bluuebunny/crossref_metadata_2025 huggingface dataset:
Structural barriers and facilitators to accessing HIV services for marginalized working populations: insights from farm workers in South Africa
Authors: Mlangeni Nosimilo , Lembani Martina , Adetokunboh Olatunji , Nyasulu Peter S
Published: October 2024

Farm workers are vulnerable working populations who face significant inequalities in accessing health services, including those for human immunodeficiency virus (HIV) prevention, treatment and care. This descriptive phenomenological study aimed to explore farm workers’ experiences when accessing HIV services and was conducted in Limpopo province, South Africa. Eighteen in-depth interviews were conducted in four health facilities from two districts, and two focus group discussions were conducted in one of the farms within the province. Purposive sampling and systematic random sampling were used to select study participants. A deductive thematic approach was used to analyse data, informed by the social–ecological model of health. The results reveal that farm workers perceive multiple interdependent factors that inhibit or enable their access to HIV healthcare services. Key barriers to HIV healthcare were transport affordability, health worker attitudes, stigma and discrimination, models of HIV healthcare delivery, geographic location of health facilities and difficult working conditions. Key facilitators to HIV healthcare included the availability of mobile health services, the presence of community health workers and a supportive work environment. The findings suggest disparities in farm workers’ access to HIV services, with work being the main determinant of access. We, therefore, recommend a review of HIV policies and programmes for the agricultural sector and models of HIV healthcare delivery that address the unique needs of farm workers.
The Effectiveness of Risankizumab as Induction Therapy for Crohn’s Disease: Data From the Sicilian Network for Inflammatory Bowel Diseases
Authors: Macaluso Fabio Salvatore , Renna Sara , Fries Walter , Viola Anna , Cappello Maria , Salerno Ivan Alberto , Mocciaro Filippo , Scrivo Barbara , Giangreco Emiliano , Ferracane Concetta , Minissale Maria Giovanna , Distefano Maria Emanuela , Tortorella Vincenza , Termini Alessandro , Bertoncello Luca , Orlando Ambrogio
Published: October 2024

Lay Summary

This multicentre cohort study showed that Risankizumab is an effective induction therapy in patients with Crohn’s disease, and that the best results are obtained when Risankizumab is used as second-line therapy following a previous failure with a TNF inhibitor.
Transcatheter aortic valve replacement failure: surgical valve explantation after more than a decade
Authors: Yamashita Go , Hirao Shingo , Komiya Tatsuhiko
Published: October 2024

Transcatheter aortic valve replacement (TAVR) has become an established alternative to surgical aortic valve replacement for severe aortic stenosis. However, the long-term outcomes and need for surgical reintervention following TAVR remain uncertain. This case report describes a 76-year-old woman who underwent surgical explantation of a SAPIEN-XT valve more than a decade after initial TAVR implantation due to late valve failure. The patient presented with severe aortic insufficiency and heart failure symptoms. Surgical intervention involved concomitant ascending aortic replacement, tricuspid annuloplasty and coronary artery bypass grafting. The TAVR valve was successfully explanted using careful blunt dissection to avoid annulus damage. Postoperative recovery was uneventful, with the patient discharged after 4 weeks. This case highlights the potential need for long-term surgical management of patients after TAVR and emphasizes the importance of surgical preparedness as TAVR indications expand. It also provides valuable insights for surgeons encountering similar cases of late TAVR failure requiring explantation.
Ro5-4864, a translocator protein ligand, regulates T cell-mediated inflammatory responses in skin
Authors: Sendai Yuka , Takeda Kazuyoshi , Ohta Keisuke , Nakae Susumu , Koshika Kyotaro , Kitamura Kei , Higuchi Makoto , Ichinohe Tatsuya , Azuma Toshifumi , Okumura Ko , Ohno Tatsukuni
Published: October 2024

Translocator protein (TSPO) is a mitochondrial outer membrane protein expressed on a variety of immune cells, including macrophages, dendritic cells, and T cells, in addition to neurons and steroid-producing cells. Previous studies of TSPO ligands have suggested that TSPO is involved in multiple cellular functions, including steroidogenesis, immunomodulation, and cell proliferation. Currently, there are limited reports on the effects of TSPO or TSPO ligands on T cell-mediated immune responses. Here, we investigated the involvement of TSPO/TSPO ligand in T cell responses using a 2,4-dinitro-1-fluorobenzene (DNFB)-induced contact hypersensitivity (CH) model. Treatment with Ro5-4864, a TSPO ligand, during DNFB sensitization reduced the number and activation status of CD4+ and CD8+ T cells in draining lymph nodes and alleviated skin inflammation after DNFB challenge. Adoptive transfer of Ro5-4864-treated mouse-derived DNFB-sensitized T cells to naive mice inhibited CH responses after DNFB challenge. Ro5-4864-treated sensitized T cells showed lower proliferative responses when stimulated with DNFB-pulsed antigen-presenting cells compared to control-treated sensitized T cells. Ro5-4864 also suppressed cell proliferation, as well as adenosine triphosphate and lactate production, during T cell activation. Moreover, the inhibitory effects of Ro5-4864 on T cell responses were conserved in TSPO-deficient cells. Our results suggest that Ro5-4864 inhibits CH responses by suppressing energy metabolism, at least via glycolysis, to reduce the T cell primary response in a TSPO-independent manner.
Environmental benefits of crude protein reduction in growing pig diets: is it worth going further?
Authors: Cappelaere Léa , Garcia-Launay Florence , Larios Dalila , Simongiovanni Aude , Godbout Stéphane , Letourneau-Montminy Marie-Pierre
Published: October 2024

