bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of the CagY antenna projection in
Helicobacter pylori
Cag type IV secretion system activity
Authors: Tran Sirena C. , McClain Mark S. , Cover Timothy L. 
Published: August 2023

ABSTRACT

Helicobacter pylori
strains containing the
cag
pathogenicity island (PAI) are associated with the development of gastric adenocarcinoma and peptic ulcer disease. The
cag
PAI encodes a secreted effector protein (CagA) and a type IV secretion system (Cag T4SS). Cag T4SS activity is required for the delivery of CagA and non-protein substrates into host cells. The Cag T4SS outer membrane core complex (OMCC) contains a channel-like domain formed by helix-loop-helix elements (antenna projections, AP) from 14 copies of the CagY protein (a VirB10 ortholog). Similar VirB10 antenna regions are present in T4SS OMCCs from multiple bacterial species and are predicted to span the outer membrane. In this study, we investigated the role of the CagY antenna region in Cag T4SS OMCC assembly and Cag T4SS function. An
H. pylori
mutant strain with deletion of the entire CagY AP (∆AP) retained the capacity to produce CagY and assemble an OMCC, but it lacked T4SS activity (CagA translocation and IL-8 induction in AGS gastric epithelial cells). In contrast, a mutant strain with Gly-Ser substitutions in the unstructured CagY AP loop retained Cag T4SS activity. Mutants containing CagY AP loops with shortened lengths were defective in CagA translocation and exhibited reduced IL-8-inducing activity compared to control strains. These data indicate that the CagY AP region is required for Cag T4SS activity and that Cag T4SS activity can be modulated by altering the length of the CagY AP unstructured loop.
Supplemental Material: A record of the Pleistocene: Periglacial landforms, deposits, and fauna in the Appalachian highlands of Maryland, West Virginia, and Pennsylvania, USA
Authors: Kavage Adams Rebecca , al. et 
Published: August 2023

<p>Mark Swift’s unpublished presentation, “An Elevation Analysis of Lacustrine Soils in the Tenmile Creek Watershed, Greene County, Pennsylvania.” </p>
Factors influencing myopia stabilisation in young myopic adult Singaporeans
Authors: Foo Li Lian , Tan Chuen-Seng , Noel Brennan , Htoon Hla M , Najjar Raymond P , Kathrani Biten , Sabanayagam Charumathi , Saw Seang-Mei 
Published: August 2023

PurposeTo evaluate factors influencing stabilisation of myopia in the Singapore Cohort of Risk factors for Myopia.MethodsWe evaluated the longitudinal natural history of 424 myopic participants from 1999 to 2022. The outcome was the change in myopia from the adolescence follow-up visit (aged 12–19 years) to the adulthood follow-up visit (aged 26–33 years). Association of predictive factors, including baseline spherical error, gender, ethnicity, parental myopia, time outdoor, near work and age at adolescence, was examined with the dichotomous outcome of adult myopia progression (≤ −1.00 dioptres (D) over 10 years) using multiple logistic regression and progression in linear regression models.ResultsFor the primary outcome, the mean rate of progression of the outcome was found to be −0.04±0.09 D per year from the adolescent to the adulthood follow-up visits. 82.3% (95% CI 78.3% to 85.8%) had myopia stabilisation, with progression of less than 1.00 D over 10 years while 61.3% (95% CI 56.5% to 66.0%) of the subjects had progression of less than 0.50 D. In logistic regression models, both male gender (p=0.035) and non-Chinese ethnicity (p=0.032) were more likely to achieve myopia stabilisation while in linear multivariate regression models, males had a significantly slower degree of myopia progression (p=0.021).Conclusion5 in 6 Singaporean young adults had myopia stabilisation. Male gender is 2 times and non-Chinese ethnicities are 2.5 times more likely to achieve myopia stabilisation. However, a proportion of myopes continue to exhibit a clinically significant degree of progression in adulthood.
Public health insurance coverage in India before and after PM-JAY: repeated cross-sectional analysis of nationally representative survey data
Authors: Mohanty Sanjay K , Upadhyay Ashish Kumar , Maiti Suraj , Mishra Radhe Shyam , Kämpfen Fabrice , Maurer Jürgen , O'Donnell Owen 
Published: August 2023

