bluuebunny/crossref_metadata_2025_split huggingface dataset:
Proposal of a vaccination needs index to prioritize municipal interventions in Brazil
Authors: Diaz-Quijano Fredi Alexander , Schrarstzhaupt Isaac Negretto , Fantinato Francieli Fontana Sutile Tardetti , Guzmán-Barrera Lely Stella , Croda Julio 
Published: September 2023

AbstractIntroductionTo address the health needs of a population, it is essential to integrate several indicators that are expressed on non-comparable scales. Vaccination is a crucial aspect of public health, and prioritizing vaccination needs through immunization registries can help allocate resources and funding to integral approaches.ObjectiveTo propose and implement an index of vaccination needs (VNI) based on national administrative data on tracer vaccines for children, born between 2019 and 2022, to help prioritize Brazilian municipalities.MethodologyWe analyzed data from 5,570 municipalities in Brazil. The VNI integrated indicators of vaccination coverage and the number of susceptible children regarding tracer vaccines for children including DTP – Diphtheria-Tetanus-Pertussis (third dose), polio (third dose), and MMR – Measles-Mumps and Rubella (second dose). We assessed how the VNI could identify a group of municipalities in challenging situations to improve vaccination.ResultsCompared with criteria based only on the absolute number of unvaccinated children (susceptible children) or the vaccination coverage, the group prioritized for having high VNI exhibited more similar proportions of large, medium, and small municipalities. Additionally, this group included more municipalities located in the Legal Amazon region and Special Sanitary Indigenous Districts than groups prioritized with the other criteria. The VNI also outperformed the other criteria to prioritize municipalities that differed from the rest regarding the Gini coefficient.ConclusionThe proposed VNI can facilitate the identification of populations that need differentiated interventions to prevent the resurgence of eliminated or controlled vaccine-preventable diseases.
Structure of γ-secretase (PSEN1/APH-1B) in complex with Aβ46 provides insights into amyloid-β processing and modulation by the APH-1B isoform
Authors: Odorcic Ivica , Hamed Soliman Mohamed Belal , Lismont Sam , Chávez-Gutiérrez Lucía , Efremov Rouslan G. 
Published: September 2023

AbstractDeposition of amyloid-β (Aβ) peptides in the brain is a hallmark of Alzheimer’s disease. Aβs are generated through sequential proteolysis of the amyloid precursor protein by the γ-secretase complexes (GSECs). Aβ peptide length, which is modulated by the Presenilin (PSEN) and APH-1 subunits of GSEC, is critical for Alzheimer’s pathogenesis. Despite high relevance, mechanistic understanding of the proteolysis of Aβ, and its modulation by APH-1, remain incomplete. Here, we report cryo-EM structures of human GSEC (PSEN1/APH-1B) reconstituted into lipid nanodiscs in apo form and in complex with the intermediate Aβ46 substrate. We found a divergent APH-1 loop to be involved with PSEN1 in substrate-binding-induced concerted rearrangements. Upstream the catalytic site, Aβ46 structure is similar to the endopeptidase substrates and is stabilised by polar interactions including a previously unseen interaction with PSEN1 loop1. The hybrid β-sheet was not observed downstream the catalytic site.
Evolutionarily Conserved CKI1-Mediated Two-Component Signaling is Required for Female Germline Specification inMarchantia polymorpha
Authors: Bao Haonan , Sun Rui , Iwano Megumi , Yoshitake Yoshihiro , Aki Shiori S , Umeda Masaaki , Nishihama Ryuichi , Yamaoka Shohei , Kohchi Takayuki 
Published: September 2023

