bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of SLC22A17 DNA methylation hotspot as a potential biomarker in cutaneous melanoma
Authors: Lavoro Alessandro , Falzone Luca , Gattuso Giuseppe , Conti Giuseppe N. , Caltabiano Rosario , Madonna Gabriele , Capone Mariaelena , McCubrey James A. , Ascierto Paolo A. , Libra Massimo , Candido Saverio 
Published: October 2024

Abstract
Background
Cancer onset and progression are driven by genetic and epigenetic alterations leading to oncogene activation and the silencing of tumor suppressor genes. Among epigenetic mechanisms, DNA methylation (methDNA) is gaining growing interest in cancer. Promoter hypomethylation is associated with oncogene activation while intragenic methDNA can be involved in transcriptional elongation, alternative spicing, and the activation of cryptic start sites. Several genes involved in the modulation of the tumor microenvironment are regulated by methDNA, including the Solute Carrier Family 22 Member 17 (SLC22A17), which is involved in iron trafficking and extracellular matrix remodeling cooperating with the Gelatinase-Associated Lipocalin (NGAL) ligand. However, the exact role of intragenic methDNA in cancer has not been fully investigated. Therefore, the aim of the present study is to explore the role of methDNA in the regulation of SLC22A17 in cutaneous melanoma (CM), used as a tumor model.

Methods
Correlation and differential analyses between SLC22A17 expression and methDNA were performed using the data contained in The Cancer Genome Atlas and Gene Expression Omnibus databases. Functional studies on melanoma cell lines treated with 5-Azacytidine (5-Aza) were conducted to assess the correlation between methDNA and SLC22A17 expression. A validation study on the diagnostic potential of the in silico-identified SLC22A17 methDNA hotspot was finally performed by analyzing tissue samples obtained from CM patients and healthy controls.

Results
The computational analyses revealed that SLC22A17 was significantly downregulated in CM, and its expression was related to promoter hypomethylation and intragenic hypermethylation. Moreover, SLC22A17 overexpression and hypermethylation of two intragenic methDNA hotspots were associated with a better clinical outcome in CM patients. The correlation between SLC22A17 methDNA and expression was confirmed in 5-Aza-treated cells. In agreement with in silico analyses, the SLC22A17 promoter methylation hotspot showed higher methDNA levels in CM samples compared to nevi. In addition, the methDNA levels of this hotspot were positively correlated with advanced CM.

Conclusions
The SLC22A17 methDNA hotspot could represent a promising biomarker for CM, highlighting the regulatory role of methDNA on SLC22A17 expression. These results pave the way for the identification of novel epigenetic biomarkers and therapeutic targets for the management of CM patients.
Exploring transparent reporting and data availability in systematic reviews to identify subgroup evidence: imaging for suspected hepatocellular carcinoma in the non-cirrhotic liver
Authors: Oerbekke Michiel S. , de Man Robert A. , van Vilsteren Frederike G. I. , Nijkamp Maarten W. , Tjwa Eric , Gaasterland Charlotte M. W. , van der Laan Maarten J. , Hooft Lotty 
Published: October 2024

AbstractWe aim to illustrate the role of complete and transparent reporting coupled with access to data sourced from published systematic reviews, especially assisting in the identification of evidence for subgroups within the context of a rare disease. To accomplish this principle, we provide a real-world example encountered during the revision of the Dutch clinical practice guideline for hepatocellular carcinoma. Specifically, we retrieved insights from two Cochrane reviews to identify direct evidence concerning the diagnostic test accuracy of computed tomography and magnetic resonance imaging for detecting hepatocellular carcinomas in suspected patients without liver cirrhosis. Through reusing the Cochrane review authors’ efforts already undertaken in their exhaustive literature search and selection, we successfully identified relevant direct evidence for this subgroup of suspected patients without cirrhosis and performed an evidence synthesis within the constraints of limited resources for the guideline revision. This approach holds the potential for replication in other subgroups in the context of rare diseases, contingent on the transparent and complete reporting of systematic reviews, as well as the availability and accessibility of their extracted data. Consequently, we underscore the importance of adhering to established reporting guidelines for systematic reviews, while simultaneously advocating for increased availability and accessibility to data. Such practices would not only increase the transparency and reproducibility of systematic reviews but could also increase reusability of their data. In turn, the increased reusability could result in reduced resource utilization in other sectors such as the guideline developing community as we show in our example.
Resilience and coping during protracted conflict: a comparative analysis of general and evacuees populations
Authors: Marciano Hadas , Kimhi Shaul , Eshel Yohanan , Adini Bruria 
Published: October 2024

