bluuebunny/crossref_metadata_2025_split huggingface dataset:
A prospective cohort study on active surveillance after neoadjuvant chemoradiotherapy for esophageal cancer: protocol of Surgery As Needed for Oesophageal cancer-2
Authors: van der Zijden Charlène J. , Lagarde Sjoerd M. , Hermus Merel , Kranenburg Leonieke W. , van Lanschot J. Jan B. , Mostert Bianca , Nuyttens Joost J. M. E. , Oudijk Lindsey , van der Sluis Pieter C. , Spaander Manon C. W. , Valkema Maria J. , Valkema Roelf , Wijnhoven Bas P. L. ,   SANO-2 study group, Dekker Jan Willem T. , Fiets Willem E. , Hartgrink Hendrik H. , Hazen Wouter L. , Kouwenhoven Ewout A. , Nieuwenhuijzen Grard A. P. , Rosman Camiel , van Sandick Johanna W. , Sosef Meindert N. , van der Zaag Edwin S. 
Published: April 2023

Abstract
Background
Neoadjuvant chemoradiotherapy (nCRT) followed by esophagectomy is a standard treatment for potentially curable esophageal cancer. Active surveillance in patients with a clinically complete response (cCR) 12 weeks after nCRT is regarded as possible alternative to standard surgery. The aim of this study is to monitor the safety, adherence and effectiveness of active surveillance in patients outside a randomized trial.

Methods
This nationwide prospective cohort study aims to accrue operable patients with non-metastatic histologically proven adenocarcinoma or squamous cell carcinoma of the esophagus or esophagogastric junction. Patients receive nCRT and response evaluation consists of upper endoscopy with bite-on-bite biopsies, endoscopic ultrasonography plus fine-needle aspiration of suspicious lymph nodes and 18F-fluorodeoxyglucose positron emission tomography/computed tomography scan. When residue or regrowth of tumor in the absence of distant metastases is detected, surgical resection is advised. Patients with cCR after nCRT are suitable to undergo active surveillance. Patients can consult an independent physician or psychologist to support decision-making. Primary endpoint is the number and severity of adverse events in patients with cCR undergoing active surveillance, defined as complications from response evaluations, delayed surgery and the development of distant metastases. Secondary endpoints include timing and quality of diagnostic modalities, overall survival, progression-free survival, fear of cancer recurrence and decisional regret.

Discussion
Active surveillance after nCRT may be an alternative to standard surgery in patients with esophageal cancer. Similar to organ-sparing approaches applied in other cancer types, the safety and efficacy of active surveillance needs monitoring before data from randomized trials are available.

Trial registration
The SANO-2 study has been registered at ClinicalTrials.gov as NCT04886635 (May 14, 2021) – Retrospectively registered.
HOXA9 gene promotor methylation and copy number variation of SOX2 and HV2 genes in cell free DNA: A potential diagnostic panel for non-small cell lung cancer
Authors: Abou-Zeid Abla , Hashad Doaa , Baess Ayman , Mosaad Mai , Tayae Eman 
Published: April 2023

Abstract
Background
Most cases of lung cancer are diagnosed at advanced stage. Detection of genetic and epigenetic markers in cell-free DNA (cfDNA) is a promising tool for the diagnosis of lung cancer at an early stage. The aim of this study was to identify non-invasive diagnostic markers in cell free DNA (cfDNA) for non-small cell lung cancer (NSCLC) as it is the most common type of lung cancer.

Methods
We investigated the cfDNA HOXA9 gene promotor methylation by pyrosequencing. Copy number variation of SOX2 and HV2 genes were detected by real-time PCR in cfDNA extracted from plasma samples of 25 newly diagnosed NSCLC patients and 25 age and sex matched controls.

Results
Methylation level of HOXA9 was significantly higher in NSCLC patients than controls (p > 0.001). SOX2 showed significantly higher CNV and HV2 showed lower CNV in patients than controls (p > 0.001, p = 0.001 respectively). Receiver Operating Characteristic (ROC) curve analysis for HOXA9 methylation, SOX2 CNV and HV2 CNV showed a discrimination power of 79.4%, 80% and 77.5% respectively and the area under the curve for the combined analysis of the three genes was 0.958 with 88% sensitivity and 100% specificity.