SummaryIn land plants, gametes derive from a small number of dedicated haploid cells.1In angiosperms, one central cell and one egg cell are differentiated in the embryo sac as female gametes for double fertilization, while in non-flowering plants, only one egg cell is generated in the female sexual organ, called the archegonium.2,3The central cell specification ofArabidopsis thalianais controlled by the histidine kinase CYTOKININ-INDEPENDENT 1 (CKI1), which is a two-component signaling (TCS) activator sharing downstream regulatory components with the cytokinin signaling pathway.4–7Our phylogenetic analysis suggested that CKI1 orthologs broadly exist in land plants. However, the role of CKI1 in the archegonium-bearing non-flowering plants remains unclear. Here we found that the sole CKI1 ortholog in the liverwortMarchantia polymorpha, MpCKI1, which functions through conserved downstream TCS components, regulates the female germline specification for egg cell development in the archegonium. InM. polymorpha, the archegonium develops three-dimensionally from a single cell, accumulating MpBONOBO (MpBNB), a master regulator for germline initiation and differentiation.8We visualized female germline specification by capturing the distribution pattern of MpBNB in the discrete stages of early archegonium development, and found that the MpBNB accumulation is restricted to female germline cells. MpCKI1 is required for the proper MpBNB accumulation in the female germline, and is critical for the asymmetric cell divisions that specify the female germline cells. These results suggest that CKI1-mediated TCS originated during early land plant evolution and participates in female germ cell specification in deeply-diverged plant lineages.
Decision bias and sampling asymmetry in reward-guided learning
Authors: Cao Yinan , Tsetsos Konstantinos 
Published: September 2023

AbstractHuman economic decisions are highly sensitive to contexts. Deciding between two competing alternatives can be notoriously biased by their overall value (‘magnitude effect’) or by a third decoy option (‘distractor effect’). Some prominent explanations appeal to diminishing value sensitivity and divisive normalization in value representations, i.e., representational bias, that feed into the choice stage. However, these explanations have recently come under scrutiny due to empirical inconsistencies and mounting alternative theories. Here, we posit that context-sensitive choices may not stem from representational biases but rather emerge as by-products of asymmetric sampling during value learning. In a reward-guided choice task, participants aimed to maximize cumulative rewards through trial and error. The task introduced alternating blocks with either a colored distractor or a neutral ‘notional’ distractor. We observed decreased choice accuracy when higher-value distractors were present, a pattern that persisted even in the notional distractor blocks. Using computational modeling, we show that this phenomenon falls out naturally from a simple learning rule without relying on any additional mechanism such as divisive normalization or nonlinear utility. Furthermore, we found that, contrary to divisive normalization, choice accuracy was not influenced by distractor value but strongly depended on the magnitude of the targets’ values per se. This ‘magnitude sensitivity’ was also found in the ‘notional distractor’ conditions and could lawfully be reproduced by the learning model. Importantly, when counterfactual feedback eliminated sampling asymmetry, the observed decision bias vanished. Our results suggest that the genesis of context-sensitive choices may lie in the learning dynamics themselves, specifically sampling asymmetry, rather than in pre-decisional representational biases. This finding reframes the discourse on irrational decision-making, attributing it to acquired biases during the learning process, not necessarily computational intricacies at the choice stage.
Interplay of Race and Neighborhood Deprivation on Ambulatory Blood Pressure in Young Adults
Authors: Jeong Soolim , Linder Braxton A. , Barnett Alex M. , Tharpe McKenna A. , Hutchison Zach J. , Culver Meral N. , Sanchez Sofia O. , Nichols Olivia I. , Grosicki Gregory J. , Bunsawat Kanokwan , Nasci Victoria L. , Gohar Eman Y. , Fuller-Rowell Thomas E. , Robinson Austin T. 
Published: September 2023