Nitrogen (N) excretion and emissions can be reduced in fattening pigs by reducing dietary crude protein (CP) levels. Effects of this strategy are well documented for moderate CP reduction, but little literature exists on further CP reduction made possible by free isoleucine, histidine, and leucine. This trial evaluated the effects of 2 levels of reduction in CP on growth performance, N balance, and gaseous emissions. Forty-eight pigs were allocated to 12 gaseous emission-measuring chambers at 28 kg live weight. Three dietary treatments (CTRL; −1.2pt; −2.4pt), with a CP content, respectively, of 18.1%, 16.9%, and 15.0% in phase 1 (28 to 48 kg) and 16.1%, 15.0%, and 13.8% in phase 2 (48 to 80 kg), were fed ad libitum. Growth performance was recorded for each phase. Body lipid and protein composition were analyzed by dual-energy X-ray absorptiometry in 2 animals per chamber at the beginning and end of the trial. These results were used to calculate the N balance. Slurry volume and composition were measured at the end of the trial. Ammonia, methane, and nitrous oxide emissions were recorded continuously. Data were analyzed with a general linear model including the linear and quadratic effect of CP reduction and phase as fixed effects. A trend for a quadratic effect of CP reduction on feed intake was observed (P = 0.085) with a decrease from CTRL to −1.2pt and then an increase with the −2.4pt treatment. Daily gain and gain to feed were improved by the low CP diets in phase 1 but were degraded in phase 2 (phase × CP interaction, P < 0.001) while body composition was not affected. Nitrogen excretion decreased with CP reduction (linear effect, P = 0.023) but tended to plateau with the low CP diets (quadratic effect, P = 0.081). Methane emissions per kg of gain were reduced with CP reduction (linear effect, P = 0.031). Ammonia emissions decreased with CP reduction, mostly in phase 1 (phase × CP interaction, P = 0.015); however, the emission factor (g N-NH3 / g urinary N) was not affected. Nitrous oxide emissions were not affected by CP reduction and its emission factor (g N-N2O / g N) tended to increase (linear effect, P = 0.07). Slurry ammonia-N decreased (linear effect, P < 0.023; quadratic effect, P = 0.049), but other slurry components were not significantly impacted. In this trial, a plateau in N excretion and emission reduction was reached with the −2.4pt treatment. Nevertheless, it is important to study such a reduction in conditions closer to commercial ones.
Lactation-related dynamics of bacterial and fungal microbiomes in feces of sows and gut colonization in suckling and newly weaned piglets
Authors: Yosi Fitra , Lerch Frederike , Vötterl Julia C , Koger Simone , Verhovsek Doris , Metzler-Zebeli Barbara U
Published: October 2024

Changes in the gut microbial composition of the sow during lactation may influence the gut microbial colonization in their offspring, for which less information was available in the literature. This study aimed to assess: 1) the changes that occur in the bacterial and fungal communities in sow feces during the 28-d lactation period as well as in gastric and cecal digesta of piglets until one week after weaning, and 2) bacterial and fungal taxa in cecal digesta of the piglets postweaning that associate with fecal consistency. Aside from sow milk, piglets had access to creep feed from day of life (DoL) 3. Fecal samples from sows for microbial analysis were collected (n = 20) on days postpartum (DPP) 1, 6, 13, 20, and 27, as well as from weaned piglets for fecal scoring on DoL 30 and 34. Gastric and cecal digesta of piglets was collected on DoL3, 7, 14, 21, 28, 31, and 35 (n = 5/sex/DoL). Progressing lactation affected bacterial and fungal communities in sow feces, including 10.3- and 3.0-fold increases in the relative abundances of Lactobacillus from DPP1 to 6 and Kazachstania from DPP1 to 13, respectively (P < 0.001). Although time- and gut-site-related differences existed, bacterial and fungal taxa found in sow feces were also present in gastric and cecal digesta of piglets, which supports their role in gut colonization in neonatal piglets. In piglets, bacterial and fungal alpha-diversities showed certain fluctuations during the suckling period, whereby weaning affected the fungal than bacterial diversity at both gut sites (P < 0.05). At both gut sites, Lactobacillus largely increased from DoL3 to 7 and remained a dominating taxon until DoL35 (P < 0.05). Postweaning, plant-glycan fermenters (e.g., Prevotella-9) seemed to replace milk-glycan fermenting Fusobacterium and Bacteroides (P < 0.05). In gastric and cecal digesta, Kazachstania, Tausonia, Candida, and Blumeria were dominating fungi from DoL3 to 35, with Kazachstania becoming even more dominant postweaning (P < 0.001). Fecal consistency was softer on DoL34 than 30 (P < 0.05). Correlation analysis identified that softer feces were linked to the relative abundances of plant-glycan and proteolytic bacterial taxa including pathobionts (e.g., Clostridium sensu stricto) in the cecum on DoL34. However, the potential association between cecal mold and plant-pathogenic fungi Talaromyces, Mrakia, and Blumeria and softer feces are worth investigating in the future in relation to (gut) health of piglets.
Adding gastrointestinal parasite resistance to the breeding objective in hair sheep: initial steps
Authors: Forbes Robert M , Murphy Thomas W , Burke Joan M , Notter David R , Spangler Matthew L , MacNeil Michael D , Lewis Ronald M
Published: October 2024

