bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of lymph node degeneration on metastases in prostate cancer: or why we must look for a needle in a haystack
Authors: Gödde Daniel , Degener Stephan , Walles Christine , Keller Rosalie , Dreger Nici Markus , Graf Katharina , von Rundstedt Friedrich-Carl , Kvasnicka Hans Michael , Krege Susanne , Störkel Stephan 
Published: January 2023

Abstract
Background
To evaluate the incidence of lymph node degeneration and its association with nodal metastatic pattern in prostate cancer.

Methods
A retrospective analysis of the submitted lymph node specimen of 390 prostatectomies in 2011 was performed. All lymph nodes were histologically re-evaluated and the degree of lymph node degeneration e.g. lipomatous atrophy, capsular and framework fibrosis, and calcifications as well as the lymph node size were recorded. Lymph node degeneration was compared in the anatomic regions of the pelvis as well as in lymph nodes with and without metastases of prostatic cancer.

Results
Eighty-one of 6026 lymph nodes demonstrated metastases. Complete histologic examination with analysis of a complete cross-section was possible in 5173 lymph nodes including all lymph nodes with metastases. The incidence of lymph node degeneration was different across the various landing sites. Lymph node metastases were primarily detected in less degenerative and therefore more functional lymph nodes. In metastatic versus non-metastatic lymph nodes low lipomatous atrophy was reported in 84.0% versus 66.7% (p = 0.004), capsular fibrosis in 14.8% versus 35.4% (p < 0.001), calcifications in 35.8% versus 46.1% (p = 0.072) and framework fibrosis in 69.8% versus 75.3% (p = 0.53). Metastases were also identified more frequently in larger than in smaller lymph nodes (63.0% vs. 47.5%; p = 0.007).

Conclusions
Degenerative changes in pelvic lymph nodes are commonly detectable but occur with variable frequency in the various nodal landing sites in the pelvis. The degree of lymph node degeneration of single lymph nodes has a significant influence on whether a lymph node is infiltrated by tumor cells and may harbour metastases.
Value of preoperative ureteral wall thickness in prediction of impaction of ureteric stones stratified by size in laser ureteroscopic lithotripsy
Authors: Abdrabuh Abdrabuh M. , El-Agamy El-Sayed I. , Elhelaly Mohamed A. , Abouelgreed Tamer A. , Abdel-Al Ibrahim , Youssof Hamada A. , Elatreisy Adel , Shalkamy Osama , Elebiary Mohamed , Agha Mohammed , Tagreda Ibrahim , Alrefaey Ahmed , Elawadey Elsayed 
Published: January 2023

Abstract
Objectives
To evaluate the role of preoperative UWT in the prediction of impaction of ureteral stones stratified according to stone size in ureteroscopic laser lithotripsy.

Patient and methods
This study included 154 patients submitted to URSL for ureteral stones. Radiological data comprised the presence of hydronephrosis, anteroposterior pelvic diameter (PAPD), proximal ureteric diameter (PUD), and maximum UWT at the stone site. Collected stone characteristics were stone size, side, number, site, and density.

Results
The study included 154 patients subjected to URSL. They comprised 74 patients (48.1%) with impacted stones and 80 (51.9%) with non-impacted stones. Patients were stratified into those with stone size ≤ 10 mm and others with stone size > 10 mm. In the former group, we found that stone impaction was significantly associated with higher PAPD, PUD, and UWT. In patients with stone size > 10 mm, stone impaction was related to higher UWT, more stone number, and higher frequency of stones located in the lower ureter. ROC curve analysis revealed good power of UWT in discrimination of stone impaction in all patients [AUC (95% CI) 0.65 (0.55–0.74)] at a cut-off of 3.8 mm, in patients with stone size ≤ 10 mm [AUC (95% CI) 0.76 (0.61–0.91)] at a cut-off of 4.1 mm and in patients with stone size > 10 mm [AUC (95% CI) 0.72 (0.62–0.83)] at a cut-off of 3.0 mm.

Conclusions
Stratifying ureteric stones according to size would render UWT a more practical and clinically-oriented approach for the preoperative prediction of stone impaction.
Coincidence of primary adrenocortical carcinoma and melanoma: three CASE reports
Authors: Ko Ye Lynn , Kumar Vaishnavi , Lippert Juliane , Diaz-Cano Salvador , Skordilis Kassiani , Kimpel Otilia , Kircher Stefan , Asia Miriam , Elhassan Yasir S. , Altieri Barbara , Ronchi Cristina L. 
Published: January 2023

Abstract
Background
Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a heterogeneous prognosis, while adrenal metastasis from other primary cancers, including melanoma, may occur more frequently. ACC may rarely occur as part of familial cancer syndromes, but even in sporadic cases, a significant proportion of patients had other malignancies before or after diagnosis of ACC. Herein we present three cases where sporadic ACC was identified in patients with coexistent or previous history of melanoma.

