bluuebunny/crossref_metadata_2025 huggingface dataset:
Availability, market share and price of quality assured artemisinin-based combination therapies in private drug outlets after over a decade of Copayment mechanism in Uganda
Authors: Ocan Moses , Nambatya Winnie , Otike Caroline , Nakalembe Loyce , Nsobya Sam
Published: November 2023

Background

Malaria remains one of the leading causes of morbidity, and mortality in Uganda. A large proportion of malaria symptomatic patients seek healthcare in the private sector. However, availability and affordability are major barriers to access to effective treatment. The private sector copayment mechanism in Uganda aims to increase availability and affordability of antimalarial agents. Our study assessed the availability, price, and market share of quality assured artemisinin-based combination therapies (QAACTs) in private drug outlets after over a decade of copayment mechanism in the private sector in Uganda.

Methods

This was a cross-sectional survey of anti-malarial agents in private drug outlets in high (Tororo, and Apac districts) and low (Kabale and Mbarara districts) malaria transmission settings. Following the World Health Organization Health Action International (WHO/HAI) criteria, an audit of the antimalarial agents was done using a checklist to determine availability, price, and market share of QAACTs. Data was entered in Epi-data and analyzed in STATAver14.0 at 95% confidence level.

Results

A total of twenty-eight (28) private drug outlets (pharmacies and drug shops) were included in the survey. One in seven Artemisinin-based combination therapies (ACTs) in the drug outlets were quality assured (QAACTs). Artemether-lumefantrine (AL), 8.9% (11/124) and Artesunate-Amodiaquine (AQ), 7.3% (9/124) were the only QAACTs present in the drug outlets at the time of the survey. The majority, 86.1%% (124/144) of antimalarial agents present in stock in the drug outlets were artemisinin based. The most common, 38.9% (56/144) ACT in the drug outlets was Dihydroartemisinin-Piperaquine (DHP). Most, 69.4% (100/144) of the antimalarial agents were in high malaria transmission settings. The cost of ACT antimalarial agents is high in the country, USD 1.4 (Artemether-Lumefantrine, AL), USD 2.4 (Dihydroartemisinin-Piperaquine, DP), the first line and second-line agents respectively for treatment of uncomplicated malaria in Uganda. There was a statistically significant difference between the dispensing price of the ‘Green leaf’ ACTs and the recommended price (p<0.001).

Conclusion

Quality assured artemisinin-based combination therapies (QAACTs) are not common in private drug outlets in low and high malaria transmission settings. All the drug outlets had at least one ACT antimalarial agent present on the day of the survey. The dispensing price of QAACTs was significantly higher than the recommended markup price. There is need for awareness creation, surveillance, and monitoring of the implementation of Copayment mechanism in the country.
Exploring virtual funding committee practices in the allocation of National Institute for Health and Care Research funding: A netnographic study
Authors: Blatch-Jones Amanda Jane , Boxall Cherish , Asante Emmanuel , Meadmore Katie
Published: November 2023

Objectives

Funding committees, comprising members with a range of knowledge, skills, and experience, are considered integral to the decision-making process of funding organisations for recommending or allocating research funding. However, there is limited research investigating the decision-making processes, the role of members and their social interactions during funding committee meetings conducted both virtually and face-to-face.

Methods

Using a mixed-methods design and following netnography principles, the study observed nine National Institute for Health and Care Research programmes funding committee meetings conducted virtually during October 2020 to December 2021; complemented by interviews with committee chairs and members (18 interviews) and NIHR staff (12 interviews); an online survey (50 responses); and documentary analysis. Personal reflections through immersive journals also formed part of the analysis.

Results

Three main themes were identified from the observations, interviews, and online survey:efficiency of virtual committee meetings(importance of preparation, and the role of formality, process, and structure);understanding the effect of virtual committee meetings on well-being(effects of fatigue and apprehension, and the importance of work life balance); and,understanding social interactions and engagement(levels of engagement, contribution and inclusivity, awareness of unconscious bias and the value of social networking).

Conclusions

Examining the decision-making practices of one funding organisation across several research programmes, across multiple committee meetings over one year has generated new insights around funding committee practices that previous studies have not been able to explore or investigate. Overall, it was observed that fair and transparent funding recommendations and outcomes can be achieved through virtual funding committees. However, whilst virtual funding committees have many benefits and opportunities, such as the potential to increase membership diversity and inclusivity, and be more environmentally sustainable, more evidence is needed to evaluate their effectiveness, with particular focus on issues of fatigue, engagement, and committee cohesion, especially when new committee members join.
Effect of real-time feedback-based core stabilization training using a sling on balance and gait in patients with stroke: Randomized Controlled Trial
Authors: Yoo Ja-young , An Jungae , Lee Byounghee
Published: November 2023

Background

Balance impairments commonly occur in patients after stroke. Research is warranted to improve the efficiency of rehabilitation by combining core stabilization training, such as trunk exercises, and real-time feedback. This study aimed to evaluate the effect of real-time feedback-based core stabilization training (RFCST) using a sling on the dynamic balance and gait of patients with stroke.

Methods

Thirty-eight patients with stroke were randomly assigned to either RFCST using a sling group (n=19) or a control group (n=19). Each group was trained for 30 min daily, 3 times a week for 4 weeks. The Trunk Impairment Scale (TIS), Functional Reach Test (FRT), Postural Assessment Scale for Stroke (PASS), Timed Up and Go (TUG) test, and gait parameters were assessed using the GAITRite system before and after the intervention.

