bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti-Tumor Effect of Apatinib and Relevant Mechanisms in Liposarcoma
Authors: Cui Lixuan , Yan Liang , Guan Xiaoya , Dong Bin , Zhao Min , Lv Ang , Liu Daoning , Wang Zhen , Liu Faqiang , Wu Jianhui , Tian Xiuyun , Hao Chunyi 
Published: November 2021

BackgroundPrimary retroperitoneal liposarcomas (RLPSs) are rare heterogeneous tumors for which there are few effective therapies. Certain anti-angiogenic tyrosine kinase inhibitors have demonstrated efficacy against various solid tumors. The aims of this study were to investigate the effect of Apatinib against retroperitoneal liposarcoma cells and its underlying mechanism and to explore the anti-tumor efficacy of a combination of Apatinib and Epirubicin.MethodsCD34 immunohistochemical staining was used to measure microvessel density (MVD) in 89 retroperitoneal liposarcoma tissues. We used CCK-8 cell proliferation, clone formation, Transwell migration, invasion assays and flow cytometry to evaluate the effects of Apatinib alone and the combination of Apatinib and Epirubicin on liposarcoma cells. High-throughput RNA sequencing and western-blotting was used to identify key differentially expressed genes (DEGs) in SW872 cell line after application of Apatinib. Murine patient-derived tumor xenograft (PDX) was established to assess the efficacy and safety of Apatinib monotherapy and the combination of Apatinib and Epirubicin in RLPS.ResultsThe microvessel density (MVD) varied widely among retroperitoneal liposarcoma tissues. Compared with the low-MVD group, the high-MVD group had poorer overall survival. Apatinib inhibited the liposarcoma cell proliferation, invasion and migration, increased the proportion of apoptosis, and induced G1 phase arrest. In addition, the combination of Apatinib and Epirubicin enhanced the foregoing inhibitory effects. High-throughput RNA sequencing showed that Apatinib downregulated the expression of TYMS and RRM2. Western blotting verified that Apatinib downregulated the TYMS/STAT3/PD-L1 pathway and inhibited liposarcoma proliferation by suppressing the RRM2/PI3K/AKT/mTOR pathway. In the murine PDX model of retroperitoneal liposarcoma, Apatinib and its combination with Epirubicin significantly inhibited microvessel formation and repressed tumor growth safely and effectively.ConclusionsApatinib and its combination with Epirubicin showed strong efficacy against liposarcoma both in vitro and in vivo. Apatinib might inhibit liposarcoma cell proliferation through the RRM2/PI3K/AKT/mTOR signaling pathway and downregulate PD-L1 via the TYMS/STAT3 signaling pathway.
Understanding the Complex Milieu of Epithelial-Mesenchymal Transition in Cancer Metastasis: New Insight Into the Roles of Transcription Factors
Authors: Imodoye Sikiru O. , Adedokun Kamoru A. , Muhammed Abdurrasheed Ola , Bello Ibrahim O. , Muhibi Musa A. , Oduola Taofeeq , Oyenike Musiliu A. 
Published: November 2021

Epithelial-mesenchymal transition (EMT) is a physiological program during which polarised, immobile epithelial cells lose connection with their neighbours and are converted to migratory mesenchymal phenotype. Mechanistically, EMT occurs via a series of genetic and cellular events leading to the repression of epithelial-associated markers and upregulation of mesenchymal-associated markers. EMT is very crucial for many biological processes such as embryogenesis and ontogenesis during human development, and again it plays a significant role in wound healing during a programmed replacement of the damaged tissues. However, this process is often hijacked in pathological conditions such as tumour metastasis, which constitutes the most significant drawback in the fight against cancer, accounting for about 90% of cancer-associated mortality globally. Worse still, metastatic tumours are not only challenging to treat with the available conventional radiotherapy and surgical interventions but also resistant to several cytotoxic agents during treatment, owing to their anatomically diffuse localisation in the body system. As the quest to find an effective method of addressing metastasis in cancer intervention heightens, understanding the molecular interplay involving the signalling pathways, downstream effectors, and their interactions with the EMT would be an important requisite while the challenges of metastasis continue to punctuate. Unfortunately, the molecular underpinnings that govern this process remain to be completely illuminated. However, it is becoming increasingly clear that EMT, which initiates every episode of metastasis, significantly requires some master regulators called EMT transcription factors (EMT-TFs). Thus, this review critically examines the roles of TFs as drivers of molecular rewiring that lead to tumour initiation, progression, EMT, metastasis, and colonisation. In addition, it discusses the interaction of various signalling molecules and effector proteins with these factors. It also provides insight into promising therapeutic targets that may inhibit the metastatic process to overcome the limitation of “undruggable” cancer targets in therapeutic design and upturn the current spate of drug resistance. More so, it extends the discussion from the basic understanding of the EMT binary switch model, and ultimately unveiling the E/M cellular plasticity along a phenotypic spectrum via multiple trans-differentiations. It wraps up on how this knowledge update shapes the diagnostic and clinical approaches that may demand a potential shift in investigative paradigm using novel technologies such as single-cell analyses to improve overall patient survival.
Did the National Lockdown in Saudi Arabia Reduce Lower Respiratory Illnesses in Children?
Authors: Alharbi Nasser S. , Alnasser Yossef , Alenizi Ahmed S. , Alanazi Alnashmi S. , Alharbi Abeer H. , AlQurashi Faisal O. , Nafisah Ibrahim , Yousef Abdullah A. 
Published: November 2021

