bluuebunny/crossref_metadata_2025_split huggingface dataset:
Market making and the production of nurses for export: a case study of India–UK health worker migration
Authors: Merz Sibille , Hunter Benjamin M , Murray Susan F , Bisht Ramila 
Published: February 2024

BackgroundHigh-income countries increasingly look to the international recruitment of health workers to address domestic shortages, especially from low-income and middle-income countries. We adapt conceptual frameworks from migration studies to examine the networked and commercialised nature of the Indian market for nurse migration to the UK.MethodsWe draw on data from 27 expert interviews conducted with migration intermediaries, healthcare providers and policymakers in India and the UK.FindingsIndia–UK nurse migration occurs within a complex and evolving market encompassing ways to educate, train and recruit nursing candidates. For-profit actors shape the international orientation of nursing curricula, broker on-the-job training and offer language, exam and specialised clinical training. Rather than merely facilitate travel, these brokers produce both generic, emigratory nurses as well as more customised nurses ready to meet specific shortages in the UK.DiscussionThe dialectic of producing emigratory and customised nurses is similar to that seen in the Post-Fordist manufacturing model characterised by flexible specialisation and a networked structure. As the commodity in this case are people attempting to improve their position in life, these markets require attention from health policy makers. Nurse production regimes based on international market opportunities are liable to change, subjecting nurses to the risk of having trained for a market that can no longer accommodate them. The commercial nature of activities further entrenches existing socioeconomic inequalities in the Indian nurse force. Negative repercussions for the source healthcare system can be anticipated as highly qualified, specialised nurses leave to work in healthcare systems abroad.
Work Engagement and Well-being Study (SWELL): a randomised controlled feasibility trial evaluating the effects of mindfulness versus light physical exercise at work
Authors: Vainre Maris , Dalgleish Tim , Watson Peter , Haag Christina , Dercon Quentin , Galante Julieta , Hitchcock Caitlin 
Published: February 2024

BackgroundMindfulness-based programmes (MBPs) are increasingly offered at work, often in online self-guided format. However, the evidence on MBPs’ effect on work performance (WP) is inconsistent.ObjectiveThis pragmatic randomised controlled feasibility trial assessed procedural uncertainties, intervention acceptability and preliminary effect sizes of an MBP on WP, relative to an alternative intervention.Methods241 employees from eight employers were randomised (1:1) to complete a 4-week, self-guided, online MBP or a light physical exercise programme (LE)(active control). Feasibility and acceptability measures were of primary interest. WP at postintervention (PostInt) was the primary outcome for preliminary assessment of effect sizes. Secondary outcomes assessed mental health (MH) and cognitive processes hypothesised to be targeted by the MBP. Outcomes were collected at baseline, PostInt and 12-week follow-up (12wFUP). Prospective trial protocol:NCT04631302.Findings87% of randomised participants started the course. Courses had high acceptability. Retention rates were typical for online trials (64% PostInt; 30% 12wFUP). MBP, compared with the LE control, offered negligible benefits for WP (PostInt (d=0.06, 95% CI −0.19 to 0.32); 12wFUP (d=0.02, 95% CI −0.30 to 0.26)). Both interventions improved MH outcomes (ds=−0.40 to 0.58, 95% CI −0.32 to 0.18); between-group differences were small (ds=−0.09 to 0.04, 95% CI −0.15 to 0.17).ConclusionThe trial is feasible; interventions are acceptable. Results provide little support for a later phase trial comparing an MBP to a light exercise control. To inform future trials, we summarise procedural challenges.Clinical implicationsResults suggest MBPs are unlikely to improve WP relative to light physical exercise. Although the MBP improved MH, other active interventions may be just as efficacious.Trial registration numberNCT04631302.
Comparison of standard-dose and reduced-dose treatment of metastatic prostate cancer with enzalutamide, apalutamide or darolutamide: a rapid review
Authors: Bromley Hannah Louise , Varughese Mohini , Gilbert Duncan C , Hoskin Peter , Tannock Ian F , Reeves Kimberley , Choudhury Ananya 
Published: February 2024