Abstract
Background
On October 7th, 2023, Hamas launched a surprise attack on Israel, triggering a conflict with Israel in the Gaza Strip. This ongoing war, now six months old, has also seen threats from Hezbollah in Lebanon, as well as from Yemen and Iran. The precarious security situation along Israel’s southern and northern borders led to extensive evacuations, with residents relocating within Israel under uncertain conditions concerning their return and property safety. This study compares resilience (societal, SR; community, CR; and individual, IR), hope, morale, distress symptoms (anxiety and depression symptoms), and perceived danger between general Hebrew-speaking adults and evacuee adults a few months post-conflict initiation.

Methods
Data was collected using structured self-reported questionnaires focusing on resilience and coping strategies, administered through two online panel companies. The general population data was collected from January 14–21, 2024 (N = 1,360), and the evacuees’ data from March 1–9, 2024 (N = 372; 133 from the north, 239 from the south).

Results
Evacuees reported lower SR and CR, hope, and morale, and higher distress symptoms and perceived danger compared to the general population. No differences in IR were found. Regression analyses identified different primary predictors of SR for each group: hope for the general population and governmental support for evacuees. Additionally, IR significantly predicted outcomes only among evacuees, whereas age, religiosity, and education were significant predictors solely in the general population. One notable similarity emerged: CR served as the second most influential predictor in both samples.

Conclusions
The entire population of Israel is affected by the ongoing war, yet evacuees endure a disproportionately severe impact, with potential for increased harm as the conflict persists. The adjustment to a new wartime emergency routine is more complex for evacuees than for the general population. It is crucial for policy and decision-makers to address the distinct differences between evacuees and the general populace to effectively meet their specific needs. Yet, it should be acknowledged that the evacuees represent a heterogenic group, necessitating a detailed subdivision into subgroups to accurately assess and address their unique challenges.
Development and Portability of a Text Mining Algorithm for Capturing Disease Progression in Electronic Health Records of Patients With Stage IV Non–Small Cell Lung Cancer
Authors: Verschueren M.V. , Abedian Kalkhoran H. , Deenen M. , van den Borne B.E.E.M. , Zwaveling J. , Visser L.E. , Bloem L.T. , Peters B.J.M. , van de Garde E.M.W. 
Published: October 2024

PURPOSE
The objective was to develop and evaluate the portability of a text mining algorithm for prospectively capturing disease progression in electronic health record (EHR) data of patients with metastatic non–small cell lung cancer (mNSCLC) treated with immunochemotherapy.

METHODS
This study used EHR data from patients with mNSCLC receiving immunochemotherapy (between October 1, 2018, and December 31, 2022) in four Dutch hospitals. A text mining algorithm for capturing disease progression was developed in hospitals 1 and 2 and then transferred to hospitals 3 and 4 to evaluate portability. Performance metrics were calculated by comparing its outcomes with manual chart review. In addition, data were simulated to come available over time to assess performance in real-time applications. Median progression-free survival (PFS) was calculated using the Kaplan-Meier method to compare text mining with manual chart review.

