bluuebunny/crossref_metadata_2025 huggingface dataset:
Real-World Continuous EEG Utilization and Outcomes in Hospitalized Patients With Acute Cerebrovascular Diseases
Authors: Amerineni Rajesh , Sun Haoqi , Fernandes Marta Bento , Westover M. Brandon , Moura Lidia , Patorno Elisabetta , Hsu John , Zafar Sahar F.
Published: November 2023

Purpose:

Continuous electroencephalography (cEEG) is recommended for hospitalized patients with cerebrovascular diseases and suspected seizures or unexplained neurologic decline. We sought to (1) identify areas of practice variation in cEEG utilization, (2) determine predictors of cEEG utilization, (3) evaluate whether cEEG utilization is associated with outcomes in patients with cerebrovascular diseases.

Methods:

This cohort study of the Premier Healthcare Database (2014–2020), included hospitalized patients age >18 years with cerebrovascular diseases (identified by ICD codes). Continuous electroencephalography was identified by International Classification of Diseases (ICD)/Current Procedural Terminology (CPT) codes. Multivariable lasso logistic regression was used to identify predictors of cEEG utilization and in-hospital mortality. Propensity score-matched analysis was performed to determine the relation between cEEG use and mortality.

Results:

1,179,471 admissions were included; 16,777 (1.4%) underwent cEEG. Total number of cEEGs increased by 364% over 5 years (average 32%/year). On multivariable analysis, top five predictors of cEEG use included seizure diagnosis, hospitals with >500 beds, regions Northeast and South, and anesthetic use. Top predictors of mortality included use of mechanical ventilation, vasopressors, anesthetics, antiseizure medications, and age. Propensity analysis showed that cEEG was associated with lower in-hospital mortality (Average Treatment Effect −0.015 [95% confidence interval −0.028 to −0.003], Odds ratio 0.746 [95% confidence interval, 0.618–0.900]).

Conclusions:

There has been a national increase in cEEG utilization for hospitalized patients with cerebrovascular diseases, with practice variation. cEEG utilization was associated with lower in-hospital mortality. Larger comparative studies of cEEG-guided treatments are indicated to inform best practices, guide policy changes for increased access, and create guidelines on triaging and transferring patients to centers with cEEG capability.
Recombinant human erythropoietin protects against immature brain damage induced by hypoxic/ischemia insult
Authors: Sun Zhengda , Song Jiqing , Song Qijun , Li Lin , Tian Xinxin , Wang Lijun
Published: November 2023

To investigate the neuroprotection of recombinant human erythropoietin (rhEPO) against hypoxic/ischemic (HI) insult in three-day-old rats. Postnatal day 3 (PD3) rats were randomly divided into three groups: Sham group, HI group and HI+rhEPO group. Ligation of the right common carotid artery and hypoxia to induce HI brain injury. After HI insult, the rats received intraperitoneal injection of rhEPO (5000 IU/Kg, qod) in HI+rhEPO group or equal saline in other groups. On PD10, damage of brain tissue was examined by hematoxylin-eosin (HE) staining, observation of neuronal apoptosis in the hippocampus and cortex using immunofluorescence assay (marker: TUNEL). Immunohistochemical staining or western blotting was performed to detect the expression of cyclooxygenase-2 (COX-2), Caspase-3 and phosphorylated Akt (p-Akt) protein. On PD28, cognitive ability of rats was assessed by Morris water maze test. HI injury causes brain pathological morphology and cognitive function damage in PD3 rats, which can be alleviated by rhEPO intervention. Compared with the HI group, the HI+rhEPO group showed an increase in platform discovery rate and cross platform frequency, while the search platform time was shortened (P < 0.05). The proportion of TUNEL positive neurons and the expression of COX-2 and Caspase-3 proteins in brain tissue in the hippocampus and cortex was decreased, while the expression of p-Akt protein was upregulated (P < 0.05). RhEPO could protect against the pathological and cognitive impairment of immature brain induced by HI insult. This neuroprotective activity may involve in inhibiting inflammatory and apoptosis by activation of PI3K/Akt signaling pathway.
Inhibition of the TLR4/NF-κB pathway promotes the polarization of LPS-induced BV2 microglia toward the M2 phenotype
Authors: Xie Jiehong , Tuo Peng , Zhang Wei , Wang Shouping
Published: November 2023

This study aimed to investigate whether the inhibition of the TLR4/NF-κB pathway can promote lipopolysaccharide (LPS)-induced microglial polarization from the M1 to M2 phenotype, and thus exert neuroprotection. LPS-induced microglia were used as a model for inflammation in vitro. TLR4-specific inhibitor resatorvid (TAK-242) and NF-κB inhibitor pyrrolidine dithiocarbamate (PDTC) were used to verify the effect of the TLR4/NF-κB pathway on microglia activation and polarization. Cell proliferation was measured by cell counting, and nitric oxide (NO) and reactive oxygen species (ROS) release was measured using the Griess reagent and ROS kit, respectively. Immunofluorescence and RT-qPCR analyses were used to detect the expression of microglial activation markers, phenotypic markers, related pathway molecules, and inflammatory factors. TLR4 specific inhibitor TAK-242 and NF-κB inhibitor PDTC alleviated LPS-induced microglia over-activation by inhibiting the TLR4/NF-κB pathway, and reduced LPS-stimulated cell proliferation and the release of NO, ROS, TNF-a, and IL-6 and IL-1β. Meanwhile, TAK-242 and PDTC promoted LPS-induced polarization of microglia from M1 to M2 phenotype, decreased the expression of microglial activation marker Iba1 and M1 phenotypic markers (TNF-a and CD86), and increased the expression of M2 phenotypic markers (Arg-1 and CD206). The mechanism may be related to inhibiting the TLR4/NF-κB pathway. The inhibition of the TLR4/NF-κB pathway can promote LPS-induced polarization of BV2 microglia from M1 phenotype to M2 phenotype.
Differential modulation of innate immune response by lipopolysaccharide of
Leptospira
Authors: Varma Vivek P. , Bankala Ramudu , Kumar Ajay , Gawai Shashikant , Faisal Syed M.
Published: November 2023

