bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prognostic impact of the number of metastatic lymph nodes after surgery in locally advanced hypopharyngeal cancer
Authors: Nishimura Ari , Yokota Tomoya , Hamauchi Satoshi , Onozawa Yusuke , Notsu Akifumi , Sato Fuyuki , Kawakami Takeshi , Ogawa Hirofumi , Onoe Tsuyoshi , Mukaigawa Takashi 
Published: October 2022

Abstract
Background
Postoperative chemoradiotherapy (CRT) is a standard therapy for patients with high-risk factors for head and neck squamous cell carcinoma, including positive margin and extra-nodal extension (ENE). However, the prognostic impact of the number of pathological metastatic lymph nodes (pLNs) in hypopharyngeal carcinoma (HPC) is unclear. Thus, this study aimed to investigate postoperative prognostic factors for locally advanced hypopharyngeal squamous cell carcinoma (LA-HPSCC) with a focus on the number of pLNs.

Methods
We retrospectively analyzed medical records of 99 consecutive patients with LA-HPSCC who underwent total pharyngo-laryngo-esophagectomy (TPLE) and bilateral neck dissection (ND) between December 2002 and May 2019.

Results
The median follow-up time for all censored patients was 63.2 months. The median overall survival (OS) was 101.0 months (95% confidence interval [CI] 48.1–134.9). patients had pLNs ≥ 3. Forty-six (45.5%) patients were diagnosed with ENE. Twenty (20.2%) patients received postoperative CRT. The multivariate analysis revealed that pLNs ≥ 3 (median OS: 163.2 vs. 31.8 months, hazard ratio [HR] 2.39, 95% CI 1.16–4.94, p < 0.01) and ENE (median OS: 161.0 vs. 26.3 months, HR 4.60, 95% CI 2.26–9.36, p < 0.01) were significantly associated with poor prognosis and that postoperative CRT (HR 0.34, 95% CI 0.16–0.72, p < 0.01) was significantly associated with better prognosis. The cumulative incidence of distant metastasis was higher in patients with pLNs ≥ 3 than in those with pLNs < 3 (p < 0.01).

Conclusion
pLNs ≥ 3 and ENE were significant poor prognostic factors for patients with LA-HPSCC who underwent TPLE and bilateral ND.
Determinants of choice of usual source of care among older people with cardiovascular diseases in China: evidence from the Study on Global Ageing and Adult Health
Authors: Xu Tiange , Loban Katya , Wei Xiaolin , Wang Wenhua 
Published: October 2022

Abstract
Background
Cardiovascular diseases (CVD) are emerging as the leading contributor to death globally. The usual source of care (USC) has been proven to generate significant benefits for the elderly with CVD. Understanding the choice of USC would generate important knowledge to guide the ongoing primary care-based integrated health system building in China. This study aimed to analyze the individual-level determinants of USC choices among the Chinese elderly with CVD and to generate two exemplary patient profiles: one who is most likely to choose a public hospital as the USC, the other one who is most likely to choose a public primary care facility as the USC.

Methods
This study was a secondary analysis using data from the World Health Organization’s Study on Global AGEing and Adult Health (SAGE) Wave 1 in China. 3,309 individuals aged 50 years old and over living with CVD were included in our final analysis. Multivariable logistic regression was built to analyze the determinants of USC choice. Nomogram was used to predict the probability of patients’ choice of USC.

Results
Most of the elderly suffering from CVD had a preference for public hospitals as their USC compared with primary care facilities. The elderly with CVD aged 50 years old, being illiterate, residing in rural areas, within the poorest income quintile, having functional deficiencies in instrumental activities of daily living and suffering one chronic condition were found to be more likely to choose primary care facilities as their USC with the probability of 0.85. Among those choosing primary care facilities as their USC, older CVD patients with the following characteristics had the highest probability of choosing public primary care facilities as their USC, with the probability of 0.77: aged 95 years old, being married, residing in urban areas, being in the richest income quintile, being insured, having a high school or above level of education, and being able to manage activities living.

