bluuebunny/crossref_metadata_2025 huggingface dataset:
Soybean yield dependence on the timing of sowing in the conditions of the foothill zone of the RNO-Alania
Authors: Tedeeva Victoria , Tedeeva Albina
Published: January 2024

The article presents the results of research on the reaction of soybean plants depending on the timing of sowing in the foothill zone of the Republic of North Ossetia-Alania. The need to improve the timing of sowing occurs with the introduction of new varieties of various ripeness in the main and intermediate crops. The purpose of the paper is to study the effect of sowing dates on the yield of soybean seeds in the conditions of the foothill zone of the RNO-Alania. The scientific novelty was to establish optimal sowing dates that would ensure optimal plant growth and development and high productivity. Our research was carried out in the experimental fields of the North Caucasian Research Institute of Mountain and Piedmont Agriculture of the VSC RAS in 2018-2021. The object of research was the varieties of breeding of the Federal scientific center "V.S. Pustovoit All-Russian Research Institute of Oil Crops. Two main types of soils prevail in the foothill zone: chernozems of varying degrees of leaching, as well as meadow and meadow-boggy soils. The arable layer contains from 3 to 4.4% humus. Down the profile, the amount of humus decreases gradually. The reaction of the soil solution in the upper horizons is neutral, in horizons deeper than 80-90 cm – slightly alkaline. The predecessor of the experimental plots was corn for grain. It was found that at early sowing dates (April 20 - May 5) resulted in higher field germination (87-93%), plant foliage of 46.9 thousand m2/ha and their survival rate for harvesting 84-91%. More nodules formed on the roots of the plants. The maximum yield is 2.6 t/ha, obtained during sowing on April 30.
Endocrine changes induced by GnRH immunisation and subsequent early re-stimulation of testicular function with a GnRH agonist in stallions
Authors: Gautier Camille , Aurich Jörg , Melchert Maria , Wagner Lisa-Hélène , Kaps Martim , Okada Carolina T. C. , Ertl Reinhard , Walter Ingrid , Aurich Christine
Published: January 2024

Context Resumption of testicular function after gonadotrophin-releasing hormone (GnRH) immunisation varies among individual animals and some stallions regain fertility only after a prolonged time. Aims This study evaluated endocrine effects of GnRH immunisation and early subsequent re-stimulation with a GnRH agonist. We hypothesised that GnRH agonist treatment advances resumption of normal endocrine function in GnRH-vaccinated stallions. Methods Shetland stallions were assigned to an experimental and a control group (n = 6 each). Experimental stallions were GnRH-immunised twice, 4 weeks apart. Each experimental stallion was hemicastrated together with an age-matched control animal when testosterone concentration decreased below 0.3 ng/mL. Three weeks later, daily treatment with the GnRH agonist buserelin was initiated (4 μg/day for 4 weeks followed by 8 μg/day). The remaining testicle was removed when testosterone concentration exceeded 0.5 ng/mL in vaccinated stallions. Blood was collected for LH, FSH, oestradiol and anti-müllerian hormone (AMH) analyses, and testicular and epididymal tissue were conserved for real-time qPCR and histology. Key results GnRH vaccination reduced blood concentrations of LH and FSH, with a structural deterioration of testicular tissue and disruption of spermatogenesis. Daily buserelin treatment for approximately 60 days partially restored gonadotropin secretion and induced a recovery of the functional organisation of the testicular tissue with effective spermatogenesis. Conclusions Endocrine testicular function can be restored in GnRH-vaccinated stallions by daily low-dose buserelin treatment. The buserelin treatment protocol may potentially be improved regarding the dose, interval and duration. Implications Daily buserelin treatment can be recommended for treatment of GnRH-vaccinated stallions with prolonged inhibition of testicular function.
Bacterial flagella hijack type IV pili proteins to control motility
Authors: Liu Xiaolin , Tachiyama Shoichi , Zhou Xiaotian , Mathias Rommel A. , Bonny Sharmin Q. , Khan Mohammad F. , Xin Yue , Roujeinikova Anna , Liu Jun , Ottemann Karen M.
Published: January 2024

Bacterial flagella and type IV pili (TFP) are surface appendages that enable motility and mechanosensing through distinct mechanisms. These structures were previously thought to have no components in common. Here, we report that TFP and some flagella share proteins PilO, PilN, and PilM, which we identified as part of the
Helicobacter pylori
flagellar motor.
H. pylori
mutants lacking PilO or PilN migrated better than wild type in semisolid agar because they continued swimming rather than aggregated into microcolonies, mimicking the TFP-regulated surface response. Like their TFP homologs, flagellar PilO/PilN heterodimers formed a peripheral cage that encircled the flagellar motor. These results indicate that PilO and PilN act similarly in flagella and TFP by differentially regulating motility and microcolony formation when bacteria encounter surfaces.
Pacific transformations of the ‘Country of Babel’
Authors: Neuenschwander Christoph
Published: January 2024