The U.S. Maternal Hair Index was designed by the National Sheep Improvement Program (NSIP) to increase total weight of lamb weaned per ewe lambing (TW). Producers are interested in adding gastrointestinal nematode (GIN) resistance to this breeding objective since parasitism causes substantial economic losses. The NSIP provides producers with estimated breeding values (EBV) for postweaning fecal egg count (PFEC), an indicator of GIN resistance. Our objective was to gauge the effects of including PFEC as another selection criterion and goal trait. Selection index theory was used to construct 11 indexes. First was a benchmark index with TW as the goal. Weaning weight, and number of lambs born and weaned, were selection criteria. An index was then designed with PFEC added as a selection criterion. In 9 more indices, PFEC was also included as a goal trait, where the economic value of TW was scaled relative to that of PFEC. PFEC received a scaled economic value of −1 with that of TW increasing from +1 to +5 at +0.5 increments. Selection criteria were modeled as EBV or phenotypes. Annual genetic responses in goal traits were predicted. The top 3% of males and 26% of females were selected. Breeding values and phenotypes were simulated for 200 lambs by Cholesky decomposition and used to generate index scores, with 100 replicates run. Concordances with the animals selected in the benchmark scenario were determined. Using EBV as the selection criteria, TW increased by 1.46 kg/yr in the benchmark scenario. However, unfavorably, PFEC increased by 2.24%/yr. When using phenotypic criteria, TW increased by 0.52 kg/yr and PFEC by 0.28%/yr. Once added as a goal trait, PFEC decreased regardless of the scaled economic value of TW. However, responses in TW were also reduced, although less so as its scaled economic value increased. A scaled economic value of +3 for TW appeared reasonable over other choices with 79% of the emphasis placed on TW in the breeding objective. With EBV as selection criteria, PFEC declined by 7.96%/yr with 98% of the response in TW retained. Also, on average, 64% of males and 80% of females were chosen in common with the benchmark. With phenotypic selection criteria, PFEC declined by 5.13%/yr and 94% of the response in TW was retained; 61% of males and 80% of females were chosen in common with the benchmark. Implementing an index with scaled economic values of +3 for TW and −1 for PFEC would balance gains in TW with reductions in PFEC.
Effects of development and parental care on Hamilton’s force of selection
Authors: Netz Christoph
Published: October 2024

The force of selection describes the sensitivity of population growth to changes in life history parameters, with a focus usually on the survival probabilities from one age class to the next. Importantly, according to Hamilton the force of selection generally decreases after the onset of reproduction, thereby providing a possible explanation for patterns of senescence. A second characteristic feature is that the force of selection remains constant up to the age of first reproduction. This latter observation, however, rests on the assumption that offspring become independent from their parents right after birth. I show here in a minimal model that if offspring are fully reliant on their parents, either during early embryonal development or via parental care at later stages, and during this time prevent their parents from entering a new bout of reproduction, the force of selection on offspring survival generally increases up until the age at which offspring become independent. This provides a possible explanation for the commonly observed pattern of decreasing mortality during early ontogeny. Furthermore, genes acting during recurrent life stages are observed to experience a heightened force of selection compared with genes that act strictly age specifically, demonstrating the need to develop a mechanistic understanding of gene activation patterns through which to consider life history evolution.
Balance of Power, System Polarity and Irredentism
Authors: Mylonas Harris
Published: October 2024

When and where are kin-states more likely to engage in militarized territorial expansion against a kin-group's state of residence, i.e., irredentism, rather than merely employing irredentist rhetoric or engaging in non-irredentist kin-state politics that focus on nurturing cultural ties with co-ethnics abroad? For example, Why did Russia pursue an irredentist policy and annex Crimea but a non-irredentist one toward Narva? Why pursue the annexation of Crimea in 2014 but not in the 1990s or the early 2000s? Various valuable domestic explanations have been proposed, including diversionary war theory, shifts in regime type, and socioeconomic changes; but none has centered on balance of power considerations. I emphasize the role of two variables, whether the kin-group’s state of residence is within or outside the core alliance network of a particular pole and the polarity of the international system at any given point in time, operationalized through the number of poles in the system (one, two, or many). I contend that kin-states are unlikely to target any state of residence that is affiliated with the core alliance network of a pole. Furthermore, I argue that variations in polarity shape the nature and location of irredentism. In a bipolar system, irredentism is likely to take the form of proxy warfare outside each bloc. In a unipolar system, irredentism is more likely in areas where the hegemon exercises the least influence—such as areas linked to a former pole. Finally, in a multipolar system, irredentism is more likely to be pursued by rising powers against neighbors not affiliated with alliance networks of a pole in the international system. I evaluate my argument using an existing dataset of both actual and potential irredentist cases from 1946 to 2014, supplemented by illustrative case studies.
Antimicrobial Resistance in Enterobacterales, Acinetobacter spp. and Pseudomonas aeruginosa Isolates From Bloodstream Infections in Australian Children, 2013–2021
Authors: Williams Anita , Coombs Geoffrey W , Bell Jan M , Daley Denise A , Mowlaboccus Shakeel , Bryant Penelope A , Campbell Anita J , Cooley Louise , Iredell Jon , Irwin Adam D , Kesson Alison , McMullan Brendan , Warner Morgyn S , Williams Phoebe C M , Blyth Christopher C
Published: October 2024

Background

Gram-negative bloodstream infections are associated with significant morbidity and mortality in children. Increasing antimicrobial resistance (AMR) is reported globally, yet efforts to track pediatric AMR at a national level over time are lacking.