IntroductionThe provision of non-contributory public health insurance (NPHI) to marginalised populations is a critical step along the path to universal health coverage. We aimed to assess the extent to which Ayushman Bharat-Pradhan Mantri Jan Arogya Yojana (PM-JAY)—potentially, the world’s largest NPHI programme—has succeeded in raising health insurance coverage of the poorest two-fifths of the population of India.MethodsWe used nationally representative data from the National Family Health Survey on 633 699 and 601 509 households in 2015–2016 (pre-PM-JAY) and 2019–2021 (mostly, post PM-JAY), respectively. We stratified by urban/rural and estimated NPHI coverage nationally, and by state, district and socioeconomic categories. We decomposed coverage variance between states, districts, and households and measured socioeconomic inequality in coverage. For Uttar Pradesh, we tested whether coverage increased most in districts where PM-JAY had been implemented before the second survey and whether coverage increased most for targeted poorer households in these districts.ResultsWe estimated that NPHI coverage increased by 11.7 percentage points (pp) (95% CI 11.0% to 12.4%) and 8.0 pp (95% CI 7.3% to 8.7%) in rural and urban India, respectively. In rural areas, coverage increased most for targeted households and pro-rich inequality decreased. Geographical inequalities in coverage narrowed. Coverage did not increase more in states that implemented PM-JAY. In Uttar Pradesh, the coverage increase was larger by 3.4 pp (95% CI 0.9% to 6.0%) and 4.2 pp (95% CI 1.2% to 7.1%) in rural and urban areas, respectively, in districts exposed to PM-JAY and the increase was 3.5 pp (95% CI 0.9% to 6.1%) larger for targeted households in these districts.ConclusionThe introduction of PM-JAY coincided with increased public health insurance coverage and decreased inequality in coverage. But the gains cannot all be plausibly attributed to PM-JAY, and they are insufficient to reach the goal of universal coverage of the poor.
Novel IRF2BPL gene mutation manifesting as a broad spectrum of neurological disorders: a case report
Authors: Khan Wardah Javed , Maqsood Hamza , Younus Shifa 
Published: August 2023

BackgroundIRF2BPL (interferon regulatory factor 2-binding protein-like) gene is an intronless gene present ubiquitously in the human body, including the brain. Pathogenic variants lead to neurodegeneration and present with phenotypic features of a neurological disorder, including dyslexia, dyscalculia, epilepsy, dystonia, neurodevelopmental regression, loss of motor skills and cerebellar ataxia.CaseWe present a case of a 9-year-old boy who was brought to the emergency department with generalised tonic-clonic seizures and mild hypotonia. A history included neurological regression. After insignificant lab and imaging results, the patient underwent genetic testing, revealing a novel pathogenic mutation in the IRF2BPL gene (heterozygous variant), which had never been reported in the literature before. An autosomal dominant loss of function mutation was demonstrated, denoting in DNA as NM_0 24 496 c.911 C>T, which results in premature protein termination (p.Glu494).ConclusionOur case highlights the importance of early recognition of the neurological symptoms associated with various IRF2BPL gene mutations so that a timely multidisciplinary management approach can be provided.
No waiting lying in a corridor: a quality improvement initiative in an emergency department
Authors: Schmutz Thomas , Le Terrier Christophe , Ribordy Vincent , Guechi Youcef 
Published: August 2023

