The Kitsune Optimization Algorithm (KOA), inspired by the mythical Kitsune, introduces a transformative approach in the realm of metaheuristic optimization. This paper presents an in-depth analysis of KOA, underlining its exceptional capabilities in terms of enhanced convergence speed, accuracy, and robustness. Empirical results from 12 benchmark functions along with optimizing power output in Photovoltaic (PV) systems reveal KOA’s rapid convergence capabilities, significantly reducing computational time. In comparison to established algorithms, KOA shows a marked improvement in convergence speed, reaching optimal solutions faster by an average of first 5 iterations. In terms of accuracy, KOA demonstrates an impressive ability to locate global optima with a lower average error margin of 98 %, indicating a substantial increase in solution precision over traditional methods. This level of accuracy is particularly evident in complex multi-modal landscapes, where KOA consistently outperforms its counterparts. Furthermore, KOA exhibits exceptional robustness across various test scenarios, maintaining consistent performance and exhibiting a high level of stability. This robustness is further evidenced in real-world applications, such as the optimization of power output in Photovoltaic (PV) systems, where KOA adapts effectively to dynamic environmental conditions, showcasing its practical applicability and reliability. Overall, the Kitsune Optimization Algorithm sets a new benchmark in the field of metaheuristic algorithms with its enhanced convergence speed, superior accuracy, and robustness, making it a promising tool for tackling complex optimization problems in diverse domains.

The impact of PM2.5 on asthma: A two-sample Mendelian randomization studyBin Feng1, Ling Chao2*1. School of Management, Xinxiang Medical University, Environmental Health Section, Xinxiang Health Technology Supervision Center, Xinxiang, Henan Province453003, China2. School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province，453003, ChinaCorresponding author:Ling chao, Email: chaoling2004@163.com, School of Public Health, Xinxiang Medical University, Xinxiang, Henan Province 453003, China.CONFLICT OF INTEREST STATEMENT:The authors have declared that no conflict of interests.Availability of data and materials: The data are available from public datasets that could be found in IEU OPEN GWAS.Acknowledgements: All authors have made substantive contributions to the manuscript.Keywords: PM; allergic diseases; Mendelian randomization;To the Editor:In recent decades, the relationship between particulate matter (PM) and asthma has been a topic of considerable research interest and debate in the field of environmental health [1, 2]. Mendelian randomization (MR), a methodological approach that leverages genetic variants as instrumental variables to infer causal relationships between exposures and outcomes, has been employed in some studies to explore the potential causal link [3, 4]. In this study, two-sample MR was applied to GWAS summary statistics of PM2.5 and asthma using R (version 4.3.2). IVs were chosen based on genome-wide significance thresholds (p < 5×10-8) . The primary analytical approach employed was the Inverse Variance Weighted (IVW) method, while supplementary measures encompassed the Weighted Median Model, MR-Egger, Simple Model, and Weighted Model methods. Additionally, pleiotropy and heterogeneity were evaluated using MR-Egger intercept test and Cochrane’s Q test. A sensitivity analysis was conducted utilizing the leave-one-out method. Results shows eight genome-wide significant single nucleotide polymorphisms (SNPs) associated with PM2.5exposure were extracted as instrumental variables (IVs). Asthma data from three independent GWAS summary statistics were utilized to estimate the causal effect of PM2.5 exposure on asthma (ukb-b-11297 [14283 cases, 98300 controls]; ukb-a-255 [10589 cases, 72940 controls]; ukb-d-J10-asthma [1993 cases, 359201 controls]). Our MR results from three databases show that PM2.5 was not associated with the risk of Asthma. The Inverse Variance Weighted (IVW) results from the three datasets were combined using a fixed-effect model, revealing no significant evidence of a causal effect of PM on asthma (OR = 0.99, 95% CI: 0.98-1.01) (Figure 1). No heterogeneity or pleiotropy was detected in the results. MR effect of and sensitivity analyses further supported the robustness of our findings (Figure S1). Overall, this study contributes to understanding the complex relationship between PM2.5exposure and asthma, emphasizing the importance of continued research in this area. While our study contributes valuable insights into the PM2.5-asthma relationship, several limitations warrant acknowledgment. Foremost among these is the reliance on GWAS data predominantly derived from European populations, which may limit the generalizability of our findings to diverse ethnic and geographical contexts. Future research endeavors should prioritize the inclusion of diverse populations and comprehensive genetic data to enhance the external validity and generalizability of findings. Furthermore, Mendelian randomization (MR) provides a powerful framework for causal inference, it relies on the assumption of instrument validity—that the selected genetic variants are robustly associated with the exposure of interest and are not influenced by confounding factors. While we rigorously assessed the validity of instrumental variables (IVs), potential biases or unmeasured confounders may still exist, which could impact the validity of our causal inference [5].

