bluuebunny/crossref_metadata_2025_split huggingface dataset:
The changing shape of English general practice: a retrospective longitudinal study using national datasets describing trends in organisational structure, workforce and recorded appointments
Authors: Pettigrew Luisa M , Petersen Irene , Mays Nicholas , Cromwell David 
Published: September 2024

ObjectiveTo describe trends in the organisational structure, workforce and recorded appointments by role in English general practice.DesignRetrospective longitudinal study.SettingEnglish general practice.Data sources and participantsNHS England, Office for Health Improvement and Disparities and Care Quality Commission national administrative datasets covering between 5 to 10 years from 2013 to 2023.ResultsBetween 2013 and 2023, the number of general practices fell by 20% from 8044 to 6419; the average practice list size increase by 40% from 6967 to 9724 patients. The total population covered by providers with over 100 000 registered patients reached 2.3 million in 2023 compared to 0.5 million in 2017. The proportion of practices under individual ownership decreased from 13% to 11% between 2018 and 2023; there was little change in the proportion owned by partnerships, incorporated companies or NHS bodies, which respectively averaged around 80.3%, 6.9% and 0.7%. Between 2015 and 2022, there was a 20% rise in the total full-time equivalent (FTE) general practice workforce, including Primary Care Network staff, from 1.97 to 2.37 per 1000 patients because of an increase in multidisciplinary other 'Direct Patient Care' (DPC) and administrative roles. The number of nurses remained stable, and the number of qualified general practitioners (GPs) decreased by 15%. In September 2022, there were 0.45 FTE qualified GPs per 1000 patients; GPs and other DPC roles, excluding nurses, each represented 19% of the FTE per 1000 patients workforce; administrative roles represented 51%. The general practice workforce is predominantly female. A quarter of GPs qualified overseas. Between 2018 and 2023, there was no clear upward or downward trend in total appointments per 1000 patients with, on average, half provided by GPs.ConclusionsSince 2013, there has been a shift in general practice towards larger practices with more multidisciplinary teams, alongside a reduction in the number of FTE qualified GPs per 1000 patients. We recommend that the impacts of these changes on access, quality and costs are closely monitored.
Quantitative sensory testing and chronic pain syndromes: a cross-sectional study from TwinsUK
Authors: Rhee Amber , Granville Smith Isabelle , Compte Roger , Vehof Jelle , Nessa Ayrun , Wadge Samuel , Freidin Maxim B , Bennett David L , Williams Frances M K 
Published: September 2024

ObjectiveThe chronic pain syndromes (CPS) include syndromes such as chronic widespread pain (CWP), dry eye disease (DED) and irritable bowel syndrome (IBS). Highly prevalent and lacking pathognomonic biomarkers, the CPS are known to cluster in individuals in part due to their genetic overlap, but patient diagnosis can be difficult. The success of quantitative sensory testing (QST) and inflammatory biomarkers as phenotyping tools in conditions such as painful neuropathies warrant their investigation in CPS. We aimed to examine whether individual QST modalities and candidate inflammatory markers were associated with CWP, DED or IBS in a large, highly phenotyped population sample.DesignCross-sectional study.SettingCommunity-dwelling cohort.ParticipantsTwins from the TwinsUK cohortPrimary and secondary outcome measuresWe compared 10 QST modalities, measured in participants with and without a CWP diagnosis between 2007 and 2012. We investigated whether inflammatory markers measured by Olink were associated with CWP, including interleukin-6 (IL-6), IL-8, IL-10, monocyte chemoattractant protein-1 and tumour necrosis factor. All analyses were repeated in DED and IBS with correction for multiple testing.ResultsIn N=3022 twins (95.8% women), no association was identified between individual QST modalities and CPS diagnoses (CWP, DED and IBS). Analyses of candidate inflammatory marker levels and CPS diagnoses in n=1368 twins also failed to meet statistical significance.ConclusionOur findings in a large population cohort suggest a lack of true association between singular QST modalities or candidate inflammatory markers and CPS.
Genetics Navigator: protocol for a mixed methods randomized controlled trial evaluating a digital platform to deliver genomic services in Canadian pediatric and adult populations
Authors: D'Amours Guylaine , Clausen Marc , Luca Stephanie , Reble Emma , Kodida Rita , Assamad Daniel , Bernier Francois , Chad Lauren , Costain Gregory , Dhalla Irfan , Faghfoury Hanna , Friedman Jan M , Hewson Stacy , Jamieson Trevor , Silver Josh , Shuman Cheryl , Osmond Matthew , Carroll June C , Jobling Rebekah , Laberge Anne-Marie , Aronson Melyssa , Liston Eriskay , Lerner-Ellis Jordan , Marshall Christian , Brudno Michael , Pham Quynh , Rudzicz Frank , Cohn Ronald , Mamdani Muhammad , Smith Maureen , Shastri-Estrada Serena , Seto Emily , Thorpe Kevin , Ungar Wendy , Hayeems Robin Z , Bombard Yvonne 
Published: September 2024