ObjectiveTo review the efficacy and safety of low-dose versus standard-dose enzalutamide, apalutamide or darolutamide treatment for metastatic prostate cancer.Methods and analysisKeyword searches in MEDLINE and EMBASE up to 1 June 2023, with forward and backward citation searches of potentially relevant studies. Studies were included if primary outcome data were reported for patients with metastatic prostate cancer who had received reduced doses of enzalutamide, apalutamide or darolutamide. Searches were limited to original full-text and English-language studies. Key outcomes included overall survival (OS), progression-free survival (PFS), prostate-specific antigen response and treatment-related adverse events. The review was performed in accordance with Cochrane Rapid Reviews Methods Group guidelines.ResultsTen studies were identified that met the eligibility criteria: five phase I studies, two post-hoc analyses of phase III trials and three retrospective analyses. No consistent association between OS, PFS and drug dose was identified. Fewer severe treatment-related adverse events were observed at lower drug doses.ConclusionThis review provides evidence that enzalutamide, apalutamide or darolutamide could be given at a lower than the standard recommended dose without loss of antitumour activity. A prospective near-equivalence randomised trial should be undertaken to compare registered and lower doses of these agents.PROSPERO registration numberCRD42023440371.
No evidence of fascicular injury following a low-volume intraneural injection of the median nerve: a cadaveric study
Authors: Mejia Jorge , Goffin Pierre , Reina Miguel A , Sala-Blanch Xavier 
Published: February 2024

BackgroundThe test dose or hydrolocation technique allows rapid detection of spread location. Though its primary aim is to enhance safety in peripheral nerve blocks, evidence on the potential risks of an intraneural test aliquot is lacking. We conducted a cadaveric study to evaluate the risk of fascicular injury following a low-volume (<1 mL) intraneural injection of the median nerve.MethodsTen upper limbs from fresh unembalmed human cadavers were studied. In-plane ultrasound-guided intraneural injections of the median nerve were performed at mid, proximal, and distal locations using 1 mL of methylene blue and heparinized blood solution. Nerves were extracted and samples immersed in 10% buffered formalin for 4 weeks. Perpendicular 3 mm slices were obtained for H&E staining and light microscopy analysis. Our main objective was to assess the number of injured fascicles. Secondarily, we evaluated the pattern of intraneural spread. Fascicular injury was defined as the presence perineurium or axonal disruption and/or the presence of erythrocytes inside a nerve fascicle.ResultsThirty injections were performed in 10 median nerves. Sonographic swelling was confirmed in 100% of the cases. 352 histological sections were analyzed to assess study outcomes. The mean number of fascicles on each section of median nerve was 20±6 covering 49%±7% of the nerve area. No evidence of axonal disruption nor intra-fascicular erythrocytes was found in any of the analyzed sections.ConclusionsLow-volume intraneural injections do not result in evident fascicular injury. Our findings support the use of a test dose in ultrasound-guided regional anesthesia.
Rising through the ranks: flavor hierarchies from a gauged $${\varvec{\mathrm {SU(2)}}}$$ symmetry
Authors: Greljo Admir , Thomsen Anders Eller 
Published: February 2024

AbstractWe propose an economical model to address the mass hierarchies of quarks and charged leptons. The light generations of the left-handed fermions form doublets under an $$ \textrm{SU}(2) $$

SU
(
2
)

flavor symmetry, which is gauged. The generational hierarchies emerge from three independent rank-one contributions to the Yukawa matrices: one is a renormalizable contribution, the second is suppressed by a mass ratio, and the last by an additional loop factor. The model is renormalizable, features only a handful of new fields, and is remarkably simple compared to typical completions of gauged flavor symmetries or Froggatt–Nielsen. The model has a rich phenomenology, and we highlight promising signatures, especially in the context of K and B meson physics. This includes an interpretation of the latest $$B^+ \rightarrow K^+ \nu \bar{\nu }$$

B
+

→

K
+

ν

ν

¯

measurement from Belle II.
On heavy-flavour jets with Soft Drop
Authors: Caletti Simone , Ghira Andrea , Marzani Simone 
Published: February 2024

