bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disruption of herpes simplex virus type 2 pUL21 phosphorylation impairs secondary envelopment of cytoplasmic nucleocapsids
Authors: Finnen Renée L. , Muradov Jamil H. , Le Sage Valerie , Banfield Bruce W. 
Published: August 2024

ABSTRACT

The multifunctional tegument protein pUL21 of HSV-2 is phosphorylated in infected cells. We have identified two residues in the unstructured linker region of pUL21, serine 251 and serine 253, as phosphorylation sites. Both phosphorylation sites are absent in HSV-1 pUL21, which likely explains why phosphorylated pUL21 was not detected in cells infected with HSV-1. Cells infected with HSV-2 strain 186 viruses deficient in pUL21 phosphorylation exhibited reductions in both cell-cell spread of virus infection and virus replication. Defects in secondary envelopment of cytoplasmic nucleocapsids were also observed in cells infected with viruses deficient in pUL21 phosphorylation as well as in cells infected with multiple strains of HSV-2 and HSV-1 deleted for pUL21. These results confirm a role for HSV pUL21 in the secondary envelopment of cytoplasmic nucleocapsids and indicate that phosphorylation of HSV-2 pUL21 is required for this activity. Phosphorylation of pUL21 was substantially reduced in cells infected with HSV-2 strain 186 mutants lacking the viral serine/threonine kinase pUL13, indicating a requirement for pUL13 in pUL21 phosphorylation.

IMPORTANCE
It is well known that post-translational modification of proteins by phosphorylation can regulate protein function. Here, we determined that phosphorylation of the multifunctional HSV-2 tegument protein pUL21 requires the viral serine/threonine kinase pUL13. In addition, we identified serine residues within HSV-2 pUL21 that can be phosphorylated. Phenotypic analysis of mutant HSV-2 strains with deficiencies in pUL21 phosphorylation revealed reductions in both cell-cell spread of virus infection and virus replication. Deficiencies in pUL21 phosphorylation also compromised the secondary envelopment of cytoplasmic nucleocapsids, a critical final step in the maturation of all herpes virions. Unlike HSV-2 pUL21, phosphorylation of HSV-1 pUL21 was not detected. This fundamental difference between HSV-2 and HSV-1 may underlie our previous observations that the requirements for pUL21 differ between HSV species.
Refining microbial community metabolic models derived from metagenomics using reference-based taxonomic profiling
Authors: Majzoub Marwan E. , Luu Laurence D. W. , Haifer Craig , Paramsothy Sudarshan , Borody Thomas J. , Leong Rupert W. , Thomas Torsten , Kaakoush Nadeem O. 
Published: August 2024

ABSTRACT

Characterization of microbial community metabolic output is crucial to understanding their functions. Construction of genome-scale metabolic models from metagenome-assembled genomes (MAG) has enabled prediction of metabolite production by microbial communities, yet little is known about their accuracy. Here, we examined the performance of two approaches for metabolite prediction from metagenomes, one that is MAG-guided and another that is taxonomic reference-guided. We applied both on shotgun metagenomics data from human and environmental samples, and validated findings in the human samples using untargeted metabolomics. We found that in human samples, where taxonomic profiling is optimized and reference genomes are readily available, when number of input taxa was normalized, the reference-guided approach predicted more metabolites than the MAG-guided approach. The two approaches showed significant overlap but each identified metabolites not predicted in the other. Pathway enrichment analyses identified significant differences in inferences derived from data based on the approach, highlighting the need for caution in interpretation. In environmental samples, when the number of input taxa was normalized, the reference-guided approach predicted more metabolites than the MAG-guided approach for total metabolites in both sample types and non-redundant metabolites in seawater samples. Nonetheless, as was observed for the human samples, the approaches overlapped substantially but also predicted metabolites not observed in the other. Our findings report on utility of a complementary input to genome-scale metabolic model construction that is less computationally intensive forgoing MAG assembly and refinement, and that can be applied on shallow shotgun sequencing where MAGs cannot be generated.

