bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibiting PRMT5 induces DNA damage and increases anti-proliferative activity of Niraparib, a PARP inhibitor, in models of breast and ovarian cancer
Authors: O’Brien Shane , Butticello Michael , Thompson Christine , Wilson Boris , Wyce Anastasia , Mahajan Vivek , Kruger Ryan , Mohammad Helai , Fedoriw Andy 
Published: August 2023

Abstract
Background
Inhibitors of Poly (ADP-Ribose) Polymerases (PARP) provide clinical benefit to patients with breast and ovarian cancers, by compromising the DNA repair activity of cancer cells. Although these agents extend progression-free survival in many patients, responses can be short lived with many patients ultimately progressing. Identification of combination partners that increase dependence of cancer cells to the DNA repair activity of PARPs may represent a strategy to increase the utility of PARP inhibitors. Protein arginine methyltransferase 5 (PRMT5) regulates DNA damage response pathways through splicing and protein modification, and inhibitors of PRMT5 have recently entered clinical trials.

Methods
The effect of PRMT5 inhibition on the levels of DNA damage and repair markers including γH2AX, RAD51, and 53BP1 was determined using high content immunofluorescent imaging. The anti-proliferative activity of the combination of PRMT5 and PARP inhibitors was evaluated using in vitro models of breast and ovarian cancers using both cell lines and ex vivo patient derived xenografts. Finally, the combinations of PRMT5 and PARP inhibitors were evaluated in cell line xenograft models in vivo.

Results
Inhibition of PRMT5 by GSK3326595 led to increased levels of markers of DNA damage. The addition of GSK3326595 to the PARP inhibitor, niraparib, resulted in increased growth inhibition of breast and ovarian cancer cell lines and patient derived spheroids. In vivo, the combination improved the partial effects on tumor growth inhibition achieved by either single agent, producing complete tumor stasis and regression.

Conclusion
These data demonstrate that inhibition of PRMT5 induced signatures of DNA damage in models of breast and ovarian cancer. Furthermore, combination with the PARP inhibitor, Niraparib, resulted in increased anti-tumor activity in vitro and in vivo. Overall, these data suggest inhibition of PRMT5 as a mechanism to broaden and enhance the clinical application of PARP inhibitors.
Tumor microenvironment characterization in colorectal cancer to identify prognostic and immunotherapy genes signature
Authors: Guo Xian-wen , Lei Rong-e , Zhou Qing-nan , Zhang Guo , Hu Bang-li , Liang Yun-xiao 
Published: August 2023

Abstract
Background
The tumor microenvironment (TME) plays a crucial role in tumorigenesis, progression, and therapeutic response in many cancers. This study aimed to comprehensively investigate the role of TME in colorectal cancer (CRC) by generating a TMEscore based on gene expression.

Methods
The TME patterns of CRC datasets were investigated, and the TMEscores were calculated. An unsupervised clustering method was used to divide samples into clusters. The associations between TMEscores and clinical features, prognosis, immune score, gene mutations, and immune checkpoint inhibitors were analyzed. A TME signature was constructed using the TMEscore-related genes. The results were validated using external and clinical cohorts.

Results
The TME pattern landscape was for CRC was examined using 960 samples, and then the TMEscore pattern of CRC datasets was evaluated. Two TMEscore clusters were identified, and the high TMEscore cluster was associated with early-stage CRC and better prognosis in patients with CRC when compared with the low TMEscore clusters. The high TMEscore cluster indicated elevated tumor cell scores and tumor gene mutation burden, and decreased tumor purity, when compared with the low TMEscore cluster. Patients with high TMEscore were more likely to respond to immune checkpoint therapy than those with low TMEscore. A TME signature was constructed using the TMEscore-related genes superimposing the results of two machine learning methods (LASSO and XGBoost algorithms), and a TMEscore-related four-gene signature was established, which had a high predictive value for discriminating patients from different TMEscore clusters. The prognostic value of the TMEscore was validated in two independent cohorts, and the expression of TME signature genes was verified in four external cohorts and clinical samples.