The story of Babel has been used for centuries to prompt negative evaluations of linguistic diversity. It has been
instrumentalised in debates about English, to attest linguistic purity and propagate the standard variety. In (post)colonial
discourses, Babel came to project imperialist language ideologies and hierarchies onto new contexts. This paper demonstrates how
Babel, as a recurring theme in debates on Hawai‘i Creole and Tok Pisin, has undergone transformation, having been employed in
seemingly contradictory ways, variably used to legitimise or delegitimise the creoles. These competing, diametrically opposed
lines of argumentation reflect different concepts of community and nation. Yet, as I propose here, Babel remains consistent in its
core function: It serves as a topos, invoking ostensibly common knowledge about the dangers of (unmonitored) linguistic
heterogenisation. Thus, regardless of its ideological force to challenge or maintain the (post)colonial status quo, it perpetuates
a basic imperialist understanding of the nation as monolingual.
The Darkness of Enlightenment
Authors: LeDrew Stephen
Published: January 2024

This chapter examines the “Enlightenment myth” that is a foundation of scientific atheism’s critique and understanding of religion and its decline. This involves the view that there was an historical rupture in the modern period, ushered in chiefly by the Scientific Revolution, that marked the transition from a world governed by religion and superstition to one guided by reason and science, which is characterized by freedom, prosperity, and peace. While presented by its proponents as indicative of science-driven social progress, there was a dark side to the Enlightenment, which constructed a vision of Western cultural superiority that lent legitimacy to the violent project of colonialism. In adopting the Enlightenment myth as the basis of its critique of religion—as well as its overarching ideology—scientific atheism effectively endorses its racist and Orientalist features.
The Causes of Religious Decline
Authors: LeDrew Stephen
Published: January 2024

This chapter draws on the most recent scholarship on secularization to explain the decline of religious affiliation, belief, and practice. It first addresses the conflict myth: the idea that religion and science are inherently incompatible perspectives on reality and that education in science tends to lead to abandoning religious beliefs. On the contrary, research on practicing scientists demonstrates that, for the most part, they see no conflict between religion and science. Alternatively, the “existential security” theory of secularization is proposed to explain current developments. It suggests that religious belief and activity declines when people are safe from existential risks (like war, violence, famine, etc.) and that greater overall socioeconomic equality and security is a precondition for questioning, and eventually abandoning religion.
Crescas and Spinoza on Modality
Authors: Melamed Yitzhak Y.
Published: January 2024

The primary aim of this chapter it to provide a survey and outline of the chief elements of Spinoza’s modal philosophy, and its medieval Jewish philosophical background. The first section focuses on Hasdai Crescas, a bold and original, anti-Aristotelian philosopher. The rest of the chapter focuses on Spinoza’s main modal concepts, his understanding of contingency, and the extent of his commitment to necessitarianism. In addition, the chapter argues that Spinoza makes a distinction between two notions of contingency, which in turn shows how his various assertions about contingency can be rendered consistent. Second, the chapter shows how one central text in Spinoza, which is commonly taken to be the strongest and most stubborn proof against the reading of Spinoza as strict necessitarianism, has been widely misunderstood, and how it is perfectly compatible with reading Spinoza as a strict necessitarian.
Hume on Modal Discourse
Authors: Holden Thomas
Published: January 2024

Hume’s science of human nature dictates a genealogical approach to the phenomena of modal language and judgment. Ultimately Hume arrives at an account of talk about causal necessity as a systematic expression of our habit-induced inferential dispositions. This chapter argues that in a similar manner, Hume also arrives at an account of talk about absolute or metaphysical necessity as a systematic expression of the fact that we find certain propositions inconceivable. The chapter makes the case for this anti-realist reading of Hume on absolute necessity and situates Hume’s treatment of modal discourse in the context of his wider philosophy of language.
Models with migration
Authors: Barthelemy Marc , Verbavatz Vincent
Published: January 2024

Interestingly, models of urban growth seen so far do not explain where the growth comes from. They focus on explaining how cities grow but not why. Without loss of generality, there are only two possible sources of population: natural growth (births minus deaths) and migrations, including migrations between cities. These migrations represent some sort of interactions and exchanges between cities and have been addressed in a small number of papers that we will discuss in this chapter.
The generalized central limit theorem and Lévy stable laws
Authors: Barthelemy Marc , Verbavatz Vincent
Published: January 2024

Before developing other models of urban growth that include interurban migration flows, a few more mathematical results are necessary. In this chapter, we will start with a very common probabilistic result, the central limit theorem, and introduce its generalization. This will help us to define the so-called Lévy stable laws, which are typical “broad laws”: laws that describe large but rare events. These laws obey their own rules and will be paramount in the further description of migrations flows. Indeed, we will see in Chapter 9 that interurban migrations flows are actually dominated by rare, but large events.
Social procurement to promote social problem solving
Authors: Varga Eva , Hayday Malcolm
Published: January 2024

This chapter defines socially responsible public procurement (SRPP) and examines its potential to solve societal problems while engaging social economy enterprises in order to deliver innovative solutions. In focus are practices in the European Union, looking at SRPP legislation and its implementation, challenges, and opportunities. Various examples illustrate how different approaches have evolved to deliver on social policy agendas at national and local level and contribute to the sustainability of the social economy at the same time. The analysis points to what needs to change in the procurement world to harness more of the existing legislative framework and to allow new models to be employed for greater impact. The chapter identifies four main areas of challenge: (1) social value definition and measurement; (2) implementation obstacles; (3) legislation; and (4) lack of capacity of social economy enterprises. It recommends policy measures to address these challenges, as well as the opportunities identified for SRPP and social economy. It suggests that future focus should be on encouraging a collaborative and outcomes-oriented approach to public and private procurement, on taking advantage of existing SRPP legislation, and on building the capacities of public authorities and social economy enterprises. Finally, it recommends directions for further research to gauge what social value is actually delivered by socially responsible public procurement and what role it can play in scaling impactful solutions.
The New Industrial World
Authors: Romano Livio , Traù Fabrizio
Published: January 2024

