bluuebunny/crossref_metadata_2025 huggingface dataset:
A Bayesian change-point detection approach to the economic evaluation of risky projects: an application to healthcare technology assessment
Authors: Bregantini Daniele , Schmitt Laetitia H M , Thijssen Jacco J J
Published: November 2023

We propose a Bayesian hypothesis testing framework that allows for the assessment of evidence collected during a clinical trial about the cost-effectiveness of a healthcare technology. The model exploits a Bayesian updating rule that makes the link between the evidence collected in clinical research and the expected payoffs of adoption to the healthcare system. The framework takes into account the cost of decision errors in the payoff function, allowing the decision maker to compute the cost of taking a decision when evidence is far from the optimal decision triggers. We show, using a real-world cost-effectiveness study based on clinical trial evidence, how rules derived from a sequential adaptive design approach can lead to quicker decisions when compared to the value of information decision framework. Our application shows that a sequential approach has the potential to lead to quicker decisions, higher payoffs, and better health outcomes.
Seasonal dynamics of cell-to-cell transport in angiosperm wood
Authors: Słupianek Aleksandra , Myśkow Elżbieta , Kasprowicz-Maluśki Anna , Dolzblasz Alicja , Żytkowiak Roma , Turzańska Magdalena , Sokołowska Katarzyna
Published: November 2023

This study describes the seasonal changes in cell-to-cell transport in three selected angiosperm tree species, Acer pseudoplatanus (maple), Fraxinus excelsior (ash), and Populus tremula × tremuloides (poplar), with an emphasis on the living wood component, xylem parenchyma cells (XPCs). We performed anatomical studies, dye loading through the vascular system, measurements of non-structural carbohydrate content, immunocytochemistry, inhibitory assays and quantitative real-time PCR to analyse the transport mechanisms and seasonal variations in wood. The abundance of membrane dye in wood varied seasonally along with seasonally changing tree phenology, cambial activity, and non-structural carbohydrate content. Moreover, dyes internalized in vessel-associated cells and ‘trapped’ in the endomembrane system are transported farther between other XPCs via plasmodesmata. Finally, various transport mechanisms based on clathrin-mediated and clathrin-independent endocytosis, and membrane transporters, operate in wood, and their involvement is species and/or season dependent. Our study highlights the importance of XPCs in seasonally changing cell-to-cell transport in both ring-porous (ash) and diffuse-porous (maple, poplar) tree species, and demonstrates the involvement of both endocytosis and plasmodesmata in intercellular communication in angiosperm wood.
Record-breaking polarization from the interacting superluminous supernova 2017hcc
Authors: Mauerhan Jon C , Smith Nathan , Williams G Grant , Smith Paul S , Filippenko Alexei V , Bilinski Christopher , Zheng WeiKang , Brink Thomas G , Hoffman Jennifer L , Leonard Douglas C , Milne Peter , Jeffers Benjamin , Modak Shaunak , Stegman Samantha , Zhang Keto D
Published: November 2023

We present multi-epoch spectropolarimetry of Type IIn supernova SN2017hcc, 16–391 d after explosion. Continuum polarization up to 6 per cent is observed during the first epoch, making SN 2017hcc the most intrinsically polarized SN ever reported at visible wavelengths. During the first 29 d, when the polarization is strongest, the continuum polarization exhibits wavelength dependence that rises toward the blue, then becomes wavelength independent by day 45. The polarization drops rapidly during the first month, even as the flux is still climbing to peak brightness. None the less, unusually high polarization is maintained until day 68, at which point the polarization declines to levels comparable to those of previous well-studied SNe IIn. Only minor changes in position angle (PA) are measured throughout the evolution. The blue slope of the polarized continuum and polarized line emission during the first month suggests that an aspherical distribution of dust grains in pre-shock circumstellar material (CSM) is echoing the SN IIn spectrum and strongly influencing the polarization, while the subsequent decline during the wavelength-independent phase appears consistent with electron scattering near the SN/CSM interface. The persistence of the PA between these two phases suggests that the pre-existing CSM responsible for the dust scattering at early times is part of the same geometric structure as the electron-scattering region that dominates the polarization at later times. SN 2017hcc appears to be yet another, but more extreme, case of aspherical yet well-ordered CSM in Type IIn SNe, possibly resulting from pre-SN mass-loss shaped by a binary progenitor system.
The enigmatic multiple star VV Ori
Authors: Budding Edwin , Southworth John , Pavlovski Krešimir , Rhodes Michael D , Zihao Wu , Love Tom , Blackford Mark G , Banks Timothy S , Alexander Murray
Published: November 2023

New photometry, including TESS data, have been combined with recent spectroscopic observations of the Orion Ib pulsating triple-star system VV Ori. This yields a revised set of absolute parameters with increased precision. Two different programmes were utilized for the light-curve analysis, with results in predictably close agreement. The agreement promotes confidence in the analysis procedures. The spectra were analysed using the FDBinary programme. The main parameters are as follows: M1 = 11.56 ± 0.14 and M2 = 4.81 ± 0.06 (M⊙). We estimate an approximate mass of the wide companion as M3 = 2.0 ± 0.3 M⊙. Similarly, R1 = 5.11 ± 0.03, R2 = 2.51 ± 0.02, R3 = 1.8 ± 0.1 (R⊙); Te1 = 26600 ± 300, Te2 = 16250 ± 420, and Te3 = 10000 ± 1000 (K). The close binary’s orbital separation is a = 13.91 (R⊙); its age is 8 ± 2 (Myr) and its photometric distance is 396 ± 7 pc. The primary’s β Cep type oscillations support these properties and confirm our understanding of its evolutionary status. Examination of the well-defined λ6678 He i profiles reveals the primary to have a significantly low projected rotation: some 80 per cent of the synchronous value. This can be explained on the basis of the precession of an unaligned spin axis. This proposal can resolve also observed variations of the apparent inclination and address other longer term irregularities of the system reported in the literature. This topic invites further observations and follow-up theoretical study of the dynamics of this intriguing young multiple star.
An archival search for type Ia supernova siblings
Authors: Kelsey L
Published: November 2023

