bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adoption, orchestration, and deployment of artificial intelligence within the National Health Service—facilitators and barriers: an expert roundtable discussion
Authors: Lip Gerald , Novak Alex , Goyen Mathias , Boylan Katherine , Kumar Amrita 
Published: June 2024

Abstract
Clinical care, workflow, and patient outcomes within National Health Service (NHS) radiology services will potentially benefit significantly in coming years with the integration of artificial intelligence (AI) into various specialty areas. This article summarizes an expert roundtable discussion, convened by the British Institute of Radiology, comprised experts from clinical, NHS management and industry backgrounds. Facilitators and barriers to both implementation and integration of AI platforms into daily practice are discussed alongside examples including AI in emergency care and breast screening. Issues addressed include the need to generate more real-world evidence that helps developers and service providers to determine the optimal way for patients to reap the benefits of AI with faster reporting turnaround time, faster diagnoses, and treatment times, for example. To ensure the effective and timely wide-scale implementation, adoption requires a national policy drive and national level coordination but specific, local needs of NHS Trusts and any particular service within Trusts will also need to be met. By embedding AI-capabilities into scanners, ultrasound-devices, X-ray equipment, and Picture archiving and communication system (PACS), local services will benefit, while AI applications can streamline workflows across and between departments and potentially Trusts. AI predictive analytics and systems engineering can be used to better manage patient volume and movement. In the short term, education, training, and confidence in adapting and adopting AI in radiology require dedicated local, national, and governmental effort but the future benefits promise to justify the means.
Ligation of intersphincteric fistula tract (LIFT) for trans-sphincteric cryptoglandular anal fistula: long-term impact on faecal continence
Authors: van Oostendorp Justin Y , Verkade Carolien , Han-Geurts Ingrid J M , van der Mijnsbrugge Grietje J H , Wasowicz-Kemps Dareczka K , Zimmerman David D E 
Published: June 2024

Abstract

Background
The ligation of intersphincteric fistula tract is a surgical technique designed to treat trans-sphincteric anal fistulas aiming to preserve sphincter integrity. Recent studies suggest its efficacy in short-term fistula healing with limited impact on continence. However, comprehensive prospective data on long-term outcomes, including recurrence and bowel continence, are limited. The present study aims to report on the long-term functional outcomes.

Methods
Patients who underwent the ligation of intersphincteric fistula tract procedure for trans-sphincteric cryptoglandular anal fistulas between July 2012 and October 2018 at two Dutch referral centres were retrospectively reviewed. The primary outcome of interest was the long-term bowel continence after the ligation of intersphincteric fistula tract procedure, using the faecal incontinence severity index. Short-term data (collected in 2018) and long-term data (collected in 2023) on bowel continence, healing rates and recurrences were obtained through electronic records and Rockwood questionnaires. Sankey diagrams were used to visually represent individual variations in continence status (preoperative versus follow-up).

Results
Among 110 patients included (50% female, median follow-up 92 months), 101 patients (92%) were treated with previous surgeries (median 2, range 0–6) and 80% had previous seton drainage. Preligation of intersphincteric fistula tract, 16% of the patients reported incontinence (mean(s.d.) faecal incontinence severity index: 2.4(7.5), increasing to 18% after ligation of intersphincteric fistula tract at short-term follow-up, including 11% newly induced cases. Long-term follow-up collected using Rockwood questionnaires (63% response rate) in 69 patients uncovered a 74% incontinency rate (mean(s.d.) faecal incontinence severity index: 9.22(9.5). In those patients without subsequent surgery 49% (17 of 35) reported incontinence at long-term follow-up. Primary fistula healing after ligation of intersphincteric fistula tract was 28%. Preoperative seton drainage significantly improved healing rates (33% versus 9%). Notably, 43% (34 of 79) of unhealed fistulas transitioned into intersphincteric tracts; in these patients, 19 were treated with subsequent fistulotomy achieving cure in 18 cases.

