bluuebunny/crossref_metadata_2025 huggingface dataset:
Time Series Quantile Regression Using Random Forests
Authors: Shiraishi Hiroshi , Nakamura Tomoshige , Shibuki Ryotato
Published: January 2024

We discuss an application of Generalized Random Forests (GRF) proposed to quantile regression for time series data. We extended the theoretical results of the GRF consistency for i.i.d. data to time series data. In particular, in the main theorem, based only on the general assumptions for time series data and trees, we show that the tsQRF (time series Quantile Regression Forest) estimator is consistent. Compare with existing article, different ideas are used throughout the theoretical proof. In addition, a simulation and real data analysis were conducted. In the simulation, the accuracy of the conditional quantile estimation was evaluated under time series models. In the real data using the Nikkei Stock Average, our estimator is demonstrated to capture volatility more efficiently, thus preventing underestimation of uncertainty.
The transcription factor Ofi1 is critical for white‐opaque switching in natural MTLa/α isolates of Candida albicans
Authors: Cui Hao , Yang Dandan , Gong Shengwei , Zhang Yaling , Dong Bin , Su Chang , Yang Lianjuan , Lu Yang
Published: January 2024

Candida albicans, an opportunistic fungal pathogen, is able to switch between two distinct cell types: white and opaque. While white‐to‐opaque switching is typically repressed by the a1/α2 heterodimer in MTLa/α cells, it was recently reported that switching can also occur in some natural MTLa/α strains under certain environmental conditions. However, the regulatory program governing white‐opaque switching in MTLa/α cells is not fully understood. Here, we collected 90 clinical isolates of C. albicans, 16 of which possess the ability to form opaque colonies. Among the known regulators implicated in white‐opaque switching, only OFI1 exhibited significantly higher expression in these 16 strains compared to the reference strain SC5314. Importantly, ectopic expression of OFI1 in both clinical isolates and laboratory strains promoted switching frequency even in the absence of N‐acetylglucosamine and high CO2, the optimal condition for white‐to‐opaque switching in MTLa/α strains. Deleting OFI1 resulted in a reduction in opaque‐formation frequency and the stability of the opaque cell in MTLa/α cells. Ofi1 binds to the promoters of WOR1 and WOR3 to induce their expression, which facilitates white‐to‐opaque switching. Ofi1 is conserved across the CTG species. Altogether, our study reported the identification of a transcription factor Ofi1 as the critical regulator that promotes white‐to‐opaque switching in natural MTLa/α isolates of C. albicans.
Plant‐derived monoterpene S‐linalool and β‐ocimene generated by CsLIS and CsOCS‐SCZ are key chemical cues for attracting parasitoid wasps for suppressing Ectropis obliqua infestation in Camellia sinensis L
Authors: Liu Guanhua , Wang Qian , Chen Hui , Wang Yuxi , Zhou Xiaogui , Bao Demeng , Wang Nuo , Sun Juan , Huang Fuyin , Yang Mei , Zhang Han , Yan Peng , Li Xin , Shi Jiang , Fu Jianyu
Published: January 2024

Insect‐induced plant volatile organic compounds (VOCs) may function as either direct defence molecules to deter insects or indirect defence signals to attract the natural enemies of the invading insects. Tea (Camellia sinensis L.), an important leaf‐based beverage crop, is mainly infested by Ectropis obliqua which causes the most serious damage. Here, we report a mechanistic investigation of tea plant‐derived VOCs in an indirect defence mechanism against E. obliqua. Parasitoid wasp Parapanteles hyposidrae, a natural enemy of E. obliqua, showed strong electrophysiological response and selection behaviour towards S‐linalool and β‐ocimene, two monoterpenes with elevated emission from E. obliqua‐damaged tea plants. Larvae frass of E. obliqua, which also released S‐linalool and β‐ocimene, was found to attract both mated female or male Pa. hyposidrae according to gas chromatography‐electroantennogram detection and Y‐tube olfactometer assays. In a field setting, both S‐linalool and β‐ocimene were effective in recruiting both female and male Pa. hyposidrae wasps. To understand the molecular mechanism of monoterpenes‐mediated indirect defence in tea plants, two novel monoterpene synthase genes, CsLIS and CsOCS‐SCZ, involved in the biosynthesis of S‐linalool or β‐ocimene, respectively, were identified and biochemically characterised. When the expression of these two genes in tea plants was inhibited by antisense oligodeoxynucleotide, both volatile emission and attraction of wasps were reduced. Furthermore, gene expression analysis suggested that the expression of CsLIS and CsOCS‐SCZ is regulated by the jasmonic acid signalling pathway in the tea plant.
Pass‐through of shocks into different U.S. prices
Authors: Yilmazkuday Hakan
Published: January 2024

This article estimates the pass‐through of different shocks into different U.S. prices that are important for policy makers. The investigation is based on a structural vector autoregression model, where quarterly data are used. The empirical results depict oil price pass‐through, exchange rate pass‐through, import‐price pass‐through, and producer price pass‐through into import prices, producer prices, and consumer prices for the U.S. economy. Policy implications suggest that achieving and sustaining consumer price stability highly depend on monitoring the developments in oil prices, followed by import prices and producer prices.
“Be All That You Can Be”: The Role of Identity, Pro‐Social Labeling, and Narratives in Veterans Treatment Courts*
Authors: Sherman Nicole
Published: January 2024

