bluuebunny/crossref_metadata_2025_split huggingface dataset:
Recognition, prevention and management of ‘digital harm’
Authors: Joustra Arthur , Quinn Lauren , Walker Vicki 
Published: January 2024

The digital world continues to evolve and is apparent in all aspects of daily life. For children and young people, their online life is as real to them as their in-person life. Health professionals urgently need to update their knowledge and awareness of the positive and negative impacts of the myriad of online content and how this is viewed and used by children and young people. Digital harm can contribute to multiple clinical presentations and paediatricians must ask about online life in consultations and be able to provide holistic digital safety advice, while recognising serious digital harm requiring safeguarding input.This article will introduce the main areas of harm and how to include assessment in routine clinical practice. It will equip paediatricians to offer advice and safeguard children and young people and offer resources and links to further learning.
Perceptions of and responses of young adults who use e-cigarettes to flavour bans in China: a qualitative study
Authors: Weng Xue , Song Chu Yu , Liu Kefeng , Wu Yongda Socrates , Lee Jung Jae , Guo Ningyuan , Wang Man Ping 
Published: January 2024

BackgroundChina has banned all flavoured e-cigarettes to reduce e-cigarette use among young people, but little is known about the views and reactions of people who use e-cigarettes. This study explored the perceptions of, and responses by, young adults who use e-cigarettes to the flavour ban.MethodsSemistructured interviews were conducted with 25 Chinese young adults aged 18–25 years who had used e-cigarettes daily in the past 3 months. Thematic analysis was used to analyse the interview data.FindingsFour themes were identified from the data: (1) understanding of the public health benefits, (2) resistance to and misperceptions of the flavour ban, (3) circumvention of the flavour ban and (4) acceptance of the flavour ban. Some participants expressed support for the ban due to perceived public health benefits, while others who resisted the ban emphasised their right to choose preferred flavours and questioned the rationale behind the policy. Participants responded to the flavour ban by utilising a variety of adaptive strategies, including purchasing flavoured e-cigarettes through illegal channels or exploring alternative ways to obtain flavours. Those who complied with the ban responded with different strategies, including switching back to combustible cigarettes, using tobacco-flavoured e-cigarettes, or quitting vaping.ConclusionsThe findings suggest the need for comprehensive regulatory measures, including stringent enforcement measures, transparent health communication and vigilant monitoring of e-cigarette manufacturers’ tactics, to reduce e-cigarette use among young adults.
TFE3-Splicing Factor Fusions Represent Functional Drivers and Druggable Targets in Translocation Renal Cell Carcinoma
Authors: Damayanti Nur P. , Cordova Ricardo A. , Rupert Christopher , Delle Fontane Ilaria , Shen Li , Orsi Sabrina , Klunk Angela J. , Linehan W. Marston , Staschke Kirk A. , Hollenhorst Peter C. , Heppner David E. , Pili Roberto 
Published: January 2024

Abstract

TFE3 is a member of the basic helix–loop–helix leucine zipper MiT transcription factor family, and its chimeric proteins are associated with translocation renal cell carcinoma (tRCC). Despite the variety of gene fusions, most TFE3 fusion partner genes are related to spliceosome machinery. Dissecting the function of TFE3 fused to spliceosome machinery factors (TFE3-SF) could direct the development of effective therapies for this lethal disease, which is refractory to standard treatments for kidney cancer. Here, by using a combination of in silico structure prediction, transcriptome profiling, molecular characterization, and high-throughput high-content screening (HTHCS), we interrogated a number of oncogenic mechanisms of TFE3-SF fusions. TFE3-SF fusions drove the transformation of kidney cells and promoted distinct oncogenic phenotypes in a fusion partner-dependent manner, differentially altering the transcriptome and RNA splicing landscape and activating different oncogenic pathways. Inhibiting TFE3-SF dimerization reversed its oncogenic activity and represented a potential target for therapeutic intervention. Screening the FDA-approved drugs library LOPAC and a small-molecule library (Microsource) using HTHCS combined with FRET technology identified compounds that inhibit TFE3-SF dimerization. Hit compounds were validated in 2D and 3D patient-derived xenograft models expressing TFE3-SF. The antihistamine terfenadine decreased cell proliferation and reduced in vivo tumor growth of tRCC. Overall, these results unmask therapeutic strategies to target TFE3-SF dimerization for treating patients with tRCC.

