bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protein kinase C activation upregulates human L-type amino acid transporter 2 function
Authors: Morio Hanae , Reien Yoshie , Hirayama Yuri , Hashimoto Hirofumi , Anzai Naohiko 
Published: March 2021

AbstractL-type amino acid transporter 2 (LAT2) is a Na+-independent neutral amino acid transporter, whose function regulation system remains unclarified. Since protein kinase C (PKC) is known to regulate the functions of various transporters, we investigated whether human LAT2 (hLAT2) function is regulated by PKC. In mouse proximal tubule S2 cells, hLAT2 transport activity was upregulated by PKC activation. However, we found that the mRNA and protein expression of hLAT2 was not affected by PKC activation and that the upregulation was independent of the three potential PKC consensus sites in the hLAT2 amino acid sequence. Moreover, we found that PKC activation upregulated the Vmax value for hLAT2-mediated alanine transport, which was not accompanied by the induction of hLAT2 membrane insertion. In conclusion, we showed that hLAT2 function is upregulated by PKC activation, which is not related to either the de novo synthesis, the phosphorylation or the membrane insertion of hLAT2.
A novel end-to-end method to predict RNA secondary structure profile based on bidirectional LSTM and residual neural network
Authors: Wang Linyu , Zhong Xiaodan , Wang Shuo , Zhang Hao , Liu Yuanning 
Published: March 2021

AbstractBackgroundStudies have shown that RNA secondary structure, a planar structure formed by paired bases, plays diverse vital roles in fundamental life activities and complex diseases. RNA secondary structure profile can record whether each base is paired with others. Hence, accurate prediction of secondary structure profile can help to deduce the secondary structure and binding site of RNA. RNA secondary structure profile can be obtained through biological experiment and calculation methods. Of them, the biological experiment method involves two ways: chemical reagent and biological crystallization. The chemical reagent method can obtain a large number of prediction data, but its cost is high and always associated with high noise, making it difficult to get results of all bases on RNA due to the limited of sequencing coverage. By contrast, the biological crystallization method can lead to accurate results, yet heavy experimental work and high costs are required. On the other hand, the calculation method is CROSS, which comprises a three-layer fully connected neural network. However, CROSS can not completely learn the features of RNA secondary structure profile since its poor network structure, leading to its low performance.ResultsIn this paper, a novel end-to-end method, named as “RPRes, was proposed to predict RNA secondary structure profile based on Bidirectional LSTM and Residual Neural Network.ConclusionsRPRes utilizes data sets generated by multiple biological experiment methods as the training, validation, and test sets to predict profile, which can compatible with numerous prediction requirements. Compared with the biological experiment method, RPRes has reduced the costs and improved the prediction efficiency. Compared with the state-of-the-art calculation method CROSS, RPRes has significantly improved performance.
GroEL protein of the Leptospira spp. interacts with host proteins and induces cytokines secretion on macrophages
Authors: Ho Joana Dias , Takara Luiz Eduardo Massao , Monaris Denize , Gonçalves Aline Patrícia , Souza-Filho Antonio Francisco , de Souza Gisele Oliveira , Heinemann Marcos Bryan , Ho Paulo Lee , Abreu Patrícia Antonia Estima 
Published: March 2021

AbstractBackgroundLeptospirosis is a zoonotic disease caused by infection with spirochetes fromLeptospiragenus. It has been classified into at least 17 pathogenic species, with more than 250 serologic variants. This wide distribution may be a result of leptospiral ability to colonize the renal tubules of mammalian hosts, including humans, wildlife, and many domesticated animals. Previous studies showed that the expression of proteins belonging to the microbial heat shock protein (HSP) family is upregulated during infection and also during various stress stimuli. Several proteins of this family are known to have important roles in the infectious processes in other bacteria, but the role of HSPs inLeptospiraspp. is poorly understood. In this study, we have evaluated the capacity of the protein GroEL, a member of HSP family, of interacting with host proteins and of stimulating the production of cytokines by macrophages.ResultsThe binding experiments demonstrated that the recombinant GroEL protein showed interaction with several host components in a dose-dependent manner. It was also observed that GroEL is a surface protein, and it is secreted extracellularly. Moreover, two cytokines (tumor necrosis factor-α and interleukin-6) were produced when macrophages cells were stimulated with this protein.ConclusionsOur findings showed that GroEL protein may contribute to the adhesion of leptospires to host tissues and stimulate the production of proinflammatory cytokines during infection. These features might indicate an important role of GroEL in the pathogen-host interaction in the leptospirosis.
Effect of physician attire on patient perceptions of empathy in Japan: a quasi-randomized controlled trial in primary care
Authors: Matsuhisa Takaharu , Takahashi Noriyuki , Takahashi Kunihiko , Yoshikawa Yuki , Aomatsu Muneyoshi , Sato Juichi , Mercer Stewart W. , Ban Nobutaro 
Published: March 2021

