bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comprehensive analysis of penile cancer in the region with the highest worldwide incidence reveals new insights into the disease
Authors: Teixeira Júnior Antonio Augusto Lima , da Costa Melo Syomara Pereira , Pinho Jaqueline Diniz , Sobrinho Thaís Bastos Moraes , Rocha Thalita Moura Silva , Duarte Denner Rodrigo Diniz , de Oliveira Barbosa Liseana , Duarte Wesliany Everton , de Castro Belfort Marta Regina , Duarte Kelly Gomes , da Silva Neto Antonio Lima , de Ribamar Rodrigues Calixto José , Paiva Paiva Lúcio Cristiano , do Nascimento Francisco Sérgio Moura Silva , Alencar Junior Antonio Machado , Khayat André Salim , da Graça Carvalhal Frazão Corrêa Rita , Lages Joyce Santos , dos Reis Rodolfo Borges , Araújo Wilson Silva , Silva Gyl Eanes Barros 
Published: October 2022

Abstract
Background
Although penile cancer (PC) is uncommon in developed countries, it is widespread in developing countries. The state of Maranhão (Northeast, Brazil) has the highest global incidence recorded for PC, and, despite its socioeconomic vulnerability, it has been attributed to human papillomavirus (HPV) infection. This study aimed to determine the histopathological features, the prevalence of HPV infection, and the immunohistochemical profile of PC in Maranhão.

Methods
A retrospective cohort of 200 PC cases were evaluated. HPV detection was performed using nested-PCR followed by direct sequencing for genotyping. Immunohistochemistry (IHC) was performed using monoclonal antibodies anti-p16INK4a, p53, and ki-67.

Results
Our data revealed a delay of 17 months in diagnosis, a high rate of penile amputation (96.5%), and HPV infection (80.5%) in patients from Maranhão (Molecular detection). We demonstrated the high rate of HPV in PC also by histopathological and IHC analysis. Most patients presented koilocytosis (75.5%), which was associated with those reporting more than 10 different sexual partners during their lifetime (p = 0.001). IHC revealed frequent p16INK4a overexpression (26.0%) associated with basaloid (p < 0.001) and high-grade tumors (p = 0.008). Interestingly, p16 appears not to be a better prognostic factor in our disease-free survival analysis, as previously reported. We also demonstrated high ki-67 and p53 expression in a subset of cases, which was related to worse prognostic factors such as high-grade tumors, angiolymphatic and perineural invasion, and lymph node metastasis. We found a significant impact of high ki-67 (p = 0.002, log-rank) and p53 (p = 0.032, log-rank) expression on decreasing patients’ survival, as well as grade, pT, stage, pattern, and depth of invasion (p < 0.05, log-rank).

Conclusions
Our data reaffirmed the high incidence of HPV infection in PC cases from Maranhão and offer new insights into potential factors that may contribute to the high PC incidence in the region. We highlighted the possible association of HPV with worse clinical prognosis factors, differently from what was observed in other regions. Furthermore, our IHC analysis reinforces p16, ki-67, and p53 expression as important diagnosis and/or prognosis biomarkers, potentially used in the clinical setting in emerging countries such as Brazil.
Antitumor activity of the protein kinase inhibitor 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo- 1H-benzimidazole in breast cancer cell lines
Authors: Koronkiewicz Mirosława , Kazimierczuk Zygmunt , Orzeszko Andrzej 
Published: October 2022

Abstract
Background
The protein kinases CK2 and PIM-1 are involved in cell proliferation and survival, the cell cycle, and drug resistance, and they are found overexpressed in virtually all types of human cancer, including breast cancer. In this study, we investigated the antitumor activity of a deoxynucleoside derivative, the protein kinase inhibitor compound 1-(β-D-2′-deoxyribofuranosyl)-4,5,6,7-tetrabromo-1H-benzimidazole (K164, also termed TDB), inter alia CK2 and PIM-1, on breast cancer cell lines (MDA-MB-231, MCF-7, and SK-BR-3).

Methods
An evaluation of the cytotoxic and proapoptotic effects, mitochondrial membrane potential (ΔΨm), and cell cycle progression was performed using an MTT assay, flow cytometry, and microscopic analysis. The Western blotting method was used to analyze the level of proteins important for the survival of breast cancer cells and proteins phosphorylated by the CK2 and PIM-1 kinases.