By searching the Open Supernova Catalog, an extragalactic transient host galaxy database, and literature analyses, I present the largest sample of type Ia supernova (SN Ia) siblings to date. The sample comprises 158 galaxies, consisting of 327 confirmed SNe Ia, over 10 times larger than existing sibling SN Ia samples. SN siblings share host galaxies, and thus share global environmental properties and associated systematic uncertainties. This makes them valuable for both cosmological and astrophysical analyses; for example, sibling SNe Ia allow for comparison of environmental properties within the same galaxy, progenitor comparisons, rates analyses, and multiple calibrations of the Hubble–Lemaître constant. This large sample will provide a variety of new avenues of research, and be of great interest to the wider SN Ia community. To give an example use of this sample, I define a cosmology subsample of 44 siblings; and use it to compare light-curve properties between sibling pairs. I find no evidence for correlations in stretch (x1) and colour (c) between pairs of siblings. Moreover, by comparing a comparable set of random pairs of SNe Ia through boot-strapping, I find that siblings are no more similar in x1 and c than any random pair of SNe Ia. Given that siblings share the same hosts, differences in x1 and c between siblings cannot be due to global galaxy properties. This raises important questions regarding environmental systematics for SN Ia standardization in cosmology, and motivates future analyses of sibling SNe Ia.
The first analysis of three long-period low mass-ratio contact binaries
Authors: Liu Fei , Li Kai , Gao Xiang , Guo Ya-Ni , Li Ling-Zhi , Liu Xin-Yi , Li Ke-Xin , Gao Xin-Yi , Gao Xing , Sun Guo-You , Wang Xi , Yin Shi-Peng
Published: November 2023

The photometric and spectroscopic studies of three contact binaries, ASASSN-V J052036.28+144711.0, ASASSN-V J064846.22+241709.9, and ASASSN-V J073441.02+555833.0 were performed for the first time. The periods of all the three targets are longer than 0.5 d, and we discovered that their mass ratios are all smaller than 0.25. So, they are long-period low mass-ratio contact binaries. ASASSN-V J052036.28+144711.0 and ASASSN-V J064846.22+241709.9 are medium contact binaries. ASASSN-V J073441.02+555833.0 is a deep contact binary, which is also the only one existing O’Connell effect. We attached a dark spot on its secondary component for a better fit of light curves featuring asymmetry. From orbital period analysis, two of the three targets are believed to demonstrate a secular period increase, while one shows no long-term variation. We employed the spectral subtraction approach to investigate the LAMOST spectra, while all of the three binaries show no H α emission line, implying no chromospheric activity. Their initial masses, current average densities, and mass transfer rates between the two components were calculated. We obtained that the three targets are stable for the moment.
Amorphous oxide semiconductor for monolithic 3D DRAM: an enabler or passer-by?
Authors: Mao Shujuan , Wang Guilei , Zhao Chao
Published: November 2023

Whether amorphous oxide semiconductor (AOS) is an enabler or pass-by for monolithic 3D DRAM is discussed, with current challenges and future directions proposed in this perspective.
Efficacy of Sitafloxacin for Mycoplasma genitalium in an Era of Increasing Antimicrobial Resistance
Authors: Samra Ranjit S , Plummer Erica L , Vodstrcil Lenka A , Aguirre Ivette , Clarke Emily J , Fairley Christopher K , Chow Eric P F , Bradshaw Catriona S
Published: November 2023

Antimicrobial resistance in Mycoplasma genitalium is rising globally and antimicrobial options are limited. We evaluated the efficacy of sitafloxacin regimens for macrolide-resistant M genitalium at Melbourne Sexual Health Centre, Australia, between January 2017 and February 2022. Before June 2017, patients received doxycycline followed by sitafloxacin; subsequently, patients received doxycycline followed by combined doxycycline + sitafloxacin. Of 229 patients treated with a sitafloxacin regimen, 80.6% experienced microbial cure. Sitafloxacin cured 94.2% of infections that had not previously failed moxifloxacin and 69.5% of infections that had; prior failure of moxifloxacin was associated with an 8-fold odds of sitafloxacin failure. There was no difference in cure between sequential monotherapy and combination therapy when patients were stratified by past failure of moxifloxacin (P > .05); however, small numbers limited comparisons. Sitafloxacin was well tolerated and still achieved 70% cure in patients in whom moxifloxacin had failed. These data highlight the benefit of incorporating relevant fluoroquinolone resistance markers into assays to assist clinical decision making.
A History of the Scots Language
Authors: Millar Robert McColl
Published: November 2023