Abstract
Background
There is limited quantitative research on the effect of physician attire on patient–physician relationships. This study aimed to measure the influence of Japanese family physicians’ attire on the “human” aspects of medical care in terms of patient-perceived relational empathy.

Methods
This was a multicenter, prospective, controlled trial conducted in primary clinics in Japan. We explored the effects of family physician attire (white coat vs. casual attire) on patient-perceived empathy. Family physicians were allocated to alternate weeks of wearing a white coat or casual attire during consultations. Patients’ perceptions of physician empathy were evaluated using the self-rated Japanese Consultation and Relational Empathy (CARE) Measure. We used a linear mixed model to analyze the CARE Measure scores, adjusting for cluster effects of patients nested within doctor, age, and sex of patients, and doctors’ sex and years of clinical experience. We used the same method with Bonferroni adjustment to analyze patient sex differences in perceived empathy.

Results
A total of 632 patients of seven family physicians were allocated to white coat-wearing consultations (n = 328), and casual attire-wearing consultations (n = 304). There was no difference in CARE Measure scores between white coat and casual primary care consultations overall (p = 0.162). Subgroup analysis of patient sex showed that CARE Measure scores of male patients were significantly higher in the Casual group than in the White coat group (adjusted p-value = 0.044). There was no difference in female patient scores between White coat and Casual groups (adjusted p-value = 1.000).

Conclusions
This study demonstrated that physician attire (white coat or casual attire) in a primary care setting did not affect patient-perceived relational empathy overall. However, male patients of physicians wearing casual attire reported higher physician empathy. Although empathy cannot be reduced to simple variables such as attire, white coats may have a negative effect on patients, depending on the context. Family physicians should choose their attire carefully.

Trial registration
Japanese University Hospital Medical Information Network (UMIN-ICDR). Clinical Trial identifier number UMIN000037687 (Registered August 14, 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042749). The study was prospectively registered.
Comparison of preoperative two-dimensional shear wave elastography, indocyanine green clearance test and biomarkers for post hepatectomy liver failure prediction in patients with hepatocellular carcinoma
Authors: Fu Rong , Qiu Tingting , Ling Wenwu , Lu Qiang , Luo Yan 
Published: March 2021

Abstract
Background
The preoperative prediction of post hepatectomy liver failure (PHLF) is essential, but there is no gold standard for the prediction at present, and the efficacy of different methods for the prediction has not been compared systematically. In this study, we aimed to compare the efficacy of preoperative two-dimensional shear wave elastography (2D-SWE), indocyanine green (ICG) clearance test and biomarkers for PHLF prediction in patients with hepatocellular carcinoma (HCC).

Methods
We retrospectively studied 215 patients with HCC, who had undergone major liver resection in our hospital. Preoperative data of each patient, including liver stiffness value (LSV) of underlying hepatic parenchyma measured by 2D-SWE, ICG retention rate at 15 min (ICG-R15) measured by ICG clearance test, albumin-bilirubin (ALBI) scores, aspartate aminotransferase–platelet ratio index (APRI), and Fibrosis-4 (FIB-4) were collected for analysis. Post hepatectomy outcomes of study patients were also recorded for assessment of PHLF. The study patients were divided into development cohort (133 patients without PHLF, and 17 patients with PHLF) and validation cohort (59 patients without PHLF, and 6 patients with PHLF) randomly.

