bluuebunny/crossref_metadata_2025_split huggingface dataset:
SARIFA as a new histopathological biomarker is associated with adverse clinicopathological characteristics, tumor-promoting fatty-acid metabolism, and might predict a metastatic pattern in pT3a prostate cancer
Authors: Enke Johanna S. , Groß Matthias , Grosser Bianca , Sipos Eva , Steinestel Julie , Löhr Phillip , Waidhauser Johanna , Lapa Constantin , Märkl Bruno , Reitsam Nic G. 
Published: January 2024

Abstract
Background
Recently, we introduced Stroma-AReactive-Invasion-Front-Areas (SARIFA) as a novel hematoxylin–eosin (H&E)-based histopathologic prognostic biomarker for various gastrointestinal cancers, closely related to lipid metabolism. To date, no studies on SARIFA, which is defined as direct tumor-adipocyte-interaction, beyond the alimentary tract exist. Hence, the objective of our current investigation was to study the significance of SARIFA in pT3a prostate cancer (PCa) and explore its association with lipid metabolism in PCa as lipid metabolism plays a key role in PCa development and progression.

Methods
To this end, we evaluated SARIFA-status in 301 radical prostatectomy specimens and examined the relationship between SARIFA-status, clinicopathological characteristics, overall survival, and immunohistochemical expression of FABP4 and CD36 (proteins closely involved in fatty-acid metabolism). Additionally, we investigated the correlation between SARIFA and biochemical recurrence-free survival (BRFS) and PSMA-positive recurrences in PET/CT imaging in a patient subgroup. Moreover, a quantitative SARIFA cut-off was established to further understand the underlying tumor biology.

Results
SARIFA positivity occurred in 59.1% (n = 178) of pT3a PCas. Our analysis demonstrated that SARIFA positivity is strongly associated with established high-risk features, such as R1 status, extraprostatic extension, and higher initial PSA values. Additionally, we observed an upregulation of immunohistochemical CD36 expression specifically at SARIFAs (p = 0.00014). Kaplan–Meier analyses revealed a trend toward poorer outcomes, particularly in terms of BRFS (p = 0.1). More extensive tumor-adipocyte interaction, assessed as quantity-dependent SARIFA-status on H&E slides, is also significantly associated with high-risk features, such as lymph node metastasis, and seems to be associated with worse survival outcomes (p = 0.16). Moreover, SARIFA positivity appeared to be linked to more distant lymph node and bone metastasis, although statistical significance was slightly not achieved (both p > 0.05).

Conclusions
This is the first study to introduce SARIFA as easy-and-fast-to-assess H&E-based biomarker in locally advanced PCa. SARIFA as the histopathologic correlate of a distinct tumor biology, closely related to lipid metabolism, could pave the way to a more detailed patient stratification and to the development of novel drugs targeting lipid metabolism in pT3a PCa. On the basis of this biomarker discovery study, further research efforts on the prognostic and predictive role of SARIFA in PCa can be designed.
Differential efficacy of tyrosine kinase inhibitors according to the types of EGFR mutations and agents in non-small cell lung cancer: a real-world study
Authors: Kim Tae-Hwan , Choi Jin-Hyuk , Ahn Mi Sun , Lee Hyun Woo , Kang Seok Yun , Choi Yong Won , Koh Young Wha , Sheen Seung-Soo 
Published: January 2024

Abstract
Background
Both first and second-generation EGFR-TKIs are recommended in advanced NSCLC with common EGFR mutations. However, there are few data on the difference in efficacy of EGFR-TKIs based on the type of EGFR mutation and agents.

Methods
This retrospective real-world study evaluated the outcomes and clinicopathologic characteristics, including the type of EGFR mutations, of 237 advanced NSCLC patients treated with first- or second-generation (afatinib) EGFR-TKIs as first-line therapy.