IMPORTANCE
Little is known about the accuracy of genome-scale metabolic models (GEMs) of microbial communities despite their influence on inferring community metabolic outputs and culture conditions. The performance of GEMs for metabolite prediction from metagenomes was assessed by applying two approaches on shotgun metagenomics data from human and environmental samples, and validating findings in the human samples using untargeted metabolomics. The performance of the approach was found to be dependent on sample type, but collectively, the reference-guided approach predicted more metabolites than the MAG-guided approach. Despite the differences, the predictions from the approaches overlapped substantially but each identified metabolites not predicted in the other. We found significant differences in biological inferences based on the approach, with some examples of uniquely enriched pathways in one group being invalidated when using the alternative approach, highlighting the need for caution in interpretation of GEMs.
Birth outcomes and survival by sex among newborns and children under 2 in the Birhan Cohort: a prospective cohort study in the Amhara Region of Ethiopia
Authors: Thompson Emily , Kassa Getachew Mullu , Fite Robera Olana , Pons-Duran Clara , Goddard Frederick G B , Worku Alemayehu , Haneuse Sebastien , Hunegnaw Bezawit Mesfin , Bekele Delayehu , Alemu Kassahun , Taddesse Lisanu , Chan Grace J 
Published: August 2024

IntroductionDespite the progress in reducing child mortality, the rate remains high, particularly in sub-Saharan African countries. Limited data exist on child survival and other birth outcomes by sex. This study compared survival rates and birth outcomes by sex among neonates and children under 2 in Ethiopia.MethodsWomen who gave birth after 28 weeks of gestation and their newborns were included in the analysis. Survival probabilities were estimated for males and females in the neonatal period as well as the 2-year period following birth using Kaplan-Meier curves. HRs and 95% CIs were compared between males and females under 2. Descriptive statistics and χ2tests were used to determine the sex-disaggregated variation in the birth outcomes of preterm birth, low birth weight (LBW), stillbirth, small for gestational age (SGA) and large for gestational age (LGA).ResultsThe study included a total of 3904 women and child pairs. The neonatal mortality rate for males (3.4%, 95% CI 2.6% to 4.2%) was higher compared with females (1.7%, 95% CI 1.1% to 2.3%). The hazard of death during the first 28 days of life was approximately two times higher for males compared with females (HR 1.99, 95% CI 1.30 to 3.06) but was not significantly different after this period. While there was a non-significant difference between males and females in the proportion of preterm, LBW and LGA births, we found a significantly higher proportion of stillbirth (2.7% vs 1.3%, p=0.003) and SGA (20.5% vs 15.6%, p<0.001) for males compared with females.ConclusionsThis study identified a significant sex difference in mortality and birth outcomes. We recommend focusing future research on the mechanisms of these sex differences in order to better design intervention programmes to reduce disparities and improve outcomes for neonates.
Testing a persuasive health communication intervention (PHCI) for emergency department patients who declined rapid HIV/HCV screening: a randomised controlled trial study protocol
Authors: Merchant Roland C , Harrington Nancy , Clark Melissa A , Liu Tao , Morgan Jake , Cowan Ethan , Solnick Rachel , Wyler Benjamin 
Published: August 2024

Introduction
Previous studies have shown that substantial percentages of emergency department (ED) patients in the USA recommended for HIV or hepatitis C (HCV) decline testing. Evidence-based and cost-effective interventions to improve HIV/HCV testing uptake are needed, particularly for people who inject drugs (PWIDs) (currently or formerly), who comprise a group at higher risk for these infections. We developed a brief persuasive health communication intervention (PHCI) designed to convince ED patients who had declined HIV/HCV testing to agree to be tested. In this investigation, we will determine if the PHCI is more efficacious in convincing ED patients to be tested for HIV/HCV when delivered by a video or in person, and whether efficacy is similar among individuals who currently, previously or never injected drugs.