Results
In the development cohort, LSV, ICG-R15 and ALBI scores were significantly different between patients with and without PHLF, while no significant difference of APRI and FIB-4 scores was found. LSV had higher AUC (the area under the receiver operating characteristic curve) (AUC = 0.795) for PHLF prediction than ICG-R15 (AUC = 0.619) and ALBI scores (AUC = 0.686) (p < 0.05 for all comparisons). In the validation cohort, the cutoff value of LSV obtained from the development cohort, 10.35 kPa, revealed higher specificity (76.3%) for PHLF prediction than ICG-R15 (specificity: 66.1%) and ALBI scores (specificity: 69.5%) (p < 0.0001).

Conclusions
Compared with ICG-R15, ALBI scores, APRI and FIB-4, LSV measured by 2D-SWE may demonstrate better efficacy for preoperative PHLF prediction in patients with HCC.
Circadian variations in the occurrence of first‐ever intracerebral hemorrhage from different sources of income: a hospital‐based cross‐sectional study
Authors: Wang Yan-Yue , Yan Ning , Wang En-Yuan , Pu Yun-Tao 
Published: March 2021

Abstract
Background
The onset time of intracerebral hemorrhage (ICH) may be closely related to the working style and living habits of people, which are determined by different income sources in China. Therefore, the purpose of our study was to investigate the Circadian Variations in the occurrence of ICH from different sources of income.

Methods
This retrospective study enrolled 4,327 patients with first-ever ICH. Based on the time of day at which the patients developed symptoms, the classifiable onset time was assigned to one of eight three-hour intervals. And based on different income sources, they were categorized into three groups: Farmers, Wage-earners, and Freelancers. Demographic and risk factors of patients were then summarized, and the circadian variation of the 3 groups of patients’ known time of onset and those stratified by sex and age were analyzed.

Results
The frequency of ICH onset exhibited significant circadian variation among the 3 income groups, demonstrating a bimodal distribution in the daytime, with a nadir during the night (all P < 0.001). Three groups showed a significant initial peak between 06:01 and 09:00, and the same peak was observed in their subgroups of sex and age. In the 3 income source groups, there was a smaller second peak that between 15:01 and 18:00 for Farmers and Wage-earners and 18:01 and 21:00 for Freelancers. After stratification by sex and age, the second peak was between 18:01 and 21:00 for female in Farmers, female in Freelancers, under 65 years of age in Wage-earners and 65 years or older in Freelancers, while 15:01 and 18:00 for the other groups.

Conclusions
Different circadian variations of ICH onset time are found in patients with different income sources in southwest China’s Chongqing Municipality cohort. Moreover, the frequency and distribution pattern of peak hours may be closely related to the working style and living habits of people with different income sources.
Co-expression of SOX2 and HR-HPV RISH predicts poor prognosis in small cell neuroendocrine carcinoma of the uterine cervix
Authors: Zhang Shi-Wen , Luo Rong-Zhen , Sun Xiao-Ying , Yang Xia , Yang Hai-Xia , Xiong Si-Ping , Liu Li-Li 
Published: March 2021

Abstract
Background
Small cell neuroendocrine carcinoma of the uterine cervix (SCNEC) is a rare cancer involving the human papilloma virus (HPV), and has few available treatments. The present work aimed to assess the feasibility of SOX2 and HPV statuses as predictive indicators of SCNEC prognosis.

Methods
The associations of SOX2 and/or high-risk (HR)-HPV RNA in situ hybridization (RISH) levels with clinicopathological characteristics and prognostic outcomes for 88 neuroendocrine carcinoma (NEC) cases were analyzed.

Results
Among these patients with SCNEC, SOX2, P16INK4A and HR-HPV RISH expression and SOX2/HR-HPV RISH co-expression were detected in 68(77.3%), 76(86.4%), 73(83.0%), and 48(54.5%), respectively. SOX2-positive and HR-HPV RISH-positive SCNEC cases were associated with poorer overall survival (OS, P = 0.0170, P = 0.0451) and disease-free survival (DFS, P = 0.0334, P = 0.0309) compared with those expressing low SOX2 and negative HR-HPV RISH. Alternatively, univariate analysis revealed that SOX2 and HR-HPV RISH expression, either separately or in combination, predicted the poor prognosis of SCNEC patients. Multivariate analysis revealed that the co-expression of SOX2 with HR-HPV RISH may be an independent factor of OS [hazard ratio = 3.597; 95% confidence interval (CI): 1.085–11.928; P = 0.036] and DFS [hazard ratio = 2.880; 95% CI: 1.199–6.919; P = 0.018] prediction in SCNEC.