Methods

The Australian Group on Antimicrobial Resistance (AGAR) surveillance program captures clinical and microbiological data of isolates detected in blood cultures across Australia. EUCAST 2022 was used for MIC interpretation and the AMR package in R for data analysis.

Results

Over a 9-year period, there were 3145 bloodstream infections with 3266 gram-negative isolates reported in hospitalized children aged <18 years; 21.0% were from neonates. The median length of stay was 9 days, and 30-day all-cause mortality was 5.2%. A greater odds of death was observed in those with a multi-drug resistant organism (aOR: 2.1, 95% CI: 1.3, 3.3, p: 0.001). Escherichia coli (44.5%) and Klebsiella pneumoniae complex (12.6%) were the two most frequently reported organisms. Overall resistance in Enterobacterales to gentamicin/tobramycin was 11.6%, to ceftazidime/ceftriaxone was 12.9%, and 13.2% to ciprofloxacin. Resistance increased over time. Of the 201 Pseudomonas aeruginosa isolates reported, 19.7% were resistant to piperacillin-tazobactam, 13.1% resistant to cefepime/ceftazidime, and 9.8% to ciprofloxacin. Of 108 Acinetobacter spp. isolates, one was resistant to meropenem, and two were resistant to ciprofloxacin. Resistance did not increase over time.

Conclusions

AMR in gram-negative organisms causing bloodstream infections in Australian children is increasing, which should be considered when updating guidelines and empiric treatment regimens. Ongoing pediatric-specific national surveillance with pediatric reporting must remain a priority to strengthen antimicrobial stewardship and infection control programs.
Detection of Ophidiomyces and Nannizziopsis spp. in the dermal lesions of free-roaming native snakes in Taiwan
Authors: Lai Wei-Yin , Yang Chun-Kai , Sun Pei-Lun , Li Wen-Ta , Liu Xuan-Rui , Chen Chiao-Wen , Yu Pin-Huan
Published: October 2024

Chrysosporium-related fungi refers to an assemblage of fungi belonging to the Nannizziopsis, Ophidiomyces, and Paranannizziopsis genera. Chrysosporium-related fungi infection results in various skin lesions, such as necrosis and ulcers, in both captive and free-roaming reptiles. To update the prevalence of ophidiomycosis in Taiwan, which was first detected in 2019, we conducted a large-scale ecological survey of free-roaming native snakes with skin lesions in Taiwan. To the best of our knowledge, this is the first study on Chrysosporium-related fungi prevalence in Southeast Asia. Fungal samples collected from the skin lesions of snakes were cultured and subjected to morphological, histopathological, and molecular analyses. We examined 2382 free-roaming snakes representing 42 snake species; among them, 132 (5.54%) had skin lesions. Ten (0.42%) snakes, representing four species, tested positive for Ophidiomyces (five snakes, four species) or a possibly novel Nannizziopsis species (five snakes, three species). The infected snakes were generally healthy, with mild clinical signs. The low prevalence rate, mild clinical signs, and broad pathogen/host range suggest that Ophidiomyces and Nannizziopsis are endemic to Southeast Asia. The newly reported presence of Nannizziopsis in free-roaming snakes suggests the need for modifying the currently used surveillance strategy.
Spatio-spectral-temporal modelling of two young pulsar wind nebulae
Authors: Kundu A , Joshi Jagdish C , Venter C , Engelbrecht N E , Zhang W , Torres Diego F , Sushch I , Tanaka Shuta J
Published: October 2024

Recent observations of a few young pulsar wind nebulae (PWNe) have revealed their morphologies in some detail. Given the availability of spatio-spectral-temporal data, we use our multi-zone (1D) leptonic emission code to model the PWNe associated with G29.7$-$0.3 (Kes 75) and G21.5$-$0.9 (G21.5), and obtain (by-eye) constraints on additional model parameters compared to spectral-only modelling. Kes 75 is a Galactic composite supernova remnant (SNR) with an embedded pulsar, PSR J1846$-$0258. X-ray studies reveal rapid expansion of Kes 75 over the past two decades. PWN G21.5 is also a composite SNR, powered by PSR J1833$-$1034. For Kes 75, we study a sudden plasma bulk speed increase that may be due to the magnetar-like outbursts of the central pulsar. An increase of a few per cent in this speed does not result in any significant change in the model outputs. For G21.5, we investigate different diffusion coefficients and pulsar spin-down braking indices. We can reproduce the broad-band spectra and X-ray surface brightness profiles for both PWNe, and the expansion rate, flux over different epochs, and X-ray photon index versus epoch and central radius for Kes 75 quite well. The latter three features are also investigated for G21.5. Despite obtaining reasonable fits overall, some discrepancies remain, pointing to further model revision. We find similar values to overlapping parameters between our 1D code and those of an independent 0D dynamical code (tide). Future work will incorporate spatial data from various energy wavebands to improve model constraints.
Characterizing the features of the low-amplitude peaks in delta Scuti stars with TESS
Authors: Barceló Forteza S , Pascual-Granado J , Suárez J C , García Hernández A , Mirouh G M , Lares-Martiz M
Published: October 2024