Results
The examined compound demonstrated the inhibition of cell viability in all the tested cell lines and apoptotic activity, especially in the MCF-7 and SK-BR-3 cells. Changes in the mitochondrial membrane potential (ΔΨm), cell cycle progression, and the level of the proteins studied were also observed.

Conclusions
The investigated CK2 and PIM-1 kinase inhibitor K164 is a promising compound that can be considered a potential agent in targeted therapy in selected types of breast cancer; therefore, further research is necessary.
Effects of let-7a microRNA and C–C chemokine receptor type 7 expression on cellular function and prognosis in esophageal squamous cell carcinoma
Authors: Yura Masahiro , Fukuda Kazumasa , Matsuda Satoru , Irino Tomoyuki , Nakamura Rieko , Kawakubo Hirofumi , Takeuchi Hiroya , Kitagawa Yuko 
Published: October 2022

Abstract
Background
C–C chemokine receptor type 7 (CCR7) participates in chemotactic and metastatic responses in various cancers, including in esophageal squamous cell carcinoma (ESCC). The microRNA (miRNA) let-7a suppresses migration and invasion of various types of cancer cells by downregulating CCR7 expression.

Methods
The expression levels of CCR7 and let-7a were measured in the cell lines, tumor, and peritumoral tissues of ESCC patients. KYSE cell lines were transfected with synthetic let-7a miRNA and a let-7a miRNA inhibitor, and their CCR7 expression levels as well as invasive ability were evaluated. A highly invasive cell line was established via an invasion assay, and CCR7 expression level along with let-7a level was subsequently evaluated. Cancer cells overexpressing CCR7 were injected subcutaneously into mice, and the animals were monitored for tumor growth along with lymph node metastasis.

Results
A negative correlation between CCR7 and let-7a expression was observed in the ESCC cell lines as well as in tissue samples from patients. Synthetic let-7a decreased CCR7 expression level, while the let-7a inhibitor increased it. In vitro, the established highly invasive cancer cells with high and low levels of CCR7 and let-7a expression, respectively, exhibited a greater invasive ability than the wild-type cell line. The cells were associated with tumor growth and lymph node metastasis in mice. Patients in the high-CCR7/low-let-7a group had the worst prognosis, with a five-year recurrence free survival (5-RFS) rate of 37.5%, followed by the high-CCR7/high-let-7a (5-RFS: 60.0%) and low-CCR7 (5-RFS: 85.7%; p = 0.038) groups.

Conclusions
The expression of CCR7 was downregulated by let-7a miRNA in esophageal cancer cells. The decrease in let-7a expression level led to the increased expression level of CCR7 in ESCC cells, consequently increasing their invasive ability and malignancy and resulting in a worse prognosis for ESCC patients.
Trial registration.
Retrospectively registered.
Hoarding symptoms are associated with higher rates of disability than other medical and psychiatric disorders across multiple domains of functioning
Authors: Nutley Sara K. , Read Michael , Martinez Stephanie , Eichenbaum Joseph , Nosheny Rachel L. , Weiner Michael , Mackin R. Scott , Mathews Carol A. 
Published: October 2022

Abstract
Background
Hoarding symptoms are associated with functional impairment, though investigation of disability among individuals with hoarding disorder has largely focused on clutter-related impairment to home management activities and difficulties using space because of clutter. This analysis assesses disability among individuals with hoarding symptoms in multiple domains of everyday functioning, including cognition, mobility, self-care, interpersonal and community-level interactions, and home management. The magnitude of the association between hoarding and disability was compared to that of medical and psychiatric disorders with documented high disability burden, including major depressive disorder (MDD), diabetes, and chronic pain.

Methods
Data were cross-sectionally collected from 16,312 adult participants enrolled in an internet-based research registry, the Brain Health Registry. Pearson’s chi-square tests and multivariable logistic regression models were used to quantify the relationship between hoarding and functional ability relative to MDD, diabetes, and chronic pain.