Results

The results showed a significant interaction between Group*Time effect F(1, 36)= 36.068,p<0.001, η²p= 0.5 in TIS; F(1, 36)= 63.890,p<0.001, η²p= 0.640 in FRT; F(1, 36)= 89.283,p<0.001, η²p= 0.713 in PASS, F(1, 36)= 150.893,p<0.001, η²p= 0.807 in TUG; F(1, 36)= 27.275,p<0.001, η²p= 0.431 in gait velocity; F(1, 36)= 54.401,p<0.001, η²p= 0.447 in cadence; F(1, 36)= 5.601,p=0.023, η²p= 0.135 in step length; F(1, 36)= 22.559,p<0.001, η²p= 0.385 in stride length; F(1, 36)= 15.516,p<0.001, η²p= 0.301 in swing phase rate; and F(1, 36)= 28.451,p<0.001, η²p= 0.441 in stance phase rate.

Conclusion

Based on these results, it can be concluded that RFCST using a sling can improve dynamic balance and gait parameters in patients with stroke.
Improving Individualized Treatment Decisions: A Bayesian Multivariate Hierarchical Model for Developing a Treatment Benefit Index using Mixed Types of Outcomes
Authors: Wu Danni , Goldfeld Keith S. , Petkova Eva , Park Hyung G.
Published: November 2023

Background

Precision medicine has led to the development of targeted treatment strategies tailored to individual patients based on their characteristics and disease manifestations. Although precision medicine often focuses on a single health outcome for individualized treatment decision rules (ITRs), relying only on a single outcome rather than all available outcomes information leads to suboptimal data usage when developing optimal ITRs.

Methods

To address this limitation, we propose a Bayesian multivariate hierarchical model that leverages the wealth of correlated health outcomes collected in clinical trials. The approach jointly models mixed types of correlated outcomes, facilitating the “borrowing of information” across the multivariate outcomes, and results in a more accurate estimation of heterogeneous treatment effects compared to using single regression models for each outcome. We develop a treatment benefit index, which quantifies the relative treatment benefit of the experimental treatment over the control treatment, based on the proposed multivariate outcome model.

Results

We demonstrate the strengths of the proposed approach through extensive simulations and an application to an international Coronavirus Disease 2019 (COVID-19) treatment trial. Simulation results indicate that the proposed method reduces the occurrence of erroneous treatment decisions compared to a single regression model for a single health outcome. Additionally, the sensitivity analysis demonstrates the robustness of the model across various study scenarios. Application of the method to the COVID-19 trial exhibits improvements in estimating the individual-level treatment efficacy (indicated by narrower credible intervals for odds ratios) and optimal ITRs.

Conclusion

The study jointly models mixed types of outcomes in the context of developing ITRs. By considering multiple health outcomes, the proposed approach can advance the development of more effective and reliable personalized treatment
Fast and accurate local ancestry inference with Recomb-Mix
Authors: Wei Yuan , Zhi Degui , Zhang Shaojie
Published: November 2023

The availability of large genotyped cohorts brings new opportunities for revealing the high-resolution genetic structure of admixed populations via local ancestry inference (LAI), the process of identifying the ancestry of each segment of an individual haplotype. Though current methods achieve high accuracy in standard cases, LAI is still challenging when reference populations are more similar (e.g., intra-continental), when the number of reference populations is too numerous, or when the admixture events are deep in time, all of which are increasingly unavoidable in large biobanks. Here, we present a new LAI method, Recomb-Mix. Recomb-Mix integrates the elements of existing methods of the site-based Li and Stephens model and introduces a new graph collapsing trick to simplify counting paths with the same ancestry label readout. Through comprehensive benchmarking on various simulated datasets, we show that Recomb-Mix is more accurate than existing methods in diverse sets of scenarios while being competitive in terms of resource efficiency. We expect that Recomb-Mix will be a useful method for advancing genetics studies of admixed populations.
Neurotechnology-based intensive upper-extremity supplementary training for inpatients with sub-acute stroke: A feasibility study
Authors: Binyamin-Netser Reut , Handelzalts Shirley , Goldhamer Noy , Avni Inbar , Tayer Adi Yeshurun , Koren Yogev , Levy Ofri Bibas , Kramer Shilo , Haim Simona Bar , Shmuelof Lior
Published: November 2023

Background

Intensive and high-dose upper extremity training, concentrating on movement quality in the early phase after a stroke, can enhance motor recovery compared to standard care. Unfortunately, such programs do not exist due to limited resources, patient compliance, and administrative challenges.

Objective

To examine the feasibility and potential efficacy, and to evaluate the resources of an intensive technology-based upper extremity training emphasizing movement quality during inpatient stroke rehabilitation.

Methods

Twelve subjects with hemiparesis underwent 40 60-minute sessions over a 4-week period, in addition to standard care. The training included two game-based virtual reality platforms to practice proximal (tech 1) and distal (tech 2) movements with daily assessments.

Results

Eight subjects completed the entire protocol, three subjects completed 34–38 sessions, and one subject completed only 27 sessions. The mean time on each task was 35±4 (tech 1) and 37±2 (tech 2) minutes per hour. The intervention was perceived as motivating and enjoyable [Intrinsic Motivation Inventory (IMI) enjoyment and interest= 6.49±0.66 out of 7] and was not associated with pain [Visual Analogue Scale (VAS) mean= 2.00±2.32]. Subjects showed large improvements in all impairment measurements (mean FMA delta= 16.5 points and ARAT delta= 22.9 points).

