bluuebunny/crossref_metadata_2025 huggingface dataset:
Parent‐reported problematic lying tendencies and BIS/BAS activity as predictors of children's antisocial lie‐telling
Authors: Tong Donia , Caivano Oksana , Lavoie Jennifer , Talwar Victoria
Published: July 2024

The current study examined whether age and parental reports of children's problematic lying, behavioural inhibition system (BIS) activity, and reward responsiveness predicted children's antisocial lie‐telling. Children from mostly middle and upper‐class Canadian families (ages 3–12, M = 6.23, SD = 2.52) participated in a modified Temptation Resistance Paradigm (TRP), where they were given opportunities to tell a self‐protective lie (to conceal a transgression) and an instrumental lie (to obtain a reward). Parents completed measures of their children's problematic lying tendencies, BIS activity, and reward responsiveness. Age and parent‐reported problematic lying and BIS activity were significant predictors of lie‐telling behaviour in the TRP. Instrumental liars were younger than dual liars (those who told both types of lies) and truth‐tellers. Truth‐tellers had lower parent‐reported problematic lying than instrumental and dual liars but not self‐protective liars. Dual liars had lower parent‐reported BIS activity than truth‐tellers; there were no differences among truth‐tellers, self‐protective liars, and instrumental liars. This study contributes to our understanding of the role of temperamental factors in children's lie‐telling propensity and the predictive utility of parent‐reported predictors for children's antisocial lie‐telling propensity. Our findings indicate that parents can identify and potentially address their children's problematic lying using their knowledge about their children's temperamental traits.
A new disease mapping method for improving data completeness of syndromic surveillance with high missing rates
Authors: Liao Yilan , Shi Yuanhao , Fan Zhirui , Zhu Zhiyu , Huang Binghu , Du Wei , Wang Jinfeng , Wang Liping
Published: July 2024

Syndromic surveillance is a type of public health surveillance that utilizes nonspecific indicators or symptoms associated with a particular disease or condition to detect and track disease outbreaks early. However, data completeness has been a significant challenge for syndromic surveillance systems in many countries. Incomplete data may make it difficult to accurately identify anomalies or trends in surveillance data. In this study, a new disease mapping method based on a high‐accuracy, low‐rank tensor completion (HaLRTC) algorithm is proposed to estimate the quarterly positivity rate of the human influenza virus (IFV) based on highly insufficient 2010–2015 respiratory syndromic surveillance data from the subtropical monsoon region of China. The HaLRTC algorithm is a spatiotemporal interpolation method applied to fill in missing or incomplete data using a low‐rank tensor structure. The results show that the accuracy (R2 = 0.880, RMSE = 0.037) of the proposed method is much higher than that of three traditional disease mapping methods: Cokriging, hierarchical Bayesian, and sandwich estimation methods. This study provides a new disease mapping approach to improve the quality and completeness of data in syndrome surveillance or other familiar systems with a large proportion of missing data.
Correctness of assertion and validity of inference
Authors: Martin‐Löf Per
Published: July 2024

This is a slightly edited transcript of a lecture given by Per Martin‐Löf on 26 October 2022 at the Rolf Schock Symposium in Stockholm. In 2020, the Rolf Schock Prize in Logic and Philosophy was awarded to Dag Prawitz and Per Martin‐Löf, and the symposium was organised in their honour. The transcript was prepared by Ansten Klev and edited by the author.
Hotspot Exon 15 Mutations in BRAF Are Uncommon in Feline Tumours
Authors: Kuroki Kei , Hoang Christine Tran , Rogic Anita M. , Rindt Hans , Simenson Angelynn , Noall Lucie G. , Bryan Jeffrey N. , Johnson Gayle C. , Chu Shirley
Published: July 2024

BRAF is one of multiple RAF proteins responsible for the activation of the MAPK cell signalling cascade involved in cell growth, differentiation, and survival. A hotspot BRAFV600E mutation, in exon 15, was determined to be a driver in 100% hairy cell leukaemias, 50%–60% of human melanomas, 30%–50% of human thyroid carcinomas and 10%–20% of human colorectal carcinomas. The orthologous BRAFV595E mutation was seen in 67% and 80% of canine bladder transitional cell carcinomas and prostatic adenocarcinomas, respectively. Since veterinary and human cancers exploit similar pathways and BRAF is highly conserved across species, BRAF can be expected to be a driver in a feline cancer. Primers were developed to amplify exon 15 of feline BRAF. One hundred ninety‐six feline tumours were analysed. Sanger sequencing of the 211 bp PCR amplicon was done. A BRAF mutation was found in one tumour, a cutaneous melanoma. The mutation was a BRAFV597E mutation, orthologous to the canine and human hotspot mutations. A common synonymous variant, BRAFT586T, was seen in 23% (47/196) of tumours. This variant was suspected to be a single nucleotide polymorphism. BRAF was not frequently mutated in common feline tumours or in tumour types that frequently harbour BRAF mutations in human and canine cancers. As is seen in canine cancer genomics, the mutational profile in feline tumours may not parallel the histologic equivalent in human oncology.
Investigation of ocular surface parameters in dogs with different cephalic conformations using veterinary ocular surface analyzer (OSA‐VET)
Authors: Li Yan‐Hui , Martins Bianca , Lin Chung‐Tien
Published: July 2024

Objective

To compare ocular surface parameters in dogs with different cephalic conformations and evaluate correlations among tests.

Animals Studied

Sixty‐eight privately owned dogs.

