Eyeing DNA barcoding for species identification of fish larvae.

Identification of fish larvae based on morphology is typically limited to higher taxonomic ranks (e.g., family or order), as larvae possess few morphological diagnostic characters for precise discrimination to species. When many samples are presented at any one time, the use of morphology to identify such specimens can be laborious and time-consuming. Using a reverse workflow for specimen sorting and identification leveraging high-throughput DNA sequencing, thousands of fish larvae can be DNA barcoded and sorted into molecular operational taxonomic units (mOTUs) in a single sequencing run with the nanopore sequencing technology (e.g., MinION). This process reduces the time and financial costs of morphology-based sorting and instead deploys experienced taxonomists for species taxonomic work where they are needed most. In this study, a total of 3022 fish larval specimens from plankton tows across four sites in Singapore were collected and sorted based on this workflow. Eye tissue from individual samples was used for DNA extraction and sequencing of cytochrome c oxidase subunit I. We generated a total of 2746 barcodes after quality filtering (90.9% barcoding success), identified 2067 DNA barcodes (75.3% identification success), and delimited 256 mOTUs (146 genera, 52 families). Our analyses identified specific challenges to species assignment, such as the potential misidentification of publicly available sequences used as reference barcodes. We highlighted how the conservative application and comparison of a local sequence database can help resolve identification conflicts. Overall, this proposed approach enables and expedites taxonomic identification of fish larvae, contributing to the enhancement of reference barcode databases and potentially better understanding of fish connectivity.

Effectiveness of Multilevel and Multidomain Interventions to Improve Glycemic Control in U.S. Racial and Ethnic Minority Populations: A Systematic Review and Meta-analysis.

BACKGROUND: Racial and ethnic disparities in type 2 diabetes outcomes are a major public health concern. Interventions targeting multiple barriers may help address disparities. PURPOSE: To conduct a systematic review and meta-analysis of diabetes self-management education (DSME) interventions in minority populations. We hypothesized that interventions addressing multiple levels (individual, interpersonal, community, and societal) and/or domains (biological, behavioral, physical/built environment, sociocultural environment, and health care system) would have the greatest effect on hyperglycemia. DATA SOURCES: We performed an electronic search of research databases PubMed, Scopus, CINAHL, and PsycINFO (1985-2019). STUDY SELECTION: We included randomized controlled trials of DSME interventions among U.S. adults with type 2 diabetes from racial and ethnic minority populations. DATA EXTRACTION: We extracted study parameters on DSME interventions and changes in percent hemoglobin A1c (HbA1c). DATA SYNTHESIS: A total of 106 randomized controlled trials were included. Twenty-five percent (n = 27) of interventions were exclusively individual-behavioral, 51% (n = 54) were multilevel, 66% (n = 70) were multidomain, and 42% (n = 45) were both multilevel and multidomain. Individual-behavioral interventions reduced HbA1c by -0.34 percentage points (95% CI -0.46, -0.22; I2 = 33%) (-3.7 [-5.0, -2.4] mmol/mol). Multilevel interventions reduced HbA1c by -0.40 percentage points (95% CI -0.51, -0.29; I2 = 68%) (-4.4 [-5.6, -3.2] mmol/mol). Multidomain interventions reduced HbA1c by -0.39 percentage points (95% CI -0.49, -0.29; I2 = 68%) (-4.3 [-5.4, -3.2] mmol/mol). Interventions that were both multilevel and multidomain reduced HbA1c by -0.43 percentage points (95% CI -0.55, -0.31; I2 = 69%) (-4.7 [-6.0, -3.4] mmol/mol). LIMITATIONS: The analyses were restricted to RCTs. CONCLUSIONS: Multilevel and multidomain DSME interventions had a modest impact on HbA1c. Few DSME trials have targeted the community and society levels or physical environment domain. Future research is needed to evaluate the effects of these interventions on outcomes beyond HbA1c.

Recent progress in one-pot enzymatic synthesis and regeneration of high-value cofactors.

One-pot enzymatic synthesis is flourishing in synthetic chemistry, heralding a sustainable and green era. Recent advancements enable the creation of complex enzymatic prosthetic groups and regeneration of enzymatic cofactors such as S-adenosylmethionine. The next frontier is to develop the effective and innovative cofactors for essential micronutrients, metabolic modulators, and biomedicines.

Cluster Randomized Trial of Diabetes Group Visits in Community Health Centers across the Midwest.