Conclusions

The results support the feasibility of a high-dose high-intensity supplementary training protocol during sub-acute hospitalization and provide suggestive evidence of its efficacy.
Diurnal variation of 8-hydroxy-2’-deoxyguanosine in continuous time series of two breast cancer survivors
Authors: Geuter Joschua , Seizer Lennart , Cornelissen Guillaume Germaine , Engin Ayse Basak , Fuchs Dietmar , Schubert Christian
Published: November 2023

8-hydroxy-2’deoxyguanosine (8-OHdG) is an oxidative product removed from DNA following radical oxygen species-induced damage. Being water-soluble, it can be measured non-invasively in the urine and has thus been established as a marker for ‘whole-body’ oxidative stress. Its validity and reliability as an oxidative stress marker in various chronic diseases and early carcinogenesis screening in clinical diagnosis and research are widely debated. To determine optimal measurement timing and duration, it is essential to establish the circadian profile of 8-OHdG under everyday life conditions and use reliable sampling methods. Here, we show the presence of day-night differences for 8-OHdG normalized by creatinine or urine volume in continuous time series of two breast cancer survivors who participated in integrative single-case studies and sampled their urine in 12-h-pooled collections over one month. These findings support the importance of appropriately considering the dynamic characteristics of stress indicators to reduce the risk of inconsistent or false results in clinical diagnostics.
Brain-derived Tau for Monitoring Brain Injury in Acute Ischemic Stroke
Authors: Vlegels Naomi , Gonzalez-Ortiz Fernando , Knuth Nicoló Luca , Khalifeh Nada , Gesierich Benno , Müller Franziska , Müller Philipp , Klein Matthias , Dimitriadis Konstantinos , Franzmeier Nicolai , Liebig Thomas , Duering Marco , Reidler Paul , Dichgans Martin , Karikari Thomas K. , Blennow Kaj , Tiedt Steffen
Published: November 2023

The evolution of infarcts varies widely among patients with acute ischemic stroke (IS) and influences treatment decisions. Neuroimaging is not applicable for frequent monitoring and there is no blood-based biomarker to track ongoing brain injury in acute IS. Here, we examined the utility of plasma brain-derived tau (BD-tau) as a biomarker for brain injury in acute IS. We conducted the prospective, observational Precision Medicine in Stroke [PROMISE] study with serial blood sampling upon hospital admission and at days 2, 3, and 7 in patients with acute ischemic stroke (IS) and for comparison, in patients with stroke mimics (SM). We determined the temporal course of plasma BD-tau, its relation to infarct size and admission imaging-based metrics of brain injury, and its value to predict functional outcome. Upon admission (median time-from-onset, 4.4h), BD-tau levels in IS patients correlated with ASPECTS (ρ=-0.21,P<.0001) and were predictive of final infarct volume (ρ=0.26,P<.0001). In contrast to SM patients, BD-tau levels in IS patients increased from admission (median, 2.9 pg/ml [IQR, 1.8-4.8]) to day 2 (median time-from-onset, 22.7h; median BD-tau, 5.0 pg/ml [IQR, 2.6-10.3];P<.0001). The rate of change of BD-tau from admission to day 2 was significantly associated with collateral supply (R2=0.10,P<.0001) and infarct progression (ρ=0.58,P<.0001). At day 2, BD-tau was predictive of final infarct volume (ρ=0.59,P<.0001) and showed superior value for predicting the 90-day mRS score compared with final infarct volume. In conclusion, in 502 patients with acute IS, plasma BD-tau was associated with imaging-based metrics of brain injury upon admission, increased within the first 24 hours in correlation with infarct progression, and at 24 hours was superior to final infarct volume in predicting 90-day functional outcome. Further research is needed to determine whether BD-tau assessments can inform decision-making in stroke care.
Optical constraints on two-photon voltage imaging
Authors: Brooks F. Phil , Davis Hunter C. , Wong-Campos J. David , Cohen Adam E.
Published: November 2023

Significance

Genetically encoded voltage indicators (GEVIs) are a valuable tool for studying neural circuitsin vivo, but the relative merits and limitations of one-photon (1P) vs. two-photon (2P) voltage imaging are not well characterized.

Aim

We consider the optical and biophysical constraints particular to 1P and 2P voltage imaging and compare the imaging properties of commonly used GEVIs under 1P and 2P excitation.

Approach

We measure brightness and voltage sensitivity of voltage indicators from commonly used classes under 1P and 2P illumination. We also measure the decrease in fluorescence as a function of depth in mouse brain. We develop a simple model of the number of measurable cells as a function of reporter properties, imaging parameters, and desired signal-to-noise ratio (SNR). We then discuss how the performance of voltage imaging would be affected by sensor improvements and by recently introduced advanced imaging modalities.

Results

Compared to 1P excitation, 2P excitation requires ∼104-fold more illumination power per cell to produce similar photon count rates. For voltage imaging with JEDI-2P in mouse cortex with a target SNR of 10 (spike height:baseline shot noise), a measurement bandwidth of 1 kHz, a thermally limited laser power of 200 mW, and an imaging depth of > 300 μm, 2P voltage imaging using an 80 MHz source can record from no more 12 cells simultaneously.

