bluuebunny/crossref_metadata_2025 huggingface dataset:
US–UK–France relations amid the Russia–Ukraine war: a new strategic alignment?
Authors: Rees Wyn , Xu Ruike
Published: April 2024

The Russian invasion of Ukraine and the recognition of the rising challenge from China have resulted in a closer alignment of American, British and French strategic interests. This policy paper explores how the strategic relationship between the United States, the United Kingdom and France has evolved amid this changed threat environment. The Russia–Ukraine war exposed the limitations of France's policy of ‘strategic autonomy’ and reasserted the importance of an American role in European security. The war has re-focused attention upon the Lancaster House framework in which the UK and France have the potential to enhance their contribution to European defence. The UK still regards its ‘special relationship’ with the US as being of critical importance to its foreign policy. But the UK's diminishing military power makes it a less valuable ally to the US whose attention is increasingly upon the Indo-Pacific region. The paper argues that the alignment between the three countries has been closer over the Russian war in Ukraine compared to attitudes towards China, where tensions between France and the ‘Anglo-Saxons’ persist. France has been unwilling to adopt the American approach towards China and has stuck to its vision of a multipolar world. The AUKUS deal arranged between the US, UK and Australia had the effect of alienating France. The policy paper contends that the temporary alignment between US, UK and French interests will erode as long-standing conflicts of interest re-emerge. In particular, the unpredictability of US leadership will damage the trilateral relationship if Donald Trump regains the presidency in November 2024.
Prospective Evaluation of the Prediction Score for a Mild Course of Crohn’s Disease (PreMiCC) in Newly Diagnosed Patients With Crohn’s Disease: The PROGNOS Study
Authors: Kruis Wolfgang , Bokemeyer Bernd , Jessen Petra , Hoesl Mark , Mroß Michael , Morgenstern Julia , Reimers Birgitta , Müller-Grage Nike , Leifeld Ludger
Published: April 2024

Background and Aims

The course of Crohn’s disease (CD) is highly variable. The Prospektive Evaluation eines Score zur Vorhersage eines milden Verlaufsbei neu diagnostizierten Morbus Crohn-Patienten in gastroenterologischen Fachpraxen (PROGNOS) study aimed to determine the frequency of a mild disease course and validate a proposed prediction score.

Methods

The PROGNOS study is a prospective study of CD patients who were newly diagnosed and, except for 1 course of 5-aminosalicylic acid or steroids for ≤10 days, therapy-naïve. Among other predefined inclusion criteria, the initial diagnosis had to be made ≤6 weeks before enrollment. All inception cohort patients were diagnosed and screened consecutively in participating gastroenterology practices in Germany specialized in inflammatory bowel disease. All screened CD patients were scored and, if possible, included in the study for up to 5 years (NCT02193048).

Results

A total of 201 CD patients were included in the study (43.3% male; mean age 33 years, mean follow-up 38 months). Altogether, 29.5% of the patients had a mild course at 36 months. Among those with a score ≤2, therapy escalation at 36 months was necessary for only 24.2%, whereas in the group with a score >2, therapy escalation was necessary for 70.2% of patients. In the Kaplan-Meier curve showing time to therapy escalation in the 2 groups, there was a pronounced and statistically significant divergence of the curves starting at 3 months and extending to 48 months (P < .001).

Conclusions

In this prospective study, about 30% of incident CD patients had a mild disease course. Our suggested PreMiCC (prediction score for a mild course of Crohn’s disease) successfully predicted this.
Surfaces of General Type with Maximal Picard Number Near the Noether Line
Authors: Bin Nguyen , Lorenzo Vicente
Published: April 2024

The first published non-trivial examples of algebraic surfaces of general type with maximal Picard number are due to Persson, who constructed surfaces with maximal Picard number on the Noether line $K^{2}=2\chi -6$ for every admissible pair $(K^{2},\chi )$ such that $\chi \not \equiv 0 \ \text {mod}\ 6$. In this note, given a non-negative integer $k$, algebraic surfaces of general type with maximal Picard number lying on the line $K^{2}=2\chi -6+k$ are constructed for every admissible pair $(K^{2},\chi )$ such that $\chi \geq 2k+10$. These constructions, obtained as bidouble covers of rational surfaces, not only allow to fill in Persson’s gap on the Noether line, but also provide infinitely many new examples of algebraic surfaces of general type with maximal Picard number above the Noether line.
The Global Gig Economy: How Transport Platform Companies Adapt to Regulatory Challenges—A Comparative Analysis of Six Countries
Authors: Muldoon James , Sun Ping
Published: April 2024

Non-standard employment practises in the gig economy have recently drawn critical attention from regulators and the courts in a number of jurisdictions across the globe. Transport platform companies have responded to these challenges in several distinct ways in an emerging global battle to preserve their business model. This article provides a typology of the different strategies employed by these companies in six countries, highlighting five key strategies of regulatory activism, strategic litigation in defence of a business model, tactical subcontracting, negotiations with labour unions and threatening to withdraw services. It then shows how the structural features of the gig economy may be diverging into four distinct models in the European Union, China, the United States and the rest of the world. The study contributes to our understanding of the global nature of the struggle for fair working conditions and how platform companies operate in different institutional and regulatory contexts.
Identification and characterization of putative enhancer regions that direct Il6 transcription in murine macrophages
Authors: Kano Norisuke , Miki Takeo , Uehara Yurina , Ori Daisuke , Kawai Taro
Published: April 2024