Conclusions
Ligation of intersphincteric fistula tract healing rates fell below recent literature standards. Although the immediate impact on postoperative continence appears minimal, long-term incontinence rates are concerning. In recognizing the deterioration of individual continence, we advocate for a patient-centered approach and urge fellow researchers and clinicians to collect comprehensive prospective continence data.
CipherTrace: automatic detection of ciphers from execution traces to neutralize ransomware
Authors: Hassanin Mostafa AbdelMoez , Martinovic Ivan 
Published: June 2024

Abstract
In 2021, the largest US pipeline system for refined oil products suffered a 6-day shutdown due to a ransomware attack [1]. In 2023, the sensitive systems of the US Marshals Service were attacked by a ransomware [2]. One of the most effective ways to fight ransomware is to extract the secret keys. The challenge of detecting and identifying cryptographic primitives has been around for over a decade. Many tools have been proposed, but the vast majority of them use templates or signatures, and their support for different operating systems and processor architectures is rather limited; neither have there been enough tools capable of extracting the secret keys. In this paper, we present CipherTrace, a generic and automated system to detect and identify the class of cipher algorithms in binary programs, and additionally, locate and extract the secret keys and cryptographic states accessed by the cipher. We focus on product ciphers, and evaluate CipherTrace using four standard cipher algorithms, four different hashing algorithms, and five of the most recent and popular ransomware specimens. Our results show that CipherTrace is capable of fully dissecting Fixed S-Box block ciphers (e.g. AES and Serpent) and can extract the secret keys and other cryptographic artefacts, regardless of the operating system, implementation, or input- or key-size, and without using signatures or templates. We show a significant improvement in performance and functionality compared to the closely related works. CipherTrace helps in fighting ransomware, and aids analysts in their malware analysis and reverse engineering efforts.
DRGKB: a knowledgebase of worldwide diagnosis-related groups’ practices for comparison, evaluation and knowledge-guided application
Authors: Ren Shumin , Yang Lin , Du Jiale , He Mengqiao , Shen Bairong 
Published: June 2024

Abstract
As a prospective payment method, diagnosis-related groups (DRGs)’s implementation has varying effects on different regions and adopt different case classification systems. Our goal is to build a structured public online knowledgebase describing the worldwide practice of DRGs, which includes systematic indicators for DRGs’ performance assessment. Therefore, we manually collected the qualified literature from PUBMED and constructed DRGKB website. We divided the evaluation indicators into four categories, including (i) medical service quality; (ii) medical service efficiency; (iii) profitability and sustainability; (iv) case grouping ability. Then we carried out descriptive analysis and comprehensive scoring on outcome measurements performance, improvement strategy and specialty performance. At last, the DRGKB finally contains 297 entries. It was found that DRGs generally have a considerable impact on hospital operations, including average length of stay, medical quality and use of medical resources. At the same time, the current DRGs also have many deficiencies, including insufficient reimbursement rates and the ability to classify complex cases. We analyzed these underperforming parts by domain. In conclusion, this research innovatively constructed a knowledgebase to quantify the practice effects of DRGs, analyzed and visualized the development trends and area performance from a comprehensive perspective. This study provides a data-driven research paradigm for following DRGs-related work along with a proposed DRGs evolution model. Availability and implementation: DRGKB is freely available at http://www.sysbio.org.cn/drgkb/.
Database URL: http://www.sysbio.org.cn/drgkb/
Cardiovascular medications, high-sensitivity cardiac troponin T concentrations, and long-term outcome in non-ST segment elevation acute coronary syndrome
Authors: Eggers Kai M , Lindhagen Lars , Lindahl Bertil 
Published: June 2024

Abstract

Aims
Cardiac troponin plays an essential role in the management of non-ST segment elevation acute coronary syndrome (NSTE-ACS). However, it is not clear whether troponin concentrations provide guidance regarding the initiation of prognostically beneficial cardiovascular medications [i.e. betablockers, renin–angiotensin–aldosterone system (RAAS) inhibitors, and statins] in NSTE-ACS.