Case description
Patient 1 - A 37-yr-old man with a superficial spreading BRAF-positive melanoma was found to harbour a progressively growing left adrenal mass. Initially, he was suspected of having adrenal metastasis, but the histology after adrenalectomy confirmed ACC. Patient 2 - A 68-year-old man with a history of recurrent BRAF-positive melanoma was diagnosed with disseminated metastatic melanoma recurrence, including a rapidly enlarging left adrenal mass. Consequently, he underwent left adrenalectomy, and histology again confirmed ACC. Patient 3 – A 50-yr-old man was referred with histological diagnosis of metastatic ACC. He had a background history of pT1 melanoma.
We undertook targeted sequencing of ACC tissue samples in all cases. Somatic variants were observed in the known driver genes CTNNB1 (Patient 1), APC and KMT2D (Patient 2), and APC and TP53 (Patient 3). Germline TP53 variants (Li-Fraumeni syndrome) were excluded in all cases.
Retrospective review of our patient cohort in the last 21 years revealed a frequency of 0.5% of histologically diagnosed melanoma metastasis among patients referred for adrenal masses. On the other hand, 1.6% of patients with histologically confirmed ACC had a previous history of melanoma.

Conclusion
Sporadic ACC can occur in the background of melanoma, even if adrenal metastasis might appear to be the most likely diagnosis. Coexistent primary adrenal malignancy should be considered and investigated for in all patients with a history of melanoma with suspicious adrenal lesions.
Exploring the social accountability challenges of nursing education system in Iran
Authors: Ezzati Ebrahim , Molavynejad Shahram , Jalali Amir , Cheraghi Mohammad-Ali , Jahani Simin , Rokhafroz Dariush 
Published: January 2023

Abstract
Background
Nursing education in Iran is one of the disciplines of medical sciences and it needs a design tailored to the community needs in terms of theoretical and clinical approaches. This system is currently faced with various challenges. This study aims to explore the challenges of Iranian nursing education system to address community needs.

Methods
A study was carried out through an exploratory descriptive qualitative design with content analysis method. In-depth semi-structured interviews were conducted with 21 participants from the nursing society, selected through purposive sampling. The interviews were continued until data saturation. Data analysis was performed simultaneous with data collection by using Graneheim & Lundman approach.

Results
Based on the interviews and simultaneous analyses, a total of 471 codes, 14 subcategories, six main categories, and two themes were extracted. The first theme, “system structure," consisted of three categories: "the need for ongoing revision of curriculum," "the need to recruit qualified students," and "the need for a proportionate educational environment." The second theme was “the education process” with three categories "the need for purposive educational design," "the need for purposive monitoring and feedback," and "the need for appropriate and early interaction with the community." The participants emphasized the continuous revision of the educational curriculum based on the current needs of the community and community-based nursing education.

Conclusions
In general, the results showed that Iranian nursing education system is faced with many challenges in the educational system structure and processes. It is necessary to make appropriate plans to enhance the status of the educational system structure and develop educational designs to address community needs using a hospital/community-based approach.
Risk of heart failure in elderly patients with atrial fibrillation and diabetes taking different oral anticoagulants: a nationwide cohort study
Authors: Lin Shu-Man , Liu Peter Pin-Sung , Tu Yu-Kang , Lai Edward Chia-Cheng , Yeh Jih-I , Hsu Jin-Yi , Munir Kashif M. , Peng Carol Chiung-Hui , Huang Huei-Kai , Loh Ching-Hui 
Published: January 2023

Abstract
Background
Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin.

Methods
A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged  ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models.

Results
The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74–0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80–0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74–0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68–0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60–0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings.

Conclusions
This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms.
Current view of liver cancer cell-of-origin and proposed mechanisms precluding its proper determination
Authors: Gromowski Tomasz , Lukacs-Kornek Veronika , Cisowski Jaroslaw 
Published: January 2023