This book provides both a sociolinguistic and a linguistic history of the Scots language, spoken both in Scotland and Ulster. It provides this material in two ways, reflecting both the historical, political, and economic forces which affected the status and use of Scots and the linguistic developments through which, like all languages, Scots has passed. Chapters 1 and 2 act as introductions, the first attempting to provide an analysis of what Scots is, in particular in relation to Standard English. The second chapter discusses the Indo-European background of Scots, while also discussing the linguistic ecology of what is now Scotland before Anglian dialects were introduced in the post-Roman period. Chapters 3 and 4 describe the sociolinguistic factors which have influenced the development of the language. Chapter 3 discusses the ‘rise’ of the language to being the de facto official language of Scotland; Chapter 4 considers its ‘fall’, analysing the social, economic, and political forces which led to its dialectalization under English. The formation of Scottish Standard English is also discussed in depth. Chapters 5, 6, and 7 analyse system-internal change in, respectively, the phonological, morphosyntactic, and lexical systems of Scotland. While a coherent narrative is maintained throughout, dialect-based development and change is given prominence. Chapter 8 provides a brief summary of what has been covered in the book, while at the same time suggesting future research projects which might prove productive.
Net zero electricity: the UK 2035 target
Authors: Helm Dieter
Published: November 2023

The UK is, like its peers in the EU, just under 80% dependent on fossil fuels. This figure has come down just over 10% since the 1970s, a period when the UK had major energy-intensive industries, most of which are now gone. The government is committed to achieving net zero for the electricity sector by 2035 on the pathway to net zero for the whole economy by 2050.. The Labour opposition has set 2030 as its electricity target. Setting out the scale of this challenge, this paper demonstrates how implausible the 2035 target is. On present policies there is little prospect that the 2035 target will be met (and virtually none for the Labour 2030 target). This paper reviews the multiple current policies and the capacity objectives and explores what would have to happen to meet the target. It sets out some of the consequences of failure to deliver, and the expectation of that failure.
Sensitive intervention points: a strategic approach to climate action
Authors: Mealy Penny , Barbrook-Johnson Pete , Ives Matthew C , Srivastav Sugandha , Hepburn Cameron
Published: November 2023

While some countries are making progress reducing greenhouse gas emissions, few are progressing rapidly enough to be on track to reach net zero emissions by mid-century. The transition to net zero involves deep structural transformation of the global economy and its associated complex socio-technical systems. Here, we set out a conceptual framework to identify ‘sensitive intervention points’ (SIPs) in systems where a small or moderately-sized intervention could drive outsized impacts and transformational change. These points take three forms: (i) critical tipping points, such as a critical price threshold, (ii) critical nodes in networks, such as an influential actor in a social network, and (iii) critical points in time, where windows of opportunity for change open up. We also propose an assessment methodology for prioritizing interventions in terms of their potential impacts, risks, and ease of implementation. We apply our framework and assessment methodology to evaluate a list of proposed interventions for accelerating global decarbonization. Promising interventions include investing in key clean energy technologies with consistent cost declines, introducing central bank policies to reduce the value of polluting collateral, and enhancing climate-related financial risk disclosure.
Policy complementarity and the paradox of carbon pricing
Authors: Grubb Michael , Poncia Alexandra , Drummond Paul , Neuhoff Karsten , Hourcade Jean-Charles
Published: November 2023

We present an economics framework appropriate to the exceptionally broad scope of the climate change problem. This considers that economic and social processes, particularly those involved in purposive transitions of energy technologies and systems, involve the interplay between three distinct domains of decision-making and associated actors. The first concerns small-scale and often short-term decision-making, much of which reflects extensive ‘satisficing’ and habituation as identified in behavioural economics. Calculated economic optimization decisions, especially of companies in the energy and energy-intensive industries, then best reflect the core assumptions of neoclassical and welfare economics, including discrete market failures. Third, at the largest scale are strategic judgements made by big actors (e.g. governments, large multinational companies) relevant to transformation of complex systems over long periods—particularly concerning innovation and structural changes, for which lessons from theories of evolutionary and institutional economics are most relevant.

Economically, these can be logically mapped in relation to the technology (or more accurately, ‘best practice’) frontier. Each has corresponding policy implications: most directly, respectively in terms of (i) standards and engagement to establish norms; (ii) competitive markets with the critical role of prices; and (iii) strategic investment in innovation and infrastructure. Each faces challenges of implementation and government failure, as observed, for example, with wholly inadequate carbon pricing to date, naïve and ineffective approaches to enhancing energy efficiency, or misdirected support to R&D. Based on the domain distinctions, we argue that the corresponding pillars of policy are naturally complementary, and can be mutually supportive: strong standards and norms on energy efficiency, for example, would enhance the political space for carbon pricing by reducing its direct consumer impacts, while carbon pricing has multiple positive two-way interactions with enhanced low-carbon innovation.

