Large-scale Comparative Studies Research Articles

A message passing framework with multiple data integration for miRNA-disease association prediction

Micro RNA or miRNA is a highly conserved class of non-coding RNA that plays an important role in many diseases. Identifying miRNA-disease associations can pave the way for better clinical diagnosis and finding potential drug targets. We propose a biologically-motivated data-driven approach for the miRNA-disease association prediction, which overcomes the data scarcity problem by exploiting information from multiple data sources. The key idea is to enrich the existing miRNA/disease-protein-coding gene (PCG) associations via a message passing framework, followed by the use of disease ontology information for further feature filtering. The enriched and filtered PCG associations are then used to construct the inter-connected miRNA-PCG-disease network to train a structural deep network embedding (SDNE) model. Finally, the pre-trained embeddings and the biologically relevant features from the miRNA family and disease semantic similarity are concatenated to form the pair input representations to a Random Forest classifier whose task is to predict the miRNA-disease association probabilities. We present large-scale comparative experiments, ablation, and case studies to showcase our approach’s superiority. Besides, we make the model prediction results for 1618 miRNAs and 3679 diseases, along with all related information, publicly available at http://software.mpm.leibniz-ai-lab.de/ to foster assessments and future adoption.

268. COMPARISON OF OUTCOME OF GASTRIC TUBE RECONSTRUCTION FOR ESOPHAGEAL CANCER BETWEEN RECONSTRUCTIVE ROUTES

Abstract The route of gastric tube reconstruction after esophageal cancer resection is generally adopted as either posterior sternal or posterior mediastinal. There have been no large-scale comparative studies, and each institution has chosen a route based on its own experience. Therefore, we conducted an observational study at our institution to compare the postoperative outcomes of posterior sternal and posterior mediastinal reconstruction in gastric tube reconstruction for esophageal cancer. The study included 159 patients with thoracic esophageal cancer who underwent subtotal esophagectomy and gastric tube reconstruction (73 patients in the posterior sternal reconstruction (RS) group and 86 patients in the posterior mediastinal reconstruction (PM) group) from 2016 to 2018 and compared perioperative and postoperative complications and postoperative nutritional status. There were no differences in age, location, or pStage between the reconstructive routes, but BMI was significantly higher in RS (22.0 ± 2.9) and PM (20.8 ± 3.1). Anastomotic leakage (RS:PM = 8%:3%) and respiratory complications (RS:PM = 6%:15%) were not significantly different. PM was also significantly more common with ileus (13%). Anastomotic stenosis requiring dilation was significantly less common in PM than RS (31%:17%, p = 0.04). Weight loss was significantly higher in the RS group at 1 year postoperatively (RS/PM:13.9%/10.2%, p = 0.02). We have changed to PM with gastrostomy and the modified Collard anastomosis. These procedures have decreased the occurrence of ileus due to jejunostomy. Anastomotic stenosis was reduced to 5%. In gastric tube reconstruction after subtotal esophageal resection for esophageal cancer, the reconstructive route (posterior sternal or posterior mediastinal route) showed no significant difference in the incidence of postoperative pneumonia or anastomotic leakage. By changing the anastomotic procedure, a decrease in anastomotic stenosis was observed even with posterior sternal reconstruction. We plan to accumulate more cases and investigate the effects on quality of life and nutritional status in the future.

Backlash policy diffusion to populists in power.

We analyze how parties respond programmatically to populist parties in power abroad. Political parties often copy the policies of governing parties in other countries–a phenomenon that contributes to waves of transnational policy diffusion. We report the first large-scale comparative study showing that populist parties in government abroad trigger the opposite reaction: instead of inspiring emulation, their highly visible governing dilemmas provoke a policy backlash by parties in other states. We argue that dilemmas arise because populist parties confront unique and debilitating trade-offs between maintaining their anti-system posture and governing effectively, which make them electorally vulnerable. Other parties observe foreign populists’ governing dilemmas and respond by distancing themselves in order to avoid these problems. We detect this “foreign populist backlash effect” using spatial econometric analysis, a method that allows us to estimate international policy connections between parties, applied to over 200 European parties’ programmatic positions since the 1970s. Our findings illuminate parties’ election strategies and show that this backlash effect constrains the spread of populism across Western democracies.

Linking large-scale genetic structure of three Argynnini butterfly species to geography and environment.