Procedures

The study categorized canine eyes into three groups based on the craniofacial ratio (CFR): brachycephaly (≤0.52), mesocephaly (>0.52 to <0.67), and dolichocephaly (≥0.67). All eyes were examined using an ocular surface analyzer (OSA‐VET) to determine lipid layer thickness (LLT) of the tear film, tear meniscus height (TMH), non‐invasive tear breakup time (NIBUT), and meibomian gland loss rate of the lower eyelids (MGLRL). Schirmer tear test 1 (STT‐1) and tear film breakup time (TBUT) were also performed. Statistical analyses involved one‐way ANOVA, Kruskal–Wallis H test, post hoc Holm–Sidak test, and Pearson correlation coefficient.

Results

While STT‐1 showed no significant difference among dog groups, brachycephalic dogs had significantly lower values in TBUT, NIBUT, and LLT, and a higher TMH, compared to mesocephalic and dolichocephalic dogs. Additionally, brachycephalic dogs exhibited a significantly higher MGLRL than dolichocephalic dogs. Correlations among tests were generally weak to moderate (r < .6) except for a strong correlation between CFR and LLT (r = .641, p < .001), and between TBUT and NIBUT (r = .899, p < .001).

Conclusions

Brachycephalic morphology predisposes dogs to a significantly thinner lipid layer and diminished tear film stability, likely due to factors such as impaired meibomian gland function and increased ocular exposure compared to other cephalic conformations, thereby increasing their risk of keratoconjunctivitis sicca (KCS). OSA‐VET shows a valuable tool to provide more comprehensive and precise diagnosis for canine ocular surface disorders.
New records of flowering plants for the flora of Myanmar collected from Southern Shan State II
Authors: JUNG Eui-Kwon , KANG Dae-Hyun , ONG Homervergel G. , KYAW Naing Oo , KIM Young-Dong
Published: July 2024

A three-year collaborative plant survey among researchers from Korean and Myanmar in the vicinity of the Panlaung-Pyadalin Cave Wildlife Sanctuary (PPCWS) in the southern Shan State of Myanmar led to the addition of four newly recorded flowering plant taxa for the country’s flora. Some of the notable species are Aeschynanthus minutifolius (Gesneriaceae), which was previously known to be distributed only in Thailand, and Trailliaedoxa gracilis (Rubiaceae), the only species in its genus, known only to occur in China narrowly. These additional findings are expected to augment our understanding of the plant diversity in Myanmar and can be instrumental in advancing botanical knowledge in general in the region.
On the variance of the mean width of random polytopes circumscribed around a convex body
Authors: Bakó‐Szabó Alexandra , Fodor Ferenc
Published: July 2024

Let be a convex body in in which a ball rolls freely and which slides freely in a ball. Let be the intersection of i.i.d. random half‐spaces containing chosen according to a certain prescribed probability distribution. We prove an asymptotic upper bound on the variance of the mean width of as . We achieve this result by first proving an asymptotic upper bound on the variance of the weighted volume of random polytopes generated by i.i.d. random points selected according to certain probability distributions, then, using polarity, we transfer this to the circumscribed model.
Myths and methodologies: Assessing glycaemic control and associated regulatory mechanisms in human physiology research
Authors: Wrench Elizabeth , Subar Daren A. , Bampouras Theodoros M. , Lauder Robert M. , Gaffney Christopher J.
Published: July 2024

Accurate measurements of glycaemic control and the underpinning regulatory mechanisms are vital in human physiology research. Glycaemic control is the maintenance of blood glucose concentrations within optimal levels and is governed by physiological variables including insulin sensitivity, glucose tolerance and β‐cell function. These can be measured with a plethora of methods, all with their own benefits and limitations. Deciding on the best method to use is challenging and depends on the specific research question(s). This review therefore discusses the theory and procedure, validity and reliability and any special considerations of a range common methods used to measure glycaemic control, insulin sensitivity, glucose tolerance and β‐cell function. Methods reviewed include glycosylated haemoglobin, continuous glucose monitors, the oral glucose tolerance test, mixed meal tolerance test, hyperinsulinaemic euglycaemic clamp, hyperglycaemic clamp, intravenous glucose tolerance test and indices derived from both fasting concentrations and the oral glucose tolerance test. This review aims to help direct understanding, assessment and decisions regarding which method to use based on specific physiology‐related research questions.
Cold Gas Spraying Copper Metal on AlN Ceramics as an Alternative to Thick Direct Bond Copper Substrates for Power Electronics
Authors: Guerrero-Fernandez Margie , Quintero Pedro , Ozdemir Ozan Cagatay
Published: July 2024

This study investigates the use of cold gas spraying (CGS) as a low-temperature additive manufacturing method to bond copper onto aluminum nitride (AlN) substrates for electronic packaging of high-power applications. While the direct bond copper (DBC) technique is commonly used, it has limitations due to the large mismatch in the coefficient of thermal expansion, which affects substrate reliability. This work employed CGS to mechanically bond Cu on AlN. The study explores the effect of multiple sprays, spray angle, and spraying direction on deposition thickness, coating surface roughness, and deposited volume through a factorial design of experiments (DOE). The results, based on optical and scanning electron microscopy combined with profilometry data, showed that coatings sprayed at a 60 deg angle had a smoother profile topography and less surface roughness than those sprayed at a 90 deg angle. After depositing ten layers, a surface roughness (Sa) of around 30 μm and a coating thickness of over 300 μm were successfully attained. These findings provide valuable insights into the processing factors affecting the growth and quality of copper coatings on AlN substrates via multiple sprays, thus enabling the realization of CGS technology as a potential solution to DBC substrates for electronic packaging of wide-bandgap semiconductors.
Variable Area Jet Impingement for Enhanced Junction Temperature Control of High-Power Electronics
Authors: Whitt Reece , Huitink David
Published: July 2024

