bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transcriptomic changes in oligodendrocytes and precursor cells associate with clinical outcomes of Parkinson’s disease
Authors: Dehestani Mohammad , Kozareva Velina , Blauwendraat Cornelis , Fraenkel Ernest , Gasser Thomas , Bansal Vikas 
Published: August 2024

AbstractSeveral prior studies have proposed the involvement of various brain regions and cell types in Parkinson’s disease (PD) pathology. Here, we performed snRNA-seq on the prefrontal cortex and anterior cingulate regions from a small cohort of post-mortem control and PD brain tissue. We found a significant association of oligodendrocytes (ODCs) and oligodendrocyte precursor cells (OPCs) with PD-linked risk loci and report several dysregulated genes and pathways, including regulation of tau-protein kinase activity, regulation of inclusion body assembly and protein processing involved in protein targeting to mitochondria. In an independent PD cohort with clinical measures (681 cases and 549 controls), polygenic risk scores derived from the dysregulated genes significantly predicted Montreal Cognitive Assessment (MoCA)-, and Beck Depression Inventory-II (BDI-II)-scores but not motor impairment (UPDRS-III). We extended our analysis of clinical outcome prediction by incorporating differentially expressed genes from three separate datasets that were previously published by different laboratories. In the first dataset from the anterior cingulate cortex, we identified an association between ODCs and BDI-II. In the second dataset obtained from the substantia nigra (SN), OPCs displayed an association with UPDRS-III. In the third dataset from the SN region, a distinct subtype of OPCs, labeled OPC_ADM, exhibited an association with UPDRS-III. Intriguingly, the OPC_ADM cluster also demonstrated a significant increase in PD samples. These results suggest that by expanding our focus to glial cells, we can uncover region-specific molecular pathways associated with PD symptoms.
Building a performance measurement framework for telephone triage services in Finland: a consensus-making study based on nominal group technique
Authors: Vainio Hanna , Soininen Leena , Torkki Paulus 
Published: August 2024

Abstract
Background
There has been a significant expansion in the measurement of healthcare system performance. However, there is a lack of a comprehensive performance measurement framework to assess the effects of telephone triage services on the urgent care system. The aim of our Delphi study was to construct and validate a performance measurement framework designed explicitly for telephone triage services.

Methods
This study was conducted in Finland with a group of eight experienced senior physicians from the country's 20 largest joint emergency departments, serving over 90% of the population for urgent care. The Nominal Group Technique (NGT) was utilised to achieve consensus on measuring telephone triage performance. Initially, performance indicators (PIs) were identified through Delphi method rounds from December 10th to December 27th, 2021, with eight experts participating, and from December 29th, 2021, to January 23rd, 2022, where five of these experts responded. NGT further deepened these themes and perspectives, aiding in the development of a comprehensive performance measurement framework. The final framework validation began with an initial round from February 13th to March 3rd, 2022, receiving five responses. Due to the limited number of responses, an additional validation round was conducted from October 29th to November 7th, 2023, resulting in two more responses, increasing the total number of respondents in the validation phase to seven.

Results
The study identified a strong desire among professionals to implement a uniform framework for measuring telephone triage performance. The finalised framework evaluates telephone triage across five dimensions: service accessibility, patient experience, quality and safety, process outcome, and cost per case. Eight specific PIs were established, including call response metrics, service utility, follow-up care type and distribution, ICPC-2 classified encounter reasons, patient compliance with follow-up care, medical history review during assessment, and service cost per call.

Conclusions
This study validated a performance measurement framework for telephone triage services, utilising existing literature and the NGT method. The framework includes five key dimensions: patient experience, quality and safety, outcome of the telephone triage process, cost per case, and eight PIs. It offers a structured and comprehensive approach to measuring the overall performance of telephone triage services, enhancing our ability to evaluate these services effectively.
Catheters linked thrombosis in neonates: a single center observational study
Authors: Farag Marwa Mohamed , Ghazal Hesham Abd El Rahim , Radwan Mohamed Masoud , El-sayed Nada Saeid 
Published: August 2024

Abstract
Background
Central venous catheters (CVCs) are the major risk factors for neonatal thrombosis that might negatively affect morbidity and mortality in neonates. The aim of the present work was to estimate the incidence of CVC-linked thrombosis, among neonates in the NICU of Alexandria University Maternity Hospital, Egypt, over 1year, and to determine its possible risk factors.