BackgroundOvercrowding in the emergency department (ED) is a global problem and a source of morbidity and mortality and exhaustion for the teams. Despite multiple strategies proposed to overcome overcrowding, the accumulation of patients lying in bed awaiting treatment or hospitalisation is often inevitable and a major obstacle to quality of care. We initiated a quality improvement project with the objective of zero patients lying in bed awaiting care/referral outside a care area.MethodsSeveral plan–do–study–act (PDSA) cycles were tested and implemented to achieve and especially maintain the goal of having zero patients waiting for care outside the ED care area. The project team introduced and adapted five rules during these cycles: (1) no patients lying down outside of a care unit; (2) forward movement; (3) examination room always available; (4) team huddle and (5) an organisation overcrowding plan.ResultsAdaptation of ED organisation in the form of PDSA cycles allowed to obtain a collective team dimension to patient flow management. Since December 2021, despite an increase in activity, no patient is placed in a lying-in waiting area outside a care zone, irrespective of their care level. Vital distress and fragile patients who need to be kept in a supine position are treated immediately. In 2022, waiting time before medical contact was <2 hours for 90% of all patients combined.ConclusionsThe PDSA strategy based on these five measures allowed to remove in-house obstacles to the internal flow of patients and to fight against their installation outside the care area. These measures are easily replicable by other management teams. Quality indicators of EDs are often heterogeneous, but we propose that the absence of patients lying on a stretcher outside a care area could be part of these indicators, and thus contribute to the improvement and safety of care provided to all patients.
Tenecteplase versus alteplase for acute ischaemic stroke: a meta-analysis of phase III randomised trials
Authors: Xiong Yunyun , Wang Liyuan , Li Guangshuo , Yang Kai-Xuan , Hao Manjun , Li Shuya , Pan Yuesong , Wang Yongjun 
Published: August 2023

BackgroundTenecteplase (TNK) was found non-inferior to alteplase in recent clinical trials. We aimed to elucidate the efficacy and safety of TNK versus alteplase for acute ischaemic stroke (AIS).MethodsSystematic literature search and a meta-analysis of phase III clinical trials in ischaemic stroke patients with TNK use were conducted. The primary outcome was excellent functional outcome which was defined as modified Rankin Scale score of 0–1 at 90 days and safety outcomes included symptomatic intracerebral haemorrhage and death at 90 days. We used random-effects model to estimate the pooled risk difference and 95% CI in R package ‘Meta’. The included trials were adapted to the non-inferiority analysis with a margin of −4%.ResultsThree trials enrolling 4094 patients were identified by systematic search. All trials included AIS patients within 4.5 hours time window. Meta-analysis indicated that 1089 (53.0%) of 2056 patients in the TNK arm and 1016 (50.5%) of 2012 in the alteplase arm had excellent functional outcome at 90 days (0.03 (95% CI −0.00 to 0.06); I2=0%), meeting the prespecified non-inferiority threshold. And TNK thrombolysis was not correlated with increased risk of symptomatic intracerebral haemorrhage (0.00 (95% CI −0.01 to 0.01); I2=0%) or death (0.01 (95% CI −0.01 to 0.02); I2=0%) at 90 days. The sensitivity analysis with the 0.25 mg/kg trials exclusively showed similar results to the main analysis.ConclusionsTNK was non-inferior to alteplase for achieving excellent functional outcome at 90 days without increasing the safety concern in treating patients with AIS. These findings suggest that TNK can be an alternative to alteplase.PROSPERO registration numberCRD42022354342.
Associations of polygenic risk scores with risks of stroke and its subtypes in Chinese
Authors: Yang Songchun , Sun Zhijia , Sun Dong , Yu Canqing , Guo Yu , Sun Dianjianyi , Pang Yuanjie , Pei Pei , Yang Ling , Millwood Iona Y , Walters Robin G , Chen Yiping , Du Huaidong , Lu Yan , Burgess Sushila , Avery Daniel , Clarke Robert , Chen Junshi , Chen Zhengming , Li Liming , Lv Jun 
Published: August 2023