Interleukin-6 (IL-6) plays a crucial role in various cellular functions, including innate and adaptive immune responses. Dysregulated expression of IL-6 is associated with hyperinflammation and chronic inflammatory diseases. In this study, we aimed to identify the enhancer regions responsible for robust Il6 mRNA expression in murine macrophages. Through comprehensive genome-wide ChIP- and ATAC-seq analyses, we identified two distinct clusters, termed E1 and E2 regions, located at −144 to −163 kb relative to the Il6 transcription start site in lipopolysaccharide (LPS)-activated murine macrophages. These clusters exhibited an accumulation of histone modification marks (H3K27ac and H3K4me1), as well as open chromatin, and were found to contain binding sites for the transcription factors PU.1, NF-κB, C/EBPβ, and JunB. Upregulation of non-coding RNA (ncRNA) transcripts from the E1 and E2 regions was observed upon LPS stimulation, and repression of these ncRNAs resulted in abrogation of Il6 expression. Additionally, deletion of either E1 or E2 region significantly impaired Il6 expression, while CRISPR/dCas9 activation-mediated recruitment of the co-activator p300 to the E1 and E2 regions facilitated Il6 expression. Collectively, our findings suggest that the E1 and E2 regions serve as putative enhancers for Il6 expression.
The Normalization of Contestation: The Sociology of Knowledge and the Challenges to the Liberal International Order
Authors: Adler-Nissen Rebecca
Published: April 2024

Many of the in-built contradictions in the liberal international order were pointed out by critics early on. Why were these voices not heard? How was contestation ignored or made acceptable by the people governing within liberal sub-orders, articulating progress, rationality, and equality? Drawing on insights from the sociology of knowledge and theories of organizational culture, I address this puzzle through the lens of the “normalization of deviance.” Beyond understanding the challenges as a crisis of and within the liberal international order, I argue that they unveil the limitations of hegemonic expertise governing this order. Part of the current predicament of the liberal international order has to do with the entrenched positioning and organizational cultures of political leaders and experts, making them blind to their own blindness. As they justify deviations and defend “their” order, they normalize contestation. The implications extend beyond the immediate challenges to the liberal international order, offering insights into reimagining its future and prompting a reconsideration of the discipline dedicated to understanding it.
Ecological relevance of flagellar motility in soil bacterial communities
Authors: Ramoneda Josep , Fan Kunkun , Lucas Jane M , Chu Haiyan , Bissett Andrew , Strickland Michael S , Fierer Noah
Published: April 2024

Flagellar motility is a key bacterial trait as it allows bacteria to navigate their immediate surroundings. Not all bacteria are capable of flagellar motility, and the distribution of this trait, its ecological associations, and the life history strategies of flagellated taxa remain poorly characterized. We developed and validated a genome-based approach to infer the potential for flagellar motility across 12 bacterial phyla (26 192 unique genomes). The capacity for flagellar motility was associated with a higher prevalence of genes for carbohydrate metabolism and higher maximum potential growth rates, suggesting that flagellar motility is more prevalent in environments with higher carbon availability. To test this hypothesis, we applied a method to infer the prevalence of flagellar motility in whole bacterial communities from metagenomic data and quantified the prevalence of flagellar motility across four independent field studies that each captured putative gradients in soil carbon availability (148 metagenomes). We observed a positive relationship between the prevalence of bacterial flagellar motility and soil carbon availability in all datasets. Since soil carbon availability is often correlated with other factors that could influence the prevalence of flagellar motility, we validated these observations using metagenomic data from a soil incubation experiment where carbon availability was directly manipulated with glucose amendments. This confirmed that the prevalence of bacterial flagellar motility is consistently associated with soil carbon availability over other potential confounding factors. This work highlights the value of combining predictive genomic and metagenomic approaches to expand our understanding of microbial phenotypic traits and reveal their general environmental associations.
Antibiotic resistance in Sudan: assessing the knowledge and practices of healthcare workers in Khartoum
Authors: Osman Einas A , Omer Sara A , Elmubarak Rashida M A , Abdelnabi Manal , Abdelgadir Safaa , Ahmed Dalal G , Arbab Nasr Mohamed H , Yousif Muna , Mukhtar Maowia , Al-Hassan Leena
Published: April 2024

Background

Antibiotic resistance (ABR) is a major public health issue, associated with increased patient morbidity and mortality globally, with significantly higher rates in low- and middle-income countries (LMICs). Assessment of contextual factors, such as information, education, infrastructure and regulations are important for developing local solutions against ABR.

Objectives

To determine the knowledge and practices of healthcare workers (HCWs) towards ABR in hospitals in Sudan.

Materials and methods

A survey was conducted in three different hospitals in Khartoum, Sudan from February to December 2020. HCWs of different specialties and expertise were invited to participate. Data were descriptively analysed using Statistical Package for Social Sciences (SPSS).

Results

ABR was identified as a big challenge by 89% of 345 HCWs who participated. The results show that 79% of doctors don’t rely on the clinical microbiology laboratory (CML) results for antibiotic prescription or clinical decision-making. Sixty percent of HCWs agreed there are infection prevention and control (IPC) guidelines in their hospital, but 74% of them don’t have access to them, and infrequently receive relevant IPC training. Furthermore, HCWs obtain ABR information from other colleagues informally, not through local data or reports.