From this we also posit a ‘carbon pricing paradox’: that adequate carbon prices, the central recommendation of most economists, are in most jurisdictions only feasible (or even optimal) if equal analytic and policy attention is devoted to the other pillars, and the wider context of macroeconomic and fiscal policies. Only these other aspects can reduce the absolute cost impact of carbon pricing (potentially turning into a gain) and offer consumers and businesses better lower-carbon alternatives, which are critical to establishing climate-compatible pricing structures across our economies.
Rice requires a chromatin remodeler for Polymerase IV-small interfering RNA production and genomic immunity
Authors: Xu Dachao , Zeng Longjun , Wang Lili , Yang Dong-Lei
Published: November 2023

Transgenes are often spontaneously silenced, which hinders the application of genetic modifications to crop breeding. While gene silencing has been extensively studied in Arabidopsis (Arabidopsis thaliana), the molecular mechanism of transgene silencing remains elusive in crop plants. We used rice (Oryza sativa) plants silenced for a 35S::OsGA2ox1 (Gibberellin 2-oxidase 1) transgene to isolate five elements mountain (fem) mutants showing restoration of transgene expression. In this study, we isolated multiple fem2 mutants defective in a homolog of Required to Maintain Repression 1 (RMR1) of maize (Zea mays) and CLASSY (CLSY) of Arabidopsis. In addition to failing to maintain transgene silencing, as occurs in fem3, in which mutation occurs in NUCLEAR RNA POLYMERASE E1 (OsNRPE1), the fem2 mutant failed to establish transgene silencing of 35S::OsGA2ox1. Mutation in FEM2 eliminated all RNA POLYMERASE IV (Pol-IV)–FEM1/OsRDR2 (RNA-DEPENDENT RNA POLYMERASE 2)-dependent small interfering RNAs (siRNAs), reduced DNA methylation on genome-wide scale in rice seedlings, caused pleiotropic developmental defects, and increased disease resistance. Simultaneous mutation in 2 FEM2 homologous genes, FEM2-Like 1 (FEL1) and FEL2, however, did not affect DNA methylation and rice development and disease resistance. The predominant expression of FEM2 over FEL1 and FEL2 in various tissues was likely caused by epigenetic states. Overexpression of FEL1 but not FEL2 partially rescued hypomethylation of fem2, indicating that FEL1 maintains the cryptic function. In summary, FEM2 is essential for establishing and maintaining gene silencing; moreover, FEM2 is solely required for Pol IV–FEM1 siRNA biosynthesis and de novo DNA methylation.
A Cross-sectional Conceptual Replication and Longitudinal Evaluation of the PANSS-Autism-Severity-Score Measure Suggests it Does Not Capture Autistic Traits in Individuals With Psychosis
Authors: Chisholm Katharine , Schirmbeck Frederike , Pinkham Amy E , Sasson Noah J , Simons Claudia J P , de Haan Lieuwe , Harvey Philip D , Penn David L , Ziermans Tim
Published: November 2023

Background

Autism and psychosis co-occur at elevated rates, with implications for clinical outcomes, functioning, and suicidality. The PANSS-Autism-Severity-Score (PAUSS) is a measure of autism trait severity which has not yet been validated externally or longitudinally.

Study Design

Participants were derived from the GROUP and SCOPE datasets. Participants included 1448 adults with schizophrenia spectrum disorder (SSD), 800 SSD-siblings, 103 adults diagnosed with an autistic spectrum condition (ASC), and 409 typically-developing controls (TC). Analyses from the original validation study were conducted with SSD participants, and extended into ASC, SSD-sibling, and TC participants. Test–retest reliability of the PAUSS at 2-weeks and long-term stability 3 and 6-years was also examined.

Study Results

Results differed in important ways from the original validation. SSD participants reported higher PAUSS scores than other groups, with only a fraction of ASC participants scoring as “PAUSS-Autistic.” Cronbach’s alpha was acceptable for the SSD cohort only. Two-week stability of the PAUSS was fair to good for all PAUSS scores. Long-term stability was poor for most PAUSS items but fair for total PAUSS score.

Conclusions

Results suggest that the PAUSS does not appear appropriate for assessing autism, with the low rate of PAUSS-Autistic in the ASC population suggesting the PAUSS may not accurately reflect characteristics of autism. The relative lack of long-term stability is cause for concern and suggestive that the PAUSS is capturing features of psychosis rather than autism traits.
Comparing regulatory options: the role of epistemic policies and pragmatic consequences
Authors: López-Mas Roberto , Luján José Luis
Published: November 2023

The controversies surrounding the regulation of technology depend, among other factors, on the diversity of the regulatory objectives prioritized by the distinct social actors. These differences may also lead to controversies in the realm of regulatory science: controversies between distinct epistemic policies. As controversies are partly the result of prioritizing different objectives, comparing alternative regulatory options is a seemingly impossible endeavour. In this paper, we offer a partial solution to this problem by proposing a means of comparing different regulatory options. This proposal makes it possible to analyse and assess the different options and facilitates the adoption of compromises between the various parties to the controversy, even if it is unable to eliminate the differences in the prioritization of objectives. The case study we have used to illustrate the main ideas of this paper is the controversy surrounding the regulation of health claims in the European Union.
The Association of Race With Decreased Access to Pediatric Hearing Healthcare in the United States
Authors: Cadieux Jamie H. , Davidson Lisa S. , Mazul Angela , Ortmann Amanda
Published: November 2023

Successful intervention to support a child with congenital hearing loss requires early identification and consistent access to frequent professional services. In the early 2000s, the United States implemented an initiative, Early Hearing Detection and Intervention (EHDI), to provide timely identification and treatment of congenital hearing loss. This national program aims to screen hearing by 1 month of age, diagnose hearing loss by 3 months of age, and provide intervention to infants with hearing loss by 6 months of age. To date, the United States is successfully implementing hearing screening by 1 month of age but continually struggling to diagnose and treat congenital hearing loss promptly for many infants. This article begins by exploring the current state of American children and families, focusing on social determinants of health, specifically race and poverty. The objective is to understand how race affects social determinants of health, and ultimately hearing healthcare access for children. A narrative literature review spanning public health, sociology, and hearing research was completed to inform this work. The current body of literature supports the conclusion that race and racism, separate from poverty, lead to decreased access to pediatric hearing healthcare. Interventions targeting these issues are necessary to improve timely access to hearing loss diagnosis and treatment for American children.
The Greco-Nice-Lag: Lag Screw and Double Nice Knot Fixation for Spiral Proximal Phalanx Fractures—Connecting the Shoulder to the Finger
Authors: Greco Victor E. , Wiesler Ethan
Published: November 2023