Veterans Treatment Courts (VTCs) are one of the ever‐developing brands of specialty or problem‐solving courts that have emerged in recent decades. These courts recognize that the criminal behavior stems from a variety of issues, and that punishment should represent a therapeutic jurisprudential approach in its strategies. As such, VTCs treat substance abuse and mental health issues and address criminality in a manner that recognizes a need for individualized treatment and accountability in structure. This research provides an in‐depth institutional ethnography of one Southern California VTC (SC VTC). To understand the powerful transformative tools of identity and narrative, this research utilized over 3 years of non‐participant observation at 117 court sessions in the SC VTC, and 23 in‐depth interviews with both current court participants and graduates and a judge, exploring participants' experiences with and perceptions of the SC VTC. This study demonstrates the utility of identity‐based narratives to navigate legal systems and potentially desist from crime. These mechanisms of narrative and identity provide a powerful illumination of these courts that have ramifications for successful reintegration into society post‐criminal justice interaction.
Texts and contexts: Linguistic landscapes, graffiti, film, and literature in L2 classes
Authors: Wagner Susanne M. , Hoecherl‐Alden Gisela
Published: January 2024

Given that societies across the globe are increasingly multicultural and multilingual, the notion of communicative competence grounded in constricting definitions of national cultures and languages reflects neither our instructional realities nor the sociolinguistic reality of the languages and cultures we teach. To foster students’ development of second language (L2) competence grounded in an awareness of the symbolic construction of language and culture as well as “tolerance for ambiguity” (Kramsch, 2006), students must create with L2, rather than just reproduce what they have learned. After briefly outlining changing conceptions of language competency, this paper first describes how public uses of language and images through signs and graffiti make up a given place's linguistic landscape (LL), defines an evolving concept, and illustrates how it can be effectively used in L2 instruction. Then it highlights how a variety of LL‐based activities help language learners become cognizant of their own sociolinguistic contexts and provides concrete examples from intermediate to advanced‐level classes in two distinctly different German programs. The different approaches encourage students to combine LL‐based activities with visual, literary, and film analysis to develop symbolic competencies that prepare them to negotiate unpredictable and diverse cultural norms.
Epidemiological, anatomoclinical, and therapeutic profile of obstetric fistula in the Democratic Republic of the Congo: About 1267 patients
Authors: Paluku Justin Lussy , Sikakulya Franck Katembo , Furaha Cathy Mufungizi , Kamabu Eugénie Mukekulu , Aksanti Barthelemy Kasi , Tsongo Zacharie Kibendelwa , Wembonyama Stanis Okitotsho , Mpoy Charles Wembonyama , Juakali Jeannot Sihalikyolo
Published: January 2024

Objective

Our aim is to describe the epidemiological, anatomoclinical and therapeutic profile of obstetric fistula (OF) in the Democratic Republic of the Congo (DRC).

Methodology

This was a descriptive retrospective study that collected 1416 obstetric fistulas in 1267 patients in seven provinces of the DRC, treated between January 2017 and December 2022. The variables studied were epidemiological, anatomoclinical and therapeutic.

Results

The mean age of patients at the time of surgical repair was 33.2 years (range: 15 and 77 years) and 32.8% of patients were aged between 20 and 29 years. The mean age of the fistula at repair was 10 years (range: 3.5 months and 56 years). At the time of fistula, 61.7% of patients had delivered vaginally and 28.7% by caesarean section and 8.2% of patients had a haemostasis hysterectomy. Labour lasted at least 3 days in 47.3% of these patients for the fistula birth. Deliveries took place either at home (27.4%) or in a health facility (72.6%); 83.6% of newborns resulting from these births had died. Taken as a whole, urogenital fistulas are more common than genito‐digestive fistulas. Urethro‐vaginal (26.2%) and vesico‐uterine (24.7%) anatomoclinical entities were predominant among urogenital fistulas. A total of 1416 fistulas were surgically repaired in 1267 patients. These repairs were successful for 1226 (86.6%) fistulas. The main surgical route used was transvaginal (68.8%).

Conclusion

In the DRC, obstetric fistula is common in young adult women. It often results from vaginal delivery, after prolonged labour. Fistula births often result in the death of newborns. Uro‐genital obstetric fistulas are the most frequent with predominance of urethro‐vaginal and vesico‐uterine anatomoclinical entities. Fistulas remain untreated for a long time. Mostly done transvaginally, surgical repair gives a good result.
The influence of supportive work environment on work‐related stress and conflict management style among emergency care nurses: A descriptive correlational study
Authors: Farghaly Abdelaliem Sally Mohammed , Abdallah Haitham Mokhtar Mohamed , Abdelgawad Mohamed Ezzelregal , El‐Sayed Ahmed Abdelwahab Ibrahim
Published: January 2024

Background

Stress and conflict in emergency departments are inevitable but can be managed. A supportive work environment is key to helping emergency care providers, especially nurses, constructively manage work‐related stress and conflict.

Aim

The aim of this study was to assess the influence of supportive work environments on work‐related stress and conflict management style among emergency care nurses.

Methods

A descriptive correlational research design was utilized. Data were collected from 221 staff nurses recruited from two university hospital emergency departments in Alexandria, Egypt. Three instruments were used: (1) perceived organizational support scale, (2) nurses' occupational stressors scale, and (3) conflict management style inventory.