Results
More than one in ten participants endorsed clinical (5.7%) or subclinical (5.7%) hoarding symptoms (CHS and SCHS, respectively). After adjusting for participant demographic characteristics and psychiatric and medical comorbidity, CHS and SCHS were associated with increased odds of impairment in all domains of functioning. Moderate to extreme impairment was endorsed more frequently by those with CHS or SCHS compared to those with self-reported MDD, diabetes, and/or chronic pain in nearly all domains (e.g., difficulty with day-to-day work or school: CHS: 18.7% vs. MDD: 11.8%, p < 0.0001) except mobility and self-care. While those with current depressive symptoms endorsed higher rates of impairment than those with hoarding symptoms, disability was most prevalent among those endorsing both hoarding and comorbid depressive symptoms.

Conclusions
Hoarding symptoms are associated with profound disability in all domains of functioning. The burden of hoarding is comparable to that of other medical and psychiatric illnesses with known high rates of functional impairment. Future studies should examine the directionality and underlying causality of the observed associations, and possibly identify target interventions to minimize impairment associated with hoarding symptomatology.
Awareness and willingness to accept syphilis chemoprophylaxis among men who have sex with men from three cities in China: a cross-sectional study
Authors: Zhang Xu , Qi Shu-Zhen , Du Fang-Zhi , Zheng Zhi-Ju , Cao Ning-Xiao , Zheng Xiao-Li , Zhang Rui-Li , Wang Qian-Qiu 
Published: October 2022

Abstract
Background
The awareness and willingness to use doxycycline-based syphilis chemoprophylaxis among men who have sex with men (MSM) in China remain largely unknown.

Methods
We recruited MSM online from Nanjing, Wuhan and Changsha between August and October of 2021, collected data from online survey, analyzed their data using descriptive statistics, and constructed binary logistic regression for factors associated with awareness and willingness to use chemoprophylaxis for syphilis and HIV.

Results
Of 725 participants (44.0% of which resided in Nanjing, 37.7% in Changsha, and 18.3% in Wuhan), a majority were under 25 years of age; 62.2% had college degrees; 11.3% were HIV positive; and 5.10% had prior syphilis infection. Only 28.83% of participants had heard of syphilis chemoprophylaxis before. Odds of knowing syphilis chemoprophylaxis were higher in those who think it is necessary to have syphilis chemoprophylaxis versus those who think it is unnecessary (P = 0.002), and were higher in those whose acquaintance had chemoprophylaxis experience before (P < 0.001). Meanwhile, those who had no previous doxycycline using history, or had positive attitude were more likely to be willing to accept syphilis chemoprophylaxis (P = 0.009, P < 0.001). Over two-thirds (67.8%) of participants preferred the PEP mode in syphilis chemoprophylaxis, and side-effects of drugs remains their most worrying aspect.

Conclusions
We observed elevated interest in syphilis chemoprophylaxis in MSM in our investigational areas, indicating that the combination of HIV and syphilis chemoprophylaxis in China is promising.
Impact of cage position on biomechanical performance of stand-alone lateral lumbar interbody fusion: a finite element analysis
Authors: Nan Chong , Ma Zhanbei , Liu Yuxiu , Ma Liang , Li Jiaqi , Zhang Wei 
Published: October 2022

Abstract
Background
This study aimed to compare the biomechanical performance of various cage positions in stand-alone lateral lumbar interbody fusion(SA LLIF).

Methods
An intact finite element model of the L3-L5 was reconstructed. The model was verified and analyzed. Through changing the position of the cage, SA LLIF was established in four directions: anterior placement(AP), middle placement(MP), posterior placement(PP), oblique placement(OP). A 400 N vertical axial pre-load was imposed on the superior surface of L3 and a 10 N/m moment was applied on the L3 superior surface along the radial direction to simulate movements of flexion, extension, lateral bending, and axial rotation. Various biomechanical parameters were evaluated for intact and implanted models in all loading conditions, including the range of motion (ROM) and maximum stress.

Results
In the SA LLIF models, the ROM of L4-5 was reduced by 84.21–89.03% in flexion, 72.64–82.26% in extension, 92.5-95.85% in right and left lateral bending, and 87.22–92.77% in right and left axial rotation, respectively. Meanwhile, ROM of L3-4 was mildly increased by an average of 9.6% in all motion directions. Almost all stress peaks were increased after SA LLIF, including adjacent disc, facet joints, and endplates. MP had lower stress peaks of cage and endplates in most motion modes. In terms of the stress on facet joints and disc of the cephalad segment, MP had the smallest increment.