Results
The median progression-free survival (PFS) and overall survival (OS) of all patients were 11 months (M) and 25M, respectively. In the univariate analysis, patients with exon 19 deletion (del) (n=130) had significantly longer median OS compared to those with other mutations (L858R: 84, others: 23) (30 vs. 22 M, p=0.047), without a difference in PFS (p=0.138). Patients treated with afatinib (n=60) showed significantly longer median OS compared to those treated with first-generation TKIs (gefitinib: 159, erlotinib: 18) (30 vs. 23 M, p=0.037), without a difference in PFS (p=0.179). In patients with exon 19 del, there was no significant difference in median PFS (p=0.868) or OS (p=0.361) between patients treated with afatinib and those treated with first-generation TKIs, while significantly better PFS (p=0.042) and trend in OS (p=0.069) were observed in patients receiving afatinib in other mutations. Exon 19 del was independently associated with favorable OS (p=0.028), while age >70 years (p=0.017), ECOG performance status ≥2 (p=0.001), primary metastatic disease (p=0.007), and synchronous brain metastasis (p=0.026) were independent prognostic factors of poor OS.

Conclusions
The EGFR exon 19 del was associated with favorable OS in advanced NSCLC patients receiving first-line EGFR-TKIs. Moreover, in patients with exon 19 del, first-generation TKIs seem to be a reasonable treatment option if osimertinib is unavailable.
Survival outcome of different treatment sequences in patients with locally advanced and metastatic pancreatic cancer
Authors: Fan Mengjiao , Deng Guochao , Ma Yue , Si Haiyan , Wang Zhikuan , Dai Guanghai 
Published: January 2024

Abstract
Background
Despite some therapeutic advances, improvement in survival rates of unresectable and/or metastatic pancreatic ductal adenocarcinoma (PDAC) has been minimal over recent decade. We aimed to evaluate the impact of different treatment sequences on clinical outcomes of advanced PDAC at our academic institution.

Methods
In this single institution retrospective analysis, we assessed characteristics and survival rates of unresectable and/or metastatic pancreatic PDAC patients who started a systemic treatment between 01/2015 and 12/2021. Survival analyses were performed by Kaplan-Meier and Cox proportional hazards model.

Results
The number of 285 patients received at least two lines of treatment, but only 137 patients were suitable for third-line treatment. Subgroup analysis showed that thirty-seven patients received A line (gemcitabine/nab-paclitaxel or nab-paclitaxel combined therapy to FOLFIRINOX) therapy, 37 patients received B line (nab-paclitaxel combined therapy to gemcitabine combined therapy to FOLFIRINOX) therapy, 21 patients received C line (nab-paclitaxel combined therapy to gemcitabine combined therapy to oxaliplatin or irinotecan combined therapy) therapy. Survival rates for different treatment lines were significantly different and median overall survival (OS) was 14.00, 18.00, and 14.00 months, respectively (p<0.05).

Conclusion
Our study provides real-world evidence for the effectiveness of different treatment sequences and underscores the treatment sequences on survival outcome when considering the entire management in advanced PDAC.
An integrated model incorporating deep learning, hand-crafted radiomics and clinical and US features to diagnose central lymph node metastasis in patients with papillary thyroid cancer
Authors: Gao Yang , Wang Weizhen , Yang Yuan , Xu Ziting , Lin Yue , Lang Ting , Lei Shangtong , Xiao Yisheng , Yang Wei , Huang Weijun , Li Yingjia 
Published: January 2024

Abstract
Objective
To evaluate the value of an integrated model incorporating deep learning (DL), hand-crafted radiomics and clinical and US imaging features for diagnosing central lymph node metastasis (CLNM) in patients with papillary thyroid cancer (PTC).

Methods
This retrospective study reviewed 613 patients with clinicopathologically confirmed PTC from two institutions. The DL model and hand-crafted radiomics model were developed using primary lesion images and then integrated with clinical and US features selected by multivariate analysis to generate an integrated model. The performance was compared with junior and senior radiologists on the independent test set. SHapley Additive exPlanations (SHAP) plot and Gradient-weighted Class Activation Mapping (Grad-CAM) were used for the visualized explanation of the model.