The presence of low-amplitude peaks over the noise in the power spectra of $\delta$ Scuti stars is frequently disregarded. These seemingly insignificant peaks, collectively referred to as grass, might contain valuable information about the origin of these stars and the reasons behind the occurrence or absence of a plateau. It is crucial to systematically parametrize the grass phenomenon throughout a comprehensive sample that covers the entire $\delta$ Scuti star parameter range. Thus, we conduct a quantitative study of long-duration, high-duty-cycle Transiting Exoplanet Survey Satellite light curves, leading to improved detection methods for plateaus and a deeper understanding of their nature. This approach minimizes the impact of unresolved peaks caused by mode variations over time. Additionally, we present appropriate analysis techniques to mitigate window effects and identify and eliminate spurious peaks. We demonstrate here that the grass can be effectively parametrized based on peak density. With such parametrization two distinct regimes are found: the sparse grass regime, characterized by low peak density and the absence of a plateau in the power spectra, and the dense grass regime, characterized by high peak densities and the presence of an observable plateau. Our study is the first rigorous quantification of the emergence of such a plateau in the power spectra of $\delta$ Scuti stars. Since the grass might be related with fractality, mode variability, and stellar rotation rate, its parametrization opens a new way to analyse these stars.
Joining the dots: high redshift black holes
Authors: King Andrew
Published: October 2024

A recent paper suggested that emission from the central supermassive black holes in high-redshift galaxies must be tightly collimated by the effects of partly expelling a super-Eddington mass supply. I show here that this idea predicts that these galaxies should produce very little detectable rest-frame X-ray emission, appear Compton thick, and show no easily detectable sign of outflows. All of these properties agree with current observations. To produce these effects, the mass supply to the black holes should exceed the Eddington rate by factors ${\sim} 50{\!-\!}100$, which appears in line with conditions during the early growth of the holes. I note that theoretical derivations of the ratio of black hole mass to host galaxy stellar mass already predict that this should increase significantly at high redshift, in line with recent observations.
ZNF512B binds RBBP4 via a variant NuRD interaction motif and aggregates chromatin in a NuRD complex-independent manner
Authors: Wunderlich Tim Marius , Deshpande Chandrika , Paasche Lena W , Friedrich Tobias , Diegmüller Felix , Haddad Elias , Kreienbaum Carlotta , Naseer Haniya , Stebel Sophie E , Daus Nadine , Leers Jörg , Lan Jie , Trinh Van Tuan , Vázquez Olalla , Butter Falk , Bartkuhn Marek , Mackay Joel P , Hake Sandra B
Published: October 2024

The evolutionarily conserved histone variant H2A.Z plays a crucial role in various DNA-based processes, but the mechanisms underlying its activity are not completely understood. Recently, we identified the zinc finger (ZF) protein ZNF512B as a protein associated with H2A.Z, HMG20A and PWWP2A. Here, we report that high levels of ZNF512B expression lead to nuclear protein and chromatin aggregation foci that form in a manner that is dependent on the ZF domains of ZNF512B. Notably, we demonstrate ZNF512B binding to the nucleosome remodeling and deacetylase (NuRD) complex. We discover a conserved amino acid sequence within ZNF512B that resembles the NuRD-interaction motif (NIM) previously identified in FOG-1 and other transcriptional regulators. By solving the crystal structure of this motif bound to the NuRD component RBBP4 and by applying several biochemical and biophysical assays, we demonstrate that this internal NIM is both necessary and sufficient for robust and high-affinity NuRD binding. Transcriptome analyses and reporter assays identify ZNF512B as a repressor of gene expression that can act in both NuRD-dependent and -independent ways. Our study might have implications for diseases in which ZNF512B expression is deregulated, such as cancer and neurodegenerative diseases, and hints at the existence of more proteins as potential NuRD interactors.
PIPdb: a comprehensive plasmid sequence resource for tracking the horizontal transfer of pathogenic factors and antimicrobial resistance genes
Authors: Zhu Qianhui , Chen Qi , Gao Shenghan , Li Zhenpeng , Zhou Haijian , Cui Zhigang , Fan Guomei , Liu Xiao , Wu Xinmiao , Ma Juncai , Kan Biao , Hu Songnian , Wu Linhuan , Lu Xin
Published: October 2024

Plasmids, as independent genetic elements, carrying resistance or virulence genes and transfer them among different pathogens, posing a significant threat to human health. Under the ‘One Health’ approach, it is crucial to control the spread of plasmids carrying such genes. To achieve this, a comprehensive characterization of plasmids in pathogens is essential. Here we present the Plasmids in Pathogens Database (PIPdb), a pioneering resource that includes 792 964 plasmid segment clusters (PSCs) derived from 1 009 571 assembled genomes across 450 pathogenic species from 110 genera. To our knowledge, PIPdb is the first database specifically dedicated to plasmids in pathogenic bacteria, offering detailed multi-dimensional metadata such as collection date, geographical origin, ecosystem, host taxonomy, and habitat. PIPdb also provides extensive functional annotations, including plasmid type, insertion sequences, integron, oriT, relaxase, T4CP, virulence factors genes, heavy metal resistance genes and antibiotic resistance genes. The database features a user-friendly interface that facilitates studies on plasmids across diverse host taxa, habitats, and ecosystems, with a focus on those carrying antimicrobial resistance genes (ARGs). We have integrated online tools for plasmid identification and annotation from assembled genomes. Additionally, PIPdb includes a risk-scoring system for identifying potentially high-risk plasmids. The PIPdb web interface is accessible at https://nmdc.cn/pipdb.
The UCSC Genome Browser database: 2025 update
Authors: Perez Gerardo , Barber Galt P , Benet-Pages Anna , Casper Jonathan , Clawson Hiram , Diekhans Mark , Fischer Clay , Gonzalez Jairo Navarro , Hinrichs Angie S , Lee Christopher M , Nassar Luis R , Raney Brian J , Speir Matthew L , van Baren Marijke J , Vaske Charles J , Haussler David , Kent W James , Haeussler Maximilian
Published: October 2024