Results

There was a highly significant correlation between supportive work environments and work‐related stress (p = .000) and a significant correlation between supportive work environments and conflict management style (p = .026). Supportive work environments had a significant inverse negative relationship with work‐related stress experienced by nurses (p = .001) and accounted for 51% of variance in work‐related stress. Meanwhile, supportive work environments had a significant positive relationship with conflict management styles of nurses (p = .026). Work‐related stress had a significant relationship with nurses' conflict management style (p = .000) and accounted for 45% of the variance in conflict management style.

Linking Evidence to Action

The style of conflict management modeled by staff within emergency departments can positively or negatively influence the work environment and level of work‐related stress. There is a necessity to cultivate a supportive culture for nurses in emergency departments to develop skills for constructive conflict management styles to reduce work‐related stress.
Transcriptional determinants of lipid mobilization in human adipocytes
Authors: Ludzki Alison C. , Hansen Mattias , Zareifi Danae , Jalkanen Jutta , Huang Zhiqiang , Omar-Hmeadi Muhmmad , Renzi Gianluca , Klingelhuber Felix , Boland Sebastian , Ambaw Yohannes A. , Wang Na , Damdimopoulos Anastasios , Liu Jianping , Jernberg Tomas , Petrus Paul , Arner Peter , Krahmer Natalie , Fan Rongrong , Treuter Eckardt , Gao Hui , Rydén Mikael , Mejhert Niklas
Published: January 2024

Defects in adipocyte lipolysis drive multiple aspects of cardiometabolic disease, but the transcriptional framework controlling this process has not been established. To address this, we performed a targeted perturbation screen in primary human adipocytes. Our analyses identified 37 transcriptional regulators of lipid mobilization, which we classified as (i) transcription factors, (ii) histone chaperones, and (iii) mRNA processing proteins. On the basis of its strong relationship with multiple readouts of lipolysis in patient samples, we performed mechanistic studies on one hit,
ZNF189
, which encodes the zinc finger protein 189. Using mass spectrometry and chromatin profiling techniques, we show that ZNF189 interacts with the tripartite motif family member TRIM28 and represses the transcription of an adipocyte-specific isoform of phosphodiesterase 1B (PDE1B2). The regulation of lipid mobilization by ZNF189 requires PDE1B2, and the overexpression of PDE1B2 is sufficient to attenuate hormone-stimulated lipolysis. Thus, our work identifies the ZNF189-PDE1B2 axis as a determinant of human adipocyte lipolysis and highlights a link between chromatin architecture and lipid mobilization.
Mechanical manipulation for ordered topological defects
Authors: Gao Ziyan , Zhang Yixuan , Li Xiaomei , Zhang Xiangping , Chen Xue , Du Guoshuai , Hou Fei , Gu Baijun , Lun Yingzhuo , Zhao Yao , Zhao Yingtao , Qu Zhaoliang , Jin Ke , Wang Xiaolei , Chen Yabin , Liu Zhanwei , Huang Houbing , Gao Peng , Mostovoy Maxim , Hong Jiawang , Cheong Sang-Wook , Wang Xueyun
Published: January 2024

Randomly distributed topological defects created during the spontaneous symmetry breaking are the fingerprints to trace the evolution of symmetry, range of interaction, and order parameters in condensed matter systems. However, the effective mean to manipulate topological defects into ordered form is elusive due to the topological protection. Here, we establish a strategy to effectively align the topological domain networks in hexagonal manganites through a mechanical approach. It is found that the nanoindentation strain gives rise to a threefold Magnus-type force distribution, leading to a sixfold symmetric domain pattern by driving the vortex and antivortex in opposite directions. On the basis of this rationale, sizeable mono-chirality topological stripe is readily achieved by expanding the nanoindentation to scratch, directly transferring the randomly distributed topological defects into an ordered form. This discovery provides a mechanical strategy to manipulate topological protected domains not only on ferroelectrics but also on ferromagnets/antiferromagnets and ferroelastics.
Atomistic, macromolecular model of the
Populus
secondary cell wall informed by solid-state NMR
Authors: Addison Bennett , Bu Lintao , Bharadwaj Vivek , Crowley Meagan F. , Harman-Ware Anne E. , Crowley Michael F. , Bomble Yannick J. , Ciesielski Peter N.
Published: January 2024

Plant secondary cell walls (SCWs) are composed of a heterogeneous interplay of three major biopolymers: cellulose, hemicelluloses, and lignin. Details regarding specific intermolecular interactions and higher-order architecture of the SCW superstructure remain ambiguous. Here, we use solid-state nuclear magnetic resonance (ssNMR) measurements to infer refined details about the structural configuration, intermolecular interactions, and relative proximity of all three major biopolymers within air-dried
Populus
wood. To enhance the utility of these findings and enable evaluation of hypotheses in a physics-based environment in silico, the NMR observables are articulated into an atomistic, macromolecular model for biopolymer assemblies within the plant SCW. Through molecular dynamics simulation, we quantitatively evaluate several variations of atomistic models to determine structural details that are corroborated by ssNMR measurements.
Long-distance continuous-variable quantum key distribution over 100-km fiber with local local oscillator
Authors: Hajomer Adnan A. E. , Derkach Ivan , Jain Nitin , Chin Hou-Man , Andersen Ulrik L. , Gehring Tobias
Published: January 2024

