bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and MRI based radiomics nomograms can predict iPFS and short-term efficacy of third-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma with brain metastases
Authors: Qi Haoran , Hou Yichen , Zheng Zhonghang , Zheng Mei , Qiao Qiang , Wang Zihao , Sun Xiaorong , Xing Ligang 
Published: March 2024

Abstract
Background
Predicting short-term efficacy and intracranial progression-free survival (iPFS) in epidermal growth factor receptor gene mutated (EGFR-mutated) lung adenocarcinoma patients with brain metastases who receive third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy was of great significance for individualized treatment. We aimed to construct and validate nomograms based on clinical characteristics and magnetic resonance imaging (MRI) radiomics for predicting short-term efficacy and intracranial progression free survival (iPFS) of third-generation EGFR-TKI in EGFR-mutated lung adenocarcinoma patients with brain metastases.

Methods
One hundred ninety-four EGFR-mutated lung adenocarcinoma patients with brain metastases who received third-generation EGFR-TKI treatment were included in this study from January 1, 2017 to March 1, 2023. Patients were randomly divided into training cohort and validation cohort in a ratio of 5:3. Radiomics features extracted from brain MRI were screened by least absolute shrinkage and selection operator (LASSO) regression. Logistic regression analysis and Cox proportional hazards regression analysis were used to screen clinical risk factors. Single clinical (C), single radiomics (R), and combined (C + R) nomograms were constructed in short-term efficacy predicting model and iPFS predicting model, respectively. Prediction effectiveness of nomograms were evaluated by calibration curves, Harrell’s concordance index (C-index), receiver operating characteristic (ROC) curves and decision curve analysis (DCA). Kaplan-Meier analysis was used to compare the iPFS of high and low iPFS rad-score patients in the predictive iPFS R model and to compare the iPFS of high-risk and low-risk patients in the predictive iPFS C + R model.

Results
Overall response rate (ORR) was 71.1%, disease control rate (DCR) was 91.8% and median iPFS was 12.67 months (7.88–20.26, interquartile range [IQR]). There were significant differences in iPFS between patients with high and low iPFS rad-scores, as well as between high-risk and low-risk patients. In short-term efficacy model, the C-indexes of C + R nomograms in training cohort and validation cohort were 0.867 (0.835-0.900, 95%CI) and 0.803 (0.753–0.854, 95%CI), while in iPFS model, the C-indexes were 0.901 (0.874–0.929, 95%CI) and 0.753 (0.713–0.793, 95%CI).

Conclusions
The third-generation EGFR-TKI showed significant efficacy in EGFR-mutated lung adenocarcinoma patients with brain metastases, and the combined line plot of C + R can be utilized to predict short-term efficacy and iPFS.
Awareness of somatisation disorder among Swedish physicians at emergency departments: a cross-sectional survey
Authors: Iloson Carina , Praetorius Björk Marcus , Möller Anna , Sundfeldt Karin , Bernhardsson Susanne 
Published: March 2024

Abstract
Background
Somatisation is a highly prevalent psychiatric syndrome in both women and men, in which psychological distress is manifested in physical symptoms without a medical explanation. Many patients with somatisation disorder are high healthcare utilisers, particularly at emergency departments. Unnecessary investigations and diagnostic operations occur frequently, which cause both patient suffering and a significant burden on the healthcare system. Emergency department physicians’ awareness of somatisation and its manifestations has not previously been studied. This study aimed to investigate awareness about somatisation disorder among physicians working at emergency departments in western Sweden, and to explore differences between gender, specialty, and work experience.

Methods
A web-based, cross-sectional survey consisting of six dichotomous questions about somatisation disorder was conducted, in December 2021 – January 2022, among licensed physicians of various specialties working at emergency departments in western Sweden. Descriptive analyses and comparative analyses were performed to investigate differences between gender, type of specialty, and years of practice. Data were analysed using chi2 tests and Fisher’s exact test.