Conclusion
In our study, SA LLIF risked accelerating the adjacent segment degeneration. The cage position had an influence on the distribution of endplate stress and the magnitude of facet joint stress. Compared with other positions, MP had the slightest effect on the stress in the adjacent facet joints. Meanwhile, MP seems to play an important role in reducing the risk of cage subsidence.
Identification of castration-dependent and -independent driver genes and pathways in castration-resistant prostate cancer (CRPC)
Authors: Li Yan , Shi Hui , Zhao Zhenjun , Xu Minghui 
Published: October 2022

Abstract
Background
Prostate cancer (PCa) is one of the most diagnosed cancers in the world. PCa inevitably progresses to castration-resistant prostate cancer (CRPC) after androgen deprivation therapy treatment, and castration-resistant state means a shorter survival time than other causes. Here we aimed to define castration-dependent and -independent diver genes and molecular pathways in CRPC which are responsible for such lethal metastatic events.

Methods
By employing digital gene expression (DGE) profiling, the alterations of the epididymal gene expression profile in the mature and bilateral castrated rat were explored. Then we detect and characterize the castration-dependent and -independent genes and pathways with two data set of CPRC-associated gene expression profiles publicly available on the NCBI.

Results
We identified 1,632 up-regulated and 816 down-regulated genes in rat’s epididymis after bilateral castration. Differential expression analysis of CRPC samples compared with the primary PCa samples was also done. In contrast to castration, we identified 97 up-regulated genes and 128 down-regulated genes that changed in both GEO dataset and DGE profile, and 120 up-regulated genes and 136 down-regulated genes changed only in CRPC, considered as CRPC-specific genes independent of castration. CRPC-specific DEGs were mainly enriched in cell proliferation, while CRPC-castration genes were associated with prostate gland development. NUSAP1 and NCAPG were identified as key genes, which might be promising biomarkers of the diagnosis and prognosis of CRPC.

Conclusion
Our study will provide insights into gene regulation of CRPC dependent or independent of castration and will improve understandings of CRPC development and progression.
Unintended medication discrepancies and associated factors upon patient admission to the internal medicine wards: identified through medication reconciliation
Authors: Moges Tilaye Arega , Akalu Temesgen Yihunie , Sema Faisel Dula 
Published: October 2022

Abstract
Background
Medication reconciliation (MedRec) is a widely accepted tool for the identification and resolution of unintended medication discrepancies (UMD).

Objective
This study aimed at assessing the magnitude and associated factors of UMD identified through medication reconciliation upon patient admission to the internal medicine wards.

Methods
Prospective cross-sectional study was conducted at the internal medicine wards of Felege Hiwot and Tibebe Ghion comprehensive specialized hospitals in Bahir Dar city, Northwest Ethiopia, from May 01 to July 30, 2021. Data were collected by using a data abstraction format prepared based on standard MedRec tools and previous studies on medication discrepancy. Pharmacists-led MedRec was made by following the WHO High5s “retroactive medication reconciliation model”. SPSS® (IBM Corporation) version 25.0 was used to analyze the data with descriptive and inferential statistics. A binary logistic regression analysis was used to identify factors associated with UMD. A statistical significance was declared at a p-value < 0.05.

Results
Among 635 adult patients, 248 (39.1%) of them had at least one UMD. The most frequent types of UMDs were omission (41.75%) and wrong dose (21.9%). The majority (75.3%) of pharmacists’ interventions were accepted. Polypharmacy at admission (p-value < 0.001), age ≥ 65 (p-value = 0.001), a unit increase on the number of comorbidities (p-value = 0.008) and information sources used for MedRec (p-value < 0.001), and medium (p-value = 0.019) and low adherence (p-value < 0.001) were significantly associated with UMD.