Quantum key distribution (QKD) enables two remote parties to share encryption keys with security based on the laws of physics. Continuous-variable (CV) QKD with coherent states and coherent detection integrates well with existing telecommunication networks. Thus far, long-distance CV-QKD has only been demonstrated using a highly complex scheme where the local oscillator is transmitted, opening security loopholes for eavesdroppers and limiting potential applications. Here, we report a long-distance CV-QKD experiment with a locally generated local oscillator over a 100-kilometer fiber channel with a total loss of 15.4 decibels. This record-breaking distance is achieved by controlling the phase noise–induced excess noise through a machine learning framework for carrier recovery and optimizing the modulation variance. We implement the full CV-QKD protocol and demonstrate the generation of keys secure against collective attacks in the finite-size regime. Our results mark a substantial milestone for realizing CV quantum access networks with a high loss budget and pave the way for large-scale deployment of secure QKD.
Regional spread of an atypical ESBL-producing
Escherichia coli
ST131H89 clone among different human and environmental reservoirs in Western Switzerland
Authors: Martischang Romain , Seth-Smith Helena , Verschuuren Tess D. , Héquet Delphine , Gaïa Nadia , François Patrice , Fluit Ad C. , Kluytmans Jan A. J. W. , Seiffert Salome N. , Tacconelli Evelina , Cherkaoui Abdessalam , Harbarth Stephan , Egli Adrian , Kohler Philipp
Published: January 2024

We describe the inter-regional spread of a novel ESBL-producing
Escherichia coli
subclone (ST131H89) in long-term care facility residents, general population, and environmental water sources in Western Switzerland between 2017 and 2020. The study highlights the importance of molecular surveillance for tracking emerging antibiotic-resistant pathogens in healthcare and community settings.
The catabolic specialization of the marine bacterium
Polaribacter
sp. Q13 to red algal β1,3/1,4-mixed-linkage xylan
Authors: Zhao Fang , Yu Chun-Mei , Sun Hai-Ning , Xu Ting-Ting , Sun Zhong-Zhi , Qin Qi-Long , Wang Ning , Chen Xiu-Lan , Yu Yang , Zhang Yu-Zhong
Published: January 2024

Catabolism of algal polysaccharides by marine bacteria is a significant process of marine carbon cycling. β1,3/1,4
-
Mixed-linkage xylan (MLX) is a class of xylan in the ocean, widely present in the cell walls of red algae. However, the catabolic mechanism of MLX by marine bacteria remains elusive. Recently, we found that a marine Bacteroidetes strain,
Polaribacter
sp. Q13, is a specialist in degrading MLX, which secretes a novel MLX-specific xylanase. Here, the catabolic specialization of strain Q13 to MLX was studied by multiomics and biochemical analyses. Strain Q13 catabolizes MLX with a canonical starch utilization system (Sus), which is encoded by a single xylan utilization locus, XUL-Q13. In this system, the cell surface glycan-binding protein SGBP-B captures MLX specifically, contributing to the catabolic specificity. The xylanolytic enzyme system of strain Q13 is unique, and the enzymatic cascade dedicates the stepwise hydrolysis of the β1,3- and β1,4-linkages in MLX in the extracellular, periplasmic, and cytoplasmic spaces. Bioinformatics analysis and growth observation suggest that other marine Bacteroidetes strains harboring homologous MLX utilization loci also preferentially utilize MLX. These results reveal the catabolic specialization of MLX degradation by marine Bacteroidetes, leading to a better understanding of the degradation and recycling of MLX driven by marine bacteria.

IMPORTANCE

Red algae contribute substantially to the primary production in marine ecosystems. The catabolism of red algal polysaccharides by marine bacteria is important for marine carbon cycling. Mixed-linkage β1,3/1,4-xylan (MLX, distinct from hetero-β1,4-xylans from terrestrial plants) is an abundant red algal polysaccharide, whose mechanism of catabolism by marine bacteria, however, remains largely unknown. This study reveals the catabolism of MLX by marine Bacteroidetes, promoting our understanding of the degradation and utilization of algal polysaccharides by marine bacteria. This study also sets a foundation for the biomass conversion of MLX.
Macrophages inhibit extracellular hyphal growth of
A. fumigatus
through Rac2 GTPase signaling
Authors: Tanner Christopher D. , Rosowski Emily E.
Published: January 2024

Macrophages act as a first line of defense against pathogens. Against
Aspergillus fumigatus
, a fungus with pathogenic potential in immunocompromised patients, macrophages can phagocytose fungal spores and inhibit spore germination to prevent the development of tissue-invasive hyphae. However, the cellular pathways that macrophages use to accomplish these tasks and any roles macrophages have later in infection against invasive forms of fungi are still not fully known. Rac-family Rho GTPases are signaling hubs for multiple cellular functions in leukocytes, including cell migration, phagocytosis, reactive oxygen species (ROS) generation, and transcriptional activation. We therefore aimed to further characterize the function of macrophages against
A. fumigatus
in an
in vivo
vertebrate infection model by live imaging of the macrophage behavior in
A. fumigatus
-infected
rac2
mutant zebrafish larvae. While Rac2-deficient zebrafish larvae are susceptible to
A. fumigatus
infection, Rac2 deficiency does not impair macrophage migration to the infection site, interaction with and phagocytosis of spores, spore trafficking to acidified compartments, or spore killing. However, we reveal a role for Rac2 in macrophage-mediated inhibition of spore germination and control of invasive hyphae. Re-expression of Rac2 under a macrophage-specific promoter rescues the survival of
A. fumigatus
-infected
rac2
mutant larvae through increased control of germination and hyphal growth. Altogether, we describe a new role for macrophages against extracellular hyphal growth of
A. fumigatus
and report that the function of the Rac2 Rho GTPase in macrophages is required for this function.
Implications of the 375W mutation for HIV-1 tropism and vaccine development
Authors: Verdejo-Torres Odette , Vargas-Pavia Tania , Fatima Syeda , Clapham Paul R. , Duenas-Decamp Maria J.
Published: January 2024

