on the overlap with the reference annotations in the time-domain. Results Sensitivity and Precision of heartbeat detection compared to the reference databases exceeded 99% Figure 1 displays the results of heartbeat classification. Normal heartbeats were classified with a sensitivity of 99.6%, precision of 99.9% and specificity of 99.6%. For ventricular heartbeats, a sensitivity of 99.58 %, precision of 99.88 and specificity of 99.99% were achieved. Premature supraventricular contractions were recognized with a sensitivity of 99.58 %, precision of 100% and specificity of 100%. When comparing the 248,187 QRS complex classifications of MITDB and AHADB to the AI-powered analysis, 128 discrepancies were revealed. 43 were due to a discrepancy of convention as these beats were in sections that were also marked as AF episodes by the databases and the AI-powered analysis marks all beats in AF episodes as normal. Of the 85 remaining discrepancies, more than 87% were adjudicated in favor of the AI-powered analysis by the experts. Figure 2 shows the comparison of AF detection results showing Sensitivity and Precision above 99%. Conclusion AI-powered Holter ECG analysis compared to reference ECG stripes exceed 99% of sensitivity, specificity and precision.QRS complex detectionAF/ AFib detection

The spatial and seasonal patterns and stability of the Lake Whitefish fishery in Michigan waters of southern Lake Huron

AbstractObjectiveGiven that the harvested fish from five separate fishing grounds belong to one large mixed population, our objective is to develop an overall abundance index for Lake Whitefish Coregonus clupeaformis in Michigan waters of southern Lake Huron.MethodsWe analyzed catch‐and‐effort data for individual fishing trips to five separate fishing grounds and used Bayesian information criterion to select the best model struture.ResultThe best model included the year × area × month interaction as a random effect, representing the random component in fishery dynamics that were influenced by both fishing practices and fish abundance. The best model also included the fixed effects of area × month interaction, a result consistent with our hypothesis that the seasonal spatial migrations of Lake Whitefish provide the links among the fisheries in separate fishing grounds, and the fishery yields from these separate areas were all dependent on the production in southern Lake Huron as a whole. After adjusting for the random effect of year × area × month interaction and the fixed effects of area × month interaction, the estimated patterns for the fixed year effect indicated that the Lake Whitefish abundance in Michigan waters of southern Lake Huron declined during the late 2000s but has been relatively constant after 2012.ConclusionThe declines in annual fishery yield were due to and could be explained more by the decreases in fish abundance through 2012 but thereafter primarily reflected the declines in annual fishing effort as the fisheries continued to adjust to the changed fishing conditions. We also provided general lessons for studying fisheries without fishery independent surveys but with detailed seasonal and spatial catch‐and‐effort data.

UTILIZAÇÃO DE SACUBITRIL PARA O TRATAMENTO DE INSUFICIENCIA CARDIACA COM FRAÇÃO DE EJEÇÃO REDUZIDA

The development of heart failure occurs initially due to heart injury, whether chronic or acute. The high rate of morbidity and mortality and hospitalization of heart failure has become a concern over the last few years in view of the challenge of its therapeutic management. The inclusion of sacubitril/valsartan in the treatment protocol of the disease was an achievement for a good prognosis of the disease and has shown good results in reducing the hospitalization rate. The objective is to make a narrative and integrative review of the impact of the use of Sacubitril/valsartan in reducing the hospitalization rate of patients with Heart Failure. This is a narrative and integrative review carried out in the Pubmed/Medline, Google Scholar, Lilacs and SciELO databases. Knowledge of the pathophysiology of HF has become essential for the development of strategies for the pharmacotherapy of the disease. the recommended pharmacotherapy has been expanded to include four types of basic medications, also referred to as quadruple therapy for HFrEF. Among them, the Neprilysin Inhibitor and the Angiotensin II receptor, Sacubitril/valsartan. Although the PARADIGM-HF study showed a benefit of the use of sacubitril/valsartan over enalapril, studies with a larger population scope in relation to the degree of more severe symptoms (NYHA class IV) and with more representative samples of different ethnicities are still needed to evaluate the therapeutic response in a mixed population such as that of Brazil

5hmC-profiles in Puerto Rican Hispanic/Latino men with aggressive prostate cancer.

Puerto Rican (PR) Hispanic/Latino (H/L) men are an understudied population that has the highest prostate cancer (PCa) specific mortality among other Hispanic populations. Little information is known about the higher mortality in PR H/L men. It is thought that epigenetic changes in key genes may play a critical role in aggressive tumors. We aimed to identify key 5-hydroxymethylcytosine (5hmC) changes in PR H/L men with aggressive PCa. We performed sequencing analysis using the 5hmC-enriched DNA from 22 prostate tumors and 24 adjacent normal FFPE samples. We identified 808 differentially methylated genes (DMGs) in tumors compared to adjacent normal tissues (FDR<0.05, log2FC>|0.4|). Pathway analysis of DMGs demonstrated that DNA repair pathway was most upregulated in tumors. Since 5hmC abundance positively correlates with gene expression levels, we further investigated 808 DMGs in TCGA PCa gene expression data. Further, we identified 59 DMGs (80.1%, FDR<0.05, ΔGE (gene expression) >|1|) with significant gene expression changes in the same direction. Additionally, we identified 111 aggressiveness-related DMGs, of which, two hypomethylated genes ( CCDC122 , NUDT15 ) and four hypermethylated genes ( PVT1 , RPL30 , TRMT12 , UBR5 ) were found to be altered at transcriptomic level in a concordant manner in PR H/L PCa patients (N=86). The aberrant 5hmC (N=55) and GE (N=497) changes in these six genes were also associated with progression-free survival in the mixed PCa population. In conclusion, our study identified 59 DMGs showing concordant epigenetic and transcriptomic changes in tumor tissues and 111 DMGs showing association with aggressive PCa among PR H/L men.