BACKGROUND: Diabetes group visits (GVs) have not been rigorously evaluated in community health centers. METHODS: This cluster randomized controlled study recruited adults with diabetes mellitus with glycosylated hemoglobin, A1C greater than or equal to eight percent: 75 intervention and 120 usual care. Group visit patients completed a six-month program. Primary outcome was A1C change from baseline to 12 months. RESULTS: Participants improved their A1C by 0.38%-0.40% with no difference across arms (p=.63). Group visit patients improved their diabetes social support, knowledge, and distress and were more likely to receive guideline-based care compared with control. Group visit patients with anxiety or depression were more likely to have a visit with behavioral health compared with usual care (p=.02). CONCLUSIONS: Community health center patients with diabetes had improvements in glucose control across arms. Group visits improved the receipt of mental health care and guideline-based care.

Patient compliance to sublingual immunotherapy for mite-induced allergic rhinitis: A retrospective study.

Background: Compliance to sublingual immunotherapy (SLIT) is generally low, resulting in reduced short- and long-term clinical efficacy. Compliance is a critical factor determining the success of allergic rhinitis (AR) treatment. Objective: To analyze the compliance of patients with house dust mite (HDM)-induced AR to SLIT and the impact of coronavirus disease 2019 (COVID-19) on compliance. Methods: The clinical data of 3117 patients with HDM-induced AR who started SLIT between July 2018 and April 2022 were retrospectively reviewed. We assessed the reasons for non-compliance and the changes in non-compliance during the COVID-19 pandemic compared to the pre-pandemic period. Results: Of 3117 patients, 507 (16.27%) patients (ages, 5-67 years) were identified as non-compliant. The most common reason for non-compliance was poor efficacy (27.22%). The non-compliance rate was highest during 24-36 months of SLIT (28.13%, 153/544), followed by 12-24 months (7.02%, 91/1296). Non-compliance was significantly higher in adolescents/adults than in children (P = 0.000). Although the generalized linear model analysis indicated that compliance was affected by the COVID-19 pandemic during 3-6 months of SLIT, the overall compliance to SLIT was not significantly affected by the pandemic, according to the Kaplan-Meier survival analysis. Conclusions: The non-compliance rate of SLIT in this study was low, and poor efficacy was the most common reason for non-compliance. The compliance of adolescents/adults was lower than that of children. The COVID-19 pandemic did not significantly impact compliance to SLIT, which is an appropriate strategy for the home treatment of AR patients during major public health events.

Investigation of the mechanical behavior of rock-like material with two flaws subjected to biaxial compression.

The biaxial compression experiments of rock-like materials with two flaws are carried out under different flaw inclination angle, rock bridge ligament angle, lateral stress. The experimental studies show that crack propagation modes of rock-like material are as follows: wing crack through mode (Y mode), shear crack through mode (J mode), mixed crack through mode (wing shear JY mode), longitudinal extension of crack and transverse shear splitting. prefabricated fractured rock specimens have experienced the closing stage of prefabricated fractures, the elastic deformation stage, the generation and expansion of cracks (or plastic strengthening), and the residual loading stage. The peak strength of the specimen is increases with the increase of flaw inclination angle and lateral stress. With the increase of the rock bridge ligament angle, the failure of the rock bridge region changes from the shear crack failure to composite failure of shear crack and the wing type tensile crack failure, and then to the wing crack failure. With the increase of the lateral pressure, the failure of the specimen changes from the wing type tensile crack failure to the wing type and shear crack failure, and then to shear crack failure. The flaw inclination angle mainly changes the form of crack growth but does not effect on the failure modes. The counting number of acoustic emission events at the center of the sample is relative large, indicating that the cacks appear in the part of the rock bridge firstly. With the increasing of loads, the cracks of the rock bridge expanding constantly and connecting finally. The changes of acoustic emission event counts is consistent with the macroscopic damage form obtained from the experiments.

Comparison of two propensity score-based methods for balancing covariates: the overlap weighting and fine stratification methods in real-world claims data.