Background and purposePrevious studies, mostly focusing on the European population, have reported polygenic risk scores (PRSs) might achieve risk stratification of stroke. We aimed to examine the association strengths of PRSs with risks of stroke and its subtypes in the Chinese population.MethodsParticipants with genome-wide genotypic data in China Kadoorie Biobank were split into a potential training set (n=22 191) and a population-based testing set (n=72 150). Four previously developed PRSs were included, and new PRSs for stroke and its subtypes were developed. The PRSs showing the strongest association with risks of stroke or its subtypes in the training set were further evaluated in the testing set. Cox proportional hazards regression models were used to estimate the association strengths of different PRSs with risks of stroke and its subtypes (ischaemic stroke (IS), intracerebral haemorrhage (ICH) and subarachnoid haemorrhage (SAH)).ResultsIn the testing set, during 872 919 person-years of follow-up, 8514 incident stroke events were documented. The PRSs of any stroke (AS) and IS were both positively associated with risks of AS, IS and ICH (p<0.05). The HR for per SD increment (HRSD) of PRSASwas 1.10 (95% CI 1.07 to 1.12), 1.10 (95% CI 1.07 to 1.12) and 1.13 (95% CI 1.07 to 1.20) for AS, IS and ICH, respectively. The corresponding HRSDof PRSISwas 1.08 (95% CI 1.06 to 1.11), 1.08 (95% CI 1.06 to 1.11) and 1.09 (95% CI 1.03 to 1.15). PRSICHwas positively associated with the risk of ICH (HRSD=1.07, 95% CI 1.01 to 1.14). PRSSAHwas not associated with risks of stroke and its subtypes. The addition of current PRSs offered little to no improvement in stroke risk prediction and risk stratification.ConclusionsIn this Chinese population, the association strengths of current PRSs with risks of stroke and its subtypes were moderate, suggesting a limited value for improving risk prediction over traditional risk factors in the context of current genome-wide association study under-representing the East Asian population.
How cigarette excise tax pass-through to prices responds to the uptake and evolution of e-cigarettes (ECs)
Authors: He Yanyun , Ma Shaoying , Yang Qian , Shang Ce 
Published: August 2023

Background
How excise taxes are passed through to prices determines whether tax policies will be effective in changing smoking behaviours. Though previous literature has documented that cigarette taxes are overly shifted to prices, there is limited evidence on how cigarette tax pass-through to prices is affected by the uptake and evolution of e-cigarettes (ECs) in the US market.

Objective
This study investigates how cigarette excise tax pass-through rate varied by price levels (the 25th, 50th, and 75th percentile prices) and the uptake and evolution of ECs.

Methods
Tax pass-through rates were assessed using ordinary least squares regressions while controlling for state, year and month fixed effects. Different trends were then tested for the pre-EC uptake era (2006–2011), EC uptake era (2012–2016) and the evolution of nicotine salt-based ECs era (2017 and later).

Findings
Cigarette excise taxes were fully shifted to the 25th and 50th percentile prices and overly shifted to the 75th percentile prices at a 1:1.1 rate. While cigarette excise taxes had a continuous impact on raising prices, the tax pass-through rates were lower for lower priced cigarettes, and states imposed lower taxes.

Conclusions
Continuing to raise cigarette taxes may be needed to create financial incentives to encourage people who smoke to switch to ECs. In addition, continuing to raise cigarette taxes and additional pricing policies such as price promotion restrictions are needed to increase retail prices and reduce price minimisation opportunities.
Respiratory management and outcomes in high-risk preterm infants with development of a population outcome dashboard
Authors: Kwok Tng Chang , Poulter Caroline , Algarni Saleh , Szatkowski Lisa , Sharkey Don 
Published: August 2023