The book argues that the logic of the industrialization process in the course of the Globalization Age—linking together the Global North and South on productive grounds—has been hinging upon quite exceptional conditions and that the gradual vanishing of such conditions asks for a rethinking of that logic. In the years following the great financial crisis, major changes relate to the slowdown in world output growth and in the return of distance as a key determinant of firms’ strategic decisions. In this connection the book pays attention in particular to the following issues: (1) the structural reasons behind the worldwide slowdown of manufacturing growth; (2) the fall of external demand as a driver of manufacturing development; (3) the decoupling of Chinese productions from global sourcing (as well as some evidence of supply-side disengagement coming from advanced economies in terms of back-shoring); (4) the resurgence of regionalism in international trade; (5) the economic consequences of the advancements of the digital and green transitions.
Bottled
Authors: Byala Sara
Published: January 2024

Travel to virtually any African country and you are likely to find a Coca-Cola, often a cold one at that. Bottled asks how this carbonated drink became ubiquitous across the continent, and what this reveals about the realities of globalisation, development and capitalism.Bottled is the first assessment of the social, commercial and environmental impact of one of the planet’s biggest brands and largest corporations, in Africa. Sara Byala charts the company’s century-long involvement in everything from recycling and education to the anti-apartheid struggle, showing that Africans have harnessed Coca-Cola in varied expressions of modernity and self-determination: this is not a story of American capitalism running amok, but rather of a company becoming African, bending to consumer power in ways big and small.In late capitalism, everyone’s fates are bound together. A beverage in Atlanta and a beverage in Johannesburg pull us all towards the same end narrative. This story matters for more than just the local reasons, enhancing our understanding of our globalised, integrated world. Drawing on fieldwork and research in company archives, Byala asks a question for our time: does Coca-Cola’s generative work offset the human and planetary costs associated with its growth in the twenty-first century?
The Bottom Line
Authors: Byala Sara
Published: January 2024

Chapter Seven explores Coca-Cola’s twenty-first-century sustainability efforts, highlighting those around water, women, and energy. This chapter draws heavily from fieldwork to show what on-the-ground sustainability efforts look like in at least eight countries on the continent. It explores Coca-Cola’s convening power and its Golden Triangle collaborations, where Coca-Cola brings an international NGO, a local NGO, and a government to the table, all in the service of betterment. This chapter demonstrates some of the ways that Coca-Cola does work that no one else either can or will do in Africa while querying the implications of such activities. It also suggests that Coca-Cola’s sustainability work might best be thought of as a new kind of missionary endeavor.
Conservation and Geometry
Authors: Gryb Sean , Thébault Karim P. Y.
Published: January 2024

This chapter considers the geometric structure of theories with regular nomic structure within the framework of Hamiltonian mechanics. In this context, broad symmetries facilitate the identification of dynamically isolated substructures of a theory. In particular, the space of conserved charges and the Poisson sub-algebras of this space give representations of the interesting dynamically stable structures of a theory. However, there are good reasons to avoid a naïve reductionism in which the isolated structures of a theory are removed. Rather, once the broad symmetries are parameterized so that the isolated structures and conserved charges are identified, one can then proceed to identify the narrow symmetries in a second step based upon physical reasoning. The preliminary stance, that narrow symmetries are all broad symmetries which are variational symmetries of the full system under study are narrow symmetries, is the basic starting point in this approach.
Implementing the UK–EU Withdrawal Agreement in UK Law
Authors: Whitten Lisa Claire
Published: January 2024

This chapter sets out the impact of the domestic implementation of UK withdrawal from the EU on the four components of the Northern Ireland constitution: the principle of consent, devolved government, the North–South and the East–West dimensions. Findings can be summarised as follows: (1) there are discrepancies between existing UK legal definitions of the 1998 Agreement and territory of Northern Ireland and those introduced onto the UK statute book by Brexit-implementing legislation; (2) the ‘democratic consent mechanism’ is constitutionally novel in the UK; (3) lack of requirement for Northern Ireland input to the implementation of the Protocol strengthened UK central government powers; (4) discrepancies between international and domestic provisions for North–South cooperation creates some uncertainty regarding its post-Brexit development; (5) the ‘power-hoarding’ effect of UK internal market legislation poses a challenge to the operation of the British-Irish Council; (6) events during the transition period suggest British-Irish relations will remain strained in the aftermath of Brexit.
City of Equals
Authors: Wolff Jonathan , de Shalit Avner
Published: January 2024