Conclusions

Due to the stringent photon-count requirements of voltage imaging and the modest voltage sensitivity of existing reporters, 2P voltage imagingin vivofaces a stringent tradeoff between shot noise and tissue photodamage. 2P imaging of hundreds of neurons with high SNR at depth > 300 μm will require either major improvements in 2P GEVIs or qualitatively new approaches to imaging.
Cell morphology QTL reveal gene by environment interactions in a genetically diverse cell population
Authors: O’Connor Callan , Keele Gregory R. , Martin Whitney , Stodola Timothy , Gatti Daniel , Hoffman Brian R. , Korstanje Ron , Churchill Gary A. , Reinholdt Laura G.
Published: November 2023

Genetically heterogenous cell lines from laboratory mice are promising tools for population-based screening as they offer power for genetic mapping, and potentially, predictive value forin vivoexperimentation in genetically matched individuals. To explore this further, we derived a panel of fibroblast lines from a genetic reference population of laboratory mice (the Diversity Outbred, DO). We then used high-content imaging to capture hundreds of cell morphology traits in cells exposed to the oxidative stress-inducing arsenic metabolite monomethylarsonous acid (MMAIII). We employed dose-response modeling to capture latent parameters of response and we then used these parameters to identify several hundred cell morphology quantitative trait loci (cmQTL). Response cmQTL encompass genes with established associations with cellular responses to arsenic exposure, includingAbcc4andTxnrd1, as well as novel gene candidates likeXrcc2. Moreover, baseline trait cmQTL highlight the influence of natural variation on fundamental aspects of nuclear morphology. We show that the natural variants influencing response include both coding and non-coding variation, and that cmQTL haplotypes can be used to predict response in orthogonal cell lines. Our study sheds light on the major molecular initiating events of oxidative stress that are under genetic regulation, including the NRF2-mediated antioxidant response, cellular detoxification pathways, DNA damage repair response, and cell death trajectories.
In VivoPhenotypic Vascular Dysfunction Extends Beyond the Aorta in a Mouse Model for Fibrillin-1 (FBN1) Mutation
Authors: Curry T , Barrameda M.E. , Currier Thomas T. , Esfandiarei M.
Published: November 2023

In individuals with Marfan Syndrome (MFS), fibrillin-1 gene (FBN1) mutations can lead to vascular wall weakening and dysfunction. The experimental mouse model of MFS (FBN1C1041G/+) has been advantageous in investigating MFS-associated life-threatening aortic aneurysms. Although the MFS mouse model presents an accelerated-aging phenotype in elastic organs (e.g., lung, skin), the impact ofFBN1mutations on other central and peripheral arteries function and structure with the consideration of the impact of sex remains underexplored. In this study, we investigate ifFBN1mutation contributes to sex-dependent alterations in central and cerebral vascular function similar to phenotypic changes associated with normal aging in healthy control mice.In vivoultrasound imaging of central and cerebral vasculature was performed in 6-month-old male and female MFS and C57BL/6 mice and sex-matched 12-month-old (middle-aged) healthy control mice. Our findings confirm aortic enlargement (aneurysm) and wall stiffness in MFS mice, but with exacerbation in male diameters. Coronary artery blood flow velocity (BFV) in diastole was not different but left pulmonary artery BFV was decreased in MFS and 12-month-old control mice regardless of sex. At 6 months of age, MFS male mice show decreased posterior cerebral artery BFV as compared to age-matched control males, with no difference observed between female cohorts. Reduced mitral valve early-filling velocities were indicated in MFS mice regardless of sex. Male MFS mice also demonstrated left ventricular hypertrophy. Overall, these results underscore the significance of biological sex in vascular function and structure in MFS mice, while highlighting a trend of pre-mature vascular aging phenotype in MFS mice that is comparable to phenotypes observed in older healthy controls.
Herbivore insect small RNA effector suppress plant defense by cross-kingdom gene silencing
Authors: Han Wen-Hao , Ji Shun-Xia , Zhang Feng-Bin , Song Hong-Da , Wang Jun-Xia , Xie Rui , Wang Xiao-Wei
Published: November 2023

Herbivore insects deploy salivary effectors to manipulate the defense of their host plants, however, whether insect small RNAs (sRNAs) act as effectors to regulate plant-insect interaction is currently unclear. Here, we report that a microRNA (miR29-b) from the saliva of phloem-feeding insects can transfer into the host plant phloem and fine-tune the host defense. The salivary gland’s abundant miR29-b was produced by insect Dicer 1 and insect salivary exosome is involved in its transferring and releasing into the host plant. Insect miR29-b effector hijacks plant Argonaute 1 to silence host defense geneBcl-2-associated athanogene 4(BAG4). Silencing ofBAG4suppressed the expression of phenylalanine ammonia-lyase and the accumulation of salicylic acid (SA), therefore negatively regulating host defense against herbivore insects. miR29-b is highly conserved in Hemiptera, Coleoptera, Hymenoptera, Orthoptera, and Blattaria insects and also targets theBAG4gene. Notably,BAG4orthologs exist in a wide range of plant species and may as the target of insect miR29-b. Our work provides new insight into the intriguing defense and counter-defense between herbivores and plants.