A colorful array of fixation options exists for the management of operative long oblique or spiral proximal phalanx fractures. These include lag screws, intramedullary devices, Kirschner wires, dorsal or lateral plating, and cerclage wiring. The “Nice double-suture knot,” described by Boileau and colleagues, is a sliding, self-stabilizing knot initially created for tuberosity fixation in the shoulder. Nice knot cerclage has been described in shoulder arthroplasty, as well as for comminuted patella fractures. Here we describe a technique utilizing a single lag screw with 2 Nice knot cerclage sutures for the treatment of a spiral proximal phalanx fracture in a 65-year-old active smoker with osteopenia.
The association between histological subtypes and lymph node metastasis and prognosis in early esophageal cancer: a population-based study
Authors: Lin Jun-Peng , Chen Xiao-Feng , Zhou Hang , Zhuang Feng-Nian , He Hao , Chen Wei-Jie , Wang Feng , Liu Shuo-Yan
Published: November 2023

Background

There is still a lack of high-level clinical evidence and uniform conclusions on whether there are differences in lymph node metastasis (LNM) and prognosis between early esophageal adenocarcinoma (EAC) and squamous cell carcinoma (ESCC).

Methods

Patients with surgically resected, histologically diagnosed, pT1 EAC or ESCC in the Surveillance, Epidemiology and End Results registries database from 2004 to 2015 were included. Multivariable logistic regression, Cox regression, multivariate competing risk model, and propensity score matching were used to analyze association the histology and LNM or prognosis.

Results

A total of 570 early esophageal cancer patients were included. The LNM rates were 13.8% and 15.1% for EAC and ESCC (P = 0.757), respectively. Multivariate logistic regression analysis showed no significant association between histological type and LNM (odds ratio [OR], 1.209; 95% CI, 0.538–2.715; P = 0.646). Moreover, the prognosis of early EAC and ESCC was shown to be comparable in both multivariate Cox regression (hazard ratio [HR], 1.483; 95% CI, 0.699–3.150; P = 0.305) and the multivariate competing risk model (subdistribution HR, 1.451; 95% CI, 0.628–3.354; P = 0.383). After propensity score matching, there were no significant differences between early EAC and ESCC in terms of LNM (10.6% vs.18.2%, P = 0.215), 5-year CSS (89.8% [95% CI, 81.0%–98.6%] vs. 79.1% [95% CI, 67.9%–90.3%], P = 0.102) and 5-year cumulative incidence of CSS (10.2% [95% CI, 1.4%–19.0%] vs. 79.1% [95% CI, 9.7%–32.1%], P = 0.124).

Conclusion

The risk of LNM and prognosis of early ESCC and EAC are comparable, so the treatment choice for early esophageal cancer does not depend on the histologic type.
Agile: Its Evolution and Potential Value in Hospitals
Authors: Cummings Bruce D. , DeChant Paul
Published: November 2023

As hospitals and health systems struggle to maintain operations and financial solvency in a changing external environment, many find that new approaches to innovation are crucial to survival and strategic success. This article reviews the history of Agile, provides a high-level overview of the process, compares Agile to other innovation approaches, and shares how Agile can help reduce clinician burnout.
Using Agile Science for Rapid Innovation and Implementation of a New Care Model
Authors: Azar Jose , Glantz Erin , Solid Craig , Holden Richard , Boustani Malaz
Published: November 2023

As industry consolidation leads to a growing number of large new healthcare delivery networks, patients and their clinicians are losing the important human-centric and relationship-based nature of medical care. The leadership of Hackensack Meridian Health (HMH), a New Jersey-based network of hospitals, research center, and medical school, made an organizational commitment to reverse such loss and restore the social nature of medicine. To attain that goal, HMH engaged both clinicians and administrators to confirm the demand for change, foster a collaborative culture design, and address the unique nature of the individual components in the HMH network. Efforts to transform the HMH care delivery model illustrate the effectiveness of Agile science and its problem-solving methods.
Efficiency and Related Factors of Multifocal Soft Contact Lenses in Controlling Myopia
Authors: Peng Tianli , Jiang Jun
Published: November 2023

Objective:

To evaluate ocular changes in Chinese myopic children wearing multifocal soft contact lenses and explore their efficiency and related factors.

Method:

This was a prospective, double-blind, randomized controlled study. A total of 36 myopic children aged 7 to 12 years were randomly divided into groups wearing multifocal soft contact lenses (MFCLs) or single-vision soft contact lenses (SVCLs) and followed up for 12 months. The spherical equivalent (SE), axial length (AL), choroidal thickness, and vascularity were measured before commencement and after 6 and 12 months of lens wear. Correlation between ocular changes and myopia progression was determined.

