bluuebunny/crossref_metadata_2025 huggingface dataset:
Geometric and topological characterization of the cytoarchitecture of islets of Langerhans
Authors: Aggarwal Manu , Striegel Deborah A. , Hara Manami , Periwal Vipul
Published: November 2023

The islets of Langerhans are critical endocrine micro-organs that secrete hormones regulating energy metabolism in animals. Insulin and glucagon, secreted by beta and alpha cells, respectively, are responsible for metabolic switching between fat and glucose utilization. Dysfunction in their secretion and/or counter-regulatory influence leads to diabetes. Debate in the field centers on the cytoarchitecture of islets, as the signaling that governs hormonal secretion depends on structural and functional factors, including electrical connectivity, innervation, vascularization, and physical proximity. Much effort has therefore been devoted to elucidating which architectural features are significant for function and how derangements in these features are correlated or causative for dysfunction, especially using quantitative network science or graph theory characterizations. Here, we ask if there are non-local features in islet cytoarchitecture, going beyond standard network statistics, that are relevant to islet function. An example is ring structures, or cycles, ofαandδcells surroundingβcell clusters or the opposite,βcells surroundingαandδcells. These could appear in two-dimensional islet section images if a sphere consisting of one cell type surrounds a cluster of another cell type. To address these issues, we developed two independent computational approaches, geometric and topological, for such characterizations. For the latter, we introduce an application of topological data analysis to determine locations of topological features that are biologically significant. We show that both approaches, applied to a large collection of islet sections, are in complete agreement in the context both of developmental and diabetes-related changes in islet characteristics. The topological approach can be applied to three-dimensional imaging data for islets as well.
Coordination of Pickpocket ion channel delivery and dendrite growth in Drosophila sensory neurons
Authors: Mitchell Josephine W. , Midillioglu Ipek , Schauer Ethan , Wang Bei , Han Chun , Wildonger Jill
Published: November 2023

Sensory neurons enable an organism to perceive external stimuli, which is essential for survival. The sensory capacity of a neuron depends on the elaboration of its dendritic arbor and the localization of sensory ion channels to the dendritic membrane. However, it is not well understood when and how ion channels localize to growing sensory dendrites and whether their delivery is coordinated with growth of the dendritic arbor. We investigated the localization of the DEG/ENaC/ASIC ion channel Pickpocket (Ppk) in the peripheral sensory neurons of developing fruit flies. We used CRISPR-Cas9 genome engineering approaches to tag endogenous Ppk1 and visualize it live, including monitoring Ppk1 membrane localization via a novel secreted split-GFP approach. Fluorescently tagged endogenous Ppk1 localizes to dendrites, as previously reported, and, unexpectedly, to axons and axon terminals. In dendrites, Ppk1 is present throughout actively growing dendrite branches and is stably integrated into the neuronal cell membrane during the expansive growth of the arbor. Although Ppk channels are dispensable for dendrite growth, we found that an over-active channel mutant severely reduces dendrite growth, likely by acting at an internal membrane and not the dendritic membrane. Our data reveal that the molecular motor dynein and recycling endosome GTPase Rab11 are needed for the proper trafficking of Ppk1 to dendrites. Based on our data, we propose that Ppk channel transport is coordinated with dendrite morphogenesis, which ensures proper ion channel density and distribution in sensory dendrites.
Context-dependent ciliary regulation of hedgehog pathway repression in tissue morphogenesis
Authors: Hwang Sun-Hee , White Kevin Andrew , Somatilaka Bandarigoda Nipunika , Wang Baolin , Mukhopadhyay Saikat
Published: November 2023

A fundamental problem in tissue morphogenesis is identifying how subcellular signaling regulates mesoscale organization of tissues. The primary cilium is a paradigmatic organelle for compartmentalized subcellular signaling. How signaling emanating from cilia orchestrates tissue organization—especially, the role of cilia-generated effectors in mediating diverse morpho-phenotypic outcomes—is not well understood. In the hedgehog pathway, bifunctional GLI transcription factors generate both GLI-activators (GLI-A) and GLI-repressors (GLI-R). The formation of GLI-A/GLI-R requires cilia. However, how these counterregulatory effectors coordinate cilia-regulated morphogenetic pathways is unclear. Here we determined GLI-A/GLI-R requirements in phenotypes arising from lack of hedgehog pathway repression (derepression) during mouse neural tube and skeletal development. We studied hedgehog pathway repression by the GPCR GPR161, and the ankyrin repeat protein ANKMY2 that direct cAMP/protein kinase-A signaling by cilia in GLI-R generation. We performed genetic epistasis betweenGpr161orAnkmy2mutants, andGli2/Gli3knockouts,Gli3Rknock-in and knockout ofSmoothened, the hedgehog pathway transducer. We also tested the role of cilia-generated signaling using aGpr161ciliary localization knock-in mutant that is cAMP signaling competent. We found that the cilia-dependent derepression phenotypes arose in three modes: lack of GLI-R only, excess GLI-A formation only, or dual regulation of either lack of GLI-R or excess GLI-A formation. These modes were mostly independent of Smoothened. The cAMP signaling-competent non-ciliaryGpr161knock-in recapitulatedGpr161loss-of-function tissue phenotypes solely from lack of GLI-R only. Our results show complex tissue-specific GLI-effector requirements in morphogenesis and point to tissue-specific GLI-R thresholds generated by cilia in hedgehog pathway repression. Broadly, our study sets up a conceptual framework for rationalization of different modes of signaling generated by the primary cilium in mediating morphogenesis in diverse tissues.
A systematic review of the clinical profile of patients with bubonic plague and the outcome measures used in research settings
Authors: Bourner Josephine , Andriamarohasina Lovarivelo , Salam Alex , Kayem Nzelle Delphine , Randremanana Rindra , Olliaro Piero
Published: November 2023

