bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcomes of Catheter Directed Thrombolysis for Early and Late Re-occlusions in Acute Lower Limb Ischemia
Authors: Oukrich S. , Doelare S.A.N. , Wiersema A.M. , Hoksbergen A.W.J. , Yeung K.K. , Jongkind V. 
Published: October 2024

Purpose: Acute lower limb ischemia (ALI) is a sudden decrease in arterial limb perfusion due to an arterial blockage, threatening limb and life. Catheter-directed thrombolysis (CDT) is a minimally invasive procedure to remove such obstructions. However, approximately one-third of patients endure a re-occlusion after successful CDT. This study aimed to investigate the short- and long-term outcomes of CDT for early (<1 year) and late (>1 year) re-occlusions. Material and Methods: This retrospective multicenter study reviewed patients from 2 medical centers with an acute arterial re-occlusion of the lower limb after successful CDT between December 1996 and April 2021. The primary endpoints were angiographic success, defined as thrombus dissolution over 95% with outflow to at least 1 crural artery, and clinical success, defined as a score of ≥1 on the Rutherford scale for assessing changes in clinical status. Secondary endpoints included bleeding complications, patency, amputation, and mortality. Kaplan-Meier analyses were used to estimate patency, survival, and freedom from amputation. Results: Seventy-seven cases were included, with 52 early re-occlusions (<1 year) and 25 late re-occlusions (>1 year). The median time to re-occlusion since the last CDT treatment was 4 months in the early re-occlusion group and 24 months in the late re-occlusion group. Angiographic success was achieved in 73% of early and 64% of late re-occlusions. Clinical success rates were 80.8% for the early and 80.0% of the late re-occlusion cases. Major bleeding occurred in 2% of the early and 8% of the late re-occlusion group. Patients were followed up until symptoms or signs of limb ischemia were resolved, with a median follow-up time of 15 months for the early and 22 months for the late re-occlusion group. During follow-up, secondary re-occlusions were observed in 59.6% of the early and 44% in the late group. Cumulative amputation rates at 1, 5, and 8 years were 36%, 36%, and 52% for early and 18%, 30%, and 30% for the late re-occlusions, respectively. Conclusion: In our experience, CDT is an effective short-term revascularization strategy for the majority of patients with both early and late re-occlusions. Long-term results are limited by secondary re-occlusions and limb loss. Clinical Impact Catheter-directed thrombolysis (CDT) is a well-established treatment for acute lower limb ischemia (ALI). Re-occlusions after successful treatment are, however, observed in almost a third of the patients. Yet, the outcomes of CDT for re-occlusions for patients who were previously treated with CDT are not well known. This study showed that CDT is effective in achieving revascularization in cases of early and late re-occlusion after treatment for ALI, but the risk for further re-occlusions is high. Future studies should focus on maintaining patency after successful CDT for ALI.
Adapting a Remotely Delivered Patient Navigation Program for Colorectal Cancer Screening in Primary Care: Important Considerations for Rural Contexts
Authors: Ike Brooke , Keppel Gina A. , Osterhage Katie P. , Ko Linda K. , Cole Allison 
Published: October 2024

Introduction: Colonoscopy is a critical component of colorectal cancer (CRC) screening and patient navigation (PN) improves colonoscopy completion. A lay navigator remotely providing navigation across rural primary care organizations (PCOs) could increase PN access. In preparation for the Colonoscopy Outreach for Rural Communities (CORC) study, we examined partners’ perspectives on contextual factors that could influence CORC program implementation, and adaptations to mitigate potential barriers. Methods: We interviewed 29 individuals from 6 partner PCOs and the community-based organization (CBO) delivering the PN program. An analysis approach informed by Miles, Huberman, and Saldana identified critical themes. Results are reported using the Framework for Reporting Adaptations and Modifications-Enhanced (FRAME). Results: Potential barriers included that rural patients are hard to reach remotely and might mistrust the navigator, and the CBO is unfamiliar with the patient communities and does not have patient care experience or pre-existing communication pathways with the PCOs. Program content and navigator training was adapted to mitigate these challenges. Conclusions: Our study highlights contextual factors to account for before implementing a remote, centralized patient navigation program serving rural communities. Gathering partner perspectives led to intervention adaptations intended to address potential barriers while leaving the core components of the evidence-based intervention intact.
CNS relapse in high-grade B-cell lymphoma with MYC and BCL2 rearrangements and dark-zone signature–expressing DLBCL
Authors: Alduaij Waleed , Jiang Aixiang , Villa Diego , Collinge Brett , Ben-Neriah Susana , Boyle Merrill , Meissner Barbara , Hilton Laura K. , Farinha Pedro , Slack Graham W. , Craig Jeffrey W. , Gerrie Alina S. , Freeman Ciara L. , Mungall Andrew J. , Steidl Christian , Sehn Laurie H. , Scott David W. , Savage Kerry J. 
Published: October 2024