Significance:
TFE3-splicing factor fusions possess both transcription and splicing factor functions that remodel the transcriptome and spliceosome and can be targeted with dimerization inhibitors to suppress the growth of translocation renal cell carcinoma.
Chromatin Remodelers Are Regulators of the Tumor Immune Microenvironment
Authors: Chaudhri Apoorvi , Lizee Gregory , Hwu Patrick , Rai Kunal 
Published: January 2024

Abstract
Immune checkpoint inhibitors show remarkable responses in a wide range of cancers, yet patients develop adaptive resistance. This necessitates the identification of alternate therapies that synergize with immunotherapies. Epigenetic modifiers are potent mediators of tumor-intrinsic mechanisms and have been shown to regulate immune response genes, making them prime targets for therapeutic combinations with immune checkpoint inhibitors. Some success has been observed in early clinical studies that combined immunotherapy with agents targeting DNA methylation and histone modification; however, less is known about chromatin remodeler-targeted therapies. Here, we provide a discussion on the regulation of tumor immunogenicity by the chromatin remodeling SWI/SNF complex through multiple mechanisms associated with immunotherapy response that broadly include IFN signaling, DNA damage, mismatch repair, regulation of oncogenic programs, and polycomb-repressive complex antagonism. Context-dependent targeting of SWI/SNF subunits can elicit opportunities for synthetic lethality and reduce T-cell exhaustion. In summary, alongside the significance of SWI/SNF subunits in predicting immunotherapy outcomes, their ability to modulate the tumor immune landscape offers opportunities for therapeutic intervention.
Facts and Hopes in Immunotherapy Strategies Targeting Antigens Derived from KRAS Mutations
Authors: Linette Gerald P. , Bear Adham S. , Carreno Beatriz M. 
Published: January 2024

Abstract
In this commentary, we advance the notion that mutant KRAS (mKRAS) is an ideal tumor neoantigen that is amenable for targeting by the adaptive immune system. Recent progress highlights key advances on various fronts that validate mKRAS as a molecular target and support further pursuit as an immunological target. Because mKRAS is an intracellular membrane localized protein and not normally expressed on the cell surface, we surmise that proteasome degradation will generate short peptides that bind to HLA class I (HLA-I) molecules in the endoplasmic reticulum for transport through the Golgi for display on the cell surface. T-cell receptors (TCR)αβ and antibodies have been isolated that specifically recognize mKRAS encoded epitope(s) or haptenated-mKRAS peptides in the context of HLA-I on tumor cells. Case reports using adoptive T-cell therapy provide proof of principle that KRAS G12D can be successfully targeted by the immune system in patients with cancer. Among the challenges facing investigators is the requirement of precision medicine to identify and match patients to available mKRAS peptide/HLA therapeutics and to increase the population coverage by targeting additional mKRAS epitopes. Ultimately, we envision mKRAS-directed immunotherapy as an effective treatment option for selected patients that will complement and perhaps synergize with small-molecule mKRAS inhibitors and targeted mKRAS degraders.
Preconception Blood Pressure and Adverse Pregnancy Outcomes: A Population-Based Cohort Study
Authors: Xiong Wenxue , Han Lu , Tang Xijia , Wang Qiong , Chen Wen , Li Rui , Zhang Hui , Liu Xiaohua , Nie Hua , Qin Weibing , Hu Yang , Zhang Zhirong , Ling Li 
Published: January 2024

BACKGROUND:
Adverse pregnancy outcomes (APOs) share clinical features and risk factors with cardiovascular disease and there is an increasing prevalence of hypertension among reproductive women. However, the associations between maternal preconception blood pressure (BP) and APOs remain controversial and inconclusive.

METHODS:
This population-based cohort study used data of 567 127 mother-neonate-father triads from the National Free Preconception Checkup Project in Guangdong Province, China. Maternal BP levels within 1 year before pregnancy were classified using the American College of Obstetricians and Gynecologists definition of hypertension. The primary outcome was a composite of APOs, including preterm birth, small for gestational age, and perinatal infant death. Log-binomial and marginal structural binomial regressions were employed to estimate adjusted risk ratios and absolute risk differences, respectively.