Background

Plague is a zoonotic disease that, despite affecting humans for more than 5000 years, has historically been the subject of limited drug development activity. Drugs that are currently recommended in treatment guidelines have been approved based on animal studies alone–no pivotal clinical trials in humans have yet been completed. As a result of the sparse clinical research attention received, there are a number of methodological challenges that need to be addressed in order to facilitate the collection of clinical trial data that can meaningfully inform clinicians and policy-makers. One such challenge is the identification of clinically-relevant endpoints, which are informed by understanding the clinical characterisation of the disease–how it presents and evolves over time, and important patient outcomes, and how these can be modified by treatment.

Methodology/Principal findings

This systematic review aims to summarise the clinical profile of 1343 patients with bubonic plague described in 87 publications, identified by searching bibliographic databases for studies that meet pre-defined eligibility criteria. The majority of studies were individual case reports. A diverse group of signs and symptoms were reported at baseline and post-baseline timepoints–the most common of which was presence of a bubo, for which limited descriptive and longitudinal information was available. Death occurred in 15% of patients; although this varied from an average 10% in high-income countries to an average 17% in low- and middle-income countries. The median time to death was 1 day, ranging from 0 to 16 days.

Conclusions/Significance

This systematic review elucidates the restrictions that limited disease characterisation places on clinical trials for infectious diseases such as plague, which not only impacts the definition of trial endpoints but has the knock-on effect of challenging the interpretation of a trial’s results. For this reason and despite interventional trials for plague having taken place, questions around optimal treatment for plague persist.
Memory-type variance estimators using exponentially weighted moving average statistic in presence of measurement error for time-scaled surveys
Authors: Qureshi Muhammad Nouman , Alamri Osama Abdulaziz , Riaz Naureen , Iftikhar Ayesha , Tariq Muhammad Umair , Hanif Muhammad
Published: November 2023

The present study suggested memory-type ratio and product estimators for variance estimation in the presence of measurement errors. We applied the exponentially weighted moving averages statistic which simultaneously utilizes the current and prior information for better estimation in surveys based on the time-scale. The expressions of approximate mean square errors of memory-type estimators are derived using Taylor series up to first order. Mathematical conditions are also obtained for which the suggested memory-type ratio and product estimators perform better than the conventional ratio and product estimators. The efficiency of the proposed estimators is observed using an extensive simulation study in the presence of measurement errors. A real data application is also carried out to support the mathematical expressions. From the results, it is shown that the use of prior sample information significantly increased the efficiency of the proposed estimators.
Improved electrochemical performance of multi-walled carbon nanotube reinforced gelatin biopolymer for transient energy storage applications
Authors: Alam Rabeya Binta , Ahmad Md. Hasive , Islam Muhammad Rakibul
Published: November 2023

Multi-walled carbon nanotube (MWCNT) incorporated biodegradable gelatin nanocomposites (Gel/MWCNT) have been prepared following a facile solution processing method. The Fourier-transform infrared (FTIR) spectroscopy, field emission scanning electronic microscopy (FESEM), and water contact angle (WCA) measurements revealed improved structural properties and surface morphological features of the nanocomposite films due to the incorporation of MWCNT. A four-fold decrease in the DC resistivity was obtained due to the addition of MWCNTs. The specific capacitance of the nanocomposite increased from 0.12 F/g to 12.7 F/g at a current density of 0.3 μA/cm2 due to the incorporation of 0.05 wt.% MWCNT. EIS analysis and the corresponding Nyquist plots demonstrated the contributions of the different electrical components responsible for the improved electrochemical performance were evaluated using an equivalent AC circuit. The incorporation of MWCNTs was found to reduce the charge-transfer resistance from 127 Ω to 75 Ω and increase the double-layer capacitance from 4 nF to 9 nF. The Gel/MWCNT nanocomposite demonstrated improved cyclic stability with a retention of 95% of the initial capacitance even after 5000 charging/discharging cycles. The biodegradability test showed that the nanocomposite degraded completely after 30 hours of immersion in water. This fully biocompatible nature of the nanocomposites with high specific capacitance and low charge transfer resistance may offer a promising route to fabricate a nature-friendly electrode material for energy storage applications.
Pharmacophore mapping approach to find anti-cancer phytochemicals with metformin-like activities against transforming growth factor (TGF)-beta receptor I kinase: An in silico study
Authors: Reza Rumman , Morshed Niaz , Samdani Md. Nazmus , Reza Md. Selim
Published: November 2023