Abstract
High-grade B-cell lymphoma with MYC and BCL2 rearrangements (HGBCL-DH-BCL2), or “double-hit lymphoma,” has been associated with a high risk of central nervous system (CNS) relapse. However, historic estimates are impacted by selection bias. We report CNS relapse rates associated with HGBCL-DH-BCL2 from a population-based cohort with complete fluorescence in situ hybridization testing, as well as diffuse large B-cell lymphoma morphology (DLBCL) tumors expressing the dark-zone gene expression signature (DZsig), which was originally derived from HGBCL-DH-BCL2. The 2-year CNS relapse risk in HGBCL-DH-BCL2 was 6.8%. CNS relapses were early, predominantly leptomeningeal (73%), and co-occurred with systemic relapse (64%). High-risk CNS International Prognostic Index (CNS-IPI) and concordant bone marrow involvement were associated with an elevated CNS relapse risk in HGBCL-DH-BCL2. The “refined cell-of-origin” classification assigned 20% of DLBCL morphology tumors with germinal center B-cell–like phenotype (GCB-DLBCL) into a distinct subgroup based on DZsig expression (DZsig+). CNS relapse risk in DZsig+ (2 year: 6.4%) was independent of HGBCL-DH-BCL2 status and was further stratified by the CNS-IPI. CNS relapse in DZsig-negative GCB-DLBCL was rare (2-year risk, 1.4%; P = .04 vs DZsig+) and exclusively parenchymal. Altogether, the CNS relapse risk in HGBCL-DH-BCL2 is lower than previously reported, and DZsig refines risk stratification in GCB-DLBCL.
Novel plasmon-coupled Ag/Ag2O nano-particles to downregulate β-catenin pathway in triple negative breast cancer
Authors: Mohamed A. Kamal , El-Dek S. I. , EL-Gendy Saad M. , El-Shahawy Ahmed. A. G. 
Published: October 2024

AbstractWe prepared novel plasmon-coupled silver (Ag) and silver oxide (Ag2O) nanoparticles using green synthesis and a magnetic stirrer device from lemon juice. Firstly, we prepared six Ag samples from green tea and lemon juice, characterized by XRD, FTIR, UV, and HRTEM. We selected just two samples to apply to MDA-MB-231 cells. The samples entered the cell through endocytosis, showed moderate cytotoxicity and ROS levels, caused cell growth arrest at the G2M phase, exhibited higher inhibition of Cyclin D1, and induced early apoptosis. β-Catenin is an abundant protein in triple-negative breast cancer TNBC. Both samples showed inhibition of the β-catenin proteins pathway. Plasmon-coupled nanoparticles effectively inhibited β-catenin, physically capturing β-catenin and its pathway proteins, mimicking the action of a degradation protein complex due to their geometric properties. The prepared materials could be considered a promising treatment for TNBC that has not responded to chemotherapy and radiotherapy. As they have low toxicity to normal cells; this paves the way for new material designs without strict size limitations.
Where do UK clinicians find information at the point of care? A pragmatic, exploratory study
Authors: McCartney Margaret , Connolly Kate , Sullivan Frank , Heneghan Carl , Heng Ho Elijah Yu , Hendry Brid , Salisbury Charlotte , Offer Sam , Nunan David 
Published: October 2024

Abstract
Aim
To describe where clinical information is contemporarily and commonly found in UK primary care, what is favoured by clinicians, and whether this is (1) publicly funded (2) has commercial potential conflicts of interest.