Conclusion
Our study provides a comprehensive description of TME characteristics in CRC and demonstrates that the TMEscore is a reliable prognostic biomarker and predictive indicator for patients with CRC undergoing immunotherapy.
Buffering against exposure to mental health misinformation in online communities on Facebook: the interplay of depression literacy and expert moderation
Authors: Bizzotto Nicole , de Bruijn Gert-Jan , Schulz Peter Johannes 
Published: August 2023

Abstract
Background
The proliferation of health misinformation on social media is a growing public health concern. Online communities for mental health (OCMHs) are also considered an outlet for exposure to misinformation. This study explored the impact of the self-reported volume of exposure to mental health misinformation in misinformation agreement and the moderating effects of depression literacy and type of OCMHs participation (expert vs. peer-led).

Methods
Participants (n = 403) were recruited in Italian-speaking OCMHs on Facebook. We conducted regression analyses using PROCESS macro (moderated moderation, Model 3). Measures included: the Depression Literacy Questionnaire (Griffiths et al., 2004), the self-reported misinformation exposure in the OCMHs (3 items), and misinformation agreement with the exposure items (3 items). Whether participants were members of expert or peer-led OCMHs was also investigated.

Results
The final model explained the 12% variance in the agreement. There was a positive and significant relationship between misinformation exposure and misinformation agreement (β = 0.3221, p < .001), a significant two-way interaction between misinformation exposure and depression literacy (β = − 0.2179, p = .0014 ), and between self-reported misinformation exposure and type of OCMH (β = − 0.2322, p = .0254), such that at higher levels of depression literacy and in case of participation to expert-led OCMHs, the relationship misinformation exposure-misinformation agreement was weaker. Finally, a three-way interaction was found (β = 0.2497, p = .0144) that showed that depression literacy moderated the positive relationship between misinformation exposure and misinformation agreement such that the more misinformation participants were exposed to, the more they agreed with it unless they had higher levels of depression literacy; this, however, occurred only if they participated in peer-led groups.

Conclusions
Results provide evidence that the more members reported being exposed to mental health misinformation, the more they tended to agree with it, however this was only visible when participants had lower depression literacy and were participating in peer-led OCMHs. Results of this study suggest that both internal factors (i.e., high depression literacy) and external factors (the type of online community individuals were participating in) can buffer the negative effects of misinformation exposure. It also suggests that increasing depression literacy and expert community moderation could curb the negative consequences of misinformation exposure related to mental health. Results will guide interventions to mitigate the effects of misinformation in OCMHs, including encouraging health professionals in their administration and implementing health education programs.
Are there differences in the patient-reported medication-related problems among asthma and allergy patients? A community pharmacy survey in Finland
Authors: Heikkilä Juha Markus , Bergman Paula , Jantunen Juha , Salimäki Johanna , Pohjanoksa-Mäntylä Marika , Kauppi Paula 
Published: August 2023

Abstract
Background
A medication-related problem is an event involving medication that interferes with desired health outcomes. Those are largely studied among asthma patients, but little is known about medication-related problems among allergy patients. The objective of this study was to determine the most common patient-reported medication-related problems among asthma patients compared to allergy patients during the self-management of diseases. The other objective was to identify how demographic variables and the received treatment information influence reported problems.

Methods
A nationwide survey was conducted in Finnish community pharmacies (n = 785) in September 2016. The survey targeted patients buying prescription medicines for asthma or allergy.

Results
Responses were received from 46% of targeted pharmacies from 956 respondents. At least one medication problem was reported by 24% of asthma patients and 12% of allergy patients. The most common problems among asthma patients were having problems taking medicines on time (16%), problems in the administration technique (7%) and in the use of the inhaler (4%). Among allergy patients, 10% reported problems remembering to take medicines on time. Severe asthma and allergy increased the risk for medication-related problems (OR 1.20, 95% CI 1.04–1.40 and OR 1.17, 95% CI 1.0–1.37). A higher age and less education were associated with fewer reported medication-related problems among both patient groups.

Conclusions
Asthma patients reported more medication-related problems than allergy patients. Among both investigated patient groups, remembering to take medicines on time was the most common. Health care professionals should educate younger patients but also older and less educated asthma and allergy patients to recognize and, to solve medication-related problems. In addition, severe asthma patients still need medication counseling.
Association between white blood cell count to hemoglobin ratio and risk of in-hospital mortality in patients with lung cancer
Authors: Gao Tingting , Wang Yurong 
Published: August 2023

Abstract
Background
The objective of this study was to investigate the association between white blood cell count to hemoglobin ratio (WHR) and risk of in-hospital mortality in patients with lung cancer.