The most frequently prescribed first-line treatment for type II diabetes mellitus is metformin. Recent reports asserted that this diabetes medication can also shield users from cancer. Metformin induces cell cycle arrest in cancer cells. However, the exact mechanism by which this occurs in the cancer system is yet to be elucidated. Here, we investigated the impact of metformin on cell cycle arrest in cancer cells utilizing transforming growth factor (TGF)-beta pathway. TGF-ß pathway has significant effect on cell progression and growth. In order to gain an insight on the underlying molecular mechanism of metformin’s effect on TGF beta receptor 1 kinase, molecular docking was performed. Metformin was predicted to interact with transforming growth factor (TGF)-beta receptor I kinase based on molecular docking and molecular dynamics simulations. Furthermore, pharmacophore was generated for metformin-TGF-ßR1 complex to hunt for novel compounds having similar pharmacophore as metformin with enhanced anti-cancer potentials. Virtual screening with 29,000 natural compounds from NPASS database was conducted separately for the generated pharmacophores in Ligandscout® software. Pharmacophore mapping showed 60 lead compounds for metformin-TGF-ßR1 complex. Molecular docking, molecular dynamics simulation for 100 ns and ADMET analysis were performed on these compounds. Compounds with CID 72473, 10316977 and 45140078 showed promising binding affinities and formed stable complexes during dynamics simulation with aforementioned protein and thus have potentiality to be developed into anti-cancer medicaments.
The practice of defensive medicine among Jordanian physicians: A cross sectional study
Authors: Al-Balas Qosay , Altawalbeh Shoroq , Rinaldi Carmela , Ibrahim Ibtihal
Published: November 2023

Background

Defensive medicine (DM) is a deviation from medical practice that is induced primarily by a threat of liability. While the DM behavior is well studied in the developed countries, little is known in developing countries and never been evaluated in Jordan.

Objective

To evaluate the prevalence of DM practice in Jordan among physicians and to investigate reasons behind its practice and potential strategies to alleviate this practice.

Methods

In this Cross-sectional study, self-administered questionnaire was distributed to a sample of physicians in both public and private sectors in Jordan. The collection period was from Jan 2021 to June 2021. The prevalence of DM practice was estimated among the study sample. Frequency scores of different DM behaviors, reasons of DM behaviors, and effectiveness of strategies in changing DM behaviors were summarized as average frequency scores with standard deviations. Multivariable linear regression models were conducted to evaluate potential predictors of total assurance and avoidance behavior scores.

Results

A total of 175 Jordanian physicians completed the survey. The prevalence of adopting (or witnessing) DM behaviors among the study sample was 68% (n = 119). Diagnostic laboratory exams followed by prescribed medications were the most practiced behaviors in excessive rate during a typical working week. Unfavorable legislation for the physician was reported as the headmost reason for practicing DM, followed by pressure from the public and mass media opinion. Continuous update of knowledge, abilities, and performance and following specific protocols and/or appropriate clinical evidence and appropriate multidisciplinary and multi-professional communication were the most effective strategies that can mitigate DM behaviors.

Conclusions

Defensive medicine practice is common among Jordanian physicians with concerns about increasing pattern in the future.
A study of user switching intention for ERP systems based on push-pull-mooring model: Focusing on the important role of information quality for users
Authors: Jo Hyeon , Park Do-Hyung
Published: November 2023

Enterprise resource planning (ERP) systems have become indispensable within companies due to their substantial functions and benefits. With a plethora of ERP systems available in the market, management is offered a broad array of options. This paper endeavours to identify the determinants influencing the switching intention of ERP users. Utilizing a conceptual model that adapts the push-pull-mooring paradigm, we seek to construct a formation mechanism of switching intention. Through structural equation modeling conducted on data collected from 236 users, our study uncovers several key findings. The study indicates that system quality, information quality, and top management support exert considerable influence on switching intention via satisfaction. Notably, we found that user satisfaction has a negative impact on switching intention. Our analysis also reveals that alternative attractiveness significantly determines switching intention. These findings provide valuable insights for organizations and ERP vendors to better understand user behaviour and to strategically manage user retention and switching decisions.
Physical therapy in the intensive care unit: A cross-sectional study of three Asian countries
Authors: Viloria Mary Audrey Domingo , Lee Shin-Da , Takahashi Tetsuya , Cheng Yu-Jung
Published: November 2023

Background

Physical therapy (PT) is beneficial for critically ill patients, but the extent of its application in the intensive care unit (ICU) differs between countries. Here, we compared the extent of PT intervention in the ICU in Japan, the Philippines, and Taiwan by evaluating the sociodemographic and ICU-related profiles of ICU physical therapists.

Materials and methods

In this cross-sectional study, a semistructured nationwide online survey was distributed to ICU physical therapists in the three countries.

Results

We analyzed the responses of 164 physical therapists from Japan, Philippines, and Taiwan. Significant differences were observed between the countries in all sociodemographic variables and the following ICU-related profiles of physical therapists: ICU work experience, duration of the ICU posting, number of hours per day spent in the ICU, on-call ICU PT service engagement, source of ICU patient referral, therapist–patient ratio, and ICU-related PT training participation (p < 0.05). Medical, surgical, and neurologic ICUs were the most common ICU workplaces of the ICU physical therapists, but only surgical and neurologic ICUs exhibited significant differences between the countries (p < 0.05). Standard PT techniques in the ICU were passive and active-assisted range of motion, positioning, and breathing exercises but were implemented with significantly different frequencies between the countries (p < 0.05). The most common challenge faced in ICU PT service delivery by respondents from all three countries was lack of training prior to ICU duty, and lack of training was even bigger challenge in Japan than in other two countries after adjustment of age, highest educational attainment, and work experience.