Understanding how different amino acids affect the HIV-1 envelope (Env) trimer will greatly help the design and development of vaccines that induce broadly neutralizing antibodies (bnAbs). A tryptophan residue at position 375 that opens the CD4 binding site without modifying the trimer apex was identified using our saturation mutagenesis strategy. 375W was introduced into a large panel of 27 transmitted/founder, acute stage, chronic infection, and AIDS macrophage-tropic and non-macrophage-tropic primary envelopes from different clades (A, B, C, D, and G) as well as complex and circulating recombinants. We evaluated soluble CD4 and monoclonal antibody neutralization of WT and mutant Envs together with macrophage infection. The 375W substitution increased sensitivity to soluble CD4 in all 27 Envs and macrophage infection in many Envs including an X4 variant. Importantly, 375W did not impair or abrogate neutralization by potent bnAbs. Variants that were already highly macrophage tropic were compromised for macrophage tropism, indicating that other structural factors are involved. Of note, we observed a macrophage-tropic (clade G) and intermediate macrophage-tropic (clades C and D) primary Envs from the blood and not from the central nervous system (CNS), indicating that such variants could be released from the brain or evolve outside the CNS. Our data also indicate that “intermediate” macrophage-tropic variants should belong to a new class of HIV-1 tropism. These Envs infected macrophages more efficiently than non-macrophage-tropic variants without reaching the high levels of macrophage-tropic brain variants. In summary, we show that 375W is ideal for inclusion into HIV-1 vaccines, increasing Env binding to CD4 for widely diverse Envs from different clades and disease stages.

IMPORTANCE

Substitutions exposing the CD4 binding site (CD4bs) on HIV-1 trimers but still occluding non-neutralizing, immunogenic epitopes are desirable to develop HIV-1 vaccines. If such substitutions induce similar structural changes in trimers across diverse clades, they could be exploited for the development of multi-clade envelope (Env) vaccines. We show that the 375W substitution increases CD4 affinity for envelopes of all clades, circulating recombinant forms, and complex Envs tested, independent of disease stage. Clade B and C Envs with an exposed CD4bs were described for macrophage-tropic strains from the central nervous system (CNS). Here, we show that intermediate (clades C and D) and macrophage-tropic (clade G) envelopes can be detected outside the CNS. Vaccines targeting the CD4bs will be particularly effective against such strains and CNS disease.
Tailam paramyxovirus C protein inhibits viral replication
Authors: Zhou Lu , Kang Haixian , Xu Shuya , Chen Jinbi , Wang Xianyang , Long Haishang , Li Geng , Xu Pei , He Biao
Published: January 2024

Jeilongviruses are emerging single-stranded negative-sense RNA viruses in the Paramyxoviridae family. Tailam paramyxovirus (TlmPV) is a
Jeilongvirus
that was identified in 2011. Very little is known about the mechanisms that regulate viral replication in these newly emerging viruses. Among the non-structural viral proteins of TlmPV, the C protein is predicted to be translated from an open reading frame within the phosphoprotein gene through alternative translation initiation. Though the regulatory roles of C proteins in virus replication of other paramyxoviruses have been reported before, the function of the TlmPV C protein and the relevant molecular mechanisms have not been reported. Here, we show that the C protein is expressed in TlmPV-infected cells and negatively modulates viral RNA replication. The TlmPV C protein interacts with the P protein, negatively impacting the interaction between N and P, resulting in inhibition of viral RNA replication. Deletion mutagenesis studies indicate that the 50 amino-terminal amino acid residues of the C protein are dispensable for its inhibition of virus RNA replication and interaction with the P protein.

IMPORTANCE

Tailam paramyxovirus (TlmPV) is a newly identified paramyxovirus belonging to the
Jeilongvirus
genus, of which little is known. In this work, we confirmed the expression of the C protein in TlmPV-infected cells, assessed its function, and defined a potential mechanism of action. This is the first time that the existence of a
Jeilongvirus
C protein has been confirmed and its role in viral replication has been reported.
The role of hypermutation and collateral sensitivity in antimicrobial resistance diversity of
Pseudomonas aeruginosa
populations in cystic fibrosis lung infection
Authors: Vanderwoude Jelly , Azimi Sheyda , Read Timothy D. , Diggle Stephen P.
Published: January 2024