Convective heat transfer by jet impingement cooling offers a suitable solution for high heat flux applications. Compared to techniques that rely on bulk conduction in series with convection, direct liquid impingement reduces the thermal resistance between power device hot spots and the coolant. Although capable of highly efficient cooling, static impingement devices must be designed for the worst-case cooling requirements for a transient power profile. This can result in wasted hydraulic performance. Aircraft, highway vehicles, and heavy machinery fall into this category where a substantial factor of safety is required. This work proposes a method for improving power electronics reliability by limiting temperature fluctuations at reduced coolant pressure requirements during transient power cycling using a variable area jet. Single phase jet impingement cooling is implemented in an active control scheme using a variable diameter iris mechanism as the primary nozzle architecture. In addition to pressure drop and temperature control, the active nozzle structure introduces the ability to create pulsating jet flows to further enhance the heat transfer compared to fixed-geometry nozzles. The key underlying fluid mechanics characteristic of pulsating flows is the effect of disrupting the thermal boundary layer on the electrical device surface. By introducing a variable diameter jet, eddy formation can be fine-tuned for optimal boundary layer disruption. Using the definition of the Strouhal number, vortex shedding created by the nonsteady jet flows is directly correlated with the resulting Nusselt number as a function of the iris kinematics. An experimental apparatus for jet impingement thermal-fluid testing is used to evaluate the Nusselt number versus Strouhal number for a parametric study of variable diameter iris configurations. The apparatus utilizes a voice coil actuator to achieve sine and square waveforms, to vary the amplitude of actuation, and to vary the mean of actuation. Finally, power cycling with a single emulated hot spot is performed to estimate the reliability increase as a result of maintaining constant junction temperatures with the active jet impingement scheme.
Microstructural and kinetics analysis of FeB–Fe2B layer grown by pulsed-DC powder-pack boriding on AISI 316 L steel
Authors: Campos-Silva I. , Cedeño-Velázquez J. , Contla-Pacheco A. D. , Arzate-Vázquez I. , Castillo-Vela L. E. , Olivares-Luna M. , Rosales-Lopez J. L. , Espino-Cortes F. P.
Published: July 2024

In this study, novel findings were obtained regarding the influence of a 10 A current intensity on the growth of an FeB–Fe2B layer during pulsed-DC powder-pack boriding. Boride layer formation was carried out on AISI 316 L steel at 1123–1223 K for different exposure times at each temperature, considering 10 s polarity inversion cycles. The boride layer was characterized by x-ray diffraction and high-speed Berkovich nanoindentation, the latter being used to determine the hardness and reduced Young’s modulus mappings along the depth of the layer-substrate system. Moreover, the growth kinetics of the FeB–Fe2B layer on the steel’s surface was modeled using the heat balance integral method (HBIM). This involved transforming Fick’s second law into ordinary differential equations over time, assuming a quadratic boron concentration profile in space to determine the B diffusion coefficients in FeB and Fe2B, respectively. From the Arrhenius relationship, the B activation energies in the boride layer were estimated considering the contribution of the electromigration effect; the results showed an approximately 30% reduction compared to the values obtained in the conventional powder-pack boriding for AISI 316 L steel. Finally, the theoretical layer thickness obtained by the HBIM demonstrated an error of no more than 5% against the experimental FeB and FeB + Fe2B layer thickness values.
Development of a luciferase-based Gram-positive bacterial reporter system for the characterization of antimicrobial agents
Authors: Lam Nga Man , Tsang Tsz Fung , Qu Jiayi , Tsang Man Wai , Tao Yuan , Kan Cheuk Hei , Zou Qingyu , Chan King Hong , Chu Adrian Jun , Ma Cong , Yang Xiao
Published: July 2024

Mechanistic investigations are of paramount importance in elucidating the modes of action of antibiotics and facilitating the discovery of novel drugs. We reported a luciferase-based reporter system using bacterial cells to unveil mechanisms of antimicrobials targeting transcription and translation. The reporter gene
Nluc
encoding NanoLuciferase (NanoLuc) was integrated into the genome of the Gram-positive model organism,
Bacillus subtilis
, to generate a reporter strain BS2019. Cellular transcription and translation levels were assessed by quantifying the amount of
Nluc
mRNA as well as the luminescence catalyzed by the enzyme NanoLuc. We validated this system using three known inhibitors of transcription (rifampicin), translation (chloramphenicol), and cell wall synthesis (ampicillin). The
B. subtilis
reporter strain BS2019 successfully revealed a decline in
Nluc
expression by rifampicin and NanoLuc enzyme activity by chloramphenicol, while ampicillin produced no observable effect. The assay was employed to characterize a previously discovered bacterial transcription inhibitor, CUHK242, with known antimicrobial activity against drug-resistant
Staphylococcus aureus
. Production of
Nluc
mRNA in our reporter BS2019 was suppressed in the presence of CUHK242, demonstrating the usefulness of the construct, which provides a simple way to study the mechanism of potential antibiotic candidates at early stages of drug discovery. The reporter system can also be modified by adopting different promoters and reporter genes to extend its scope of contribution to other fields of work.