Results
Of the 526 eligible physicians who received the survey, 241 responded; response rate 45.8%. The majority of the respondents (56.4%) were women, and most (35.3%) were specialised in obstetrics/gynaecology. Average years of work experience was 11.1 (SD 8.7) years. Although 71% of respondents were aware of the diagnosis, only 7% knew the diagnostic criteria and only 6% had ever diagnosed a patient with somatisation disorder. Female physicians were more aware of underlying factors than their male colleagues (55.7% vs. 38.2%; p = .010). Type of specialty or years of practice did not affect awareness.

Conclusions
Awareness of somatisation disorder is low among physicians working at emergency departments in western Sweden. The findings suggest a need to increase awareness and knowledge and provide training in diagnosing the condition, to ensure correct decisions and optimal patient management. Clinical guidelines need to be developed to support diagnosis, investigation, and treatment, in Sweden as well as internationally.
GRADE-ADOLOPMENT of hyperthyroidism treatment guidelines for a Pakistani context
Authors: Martins Russell Seth , Nadeem Sarah , Aziz Abeer , Raja Sajjan , Pervez Alina , Islam Najmul , Ahmed Asma , Sheikh Aisha , Furqan Saira , Ram Nanik , Rizwan Azra , Rizvi Nashia Ali , Mustafa Mohsin Ali , Aamdani Salima Saleem , Ayub Bushra , Masood Muhammad Qamar 
Published: March 2024

Abstract
Introduction
The prevalence of hyperthyroidism in Pakistan is 2.9%, which is two times higher than in the United States. Most high-quality hyperthyroidism clinical practice guidelines (CPGs) used internationally originate from high-income countries in the West. Local CPGs in Pakistan are not backed by transparent methodologies. We aimed to produce comprehensive, high-quality CPGs for the management of hyperthyroidism in Pakistan.

Methods
We employed the GRADE-ADOLOPMENT approach utilizing the 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis as the source CPG. Recommendations from the source guideline were either adopted as is, excluded, or adapted according to our local context.

Results
The source guideline included a total of 124 recommendations, out of which 71 were adopted and 49 were excluded. 4 recommendations were carried forward for adaptation via the ETD process, with modifications being made to 2 of these. The first addressed the need for liver function tests (LFTs) amongst patients experiencing symptoms of hepatotoxicity while being treated with anti-thyroid drugs (ATDs). The second pertained to thyroid status testing post-treatment by radioactive iodine (RAI) therapy for Graves’ Disease (GD). Both adaptations centered around the judicious use of laboratory investigations to reduce costs of hyperthyroidism management.

Conclusion
Our newly developed hyperthyroidism CPGs for Pakistan contain two context-specific modifications that prioritize patients’ finances during the course of hyperthyroidism management and to limit the overuse of laboratory testing in a resource-constrained setting. Future research must investigate the cost-effectiveness and risk-benefit ratio of these modified recommendations.
The mediating and moderating effects of resilience on the relationship between sleep quality and psychological distress in Chinese women with infertility
Authors: Jiang Zhenhua , Hou Sen , Zhang Yajie , Zong Liping 
Published: March 2024

Abstract
Background
Research has widely indicated that the psychological distress experienced by infertile patients during fertility treatments may have a negative effect on the results of assisted reproduction. Although numerous studies have shown that psychological resilience and sleep quality are important influencing factors for psychological distress, the mediating mechanisms of psychological resilience in the relationship between sleep quality and psychological distress for Chinese women in particular remain unclear. Therefore, the current study investigates the association between sleep quality, resilience, and psychological distress in Chinese women with infertility and examines the mediating and moderating roles of resilience on the relationship between sleep quality and psychological distress.

Methods
In this cross-sectional study, a total of 595 women with infertility who were undergoing IVF-ET were recruited at the Reproductive Medicine, Shandong University, from April to November 2019. Participants were instructed to complete four questionnaires, including a questionnaire about socio-demographic and clinical-related information, the Pittsburgh Sleep Quality Index (PSQI), the 10-item Connor-Davidson Resilience Scale (CD-RISC-10), and the Kessler-10 (K10). Pearson’s correlation analysis was conducted preliminarily to describe the relationships between sleep quality, resilience, and psychological distress. A mediation model and a moderated model were constructed and analyzed using the PROCESS macro for SPSS. The Johnson-Neyman (J-N) technique was then used to identify the regions of significance across the levels of moderator values.