Understanding which factors and processes are associated with genetic differentiation within and among species remains a major goal in evolutionary biology. To explore differences and similarities in genetic structure and its association with geographical and climatic factors in sympatric sister species, we conducted a large‐scale (>32° latitude and >36° longitude) comparative phylogeographical study on three Argynnini butterfly species (Speyeria aglaja, Fabriciana adippe and F. niobe) that have similar life histories, but differ in ecological generalism and dispersal abilities. Analyses of nuclear (ddRAD‐sequencing derived SNP markers) and mitochondrial (COI sequences) data revealed differences between species in genetic structure and how genetic differentiation was associated with climatic factors (temperature, solar radiation, precipitation, wind speed). Geographical proximity accounted for much of the variation in nuclear and mitochondrial structure and evolutionary relationships in F. adippe and F. niobe, but only explained the pattern observed in the nuclear data in S. aglaja, for which mitonuclear discordance was documented. In all species, Iberian and Balkan individuals formed genetic clusters, suggesting isolation in glacial refugia and limited postglacial expansion. Solar radiation and precipitation were associated with the genetic structure on a regional scale in all species, but the specific combinations of environmental and geographical factors linked to variation within species were unique, pointing to species‐specific responses to common environments. Our findings show that the species share similar colonization histories, and that the same ecological factors, such as niche breadth and dispersal capacity, covary with genetic differentiation within these species to some extent, thereby highlighting the importance of comparative phylogeographical studies in sympatric sister species.

A large-scale real-world comparative study using pre-COVID lockdown and post-COVID lockdown data on predicting shipment times of therapeutics in e-pharmacy supply chains

PurposeThe purpose of this study is to present a large-scale real-world comparative study using pre-COVID lockdown data versus post-COVID lockdown data on predicting shipment times of therapeutic supplies in e-pharmacy supply chains and show that our proposed methodology is robust to lockdown effects.Design/methodology/approachThe researchers used organic data of over 5.9 million records of therapeutic shipments, with 2.87 million records collected pre-COVID lockdown and 3.03 million records collected post-COVID lockdown. The researchers built various Machine Learning (ML) classifier models on the two datasets, namely, Random Forest (RF), Extra Trees (XRT), Decision Tree (DT), Multi-Layer Perceptron (MLP), XGBoost (XGB), CatBoost (CB), Linear Stochastic Gradient Descent (SGD) and the Linear Naïve Bayes (NB). Then, the researchers stacked these base models and built meta models on top of them. Further, the researchers performed a detailed comparison of the performances of ML models on pre-COVID lockdown and post-COVID lockdown datasets.FindingsThe proposed approach attains performance of 93.5% on real-world post-COVID lockdown data and 91.35% on real-world pre-COVID lockdown data. In contrast, the turn-around times (TAT) provided by therapeutic supply logistics providers are 62.91% accurate compared to reality in post-COVID lockdown times and 73.68% accurate compared to reality pre-COVID lockdown times. Hence, it is clear that while the TAT provided by logistics providers has deteriorated in the post-pandemic business climate, the proposed method is robust to handle pandemic lockdown effects on e-pharmacy supply chains.Research limitations/implicationsThe implication of the study provides a novel ML-based framework for predicting the shipment times of therapeutics, diagnostics and vaccines, and it is robust to COVID-19 lockdown effects.Practical implicationsE-pharmacy companies can readily adopt the proposed approach to enhance their supply chain management (SCM) capabilities and build resilience during COVID lockdown times.Originality/valueThe present study is one of the first to perform a large-scale real-world comparative analysis on predicting therapeutic supply shipment times in the e-pharmacy supply chain with novel ML ensemble stacking, obtaining robust results in these COVID lockdown times.

The evolution of multi-gene families and metabolic pathways in the evening primroses (Oenothera: Onagraceae): A comparative transcriptomics approach.