AbstractHepatocellular carcinoma and intrahepatic cholangiocarcinoma are devastating primary liver cancers with increasing prevalence in many parts of the world. Despite intense investigation, many aspects of their biology are still largely obscure. For example, numerous studies have tackled the question of the cell-of-origin of primary liver cancers using different experimental approaches; they have not, however, provided a clear and undisputed answer. Here, we will review the evidence from animal models supporting the role of all major types of liver epithelial cells: hepatocytes, cholangiocytes, and their common progenitor as liver cancer cell-of-origin. Moreover, we will also propose mechanisms that promote liver cancer cell plasticity (dedifferentiation, transdifferentiation, and epithelial-to-mesenchymal transition) which may contribute to misinterpretation of the results and which make the issue of liver cancer cell-of-origin particularly complex.
Distance from human dwellings differentially affects the efficacy of a synthetic cattle urine odour lure to trap malaria vectors
Authors: Katusi Godfrey C. , Makayula Samwely M. , Govella Nicodem J. , Mnyone Ladslaus L. , Hill Sharon R. , Ignell Rickard 
Published: January 2023

Abstract
Background
Cost–effective outdoor–based devices for surveillance and control of outdoor mosquito vector populations can substantially improve their efficacy when baited with synthetic human and animal odours. This study aimed at assessing the dose–dependent efficacy of a previously developed synthetic cattle urine odour to lure malaria vectors, and other mosquito species, to traps placed at different distances from human dwellings outdoors.

Methods
The efficacy of the cattle urine odour lure was assessed through a 5 × 5 Latin square design, using two sets of 5 Suna traps placed at either 1.5 m or 5 m from an adjacent human dwelling, in the rural village of Sagamaganga, Tanzania. Each trap was deployed with one of four doses of the synthetic cattle urine odour blend or a solvent control (heptane). Traps were rotated daily so that each dose and control visited each position twice over a period of 20 experimental nights. The relative attractiveness of each treatment dose and control was compared using a generalized linear mixed model for each species caught.

Results
A total of 1568 mosquitoes were caught, of which 783 were anophelines and 785 were culicines. Of the anophelines, 41.6 and 58.3% were primary and secondary vector species, respectively. Unfed and fed females of the primary vector, Anopheles arabiensis, were caught dose–dependently, close to human dwellings (1.5 m), whereas unfed, fed and gravid secondary vector Anopheles pharoensis females were caught dose–dependently, but at a farther distance from the dwellings (5 m). Females of Culex spp. were caught dose–dependently in similar numbers irrespective of the distance from human dwellings.

Conclusions
This study further clarifies the factors to be considered for the implementation of outdoor trapping using the synthetic cattle urine lure to target exophilic and exophagic malaria vectors, for which efficient surveillance and control tools are currently lacking. The findings resulting from this study make significant progress in providing the needed information to overcome the regulatory obstacles to make this tool available for integrated vector management programs, including registration, as well as evaluation and regulation by the World Health Organization.
Prospective association between phthalate exposure in childhood and liver function in adolescence: the Ewha Birth and Growth Cohort Study
Authors: Lee Seonhwa , Lee Hye Ah , Park Bohyun , Han Hyejin , Hong Young Sun , Ha Eun Hee , Park Hyesook 
Published: January 2023

Abstract
Background
Phthalate exposure is ubiquitous due to the widespread use of plastic products in daily life, and affects several health outcomes, including metabolic diseases. In this study, we evaluated the effects of phthalate exposure in childhood on liver function in adolescence.

Methods
Among 164 Ewha Birth and Growth Cohort Study participants followed up during two exposure periods (when the children were aged 3–5 and 7–9 years), 126 were followed up at age 10–15 years. To investigate the relationship between phthalate exposure during the two periods and liver enzyme levels (ALT, AST, γ-GTP) in adolescence, differences between groups and the dose–response relationship were analyzed. In addition, we investigated differences in liver enzymes between groups based on the combined exposure levels (high or low) during the two periods. The interaction effect between phthalates and BMI on liver enzyme levels was evaluated, stratified by sex.

Results
In the 3–5 year-old exposure period, ALT levels tended to increase as MECPP levels increased, while γ-GTP levels tended to increase as MiBP, MnBP, and ∑DBP levels increased. In addition, the group exposed to consistently high levels of phthalates at both time points had higher liver enzyme levels compared to the group that had lower exposure. In particular, the interaction effect between some phthalate metabolites and BMI in 3–5 year olds affected AST and γ-GTP levels in adolescence only in girls.

Conclusions
Exposure to phthalates in daily life during childhood affects liver enzyme levels in adolescence. Elevated liver enzyme levels are associated with the development of metabolic syndrome, implying that attention should be paid to phthalate exposure during childhood.
Fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) as predictive values for nonalcoholic steatohepatitis (NASH)
Authors: Wagner Jonas , Kumar Yogesh , Lautenbach Anne , von Kroge Philipp , Wolter Stefan , Mann Oliver , Izbicki Jakob , Gagliani Nicola , Duprée Anna 
Published: January 2023

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD), especially nonalcoholic steatohepatitis (NASH) increases the risk for liver cirrhosis. Noninvasive tests for NAFLD/NASH exist, but they are unreliable and thus liver biopsy remains the standard for diagnosis and new noninvasive diagnostic approaches are of great interest. The aim of this study was to test whether the serum levels of fatty acid-binding protein-4 (FABP4) and matrix metalloproteinase-9 (MMP9) could be used as a diagnostic tool for NASH.