Conclusions

Despite adequate knowledge of ABR locally, there are significant contextual technical challenges facing HCWs in Sudan, such as availability of policies and accurate data from CMLs. The results indicate a poor link between HCWs and the CMLs for infection management and it is essential to improve communication between the different hospital departments with regard to ABR transmission, and ensure the effectiveness of local IPC policies based on locally available data.
Cross-reactivity of 24 cannabinoids and metabolites in blood using the Immunalysis Cannabinoids Direct enzyme-linked immunosorbent assay
Authors: Patton Amy L , Pacheco Igor C , Seither Joshua Z , Brown Jordan T , Walterscheid Jeffrey P , Karschner Erin L
Published: April 2024

With wider availability of synthetic and semi-synthetic cannabinoids in the consumer space, there is a growing impact on public health and safety. Forensic toxicology laboratories should keep these compounds in mind as they attempt to remain effective in screening for potential sources of human performance impairment. Enzyme-linked immunosorbent assay (ELISA) is a commonly utilized tool in forensic toxicology, as its efficiency and sensitivity make it useful for rapid and easy screening for a large number of drugs. This screening technique has lower specificity, which allows for broad cross-reactivity among structurally similar compounds. In this study, the Cannabinoids Direct ELISA kit from Immunalysis was utilized to assess the cross-reactivities of 24 cannabinoids and metabolites in whole blood. The assay was calibrated with 5 ng/mL of 11-nor-9-carboxy-Δ9-tetrahydrocannabinol and the analytes of interest were evaluated at concentrations ranging from 5 to 500 ng/mL. Most parent compounds demonstrated cross-reactivity ≥20 ng/mL, with increasing alkyl side-chain length relative to Δ9-tetrahydrocannabinol resulting in decreased cross-reactivity. Of the 24 analytes, only the carboxylic acid metabolites, 11-nor-9-carboxy-Δ8-tetrahydrocannabinol, 11-nor-9(R)-carboxy-hexahydrocannabinol and 11-nor-9(S)-carboxy-hexahydrocannabinol, were cross-reactive at levels ≤10 ng/mL. Interestingly, 11-nor-9(R)-carboxy-hexahydrocannabinol demonstrated cross-reactivity at 5 ng/mL, where its stereoisomer 11-nor-9(S)-carboxy-hexahydrocannabinol, did not. As more information emerges about the prevalence of these analytes in blood specimens, it is important to understand and characterize their impact on current testing paradigms.
Political Power, Elite Control, and Long-Run Development: Evidence from Brazil
Authors: Ferraz Claudio , Finan Frederico , Martinez-Bravo Monica
Published: April 2024

This paper analyzes how changes in the concentration of political power affect long-run development. We study Brazil’s military dictatorship whose rise to power dramatically altered the distribution of power of local political elites. We document that municipalities that were more politically concentrated prior to the dictatorship in the 1960s are relatively richer in 2000, despite being poorer initially. Our evidence suggests that this reversal of fortune was the result of the military’s policies aimed at undermining the power of traditional elites. These policies increased political competition among traditional elites, leading to better governance, more public goods, and higher income levels.
Leukocyte activation patterns in hospitalized children: comparing SARS-CoV-2, bacterial infections, and inflammatory pathologies
Authors: Domitien Payet Léa , Bedin Anne Sophie , Desselas Émilie , Marie-Jeanne Carole , Mollevi Caroline , Malergue Fabrice , Bourgoin Penelope , Van de Perre Philippe , Tuaillon Édouard , Jeziorski Éric
Published: April 2024

In adults, monocytes and neutrophils play important roles in the hyperinflammatory responses characteristic of severe forms of SARS-CoV-2 infection. We assessed leukocyte activation in 55 children attending the emergency department for acute fever between March 2020 and September 2021. The following markers were analyzed by flow cytometry: CD169 and HLA-DR on monocytes, CD64 and CD16 on neutrophils, and CD38 on lymphocytes TCD8. Fifteen of the children had SARS-CoV-2 infection, 15 had bacterial infections, and 15 had inflammatory diseases. We observed overexpression of CD169 on monocytes and CD38 on T lymphocytes in all patients with a diagnosis of SARS-CoV-2, while overexpression of CD64 on neutrophils was observed with bacterial infections and inflammatory diseases. There was a decrease in the expression of HLA-DR on monocytes in the bacterial infection and inflammatory pathology groups. Leukocyte analysis identifies distinct activation patterns in children during SARS-CoV-2 infections, bacterial infections, and inflammatory diseases.
Screening for diabetes distress and depression in routine clinical care for youth with type 1 diabetes
Authors: Albright Dana , Wardell Joseph , Harrison Annalise , Mizokami-Stout Kara , Hirschfeld Emily , Garrity Ashley , Thomas Inas , Lee Joyce
Published: April 2024

Objective

The purpose of this study is to examine diabetes distress as a potential mediator of the relationship between depression symptoms and diabetes outcomes, including hemoglobin A1c (hemoglobin A1c [HbA1c]) and diabetes management behaviors in a clinical sample of adolescents and young adults.

Methods

In a pediatric diabetes clinic, 716 youth (ages 12–21 years) completed measures of diabetes distress (Problem Areas in Diabetes-Teen [PAID-T]), a single-item of diabetes distress, and depression (Patient Health Questionnaire [PHQ-9]) as part of standard care. Electronic health records were extracted for the “Six Habits” and glycemic management (HbA1c).