Conclusions
In this study, we suggest a potentially diagnostic panel that may help in detection of lung cancer with high sensitivity and specificity using cell free DNA. This Panel included HOXA9 gene methylation and the CNV of SOX2 and HV2 genes.
Adverse childhood experiences as a risk factor for non-suicidal self-injury and suicide attempts in forensic psychiatric patients
Authors: Laporte Natalie , Ozolins Andrejs , Westling Sofie , Westrin Åsa , Wallinius Märta 
Published: April 2023

Abstract
Background
Exposure to adverse childhood experiences (ACE) have been found to have profound negative consequences on an individuals’ health. Non-suicidal self-injury (NSSI) is a clinically complex and serious global health issue and is closely related to suicide attempts. Previous research has found associations between ACE and NSSI and suicide attempts in clinical samples. However, this association has to our knowledge not been studied to this extent in a sample of forensic psychiatric patients. The aim of this study was therefore to describe the prevalence of adverse childhood experiences (ACE) and their associations with non-suicidal self-injury (NSSI) and/or suicide attempts in forensic psychiatric patients.

Methods
The current study is a cross-sectional study of a consecutive cohort of 98 forensic psychiatric patients (86.7% male) in Sweden. We invited 184 patients with a predicted stay of > 8 weeks who had been cleared for participation by their treating psychiatrist. Of these, 83 declined and 98 eligible patients provided informed consent. Information on ACE, NSSI, and suicide attempts derived from files, self-reports (Childhood Trauma Questionnaire-Short Form; CTQ-SF), and interviews were compared separately among participants with and without NSSI or suicide attempts using t-tests. The dose–response association between ACE and NSSI/suicide attempts was analysed using binary logistic regression.

Results
In file reviews, 57.2% of participants reported physical abuse, 20% sexual abuse, and 43% repeated bullying by peers during childhood. NSSI and suicide attempts were associated significantly with CTQ-SF total scores, with medium effect sizes (d = .60 to .63, p < .01), and strongly with several CTQ-SF subscales. Parental substance abuse was also associated with NSSI (p = .006, OR = 3.23; 95% confidence interval [CI] = 1.36 to 7.66) and suicide attempts (p = .018, OR = 2.75; 95% CI = 1.18 to 6.42). Each additional ACE factor predicted an increased probability of NSSI (p = .016, OR = 1.29; CI = 1.04 to 1.59) but not of suicide attempts. When anxiety and depressive disorders were included in the model, ACE remained a significant predictor of NSSI.

Conclusions
We report extensive ACE, from both files and self-reports. When comparing groups, correlations were found between ACE and NSSI, and ACE and suicide attempts among forensic psychiatric patients. ACE seem to predict NSSI but not suicide attempts in this group, even when controlling for affective and anxiety disorders. Early ACE among forensic psychiatric patients, especially physical and emotional abuse and parental substance abuse, have important impacts on self-harming behaviours that must be acknowledged both by the institutions that meet them as children and in their later assessment and treatment.
Dynamic ultrasound reveals the specific behavior of the medial meniscus extrusion in patients with knee osteoarthritis
Authors: Ishii Yosuke , Ishikawa Masakazu , Nakashima Yuko , Hashizume Takato , Okamoto Saeko , Iwamoto Yoshitaka , Okada Kaoru , Takagi Kazuya , Takahashi Makoto , Adachi Nobuo 
Published: April 2023

Abstract
Background
In the dynamic condition, knee osteoarthritis (OA) usually presents with pain. In the weight-bearing condition, a medial meniscus extrusion (MME) may cause severe symptoms and pathological progression. However, the correlation between a dynamic MME and pain has not been elucidated. Now, an MME can be evaluated under dynamic conditions and reflect the characteristics of symptomatic knee OA. This study investigated MMEs during walking and their correlation with knee pain.

Methods
Thirty-two symptomatic patients with knee OA (mean age, 60.5 ± 9.9 years) were enrolled in this study. The medial meniscus was evaluated using ultrasonograms during walking, and in the static supine and unipedal standing positions, as dynamic and static conditions, respectively. The ΔMME (the difference between the maximum and minimum MMEs) was obtained in each condition. The intensity of the knee pain during walking was measured by the visual analog scale (VAS).

Results
The ΔMME in the dynamic condition was significantly higher than that in the static condition (P < 0.01). There was a significant correlation between VAS and ΔMME only in the dynamic condition.

