bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurological outcome following out of hospital cardiac arrest: Evaluation of performance of existing risk prediction models in a UK cohort
Authors: Livesey John A , Lone Nazir , Black Emily , Broome Richard , Syme Alastair , Keating Sean , Elliott Laura , McCahill Cara , Simpson Gavin , Grant Helen , Auld Fiona , Garrioch Sweyn , Hay Alasdair , Craven Thomas H 
Published: December 2023

Introduction: Out of hospital cardiac arrest (OHCA) is a common problem. Rates of survival are low and a proportion of survivors are left with an unfavourable neurological outcome. Four models have been developed to predict risk of unfavourable outcome at the time of critical care admission – the Cardiac Arrest Hospital Prognosis (CAHP), MIRACLE2, Out of Hospital Cardiac Arrest (OHCA), and Targeted Temperature Management (TTM) models. This evaluation evaluates the performance of these four models in a United Kingdom population and provides comparison to performance of the Acute Physiology and Chronic Health Evaluation II (APACHE-II) score. Methods: A retrospective evaluation of the performance of the models was conducted over a 43-month period in 414 adult, non-pregnant patients presenting consecutively following non-traumatic OHCA to the five units in our regional critical care network. Scores were generated for each model for where patients had complete data (CAHP = 347, MIRACLE2 = 375, OHCA = 356, TTM = 385). Cerebral Performance Category (CPC) outcome was calculated for each patient at last documented follow up and an unfavourable outcome defined as CPC ⩾ 3. Performance for discrimination of unfavourable outcome was tested by generating receiver operating characteristic (ROC) curves for each model and comparing the area under the curve (AUC). Results: Best performance for discrimination of unfavourable outcome was demonstrated by the high risk group of the CAHP score with an AUC of 0.87 [95% CI 0.83–0.91], specificity of 97.1% [95% CI 93.8–100] and positive predictive value (PPV) of 96.3% [95% CI 92.2–100]. The high risk group of the MIRACLE2 model, which is significantly easier to calculate, had an AUC of 0.81 [95% CI 0.76–0.86], specificity of 92.3% [95% CI 87.2–97.4] and PPV of 95.2% [95% CI 91.9–98.4]. Conclusion: The CAHP, MIRACLE2, OHCA and TTM scores all perform comparably in a UK population to the original development and validation cohorts. All four scores outperform APACHE-II in a population of patients resuscitated from OHCA. CAHP and TTM perform best but are more complex to calculate than MIRACLE2, which displays inferior performance.
Peripheral blood lymphocytes predict clinical outcomes in hormone receptor-positive HER2-negative advanced breast cancer patients treated with CDK4/6 inhibitors
Authors: Zattarin Emma , Mariani Luigi , Menichetti Alice , Leporati Rita , Provenzano Leonardo , Ligorio Francesca , Fucà Giovanni , Lobefaro Riccardo , Lalli Luca , Vingiani Andrea , Nichetti Federico , Griguolo Gaia , Sirico Marianna , Bernocchi Ottavia , Marra Antonio , Corti Chiara , Zagami Paola , Agostinetto Elisa , Jacobs Flavia , Di Mauro Pierluigi , Presti Daniele , Sposetti Caterina , Giorgi Carlo Alberto , Guarneri Valentina , Pedersini Rebecca , Losurdo Agnese , Generali Daniele , Curigliano Giuseppe , Pruneri Giancarlo , de Braud Filippo , Dieci Maria Vittoria , Vernieri Claudio 
Published: December 2023

Background: Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2− aBC). Objectives: While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown. Design: A multicenter, retrospective-prospective Italian study. Methods: We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2− aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables. Results: We evaluated 638 HR+/HER2− aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66–0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73–0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively). Conclusion: Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2− aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2− aBC treated with ETs plus CDK4/6i.
Diagnostic accuracy of two confirmatory tests for diabetes mellitus in adult Ugandans with recently diagnosed tuberculosis
Authors: Kibirige Davis , Zawedde-Muyanja Stella , Andia-Biraro Irene , Olum Ronald , Adakun Susan , Sekaggya-Wiltshire Christine , Kimuli Ivan 
Published: December 2023