Conclusions
Whilst public primary care facilities are the optimal USC for the elderly with CVD in China, most of them preferred to receive health care in public hospitals. This study suggests that the choice of USC for the elderly living with CVD was determined by different individual characteristics. It provides evidence regarding the choice of USC among older Chinese patients living with CVD.
Ttc39c is a potential target for the treatment of lung cancer
Authors: Rong Hao , Peng Jun , Ma Ke , Zhu Jiang , He Jin-Tao 
Published: October 2022

Abstract
Background
The novel TTC gene, tetratricopeptide repeat domain 39 C (Ttc39c), mainly mediates the interaction between proteins. It is involved in the progression of various tumors. In this study, we determined the effect of Ttc39c on lung adenocarcinoma and found that it might be used as a potential intervention target.

Methods
We performed a difference analysis of Ttc39c samples from the TCGA database. Transwell experiments were conducted to determine the ability of cell metastasis. Celigo and MTT assays were performed to determine the effect of Ttc39c gene subtraction on cell proliferation. FACS was performed to determine the effect of Ttc39c gene subtraction on apoptosis. Clone-formation experiments were conducted to determine the effect of Ttc39c gene subtraction on cloning ability. Transcriptomics, proteomics, and metabolomics were used to elucidate the enrichment pathway of the Ttc39c gene in the progression of lung adenocarcinoma.

Results
The expression of Ttc39c increased significantly in lung adenocarcinoma. The proliferation, metastasis, and cloning ability of human lung cancer cells were inhibited, while the apoptosis of cells increased significantly after the depletion of Ttc39c. Our results based on the transcriptomics, proteomics, and metabolomics analyses indicated that Ttc39c might be involved in the progression of lung adenocarcinoma (LUAD) mainly through the metabolic pathway and the p53 pathway.

Conclusion
To summarize, Ttc39c strongly regulates the proliferation and metastasis of lung adenocarcinoma cells. The main pathways involved in Ttc39c in lung adenocarcinoma include the energy metabolism and p53 pathways.
Classification and reconstruction of femoral bone defect in the revision of aseptic loosening of distal femoral endoprostheses: a 10-year multicenter retrospective analysis
Authors: Hou Zi-Wei , Xu Ming , Zheng Kai , Yu Xiu-Chun 
Published: October 2022

AbstractObjectiveThis study proposes a system for classifying the aseptic loosening of distal femoral endoprostheses and discusses reconstruction methods for revision surgery, based on different classification types.MethodsWe retrospectively analyzed the data of patients who received revision surgery for aseptic loosening in distal femoral tumor endoprosthesis from January 2008 to December 2020 at 3 bone tumor treatment centers in China. Based on the patient imaging data, we proposed a classification system for the aseptic loosening of distal femoral endoprostheses and discussed its revision surgery strategy for various bone defects.ResultsA total of 31 patients were included in this study, including 21 males and 10 females aged 15–75 y (average: 44.3 y). First-revision surgery was performed on 24 patients, whereas second-revision surgery was conducted on 7 patients. The 31 patients were classified into different types based on the degree of aseptic loosening: Type I, 12 patients (38.7%); Type IIa, 7 patients (22.5%); Type IIb, 7 patients (22.5%); Type III, 4 patient (12.9%); and Type IV, 1 patient (3.2%). For type I, 11 patients underwent revisions with standard longer-stem prostheses (one with the original prosthesis), and one patient had the original prosthesis plus cortical allograft strut. For type II (a and b), 10 patients underwent revisions with original prosthesis or longer-stem prosthesis and 4 patients combined with cortical allograft strut. For type III, one patient underwent revision with a longer-stem prosthesis and the other 3 patients with a custom short-stem prosthesis. For type IV, only one patient underwent revision with a custom short-stem prosthesis.ConclusionsAseptic loosening of the distal femoral prosthesis can be divided into 4 types: type I, type II (a, b), type III and type IV. The reconstruction methods of our centers for different types of bone defects can offer some reference value in the revision of aseptic loosening.
Effect of fixed orthodontic appliances on gingival status and oral microbiota: a pilot study
Authors: Marincak Vrankova Zuzana , Rousi Margarita , Cvanova Michaela , Gachova Daniela , Ruzicka Filip , Hola Veronika , Lochman Jan , Izakovicova Holla Lydie , Brysova Alena , Borilova Linhartova Petra 
Published: October 2022

Abstract
Background
This pilot study aimed to investigate how fixed orthodontic appliances simultaneously applied on the upper and lower arches affect the oral environment in the medium term.

