bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating awareness and implementation of adrenaline auto-injectors (AAI) via the ‘Spare Pens in Schools’ scheme in Wales: a cross-sectional pilot study
Authors: Panayiotou Eliana , Hassoulas Athanasios , Tuthill David , Miles Elizabeth , Holloway Judith 
Published: November 2024

ObjectiveTo investigate awareness and implementation of the Spare Pens (ie, adrenaline auto-injectors (AAIs)) scheme in primary and secondary schools in two regions in Wales.DesignA cross-sectional pilot study employing a mixed research methods approach was carried out.Setting and participantsState primary and secondary schools within Swansea and Pembrokeshire regional authorities were invited to take part. For geographical context, Swansea is the second largest city in Wales and is situated in the southwest of the country. Pembrokeshire is located in West Wales, with a large rural population outside of its main towns.Main outcome measuresAwareness and implementation of the Spare Pens in Schools scheme. Additionally, compliance with national guidance was measured by administering a questionnaire capturing data on registers, procedures, storage and training in the use of AAIs.Results35 schools (30 primary, 5 secondary) participated, with 11% and 6% reporting awareness and implementation of the scheme, respectively. No significant differences in awareness or implementation of the scheme were revealed for school type or region. Secondary schools reportedly stored more AAI devices compared with primary schools. The location of stored AAIs varied by school type, with 46.7% of primary schools storing AAIs in the classroom while 80% of secondary schools stored AAIs in the school office. Procedures for accessing AAI training differed, with 83% of primary schools receiving training by school nurses and 60% of secondary schools accessing training via an allergy team.ConclusionsThe overall poor awareness of the Spare Pens in Schools scheme has resulted in a worrying lack of implementation of generic AAI devices. An urgent review of information dissemination regarding the scheme is required.
Industry marketing payments to physicians and prescription patterns for sacubitril/valsartan in the USA
Authors: Murayama Anju 
Published: November 2024

ObjectivesAlthough financial interactions between physicians and pharmaceutical and medical device companies could be potential conflicts of interest, in certain instances, industry promotion targeted at physicians may facilitate the early adoption of effective, novel care for patients such as sacubitril/valsartan in the USA. This study aims to evaluate associations between industry-sponsored meal payments to physicians and their prescribing patterns for sacubitril/valsartan in the USA.MethodsUsing the publicly accessible Centers for Medicare and Medicaid Services Medicare Part D database and the Open Payments Database, this study assessed associations between industry-sponsored meal payments to physician prescribers and total amounts of Medicare claims and spending for sacubitril/valsartan between 2015 and 2021.ResultsAmong 220 147 eligible physician prescribers, 60 568 (27.5%) received at least one meal payment related to sacubitril/valsartan from the manufacturer, totaling US$13.9 million. The receipt of meal payments was significantly associated with a higher proportion of sacubitril/valsartan prescriptions to all sacubitril/valsartan, angiotensin receptor blocker and angiotensin-converting enzyme inhibitor prescriptions, with an OR of 2.04 (95% CI: 1.98 to 2.10, p<0.001). Moreover, a 10% increase in the annual number of meal payments was associated with a 2.6% (95% CI: 2.5% to 2.6%, p<0.001) increase in the annual number of Medicare claims and a 7.3% (95% CI: 7.1% to 7.5%, p<0.001) increase in annual Medicare spending per physician.ConclusionsGiven the underprescription of sacubitril/valsartan in the USA, the positive associations between meal payments and physicians' prescribing patterns suggest that industry-sponsored meals may contribute to the early adoption of this cost-effective, novel heart failure drug among US Medicare beneficiaries.
Systemic chemokine-modulatory regimen combined with neoadjuvant chemotherapy in patients with triple-negative breast cancer
Authors: Gandhi Shipra , Slomba Ronald T , Janes Cayla , Fitzpatrick Victoria , Miller Janine , Attwood Kristopher , Ioannou Giorgio , Ozbey Sinem , De Souza Igor , Roudko Vladimir , Kumar Prasanna , Kalathil Suresh , Kokolus Kathleen M , Wang Jianming , Cortes Gomez Eduardo , Takabe Kazuaki , Edge Stephen , Young Jessica , Cappuccino Helen , Opyrchal Mateusz , O’Connor Tracey , Levine Ellis G , Gnjatic Sacha , Kalinski Pawel 
Published: November 2024