Methods
In this retrospective cohort study, the medical records of patients with lung cancer were retrieved from the electronic ICU (eICU) Collaborative Research Database between 2014 and 2015. The primary outcome was in-hospital mortality. The secondary outcome was the length of stay in intensive care unit (ICU). The cut-off value for the WHR was calculated by the X-tile software. The Cox model was applied to assess the association between WHR and in-hospital mortality among patients with lung cancer and the linear regression model was used to investigate the association between WHR and length of ICU stay. Subgroup analyses of age (< 65 years or >  = 65 years), Acute Physiology and Chronic Health Evaluation (APACHE) score (< 59 or >  = 59), gender, ventilation (yes or no), and vasopressor (yes or no) in patients with lung cancer were conducted.

Results
Of the 768 included patients with lung cancer, 153 patients (19.92%) died in the hospital. The median total follow-up time was 6.88 (4.17, 11.23) days. The optimal cut-off value for WHR was 1.4. ICU lung cancer patients with WHR >  = 1.4 had a significantly higher risk of in-hospital mortality [Hazard ratio: (HR): 1.65, 95% confidence interval (CI): 1.15 to 2.38, P = 0.007) and length of stay in ICU (HR: 0.63, 0.01, 95% CI: 1.24 to 0.045, P = 0.045). According to the subgroup analysis, WHR was found to be associated with in-hospital mortality in patients with higher APACHE score (HR: 1.60, 95% CI: 1.06 to 2.41, P = 0.024), in male patients (HR: 1.87, 95% CI: 1.15 to 3.04, P = 0.012), and in patients with the treatment of ventilation (HR: 2.33, 95% CI: 1.49 to 3.64, P < 0.001).

Conclusion
This study suggests the association between WHR and risk of in-hospital mortality in patients with lung cancer and length of stay, which indicates the importance of attention to WHR for patients with lung cancer.
An evaluation of the relationship between clinical requirements and tests of competence in a competency-based curriculum in dentistry
Authors: Marchan Shivaughn M. , Coldero Larry G. , Smith William A.J. 
Published: August 2023

Abstract
Background
The development of competencies in dentistry is a complicated process that calls for the development of not just cognitive and psychomotor abilities but also behaviors and attitudes that change as technical proficiency increases and meaningful patient encounters occur. This study examined the relationship between the number of clinical requirements completed by dental students and subsequent performance on tests of competence. The null hypothesis stated there would be no significant linear relationship different from zero between absolute clinical requirements and grades attained in various tests of clinical competence.

Methods
Retrospective assessment data for 81 students were used in this analysis. Data included the amounts of clinical requirements completed for operative dentistry, endodontics, periodontics, and fixed prosthodontics together with data on the respective performance in tests of competence. Correlation was ascertained between grades for tests of competence and the corresponding clinical requirements using a non-parametric Spearman’s Rho test at an alpha level of 0.05.

Results
Fixed prosthodontics and posterior endodontics were the least common procedures completed by dental students. Statistically significant weak correlations were found between the amounts of clinical requirements performed for posterior endodontic(p = 0.005) and operative procedures (p = 0.006) and associated performance in tests of competence. A moderate correlation was found between the number of fixed prosthodontic procedures completed and associated performance in tests of competence. This latter correlation, however, was not statistically significant (p = 0.654). A significant weak correlation was found between requirements completed for periodontics and the associated test of competence (p = 0.04). A highly statistically significant moderate correlation was found between clinical requirements for anterior endodontics and the associated performance in the tests of competence (p < 0.001).

Conclusion
The null hypothesis was rejected since a positive correlation was found between the absolute clinical requirements completed and grades in tests of competence. However, only a weak to moderate degree of correlation was found between the completion of clinical requirements and performance in tests of competence for common clinical procedures that new dental graduates should be able to perform.
Transition to professional practice: Perspectives of new nursing graduates of Nepal
Authors: Gautam Sital , Poudel Anju , Paudyal Kalpana , Prajapati Mangal Maya 
Published: August 2023

Abstract
Background
Internationally, the transition from student nurse to practicing nurse is recognized as being the most stressful period. Yet very little is known about how new nursing graduates perceive this transition in Nepal. The study aimed to explore new nursing graduates’ perceptions of the transition to professional practice.