Results
The integrated model yielded the best performance with an AUC of 0.841. surpassing that of the hand-crafted radiomics model (0.706, p < 0.001) and the DL model (0.819, p = 0.26). Compared to junior and senior radiologists, the integrated model reduced the missed CLNM rate from 57.89% and 44.74–27.63%, and decreased the rate of unnecessary central lymph node dissection (CLND) from 29.87% and 27.27–18.18%, respectively. SHAP analysis revealed that the DL features played a primary role in the diagnosis of CLNM, while clinical and US features (such as extrathyroidal extension, tumour size, age, gender, and multifocality) provided additional support. Grad-CAM indicated that the model exhibited a stronger focus on thyroid capsule in patients with CLNM.

Conclusion
Integrated model can effectively decrease the incidence of missed CLNM and unnecessary CLND. The application of the integrated model can help improve the acceptance of AI-assisted US diagnosis among radiologists.
Serum levels of interleukin-33 and mesencephalic astrocyte derived neurotrophic factors in patients with major depressive disorder: a cross-sectional comparative design
Authors: Nahar Zabun , Nowshin Delruba Tabassum , Roknuzzaman A. S. M. , Sohan Md. , Islam Salsabil , Qusar M. M. A. Shalahuddin , Islam Md. Rabiul 
Published: January 2024

Abstract
Background
Major depressive disorder (MDD) is a debilitating health condition that has significant morbidity and mortality rates. Depression can be caused due to social, biological, environmental, psychological, and genetic factors. A few biological processes have been proposed as the pathophysiological pathways of depression. Neurotrophic factors and inflammatory cytokines have been linked to depression. Thus, we aimed to investigate the serum interleukin-33 (IL-33) and mesencephalic astrocyte-derived neurotrophic factor (MANF) in MDD patients and corresponding healthy controls (HCs).

Method
This study involved the inclusion of 129 MDD patients and 125 HCs matched by sex and age. A psychiatrist evaluated the study participants following DSM-5 criteria. The severity of the illness was assessed utilizing the Hamilton Depression Rating Scale (Ham-D). The serum concentrations of IL-33 and MANF were measured using enzyme-linked immunosorbent assay (ELISA) kits.

Results
The mean serum levels of IL-33 were decreased (159.12 ± 6.07 pg/ml vs. 180.60 ± 8.64 pg/ml, p = 0.042), and the MANF levels were increased (5.40 ± 0.19 ng/ml vs. 4.46 ± 0.21 ng/ml, p = 0.001) in MDD patients when compared to HCs.

Conclusions
The current study proposes that lower IL-33 and higher MANF serum levels are associated with MDD progression and depression severity. These biomarkers could be used as risk assessment tools for MDD. We recommend more investigation, including a significant population, to determine the precise function of IL-33 and MANF in depression.
The relationship between academic stress and depression among college students during the COVID-19 pandemic: a cross-sectional study from China
Authors: Chen Baoling , Wang Weiwei , Yang Shanlin 
Published: January 2024

Abstract
Background
The COVID-19 pandemic is a global public health crisis. During the COVID-19 pandemic, mental health has attracted great attention. However, there is a lack of research on the relationship between academic stress and depression in Chinese college students and its mechanisms. Therefore, this study investigated the mechanisms of coping style, sleep quality, and interpersonal relationship in academic stress and depression among college students.

Methods
The cross-sectional study was conducted from May to June 2022 through face-to-face questionnaires with college students in Anhui Province, China. The questionnaires included sociodemographic information, the Simplified Coping Style Questionnaire, and the Self-Rating Depression Scale. Ordered logistic regression model was used to study the relationship between academic stress and depression of college students during the COVID-19 pandemic through the mechanism analysis of coping style, sleep quality and interpersonal relationship.

Results
Two thousand thirty-three Chinese college students participated in the study, including 1,285 female and 748 male college students, with an average age 19.81 years old (SD = 1.22 years old). The results showed that (1) Academic stress had a significant impact on depression in college students under the background of COVID-19 (p < 0.01); (2) The influence of academic stress on depression had a difference in work experience as student cadres, which showed that college students who had served as student cadres were less affected by academic stress (p < 0.10), college students who had not served as student cadres were greatly affected by the academic stress (p < 0.05); (3) College students’ attitudes toward COVID-19 significantly affected depression (p < 0.01); (4) Counselors’ concern had a significant impact on college students’ depression (p < 0.01); (5) Positive coping style, high quality sleep and good interpersonal relationship were the important mechanisms of the impact of academic stress on college students’ depression.