AbstractBackgroundAmbulatory blood pressure (BP) monitoring measures nighttime BP and BP dipping, which are superior to in-clinic BP for predicting cardiovascular disease (CVD), the leading cause of death in America. Compared with other racial/ethnic groups, Black Americans exhibit elevated nighttime BP and attenuated BP dipping, including in young adulthood. Social determinants of health contribute to disparities in CVD risk, but the contribution of neighborhood deprivation on nighttime BP is unclear. Therefore, we examined associations between neighborhood deprivation with nighttime BP and BP dipping in young Black and White adults.MethodsWe recruited 21 Black and 26 White participants (20 M/27 F, mean age: 21 years, body mass index: 25±4 kg/m2) for 24-hour ambulatory BP monitoring. We assessed nighttime BP and BP dipping (nighttime:daytime BP ratio). The area deprivation index (ADI) was used to measure neighborhood deprivation. Associations between ADI and ambulatory BP were examined.ResultsBlack participants exhibited higher nighttime diastolic BP compared with White participants (63±8 mmHg vs 58±7 mmHg,p=0.003), and attenuated BP dipping ratios for both systolic (0.92±0.06 vs 0.86±0.05,p=0.001) and diastolic BP (0.86±0.09 vs 0.78±0.08,p=0.007). Black participants experienced greater neighborhood deprivation compared with White participants (ADI scores: 110±8 vs 97±21,p<0.001), and ADI was associated with attenuated systolic BP dipping (ρ=0.342,p=0.019).ConclusionsOur findings suggest neighborhood deprivation may contribute to higher nighttime BP and attenuated BP dipping, which are prognostic of CVD, and more prevalent in Black adults. Targeted interventions to mitigate the effects of neighborhood deprivation may help to improve nighttime BP.Clinical Trial RegistryURL:https://www.clinicaltrials.gov; Unique identifier:NCT04576338Clinical PerspectiveWe demonstrate young Black adults exhibit higher nighttime blood pressure and attenuated nighttime blood pressure dipping compared with young White adults.Black adults were exposed to greater neighborhood deprivation, which was associated with attenuated blood pressure dipping, irrespective of race.Our findings add to a growing body of literature indicating neighborhood deprivation may contribute to increased cardiovascular disease risk.
Rab35 is required for embryonic development and kidney and ureter homeostasis through regulation of epithelial cell junctions
Authors: Clearman Kelsey R. , Timpratoom Napassawon , Patel Dharti , Rains Addison B. , Haycraft Courtney J. , Croyle Mandy J. , Reiter Jeremy F. , Yoder Bradley K. 
Published: September 2023

Structured AbstractBackgroundRab35 is a member of a GTPase family of endocytic trafficking proteins. Studies in cell lines have indicated that Rab35 participates in cell adhesion, polarity, cytokinesis, and primary cilia length and composition. Additionally, sea urchin Rab35 regulates actin organization and is required for gastrulation. In mice, loss of Rab35 in the CNS disrupts hippocampal development and neuronal organization. Outside of the CNS, the functions of mammalian Rab35in vivoare unknown.MethodsWe generated and analyzed the consequences of both congenital and conditional nullRab35mutations in mice. Using a LacZ reporter allele, we assessedRab35expression during development and postnatally. We assessed Rab35 loss in the kidney and ureter using histology, immunofluorescence microscopy, and western blotting.ResultsCongenitalRab35loss of function caused embryonic lethality: homozygous mutants arrested at E7.5 with cardiac edema. Conditional loss of Rab35, either during gestation or postnatally, caused hydronephrosis. The kidney and ureter phenotype were associated with disrupted actin cytoskeletal architecture, altered Arf6 epithelial polarity, reduced adherens junctions, loss of tight junction formation, defects in EGFR expression and localization, disrupted cell differentiation, and shortened primary cilia.ConclusionRab35 is essential for mammalian development and the maintenance of kidney and ureter architecture. Loss of Rab35 leads to non-obstructive hydronephrosis, making theRab35mutant mouse a novel mammalian model to study mechanisms underlying this disease.Significance StatementHydronephrosis, distention of the renal calyces and pelvis, affects 1 in 100 infants. Most cases of hydronephrosis are associated with obstruction. Non-obstructive hydronephrosis is typically associated with impaired ureter development, and requires surgical intervention. Here, we describe a mouse model of non-obstructive hydronephrosis caused by mutations inRab35.Hydronephrosis inRab35mutants is associated with the inability to maintain epithelial cell junctions, defects in EGFR expression, and altered urothelium and smooth muscle integrity of the ureter. TheRab35mutant mouse is a novel model to study mechanisms and treatment strategies for non-obstructive hydronephrosis.
A novel workflow for unbiased quantification of autophagosomes in 3D inArabidopsis thalianaroots
Authors: Daněk Michal , Kocourková Daniela , Podmanická Tereza , Eliášová Kateřina , Nesvadbová Kristýna , Krupař Pavel , Martinec Jan 
Published: September 2023