Conclusion

The differences in the health-care system between Japan, the Philippines, and Taiwan were related to differences in the compliance with internationally recommended PT practice standards in the ICU, differences in the type of PT intervention prioritized, and the challenges encountered in ICU PT service delivery.
A Single nucleotide polymorphism in the ALDH2 gene modifies the risk of esophageal squamous cell carcinoma in BRCA2 p.K3326* carriers
Authors: Zamani Neda , Szymiczek Agata , Shakeri Ramin , Poustchi Hossein , Pourshams Akram , Narod Steven , Malekzadeh Reza , Akbari Mohammad R.
Published: November 2023

Esophageal squamous cell carcinoma (ESCC) has a very high incidence rate in northeastern Iran. Our team previously reported the BReast CAncer gene 2 (BRCA2) p.K3326* mutation as a moderately penetrant ESCC susceptibility variant in northern Iran (odds ratio (OR) = 3.64, 95% confidence interval (CI) = 1.74–7.59, P = 0.0003). Recently, it has been reported that aldehydes can induce BRCA2 haploinsufficiency in cells with a heterozygous pathogenic BRCA2 mutation and predispose them to carcinogenic effects. Based on this observation, we speculate that dysfunctional variants in Aldehyde Dehydrogenase 2 Family Member (ALDH2) may result in aldehyde-induced BRCA2 haploinsufficiency and increase cancer risk in BRCA2 mutation carriers. In support of this hypothesis, our team recently reported the breast cancer risk modifying effect of an ALDH2 common polymorphism, rs10744777, among Polish carriers of the BRCA2 p.K3326* mutation. In the current case-control study, we aimed to investigate the ESCC risk modifying effect of this ALDH2 polymorphism among BRCA2 p.K3326* mutation carriers. We assessed the interaction between the ALDH2 rs10744777 polymorphism and BRCA2 p.K3326* mutation in ESCC risk by genotyping this ALDH2 variant in the germline DNA of 746 ESCC cases and 1,373 controls from northern Iran who were previously genotyped for the BRCA2 p.K3326* mutation. Among a total of 464 individuals with TT genotype of the ALDH2 rs10744777 polymorphism, which is associated with lower ALDH2 expression, we found 9 of 164 cases versus 3 of 300 controls who carried the BRCA2 p.K3326* variant (OR = 5.66, 95% CI = 1.22–26.2, P = 0.018). This finding supports our hypothesis that the ALDH2-rs10744777 TT genotype may be a significant risk modifier of ESCC in individuals with a BRCA2 p.K3326* mutation.
Tree species differ in plant economic spectrum traits in the tropical dry forest of Mexico
Authors: Alvarado Marco V. , Terrazas Teresa
Published: November 2023

In tropical dry forests, studies on wood anatomical traits have concentrated mainly on variations in vessel diameter and frequency. Recent research suggests that parenchyma and fibers also play an important role in water conduction and in xylem hydraulic safety. However, these relationships are not fully understood, and wood trait variation among different functional profiles as well as their variation under different water availability scenarios have been little studied. In this work, we aim to (1) characterize a set of wood anatomical traits among six selected tree species that represent the economic spectrum of tropical dry forests, (2) assess the variation in these traits under three different rainfall regimes, and (3) determine the relationships between wood anatomical traits and possible functional trade-offs. Differences among species and sites in wood traits were explored. Linear mixed models were fitted, and model comparison was performed. Most variation occurred among species along the economic spectrum. Obligate deciduous, low wood density species were characterized by wood with wide vessels and low frequency, suggesting high water transport capacity but sensitivity to drought. Moreover, high cell fractions of carbon and water storage were also found in these tree species related to the occurrence of abundant parenchyma or septate fibers. Contrary to what most studies show, Cochlospermum vitifolium, a succulent tree species, presented the greatest variation in wood traits. Facultative deciduous, high wood density species were characterized by a sturdy vascular system that may favor resistance to cavitation and low reserve storage. Contrary to our expectations, variation among the rainfall regimes was generally low in all species and was mostly related to vessel traits, while fiber and parenchyma traits presented little variation among species. Strong functional associations between wood anatomical traits and functional trade-offs were found for the six tree species studied along the economic spectrum of tropical dry forests.
Diacerein provokes apoptosis, improves redox balance, and downregulates PCNA and TNF-α in a rat model of testosterone-induced benign prostatic hyperplasia: A new non-invasive approach
Authors: Rasheed Rabab Ahmed , Sadek A. S. , Khattab R. T. , Elkhamisy Fatma Alzahraa A. , Abdelfattah Heba Abdelrazak , Elshaer Mohamed M. A. , Almutairi Saeedah Musaed , Hussein Dina S. , Embaby Azza Saleh , Almoatasem Mai A. M.
Published: November 2023