RESULTS
During development and portability, the text mining algorithm performed well in capturing disease progression, with all performance scores >90%. When real-time performance was simulated, the performance scores in all four hospitals exceeded 90% from week 15 after the start of follow-up. Although the exact progression dates varied in 46 patients of 157 patients with progressive disease, the number of patients labeled with progression too early (n = 24) and too late (n = 22) was well balanced with discrepancies ranging from –116 to 384 days. Nevertheless, the PFS curves constructed with text mining and manual chart review were highly similar for each hospital.

CONCLUSION
In this study, an accurate text mining algorithm for capturing disease progression in the EHR data of patients with mNSCLC was developed. The algorithm was portable across different hospitals, and the performance over time was good, making this an interesting approach for prospective follow-up of multicenter cohorts.
Phase Ib Study for the Combination of Doxorubicin, Dacarbazine, and Nivolumab as the Upfront Treatment in Patients With Advanced Leiomyosarcoma: A Study by the Spanish Sarcoma Group (GEIS)
Authors: Martin-Broto Javier , Diaz-Beveridge Roberto , Moura David , Ramos Rafael , Martinez-Trufero Javier , Carrasco Irene , Sebio Ana , González-Billalabeitia Enrique , Gutierrez Antonio , Fernandez-Jara Javier , Hernández-Vargas Laura , Cruz Josefina , Valverde Claudia , Hindi Nadia 
Published: October 2024

PURPOSE
Doxorubicin, alongside a select group of cytotoxic agents, is capable of inducing an adaptive immune response via a well-established peculiar type of tumor cell death called immunogenic cell death (ICD). We hypothesize that combining doxorubicin and dacarbazine with nivolumab may enhance therapeutic efficacy by exerting synergy in the ICD circuit. We hereby present a phase Ib trial with this combination.

PATIENTS AND METHODS

Patients with advanced leiomyosarcoma and anthracycline-naïve were eligible. The initial dose level consisted of doxorubicin 75 mg/m
2
once on day 1, once every three weeks, followed by dacarbazine 400 mg/m
2
once on days 1 and 2, once every three weeks, plus nivolumab 360 mg once on day 2, once every 3 weeks, for six courses and then 1 year of nivolumab. A (–1) dose level was the same regimen but with nivolumab 240 mg. A classic 3 + 3 phase-I design was used to determine the recommended phase-II dose (RP2D). Secondary end points included overall response rate, safety profile, survival, and translational research.

RESULTS
From January 2002 to July 2023, 24 patients were enrolled and 23 were evaluable for efficacy, excluding one patient because of noncompliant dose. All patients were treated with the initial dose level, then the RP2D. Toxicity was mild, with the most frequent being grade 4 toxicity neutropenia (16.7%) and thrombocytopenia (8.3%), while no grade 5 toxicity occurred. The centrally reviewed objective response rate was as follows: partial response 56.5%, stable disease 39.1%, and progression 4.4%. The 6-month progression-free survival (PFS) rate was 80% (95% CI, 63 to 98). Dynamic increases of HMGB1 in blood significantly correlated with longer PFS.

CONCLUSION
This scheme of doxorubicin, dacarbazine, and nivolumab is feasible and well tolerated. Clinical activity is encouraging and the prognostic impact of HMGB1 supports the relevance of ICD activation. Further clinical research is already underway with this concept in leiomyosarcoma.
Chronic Pain Psychology in Neurology Practice
Authors: Serdarevic Mirsad 
Published: October 2024

ABSTRACT

OBJECTIVE
This article reviews the latest literature regarding chronic pain epidemiology and describes pain-specific psychological factors associated with the development and maintenance of chronic pain, mental health conditions that co-occur with chronic pain, and advances in the psychobehavioral treatment of chronic pain, including established treatments (ie, cognitive behavioral therapy [CBT], acceptance and commitment therapy, and mindfulness-based stress reduction) and emerging treatments (ie, pain reprocessing therapy).