When we think about equality in the city, we are very likely to think first of the wide and growing divide between rich and poor, in material terms. Yet when we think more about a ‘city of equals’ it becomes apparent that how people feel treated by the city and those around them, and whether they can live according to their values, are much more central. Accordingly, based on the authors’ reflections, a multi-disciplinary literature review, and, distinctively, more than 180 interviews in ten cities in six countries, the book offers an account of a city of equals based on the idea that it should give each of its city-zens a secure sense of place or belonging. Four underlying values structure this account. First, access to the goods and services of the city should not be based purely on the market. Second, each city-zen should be able to live a life they find meaningful. Third, there should be diversity and wide social mixing. Fourth, there should be ‘non-deferential inclusion’, that is, each person in the city should be able to get access to what they are entitled to without being treated as less worthy than others. They should be able to enjoy their rights without bowing and scraping, waiting longer than others, or going through special bureaucratic hurdles. In sum, in a city of equals each person is proud of their city and has the (justified) feeling that their city is proud of (people like) them.
Robotic-Assisted In-Bed Mobilization in Ventilated ICU Patients With COVID-19: An Interventional, Randomized, Controlled Pilot Study (ROBEM II Study)*
Authors: Lorenz Marco , Baum Felix , Kloss Philipp , Langer Nadine , Arsene Vanessa , Warner Linus , Panelli Alessandro , Hartmann Frederike V. , Fuest Kristina , Grunow Julius J. , Enghard Philipp , Schaller Stefan J.
Published: January 2024

OBJECTIVES:

The COVID-19 pandemic significantly impacted global healthcare systems, particularly in managing critically ill mechanically ventilated patients. This study aims to assess the feasibility of robotic-assisted mobilization in COVID-19 patients.

DESIGN:

Randomized controlled pilot study.

SETTING:

Four COVID-19 specialized ICUs at Charité-Universitätsmedizin Berlin (March 2021 to February 2022).

PATIENTS:

Twenty critically ill COVID-19 patients expected to require greater than 24 hours of ventilation.

INTERVENTIONS:

A 5-day intervention phase with bid robotic-assisted mobilization greater than or equal to 20 minutes and follow-up at day 180, compared with standard care.

MEASUREMENTS AND MAIN RESULTS:

Intervention sessions were conducted in 98.9% according to protocol, with one session missing due to staff shortage. Primary outcome was the mobilization level measured with the ICU Mobility Scale (IMS) and Surgical ICU Optimal Mobilization Score (SOMS), assessed until day 5 or extubation. Safety events were recorded during mobilization. The median IMS and SOMS were 0 (0–0.16) and 1 (1–1.03) in the intervention group, and 0 (0–0.15) (p = 0.77) and 0.8 (0.65–1.20) (p = 0.08) in the standard care group, respectively. Significant secondary outcomes included average number of mobilization sessions (intervention: 8.5 [7.75–10] vs. standard care: 4.5 [3.5–5]; p = 0.001), total mobilization time (intervention: 232.5 min [187.25–266.5 min] vs. standard care: 147.5 min [107.5–167.5 min]; p = 0.011), and healthcare providers per session (intervention: 2 [2–2] vs. standard care: 1 [1–1.4]; p = 0.001) during intervention. Four safety events (hypertension and agitation, n = 2 each) in the intervention group and none in the standard care group were reported.

CONCLUSIONS:

Robotic-assisted mobilization in mechanically ventilated COVID-19 patients appears to be safe and feasible.
The Intersection of Gender and Occupational Roles in Agriculture
Authors: Proctor Christina , Hopkins Noah , Reece Chase
Published: January 2024

Objectives

The purposes of this study were to explore behavioral and mental health outcomes among a sample of farmers living in the United States and to compare differences between male and female farmers.

Methods

An online cross-sectional survey was distributed within the farming community by researchers, farming consultants, and community partners. χ2 and analysis or variance analyses were used to explore relationships between variables of interest.

Results

Female survey respondents reported significantly higher perceived stress and significantly lower resilience than their male counterparts. A significant interaction effect was observed between gender and farm roles on alcohol consumption patterns, with female farm owners and managers reporting binge drinking behavior most frequently.

Conclusions

This study identified distinct differences between respondents in terms of stress, resilience, and alcohol consumption patterns, based on both gender and occupational roles.
Multicenter benchmarking of short and long read wet lab protocols for clinical viral metagenomics
Authors: Lopez-Labrador F. Xavier , Huber Michael , Sidorov Igor A. , Brown Julianne R. , Cuypers Lize , Laenen Lies , Vanmechelen Bert , Maes Piet , Fischer Nicole , Pichler Ian , Storey Nathaniel , Schmutz Stefan , Kufner Verena , van Boheemen Sander , Mulders Claudia E. , Grundhoff Adam , Blümke Patrick , Robitaille Alexis , Cinek Ondrej , Hubáčková Klára , Mourik Kees , Boers Stefan A. , Stauber Lea , Salmona Maud , Cappy Pierre , Ramette Alban , Franze’ Alessandra , LeGoff Jerome , Claas Eric C.J. , Rodriguez Christophe , de Vries Jutte J.C. ,   European Society of Clinical Virology (ESCV) Network on Next-Generation Sequencing (ENNGS)
Published: January 2024

Metagenomics is gradually being implemented for diagnosing infectious diseases. However, in-depth protocol comparisons for viral detection have been limited to individual sets of experimental workflows and laboratories. In this study, we present a benchmark of metagenomics protocols used in clinical diagnostic laboratories initiated by the European Society for Clinical Virology (ESCV) Network on NGS (ENNGS).

