bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cognitive function and ability to complete a web‐based geriatric assessment among older adults with cancer
Authors: Hoffmann Alexxandra J. , Tin Amy L. , Vickers Andrew J. , Shahrokni Armin 
Published: November 2023

AbstractBackgroundThe purpose of this study was determined whether cognitive impairment is associated with time taken to complete the electronic rapid fitness assessment (eRFA). We hypothesized that taking more time to complete the eRFA will indicate worsened cognitive function.MethodsWe retrospectively identified patients who presented to the Memorial Sloan Kettering Cancer Center Geriatrics Service for preoperative evaluation and completed the eRFA as a part of their preoperative assessment from February 2015 to December 2020. Cognitive function was assessed using the Mini‐Cog©, which is a screening test for cognitive function status. Patients in this study underwent elective surgery and had a hospital length of stay ≥1 day. Time to complete the eRFA was automatically recorded by a web‐based tool; assistance with eRFA completion was self‐reported by the patient. In total, 2599 patients were included, of which 2387 had available Mini‐Cog© scores.ResultsOverall, 50% of surveys were completed without assistance, 37% were completed with assistance, and 13% were completed by somebody else; Mini‐Cog© scores were lower, corresponding to worsened cognitive function status, in patients requiring assistance (median score respectively, 5 vs. 4 vs. 3; p‐value <0.0001; rates of cognitive impairment 7.5%, 22%, and 38%). Among patients who completed the questionnaire independently, greater cognitive impairment was associated with longer time to complete the eRFA (change in score per 5 min = −0.09; 95% CI −0.14, −0.03; p = 0.002).ConclusionsWe found evidence that requirement for assistance in completing web‐based questionnaires, and time taken to complete a questionnaire, predict which patients benefit from more comprehensive cognitive function assessments. Future studies should further validate this finding in a more diverse population and establish optimal clinical pathways.
OsNAC5 orchestrates OsABI5 to fine‐tune cold tolerance in rice
Authors: Li Ruiqing , Song Yue , Wang Xueqiang , Zheng Chenfan , Liu Bo , Zhang Huali , Ke Jian , Wu Xuejing , Wu Liquan , Yang Ruifang , Jiang Meng 
Published: November 2023

ABSTRACTDue to its tropical origins, rice (Oryza sativa) is susceptible to cold stress, which poses severe threats to production. OsNAC5, a NAC‐type transcription factor, participates in the cold stress response of rice, but the detailed mechanisms remain poorly understood. Here, we demonstrate that OsNAC5 positively regulates cold tolerance at germination and in seedlings by directly activating the expression of ABSCISIC ACID INSENSITIVE 5 (OsABI5). Haplotype analysis indicated that single nucleotide polymorphisms in a NAC‐binding site in the OsABI5 promoter are strongly associated with cold tolerance. OsNAC5 also enhanced OsABI5 stability, thus regulating the expression of cold‐responsive (COR) genes, enabling fine‐tuned control of OsABI5 action for rapid, precise plant responses to cold stress. DNA affinity purification sequencing coupled with transcriptome deep sequencing identified several OsABI5 target genes involved in COR expression, including DEHYDRATION‐RESPONSIVE ELEMENT BINDING FACTOR 1A (OsDREB1A), OsMYB20, and PEROXIDASE 70 (OsPRX70). In vivo and in vitro analyses suggested that OsABI5 positively regulates COR gene transcription, with marked COR upregulation in OsNAC5‐overexpressing lines and downregulation in osnac5 and/or osabi5 knockout mutants. This study extends our understanding of cold tolerance regulation via OsNAC5 through the OsABI5‐CORs transcription module, which may be used to ameliorate cold tolerance in rice via advanced breeding.
Bayesian backcalculation of pavement properties using parallel transitional Markov chain Monte Carlo
Authors: Coletti Keaton , Romeo Ryan C. , Davis R. Benjamin 
Published: November 2023

AbstractThis paper presents a novel Bayesian method for backcalculation of pavement dynamic modulus, stiffness, thickness, and damping using falling weight deflectometer (FWD) data. The backcalculation procedure yields estimates and uncertainties for each pavement property of interest. As a by‐product of the Bayesian procedure, information about measurement error is recovered. The Bayesian method is tested on simulated FWD backcalculations and compared with a state‐of‐the‐art trust‐region optimization algorithm, and it achieves estimation errors that are nearly an order of magnitude lower than the trust‐region solver. Confidence intervals are computed from thousands of simulated backcalculations and are shown to quantify uncertainty in estimated pavement properties. To cope with the computational expense of backcalculation, a fully parallel transitional Markov chain Monte Carlo procedure is developed. The fully parallel algorithm scales well to computation with many processor cores, and it yields up to a 50% reduction in computation time when compared to existing parallel implementations.
Educated workers and firms' exporting behavior: The case of China
Authors: Che Yi , Lv Jinqiu , Zhang Yan 
Published: November 2023