BackgroundHigher cytotoxic T lymphocyte (CTL) numbers in the tumor microenvironment (TME) predict pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) and positive long-term outcomes in triple-negative breast cancer (TNBC). pCR to NAC is achieved only in 30–40% of patients. The combination of NAC with pembrolizumab increases the pCR rate but at the cost of immune-related adverse events (irAEs). Based on these considerations, we tested if systemic infusion of the chemokine modulatory regimen (CKM; selective toll-like receptor 3 (TLR3) agonist rintatolimod, interferon (IFN)-α2b, and cyclooxygenase-2 (COX-2) inhibitor celecoxib) regimen can be safely combined with NAC to enhance intratumoral CTL numbers and NAC effectiveness.MethodsPhase I studyNCT04081389evaluated nine patients with early-stage TNBC who received 3 weeks of paclitaxel with CKM (dose-escalation of IFN-α2b), followed by 9 weeks of paclitaxel alone, dose-dense doxorubicin and cyclophosphamide, and surgery. Primary and secondary endpoints were safety and clinical efficacy, respectively.ResultsThe combination treatment was well-tolerated with no dose-limiting toxicities or irAEs. 5/9 patients achieved pCR and one patient had microinvasive disease (ypTmic). We observed elevated IFN signature and uniform decreases in CTL numbers (average 8.3-fold) in the blood of all treated patients. This was accompanied by reciprocal uniform increases in CD8β (overall 5.9-fold), CD8α/FoxP3 (2.11-fold), and CCL5 (4.73-fold) transcripts in TME, particularly pronounced in patients with pCR. Multiplex immunohistochemistry revealed selectively increased numbers of CTL (but not regulatory T cells) in both the epithelial and stromal tumor compartments and early decreases in the numbers of αSMA+vascular/stromal cells in the tumors of all pCR patients.ConclusionsCombined paclitaxel/CKM regimen was safe, with desirable TME changes and preliminary indications of promising pCR+ypTmic of 66%, comparable to the combination of NAC with pembrolizumab.
FOXA1 enhances antitumor immunity via repressing interferon-induced PD-L1 expression in nasopharyngeal carcinoma
Authors: Ge Junshang , Liu Ying , Chen Pan , Zeng Zhaoyang , Li Guiyuan , Xiong Wei , Yi Mei , Xiang Bo 
Published: November 2024

BackgroundNasopharyngeal carcinoma (NPC) is a distinct subtype of head and neck cancer which is prevalent in south of China and southeastern of Asia. Consistent activation of interferon (IFN) signaling, and impairment of T cell mediated antitumor immunity is frequent in NPC. Forkhead box A1 (FOXA1) is one of the earliest discovered pioneer factors, which can open up compact chromatin structures to facilitate the binding of other proteins to chromatin.MethodsBy using RNA sequencing, it was discovered that FOXA1 suppresses the activation of the interferon signaling pathway and the expression of the related interferon-responsive genes in NPC cells. The effect of FOXA1 on programmed death-ligand 1 (PD-L1) expression in C666-1 and HK1 cells under conditions with or without IFN-γ was detected through quantitative PCR (qPCR), western blot, and flow cytometry. After co-culturing T cells with IFN-γ-treated NPC cells in vitro, apoptosis of CD8+T cells and the expression of cytotoxic cytokines were assessed by flow cytometry. The cytotoxic effects of T cells on tumor cells in nude mice were measured by tumorigenesis in nude mice and adoptive T cell therapy. The effects of IFN-γ on the expression and nuclear localization of STAT1, as well as the colocalization of FOXA1 with STAT1 were detected by immunofluorescence, qPCR, western blot, and co-immunoprecipitation experiments.ResultsIn this study, we reported that loss of FOXA1, a pioneer factor downregulated in NPC, results in activation of IFN signaling in NPC cells. Repression of FOXA1 facilitates IFN-γ induced PD-L1 expression, whereas overexpression of FOXA1 exerts the opposite effect. Mechanistically, FOXA1 interacts with STAT1 and inhibits IRF1 expression and binding to PD-L1 promoter on IFN-γ treatment. Co-culture with FOXA1-silenced NPC cells promotes apoptosis of in vitro activated tumor-specific CD8+T cells and reduces the expression of cytotoxic effector molecules. Furthermore, overexpression of FOXA1 increases the therapeutic efficacy of PD-L1 antibody (atezolizumab) against NPC in nude mice receiving adoptive T-cell therapy.ConclusionsWe demonstrated that FOXA1 prevents tumor immune evasion by inhibiting IFN-γ induced PD-L1 expression in NPC cells. Our research findings provide new insights into the immunotherapeutic biomarkers and targets for NPC, which is important for the clinical application of programmed cell death protein-1/PD-L1 antibodies in NPC.
Therapeutic serum level for adalimumab in rheumatoid arthritis: explorative analyses of data from a randomised phase III trial
Authors: Gehin Johanna Elin , Klaasen Rolf Anton , Klami Kristianslund Eirik , Jyssum Ingrid , Sexton Joseph , Warren David John , Aletaha Daniel , Haavardsholm Espen Andre , Syversen Silje Watterdal , Goll Guro Løvik , Bolstad Nils 
Published: November 2024