Conclusions
This study provides new findings for in-depth understanding of the relationship between academic stress and depression among college students in China during the COVID-19 pandemic, which is conducive to the provision of targeted intervention measures for the mental health of college students.
Orthopnea secondary to brachial plexitis with bilateral diaphragmatic paralysis
Authors: El Labban Mohamad , Bauer Philippe R. 
Published: January 2024

Abstract
Background
Diaphragmatic paralysis can present with orthopnea. We report a unique presentation of bilateral diaphragmatic paralysis, an uncommon diagnosis secondary to an unusual cause, brachial plexitis. This report thoroughly describes the patient’s presentation, workup, management, and outcome. It also reviews the literature on diaphragmatic paralysis and Parsonage-Turner syndrome.

Case presentation
A 50-year-old male patient developed insidious orthopnea associated with left shoulder and neck pain over three months with no associated symptoms. On examination, marked dyspnea was observed when the patient was asked to lie down; breath sounds were present and symmetrical, and the neurological examination was normal. The chest radiograph showed an elevated right hemidiaphragm. Echocardiogram was normal. There was a 63% positional reduction in Forced Vital Capacity and maximal inspiratory and expiratory pressures on pulmonary function testing. The electromyogram was consistent with neuromuscular weakness involving both brachial plexus and diaphragmatic muscle (Parsonage and Turner syndrome).

Conclusions
Compared to unilateral, bilateral diaphragmatic paralysis may be more challenging to diagnose. On PFT, reduced maximal respiratory pressures, especially the maximal inspiratory pressure, are suggestive. Parsonage-Turner syndrome is rare, usually with unilateral diaphragmatic paralysis, but bilateral cases have been reported.
In vitro anti-HIV, cytotoxicity and nutritional analysis of Trianthema portulacastrum L. (Aizoaceae)
Authors: Jimoh Mahboob Adekilekun , Jimoh Muhali Olaide , Bello Mujidat , Raimi Idris Olawale , Okunlola Gideon Olarewaju , Mkhwanazi Nompumelelo , Laubscher Charles Petrus 
Published: January 2024

AbstractThe development of antiretroviral therapy has brought a tremendous relief to the world as it minimizes mortality, reduces HIV transmission, and suppresses progression in infected patients. However, the orthodox antiretroviral therapy is faced with limitations which have necessitated a continuous search for more novel plant-based antiviral compounds, which can bypass the existing barriers created by drug resistance and target more viral proteins. Despite the edibility and enormous pharmacological benefits of T. portulacastrum, little is known about its nutrient profiles and potential use as a natural source of antiviral drug. This study focuses on the full feed analysis and anti-HIV potential of two biotypes of T. portulacastrum. Ethanolic extracts of both biotypes of T. portulacastrum (T01 and T02) had significant inhibitory effects on the level of replication of the HIV-1. Both extracts induced the inhibition of at least 50% of the HIV-1 viral load at considerably low IC50 values of 1.757 mg/mL (T01) and 1.205 mg/mL (T02) which is comparable to the AZT standard. The protein composition ranged between 8.63-22.69%; fat (1.84-4.33%); moisture (7.89-9.04%); fibre (23.84-49.98%); and carbohydrate content (38.54-70.14%). Mineral contents of tested T. portulacastrum varied considerably in different parts of the plant. Nitrogen N mineral ranged between 13.8-36.3 mg/g; sodium Na (2.0-14.0 mg/g); potassium K (14.0-82.0 mg/g); magnesium Mg (2.8-7.1 mg/g); calcium Ca (9.1-24.7 mg/g); phosphorus P (1.3-3.6 mg/g); iron Fe (193.5-984.0 ppm); zinc Zn (42.5-96.0 ppm); manganese Mn (28.5-167.5 ppm); and copper Cu (2.0-8.5 ppm). These mineral values are comparable or higher than values quoted for common vegetables, suggesting that T. portulacastrum is a nutrient-dense vegetable that could provide alternative sources of antiviral nutrients to HIV-infected individuals. Further studies are recommended to unravel key metabolites responsible for high nutrient profiles and antiretroviral effects in T. portulacastrum.
Satisfaction and use of the didactic simulator for learning the nursing process: an observational study
Authors: Cruz-Barrientos Alberto , Cotobal-Calvo Eva Manuela , Sainz-Otero Ana María , De-La-Fuente-Rodríguez José Manuel , Román-Sánchez Daniel , Carmona-Barrientos Inés 
Published: January 2024