LATEST DEVELOPMENTS
In addition to CBT and acceptance and commitment therapy for pain, numerous other psychological treatment modalities have been integrated into chronic pain management, including mindfulness-based stress reduction, mindfulness meditation, chronic pain self-management, relaxation response, pain neuroscience education, biofeedback, hypnosis, and, more recently, integrative psychological treatment for centralized pain. This article gives an overview of these methods and contextualizes their use within the standard psychological treatment of chronic pain.

ESSENTIAL POINTS
Guided by the biopsychosocial treatment model, pain psychologists use numerous evidence-based psychological methods to treat patients with chronic pain conditions. Familiarity with the psychological tools available for pain management will aid neurologists and their patients in navigating the psychological aspects of living with chronic pain.
Spine Pain
Authors: Williams Vernon B. 
Published: October 2024

ABSTRACT

OBJECTIVE
Spine pain is one of the most common presenting concerns in health care settings. This article reviews clinical strategies for evaluating and managing patients with spine pain.

LATEST DEVELOPMENTS
Minimally invasive interventional procedures, virtual reality, predictive analytics, neuromodulation, and other evolving technologies are significantly impacting the management of spine pain. Advances in modern pain science have also led to effective skills and treatment strategies, including patient interviews and queries for insight regarding pain, education, and cognitive restructuring, and adjusting the timing of examination (after reeducation) and examination techniques to encourage the experience of movement in the absence of assumed tissue damage. An evolving understanding of the influence of patient-centric thoughts, framing, emotional status, and cognitive restructuring’s influence on the brain’s response to perceived threat are important aspects of spine pain management.

ESSENTIAL POINTS
The correlation of clinical presentations with structural abnormalities is necessary but insufficient to evaluate and manage spine pain. Modern pain science acknowledges pain as a subjective experience but recognizes a critical distinction between tissue damage, nociception, and the experience of pain. What and how we communicate with patients, as well as evolving neuromodulation technologies, augment conventional approaches.
Use of Sugammadex in “Cannot Intubate, Cannot Ventilate” Scenarios: A Systematic Review of Case Reports
Authors: Abou Nafeh Nancy G. , Aouad Marie T. , Khalili Amro F. , Serhan Fatima G. , Sokhn Anthony M. , Kaddoum Roland N. 
Published: October 2024

After an induction dose of rocuronium, sugammadex in a dose of 16 mg.kg−
1 has been shown to provide early reversal of the neuromuscular blockade. However, the use of sugammadex to rescue a “cannot intubate, cannot ventilate” (CICV) scenario remains controversial. The aim of this systematic review was to discuss case reports describing the use of sugammadex as a rescue reversal in CICV scenarios and analyze the influencing factors potentially shaping the outcome of such reversal. The study has been registered on International Prospective Register of Systematic Reviews (PROSPERO) (CRD42024514255). We conducted a systematic review of the literature using PubMed, Medline, and Embase. Records were included if they were case reports or case series published in peer-reviewed journals, describing the administration of sugammadex as a rescue reversal in CICV scenarios, and including clinical outcomes and details of the management. Sources were last searched on November 30, 2023. The articles selected were initially screened based on their titles and abstracts, and then complete articles were examined to determine their eligibility and compliance with the inclusion criteria. Two independent authors evaluated the quality of the individual studies using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. Eight articles were included in our review. In all patients, CICV scenarios were declared minutes following induction. In 6/8 cases (75%), adequate spontaneous ventilation was restored after the administration of sugammadex. In the remaining 2 cases, sugammadex administration resulted in an obstructed pattern of breathing, and surgical airway was the successful rescue technique. There was wide variability in the sugammadex dose with a median (range) of 14 (5–16) mg.kg−1 and median timing (range) from rocuronium administration of 6 (2–10) minutes.
This case-report-based review is susceptible to reporting bias and may not encompass all pertinent data and adverse events. Also, cases with both favorable and unfavorable outcomes may have not been published, and the heterogeneity of cases limits the ability to draw definitive conclusions. In summary, although these case reports suggest that sugammadex might be helpful in CICV scenarios, further research is needed to confirm its effectiveness. However, due to the rare occurrence of CICV events, gathering sufficient data for conclusive evidence may be challenging.
The Effect of Social Media on Corporate Innovation: Evidence from Seeking Alpha Coverage
Authors: He Qiyang , Leung Henry , Qiu Buhui , Zhou Zhou 
Published: October 2024