Methods and results
Registry-based study investigating three NSTE-ACS cohorts (n = 43 075, 40 162, and 46 698) with elevated high-sensitivity cardiac troponin concentrations &gt;14 ng/L. Cox proportional regression models with the addition of interaction terms were used to analyse the interrelations of high-sensitivity cardiac troponin T (hs-cTnT) concentrations, new initiated medications with the respective three drug classes, and long-term risk of all-cause mortality and major adverse events (MAE). Betablockers were associated with risk reductions of 8 and 5% regarding all-cause mortality and MAE, respectively. There was no evidence of an interaction with hs-cTnT concentrations. RAAS inhibitors were associated with 13 and 8% risk reductions, respectively, with a weak interaction between hs-cTnT and MAE (Pinteraction = 0.016). However, no increasing prognostic benefit was noted at hs-cTnT concentrations &gt;100 ng/L. Statins were associated with 38 and 32% risk reductions, respectively, with prognostic benefit across the entire range of hs-cTnT concentrations, and with a weak interaction regarding MAE (Pinteraction = 0.011).

Conclusion
Cardiovascular medications provide different prognostic benefit in patients with NSTE-ACS with elevated hs-cTnT, and there was some evidence of greater treatment effects regarding MAE along with higher hs-cTnT concentrations. However, hs-cTnT appears only to have limited value overall for customizing such treatments.
Xylitol is prothrombotic and associated with cardiovascular risk
Authors: Witkowski Marco , Nemet Ina , Li Xinmin S , Wilcox Jennifer , Ferrell Marc , Alamri Hassan , Gupta Nilaksh , Wang Zeneng , Tang Wai Hong Wilson , Hazen Stanley L 
Published: June 2024

Abstract

Background and Aims
The pathways and metabolites that contribute to residual cardiovascular disease risks are unclear. Low-calorie sweeteners are widely used sugar substitutes in processed foods with presumed health benefits. Many low-calorie sweeteners are sugar alcohols that also are produced endogenously, albeit at levels over 1000-fold lower than observed following consumption as a sugar substitute.

Methods
Untargeted metabolomics studies were performed on overnight fasting plasma samples in a discovery cohort (n = 1157) of sequential stable subjects undergoing elective diagnostic cardiac evaluations; subsequent stable isotope dilution liquid chromatography tandem mass spectrometry (LC-MS/MS) analyses were performed on an independent, non-overlapping validation cohort (n = 2149). Complementary isolated human platelet, platelet-rich plasma, whole blood, and animal model studies examined the effect of xylitol on platelet responsiveness and thrombus formation in vivo. Finally, an intervention study was performed to assess the effects of xylitol consumption on platelet function in healthy volunteers (n = 10).

Results
In initial untargeted metabolomics studies (discovery cohort), circulating levels of a polyol tentatively assigned as xylitol were associated with incident (3-year) major adverse cardiovascular event (MACE) risk. Subsequent stable isotope dilution LC-MS/MS analyses (validation cohort) specific for xylitol (and not its structural isomers) confirmed its association with incident MACE risk [third vs. first tertile adjusted hazard ratio (95% confidence interval), 1.57 (1.12–2.21), P &lt; .01]. Complementary mechanistic studies showed xylitol-enhanced multiple indices of platelet reactivity and in vivo thrombosis formation at levels observed in fasting plasma. In interventional studies, consumption of a xylitol-sweetened drink markedly raised plasma levels and enhanced multiple functional measures of platelet responsiveness in all subjects.

Conclusions
Xylitol is associated with incident MACE risk. Moreover, xylitol both enhanced platelet reactivity and thrombosis potential in vivo. Further studies examining the cardiovascular safety of xylitol are warranted.
Point-of-care high-sensitivity cardiac troponin in suspected acute myocardial infarction assessed at baseline and 2 h
Authors: Cullen Louise , Greenslade Jaimi , Parsonage William , Stephensen Laura , Smith Stephen W , Sandoval Yader , Ranasinghe Isuru , Gaikwad Niranjan , Khorramshahi Bayat Maryam , Mahmoodi Ehsan , Schulz Karen , Than Martin , Apple Fred S ,   SAMIE and SEIGE investigators, Brownlee Emily , Fincher Gavin , Hall Emma , Hancock Rebecca , Gangathimmaiah Vinay , Hamilton-Craig Christian , Hobbins-King Andrew , Keijzers Gerben , McCormick Ellyse , Perez Siegfried , Staib Andrew , Zournazi Anna , Than Martin 
Published: June 2024

Abstract

Background and Aims
Strategies to assess patients with suspected acute myocardial infarction (AMI) using a point-of-care (POC) high-sensitivity cardiac troponin I (hs-cTnI) assay may expedite emergency care. A 2-h POC hs-cTnI strategy for emergency patients with suspected AMI was derived and validated.