Objective: The optimal confirmatory tests for diabetes mellitus (DM) in patients with tuberculosis (TB) vary across populations. This study aimed to evaluate the performance of two confirmatory tests for DM against the oral glucose tolerance test (OGTT) as the reference test in adult Ugandans with recently diagnosed TB. Methods: A total of 232 adult participants receiving TB treatment underwent initial screening for DM with random blood glucose (RBG) measurement. Participants with a RBG level ⩾6.1 mmol/l received additional screening with fasting blood glucose (FBG), laboratory-measured glycated haemoglobin (HbA1c) and an OGTT. Using the latter as the gold standard and reference test, we evaluated the diagnostic accuracy of laboratory-measured HbA1c and FBG. Results: Of the 232 participants initially screened for DM using RBG measurement, 117 participants (50.4%) had RBG level ⩾6.1 mmol/l and were scheduled to return for additional blood glucose testing. Of these, 75 (64.1%) participants returned for FBG and HbA1c measurements. A diagnosis of DM was made in 32 participants, corresponding to a prevalence of 13.8% [95% CI 9.9–18.9]. The areas under the curve (AUC) for FBG and laboratory-measured HbA1c were 0.69 [95% CI 0.47–0.90] and 0.65 [95% CI 0.43–0.87], respectively. The sensitivity and specificity of a FBG level of ⩾7 mmol/l were 57.1% [95% CI 18.4–90.1] and 74.6% [95% CI 62.5–84.5], respectively, whereas the sensitivity and specificity for laboratory-measured HbA1c of ⩾6.5 mmol/l (48 mmol/mol) were 14.3% [95% CI 0.40–57.9] and 95.3% (86.9–99.0%), respectively. Conclusion: FBG may be better than laboratory-measured HbA1c in confirming DM in adult Ugandans with recently diagnosed TB. However, because of the small study sample size, larger studies evaluating the diagnostic utility of these diabetes screening tests in adult Ugandans with TB are needed to confirm these findings.
Radiographic Outcomes of Mineral Trioxide Aggregate (MTA) with and Without Platelet-Rich Fibrin (PRF) In Direct Pulp Capping: A Clinical Pilot Study
Authors: Singh Meena , Tikku A. P. , Verma Promila , Yadav Rakesh K. , Bharti Ramesh , Bains Rhythm 
Published: December 2023

Aim: The purpose of the current investigation was to determine by radiographic means if a calcific dentinal bridge had formed following direct pulp capping (DPC) with calcium hydroxide (CH), mineral trioxide aggregate (MTA), or a combination of platelet-rich fibrin (PRF) and MTA. Materials and Methods: In the beginning, 45 systemically healthy patients who needed DPC and had pulpal exposure were enrolled in the trial. They were then randomly assigned to one of three groups: CH (control, n = 15), MTA ( n = 15), or PRF + MTA ( n = 15). To determine the radiographic density of the dentin immediately underneath the location of pulpal exposure, pre-operative intraoral digital radiographs of the afflicted teeth were acquired. Through sequential imaging, the radiographic evaluation of dentinal bridge formation was performed. All images were studied carefully, keeping the reference point constant. Results: Out of the 45 patients, finally 10 per group were analysed. According to an analysis of variance, difference in mean density values among the various groups was found to be significant [( p = .001). On bi-group comparison (using post-Tukey HSD), difference between CH and PRF + MTA was significant ( p = .001), between MTA and PRF + MTA was significant ( p = .022), and between CH and MTA not significant ( p = .347)]. The PRF + MTA group showed the highest increase in mean density values. Conclusion: The results of the present study suggest that PRF and MTA when used in combination have better radiographic outcomes compared to MTA alone when used as DPC agents.
Risk Factors for Ipsilateral Versus Contralateral Reinjury After ACL Reconstruction in Athletes: A Systematic Review and Meta-analysis
Authors: Gao Han , Hu Haichen , Sheng Dandan , Sun Luyi , Chen Jun , Chen Tianwu , Chen Shiyi 
Published: December 2023