ABSTRACTMacroautophagy is frequently quantified by live imaging of autophagosomes decorated with a marker of fluorescently tagged ATG8 protein (FT-ATG8) inArabidopsis thaliana. This requires generation of suitable plant material by time-consuming crossing or transformation with FT-ATG8 marker. Autophagosome quantification by image analysis often relies on their counting in individual focal planes. This approach is prone to deliver biased results due to inappropriate sampling of the regions of interest in the Z-direction, as the actual 3D distribution of autophagosomes is usually not taken into account. To overcome such drawbacks, we have developed and tested a workflow consisting of immunofluorescence microscopy of autophagosomes labelled with anti-ATG8 antibody followed by stereological image analysis employing the optical disector and the Cavalieri principle. Our immunolabelling protocol specifically recognized autophagosomes in epidermal cells ofA. thalianaroot. Higher numbers of immunolabelled autophagosomes were observed when compared with those recognized with FT-AtATG8e marker, suggesting that singleAtATG8 isoform markers cannot detect all autophagosomes in a cell. Therefore, immunolabelling provides more precise information as the anti-ATG8 antibody recognizes virtually allAtATG8 isoforms. The number of autophagosomes per tissue volume determined by stereological methods correlated with the intensity of autophagy induction treatment. Compared to autophagosome quantifications in maximum intensity projections, stereological methods detected autophagosomes present in a given volume with higher accuracy. Our novel application of immunolabelling combined with stereological methods constitutes a powerful toolbox for unbiased and reproducible quantification of autophagosomes and offers a convenient alternative to the standard of live imaging using FP-ATG8 marker.
GC content across insect genomes: phylogenetic patterns, causes and consequences
Authors: Kyriacou Riccardo G. , Mulhair Peter O. , Holland Peter W. H. 
Published: September 2023

AbstractThe proportions of A:T and G:C nucleotide pairs are often unequal and can vary greatly between animal species and along chromosomes. The causes and consequences of this variation are incompletely understood. The recent release of high-quality genome sequences from the Darwin Tree of Life and other large-scale genome projects provides an opportunity for GC heterogeneity to be compared across a large number of insect species. Here we analyse GC content along chromosomes, and within protein-coding genes and codons, of 150 insect species from four holometabolous orders: Coleoptera, Diptera, Hymenoptera, and Lepidoptera. We find that protein-coding sequences have higher GC content than the genome average, and that Lepidoptera generally have higher GC content than the other three insect orders examined. GC content is higher in small chromosomes in most Lepidoptera species, but this pattern is less consistent in other orders. GC content also increases towards subtelomeric regions within protein-coding genes in Hymenoptera, Coleoptera and, most strikingly, Lepidoptera. Two species of Diptera,Bombylius majorandB. discolor, have very atypical genomes with ubiquitous increase in AT content, especially at third codon positions. Despite dramatic AT-biased codon usage, we find no evidence that this has driven divergent protein evolution. We argue that the GC landscape of Lepidoptera, Hymenoptera and Coleoptera genomes is influenced by GC-biased gene conversion, strongest in Lepidoptera, with some outlier taxa affected drastically by counteracting processes.
Clustering of cortical dynein regulates the mechanics of spindle orientation in human mitotic cells
Authors: Anjur-Dietrich Maya I. , Hererra Vicente Gomez , Farhadifar Reza , Wu Haiyin , Merta Holly , Bahmanyar Shirin , Shelley Michael J. , Needleman Daniel J. 
Published: September 2023