Objectives: This study aims to explore the effect of lockdown and early precautionary measures implemented in Saudi Arabia on number of pediatric hospitalizations due to lower respiratory illnesses (bronchiolitis, asthma, and pneumonia).Methods: This is a retrospective cross-sectional study aims to review patients from four major hospitals in Saudi Arabia. All pediatric hospitalizations secondary to asthma, bronchiolitis, and pneumonia during the months of the lockdown (March, April, and May) in 2020 were documented. Then, they were compared to the previous 2 years. Variables like number of hospitalizations, oxygen requirement, mechanical ventilation, admission to the intensive care unit (ICU), length of stay, and results of viral studies were collected.Results: We included 1,003 children from four different centers. Males were slightly higher than females (55.8% vs. 44.2%). Total number of hospitalizations in 2020 was 201, significantly lower than 399 and 403 hospitalizations in 2019 and 2018, respectively (P &lt; 0.01). The major drop happened on the months of April and May. Although bronchiolitis hospitalizations' dropped by more than half in 2020 compared to the previous 2 years, it was not statistically significant (P = 0.07). But, asthma hospitalizations were significantly less in 2020 compared to the previous 2 years (49–65% reduction, P = 0.003). Number of pneumonia cases were lowered in 2020 compared to the previous 2 years. However, proportion of pneumonia diagnosis to total hospitalizations increased in 2020 (55% compared to 50% and 35%). There was a surge of viral testing during a period of uncertainty in the early phase of the pandemic. This total reduction in hospitalization was not associated with higher oxygen requirements, mechanical ventilation, ICU admissions or longer hospital stay.Conclusions: Lockdown and precautionary measures executed during the early phase of COVID-19 pandemic helped decrease the number of hospitalizations due to lower respiratory illnesses in Saudi Arabia. Reduction in hospitalizations seems less likely to be secondary to hospital avoidance or delayed presentations as number of ICU admission and oxygen requirements did not increase. The post pandemic pattern of respiratory illnesses among children needs further research.
Diagnostic Errors Are Common in Acute Pediatric Respiratory Disease: A Prospective, Single-Blinded Multicenter Diagnostic Accuracy Study in Australian Emergency Departments
Authors: Porter Paul , Brisbane Joanna , Tan Jamie , Bear Natasha , Choveaux Jennifer , Della Phillip , Abeyratne Udantha 
Published: November 2021