One of the most prevalent chronic conditions affecting older men is benign prostatic hyperplasia (BPH), causing severe annoyance and embarrassment to patients. The pathogenesis of BPH has been connected to epithelial proliferation, inflammation, deranged redox balance, and apoptosis. Diacerein (DIA), the anthraquinone derivative, is a non-steroidal anti-inflammatory drug. This study intended to investigate the ameliorative effect of DIA on the prostatic histology in testosterone-induced BPH in rats. BPH was experimentally induced by daily subcutaneous injection of testosterone propionate for four weeks. The treated group received DIA daily for a further two weeks after induction of BPH. Rats’ body and prostate weights, serum-free testosterone, dihydrotestosterone, and PSA were evaluated. Prostatic tissue was processed for measuring redox balance and histopathological examination. The BPH group had increased body and prostate weights, serum testosterone, dihydrotestosterone, PSA, and oxidative stress. Histologically, there were marked acinar epithelial and stromal hyperplasia, inflammatory infiltrates, and increased collagen deposition. An immunohistochemical study showed an increase in the inflammatory TNF-α and the proliferative PCNA markers. Treatment with DIA markedly decreased the prostate weight and plasma hormones, improved tissue redox balance, repaired the histological changes, and increased the proapoptotic caspase 3 expression besides the substantial reduction in TNF-α and PCNA expression. In conclusion, our study underscored DIA’s potential to alleviate the prostatic hyperplastic and inflammatory changes in BPH through its antioxidant, anti-inflammatory, antiproliferative, and apoptosis-inducing effects, rendering it an effective, innovative treatment for BPH.
Shallow subtidal marine benthic communities of Nachvak Fjord, Nunatsiavut, Labrador: A glimpse into species composition and drivers of their distribution
Authors: Friedlander Alan M. , Ballesteros Enric , Adler Alyssa M. , Goodell Whitney , Jenkinson Ryan , Knopp Jennie A. , Thompson Christopher D. H. , Timmers Molly , Walsh Cameron A. J. , Sala Enric
Published: November 2023

Marine fjords along the northern Labrador coast of Arctic Canada are influenced by freshwater, nutrients, and sediment inputs from ice fields and rivers. These ecosystems, further shaped by both Atlantic and Arctic water masses, are important habitats for fishes, marine mammals, seabirds, and marine invertebrates and are vital to the Labrador Inuit who have long depended on these areas for sustenance. Despite their ecological and socio-cultural importance, these marine ecosystems remain largely understudied. Here we conducted the first quantitative underwater scuba surveys, down to 12 m, of the nearshore marine ecology of Nachvak Fjord, which is surrounded by Torngat Mountains National Park located in Nunatsiavut, the Indigenous lands claim region of northeastern Canada. Our goal was to provide the Nunatsiavut Government with a baseline of the composition and environmental influences on the subtidal community in this isolated region as they work towards the creation of an Indigenous-led National Marine Conservation Area that includes Nachvak Fjord. We identified four major benthic habitat types: (1) boulders (2) rocks with sediment, (3) sediment with rocks, and (4) unconsolidated sediments, including sand, gravel, and cobble. Biogenic cover (e.g., kelp, coralline algae, and sediment) explained much of the variability in megabenthic invertebrate community structure. The kelp species Alaria esculenta, Saccharina latissima, and Laminaria solidungula dominated the boulder habitat outside of the fjord covering 35%, 13%, and 11% of the sea floor, respectively. In contrast, the middle and inner portions of the fjord were devoid of kelp and dominated by encrusting coralline algae. More diverse megabenthic invertebrate assemblages were detected within the fjord compared to the periphery. Fish assemblages were depauperate overall with the shorthorn sculpin, Myoxocephalus scorpius, and the Greenland cod, Gadus ogac, dominating total fish biomass contributing 64% and 30%, respectively. Understanding the composition and environmental influences within this fjord ecosystem not only contributes towards the protection of this ecological and culturally important region but serves as a baseline in a rapidly changing climatic region.
Spatial variation in risk for tick-borne diseases in residential areas of Dutchess County, New York
Authors: Keesing Felicia , Tilley Emma , Mowry Stacy , Adish Sahar , Bremer William , Duerr Shannon , Evans Andrew S. , Fischhoff Ilya R. , Keating Fiona , Pendleton Jennifer , Pfister Ashley , Teator Marissa , Ostfeld Richard S.
Published: November 2023

Although human exposure to the ticks that transmit Lyme-disease bacteria is widely considered to occur around people’s homes, most studies of variation in tick abundance and infection are undertaken outside residential areas. Consequently, the patterns of variation in risk of human exposure to tick-borne infections in these human-dominated landscapes are poorly understood. Here, we report the results of four years of sampling for tick abundance, tick infection, tick encounters, and tick-borne disease reports on residential properties nested within six neighborhoods in Dutchess County, New York, USA, an area of high incidence for Lyme and other tick-borne diseases. All properties were within neighborhoods that had been randomly assigned as placebo controls in The Tick Project; hence, none were treated to reduce tick abundance during the period of investigation, providing a unique dataset of natural variation within and between neighborhoods. We estimated the abundance of host-seeking blacklegged ticks (Ixodes scapularis) in three types of habitats on residential properties–forests, lawns, and gardens. In forest and lawn habitats, some neighborhoods had consistently higher tick abundance. Properties within neighborhoods also varied consistently between years, suggesting hot spots and cold spots occurring at a small (~ 1-hectare) spatial scale. Across neighborhoods, the abundance of nymphal ticks was explained by neither the amount of forest in that neighborhood, nor by the degree of forest fragmentation. The proportion of ticks infected with three common tick-borne pathogens did not differ significantly between neighborhoods. We observed no effect of tick abundance on human encounters with ticks, nor on either human or pet cases of tick-borne diseases. However, the number of encounters between ticks and outdoor pets in a neighborhood was negatively correlated with the abundance of questing ticks in that neighborhood. Our results reinforce the need to understand how human behavior and neglected ecological factors affect variation in human encounters with ticks and cases of tick-borne disease in residential settings.
An international consensus on effective, inclusive, and career-spanning short-format training in the life sciences and beyond
Authors: Williams Jason J. , Tractenberg Rochelle E. , Batut Bérénice , Becker Erin A. , Brown Anne M. , Burke Melissa L. , Busby Ben , Cooch Nisha K. , Dillman Allissa A. , Donovan Samuel S. , Doyle Maria A. , van Gelder Celia W. G. , Hall Christina R. , Hertweck Kate L. , Jordan Kari L. , Jungck John R. , Latour Ainsley R. , Lindvall Jessica M. , Lloret-Llinares Marta , McDowell Gary S. , Morris Rana , Mourad Teresa , Nisselle Amy , Ordóñez Patricia , Paladin Lisanna , Palagi Patricia M. , Sukhai Mahadeo A. , Teal Tracy K. , Woodley Louise
Published: November 2023