Results:

A total of 32 subjects (6 males and 26 females) completed the study and were included in the analysis. After 12 months of lens wear, both the AL elongation (0.25±0.22 vs. 0.43±0.16 mm, P=0.011) and the SE progression (−0.69±0.69 D vs. −1.45±0.56 D, P=0.002) of the MFCL group were significantly lower than those of the SVCL group. After 12 months, the progression of myopia was significantly correlated with changes of the choroid in the MFCL wearers, whereas no such correlation was observed in the SVCL group.

Conclusion:

Multifocal soft contact lens can slow myopia progression, and this effect may be related to the changes of the choroid.
The effect of gender on clinical outcomes following routine revascularizations with polymer-free sirolimus-eluting stents
Authors: Krackhardt Florian , Yan Guangyao , Kherad Behrouz , Blaich Birgit , Leschke Matthias , Waliszewski Matthias
Published: November 2023

Background:

Gender-specific outcomes after percutaneous coronary interventions were studied by a number of research groups with different endpoints and cohorts of different ethnic extractions. The purpose of this report is to use propensity score matching to determine gender-specific differences in clinical outcomes after percutaneous coronary interventions with polymer-free sirolimus-coated stents.

Materials and methods:

The basis for this post hoc analysis was two large all-comers studies with prospectively enrolled patients from Europe and Asia. Data were pooled and analyzed in terms of clinical outcomes to assess the impact of gender in patients with stable coronary artery disease and acute coronary syndrome. The primary endpoint was the accumulated target-lesion revascularization rate whereas secondary endpoints consisted of the event rates for major adverse cardiac events (MACE), myocardial infarction, bleeding events and death from all causes. The purpose of these post hoc analyses was to detect potential differences in clinical outcomes between females and males in unselected and propensity-score-matched cohorts.

Results:

Overall, in the unmatched cohorts, accumulated target-lesion revascularization rates did not differ between both genders (2.7% vs. 2.0%; P = 0.101), however, accumulated MACE rates were higher in females than in males (5.2% vs. 3.9%; P = 0.020). After propensity-score-matching, primarily adjusting for age, hypertension and diabetes, our data revealed similar accumulated MACE in women and men (5.5% vs. 5.2%; P = 0.749). In the unmatched STEMI subgroup, all-cause mortality was significantly higher in females driven by older age (P < 0.001).

Conclusion:

In the propensity-score-matched real-world cohorts, female gender was not a predictor for increased rates of accumulated MACE. In the unmatched STEMI subgroup, all-cause mortality was significantly higher in females due to older age. Age seems to be the determining factor for increased clinical event rates and not gender.
The prognostic importance of the Naples prognostic score for in-hospital mortality in patients with ST-segment elevation myocardial infarction
Authors: Saygi Mehmet , Tanalp Ali Cevat , Tezen Ozan , Pay Levent , Dogan Remziye , Uzman Osman , Karabay Can Yucel , Tanboga Ibrahim Halil , Kacar Flora Ozkalayci , Karagoz Ali
Published: November 2023

Background

The Naples prognostic score (NPS) is an effective inflammatory and nutritional scoring system widely applied as a prognostic factor in various cancers. However, the prognostic significance of NPS is unknown in ST-segment elevation myocardial infarction (STEMI). We aimed to analyze the prognostic value of the NPS in-hospital mortality in patients with STEMI.

Methods

The study consisted of 3828 patients diagnosed with STEMI who underwent primer percutaneous coronary intervention. As the primary outcome, in-hospital mortality was defined as all-cause deaths during hospitalization. The included patients were categorized into three groups based on NPS (group 1:NPS = 0,1,2; group 2:NPS = 3; group 3:NPS = 4)

Results

Increased NPS was associated with higher in-hospital mortality rates(P < 0.001). In the multivariable logistic regression analysis, the relationship between NPS and in-hospital mortality continued after adjustment for age, male sex, diabetes, hypertension, Killip score, SBP, heart rate, left ventricular ejection fraction, myocardial infarction type and postprocedural no-reflow. A strong positive association was found between in-hospital mortality and NPS by multivariable logistic regression analysis [NPS 0–1–2 as a reference, OR = 1.73 (95% CI, 1.04–2.90) for NPS 3, OR = 2.83 (95% CI, 1.76–4.54) for NPS 4].

Conclusion

The present study demonstrates that the NPS could independently predict in-hospital mortality in STEMI. Prospective studies will be necessary to confirm the performance, clinical applicability and practicality of the NPS for in-hospital mortality in STEMI.
Non-atherosclerotic acute cardiac syndromes: spontaneous coronary artery dissection and Takotsubo syndrome. Comparison of long-term clinical outcomes
Authors: Salamanca Jorge , García-Guimaraes Marcos , Sabaté Manel , Sanz-Ruiz Ricardo , Macaya Fernando , Roura Gerard , Jimenez-Kockar Marcelo , Nogales Juan Manuel , Tizón-Marcos Helena , Velazquez Maite , Veiga Gabriela , Gamarra Alvaro , Aguilar Rio , Jiménez-Borreguero Luis Jesús , Díez-Villanueva Pablo , Bastante Teresa , Núñez-Gil Iván , Alfonso Fernando
Published: November 2023

Background

Spontaneous coronary artery dissection (SCAD) and Takotsubo syndrome (TTS) constitute two common causes of nonatherosclerotic acute cardiac syndrome particularly frequent in women. Currently, there is no information comparing long-term clinical outcomes in unselected patients with these conditions.

Methods

We compared the baseline characteristics, in-hospital outcomes, and the 12-month and long-term clinical outcomes of two large prospective registries on SCAD and TTS.