Design and setting
A mixed methods study, consisting of (1) site visits to general practices in Scotland, (2) online questionnaire, focused on UK general practice (3) analysis of materials cited by professionals.

Methods
Data about sources of clinical information used was obtained verbally, visually and via search histories on computers from visits. This was used to inform a questionnaire in which primary care clinicians in the four nations of the UK were invited to participate. This obtained data about the information sources used and preferred by clinicians. This information was searched for data about funding and conflicts of interest.

Results
Over 2022, four practices were visited. 337 clinicians, 280 of whom were general practitioners completed an online questionnaire. 136 different resources were identified. These were mainly websites but sources of information included colleagues, either in practice or through online networks, apps, local guidelines, health charities, and learning resources aimed at GPs. Of these, 70 were not publicly funded, and were a mixture of membership organisations, charities, or sponsored venues.

Conclusions
Primary care clinicians obtain information for themselves and patients from a wide variety of sources. Funding is from a variety of sources and some contain advertising and/or sponsorship, risking commercial bias.

Protocol
Pre-published at https://osf.io/wrzqk.
A 5-year natural history study in LAMA2-related muscular dystrophy and SELENON-related myopathy: the Extended LAST STRONG study
Authors: de Laat E. C. M. , Houwen- van Opstal S.L.S. , Bouman K. , van Doorn J. L. M. , Cameron D. , van Alfen N. , Dittrich A. T. M. , Kamsteeg E. J. , Smeets H. J. M. , Groothuis J. T. , Erasmus C. E. , Voermans Nicol C. 
Published: October 2024

Abstract
Background
SELENON-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive axial muscle weakness, rigidity of the spine, scoliosis, and respiratory insufficiency. Laminin-a2-related muscular dystrophy (LAMA2-MD) has a similar clinical phenotype, which ranges from severe, early-onset congenital muscular dystrophy type 1A (MDC1A) to milder forms presenting as childhood- or adult-onset limb-girdle type muscular dystrophy. The first 1.5-year natural history follow-up showed that 90% of the patients had low bone quality, respiratory impairments were found in all SELENON-RM and most of the LAMA2-MD patients, and many had cardiac risk factors. However, further extensive knowledge on long-term natural history data, and clinical and functional outcome measures is needed to reach trial readiness. Therefore, we extended the natural history study with 3- and 5-year follow-up visits (Extended LAST STRONG).

Methods
The Extended LAST STRONG is a long-term natural history study in Dutch-speaking patients of all ages diagnosed with genetically confirmed SELENON-RM or LAMA2-MD, starting in September 2023. Patients visit our hospital twice over a period of 2 years to complete a 5-year follow up from the initial LAST-STRONG study. At both visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, muscle ultrasound, respiratory assessments (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), Dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years), X-ray of the left hand (age ≤ 17 years), lower extremity MRI (age ≥ 10 years), accelerometry for 8 days (age ≥ 2 years), and questionnaires (patient report and/or parent proxy; age ≥ 2 years). All examinations are adapted to the patient’s age and functional abilities. Disease progression between all subsequent visits and relationships between outcome measures will be assessed.

Discussion
This study will provide valuable insights into the 5-year natural history of patients with SELENON-RM and LAMA2-MD and contribute to further selecting relevant and sensitive to change clinical and functional outcome measures. Furthermore, this data will help optimize natural history data collection in clinical care and help develop clinical care guidelines.

Trial registration
This study protocol including the patient information and consent forms has been approved by medical ethical reviewing committee (‘METC Oost-Nederland’; https://www.ccmo.nl/metcs/erkende-metcs/metc-oost-nederland, file number: 2023–16401). It is registered at ClinicalTrials.gov (NCT06132750; study registration date: 2023-10-05; study first passed date: 2023-11-15).
A retrospective analysis using comorbidity detecting algorithmic software to determine the incidence of International Classification of Diseases (ICD) code omissions and appropriateness of Diagnosis-Related Group (DRG) code modifiers
Authors: Gabel Eilon , Gal Jonathan , Grogan Tristan , Hofer Ira 
Published: October 2024

Abstract
Background
The mechanism for recording International Classification of Diseases (ICD) and diagnosis related groups (DRG) codes in a patient’s chart is through a certified medical coder who manually reviews the medical record at the completion of an admission. High-acuity ICD codes justify DRG modifiers, indicating the need for escalated hospital resources. In this manuscript, we demonstrate that value of rules-based computer algorithms that audit for omission of administrative codes and quantifying the downstream effects with regard to financial impacts and demographic findings did not indicate significant disparities.

