bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetic diversity of highly pathogenic avian influenza H5N6 and H5N8 viruses in poultry markets in Guangdong, China, 2020-2022
Authors: Yang Kang , Nizami Sarea , Hu Shu , Zou Lirong , Deng Huishi , Xie Jiamin , Guo Qianfang , Edwards Kimberly M. , Dhanasekaran Vijaykrishna , Yen Hui-Ling , Wu Jie 
Published: December 2024

ABSTRACT

H5 highly pathogenic avian influenza (HPAI) viruses of the A/Goose/Guangdong/1/96 (Gs/Gd) lineage continue to evolve and cause outbreaks in domestic poultry and wild birds, with sporadic spillover infections in mammals. The global spread of clade 2.3.4.4b viruses via migratory birds since 2020 has facilitated the introduction of novel reassortants to China, where avian influenza of various subtypes have been epizootic or enzootic among domestic birds. To determine the impact of clade 2.3.4.4b re-introduction on local HPAI dynamics, we analyzed the genetic diversity of H5N6 and H5N8 detected from monthly poultry market surveillance in Guangdong, China, between 2020 and 2022. Our findings reveal that H5N6 viruses clustered in clades 2.3.4.4b and 2.3.4.4h, while H5N8 viruses were exclusively clustered in clade 2.3.4.4b. After 2020, the re-introduced clade 2.3.4.4b viruses replaced the clade 2.3.4.4h viruses detected in 2020. The N6 genes were divided into two clusters, distinguished by an 11 amino acid deletion in the stalk region, while the N8 genes clustered with clade 2.3.4.4 H5N8 viruses circulating among wild birds. Genomic analysis identified 10 transient genotypes. H5N6, which was more prevalently detected, was also clustered into more genotypes than H5N8. Specifically, H5N6 isolates contained genes derived from HPAI H5Nx viruses and low pathogenic avian influenza in China, while the H5N8 isolates contained genes derived from HPAI A(H5N8) 2.3.4.4b and A(H5N1) 2.3.2.1c. No positive selection on amino acid residues associated with mammalian adaptation was found. Our results suggest expanded genetic diversity of H5Nx viruses in China since 2021 with increasing challenges for pandemic preparedness.

IMPORTANCE

Since 2016/2017, clade 2.3.4.4b H5Nx viruses have spread via migratory birds to all continents except Oceania. Here, we evaluated the impact of the re-introduction of clade of 2.3.4.4b on highly pathogenic avian influenza (HPAI) virus genetic diversity in China. Twenty-two H5N6 and H5N8 HPAI isolated from monthly surveillance in two poultry markets in Guangdong between 2020 and 2022 were characterized. Our findings showed that clade 2.3.4.4h, detected in 2020, was replaced by clade 2.3.4.4b in 2021–2022. H5N6 (
n
= 18) were clustered into more genotypes than H5N8 (
n
= 4), suggesting that H5N6 may possess better replication fitness in poultry. Conversely, the H5N8 genotypes are largely derived from the clade 2.3.4.4b wild bird isolates. As clade 2.3.4.4b continues to spread via migratory birds, it is anticipated that the genetic diversity of H5N6 viruses circulating in China may continue to expand in the coming years. Continuous efforts in surveillance, genetic analysis, and risk assessment are therefore crucial for pandemic preparedness.
Identification of viral protease-dependent cleavage sites within the human astrovirus polyprotein
Authors: Mehri Samaneh , Bengert Brooke , Holliday Madeline , Corliss Lochlain , Prevelige Peter E. , Lennemann Nicholas J. 
Published: December 2024