Seeking Alpha (SA) is the most popular crowdsourced social media platform specializing in the financial analysis of U.S. firms, and it attracts over 17 million visitors per month. We find that firm coverage initiation on SA significantly promotes corporate innovation activities. SA coverage promotes corporate innovation by disseminating innovation-related information about the covered firm to external investors, thereby alleviating the firm’s financial constraints. Moreover, firms with higher information asymmetry, firms facing greater product market competition, and firms having lower levels of managerial short-termism reveal a greater increase in innovation outcomes following SA coverage initiation. Taken together, our findings suggest that third party-generated information on specialized social media mitigates the information asymmetry between firms and investors on corporate innovation activities and encourages corporate innovation. This paper was accepted by Bo Becker, finance. Supplemental Material: The data files are available at https://doi.org/10.1287/mnsc.2023.00995 .
Analysis of HOTS and LOTS of instructional questions in the English textbook "When English Rings a Bell" for grade VIII
Authors: Surono Surono , Pratolo Bambang Widi , Hanun Siti Latifah 
Published: October 2024

English textbooks have an essential role in learning English subjects for students in junior high school, so the quality of textbooks must be of high quality. To make students master English language skills, they need a good quality of textbooks to improve their critical thinking skills. This research aims to find out the representation of higher order thinking skills (HOTS) and lower order thinking skills (LOTS) and the appearance frequency in the instructional questions in English textbook entitled “When English Rings A Bell” grade VIII. This study used a content analysis with qualitative approach. Six chapters of the textbook were taken as the sample. Observation and note-taking techniques were used to collect the data using observation sheet. The data were analyzed by using Miles’s et al. model regarding coding method. The research findings showed that chapters I, VI, and VII represented LOTS with the most dominant in remembering and applying. Meanwhile, the appearance of LOTS and HOTS in chapters V and XII looked nearly in balance dominating the verb remembering for LOTS and the verbs evaluating and creating for HOTS. The realization of HOTS in the chapters was less than LOTS, except chapter XIII. After the instructional questions in all activities were categorized, the distribution of LOTS in the textbook appeared in 66 (58%) and HOTS in 47 questions (42%). It is concluded that the textbook distributed less evenly in HOTS and LOTS composition. It implies that the textbook still focuses on LOTS. It is recommended that the authors of the textbook balance the HOTS and LOTS in the instructional questions proportionally to encourage students to think critically. Teachers should creatively modify the instructional questions to meet the balance.
Engaging future educators: Perceptions of project-based learning among pre-service EYL teachers
Authors: Soviyah Soviyah 
Published: October 2024

In a globalized era with very rapid changes in life nowadays, project-based learning is considered as one of the most suitable learning models. Project-based learning provides learning that develops students' skills in communication, collaboration, critical thinking, and creativity. Therefore, EYL teacher education programs should provide opportunities for pre-service EYL teachers to improve their knowledge and skills in project-based learning. The purpose of this study was to determine pre-service EYL teachers' perceptions of project-based learning and its implementation. Conducted in 2022/2023, a total of 55 pre-service EYL teachers from TEYL PD course who were purposively selected participated in this study. Data were collected using a 25-item perception of project-based learning scale. Descriptive quantitative analysis was used to analyze the data. The results showed that out of 55 student respondents, 18 respondents (33%) had a very positive perception, 33 respondent (60%) had a positive perception, 4 respondents (7%) had a neutral perception, and no respondents had a negative perception.