IntroductionGenetic testing is used across medical disciplines leading to unprecedented demand for genetic services. This has resulted in excessive waitlists and unsustainable pressure on the standard model of genetic healthcare. Alternative models are needed; e-health tools represent scalable and evidence-based solution. We aim to evaluate the effectiveness of the Genetics Navigator, an interactive patient-centred digital platform that supports the collection of medical and family history, provision of pregenetic and postgenetic counselling and return of genetic testing results across paediatric and adult settings.Methods and analysisWe will evaluate the effectiveness of the Genetics Navigator combined with usual care by a genetics clinician (physician or counsellor) to usual care alone in a randomised controlled trial. One hundred and thirty participants (adults patients or parents of paediatric patients) eligible for genetic testing through standard of care will be recruited across Ontario genetics clinics. Participants randomised into the intervention arm will use the Genetics Navigator for pretest and post-test genetic counselling and results disclosure in conjunction with their clinician. Participants randomised into the control arm will receive usual care, that is, clinician-delivered pretest and post-test genetic counselling, and results disclosure. The primary outcome is participant distress 2 weeks after test results disclosure. Secondary outcomes include knowledge, decisional conflict, anxiety, empowerment, quality of life, satisfaction, acceptability, digital health literacy and health resource use. Quantitative data will be analysed using statistical hypothesis tests and regression models. A subset of participants will be interviewed to explore user experience; data will be analysed using interpretive description. A cost-effectiveness analysis will examine the incremental cost of the Navigator compared with usual care per unit reduction in distress or unit improvement in quality of life from public payer and societal perspectives.Ethics and disseminationThis study was approved by Clinical Trials Ontario. Results will be shared through stakeholder workshops, national and international conferences and peer-reviewed journals.Trial registration numberNCT06455384.
Targeting IL-33 reprograms the tumor microenvironment and potentiates antitumor response to anti-PD-L1 immunotherapy
Authors: Nan Yanyang , Bai Yu , Hu Xiaozhi , Zhou Kaicheng , Wu Tao , Zhu An , Li Mengyang , Dou Zihan , Cao Zhonglian , Zhang Xumeng , Xu Shuwen , Zhang Yuanzhen , Lin Jun , Zeng Xian , Fan Jiajun , Zhang Xuyao , Wang Xuebin , Ju Dianwen 
Published: September 2024

BackgroundThe main challenge against patients with cancer to derive benefits from immune checkpoint inhibitors targeting PD-1/PD-L1 appears to be the immunosuppressive tumor microenvironment (TME), in which IL-33/ST2 signal fulfills critical functions. However, whether IL-33 limits the therapeutic efficacy of anti-PD-L1 remains uncertain.MethodsMolecular mechanisms of IL-33/ST2 signal on anti-PD-L1 treatment lewis lung carcinoma tumor model were assessed by RNA-seq, ELISA, WB and immunofluorescence (IF). A sST2-Fc fusion protein was constructed for targeting IL-33 and combined with anti-PD-L1 antibody for immunotherapy in colon and lung tumor models. On this basis, bifunctional fusion proteins were generated for PD-L1-targeted blocking of IL-33 in tumors. The underlying mechanisms of dual targeting of IL-33 and PD-L1 revealed by RNA-seq, scRNA-seq, FACS, IF and WB.ResultsAfter anti-PD-L1 administration, tumor-infiltrating ST2+regulatory T cells (Tregs) were elevated. Blocking IL-33/ST2 signal with sST2-Fc fusion protein potentiated antitumor efficacy of PD-L1 antibody by enhancing T cell responses in tumor models. Bifunctional fusion protein anti-PD-L1-sST2 exhibited enhanced antitumor efficacy compared with combination therapy, not only inhibited tumor progression and extended the survival, but also provided long-term protective antitumor immunity. Mechanistically, the superior antitumor activity of targeting IL-33 and PD-L1 originated from reducing immunosuppressive factors, such as Tregs and exhausted CD8+T cells while increasing tumor-infiltrating cytotoxic T lymphocyte cells.ConclusionsIn this study, we demonstrated that IL-33/ST2 was involved in the immunosuppression mechanism of PD-L1 antibody therapy, and blockade by sST2-Fc or anti-PD-L1-sST2 could remodel the inflammatory TME and induce potent antitumor effect, highlighting the potential therapeutic strategies for the tumor treatment by simultaneously targeting IL-33 and PD-L1.
Cyclic response of pre-failed and reinstalled single-helix piles in sand
Authors: Schiavon José Antonio , Neme Gamarra Mariano , Tsuha Cristina de Hollanda Cavalcanti , Thorel Luc 
Published: September 2024