IMPORTANCE

Discovering new classes of antibiotics is desperately needed to combat the emergence of multidrug-resistant pathogens. To facilitate the drug discovery process, a simple cell-based assay for mechanistic studies is essential to characterize antimicrobial candidates. In this work, we developed a luciferase-based reporter system to quantify the transcriptional and translational effects of potential compounds and validated our system using two currently marketed drugs. Reporter strains generated in this study provide readily available means for identifying bacterial transcription inhibitors as prospective novel antibacterials. We also provided a series of plasmids for characterizing promoters under various conditions such as stress.
Viral communities in a pH>10 serpentinite-like environment: insight into diversity and potential roles in modulating the microbiomes by bioactive vitamin B
9
synthesis
Authors: He Yu , Zhuo Shiyan , Gao Donghao , Pan Yue , Li Meng , Pan Jie , Jiang Yongguang , Hu Yidan , Guo Jinzhi , Lin Qin , Sanford Robert A. , Sun Weimin , Shang Jianying , Wei Na , Peng Shuming , Jiang Zhou , Li Shuyi , Li Yongzhe , Dong Yiran , Shi Liang
Published: July 2024

Viral communities exist in a variety of ecosystems and play significant roles in mediating biogeochemical processes, whereas viruses inhabiting strongly alkaline geochemical systems remain underexplored. In this study, the viral diversity, potential functionalities, and virus–host interactions in a strongly alkaline environment (pH = 10.4–12.4) exposed to the leachates derived from the serpentinization-like reactions of smelting slags were investigated. The viral populations (e.g., Herelleviridae, Queuovirinae, and Inoviridae) were closely associated with the dominating prokaryotic hosts (e.g.,
Meiothermus
, Trueperaceae, and
Serpentinomonas
) in this ultrabasic environment. Auxiliary metabolic genes (AMGs) suggested that viruses may enhance hosts’ fitness by facilitating cofactor biosynthesis, hydrogen metabolism, and carbon cycling. To evaluate the activity of synthesis of essential cofactor vitamin B
9
by the viruses, a viral
folA
(v
folA
) gene encoding dihydrofolate reductase (DHFR) was introduced into a thymidine-auxotrophic strain
Escherichia coli
MG1655 Δ
folA
mutant, which restored the growth of the latter in the absence of thymidine. Notably, the homologs of the validated vDHFR were globally distributed in the viromes across various ecosystems. The present study sheds new light on the unique viral communities in hyperalkaline ecosystems and their potential beneficial impacts on the coexisting microbial consortia by supplying essential cofactors.

IMPORTANCE

This study presents a comprehensive investigation into the diversity, potential functionalities, and virus–microbe interactions in an artificially induced strongly alkaline environment. Functional validation of the detected viral
folA
genes encoding dihydrofolate reductase substantiated the synthesis of essential cofactors by viruses, which may be ubiquitous, considering the broad distribution of the viral genes associated with folate cycling.
Immunization with an mRNA DTP vaccine protects against pertussis in rats
Authors: Bitzer Graham J. , Fitzgerald Nicholas A. , DeJong Megan A. , Cunningham Casey , Chapman Joshua A. , Boehm Dylan T. , Pyles Gage M. , Huckaby Annalisa B. , Miller Sarah J. , Dublin Spencer R. , Warden Matthew D. , Barbier Mariette , Damron F. Heath
Published: July 2024

Bordetella pertussis
is a Gram-negative bacterium that is the causative agent of the respiratory disease known as pertussis. Since the switch to the acellular vaccines of DTaP and Tap, pertussis cases in the US have risen and cyclically fallen. We have observed that mRNA pertussis vaccines are immunogenic and protective in mice. Here, we further evaluated the pertussis toxoid mRNA antigen and refined the formulation based on optimal pertussis toxin neutralization
in vivo
. We next evaluated the mRNA pertussis vaccine in Sprague-Dawley rats using an aerosol
B. pertussis
challenge model paired with whole-body plethysmography to monitor coughing and respiratory function. Female Sprague-Dawley rats were primed and boosted with either commercially available vaccines (DTaP or wP-DTP), an mRNA-DTP vaccine, or mock-vaccinated. The mRNA-DTP vaccine was immunogenic in rats and induced antigen-specific IgG antibodies comparable to DTaP. Rats were then aerosol challenged with a streptomycin-resistant emerging clinical isolate D420Sm1. Bacterial burden was assessed at days 1 and 9 post-challenge, and the mRNA vaccine reduced burden equal to both DTaP and wP-DTP. Whole-body plethysmography revealed that mRNA-DTP vaccinated rats were well protected against coughing which was comparable to the non-challenged group. These data suggest that an mRNA-DTP vaccine is immunogenic in rats and provides protection against aerosolized
B. pertussis
challenge in Sprague-Dawley rats.
Evaluation of a BioFire multiplex PCR panel for detection of joint infections using retrospective and prospectively collected specimens
Authors: Moran Angelica , Arellano Jekzaly , Bregman Karen , McElvania Erin
Published: July 2024

The BioFire Joint Infection Panel (JI panel) is a newly FDA-approved multiplex PCR assay for detection of common bone and joint pathogens with 39 targets which include select Gram-positive and Gram-negative bacteria, yeast, and antimicrobial resistance genes. We evaluated the performance of the JI panel in detecting joint infections in our patient population. Sixty-three frozen, residual joint fluid specimens were retrospectively tested using the JI panel. An additional 104 residual joint fluid specimens were de-identified and prospectively tested within 1 week of collection. Results from routine bacterial cultures were used as the reference standard, which included inoculation to agar plates and blood culture bottles. For the frozen specimens, the JI panel showed a positive percent agreement (PPA) of 92.8% and a negative percent agreement (NPA) of 97.1%. PPA was 71.4% and NPA was 94.8% for fresh specimens. A total of 12 discrepancies were observed among the 167 specimens tested. The JI panel demonstrated good overall agreement with routine culture for the detection of joint infections and may improve timely diagnosis when used in conjunction with bacterial culture. However, potential false-positive and false-negative results were observed in both retrospective and prospective testing of specimens.