Leptospirosis is a worldwide zoonosis caused by pathogenic
Leptospira
spp. having more than 300 serovars. These serovars can infect a variety of hosts, some being asymptomatic carriers and others showing varied symptoms of mild to severe infection. Since lipopolysaccharide (LPS) is the major antigen which defines serovar specificity, this different course of infection may be attributed to a differential innate response against this antigen. Previous studies have shown that
Leptospira
LPS is less endotoxic. However, it is unclear whether there is a difference in the ability of LPS isolated from different serovars to modulate the innate response. In this study, we purified LPS from three widely prevalent pathogenic serovars, i.e. Icterohaemorrhagiae strain RGA, Pomona, Hardjo, and from non-pathogenic
L. biflexa
serovar semeranga strain Potac 1 collectively termed as L-LPS and tested their ability to modulate innate response in macrophages from both resistant (mice) and susceptible (human and bovine) hosts. L-LPS induced differential response being more proinflammatory in mouse and less proinflammatory in human and bovine macrophages but overall less immunostimulatory than
E. coli
LPS (E-LPS). Irrespective of serovar, this response was TLR2-dependent in humans, whereas TLR4-dependent/CD14-independent in mouse using MyD88 adapter and signalling through P38 and ERK-dependent MAP kinase pathway. L-LPS-activated macrophages were able to phagocytose
Leptospira
and this effect was significantly higher or more pronounced when the macrophages were stimulated with L-LPS from the corresponding serovar. L-LPS activated both canonical and non-canonical inflammasome, producing IL-1β without inducing pyroptosis. Further, L-LPS induced both TNF-mediated early and NO-mediated late apoptosis. Altogether, these results indicate that L-LPS induces a differential innate response that is quite distinct from that induced by E-LPS and may be attributed to the structural differences and its atypical nature.
Structure and molecular basis of spermatid elongation in theDrosophilatestis
Authors: Huang Qiuru , Chen Xia , Yu Hao , Ji Li , Shi Yi , Cheng Xinmeng , Chen Hao , Yu Jun
Published: November 2023

Spermatid elongation is a crucial event in the late stage of spermatogenesis in theDrosophilatestis, eventually leading to the formation of mature sperm after meiosis. During spermatogenesis, significant structural and morphological changes take place in a cluster of post-meiotic germ cells, which are enclosed in a microenvironment surrounded by somatic cyst cells. Microtubule-based axoneme assembly, formation of individualization complexes and mitochondria maintenance are key processes involved in the differentiation of elongated spermatids. They provide important structural foundations for accessing male fertility. How these structures are constructed and maintained are basic questions in theDrosophilatestis. Although the roles of several genes in different structures during the development of elongated spermatids have been elucidated, the relationships between them have not been widely studied. In addition, the genetic basis of spermatid elongation and the regulatory mechanisms involved have not been thoroughly investigated. In the present review, we focus on current knowledge with regard to spermatid axoneme assembly, individualization complex and mitochondria maintenance. We also touch upon promising directions for future research to unravel the underlying mechanisms of spermatid elongation in theDrosophilatestis.
Multi-epitope vaccine candidates based on mycobacterial membrane protein large (MmpL) proteins against
Mycobacterium ulcerans
Authors: Ishwarlall Tamara Z. , Adeleke Victoria T. , Maharaj Leah , Okpeku Moses , Adeniyi Adebayo A. , Adeleke Matthew A.
Published: November 2023

Buruli ulcer (BU) is a neglected tropical disease. It is caused by the bacterium
Mycobacterium ulcerans
and is characterized by skin lesions. Several studies were performed testing the Bacillus Calmette-Guérin (BCG) vaccine in human and animal models and
M. ulcerans-
specific vaccines in animal models. However, there are currently no clinically accepted vaccines to prevent
M. ulcerans
infection. The aim of this study was to identify T-cell and B-cell epitopes from the mycobacterial membrane protein large (MmpL) proteins of
M. ulcerans.
These epitopes were analysed for properties including antigenicity, immunogenicity, non-allergenicity, non-toxicity, population coverage and the potential to induce cytokines. The final 8 CD8
+
, 12 CD4
+
T-cell and 5 B-cell epitopes were antigenic, non-allergenic and non-toxic. The estimated global population coverage of the CD8
+
and CD4
+
epitopes was 97.71%. These epitopes were used to construct five multi-epitope vaccine constructs with different adjuvants and linker combinations. The constructs underwent further structural analyses and refinement. The constructs were then docked with Toll-like receptors. Three of the successfully docked complexes were structurally analysed. Two of the docked complexes successfully underwent molecular dynamics simulations (MDS) and post-MDS analysis. The complexes generated were found to be stable. However, experimental validation of the complexes is required.
Can fish species co-occurrence patterns be predicted by their trait dissimilarities?
Authors: Cordero Ruben D. , Jackson Donald A.
Published: November 2023