Methods
A qualitative descriptive methodology was used. In-depth semi-structured interviews were conducted with 10 purposively recruited participants from two private hospitals in Nepal. Data were analyzed using inductive thematic analysis. The Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines were used to report the findings of this study.

Results
New nursing graduates perceived the transition to professional practice as an intense experience. Inductive thematic analysis yielded four intrinsically linked themes that encompassed new nursing graduates’ transition experiences: ‘getting hit by reality’, ‘losing confidence’, ‘feeling unsupported’, and ‘gathering strengths.’ The theme ‘getting hit by reality’ included three sub-themes: ‘gap between theory and practice,’ ‘no protective shield,’ and ‘plethora of responsibilities’, which explains nurses’ initial encounter with real-world practice. The theme ‘losing confidence’ contained three sub-themes: ‘being fearful,’ ‘being ignored,’ and ‘being accused,’ which describes how nurses started losing confidence as they confronted the real side of the profession. The theme ‘feeling unsupported’ included two sub-themes: ‘left without guidance,’ and ‘limited support from seniors,’ which explains how nurses perceived their work environment. The theme ‘gathering strength’ contained two sub-themes: ‘reflecting’ and ‘asking for help,’ which describes how nurses coped with the challenges related to the transition.

Conclusion
To facilitate the transition to practice, educational institutions must impart to students a realistic understanding of the transition process, address the theory-practice gap, and collaborate with hospitals. Similarly, hospitals should have realistic expectations from new nurses, assign work according to their capabilities, and allow them sufficient time for role integration. Likewise, well-conceived detailed orientation, mentorship or preceptorship programs, and regular professional development programs are vital to easing the transition. Furthermore, establishing and maintaining a supportive work culture, which promotes equity, respect, and safety among employees, is crucial for positive transition experiences.
ITC-6102RO, a novel B7-H3 antibody-drug conjugate, exhibits potent therapeutic effects against B7-H3 expressing solid tumors
Authors: Shin Seol Hwa , Ju Eun Jin , Park Jin , Ko Eun Jung , Kwon Mi Ri , Lee Hye Won , Son Ga Won , Park Yun-Yong , Kim Yeon Joo , Song Si Yeol , Lee Sangkwang , Seo Beom Seok , Song Jin-A , Lim Sangbin , Jung Doohwan , Kim Sunyoung , Lee Hyangsook , Park Seok Soon , Jeong Seong-Yun , Choi Eun Kyung 
Published: August 2023

Abstract
Background
The B7-H3 protein, encoded by the CD276 gene, is a member of the B7 family of proteins and a transmembrane glycoprotein. It is highly expressed in various solid tumors, such as lung and breast cancer, and has been associated with limited expression in normal tissues and poor clinical outcomes across different malignancies. Additionally, B7-H3 plays a crucial role in anticancer immune responses. Antibody-drug conjugates (ADCs) are a promising therapeutic modality, utilizing antibodies targeting tumor antigens to selectively and effectively deliver potent cytotoxic agents to tumors.

Methods
In this study, we demonstrate the potential of a novel B7-H3-targeting ADC, ITC-6102RO, for B7-H3-targeted therapy. ITC-6102RO was developed and conjugated with dHBD, a soluble derivative of pyrrolobenzodiazepine (PBD), using Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linkers with high biostability. We assessed the cytotoxicity and internalization of ITC-6102RO in B7-H3 overexpressing cell lines in vitro and evaluated its anticancer efficacy and mode of action in B7-H3 overexpressing cell-derived and patient-derived xenograft models in vivo.

Results
ITC-6102RO inhibited cell viability in B7-H3-positive lung and breast cancer cell lines, inducing cell cycle arrest in the S phase, DNA damage, and apoptosis in vitro. The binding activity and selectivity of ITC-6102RO with B7-H3 were comparable to those of the unconjugated anti-B7-H3 antibody. Furthermore, ITC-6102RO proved effective in B7-H3-positive JIMT-1 subcutaneously xenografted mice and exhibited a potent antitumor effect on B7-H3-positive lung cancer patient-derived xenograft (PDX) models. The mode of action, including S phase arrest and DNA damage induced by dHBD, was confirmed in JIMT-1 tumor tissues.