Methods
In two international, multi-centre, prospective, observational studies of adult emergency patients (1486 derivation cohort and 1796 validation cohort) with suspected AMI, hs-cTnI (Siemens Atellica® VTLi) was measured at admission and 2 h later. Adjudicated final diagnoses utilized the hs-cTn assay in clinical use. A risk stratification algorithm was derived and validated. The primary diagnostic outcome was index AMI (Types 1 and 2). The primary safety outcome was 30-day major adverse cardiac events incorporating AMI and cardiac death.

Results
Overall, 81 (5.5%) and 88 (4.9%) patients in the derivation and validation cohorts, respectively, had AMI. The 2-h algorithm defined 66.1% as low risk with a sensitivity of 98.8% [95% confidence interval (CI) 89.3%–99.9%] and a negative predictive value of 99.9 (95% CI 99.2%–100%) for index AMI in the derivation cohort. In the validation cohort, 53.3% were low risk with a sensitivity of 98.9% (95% CI 92.4%–99.8%) and a negative predictive value of 99.9% (95% CI 99.3%–100%) for index AMI. The high-risk metrics identified 5.4% of patients with a specificity of 98.5% (95% CI 96.6%–99.4%) and a positive predictive value of 74.5% (95% CI 62.7%–83.6%) for index AMI.

Conclusions
A 2-h algorithm using a POC hs-cTnI concentration enables safe and efficient risk assessment of patients with suspected AMI. The short turnaround time of POC testing may support significant efficiencies in the management of the large proportion of emergency patients with suspected AMI.
A transcriptome-wide association study identified susceptibility genes for hepatocellular carcinoma in East Asia
Authors: Zhang Jingjing , Zhang Qingrong , Hu Wenyan , Liang Yuxuan , Jiang Deke , Chen Haitao 
Published: June 2024

Abstract

Background
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide and is prevalent in East Asia. Although genome-wide association studies (GWASs) of HCC have identified 23 risk regions, the susceptibility genes underlying these associations largely remain unclear. To identify novel candidate genes for HCC, we conducted liver single-tissue and cross-tissue transcriptome-wide association studies (TWASs) in two populations of East Asia.

Methods
GWAS summary statistics of 2,514 subjects (1,161 HCC cases and 1,353 controls) from the Chinese Qidong cohort and 161,323 subjects (2,122 HCC cases and 159,201 controls) from the BioBank Japan project were used to conduct TWAS analysis. The single-tissue and cross-tissue TWAS approaches were both used to detect the association between susceptible genes and the risk of HCC. TWAS identified genes were further annotated by Metascape, UALCAN, GEPIA2, and DepMap.

Results
We identified 22 novel genes at 16 independent loci significantly associated with HCC risk after Bonferroni correction. Of these, 13 genes were located in novel regions. Besides, we found 83 genes overlapped in the Chinese and Japanese cohorts with P &lt; 0.05, of which, three genes (NUAK2, HLA-DQA1, and ATP6V1G2) were discerned by both single-tissue and cross-tissue TWAS approaches. Among the genes identified through TWAS, a significant proportion of them exhibit a credible role in HCC biology, such as FAM96B, HSPA5, POLRMT, MPHOSPH10, and RABL2A. HLA-DQA1, NUAK2, and HSPA5 associated with the process of carcinogenesis in HCC as previously reported.