Trait-based analyses have been successful in determining and predicting species association outcomes in diverse communities. Most studies have limited the scope of this approach to the biotic responses of a small number of species or geographical regions. We focused on determining whether three biologically relevant traits (body size, temperature preference and trophic level) influence the patterns of co-occurrence between multiple species. We used fish species presence/absence from 9
204
lakes in Ontario, Canada, to obtain effect sizes of 2001 species-pair co-occurrence values, using a null model approach. Euclidean distances between each species-pair were calculated for each of the three traits selected. Multiple regression models and randomization tests were used to determine the direction and significance of the relationship of each trait with the observed co-occurrence values. The results show that species temperature preference was significantly related to co-occurrence patterns, indicating the effect of environmental filtering. Trophic level was significantly related to co-occurrence values for both linear and quadratic terms, suggesting that segregation between species is driven by large differences in this trait (predation effects). Unexpectedly, body size was not significantly related to the observed co-occurrence patterns. We provide a new approach to test relationships between species assemblages and trait conditions.
Botanical memory: five centuries of floristic changes revealed by a Renaissance herbarium (Ulisse Aldrovandi, 1551–1586)
Authors: Buldrini Fabrizio , Alessandrini Alessandro , Mossetti Umberto , Muzzi Enrico , Pezzi Giovanna , Soldano Adriano , Nascimbene Juri
Published: November 2023

We analysed the spatially explicit floristic information available in the herbarium of Ulisse Aldrovandi (1551–1586) to track floristic changes in the surroundings of Bologna across five centuries. Aldrovandi's data were compared with the
Flora della Provincia di Bologna
by Girolamo Cocconi (1883) and the Floristic Database of Emilia-Romagna (1965–2021). We explored potential variations in native range and life forms composition, and habitat affinity of the species in the three floras, also contrasting between native and alien species. Native species, mainly in terms of variations of hydro-hygrophytes, chamaephytes and therophytes, provide clear signals of human disturbance and habitat loss. Signals of climate change are provided by the high-mountain species, that were comparably rare between Aldrovandi and current flora and more represented in Cocconi, probably reflecting the effect of the Little Ice Age. Our findings also indicate the increasing importance of alien species from the Renaissance onwards. In this perspective, Aldrovandi's herbarium preserves the memory of the first signs of a radical transformation of the European flora and habitats. Finally, the study warns about the risk of dismissing herbaria and herbarium specimens collection, which would cause irreparable lacunas in our botanical memory, hindering our ability to predict biodiversity trajectories.
Detection of antimicrobial-resistant Enterobacterales in insectivorous bats from Chile
Authors: Rojas-Sereno Zulma Esperanza , Streicker Daniel G. , Suarez-Yana Tania , Lineros Michelle , Yung Verónica , Godreuil Sylvain , Benavides Julio A.
Published: November 2023

Enterobacterales of clinical importance for humans and domestic animals are now commonly detected among wildlife worldwide. However, few studies have investigated their prevalence among bats, particularly in bat species living near humans. In this study, we assessed the occurrence of Extended-spectrum beta-lactamase-producing (ESBL) and carbapenemase-resistant (CR) Enterobacterales in rectal swabs of bats submitted to the Chilean national rabies surveillance program from 2021 to 2022. From the 307 swabs screened, 47 (15%) harboured cefotaxime-resistant Enterobacterales. Bats carrying these bacteria originated from 9 out of the 14 Chilean regions. Most positive samples were obtained from
Tadarida brasiliensis
(
n
= 42), but also
Lasiurus varius
,
L. cinereus
and
Histiotus macrotus
. No Enterobacterales were resistant to imipenem. All ESBL-Enterobacterales were confirmed as
Rahnella aquatilis
by MALDI-TOF. No other ESBL or CR Enterobacterales were detected. To our knowledge, this is the first screening of antibiotic-resistant bacteria in wild bats of Chile, showing the bat faecal carriage of
R. aquatilis
naturally resistant to cephalosporins, but also including acquired resistance to important antibiotics for public health such as amoxicillin with clavulanic acid. Our results suggest unknown selective pressures on
R. aquatilis
, but low or no carriage of ESBL or CR
Escherichia coli
and
Klebsiella
spp. Future studies should assess the zoonotic and environmental implications of
R. aquatilis
, which are likely present in the guano left by bats roosting in human infrastructures.
Intraspecific interference retards growth and development of cane toad tadpoles, but those effects disappear by the time of metamorphosis
Authors: Crossland M. R. , Shine R.
Published: November 2023