A mock viral reference panel was designed to mimic low biomass clinical specimens. The panel was used to assess the performance of twelve metagenomic wet-lab protocols in use in the diagnostic laboratories of participating ENNGS member institutions. Both Illumina and Nanopore, shotgun and targeted capture probe protocols were included. Performance metrics sensitivity, specificity, and quantitative potential were assessed using a central bioinformatics pipeline.

Overall, viral pathogens with loads down to 104copies/ml (corresponding to C values of 31 in our assays) were detected by all the evaluated metagenomic wet-lab protocols. In contrast, lower abundant mixed viruses of CTvalues of 35 and higher were detected only by a minority of the protocols. Considering the reference panel as the gold standard, optimal thresholds to define a positive result were determined per protocol, based on the horizontal genome coverage. Implementing these thresholds, sensitivity and specificity of the protocols ranged from 67 to 100% and 87 to 100%, respectively.

A variety of metagenomic protocols are currently in use in clinical diagnostic laboratories. Detection of low abundant viral pathogens and mixed infections remains a challenge, implying the need for standardization of metagenomic analysis for use in clinical settings.
ImmCellTyper: an integrated computational pipeline for systematic mining of Mass Cytometry data to assist deep immune profiling
Authors: Sun Jing , Choy Desmond , Sompairac Nicolas , Jamshidi Shirin , Mishto Michele , Kordasti Shahram
Published: January 2024

Mass cytometry, also known as Cytometry by time-of-flight (CyTOF), is a cutting-edge high-dimensional technology for profiling marker expression at the single-cell level. This technology significantly advances clinical research in immune monitoring and the interrogation of immune cell populations. Nevertheless, the vast amount of data generated by CyTOF poses a daunting challenge for analysis. To address this, we describe ImmCellTyper (https://github.com/JingAnyaSun/ImmCellTyper), a novel and robust toolkit designed for CyTOF data analysis. The analytical framework incorporates an in-house developed semi-supervised clustering tool named BinaryClust, which first characterises main cell lineages, followed by in-depth interrogation for population of interest using unsupervised methods.

BinaryClust was benchmarked with existing clustering tools and demonstrated superior accuracy and speed across two datasets comprising around 4 million cells, performing as good as manual gating by human experts. Furthermore, this computational pipeline provides a variety of visualization and analytical tools spanning from quality control to differential analysis, which can be tailored to user’s specific needs, aiming to provide a one-stop solution for CyTOF data analysis. The general workflow consists of five key steps: 1) Batch effect evaluation and correction, 2) Data quality control and pre-processing, 3) Main cell lineage characterisation and quantification, 4) Extraction and in-depth investigation of cell type of interest; 5) Differential analysis of cell abundance and functional marker expression (supporting multiple study groups). Overall, ImmCellTyper integrates expert’s biological knowledge in a semi-supervised fashion to accurately deconvolute well-defined main cell lineages, while also preserving the potential of unsupervised approaches to discover novel cell subsets and providing a user-friendly toolset to remove the analytical barrier for high-dimensional immune profiling.
Subfamily evolution analysis using nuclear and chloroplast data from the same reads
Authors: Witharana Eranga Pawani , Iwasaki Takaya , San Myat Htoo , Jayawardana Nadeeka U. , Kotoda Nobuhiro , Yamamoto Masashi , Nagano Yukio
Published: January 2024

The chloroplast (cp) genome is a widely used tool for exploring plant evolutionary relationships, yet its effectiveness in fully resolving these relationships remains uncertain. Integrating cp genome data with nuclear DNA information offers a more comprehensive view but often requires separate datasets. In response, we employed the same raw read sequencing data to construct cp genome-based trees and nuclear DNA phylogenetic trees using Read2Tree, a cost-efficient method for extracting conserved nuclear gene sequences from raw read data, focusing on the Aurantioideae subfamily, which includesCitrusand its relatives. The resulting nuclear DNA trees were consistent with existing nuclear evolutionary relationships derived from high-throughput sequencing, but diverged from cp genome-based trees. To elucidate the underlying complex evolutionary processes causing these discordances, we implemented an integrative workflow that utilized multiple alignments of each gene generated by Read2Tree, in conjunction with other phylogenomic methods. Our analysis revealed that incomplete lineage sorting predominantly drives these discordances, while introgression and ancient introgression also contribute to topological discrepancies within certain clades. This study underscores the cost-effectiveness of using the same raw sequencing data for both cp and nuclear DNA analyses in understanding plant evolutionary relationships.
Drug Supply Management at First-level Public Health Facilities: Case of Pyay District, Myanmar
Authors: Hlaing Thein , Lat Tun Win
Published: January 2024

Background

First-level public health facilities (PHFs) serve as primary providers of essential medicines, necessitating critical attention to drug availability and quality assurance. This study aimed to examine the status of functional areas within the drug supply chain management framework and assess the overall capability maturity at first-level PHFs.

Methods

The cross-sectional study was conducted among 183 drug store sites from six townships of Pyay District. Only situational analysis was exercised to determine the existing situations. The overall capability maturity was determined according to the definitions of levels of the Capability Maturity Module Tool.