Methods
Patients who underwent bariatric surgery and simultaneous liver biopsy were identified. Biopsies were assigned a NAFLD activity score (NAS). MMP9- and FABP4- Enzyme-linked Immunosorbent Assays (ELISAs) on serum samples were performed. The serum levels of FABP4/MMP9 were compared and different models to predict NASH were developed.

Results
A total of 84 patients were included, 28 patients (33.3%) were diagnosed with NASH. Higher concentrations of MMP9 in NASH patients (p < 0.01) were detected. FABP4 concentrations were not significantly increased. A moderate correlation between the NAS and MMP9 concentrations (r = 0.32, P < 0.01) was observed. The neural network model fit best with the dataset, with an area under the curve (AUC) of 83% and an accuracy of 88%.

Conclusion
Serum MMP9 levels are increased in patients with NASH and should routinely be measured in patients with obesity, but further investigations are needed to improve noninvasive NASH diagnosis.
PDGFB-targeted functional MRI nanoswitch for activatable T1–T2 dual-modal ultra-sensitive diagnosis of cancer
Authors: Zhang Ya’nan , Liu Lu , Li Wenling , Zhang Caiyun , Song Tianwei , Wang Peng , Sun Daxi , Huang Xiaodan , Qin Xia , Ran Lang , Tian Geng , Qian Junchao , Zhang Guilong 
Published: January 2023

AbstractAs one of the most significant imaging modalities currently available, magnetic resonance imaging (MRI) has been extensively utilized for clinically accurate cancer diagnosis. However, low signal-to-noise ratio (SNR) and low specificity for tumors continue to pose significant challenges. Inspired by the distance-dependent magnetic resonance tuning (MRET) phenomenon, the tumor microenvironment (TME)-activated off–on T1–T2 dual-mode MRI nanoswitch is presented in the current study to realize the sensitive early diagnosis of tumors. The tumor-specific nanoswitch is designed and manufactured on the basis of PDGFB-conjugating ferroferric oxide coated by Mn-doped silica (PDGFB-FMS), which can be degraded under the high-concentration GSH and low pH in TME to activate the T1–T2 dual-mode MRI signals. The tumor-specific off–on dual-mode MRI nanoswitch can significantly improve the SNR and is used successfully for the accurate diagnosis of early-stage tumors, particularly for orthotopic prostate cancer. In addition, the systemic delivery of the nanoswitch did not cause blood or tissue damage, and it can be excreted out of the body in a timely manner, demonstrating excellent biosafety. Overall, the strategy is a significant step in the direction of designing off–on dual-mode MRI nanoprobes to improve imaging accuracy, which opens up new avenues for the development of new MRI probes.
PHF5A facilitates the development and progression of gastric cancer through SKP2-mediated stabilization of FOS
Authors: Zhang Zhandong , Peng Liangqun , Yang Wei , Li Baodong , Hua Yawei , Luo Suxia 
Published: January 2023

Abstract
Background
Gastric cancer (GC) is the fifth most common cancer and the third most common cause of cancer death worldwide. Plant homeodomain (PHD)-finger domain protein PHF5A has been demonstrated to play a promoting role in a variety of cancers. This study aimed to clarify the role of PHF5A in the progression of GC and its potential mechanism of action.

Methods
Immunohistochemical staining experiments were performed based on tissues from clinical GC patients to reveal PHF5A expression. A series of functional experiments in vitro and in vivo were used to clarify the role of PHF5A in GC.

Results
Clinically, PHF5A was abundantly expressed in GC and existed clinical value indicating poor prognosis. In addition, GC cells with knockdown of PHF5A expression showed slowed proliferation, enhanced sensitivity to apoptosis and inhibition of migration. Mechanically, knockdown of PHF5A led to decreased protein stability of FOS, which was mediated ubiquitination of E3 ubiquitin ligase S-phase kinase-associated protein 2 (SKP2). Moreover, downregulation of FOS attenuated the promotion of PHF5A overexpression on GC cells. Consistently, Pladienolide B (PHF5A inhibitor) treatment reversed the induction of PHF5A overexpression on the malignant phenotypes and tumor formation of GC cells.

Conclusion
Knockdown of PHF5A inhibited the progression of GC through SKP2-mediated ubiquitination of FOS, which may be a promising candidate target with potential therapeutic value.