Competition among larval anurans can occur via interference as well as via a reduction in per-capita food supply. Previous research on intraspecific interference competition in cane toad (
Rhinella marina
) tadpoles found conflicting results, with one study detecting strong effects on tadpoles and another detecting no effects on metamorphs. A capacity to recover from competitive suppression by the time of metamorphosis might explain those contrasting impacts. In a laboratory experiment, we found that nine days of exposure to intraspecific interference competition strongly reduced tadpole growth and development, especially when the competing tadpoles were young (early-stage) individuals. Those competitive effects disappeared by the time of metamorphosis, with no significant effect of competition on metamorph body condition, size, larval period or survival. Temporal changes in the impact of competition were not related to tadpole density or to variation in water quality. The ability of larval cane toads to recover from intraspecific interference competition may enhance the invasive success of this species, because size at metamorphosis is a significant predictor of future fitness. Our study also demonstrates a cautionary tale: conclusions about the existence and strength of competitive interactions among anuran larvae may depend on which developmental stages are measured.
Long-term female bias in sex ratios across life stages of Harpy Eagle, a large raptor exhibiting reverse sexual size dimorphism
Authors: Banhos Aureo , Sanaiotti Tânia Margarete , Coser Renan , Gravena Waleska , Aguiar-Silva Francisca Helena , Kaizer Mylena , Hrbek Tomas , Farias Izeni Pires
Published: November 2023

The primary (PSR), secondary (SSR) and adult (ASR) sex ratios of sexually reproducing organisms influence their life histories. Species exhibiting reversed sexual size dimorphism (RSD) may imply a higher cost of female production or lower female survival, thus generating biases in PSR, SSR and/or ASR towards males. The Harpy Eagle is the world's largest eagle exhibiting RSD. This species is found in the Neotropical region and is currently threatened with extinction. We used molecular markers to determine the sex of 309 Harpy Eagles spanning different life stages—eaglets, subadults and adults—from 1904 to 2021 within the Amazon Rainforest and Atlantic Forest. Sex ratios for all life stages revealed a female-biased deviation across all periods and regions. Our results suggest that the population bias towards females is an evolutionary ecological pattern of this species, and SSR and ASR likely emerged from the PSR. This natural bias towards females may be compensated by an earlier sexual maturation age of males, implying a longer reproductive lifespan and a higher proportion of sexually active males. A better understanding of the Harpy Eagle's life history can contribute to understanding sex-role evolution and enable more appropriate conservation strategies for the species.
Increasing ambient temperatures trigger shifts in activity patterns and temporal partitioning in a large carnivore guild
Authors: Rafiq Kasim , Jordan Neil R. , Golabek Krystyna , McNutt John W. , Wilson Alan , Abrahms Briana
Published: November 2023

Shifts in species’ interactions are implicated as an important proximate cause underpinning climate-change-related extinction. However, there is little empirical evidence on the pathways through which climate conditions, such as ambient temperature, impact community dynamics. The timing of activities is a widespread behavioural adaptation to environmental variability, and temporal partitioning is a key mechanism that facilitates coexistence, especially within large carnivore communities. We investigated temperature impacts on community dynamics through its influence on the diel activity of, and temporal partitioning amongst, four sympatric species of African large carnivores: lions (Panthera leo), leopards (Panthera pardus), cheetahs (Acinonyx jubatus) and African wild dogs (Lycaon pictus). Activity of all species was shaped by a combination of light availability and temperature, with most species becoming more nocturnal and decreasing activity levels with increasing temperatures. A nocturnal shift was most pronounced in cheetahs, the most diurnal species during median temperatures. This shift increased temporal overlap between cheetahs and other carnivore species by up to 15.92%, highlighting the importance of considering the responses of interacting sympatric species when inferring climate impacts on ecosystems. Our study provides evidence that temperature can significantly affect temporal partitioning within a carnivore guild by generating asymmetrical behavioural responses amongst functionally similar species.
Erysipelothrix spp. and other Erysipelotrichales detected by 16S rRNA microbial community profiling in samples from healthy conventionally reared chickens and their environment
Authors: Wattrang Eva , Sørensen Dalgaard Tina , Eriksson Helena , Söderlund Robert
Published: November 2023

Outbreaks of erysipelas, a disease caused by infection with Erysipelothrix rhusiopathiae (ER), is a re-emerging problem in cage-free laying hen flocks. The source of ER infection in hens is usually unknown and serological evidence has indicated the presence of ER or other antigenically related bacteria also in healthy flocks. The aim of the present study was to evaluate sample collection, culture methods and DNA-based methodology to detect ER and other Erysipelotrichales in samples from healthy chickens and their environment.
We used samples from a research facility with conventionally reared chickens with no history of erysipelas outbreaks where hens with high titers of IgY recognising ER previously have been observed. Microbial DNA was extracted from samples either directly or after pre-culture in nonselective or ER-selective medium. Real-time PCR was used for detection of Erysipelothrix spp. and high-throughput amplicon sequencing of 16S rRNA sequencing was used for detection of Erysipelotrichales. A pilot serological analysis of some Erysipelotrichales members with IgY from unvaccinated and ER vaccinated high biosecurity-chickens as well as conventionally reared chickens was also performed.
All samples were negative for ER, E. tonsillarum and E. piscisicarius by PCR analysis. However, 16S rRNA community profiling indicated the presence of several Erysipelotrichales genera in both environmental samples and chicken intestinal samples including Erysipelothrix spp. that were detected in environmental samples. Sequences from Erysipelothrix spp. were most frequently detected in samples pre-cultured in ER-selective medium. On species level the presence of E. anatis and/or E. aquatica was indicated. Serological results indicated that IgY raised to ER showed some cross-reactivity with E. anatis.
Hence, environmental samples pre-cultured in selective medium and analysis by 16S rRNA sequencing proved a useful method for detection of Erysipelotrichales including Erysipelothrix spp. in chicken flocks. The observation of such bacteria in environmental samples offers a possible explanation for the observation of high antibody titres to ER in flocks without a history of clinical erysipelas.
A vasopressin circuit that modulates sex-specific social interest and anxiety-like behavior in mice
Authors: Rigney Nicole , Campos-Lira Elba , Kirchner Matthew K. , Wei Wei , Belkasim Selma , Beaumont Rachael , Singh Sumeet , de Vries Geert J. , Petrulis Aras
Published: November 2023