Background: Anterior cruciate ligament (ACL) reinjury after ACL reconstruction (ACLR) can occur on the ipsilateral or contralateral side. Limited evidence exists regarding the difference between the incidence of reinjury to either knee, which is important in developing interventions to prevent ACL reinjury. Purpose: To compare the reinjury rate of the ACL on the ipsilateral side versus the contralateral side in athletes after ACLR and investigate the risk factors that may cause different reinjury rates between the sides. Study Design: Systematic review; Level of evidence, 4. Methods: A systematic review was performed based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies that involved ACL reinjury in athletes after ACLR were reviewed. Considering several risk factors, including age and sex, a comparison of ACL reinjury incidence on the ipsilateral and contralateral sides was performed using a meta-analysis. Results: Of the 17 selected studies, 3 were found to be at high risk of bias, and thus, 14 (n = 3424 participants) studies were included in the meta-analysis. In this athletic population, the contralateral ACL had a significantly higher rupture rate than the ipsilateral graft (risk ratio [RR], 1.41; P < .0001). Female athletes were found to have a greater risk of ACL reinjury on the contralateral versus the ipsilateral side (RR, 1.65; P = .0005), but different results were found in male athletes. (RR, 0.81; P = .21). There was no statistical difference in the incidence rate of ACL reinjury to either side in adolescent athletes (RR, 1.15; P = .28). Conclusion: The contralateral ACL was more vulnerable to reinjury than the ipsilateral side in athletes after ACLR. Female athletes were more likely to reinjure their contralateral native ACL, while the same trend was not found in their male counterparts. The reinjury rate was comparable in both knees in adolescent athletes.
Comparison of Glenohumeral Bone Morphology Between Patients With Versus Without Anterior Shoulder Instability
Authors: Niu Zhixin , Shen Xianyue , Li Menglong , Fan Mingrui , Zuo Jianlin , Liu Tong 
Published: December 2023

Background: The stability of the glenohumeral joint is associated with anatomic characteristics including bony structures and soft tissues. Purpose: To compare the differences in specific bony glenohumeral geometries between shoulders with anterior shoulder instability (ASI), unaffected contralateral shoulders, and healthy control shoulders. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Shoulder computed tomography (CT) scans of 36 patients with ASI and 36 matched healthy controls were retrieved and 3-dimensionally reconstructed. We measured the glenoid radius of curvature (GROC) in the anterior-posterior (AP) and superior-inferior directions, humeral head radius of curvature (HROC) in the AP direction, conformity index, glenoid height, glenoid width, glenoid index, stability angle, glenoid version, and glenoid depth. The differences between the groups were statistically calculated. CT scans of the unaffected contralateral shoulders from 21 of the ASI patients were also collected to identify the consistency of the bony structures in bilateral shoulders. Results: Patients with ASI had greater GROC in the AP direction ( P < .001), HROC in the AP direction ( P = .002), glenoid height ( P = .005), and glenoid index ( P < .001) and smaller conformity index ( P < .001), glenoid width ( P = .002), stability angle ( P < .001), and glenoid depth ( P < .001). In addition, the glenoid of the ASI patients was more anteverted compared with that of controls ( P = .001). There was no statistical difference in half the measurements between the bilateral shoulder joints in patients with ASI. Conclusion: In this study, glenohumeral geometric differences were found between ASI patients and healthy control participants. Glenoid curvature and conformity index, based on bilateral comparisons of affected and contralateral shoulders, appear inherent and may predict ASI risk.
Emicizumab prophylaxis in infants with hemophilia A (HAVEN 7): primary analysis of a phase 3b open-label trial
Authors: Pipe Steven W. , Collins Peter , Dhalluin Christophe , Kenet Gili , Schmitt Christophe , Buri Muriel , Jiménez-Yuste Víctor , Peyvandi Flora , Young Guy , Oldenburg Johannes , Mancuso Maria Elisa , Kavakli Kaan , Kiialainen Anna , Deb Sonia , Niggli Markus , Chang Tiffany , Lehle Michaela , Fijnvandraat Karin 
Published: December 2023