ObjectivesThe objectives of this study are to identify a therapeutic serum level for adalimumab associated with remission and low disease activity in patients with rheumatoid arthritis.MethodsAssociations between serum adalimumab trough levels and disease activity were examined using longitudinal data from a 48-week randomised phase III trial including patients with tumour necrosis factor inhibitor-naïve rheumatoid arthritis with active disease starting adalimumab treatment. Disease activity was classified according to 28-joint Disease Activity Score (DAS28)-erythrocyte sedimentation rate and C reactive protein (CRP) levels.ResultsAdalimumab trough levels were recorded longitudinally for 336, 330 and 302 patients at weeks 12, 24 and 48, respectively. All patients received concomitant methotrexate. Median adalimumab trough levels were 6.4 mg/L (IQR 3.4–9.5) at week 12, 7.5 mg/L (IQR 3.5–10.9) at week 24 and 7.6 mg/L (IQR 3.6–12.0) at week 48. In serial serum samples from weeks 12, 24 and 48, trough levels ≥3.9 mg/L were associated with DAS28 remission (OR 3.88 (95% CI 1.80, 8.38), p<0.001) and lower CRP levels (p<0.001). Week 12 trough levels ≥3.5 mg/L were associated with DAS28 low disease activity at week 24 (OR 2.62 (1.50, 4.56), p<0.001) and remission at week 48 (OR 1.99 (1.02, 3.88), p=0.04), as well as lower CRP levels at both time points (p<0.001).ConclusionAdalimumab trough levels above 4.0 mg/L were associated with remission/low disease activity throughout the first year of adalimumab therapy and can be considered a lower target level for therapeutic drug monitoring of adalimumab therapy.
Morphological Characterization and Genotyping of Acanthamoeba Isolates From Oral and Nasal Samples of Cancer Patients in Kashan, Iran
Authors: Rasti Sima , Taghipour Tayebeh , Delavari Mahdi , Hooshyar Hossein , Moosavi Gholam Abbas , Arbabi Mohsen 
Published: November 2024