IMPORTANCE

The BioFire JI panel is a new commercially available multiplex PCR assay for detecting common pathogens causing bone and joint infections. The test is performed directly on joint fluids with a fast turnaround time of 1 hour. Our study shows that while the JI panel overall shows good agreement with routine culture, discrepancies were observed in 7% of cases and results should be interpreted with appropriate clinical context.
Vaccine strains of Rift Valley fever virus exhibit attenuation at the maternal–fetal placental interface
Authors: McMillen Cynthia M. , Megli Christina , Radisic Rebecca , Skvarca Lauren B. , Hoehl Ryan M. , Boyles Devin A. , McGaughey Jackson J. , Bird Brian H. , McElroy Anita K. , Hartman Amy L.
Published: July 2024

Rift Valley fever virus (RVFV) infection causes abortions in ruminant livestock and is associated with an increased likelihood of miscarriages in women. Using sheep and human placenta explant cultures, we sought to identify tissues at the maternal–fetal interface targeted by RVFV. Sheep villi and fetal membranes were highly permissive to RVFV infection resulting in markedly higher virus titers than human cultures. Sheep cultures were most permissive to wild-type RVFV and ΔNSm infection, while live-attenuated RVFV vaccines (LAVs; MP-12, ΔNSs, and ΔNSs/ΔNSm) exhibited reduced replication. The human fetal membrane restricted wild-type and LAV replication, and when infection occurred, it was prominent on the maternal-facing side. Type I and type III interferons were induced in human villi exposed to LAVs lacking the NSs protein. This study supports the use of sheep and human placenta explants to understand vertical transmission of RVFV in mammals and whether LAVs are attenuated at the maternal–fetal interface.

IMPORTANCE

A direct comparison of replication of Rift Valley fever virus (RVFV) in sheep and human placental explants reveals comparative efficiencies and permissivity to infection and replication. Vaccine strains of RVFV demonstrated reduced infection and replication capacity in the mammalian placenta. This study represents the first direct cross-host comparison of the vertical transmission capacity of this high-priority emerging mosquito-transmitted virus.
In vitro
higher-order oligomeric assembly of the respiratory syncytial virus M2-1 protein with longer RNAs
Authors: Gao Yunrong , Raghavan Anirudh , Espinosa Garcia Sara Andrea , Deng Bowei , Hurtado de Mendoza Diego , Liang Bo
Published: July 2024

The respiratory syncytial virus (RSV) M2-1 protein is a transcriptional antitermination factor crucial for efficiently synthesizing multiple full-length viral mRNAs. During RSV infection, M2-1 exists in a complex with mRNA within cytoplasmic compartments called inclusion body-associated granules (IBAGs). Prior studies showed that M2-1 can bind along the entire length of viral mRNAs instead of just gene-end (GE) sequences, suggesting that M2-1 has more sophisticated RNA recognition and binding characteristics. Here, we analyzed the higher oligomeric complexes formed by M2-1 and RNAs
in vitro
using size exclusion chromatography (SEC), electrophoretic mobility shift assays (EMSA), negative stain electron microscopy (EM), and mutagenesis. We observed that the minimal RNA length for such higher oligomeric assembly is about 14 nucleotides for polyadenine sequences, and longer RNAs exhibit distinct RNA-induced binding modality to M2-1, leading to enhanced particle formation frequency and particle homogeneity as the local RNA concentration increases. We showed that particular cysteine residues of the M2-1 cysteine-cysteine-cystine-histidine (CCCH) zinc-binding motif are essential for higher oligomeric assembly. Furthermore, complexes assembled with long polyadenine sequences remain unaffected when co-incubated with ribonucleases or a zinc chelation agent. Our study provided new insights into the higher oligomeric assembly of M2-1 with longer RNA.

IMPORTANCE

Respiratory syncytial virus (RSV) causes significant respiratory infections in infants, the elderly, and immunocompromised individuals. The virus forms specialized compartments to produce genetic material, with the M2-1 protein playing a pivotal role. M2-1 acts as an anti-terminator in viral transcription, ensuring the creation of complete viral mRNA and associating with both viral and cellular mRNA. Our research focuses on understanding M2-1’s function in viral mRNA synthesis by modeling interactions in a controlled environment. This approach is crucial due to the challenges of studying these compartments
in vivo
. Reconstructing the system
in vitro
uncovers structural and biochemical aspects and reveals the potential functions of M2-1 and its homologs in related viruses. Our work may contribute to identifying targets for antiviral inhibitors and advancing RSV infection treatment.
Complete genome sequence of
Cereibacter sphaeroides
f. sp. denitrificans strain IL106
Authors: Stock Emma K. , Terrell Kaziah J. , Rayyan Amiera A. , Kyndt John A.
Published: July 2024

Cereibacter sphaeroides
is a non-sulfur purple bacterium, one of the most versatile and thoroughly studied species of its kind, can grow on a variety of compounds photoheterotrophically, and is often used in bioremediation. We present the complete genome of
Cereibacter sphaeroides
f. sp. denitrificans underscoring its unique features.
Updating the Upper Cretaceous (Campanian) Two Medicine Formation of Montana: Lithostratigraphic revisions, new CA-ID-TIMS U-Pb ages, and a calibrated framework for dinosaur occurrences
Authors: Rogers Raymond R. , Horner John R. , Ramezani Jahandar , Roberts Eric M. , Varricchio David J.
Published: July 2024