SummaryThe forces which orient the spindle in human cells remain poorly understood due to a lack of direct mechanical measurements in mammalian systems. We use magnetic tweezers to measure the force on human mitotic spindles. Combining the spindle’s measured resistance to rotation, the speed it rotates after laser ablating astral microtubules, and estimates of the number of ablated microtubules reveals that each microtubule contacting the cell cortex is subject to ∼1 pN of pulling force, suggesting that each is pulled on by an individual dynein motor. We find that the concentration of dynein at the cell cortex and extent of dynein clustering are key determinants of the spindle’s resistance to rotation, with little contribution from cytoplasmic viscosity, which we explain using a biophysically based mathematical model. This work reveals how pulling forces on astral microtubules determine the mechanics of spindle orientation and demonstrates the central role of cortical dynein clustering.HighlightsCytoplasmic viscosity does not determine the spindle’s resistance to rotationEach astral microtubule that contacts the cell cortex is pulled on by a single dynein motorPulling forces on astral microtubules determine the mechanics of spindle orientationThe mechanics of spindle orientation is regulated by clustering of dynein motors at the cell cortexGraphical Abstract
Instinct to insight: Neural correlates of ethological strategy learning
Authors: Lu Kai , Wong Kelvin T. , Zhou Lin N. , Shi Yike T. , Yang Chengcheng J. , Liu Robert C. 
Published: September 2023

AbstractIn ethological behaviors like parenting, animals innately follow stereotyped patterns of choices to decide between uncertain outcomes but can learn to modify their strategies to incorporate new information. For example, female mice in a T-maze instinctively use spatial-memory to search for pups where they last found them but can learn more efficient strategies employing pup-associated acoustic cues. We uncovered neural correlates for transitioning between these innate and learned strategies. Auditory cortex (ACx) was required during learning. ACx firing at the nest increased with learning and correlated with subsequent search speed but not outcome. Surprisingly, ACxsuppressionrather than facilitation during search was more prognostic of correct sound-cued outcomes – even before adopting a sound-cued strategy. Meanwhile medial prefrontal cortex encoded the last pup location, but this decayed as the spatial-memory strategy declined. Our results suggest a neural competition between a weakening spatial-memory and strengthening sound-cued neural representation to mediate strategy switches.
Stakeholder management challenges in a health-care medical device project in India – an SME perspective
Authors: Kaur Amrinder 
Published: September 2023

Learning outcomes
The learning outcomes are as follows: understanding the impact on company growth through identification and alignment of stakeholder priorities in a project for SME in an emerging market; analyzing the impact of stakeholder alignment and relationship management on the project outcome; and evaluating the importance of Stakeholder Management for effective Project Management.

Case overview/synopsis
The case of ‘Hospedia Medicare,’ a medical device manufacturing company based in India, was started by a family involved in the medical devices business for over two decades. The company began operations in a new avatar and focused on one medical device or product by 2013. The product was designed with quality features to solve customer problems, making the cost relatively high compared to other domestic peers. Creating new product lines or updating the existing product attributes was imperative for the company to attain its growth objectives. The protagonist was dealing with a dilemma involving managing various stakeholders, aligning the project scope to create a growth story for the company in line with its vision and managing the stakeholders by understanding and analyzing their needs, expectations and interest, thus influencing the project outcome. The case can be used by instructors to identify, understand and evaluate the importance of different stakeholders on project outcome or success. Furthermore, it can be used to analyze and critique the impact of stakeholders on project scope, which can affect the long-term sustainability of the company, as different stakeholders have different expectations and needs. The case also details how regular communication, collaboration and awareness became essential for the project's success. Lack of an effective engagement strategy at the project planning stage can have risks concerning cost and achieving the overall vision, which creates a positive outcome for all the stakeholders.

Complexity academic level
The case study can be introduced to graduate and undergraduate students to reflect on and critique the importance of Stakeholder Management in Project Management. It can be used for, entrepreneurship, project management, operations and strategy, particularly emphasizing for small and medium enterprises (SMEs).

Supplementary material
Teaching notes are available for educators only.

Subject code
CSS 9: Operations and Logistics.