IntroductionBronchopulmonary dysplasia (BPD) is associated with adverse long-term respiratory and neurodevelopmental outcomes. No recent studies examined the changing respiratory management and outcomes, particularly severe BPD, across a whole population.PurposeEvaluate the temporal trends in the respiratory management and outcomes of preterm infants born below 32 weeks gestational age and develop an individualised dashboard of the incidence of neonatal outcome.MethodsUsing the National Neonatal Research Database, we determined changes in respiratory management, BPD rates, postdischarge respiratory support and mortality in 83 463 preterm infants in England and Wales from 2010 to 2020.ResultsBetween 2010 and 2020, antenatal corticosteroids use increased (88%–93%, p<0.0001) and neonatal surfactant use decreased (65%–60%, p<0.0001). Postnatal corticosteroid use increased, especially dexamethasone (4%–6%, p<0.0001). More recently, hydrocortisone and budesonide use increased from 2% in 2017 to 4% and 3%, respectively, in 2020 (p<0.0001). Over the study period, mortality decreased (10.1%–8.5%), with increases in BPD (28%–33%), severe BPD (12%–17%), composite BPD/death (35%–39%) and composite severe BPD/death (21%–24%) (all p<0.0001). Overall, 11 684 infants required postdischarge respiratory support, increasing from 13% to 17% (p<0.0001), with 1843 infants requiring respiratory pressure support at discharge. A population dashboard (https://premoutcome.github.io/) depicting the incidence of mortality and respiratory outcomes, based on gestation, sex and birthweight centile, was developed.ConclusionMore preterm infants are surviving with worse respiratory outcomes, particularly severe BPD requiring postdischarge respiratory support. Ultimately, these survivors will develop chronic respiratory diseases requiring greater healthcare resources.
Probing lepton flavor violation in meson decays with LHC data
Authors: Descotes-Genon S. , Faroughy D. A. , Plakias I. , Sumensari O. 
Published: August 2023

AbstractIn this letter, we use LHC data from the Drell–Yan processes $$pp\rightarrow \ell _i\ell _j$$

p
p
→

ℓ
i

ℓ
j

(with $$i\ne j$$

i
≠
j

) to derive model-independent upper limits on lepton-flavor-violating meson decays. Our analysis is based on an Effective Field Theory (EFT) approach and it does not require a specific assumption regarding the basis of effective operators. We find that current LHC data (140 $$\textrm{fb}^{-1}$$

fb

-
1

) already provides competitive limits on $${\mathcal {B}}(B\rightarrow \pi e \tau )$$

B
(
B
→
π
e
τ
)

and $${\mathcal {B}}(B\rightarrow \pi \mu \tau )$$

B
(
B
→
π
μ
τ
)

with respect to the ones obtained through experimental searches at the B-factories. Moreover, we derive upper limits on several decays that have not been searched for experimentally yet, such as $$D^0\rightarrow e\tau $$

D
0

→
e
τ

in the charm sector, and various semileptonic decays such as $$B\rightarrow \rho \mu \tau $$

B
→
ρ
μ
τ

, $$B_s\rightarrow K \mu \tau $$

B
s

→
K
μ
τ

and $$B_s\rightarrow \phi \mu \tau $$

B
s

→
ϕ
μ
τ

. Lastly, we discuss the validity of the EFT description of LHC data and the impact of loop corrections in our analysis.
AKR1C3 Converts Castrate and Post-Abiraterone DHEA-S into Testosterone to Stimulate Growth of Prostate Cancer Cells via 5-Androstene-3β,17β-Diol
Authors: Detlefsen Andrea J. , Mesaros Clementina A. , Duan Ling , Penning Trevor M. 
Published: August 2023