One of the largest sex differences in brain neurochemistry is the male-biased expression of the neuropeptide arginine vasopressin (AVP) within the vertebrate social brain. Despite the long-standing implication of AVP in social and anxiety-like behavior, the precise circuitry and anatomical substrate underlying its control are still poorly understood. By employing optogenetic manipulation of AVP cells within the bed nucleus of the stria terminalis (BNST), we have unveiled a central role for these cells in promoting social investigation, with a more pronounced role in males relative to females. These cells facilitate male social investigation and anxiety-like behavior through their projections to the lateral septum (LS), an area with the highest density of sexually-dimorphic AVP fibers. Blocking the vasopressin 1a receptor (V1aR) in the LS eliminated stimulation-mediated increases in these behaviors. Together, these findings establish a distinct BNST AVP → LS V1aR circuit that modulates sex-specific social interest and anxiety-like behavior.

Significance Statement

The function of sex differences in the brain is poorly understood. Here we test the function of one of the most consistently found sex differences in vertebrate brains, the male-biased vasopressin projections from the bed nucleus of the stria terminalis. Using optogenetic techniques, we demonstrate that these cells and their projection to the lateral septum are much more important in driving male than female social investigation. These studies make a strong contribution to understanding how sexually dimorphic circuitry controls social behavior.
Allosteric modulation by the fatty acid site in the glycosylated SARS-CoV-2 spike
Authors: Oliveira A Sofia F , Kearns Fiona L , Rosenfeld Mia A , Casalino Lorenzo F , Tulli Lorenzo , Berger Imre , Schaffitzel Christiane , Davidson Andrew D , Amaro Rommie E , Mulholland Adrian J
Published: November 2023

The trimeric spike protein plays an essential role in the SARS-CoV-2 virus lifecycle, facilitating virus entry through binding to the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediating viral-host membrane fusion. The SARS-CoV-2 spike contains a fatty acid (FA) binding site at the interface between two neighbouring receptor-binding domains. This site, also found in some other coronaviruses, binds free fatty acids such as linoleic acid. Binding at this site locks the spike in a non-infectious, closed conformation. This site is coupled to functionally important regions, but the effects of glycans on these allosteric effects have not been investigated. Understanding allostery and how this site modulates the behaviour of the spike protein could potentiate the development of promising alternative strategies for new coronavirus therapies. Here, we apply dynamical nonequilibrium molecular dynamics (D-NEMD) simulations to investigate allosteric effects of the FA site in the fully glycosylated spike of the original SARS-CoV-2 ancestral variant. The results show allosteric networks that connect the FA site to important functional regions of the protein, including some more than 40 Å away, including the receptor binding motif, an antigenic supersite in the N-terminal domain, the furin cleavage site, regions surrounding the fusion peptide, and another allosteric site known to bind heme and biliverdin. The networks identified here highlight the complexity of the allosteric modulation in this protein and reveal a striking and unexpected connection between different allosteric sites. Notably, 65% of amino acid substitutions, deletions and insertions in the Alpha, Beta, Delta, Gamma and Omicron variants map onto or close to the identified allosteric pathways. Comparison of the FA site connections from D-NEMD in the glycosylated and non-glycosylated spikes revealed that the presence of glycans does not qualitatively change the internal allosteric pathways within the protein, with some glycans facilitating the transmission of the structural changes within and between subunits.
Dynamics of the viral community on the surface of a French smear-ripened cheese during maturation and persistence across production years
Authors: Paillet Thomas , Lamy-Besnier Quentin , Figueroa Clarisse , Petit Marie-Agnès , Dugat-Bony Eric
Published: November 2023

The surface of smear-ripened cheeses constitutes a dynamic microbial ecosystem resulting from the successive development of different microbial groups such as lactic acid bacteria, fungi and ripening bacteria. Recent studies indicate that a viral community, mainly composed of bacteriophages, also represents a common and substantial part of the cheese microbiome. However, the composition of this community, its temporal variations and associations between bacteriophages and their hosts remain poorly characterized. Here, we studied a French smear-ripened cheese by both viral metagenomics and 16S metabarcoding approaches to assess both the succession of phages and bacterial communities on the cheese surface during cheese ripening, and their temporal variations in ready-to-eat cheeses over the years of production. We observed a clear transition of the phage community structure during ripening with a decreased relative abundance of viral species (vOTUs) associated withLactococcusphages, which were replaced by vOTUs associated with phages infecting ripening bacteria such asBrevibacterium, Glutamicibacter, PseudoalteromonasandVibrio. The dynamics of the phage community was strongly associated with bacterial successions observed on the cheese surface. Finally, while some variations in the distribution of phages were observed in ready-to-eat cheeses produced at different dates spanning more than 4 years of production, the most abundant phages were detected throughout. This result revealed the long-term persistence of the dominant phages in the cheese production environment. Together, these findings offer novel perspectives on the ecology of bacteriophages in smear-ripened cheese and emphasize the significance of incorporating bacteriophages in the microbial ecology studies of fermented foods.