The identification of key features related to the phenotype of interest (POI) from high-dimensional data has been one of the most important issues for omics-data studies, such as transcriptome or DNA methylome data. However, these data are commonly contaminated by sources of unwanted variation caused by platforms, batches or other types of biological factors. Thus, the data can be considered as a combination of variation derived from POI and other confounding factors. Not taking these factors into consideration could lead to spurious associations and missing important signals. Based on this idea, we propose a novel feature selection method called Decision Variable Analysis (DVA) to extract the important features related to POI from the data containing potential confounding factors. Using this method on the simulated data and real data, respectively, we found DVA performed better in identifying confounding factors compared to other methods, including linear regression and surrogate variable analysis. Especially, our method is more efficient for the data in which there are much more feature numbers than sample sizes. We show improvements of DVA across high-dimensional datasets with smaller sample sizes compared to feature numbers on different platforms. The results indicate that DVA is an effective method to dissect sources of variation for omics-data with potential confounding factors. DVA is freely available for use at https://github.com/xvon1/DVA.

The low incidence of vincristine-induced peripheral neuropathy (VIPN) in Kenyan children may result from low vincristine exposure. We performed a pharmacokinetically (PK) guided dose-escalation feasibility study of vincristine in Kenyan children (NCT05844670). Vincristine PK exposure was assessed with a previously developed nomogram. A 20% dose increase was recommended for participants with low exposure and no VIPN, hyperbilirubinemia or malnutrition. None of the fifteen participants developed VIPN. Low vincristine exposure was seen in only one participant: a dose increase was implemented without side-effects. Average vincristine exposure was high. In conclusion, the participants did not develop VIPN despite having high vincristine exposure.

An 11-year-old boy with Lowe syndrome developed secondary sexual characteristics within a few weeks, suggestive of precocious puberty. His blood tests were positive for serum-human chorionic gonadotropin, and imaging revealed a right thymic lobe mass containing small cystic lesions. A germ cell tumor with malignant potential was suspected. Thus, we performed an extended thymectomy with mediastinal lymph node dissection and confirmed germinoma of the right thymic lobe without lymph node metastasis; the patient underwent four courses of chemotherapy. Follow-up evaluations indicated no recurrence. Thus, we present a highly rare case report of thymic germinoma complicated by Lowe syndrome.

Synergistic changes between tumor-associated macrophages (TAMs) and tumor-associated fibroblasts (CAFs) aggravated immune evasion of hepatocellular carcinoma (HCC), however, the underlying molecular mechanisms remain elusive. Their continuous and dynamic interactions are subject to bioactive molecule changes. A real-time and in-situ monitoring method suitable for in vivo research of these processes would be indispensable but is scarce. In this study, a dual imaging strategy that tracing the TAMs and CAFs simultaneously was developed using a new arginase-specific probe and established CAFs-specific probe. The emerging roles of arginase in mediating CAFs activation in mice were explored. Results showed arginase up-regulation in TAMs, followed by proline increase. Subsequently, proline produced by TAMs initiated the activation of CAFs. Through the JAK-STAT signaling, CAFs up-regulated the PD-L1 and CTLA-4, ultimately promoting immune evasion of HCC. This study revealed a new mechanism by which TAMs and CAFs collaborate in immune evasion, providing new targets for HCC immunotherapy.

It has been reported that the intrinsic open-shell quinone radical electronic ground state is commonly present in classic narrow bandgap donor-acceptor organic semiconductors. Among them, aromatic inorganic acid radicals are one of the important categories of classical narrow bandgap donor-acceptor type organic semiconductors and display unique physical properties and electronic ground states. Generally, the conjugated planes play a crucial role in stabilizing multi-radical electronic systems. In this paper, we are the first to design, synthesize, and report fully planar graphene-like two-dimensional aromatic oxalic acid radical IDF-O8 based on the aromatic inorganic acid radical system, and study the physical properties of this aromatic high spin pan. In this graphene-like structure, the electron-withdrawing group of ketones can effectively delocalize radical electrons and achieve stability. In addition to exhibiting strong spin signals, the temperature of IDF-O8 reached 147 °C in aggregated state under the irradiation of 808 nm (1.2 W cm-2). This work provides a novel planarized radical design strategy and has great potential in seawater desalination.