Evaluation of the Steno Type 1 Risk Engine in predicting cardiovascular events in an ethnic mixed population of type 1 diabetes mellitus and its association with chronic microangiopathy complications

BackgroundThe Steno Type 1 Risk Engine (ST1RE) was developed to aid clinical decisions in primary prevention for individuals with type 1 diabetes (T1D), as existing cardiovascular (CV) risk models for the general population and type 2 diabetes tend to underestimate CV risk in T1D. However, the applicability of ST1RE in different populations remains uncertain, as prediction models developed for one population may not accurately estimate risk in another. This study aimed to evaluate the performance of the ST1RE in predicting CV events among ethnically mixed T1D individuals and its association with the progression of microangiopathy complications.MethodsA retrospective survey of 435 adults with T1D who were free of CV events at baseline was assessed by ST1RE and chronic diabetes complications at 5 and 10 years of follow-up. The estimated CV risk rates were compared with the observed rates at 5 and 10 years using statistical analyses, including Receiver Operating Characteristic (ROC) curve analysis, Hosmer-Lemeshow test, Kaplan-Meier curves analysis and Cox-regression models.ResultsAmong 435 patients (aged 25 years; interquartile range [IQR]: 21–32) with a median T1D duration of 13 years (IQR: 9–18), only 5% were categorized into the high ST1RE group. Within a median follow-up of 9.2 years (IQR 6.0-10.7), 5.5% of patients experienced a CV event (1.6%, 14.9%, and 50% from the low, moderate, and high-risk groups, respectively). The hazard ratios (HRs) for CV events were greater in the high-risk group (HR 52.02; 95% CI 18.60–145.51, p < 0.001) and in the moderate-risk group (HR 8.66; 95% CI 2.90–25.80, p < 0.001) compared to the low-risk group. The ST1RE estimated CV events were similar to the observed at 5 years (3.4% vs. 3.5%; χ2 = 10.12, p = 0.899) and 10 years (6.8% vs. 9.9%; χ2 = 14.80, p = 0.676) of follow-up. The progression of microangiopathies was greater in the high vs. low for retinopathy (p = 0.008), diabetic kidney disease (p < 0.001), peripheral neuropathy (p = 0.021), and autonomic neuropathy (p = 0.008).ConclusionsST1RE performed well in predicting CV events at 5 and 10 years of follow-up. Moreover, higher ST1RE scores were associated with the progression of microangiopathy complications in this genetically heterogeneous T1D population.Graphical abstract

Genetic Diversity of Yellow and Red Berries Arabica Coffee Populations Grown in a Mix Populations in Garut, West Java, Indonesia, Based on SSR Markers

Farmers in Garut, West Java, grow mixed varieties of Arabica coffee (Coffea arabica L.). Subsequently, they use harvested beans as seeds. Intercrossing among varieties may result in hybrid progenies and harvesting hybrid progenies as seed results in genetic variations. This research aims to evaluate the genetic diversity of Arabica coffee grown in a mixed population. Ninety-one Arabica coffees comprised 37 Arabica cv. “Ahernt GRT KN” (yellow-), 45 “Sigararutang” (red-), and nine “S795” (red berries) were sampled. Twenty SSR primer pairs were validated using 15 samples representing three varieties; six were polymorphic and used to genotype 91 Arabica accessions. Genetic data were analyzed using PowerMaker 3.25 and Darwin version 6 software. The results showed that the six SSR loci generated from 2 – 3 alleles, with an average of 2.17 alleles per locus. Genetic analysis of Arabica coffee from Garut, West Java, generated SSR markers with an average PIC of 0,33 across loci and varieties. The PIC within Arabica coffee cv. “Ahernt GRT KN” and “Sigararutang” were low, and within “S795” was moderate. Those PICs indicate the presence of more genetic diversity within “S795” than the other two cultivars. The Ho across Arabica coffee cv. “Sigararutang” and “S795” were lower than the He values, confirming their self-pollination nature. However, the Ho values of Arabica coffee cv. “Ahernt GRT KN” was larger than the others, indicating the presence of residual heterozygosity and a low percentage of recent outcrossing. The low Ho values of “Sigararutang” suggest that Arabica coffee is homozygous. Arabica coffee cv. “S795” also showed a low Ho value, but its moderate He value indicates the presence of more genetic diversity than the othercultivars.

Relationship Between C-Peptide Levels, Clinical Features, and Serum Data in a Brazilian Type 1 Diabetes Population with Large Variations in Genomic Ancestry.

Type 1 diabetes (T1D) is a chronic disease characterized by the immune-mediated destruction of the pancreatic beta cells responsible for insulin production. The secreted insulin and C-peptide are equimolar. Due to its longer half-life, C-peptide has become a safer means of assessing the pancreatic reserve. C-peptide levels were evaluated in a population of patients with T1D, focusing on the relationship between this variable and other factors. In addition, the influence of C-peptide on metabolic control and microvascular complications was investigated. This cross-sectional study included 95 patients who had been diagnosed with T1D at least five years earlier. These patients were evaluated using a clinical demographic survey, anthropometric data, laboratory tests, and fundoscopy. This study showed that 29.5% of patients had residual insulin secretion, which correlated directly with their age at diagnosis. No statistically significant differences in metabolic control or microvascular complications were observed between the C-peptide level groups. In addition, our results indicate that ancestry does not influence the persistence of residual C-peptide function in our highly mixed population. It is recommended that future research consider incorporating new variables, such as HLA and pancreatic autoimmunity, as factors that may influence residual β-cell function.