Conclusion
The magnitude of UMD upon patient admission to the internal medicine wards was considerably high. Omission and the wrong dose of medication were common. Older age, polypharmacy, low and medium adherence, and an increase in the number of comorbidities and information sources used for MedRec are significantly associated with UMDs. Pharmacists' interventions were mostly acceptable. Thus, the implementation of pharmacists-led MedRec in the two hospitals is indispensable for patient safety.
Characterization of data-driven clusters in diabetes-free adults and their utility for risk stratification of type 2 diabetes
Authors: Yacamán Méndez Diego , Zhou Minhao , Trolle Lagerros Ylva , Gómez Velasco Donaji V. , Tynelius Per , Gudjonsdottir Hrafnhildur , Ponce de Leon Antonio , Eeg-Olofsson Katarina , Östenson Claes-Göran , Brynedal Boel , Aguilar Salinas Carlos A. , Ebbevi David , Lager Anton 
Published: October 2022

Abstract
Background
The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes.

Methods
Data on 7317 diabetes-free adults from Sweden were used in the main analysis and on 2332 diabetes-free adults from Mexico for external validation. Clusters were based on sex, family history of diabetes, educational attainment, fasting blood glucose and insulin levels, estimated insulin resistance and β-cell function, systolic and diastolic blood pressure, and BMI. The risk of type 2 diabetes was assessed using Cox proportional hazards models. The predictive accuracy and long-term stability of the clusters were then compared to different definitions of prediabetes.

Results
Six risk phenotypes were identified independently in both cohorts: very low-risk (VLR), low-risk low β-cell function (LRLB), low-risk high β-cell function (LRHB), high-risk high blood pressure (HRHBP), high-risk β-cell failure (HRBF), and high-risk insulin-resistant (HRIR). Compared to the LRHB cluster, the VLR and LRLB clusters showed a lower risk, while the HRHBP, HRBF, and HRIR clusters showed a higher risk of developing type 2 diabetes. The high-risk clusters, as a group, had a better predictive accuracy than prediabetes and adequate stability after 20 years.

Conclusions
Phenotypes derived using cluster analysis were useful in stratifying the risk of type 2 diabetes among diabetes-free adults in two independent cohorts. These results could be used to develop more precise public health interventions.
Mild pulmonary hemodynamic alterations in patients with systemic sclerosis: relevance of the new 2022 ESC/ERS definition of pulmonary hypertension and impact on mortality
Authors: Puigrenier Sébastien , Giovannelli Jonathan , Lamblin Nicolas , De Groote Pascal , Fertin Marie , Bervar Jean-François , Lamer Antoine , Edmé Jean-Louis , Balquet Marie-Hélène , Sobanski Vincent , Launay David , Hachulla Éric , Sanges Sébastien 
Published: October 2022

Abstract
Background and objective
The definition of pre-capillary pulmonary hypertension (PH) has been modified, with lowering of the mean pulmonary arterial pressure (mPAP) threshold from 25 to 20 mmHg and addition of a mandatory criterion of pulmonary vascular resistance (PVR) ≥ 2 Wood units (WU). Our objectives were: 1/ to estimate the proportion of patients reclassified as having pre-capillary PH when using the new 2022 ESC/ERS hemodynamic criteria (i.e. mPAP 21-24 mmHg and PVR ≥ 2 WU), and to describe their clinical characteristics and outcome; and 2/ to study the relationship between PVR and survival in patients with mPAP > 20 mmHg.

Methods
We retrospectively analyzed consecutive SSc patients included in our National Reference Center for a first right-heart catheterization between 2003 and 2018. The association between survival and PVR was studied using smoothing splines.

Results
We included 126 SSc patients with mPAP > 20 mmHg. Among them, 16 (13%) had a baseline mPAP value between 21 and 24 mmHg and PVR ≥ 2 mmHg and were reclassified as pre-capillary PH; 10 of which (62%) raised their mPAP ≥ 25 mmHg during follow-up. In patients with mPAP > 20 mmHg, we observed a linear relation between PVR and mortality for values < 6 WU.

Conclusion
A significant proportion of SSc patients is reclassified as having pre-capillary PH with the new 2022 ESC/ERS hemodynamic definition. Lowering the PVR threshold from 3 to 2 WU captures patients at risk of raising their mPAP > 25 mmHg, with a possibly less severe disease.