Results

A total of 289 SCAD and 150 TTS patients were included; 89% were women. TTS patients were older with a higher prevalence of cardiovascular risk factors. Precipitating triggers were more frequent in TTS patients, while emotional triggers and depressive disorders were more common in the SCAD group. Left ventricular ejection fraction was lower in TTS patients, but SCAD patients showed higher cardiac biomarkers. In-hospital events (43.3% vs. 5.2%, P<0.01) occurred more frequently in TTS patients. TTS patients also presented more frequent major adverse events at 12-month (14.7% vs. 7.1%, HR 5.3, 95% CI: 2.4–11.7, P<0.01) and long-term (median 36 vs. 31 months, P=0.41) follow-up (25.8% vs. 9.6%, HR 4.5, 95% CI: 2.5–8.2, P<0.01). Atrial fibrillation was also more frequent in TTS patients. Moreover, TTS patients presented a higher 12-month and long-term mortality (5.6% vs. 0.7%, P=0.01; and 12.6% vs. 0.7%, P<0.01) mainly driven by noncardiovascular deaths.

Conclusion

Compared to SCAD, TTS patients are older and present more cardiovascular risk factors but less frequent depressive disorder or emotional triggers. TTS patients have a worse in-hospital, mid-term, and long-term prognosis with higher noncardiac mortality than SCAD patients.
Novel therapies for pediatric acute lymphoblastic leukemia
Authors: Graff Zachary , Burke Michael J. , Gossai Nathan
Published: November 2023

Purpose of review

This review summarizes the current novel therapy landscape in pediatric acute lymphoblastic leukemia (ALL), with a focus on key clinical trials which will shape the future direction of care for these children.

Recent findings

Recent landmark immunotherapy trials in B-ALL have demonstrated significant benefit for children, adolescents, and young adults with relapsed/refractory high-risk leukemia. Due to these successes, current trials are asking the question as to whether immunotherapy can be successfully incorporated upfront. Additionally, therapies targeting novel antigens or molecular pathways are being developed, providing new options for children previously thought to have incurable leukemia.

As survival for ALL has relatively plateaued with maximizing intensity through conventional chemotherapy, continued preclinical and clinical study of novel immunotherapeutic and targeted agents is crucial to further improve outcomes in childhood leukemia.
Controlling infections in hospitalized pretransplant candidates
Authors: Lacy Marian G. , Filippov Evgenii , Nematollahi Saman
Published: November 2023

Purpose of review

Infections in hospitalized patients awaiting solid organ transplantation can pose complicated diagnostic and therapeutic challenges. Goals of management include stabilizing the patient, treating or controlling infections, and decreasing the risk of reactivation of infection after transplant.

Recent findings

Groups such as The Organ Procurement and Transplantation Network, American Society of Transplantation Infectious Diseases Community of Practice and the European Society of Clinical Microbiology and Infectious Diseases have updated their guidelines on screening and treatment of infection in transplant candidates. There are also recent developments in therapeutic options for tuberculosis, COVID-19, Clostridioides difficile colitis, bloodstream infections, and other common infections.

Ideally, antimicrobial therapy should be complete prior to transplantation. In situations in which completion of therapy prior to transplant is not feasible, therapy may need to be prolonged or modified. In most situations, infections can be managed similarly to the general population, although some infections, particularly fungal and mycobacterial, require a different management approach. We review disease- and organ-specific management.
Fetal growth assessed via ultrasound in relation to maternal HIV infection status and antiretroviral regimens
Authors: Williams Paige L. , Karalius Brad , Patel Kunjal , Aschengrau Ann , Chakhtoura Nahida , Enriquez Naomi , Moye Jack , Garvie Patricia A. , Monte Dina , Seage George R. , Zorrilla Carmen , Mussi-Pinhata Marisa M. ,   for the HIV ZIP Study
Published: November 2023

Objective:

To evaluate effects of maternal HIV and antiretroviral treatment (ART) on intrauterine fetal growth.

Design:

Prospective cohort studies of HIV and ZIKA infection among women living with HIV (WLHIV) and women not living with HIV (WNLHIV) conducted in Brazil and the US from 2016 to 2020.

Methods:

We evaluated fetal growth via repeated ultrasounds and calculated z scores for fetal growth measures using Intergrowth-21st standards among women with singleton pregnancies. Adjusted linear mixed models were fit for each fetal growth z score by HIV status. Among WLHIV, we compared fetal growth z scores by the most common maternal ART regimens, stratified by timing of ART initiation.

Results:

We included 166 WLHIV and 705 WNLHIV; none had Zika infection. The z scores were similar for WLHIV and WNLHIV for femur length (latest third trimester median = 1.08) and estimated fetal weight (median ≈0.60); adjusted mean differences in fetal weight z scores by HIV status were less than 0.1 throughout gestation. Other fetal growth measurements were lower for WLHIV than WNLHIV early in gestation but increased more rapidly over gestation. Among WLHIV not on ART at conception, adjusted mean z scores were generally similar across regimens initiated during pregnancy but somewhat lower for atazanavir-based regimens for biparietal diameter compared with efavirenz-based or raltegravir-based regimens. Among WLHIV on ART at conception, mean z scores were similar across ART regimens.