Methods
This observational cohort study involved 134 newborn infants born from July 2020 to July 2021with CVCs insertion during their hospital stay. Patients who had congenital anomalies, had thrombosis unrelated to the implantation of CVCs or died before 7 days of catheter placement were excluded from the analysis. The 134 neonates who met the study’s eligibility requirements had 142 CVCs inserted. Serial ultrasound and Doppler scans on site of venous insertion of catheters were performed.

Results
Seventeen patients with catheter’s thrombosis (12%) were found during the placement of 142 catheters or 1615 CVCs’ days, resulting in an overall rate of 10.5 thrombotic events per 1000 catheters’ days. We constructed a logistic regression model to identify risk factors behind CVC-linked thrombosis. In univariate analysis, femoral central venous lines (CVLs), catheter dwell-time, sepsis, packed red cells (PRBCs) transfusions and low platelet count were risk factors for CVC-linked thrombosis. Nevertheless, only PRBCs transfusion was significant in the multivariate analysis, with OR and 95% confidence level 5.768 (1.013–32.836).

Conclusion
Many factors should be considered in prediction of patients at risk of thrombosis including sepsis, femoral line insertion, low platelet count and PRBCs-transfusions. In our analysis, PRBCs-transfusion through peripheral intravenous lines (PIVs) was the strongest factor associated with CVC-linked thrombosis.
The SEMA3F-NRP1/NRP2 axis is a key factor in the acquisition of invasive traits in in situ breast ductal carcinoma
Authors: Moragas Núria , Fernandez-Nogueira Patricia , Recalde-Percaz Leire , Inman Jamie L. , López-Plana Anna , Bergholtz Helga , Noguera-Castells Aleix , del Burgo Pedro J. , Chen Xieng , Sorlie Therese , Gascón Pere , Bragado Paloma , Bissell Mina , Carbó Neus , Fuster Gemma 
Published: August 2024

Abstract
Background
A better understanding of ductal carcinoma in situ (DCIS) is urgently needed to identify these preinvasive lesions as distinct clinical entities. Semaphorin 3F (SEMA3F) is a soluble axonal guidance molecule, and its coreceptors Neuropilin 1 (NRP1) and NRP2 are strongly expressed in invasive epithelial BC cells.

Methods
We utilized two cell line models to represent the progression from a healthy state to the mild-aggressive or ductal carcinoma in situ (DCIS) stage and, ultimately, to invasive cell lines. Additionally, we employed in vivo models and conducted analyses on patient databases to ensure the translational relevance of our results.

Results
We revealed SEMA3F as a promoter of invasion during the DCIS-to-invasive ductal carcinoma transition in breast cancer (BC) through the action of NRP1 and NRP2. In epithelial cells, SEMA3F activates epithelialmesenchymal transition, whereas it promotes extracellular matrix degradation and basal membrane and myoepithelial cell layer breakdown.

Conclusions
Together with our patient database data, these proof-of-concept results reveal new SEMA3F-mediated mechanisms occurring in the most common preinvasive BC lesion, DCIS, and represent potent and direct activation of its transition to invasion. Moreover, and of clinical and therapeutic relevance, the effects of SEMA3F can be blocked directly through its coreceptors, thus preventing invasion and keeping DCIS lesions in the preinvasive state.
Hepatocellular adenomas with severe intra-abdominal bleeding, related to an underlying coagulation disorder: a case report
Authors: Oudmaijer C. A. J. , Sprakel J. , Sprengers D. , Wiese K. A. , Tintel N. Vogelaar - , Franken J. I. , Terkivatan T. , Porte R. J. , IJzermans J. N. M. 
Published: August 2024

Abstract
Background
Hepatocellular adenoma is a rare benign liver tumor. Typically, hepatocellular adenomas are solitary and are found in young women who use estrogen-containing contraceptives. The occurrence of multiple hepatocellular adenoma has been linked to higher body mass index, and as the prevalence of overweight increases, multiple hepatocellular adenomas are seen more often. An hepatocellular adenoma does not always necessitate treatment, as they can regress under conservative strategies. In incidental cases, an adenoma presents owing to bleeding, which is mostly self-limiting. If it is not, embolization of hepatic involved vessels is indicated.