The UCSC Genome Browser (https://genome.ucsc.edu) is a widely utilized web-based tool for visualization and analysis of genomic data, encompassing over 4000 assemblies from diverse organisms. Since its release in 2001, it has become an essential resource for genomics and bioinformatics research. Annotation data available on Genome Browser includes both internally created and maintained tracks as well as custom tracks and track hubs provided by the research community. This last year's updates include over 25 new annotation tracks such as the gnomAD 4.1 track on the human GRCh38/hg38 assembly, the addition of three new public hubs, and significant expansions to the Genome Archive[GenArk) system for interacting with the enormous variety of assemblies. We have also made improvements to our interface, including updates to the browser graphic page, such as a new popup dialog feature that now displays item details without requiring navigation away from the main Genome Browser page. GenePred tracks have been upgraded with right-click options for zooming and precise navigation, along with enhanced mouseOver functions. Additional improvements include a new grouping feature for track hubs and hub description info links. A new tutorial focusing on Clinical Genetics has also been added to the UCSC Genome Browser.
Out-of-pocket costs for patients diagnosed with high-grade glioma and their carers
Authors: Newton Jade C , Halkett Georgia K B , Wright Cameron , O.’Connor Moira , Nowak Anna K , Moorin Rachael
Published: October 2024

Background

This study aimed to describe the out-of-pocket costs incurred by patients diagnosed with high-grade glioma (HGG) and their carers in the standard care arm of the Care-IS trial in the 6 to 8 months following their diagnosis.

Methods

Carers completed monthly cost surveys detailing the out-of-pocket costs incurred by patients and carers over a 6-month period. Seventy carers reported out-of-pocket costs at baseline (within 2 months following patient diagnosis), and a maximum of 50% of participants reported costs in any subsequent month. Costs were adjusted to 2023 AUD and reported as medians with an interquartile range. Demographic factors were assessed to determine if any were significantly associated with being in the first or fourth quartile of total out-of-pocket costs at baseline.

Results

Median monthly costs for patient-carer dyads were highest at baseline ($535[IQR:$170–$930]), and 2 months post-recruitment ($314 [IQR:$150–$772]). The largest contributors to patient-carer costs were patient health service use and patient medications. Patient and carer health service use and medication costs varied over time. The median health service use and medication out-of-pocket costs for patients and carers were mostly below $100 per month; however, there was a large variance in the upper 75th percentile for these cost categories. No factors were significantly associated with higher baseline out-of-pocket costs.

Conclusions

A HGG diagnosis has a significant and sustained financial impact on people who are diagnosed and their carers. Patients experience significant additional costs relating to their diagnosis and travel to receive care, and their carers also continue to experience sustained costs whilst managing the additional tasks associated with informal caregiving.
Noted, but not decisive. A cross-disciplinary analysis of metrics usage in Polish evaluative cultures
Authors: Remisiewicz Łukasz
Published: October 2024

Metrics-based reasoning patterns diffuse from core to periphery as peripheral and semi-peripheral countries adopt Western evaluation standards as formal categories or cultural scripts. While these scripts are applied across disciplines, each field maintains its own traditional criteria for scientific assessment. Consequently, scholars navigate between internalized and externally imposed evaluative frameworks when writing reviews. This study examines how metrics-based reasoning diffuses differently across disciplines through evaluative practices, with metrics being transformed and interpreted within the context of each field's unique evaluative culture. To compare diffusion patterns, this article analyzes 174 negative habilitation reviews across four Polish disciplines: art history, mathematics, materials engineering, and sociology. Despite uniform policy incentives, reviewers employed diverse criteria when assessing publication records. Materials engineering exhibited the most extensive use and emphasis on metrics, while art history relied minimally on indicators. Crucially, metrics were never the sole basis for negative conclusions but were consistently accompanied by additional forms of reasoning.
Designing Pension Plans According to Consumption-Savings Theory
Authors: Schlafmann Kathrin , Setty Ofer , Vestman Roine
Published: October 2024

We derive optimal characteristics of contribution rates into defined contribution pension plans based on consumption-savings theory. Contribution rates should increase with age and decrease with the balance-to-income ratio. Using Swedish registry data, we show that on average, individuals save according to those principles. However, almost half of the population behaves hand-to-mouth and does not undo the mandated constant contribution rates. In a quantitative model, designing contribution rates to follow the principles implies a 1.8% welfare gain and less dispersed replacement rates, while maintaining the same average replacement rate. Results are robust to various sources of model misspecification, including temptation preferences.
Impressions about harm are formed rapidly and then refined, modulated by serotonin
Authors: Moutoussis Michael , Barnby Joe , Durand Anais , Croal Megan , Dilley Laura , Rutledge Robb B , Mason Liam
Published: October 2024