The plant genus Oenothera has played an important role in the study of plant evolution of genomes and plant defense and reproduction. Here, we build on the 1kp transcriptomic dataset by creating 44 new transcriptomes and analyzing a total of 63 transcriptomes to present a large-scale comparative study across 29 Oenothera species. Our dataset included 30.4 million reads per individual and 2.3 million transcripts on average. We used this transcriptome resource to examine genome-wide evolutionary patterns and functional diversification by searching for orthologous genes and performed gene family evolution analysis. We found wide heterogeneity in gene family evolution across the genus, with section Oenothera exhibiting the most pronounced evolutionary changes. Overall, more significant gene family expansions occurred than contractions. We also analyzed the molecular evolution of phenolic metabolism by retrieving proteins annotated for phenolic enzymatic complexes. We identified 1,568 phenolic genes arranged into 83 multigene families that varied widely across the genus. All taxa experienced rapid phenolic evolution (fast rate of genomic turnover) involving 33 gene families, which exhibited large expansions, gaining about 2-fold more genes than they lost. Upstream enzymes phenylalanine ammonia-lyase (PAL) and 4-coumaroyl: CoA ligase (4CL) accounted for most of the significant expansions and contractions. Our results suggest that adaptive and neutral evolutionary processes have contributed to Oenothera diversification and rapid gene family evolution.

AnimalTraits - a curated animal trait database for body mass, metabolic rate and brain size

Trait databases have become important resources for large-scale comparative studies in ecology and evolution. Here we introduce the AnimalTraits database, a curated database of body mass, metabolic rate and brain size, in standardised units, for terrestrial animals. The database has broad taxonomic breadth, including tetrapods, arthropods, molluscs and annelids from almost 2000 species and 1000 genera. All data recorded in the database are sourced from their original empirical publication, and the original metrics and measurements are included with each record. This allows for subsequent data transformations as required. We have included rich metadata to allow users to filter the dataset. The additional R scripts we provide will assist researchers with aggregating standardised observations into species-level trait values. Our goals are to provide this resource without restrictions, to keep the AnimalTraits database current, and to grow the number of relevant traits in the future.

Midostaurin in advanced systemic mastocytosis: A systematic review and meta-analysis.

e19084 Background: Midostaurin, an oral multikinase inhibitor including inhibition of KIT D816V, is approved for the treatment of advanced systemic mastocytosis (SM). Few studies have investigated the use of midostaurin in patients with advanced SM, but the data on its efficacy and safety in this population remains limited and uncertain. Therefore, we conducted this systematic review and meta-analysis to better assess the efficacy and safety of midostaurin in advanced SM. Methods: We systematically searched the following databases: PubMed/MEDLINE, Embase, and Cochrane through February 02, 2022, to include all studies that assessed the effect of midostaurin on clinical outcomes of patients with advanced SM. Our primary outcome was the overall response rate (ORR). The secondary outcomes included the rates of progressive disease (PD), stable disease (SD), and treatment discontinuation due to adverse events (AEs). All statistical analyses were performed using Open Meta Analyst (CEBM, University of Oxford). Pooled rates and corresponding 95% confidence intervals (CI) were calculated using DerSimonian-Laird/Random-effects approach. Results: Four studies (two clinical trials and two observational studies) with a total of 156 patients with advanced SM were included in the pooled analysis. The mean age of the patients was 59.6±15.8 years, and males represented 64.7% of total patients. The most common subtype of advanced SM was SM associated with hematological neoplasm (59%) followed by aggressive SM (23.1%). Three studies reported the KIT D816V mutation status, and 85.2% of patients were positive for KIT D816V mutation. The mean duration of treatment with midostaurin was 10±15.3 months. The pooled ORR was 60% (95% CI 46.5%-73.5%) over a mean follow-up duration of 41.1±38.7 months. The PD and SD rates were 12.8% (95% CI 7.6%-18%) and 10.6% (5.3%-15.9%), respectively. Treatment discontinuation due to AEs occurred in 25.6% (95% CI 18.8%-32.4%). The most common hematological grade ≥3 treatment-related AE was anemia (29%), while fatigue (7.1%) was the most common non-hematological grade ≥3 treatment-related AE. Conclusions: Our study demonstrated that midostaurin is very effective in patients with advanced SM with an acceptable safety profile. Our meta-analysis is hampered by a limited number of studies, a small sample size, and a lack of a control group. Future large-scale comparative studies are warranted to evaluate the efficacy and safety of midostaurin in these patients.