Androgen receptor signaling inhibitors (ARSI) are used to treat castration-resistant prostate cancer (CRPC) to stop a resurgence of androgen receptor (AR) signaling. Despite early success, patients on ARSIs eventually relapse, develop drug resistance, and succumb to the disease. Resistance may occur through intratumoral steroidogenesis mediated by upregulation of aldo-keto reductase family 1C member 3 (AKR1C3). Patients treated with leuprolide (castrate) and those treated with leuprolide plus abiraterone (post-Abi) harbor a reservoir of DHEA-S which could fuel testosterone (T) biosynthesis via AKR1C3 to cause a resurgence of prostate cancer cell growth. We demonstrate that concentrations of DHEA-S found in castrate and post-Abi patients are (i) converted to T in an AKR1C3-dependent manner in prostate cancer cells, and (ii) in amounts sufficient to stimulate AKR1C3-dependent cell growth. We observed this in primary and metastatic prostate cancer cell lines, CWR22PC and DuCaP, respectively. Androgen measurements were made by stable isotope dilution LC-MS/MS. We demonstrate AKR1C3 dependence using stable short hairpin RNA knockdown and pharmacologic inhibitors. We also demonstrate that free DHEA is reduced to 5-androstene-3β,17β-diol (5-Adiol) by AKR1C3 and that this is a major metabolite, suggesting that in our cell lines 5-Adiol is a predominant precursor of T. We have identified a mechanism of ARSI resistance common to both primary and metastatic cell lines that is dependent on the conversion of DHEA to 5-Adiol on route to T catalyzed by AKR1C3.

Significance:
We show that reservoirs of DHEA-S that remain after ARSI treatment are converted into T in primary and metastatic prostate cancer cells in amounts sufficient to stimulate cell growth. Pharmacologic and genetic approaches demonstrate that AKR1C3 is required for these effects. Furthermore, the route to T proceeds through 5-Adiol. We propose that this is a mechanism of ARSI drug resistance.
Diversity of the Austral Summer Quasi-Biweekly Oscillation in the Southwestern Indian Ocean
Authors: Yang Yang , Liu Yanliang , Li Kuiping , Liu Lin , Yu Weidong 
Published: August 2023

Abstract
The 10–20-day quasi-biweekly oscillation (QBWO) is active in the southwestern Indian Ocean (SWIO) during austral summer. Compared with comprehensive analyses of the QBWO in the Asian monsoon regions during boreal summer, studies focusing on the austral summer QBWO in the SWIO are relatively scarce. In this study, the diversity of the austral summer QBWO in the SWIO is examined based on K-means cluster analysis, which objectively classifies two distinct modes: an eastward-propagating mode (EM) and a poleward-propagating mode (PM). For the EM (PM), an active convection center originates from the subtropical ocean (tropical ocean) and exhibits an eastward (poleward) propagation path. Moisture budget analysis reveals that positive moisture time tendency anomalies show a phase-leading relationship relative to both QBWO convection centers. This phase leading in moisture tendency anomalies is mainly due to horizontal moisture advection. Further analysis demonstrates that meridional moisture transport (i.e., the summer mean moisture advected by the meridional quasi-biweekly wind) is fundamentally responsible for moisture phase leading in both QBWO modes in their mature phases. The combined scale interaction among low frequency, quasi-biweekly, and high frequency contributes to the initial movement for both modes in the growing phases. Although the two modes in the SWIO are initiated in different regions and exhibit distinct evolutionary features, they are regulated by similar moisture dynamics: the northerlies (northeasterlies) of the cyclonic wind response bring higher mean moisture levels east (south) of the convective center, which leads to the eastward (southward) movement of the EM (PM).

Significance Statement
The quasi-biweekly oscillation (QBWO), which can affect extreme weather events, such as extreme precipitation and heat waves, is active in the southwestern Indian Ocean (SWIO) during austral summer. Compared with previous studies of the QBWO in the Asian monsoon regions during boreal summer, studies focusing on the austral summer QBWO in the SWIO are relatively scarce. Specifically, we objectively classify the austral summer QBWO in the SWIO into two distinct modes: an eastward-propagating mode (EM) and a poleward-propagating mode (PM). Through moisture tendency diagnosis, we find that the two QBWO modes are regulated by similar moisture dynamics, although they are initiated in different regions and exhibit distinct evolutionary features. This improved understanding may provide insights into the monitoring and prediction of the QBWO.