ABSTRACT

Infection by human astrovirus (HAstV), a small, positive-strand RNA virus, is a major cause of gastroenteritis and has been implicated in an increasing number of severe, sometimes fatal, neurological diseases since 2008. Currently, there are no vaccines or antiviral treatments available to treat HAstV infection. An attractive target for antiviral therapeutics is the viral protease due to its essential functions throughout infection. However, the molecular mechanisms of the HAstV protease, nonstructural protein 1a/3 (nsp1a/3), are poorly understood. In fact, the specific residues within the cleavage junctions that are targeted by nsp1a/3 during polyprotein processing have yet to be experimentally identified. To identify the junctions between viral proteins, we performed mass spectrometry and site-directed mutagenesis using epitope-tagged viral polyprotein expression plasmids. Using these strategies, we identified a consensus motif that is found throughout the polyprotein near previously proposed junctions. We found that cleavage occurs after a hydrophobic residue – X – Gln motif. Further mutagenesis of surrounding sequence identified the importance of basic residues following the motif for efficient processing. Cleavage at each junction was determined to be essential for the production of progeny virions. However, abolishing nsp1a/4-VPg cleavage allowed efficient replication, suggesting that VPg can function in an intermediate form. Overall, our results identify a conserved cleavage motif that is recognized by the nsp1a/3 protease within the viral polyprotein, and cleavage at this motif was found to be essential for the recovery of progeny virions. These findings will be instrumental in further understanding the basic functions of HAstV polyprotein processing during infection.

IMPORTANCE
Human astroviruses (HAstVs) are a leading cause of non-bacterial gastroenteritis in children, elderly individuals, and immunocompromised patients. However, infection by divergent strains of HAstV is now recognized as a causative agent of severe neurological diseases, which can have fatal outcomes. Despite the global prevalence of HAstV, we currently have a limited understanding of the biology of these viruses. Translation of the viral genome leads to the production of polyproteins that are processed by viral and host proteases into functional proteins. In this study, we identified a conserved recognition sequence targeted by the viral protease for cleavage. Importantly, these findings elucidate the N- and C-termini of the nonstructural proteins within the HAstV polyprotein, offering valuable information for future studies on the function of individual viral proteins. Similar to other positive-sense RNA viruses, the necessity of proteolytic processing for the HAstV polyprotein highlights the viral protease as a promising target for antiviral development.
Genomes of novel
Serratia
strains from suburban soil
Authors: Markert E. X. , Severe Landon , Severe Kaeson , Twing Katrina I. , Ward L. M. 
Published: December 2024

ABSTRACT

Here, we present genomes of three strains of
Serratia
initially isolated from suburban soil—one strain of
S. ureilytica
and two strains of
S. quinivorans
—resistant to multiple classes of antibiotics. This expands the genomic sampling of a group relevant to the ecosystem and human health.
Effect of flexor tendon tenotomy of the diabetic hammertoe on plantar pressure: a randomized controlled trial
Authors: Askø Andersen Jonas , Rasmussen Anne , Engberg Susanne , Bencke Jesper , Frimodt-Møller Marie , Kirketerp-Møller Klaus , Rossing Peter 
Published: December 2024

IntroductionThe aim of this study was to evaluate the effects of flexor tendon tenotomy treatment of the diabetic hammertoe deformity on plantar pressure.Research design and methodsThe study was a substudy including participants from a randomized study on tenotomy treatment of diabetic hammertoes. This study was conducted between December 20, 2019 and June 22, 2021. Participants were randomized to tenotomy and standard non-surgical treatmentorstandard non-surgical treatment alone. Barefoot plantar pressure measurement was performed pre-intervention and 3 months post-intervention. Primary outcome was change in peak plantar pressure post tenotomy treatment.ResultsOf the 95 participants screened in the original study, 45 (57.8% male) were included andcompleted this substudy. Of the 45 participants, 22 were randomized to intervention. The average age of participants was 65.6 ((SD±) 9.5) years and 30 (66.7%) had type 2 diabetes.The average peak plantar pressure (PPP) in toe regions of the participants in the intervention group was significantly (p<0.0001) reduced from 205.6 kPa ((Q1–Q3) 152.0–289.1) pre-intervention to 61.3 kPa (39.1–100.5) post-intervention. The average reduction in PPP of toe regions for participants in the intervention group (−145.3 kPa (−225.9 to −56.2)) was significantly (p=0.00017) higher than what was observed for participants in the control group (−1.6 kPa (−30.2 to 27.9)).ConclusionThis study found that tenotomies of the diabetic hammertoe reduces plantar pressure affecting the treated toes. This likely explains the positive effects of tenotomy treatment on diabetic foot ulcers.
Ten-year health impact, economic impact and return on investment of the South African molecular diagnostics programme for HIV, tuberculosis and SARS-CoV-2
Authors: Nichols Brooke E , de Nooy Alexandra , Cassim Naseem , Hans Lucia , da Silva Manuel Pedro , Chetty Kamy , Grantz Kyra H , Han Alvin X , Phillips Andrew N , Jamieson Lise , Scott Lesley E , Stevens Wendy S 
Published: December 2024