Science, technology, engineering, mathematics, and medicine (STEMM) fields change rapidly and are increasingly interdisciplinary. Commonly, STEMM practitioners use short-format training (SFT) such as workshops and short courses for upskilling and reskilling, but unaddressed challenges limit SFT’s effectiveness and inclusiveness. Education researchers, students in SFT courses, and organizations have called for research and strategies that can strengthen SFT in terms of effectiveness, inclusiveness, and accessibility across multiple dimensions. This paper describes the project that resulted in a consensus set of 14 actionable recommendations to systematically strengthen SFT. A diverse international group of 30 experts in education, accessibility, and life sciences came together from 10 countries to develop recommendations that can help strengthen SFT globally. Participants, including representation from some of the largest life science training programs globally, assembled findings in the educational sciences and encompassed the experiences of several of the largest life science SFT programs. The 14 recommendations were derived through a Delphi method, where consensus was achieved in real time as the group completed a series of meetings and tasks designed to elicit specific recommendations. Recommendations cover the breadth of SFT contexts and stakeholder groups and include actions for instructors (e.g., make equity and inclusion an ethical obligation), programs (e.g., centralize infrastructure for assessment and evaluation), as well as organizations and funders (e.g., professionalize training SFT instructors; deploy SFT to counter inequity). Recommendations are aligned with a purpose-built framework—“The Bicycle Principles”—that prioritizes evidenced-based teaching, inclusiveness, and equity, as well as the ability to scale, share, and sustain SFT. We also describe how the Bicycle Principles and recommendations are consistent with educational change theories and can overcome systemic barriers to delivering consistently effective, inclusive, and career-spanning SFT.
Population-wise labeling of sulcal graphs using multi-graph matching
Authors: Yadav Rohit , Dupé François-Xavier , Takerkart Sylvain , Auzias Guillaume
Published: November 2023

Population-wise matching of the cortical folds is necessary to compute statistics, a required step for e.g. identifying biomarkers of neurological or psychiatric disorders. The difficulty arises from the massive inter-individual variations in the morphology and spatial organization of the folds. The task is challenging both methodologically and conceptually. In the widely used registration-based techniques, these variations are considered as noise and the matching of folds is only implicit. Alternative approaches are based on the extraction and explicit identification of the cortical folds. In particular, representing cortical folding patterns as graphs of sulcal basins—termedsulcal graphs—enables to formalize the task as a graph-matching problem. In this paper, we propose to address the problem of sulcal graph matching directly at the population level using multi-graph matching techniques. First, we motivate the relevance of the multi-graph matching framework in this context. We then present a procedure for generating populations of artificial sulcal graphs, which allows us to benchmark several state-of-the-art multi-graph matching methods. Our results on both artificial and real data demonstrate the effectiveness of multi-graph matching techniques in obtaining a population-wise consistent labeling of cortical folds at the sulcal basin level.
AUM302, a novel triple kinase PIM/PI3K/mTOR inhibitor, is a potent in vitro pancreatic cancer growth inhibitor
Authors: Ingle Komala , LaComb Joseph F. , Graves Lee M. , Baines Antonio T. , Bialkowska Agnieszka B.
Published: November 2023

Pancreatic cancer is one of the leading causes of cancer deaths, with pancreatic ductal adenocarcinoma (PDAC) being the most common subtype. Advanced stage diagnosis of PDAC is common, causing limited treatment opportunities. Gemcitabine is a frequently used chemotherapeutic agent which can be used as a monotherapy or in combination. However, tumors often develop resistance to gemcitabine. Previous studies show that the proto-oncogene PIM kinases (PIM1 and PIM3) are upregulated in PDAC compared to matched normal tissue and are related to chemoresistance and PDAC cell growth. The PIM kinases are also involved in the PI3K/AKT/mTOR pathway to promote cell survival. In this study, we evaluate the effect of the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, and commercially available PIM inhibitor, TP-3654. Using five human PDAC cell lines, we found AUM302 to be a potent inhibitor of cell proliferation, cell viability, cell cycle progression, and phosphoprotein expression, while TP-3654 was less effective. Significantly, AUM302 had a strong impact on the viability of gemcitabine-resistant PDAC cells. Taken together, these results demonstrate that AUM302 exhibits antitumor activity in human PDAC cells and thus has the potential to be an effective drug for PDAC therapy.
Maternal separation modifies spontaneous synaptic activity in the infralimbic cortex of stress-resilient male rats
Authors: Ayala-Rodríguez Jesús David , García-Colunga Jesús
Published: November 2023