Background: Diagnostic errors are a global health priority and a common cause of preventable harm. There is limited data available for the prevalence of misdiagnosis in pediatric acute-care settings. Respiratory illnesses, which are particularly challenging to diagnose, are the most frequent reason for presentation to pediatric emergency departments.Objective: To evaluate the diagnostic accuracy of emergency department clinicians in diagnosing acute childhood respiratory diseases, as compared with expert panel consensus (reference standard).Methods: Prospective, multicenter, single-blinded, diagnostic accuracy study in two well-resourced pediatric emergency departments in a large Australian city. Between September 2016 and August 2018, a convenience sample of children aged 29 days to 12 years who presented with respiratory symptoms was enrolled. The emergency department discharge diagnoses were reported by clinicians based upon standard clinical diagnostic definitions. These diagnoses were compared against consensus diagnoses given by an expert panel of pediatric specialists using standardized disease definitions after they reviewed all medical records.Results: For 620 participants, the sensitivity and specificity (%, [95% CI]) of the emergency department compared with the expert panel diagnoses were generally poor: isolated upper respiratory tract disease (64.9 [54.6, 74.4], 91.0 [88.2, 93.3]), croup (76.8 [66.2, 85.4], 97.9 [96.2, 98.9]), lower respiratory tract disease (86.6 [83.1, 89.6], 92.9 [87.6, 96.4]), bronchiolitis (66.9 [58.6, 74.5], 94.3 [80.8, 99.3]), asthma/reactive airway disease (91.0 [85.8, 94.8], 93.0 [90.1, 95.3]), clinical pneumonia (63·9 [50.6, 75·8], 95·0 [92·8, 96·7]), focal (consolidative) pneumonia (54·8 [38·7, 70·2], 86.2 [79.3, 91.5]). Only 59% of chest x-rays with consolidation were correctly identified. Between 6.9 and 14.5% of children were inappropriately prescribed based on their eventual diagnosis.Conclusion: In well-resourced emergency departments, we have identified a previously unrecognized high diagnostic error rate for acute childhood respiratory disorders, particularly in pneumonia and bronchiolitis. These errors lead to the potential of avoidable harm and the administration of inappropriate treatment.
Designing Support Structures Post Sepsis in Children: Perspectives of the Queensland Paediatric Sepsis Program
Authors: Raman Sainath , English Alana , O'Keefe Meagan , Harley Amanda , Steele Mary , Minogue Jess , Weller Kate , Long Debbie , Irwin Adam , Lister Paula 
Published: November 2021

Introduction: Paediatric post sepsis syndrome is poorly defined and causes physical, neurocognitive, psychosocial morbidity, and family dysfunction. Families of sepsis survivors report unmet needs during care. Worldwide, the provision of post sepsis care is in its infancy with limited evidence to design clinical support pathways.Perspective: The Queensland Paediatric Sepsis Program (QPSP) developed a family support structure (FSS) to improve care during all stages of childhood sepsis. It was designed in partnership with consumers guided by information from consumers and it is partly delivered by consumers. Key areas include online, multimodal education for families and the ability to connect with other families affected by sepsis. The FSS is delivered by a multidisciplinary team (MDT) acting with clinicians local to the child. Families can join the FSS registry at any stage of their sepsis journey which connects them to our MDT team and opens opportunities to participate in future research and other initiatives. Improving public awareness is a critical outcome for our consumers and they have co-designed media and digital campaigns.Discussion: The ideal FSS for post sepsis syndrome management is a clinical pathway designed in partnership with consumers of interventions proven to improve outcomes from sepsis that meets their requirements. The QPSP FSS is novel as it is co-designed with, and partly delivered by, consumers with interventions aimed to improve the entire spectrum of morbidities suffered by survivors and their families, not just physical sequelae. Evaluation is embedded in the program and outcomes will guide evolution of the FSS.
Safety of Inulin and Sinistrin: Combining Several Sources for Pharmacovigilance Purposes
Authors: Bui T-V. , Prot-Bertoye C. , Ayari H. , Baron S. , Bertocchio J-P. , Bureau C. , Davis P. , Blanchard A. , Houillier P. , Prie D. , Lillo-Le Louet A. , Courbebaisse M. 
Published: November 2021

Introduction: Inulin and its analog sinistrin are fructose polymers used in the food and pharmaceutical industries. In 2018, The French National Agency for the Safety of Medicines and Health Products (ANSM) decided to withdraw products containing sinistrin and inulin due to several reports of serious hypersensitivity reactions, including a fatal outcome.Objective: To assess the safety of inulin and sinistrin use in France.Methods: We searched multiple sources to identify adverse reactions (ARs) to inulin or sinistrin: first, classical pharmacovigilance databases including the French Pharmacovigilance (FPVD) and the WHO Database (VigiBase); second, data from a clinical trial, MultiGFR; third, data regarding current use in an hospital. All potential ARs to inulin or sinistrin were analyzed with a focus on hypersensitivity reactions and relationships to batches of sinistrin.Results: From 1991 to 2018, 134 ARs to inulin or sinistrin were registered in the FPVD or VigiBase. Sixty-three cases (47%) were classified as serious, and 129 cases (96%) were hypersensitivity reactions. We found an association between a batch of sinistrin and the occurrence of hypersensitivity reactions. During the MultiGFR clinical trial, 7 patients (7/163 participants) had an Adverse reaction; of these, 4 were hypersensitivity reactions including one case of grade 4 anaphylactic shock. In the hospital, no ARs were observed. In the literature, ARs to inulin and sinistrin are very rarely reported and mostly benign.Conclusion: Most ARs to inulin and sinistrin are hypersensitivity reactions that appear to be associated with sinistrin batches.
Prevalence of Chronic Polypharmacy in Community-Dwelling Elderly People in Poland: Analysis of National Real-World Database Helps to Identify High Risk Group
Authors: Kardas Przemysław , Lichwierowicz Aneta , Urbański Filip , Chudzyńska Ewa , Czech Marcin , Kardas Grzegorz 
Published: November 2021