Abstract
Introduction
The implementation of Information and Communication Technology (ICT) in daily healthcare practice has become standardized. In relation to education within the nursing degree, ICTs make it possible to carry out practical immersion training from the” classroom or from any other place with an Internet connection, as evidenced by circumstances that have occurred in recent years, such as the pandemic caused by COVID-19.

Objective
Design and assess a didactic simulation program for the training of the nursing process that promotes learning in the nursing care

Methodology
The methodological approach is quantitative and it is a descriptive cross-sectional study. The sampling method used was non-probabilistic by convenience.

Results
When observing the comparison of the averages of student satisfaction with respect to the didactic simulator, it is worth mentioning that all the items are above 2.80 on a score in which “0” is the minimum value and “5” the maximum value.
The results of the use of the computer tool by the students, we highlight as significant data that all the items present an average equal to or lower than 3.04 out of 7, where “1” corresponds to a lot of use and “7” to little use.

Conclusion
The implication of ICT in the teaching–learning process among Nursing Degree students, it is considered optimal. when analyzing the answers obtained in the items that refer to a higher ease in the execution of development of Care plans, a fundamental work in Nursing performance.
Engaging stakeholders to level up COPD care in LMICs: lessons learned from the “Breathe Well” programme in Brazil, China, Georgia, and North Macedonia
Authors: Fernandes Genevie , Williams Siân , Adab Peymané , Gale Nicola , de Jong Corina , de Sousa Jaime Correia , Cheng KK , Chi Chunhua , Cooper Brendan G. , Dickens Andrew P. , Enocson Alexandra , Farley Amanda , Jolly Kate , Jowett Sue , Maglakelidze Maka , Maghlakelidze Tamaz , Martins Sonia , Sitch Alice , Stamenova Aleksandra , Stavrikj Katarina , Stelmach Rafael , Turner Alice , Pan Zihan , Pang Hui , Zhang Jianxin , Jordan Rachel E. 
Published: January 2024

Abstract
Background
Effective stakeholder engagement in health research is increasingly being recognised and promoted as an important pathway to closing the gap between knowledge production and its use in health systems. However, little is known about its process and impacts, particularly in low-and middle-income countries. This opinion piece draws on the stakeholder engagement experiences from a global health research programme on Chronic Obstructive Pulmonary Disease (COPD) led by clinician researchers in Brazil, China, Georgia and North Macedonia, and presents the process, outcomes and lessons learned.

Main body
Each country team was supported with an overarching engagement protocol and mentored to develop a tailored plan. Patient involvement in research was previously limited in all countries, requiring intensive efforts through personal communication, meetings, advisory groups and social media. Accredited training programmes were effective incentives for participation from healthcare providers; and aligning research findings with competing policy priorities enabled interest and dialogue with decision-makers. The COVID-19 pandemic severely limited possibilities for planned engagement, although remote methods were used where possible. Planned and persistent engagement contributed to shared knowledge and commitment to change, including raised patient and public awareness about COPD, improved skills and practice of healthcare providers, increased interest and support from clinical leaders, and dialogue for integrating COPD services into national policy and practice.

Conclusion
Stakeholder engagement enabled relevant local actors to produce and utilise knowledge for small wins such as improving day-to-day practice and for long-term goals of equitable access to COPD care. For it to be successful and sustained, stakeholder engagement needs to be valued and integrated throughout the research and knowledge generation process, complete with dedicated resources, contextualised and flexible planning, and commitment.