Abstract
Subcutaneous emicizumab enables prophylaxis for people with hemophilia A (HA) from birth, potentially reducing risk of bleeding and intracranial hemorrhage (ICH). HAVEN 7 (NCT04431726) is the first clinical trial of emicizumab dedicated to infants, designed to investigate the efficacy, safety, pharmacokinetics, and pharmacodynamics of emicizumab in those aged ≤12 months with severe HA without factor VIII (FVIII) inhibitors. Participants in this phase 3b trial received emicizumab 3 mg/kg maintenance dose every 2 weeks for 52 weeks and are continuing emicizumab during the 7-year long-term follow-up. Efficacy end points included annualized bleed rate (ABR): treated, all, treated spontaneous, and treated joint bleeds. Safety end points included adverse events (AEs), thromboembolic events (TEs), thrombotic microangiopathies (TMAs), and immunogenicity (anti-emicizumab antibodies [ADAs] and FVIII inhibitors). At primary analysis, 55 male participants had received emicizumab (median treatment duration: 100.3; range, 52-118 weeks). Median age at informed consent was 4.0 months (range, 9 days to 11 months 30 days). Model-based ABR for treated bleeds was 0.4 (95% confidence interval, 0.30–0.63), with 54.5% of participants (n = 30) having zero treated bleeds. No ICH occurred. All 42 treated bleeds in 25 participants (45.5%) were traumatic. Nine participants (16.4%) had ≥1 emicizumab-related AE (all grade 1 injection-site reactions). No AE led to treatment changes. No deaths, TEs, or TMAs occurred. No participant tested positive for ADAs. Two participants were confirmed positive for FVIII inhibitors. This primary analysis of HAVEN 7 indicates that emicizumab is efficacious and well tolerated in infants with severe HA without FVIII inhibitors.
Advanced practice providers in hematology: actionable findings from national paired APP and physician surveys
Authors: Marshall Ariela L. , Masselink Leah E. , Kouides Peter A. , Davies Faith E. , Farooqui Azam , Nagalla Srikanth , Herrera Alex , Mortier Nicole , Brodsky Robert , Erikson Clese E. 
Published: December 2023

Abstract
Advanced practice providers (APPs) are critical to the hematology workforce. However, there is limited knowledge about APPs in hematology regarding specialty-specific training, scope of practice, challenges and opportunities in APP-physician interactions, and involvement with the American Society of Hematology (ASH). We conducted APP and physician focus groups to elucidate major themes in these areas and used results to inform development of 2 national surveys, 1 for APPs and 1 for physicians who work with APPs. The APP survey was distributed to members of the Advanced Practitioner Society of Hematology and Oncology, and the physician survey was distributed to physician members of ASH. A total of 841 APPs and 1334 physicians completed the surveys. APPs reported most hematology-specific knowledge was obtained via on-the-job training and felt additional APP-focused training would be helpful (as did physicians). Nearly all APPs and physicians agreed that APPs were an integral part of their organizations and that physician-APP collaborations were generally positive. A total of 42.1% of APPs and 29.3% of physicians reported burnout, and &gt;50% of physicians felt that working with APPs had reduced their burnout. Both physicians and APPs reported interest in additional resources including “best practice” guidelines for APP-physician collaboration, APP access to hematology educational resources (both existing and newly developed resources for physicians and trainees), and greater APP integration into national specialty-specific professional organizations including APP-focused sessions at conferences. Professional organizations such as ASH are well positioned to address these areas.
The many faces of COPD in real life: a longitudinal analysis of the NOVELTY cohort
Authors: Agustí Alvar , Hughes Rod , Rapsomaki Eleni , Make Barry , del Olmo Ricardo , Papi Alberto , Price David , Benton Laura , Franzen Stefan , Vestbo Jørgen , Mullerova Hana 
Published: December 2023