BACKGROUND: Two propensity score (PS) based balancing covariate methods, the overlap weighting method (OW) and the fine stratification method (FS), produce superb covariate balance. OW has been compared with various weighting methods while FS has been compared with the traditional stratification method and various matching methods. However, no study has yet compared OW and FS. In addition, OW has not yet been evaluated in large claims data with low prevalence exposure and with low frequency outcomes, a context in which optimal use of balancing methods is critical. In the study, we aimed to compare OW and FS using real-world data and simulations with low prevalence exposure and with low frequency outcomes. METHODS: We used the Texas State Medicaid claims data on adult beneficiaries with diabetes in 2012 as an empirical example (N = 42,628). Based on its real-world research question, we estimated an average treatment effect of health center vs. non-health center attendance in the total population. We also performed simulations to evaluate their relative performance. To preserve associations between covariates, we used the plasmode approach to simulate outcomes and/or exposures with N = 4,000. We simulated both homogeneous and heterogeneous treatment effects with various outcome risks (1-30% or observed: 27.75%) and/or exposure prevalence (2.5-30% or observed:10.55%). We used a weighted generalized linear model to estimate the exposure effect and the cluster-robust standard error (SE) method to estimate its SE. RESULTS: In the empirical example, we found that OW had smaller standardized mean differences in all covariates (range: OW: 0.0-0.02 vs. FS: 0.22-3.26) and Mahalanobis balance distance (MB) (< 0.001 vs. > 0.049) than FS. In simulations, OW also achieved smaller MB (homogeneity: <0.04 vs. > 0.04; heterogeneity: 0.0-0.11 vs. 0.07-0.29), relative bias (homogeneity: 4.04-56.20 vs. 20-61.63; heterogeneity: 7.85-57.6 vs. 15.0-60.4), square root of mean squared error (homogeneity: 0.332-1.308 vs. 0.385-1.365; heterogeneity: 0.263-0.526 vs 0.313-0.620), and coverage probability (homogeneity: 0.0-80.4% vs. 0.0-69.8%; heterogeneity: 0.0-97.6% vs. 0.0-92.8%), than FS, in most cases. CONCLUSIONS: These findings suggest that OW can yield nearly perfect covariate balance and therefore enhance the accuracy of average treatment effect estimation in the total population.

Hallmarks of cancer resistance.

This review explores the hallmarks of cancer resistance, including drug efflux mediated by ATP-binding cassette (ABC) transporters, metabolic reprogramming characterized by the Warburg effect, and the dynamic interplay between cancer cells and mitochondria. The role of cancer stem cells (CSCs) in treatment resistance and the regulatory influence of non-coding RNAs, such as long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and circular RNAs (circRNAs), are studied. The chapter emphasizes future directions, encompassing advancements in immunotherapy, strategies to counter adaptive resistance, integration of artificial intelligence for predictive modeling, and the identification of biomarkers for personalized treatment. The comprehensive exploration of these hallmarks provides a foundation for innovative therapeutic approaches, aiming to navigate the complex landscape of cancer resistance and enhance patient outcomes.

Cellular Aging and Senescence in Cancer: A Holistic Review of Cellular Fate Determinants.

This comprehensive review navigates the complex relationship between cellular aging, senescence, and cancer, unraveling the determinants of cellular fate. Beginning with an overview of cellular aging's significance in cancer, the review explores processes, changes, and molecular pathways influencing senescence. The review explores senescence as a dual mechanism in cancer, acting as a suppressor and contributor, focusing on its impact on therapy response. This review highlights opportunities for cancer therapies that target cellular senescence. The review further examines the senescence-associated secretory phenotype and strategies to modulate cellular aging to influence tumor behavior. Additionally, the review highlights the mechanisms of senescence escape in aging and cancer cells, emphasizing their impact on cancer prognosis and resistance to therapy. The article addresses current advances, unexplored aspects, and future perspectives in understanding cellular aging and senescence in cancer.

A nurse driven care management program to engage older diabetes patients in personalized goal setting and disease management.

Background and Aims: Multiple diabetes care guidelines have called for the personalization of risk factor goals, medication management, and self-care plans among older patients. Study of the implementation of these recommendations is needed. This study aimed to test whether a patient survey embedded in the Electronic Healthcare Record (EHR), coupled with telephonic nurse care management, could engage patients in personalized goal setting and chronic disease management. Methods: We conducted a single-center equal-randomization delayed comparator trial at the primary care clinics of the University of Chicago Medicine from 2018.6 to 2019.12. Patients over the age of 65 years with type 2 diabetes with an active patient portal account were recruited and randomized to receive an EHR embedded goal setting and preference survey immediately in the intervention arm or after 6 months in the delayed intervention control arm. In the intervention arm, nurses reviewed American Diabetes Association recommendations for A1C goals based on health status class, established personalized goals, and provided monthly telephonic care management phone calls for a maximum of 6 months. Our primary outcome was the documentation of a personalized A1C goal in the EHR. Results: A total of 100 patients completed the trial (mean age, 72.51 [SD, 5.22] years; mean baseline A1C, 7.14% [SD, 1.06%]; 68% women). The majority were in the Healthy (59%) followed by Complex (30%) and Very Complex (11%) health status classes. Documentation of an A1C goal in the EHR increased from 42% to 90% (p < 0.001) at 6 months in the intervention group and from 54% to 56% in the control group. Across health status classes, patients set similar A1C goals. Conclusions: Older patients can be engaged in personalized goal setting and disease management through an embedded EHR intervention. The clinical impact of the intervention may differ if deployed among older patients with more complex health needs and higher glucose levels. Trial Registration: ClinicalTrials.gov Identifier: NCT03692208.