Upon infection in the cystic fibrosis (CF) lung,
Pseudomonas aeruginosa
rapidly acquires genetic mutations, especially in genes involved in antimicrobial resistance (AMR), often resulting in diverse, treatment-resistant populations. However, the role of bacterial population diversity within the context of chronic infection is still poorly understood. In this study, we found that hypermutator strains of
P. aeruginosa
in the CF lung undergoing treatment with tobramycin evolved increased sensitivity to tobramycin relative to non-hypermutators within the same population. This finding suggests that antimicrobial treatment may only exert weak selection pressure on
P. aeruginosa
populations in the CF lung. We further found no evidence for collateral sensitivity in these clinical populations, suggesting that collateral sensitivity may not be a robust, naturally occurring phenomenon for this microbe.
Calcineurin-dependent contributions to fitness in the opportunistic pathogen
Candida glabrata
Authors: Pavesic Matthew W. , Gale Andrew N. , Nickels Timothy J. , Harrington Abigail A. , Bussey Maya , Cunningham Kyle W.
Published: January 2024

The protein phosphatase calcineurin is vital for the virulence of the opportunistic fungal pathogen
Candida glabrata
. The host-induced stresses that activate calcineurin signaling are unknown, as are the targets of calcineurin relevant to virulence. To potentially shed light on these processes, millions of transposon insertion mutants throughout the genome of
C. glabrata
were profiled
en masse
for fitness defects in the presence of FK506, a specific inhibitor of calcineurin. Eighty-seven specific gene deficiencies depended on calcineurin signaling for full viability
in vitro
both in wild-type and
pdr1∆
null strains lacking pleiotropic drug resistance. Three genes involved in cell wall biosynthesis (
FKS1
,
DCW1
,
FLC1
) possess co-essential paralogs whose expression depended on calcineurin and Crz1 in response to micafungin, a clinical antifungal that interferes with cell wall biogenesis. Interestingly, 80% of the FK506-sensitive mutants were deficient in different aspects of vesicular trafficking, such as endocytosis, exocytosis, sorting, and biogenesis of secretory proteins in the endoplasmic reticulum (ER). In response to the experimental antifungal manogepix that blocks GPI-anchor biosynthesis in the ER, calcineurin signaling increased and strongly prevented cell death independent of Crz1, one of its major targets. Comparisons between manogepix, micafungin, and the ER-stressing tunicamycin reveal a correlation between the degree of calcineurin signaling and the degree of cell survival. These findings suggest that calcineurin plays major roles in mitigating stresses of vesicular trafficking. Such stresses may arise during host infection and in response to antifungal therapies.

IMPORTANCE

Calcineurin plays critical roles in the virulence of most pathogenic fungi. This study sheds light on those roles in the opportunistic pathogen
Candida glabrata
using a genome-wide analysis
in vitro
. The findings could lead to antifungal developments that also avoid immunosuppression.
Multiple microbial guilds mediate soil methane cycling along a wetland salinity gradient
Authors: Hartman Wyatt H. , Bueno de Mesquita Clifton P. , Theroux Susanna M. , Morgan-Lang Connor , Baldocchi Dennis D. , Tringe Susannah G.
Published: January 2024

Estuarine wetlands harbor considerable carbon stocks, but rising sea levels could affect their ability to sequester soil carbon as well as their potential to emit methane (CH
4
). While sulfate loading from seawater intrusion may reduce CH
4
production due to the higher energy yield of microbial sulfate reduction, existing studies suggest other factors are likely at play. Our study of 11 wetland complexes spanning a natural salinity and productivity gradient across the San Francisco Bay and Delta found that while CH
4
fluxes generally declined with salinity, they were highest in oligohaline wetlands (ca. 3-ppt salinity). Methanogens and methanogenesis genes were weakly correlated with CH
4
fluxes but alone did not explain the highest rates observed. Taxonomic and functional gene data suggested that other microbial guilds that influence carbon and nitrogen cycling need to be accounted for to better predict CH
4
fluxes at landscape scales. Higher methane production occurring near the freshwater boundary with slight salinization (and sulfate incursion) might result from increased sulfate-reducing fermenter and syntrophic populations, which can produce substrates used by methanogens. Moreover, higher salinities can solubilize ionically bound ammonium abundant in the lower salinity wetland soils examined here, which could inhibit methanotrophs and potentially contribute to greater CH
4
fluxes observed in oligohaline sediments.

IMPORTANCE

Low-level salinity intrusion could increase CH4 flux in tidal freshwater wetlands, while higher levels of salinization might instead decrease CH4 fluxes. High CH4 emissions in oligohaline sites are concerning because seawater intrusion will cause tidal freshwater wetlands to become oligohaline. Methanogenesis genes alone did not account for landscape patterns of CH4 fluxes, suggesting mechanisms altering methanogenesis, methanotrophy, nitrogen cycling, and ammonium release, and increasing decomposition and syntrophic bacterial populations could contribute to increases in net CH4 flux at oligohaline salinities. Improved understanding of these influences on net CH4 emissions could improve restoration efforts and accounting of carbon sequestration in estuarine wetlands. More pristine reference sites may have older and more abundant organic matter with higher carbon:nitrogen compared to wetlands impacted by agricultural activity and may present different interactions between salinity and CH4. This distinction might be critical for modeling efforts to scale up biogeochemical process interactions in estuarine wetlands.
Genome-based assessment of antimicrobial resistance reveals the lineage specificity of resistance and resistance gene profiles in
Riemerella anatipestifer
from China
Authors: Yang Zhishuang , Wang Mingshu , Jia Renyong , Chen Shun , Liu Mafeng , Zhao Xinxin , Yang Qiao , Wu Ying , Zhang Shaqiu , Huang Juan , Ou Xumin , Mao Sai , Gao Qun , Sun Di , Tian Bin , He Yu , Wu Zhen , Zhu Dekang , Cheng Anchun
Published: January 2024