IntroductionTo ensure there is adequate investment into diagnostics, an understanding of the magnitude of impact and return on investment is necessary. We, therefore, sought to understand the health and economic impacts of the molecular diagnostic programme in South Africa, to deepen the understanding of the broad value of diagnostics and guide future healthcare investments.MethodsWe calculated the 10-year (where data were available) total cost and disability-adjusted life-years (DALYs) averted associated with molecular testing for tuberculosis diagnosis (2013–2022), HIV viral load monitoring (2013–2022), early infant diagnosis of HIV infection (2013–2022) and SARS-CoV-2 testing (2020–2022), based on the actual number of molecular tests conducted in South Africa for the respective time periods. We then calculated the economic value associated with those health gains and subsequent return on investment.ResultsSince the inception of the molecular diagnostics programme in South Africa, approximately 4.3 million DALYs (uncertainty range (UR): 2.8–5.8 million) have been averted as a direct consequence of this programme. This has generated an estimated US$28.3 billion in economic value due to these health gains (UR$18.4–UR$38.7 billion). The return on investment varied by specific diagnostic test (20.3 (UR 15.2–25.4) for tuberculosis, 7.7 (UR 1.6–13.9) for HIV viral load testing, 63.0 (UR 63.0–65.5) for early infant diagnosis of HIV and 2.5 (UR 0.7–4.6) for SARS-CoV-2), for an average of 13.9 (UR 9.0–18.9) for the entire molecular diagnostics programme or US$13.9 of value for each UR$1 invested.ConclusionsThe molecular diagnostics programme in South Africa generated a significant amount of health gains and economic value associated with these health gains. The return on investment rivals other high-impact public health interventions such as childhood vaccination. The molecular diagnostics programme in South Africa is highly impactful and will continue to be an excellent investment in South African public health expenditure.
Third-grade school performance in children with special healthcare needs: a prospective cohort study
Authors: Schlecht Jennifer , König Jochem , Kuhle Stefan , Urschitz Michael S 
Published: December 2024

ObjectiveChildren with special healthcare needs (SHCN) due to a chronic health condition perform more poorly at school compared with their classmates. We aimed to estimate the effects of past, current, transient, emerging and persistent SHCN on school performance in primary school children.MethodsData from the German population-based prospective cohort study ikidS were used. The children withSHCN screener was administered before school entry (T1) and at the end of first (T2) and third grade (T3). Grades for German, maths and science (range: 1 (Very Good) to 6 (Failure)) were obtained at the end of third grade (age 8–9 years), and an average grade was calculated. Associations between the timing of SHCN and average grade were estimated by mixed linear regression models adjusted for potential confounding variables.Results751 children were included, and 21% had ever SHCN. Children with ever SHCN had poorer school performance than children with never SHCN (adjusted mean difference in average grade [95% CI]: 0.17 [0.06; 0.28]). SHCN in the third year were associated with a poorer average grade (0.29 [0.16; 0.41]) compared with healthy children. Only emerging (0.31 [0.15; 0.48]) and persistent (0.25 [0.07; 0.43]) SHCN were associated with average grade.ConclusionsThis study demonstrates the negative effect of current, emerging and persistent SHCN on academic performance in primary school children. Consequently, students should be regularly assessed for SHCN during school age. Timely interventions may help reduce the adverse effects of chronic health conditions on academic achievements in childhood.
Prevalence and prognostic significance of pulmonary hypertension in adults with left ventricular diastolic dysfunction
Authors: Ratwatte Seshika , Playford David , Strange Geoff , Celermajer David S , Stewart Simon 
Published: December 2024