AbstractWe study hadronic jets that are tagged as heavy-flavoured, i.e. they contain either beauty or charm. In particular, we consider heavy-flavour jets that have been groomed with the Soft Drop algorithm. In order to achieve a deeper understanding of these objects, we apply resummed perturbation theory to jets initiated by a massive quark and we perform analytic calculations for two variables that characterise Soft Drop jets, namely the opening angle and the momentum fraction of the splitting that passes Soft Drop. We compare our findings to Monte Carlo simulations. Furthermore, we investigate the correlation between the Soft Drop energy fraction and alternative observables that aim to probe heavy-quark fragmentation functions.
Representations of flat virtual braids which do not preserve the forbidden relations
Authors: Bardakov Valeriy , Chuzhinov Bogdan , Emel’yanenkov Ivan , Ivanov Maxim , Markhinina Elizaveta , Nasybullov Timur , Panov Sergey , Singh Nina , Vasyutkin Sergey , Yakhin Valeriy , Vesnin Andrei 
Published: February 2024

In the paper, we construct a representation [Formula: see text] of the flat virtual braid group [Formula: see text] on [Formula: see text] strands by automorphisms of the free group [Formula: see text] with [Formula: see text] generators which does not preserve the forbidden relations in the flat virtual braid group. This representation gives a positive answer to the problem formulated by Bardakov in the list of unsolved problems in virtual knot theory and combinatorial knot theory by Fenn et al. Also we find the set of normal generators of the groups [Formula: see text] in [Formula: see text], [Formula: see text] in [Formula: see text], [Formula: see text] in [Formula: see text], which play an important role in the study of the kernel of the representation [Formula: see text].
Spatial Mapping of Hematopoietic Clones in Human Bone Marrow
Authors: Young Andrew L. , Davis Hannah C. , Cox Maggie J. , Parsons Tyler M. , Burkart Samantha C. , Bender Diane E. , Sun Lulu , Oh Stephen T. , Challen Grant A. 
Published: February 2024

Abstract

Clonal hematopoiesis (CH) is the expansion of somatically mutated cells in the hematopoietic compartment of individuals without hematopoietic dysfunction. Large CH clones (i.e., &gt;2% variant allele fraction) predispose to hematologic malignancy, but CH is detected at lower levels in nearly all middle-aged individuals. Prior work has extensively characterized CH in peripheral blood, but the spatial distribution of hematopoietic clones in human bone marrow is largely undescribed. To understand CH at this level, we developed a method for spatially aware somatic mutation profiling and characterized the bone marrow of a patient with polycythemia vera. We identified the complex clonal distribution of somatic mutations in the hematopoietic compartment, the restriction of somatic mutations to specific subpopulations of hematopoietic cells, and spatial constraints of these clones in the bone marrow. This proof of principle paves the way to answering fundamental questions regarding CH spatial organization and factors driving CH expansion and malignant transformation in the bone marrow.

Significance:
CH occurs commonly in humans and can predispose to hematologic malignancy. Although well characterized in blood, it is poorly understood how clones are spatially distributed in the bone marrow. To answer this, we developed methods for spatially aware somatic mutation profiling to describe clonal heterogeneity in human bone marrow.
See related commentary by Austin and Aifantis, p. 139.
Nanoparticle-mediated Photodynamic Therapy as a Method to Ablate Oral Cavity Squamous Cell Carcinoma in Preclinical Models
Authors: Sahovaler Axel , Valic Michael S. , Townson Jason L. , Chan Harley H.L. , Zheng Mark , Tzelnick Sharon , Mondello Tiziana , Pener-Tessler Alon , Eu Donovan , El-Sayes Abdullah , Ding Lili , Chen Juan , Douglas Catriona M. , Weersink Robert , Muhanna Nidal , Zheng Gang , Irish Jonathan C. 
Published: February 2024