Riemerella anatipestifer
(
R. anatipestifer
) is an important pathogen that causes severe systemic infections in domestic ducks, resulting in substantial economic losses for China’s waterfowl industry. Controlling
R. anatipestifer
with antibiotics is extremely challenging due to its multidrug resistance. Notably, large-scale studies on antimicrobial resistance (AMR) and the corresponding genetic determinants in
R. anatipestifer
remain scarce. To solve this dilemma, more than 400 nonredundant
R. anatipestifer
isolates collected from 22 provinces in China between 1994 and 2021 were subjected to broth dilution antibiotic susceptibility assays, and their resistance-associated genetic determinants were characterized by whole-genome sequencing. While over 90% of the isolates was resistant to sulfamethoxazole, kanamycin, gentamicin, ofloxacin, norfloxacin, and trimethoprim, 88.48% of the isolates was resistant to the last-resort drug (tigecycline). Notably,
R. anatipestifer
resistance to oxacillin, norfloxacin, ofloxacin, and tetracycline was found to increase relatively over time. Genome-wide analysis revealed the alarmingly high prevalence of
bla
OXA
-like (93.05%) and
tet
(X) (90.64%) genes and the uneven distribution of resistance genes among lineages. Overall, this study reveals a serious AMR situation regarding
R. anatipestifer
in China, with a high prevalence and high diversity of antimicrobial resistance genes, providing important data for the rational use of antibiotics in veterinary practice.

IMPORTANCE

Riemerella anatipestifer (R. anatipestifer
), an important waterfowl pathogen, has caused substantial economic losses worldwide, especially in China. Antimicrobial resistance (AMR) is a major challenge in controlling this pathogen. Although a few studies have reported antimicrobial resistance in
R. anatipestifer
, comprehensive data remain a gap. This study aims to address the lack of information on
R. anatipestifer
AMR and its genetic basis. By analyzing more than 400 isolates collected over two decades, this study reveals alarming levels of resistance to several antibiotics, including drugs of last resort. The study also revealed the lineage-specificity of resistance profiles and resistance gene profiles. Overall, this study provides new insights and updated data support for understanding AMR and its genetic determinants in
R. anatipestifer
.
Mechanisms of nitrogen isotope fractionation at an ancient black smoker in the 2.7 Ga Abitibi greenstone belt, Canada
Authors: Martin A.N. , Stüeken E.E. , Michaud J.A.-S. , Münker C. , Weyer S. , van Hees E.H.P. , Gehringer M.M.
Published: January 2024

The biological nitrogen (N) cycle on early Earth is enigmatic because of limited data from Archean (meta-)sediments and the potential alteration of primary biotic signatures. Here we further investigate unusual 15N enrichments reported in 2.7 Ga meta-sediments from the Abitibi greenstone belt, Canada, purportedly related to a 15N-enriched Archean atmosphere. Given that sediments from this region are contemporaneous with large-scale volcanogenic massive sulfide deposits, we utilize Cu and Zn contents to trace the effects of hydrothermal circulation on N isotope fractionation. We show that high δ15Nbulk values as high as +23‰ are associated with Cu-Zn mineralization, whereas unmineralized organic-rich shales exhibit much lower δ15Nbulk and δ15Nkerogen values. Moreover, we find a large offset between δ15Nbulk and δ15Nkerogen of as much as 17‰ and relate this to the addition of organic-bound N during the late-stage emplacement of organic-rich veins. We conclude that the previously reported high δ15N values are most parsimoniously explained by biotic and abiotic mechanisms rather than a 15N-enriched atmosphere. Crucially, both mechanisms require the presence of NH4+ in hydrothermal fluids, supporting the hypothesis that hydrothermal discharge was an important nutrient source for Neoarchean marine life.
Clinical decision support systems to improve drug prescription and therapy optimisation in clinical practice: a scoping review
Authors: Armando Lucrezia Greta , Miglio Gianluca , de Cosmo Pierluigi , Cena Clara
Published: January 2024

Objective

Clinical decision support systems (CDSSs) can reduce medical errors increasing drug prescription appropriateness. Deepening knowledge of existing CDSSs could increase their use by healthcare professionals in different settings (ie, hospitals, pharmacies, health research centres) of clinical practice. This review aims to identify the characteristics common to effective studies conducted with CDSSs.

Materials and methods

The article sources were Scopus, PubMed, Ovid MEDLINE and Web of Science, queried between January 2017 and January 2022. Inclusion criteria were prospective and retrospective studies that reported original research on CDSSs for clinical practice support; studies should describe a measurable comparison of the intervention or observation conducted with and without the CDSS; article language Italian or English. Reviews and studies with CDSSs used exclusively by patients were excluded. A Microsoft Excel spreadsheet was prepared to extract and summarise data from the included articles.