RESULTS:
Compared with women with normal BP, women with elevated BP (adjusted risk ratio, 1.07 [95% CI, 1.05–1.09]; absolute risk difference, 1.03% [95% CI, 0.72%–1.29%]), hypertension (adjusted risk ratio, 1.25 [95% CI, 1.18–1.32]; and absolute risk difference, 3.42% [95% CI, 1.97%–5.42%]) had a higher risk of a composite of APOs. Compared with women with normal BP, women with elevated BP and hypertension had higher risks of multiple APOs, preterm birth, small for gestational age, and perinatal infant death. However, these associations attenuated with increasing duration of pregnancy preparation and were not statistically significant beyond 90 days of pregnancy preparation.

CONCLUSIONS:
Women with elevated BP or hypertension before pregnancy were associated with an increased risk of APOs. Preconception hypertension screening and control among women should not be ignored by policymakers, clinicians, and the general population.
Six Years Later: Examining the Academic and Employment Outcomes of the Original and Reinstated Summer Pell Grant
Authors: Liu Vivian Yuen Ting , Zhou Rachel Yang , Matsudaira Jordan 
Published: January 2024

Abstract
The Pell Grant, while offering substantial financial support for low-income students pursuing higher education, historically covered only the costs of two full-time semesters per year and did not include assistance for summer courses. Research has consistently demonstrated that continuous enrollment throughout the academic year enhances college persistence and degree completion. In response to this understanding, the Summer Pell (SP) program was introduced in the summer of 2009, providing eligible low-income students with an additional grant to cover summer tuition and related expenses. However, after a brief period of operation, the SP program was discontinued in 2011, only to be reinstated in 2017. We utilize administrative data obtained from New York City in the context of differences-in-differences analyses spanning both program periods, and find that SP-eligible students exhibited a higher retention rate in the fall of their second year, achieved higher rates of associate's and bachelor's degree attainment, and experienced greater earnings gains up to nine years after college entry compared with SP-ineligible students. Our analysis of heterogeneity further underscores that the benefits of the SP program were pronounced among Black students and older students.
Provoking Politeness
Authors: Goldman Oscar 
Published: January 2024

Abstract
Dialogic interaction plays important generic, poetic, and structural roles within hexametric Latin satire. One aspect of this interaction which has received little prior exegesis is the presence, or lack, of politeness. By adapting and applying existing models which study this sociolinguistic phenomenon, we can perceive not only patterned use of politeness across the genre, but further intertextuality between Latin satire and Roman comedy. Interactions in the works of Horace and Juvenal are illustrative of both shared ‘politeness-motifs’, as well as divergent stylistic adaptations which suit each poet’s literary agenda.
The Impact of “Hot Models” on a CMIP6 Ensemble Used by Climate Service Providers in Canada: Do Global Constraints Lead to Appreciable Differences in Regional Projections?
Authors: Cannon Alex J. 
Published: January 2024

Abstract
Canadian climate service providers offer projections from the Coupled Model Intercomparison Project (CMIP6) to help inform climate change mitigation and adaptation decisions. CMIP6 includes several “hot” climate models whose sensitivity to greenhouse gas forcings exceeds the likely range inferred from multiple lines of evidence. Global warming estimates assessed in the Sixth Assessment Report (AR6) of the Intergovernmental Panel on Climate Change (IPCC) were reduced by applying observational constraints on the historical rate of warming to the CMIP6 ensemble. This study assesses whether globally constrained CMIP6 projections for Canada are appreciably different from unconstrained projections. Two constraints are considered: one that removes models whose transient climate response lies outside the AR6 assessed range (TCRlikely), and the other that weights models to match the assessed distribution of equilibrium climate sensitivity (ECSall). Both constraints lead to appreciably cooler and drier projections than the unconstrained ensemble, with the strongest reductions seen in the upper end of the ensemble range, high-emissions scenario, end-of-century time period, and northern regions of Canada. In this case, constrained projections of annual mean temperature are 2°–3°C cooler than the unconstrained projections, whereas projections of annual total precipitation are typically 20%–40% drier. Appreciable differences are also detected in the ensemble median of temperature extreme indices. Based on these results, it is recommended that a constrained ensemble be considered for regional projections to avoid the “hot model” problem. Alternatively, projections can be communicated conditional on a specified level of global warming, with global constraints then used to inform the timing of the warming level exceedance.
Randomized Controlled Trial of Bifrontal Transcranial Direct Current Stimulation on Craving in Alcohol Use Disorder
Authors: Gairola Arundhati , Nischal Anil , Kar Sujita Kumar , Arya Amit , Singh Amit 
Published: January 2024