Results

The study encompassed 6 Maternal and Child Health Centers, 43 Rural Health Centers, and 134 Sub-rural Health Centers. In terms of drug supply management training, 58.47% lacked formal training, with 23.5% not undergoing performance reviews. Drug forecasting predominantly relied on a pen-paper system (91.6%) and factors like patient load (87.39%), drug consumption (85.71%), and disease prevalence (64.71%). Store site analysis revealed that 65.03% exhibited marginal capability, lacking standardized drugstores and employing unstandardized procedures. Storage practices varied, with 48.69% storing drugs conveniently and others categorizing them by drug type (32.79%) or using the first-expired-first-out system (40.98%). Approximately 42.69% reported having expired drugs. Concerning transportation costs, 37.16% incurred expenses exceeding 20,000 Kyats per time, with management staff often covering the costs. Waste management methods included burial pits (49.18%), incineration (62.84%), and sharp pits (55.19%). A majority (78.14%) used safety boxes, and 57.38% implemented a color-coded system for waste bins. The logistics management information system was entirely paper-based (100%), with key challenges attributed to insufficient training (62.84%), capacity issues (19.13%), and staffing concerns (38.25%). On average, assessments of drug quality conditions and physical damages scored 46.51% and 48.20%, respectively.

Conclusion

The study revealed that the overall supply chain maturity at first-level public health facilities is at a marginal capability level (36.35%). While some basic drug supply chain management procedures were in place, they were not consistently followed, and many systems remain manual. The findings underscored significant inconsistencies in the management functions of supplied drugs, with poor adherence to Standard Operating Procedure (SOP) guidelines.
Proteome-scale tagging and functional screening in mammalian cells by ORFtag
Authors: Nemčko Filip , Himmelsbach Moritz , Loubiere Vincent , Yelagandula Ramesh , Pagani Michaela , Fasching Nina , Brennecke Julius , Elling Ulrich , Stark Alexander , Ameres Stefan L.
Published: January 2024

Determining protein function in a systematic manner is a key goal of modern biology, but remains challenging with current approaches. Here, we present ORFtag, a versatile, cost-effective and highly efficient method for the massively-parallel tagging and functional interrogation of proteins at proteome scale. Using mouse embryonic stem cells, we showcase ORFtag’s utility through screens for transcriptional activators, repressors and post-transcriptional regulators. Each screen finds known and novel regulators, including long ORFs not accessible to other methods, revealing that Zfp574 is a highly selective transcriptional activator and that oncogenic fusions frequently function as transactivators.
Increased positive selection in highly recombining genes does not necessarily reflect an evolutionary advantage of recombination
Authors: Joseph Julien
Published: January 2024

It is commonly thought that the long-term advantage of meiotic recombination is to dissipate genetic linkage, allowing natural selection to act independently on different loci. It is thus theoretically expected that genes with higher recombination rates evolve under more effective selection. On the other hand, recombination is often associated with GC-biased gene conversion (gBGC), which theoretically interferes with selection by promoting the fixation of deleterious GC alleles. To test these predictions, several studies assessed whether selection was more effective in highly recombining genes (due to dissipation of genetic linkage) or less effective (due to gBGC), assuming a fixed distribution of fitness effects (DFE) for all genes. In this study, I directly derive the DFE from a gene’s evolutionary history (shaped by mutation, selection, drift and gBGC) under empirical fitness landscapes. I show that genes that have experienced high levels of gBGC are less fit and thus have more opportunities for beneficial mutations. Only a small decrease in the genome-wide intensity of gBGC leads to the fixation of these beneficial mutations, particularly in highly recombining genes. This results in increased positive selection in highly recombining genes that is not caused by more effective selection. Additionally, I show that the death of a recombination hotspot can lead to a higherdN/dSthan its birth, but with substitution patterns biased towards AT, and only at selected positions. This shows that controlling for a substitution bias towards GC is therefore not sufficient to rule out the contribution of gBGC to signatures of accelerated evolution. Finally, although gBGC does not affect the fixation probability of GC-conservative mutations, I show that by altering the DFE, gBGC can also significantly affect non-synonymous GC-conservative substitution patterns.
The human complement factor B-C3b complex: Investigation of the interaction using C3b bound to thiol-Sepharose
Authors: Williams Samantha , Pondman Kirsten , Varghese Praveen M. , Aiyan Ahmad Al , Kishore Uday , Sim Robert B.
Published: January 2024

Factor B, a serine protease proenzyme and part of the complement system, binds to other complement proteins such as C3b and properdin. While it is known to be activated by factor D, other interactions that interfere with the binding between Factor B and C3b are less well-understood. We attached C3b to a thiol Sepharose via its free SH group and conducted a competition assay employing125I-labelled factor B to study competitive binding. Two anti-C3d monoclonal antibodies (F49b and 4C2) were found to partially inhibit the binding of Factor B to C3b. The inhibitory effects of these monoclonal antibodies were found to be dose-dependent. 4C2 was found to have a maximum inhibition of 50%, while the maximum inhibition by F49b was ∼40%. In contrast, two anti-C3c monoclonal antibodies (F39b and F20b) were able to enhance the formation of the factor B-C3b complex in a dose-dependent manner. Competition binding studies with isolated C3 fragments further supported the involvement of the C3d region in factor B binding, as C3d inhibited the binding of factor B to C3b completely. Furthermore, additional competition binding studies conducted with each of the three domains of factor B (Ba, vWF and SP) demonstrated that each domain independently inhibited the binding of intact factor B to C3b by ∼50%.
VPAC2 receptor signaling promotes pancreatic cancer cell growth and decreases the immunogenicity of the tumor microenvironment
Authors: Passang Tenzin , Wang Shuhua , Zhang Hanwen , Zeng Fanyuan , Hsu Po-Chih , Wang Wenxi , Li Jian Ming , Liu Yuan , Ravindranathan Sruthi , Lesinski Gregory B. , Waller Edmund K.
Published: January 2024