AbstractThis article investigates the effect of China's college expansion policy on firms' exporting behavior. Taking advantage of this policy‐induced exogenous surge in skilled labor starting in 2002, our difference‐in‐differences estimates indicate that firms in more human‐capital‐intensive industries have been able to export more since 2002. We further show that this result is robust to a battery of sensitivity tests and controlling for other contemporaneous changes in economic environment. Turning to channels, we find that after 2002, the affected firms experienced greater improvements in product quality and exported relatively more to richer countries.
Evaluation of an online suicide prevention campaign targeting men
Authors: Stas Pauline , De Jaegere Eva , van Heeringen Kees , Ballon Anne , Portzky Gwendolyn 
Published: November 2023

AbstractBackgroundMen are at elevated risk of suicide compared to women. Adherence to traditional norms of masculinity can interfere with potential protective factors such as openness to talk and seeking social support, which can contribute to the increased suicide risk. An online public health campaign was developed to improve mental health among men and tackle the stigma surrounding it. This study aimed at examining whether the online suicide prevention campaign targeting men increased openness to talk about emotions and help‐seeking behavior and decreased hopelessness and adherence to traditional gender norms concerning self‐reliance.Method250 men (18+) from Flanders (Belgium) were recruited online and given access to the campaign website for a period of 3 days. Before and after viewing the campaign website, participants were asked to complete an online survey.ResultsViewing the campaign was associated with a small increase in help‐seeking intention when experiencing suicidal thoughts. Among men who reported mental health problems, a small increase in openness to communicating and expressing emotions was found after viewing the campaign. In general, participants evaluated the campaign positively.ConclusionThis study demonstrated the potential beneficial impact of an online prevention campaign specifically targeting men on health behaviors that may protect against suicidal behavior.
Adaptation of von Karman Institute for Fluid Dynamics’ Isentropic Compression Tube Facility for High-Speed Low-Pressure Turbines Testing
Authors: Torre Antonino Federico Maria , Merli Filippo , Valle Lorenzo Da , Patinios Marios , Lavagnoli Sergio , Ludovic Pintat 
Published: November 2023

Abstract
This paper presents the commissioning of a newly designed High-Speed Low-Pressure Turbine (LPT) stage, operating at transonic exit Mach numbers and low Reynolds numbers, typical of modern geared turbofan (GTF) applications. The work falls within the scope of the Clean Sky 2 project SPLEEN (Secondary and Leakage Flow Effects in High-speed Low-pressure Turbines), which consists of an extensive experimental characterization of LPTs for GTFs. Geometries and measurements will constitute a valuable open-access database for the validation of simulation methods and data analysis tools. At first, the characteristics of the research turbine are illustrated. The LPT stage is designed with an equal number of stationary vanes and shrouded rotor blades. The upstream and downstream hub cavities are purged and feature engine-realistic rim seals. The nominal operating condition of the stage is reported, along with a set of off-design conditions, obtained by varying rotor speed and purge mass flows. The second part of the paper describes the substantial revamping of the CT3 large-scale compression tube at Von Karman Institute for Fluid Dynamics, traditionally employed for high-pressure turbine testing, now adapted to host a high-speed LPT stage. The third section is an overview of the time-averaged and fast-response instrumentation. The test article is heavily instrumented, to maximize the amount of acquired data, while minimizing the number of blowdown tests. The dataset for each operating conditions includes aerothermal measurements in the annulus flow, in the hub cavities and in the shroud labyrinth seal. In addition, this section presents the design of an in-house traversing system for continuous probe traversing during the test. Finally, the outcome of the commissioning phase is discussed, with particular emphasis on the operating conditions stability, as well as on the inlet and cavity injection uniformity. The commissioning of a traversing system for continuous probe traversing during the short-duration test is also discussed.
Optimizing dosing of the cycloserine pro-drug terizidone in children with rifampicin-resistant tuberculosis
Authors: van der Laan Louvina E. , Garcia-Prats Anthony J. , McIlleron Helen , Abdelwahab Mahmoud T. , Winckler Jana L. , Draper Heather R. , Wiesner Lubbe , Schaaf H. Simon , Hesseling Anneke C. , Denti Paolo 
Published: November 2023