Background: Acanthamoeba​ species are recognized as the most prevalent free‐living amoebae (FLA). They can cause granulomatous amebic encephalitis (GAE) and pulmonary and ocular infections. The present study aimed to isolate and identify Acanthamoeba genotypes in cancer patients referred to Kashan’s hospitals in Central Iran.Methods: This cross‐sectional study was conducted with oral and nasal swab samples collected from a hundred cancer patients referred to Kashan’s Beheshti and Yasrebi hospitals during 2019–2020. The samples were cultured in 1.5% non‐nutrient agar (NNA) with heat‐killed Escherichia coli and examined for “FLA.” A polymerase chain reaction (PCR) assay amplifying the 18S rRNA gene was performed, and Acanthamoeba‐positive isolates were subjected to nucleotide sequencing to identify their genotypes.Results: The prevalence of Acanthamoeba infection was 51% in the oral cavity and 38% in the nasal samples of cancer patients. The most frequent Acanthamoeba cysts were (51.3%) wrinkled polygonal and sized 9.55‐11.5 μm (Group II). Acanthamoeba genotypes T4, T11, and T5 were identified in the oral cavity samples, whereas T4 and T11 were detected in the nasal samples.Conclusion: The prevalence of Acanthamoeba infection in oral and nasal cancer patients was higher in Kashan, Iran, compared to other countries. Due to the high rate of oral Acanthamoeba contamination, oral sampling is recommended for better detection of this protozoan. Since T4 is the predominant genotype that can cause serious diseases in high‐risk groups, increasing physicians’ awareness of infections associated with Acanthamoeba and preventive and control measures are strongly suggested.
Understanding Parental Emotions
Authors: Odeh Ruba , Brigi Carel , Walia Tarun , Hashim Raghad 
Published: November 2024

Objectives: The presence of parents during dental treatment in children is a controversial concern in dental practice. This is because of conflicting views and practices regarding the presence of parents. Therefore, the objective of this study was to evaluate parental response to their presence/absence during their child’s dental treatment and to determine the factors that would influence their decision.Methods: A cross‐sectional survey questionnaire was administered to United Arab Emirates (UAE) parents. A total of 240 parents participated in the survey, which contained 15 questions that analyzed the participants’ demographic details, dental procedures influencing parental separation, and factors influencing their desire to be present during their child’s dental treatment.Results: Data were analyzed using descriptive statistics and chi‐square tests (p  < 0.05). The majority (78%) of the parents chose to stay with their children during dental treatment, with a higher prevalence of female parents. The results showed that more parents opted to be with their children during invasive procedures. Younger parents are more likely to stay with their children during dental treatment. The factors influencing parental presence/absence in the dental treatment room depended on the age and nationality of the parent and the type of dental procedure (p  < 0.05).Conclusions: Dental practitioners must provide parents with sufficient opportunities to be present during their children’s dental procedures. The factors influencing parental presence/absence should be considered before deciding whether to include or exclude parents in the dental treatment room.
The Role of Varicella Zoster Virus (VZV) in Central Nervous System Infectious Syndromes
Authors: Yakovenko Viktoria , Ciobotaro Pnina , Bardenstein Rita , Zusev Margalit , Zimhony Oren 
Published: November 2024

Background: We describe the proportion of VZV infection in central nervous system (CNS) infectious syndromes in a single Israeli medical center.Methods: An observational cohort study was conducted in Kaplan Medical Center (a secondary hospital, Israel) between July 1, 2014, and March 31, 2019. Included were adult patients (≥ 16 years old) with CNS infection with an aseptic CSF profile that were subjected to molecular tests for herpes viruses, HSV either 1 or 2, VZV, enteroviruses, and IgM for West Nile virus (WNV).Results: Clinical presentation suggestive of CNS infection led to lumbar puncture and CSF analysis in 1500 patients yielding 178 cases with aseptic CSF profile. For 62/109 (55.9%) cases of meningitis, the etiology remained unknown, enterovirus accounted for 21 cases (18.9%), VZV for 16 (14.4%), and HSV 1 for 7 (6.3%). One case each of bacterial, fungal, and parainfluenza virus accounted for the other 3 cases. For 30/63 (47.6%) cases of encephalitis, the etiology remained unknown, HSV accounted for 11 cases (17.5%), VZV for 8 (12.7%), and WNV for 10 (15.9%); in two cases, enterovirus was identified and one case of influenza A and one of mycoplasma, accounted for the rest. In six patients with myelitis VZV was identified in 4 (66.7%). Notably, a typical herpetic rash was identified in only 11/28 (39.28%) of cases of VZV CNS infection.Conclusions: VZV is a significant cause of viral CNS infections. In the majority of patients with neurologic syndrome and evident VZV there is no association with a typical herpetic rash. These results apply to Israeli population and likely to other populations with similar background of VZV past infections.
Using AI to Predict Patients’ Length of Stay: PACU Staff’s Needs and Expectations for Developing and Implementing an AI System
Authors: Lundsten Sara , Jacobsson Maritha , Rydén Patrik , Mattsson Lars , Lindgren Lenita 
Published: November 2024