The Campanian Two Medicine Formation of northwestern Montana, USA, is richly fossiliferous, and discoveries made within the unit over the past century have greatly advanced our appreciation of dinosaur paleobiology and evolution. Previously undifferentiated from a lithostratigraphic perspective, the formation is now subdivided into four new members that include (from base to top) (1) the Rock City Member, (2) the Shields Crossing Member, (3) the Hagans Crossing Member, and (4) the Flag Butte Member. These new formal units and their associated fossil occurrences are also now included in an age model founded on eight high-resolution chemical abrasion–isotope dilution–thermal ionization mass spectrometry (CA-ID-TIMS) U-Pb ages. New age data confirm that the Two Medicine Formation accumulated during much of the Campanian, with deposition spanning ca. 82.4 Ma to 74.4 Ma. New age data further indicate that a major reorganization of depositional systems, marked by a shift from predominantly lacustrine to alluvial facies and accompanied by a dramatic increase in accommodation, transpired near the base of the new Flag Butte Member at ca. 76.3 Ma. This change in depositional regime correlates in age with the Judith River–Belly River discontinuity, which marks the contact between the McClelland Ferry and Coal Ridge Members in the Judith River Formation and coincides with the onset of the Bearpaw transgression in north-central Montana. The new lithostratigraphic and chronostratigraphic framework for the Two Medicine Formation serves to contextualize and calibrate the formation’s rich dinosaur fossil record, which can now be interrogated with increased clarity and precision. These results also provide ground truth for numerical models that explore the structure of the fossil record in relation to alluvial architecture and terrestrial sequence stratigraphy.
Neurosarcoidosis manifesting as cavernous sinus syndrome in systemic sarcoidosis
Authors: Gao Manxin , Kwon Gi Tae , Amin Mohammad Ruhul
Published: July 2024

Neurosarcoidosis can manifest in various neurological presentations. The occurrence of cavernous sinus involvement in neurosarcoidosis is rare, which can complicate the diagnostic process. We present a case of neurosarcoidosis demonstrating progressively deteriorating right cavernous sinus syndrome in a woman in her 50s, affecting the oculomotor, abducens and the ophthalmic division of the trigeminal nerves. MRI demonstrated meningeal thickening along the lateral wall of the right cavernous sinus, and a pan-CT scan of the chest, abdomen and pelvis revealed disseminated sarcoidosis involving the lungs and the liver. Histopathological analysis of the liver lesion ultimately confirmed the diagnosis of sarcoidosis. This case underscores the significance of considering neurosarcoidosis as a potential cause of cavernous sinus syndrome. In such cases, early initiation of corticosteroid treatment, with or without steroid-sparing agents, is crucial to prevent disease progression and relapse.
Adult granulosa cell tumour camouflaged as mucinous neoplasm
Authors: Nerune Savitri M , Das Sayandeep K , Pawar Monika
Published: July 2024

This case report delves into the diagnostic intricacies and clinical management of adult granulosa cell tumour (AGCT) in a woman in her 50s, presenting with pain abdomen. Initial imaging investigations like ultrasound suggested diagnosis of benign cystadenoma. Further MRI revealed a large well-defined multiloculated lesion so a diagnosis of neoplastic aetiology/likely mucinous cystadenocarcinoma was offered. However, the definitive diagnosis was established through meticulous histopathological examination, revealing characteristic features of AGCT, a rare ovarian neoplasm. The case underscores the diagnostic challenges posed by AGCT, the importance of integrating clinical, radiological and histopathological data, and the necessity for a multidisciplinary approach for accurate diagnosis and optimal patient management.
Methotrexate versus conventional disease-modifying antirheumatic drugs in the treatment of non-anterior sarcoidosis-associated uveitis
Authors: Leclercq Mathilde , Sève Pascal , Biard Lucie , Vautier Mathieu , Maalouf Georgina , Leroux Gaëlle , Domont Fanny , Toutée Adélaïde , Fardeau Christine , Sales de Gauzy Thomas , Touhami Sara , Kodjikian Laurent , Cacoub Patrice , Bodaghi Bahram , Saadoun David , Desbois Anne-Claire
Published: July 2024

Aims

To compare the safety and efficacy of methotrexate (MTX), mycophenolate mofetil (MMF) and azathioprine (AZA) in non-anterior sarcoidosis-associated uveitis.

Methods

Retrospective study including non-anterior sarcoidosis-associated uveitis according to the revised International Workshop on Ocular Sarcoidosis criteria. The primary outcome was defined as the median time to relapse or occurrence of serious adverse events leading to treatment discontinuation.

Results

58 patients with non-anterior sarcoidosis-associated uveitis (MTX (n=33), MMF (n=16) and AZA (n=9)) were included. The time to treatment failure (ie, primary outcome) after adjustment for corticosteroids dose and the presence of vasculitis was significantly higher with MTX (median time of 34.5 months with MTX (IQR: 11.8 –not reached) vs 8.4 months (3.1–22.9) with MMF and 16.8 months (8.0–90.1) with AZA (p=0.020)). The risk of relapse at 12 months was more than twice lower in MTX as compared with MMF (p=0.046). Low visual acuity at the last visit was significantly lower with MTX (4% vs 9% in MMF vs 57% in AZA group (p=0.008)). Regarding all 75 lines of treatment (MTX (n=39), MMF (n=24) and AZA (n=12)), MTX was more effective than MMF and AZA to obtain treatment response at 3 months (OR 10.85; 95% CI 1.13 to 104.6; p=0.039). Significant corticosteroid-sparing effect at 12 months (p=0.035) was only observed under MTX. Serious adverse events were observed in 6/39 (15%), 5/24 (21%) and 2/12 (17%) with MTX, MMF and AZA, respectively.