ABSTRACT
There are no pharmacokinetic data in children on terizidone, a pro-drug of cycloserine and a World Health Organization (WHO)-recommended group B drug for rifampicin-resistant tuberculosis (RR-TB) treatment. We collected pharmacokinetic data in children <15 years routinely receiving 15–20 mg/kg of daily terizidone for RR-TB treatment. We developed a population pharmacokinetic model of cycloserine assuming a 2-to-1 molecular ratio between terizidone and cycloserine. We included 107 children with median (interquartile range) age and weight of 3.33 (1.55, 5.07) years and 13.0 (10.1, 17.0) kg, respectively. The pharmacokinetics of cycloserine was described with a one-compartment model with first-order elimination and parallel transit compartment absorption. Allometric scaling using fat-free mass best accounted for the effect of body size, and clearance displayed maturation with age. The clearance in a typical 13 kg child was estimated at 0.474 L/h. The mean absorption transit time when capsules were opened and administered as powder was significantly faster compared to when capsules were swallowed whole (10.1 vs 72.6 min) but with no effect on bioavailability. Lower bioavailability (−16%) was observed in children with weight-for-age z-score below -2. Compared to adults given 500 mg daily terizidone, 2022 WHO-recommended pediatric doses result in lower exposures in weight bands 3–10 kg and 36–46 kg. We developed a population pharmacokinetic model in children for cycloserine dosed as terizidone and characterized the effects of body size, age, formulation manipulation, and underweight-for-age. With current terizidone dosing, pediatric cycloserine exposures are lower than adult values for several weight groups. New optimized dosing is suggested for prospective evaluation.
Unraveling the mechanism of ceftaroline-induced allosteric regulation in penicillin-binding protein 2a: insights for novel antibiotic development against methicillin-resistant
Staphylococcus aureus
Authors: Jiao Fangfang , Bao Yiqiong , Li Mengrong , Zhang Yan , Zhang Feng , Wang Pinkai , Tao Jun , Tong Henry H. Y. , Guo Jingjing 
Published: November 2023

ABSTRACT

Methicillin-resistant
Staphylococcus aureus
(MRSA) acquires high-level resistance against β-lactam antibiotics by expressing penicillin-binding protein 2a (PBP2a). PBP2a is a cell wall-synthesizing protein whose closed active site exhibits a reduced binding affinity toward β-lactam antibiotics. Ceftaroline (CFT), a fifth-generation cephalosporin, can effectively inhibit the PBP2a activity by binding to an allosteric site to trigger the active site opening, allowing a second CFT to access the active site. However, the essential mechanism behind the allosteric behavior of PBP2a remains unclear. Herein, computational simulations are employed to elucidate how CFT allosterically regulates the conformation and dynamics of the active site of PBP2a. While CFT stabilizes the allosteric domain surrounding it, it simultaneously enhances the dynamics of the catalytic domain. Specifically, the study successfully captured the opening process of the active pocket in the allosteric CFT-bound systems and discovered that CFT alters the potential signal-propagating pathways from the allosteric site to the active site. These findings reveal the implied mechanism of the CFT-mediated allostery in PBP2a and provide new insights into dual-site drug design or combination therapy against MRSA targeting PBP2a.
Subcutaneous infusion of high-dose benzathine penicillin G is safe, tolerable, and suitable for less-frequent dosing for rheumatic heart disease secondary prophylaxis: a phase 1 open-label population pharmacokinetic study
Authors: Kado Joseph , Salman Sam , Hla Thel K. , Enkel Stephanie , Henderson Robert , Hand Robert M. , Hort Adam , Page-Sharp Madhu , Batty Kevin , Moore Brioni R. , Bennett Julie , Anderson Anneka , Carapetis Jonathan , Manning Laurens 
Published: November 2023