Glutamate and GABA signaling systems are necessary to maintain proper function of the central nervous system through excitation/inhibition (E/I) balance. Alteration of this balance in the medial prefrontal cortex (mPFC), as an effect of early-life stress, may lead to the development of anxiety and depressive disorders. Few studies exist in the infralimbic division of the mPFC to understand the effect of early-life stress at different ages, which is the purpose of the present work. Newborn Sprague Dawley male rats were subjected to maternal separation (MS) for two weeks. First, tests measuring anxiety- and depression-like behaviors were performed on adolescent and adult rats subjected to MS (MS-rats). Then, to establish a relationship with behavioral results, electrophysiological recordings were performed in neurons of the infralimbic cortex in acute brain slices of infant, adolescent, and adult rats. In the behavioral tests, there were no significant differences in MS-rats compared to control rats at any age. Moreover, MS had no effect on the passive membrane properties nor neuronal excitability in the infralimbic cortex, whereas spontaneous synaptic activity in infralimbic neurons was altered. The frequency of spontaneous glutamatergic synaptic events increased in infant MS-rats, whereas in adolescent MS-rats both the frequency and the amplitude of spontaneous GABAergic events increased without any effect on glutamatergic synaptic responses. In adult MS-rats, these two parameters decreased in spontaneous GABAergic synaptic events, whereas only the frequency of glutamatergic events decreased. These data suggest that rats subjected to MS did not exhibit behavioral changes and presented an age-dependent E/I imbalance in the infralimbic cortex, possibly due to differential changes in neurotransmitter release and/or receptor expression.
Exploring the impact of mobility and selection on stone tool recycling behaviors through agent-based simulation
Authors: Coco Emily
Published: November 2023

Recycling behaviors are becoming increasingly recognized as important parts of the production and use of stone tools in the Paleolithic. Yet, there are still no well-defined expectations for how recycling affects the appearance of the archaeological record across landscapes. Using an agent-based model of recycling in surface contexts, this study looks how the archaeological record changes under different conditions of recycling frequency, occupational intensity, mobility, and artifact selection. The simulations also show that while an increased number of recycled artifacts across a landscape does indicate the occurrence of more scavenging and recycling behaviors generally, the location of large numbers of recycled artifacts is not necessarily where the scavenging itself happened. This is particularly true when mobility patterns mean each foraging group spend more time moving around the landscape. The results of the simulations also demonstrate that recycled artifacts are typically those that have been exposed longer in surface contexts, confirming hypothesized relationships between recycling and exposure. In addition to these findings, the recycling simulation shows how archaeological record formation due to recycling behaviors is affected by mobility strategies and selection preferences. While only a simplified model of recycling behaviors, the results of this simulations give us insight into how to better interpret recycling behaviors from the archaeological record, specifically demonstrating the importance of contextualizing the occurrence of recycled artifacts on a wider landscape-level scale.
Sustainable Consumption in the Behavior of Young Consumers
Authors: Wyrwa Joanna , Barska Anetta , Jędrzejczak-Gas Janina , Kononowicz Krzysztof
Published: November 2023

The aim of the article is to characterize the attitude of young consumers towards the concept of sustainable consumption in the area of food consumption, which is manifested, among others, in the declared engagement in sustainable behaviors both in the market as well as in households. The research was conducted using the CAWI method on a sample of Polish consumers from the Lubuskie region. The article consists of two parts. The first part explores the problems of sustainable consumption. The second part presents the results of research on consumer attitudes towards the concept of sustainable consumption in the area of food consumption. Particular attention was paid to the awareness of the implications of consumer behavior in the process of satisfying food needs. Behaviors, attitudes and beliefs of consumers related to sustainable consumption were characterized, and an attempt was subsequently made to determine the extent of the gap existing between behaviors and attitudes. The conducted survey research constituted an attempt at highlighting certain consumption problems among young people, to have them share their views on the different issues of sustainable consumption, as well as to emphasize the importance of various factors in shaping sustainable food consumption patterns. The article certainly is not an exhaustive examination of all the problems areas of sustainable consumption, but it should make these more easily identifiable all while stressing the real role and importance of sustainable behaviors among young consumers in the modern economy.

Keywords: sustainable consumption, sustainable development, young consumer.
Antibiotics With or Without Rifaximin for Acute Hepatic Encephalopathy in Critically Ill Patients With Cirrhosis: A Double-Blind, Randomized Controlled (ARiE) Trial
Authors: Kulkarni Anand V. , Avadhanam Mahathi , Karandikar Puja , Rakam Kalyan , Gupta Anand , Simhadri Venu , Premkumar Madhumita , Zuberi Asim Ahmed , Gujjarlapudi Deepika , Narendran Ramyashri , Shaik Sameer , Sharma Mithun , Iyengar Sowmya , Alla Manasa , Venishetty Shantan , Reddy Duvvur Nageshwar , Rao Padaki Nagaraja
Published: November 2023

INTRODUCTION:

Critically ill patients with cirrhosis admitted to the intensive care unit (ICU) are usually on broad-spectrum antibiotics because of suspected infection or as a hospital protocol. It is unclear if additional rifaximin has any synergistic effect with broad-spectrum antibiotics in ICU patients with acute overt hepatic encephalopathy (HE).