Background: Transcranial direct current stimulation (tDCS) is a potential neuromodulation option for the management of cravings in patients with alcohol use disorder (AUD). This study aims to assess the efficacy and safety of tDCS in the management of craving for alcohol and to measure the change in subjective well-being in patients with AUD following tDCS intervention. Methods: Patients with AUD aged between 18 and 60 years were randomly assigned to active tDCS intervention and sham tDCS intervention groups, each consisting of 17 patients. Over the course of a week, five tDCS sessions were given, with the anode positioned on the scalp over the right dorsolateral prefrontal cortices (DLPFC) area, the cathode over the left DLPFC area, and a 2 mA current. After every session, a tDCS side effects checklist was used. Follow-up assessments were conducted at week 1, week 4, and week 8 of the recruitment using the alcohol urge questionnaire (AUQ) and the World Health Organization (WHO) (five) Well-Being Index (WHO-5). Results: A significantly greater reduction in AUQ scores was present in the active tDCS intervention group compared to the sham tDCS intervention at week 1 and week 4, but the difference was not significant at the end of 8 weeks. A significant improvement in WHO-5 scores was found in both groups; however, the difference between the groups was not significant at follow-ups. The side effects observed were mild to moderate in intensity, were short-lived, and did not require any active management. Conclusions: The tDCS may be useful in the acute reduction of craving in AUD. It is a safe and well-tolerated intervention modality.
Zirconium dioxide nanoparticles induced cytotoxicity in rat cerebral cortical neurons and apoptosis in neuron-like N2a and PC12 cell lines
Authors: Alavi Mohaddeseh Sadat , Asadpour Elham , Boroushaki Mohammad Taher , Fakharzadeh Moghadam Omid , Sadeghnia Hamid R 
Published: January 2024

During recent decades, the application of zirconium dioxide nanoparticles (ZrO2-NP) has been expanded in various fields ranging from medicine to industry. It has been shown that ZrO2-NP has the potential to cross the blood–brain barrier (BBB) and induce neurotoxicity. In the current study, we investigated the in vivo neurotoxicity, as well as, the cellular mechanism of ZrO2-NP toxicity on two neuronal-like cell lines, PC12 and N2a. PC12 and N2a cells were exposed to increasing concentrations of ZrO2-NP (0-2000 µg/ml) for 48 h. The apoptotic effect of ZrO2-NP was determined using annexin V/propidium iodide double staining (by flow cytometry), and western blot analysis of relative apoptotic proteins, including caspase-3, caspase-9, bax, and bcl2. Based on our results, ZrO2-NP at concentrations of 250-2000 μg/mL increased both early and late-stage apoptosis in a concentration-dependent manner. Moreover, the expressions of cleaved-caspase-3 and -9 proteins and the bax/bcl2 ratio were significantly increased. In addition, oral administration of ZrO2-NP (50 mg/kg) to male Wistar rats for 28 days led to the loss of neuronal cells in the cerebral cortex. Taken together, our findings highlighted the role of apoptosis on cytotoxicity induced by ZrO2-NP.
Assisted teleconsultation in an outpatient pharmacy: Results of a pilot study in Geneva, Switzerland
Authors: Braillard Olivia , Mazouri Karker Sanae , Djarmouni Rafik , Lafaix Rémi , Guessous Idris , Schneider Marie P. 
Published: January 2024

Introduction Assisted teleconsultation (ATC) is the act of telemedicine involving on one side a patient in the presence of a healthcare professional, and an expert on the other side. ATC in outpatient pharmacies may be an alternative to the emergency room for patients with a semi-urgent medical problem. This project aimed at pilot testing the ATC in an outpatient pharmacy to assess its feasibility and to collect initial real-world data. Methods After initial evaluation and triage by the pharmacist, ATC was proposed to patients consulting at one outpatient pharmacy for semi-urgent medical problems. Prospective data on patients, consultation reasons, teleconsultation duration, patient's orientation and pharmacist’ satisfaction were prospectively collected. Results Between December 2020 and June 2021, 39 consultations took place, 12 with video and 27 with telephone. Patients’ median age was 37 years (IQR 26–50), 59% were women. Near half of the consultations (19) happened during the weekend. Mean ATC duration was 22 min (IC95% 18.6–26.1). Twenty-nine (74%) consultations ended with a prescription, 8 (21%) with medical recommendations and 2 (5%) with an emergency care referral. Without teleconsultation, 34 (87%) patients would have consulted a physician for their problem, and 24 (62%) would have been to the emergency room (self-reported). Fourteen (36%) consultations involved ENT, ophthalmologic and dermatologic complaints. Conclusion A young population with semi-urgent medical problems can be managed in the pharmacy using ATC with a primary care physician. Financial, technical and training aspects should be developed and optimized in the future.
Upper Extremity Fractures in the Emergency Department: A Database Analysis of National Trends in the United States
Authors: Karzon Anthony L. , Nazzal Ehab M. , Cooke Hayden L. , Heo Kevin , Okonma Onyinye , Worden Jacob , Hussain Zaamin , Chung Kevin C. , Gottschalk Michael B. , Wagner Eric R. 
Published: January 2024