Methods
The oral status of 30 orthodontic patients was evaluated using the number of decay-missing-filled teeth (DMFT), plaque (PI), and gingival indices (GI) before bonding of fixed orthodontic appliances (T0) and during the therapy (T1). Besides, the gingival crevicular fluid (GCF) and a dental plaque were collected. Samples were analyzed for selected Candida sp. and for 10 selected oral bacteria using mass spectroscopy and multiplex polymerase chain reaction, respectively.

Results
In 60% of patients, deterioration of the oral status (demonstrated by the increase in PI) was recorded (p < 0.05). Moreover, the changes in PI correlated with those of GI (p < 0.001). At the T1 time point, the mean representation of Actinomyces sp. in the total prokaryotic DNA in GCF and dental plaque of individual patients increased compared to T0 (p < 0.05). The probability of finding any of the 7 selected periodontal bacteria combined with Candida sp. was 10 times higher in patients in whom PI deteriorated between T0 and T1 (p < 0.01).

Conclusions
Changes in the oral microbial diversity and an increase in PI were observed in the medium term after bonding of orthodontic appliance. Our study highlights the importance of a complex approach in this type of research as the association between clinical characteristics and combined microbial parameters is higher than when evaluated separately.
What is the role of occupational physicians in the workplace during the COVID-19 pandemic in Japan? A qualitative interview study
Authors: Igarashi Yu , Tateishi Seiichiro , Sawajima Tomoko , Kikuchi Kodai , Kawasumi Mika , Matsuoka Juri , Harada Arisa , Mori Koji 
Published: October 2022

Abstract
Background
The coronavirus disease 2019 (COVID-19) pandemic has had various impacts on businesses and workers worldwide. The spread of infection has been reported through cluster outbreaks in the workplace, and World Health Organization has emphasized workplace infection control measures. Occupational physicians (OPs) are expected to actively support employers’ efforts to minimize the damage of the pandemic. However, there is little research on the role of these specialists during a pandemic. Clarification of the contributions of OPs to health and safety at the workplace in the COVID-19 pandemic would be beneficial to ensure that OPs can be effectively deployed in the next pandemic.

Methods
We employed semi-structured interviews and qualitative content analysis of the interview transcripts. Twenty OPs were selected as priority candidates from among 600 OPs certificated of the JSOH, and thirteen who met the eligibility criteria agreed to participate. The online interviews were conducted in November and December 2020 with thirteen OPs. We extracted meaning units (MUs) from interview transcripts according to the research question: “What was the role of OP in the COVID-19 pandemic?“ and condensed and abstracted them into codes and categorized them. Validity was confirmed by additional 5 OPs interviews.

Results
A total of 503 MUs were extracted from the transcripts. These were abstracted into 10 sub-categories and two categories. Categories 1 and 2 dealt with “Role in confronting the direct effects of the pandemic” and “Role in confronting the indirect effects of the pandemic” and accounted for 434 (86.3%) and 69 (13.7%) MUs, respectively. These results were validated by another 5 interviews.

Conclusion
This study identified the role of OPs in Japan in the COVID-19 pandemic. The results showed that they made a wide range of contributions to the direct and indirect effects of the pandemic. We hope our findings will help OPs during future pandemics or other long-term emergency situations.
Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with predictive capacity: a CORDIOPREV clinical trial study
Authors: Mora-Ortiz Marina , Alcala-Diaz Juan F. , Rangel-Zuñiga Oriol Alberto , Arenas-de Larriva Antonio Pablo , Abollo-Jimenez Fernando , Luque-Cordoba Diego , Priego-Capote Feliciano , Malagon Maria M. , Delgado-Lista Javier , Ordovas Jose M. , Perez-Martinez Pablo , Camargo Antonio , Lopez-Miranda Jose 
Published: October 2022

Abstract
Background
Type 2 diabetes mellitus (T2DM) is one of the most widely spread diseases, affecting around 90% of the patients with diabetes. Metabolomics has proven useful in diabetes research discovering new biomarkers to assist in therapeutical studies and elucidating pathways of interest. However, this technique has not yet been applied to a cohort of patients that have remitted from T2DM.