In semi-batch reactors (SBRs), exothermic reactions can still result in thermal runaway accidents due to improper process conditions. Mass transfer processes as well as the dissolution heat make the thermal behavior of gas-liquid reactions more variable. This study aims to propose safety criteria for gas-liquid reactions in SBRs. A dimensionless mathematical model of the gas-liquid reaction in SBRs was firstly established to determine the thermal runaway critical conditions by considering the mass transfer process. The safety boundary diagram and temperature diagram applicable for the gas-liquid reaction were constructed, along with a procedure for determining safe operating conditions for gas-liquid reactions in SBRs. The mass transfer coefficient, Henry’s constant and the dissolution heat all have a great influence on the thermal behavior of the reactions. A series of calorimetry experiments were carried out for the reaction between carbon dioxide and aqueous ammonia solution using RC1 to determine critical operating conditions.

Background: Post-traumatic stress disorder (PTSD) is one of the most prevalent mental health issues among emergency nurses, particularly in the aftermath of the COVID-19 pandemic. However, there is a scarcity of empirical studies on improving PTSD and related symptoms. Objective: To investigate the effectiveness of the mindfulness-based stress reduction (MBSR) program in reducing PTSD symptoms, emotional exhaustion, and coping styles among emergency nurses. Methods: A randomized clinical trial was conducted with 74 emergency nurses experiencing symptoms of PTSD who were recruited from two hospitals. Participants were randomly assigned to either the intervention group (n=38) or the comparison group (n=36) using a random number calculation procedure. The intervention group received an 8-week MBSR program, while the comparison group had the option to receive the same training upon completion of the study. Self-reported data on mindfulness, PTSD symptoms, emotional exhaustion, and coping styles were evaluated at baseline, after treatment, and 1-month of follow-up. Results: Participants in the MBSR group showed a significant improvement in PTSD symptoms (M(I-J)=-7.789, P<0.001, 95% CI=3.642~11.937), emotional exhaustion (M(I-J)=4.763, P=0.004, 95%CI=1.274~8.253) and mindfulness (M(I-J)=-7.421, P<0.001, 95%CI=-12.349~2.493) after treatment. These effects were sustained up to 1-month follow-up. No significant improvement in coping style was observed in any of the subjects. Conclusion: MBSR is feasible and effective in reducing symptoms of PTSD and emotional exhaustion among emergency nurses. However, it has a lesser effect on coping styles. MBSR has the potential to alleviate the psychological impact of occupational stress on nurses.

Majd Khadra M.D.1, Kenan Abou Chaer M.D.1, Brittany Bahri M.D.1, Rida Farook2, Camila Arellano2, Naveed Shaikh M.D.3Affiliations: 1-Internal Medicine, Detroit Medical Center/Wayne State University, Detroit, USA                        2-Wayne State University, School of medicine, Detroit, USA                         3-Internal Medicine, Veterans Affairs Medical Center, Detroit, USAAbstractNotably, instead of the superior mesenteric vein, our case had a novel combination of portal vein thrombosis and Inferior mesenteric vein thrombosis. This patient might have an underlying, undetected thrombophilia because of the presence of both inferior mesenteric vein(IMV) and portal vein thrombosis. 60-75% of mesenteric venous thrombosis cases are thought to be caused by hypercoagulable conditions brought on by heparin use, thrombocytopenia, myeloproliferative disease, and cancer, according to recent research. The usual conditions that are linked to the combination of inferior mesenteric vein and portal vein thrombosis are pancreatitis, diverticulitis, myeloproliferative neoplasms, and malignancies, none of which our patient had.IntroductionA deep-vein thrombosis (DVT) is a blood clot that forms within the deep veins, usually of the leg, but can occur in the arms, mesenteric, portal and cerebral veins. Portal vein thrombosis (PVT) is a vascular disease of the liver that occurs when a blood clot occurs in the hepatic portal vein, which can lead to increased pressure in the portal vein system and reduced blood supply to the liver.Case PresentationA 75 year old male with past medical history of hypertension, COPD, hyperlipidemia, type 2 diabetes mellitus, GERD, and polysubstance use disorder presented to the emergency department for periumbilical pain. He stated that his stomach was “not feeling right”. He attributed the discomfort to food poisoning. However he denied nausea, vomiting, and diarrhea. He reported normal, formed, non-bloody bowel movements. He denied any family history of blood clotting disorders or hypercoagulability. In the emergency department, the patient was hemodynamically stable with unremarkable lab findings. Our team ordered CT of the abdomen and pelvis [Figure 1 , 2 ] which showed non-occlusive thrombus within the inferior mesenteric vein (IMV) and the proximal branch of the right portal vein. Patient was started on intramuscular Lovenox 70 mg injection twice daily. He was admitted for management and workup of hypercoagulable state. The patient’s hospital course was uncomplicated. He did not require surgical intervention and was discharged to follow up as an outpatient.