Results

Overall, 3.6% (n = 26) of adolescents had clinically elevated diabetes distress and depression symptoms, 5.0% had diabetes distress alone, 8.7% had depression symptoms alone, and 82.7% had neither clinical elevation of diabetes distress nor depression symptoms. Results of mediation analysis demonstrated diabetes distress (both full and single-item measures) fully mediated the relationship between depression symptoms and HbA1c (p < .001). Also, mediation analysis results showcase incomplete mediation of the effect of the Six Habits score on HbA1c appears by PAID-T Diabetes Distress.

Conclusions

In a clinical sample of youth with type 1 diabetes, both depressive symptoms and diabetes distress are associated with HbA1c. Furthermore, diabetes distress fully mediates the relationship between depressive symptoms and HbA1c. As part of standard clinical care, the single-item screener for diabetes distress captured similar results as the full-scaled PAID-T. With limited clinical resources, providers may consider focusing assessment and interventions on the psychological factor of diabetes distress within the diabetes clinic to maximize the impact on glycemic control and consider the use of single-item screening to identify distress.
When a gastrostomy tube goes missing, acute bowel obstruction due to a migrated Foley catheter
Authors: Molina Gabriel A , Ludeña Carolina , Arcia Alberto C , Parrales Diana E , Heredia Andrea E , Nuñez Karen D , Narvaez Nicole Berenice
Published: April 2024

A gastrostomy is a common procedure for patients with swallowing problems or inability to maintain regular oral nutrition. These gastrostomy tubes need special attention, as complications can occur if the tubes are left unattended. In rare scenarios, these tubes can migrate and cause severe life-threatening difficulties such as bowel obstruction and pancreatitis. We present the case of a 76-year-old quadriplegic woman who had a gastrostomy tube. Suddenly, the tube was missing, and after urgent medical care, the gastrostomy tube was found within her bowel. After successful surgery, she recovered from this incident.
Exploring a rare case of juvenile psammomatoid ossifying fibroma in the ethmoid: a case study and review
Authors: Aaboudech Taha Yassine , El Ouazzani Hafsa , Kadiri Habiba , Essakalli Leila , Bouteyine Ayoub , Benadbdenbi Hanae , Rguieg Naji , Cherradi Nadia
Published: April 2024

Juvenile ossifying fibroma (JOF) and its variants, including juvenile psammomatoid ossifying fibroma (JPOF), represent rare yet clinically significant benign fibro-osseous lesions that primarily occur in children and young adolescents. They can be found in diverse anatomical sites such as the jaw, nasal cavity, paranasal sinuses, and orbit. JOF exhibits an aggressive nature, necessitating early radiological detection and surgical intervention. Similarly, JPOF, with a locally malignant potential, requires surgical removal, typically conducted through endoscopic approaches. We report a case of a 5-year-old girl with JPOF arising in the ethmoid, revealed by recurrent epistaxis and proptosis. The text emphasizes the importance of early diagnosis through histopathology as a diagnostic tool and underscores the need for appropriate management.
Characterizing the Thymic Epithelial Cell Network Structure by Fluorescence Whole Slide Scanning and 3D SEM Array Tomography
Authors: Gunther-Cummins Leslie , Lagou Maria K , Guzik Hillary , DesMarais Sophia , Karagiannis George S , DesMarais Vera , Macaluso Frank P
Published: April 2024

The goal of this study was to develop an imaging approach to assess the integrity of the thymic epithelium in preclinical mouse models. The thymus is the most sensitive organ to cytoreductive treatments, and it rapidly involutes after chemotherapy insult in pediatric cancer patients. By using automated fluorescent whole slide scanning and complementary 3D SEM array tomography, we were able to visualize the biological structure of the thymic epithelial cell (TEC) network, analyze branching of this network, and obtain a more complete three-dimensional morphological structure of the cortical thymic epithelial cell (cTEC) compartment. The establishment of this imaging method will allow researchers to move forward in comparing the integrity of the cTEC in different conditions, such as different treatment conditions, for example, chemotherapy and irradiation, as well as different ages.
New insights on the dynamics of satellite galaxies: Effects of the figure rotation of a host galaxy
Authors: Sato Genta , Chiba Masashi
Published: April 2024

We investigate a mechanism to form and keep a planar spatial distribution of satellite galaxies in the Milky Way (MW), which is called the satellite plane. It has been pointed out that the ΛCDM cosmological model hardly explains the existence of such a satellite plane, so it is regarded as one of the serious problems in the current cosmology. We here focus on a rotation of the gravitational potential of a host galaxy, i.e., a so-called figure rotation, following the previous suggestion that this effect can induce the tilt of a so-called tube orbit. Our calculation shows that a figure rotation of a triaxial potential forms a stable orbital plane perpendicular to the rotational axis of the potential. Thus, it is suggested that the MW’s dark halo is rotating with its axis being around the normal line of the satellite plane. Additionally, we find that a small velocity dispersion of satellites is required to keep the flatness of the planar structure, namely the standard derivation of their velocities perpendicular to the satellite plane needs to be smaller than their mean rotational velocity on the plane. Although not all the MW’s satellites satisfy this condition, a fraction of them, called member satellites, which are prominently on the plane, do satisfy it. We suggest that this picture explaining the observed satellite plane can be achieved by the filamentary accretion of dark matter associated with the formation of the MW and a group infall of member satellites along this cosmic filament.
A Journey of Innovation: 40 years of Pioneering Medical Education at the Aga Khan University Medical College in Karachi, Pakistan
Authors: Vaqar Maham , Tariq Muhammad , Khan Muhammad Rizwan , Khan Sadaf , Riaz Qamar , Mahmood Sana , Ali Natasha , Haider Adil H
Published: April 2024