Methods
All patients with a newly diagnosed T2DM at baseline (n = 190) were included. An untargeted metabolomics approach was employed to identify metabolic differences between individuals who remitted (RE), and those who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. The biostatistical pipeline consisted of an orthogonal projection on the latent structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a receiver operating characteristic (ROC), a DeLong test, a Cox regression, and pathway analyses.

Results
The model identified a significant increase in 12 metabolites in the non-RE group compared to the RE group. Cox proportional hazard models, calculated using these 12 metabolites, showed that patients in the high-score tercile had significantly (p-value < 0.001) higher remission probabilities (Hazard Ratio, HR, high versus low = 2.70) than those in the lowest tercile. The predictive power of these metabolites was further studied using GLMs and ROCs. The area under the curve (AUC) of the clinical variables alone is 0.61, but this increases up to 0.72 if the 12 metabolites are considered. A DeLong test shows that this difference is statistically significant (p-value = 0.01).

Conclusions
Our study identified 12 endogenous metabolites with the potential to predict T2DM remission following a dietary intervention. These metabolites, combined with clinical variables, can be used to provide, in clinical practice, a more precise therapy.

Trial registration
ClinicalTrials.gov, NCT00924937.
Prevalence and pattern of migration intention of doctors undergoing training programmes in public tertiary hospitals in Ekiti State, Nigeria
Authors: Akinwumi Adebowale Femi , Solomon Oluremi Olayinka , Ajayi Paul Oladapo , Ogunleye Taiwo Samuel , Ilesanmi Oladipupo Adekunle , Ajayi Adedayo Olufemi 
Published: October 2022

Abstract
Background
Emigration of Nigerian doctors, including those undergoing training, to the developed countries in Europe and Americas has reached an alarming rate.

Objective
This study aimed at assessing the prevalence, pattern, and determinants of migration intention among doctors undergoing residency and internship training programmes in the public tertiary hospitals in Ekiti state, Nigeria.

Methods
This was a cross-sectional study using a quantitative data collected from 182 doctors undergoing residency and internship training at the two tertiary hospitals. An adapted semi-structured questionnaire was used to collect information on migration intention among the eligible respondents. Univariate, bivariate and multivariate data analyses were done. The level of significance was determined at p-value < 0.05.

Results
Majority (53.9%) of doctors undergoing training were between 30–39 years, and the mean age was 33.2 ± 5.7 years, male respondents were 68.1%, and 53.8% of the respondents were married. The proportion of doctors undergoing training who had the intention to migrate abroad to practice was 74.2%. A higher proportion of the internship trainees, 79.5%, intended to migrate abroad to practice while the proportion among the resident doctors, was 70.6%. Among the respondents who intended to migrate abroad to practice, 85(63%) intend to migrate abroad within the next 2 years, while the preferred countries of destination were the United Kingdom 65(48.2%), Canada 29 (21.5%), Australia 20 (14.8%) and the United States 18(13.3%). Seventy percent of respondents who intend to migrate abroad had started working on implementation of their intention to migrate abroad. The majority of the junior resident doctors, 56(72.7%), intend to migrate abroad compared with the senior resident doctors, 21(27.3%), (χ2 = 14.039; p < 0.001). The determinants of migration intention are the stage of residency training and level of job satisfaction.

Conclusion
There is a high prevalence of migration intention among the doctors undergoing training in the public tertiary hospitals in Ekiti State, Nigeria, with the majority already working on their plans to migrate abroad. Doctors undergoing training who are satisfied with their job and those who are in the senior stage of residency training programme are less inclined to migrate abroad.

Recommendations
The hospital management in the tertiary hospitals should develop retention strategies for human resources for health, especially doctors undergoing training in their establishment, to avert the possible problems of dearth of specialists in the tertiary health facilities. Also, necessary support should be provided for the residency training programme in the tertiary health institutions to make transition from junior to senior residency stage less strenuous.
PRR34-AS1 promotes exosome secretion of VEGF and TGF-β via recruiting DDX3X to stabilize Rab27a mRNA in hepatocellular carcinoma
Authors: Zhang Zhilei , Zhou Ye , Jia Yuming , Wang Chao , Zhang Meng , Xu Zhuo 
Published: October 2022

Abstract
Background
Exosomes are deemed to be an important tool of intercellular communicators in cancer cells. Our study investigated the role of PRR34 long non-coding RNA antisense RNA 1 (PRR34-AS1) in regulating exosome secretion in hepatocellular carcinoma (HCC) cells.