Results

The search resulted in the identification of 2424 articles. After title and abstract screening, 136 studies remained, 42 of which were included for final evaluation. Most of the studies included rule-based CDSSs that are integrated into existing databases with the main purpose of managing disease-related problems. The majority of the selected studies (25 studies; 59.5%) were successful in supporting clinical practice, with most being pre–post intervention studies and involving the presence of a pharmacist.

Discussion and conclusion

A number of characteristics have been identified that may help the design of studies feasible to demonstrate the effectiveness of CDSSs. Further studies are needed to encourage CDSS use.
Measures of socioeconomic advantage are not independent predictors of support for healthcare AI: subgroup analysis of a national Australian survey
Authors: Frost Emma Kellie , O’Shaughnessy Pauline , Steel David , Braunack-Mayer Annette , Aquino Yves Saint James , Carter Stacy M
Published: January 2024

Objectives:Applications of artificial intelligence (AI) have the potential to improve aspects of healthcare. However, studies have shown that healthcare AI algorithms also have the potential to perpetuate existing inequities in healthcare, performing less effectively for marginalised populations. Studies on public attitudes towards AI outside of the healthcare field have tended to show higher levels of support for AI among socioeconomically advantaged groups that are less likely to be sufferers of algorithmic harms. We aimed to examine the sociodemographic predictors of support for scenarios related to healthcare AI.

Methods:The Australian Values and Attitudes toward AI survey was conducted in March 2020 to assess Australians’ attitudes towards AI in healthcare. An innovative weighting methodology involved weighting a non-probability web-based panel against results from a shorter omnibus survey distributed to a representative sample of Australians. We used multinomial logistic regression to examine the relationship between support for AI and a suite of sociodemographic variables in various healthcare scenarios.

Results:Where support for AI was predicted by measures of socioeconomic advantage such as education, household income and Socio-Economic Indexes for Areas index, the same variables were not predictors of support for the healthcare AI scenarios presented. Variables associated with support for healthcare AI included being male, having computer science or programming experience and being aged between 18 and 34 years. Other Australian studies suggest that these groups may have a higher level of perceived familiarity with AI.

Conclusion:Our findings suggest that while support for AI in general is predicted by indicators of social advantage, these same indicators do not predict support for healthcare AI.
Women’s health service access and associated factors in Ethiopia: application of geographical information system and multilevel analysis
Authors: Demsash Addisalem Workie , Walle Agmasie Damtew
Published: January 2024

Objectives

Women’s access to healthcare services is challenged by various factors. This study aimed to assess women’s health service access and identify associated factors.

Methods

A cross-sectional study design with a two-stage stratified sampling technique, and 12 945 women from the 2016 Ethiopia Demographic and Health Survey dataset were used. The spatial hotspot analysis and purely Bernoulli-based model scan statistics were used to highlight hot and cold spot areas, and to detect significant local clusters of women’s health service access. A multilevel logistic regression analysis was used to assess factors that affect women’s access to health services. A variable with a p<o.o5 was considered as a significant factor.

Results

Overall, 29.8%% of women had health services access. 70.2% of women had problems with health services access such as: not wanting to go alone (42%), distance to health facilities (51%), getting the money needed for treatment (55%) and getting permission to go for medical care (32.3%). The spatial distribution of health service access in Ethiopia was clustered, and low health service access was observed in most areas of the country. Women who lived in primary, secondary and tertiary clusters were 96%, 39% and 72% more likely to access health services. Educational status, rich wealth status, media exposure and rural residence were statistically significant factors.

Conclusions

In Ethiopia, women have problems with health services access. The spatial distribution of health services access was non-random, and hotspot areas of women’s health service access were visualised in parts of Benishangul Gumez, Amhara, Afar, DireDawa, Harari, and Somali regions. Creating job opportunities, public health promotion regarding maternal health service utilisation and constructing nearby health facilities are required for better healthcare service access for women.
A natural language processing approach to categorise contributing factors from patient safety event reports
Authors: Tabaie Azade , Sengupta Srijan , Pruitt Zoe M , Fong Allan
Published: January 2024

Objectives

The objective of this study was to explore the use of natural language processing (NLP) algorithm to categorise contributing factors from patient safety event (PSE). Contributing factors are elements in the healthcare process (eg, communication failures) that instigate an event or allow an event to occur. Contributing factors can be used to further investigate why safety events occurred.

Methods

We used 10 years of self-reported PSE reports from a multihospital healthcare system in the USA. Reports were first selected by event date. We calculated χ2values for each ngram in the bag-of-words then selected N ngrams with the highest χ2values. Then, PSE reports were filtered to only include the sentences containing the selected ngrams. Such sentences were called information-rich sentences. We compared two feature extraction techniques from free-text data: (1) baseline bag-of-words features and (2) features from information-rich sentences. Three machine learning algorithms were used to categorise five contributing factors representing sociotechnical errors: communication/hand-off failure, technology issue, policy/procedure issue, distractions/interruptions and lapse/slip. We trained 15 binary classifiers (five contributing factors * three machine learning models). The models’ performances were evaluated according to the area under the precision-recall curve (AUPRC), precision, recall, and F1-score.

Results

Applying the information-rich sentence selection algorithm boosted the contributing factor categorisation performance. Comparing the AUPRCs, the proposed NLP approach improved the categorisation performance of two and achieved comparable results with baseline in categorising three contributing factors.

Conclusions

Information-rich sentence selection can be incorporated to extract the sentences in free-text event narratives in which the contributing factor information is embedded.