This article presents an overview of Aga Khan University’s (AKU) pioneering medical education initiatives over the past 40 years, exploring its impact on healthcare in the region and its commitment to advancing medical education and research in the developing world. Established in 1983 as the first private university in Pakistan, AKU has evolved into a global institution with a focus on improving healthcare standards and addressing healthcare needs in the developing world. The article also discusses the undergraduate and postgraduate medical education programs at AKU Medical College, Pakistan, highlighting their unique features and pioneering approaches to medical education. The institution’s journey highlights its ability to adapt to the evolving healthcare landscape while maintaining a focus on quality and excellence, offering a model for other institutions striving to meet healthcare needs in low- and middle-income countries.
Commuting Probability for Approximate Subgroups of a Finite Group
Authors: Detomi Eloisa , Morigi Marta , Shumyatsky Pavel
Published: April 2024

For subsets $X,Y$ of a finite group G, we write $\mathrm{Pr} (X,Y)$ for the probability that two random elements $x\in X$ and $y\in Y$ commute. This paper addresses the relation between the structure of an approximate subgroup $A\subseteq G$ and the probabilities $\mathrm{Pr} (A,G)$ and $\mathrm{Pr} (A,A)$. The following results are obtained.

Theorem 1.1: Let A be a K-approximate subgroup of a finite group G, and let $\mathrm{Pr} (A,G)\geq\epsilon\gt0$. There are two $(\epsilon, K)$-bounded positive numbers γ and K0 such that G contains a normal subgroup T and a K0-approximate subgroup B such that $|A\cap B|\ge \gamma\; {\mathrm{max}}\{|A|,|B|\}$ while the index $[G:T]$ and the order of the commutator subgroup $[T,\langle B \rangle]$ are $(\epsilon, K)$-bounded.

Theorem 1.2: Let A be a K-approximate subgroup of a finite group G, and let $\mathrm{Pr} (A,A)\geq\epsilon\gt0$. There are two $(\epsilon, K)$-bounded positive numbers γ and s and a subgroup $C\leq G$ such that $|C \cap A^2| \gt \gamma |A|$ and $|C^{\prime}|\leq s$. In particular, A is contained in the union of at most $\gamma^{-1}K^2$ left cosets of the subgroup C.

It is also shown that the above results admit approximate converses.
The verification of periodicity with the use of recurrent neural networks
Authors: Miller N , Lucas P W , Sun Y , Guo Z , Cooper W J , Morris C
Published: April 2024

The ability to automatically and robustly self-verify periodicity present in time-series astronomical data is becoming more important as data sets rapidly increase in size. The age of large astronomical surveys has rendered manual inspection of time-series data less practical. Previous efforts in generating a false alarm probability to verify the periodicity of stars have been aimed towards the analysis of a constructed periodogram. However, these methods feature correlations with features that do not pertain to periodicity, such as light-curve shape, slow trends, and stochastic variability. The common assumption that photometric errors are Gaussian and well determined is also a limitation of analytic methods. We present a novel machine learning based technique which directly analyses the phase-folded light curve for its false alarm probability. We show that the results of this method are largely insensitive to the shape of the light curve, and we establish minimum values for the number of data points and the amplitude to noise ratio.
Cosmic-ray exposure assessment using particle and heavy ion transport code system: case study Douala-Cameroon
Authors: Didier Takoukam Soh Serge , Joel Guembou Shouop Cebastien , Saïdou  , Samuel Bineng Guillaume , Maurice Ndontchueng Moyo
Published: April 2024

According to UNSCEAR, cosmic radiation contributes to ~16% (0.39 mSv/y) of the total dose received by the public at sea level. The exposure to cosmic rays at a specific location is therefore a non-negligible parameter that contributes to the assessment of the overall public exposure to radiation. In this study, simulations were conducted with the Particle and Heavy Ion Transport code System, a Monte Carlo code, to determine the fluxes and effective dose due to cosmic rays received by the population of Douala. In minimum solar activity, the total effective dose considering the contribution of neutron, muon+, muon-, electron, positron and photon, was found to be 0.31 ± 0.02 mSv/y at the ground level. For maximum solar activity, it was found to be 0.27 ± 0.02 mSv/y at ground level. During maximum solar activity, galactic cosmic rays are reduced by solar flares and winds, resulting in an increase in the solar cosmic-ray component and a decrease in the galactic cosmic-ray component on Earth. This ultimately leads to a decrease in the total cosmic radiation on Earth. These results were found to be smaller than the UNSCEAR values, thus suggesting a good estimation for the population of Douala city located near the equatorial line. In fact, the cosmic radiation is more deflected at the equator than near the pole. Muons+ were found to be the main contributors to human exposure to cosmic radiation at ground level, with ~38% of the total effective dose due to cosmic exposure. However, electrons and positrons were found to be the less contributors to cosmic radiation exposure. As regards the obtained results, the population of Douala is not significantly exposed to cosmic radiation.
Effect of daridorexant on sleep architecture in patients with chronic insomnia disorder: a pooled post hoc analysis of two randomized phase 3 clinical studies
Authors: Di Marco Tobias , Djonlagic Ina , Dauvilliers Yves , Sadeghi Kolia , Little David , Datta Alexandre N , Hubbard Jeffrey , Hajak Göran , Krystal Andrew , Olivieri Antonio , Parrino Liborio , Puryear Corey B , Zammit Gary , Donoghue Jacob , Scammell Thomas E
Published: April 2024

Study Objectives

Post hoc analysis to evaluate the effect of daridorexant on sleep architecture in people with insomnia, focusing on features associated with hyperarousal.