Helical piles can be rescrewed at greater depths after failure and put back into service again as long as their integrity is preserved. However, reports on the lifetime performance after reinstallation are completely missing in the literature. This work compares the tensile cyclic response of single helix piles in dry and saturated sand after experiencing failure due to monotonic uplift and after reinstallation, using centrifuge model testing. Tensile cyclic tests were conducted on three model piles with different helix-to-shaft diameter ratios, under two different conditions: (1) cyclic loading after monotonic pile failure, and (2) cyclic loading on a pile that has been reinstalled deeper into the soil after experiencing a monotonic failure. The experiments revealed that the preceding monotonic failure causes significant influence on the post-failure cyclic performance, in which few tens of cycles are enough to lead to a critical accumulated displacement. The cyclic tests on the reinstalled helical pile at a depth of 2 D ( D = helix diameter) below the initial helix depth showed that the cyclic performance can be partially to fully recovered depending on the loading amplitude.
Quantum metrology of Schwinger effect
Authors: Fan Tingting , Liu Qianqian , Jing Jiliang , Wang Jieci 
Published: September 2024

AbstractWe propose a scheme for the quantum metrology of the Schwinger effect and the dynamics of Gaussian interference power (GIP). The ongoing reliability of the estimation strategy for the probe state prepared in particle–particle modes is demonstrated. Although the GIP sensitively depends on the strength of the external electric field and the transverse momentum, the advantage of quantum parameter estimation is still maintained even in the limit of an infinite electric field and zero transverse momentum. It is shown that the entanglement between the particle–particle modes provides a guarantee for obtaining higher precision for the black-box estimation. In contrast, for the probe state prepared in particle–antiparticle modes, the advantage of quantum parameter estimation can also be ensured even though there is no entanglement in the probe state. Put differently, some non-entanglement quantum correlations play the role of quantum resources in the estimation for particle–antiparticle modes.
Hard diffraction in SHERPA
Authors: Krauss Frank , Meinzinger Peter 
Published: September 2024

AbstractWe present the first complete simulation framework for the simulation of jet production in diffractive events at next-to leading order in QCD, matched to the parton shower. We validate the implementation in the SHERPA event generator with data from the H1 and ZEUS experiments for diffractive DIS and diffractive photoproduction. For the latter, we review different models aiming to explain the observed factorisation breaking and we argue that at NLO the direct component must also be suppressed. We provide predictions for diffractive jet production both in DIS and in photoproduction events for the upcoming EIC.
Exploring the UV and IR of a type-II holographic superconductor using a dyonic black hole
Authors: de la Cruz-López Manuel , Herrera-Mendoza Jhony A. , Cartas-Fuentevilla Roberto , Herrera-Aguilar Alfredo 
Published: September 2024

AbstractIn this study, we investigate a type-II holographic superconductor with a perturbative scalar field over a (3 + 1)-dimensional electric and magnetically charged planar AdS black hole. We review the thermodynamical properties of the background relevant for the dual description of the Ginzburg–Landau density of superconducting states, showing that the adoption of a London gauge allows a consistent description of the Abrikosov vortex lattices, typical of type-II superconductors. We further derive a new expression for the upper critical magnetic field as a function of temperature in the grand canonical ensemble, supplementary to the one previously obtained in the canonical ensemble setup. These results confirm that our perturbative scalar field model consistently reproduces the well-known temperature behavior of the upper critical magnetic field according to the Ginzburg–Landau theory and other Abelian–Higgs holographic developments for type-II superconductors. We then continue with an original analysis of the scalar field equation in terms of a Schrödinger potential that led to the observation of bound states, a signal for the condensation of Cooper pairs. These results provide robust evidence for the existence of an IR order parameter near extremality. In view of this, we performed a closer inspection of the IR effective scalar equation in which the geometry adopts a Schwarzschild $$\hbox {AdS}_{2}\times {\mathbb {R}}^{2}$$