ABSTRACT

Since 1955, the recommended strategy for rheumatic heart disease (RHD) secondary prophylaxis has been benzathine penicillin G [BPG; 1.2 MU (900 mg)] injections administered intramuscularly every 4 weeks. Due to dosing frequency, pain, and programmatic challenges, adherence is suboptimal. It has previously been demonstrated that BPG delivered subcutaneously at a standard dose is safe and tolerable and has favorable pharmacokinetics, setting the scene for improved regimens with less frequent administration. The safety, tolerability, and pharmacokinetics of subcutaneous infusions of high-dose BPG were assessed in 24 healthy adult volunteers assigned to receive either 3.6, 7.2, or 10.8 MU (three, six, and nine times the standard dose, respectively) as a single subcutaneous infusion. The delivery of the BPG to the subcutaneous tissue was confirmed with ultrasonography. Safety assessments, pain scores, and penicillin concentrations were measured for 16 weeks post-dose. Subcutaneous infusion of penicillin (SCIP) was generally well tolerated with all participants experiencing transient, mild infusion-site reactions. Prolonged elevated penicillin concentrations were described using a combined zero-order (44 days) and first-order (
t
1/2
= 12 days) absorption pharmacokinetic model. In simulations, time above the conventionally accepted target concentration of 20 ng/mL (0.02 µg/mL) was 57 days for 10.8 MU delivered by subcutaneous infusion every 13 weeks compared with 9 days of every 4-weekly dosing interval for the standard 1.2 MU intramuscular dose (i.e., 63% and 32% of the dosing interval, respectively). High-dose SCIP (BPG) is safe, has acceptable tolerability, and may be suitable for up to 3 monthly dosing intervals for secondary prophylaxis of RHD.
With a pinch of salt: metagenomic insights into Namib Desert salt pan microbial mats and halites reveal functionally adapted and competitive communities
Authors: Martínez-Alvarez Laura , Ramond Jean-Baptiste , Vikram Surendra , León-Sobrino Carlos , Maggs-Kölling Gillian , Cowan Don A. 
Published: November 2023

ABSTRACT

Salt pans or playas, which are saline-rich springs surrounded by halite evaporates in arid environments, have played an essential role in landscape erosion during the formation of the Namib Desert and are numerous in its central region. In this study, we used shotgun metagenomics to investigate the phylogenetic and functional capacities of the microbial communities from two salt pans (namely, Eisefeld and Hosabes) located in central Namib Desert, located in Southwest Africa. We studied the source and sink sediment mat communities of the saline streams, as well as those from two halites (crystallized structures on the stream margins). The microbial assemblages and potential functions were distinct in both niches. Independently from their localization (Eisfeld vs Hosabes and source vs sink), the sediment mat communities were dominated by members of the
Alpha-
and
Gamma-proteobacteria
classes, while halites were Archaea dominated and also contained high abundances of the extremely halophilic bacterium
Salinibacter
sp. (phylum
Bacteroidota
). Photoheterotrophy and chemoheterotrophy were the principal lifestyles in both niches, with halite communities having a reduced diversity of metabolic pathways. Intense microbial-virus interactions in both niches were implied by the widespread detection of CRISPR-Cas defense systems. We identified a putatively novel clade of type II CRISPR-Cas systems, as well as novel candidate viral lineages of the class Caudoviricetes and of Halobacteriales
-
infecting haloviruses. Putative gene transfer agent-like sequences within the
Alphaproteobacteria
were identified in the sediment mat communities. These horizontal gene transfer elements have the potential to drive genome plasticity and evolution of the
Alphaproteobacteria
in the Namib Desert salt pan microbiomes.

IMPORTANCE
The hyperarid Namib Desert is one of the oldest deserts on Earth. It contains multiple clusters of playas which are saline-rich springs surrounded by halite evaporites. Playas are of great ecological importance, and their indigenous (poly)extremophilic microorganisms are potentially involved in the precipitation of minerals such as carbonates and sulfates and have been of great biotechnological importance. While there has been a considerable amount of microbial ecology research performed on various Namib Desert edaphic microbiomes, little is known about the microbial communities inhabiting its multiple playas. In this work, we provide a comprehensive taxonomic and functional potential characterization of the microbial, including viral, communities of sediment mats and halites from two distant salt pans of the Namib Desert, contributing toward a better understanding of the ecology of this biome.
The potential for development of clinically relevant microbial resistance to rifaximin-α: a narrative review
Authors: DuPont Herbert L. 
Published: November 2023