Conclusion

In non-anterior sarcoidosis-associated uveitis, MTX seems to be more efficient compared with AZA and MMF and with an acceptable safety profile.
Topical glyceryl trinitrate (GTN) and eccentric exercises in the treatment of mid-portion achilles tendinopathy (the NEAT trial): a randomised double-blind placebo-controlled trial
Authors: Kirwan Paul D , Duffy Trevor , French Helen P
Published: July 2024

Objectives

To investigate if daily treatment with glyceryl trinitrate (GTN) ointment, over 24 weeks combined with a 12-week eccentric exercise programme is more effective for chronic mid-portion Achilles tendinopathy than placebo ointment and eccentric exercise.

Methods

This was a single-site randomised double-blind placebo-controlled trial at an acute hospital, Dublin, Ireland. Patients with chronic mid-portion Achilles tendinopathy were randomised to either 24 weeks of daily GTN ointment or placebo ointment. Both groups received an identical 12-week eccentric exercise programme. The primary outcome measure was the Victorian Institute of Sport Assessment–Achilles (VISA-A) questionnaire at 24 weeks, which measures pain, function and activity. Secondary outcomes included pain severity, self-reported physical function, calf muscle function, pressure pain thresholds and ultrasound changes. Statistical analyses were performed according to intention-to-treat principles.

Results

76 patients (30 women; 46 men, mean age±SD, 45.6±8.2 years) were recruited for the trial. Significant improvements in VISA-A scores occurred in both groups at 6-week, 12-week and 24-week follow-up. The increase was not significantly different between groups, adjusted mean between-group difference from baseline to week 6, –1.33 (95% CI –6.96 to 4.31); week 12, −1.25 (95% CI −8.0 to 5.49) and week 24, –3.8 (95% CI –10.6 to 3.0); negative values favour GTN. There was no significant between-group difference in any of the secondary outcome measures at 6, 12 and 24 weeks.

Conclusions

Adding daily GTN ointment over 24 weeks to a 12-week eccentric exercise programme did not improve pain, function and activity level in patients with chronic mid-portion Achilles tendinopathy when compared with placebo ointment.
Where is the research on sport-related concussion in Olympic athletes? A descriptive report and assessment of the impact of access to multidisciplinary care on recovery
Authors: Romeas Thomas , Croteau Félix , Leclerc Suzanne
Published: July 2024

Objectives

This cohort study reported descriptive statistics in athletes engaged in Summer and Winter Olympic sports who sustained a sport-related concussion (SRC) and assessed the impact of access to multidisciplinary care and injury modifiers on recovery.

Methods

133 athletes formed two subgroups treated in a Canadian sport institute medical clinic: earlier (≤7 days) and late (≥8 days) access. Descriptive sample characteristics were reported and unrestricted return to sport (RTS) was evaluated based on access groups as well as injury modifiers. Correlations were assessed between time to RTS, history of concussions, the number of specialist consults and initial symptoms.

Results

160 SRC (median age 19.1 years; female=86 (54%); male=74 (46%)) were observed with a median (IQR) RTS duration of 34.0 (21.0–63.0) days. Median days to care access was different in the early (1; nSRC=77) and late (20; nSRC=83) groups, resulting in median (IQR) RTS duration of 26.0 (17.0–38.5) and 45.0 (27.5–84.5) days, respectively (p<0.001). Initial symptoms displayed a meaningful correlation with prognosis in this study (p<0.05), and female athletes (52 days (95% CI 42 to 101)) had longer recovery trajectories than male athletes (39 days (95% CI 31 to 65)) in the late access group (p<0.05).

Conclusions

Olympic athletes in this cohort experienced an RTS time frame of about a month, partly due to limited access to multidisciplinary care and resources. Earlier access to care shortened the RTS delay. Greater initial symptoms and female sex in the late access group were meaningful modifiers of a longer RTS.
Potentially inappropriate medication as a predictor of poor prognosis of COVID-19 in older adults: a South Korean nationwide cohort study
Authors: Kim Hyungmin , Hong Song Hee
Published: July 2024

Objectives

To investigate the association between exposure to potentially inappropriate medication (PIM) and poor prognosis of COVID-19 in older adults, controlling for comorbidity and sociodemographic factors.

Design and setting

Nationwide retrospective cohort study based on the national registry of COVID-19 patients, established through the linkage of South Korea’s national insurance claims database with the Korea Disease Control and Prevention Agency registry of patients with COVID-19, up to 31 July 2020.

Participants

A total of 2217 COVID-19 patients over 60 years of age who tested positive between 20 January 2020 and 4 June 2020. Exposure to PIM was defined based on any prescription record of PIM during the 30 days prior to the date of testing positive for COVID-19.

Primary outcome measures

Mortality and utilisation of critical care from the date of testing positive until the end of isolation.

Results

Among the 2217 COVID-19 patients over 60 years of age, 604 were exposed to PIM prior to infection. In the matched cohort of 583 pairs, PIM-exposed individuals exhibited higher rates of mortality (19.7% vs 9.8%, p<0.0001) and critical care utilisation (13.4% vs 8.9%, p=0.0156) compared with non-exposed individuals. The temporal association of PIM exposure with mortality was significant across all age groups (RR=1.68, 95% CI: 1.23~2.24), and a similar trend was observed for critical care utilisation (RR: 1.75, 95% CI: 1.26~2.39). The risk of mortality and critical care utilisation increased with exposure to a higher number of PIMs in terms of active pharmaceutical ingredients and drug categories.