In this paper we tackled out a model to study the phenomena of superinfection, that is we consider two serotypes I 1 and I 2 of the same type of disease acting on the same population, a competitive system. Assuming that the total population is fixed, we reduce the model to a bidimensional systems of ODE. In the first part we consider that all coefficients in the equations are constant. Then we describe the coexistence state and its stability in terms of the Reproduction Number corresponding to both serotypes. In the second part, we introduce periodic coefficients in the same model, and analyze the corresponding model with periodic coefficients, which now is a non-autonomous system. We give the necessary and sufficient conditions to have periodic orbits and non trivial coexistence states, in the last case we also show the conditions to have local stability of them. In both cases we do several numerical simulations to illustrate some of the phenomena that we are describing.

Synthetic identity fraud poses a pervasive threat to national security, presenting formidable challenges to financial systems, government bodies, and businesses. This study scrutinizes the severity of synthetic identity fraud as a paramount national security issue, emphasizing its complex nature, the vulnerabilities it exploits, and its diverse impacts on society. Synthetic identity fraud entails fabricating identities by amalgamating authentic and falsified information, complicating detection for conventional authentication methods. This sophisticated approach empowers fraudsters to establish credit profiles, initiate account openings, and engage in unlawful activities under false pretenses, leading to significant financial losses and eroding trust in institutions. Moreover, synthetic identities are increasingly leveraged in organized crime, terrorism financing, and illicit activities, intensifying the national security threat. The anonymity provided by synthetic identities hampers law enforcement efforts, impeding the identification and apprehension of perpetrators. Tackling synthetic identity fraud necessitates a holistic strategy incorporating technological advancements, regulatory adjustments, and collaborative endeavors among stakeholders. Advanced data analytics, biometric authentication, and machine learning algorithms present promising avenues for early detection and mitigation of synthetic identity schemes. Additionally, robust identity verification protocols and information-sharing frameworks are imperative for reinforcing the resilience of financial ecosystems and protecting national interests. This study underscores the urgency for policymakers, law enforcement agencies, financial institutions, and technology providers to prioritize synthetic identity fraud as a critical national security concern. Through fostering cooperation and implementing proactive measures, stakeholders can strengthen defenses, disrupt criminal networks, and uphold the integrity of economic and societal structures amidst evolving threats.

The paradigm shift of intergenerational relationships demands investigation into parenting practices as determinants of emerging adult behaviors. The current study examined whether Pakistani emerging adults’ perceptions of parental autonomy support and control predict their filial behaviors and whether filial closeness explains this relationship. 218 university students (Mage = 20.73, SD = 1.48, 52.3% male) from Islamabad, Pakistan, recruited through convenience sampling, completed measures of perceived parental behaviors, filial behaviors, and filial closeness. Mediation analysis using PROCESS by Hayes was conducted to find that filial closeness partially and fully explains the relationship between autonomy support and control, respectively, with filial behaviors. Therefore, parental autonomy support and control lead to significant changes in perceived closeness by Pakistani emerging adults which determine the care they provide to parents. The findings direct focus on programs and policies targeted towards parents to promote healthy family dynamics by regulating parental control and autonomy supportive behaviors.