Teaser

Phloem-feeding insects produce and transfer small RNA into the host plants to fine-tune plant basal defense by cross-kingdom gene silencing.
A New Generalized Gamma-Weibull Distribution with Applications to Time-to-event Data
Authors: Dauda Kazeem Adesina , Lamidi Rasheed Kehinde , Dauda Adeshola Adediran , Yahya Waheed Babatunde
Published: November 2023

In this research, a new class of probability distributions referred to as Generalized Gamma Weibull (GGW) distributions was introduced within the context of parametric survival analysis. This distribution represents a modification of the gamma Weibull distribution and offers valuable insights, particularly when dealing with highly skewed lifetime data. The study extensively examined the mathematical characteristics of these distributions, encompassing hazard functions, moments, quantile functions, and order statistics. Furthermore, the research delved into parameter estimation methods for these newly proposed distributions, employing the maximum likelihood technique, Fisher Information (FI), and deriving asymptotic confidence intervals for both censored and uncensored scenarios. To illustrate the practical utility of these proposed distributions, the study applied them to analyze two sets of real-life survival data and two sets of real-life data, resulting in a total of four distinct datasets. To gauge the effectiveness of the GGW distributions in comparison to existing methods such as Generalized Weibull and Generalized gamma (G-Weibull and G-Gamma) distributions, the research employed statistical indices including the Akaike Information Criterion (AIC), Corrected Akaike Information Criterion (CAIC), and Bayesian Information Criterion (BIC). The outcomes of this comparative analysis demonstrated the superior performance of the newly introduced GGW distributions (AIC=338.6313, BIC=346.2794, and CAIC=339.5202) when contrasted with the existing methods (G-Weibull: AIC=376.1946, BIC=381.9307, and CAIC=376.5424) across all three criteria, thereby highlighting the enhanced suitability of GGW distributions for modeling and analyzing skewed lifetime data.
Changes in Secondary Structure and Properties of Bovine Serum Albumin as a Result of Interactions with Gold Surface
Authors: Komorek Paulina , Rakowski Kamil , Szota Magdalena , Lekka Małgorzata , Jachimska Barbara
Published: November 2023

Proteins can alter their shape when interacting with a surface. This study explores how bovine serum albumin (BSA) modifies structurally when it adheres to a gold surface, depending on the protein concentration and pH. We verified that the gold surface induces significant structural modifications to the BSA molecule using circular dichroism, infrared spectroscopy, and atomic force microscopy. Specifically, adsorbed molecules displayed increased levels of disordered structures and β-turns, with fewer α-helices than the native structure. MP-SPR spectroscopy demonstrated that the protein molecules preferred a planar orientation during adsorption. Molecular dynamics simulations revealed that the interaction between cysteines exposed to the outside of the molecule and the gold surface was vital, especially at pH = 3.5. The macroscopic properties of the protein film observed by AFM and contact angles confirm the flexible nature of the protein itself. Notably, structural transformation is joined with the degree of hydration of protein layers.

Abstract Figure
Fluoxetine promotes immunometabolic defenses to mediate host-pathogen cooperation during sepsis
Authors: Gallant Robert M. , Snyder Jessica M. , Ayres Janelle S.
Published: November 2023

Selective serotonin reuptake inhibitors (SSRIs) are some of the most prescribed drugs in the world. While they are used for their ability to increase serotonergic signaling in the brain, SSRIs are also known to have a broad range of effects beyond the brain, including immune and metabolic effects. Recent studies have demonstrated that SSRIs are protective in animal models and humans against several infections, including sepsis and COVID-19, however the mechanisms underlying this protection are largely unknown. Here we mechanistically link two previously described effects of the SSRI fluoxetine in mediating protection against sepsis. We show that fluoxetine-mediated protection is independent of peripheral serotonin, and instead increases levels of circulating IL-10. IL-10 is necessary for protection from sepsis-induced hypertriglyceridemia and cardiac triglyceride accumulation, allowing for metabolic reprogramming of the heart. Our work reveals a beneficial “off-target” effect of fluoxetine, and reveals a protective immunometabolic defense mechanism with therapeutic potential.
Comparison of urinary proteome in the first two days after mating in male rats
Authors: Wang Haitong , Zhao Chenyang , Gao Youhe
Published: November 2023

Objective

To explore whether differences between male rats on the next day of mating and on the day of mating can be reflected by the urine proteome.

Methods

Urine samples were collected from male Sprague-Dawley rats on the day of mating and the next day of mating. Urine samples were analysed by the free-labelled quantitative proteomics technique of high-performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Differential proteins of the urine proteome were analysed for protein function and biological pathways.

Results

43 differential proteins were identified by comparing the urine proteome of rats on the next day of mating with that on the day of mating, and nearly two-thirds of the differential proteins were related to spermatogenesis.

Conclusions

The urine proteome has the potential to reflect spermatogenesis without interfering with it.
Pathogen-prey-predator relations of avian raptors during epizootics of highly pathogenic avian influenza virus HPAIV H5N1 (clade 2.3.4.4b) in Germany
Authors: Günther Anne , Krone Oliver , Globig Anja , Pohlmann Anne , King Jacqueline , Fast Christine , Grund Christian , Hennig Christin , Herrmann Christof , Piro Simon , Rubbenstroth Dennis , Schulz Jana , Staubach Christoph , Stacker Lina , Ulrich Lorenz , Ziegler Ute , Harder Timm , Beer Martin
Published: November 2023