Conclusion

Exposure to PIM exacerbates the poor outcomes of older patients with COVID-19 who are already at high risk. Effective interventions are urgently needed to address PIM exposure and improve health outcomes in this vulnerable population.
How do different navigation systems affect emergency response time? A prospective simulation study
Authors: van Mark Anke , Hallstein Tim , Holzgreve Fabian , Groneberg David A. , Ohlendorf Daniela
Published: July 2024

Objective

There has not been a theoretical test run in Germany that compares different navigation systems with an industry solution (MapTrip112). The aim of this study was to compare navigation systems to elucidate whether the emergency response time (ERT) was reduced and, consequently, whether the adherence to the travel time improved.

Design

Prospective, simulation study, cross-sectional study.

Setting

Offices of the Institute of Occupational Medicine, Social Medicine and Environmental Medicine, Goethe University Frankfurt (60 590 Frankfurt am Main, Germany). The situation-adaptable industry navigation solution MapTrip112 was tested in its ‘Lights and Siren(s) (L&S)’ mode in comparison to the TomTom and Google Maps navigation systems. MapTrip112 was set to calculate a route that takes special emergency rights of way into account.

Outcome measures

All three navigation systems simultaneously calculated the distances and durations of fictitious routes. Three scenarios were tested: the University Hospital Frankfurt (60 596 Frankfurt am Main, Germany) and the Central Fire Station 1 (60435 Frankfurt am Main, Germany) served as the starting points for the urban routes, while the Odenwald Health Centre (64 711 Erbach, Germany) served as the starting point for rural routes. The routes’ endpoints were arbitrarily chosen locations inside the customary operational radius. The routes were selected for short and long distances as well as for different periods, including weekdays, weekends and evening rush hour (4–7 pm), in the German cities of Frankfurt am Main and Odenwaldkreis (Southern Hesse).

Results

The time and distance were calculated for a total of 4650 trips. When comparing travel times and distances between rural and urban areas as well as between weekdays and weekends, statistically significant results were obtained (p<0.001). With time advantages ranging from 23.5 s to 300.5 s (4.75% to 50% of the travel time) on weekdays and weekends, MapTrip112 consistently outperformed both TomTom and Google Maps. For city missions, MapTrip112 achieved time gains of up to 50% over its competitors, with significant advantages during the rush hours and around specific locations such as the University Hospital Frankfurt and Fire Station 1.

Conclusion

MapTrip112 always achieved the fastest routes although these were not always accompanied by a shortened distance. These findings underscore MapTrip112’s superiority in providing efficient routing solutions across various scenarios. For this reason, the use of this software should be considered in practice and investigated in real-world conditions in further studies.
Presentation of the first international research network to foster high-quality clinical trials testing non-pharmacological interventions (TRACTION network)
Authors: Ferreira Ricardo J O , Henriques Adriana , Moe Rikke H , Matos Cristiano , Tveter Anne-Therese , Osteras Nina , Nogueira Paulo , Costa Andreia Silva , Haavardsholm Espen A , Carmona Loreto , Richards David
Published: July 2024

Clinical trials are essential for evaluating the efficacy and safety of new treatments and health interventions. However, while pharmacological trials are well-established, non-pharmacological trials face unique challenges related to their complexity and difficulties such as recruitment, retention, intervention standardisation, selection of outcome measures and blinding of clinicians, participants and data collectors. This communication paper describes the objectives, implementation steps and bylaws of the ‘Trials foR heAlth Care inTerventIONs’ Network (TRACTION), established by an international multiprofessional task force of experts to foster high-quality non-pharmacological research, ultimately improving patient care and healthcare outcomes.

The TRACTION research network will provide information and resources through a collaborative hub for researchers, health professionals, patient research partners and stakeholders in diverse biomedical and healthcare areas, connecting people with different levels of expertise but with the same interests (eg, to evaluate the effect of non-pharmacological interventions, recruiting participants). This open network will support researchers in optimising trial design, participant recruitment, data management and analysis, and disseminating and implementing trial results.

The network will also facilitate specialisation training and provide educational materials and mentoring.
Validation of a national leadership framework to promote and protect quality residential aged care: protocol for a Delphi study
Authors: Dawes Nathan , Topp Stephanie M , Adegboye Oyelola
Published: July 2024

Introduction

Australia’s ageing population is driving an increased demand for residential aged care services, yet concerns about the quality and safety of such care remain. The recent Royal Commission into Aged Care Quality and Safety identified various limitations relating to leadership within these services. While some competency frameworks exist globally, there is a need for sector-specific leadership competencies in the Australian residential aged care setting to promote and protect quality of care.

Methods and analysis

This study uses the Delphi technique to establish the content validity of a national leadership framework (RCSM-QF) for promoting and protecting the quality of residential aged care in Australia. Participants will be identifiable experts through current employment within, policy development for or research with the aged care sector. The survey will ask participants to rate the relevance, importance and clarity of RCSM-QF items and their corresponding descriptions and seek suggestions for revisions or additional items. Content validity will be assessed using the Content Validity Index, with items meeting specific criteria retained, revised, or removed.

Ethics and Dissemination

Ethics approval has been sought via the James Cook University Human Research Ethics Committee (HREC) to ensure the well-being and convenience of participants while mitigating potential recruitment challenges. Data will be prepared for submission to an appropriate peer-reviewed journal and presentation at relevant academic conferences.