Despite of high annual rate of surgery worldwide, few national-level studies have explored the epidemiological aspects of various types of hernia repairs. Our study aims to examine the 5-year prevalence of hernia repairs in Australian adults. The number of hernia repair surgeries for femoral, inguinal, incisional, other abdominal, and epigastric hernias were extracted from the Australian Institute of Health and Welfare (AIHW) database from financial year (FY) FY2017 to FY2021. We calculated age-specific prevalence and prevalence ratio (PR) with a 95% confidence interval (CI) to compare the prevalence of hernia repairs by age group and sex. The highest prevalence per 100,000 population of hernia repairs was found in inguinal (223), followed by epigastric (111), other abdominal (59), incisional (52), and femoral hernia (10). People over 65 years old had highest PR of hernias. There was a gender-wise variation across types of hernia procedures. Around 89.6% of patients with inguinal hernia repairs were males, while only 10.4% were females. The PR was lower in males for femoral and incisional hernia when compared two genders with corresponding age groups. Women in the pregnancy group (20-39 years) had a high risk of ventral hernia repair when compared to males. Groups of patients who have higher risks of hernia repair should be prioritized for healthcare service delivery, but more research is needed in hernia epidemiology, in Australia and internationally. Our study could serve as a national and international reference for hernia repair studies, particularly for low- and middle-income countries with limited nationwide large-scale data.

：Prediction for enterprise credit risk in the era of the digital economy is important for early credit crisis warning. Existing evaluation methods for small and medium-sized enterprises (SMEs) credit levels simply using financial information have two major limitations. Firstly, it relies heavily on financial reports to ignore the soft information related to enterprise digital development. Secondly, both the process of feature selection and unbalanced sample could influence the prediction performance of model. Therefore, we introduce a novel credit risk prediction method for SMEs and improved Artificial Bee Colony (ABC) algorithm for feature selection (IABCFS). Firstly, we expand the evaluation system for credit risk with features on digital transformation, and combine SMOTE algorithm with Tomek Link Removal to do the work of data cleaning. Then we introduce an initialization method based on Tent Chaotic Map and improve the standard ABC algorithm by a new search strategy to increase the efficiency of feature selection process. To further decrease the redundancy between features, we use Symmetric Uncertainty (SU) to construct the fitness function. Finally, we develop a prediction method of credit risk based on IABCFS combined with an SVM-Adaboost ensemble model. The experiments indicate that the improvement for IABCFS is effective and our proposed method achieves competitive results both on a Chinese SMEs dataset and three public datasets.

Introduction: Hospital value analysis teams aim to scope, appraise, and procure the most cost and clinically effective alternatives, but many rely on deliberative processes and lack the use of evaluation frameworks. Multi-criteria decision analysis can complement these processes through the provision of systematic, transparent, and empirical decision support. This literature review aims to understand the applications of MCDA in local contexts. Methods: Medline (OVID), EMBASE, CINAHL, PsycINFO, and Scopus were searched, and returned 2,246 studies, of which 110 were included for full-text review, and 17 were included in the final analysis. Data relating to the context in which the study was conducted, the composition of the MCDA model used, and the reported feasibility of the use of MCDA were extracted. Results: The use of MCDA for local healthcare contexts is a recent, interprofessional, and geographically agnostic phenomenon. Diagnostics, treatment, surgical approaches, performances and preferences, education approaches, and recovery targets were the primary decision problems addressed. A combination of models was employed, and qualitative data, literature review, expert opinion, and financial measurements were used to support data requirements. Facilitating reasoning and decision-making, service quality improvement, transparency, flexibility and adaptability, participation and buy in, and feedback about MCDA were identified as key adoption characteristics. Conclusion: MCDA has numerous emerging applications to support healthcare decision makers across different decision problems and to evaluate products and processes in local settings. This review provides considerations for uptake and implementation, though further investigation into its explicit applications to hospital and perioperative value analysis is necessary to elicit the usability, feasibility, and acceptability of these models.