Methods

We studied sleep architecture in adults with chronic insomnia disorder from two randomized phase 3 clinical studies (Clinicaltrials.gov: NCT03545191 and NCT03575104) investigating 3 months of daridorexant treatment (placebo, daridorexant 25 mg, daridorexant 50 mg). We analyzed sleep–wake transition probabilities, EEG spectra, and sleep spindle properties including density, dispersion, and slow oscillation phase coupling. The wake EEG similarity index (WESI) was determined using a machine learning algorithm analyzing the spectral profile of the EEG.

Results

At month 3, daridorexant 50 mg decreased wake-to-wake transition probabilities (p < .05) and increased the probability of transitions from wake-to-N1 (p < .05), N2 (p < .05), and REM sleep (p < .05), as well as from N1-to-N2 (p < .05) compared to baseline and placebo. Daridorexant 50 mg decreased relative beta power during wake (p = .011) and N1 (p < .001) compared to baseline and placebo. During the wake, relative alpha power decreased (p < .001) and relative delta power increased (p < .001) compared to placebo. Daridorexant did not alter EEG spectra bands in N2, N3, and REM stages or in sleep spindle activity. Daridorexant decreased the WESI score during wake compared to baseline (p = .004). Effects with 50 mg were consistent between months 1 and 3 and less pronounced with 25 mg.

Conclusions

Daridorexant reduced EEG features associated with hyperarousal as indicated by reduced wake-to-wake transition probabilities and enhanced spectral features associated with drowsiness and sleep during wake and N1.

Clinical Trials

ClinicalTrials.gov NCT03545191: study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder. URL: Study Details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants with insomnia disorder | ClinicalTrials.gov ClinicalTrials.gov NCT03575104:

study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping. URL: study details | study to assess the efficacy and safety of ACT-541468 (daridorexant) in adult and elderly participants who experience difficulties sleeping | ClinicalTrials.gov
Economic assessment of using Bermudagrass stockpiling and annual cereal pasture to extend grazing in cow-calf operations
Authors: Sestak Jacob , Biermacher Jon T , Brorsen B Wade , Rogers James K
Published: April 2024

Bermudagrass (Cynodon dactylon L.) stockpiling and cool-season annual pastures can extend grazing seasons in cow-calf operations and reduce winter feeding costs, but less is known about how these practices interact and their effect on producer profitability. Data from a completely randomized-design experiment in South-Central Oklahoma were collected on three grazing systems for cows and calves: bermudagrass pasture (CONTROL), stockpiled bermudagrass and interseeded cool-season pasture (SPINT), and stockpiled bermudagrass plus cropland no-till seeded with a summer cover-crop followed by cool-season annuals (SPCROP). A mixed model was used to estimate the effects of grazing system on weaning weights, total hay, and total range cubes (crude protein [CP] = 30%) fed in each system. Enterprise budgeting was used to calculate the expected net return of each system. Weaning weight did not vary between systems (P = 0.6940), resulting in similar revenues. Relative to other treatments, the quantity of cubes fed in the CONTROL system were significantly higher (P < 0.0001) while hay fed was significantly higher in the SPCROP system (P = 0.0036). Increased machinery costs, seed costs, and fertilization requirements in bermudagrass stockpiling, interseeding, and cropland production outweighed the cost savings associated with less feeding. Total costs were $446 ha−1 ($722 hd−1), $451 ha−1 ($732 hd−1), and $553 ha−1 ($895 ha−1) for the CONTROL, SPINT, and SPCROP systems, respectively. Overall, the CONTROL system was $3.13 ha−1 ($5.08 hd−1) and $98.91 ha−1 ($160.10 hd−1) more profitable than the SPINT and SPCROP systems.
Translating a motivational interviewing intervention for childhood cancer survivors into an eHealth tool: A user-centered design process
Authors: Ruiz Sienna , Ackermann Nicole , Maki Julia , Carcone April Idalski , Hudson Melissa M , Ehrhardt Matthew J , Cloakey Danielle , DuChateau Danielle , Griffith Stanford A , Johnson Allison , Phillips Aaron , Waters Erika A
Published: April 2024

Childhood cancer survivors have a higher risk of developing cardiomyopathy than members of the general population. Screening echocardiograms can facilitate early detection and treatment of cardiomyopathy. Furthermore, motivational interviewing can increase uptake of cardiac screening. However, such approaches are time- and resource-intensive, which limits their reach to the survivors who need them. We describe how we utilized a user-centered design process to translate an in-person motivational interviewing intervention into an eHealth tool to improve cardiac screening among childhood cancer survivors. We used an iterative, three-phase, user-centered design approach: (i) setting the stage (convening advisory boards and reviewing the original intervention), (ii) content programming and development (writing and programming intervention text and flow), and (iii) intervention testing (research team testing and cognitive interviews.) For cognitive interviews, participants were recruited via institutional participant registries and medical records. Data were analyzed using rapid qualitative analysis. During Phase 1, we identified survivor and provider advisors and outlined elements of the in-person intervention to change for the eHealth tool. During Phases 2 and 3, advisors recommended several modifications that guided the final intervention content and flow. Examples include: acknowledging potential hesitation or apprehension surrounding medical screenings, addressing barriers and facilitators to obtaining screening, and improving the tool’s usability and appeal. In Phase 3, cognitive interview participants suggested additional refinements to the intervention language. This translation process shows that continued in-depth engagement of community advisors and iterative testing can improve the applicability of an eHealth to survivors’ lived experiences and social contexts.
Comparative safety, pharmacokinetics, and off-target assessment of 1,1-bis(3′-indolyl)-1-(p-chlorophenyl) methane in mouse and dog: implications for therapeutic development
Authors: Rocha Savannah M , Gustafson Daniel L , Safe Stephen , Tjalkens Ronald B
Published: April 2024