Results
Patients in the sample had a high prevalence of psychological distress (48.6%, K10 scores > 22), and mediation analysis indicated that resilience played a partially mediating role in the relationship between sleep quality and psychological distress (indict effect = 0.072, P < 0.001). Moderation analysis indicated that resilience also moderated the association between sleep quality and psychological distress.

Conclusions
Resilience may play a key role in the relationship between sleep quality and psychological distress. Our findings imply that resilience training may therefore be an effective component of psychological distress intervention in women with infertility.
Supporting patient decision-making in non-invasive prenatal testing: a comparative study of professional values and practices in England and France
Authors: Bowman-Smart Hilary , Perrot Adeline , Horn Ruth 
Published: March 2024

Abstract
Background
Non-invasive prenatal testing (NIPT), which can screen for aneuploidies such as trisomy 21, is being implemented in several public healthcare systems across Europe. Comprehensive communication and information have been highlighted in the literature as important elements in supporting women’s reproductive decision-making and addressing relevant ethical concerns such as routinisation. Countries such as England and France are adopting broadly similar implementation models, offering NIPT for pregnancies with high aneuploidy probability. However, we do not have a deeper understanding of how professionals’ counselling values and practices may differ between these contexts.

Methods
In this paper, we explore how professionals in England and France support patient decision-making in the provision of NIPT and critically compare professional practices and values. We draw on data from semi-structured interviews with healthcare professionals.

Results
Both English and French professionals emphasised values relating to patient choice and consent. However, understandings and application of these values into the practice of NIPT provision differed. English interviewees placed a stronger emphasis on interpreting and describing the process of counselling patients and clinical care through a “principle” lens. Their focus was on non-directiveness, standardisation, and the healthcare professional as “decision-facilitator” for patients. French interviewees described their approach through a “procedural” lens. Their focus was on formal consent, information, and the healthcare professional as “information-giver”. Both English and French professionals indicated that insufficient resources were a key barrier in effectively translating their values into practice.

Conclusion
Our findings illustrate that supporting patient choice in the provision of NIPT may be held as an important value in common on a surface level, but can be understood and translated into practice in different ways. Our findings can guide further research and beneficially inform practice and policy around NIPT provision.
Assessment of patient safety culture in Moroccan primary health care: a multicentric study
Authors: Fassi Chaima Fihri , Mourajid Yasmine , Azilagbetor David Mawufemor , Sabri Asma , Chahboune Mohamed , Hilali Abderraouf 
Published: March 2024

Abstract
Background
Promoting patient safety is a critical concern for developing-countries health systems like Morocco. There is an increasing acknowledgment of the need to create a patient-centered culture with the aim to decrease the number of adverse events related to care and improve health-care quality in Morocco.

Objective
The purpose of this study is to examine the perceptions of health professionals working in primary care level of care facilities in Morocco about the concept of patient safety culture.

Methods
We conducted a multicentric cross-sectional study of a quantitative nature in primary healthcare facilities in ten Moroccan cities, measuring ten patient safety culture dimensions, from February 2022 to June 2022. Data was collected using the French version of the HSOPSC questionnaire.

Results
The most developed dimension of the culture of patient safety was found to be Teamwork within Units (69%), followed by Supervisor/Manager’s Expectations & Actions Promoting Patient Safety (59%). The least developed dimensions were Staffing (34%) and Nonpunitive Response to Errors (37%).

Conclusion
Improving patient safety culture should be a priority for primary healthcare facility administrators and all stakeholders, addressing, in particular, the shortage of human resources. In addition, health personnel should be encouraged to report errors without fear of punitive consequences.
First successful outcomes of pegvaliase (PALYNZIQ) in children
Authors: Alfadhel Majid , Albarakati Rayyan 
Published: March 2024