Material and methodsAs part of the revision of the Neotropical species of Celtis(Zamengo in prep.), 8,414 specimens were analyzed. Although the collections of different herbaria contain thousands of neotropical specimens of Celtis , only a few herbaria have the true C. iguanaea . With this in mind, we selected 200 specimens of C. iguanaea , as these are the most similar to the native specimens from Curaçao, from which the species was originally described (Appendix 1). The list of examined specimens of the re-established taxa can be found in Appendix 1. All examined specimens are deposited in the following herbaria: ALCB, B, BG, BHCB, BHZB, BR, CAY, CEN, CEPEC, CESJ, CGMS, CTES, E, EAC, ESA, F, FLAS, FUEL, FURB, G, GBH, GFJP, GUA, GUADA, HAL, HOXA, HUA, HUEFS, HUT, IBGE, IBUG, INPA, K, L, LPB, MA, MBM, MBML, MEXU, MO, MVFA, MY, NY, P, PMSP, RADAMBR, RB, S, SI, SP, SPF, TEFH, U, UB, UCS, UFACPZ, UFP, ULBRA, UNAM, UNR, UPCB, US, USM, VIES, and XAL (acronyms are according to Thiers 2024).All of the specimens were macro- and micro-morphologically analyzed. For some characters, we used a Mikoba S2040 magnifying glass with 20X and 40X magnification equipped with LED lights and a camera. We also used a Gadnic USB digital microscope with 40X to 1000X magnification, LED lights, and a camera. Additionally, live plants of C. iguanaeawere observed, photographed, and collected in Curaçao (where it is the only Celtis species ever recorded).For the analysis of the pyrenes, fourteen ripe or dried fruits were cleaned using the method described by Zamengo et al. (2020). After cleaning, the pyrenes were examined and measured with a precision caliper. The morphological terms used are based on Chamorro et al. (2021). The colors are according to Beentje (2010). The distribution map was made using the Q.Gis 3.22.2 program.The names reviewed in the results section are those synonymized withC. iguanaea by Berg and Dahlberg (2001), except forC. spinosa and C. spinosissima that have already been re-established (Zamengo et al. 2020, Chamorro et al. 2021). For nomenclatural considerations we followed the International Code of Nomenclature for algae, fungi, and plants (ICN, Turland et al. 2018).In this article we only give the taxonomic headings and descriptions ofC. iguanaea and the new combination. The other re-established species have not been described here as a review of all neotropical species is underway (Zamengo in prep. ) and will be published in the future. For the other reestablished species, we highlight the characters that distinguish them from C. iguanaea (Table 3).

Kowthar Salman Hassan

Background: Squamous cell carcinoma of the prostate (SCCP) is a neoplasm that comprises fewer than 1% of all primary prostate cancer diagnoses. Given its rarity, there is a paucity of data regarding the treatment of this disease. The limited literature points to the potential of local therapy in conjunction with chemotherapy to improve patient mortality. Methods: Using the National Cancer Initiative’s Surveillance, Epidemiology, and End Results (SEER) database, we conducted a retrospective analysis for patients diagnosed with primary SCCP between 2000 and 2018. We analyzed patient demographics, tumor characteristics, such as histology, and patient outcomes based on treatment modality. We generated Kaplan-Meier five-year overall survival (5y OS) curves for these variables. Results: A total of 66 patients were identified. Five-year overall survival was 18%; median overall survival was 13 months. Patients with Grade II and below disease had an increased 5y OS of 48%, compared to 10% for patients with Grade III and Grade IV disease (p < 0.05). Analysis of the 5y OS based on disease histology revealed patients with papillary SCC had a 5y OS of 50%, compared to 26% for patients with papillary carcinoma, not otherwise specified. Analysis of 5y OS stratified by treatment modality revealed no statistically significant change with any treatment (surgery, radiotherapy, and chemotherapy). Conclusions: The literature on SCCP remains sparse; the rarity of this disease limits analysis. While the investigation undertaken in this paper does not find any change in 5y OS regardless of treatment modality, the variation in 5y OS based on histologic classification of SCCP points to a potential route for the future treatment of this disease.

Introduction: Use observational methods to evaluate reliability of evidence generated by a study of the effect of glucagon-like peptide 1 receptor agonists (GLP-1RA) on chronic lower respiratory disease (CLRD) outcomes among type-2 diabetes mellites (T2DM) patients. Research Design and Methods: We independently reproduced a study comparing effects of GLP-1RA versus dipeptidyl peptidase-4 inhibitors (DPP4-i) on CLRD outcome among patients with T2DM and prior CLRD. We reproduced inputs and outputs using the original study data (national administrative claims) and evaluated robustness to alternate design/analysis decisions. To evaluate generalizability, we applied the protocol and meta-analyzed across a research network including diverse array of populations and data sources. We also produced additional analyses evaluating individual drugs within the GLP-1RA class. Results: We confirmed alignment of study inputs and outputs and closely reproduced effect estimates and sensitivity analyses. Adjusted effect estimates were robust to empirical calibration. Network meta-analysis confirmed original findings, but indicated weaker effects than originally published. Meta-analyzing drugs within the GLP-1RA class against DPP4-I provided some evidence that effects vary within the GLP-1RA class, indicating stronger effects for exenatide and weaker effects of dulaglutide. Conclusions: This study supports the reliability of the original study by 1) confirming the findings in a range of alternate databases and populations 2) demonstrating effects for multiple drugs within the GLP-1RA class, and 3) independently confirming the reproducibility original study and its findings. We propose that clinicians treating patients with T2DM and a history of CLRD consider GLP-1RA in absence of strong motivating reasons to select another therapy.