Introduction: The need for innovative technology in healthcare is apparent due to challenges posed by the lack of resources. This study investigates the adoption of AI‐based systems, specifically within the postanesthesia care unit (PACU). The aim of the study was to explore staff needs and expectations concerning the development and implementation of a digital patient flow system based on ML predictions.Methods: A qualitative approach was employed, gathering insights through interviews with 20 healthcare professionals, including nurse managers and staff involved in planning patient flows and patient care. The interview data were analyzed using reflexive thematic analysis, following steps of data familiarization, coding, and theme generation. The resulting themes were then assessed for their alignment with the modified technology acceptance model (TAM2).Results: The respondents discussed the benefits and drawbacks of the proposed ML system versus current manual planning. They emphasized the need for controlling PACU throughput and expected the ML system to improve the length of stay predictions and provide a comprehensive patient flow overview for staff. Prioritizing the patient was deemed important, with the ML system potentially allowing for more patient interaction time. However, concerns were raised regarding potential breaches of patient confidentiality in the new ML system. The respondents suggested new communication strategies might emerge with effective digital information use, possibly freeing up time for more human interaction. While most respondents were optimistic about adapting to the new technology, they recognized not all colleagues might be as convinced.Conclusion: This study showed that respondents were largely favorable toward implementing the proposed ML system, highlighting the critical role of nurse managers in patient workflow and safety, and noting that digitization could offer substantial assistance. Furthermore, the findings underscore the importance of strong leadership and effective communication as key factors for the successful implementation of such systems.
A Phase III Randomized Trial of Integrated Genomics and Avatar Models for Personalized Treatment of Pancreatic Cancer: The AVATAR Trial
Authors: Sarno Francesca , Tenorio Jair , Perea Sofia , Medina Laura , Pazo-Cid Roberto , Juez Ignacio , Garcia-Carbonero Rocío , Feliu Jaime , Guillen-Ponce Carmen , Lopez-Casas Pedro P. , Guerra Carmen , Duran Yolanda , López-Acosta José Francisco , Alonso Carolina , Esquivel Estrella , Dopazo Ana , Akshinthala Dipikaa , Muthuswamy Senthil K. , Lapunzina Pablo , Bockorny Bruno , Hidalgo Manuel 
Published: November 2024

Abstract

Purpose:
Pancreatic ductal adenocarcinoma (PDAC) has limited treatment options. We compared the efficacy of comprehensive precision medicine against that of the conventional treatment in PDAC.

Patients and Methods:
We report a phase III trial of advanced PDAC in which patients were randomized (1:2) to a conventional treatment treated at physician’s discretion (arm A) or to precision medicine (arm B). Subjects randomized to arm B underwent a tumor biopsy for whole-exome sequencing and to generate avatar mouse models and patient-derived organoids for phenotypic drug screening, with final treatment recommended by the molecular tumor board. The primary objective was median overall survival (OS).

Results:
A total of 137 patients were enrolled with 125 randomized, 44 to arm A and 81 to arm B. Whole-exome sequencing was performed in 80.3% (65/81) patients of arm B, with potentially actionable mutations detected in 21.5% (14/65). Experimental models were generated in 16/81 patients (19.8%). Second-line treatment was administered to 39 patients in the experimental arm, but only four (10.2%) received personalized treatment, whereas 35 could not receive matched therapy because of rapid clinical deterioration, delays in obtaining study results, or the absence of actionable targets. The median OS was 8.7 and 8.6 months (P = 0.849) and the median progression-free survival was 3.8 and 4.3 months (P = 0.563) for the conventional and experimental arms, respectively. Notably, the four patients who received personalized treatment had a median OS of 19.3 months.

Conclusions:
Personalized medicine was challenging to implement in most patients with PDAC, limiting the interpretation of intention-to-treat analysis. Survival was improved in the subset of patients who did receive matched therapy.