Introduction: Multimorbidity often comes with age, making elderly people particularly prone to polypharmacy. Polypharmacy, in turn, is a risk factor for adverse drug reactions, drug-drug interactions, non-adherence to medication, negative health outcomes, and increased healthcare services utilization. The longer the exposure to polypharmacy is, the higher the risk of these consequences is. Therefore, a detailed assessment of the prevalence and drivers of chronic polypharmacy in the elderly is particularly important.Aim of study: To find out the prevalence of chronic polypharmacy in the elderly population of Poland, and to characterize the subgroup with the highest risk of this problem, using real-world data.Methodology: A retrospective analysis of data on dispensation and healthcare services utilization held by the national payer organization for the year 2018. Chronic polypharmacy was defined as possession, as a result of dispensation, of five or more prescribed drugs within 80% of each of the consecutive 6 months.Results: Chronic polypharmacy was found in 554.1 thousand patients, i.e. in 19.1% of the national 65+ cohort. On average, those patients were 76 years old, and 49.3% of them were female. The vast majority (68.6%) continued their polypharmacy for the period of the whole year. There was a marked variation in geographical distribution of chronic polypharmacy with the highest value of 1.7 thousand per 100,000 inhabitants in the Łódź Voivodeship. Patients exposed to chronic polypharmacy filled prescriptions from 4.5±2.36 healthcare professionals. The average number of drugs they used was 8.3±3.84 DDD per patient per day. The most often prescribed drugs were Metformin, Atorvastatin and Pantoprazole. The average annual hospitalisation rate in those patients was 1.03±2.4.Conclusion: This study was the first of this kind involving a nationwide assessment of chronic polypharmacy in Polish elderly people. We found that this problem affected one fifth of Polish older adults and it remains stable due to its direct relation to chronic conditions. Thus, our results confirm that this phenomenon is highly important for the national health policy and requires relevant interventions. The planned introduction of pharmaceutical care in Poland is expected to help in solving the problem.
Psychological Impact of Exposure to the COVID-19 Sanitary Crisis on French Healthcare Workers: Risk Factors and Coping Strategies
Authors: Vancappel Alexis , Jansen Eline , Ouhmad Nawal , Desmidt Thomas , Etain Bruno , Bergey Chantal , d'Ussel Marguerite , Krebs Marie-Odile , Paquet Claire , Réveillère Christian , Hingray Coraline , El-Hage Wissam 
Published: November 2021

Background: COVID-19 sanitary crisis is associated with emotional difficulties such as depression, anxiety and reactional post-traumatic symptoms among healthcare workers. Indeed, healthcare workers were particularly exposed to COVID-19 sanitary crisis. This study aimed to investigate the effects of exposure to COVID-19 sanitary crisis on affective symptoms (anxiety, post-traumatic stress, burnout) among French healthcare workers and the mediating role of cognitive emotion regulation strategies (positive re-evaluation and set in perspective) and coping strategies (active coping, planning, instrumental support, emotional support, emotional expression, positive reappraisal, acceptance, denial, blame, humor, religion, distraction, substance use, behavioral disengagement).Method: This cross-sectional survey-based study collected demographic data and mental health measurements from 1,010 volunteers (838 women) who consented online to participate, from March 24 to June 28, 2020, in France. Participants filled out online questionnaires and visual analogic scales that evaluate affective symptoms related to the COVID-19 sanitary crisis, namely symptoms of post-traumatic stress, burnout, emotion regulation abilities, and coping abilities.Results: The majority (57.8%) of the participants presented post-traumatic symptoms. Depending on the sub-dimensions evaluated, a proportion of participants reported moderate (25.9–31.2%) to severe (17.2–40.7%) burnout symptoms. We found a significant effect of the level of exposure to COVID-19 on affective symptoms. Being a woman, having a lower job position and having less experience were associated with higher level of affective symptoms. Moreover, coping strategies had a mediating effect on the relation between stress and burnout, supporting the coping reserve model.Conclusion: Post-traumatic and burnout symptoms were highly prevalent among French healthcare workers at the beginning of the COVID-19 crisis. Exposure to COVID-19 is a determining factor. We can thus promote both coping training and a good environment to limit the emotional consequences of exposure to COVID-19.
Assessment of Antipsychotic Medications on Social Media: Machine Learning Study
Authors: Alvarez-Mon Miguel A. , Donat-Vargas Carolina , Santoma-Vilaclara Javier , Anta Laura de , Goena Javier , Sanchez-Bayona Rodrigo , Mora Fernando , Ortega Miguel A. , Lahera Guillermo , Rodriguez-Jimenez Roberto , Quintero Javier , Álvarez-Mon Melchor 
Published: November 2021