Conclusions
Our findings highlight the value of leveraging the gene expression data to identify new candidate genes beyond the GWAS associations and could further provide a genetic insight for the biology of HCC.
Position Statement of the Max Planck Institute for Innovation and Competition of 6 February 2024 on the Commission’s Proposal for a Regulation of the European Parliament and of the Council on Standard Essential Patents
Authors: Drexl Josef , Harhoff Dietmar , Conde Gallego Beatriz , Slowinski Peter R 
Published: June 2024

Abstract
The Max Planck Institute for Innovation and Competition is a research institute within the Max Planck Society for the Advancement of Science. The Institute is committed to fundamental legal and economic research on processes of innovation and competition and their regulation. Its research focus is on the incentives, determinants and implications of innovation. The Institute informs and guides legal and economic discourse on an impartial basis. It hereby presents its position on the European Commission’s proposal of 27 April 2023 for a Regulation of the European Parliament and of the Council on standard essential patents and amending Regulation (EU) 2017/1001.
FEM-BEM coupling in fractional diffusion
Authors: Faustmann Markus , Rieder Alexander 
Published: June 2024

Abstract
We derive and analyze a fully computable discrete scheme for fractional partial differential equations posed on the full space ${\mathbb{R}}^{d}$. Based on a reformulation using the well-known Caffarelli–Silvestre extension, we study a modified variational formulation to obtain well-posedness. Our scheme is obtained by combining a diagonalization procedure with a reformulation using boundary integral equations and a coupling of finite elements and boundary elements. For our discrete method we present a-priori estimates as well as numerical examples.
A Robust Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)–Specific T- and B-Cell Response Is Associated With Early Viral Clearance in SARS-CoV-2 Omicron-Infected Immunocompromised Individuals
Authors: Vergouwe Magda , Biemond Jason J , van der Straten Karlijn , van Pul Lisa , Kerster Gius , Claireaux Mathieu , Burger Judith A , van Dort Karel A , Kootstra Neeltje A , Jonges Marcel , Welkers Matthijs R A , Hazenberg Mette D , Peters-Sengers Hessel , van Gils Marit J , Wiersinga W Joost , Birnie Emma , de Bree Godelieve J ,   for the TURN-COVID study group, Olijhoek Wouter , Kalmoua Zakaria , Appelman Brent , Zaaijer Hans L , van Ittersum Frans J , van der Loeff Maarten F Schim , Bomers Marije K , Kersten Marie José , Heijmans Jarom , van der Valk Marc , de Boer Mark G J , Rosendaal Frits R , Kemper E Marleen 
Published: June 2024

Abstract

Background
The immunological determinants of delayed viral clearance and intrahost viral evolution that drive the development of new pathogenic virus strains in immunocompromised individuals are unknown. Therefore, we longitudinally studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)–specific immune responses in relation to viral clearance and evolution in immunocompromised individuals.

Methods
Among Omicron-infected immunocompromised individuals, we determined SARS-CoV-2–specific T- and B-cell responses, anti-spike immunoglobulin G (IgG) and IgG3 titers, neutralization titers, and monoclonal antibody (mAb) resistance–associated mutations. The 28-day post-enrollment nasopharyngeal specimen defined early (reverse-transcription polymerase chain reaction [RT-PCR] negative ≤28 days) or late (RT-PCR positive &gt;28 days) viral clearance.

Results
Of 30 patients included (median age, 61.9 [interquartile range, 47.4–72.3] years; 50% females), 20 (66.7%) received mAb therapy. Thirteen (43.3%) demonstrated early and 17 (56.7%) late viral clearance. Patients with early viral clearance and patients without resistance-associated mutations had significantly higher baseline interferon-γ release, and patients with early viral clearance had a higher frequency of SARS-CoV-2–specific B cells at baseline. In non-mAb-treated patients, day 7 IgG and neutralization titers were significantly higher in those with early versus late viral clearance.

Conclusions
An early robust adaptive immune response is vital for efficient viral clearance and associated with less emergence of mAb resistance–associated mutations in Omicron-infected immunocompromised patients. This emphasizes the importance of early SARS-CoV-2–specific T- and B-cell responses and thereby provides a rationale for development of novel therapeutic approaches.