Methods
All study data were acquired via the UCLA Department of Anesthesiology and Perioperative Medicine’s Perioperative Data Warehouse. The DataMart is a structured reporting schema that contains all the relevant clinical data entered into the EPIC (EPIC Systems, Verona, WI) electronic health record. Computer algorithms were created for eighteen disease states that met criteria for DRG modifiers. Each algorithm was run against all hospital admissions with completed billing from 2019. The algorithms scanned for the existence of disease, appropriate ICD coding, and DRG modifier appropriateness. Secondarily, the potential financial impact of ICD omissions was estimated by payor class and an analysis of ICD miscoding was done by ethnicity, sex, age, and financial class.

Results
Data from 34,104 hospital admissions were analyzed from January 1, 2019, to December 31, 2019. 11,520 (32.9%) hospital admissions were algorithm positive for a disease state with no corresponding ICD code. 1,990 (5.8%) admissions were potentially eligible for DRG modification/upgrade with an estimated lost revenue of $22,680,584.50. ICD code omission rates compared against reference groups (private payors, Caucasians, middle-aged patients) demonstrated significant p-values < 0.05; similarly significant p-value where demonstrated when comparing patients of opposite sexes.

Conclusions
We successfully used rules-based algorithms and raw structured EHR data to identify omitted ICD codes from inpatient medical record claims. These missing ICD codes often had downstream effects such as inaccurate DRG modifiers and missed reimbursement. Embedding augmented intelligence into this problematic workflow has the potential for improvements in administrative data, but more importantly, improvements in administrative data accuracy and financial outcomes.
Use of renin-angiotensin system blockers and posttraumatic stress disorder risk in the UK Biobank: a retrospective cohort study
Authors: Kang Sunghyuk , Kim Jimin , Yang Ji Su , Jeon Ye Jin , Lee Hyeok-Hee , Suglia Shakira F. , Tsai Alexander C. , Kang Jee In , Jung Sun Jae 
Published: October 2024

Abstract
Background
Previous research has shown that the use of renin-angiotensin system (RAS) blockers is linked to a lower prevalence of posttraumatic stress disorder (PTSD), but longitudinal studies are scarce. We aimed to estimate the association between the use of RAS blockers and the risk of PTSD among individuals taking antihypertensive medications.

Methods
This longitudinal study included participants aged 40–69 from the UK Biobank. Exposure data were obtained from the initial assessment (2006–10), while outcome data were obtained from the online mental health questionnaire administered 6–11 years later (2016–17). We included participants who were under antihypertensive treatment and did not have a prior diagnosis of PTSD before the initial assessment. Use of RAS blockers was defined as self-reported regular use, at the initial assessment, of angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB). Among participants who experienced adverse life experiences, cases of probable PTSD were defined with the six-item PTSD Checklist-Civilian version score ≥ 14. Logistic regression with inverse probability of treatment weighting was used to estimate the odds ratios (ORs) and 95% confidence interval (CI) for the association between RAS blocker use and the risk of probable PTSD.

Results
Of the 15,954 participants (mean age = 59.9 years; 42.6% women) under antihypertensive treatment with no prior history of PTSD at the initial assessment, 64.5% were taking RAS blockers. After a mean follow-up of 7.5 years, 1,249 (7.8%) were newly identified with probable PTSD. RAS blocker users had a lower risk of probable PTSD than RAS blocker non-users (OR = 0.84 [95% CI: 0.75–0.94]), whereas the use of other antihypertensive medications showed no such association (users vs. non-users; calcium channel blockers, OR = 0.99 [95% CI: 0.88–1.11]; beta-blockers, 1.20 [1.08–1.34]; and thiazide-related diuretics, 1.15 [1.03–1.29]). The association between probable PTSD risk and the use of ACEi vs. ARB showed no significant difference (p = 0.96).