Case presentation
In this case report, we discuss a 42-year old Caucasian woman with multiple hepatocellular bleeds, treated by multiple endovascular procedures. After the first embolization of an adenoma in the right liver lobe, a second bleed occurred in the left lobe, necessitating additional endovascular intervention. During admittance, treatment was complicated by pulmonary embolism and a pneumonia. During follow-up, our patient was diagnosed with antiphospholipid syndrome.

Conclusion
Hepatocellular adenoma is a rare diagnosis that requires centralized expertise. This particular case illustrates the complexity of treatment strategies for associated intra-abdominal bleeding and possible complications. Although liver adenoma is often an incidental finding, it can also result in significant morbidity. Centralization of treatment leads to expertise in managing complex treatment strategies.
Extended spectrum and metalo beta lactamase producing gram negative bacterial pathogens from cockroaches collected at hospital, Southern Ethiopia
Authors: Bisetegn Fithamlak Solomon , Azene Habtamu , Ahmed Khawaja Shakeel , Wadilo Fiseha , Tufa Efrata Girma 
Published: August 2024

Abstract
Background
Cockroaches can pose a significant health risk in hospital environments because they may serve as reservoirs and vectors for nosocomial pathogens. Cockroaches harbor epidemiologically significant extended spectrum and metalo beta lactamase producing Gram negative bacterial pathogens, which complicate nosocomial infections.

Objectives
The main aim of this study is to determine aetiology and phenotypic extended spectrum and metalo beta lactamase producing Gram negative bacteria pathogens from cockroaches collected in hospitals.

Methods
A cross-sectional study was employed from February to May 2022 to determine the antibiotic resistance producing bacterial isolates from cockroaches by giving special emphasis to metalo beta lactamase and extended spectrum beta lactamase production from different wards of WSUCSH. Cockroaches were collected with hands wearing sterile gloves. External homogenate was prepared and incubated microbiologically by using different culture media and differentiated biochemically. Antimicrobial susceptibility testing was performed by disk diffusion method. ESBL production was conducted using double disc synergy method and double disk method was used to detect MBL enzyme detection. Descriptive statistics was used to determine prevalence and percentage.

Result
Out of 245 cockroaches, 108 Gram negative bacteria were isolated. K. pneumoniae 29(26.9%) was the most predominant bacteria and Enetrobacter spp. 8(7.4%), was the least. All, K. pneumoniae, P. mirabilis, and Enterobacter isolates were pan-resistant to Ampicillin. P.aeruginosa and P.mirabilis antibiotics showed ≥ 80% resistant for amoxicillin/clavulanic acid antibiotics. Cefotaxime, ceftazidime, ceftriaxone and imipenem showed relative efficacy compared with other antibiotics. Out of 78 amoxicillin-clavulanic acid resistant isolates, 42(34.7%) were ESBL producers. ESBL production is more depicted by P. aeruginosa, A. baumannii, K. pneumoniae and E. coli. The overall prevalence of MBL production is 29(23.1%). K. pneumoniae P. aeruginosa, E.coli, A. baumannii, Enterobacter spp and K.oxytoca revealed MBL production.