AimsPulmonary hypertension (PHT) appears to be very common in heart failure with preserved ejection fraction but details on its prevalence, severity and prognostic implications have not been well defined. We, therefore, aimed to document PHT and its impact on mortality among adults with left ventricular (LV) diastolic dysfunction (LVDD).MethodsWe analysed the profile and outcomes of 16 058 adults with LVDD (and with preserved LV ejection fraction, >50%) from the National Echocardiography Database of Australia. Subjects were classified according to their peak tricuspid regurgitation velocity (TRV), reflecting PHT risk, and we then evaluated the relationship between conventional thresholds of increasing risk of PHT and subsequent mortality, during median follow-up of 3.1 (IQR 1.6–5.2) years.ResultsMean age was 73±12 years and 9216 (57.4%) were female. Overall, 2611 (16.3%) had normal TRV levels (<2.5 m/s) indicative of no PHT, compared with 3471 (21.6%), 8450 (52.6%) and 1526 (9.5%) with TRV levels indicative of borderline (2.5–2.8 m/s), intermediate (2.9–3.4 m/s) and high-risk for PHT (>3.4 m/s). The 1-year and 5-year actuarial mortality (1701/1546 and 4232/8445 deaths, respectively) increased from 6.5% and 34.0% to 27.7% and 78.5%, respectively (p<0.0001), from normal to severely elevated TRV. Adjusted risk (HR) of mortality increased 1.28-fold (95% CI 1.15 to 1.41), 1.51-fold (95% CI 1.38 to 1.65) and 3.47-fold (95% CI 3.13 to 3.85) in those with borderline, intermediate and high risk of PHT versus normal TRV. This observation persisted when excluding atrial fibrillation cases, and when male and female cohorts were assessed separately. Mortality rates increased perceptibly at the second decile distribution of TRV (2.37–2.55 m/s) with a marked increase in mortality from the fifth decile (2.91–3.00 m/s) upwards.ConclusionWe demonstrate the negative prognostic impact of elevated TRV levels in many adults with isolated LVDD. A threshold of increased mortality was observed at TRV levels equivalent to ‘borderline risk’ of PHT.Trial registration numberACTRN12617001387314
Level of compliance to smoke-free laws by restaurants in Karachi: an observational study
Authors: Zafar Mahrukh , Naz Sabahat , Batool Rahat , Vancy AbidAli , Khan Javaid A , Iqbal Romaina 
Published: December 2024

IntroductionExposure to secondhand smoke is a significant public health concern. Our study assessed the level of implementation of smoke-free laws in restaurants in Karachi, Pakistan.MethodsWe conducted a cross-sectional study in District East, Karachi. We randomly selected 40 restaurants based on their meal cost: 17 low (<400 PKR/meal), 12 medium (400–600 PKR/meal) and 11 high-end (>600 PKR/meal). We assessed tobacco control law implementation using an observational checklist that included questions about the presence of no-smoking signs, presence of smokers, people/children near smokers and remains of tobacco products and developed a compliance score for smoke-free laws: compliant (all criteria met), partially compliant (1–2 criteria met) and non-compliant (none met). We asked questions about knowledge, attitudes and practices regarding smoke-free laws with each restaurant’s staff. We reported frequencies and percentages for observations and questionnaire responses by restaurant category.ResultsOf the 40 restaurants, 70% (n=28) were either non-compliant or partially compliant, with 82% of low-end and 67% of medium-end were either non-compliant or partially compliant. None of the high-end restaurants were non-compliant; however, 55% partially complied with the smoke-free laws. More than half (53%, n=21) had no no-smoking signs. Smokers were observed on terraces or near children in 20% (n=8) of restaurants, and ashtrays or cigarette packs/butts were found in 40% (n=16). Fifty per cent of restaurant staff (n=20) believed that there was no tobacco control law in Pakistan, only 10% (n=4) knew the particulars of the law and 18% (n=7) were aware of any penalties for violations. In addition, 60% (n=24) reported no visits from legislative or administrative bodies to enforce compliance.ConclusionOur study reveals disparities in the compliance of smoke-free laws between low-end and high-end restaurants, highlighting the need to enforce these laws across all restaurant categories effectively.
Effects of antifreeze admixtures on masonry performance at subfreezing temperatures
Authors: Alfarra Jawdat , Wegner Leon D. , Boulfiza Moh 
Published: December 2024