IMPORTANCE

The succession of diverse microbial populations is critical for ensuring the production of high-quality cheese. We observed a temporal succession of phages on the surface of a smear-ripened cheese, with new phage communities showing up at the time when ripening bacteria start covering this surface. Interestingly, the final phage community of this cheese is also consistent over large periods of time, as the same bacteriophages were found in cheese products from the same manufacturer made over 4-years. This research highlights the importance of considering these bacteriophages when studying the microbial life of fermented foods like cheese.
Gibberellin Perception Sensors 1 and 2 reveal cellular GA dynamics articulated by COP1 and GA20ox1 that are necessary but not sufficient to pattern hypocotyl cell elongation
Authors: Griffiths Jayne , Rizza Annalisa , Tang Bijun , Frommer Wolf B. , Jones Alexander M.
Published: November 2023

The phytohormone gibberellin (GA) is critical for environmentally sensitive plant development including germination, skotomorphogenesis and flowering. The FRET biosensor GIBBERELLIN PERCEPTION SENSOR1, which permits single-cell GA measurementsin vivo, was previously used to observe a GA gradient correlated with cell length in dark-grown but not light-grown hypocotyls. We sought to understand how light signalling integrates into cellular GA regulation. Here we show how the E3 ligase COP1 and transcription factor HY5 play central roles in directing cellular GA distribution in skoto- and photomorphogenic hypocotyls, respectively. We demonstrate that the expression pattern of biosynthetic enzymeGA20ox1is the key determinant of the GA gradient in dark-grown hypocotyls and is a target of COP1 signalling. We engineered a second generation GPS2 biosensor with improved orthogonality and reversibility to show the cellular pattern of GA depletion during the transition to growth in the light. This GA depletion partly explains the resetting of hypocotyl growth dynamics during photomorphogenesis. Achieving cell-level resolution has revealed how GA distributions link environmental conditions with morphology and morphological plasticity and the GPS2 biosensor is an ideal tool for GA studies in further conditions, organs and plant species.
The Temporal Profile of Dual-task Interference in the Human Brain
Authors: Hashemirad Seyed-Reza , Vaziri-Pashkam Maryam , Abbaszadeh Mojtaba
Published: November 2023

Due to the brain’s limited cognitive capacity, simultaneous execution of multiple tasks can lead to performance impairments, mainly when the tasks occur closely in time. This limitation is known as dual-task interference. We aimed to investigate the time course of this phenomenon in the brain, utilizing a combination of EEG, multivariate pattern analysis (MVPA), and drift-diffusion modeling (DDM). Here, participants first performed a tone discrimination task, followed by a lane-change task with either short or long onset time differences (Stimulus Onset Asynchrony, SOA), in a simulated driving environment. As expected, the dual-task interference increased the second task’s (lane-change) reaction time. The DDM analysis indicated that this increase was attributable to changes in both the decision time and the post-decision time. Our MVPA findings revealed a decrease in decoding accuracy for the lane-change task in short SOA compared to both long SOA and single-task conditions throughout the trial, highlighting the presence of interference. Moreover, the temporal generalization analysis identified a significant interference effect in short SOA compared to long SOA and single-task conditions after ∼250 ms relative to stimulus onset. Additionally, the conditional generalization analysis showed a delayed response after ∼450 ms. Searchlight analysis illustrated the progression of this information reduction, starting in occipital, parietal, and parieto-occipital leads responsible for perceptual and central processing and then transferring to the frontal leads for mapping decisions onto motor actions. Consistent with the hybrid dual-task interference theory, our results suggest that the processing of the two tasks occurs in a partial parallel manner for the first few hundred milliseconds and primarily in the perceptual and decision-processing stages. Subsequently, another competition arises between the two tasks to route information to motor areas for execution, resulting in the second task’s serial processing and delay or lengthening.
Diet-induced obesity results in endothelial cell desensitization to VEGF-A and permanent islet vascular dysfunction
Authors: Xiong Yan , Dicker Andrea , Visa Montse , Ilegems Erwin , Berggren Per-Olof
Published: November 2023

Background

Pancreatic islet microvasculature is essential for optimal islet function and glucose homeostasis. However, islet vessel pathogenesis and its role in the manifestation of metabolic disorders remain understudied. Here we depict a time-resolved decline of intra-islet endothelial cell sensitivity to vascular endothelial cell growth factor A (VEGF-A) in a mouse model of diet-induced obesity.

Methods

Mice were transplanted with reporter islets in their eyes and put on different diet schemes for 48 weeks. Islet vascular morphology, VEGF-A signaling activity in islet endothelial cells and vessel function were longitudinally monitored by in vivo imaging, while the metabolic implication of islet vessel alterations was measured by glucose tolerance tests and insulin secretion assays.