Conclusions
The dynamic evaluation is a valid tool for understanding the mechanisms of knee pain and the behavior of the medial meniscus in symptomatic knee OA.
Attitudes toward depression among rural primary healthcare providers in hunan areas, China: a cross sectional study
Authors: Xie Jianfei , Liu Min , Ding Siqing , Zhong Zhuqing , Zeng Sainan , Liu Aizhong , He Shiwen , Zhou Jianda 
Published: April 2023

Abstract
Background
Mental health services are not sufficient for depression patients in rural areas of China, training in mental health knowledge for primary healthcare providers has been encouraged, but the effect of this encouragement has rarely been reported.

Methods
A cross-sectional survey was conducted in primary healthcare facilities that sought to include all the primary healthcare providers (registered physicians and nurses) in two cities in Hunan province, China by administering questionnaires that covered depression symptoms, typical depression cases, and the Revised Depression Attitude Questionnaire.

Results
In total, 315 primary healthcare providers agreed to participate in the study and finished the questionnaires, of which 12.1% had training in depression. In addition, 62.9% of the rural primary healthcare providers were able to recognize most general depression symptoms, and 8.3% were able to recognize all general depression symptoms. The primary healthcare providers in the survey held a neutral to slightly negative attitude towards depression as indicated by their professional confidence (mean scores 16.51 ± 4.30), therapeutic optimism/pessimism (mean scores 29.02 ± 5.98), and general perspective (mean scores 18.12 ± 3.12) scores. Fewer rural primary healthcare providers knew (28.3%) or applied (2.9%) psychological intervention in the clinic.

Conclusions
Our study indicated that primary healthcare providers knew about general depression symptoms, but lacked psychological intervention skills and held low confidence in and pessimistic attitudes toward depression care. We therefore speculate that existing psychological training for primary healthcare providers is insufficient in quantity and quality, making the need to explore more effective types of training urgently.
Evaluating a novel intervention in undergraduate medicine: an MBBS Curriculum Map
Authors: Wardle Katie , Chakrabarti Rima , Wright Tor , Bennie Taylor , Ntuiabane Daniel , Gishen Faye 
Published: April 2023

Abstract
Background
Following student feedback, a Curriculum Map (CM) was commissioned in 2018 at UCL Medical School (UCLMS). After exploring key requirements of a CM, the second phase focused on building a prototype before its launch. This study evaluates this novel pedagogical intervention following its implementation, from the perspective of its primary users, UCL medical students.

Methods
This multi-method study was conducted two months after the CM’s launch in 2019. Quantitative and qualitative data was gathered via a survey and focus groups across four domains: usefulness, satisfaction, appearance, and content. Reflective Thematic Analysis was used to analyse the qualitative data to build themes.

Results
One hundred ninety five participants (195/1347, 14%) responded to the survey and two focus groups were held. Higher rates of satisfaction were seen among later years compared to early years students. Five key themes emerged on the CM as a: UCLMS textbook; learning aid for assessments; tool for capturing scientific content; modern learning technology and tool for ‘levelling the playing field’. Key findings suggest that while students welcomed a centralised resource to create transparency, there were clear differences between early and later years students, with the former preferring a more prescriptive approach. Learning was assessment-driven across all years and students highlighted their desire for greater clarity on the importance of curricular content for summative assessments.

Conclusion
A CM provides a benchmark for medical educators on the undergraduate curriculum, which must be balanced with its limitations; a CM cannot provide an exhaustive syllabus and needs to be supplemented with self-directed learning and clinical preparation for practice.
A randomized controlled trial of a nurse-led psychological pain solution-focused intervention for depressed inpatients: study protocol
Authors: Chen Shu-Yan , Bian Cheng , Cheng Yin , Zhao Wei-Wei , Yan Shi-Rui , Zhang Yan-Hong 
Published: April 2023

Abstract
Background

Depressed patients commonly experience psychological pain. Research pointed to positive psychological interventions as an effective means of ameliorating psychological pain, although the exact effect is unclear. Based on the hope theory and solution-focused brief therapy (SFBT), this study combines hope theory with solution-focused brief therapy to develop a nurse-led psychological pain solution-focused (PPSF) intervention in depressed patients.

Methods
This is an assessor-blinded randomized controlled trial following the SPIRIT guidance. A total of 84 depressed patients will be recruited from the inpatient wards of a psychiatric hospital and randomly assigned to the control and experimental groups. Patients in the control group will be treated as usual. In contrast, patients in the experimental group will receive 6 sessions of the PPSF intervention for two weeks on top of the routine care. Primary outcomes are psychological pain, hope, cognitive distortions. Secondary outcomes are depression and suicidal ideation. Data will be collected at 5-time points: baseline, 1 and 2 weeks (post-intervention), 1 month (follow up), and 6 months after baseline. Generalized equation evaluation will be used to assess the effectiveness of the PPSF intervention.