Methods
Quantitative real-time polymerase chain reaction (RT-qPCR) analyzed the expression of PRR34-AS1. We assessed the function of PRR34-AS1 on the biological changes of THLE-3 cells and HCC cells. The downstream interaction between RNAS was assessed by mechanistic experiments.

Results
PRR34-AS1 expression was upregulated in HCC cells in comparison to THLE-3 cells. PRR34-AS1 depletion repressed HCC cell proliferation, migration and invasion as well as EMT phenotype, while PRR34-AS1 up-regulation accelerated the malignant phenotypes of THLE-3 cells. PRR34-AS1 recruited DDX3X to stabilize the mRNA level of exosomal protein Rab27a. Moreover, PRR34-AS1 facilitated the malignant phenotypes of THLE-3 cells by elevating Rab27a expression to promote the exosome secretion of VEGF and TGF-β in HCC cells.

Conclusions
The current study revealed a novel function of PRR34-AS1 in accelerating exosome secretion in HCC cells and offered an insight into lncRNA function in the regulation of tumor cell biology.

Graphical Abstract
A novel aquaporin-4-associated optic neuritis rat model with severe pathological and functional manifestations
Authors: Morita Yuko , Itokazu Takahide , Nakanishi Toru , Hiraga Shin-ichiro , Yamashita Toshihide 
Published: October 2022

Abstract
Background
Optic neuritis (ON) is a common manifestation of aquaporin-4 (AQP4) antibody seropositive neuromyelitis optica (NMO). The extent of tissue damage is frequently severe, often leading to loss of visual function, and there is no curative treatment for this condition. To develop a novel therapeutic strategy, elucidating the underlying pathological mechanism using a clinically relevant experimental ON model is necessary. However, previous ON animal models have only resulted in mild lesions with limited functional impairment. In the present study, we attempted to establish a feasible ON model with severe pathological and functional manifestations using a high-affinity anti-AQP4 antibody. Subsequently, we aimed to address whether our model is suitable for potential drug evaluation by testing the effect of minocycline, a well-known microglia/macrophage inhibitor.

Methods
AQP4-immunoglobulin G (IgG)-related ON in rats was induced by direct injection of a high-affinity anti-AQP4 monoclonal antibody, E5415A. Thereafter, the pathological and functional characterizations were performed, and the therapeutic potential of minocycline was investigated.

Results
We established an experimental ON model that reproduces the histological characteristics of ON in seropositive NMO, such as loss of AQP4/glial fibrillary acidic protein immunoreactivity, immune cell infiltration, and extensive axonal damage. We also observed that our rat model exhibited severe visual dysfunction. The histological analysis showed prominent accumulation of macrophages/activated microglia in the lesion site in the acute phase. Thus, we investigated the possible effect of the pharmacological inhibition of macrophages/microglia activation by minocycline and revealed that it effectively ameliorated axonal damage and functional outcome.

Conclusions
We established an AQP4-IgG-induced ON rat model with severe functional impairments that reproduce the histological characteristics of patients with NMO. Using this model, we revealed that minocycline treatment ameliorates functional and pathological outcomes, highlighting the usefulness of our model for evaluating potential therapeutic drugs for ON in NMO.
Combined anterior cruciate and lateral collateral ligaments reconstruction with ipsilateral hamstring autograft: surgical technique
Authors: Piedade Sérgio Rocha , Górios Carlos , Migliorini Filippo , Maffulli Nicola 
Published: October 2022

AbstractDifferent surgical techniques have been proposed to reconstruct combined anterior cruciate (ACL) and lateral collateral ligaments (LCL). Although these surgical techniques are reliable and reproducible, the number of autologous grafts needed for the reconstruction could be a limiting factor, especially when patients present with multi-ligament knee injuries and the posterior cruciate ligament is also torn. In addition, some of these techniques are not easy to master and have a steep learning curve. We present a surgical procedure that has been used over the last 18 years to reconstruct combined ACL and LCL injuries and has become a reproducible, feasible and time-efficient procedure to approach combined ACL and LCL injuries using an ipsilateral hamstring autograft.