SUMMARY

Rifaximin-α is a gut-targeted antibiotic indicated for numerous gastrointestinal and liver diseases. Its multifaceted mechanism of action goes beyond direct antimicrobial effects, including alterations in bacterial virulence, cytoprotective effects on host epithelial cells, improvement of impaired intestinal permeability, and reduction of proinflammatory cytokine expression via activation of the pregnane X receptor. Rifaximin-α is virtually non-absorbed, with low systemic drug levels contributing to its excellent safety profile. While there are high concentrations of drug in the colon, low water solubility leads to low colonic drug bioavailability, protecting the gut microbiome. Rifaximin-α appears to be more active in the bile-rich small bowel. Its important biologic effects are largely at sub-inhibitory concentration. Although
in vitro
testing of clinical isolates from rifaximin recipients has revealed rifaximin-resistant strains in some studies, the risk of emergent rifaximin-α resistance appears to be lower than for many other antibiotics. Rifaximin-α has been used for many years for traveler’s diarrhea with no apparent increase in resistance levels in causative pathogens. Further, rifaximin-α retains its efficacy after long-term and recurrent usage in chronic gastrointestinal disorders. There are numerous reasons why the risk of microbial resistance to rifaximin-α may be lower than that for other agents, including low intestinal bioavailability in the aqueous colon, the mechanisms of action of rifaximin-α not requiring inhibitory concentrations of drug, and the low risk of cross transmission of rifaximin-α resistance between bacterial species. Reported emergence of vancomycin-resistant
Enterococcus
in liver-disease patients maintained on rifaximin needs to be actively studied. Further studies are required to assess the possible correlation between
in vitro
resistance and rifaximin-α efficacy.
Transcription activator-like effectors from endosymbiotic bacteria control the reproduction of their fungal host
Authors: Richter Ingrid , Uzum Zerrin , Wein Philipp , Molloy Evelyn M. , Moebius Nadine , Stinear Timothy P. , Pidot Sacha J. , Hertweck Christian 
Published: November 2023

ABSTRACT

The phytopathogenic fungus
Rhizopus microsporus
harbors a bacterial endosymbiont (
Mycetohabitans rhizoxinica
) that produces a crucial virulence factor responsible for the characteristic symptoms of rice seedling blight. The persistence of this unique microbial alliance is ensured by evasion of fungal defense mechanisms by the resident endosymbionts and their strict control of fungal reproduction. A functional bacterial Type 3 secretion system (T3SS) is essential for the establishment of the symbiosis. Yet, the nature of the effector(s) secreted through the T3SS, and their effects on fungal physiology, has remained elusive. Using bioinformatic analysis, we identified genes encoding potential T3SS effectors, namely an alanine-tryptophan-arginine triad (AWR) peptide and a set of transcription activator-like (TAL) effectors, in the genomes of eight endofungal
Mycetohabitans
strains. Co-culture experiments demonstrated that the sporulating phenotype of apo-symbiotic
R. microsporus
is unaffected upon reinfection with
M. rhizoxinica
Δ
awr
compared to with wild-type
M. rhizoxinica
. In contrast, the ability of apo-symbiotic
R. microsporus
to produce mature sporangiophores when reinfected with
M. rhizoxinica
strains deficient in individual MTALs (
M. rhizoxinica
Δ
mtal1
,
M. rhizoxinica
Δ
mtal2
, and
M. rhizoxinica
Δ
mtal3
) is significantly reduced.
Trans
-complementation experiments showed restoration of fungal sporulation, thus confirming that TAL effectors produced by
M. rhizoxinica
(MTAL1, MTAL2, and MTAL3) are needed for fungal sporulation. Using fluorescence microscopy, we show that AWR- and MTAL-deficient
M. rhizoxinica
strains successfully colonize apo-symbiotic
R. microsporus
, revealing the importance of bacterial MTALs in establishing a stable symbiosis after fungal colonization. Our findings attribute a new function to members of the MTAL family of T3SS-associated effectors and provide deeper insights into host control by prokaryotic symbionts.

IMPORTANCE

Interactions between fungi and bacteria are critically important in ecology, medicine, and biotechnology. In this study, we shed light on factors that promote the persistence of a toxin-producing, phytopathogenic
Rhizopus-Mycetohabitans
symbiosis that causes severe crop losses in Asia. We present an unprecedented case where bacterially produced transcription activator-like (TAL) effectors are key to maintaining a stable endosymbiosis. In their absence, fungal sporulation is abrogated, leading to collapse of the phytopathogenic alliance. The
Mycetohabitans
TAL (MTAL)-mediated mechanism of host control illustrates a unique role of bacterial effector molecules that has broader implications, potentially serving as a model to understand how prokaryotic symbionts interact with their eukaryotic hosts.