Results

In parallel with substantial islet vasculature remodeling, diminished VEGF-A response in islet endothelial cells emerged after 12 weeks of western diet feeding. This led to vessel barrier dysfunction and hemodynamic dysregulation, which delayed transportation of secreted insulin into the blood. Islet vessels also exhibited a remarkable metabolic memory long after the removal of western diet. Neither islet endothelial cell VEGF-A sensitivity nor the vascular damage elicited by 24 weeks of western diet feeding was restored by switching to control diet for another 24 weeks. As a result, these refed mice still exhibited mild but significant impairment in glucose clearance, despite a complete normalization of body weight and insulin sensitivity. While plasma levels of soluble VEGF receptor 1 – the natural VEGF-A trap – were similar in all diet groups, increased activity of atypical protein kinase C (aPKC) was observed under both western diet and recovery conditions, which inhibited VEGF receptor 2 (VEGFR2) internalization and dampened VEGF-A triggered signal transduction in vivo and in human endothelial cells cultured under diet-mimicking conditions.

Conclusions

Long-term western diet feeding causes irreversible VEGF-A desensitization in islet endothelial cells and islet vessel dysfunction which undermines glucose homeostasis.
Prevalence and factors associated with advanced HIV disease among young people aged 15 - 24 years in a national referral hospital in Sierra Leone: A cross-sectional study
Authors: Baldeh Mamadu , Kizito Samuel , Lakoh Sulaiman , Sesay Daniel , Dennis Frida , Barrie Umu , Williams Samuel Adeyemi , Robinson Dimbintsoa Rakotomalala , Lamontagne Franck , Amahowe Franck , Turay Patrick , Sensory-Bahar Ozge , Geng Elvin , Ssewamala Fred M.
Published: November 2023

Background

Advanced HIV in young people living with HIV is an increasingly pressing public health issue in sub-Saharan Africa. Despite global progress in early HIV testing and reducing HIV-related deaths, many young people with HIV continue to experience HIV disease progression in sub-Saharan Africa. This study provides an overview of the prevalence, clinical manifestations, and factors associated with advanced HIV in young people seeking medical services in a major hospital in Sierra Leone.

Methods

We used a cross-sectional design to collect data from HIV patients aged 15 to 24 years at a major hospital in Sierra Leone between September 2022 and March 2023. Advanced HIV was defined as (i) CD4+ below 200 cells/mm3 or (ii) WHO clinical stage 3 or 4. Logistic regression models determined the association between observable independent characteristics and advanced HIV. The statistical significance level was set at 0.05 for all statistical tests.

Results

About 40% (231/574) of patients were recruited; 70.6% (163/231) were inpatients, and 29.4% (68/231) were outpatients. The mean age was approximately 21.6 years (SD ±2.43). The overall prevalence of advanced HIV was 42.9% (99/231), 51.5% (35/68) of outpatients, and 39.3% (64/163) of inpatients. Age of inpatients (OR, 1.23; 95% CI, 1.00-1.52; p= 0.047) was associated with a higher risk. Female sex (OR, 0.51; 95% CI, 0.28-0.94; p= 0.030), higher education (OR, 0.27; 95% CI, 0.10 – 0.78; p= 0.015), and Body Mass (OR, 0.10; 95% CI, 0.01-0.77; p= 0.028) were at lower risk of advance HIV. Common conditions diagnosed in this population are tuberculosis (13.58%), hepatitis B (6.13%), Kaposi sarcoma (3.07%), and esophageal candidiasis (2.45%).

Conclusion

We reported a high prevalence of advanced HIV among young patients in a referral Hospital in Sierra Leone. This emphasises the need to strengthen public health measures and policies that address challenges of access to HIV services.

Strengths and limitations of this study

This is the first study in Sierra Leone and the sub-region to examine the burden of advanced HIV and its predictors in young people living with HIV.

Calls for a more targeted approach to addressing gaps in health service delivery for young people living with HIV in Sierra Leone.

The study is limited by the unavailability of several laboratory investigations to monitor patient progress.
Capability of GPT-4V(ision) in Japanese National Medical Licensing Examination
Authors: Nakao Takahiro , Miki Soichiro , Nakamura Yuta , Kikuchi Tomohiro , Nomura Yukihiro , Hanaoka Shouhei , Yoshikawa Takeharu , Abe Osamu
Published: November 2023

Background

Previous research applying large language models (LLMs) to medicine was focused on text-based information. Recently, multimodal variants of LLMs acquired the capability of recognizing images.

Objective

To evaluate the capability of GPT-4V, a recent multimodal LLM developed by OpenAI, in recognizing images in the medical field by testing its capability to answer questions in the 117th Japanese National Medical Licensing Examination.

Methods

We focused on 108 questions that had one or more images as part of a question and presented GPT-4V with the same questions under two conditions: 1) with both the question text and associated image(s), and 2) with the question text only. We then compared the difference in accuracy between the two conditions using the exact McNemar’s test.

Results

Among the 108 questions with images, GPT-4V’s accuracy was 68% when presented with images and 72% when presented without images (P= .36).