Background: Upper extremity (UE) fractures are a common reason for emergency department (ED) visits, but recent data on their epidemiology are lacking. This study aimed to describe the incidence, demographics, patient characteristics, and associated health care factors of UE fractures, hypothesizing that they would remain prevalent in the ED setting. Methods: Using the Nationwide ED Sample database, patients presenting to the ED with UE fractures in 2016 were identified, and population estimates were used to calculate incidence rates. Data on insurance status, trauma designation, cost, and teaching status were analyzed. Results: The study identified 2 118 568 patients with UE fractures, representing 1.5% of all ED visits in 2016. Men accounted for 54.2% of UE fractures, with phalangeal fractures being most common. Distal radius and/or ulna fractures were most common in women (30.4%). The greatest proportion of UE fractures (23.2%) occurred in patients aged 5 to 14 years (1195.5 per 100 000). Nontrauma centers were the most common treating institutions (50.4%), followed by level I (19.5%), II (15.3%), and III (12.8%) centers. The greatest proportion of fractures (38.3%) occurred in the southern United States. Emergency department cost of treatment was almost 2-fold in patients with open UE fractures compared with closed. Conclusion: This study provides important epidemiological information on UE fractures in 2016. The incidence rate of UE fractures in the ED has remained high, with most occurring in the distal radius, phalanges, and clavicle. In addition, UE fractures were most common in younger patients, men, and those in the southern United States during the summer. These findings can be useful for health care providers and policymakers when evaluating and treating patients with UE fractures.
Study on the Active Components and Inhibiting Effect of Melastoma dodecandrum Lour. on Human Cervical Cancer Cells Based on Spectrum–Effect Relationship Analysis
Authors: Qian Song , Wang Zuhua , Ma Xiuping , Ming Huiyi , Liu Jing , Yang Jing , Chen Teng , Liu Linli , Ban Jibian , Guo Jiangtao 
Published: January 2024

Background The ethnic drug Melastoma dodecandrum Lour. (MDL) is an important medicinal plant with potential antitumor properties, which have been proposed as promising anticancer agents, but the material basis for its therapeutic effect is still unclear and lacks in-depth research. Methods In this study, the in vitro antitumor effects of different MDL extracts in different gynecological tumor cells were investigated by CCK-8 assay. The active components of 21 batches of MDL samples collected from different product areas and markets were determined and compared by the UPLC method. On this basis, the data was processed with the fingerprint similarity software, and the correlation between MDL fingerprint and antihuman cervical cancer activity was further analyzed by a multivariate statistical method. Results Five kinds of MDL extracts, including the aqueous extract, the crude polysaccharide, the total polyphenol, the ethyl acetate fraction of the aqueous extract and 50% ethanol extract, had inhibitory effects on human cervical cancer HeLa and SiHa cells, among which total polyphenols of MDL showed stronger inhibition effect on human cervical cancer cells. In addition, the fingerprint of the total polyphenols of MDL had sixteen common peaks, and six common peaks were checked by using diode array and UV spectra, among which peak 1 (gallic acid), peak 4 (protocatechuic acid), peak 12 (unknown), and peak 15 (ellagic acid) were negatively correlated with the IC50 value of the SiHa cells, and all variable importance values were greater than 1. Conclusion Our data demonstrated that the main active components of MDL inhibiting human cervical cancer SiHa cells may be the synergistic effect of gallic acid, protocatechuic acid and ellagic acid, and the further spectrum-effect relationship analysis provides an important reference and basis for the quality control and the development of new anticervical cancer drug of MDL.