Conclusion
The overall prevalence of ESBL and MBL producing nosocomial agents from hospital cockroaches was 34.7% and 23.1% respectively. P.aeruginosa, A.baumannii, K.pneumoniae and E.coli showed pronounced ESBL production. All bacterial isolates except P. mirabilis and C. freundii showed MBL production. The needed to evaluate our antibiotic stewardship program and antibiotic resistance detection for treatment is mandatory. The impact of cockroach as a source of AMR should be sought.
Trop2-targeted therapy in breast cancer
Authors: Hu Yixuan , Zhu Yinxing , Qi Dan , Tang Cuiju , Zhang Wenwen 
Published: August 2024

AbstractHuman trophoblastic cell surface antigen 2 (Trop2) is a glycoprotein, a cellular marker of trophoblastic and stem cells, and a calcium signaling transducer involved in several signaling pathways, leading to the proliferation, invasion, and metastasis of tumors. It is expressed at a low level in normal epithelial cells, but at a high level in many tumors, making it an ideal target for cancer therapy. According to previous literature, Trop2 is broadly expressed in all breast cancer subtypes, especially in triple negative breast cancer (TNBC). Several clinical trials have demonstrated the effectiveness of Trop2-targeted therapy in breast cancer. Sacituzumab govitecan (SG) is a Trop2-targeted antibody-drug conjugate (ADC) that has been approved for the treatment of metastatic TNBC and hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer. This article reviews the structure and function of Trop2, several major Trop2-targeted ADCs, other appealing novel Trop2-targeted agents and relevant clinical trials to provide a landscape of how Trop2-targeted treatments will develop in the future.
Diffusion–based virtual MR elastography for predicting recurrence of solitary hepatocellular carcinoma after hepatectomy
Authors: Chen Jiejun , Sun Wei , Wang Wentao , Fu Caixia , Grimm Robert , Zeng Mengsu , Rao Shengxiang 
Published: August 2024

Abstract
Background
To explore the capability of diffusion-based virtual MR elastography (vMRE) in the preoperative prediction of recurrence in hepatocellular carcinoma (HCC) and to investigate the underlying relevant histopathological characteristics.

Methods
Between August 2015 and December 2016, patients underwent preoperative MRI examination with a dedicated DWI sequence (b-values: 200,1500 s/mm2) were recruited. The ADC values and diffusion-based virtual shear modulus (μdiff) of HCCs were calculated and MR morphological features were also analyzed. The Cox proportional hazards model was used to identify the risk factors associated with tumor recurrence. A preoperative radiologic model and postoperative model including pathological features were built to predict tumor recurrence after hepatectomy.

Results
A total of 87 patients with solitary surgically confirmed HCCs were included in this study. Thirty-five patients (40.2%) were found to have tumor recurrence after hepatectomy. The preoperative model included higher μdiff and corona enhancement, while the postoperative model included higher μdiff, microvascular invasion, and histologic tumor grade. These factors were identified as significant prognostic factors for recurrence-free survival (RFS) (all p < 0.05). The HCC patients with μdiff values > 2.325 kPa showed poorer 5-year RFS after hepatectomy than patients with μdiff values ≤ 2.325 kPa (p < 0.001). Moreover, the higher μdiff values was correlated with the expression of CK19 (3.95 ± 2.37 vs. 3.15 ± 1.77, p = 0.017) and high Ki-67 labeling index (4.22 ± 1.63 vs. 2.72 ± 2.12, p = 0.001).

Conclusions
The μdiff values related to the expression of CK19 and Ki-67 labeling index potentially predict RFS after hepatectomy in HCC patients.
Protocol for a pilot cluster randomised controlled trial of PRoGRAM-A (preventing gambling-related harm in adolescents): a secondary school-based social network intervention
Authors: Dobbie Fiona , Miller Martine , Wardle Heather , Dahlby Lucia , Weir Christopher , Niven Angela , Stoddart Andrew , Griffiths David , Lee Ashley , Good Sally , Noble Leon , White James 
Published: August 2024

Abstract
Background
In the UK, recent evidence of young people and gambling indicates a higher prevalence of gambling in comparison to other addictive behaviours. Engaging in gambling-related behaviour at a young age is associated with short and long-term consequences, including financial, emotional, academic, interpersonal, and physical and mental health detriments; otherwise known as gambling-related harms (GRH). Given the unique vulnerability of this younger group, early interventions aimed at delaying or preventing gambling are critical. PRoGRAM-A (Preventing Gambling-Related Harm in Adolescents) is a school-based, social network intervention to protect young people from future GRH, by delaying or preventing gambling experimentation.