Zoonotic infections by avian influenza virus: changing global epidemiology, investigation, and control.

Avian influenza virus continues to pose zoonotic, epizootic, and pandemic threats worldwide, as exemplified by the 2020-23 epizootics of re-emerging H5 genotype avian influenza viruses among birds and mammals and the fatal jump to humans of emerging A(H3N8) in early 2023. Future influenza pandemic threats are driven by extensive mutations and reassortments of avian influenza viruses rooted in frequent interspecies transmission and genetic mixing and underscore the urgent need for more effective actions. We examine the changing global epidemiology of human infections caused by avian influenza viruses over the past decade, including dramatic increases in both the number of reported infections in humans and the spectrum of avian influenza virus subtypes that have jumped to humans. We also discuss the use of advanced surveillance, diagnostic technologies, and state-of-the-art analysis methods for tracking emerging avian influenza viruses. We outline an avian influenza virus-specific application of the One Health approach, integrating enhanced surveillance, tightened biosecurity, targeted vaccination, timely precautions, and timely clinical management, and fostering global collaboration to control the threats of avian influenza viruses.

Substrate-Controlled Divergent Synthesis of Benzimidazole-Fused Quinolines and Spirocyclic Benzimidazole-Fused Isoindoles.

A Rh(III)-catalyzed annulation of 2-arylbenzimidazoles with α-diazo carbonyl compounds via C-H activation/carbene insertion/intramolecular cyclization is explored. The switchable product selectivity is achieved by the use of distinct α-diazo carbonyl compounds. Benzimidazole-fused quinolines are obtained through [4 + 2] annulation exclusively when 2-diazocyclohexane-1,3-diones are used, where they act as a C2 synthon. Alternatively, diazonaphthalen-1(2H)-ones merely function as a one-carbon unit synthon to generate a quaternary center through [4 + 1] cyclization to afford spirocyclic benzimidazole-fused isoindole naphthalen-2-ones. A thorough mechanistic study reveals the course of the reaction.

Real-world applications of the new grading system in lung adenocarcinoma: A study of 907 patients focusing on revealing the relationship between pathologic grade and genetic status.

BACKGROUND: The status of the lung adenocarcinoma (LUAD) grading system and the association between LUAD differentiation, driver genes, and clinicopathological features remain to be elucidated. METHODS: We included patients with invasive non-mucinous LUAD, evaluated their differentiation, and collected available clinicopathological information, gene mutations, and analyzed clinical outcomes. RESULTS: Among the 907 patients with invasive non-mucinous LUAD, 321 (35.4 %) were poorly differentiated, 422 (46.5 %) were moderately differentiated, and 164 (18.1 %) were well differentiated. EGFR mutation was more common in the LUADs accompanied without CGP (complex glandular pattern) than LUADs with CGP (p < 0.001). Correlation analysis between mutations and clinical characteristics showed that EGFR gene mutation (p < 0.001), KRAS gene mutation (p < 0.05), and ALK gene rearrangement (p < 0.001) were significantly related to the degree of tumor differentiation, and the KRAS and ALK gene mutation frequencies were higher in the low-differentiation group than in the high and medium differentiation groups. The EGFR mutation frequency was higher in the well/moderately differentiated adenocarcinoma group. CONCLUSIONS: Our study adds to the evidence regarding the role of the grading system in prognosis. EGFR, KRAS, and ALK are related to the degree of tumor differentiation.

TSH Trajectories During Levothyroxine Treatment in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) Cohort.

CONTEXT: Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time. OBJECTIVE: This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period. METHODS: Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization. RESULTS: From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes. CONCLUSION: GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes.

Targeting PI3K/AKT/mTOR signaling to overcome drug resistance in cancer.

This review comprehensively explores the challenge of drug resistance in cancer by focusing on the pivotal PI3K/AKT/mTOR pathway, elucidating its role in oncogenesis and resistance mechanisms across various cancer types. It meticulously examines the diverse mechanisms underlying resistance, including genetic mutations, feedback loops, and microenvironmental factors, while also discussing the associated resistance patterns. Evaluating current therapeutic strategies targeting this pathway, the article highlights the hurdles encountered in drug development and clinical trials. Innovative approaches to overcome resistance, such as combination therapies and precision medicine, are critically analyzed, alongside discussions on emerging therapies like immunotherapy and molecularly targeted agents. Overall, this comprehensive review not only sheds light on the complexities of resistance in cancer but also provides a roadmap for advancing cancer treatment.