Transition of highly pathogenic clade 2.3.4.4b H5 avian influenza virus (HPAIV) from epizootic to enzootic status in Northern European countries was associated with severe losses and even mass mortalities among various wild bird species. Both avian and mammalian raptors hunting infected debilitated birds or scavenging on virus-contaminated avian carcasses contracted HPAIV infection. This precarious pathogen-prey-predator relation further worsened when in 2021 and 2022 outbreaks in Germany overlapped with the hatching season of avian raptor species. Retro- and prospective surveillance revealed avian raptors as important indicators of HPAIV and its genetic diversity on the one hand. On the other hand, their role as victims of HPAIV is stipulated. The first case of an HPAIV H5N1-related death of a white-tailed sea eagle (Haliaeetus albicilla;WTSE) hatch in Germany, 2021, followed by several such cases in 2022, and a low overall seropositivity rate of 5.0-7.9% among WTSE nestlings, raised fears of a serious negative impact on reproduction rates of WTSEs and other birds of prey when HPAIV becomes enzootic in an ecosystem. However, comparably stable breeding success of WTSE in the study area in 2022 and a potentially evolving natural immunity raises hope for a less severe long-term impact.

Article impact statement

Adapted surveillance measures were developed to assess risks for the conservation of avian raptors due to the panzootic spread of HPAIV.
RORγ bridges cancer-driven lipid dysmetabolism and myeloid immunosuppression
Authors: Bleve Augusto , Consonni Francesca Maria , Incerti Martina , Garlatti Valentina , Pandolfo Chiara , Monari Marta Noemi , Serio Simone , Pistillo Daniela , Sironi Marina , Alì Chiara , Manfredi Marcello , Finocchiaro Giovanna , Panico Cristina , Condorelli Gianluigi , Sica Antonio
Published: November 2023

Despite well-documented metabolic and hematopoietic alterations during tumor development1, the mechanisms underlying this crucial immunometabolic intersection have remained elusive. Of particular interest is the ligand-activated transcription factor retinoic acid-related orphan receptor 1 (RORC1/RORγ), whose activity is boosted by cholesterol metabolites2, acting as a modulator of cancer-related emergency myelopoiesis3, while hypercholesterolemia itself is associated with dysregulated myelopoiesis4,5. Here we show that both cancer growth and hypercholesterolemic diet can independently or cooperatively activate RORγ-dependent expansion of myeloid-derived suppressor cells (MDSCs) and M2 polarization of tumor-associated macrophages (TAMs), thereby supporting cancer spread. Moreover, we report that tumor development enhances the hepatic production of IL-1β and IL-6, which in turn promote upregulation of hepatic proprotein convertase subtilisin/kexin type 9 (PCSK9) gene, as we confirmed in models of fibrosarcoma, melanoma, colorectal (CRC), and lung cancer, as well as in CRC, non-small-cell lung cancer (NSCLC), breast (BRC), pancreatic ductal adenocarcinoma (PDAC), biliary tract carcinoma (BTC) and pancreatic neuroendocrine tumor (PNET) patients. Importantly, lowering cholesterol levels prevents MDSC expansion and M2 TAM accumulation in a RORγ-dependent manner, unleashing specific anti-tumor immunity and improving the efficacy of anti-PD-1 immunotherapy. Overall, we identify RORγ as a novel sensor of lipid disorders in cancer bearers, bridging hypercholesterolemia and pro-tumor myelopoiesis.
Viral expansion after transfer is a primary driver of influenza A virus transmission bottlenecks
Authors: Holmes Katie E. , VanInsberghe David , Ferreri Lucas M. , Elie Baptiste , Ganti Ketaki , Lee Chung-Young , Lowen Anice C.
Published: November 2023

For many viruses, narrow bottlenecks acting during transmission sharply reduce genetic diversity in a recipient host relative to the donor. Since genetic diversity represents adaptive potential, such losses of diversity are though to limit the opportunity for viral populations to undergo antigenic change and other adaptive processes. Thus, a detailed picture of evolutionary dynamics during transmission is critical to understanding the forces driving viral evolution at an epidemiologic scale. To advance this understanding, we used a novel barcoded virus library and a guinea pig model of transmission to decipher where in the transmission process diversity is lost for influenza A viruses. In inoculated guinea pigs, we show that a high level of viral genetic diversity is maintained across time. Continuity in the barcodes detected furthermore indicates that stochastic effects are not pronounced within inoculated hosts. Importantly, in both aerosol-exposed and direct contact-exposed animals, we observed many barcodes at the earliest time point(s) positive for infectious virus, indicating robust transfer of diversity through the environment. This high viral diversity is short-lived, however, with a sharp decline seen 1-2 days after initiation of infection. Although major losses of diversity at transmission are well described for influenza A virus, our data indicate that events that occur following viral transfer and during the earliest stages of natural infection have a predominant role in this process. This finding suggests that immune selection may have greater opportunity to operate during influenza A transmission than previously recognized.
Accurate RNA velocity estimation based on multibatch network reveals complex lineage in batch scRNA-seq data
Authors: Huang Zhaoyang , Guo Xinyang , Qin Jie , Gao Lin , Ju Fen , Zhao Chenguang , Yu Liang
Published: November 2023

RNA Velocity, as an extension of trajectory inference, is an effective method for understanding cell development using single-cell RNA sequencing (scRNA-seq) experiments. Nevertheless, existing RNA velocity methods are limited by the batch effect because they cannot directly correct for batch effects in the input data, which comprises spliced and unspliced matrices in a proportional relationship. This limitation can lead to incorrect velocity graphs. This paper introduces VeloVGI, which addresses this issue innovatively in two key ways. Firstly, it employs an optimal transport (OT) and mutual nearest neighbor (MNN) approach to construct neighbors in batch data. This strategy overcomes the limitations of existing methods that are affected by the batch effect. Secondly, VeloVGI improves upon VeloVI’s velocity estimation by incorporating the graph structure into the encoder for more effective feature extraction. The effectiveness of VeloVGI was demonstrated in various scenarios, including the mouse spinal cord and olfactory bulb, as well as on several public datasets. The results showed that VeloVGI outperformed other methods in terms of metric performance.