Invasive species are a growing global economic and ecological problem. However, it is not well understood how environmental factors mediate invasive range expansion. In this study, we investigated the recent and rapid range expansion of common tansy across environmental gradients in Minnesota, U.S.A. We densely sampled individuals across the expanding range and performed reduced representation sequencing to generate a dataset of 3071 polymorphic loci for 176 individuals. We used non-spatial and spatially-explicit analyses to determine the relative influences of geographic distance and environmental variation on patterns of genomic variation. We found no evidence for isolation-by-distance (IBD) but strong evidence for isolation-by-environment (IBE), indicating that environmental factors may have modulated patterns of range expansion. Land use classification and soils were particularly important variables related to population structure although they operated on different spatial scales; land-use classification was related to broad-scale patterns and soils were related to fine-scale patterns. All analyses indicated a distinctive genetic cluster in the most recently invaded portion of the range. Individuals from the far northwestern range margin were separated from the remainder of the range by reduced migration, which was associated with environmental resistance. This portion of the range was invaded primarily in the last 15 years. Ecological niche models also indicated that this cluster was associated with expansion of the niche. While invasion is often assumed to be primarily influenced by dispersal limitation, our results suggest that ongoing invasion and range shifts with climate change may be strongly affected by environmental heterogeneity.

Atrial fibrillation (AF) is a prevalent clinical arrhythmia characterized by an irregular cardiac rhythm, increasing the risk of developing stroke and heart failure. In order to explore the potential role of serum indicators, the study employed a combination of targeted metabolomics and Tandem Mass Tag (TMT) based proteomics to examine metabolic characteristics and biomarkers in the serum of patients with AF. Furthermore, the verification of protein expressions with diagnostic significance for AF was conducted in patients of larger sample sizes by ELISA. Proteomics and metabolomics identified 174 differentially expressed proteins (DEPs) and 294 differentially metabolites (DMs) in AF patients, respectively. The clustering and functional enrichment analysis identified the complement and coagulation cascade as the primary pathway dysregulating DEPs. According to the integrated study, the most enriched proteomics and metabolomics pathways were platelet activation and cholesterol metabolism. lactate dehydrogenase A (LDHA), lactate dehydrogenase B (LDHB), and transgelin 2 (TAGLN2) were significantly expressed in AF patients, while plasminogen (PLG) was low. In conclusion, the current study found that platelet activation, cholesterol metabolism, and the complement and coagulation cascade pathways may affect AF progression. The study also showed that LDHA, LDHB, TAGLN2, and PLG may be potential AF biomarkers.

J D GOODRIDGEjordan.goodridge@utoronto.caUniversity of Toronto, Temerty Faculty of Medicine

Anencephaly and other multiple fetal anomalies in multi-drug addictive pregnant woman (A case report).Mouna Baddouraa,b, Karam Kababeha,b, Mariam Zarkaa,b, Nafiza Martinia,b,, Sultaneh Haddadc,b,*,Rahaf Ossmand,Haya Kwarada Faculty of medicine, Damascus University, Damascus, Syrian Arab Republic.b Stemosis for Scientific Research, Damascus, Syrian Arab Republic.c Aleppo University, Faculty of Medicine, Aleppo, Syrian Arab Republic.d University Hospital of obstetrics and Gynecology in Damascus, Damascus, Syrian Arab Republic.Mouna Baddoura : baddouramouna630@gmail.comKaram Kababeh: Kababeh.karam@gmail.comMariam Zarka: mariamzarka3090@gmail.comNafiza Martini: nafiza0968@gmail.comSultaneh Haddad: sltanhhdad@gmail.comRahaf Ossman: rahaf.usman@gmail.comHaya Kwara: kwarahaya@gmail.com*Corresponding author: Sultaneh Haddad, Medical student at Aleppo university. Phone number: 00963930593703 Adress: Syria, Damascus, Aleppo street