Conclusion:

Within our cohorts, fetal growth was lower in WLHIV than WNLHIV early in gestation but similar by the end of gestation, which is reassuring. Among WLHIV, fetal growth measures were generally similar across ART regimens evaluated.
Foraging mode constrains the evolution of cephalic horns in lizards and snakes
Authors: Banfi Federico , Meiri Shai , Shine Richard , Van Damme Raoul , Baeckens Simon
Published: November 2023

A phylogenetically diverse minority of snake and lizard species exhibit rostral and ocular appendages that substantially modify the shape of their heads. These cephalic horns have evolved multiple times in diverse squamate lineages, enabling comparative tests of hypotheses on the benefits and costs of these distinctive traits. Here, we demonstrate correlated evolution between the occurrence of horns and foraging mode. We argue that although horns may be beneficial for various functions (e.g. camouflage, defence) in animals that move infrequently, they make active foragers more conspicuous to prey and predators, and hence are maladaptive. We therefore expected horns to be more common in species that ambush prey (entailing low movement rates) rather than in actively searching (frequently moving) species. Consistent with that hypothesis, our phylogenetic comparative analysis of published data on 1939 species reveals that cephalic horns occur almost exclusively in sit-and-wait predators. This finding underlines how foraging mode constrains the morphology of squamates and provides a compelling starting point for similar studies in other animal groups.
Proposed three-phenylalanine motif involved in magnetoreception signalling of an Actinopterygii protein expressed in mammalian cells
Authors: Ricker Brianna , Mitra Sunayana , Castellanos E. Alejandro , Grady Connor J. , Woldring Daniel , Pelled Galit , Gilad Assaf A.
Published: November 2023

Studies at the cellular and molecular level of magnetoreception—sensing and responding to magnetic fields—are a relatively new research area. It appears that different mechanisms of magnetoreception in animals evolved from different origins, and, therefore, many questions about its mechanisms remain left open. Here we present new information regarding the Electromagnetic Perceptive Gene (EPG) from
Kryptopterus vitreolus
that may serve as part of the foundation to understanding and applying magnetoreception. Using HaloTag coupled with fluorescent ligands and phosphatidylinositol specific phospholipase C we show that EPG is associated with the membrane via glycosylphosphatidylinositol anchor. EPG's function of increasing intracellular calcium was also used to generate an assay using GCaMP6m to observe the function of EPG and to compare its function with that of homologous proteins. It was also revealed that EPG relies on a motif of three phenylalanine residues to function—stably swapping these residues using site directed mutagenesis resulted in a loss of function in EPG. This information not only expands upon our current understanding of magnetoreception but may provide a foundation and template to continue characterizing and discovering more within the emerging field.
RNA binding protein AUF1/HNRNPD regulates nuclear export, stability and translation of
SNCA
transcripts
Authors: Kattan Fedon-Giasin , Koukouraki Pelagia , Anagnostopoulos Athanasios K. , Tsangaris George T. , Doxakis Epaminondas
Published: November 2023

Alpha-synuclein (SNCA) accumulation plays a central role in the pathogenesis of Parkinson's disease. Determining and interfering with the mechanisms that control SNCA expression is one approach to limiting disease progression. Currently, most of our understanding of SNCA regulation is protein-based. Post-transcriptional mechanisms directly regulating
SNCA
mRNA expression via its 3′ untranslated region (3′UTR) were investigated here. Mass spectrometry of proteins pulled down from murine brain lysates using a biotinylated
SNCA
3′UTR revealed multiple RNA-binding proteins, of which HNRNPD/AUF1 was chosen for further analysis. AUF1 bound both proximal and distal regions of the
SNCA
3′UTR, but not the 5′UTR or CDS. In the nucleus, AUF1 attenuated
SNCA
pre-mRNA maturation and was indispensable for the export of
SNCA
transcripts. AUF1 destabilized
SNCA
transcripts in the cytosol, primarily those with shorter 3′UTRs, independently of microRNAs by recruiting the CNOT1-CNOT7 deadenylase complex to trim the polyA tail. Furthermore, AUF1 inhibited
SNCA
mRNA binding to ribosomes. These data identify AUF1 as a multi-tasking protein regulating maturation, nucleocytoplasmic shuttling, stability and translation of
SNCA
transcripts.
Cellular and molecular signatures of motherhood in the adult and ageing rat brain
Authors: Duarte-Guterman P. , Richard J. E. , Lieblich S. E. , Eid R. S. , Lamers Y. , Galea L. A. M.
Published: November 2023

Pregnancy is marked by robust changes, including brain changes to volume, structure, connectivity and neuroplasticity. Although some brain changes are restricted to pregnancy and the postpartum, others are long-lasting. Few studies have examined possible mechanisms of these changes or the effects of multiple pregnancies. We characterized various cellular and molecular signatures of parity (nulliparous, primiparous, biparous) in the rat hippocampus. We investigated density of neural stems cells (Sox2), microglia (Iba-1) and levels of a synaptic protein (PSD-95), cell signalling pathways, neuroinflammation, and the tryptophan–kynurenine (TRP–KYN) pathway, one week after weaning their pups from the last pregnancy (age of dam: seven months) and in middle-age (age of dam: 13 months). Parity increased PSD-95 levels in both age groups and prevented the age-related decrease in neural stem cell density observed in nulliparous rats. Biparity increased cell signalling phosphoproteins (pp70S6K, S6RP) and number of microglia in the dentate gyrus, regardless of age. Parity resulted in transient changes to the TRP–KYN system. Thus, previous parity has lasting effects on synaptic plasticity with fewer lasting effects on inflammation and cell signalling phosphoproteins in the whole hippocampus.