Discussion
From a positive psychology perspective, there remains much room for developing psychological pain interventions in depressed patients. SFBT and hope theory are both based on positive psychology. With hope theory as the general framework and SFBT questions as the practical guide, the PPSF intervention program is designed that nursing staff can implement. If the intervention is effective, it will advance the development of psychological pain interventions for patients with depression.

Trial registration
ChiCTR2100048223
Transformative dimensions of resilience and brittleness during health systems’ collapse: a case study in Brazil using the Functional Resonance Analysis Method
Authors: de Carvalho Paulo Victor Rodrigues , Bellas Hugo , Viana Jaqueline , de Castro Nunes Paula , Arcuri Rodrigo , da Silva Fonseca Valéria , Carneiro Ana Paula Morgado , Jatobá Alessandro 
Published: April 2023

Abstract
Background
As health systems struggle to tackle the spread of Covid-19, resilience becomes an especially relevant attribute and research topic. More than strength or preparedness, to perform resiliently to emerging shocks, health systems must develop specific abilities that aim to increase their potential to adapt to extraordinary situations while maintaining their regular functioning.
Brazil has been one of the most affected countries during the pandemic. In January 2021, the Amazonas state's health system collapsed, especially in the city of Manaus, where acute Covid-19 patients died due to scarcity of medical supplies for respiratory therapy.

Methods
This paper explores the case of the health system's collapse in Manaus to uncover the elements that prevented the system from performing resiliently to the pandemic, by carrying out a grounded-based systems analysis of the performance of health authorities in Brazil using the Functional Resonance Analysis Method. The major source of information for this study was the reports from the congressional investigation carried out to unveil the Brazilian response to the pandemic.

Results
Poor cohesion between the different levels of government disrupted essential functions for managing the pandemic. Moreover, the political agenda interfered in the abilities of the system to monitor, respond, anticipate, and learn, essential aspects of resilient performance.

Conclusions
Through a systems analysis approach, this study describes the implicit strategy of "living with Covid-19", and an in-depth view of the measures that hampered the resilience of the Brazilian health system to the spread of Covid-19.
Phylogenomics revealed migration routes and adaptive radiation timing of Holarctic malaria mosquito species of the Maculipennis Group
Authors: Yurchenko Andrey A. , Naumenko Anastasia N. , Artemov Gleb N. , Karagodin Dmitry A. , Hodge James M. , Velichevskaya Alena I. , Kokhanenko Alina A. , Bondarenko Semen M. , Abai Mohammad R. , Kamali Maryam , Gordeev Mikhail I. , Moskaev Anton V. , Caputo Beniamino , Aghayan Sargis A. , Baricheva Elina M. , Stegniy Vladimir N. , Sharakhova Maria V. , Sharakhov Igor V. 
Published: April 2023

AbstractBackgroundPhylogenetic analyses of closely related species of mosquitoes are important for better understanding the evolution of traits contributing to transmission of vector-borne diseases. Six out of 41 dominant malaria vectors of the genusAnophelesin the world belong to the Maculipennis Group, which is subdivided into two Nearctic subgroups (Freeborni and Quadrimaculatus) and one Palearctic (Maculipennis) subgroup. Although previous studies considered the Nearctic subgroups as ancestral, details about their relationship with the Palearctic subgroup, and their migration times and routes from North America to Eurasia remain controversial. The Palearctic speciesAn. beklemisheviis currently included in the Nearctic Quadrimaculatus subgroup adding to the uncertainties in mosquito systematics.ResultsTo reconstruct historic relationships in the Maculipennis Group, we conducted a phylogenomic analysis of 11 Palearctic and 2 Nearctic species based on sequences of 1271 orthologous genes. The analysis indicated that the Palearctic speciesAn. beklemisheviclusters together with other Eurasian species and represents a basal lineage among them. Also,An. beklemisheviis related more closely toAn. freeborni, which inhabits the Western United States, rather than toAn. quadrimaculatus, a species from the Eastern United States. The time-calibrated tree suggests a migration of mosquitoes in the Maculipennis Group from North America to Eurasia about 20–25 million years ago through the Bering Land Bridge. A Hybridcheck analysis demonstrated highly significant signatures of introgression events between allopatric speciesAn. labranchiaeandAn. beklemishevi. The analysis also identified ancestral introgression events betweenAn. sacharoviand its Nearctic relativeAn. freebornidespite their current geographic isolation. The reconstructed phylogeny suggests that vector competence and the ability to enter complete diapause during winter evolved independently in different lineages of the Maculipennis Group.ConclusionsOur phylogenomic analyses reveal migration routes and adaptive radiation timing of Holarctic malaria vectors and strongly support the inclusion ofAn. beklemisheviinto the Maculipennis Subgroup. Detailed knowledge of the evolutionary history of the Maculipennis Subgroup provides a framework for examining the genomic changes related to ecological adaptation and susceptibility to human pathogens. These genomic variations may inform researchers about similar changes in the future providing insights into the patterns of disease transmission in Eurasia.
The relationship between sphingosine-1-phosphate receptor 2 and epidermal growth factor in migration and invasion of oral squamous cell carcinoma
Authors: Wongviriya Adjabhak , Shelton Richard M. , Cooper Paul R. , Milward Michael R. , Landini Gabriel 
Published: April 2023