Identifying mechanisms underlying tumor growth and immune resistance is needed to treat pancreatic ductal adenocarcinoma (PDAC) effectively. The complexity of the tumor microenvironment (TME) suggests that the crosstalk between cells in the TME could drive drug resistance and relapse in PDAC. We have previously determined that vasoactive intestinal peptide (VIP) is overexpressed in PDAC and that VIP receptors expressed on T cells are a targetable pathway that sensitizes PDAC to anti-PD1 therapy. In this study, we show that pancreatic cancer cells engage in autocrine signaling of VIP through VIP-receptor 2 (VPAC2), and that high co-expression of VIP with VPAC2 leads to reduced relapse-free survival in PDAC patients. Mechanistically, we identified piwi-like RNA-mediated gene silencing2 (Piwil2) as a tumor-cell intrinsic protein downstream of VPAC2 that regulates cancer cell growth. In addition, we discovered TGFβ-1 as a potential tumor-extrinsic inhibitor of T cell function induced by VPAC2 signaling.In vivo, knock out and knockdown of VPAC2 on PDAC cells led to reduced tumor growth rate and increased sensitivity to anti-PD-1 therapy in various mouse models of PDAC that were T-cell dependent. Overall, these findings emphasize the implications of VIP/VPAC2 signaling in the PDAC tumor microenvironment and further support the rationale for developing VPAC2-specific antagonists.

Significance

The autocrine VIP signaling via VPAC2 promotes cancer cell growth and dampens T cell function in pancreatic ductal adenocarcinoma and thus represents a potential therapeutic target in PDAC.
Advancing the Application of pXRF for Biological Samples
Authors: Brandis K.J. , Francis R. , Zawada K.J.A. , Hasselerharm C.D. , Ramp D.
Published: January 2024

Point 1: Portable x-ray fluorescent (pXRF) technology provides significant opportunities for rapid, non-destructive data collection in a range of fields of study. However, there are sources of variation and sample assumptions that may influence the data obtained, particularly in biological samples.

Point 2: We used representative species for four taxa (fish, mammals, birds, reptiles) to test the precision of replicate scans, and the impact of sample thickness, sample state, scan location and scan time on data obtained from a pXRF.

Point 3: We detected significant differences in concentration data due to sample state, scanning time and scanning location for all taxa. Infinite thickness assumptions were met for fish, reptile and mammal representatives at all body locations when samples were thawed, but not dried. Infinite thickness was not met for feathers. Scan time results found in most cases the 40, 60 and 80 second beam times were equivalent. Concentration data across replicate scans were highly correlated.

Point 4: The opportunities for the use of pXRF in biological studies are wide-ranging. These findings highlight the considerations required when scanning biological samples to ensure the required data are suitably collected, while maintaining minimal radiation exposure to live animals.
Changes in surface temperatures reveal the thermal challenge associated with catastrophic moult in captive Gentoo penguins
Authors: Lewden Agnès , du Fretay Tristan Halna , Stier Antoine
Published: January 2024

Once a year, penguins undergo a catastrophic moult replacing their entire plumage during a fasting period on land or on sea-ice during which time individuals can lose 45% of their body mass. In penguins, new feather synthesis precedes the loss of old feathers leading to an accumulation of two feathers layers (double coat) before the old plumage is shed. We hypothesize that the combination of the high metabolism required for new feathers synthesis and the potentially high thermal insulation linked to the double coat could lead to a thermal challenge requiring additional peripheral circulation to thermal windows to dissipate extra-heat. To test this hypothesis, we measured the surface temperature of different body regions of captive Gentoo penguins (Pygoscelis papua) throughout the moult under constant environmental conditions.

The surface temperature of the main body trunk decreased during the initial stages of the moult, therefore suggesting a higher thermal insulation. On the opposite, the periorbital region, a potential proxy of core temperature in birds, increased during these same early moulting stages. The surface temperature of bill, flipper and foot (thermal windows) tended to initially increase during the moult period, highlighting the likely need for extra heat dissipation in moulting penguins. These results raise questions regarding the thermoregulatory capacities of wild penguins during the challenging period of moulting on land in the current context of global warming.
Evaluation of HIV Viral Load Surveillance System, National Perspective in Tanzania
Authors: Torokaa Peter Richard , Urio Loveness John , Mwakalobo Ambwene , Magesa Alex Sifaeli , Allan James , Osima David J. , Shao Focus Medard , Mziray Joseph , Barnabas Yulitha , Joachim Agricola , Majigo Mtebe
Published: January 2024

Background

Human immunodeficiency virus (HIV) infection is still a global public health problem. The number of HIV-positive individuals was estimated to be 38.0 million worldwide in 2020, with 2.78 million being children and adolescents aged 0 to 19 years. We aimed to assess the usefulness and system attributes of the HIV Viral Load (HVL) surveillance system in Tanzania and determine whether it meets its objectives.