Methods and analysis
We will conduct a multisite, randomised controlled trial comparing PHCIs delivered by video versus in person by a health educator to determine which delivery method convinces more ED patients who had declined HIV/HCV testing instead to be tested. We will stratify randomisation by PWID status (current, former or never/non-PWID) to permit analyses comparing the PHCI delivery method by injection-drug use history. We will also perform a cost-effectiveness analysis of the interventions compared with current practice, examining the incremental cost-effectiveness ratio between the two interventions for the ED population overall and within individual strata of PWID. As an exploratory analysis, we will assess if a PHCI video with captions confers increased or decreased acceptance of HIV/HCV testing, as compared with a PHCI video without captions.

Ethics and dissemination
The study protocol has been approved by the institutional review board of the Icahn School of Medicine. The results will be disseminated at international conferences and in peer-reviewed publications.

Trial registration number

NCT05968573
.
Endovascular treatment effect in vertebrobasilar artery occlusion patients with posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) <6
Authors: Zhang Pan , Huang Zhixin , Xu Yingjie , Li Wei , Huang Xianjun , Han Zhongkui , Luan Huanhuan , Li Yongkun , Yang Yong , Zhai Dengyue , Hu Miaomiao , Luo Genpei , Sun Wen 
Published: August 2024

BackgroundEndovascular treatment (EVT) has revolutionized the standard treatment of vertebrobasilar artery occlusion (VBAO) with moderate infarct core, but its effectiveness in patients with a low posterior circulation Acute Stroke Prognosis Early CT Score (pc-ASPECTS) is unclear. This study aimed to assess EVT effects in VBAO patients with pc-ASPECTS <6.MethodsThis retrospective study enrolled patients with VBAO within 24 hours of the estimated occlusion time at 65 stroke centers in a nationwide registration in China. The primary outcome was a favorable shift in the modified Rankin Scale (mRS) at 90 days. The secondary outcomes included a favorable outcome (mRS 0–3) and functional independence (mRS 0–2). Propensity score matching and inverse probability of treatment weighting were used to compare the outcomes of patients treated with EVT and those with best medical management.ResultsA total of 431 patients with VBAO and pc-ASPECTS <6 were included. EVT was associated with a favorable shift in the mRS score at 90 days (OR 1.72, 95% CI 1.19 to 2.5), a higher probability of a favorable outcome (OR 1.66, 95% CI 1.02 to 2.74), and improved functional independence (OR 1.76, 95% CI 1.06 to 2.96). EVT also significantly reduced the risk of 90-day mortality (OR 0.62, 95% CI 0.40 to 0.96), but increased the risk of symptomatic intracranial hemorrhage (OR 2.76, 95% CI 1.06 to 8.58).ConclusionThe results of this study suggest that EVT may be a safe and effective treatment option for patients with VBAO and pc-ASPECTS <6. Further studies are needed to investigate the effect of EVT in patients with pc-ASPECTS <6 and to identify patients who may benefit from EVT.
Prevalence of sexually transmitted infections and associated risk factors among female sex workers in Guinea-Bissau
Authors: Lindman Jacob , Djalo Mamadu Aliu , Biai Ansu , Månsson Fredrik , Golparian Daniel , Esbjörnsson Joakim , Jansson Marianne , Medstrand Patrik , Unemo Magnus , Norrgren Hans 
Published: August 2024

Objective

To estimate the prevalence of the curable sexually transmitted infections (STIs)
Chlamydia trachomatis
,
Neisseria gonorrhoeae
,
Mycoplasma genitalium
,
Trichomonas vaginalis
and
Treponema pallidum
, to identify associated risk factors and to assess ciprofloxacin resistance in
N. gonorrhoeae
-positive specimens among female sex workers (FSWs) in Guinea-Bissau.

Methods

For this cross-sectional study, FSWs were recruited from October 2014 to May 2019. A questionnaire on STI risk factors was completed by the study participants, and the women were asked to provide a vaginal swab for nucleic acid amplification tests for
C. trachomatis
,
N. gonorrhoeae
,
M. genitalium
,
T. vaginalis
(Aptima, Hologica), as well as a blood sample for
T. pallidum
serological testing and discriminatory HIV-testing. The prevalence of STIs was determined, and multivariate logistic regression was used to identify STI risk factors.