AbstractBackgroundPKU is an autosomal recessive hereditary inborn error of metabolism caused by a lack of phenylalanine hydroxylase enzyme activity. Pegvaliase (PALYNZIQ®) treatment has been approved to reduce blood Phe concentrations in adult phenylketonuria patients with uncontrolled blood Phe concentrations greater than 600 micromol/L on current management. However, data regarding individuals under the age of 16 is still unavailable.Case reportWe report a 12-year-old Saudi girl who underwent pegvaliase therapy and was closely monitored for one year. Remarkably, a positive therapeutic response became apparent six months after commencing pegvaliase treatment. Phenylalanine (Phe) levels showed significant improvement, stabilising within the < 5 to 14 µmol/L range on a regular diet without any restriction. At her current age of 12, the patient maintains an unrestricted dietary regimen, consuming a diverse selection of foods, including poultry, meat, and protein sources, all while consistently maintaining normal Phe levels with no change in mental status after treatment. The parents gave their written, informed consent in allowing the research study to be carried out and clinical data to be published.ConclusionsThis report addresses the potential broader applications of Pegvaliase in children, as well as its safety and tolerability in this age group. However, larger sample sizes and robust methodologies are required to validate such findings.
Enhancing precision medicine: a nomogram for predicting platinum resistance in epithelial ovarian cancer
Authors: Li Ruyue , Xiong Zhuo , Ma Yuan , Li Yongmei , Yang Yu’e , Ma Shaohan , Ha Chunfang 
Published: March 2024

Abstract
Background
This study aimed to develop a novel nomogram that can accurately estimate platinum resistance to enhance precision medicine in epithelial ovarian cancer(EOC).

Methods
EOC patients who received primary therapy at the General Hospital of Ningxia Medical University between January 31, 2019, and June 30, 2021 were included. The LASSO analysis was utilized to screen the variables which contained clinical features and platinum-resistance gene immunohistochemistry scores. A nomogram was created after the logistic regression analysis to develop the prediction model. The consistency index (C-index), calibration curve, receiver operating characteristic (ROC) curve, and decision curve analysis (DCA) were used to assess the nomogram’s performance.

Results
The logistic regression analysis created a prediction model based on 11 factors filtered down by LASSO regression. As predictors, the immunohistochemical scores of CXLC1, CXCL2, IL6, ABCC1, LRP, BCL2, vascular tumor thrombus, ascites cancer cells, maximum tumor diameter, neoadjuvant chemotherapy, and HE4 were employed. The C-index of the nomogram was found to be 0.975. The nomogram’s specificity is 95.35% and its sensitivity, with a cut-off value of 165.6, is 92.59%, as seen by the ROC curve. After the nomogram was externally validated in the test cohort, the coincidence rate was determined to be 84%, and the ROC curve indicated that the nomogram’s AUC was 0.949.

Conclusion
A nomogram containing clinical characteristics and platinum gene IHC scores was developed and validated to predict the risk of EOC platinum resistance.
Activating mutations in JAK2 and CALR differentially affect intracellular calcium flux in store operated calcium entry
Authors: Bhuria Vikas , Franz Tobias , Baldauf Conny , Böttcher Martin , Chatain Nicolas , Koschmieder Steffen , Brümmendorf Tim H. , Mougiakakos Dimitrios , Schraven Burkhart , Kahlfuß Sascha , Fischer Thomas 
Published: March 2024

Abstract
Background
Calcium (Ca2+) signaling regulates various vital cellular functions, including integrin activation and cell migration. Store-operated calcium entry (SOCE) via calcium release-activated calcium (CRAC) channels represents a major pathway for Ca2+ influx from the extracellular space in multiple cell types. The impact of JAK2-V617F and CALR mutations which are disease initiating in myeloproliferative neoplasms (MPN) on SOCE, calcium flux from the endoplasmic reticulum (ER) to the cytosol, and related key signaling pathways in the presence or absence of erythropoietin (EPO) or thrombopoietin (TPO) is poorly understood. Thus, this study aimed to elucidate the effects of these mutations on the aforementioned calcium dynamics, in cellular models of MPN.