Background: Antipsychotic medications are the first-line treatment for schizophrenia. However, non-adherence is frequent despite its negative impact on the course of the illness. In response, we aimed to investigate social media posts about antipsychotics to better understand the online environment in this regard.Methods: We collected tweets containing mentions of antipsychotic medications posted between January 1st 2019 and October 31st 2020. The content of each tweet and the characteristics of the users were analyzed as well as the number of retweets and likes generated.Results: Twitter users, especially those identified as patients, showed an interest in antipsychotic medications, mainly focusing on the topics of sexual dysfunction and sedation. Interestingly, paliperidone, despite being among one of the newest antipsychotics, accounted for a low number of tweets and did not generate much interest. Conversely, retweet and like ratios were higher in those tweets asking for or offering help, in those posted by institutions and in those mentioning cognitive complaints. Moreover, health professionals did not have a strong presence in tweet postings, nor did medical institutions. Finally, trivialization was frequently observed.Conclusion: This analysis of tweets about antipsychotic medications provides insights into experiences and opinions related to this treatment. Twitter user perspectives therefore constitute a valuable input that may help to improve clinicians' knowledge of antipsychotic medications and their communication with patients regarding this treatment.
Clinical, Epidemiologic and Ethical Aspects of Hysterectomy in Young Females With Intellectual Disability: A Multi-Centre Study of Public Hospitals in Mexico City
Authors: Márquez-González Horacio , Valdez-Martínez Edith , Bedolla Miguel 
Published: November 2021

Background: Non-therapeutic hysterectomy has been performed to this day in Mexican women with intellectual disabilities (IDs), but the rationale for performing the procedure has been rarely submitted to clinical ethics committees. The objectives of the present research were to determine the frequency of hysterectomy and the clinical and epidemiologic characteristics that associated to the indication of hysterectomy in girls and young females with IDs and to analyse the emerging ethical issues related to the procedure.Materials and Methods: A medical chart review was conducted to identify female patients aged ≤ 25 years who had IDs based on anatomical pathologies and hospital records and underwent hysterectomy between January 2014 and December 2019 in nine high-concentration hospitals in Mexico City. Data were collected using a questionnaire developed ex professo and validated through a pilot study and analysed using the Statistical Package for the Social Sciences (SPSS) 21.0 software.Results: Information of 234 female patients with or without ID who were ≤ 25 years of age was reported by the departments of anatomical pathology and paediatrics. Of the patients, 184 (79%) were excluded because the information reported was found to be erroneous or incomplete during the medical records review. Most of the 50 emales included in the study had moderate ID (n = 23, 46%) followed by those with severe ID (n = 17, 34%). The mean age at hysterectomy was 15 ± 2.9 years. Prophylactic-total abdominal hysterectomy was the most frequently performed (n = 42, 84%). A concurrence was observed between the parental and medical reasons justifying hysterectomy. The most frequent reasons were fertility control (parents vs. physicians: 46 vs. 42%), management of menstrual hygiene (28 vs. 30%) and risk of sexual abuse (6 vs. 6%).Conclusion: This study showed that performing non-therapeutic hysterectomy is subject to the clinical judgement of physicians according to their perception of the patient's quality of life. Therefore, the ethical quality of the decision to perform the procedure in girls and young females resides in the ethical value of its consequences.