New Data on Breeding Strategies and Reproductive Success of the Globally Threatened Turtle Dove Co-Occurring with the “Competitive” Collared Dove and the “Predatory” Maghreb Magpie in Olive Orchards

Interactions between co-occurring species, including competition and predation, comprise critical processes regulating local community structure, habitat use, and diversity. We monitored nesting habitats, breeding chronology, and reproductive success rates to describe the patterns of spatiotemporal organization of three co-habiting species: the “native” turtle dove, the “invasive” collared dove, and the “predatory” Maghreb magpie. We defined nesting site parameters, breeding chronology dates, and success rates to explain how these species are dispersed in space and time. Similarly, predation attacks were evaluated. Patterns of habitat use were best explained by fear of predation and competition. Both doves selected nesting sites far away from the predatory Magpie to protect their nests. Equally, sympatric Columbidae turtle dove and collared dove were segregated horizontally and vertically only in space to reduce competition inside olive orchards. On the other side, Maghreb magpie started the breeding activity first, most probably to benefit from food abundance targeted in doves’ nests (eggs and nestlings). Further, breeding success was higher in both doves, despite predation pressure exercised by the Magpie and other reptiles. Magpie nests were colonized by the great spotted cuckoo (Clamator glandarius). Finally, this study provides the first and only detailed data on nest-niche of the turtle dove co-occurring with competitor and predator species, in the entire Northwest Africa range. Additionally, our data provide an opportunity of large-scale comparative studies of the nesting niche and breeding performances of the turtle dove, collared dove, and Maghreb magpie complex.

Nest site selection and breeding ecology of the red-billed blue magpie Urocissa erythrorhyncha in central China

Abstract While knowledge on birds’ breeding ecology is essential for understanding avian adaptation and managing conservation, it is poorly studied for many species, even for some common species. The knowledge of the natural history of the red-billed blue magpie (Urocissa erythrorhyncha), a species widely distributed in China and Southeast Asia, is sketchy. Here we present detailed data of nest site selection and the breeding ecology of red-billed blue magpie in central China, and of the effects of nest predation and brood parasitism on reproductive strategies. Most nests were built on Phyllostachys sulphurea and Quercus acutissima. Breeding season ranged from March to August. The first egg was laid between early April and late July. The incubation period lasted 15 days and the nestling period, 18 days. Average clutch size was 4.6 eggs, and brood size at fledging was 3.3 young. Overall, 43.8% of nesting attempts successfully produced at least one fledged young. Nest predation and brood parasitism were the two main reasons for fledging failure, which mainly occurred after April. Correspondingly, U. erythrorhyncha showed a tendency to build nests higher up and have a smaller clutch size in late stages of the breeding season. This study provides the first reliable and comprehensive information on the reproductive parameters of U. erythrorhyncha, which will lay a foundation for further understanding this species’ biology and opens up an avenue for large-scale comparative studies of the Urocissa genus or higher-level taxa.

An update on drug–drug interactions associated with proton pump inhibitors

ABSTRACT Introduction Proton pump inhibitors (PPIs) block the gastric H/K-ATPase, therefore inhibiting acid gastric secretion, leading to an increased pH (>4). They account for an extremely high number of prescriptions worldwide. Numerous drug–drug interactions have been described with PPIs, but all the described interactions do not have clinical significance. Areas covered This review will discuss the latest updates on drug–drug interactions with PPIs, focusing on the last 10-year publications in the following areas: anti-infective agents, anticancer drugs, antiplatelet agents and anticoagulants, and antidiabetics. Expert opinion Although pharmacokinetic interactions of PPIs have been described with many drugs, their clinical relevance remains controversial. However, given the extremely high number of people being treated with PPIs, clinicians should remain vigilant for interactions that may be clinically significant and require dose adjustment or therapeutic monitoring. Interestingly, not all PPIs have the same pharmacokinetic and pharmacodynamic profile, with some having a strong potential to inhibit CYP2C19, such as omeprazole, esomeprazole, and lansoprazole, while others, pantoprazole, rabeprazole, and dexlansoprazole, are weak CYP2C19 inhibitors. These may be preferred depending on co-prescribed treatments. In addition, new formulations have been developed to prevent some of the gastric pH-dependent drug interactions and should be evaluated in further large-scale prospective comparative studies.

Detection of F1 Hybrids from Single-genome Data Reveals Frequent Hybridization in Hymenoptera and Particularly Ants.