Abstract

Photodynamic therapy (PDT) is a tissue ablation technique able to selectively target tumor cells by activating the cytotoxicity of photosensitizer dyes with light. PDT is nonsurgical and tissue sparing, two advantages for treatments in anatomically complex disease sites such as the oral cavity. We have previously developed PORPHYSOME (PS) nanoparticles assembled from chlorin photosensitizer–containing building blocks (∼94,000 photosensitizers per particle) and capable of potent PDT. In this study, we demonstrate the selective uptake and curative tumor ablation of PS-enabled PDT in three preclinical models of oral cavity squamous cell carcinoma (OCSCC): biologically relevant subcutaneous Cal-33 (cell line) and MOC22 (syngeneic) mouse models, and an anatomically relevant orthotopic VX-2 rabbit model. Tumors selectively uptake PS (10 mg/kg, i.v.) with 6-to 40-fold greater concentration versus muscle 24 hours post-injection. Single PS nanoparticle–mediated PDT (PS-PDT) treatment (100 J/cm2, 100 mW/cm2) of Cal-33 tumors yielded significant apoptosis in 65.7% of tumor cells. Survival studies following PS-PDT treatments demonstrated 90% (36/40) overall response rate across all three tumor models. Complete tumor response was achieved in 65% of Cal-33 and 91% of MOC22 tumor mouse models 14 days after PS-PDT, and partial responses obtained in 25% and 9% of Cal-33 and MOC22 tumors, respectively. In buccal VX-2 rabbit tumors, combined surface and interstitial PS-PDT (200 J total) yielded complete responses in only 60% of rabbits 6 weeks after a single treatment whereas three repeated weekly treatments with PS-PDT (200 J/week) achieved complete ablation in 100% of tumors. PS-PDT treatments were well tolerated by animals with no treatment-associated toxicities and excellent cosmetic outcomes.

Significance:
PS-PDT is a safe and repeatable treatment modality for OCSCC ablation. PS demonstrated tumor selective uptake and PS-PDT treatments achieved reproducible efficacy and effectiveness in multiple tumor models superior to other clinically tested photosensitizer drugs. Cosmetic and functional outcomes were excellent, and no clinically significant treatment-associated toxicities were detected. These results are enabling of window of opportunity trials for fluorescence-guided PS-PDT in patients with early-stage OCSCC scheduled for surgery.
Development and Validation of Contextualized Kindergarten Module for Children with Hearing Impairment
Authors: Guzman Sammy Boy B. 
Published: February 2024

This study aimed to develop and validate a sign language-based and contextualized kindergarten module for children with hearing impairment. There is a need to develop and contextualize a module in order to cater the unmet needs of students with hearing impairment. The developed module includes a teaching guide for parents, for them to become more effective co-facilitators of learning. The distinctive feature of this module is that, the sign language interpretations are with pictures and texts. The pictures vividly show the step-by-step procedure on how to sign the specific word. The pictures are supported by the comprehensive explanation on how to sign the words. This study utilized the Research and Development (R & D) research method to systematically design, develop and evaluate the instructional material. The participants of this study are eleven (11) students with hearing impairment and eleven (11) parents of students with hearing impairment. The respondents and served as expert-validators are master teacher, kindergarten teacher, and SPED teacher. It employed a purposive sampling technique; it purposely selected a population related to children with hearing impairment. To analyze the qualitative data, it was imported to MAXQDA software with the use of Horizontalization method by Moustakas. For statistical treatment of the descriptive data, researchers used the PSPP software. The study found that the parents’ ideal module for children with hearing impairment has five emerging themes, such as 1) sign language medium of instruction, 2) disability consideration, 3) media consideration, 4) level of difficulty, and 5) technical design. Expert-validators assessed that the validity of contextualized kindergarten module is highly acceptable among the dimensions of: content, format and language, presentation, and usefulness. Effectiveness of the contextualized module as perceived by the parents yielded a total of 96.36% positive responses.
Monocytes Release Pro-Cathepsin D to Drive Blood-to-Brain Transcytosis in Diabetes
Authors: Zhao Dan , Huang Zeng-Kang , Liang Yu , Li Zhi-Jun , Zhang Xue-Wei , Li Kun-Hang , Wu Hao , Zhang Xu-Dong , Li Chen-Sheng , An Dong , Sun Xue , An Ming-Xin , Shi Jun-Xiu , Bao Yi-Jun , Tian Li , Wang Di-Fei , Wu An-Hua , Chen Yu-Hua , Zhao Wei-Dong 
Published: February 2024

BACKGROUND:
Microvascular complications are the major outcome of type 2 diabetes progression, and the underlying mechanism remains to be determined.

METHODS:
High-throughput RNA sequencing was performed using human monocyte samples from controls and diabetes. The transgenic mice expressing human CTSD (cathepsin D) in the monocytes was constructed using CD68 promoter. In vivo 2-photon imaging, behavioral tests, immunofluorescence, transmission electron microscopy, Western blot analysis, vascular leakage assay, and single-cell RNA sequencing were performed to clarify the phenotype and elucidate the molecular mechanism.