AdS
2

×

R

2

structure, finding novel condensed bound states in the IR regime.
Cross-linguistic rhythm analysis of Mising and Assamese
Authors: Gogoi Parismita , Sarmah Priyankoo , Prasanna S. R. M. 
Published: September 2024

The objective of the current study is to explore a quantitative frequency domain technique to evaluate rhythm in spontaneous speech data of 19 native speakers of Mising and Assamese, two low-resourced languages spoken in Assam, North-East India. The concept of analyzing speech rhythm using amplitude modulation (AM) low-frequency (LF) spectrum, also known as rhythm formant analysis (RFA), is initially put forth by Gibbon and Li [
17
]. We propose three features from rhythm formants of the LF spectrum and also explore discrete cosine transform (DCT)–based characterization of the retrieved LF spectrum. We aim to distinguish the rhythm of Assamese and two Mising dialects, namely Pagro and Delu, with the aid of machine learning techniques fed with the derived features as input. We have observed that the features are efficient in classifying Assamese vs Pagro and Assamese vs Delu with an accuracy of 92.73% and 91.15%, respectively. The experimental analysis further reveals that Assamese is rhythmically closer to Delu than Pagro.
Gene-Specific Machine Learning Models to Classify Driver Mutations in Clonal Hematopoiesis
Authors: Arends Christopher M. , Jaiswal Siddhartha 
Published: September 2024

Summary:There is no general consensus on the set of mutations capable of driving the age-related clonal expansions in hematopoietic stem cells known as clonal hematopoiesis, and current variant classifications typically rely on rules derived from expert knowledge. In this issue of Cancer Discovery, Damajo and colleagues trained and validated machine learning models without prior knowledge of clonal hematopoiesis driver mutations to classify somatic mutations in blood for 12 genes in a purely data-driven way.See related article by Demajo et al., p. 1717 (9).
If You Build It, Patients with Rare Cancers Will Come: A Successful Clinical Trial in Relapsed and Refractory JMML
Authors: Ben-Crentsil Nana Adjoa , Padron Eric 
Published: September 2024

Summary:Juvenile myelomonocytic leukemia (JMML) is a rare pediatric hematologic malignancy with a high relapse rate and a poor prognosis hallmarked by RAS pathway mutations. Stieglitz and colleagues conducted a phase II clinical trial using the MEK inhibitor trametinib to treat patients with relapsed and refractory juvenile myelomonocytic leukemia and observed an objective response rate of 50% and an overall survival of 80% after 4 years.See related article by Stieglitz et al., p. 1590 (4) .
Prevalence of Hyperkalemia and Familial Hyperkalemic Hypertension in 5100 Patients Referred to a Tertiary Hypertension Unit
Authors: Tetti Martina , Burrello Jacopo , Hureaux Marguerite , Billon Clarisse , Clauser Eric , Veglio Franco , Rabbia Franco , Pasini Barbara , Crisetti Annalisa , Jeunemaitre Xavier , Mulatero Paolo , Monticone Silvia 
Published: September 2024

BACKGROUND:
Hyperkalemia is a frequent electrolyte alteration whose prevalence varies widely, depending on the adopted cutoff, the setting (inpatients versus outpatients), and the characteristics of the study population. Familial hyperkalemic hypertension (FHH) is a rare cause of hypertension, hyperkalemia, and hyperchloremic metabolic acidosis.

METHODS:

In this retrospective observational study, we investigated the prevalence of hyperkalemia (serum K
+
>5.2 mmol/L on 2 repeated measurements) in 5100 referred patients affected by arterial hypertension, the potential causes, and the associated cardiovascular risk profile.

RESULTS:

Overall, 374 (7.3%) patients had hyperkalemia. This was associated with drugs known to increase K
+
levels (74.6%), chronic kidney disease (33.7%), or both (24.3%). Among the 60 patients with unexplained hyperkalemia, 3 displayed a clinical and biochemical phenotype suggestive of FHH that was genetically confirmed in 2 of them (0.04% in the entire cohort). FHH prevalence rose to 3.3% in patients with unexplained hyperkalemia and up to 29% (2/7) if they had serum K
+
>5.8 mmol/L. The genetic cause of FHH was a missense variant affecting the acidic motif of
WNK1
in 1 family and a rare
CUL3
splicing variant, whose functional significance was confirmed by a minigene assay, in another. Finally, we observed a significant association between hyperkalemia and the occurrence of cardiovascular events, metabolic syndrome, and organ damage, independent of potential confounding factors.