Hybridization occupies a central role in many fundamental evolutionary processes, such as speciation or adaptation. Yet, despite its pivotal importance in evolution, little is known about the actual prevalence and distribution of current hybridization across the tree of life. Here we develop and implement a new statistical method enabling the detection of F1 hybrids from single-individual genome sequencing data. Using simulations and sequencing data from known hybrid systems, we first demonstrate the specificity of the method, and identify its statistical limits. Next, we showcase the method by applying it to available sequencing data from more than 1,500 species of Arthropods, including Hymenoptera, Hemiptera, Coleoptera, Diptera, and Archnida. Among these taxa, we find Hymenoptera, and especially ants, to display the highest number of candidate F1 hybrids, suggesting higher rates of recent hybridization between previously isolated gene pools in these groups. The prevalence of F1 hybrids was heterogeneously distributed across ants, with taxa including many candidates tending to harbor specific ecological and life-history traits. This work shows how large-scale genomic comparative studies of recent hybridization can be implemented, uncovering the determinants of first-generation hybridization across whole taxa.

Body size and sexual selection shaped the evolution of parrot calls.

Morphology, habitat and various selective pressures (e.g. social and sexual selection) can influence the evolution of acoustic signals, but the relative importance of their effects is not well understood. The order Psittaciformes (parrots, sensu lato) is a large clade of very vocal and often gregarious species for which large-scale comparative studies of vocalizations are lacking. We measured acoustic traits (duration, sound frequency, frequency bandwidth and sound entropy) of the predominant call type for >200 parrot species to test: (1) for associations with body size; (2) the acoustic adaptation hypothesis (AAH) (predicting differences between forest and open-habitat species); (3) the social complexity hypothesis (predicting more complex calls in gregarious species) and (4) influences of sexual selection (predicting correlated evolution with colour ornamentation). Larger species had on average longer calls, lower sound frequency and wider frequency bandwidth. These associations with body size are all predicted by physical principles of sound production. We found no evidence for the acoustic adaptation and social complexity hypotheses, but perhaps social complexity is associated with vocal traits not studied here, such as call repertoire sizes. More sexually dichromatic species had on average simpler calls (shorter, with lower entropy and narrower frequency bandwidth) indicating an influence of sexual selection, namely an evolutionary negative correlation between colour ornamentation and elaborate acoustic signals, as predicted by the transference hypothesis. Our study is the first large-scale attempt at understanding acoustic diversity across the Psittaciformes, and indicates that body size and sexual selection influenced the evolution of species differences in vocal signals.

Survival of patients with metastatic prostate cancer and comorbid obesity.

116 Background: In metastatic castrate resistant prostate cancer (mCRPC), the oral treatments of enzalutamide (ENZ) and abiraterone (AA) are used interchangeably because there are few large-scale comparative studies of the therapies. However, both drugs have different mechanisms of action, AA being an androgen biosynthesis inhibitor and ENZ being an androgen receptor inhibitor, so there may be therapeutic variance between the two drugs based on their interactions with comorbid conditions like obesity. Obesity not only increases the risk of other comorbidities, like heart disease, diabetes, and stroke, but has also been implicated in the development of CRPC. Methods: Patients treated with abiraterone or enzalutamide from September 10, 2014 to June 2, 2017 in the Veterans Health Administration were identified via pharmacy records. Among this population, patients were separated into body mass index (BMI) categories for underweight ( < 18.5), normal (18.5 to < 25), overweight (25 to < 30), and obese ( > 30). Age, Charlson Comorbidity Index and mCRPC treatments were collected and analyzed for the primary outcome of survival via the Kaplan-Meier method. A multivariate Cox proportional hazard model was performed with the following variables: BMI, Charlson Comorbidity Index, age, Black race, treatment with bone-directed therapy, and baseline PSA. Results: In patients with BMI > 25, there was a significantly improved overall survival for treatment with ENZ (n = 1623) over AA (n = 2159), with medians of 30.0 and 27.0 months respectively (p = 0.002). There was no significant difference in survival for patients with BMI < 25 (p = 0.48), with median survival of 17.7 months for ENZ (n = 589) and 16.1 months for AA (n = 860). The overall survival difference between underweight (n = 113), normal (n = 1336), overweight (n = 1879), and obese (n = 1903) groups shows significant increase in survival with increasing BMI, with the median survival durations of 9.2, 15.9, 23.9, and 29.8 months respectively (p < 0.001). This finding was corroborated by the Cox proportional hazard model, with the data indicating an increased risk of death (aHR = 1.58; 95% CI: 1.29, 1.94; p < 0.001) with the underweight group and decreased risk with the overweight (aHR = 0.75; 95% CI: 0.69, 0.81; p < 0.001) and obese (aHR = 0.64; 95% CI: 0.59, 0.70; p < 0.001) groups. Conclusions: Treatment with ENZ was associated with longer survival for mCRPC patients with overweight and obesity (BMI > 25) over AA. Otherwise, for normal and underweight patients (BMI < 25), there was no significant difference in overall survival between the two drugs. Higher BMI is associated with improved survival, suggesting a protective effect of obesity in mCRPC patients. While the reason for this finding warrants further investigation, similar findings have been seen in obese patients in some hormone driven cancers, like breast cancer and myeloma.