Significance Statement

RNA Velocity is an effective method for understanding cell development using single-cell RNA sequencing (scRNA-seq) experiments. This paper introduces VeloVGI, which addresses this batch effect issue for existing RNA velocity methods. The effectiveness of VeloVGI was demonstrated in various scenarios, including the mouse spinal cord and olfactory bulb, as well as on several public datasets. The results showed that VeloVGI outperformed other methods in terms of metric performance.
Selfish grower behavior can group-optimally eradicate plant diseases caused by coinfection
Authors: Hilker Frank M. , Kolb Lea-Deborah , Hamelin Frédéric M.
Published: November 2023

Game-theoretic behavioral and epidemiological models suggest that it is impossible to eradicate a disease through voluntary control actions when individuals behave according to their own interests. The simple reason is that free-riding behavior, which is best for self-interest, leads to a control coverage on the group level that is insufficient to eradicate the disease. Here we show that, for diseases that are caused by coinfection, selfinterest can actually result in the socially optimal outcome of disease eradication. Our result challenges the conventional wisdom that selfish behavior undermines the group interest; it resolves a social dilemma in the absence of any cooperation, institutional arrangements, or social norms. Our model is motivated by coinfecting plant viruses, common among agricultural crops and natural plants, and the behavioral dynamics of growers to adopt protective action (biological or chemical control). The epidemiological scenario, in which the disease is eradicated by self-interest, is characterized by a positive feedback process in which coinfection enhances infectivity. Similar feedback structures exist for a range of typical epidemiological processes that facilitate disease persistence if prevalence is sufficiently large. The underlying mechanism may therefore be applicable to other diseases.
Mechanosensory and command contributions to theDrosophilagrooming sequence
Authors: Yoshikawa Shingo , Tang Paul , Simpson Julie H.
Published: November 2023

Flies groom in response to competing mechanosensory cues in an anterior to posterior order using specific legs. From behavior screens, we identified a pair of cholinergic command-like neurons, Mago-no-Te (MGT), whose optogenetic activation elicits thoracic grooming by hind legs. Thoracic grooming is typically composed of body sweeps and leg rubs in alternation, but clonal analysis coupled with amputation experiments revealed that MGT activation only commands the body sweeps: initiation of leg rubbing requires contact between leg and thorax. With new electron microscopy (EM) connectome data for the ventral nerve cord (VNC), we uncovered a circuit-based explanation for why stimulation of posterior thoracic mechanosensory bristles initiates cleaning by the hind legs. Our previous work showed that flies weigh mechanosensory inputs across the body to select which part to groom, but we did not know why the thorax was always cleaned last. Here, the connectome for the VNC enabled us to identify a pair of GABAergic inhibitory neurons, UMGT1, that receive diverse sensory inputs and synapse onto both MGT and components of its downstream pre-motor circuits. Optogenetic activation of UMGT1 suppresses thoracic cleaning, representing a mechanism by which mechanosensory stimuli on other body parts could take precedence in the grooming hierarchy. We also mapped the pre-motor circuit downstream of MGT, including inhibitory feedback connections that may enable rhythmicity and coordination of limb movement during thoracic grooming.
How internet use affects personal privacy risk perception: empirical evidence from China
Authors: Liu Xiao Zhou , Ling Shuang , Liu Ying
Published: November 2023

Purpose

This study aims to empirically examine the relationship between Internet use and personal privacy risk perceptions, the mediating effect of trust and the moderating effect of satisfaction on that relationship, which is exactly conducive to the practice of personal information protection.

Design/methodology/approach

A moderated mediation model will be employed to test the hypothesized relationships using the 2017 Chinese Society Survey data.

Findings

The authors find that Internet use positively relates to citizens' risk perceptions toward privacy security, and trust partially mediates the relationship between Internet use and privacy risk perception. In addition, the analysis of moderating effects showed that satisfaction with social life significantly enhances the negative impact on individuals' privacy risk perceptions of interpersonal trust. The positively moderating effect of satisfaction with local governments' work mainly reveals the relationship between interpersonal trust (or institutional trust) and citizens' privacy risk perception. Moreover, satisfaction with Internet platforms positively moderates the relationship between consumer trust and privacy risk perception.