BackgroundThe diagnosis of COPD requires the demonstration of non-fully reversible airflow limitation by spirometry in the appropriate clinical context. Yet, there are patients with symptoms and relevant exposures suggestive of COPD with either normal spirometry (pre-COPD) or preserved ratio but impaired spirometry (PRISm). Their prevalence, clinical characteristics and associated outcomes in a real-life setting are unclear.MethodsTo investigate them, we studied 3183 patients diagnosed with COPD by their attending physician included in the NOVELTY study (clinicaltrials.govidentifierNCT02760329), a global, 3-year, observational, real-life cohort that included patients recruited from both primary and specialist care clinics in 18 countries.ResultsWe found that 1) approximately a quarter of patients diagnosed with (and treated for) COPD in real life did not fulfil the spirometric diagnostic criteria recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD), and could be instead categorised as pre-COPD (13%) or PRISm (14%); 2) disease burden (symptoms and exacerbations) was highest in GOLD 3–4 patients (exacerbations per person-year (PPY) 0.82) and lower but similar in those in GOLD 1–2, pre-COPD and PRISm (exacerbations range 0.27–0.43 PPY); 3) lung function decline was highest in pre-COPD and GOLD 1–2, and much less pronounced in PRISm and GOLD 3-4; 4) PRISm and pre-COPD were not stable diagnostic categories and change substantially over time; and 5) all-cause mortality was highest in GOLD 3–4, lowest in pre-COPD, and intermediate and similar in GOLD 1–2 and PRISm.ConclusionsPatients diagnosed COPD in a real-life clinical setting present great diversity in symptom burden, progression and survival, warranting medical attention.
ICON-GEMs: integration of co-expression network in genome-scale metabolic models, shedding light through systems biology
Authors: Paklao Thummarat , Suratanee Apichat , Plaimas Kitiporn 
Published: December 2023

Abstract
Background
Flux Balance Analysis (FBA) is a key metabolic modeling method used to simulate cellular metabolism under steady-state conditions. Its simplicity and versatility have led to various strategies incorporating transcriptomic and proteomic data into FBA, successfully predicting flux distribution and phenotypic results. However, despite these advances, the untapped potential lies in leveraging gene-related connections like co-expression patterns for valuable insights.

Results
To fill this gap, we introduce ICON-GEMs, an innovative constraint-based model to incorporate gene co-expression network into the FBA model, facilitating more precise determination of flux distributions and functional pathways. In this study, transcriptomic data from both Escherichia coli and Saccharomyces cerevisiae were integrated into their respective genome-scale metabolic models. A comprehensive gene co-expression network was constructed as a global view of metabolic mechanism of the cell. By leveraging quadratic programming, we maximized the alignment between pairs of reaction fluxes and the correlation of their corresponding genes in the co-expression network. The outcomes notably demonstrated that ICON-GEMs outperformed existing methodologies in predictive accuracy. Flux variabilities over subsystems and functional modules also demonstrate promising results. Furthermore, a comparison involving different types of biological networks, including protein–protein interactions and random networks, reveals insights into the utilization of the co-expression network in genome-scale metabolic engineering.

Conclusion
ICON-GEMs introduce an innovative constrained model capable of simultaneous integration of gene co-expression networks, ready for board application across diverse transcriptomic data sets and multiple organisms. It is freely available as open-source at https://github.com/ThummaratPaklao/ICOM-GEMs.git.