Results

The study included 467 women. The prevalence of current infection with any curable STI was 46.7%, and the most common pathogen was
T. vaginalis
(26.3%), followed by
M. genitalium
(21.9%),
C. trachomatis
(11.8%),
N. gonorrhoeae
(10.1%) and
T. pallidum
(2.8%). The proportion of asymptomatic infections among the diagnosed STIs was 61.8%, 61.5%, 55.3%, 55.3% and 52.2% for
C. trachomatis, T. pallidum, N. gonorrhoeae, T. vaginalis and M. genitalium, respectively
. The prevalence of the
gyrA
S91F mutation conferring ciprofloxacin resistance in
N. gonorrhoeae
-positive specimens was 84.0%. Significant risk factors for having a curable STI were age and HIV-1 infection, while use of female condoms was a protective factor.

Conclusion
This study demonstrated that the prevalence of curable STIs was high among FSWs in Guinea-Bissau during the study period, indicating an unmet need for STI services. Moreover, the results indicated that symptomatic treatment might be insufficient, highlighting a need for periodic aetiological testing to facilitate detection of asymptomatic as well as symptomatic STIs to stop ongoing transmission.
End-of-life care in multiple system atrophy: UK survey of patients and families
Authors: Oliver David , Barrick Andy , Kobylecki Christopher , Panicker Jalesh , Quinn Niall , Rushton Emma , Schrag Anette , Walker Karen , Bhatia Kailash 
Published: August 2024

ObjectivesPeople with multiple system atrophy (MSA) and their carers may have many concerns about their disease and the future. This survey of people with MSA and their carers aimed to increase understanding of end-of-life care and palliative care for this group.MethodsA survey was undertaken by the MSA Trust of people living with MSA and carers of those with the condition between August and October 2022.Results520 people responded: 215 people with MSA, 214 carers and 91 former carers. The modal class for age in people with MSA was 65–74 years, with 52% male. 76% of people living with MSA had thought to some extent about what they wanted to happen towards the end of their lives. 38% of respondents had discussed end-of-life care options with a healthcare professional and of those who had, over 81% found the conversation helpful. Nevertheless, for 37% of former carers, the death had been unexpected. Only a minority of people living with MSA had been referred for specialist palliative care. 65% of the former carers reported that they were satisfied with the quality of end-of-life care.ConclusionPeople with MSA and their carers continue to face many complex physical and emotional issues that would benefit from palliative care. Discussions about care at the end of life were generally perceived as helpful, but although the deterioration was often discussed, many families seemed unprepared for the death. Palliative care services were involved but this appeared limited.
Herb-antitumour drug interaction risks: retrospective integrative oncology study
Authors: Samuels Noah , Shapira Shir , Ben-Arye Eran 
Published: August 2024

ObjectivesThe use of herbal medicine is widespread among oncology patients, with potentially negative interactions with anticancer drugs. This study identified herbal products being used among a cohort of oncology patients, assessing the risk for an herb-drug interaction.MethodsHerbal medicine use was examined among 42 oncology patients, identifying potential herb-drug interactions using four online sites. The risk for an interaction was scored using the Working Group on Pharmacotherapy and Drug Information of the Royal Dutch Association for the Advancement of Pharmacy (KNMP).ResultsMost patients (62%) reported herbal medicine use, with 70 products identified; 8 herbs and 13 herbal formulas with unidentified components; and 24 anticancer drugs. Herbal medicine use was more prevalent among female patients (p=0.038), with only nine potential herb-drug interactions identified on at least one site. A maximal KNMP Score of 1 (ie, incomplete published case report) was found with only one interaction.ConclusionsThe risk for interactions between herbal products and anticancer drugs is difficult to predict, with online search engines providing limited and inconsistent information. Clinical implications of herb-antitumor drug interactions need to be better understood, enabling patients and their oncology healthcare providers to make informed decisions regarding their care.
Assessment of few-hits machine learning classification algorithms for low-energy physics in liquid argon detectors
Authors: Moretti Roberto , Rossi Marco , Biassoni Matteo , Giachero Andrea , Grossi Michele , Guffanti Daniele , Labranca Danilo , Terranova Francesco , Vallecorsa Sofia 
Published: August 2024