Originality/value

This article contributes to the social risk amplification framework by applying it to the personal privacy information protection field, which was rarely discussed before. It also enriches privacy research by identifying the internal mechanism of how Internet use influences citizens' risk perceptions towards privacy information leakage.
HAZARDS IN THE BOG—REAL AND IMAGINEDxs
Authors: MEREDITH DIANNE
Published: November 2023

ABSTRACT. A rich body of geographical lore, much of it related to real or imaginary hazards, characterizes perceptions of bog landscapes. Bog bursts, will‐o‘‐the‐wisps, carnivorous plants, weird creatures, and perceptions of the “bottomless” bog all play a part in the folklore of the landscapes. Ambiguity about the features of bog landscapes is further heightened by the descriptive terminology employed by tale tellers, who present to us a world inhabited by meanings that go beyond the physical environment and touch on the primordial inner landscape.
RUNOFF PRODUCTION AND EROSION PROCESSES ON A DEHESA IN WESTERN SPAIN*
Authors: CEBALLOS ANTONIO , CERDÀ ARTEMI , SCHNABEL SUSANNE
Published: November 2023

ABSTRACT. Runoff generation and soil erosion were investigated at the Guadalperalón experimental watershed (western Spain), within the land‐use system known as dehesa, or open, managed evergreen forests. Season and type of surface were found to control runoff and soil‐loss rates. Five soil units were selected as representative of surface types found in the study area: hillslope grass, bottom grass, tree cover, sheep trails, and shrub cover. Measurements were made in various conditions with simulated rainfall to gain an idea of the annual variation in runoff and soil loss. Important seasonal differences were noted due to surface cover and moisture content of soil, but erosion rates were determined primarily by runoff. Surfaces covered with grass and shrubs always showed less erosion; surfaces covered with holm oaks showed higher runoff rates, due to the hydrophobic character of the soils. Concentrations of runoff sediment during the simulations confirmed that erosion rates at the study site depended directly on the sediment available on the soil surface.
SEASONAL FLOODPLAIN‐UPLAND MIGRATION ALONG THE LOWER AMAZON RIVER*
Authors: WINKLERPRINS ANTOINETTE M. G. A.
Published: November 2023

ABSTRACT. A current pattern of seasonal migration, particularly among smallholders, is marked by movement between the Amazon River floodplain and upland bluffs near the city of Santarém, Brazil. Nearly fifty years of jute cultivation “subsidized” residents of the floodplain, enabling them to remain there year‐round. Without this subsidy, annual flooding and the concomitant seasonal dearth of cash‐economy activities make permanent occupancy difficult. The present‐day seasonal migration and complementary use of both upland and floodplain environments has broad implications for theories about past patterns of settlement and for the region's future sustainable development.
Dynamic contexts for innovation strategy: Utilizing customer knowledge
Authors: Reinmoeller Patrick
Published: November 2023

Knowledge and knowledge processes are fundamental for innovation. Innovation strategies have to use the complex and rapidly evolving environment. Planning with static contexts risks locking companies into past experiences and established practices—that is, existing technologies, products, and routines. Augmenting the dynamics of contexts is a key to creating new knowledge.

This paper develops a framework for creating and utilizing dynamic contexts for design and innovation management. Five dimensions of dynamic contexts are illustrated: processes, people, relationships, technology, and leadership. Utilizing the dynamics enables companies to co‐create with markets—that is, create, shape, sustain, and exploit synchronic and diachronic knowledge processes for innovation.

Two case studies of Seven‐Eleven and Muji illustrate how two internationally operating Japanese retailers implement innovation and design strategies through interaction with markets. The differences and family resemblance of the cases are analyzed.

Conclusions and implications show how the business model of designing with markets can be adapted to individual companies.
Analysis of exponential corrected thermodynamic geometries in $$AdS_5\times S^5$$ black hole
Authors: Rani Shamaila , Iqbal Sadaf , Chaudhary Shahid
Published: November 2023

This paper delves the thermodynamics of 5-dimensional Schwarzschild $$AdS_5 \times S^5$$

A
d

S
5

×

S
5

black hole by considering the recently proposed effective models of exponential entropies. The conventional understanding of cosmological constant $$\Lambda $$
Λ
as thermodynamic pressure with volume being its counterpart cannot be directly applied in the framework of the AdS/CFT correspondence. In order to resolve this issue, we establish a connection between the cosmological constant $$\Lambda $$
Λ
in the boundary gauge theory and number of colors N while chemical potential is considered as thermodynamic conjugate. In this study, we replace the geometric parameters L and r of the AdS black hole with two thermodynamic parameters $$N^2$$

N
2

and S in the micro-canonical ensemble. Additionally, we explore the various thermodynamic geometry models such as Ruppeiner, Quevedo and Weinhold to derive the associated scalar curvatures for the 5-D Schwarzschild AdS BH. We analyze that these geometries exhibit microscopic attraction/repulsion forces on the particles of black hole.
Unveiling the unconventional optical signatures of regular black holes within accretion disk
Authors: Guo Sen , Huang Yu-Xiang , Cui Yu-Hao , Han Yan , Jiang Qing-Quan , Liang En-Wei , Lin Kai
Published: November 2023

The optical characteristics of three types of black holes (BHs) surrounded by a thin accretion disk are discussed, namely the Schwarzschild BH, Bardeen BH, and Hayward BH. We calculate the deflection angle of light as it traverses the vicinity of each BH using numerical integration and semi-analytical methods, revealing that both approaches can effectively elucidate the deflection of light around the BH. We investigate the optical appearance of the accretion disk and its corresponding observational images at various viewing angles, discovering that the luminosity in the region near the BH on the inner side of the accretion disk is higher than that on the outer side owing to higher material density in closer proximity to the BH. We observe a significant accumulation of brightness on the left side of the accretion disk, attributed to the motion of matter and geometric effects. Our findings emphasize the significant influence of the observation inclination angle on the observed outcomes. An increase in the observation inclination angle results in the separation of higher-order images. With the improvement in EHT observation accuracy, we believe that the feature of a minimal distance between the innermost region of the direct image of the Hayward BH and the outermost region of the secondary image can be used as an indicator for identifying Hayward BHs.