Attributing motives to others is a crucial aspect of mentalizing, can be biased by prejudice, and is affected by common psychiatric disorders. It is therefore important to understand in depth the mechanisms underpinning it. Toward improving models of mentalizing motives, we hypothesized that people quickly infer whether other’s motives are likely beneficial or detrimental, then refine their judgment (classify-refine). To test this, we used a modified Dictator game, a game theoretic task, where participants judged the likelihood of intent to harm vs. self-interest in economic decisions. Toward testing the role of serotonin in judgments of intent to harm, we delivered the task in a week-long, placebo vs. citalopram study. Computational model comparison provided clear evidence for the superiority of classify-refine models over traditional ones, strongly supporting the central hypothesis. Further, while citalopram helped refine attributions about motives through learning, it did not induce more positive initial inferences about others’ motives. Finally, model comparison indicated a minimal role for racial bias within economic decisions for the large majority of our sample. Overall, these results support a proposal that classify-refine social cognition is adaptive, although relevant mechanisms of serotonergic antidepressant action will need to be studied over longer time spans.
High-throughput solutions in tumor organoids: from culture to drug screening
Authors: Zuo Jianing , Fang Yanhua , Wang Ruoyu , Liang Shanshan
Published: October 2024

Tumor organoids have emerged as an ideal in vitro model for patient-derived tissues, as they recapitulate the characteristics of the source tumor tissue to a certain extent, offering the potential for personalized tumor therapy and demonstrating significant promise in pharmaceutical research and development. However, establishing and applying this model involves multiple labor-intensive and time-consuming experimental steps and lacks standardized protocols and uniform identification criteria. Thus, high-throughput solutions are essential for the widespread adoption of tumor organoid models. This review provides a comprehensive overview of current high-throughput solutions across the entire workflow of tumor organoids, from sampling and culture to drug screening. Furthermore, we explore various technologies that can control and optimize single-cell preparation, organoid culture, and drug screening with the ultimate goal of ensuring the automation and high efficiency of the culture system and identifying more effective tumor therapeutics.
Assessing pesticide residue levels in sweetpotato roots and slips treated with fungicides for management of southern blight and circular spot disease caused by Agroathelia rolfsii
Authors: Mascarenhas Jack Mecklin , Collins Hunter , Ahmed Khalied , Gannon Travis W. , Almeyda Christie Vanessa , Thiessen Lindsey , Huseth Anders , Quesada-Ocampo Lina
Published: October 2024

Since 1971, North Carolina (NC) has been the leading sweetpotato-producing state in the United States (US) and is now producing more than half of the nation’s annual output. Due to the high demand for US sweetpotatoes from international markets, NC allocates roughly 40% of its sweetpotatoes for export. However, low fungicide residue limits in primary export markets restricts the ability for NC producers to apply fungicides for disease management during sweetpotato production. Agroathelia rolfsii, the causal agent of southern blight and circular spot, is an important pathogen of sweetpotato. Field experiments were conducted in 2022 and 2023 to quantify the residue amount of various active ingredients and transplant-only vs. bedding and transplant applications when managing A. rolfsii in the field. High-performance liquid chromatography analyses of root and vine samples confirmed that none of the tested active ingredients and application timings resulted in residue numbers exceeding the limits of export markets, except for roots treated with thiabendazole. Results from this study provide information for development of application practices with acceptable residue levels for export markets while effectively managing diseases caused by A. rolfsii.
Propiconazole resistance phenotypes in Geotrichum candidum from South Carolina peaches are linked to point mutations in GcCYP51B gene
Authors: Gelain Jhulia , Zhao Bingyu , Price Sara , Kaur Harleen , Blank Antonia , Zhezheng Zeng , Luo Chaoxi , Schnabel Guido
Published: October 2024

Geotrichum candidum Link (1809) is a yeast-like fungus that causes sour rot of peach (Prunus persica). Outbreaks of the disease have occurred since 2021 in peach fruit kept in cold storage despite post-harvest treatments with propiconazole at a commercial farm in South Carolina (SC). A total of 58 isolates, 40 from symptomatic fruit from cold storage in Saluda County (SC packing house isolates), 11 from three SC orchards in Saluda County, Spartanburg County, and Pickens County (SC non-packing house isolates), and 7 California (CA) isolates (at least 3 from packing houses) were evaluated for propiconazole sensitivity. Mycelial growth assays revealed that 6 of 7 CA isolates had the lowest EC50 values and were considered sensitive (S) to propiconazole with an average EC50 value of 0.02 µg/ml and minimum inhibitory concentration (MIC) values >1 to < 3 µg/ml. Isolate 02J018 from CA and all SC non packing house isolates were considered reduced-sensitive (RS) to propiconazole with an average EC50 value of 0.33 µg/ml and MIC values >10 to <30 µg/ml. SC packing house isolates were considered resistant (R) to propiconazole and had an average EC50 value of 3.55 µg/ml and MIC values >300 µg/ml. Two CYP51 genes, GcCYP51A and GcCYP51B, encoding two demethylase inhibitor (DMI) target enzyme 14α-demethylases were identified, sequenced, and characterized. Two GcCYP51A and three GcCYP51B variants were found. While both GcCYP51A variants were linked to S isolates, the GcCYP51B2 variant possessing the mutation Y143F was found in RS, and the GcCYP51B3 variant possessing Y143F, E126K, and G460S mutations was identified in R isolates. The Y143F and G460S mutations had been associated with DMI fungicide resistance in other plant pathogens. No increased constitutive expression of GcCYP51A or GcCYP51B was observed in RS or R isolates. Detached fruit assays revealed that label rates of propiconazole controlled sour rot caused by S and RS but not R isolates. Our results suggest that sour rot outbreaks in a SC packing house were linked to target gene-induced propiconazole resistance in G. candidum.
Motor, mood, and memory impairments persist during remission periods in chronic colitis and are influenced by neuroinflammation and sex
Authors: Sotelo‐Parrilla Gema , Ruiz‐Calero Alejandro , García‐Miranda Pablo , Calonge María L. , Vázquez‐Carretero María D. , Peral María J.
Published: October 2024