Conclusions
Among individuals under antihypertensive treatment, the use of RAS blockers was associated with a decreased risk of probable PTSD. This added benefit of RAS blockers should be considered in the selection of antihypertensive medications.
Plasmid-free production of the plant lignan pinoresinol in growing Escherichia coli cells
Authors: Luelf U. Joost , Wassing Alexander , Böhmer Lisa M. , Urlacher Vlada B. 
Published: October 2024

Abstract

Background
The high-value aryl tetralin lignan (+)-pinoresinol is the main precursor of many plant lignans including (-)-podophyllotoxin, which is used for the synthesis of chemotherapeutics. As (-)-podophyllotoxin is traditionally isolated from endangered and therefore limited natural sources, there is a particular need for biotechnological production. Recently, we developed a reconstituted biosynthetic pathway from (+)-pinoresinol to (-)-deoxypodophyllotoxin, the direct precursor of (-)-podophyllotoxin, in the recombinant host Escherichia coli. However, the use of the expensive substrate (+)-pinoresinol limits its application from the economic viewpoint. In addition, the simultaneous expression of multiple heterologous genes from different plasmids for a multi-enzyme cascade can be challenging and limits large-scale use.

Results
In this study, recombinant plasmid-free E. coli strains for the multi-step synthesis of pinoresinol from ferulic acid were constructed. To this end, a simple and versatile plasmid toolbox for CRISPR/Cas9-assisted chromosomal integration has been developed, which allows the easy transfer of genes from the pET vector series into the E. coli chromosome. Two versions of the developed toolbox enable the efficient integration of either one or two genes into intergenic high expression loci in both E. coli K-12 and B strains. After evaluation of this toolbox using the fluorescent reporter mCherry, genes from Petroselinum crispum and Zea mays for the synthesis of the monolignol coniferyl alcohol were integrated into different E. coli strains. The product titers achieved with plasmid-free E. coli W3110(T7) were comparable to those of the plasmid-based expression system. For the subsequent oxidative coupling of coniferyl alcohol to pinoresinol, a laccase from Corynebacterium glutamicum was selected. Testing of different culture media as well as optimization of gene copy number and copper availability for laccase activity resulted in the synthesis of 100 mg/L pinoresinol using growing E. coli cells.

Conclusions
For efficient and simple transfer of genes from pET vectors into the E. coli chromosome, an easy-to-handle molecular toolbox was developed and successfully tested on several E. coli strains. By combining heterologous and endogenous enzymes of the host, a plasmid-free recombinant E. coli growing cell system has been established that enables the synthesis of the key lignan pinoresinol.
NDRG1 upregulation by ubiquitin proteasome system dysfunction aggravates neurodegeneration
Authors: Hoshino Tomonori , Mukai Atsushi , Yamashita Hirofumi , Misawa Hidemi , Urushitani Makoto , Tashiro Yoshitaka , Matsuzawa Shu-ichi , Takahashi Ryosuke 
Published: October 2024

AbstractProtein turnover is crucial for cell survival, and the impairment of proteostasis leads to cell death. Aging is associated with a decline in proteostasis, as the progressive accumulation of damaged proteins is a hallmark of age-related disorders such as neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). We previously discovered that the declining function of the ubiquitin-proteasome system (UPS) in motor neurons contributes to sporadic ALS pathologies, such as progressive motor neuron loss, protein accumulation, and glial activation. However, the mechanisms of UPS dysfunction-induced cell damage, such as cell death and aggregation, are not fully understood. This study used transcriptome analysis of motor neurons with UPS dysfunction and found that the expression of N-myc downstream regulated 1 (NDRG1) gets upregulated by UPS dysfunction. Additionally, the upregulation of NDRG1 induces cell death in the Neuro2a mouse neuroblastoma cell line. These results suggest that NDRG1 is a potential marker for UPS dysfunction and may play a role in neurodegeneration, such as that seen in ALS.