Concrete brick prisms prepared with Type S masonry mortar that included sodium nitrite and/or nanocellulose as potential antifreeze admixtures were cured for 28 days at −10 °C before measuring compressive and flexural bond strengths. Addition of sodium nitrite allowed masonry prisms cured at −10 °C to reach 88% and 86% of the compressive and flexural bond strengths, respectively, of control specimens cured at room temperature. Nanocellulose was only effective when used in combination with sodium nitrite, improving the compressive and flexural bond strengths by an additional 3% and 27%, respectively. Results are primarily attributed to the ability of the sodium nitrite to lower the freezing point, allowing hydration to continue in subfreezing conditions, as confirmed by results of companion tests on mortar samples. Both additives also reduced the required w/ c ratio and porosity. The findings offer a sustainable alternative to energy-intensive protective heating methods, potentially lengthening the construction season into colder periods.
Minimal Residual Disease as an Early Endpoint for Accelerated Drug Approval in Myeloma: A Roadmap
Authors: Landgren Ola , Devlin Sean M. 
Published: December 2024

Abstract
Improvements in multiple myeloma treatments have extended patient survival to a decade or more. Treatment response rates &gt;90% have introduced new challenges for drug development, including a need for early endpoints with greater sensitivity. The FDA, based on data from two independent academic research groups and industry, evaluated minimal residual disease (MRD) negativity as an intermediate endpoint for progression-free and overall survival, culminating in a unanimous vote by the Oncologic Drugs Advisory Committee in April 2024 supporting MRD-negative complete response as an early endpoint reasonably likely to predict clinical benefit in multiple myeloma that may be used to support accelerated approval.

Significance:
The acceptance of MRD-negative complete response as an endpoint that is reasonably likely to predict clinical benefit will allow for the design of streamlined clinical trials for accelerated approval, enabling significantly faster patient access to novel therapies. Cooperative efforts were required to obtain and analyze clinical trial data from multiple sponsors and to determine the best approach to analysis with a relatively limited number of available datasets. The process to evaluate MRD as an intermediate endpoint, undertaken jointly by myeloma researchers and industry, with feedback from the FDA, serves as a roadmap for other areas of oncology to develop intermediate endpoints.
A Q-Theoretic Solution to A’ingae Postlabial Rounding
Authors: Dąbkowski Maksymilian 
Published: December 2024

Abstract
I describe and analyze a process of postlabial rounding in A’ingae (isolate, iso 639-3: con): after labial consonants, the diphthong /ae/ may surface as [oe]. However, a postlabial monophthongal /a/ always surfaces faithfully as [a]. To capture these facts, I propose an analysis couched in Q-Theory, where one vocalic target of a diphthong corresponds to fewer subsegments than a monophthong. This predicts that diphthongs might show an emergence-of-the-unmarked (TETU) effect, while monophthongs surface faithfully. The prediction is borne out by A’ingae postlabial rounding, contributing a novel argument for the Q-Theoretic representations. Finally, I show that similar asymmetries between diphthongs and monophthongs have recurred throughout the language’s history, further strengthening the proposal.
Husserl: Psychological Epoché and Pure Psychology
Authors: Rojcewicz Richard 
Published: December 2024

Abstract
The experience error is the fallacy of attributing to our experience of a thing what we know to be true of that thing from an objective point of view. This paper argues that the “method of purification” advocated by Edmund Husserl for psychology is nothing other than avoidance of the experience error. The purity of psychology is not philosophical (transcendental) purity. Psychology remains in the natural attitude; it is pure if it is true to the subjective, psychical, genuinely lived content of experience and thus is purely descriptive. But that is easier said than done. Due to the dominance of the modern scientific outlook, the experience error is so insidious that, as the paper argues in a final section, Husserl himself was not immune to it.
Another Phenomenological Method for the Analysis of Psychological Data
Authors: Giorgi Amedeo 
Published: December 2024

Abstract
From the phenomenological perspective, intentionality is an important concept for understanding consciousness. The idea was introduced into psychology by Brentano in the 19th century who got it from Scholasticism. Husserl modified its meaning and made it a key concept in his philosophy. This paper shows one way in which intentionality can help clarify psychological phenomena.