Ulcerative colitis is a chronic pathology characterized by relapsing–remitting phases of intestinal inflammation. Additionally, some patients develop neuropsychiatric disorders, such as depression and anxiety, or cognitive deficits. We aimed to investigate whether the development of chronic colitis elicits memory, locomotion, and mood impairments. It further examined whether these impairments are influenced by the relapsing–remitting phases of the colitis or by sex. Here, we used a chronic colitis model in male and female rats, induced with sodium dextran sulfate, mirroring the phases of human ulcerative colitis. Our results revealed that the severity of colitis was slightly higher in males than females. Chronic colitis triggered motor and short‐term memory deficits and induced anxiety‐ and depression‐like behaviors that remained throughout the development of the disease. There are also sex differences under control or inflammatory conditions. Therefore, in both situations, females compared to males displayed: (i) slightly lower locomotion, (ii) increased anxiety‐like behaviors, (iii) similar depression‐like behaviors, and (iv) similar short‐term memory deficit. Additionally, under control conditions, the mRNA levels of IL‐1β, IL‐6, and TNF‐α were higher in the female hippocampus. In both sexes, when chronic colitis was established, the neuroinflammation was evidenced by increased mRNA levels of these three cytokines in the hippocampus and in the motor and prefrontal cortices. Interestingly, this neuroinflammation was slightly greater in males. In summary, we show that the development of chronic colitis caused persistent behavioral abnormalities, highlighting sex differences, and that could be a consequence, at least in part, of the increase in IL‐1β, IL‐6, and TNF‐α in the brain.
VENO-VENOUS EXTRACORPOREAL MEMBRANE OXYGENATION IMPROVES OUTCOMES IN TRAUMA PATIENTS SUFFERING RESPIRATORY FAILURE
Authors: Powell Elizabeth K. , Betzold Richard , Lammers Daniel T. , Podell Jamie , Wan Ryan , Teeter William , Hardin Ronald D. , Scalea Thomas M. , Galvagno Samuel M
Published: October 2024

Introduction: Veno-venous extracorporeal membrane oxygenation (VV ECMO) improves hypoxemia and carbon dioxide clearance in patients with severe respiratory derangements. A greater understanding of the potential benefits of VV ECMO in trauma patients could lead to broader adoption. We hypothesize that trauma patients who receive VV ECMO have improved mortality outcomes when compared to those receiving conventional ventilator management given the rapid stabilization VV ECMO promotes. Methods: We performed a single-center, propensity score-matched cohort study. All trauma patients from January 1, 2014, to October 30, 2023, who were placed on VV ECMO or who would have met institutional guidelines for VV ECMO but were managed with conventional ventilator strategies were matched 1:1. The primary outcome analysis was survival at hospital discharge. Significance was defined as P < 0.05. Results: Eighty-one trauma VV ECMO patients and 128 patients who received conventional management met criteria for inclusion. After matching, VV ECMO and conventional treatment cohort characteristics were similar in age and mechanism of injury. Matched ISS, SI, lactate levels, and frequency of traumatically brain injured were also similar. Finally, respiratory parameters including preintervention, pH, partial pressure of carbon dioxide, lactate levels, and oxygen saturation were similar between matched groups. VV ECMO patients had higher survival rates at discharge when compared to the matched conventional treatment group (70% vs. 41%, P < 0.001). Corresponding hazard ratio for VV ECMO use was 0.31 (95% CI 0.18–0.52; P < 0.001). The odds ratio of mortality in matched trauma patients who receive VV ECMO versus conventional treatment was 0.29 (95% CI 0.14–0.58; P < 0.001). Conclusion: VV ECMO may represent a safe, alternative treatment approach for appropriately screened trauma patients with acute respiratory failure; however, further studies are warranted.
SLB-msSIM: a spectral library-based multiplex segmented SIM platform for single-cell proteomic analysis
Authors: Senavirathna Lakmini , Ma Cheng , Duong Van-An , Tsai Hong-Yuan , Chen Ru , Pan Sheng
Published: October 2024

Mass spectrometry (MS)-based single-cell proteomics, while highly challenging, offers unique potential for a wide range of applications to interrogate cellular heterogeneity, trajectories, and phenotypes at a functional level. We report here the development of the spectral library-based multiplex segmented selected ion monitoring (SLB-msSIM) method, a conceptually unique approach with significantly enhanced sensitivity and robustness for single-cell analysis. The single-cell MS data is acquired by msSIM technique, which sequentially applies multiple isolation cycles with the quadrupole using a wide isolation window in each cycle to accumulate and store precursor ions in the C-trap for a single scan in the Orbitrap. Proteomic identification is achieved through spectral matching using a well-defined spectral library. We applied the SLB-msSIM method to interrogate cellular heterogeneity among multiple cell lines and to analyze cellular trajectories during epithelial-mesenchymal transition. Our results demonstrate that SLB-msSIM is a highly sensitive and robust platform applicable to a wide range of single-cell proteomic studies.