Investigation of subclinical ocular inflammation in the aqueous humor of patients with myopia following bilateral sequential collamer lens implantation.

BACKGROUND: The aqueous humor, a transparent fluid secreted by the ciliary body, supports the lens of the eyeball. In this study, we analyzed the cytokine and chemokine profiles within the aqueous humor of the contralateral eye post-implantation of an implantable collamer lens (ICL) to evaluate potential subclinical inflammation in the second eye subsequent to ICL implantation in the first eye. METHODS: Aqueous humor samples were procured from both eyes of 40 patients (totaling 80 eyes) prior to bilateral ICL insertion. Subsequently, a comprehensive statistical analysis was conducted using the Luminex assay to quantify 30 different cytokines in these samples. RESULTS: Compared to the first eye, the aqueous humor of the second eye demonstrated decreased concentrations of IFN-γ (P = 0.038), IL-13 (P = 0.027), IL-17/IL-17 A (P = 0.012), and IL-4 (P = 0.025). No significant differences were observed in other cytokine levels between the two groups. Patients were then categorized based on the postoperative rise in intraocular pressure (IOP) in the first eye. The group with elevated IOP displayed elevated levels of EGF in the aqueous humor of the first eye (P = 0.013) and higher levels of PDGF-AB/BB in the aqueous humor of the second eye (P = 0.032) compared to the group with normal IOP. Within the elevated IOP group, the levels of EGF (P = 0.013) and IL-17/IL-17 A (P = 0.016) in the aqueous humor were lower in the second eye than in the first eye. In the normal IOP group, cytokine levels did not differ notably between eyes. CONCLUSION: Following sequential ICL implantation, it appears that a protective response may be activated to mitigate subclinical inflammation in the second eye induced by the initial implantation in the first eye. Additionally, the increase in IOP subsequent to surgery in the first eye may correlate with the presence of inflammatory mediators in the aqueous humor.

Update on Musculoskeletal Pain Management.

Pain is the most common complaint reported to orthopedists in the outpatient clinic, emergency room, or booth. Numerous publications report the inadequate management of both acute and chronic pain by health professionals. This updated article aims to provide information about musculoskeletal pain, its classification, evaluation, diagnosis, and the multimodal therapeutic approach for each case. For acute pain, adequate control allows for earlier rehabilitation to work and reduces the rates of pain chronification. For chronic pain, the goal is to reduce its intensity and improve the quality of life. Currently, some procedures are increasingly used and aided by imaging tests for diagnostic and therapeutic purposes.

Utilization, quality, and spending for pediatric Medicaid enrollees with primary care in health centers vs non-health centers.

BACKGROUND: Limited research has explored the performance of health centers (HCs) compared to other primary care settings among children in the United States. We evaluated utilization, quality, and expenditures for pediatric Medicaid enrollees receiving care in HCs versus non-HCs. METHODS: This national cross-sectional study utilized 2012 Medicaid Analytic eXtract (MAX) claims to examine children 0-17 years with a primary care visit, stratified by whether majority (> 50%) of primary care visits were at HCs or non-HCs. Outcome measures include utilization (primary care visits, non-primary care outpatient visits, prescription claims, Emergency Department (ED) visits, hospitalizations) and quality (well-child visits, avoidable ED visits, avoidable hospitalizations). For children enrolled in fee-for-service Medicaid, we also measured expenditures. Propensity score-based overlap weighting was used to balance covariates. RESULTS: A total of 2,383,270 Medicaid-enrolled children received the majority of their primary care at HCs, while 18,540,743 did at non-HCs. In adjusted analyses, HC patients had 20% more primary care visits, 15% less non-primary care outpatient visits, and 21% less prescription claims than non-HC patients. ED visits were similar across the two groups, while HC patients had 7% lower chance of hospitalization than non-HC. Quality of care outcomes favored HC patients in main analyses, but results were less robust when excluding managed care beneficiaries. Total expenditures among the fee-for-service subpopulation were lower by $239 (8%) for HC patients. CONCLUSIONS: In this study of nationwide claims data to evaluate healthcare utilization, quality, and spending among Medicaid-enrolled children who receive primary care at HCs versus non-HCs, findings suggest primary care delivery in HCs may be associated with a more cost-effective model of healthcare for children.