The modified phytochemical derivative, 1,1-bis(3′-indolyl)-1-(p-chlorophenyl) methane (C-DIM12), has been identified as a potential therapeutic platform based on its capacity to improve disease outcomes in models of neurodegeneration and cancer. However, comprehensive safety studies investigating pathology and off-target binding have not been conducted. To address this, we administered C-DIM12 orogastrically to outbred male CD-1 mice for 7 days (50 mg/kg/day, 200 mg/kg/day, and 300 mg/kg/day) and investigated changes in hematology, clinical chemistry, and whole-body tissue pathology. We also delivered a single dose of C-DIM12 (1 mg/kg, 5 mg/kg, 25 mg/kg, 100 mg/kg, 300 mg/kg, 1,000 mg/kg) orogastrically to male and female beagle dogs and investigated hematology and clinical chemistry, as well as plasma pharmacokinetics over 48-h. Consecutive in-vitro off-target binding through inhibition was performed with 10 μM C-DIM12 against 68 targets in tandem with predictive off-target structural binding capacity. These data show that the highest dose C-DIM12 administered in each species caused modest liver pathology in mouse and dog, whereas lower doses were unremarkable. Off-target screening and predictive modeling of C-DIM12 show inhibition of serine/threonine kinases, calcium signaling, G-protein coupled receptors, extracellular matrix degradation, and vascular and transcriptional regulation pathways. Collectively, these data demonstrate that low doses of C-DIM12 do not induce pathology and are capable of modulating targets relevant to neurodegeneration and cancer.
Genomic and phylogenetic features of the Picobirnaviridae suggest microbial rather than animal hosts
Authors: Sadiq Sabrina , Holmes Edward C , Mahar Jackie E
Published: April 2024

The RNA virus family Picobirnaviridae has traditionally been associated with the gastrointestinal systems of terrestrial mammals and birds, with the majority of viruses detected in animal stool samples. Metatranscriptomic studies of vertebrates, invertebrates, microbial communities, and environmental samples have resulted in an enormous expansion of the genomic and phylogenetic diversity of this family. Yet picobirnaviruses remain poorly classified, with only one genus and three species formally ratified by the International Committee of Virus Taxonomy. Additionally, an inability to culture picobirnaviruses in a laboratory setting or isolate them in animal tissue samples, combined with the presence of bacterial genetic motifs in their genomes, suggests that these viruses may represent RNA bacteriophage rather than being associated with animal infection. Utilising a data set of 2,286 picobirnaviruses sourced from mammals, birds, reptiles, fish, invertebrates, microbial communities, and environmental samples, we identified seven consistent phylogenetic clusters likely representing Picobirnavirus genera that we tentatively name ‘Alpha-’, ‘Beta-’, ‘Gamma-’, ‘Delta-’, ‘Epsilon-’, ‘Zeta-’, and ‘Etapicobirnavirus’. A statistical analysis of topological congruence between virus–host phylogenies revealed more frequent cross-species transmission than any other RNA virus family. In addition, bacterial ribosomal binding site motifs were more enriched in Picobirnavirus genomes than in the two groups of established RNA bacteriophage—the Leviviricetes and Cystoviridae. Overall, our findings support the hypothesis that the Picobirnaviridae have bacterial hosts and provide a lower-level taxonomic classification for this highly diverse and ubiquitous family of RNA viruses.
Oomycete Metabolism Is Highly Dynamic and Reflects Lifestyle Adaptations
Authors: Rodenburg Sander Y. A. , de Ridder Dick , Govers Francine , Seidl Michael F.
Published: April 2024

The selective pressure of pathogen-host symbiosis drives adaptations. How these interactions shape the metabolism of pathogens is largely unknown. Here, we use comparative genomics to systematically analyze the metabolic networks of oomycetes, a diverse group of eukaryotes that includes saprotrophs as well as animal and plant pathogens, with the latter causing devastating diseases with significant economic and/or ecological impacts. In our analyses of 44 oomycete species, we uncover considerable variation in metabolism that can be linked to lifestyle differences. Comparisons of metabolic gene content reveal that plant pathogenic oomycetes have a bipartite metabolism consisting of a conserved core and an accessory set. The accessory set can be associated with the degradation of defense compounds produced by plants when challenged by pathogens. Obligate biotrophic oomycetes have smaller metabolic networks, and taxonomically distantly related biotrophic lineages display convergent evolution by repeated gene losses in both the conserved as well as the accessory set of metabolisms. When investigating to what extent the metabolic networks in obligate biotrophs differ from those in hemibiotrophic plant pathogens, we observe that the losses of metabolic enzymes in obligate biotrophs are not random and that gene losses predominantly influence the terminal branches of the metabolic networks. Our analyses represent the first metabolism-focused comparison of oomycetes at this scale and will contribute to a better understanding of the evolution of oomycete metabolism in relation to lifestyle adaptation. Numerous oomycete species are devastating plant pathogens that cause major damage in crops and natural ecosystems. Their interactions with hosts are shaped by strong selection, but how selection affects adaptation of the primary metabolism to a pathogenic lifestyle is not yet well established. By pan-genome and metabolic network analyses of distantly related oomycete pathogens and their nonpathogenic relatives, we reveal considerable lifestyle- and lineage-specific adaptations. This study contributes to a better understanding of metabolic adaptations in pathogenic oomycetes in relation to lifestyle, host, and environment, and the findings will help in pinpointing potential targets for disease control.

[Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Xanthomonas as a Model System for Studying Pathogen Emergence and Evolution
Authors: Timilsina Sujan , Kaur Amandeep , Sharma Anuj , Ramamoorthy Sivakumar , Vallad Gary E. , Wang Nian , White Frank F. , Potnis Neha , Goss Erica M. , Jones Jeffrey B.
Published: April 2024

In this review, we highlight studies in which whole-genome sequencing, comparative genomics, and population genomics have provided unprecedented insights into past and ongoing pathogen evolution. These include new understandings of the adaptive evolution of secretion systems and their effectors. We focus on Xanthomonas pathosystems that have seen intensive study and improved our understanding of pathogen emergence and evolution, particularly in the context of host specialization: citrus canker, bacterial blight of rice, and bacterial spot of tomato and pepper. Across pathosystems, pathogens appear to follow a pattern of bursts of evolution and diversification that impact host adaptation. There remains a need for studies on the mechanisms of host range evolution and genetic exchange among closely related but differentially host-specialized species and to start moving beyond the study of specific strain and host cultivar pairwise interactions to thinking about these pathosystems in a community context.
The role of morphine‐ and fentanyl‐induced impairment of intestinal epithelial antibacterial activity in dysbiosis and its impact on the microbiota‐gut‐brain axis
Authors: Muchhala Karan H. , Kallurkar Prajkta S. , Kang Minho , Koseli Eda , Poklis Justin L. , Xu Qingguo , Dewey William L. , Fettweis Jennifer M. , Jimenez Nicole R. , Akbarali Hamid I.
Published: April 2024

Recent evidence suggests that chronic exposure to opioid analgesics such as morphine disrupts the intestinal epithelial layer and causes intestinal dysbiosis. Depleting gut bacteria can preclude the development of tolerance to opioid‐induced antinociception, suggesting an important role of the gut‐brain axis in mediating opioid effects. The mechanism underlying opioid‐induced dysbiosis, however, remains unclear. Host‐produced antimicrobial peptides (AMPs) are critical for the integrity of the intestinal epithelial barrier as they prevent the pathogenesis of the enteric microbiota. Here, we report that chronic morphine or fentanyl exposure reduces the antimicrobial activity in the ileum, resulting in changes in the composition of bacteria. Fecal samples from morphine‐treated mice had increased levels of Akkermansia muciniphila with a shift in the abundance ratio of Firmicutes and Bacteroidetes. Fecal microbial transplant (FMT) from morphine‐naïve mice or oral supplementation with butyrate restored (a) the antimicrobial activity, (b) the expression of the antimicrobial peptide, Reg3γ, (c) prevented the increase in intestinal permeability and (d) prevented the development of antinociceptive tolerance in morphine‐dependent mice. Improved epithelial barrier function with FMT or butyrate prevented the enrichment of the mucin‐degrading A. muciniphila in morphine‐dependent mice. These data implicate impairment of the antimicrobial activity of the intestinal epithelium as a mechanism by which opioids disrupt the microbiota‐gut‐brain axis.
Effects of Oxygen Therapy on Patients with a Chronic Wound: A Systematic Review and Meta-analysis
Authors: Du Xinyan , Zhang Xuena , Liu Junxia , Wang Zhendi
Published: April 2024

Objective

To synthesize the effects of oxygen-based therapy on patients with a chronic wound.

Data Sources

The authors searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for relevant randomized controlled trials from database inception. Investigators measured risk of bias using the Cochrane Collaboration’s Risk of Bias tool.

Study Selection

The included randomized controlled trials focused on the effects (short- or long-term wound healing, amputation rate, percentage of reduction in ulcer size, and poststudy transcutaneous oxygen measurement [TcPO2]) of oxygen-based therapy (including hyperbaric oxygen therapy, topical oxygen therapy, and continuous diffusion of oxygen) on patients with a chronic wound.

Data Extraction

Researchers extracted information regarding participant characteristics and primary and secondary outcomes from the included studies.

Data Synthesis

Pooled effects of 31 included studies showed that patients treated with oxygen had better short-term wound healing (risk ratio [RR], 1.544; 95% CI, 1.199 to 1.987), a higher percentage reduction in the ulcer area (standardized mean difference [SMD], 0.999; 95% CI, 0.439 to 1. 599), lower amputation rates (RR, 0.529; 95% CI, 0.325 to 0.862), shorter wound healing time (SMD, −0.705; 95% CI, −0.908 to −0.501), and higher poststudy TcPO2 (SMD, 2.128; 95% CI, 0.978 to 3.278) than those in the control group. For long-term wound healing, there was no statistically significant difference (RR, 1.227; 95% CI, 0.976 to 1.542).

Conclusions

Oxygen-based therapy improves short-term parameters of wound healing in patients with chronic wounds.