ManyBirds: A multi-site collaborative Open Science approach to avian cognition and behavior research

Comparative cognitive and behavior research aims to investigate cognitive evolution by comparing performance in different species to understand how these abilities have evolved. Ideally, this requires large and diverse samples; however, these can be difficult to obtain by single labs or institutions, leading to potential reproducibility and generalization issues with small, less representative samples. To help mitigate these issues, we are establishing a multi-site collaborative Open Science approach called ManyBirds, with the aim of providing new insight into the evolution of avian cognition and behavior through large-scale comparative studies, following the lead of exemplary ManyPrimates, ManyBabies and ManyDogs projects. Here, we outline a) the replicability crisis and why we should study birds, including the origin of modern birds, avian brains and convergent evolution of cognition; b) the current state of the avian cognition field, including a ‘snapshot’ review; c) the ManyBirds project, with plans, infrastructure, limitations, implications and future directions. In sharing this process, we hope that this may be useful for other researchers in devising similar projects in other taxa, like non-avian reptiles or mammals, and to encourage further collaborations with ManyBirds and related ManyX projects. Ultimately, we hope to promote collaboration between ManyX projects to allow for wider investigation of the evolution of cognition across all animals, including potentially humans.

Education and Interpretation on Public Lands: Lessons from Research and New Directions

Decades of research confirm that interpretation and environmental education on public lands can accomplish a wide variety of positive outcomes for participants, ranging from personal learning and growth to stewardship behaviors both onand off-site. This research note offers a brief summary of the state-of-the-field of interpretation and environmental education research as applied to public lands. It highlights the general state of knowledge and identifies opportunities for researchers to further enhance our understanding about education on public lands to maximize benefits for visitors and managers alike. In particular, we emphasize the value of large-scale comparative studies as well as collaborative approaches to adaptive management, in which researchers support active experimentation through iterative data collection and analysis within a learning network of multiple program providers. This latter approach promotes evidenced-based learning within a larger community practice in which participants can benefit from the diverse knowledge, experiences, and data that each brings into the network.

Comparative Investigation of Cellular Effects of Polyethylene Glycol (PEG) Derivatives.

Nowadays, polyethylene glycols referred to as PEGs are widely used in cosmetics, consumer care products, and the pharmaceutical industry. Their advantageous properties such as chemical stability, low immunogenicity, and high tolerability explain why PEGs are applied in many fields of pharmaceutical formulations including parenteral, topical, ophthalmic, oral, and rectal preparations and also in modern drug delivery systems. Given their extensive use, they are considered a well-known group of chemicals. However, the number of large-scale comparative studies involving multiple PEGs of wide molecular weight range is low, as in most cases biological effects are estimated upon molecular weight. The aim of this publication was to study the action of PEGs on Caco-2 cells and G. mellonella larvae and to calculate the correlation of these effects with molecular weight and osmolality. Eleven PEGs of different molecular weight were used in our experiments: PEG 200, PEG 300, PEG 400, PEG 600, PEG 1000, PEG 1500, PEG 4000, PEG 8000, PEG 10,000, 12,000, and PEG 20,000. The investigated cellular effects included cytotoxicity (MTT and Neutral Red assays, flow cytometry with propidium iodide and annexin V) and autophagy. The osmolality of different molecular weight PEGs with various concentrations was measured by a vapor pressure osmometer OSMOMAT 070 and G. mellonella larvae were injected with the solutions of PEGs. Sorbitol was used as controls of the same osmolality. Statistical correlation was calculated to describe the average molecular weight dependence of the different measured effects. Osmolality, the cytotoxicity assays, flow cytometry data, and larvae mortality had significant correlation with the structure of the PEGs, while autophagosome formation and the proportion of early apoptotic cells showed no statistical correlation. Overall, it must be noted that PEGs must be tested individually for biological effects as not all effects can be estimated by the average molecular weight.