Methodology

This was a descriptive cross-sectional analysis conducted to describe the attributes and usefulness of the HVL surveillance system. From January through December 2022, we consistently captured HVL data, which we extracted and analysed. The system description, case definition, and eligibility criteria were obtained from the system guidelines. We used Updated Guidelines for Evaluating Public Health Surveillance Systems from the Centre for Disease Control and Prevention (CDC) to evaluate system attributes. We observed the data entry to determine the simplicity and time spent entering data into the system. Turnaround time were determined from the sample collected at the spoke to the result returned to the clients.

Results

The HVL surveillance system is implemented by 90.6% (4314/4764) of facilities in the country. The overall national data completeness was 97.4%. The system’s sensitivity was 84.4%, with a predictive value positive (PVP) of 52% and a national data accuracy of 97%. Of eight data clerks interviewed, 100% (8/8) said the system was simple to use.

Conclusion

The system’s overall performance achieved its goals was satisfactory. The system was representable, simple, flexible, and sensitive. Turnaround time was at a median of 13 days.
Why didn’t people get vaccinated against COVID-19? Results from a nationwide survey among Mexican adults
Authors: Wrzecionkowska Dagmara , Stephens Christopher R. , Gutiérrez Reyes Juan Pablo
Published: January 2024

Objective

To explore the reasons for not getting vaccinated against COVID-19.

Material and methods

In October 2021, a nationwide structured telephone survey (disproportionate stratified sampling) was conducted regarding COVID-19 pandemics, including vaccination experience. To examine associations between inoculation and other characteristics, the chi-square test and logistic regression analysis were applied.

Results

Out of 3 126 adults, 68% reported complete vaccination and 21% only the first dose, while 11% remained unvaccinated. Non-vaccination was associated with being younger, male, without a partner, low socioeconomic level, and no previous diagnosis of hypertension, obesity or diabetes. Furthermore, the non-vaccinated were less likely to have tested for COVID-19, and more likely to consider COVID-19 as low severe and not real compared with the vaccinated. Using logistic regression models: place of residence, marital status, educational level, age, BMI, testing for COVID-19, and the perception of COVID-19 (severe and real) were significant predictors of non-vaccination. The predominant reasons for not getting vaccinated were: 63% “external barriers” (e.g., not being able to attend an appointment), and 37% “internal motives” (e.g., “vaccine does not work”).

Conclusions

The causes of non-vaccination against COVID-19 are related to both social and geographical determinants. Addressing external barriers is necessary in order to promote equity in vaccination. Reviewing the results in the context of earlier studies on the willingness to vaccinate, the gap between intention and vaccination is notable.
Factors associated with human papillomavirus (HPV) virus load variations in genital infections in young women
Authors: Tessandier Nicolas , Boué Vanina , Kamyia Tsukushi , Supplisson Olivier , Murall Carmen Lia , Reyné Bastien , Selinger Christian , Bernat Claire , Grasset Sophie , Groc Soraya , Rahmoun Massilva , Bonneau Marine , Foulongne Vincent , Graf Christelle , Tribout Vincent , Prétet Jean-Luc , Reynes Jacques , Segondy Michel , Bravo Ignacio G , Boulle Nathalie , Alizon Samuel
Published: January 2024

Human papillomaviruses (HPVs) are the most oncogenic viruses known to humans, with 12 high-risk (HR) genotypes causing nearly all cervical cancers. Cytology is commonly used to screen for cervical lesions but is currently being replaced by testing for high-risk HPV (HR HPV). Although HR HPV screening has a higher sensitivity, its specificity is limited, and it is currently advised to repeat the first screening 4 to 6 months later. To increase the sensitivity of the screening triage, other biomarkers have been suggested, including HPV viral load. Indeed, since 1999, several independent studies have found an association between HR HPV viral load in cervical samples and the severity of cervical disease. Here, we further explore the determinants of variations in HPV viral load in genital infections in young adult women.

We analysed samples collected in the PAPCLEAR clinical cohort for participants who were infected by HPV genotypes for which we quantified virus load using qPCR targeting 13 genotypes. We developed a Bayesian statistical model estimating the effect of covariates of interest on the HPV viral load. To analyse precisely the viral load difference between HPV genotypes, phylogenetic distances between HPVs were also integrated in the Bayesian model.

Our results fail to identify an effect of anti-HPV vaccination, co-infections by multiple HPVs or tobacco smoking on the detected viral load. On the opposite, swabs contained significantly more viral copies than cervical smears. Our results also highlight that most of the viral load variance could be explained at the genotype level (80%) rather than at the individual level (20%). Our model reveals important differences in viral load detected between the different genotypes tested, with HPV16 being the highest and HPV18 the lowest. The impact of phylogenetic signal on viral load was also estimated to be low, except for a cluster comprised of HPV53, HPV66 and HPV56. These results contribute to identifying the main drivers of HPV viral load detected and could help design needed future screening policies.