AbstractThe physics potential of massive liquid argon TPCs in the low-energy regime is still to be fully reaped because few-hits events encode information that can hardly be exploited by conventional classification algorithms. Machine learning (ML) techniques give their best in these types of classification problems. In this paper, we evaluate their performance against conventional (deterministic) algorithms. We demonstrate that both Convolutional Neural Networks (CNN) and Transformer-Encoder methods outperform deterministic algorithms in one of the most challenging classification problems of low-energy physics (single- versus double-beta events). We discuss the advantages and pitfalls of Transformer-Encoder methods versus CNN and employ these methods to optimize the detector parameters, with an emphasis on the DUNE Phase II detectors (“Module of Opportunity”).
Scaling of laboratory neutron sources based on laser wakefield-accelerated electrons using Monte Carlo simulations
Authors: Scheuren Stefan , Jäger Tim , Kohl Jonas , Kuschel Stephan , Rösch Thomas F. , Schmitz Benedikt , Zimmer Marc , Rödel Christian , Roth Markus 
Published: August 2024

AbstractNeutron sources based on laser-accelerated particles have attracted interest as they may provide a compact, cost-effective alternative to conventional sources. Recently, laser-driven neutron sources, based on ion acceleration, demonstrated neutron resonance spectroscopy, imaging and resonance imaging in first proof-of-principle experiments. To drive these sources efficiently with laser-accelerated ions, high laser pulse energies, in the range of tens to hundreds of Joules, with sub-ps pulse duration are needed. This requirement currently limits ion-based laser neutron sources to large-scale laser systems, which typically have maximum repetition rates in the order of a few shots per hour. In this paper, we investigate a potential path to circumvent these limitations by utilizing high repetition rate capable laser wakefield acceleration of electrons to drive a neutron source with high conversion efficiency. Monte Carlo simulations are performed to calculate neutron yields for various electron energies and converter materials, to determine optimal working parameters for an electron-based laser-driven neutron source. The results suggest that conversion efficiencies exceeding 25% can be achieved, depending on the electron energy and converter material. This electron-based approach could provide a neutron source with up to 10$$^{11}$$

11

n/s with state-of-the-art laser sources ($$E_{\text {Laser}} \lesssim {1}\,{\rm J}$$

E
Laser

≲
1

J

, $$\tau _{\text {Laser}} \lesssim {50}\,{\rm fs}$$

τ
Laser

≲
50

fs

, $$\sim {1}\,\textrm{kHz}$$

∼
1

kHz

).
B-type Plexins Regulate Mitosis via RanGTPase
Authors: Mukhwana Nicholus , Garg Ritu , Azad Abul , Mitchell Alexandria R. , Williamson Magali 
Published: August 2024

Abstract
Aberrant mitosis can result in aneuploidy and cancer. The small GTPase, Ras-related nuclear protein (Ran), is a key regulator of mitosis. B-type plexins regulate Ran activity by acting as RanGTPase-activating proteins and have been implicated in cancer progression. However, whether B-type plexins have a role in mitosis has not so far been investigated. We show here that Plexin B1 functions in the control of mitosis. Depletion of Plexin B1 affects mitotic spindle assembly, significantly delaying anaphase. This leads to mitotic catastrophe in some cells and prolonged application of the spindle assembly checkpoint. Plexin B1 depletion also promoted acentrosomal microtubule nucleation and defects in spindle pole refocusing and increased the number of cells with multipolar or aberrant mitotic spindles. An increase in lagging chromosomes or chromosomal bridges at anaphase was also found upon Plexin B1 depletion. Plexin B1 localizes to the mitotic spindle in dividing cells. The mitotic defects observed upon Plexin B1 depletion were rescued by an RCC1 inhibitor, indicating that Plexin B1 signals, via Ran, to affect mitosis. These errors in mitosis generated multinucleate cells and nuclei of altered morphology and abnormal karyotype. Furthermore, semaphorin 4D treatment increased the percentage of cells with micronuclei, precursors of chromothripsis.
Implications: Defects in B-type plexins may contribute to the well-established role of plexins in cancer progression by inducing chromosomal instability.