On the Grammaticalization of Two Types of "ki" in Turkic

This article outlines various grammaticalization paths of the two types of the Turkic particle ki: the modal particle ki and the copied junctor ki. The element ki has been employed in Turkic languages in all documented historical periods, serving various semantic and syntactic functions as particles and junctors, i.e., subjunctors, conjunctors or adjunctors. Typological studies often blur any distinctions between semantic and syntactic properties by giving priority to semantic/cognitive criteria, which are easily applicable in large-scale comparative studies, e.g., Cristofaro (2003). Cross-Turkic comparison of the grammaticalization of ki elements shows that structures sharing semantic/cognitive properties may be syntactically different. Ki plays a special role in high-copying Turkic varieties that have throughout replaced typical Turkic bound junctors by free junctors (Johanson 2000, 2002, 2010). Areal linguistic features have influenced the grammaticalization processes.

Breastfeeding Outcomes and Associated Risks in HIV-Infected and HIV-Exposed Infants: A Systematic Review

Purpose: To critically appraise recent literature regarding breastfeeding outcomes and associated risks in HIV-infected (HI) and HIV-exposed (HE) infants, using the Preferred Reporting Items for Systematic review and Meta-Analysis Protocols (PRISMA-P) statement guidelines. Materials and Methods: Five electronic databases were systematically searched to obtain English publications from the last 10 years (2010-2020), pertaining to breastfeeding outcomes and associated risks of HI and HE infants and children. Gray literature sources were also included. Data were extracted according to various data items and were synthesized using thematic synthesis. Results: Of the initial 7,151 sources identified, 42 articles were eligible for final inclusion. The final selection included 19 cohort studies and 2 expert committee reports, classified as gray literature. The remaining 21 studies comprised case-control, cross-sectional, and randomized controlled trial studies. The following themes were identified: breastfeeding outcomes in HI and HE infants, risks for suboptimal breastfeeding, HI and HE infant growth and developmental outcomes, and barriers and facilitators to feeding decisions. Most studies highlighted HE infants' growth and developmental outcomes and did not directly interrogate breastfeeding outcomes. The most prevalent risks for suboptimal breastfeeding were maternal factors affecting decision making for breastfeeding. Conclusions: This systematic review adds to the evidence of breastfeeding in HIV-affected mother-infant dyads. Findings reiterated that exclusive breastfeeding has a positive outcome on growth and development of all infants irrespective of HIV status. The review highlighted a dearth of research on breastfeeding outcomes of HI and HE infants. Large-scale prospective comparative studies should profile breastfeeding and developmental outcomes of infants with HIV infection or exposure and antiretroviral treatment exposure to enable early identification and intervention for this vulnerable population in low-income settings.

General patterns of sexual dimorphism in graylings (Thymallus), with a comparison to other salmonid species

Among fishes, salmonids (family Salmonidae) have attracted a great deal of research attention focused on sexual dimorphism and associated selective forces. Most of this research has been directed toward anadromous and mostly semelparous salmon and trout (Oncorhynchus, Salmo), and comparatively little is known about intersexual variability in strictly iteroparous freshwater salmonids. We examined a comprehensive data set of 28 linear morphometric characters in 11 of 15 currently recognised species of grayling (Thymallinae, Thymallus), a genus consisting of iteroparous species only, to identify general patterns of intersexual morphological variability. Overall, we found that all grayling species show common sex-specific traits particularly relating to size dimensions of the dorsal, anal, pelvic and pectoral fins. Although the magnitude of sexual dimorphism differed among species, there was no significant phylogenetic signal associated with these differences across the genus. These results are discussed in terms of the assumed selection pressures driving sexual dimorphism in graylings and are compared to existing knowledge in Salmonidae as a whole where similarities and differences with both Salmoninae and Coregoninae exist. The present study provides the first detailed genus-wide comparison of sexually dimorphic phenotypic characters in graylings, and highlights the need for more large-scale comparative studies in multiple salmonid species to better understand general macroevolutionary trends among this important group of freshwater fishes.