METHODS:

In this double-blind trial, patients with overt HE admitted to ICU were randomized to receive antibiotics (ab) alone or antibiotics with rifaximin (ab + r). Resolution (or 2 grade reduction) of HE, time to resolution of HE, in-hospital mortality, nosocomial infection, and changes in endotoxin levels were compared between the 2 groups. A subgroup analysis of patients with decompensated cirrhosis and acute-on-chronic liver failure was performed.

RESULTS:

Baseline characteristics and severity scores were similar among both groups (92 in each group). Carbapenems and cephalosporin with beta-lactamase inhibitors were the most commonly used ab. On Kaplan-Meier analysis, 44.6% (41/92; 95% confidence interval [CI], 32–70.5) in ab-only arm and 46.7% (43/92; 95% CI, 33.8–63) in ab + r arm achieved the primary objective (P = 0.84).Time to achieve the primary objective (3.65 ± 1.82 days and 4.11 ± 2.01 days; P = 0.27) and in-hospital mortality were similar among both groups (62% vs 50%; P = 0.13). Seven percent and 13% in the ab and ab + r groups developed nosocomial infections (P = 0.21). Endotoxin levels were unaffected by rifaximin. Rifaximin led to lower in-hospital mortality (hazard ratio: 0.39 [95% CI, 0.2–0.76]) in patients with decompensated cirrhosis but not in patients with acute-on-chronic liver failure (hazard ratio: 0.99 [95% CI, 0.6–1.63]) because of reduced nosocomial infections.

DISCUSSION:

Reversal of overt HE in those on ab was comparable with those on ab + r.
exposiciones conceptuales de Kant
Authors: Martínez Luciana
Published: November 2023

En este artículo se examina la noción kantiana de exposición, que se encuentra en la Crítica de la razón pura y en la Crítica del Juicio. Se sostiene que hay una coherencia en el uso del concepto en la presentación de la doctrina de espacio y el tiempo, la explicación de las razones por las que el método matemático no puede ser empleado en la filosofía, la investigación analítica de los juicios de gusto y la descripción de la índole de las ideas estéticas. La exposición se presenta en todos estos pasajes como un procedimiento de carácter discursivo que permite examinar, sin definirlas, representaciones conceptuales.
De la omnipotencia no-divina
Authors: Galán Vélez Francisco Vicente
Published: November 2023

Quentin Meillassoux defiende una posición llamada “materialismo especulativo”, la cual asegura haber alcanzado –por un procedimiento estrictamente racional–  algo absoluto. Con este gesto afirma ir más allá de la crítica kantiana y del fideísmo. Esta postura es muy diferente de los materialismos tradicionales, pero también de todo tipo de absoluto metafísico, pues niega la validez del principio de razón suficiente y rechaza la existencia necesaria de cualquier entidad. Lo único necesario para Meillassoux es el principio que afirma que todo es contingente, y la concomitante irrazón de todo lo que existe. El autor objeta que se pueda sostener racionalmente que lo real carece de inteligibilidad, a la vez que argumenta que se puede justificar la tesis del surgimiento ex nihilo de la vida, el pensamiento, e incluso de la divinidad, con el razonamiento de que la contingencia radical de todo implica también que todo es posible, excepto lo contradictorio.
influencia de la escuela sociológica francesa en el pensamiento heterológico de Georges Bataille
Authors: Teruel Andrea
Published: November 2023

El artículo indaga sobre la influencia que la escuela sociológica francesa tuvo en la conformación de la heterología batailleana. Para ello se toman como eje tres conceptos clave: lo sagrado, la bipolaridad de lo sagrado y el sacrificio.  Se explora el alcance de estas nociones en el pensamiento de Bataille y se pone en tensión sus escritos con trabajos específicos de Durkheim, Hertz, Mauss y Hubert. Esto lleva a constatar la importancia fundamental de este último grupo de sociólogos en las reflexiones del heterólogo. No obstante también se evidencian las transgresiones de Bataille a los objetivos teóricos de aquel grupo al articular una motivación práctica en su heterología. Se establece así un vínculo y una distancia entre una sociología de lo sagrado y una sociología sagrada.
The Proposed Research Framework of Organizational Agility
Authors: Umbara Taufan , Pangarso Astadi , Setyorini Retno
Published: November 2023

Organizational agility is the ability of an organization to respond to organizational dynamics. This paper applies a systematic literature review (SLR) based on the PRISMA protocol and theory-context-characteristic-methodology (TCCM) analysis to find research gaps and construct a research framework concerning organizational agility. By reviewing previous research publications with the following criteria: quantitative research documents indexed by Scopus as journals; in the subject area of Business, Management, and Accounting; written across 2005â€’2020 in English and downloadable in full text; and empirical studies using structural equation modeling in data processing presents several research gaps. A research framework proposal is compiled concerning these research gaps, comprising 14 propositions. The proposed research framework of organizational agility is expected to provide the basis for future empirical studies.
François Furet, Minulosť jednej ilúzie. Esej o idei komunizmu v 20. storočí
Authors: Dobeš Jan
Published: November 2023

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