AbstractSphingosine-1-phosphate (S1P) is a lipid mediator and its binding to the S1P receptor 2 (S1PR2) is reported to regulate cytoskeletal organization. Epidermal growth factor (EGF) has been shown to induce migration and invasion in tumour cells. Since binding of S1P to S1PR2 and EGF to the EGF receptors exhibit some overlapping functionality, this study aimed to determine whether S1PR2 was involved in EGF-induced migration and invasion of oral squamous cell carcinoma (OSCC) lines and to identify any potential crosstalk between the two pathways. Migration was investigated using the scratch wound assay while invasion was studied using the transwell invasion and multicellular tumour spheroid (MCTS) assays. Activity of Rac1, a RhoGTPase, was measured using G-LISA (small GTPase activation assays) while S1P production was indirectly measured via the expression of sphingosine kinase (Sphk). S1PR2 inhibition with 10 µM JTE013 reduced EGF-induced migration, invasion and Rac1 activity, however, stimulation of S1PR2 with 10 µM CYM5478 did not enhance the effect of EGF on migration, invasion or Rac1 activity. The data demonstrated a crosstalk between EGF/EGFR and S1P/S1PR2 pathways at the metabolic level. S1PR2 was not involved in EGF production, but EGF promoted S1P production through the upregulation of Sphk1. In conclusion, OSCC lines could not migrate and invade without S1PR2 regulation, even with EGF stimulation. EGF also activated S1PR2 by stimulating S1P production via Sphk1. The potential for S1PR2 to control cellular motility may lead to promising treatments for OSCC patients and potentially prevent or reduce metastasis.
Genome-wide association testing in malaria studies in the presence of overdominance
Authors: Akoth Morine , Odhiambo John , Omolo Bernard 
Published: April 2023

AbstractBackgroundIn human genetics, heterozygote advantage (heterosis) has been detected in studies that focused on specific genes but not in genome-wide association studies (GWAS). For example, heterosis is believed to confer resistance to certain strains of malaria in patients heterozygous for the sickle-cell gene, haemoglobin S (HbS). Yet the power of allelic tests can be substantially diminished by heterosis. Since GWAS (and haplotype-associations) also utilize allelic tests, it is unclear to what degree GWAS could underachieve because heterosis is ignored.MethodsIn this study, a two-step approach to genetic association testing in malaria studies in a GWAS setting that may enhance the power of the tests was proposed, by identifying the underlying genetic model first before applying the association tests. Generalized linear models for dominant, recessive, additive, and heterotic effects were fitted and model selection was performed. This was achieved via tests of significance using the MAX and allelic tests, noting the minimump-values across all the models and the proportion of tests that a given genetic model was deemed the best. An example dataset, based on 17 SNPs, from a robust genetic association study and simulated genotype datasets, were used to illustrate the method. Case–control genotype data on malaria from Kenya and Gambia were used for validation.Results and conclusionResults showed that the allelic test returned some false negatives under the heterosis model, suggesting reduced power in testing genetic association. Disparities were observed for some chromosomes in the Kenyan and Gambian datasets, including the sex chromosomes. Thus, GWAS and haplotype associations should be treated with caution, unless the underlying genetic model had been determined.