Methods
Intracellular Ca2+ levels were measured over a time frame of 0–1080 s in Fura-2 AM labeled myeloid progenitor 32D cells expressing various mutations (JAK2-WT/EpoR, JAK2-V617F/EpoR; CALR-WT/MPL, CALR-ins5/MPL, and del52/MPL). Basal Ca2+ concentrations were assessed from 0–108 s. Subsequently, cells were stimulated with EPO/TPO in Ca2+-free Ringer solution, measuring Ca2+ levels from 109–594 s (store depletion). Then, 2 mM of Ca2+ buffer resembling physiological concentrations was added to induce SOCE, and Ca2+ levels were measured from 595–1080 s. Fura-2 AM emission ratios (F340/380) were used to quantify the integrated Ca2+ signal. Statistical significance was assessed by unpaired Student's t-test or Mann–Whitney-U-test, one-way or two-way ANOVA followed by Tukey's multiple comparison test.

Results
Following EPO stimulation, the area under the curve (AUC) representing SOCE significantly increased in 32D-JAK2-V617F cells compared to JAK2-WT cells. In TPO-stimulated CALR cells, we observed elevated Ca2+ levels during store depletion and SOCE in CALR-WT cells compared to CALR-ins5 and del52 cells. Notably, upon stimulation, key components of the Ca2+ signaling pathways, including PLCγ-1 and IP3R, were differentially affected in these cell lines. Hyper-activated PLCγ-1 and IP3R were observed in JAK2-V617F but not in CALR mutated cells. Inhibition of calcium regulatory mechanisms suppressed cellular growth and induced apoptosis in JAK2-V617F cells.

Conclusions
This report highlights the impact of JAK2 and CALR mutations on Ca2+ flux (store depletion and SOCE) in response to stimulation with EPO and TPO. The study shows that the JAK2-V617F mutation strongly alters the regulatory mechanism of EpoR/JAK2-dependent intracellular calcium balance, affecting baseline calcium levels, EPO-induced calcium entry, and PLCγ-1 signaling pathways. Our results reveal an important role of calcium flux in the homeostasis of JAK2-V617F positive cells.
Underrated aspects of a true Mediterranean diet: understanding traditional features for worldwide application of a “Planeterranean” diet
Authors: Godos Justyna , Scazzina Francesca , Paternò Castello Corrado , Giampieri Francesca , Quiles José L. , Briones Urbano Mercedes , Battino Maurizio , Galvano Fabio , Iacoviello Licia , de Gaetano Giovanni , Bonaccio Marialaura , Grosso Giuseppe 
Published: March 2024

AbstractOver the last decades, the Mediterranean diet gained enormous scientific, social, and commercial attention due to proven positive effects on health and undeniable taste that facilitated a widespread popularity. Researchers have investigated the role of Mediterranean-type dietary patterns on human health all around the world, reporting consistent findings concerning its benefits. However, what does truly define the Mediterranean diet? The myriad of dietary scores synthesizes the nutritional content of a Mediterranean-type diet, but a variety of aspects are generally unexplored when studying the adherence to this dietary pattern. Among dietary factors, the main characteristics of the Mediterranean diet, such as consumption of fruit and vegetables, olive oil, and cereals should be accompanied by other underrated features, such as the following: (i) specific reference to whole-grain consumption; (ii) considering the consumption of legumes, nuts, seeds, herbs and spices often untested when exploring the adherence to the Mediterranean diet; (iii) consumption of eggs and dairy products as common foods consumed in the Mediterranean region (irrespectively of the modern demonization of dietary fat intake). Another main feature of the Mediterranean diet includes (red) wine consumption, but more general patterns of alcohol intake are generally unmeasured, lacking specificity concerning the drinking occasion and intensity (i.e., alcohol drinking during meals). Among other underrated aspects, cooking methods are rather simple and yet extremely varied. Several underrated aspects are related to the quality of food consumed when the Mediterranean diet was first investigated: foods are locally produced, minimally processed, and preserved with more natural methods (i.e., fermentation), strongly connected with the territory with limited and controlled impact on the environment. Dietary habits are also associated with lifestyle behaviors, such as sleeping patterns, and social and cultural values, favoring commensality and frugality. In conclusion, it is rather reductive to consider the Mediterranean diet as just a pattern of food groups to be consumed decontextualized from the social and geographical background of Mediterranean culture. While the methodologies to study the Mediterranean diet have demonstrated to be useful up to date, a more holistic approach should be considered in future studies by considering the aforementioned underrated features and values to be potentially applied globally through the concept of a “Planeterranean” diet.