RESULTS:
Monocytes expressed high-level CTSD in patients with type 2 diabetes. The transgenic mice expressing human CTSD in the monocytes showed increased brain microvascular permeability resembling the diabetic microvascular phenotype, accompanied by cognitive deficit. Mechanistically, the monocytes release nonenzymatic pro-CTSD to upregulate caveolin expression in brain endothelium triggering caveolae-mediated transcytosis, without affecting the paracellular route of brain microvasculature. The circulating pro-CTSD activated the caveolae-mediated transcytosis in brain endothelial cells via its binding with low-density LRP1 (lipoprotein receptor-related protein 1). Importantly, genetic ablation of CTSD in the monocytes exhibited a protective effect against the diabetes-enhanced brain microvascular transcytosis and the diabetes-induced cognitive impairment.

CONCLUSIONS:
These findings uncover the novel role of circulatory pro-CTSD from monocytes in the pathogenesis of cerebral microvascular lesions in diabetes. The circulatory pro-CTSD is a potential target for the intervention of microvascular complications in diabetes.
Inverted U‐Shaped Association of Plasma Resolvin D2 With Atherosclerotic Cardiovascular Disease and the Mediation Effects of Serum Cholesterol: A Chinese Community‐Based Study
Authors: Liu Bingyue , Zhang Jin , Zhang Kexin , Li Mengyuan , Jing Yang , Gu Shujun , Ding Hongzhan , Liang Yanyu , Zhou Hui , Dong Chen 
Published: February 2024

Background
Resolvin D2 (RvD2) has been reported to protect against the development of atherosclerosis in animal models. The objective of this study was to examine the prospective association between plasma RvD2 and the risk of atherosclerotic cardiovascular disease (ASCVD) at the population level.

Methods and Results

A cohort of 2633 community‐dwelling individuals aged 35–60 years was followed for 8 years in this study. Adjusted hazard ratios and 95% CIs for ASCVD outcomes according to baseline RvD2 levels were calculated using Cox proportional hazards models. Mediation analysis was used to test the indirect effect of serum cholesterol indicators on the association between RvD2 and ASCVD probability. In total, 284 new cases of ASCVD were identified during follow‐up. An inverted U‐shaped association between natural log (ln)‐transformed RvD2 and incident ASCVD was determined, and the threshold value for lnRvD2 was 3.87. Below the threshold, each unit increase in lnRvD2 was associated with a 2.05‐fold increased risk of ASCVD (95% CI, 1.13–3.74;
P
=0.019). Above the threshold, each unit increase in lnRvD2 was associated with a 36% reduced risk of ASCVD (95% CI, 0.51–0.80;
P
<0.001). In addition, the association between RvD2 and ASCVD probability was partially mediated by high‐density lipoprotein cholesterol (15.81%) when lnRvD2 <3.87, but by total cholesterol (30.23%) and low‐density lipoprotein cholesterol (30.13%) when lnRvD2 ≥3.87.

Conclusions
Both lower and higher RvD2 levels are associated with a reduced risk of ASCVD, forming an inverted U‐shaped relationship. Furthermore, this association is partially mediated by total cholesterol, high‐density lipoprotein cholesterol, and low‐density lipoprotein cholesterol.
A Spatial Artificial Chemistry Implementation of a Gene Regulatory Network Aimed at Generating Protein Concentration Dynamics
Authors: Miralavy Iliya , Banzhaf Wolfgang 
Published: February 2024

Abstract
Gene regulatory networks are networks of interactions in organisms responsible for determining the production levels of proteins and peptides. Mathematical and computational models of gene regulatory networks have been proposed, some of them rather abstract and called artificial regulatory networks. In this contribution, a spatial model for gene regulatory networks is proposed that is biologically more realistic and incorporates an artificial chemistry to realize the interaction between regulatory proteins called the transcription factors and the regulatory sites of simulated genes. The result is a system that is quite robust while able to produce complex dynamics similar to what can be observed in nature. Here an analysis of the impact of the initial states of the system on the produced dynamics is performed, showing that such models are evolvable and can be directed toward producing desired protein dynamics.