Conclusions

The additional information from the images did not significantly improve the performance of GPT-4V in the Japanese Medical Licensing Examination.
Combining genomic data and infection estimates to characterize the complex dynamics of SARS-CoV-2 Omicron variants in the United States
Authors: Lopes Rafael , Pham Kien , Klaassen Fayette , Chitwood Melanie H. , Hahn Anne M. , Redmond Seth , Swartwood Nicole A. , Salomon Joshua A. , Menzies Nicolas A. , Cohen Ted , Grubaugh Nathan D.
Published: November 2023

SARS-CoV-2 Omicron surged as a variant of concern in late 2021. Subsequently, several distinct Omicron variants have appeared and overtaken each other. We combined variant frequencies and infection estimates from a nowcasting model for each US state to estimate variant-specific infections, attack rates, and effective reproduction numbers (Rt). BA.1 rapidly emerged, and we estimate that it infected 47.7% of the US population between late 2021 and early 2022 before it was replaced by BA.2. We estimate that BA.5, despite a slower takeoff than BA.1, infected 35.7% of the US population, persisting in circulation for nearly 6 months. Other Omicron variants - BA.2, BA.4, and XBB - together infected 30.7% of the US population. We found a positive correlation between the state-level BA.1 attack rate and social vulnerability and a negative correlation between the BA.1 and BA.2 attack rates. Our findings illustrate the complex interplay between viral evolution, population susceptibility, and social factors during the Omicron emergence in the US.
Comprehensive Analysis of Cell-Free DNA Fragmentation Across Cancer Stages
Authors: Guo Xin , Nie Lijuan , Yan Junjun , Ling Tinsheng , Zhang Fei , Chen Yi , Li Mengyu , Zeng Wenqi , Chen Yugen , Chu Wen-Ming , Ge Olivia , Guo Qing , Ge Dongliang , Zhou Xiqiao
Published: November 2023

Circulating cell-free DNA (cfDNA) in the bloodstream displays cancer-derived fragmentation patterns, offering a non-invasive diagnostic avenue for cancer patients. However, the association between cfDNA fragmentation patterns and cancer progression remains largely unexplored. In this study, we analyzed this relationship using 214 whole-genome cfDNA samples across seven solid cancer types and revealed that the relation between cfDNA fragmentation patterns and cancer stages vary across cancer types. Among them, cfDNA fragmentation patterns in colorectal cancer (CRC) showed a strong correlation with cancer stages. This finding is further validated with an independent targeted cfDNA dataset from 29 CRC samples. Inspired by these findings, we designed “frag2stage”, a machine learning model that exploits cfDNA fragmentation data to differentiate cancer stages of CRC. Evaluated on two independent cfDNA datasets, our model can distinguish cancer stages of CRC with the area under the curve (AUC) values ranging from 0.68 to 0.99. The results suggest that cfDNA fragmentation patterns might carry yet undiscovered genetic and epigenetic signals, highlighting their promising potential for broader diagnostic applications in oncology.
Single locus theory of admixture is insufficient for the study of complex traits in admixed populations
Authors: Lee Hanbin , Lee Moo-Hyuk , Hou Kangcheng , Pasaniuc Bogdan , Han Buhm
Published: November 2023

Admixed populations offer valuable insights into the genetic architecture of complex traits. Such an investigation demands a delicate theory that can handle the linkage disequilibrium structure of admixed genomes. With additional assumptions, we show that Pritchard-Stephens-Donnelly (PSD) can predict empirical GWAS findings. We call this the extended PSD (ePSD) model and evaluate the predictions using real data. When applied to real data of admixed genomes, the prediction of the ePSD model is very successful in explaining single-locus behaviors while falling short in predicting two-loci phenomena involving linkage disequilibrium. Our results show that a mosaic of independent single-continental segments is an insufficient approximation of contemporary admixed populations. A more advanced theory that better models linkage disequilibrium of admixed populations will be crucial to better understanding the genetic architecture of complex traits.
QRS detection in single-lead, telehealth electrocardiogram signals: benchmarking open-source algorithms
Authors: Kristof Florian , Kapsecker Maximilian , Nissen Leon , Brimicombe James , Cowie Martin R. , Ding Zixuan , Dymond Andrew , Jonas Stephan M. , Lindén Hannah Clair , Lip Gregory Y. H. , Williams Kate , Mant Jonathan , Charlton Peter H. ,   the SAFER Investigators
Published: November 2023

Background and Objectives

A key step in electrocardiogram (ECG) analysis is the detection of QRS complexes, particularly for arrhythmia detection. Telehealth ECGs present a new challenge for automated analysis as they are noisier than traditional clinical ECGs. The aim of this study was to identify the best-performing open-source QRS detector for use with telehealth ECGs.

Methods

The performance of 18 open-source QRS detectors was assessed on six datasets. These included four datasets of ECGs collected under supervision, and two datasets of telehealth ECGs collected without clinical supervision. The telehealth ECGs, consisting of single-lead ECGs recorded between the hands, included a novel dataset of 479 ECGs collected in the SAFER study of screening for atrial fibrillation (AF). Performance was assessed against manual annotations.

Results

A total of 12 QRS detectors performed well on ECGs collected under clinical supervision (F1score ≥ 0.96). However, fewer performed well on telehealth ECGs: five performed well on the TELE ECG Database; six performed well on high-quality SAFER data; and performance was poorer on low-quality SAFER data (three QRS detectors achievedF1of 0.78-0.84). The presence of AF had little impact on performance.

Conclusions

The Neurokit and University of New South Wales QRS detectors performed best in this study. These performed sufficiently well on high-quality telehealth ECGs, but not on low-quality ECGs. This demonstrates the need to handle low-quality ECGs appropriately to ensure only ECGs which can be accurately analysed are used for clinical decision making.