Conclusions
Our preclinical data indicate that ITC-6102RO is a promising therapeutic agent for B7-H3-targeted therapy. Moreover, we anticipate that OHPAS linkers will serve as a valuable platform for developing novel ADCs targeting a wide range of targets.
Diagnostic value of CT and MRI combined with serum LDH, NSE, CEA, and MYCN in pediatric neuroblastoma
Authors: Hao Jumei , Sang Jing , Xu Xiajuan , Bao Aihua 
Published: August 2023

Abstract
Background
To analyze the diagnostic value of computed tomography (CT), magnetic resonance imaging (MRI) combined with serum lactate dehydrogenase (LDH), neuron-specific enolase (NSE), carcinoembryonic antigen (CEA), and N-myc (MYCN) in the diagnosis of pediatric neuroblastoma.

Methods
Fifty-two children diagnosed with neuroblastoma were selected as the neuroblastoma group. During the same period, 52 children who visited our hospital with abdominal distension, diarrhea, constipation, and vomiting but were finally excluded from neuroblastoma were selected as the control group. CT and MRI were performed on all children.

Results
Fifty-two cases of neuroblastoma of the central nervous system were confirmed by pathological examination. The levels of LDH, NSE, CEA, and MYCN in the neuroblastoma group were clearly higher than those in the control group (P < 0.05). The results of CT and MRI combined with serum LDH, NSE, CEA, and MYCN were false positive in 10 cases and false negative in 6 cases, which were consistent with the pathological results. The sensitivity of CT and MRI combined with serum LDH, NSE, CEA, and MYCN in the diagnosis of neuroblastoma was notably higher than that of the three alone (P < 0.05).

Conclusion
The imaging findings of CT and MRI in children with central nervous system neuroblastoma were definitely characteristic. MRI had higher diagnostic value than CT. The diagnostic value of CT and MRI combined with serum LDH, NSE, CEA, and MYCN was improved to some extent.
Targeting FSCN1 with an oral small-molecule inhibitor for treating ocular neovascularization
Authors: Bai Wen , Ren Jun-Song , Xia Min , Zhao Ya , Ding Jing-Juan , Chen Xi , Jiang Qin 
Published: August 2023

Abstract
Background
Ocular neovascularization is a leading cause of blindness and visual impairment. While intravitreal anti-VEGF agents can be effective, they do have several drawbacks, such as endophthalmitis and drug resistance. Additional studies are necessary to explore alternative therapeutic targets.

Methods
Bioinformatics analysis and quantitative RT-PCR were used to detect and verify the FSCN1 expression levels in oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV) mice model. Transwell, wound scratching, tube formation, three-dimensional bead sprouting assay, rhodamine-phalloidin staining, Isolectin B4 staining and immunofluorescent staining were conducted to detect the role of FSCN1 and its oral inhibitor NP-G2-044 in vivo and vitro. HPLC–MS/MS analysis, cell apoptosis assay, MTT assay, H&E and tunnel staining, visual electrophysiology testing, visual cliff test and light/dark transition test were conducted to assess the pharmacokinetic and security of NP-G2-044 in vivo and vitro. Co-Immunoprecipitation, qRT-PCR and western blot were conducted to reveal the mechanism of FSCN1 and NP-G2-044 mediated pathological ocular neovascularization.

Results
We discovered that Fascin homologue 1 (FSCN1) is vital for angiogenesis both in vitro and in vivo, and that it is highly expressed in oxygen-induced retinopathy (OIR) and laser-induced choroidal neovascularization (CNV). We found that NP-G2-044, a small-molecule inhibitor of FSCN1 with oral activity, can impede the sprouting, migration, and filopodia formation of cultured endothelial cells. Oral NP-G2-044 can effectively and safely curb the development of OIR and CNV, and increase efficacy while overcoming anti-VEGF resistance in combination with intravitreal aflibercept (Eylea) injection.

Conclusion
Collectively, FSCN1 inhibition could serve as a promising therapeutic approach to block ocular neovascularization.