Methods
Pilot cluster RCT with an embedded process evaluation and health economic scoping study.

Participants
PRoGRAM-A will be delivered in four schools, with two control schools acting as a comparator. All are secondary schools in Scotland. Baseline surveys were conducted with students in S3 (ages 13–14). Follow-up surveys were conducted with the same cohort, six months post-baseline.

Intervention
PRoGRAM-A trainers will deliver a 2-day, out-of-school training workshop to Peer supporters. Peer supporters will be nominated by peers among their school year group (S3, age 13–14). Workshops will provide peer supporters with information on four gambling-related topics: (1) what is gambling? (2) gambling and gaming, (3) gambling marketing, (4) identifying harm and reducing risk. Peer supporters will disseminate the information (message diffusion) they have learned among their friends and family over a 10-week period. After the 2-day workshop, PRoGRAM-A trainers will conduct × 3 in-school follow-up sessions with peer supporters to offer support, encouragement, and advice to Peer Supporters as well as monitor and explore the extent of their message diffusion.

Primary outcome
The primary outcome of the pilot cluster RCT (cRCT) will be whether progression to a phase III RCT is justified.

Discussion
This will be the first pilot cluster RCT (cRCT) of an intervention to prevent gambling-related harms among young people within the UK. If findings indicate feasibility and acceptability, funding will be sought for a phase III RCT of effectiveness.

Trial registration
Researchregistry8699. Registered 21st February 2023.
109Pd/109mAg in-vivo generator in the form of nanoparticles for combined β- - Auger electron therapy of hepatocellular carcinoma
Authors: Gharibkandi Nasrin Abbasi , Wawrowicz Kamil , Walczak Rafał , Majkowska-Pilip Agnieszka , Wierzbicki Mateusz , Bilewicz Aleksander 
Published: August 2024

Abstract
Background
Convenient therapeutic protocols for hepatocellular carcinoma (HCC) are often ineffective due to late diagnosis and high tumor heterogeneity, leading to poor long-term outcomes. However, recently performed studies suggest that using nanostructures in liver cancer treatment may improve therapeutic effects. Inorganic nanoparticles represent a unique material that tend to accumulate in the liver when introduced in-vivo. Typically, this is a major drawback that prevents the therapeutic use of nanoparticles in medicine. However, in HCC tumours, this may be advantageous because nanoparticles may accumulate in the target organ, where the leaky vasculature of HCC causes their accumulation in tumour cells via the EPR effect. On the other hand, recent studies have shown that combining low- and high-LET radiation emitted from the same radionuclide, such as 161Tb, can increase the effectiveness of radionuclide therapy. Therefore, to improve the efficacy of radionuclide therapy for hepatocellular carcinoma, we suggest utilizing radioactive palladium nanoparticles in the form of 109Pd/109mAg in-vivo generator that simultaneously emits β− particles and Auger electrons.

Results
Palladium nanoparticles with a size of 5 nm were synthesized using 109Pd produced through neutron irradiation of natural palladium or enriched 108Pd. Unlike the 109Pd-cyclam complex, where the daughter radionuclide diffuses away from the molecules, 109mAg remains within the nanoparticles after the decay of 109Pd. In vitro cell studies using radioactive 109Pd nanoparticles revealed that the nanoparticles accumulated inside cells, reaching around 50% total uptake. The 109Pd-PEG nanoparticles exhibited high cytotoxicity, even at low levels of radioactivity (6.25 MBq/mL), resulting in almost complete cell death at 25 MBq/mL. This cytotoxic effect was significantly greater than that of PdNPs labeled with β− (131I) and Auger electron emitters (125I). The metabolic viability of HCC cells was found to be correlated with cell DNA DSBs. Also, successful radioconjugate anticancer activity was observed in three-dimensional tumor spheroids, resulting in a significant treatment response.

Conclusion
The results indicate that nanoparticles labeled with 109Pd can be effectively used for combined β− - Auger electron-targeted radionuclide therapy of HCC. Due to the decay of both components (β− and Auger electrons), the 109Pd/109mAg in-vivo generator presents a unique potential in this field.