CONCLUSIONS:
The identification of hyperkalemia in patients with hypertension has prognostic implications. A timely diagnosis of FHH is important for effective management of hypertension, electrolyte imbalance correction with tailored treatment, and genetic counseling.
Use and Cost Patterns of Antihypertensive Medications in the United States From 1996 to 2021
Authors: Jacobs Joshua A. , Rodgers Anthony , Bellows Brandon K. , Hernandez Inmaculada , Wang Nelson , Derington Catherine G. , King Jordan B. , Zheutlin Alexander R. , Whelton Paul K. , Egan Brent M. , Cushman William C. , Bress Adam P. 
Published: September 2024

BACKGROUND:
Antihypertensive medication use patterns have likely been influenced by changing costs and accessibility over the past 3 decades. This study examines the relationships between patent exclusivity loss, medication costs, and national health policies on antihypertensive medication use.

METHODS:
Using 1996 to 2021 Medical Expenditure Panel Survey data of US adults with hypertension taking at least 1 antihypertensive medication, we conducted a cross-sectional analysis. We explored the associations between patent exclusivity loss, per-pill costs, and Medicare Part D enactment on medication use over time, focusing on the most commonly used medications (lisinopril, amlodipine, losartan, hydrochlorothiazide, and metoprolol).

RESULTS:
The unweighted sample comprised 50 095 US adults (mean age, 62 years; 53% female). The survey-weighted number of adults taking antihypertensive medications increased from 22 million (95% CIs, 20–23 million) to 55 million (95% CI, 51–60 million) between 1996 and 2021. Loss of patent exclusivity led to increased medication fills, notably for lisinopril, amlodipine, and losartan, which all exhibited within-class dominance. However, per-pill cost decreases coinciding with Medicare Part D did not increase the number of individuals treated or the use of specific antihypertensive medications or classes.

CONCLUSIONS:
The increase in antihypertensive medication use over the past decades highlights the significant impact of loss of patent exclusivity on the uptake in the use of specific medications. These findings underscore the complexity of factors influencing medication use, beyond cost reductions alone, and suggest that policies need to consider multiple facets to effectively improve antihypertensive medication accessibility and utilization.
Finite State Machines with Data Paths in Visual Languages for Music
Authors: Tavares Tiago Fernandes , Fornari José Eduardo 
Published: September 2024

Abstract
Some music-domain visual programming languages (VPLs) have been shown to be Turing-complete. The common lack of built-in flow control structures can obstruct using VPLs to implement general-purpose algorithms, however, which harms the direct use of algorithms and algorithm theory in art-creation processes using VPLs. In this article, we show how to systematically implement general-purpose algorithms in music-domain visual languages by using the computation model known as a finite state machine with data path. The results expose a finite state machine and a set of internal state variables that traverse paths whose speed can be controlled using metronome ticks and whose path depends on the initial conditions of the algorithm. These elements can be further mapped to music elements according to the musician's intentions. We demonstrate this technique by implementing Euclid's greatest common divisor algorithm and using it to control high-level music elements in an implementation of Terry Riley's In C, and to control audio synthesis parameters in a frequency-modulator synthesizer.
Segmentation-Free Streaming Machine Translation
Authors: Iranzo-Sánchez Javier , Iranzo-Sánchez Jorge , Giménez Adrià , Civera Jorge , Juan Alfons 
Published: September 2024

Abstract
Streaming Machine Translation (MT) is the task of translating an unbounded input text stream in real-time. The traditional cascade approach, which combines an Automatic Speech Recognition (ASR) and an MT system, relies on an intermediate segmentation step which splits the transcription stream into sentence-like units. However, the incorporation of a hard segmentation constrains the MT system and is a source of errors. This paper proposes a Segmentation-Free framework that enables the model to translate an unsegmented source stream by delaying the segmentation decision until after the translation has been generated. Extensive experiments show how the proposed Segmentation-Free framework has better quality-latency trade-off than competing approaches that use an independent segmentation model.1