Conclusions
Overall, the results of the present study suggest that the co-expression of SOX2 with HR-HPV RISH in SCNEC may represent a specific subgroup exhibiting remarkably poorer prognostic outcomes compared with the expression of any one marker alone.
Efficacy of concurrent chemoradiotherapy for patients with limited-disease small-cell lung cancer: a retrospective, nationwide, population-based cohort study
Authors: Kim Seo Ree , Hong Ji Hyung , Sung Soo-Yoon , Kim Yeo Hyung , Chun Sang Hoon , Lee Hyun Woo , Lee Jung Soo , Ko Yoon Ho 
Published: March 2021

Abstract
Background
Small-cell lung cancer (SCLC) is a highly proliferative, rapidly growing tumor with a poor prognosis, even in cases of limited disease (LD). Timely and accurate high-intensity therapy is necessary. For concurrent chemoradiotherapy (CCRT), etoposide/platinum (EP)-based regimens are recommended, although irinotecan/platinum (IP)-based regimens are also effective with radiotherapy. This large-scale, retrospective, nationwide cohort study aimed to analyze the efficacy of CCRT in patients with LD-SCLC.

Methods
Population data registered between January 2008 and December 2018 was extracted from the Health Insurance Review and Assessment Service of Korea database. Survival outcomes of 4446 LD-SCLC patients who received CCRT were analyzed.

Results
Patients who received EP-CCRT (n = 4187) showed better time to first subsequent therapy (TFST: 11.2 months) and overall survival (OS: 22.2 months) than those who received IP-CCRT (n = 259; TFST: 9.6 months, P = 0.0477; OS: 16.4 months, P <  0.0001). When CCRT failed, dual-agent chemotherapy (n = 925; OS: 9.1 months) provided a better survival benefit than single-agent chemotherapy (n = 815; OS: 7.5 months). IP-based chemotherapy resulted in better OS (9.6 months) than EP-based chemotherapy (7.1 months, P = 0.017) in platinum-resistant relapsed patients; the opposite was observed for platinum-sensitive relapsed patients (OS: EP, 17.2 months; IP, 6.6 months; P <  0.0001). Poisson regression analysis demonstrated that age, EP-CCRT, and hypercholesterolemia retained significant associations with OS after adjustment for all variables.

Conclusion
In the Korean population, the effects of EP-CCRT on OS and TFST are significantly more favorable than those of IP-CCRT.
Case report: restored vision after ocular Closantel intoxication and blindness
Authors: Khalili Mohammad Reza , Zareei Athar 
Published: March 2021

Abstract
Background
Closantel is the best-known anti-parasitic medicine for veterinarians, which is contraindicated in humans. After reviewing the literature on ocular toxicity following mistaken usage of Closantel in humans, this report was found as the first complete restoration of visual function after Closantel intoxication. This report could be useful in anticipating the possibility of a further improvement based on a dose-response relationship. An important point of this report is the apparent reversibility of the vision and Electrophysiological parameters after Closantel intoxication and blindness. To conclude, the present case report demonstrates the importance of immediate referral and management in Closantel intoxication to avoid the long-term adverse effects of drug on visual function.

Case presentation
A 47-year-old man mistakenly took about 20 cc of Closantel 5% (15.87 mg/kg). Four hours after mistaken usage of Closantel, he was transferred to the district hospital due to dizziness and nausea. His stomach was washed out immediately after hospital arrival. He was being hospitalized in that hospital for 3 days. Then, he was referred to our clinic due to progressive vision loss. Methylprednisolone acetate 250 mg was injected once on 5th day after taking Closantel. His vision was reducing gradually so low that he could only detect hand motion (HM) on the 14th day after taking Closantel. ERG test was requested. It showed an exclusive reduction in b-wave amplitude under photopic and scotopic conditions. Later, his vision surprisingly improved gradually and his visual acuity was fully restored on the 28th day after the incident. After 3 years, we checked him again. His visual acuity was 20/20 in both eyes and the patient did not have any problem and his ERG report was completely normal.

Conclusions
In low dose of Closantel and immediate referral, ocular toxicity could be resolved.
The burden of chronic pain for patients with osteoarthritis in Germany: a retrospective cohort study of claims data
Authors: Schild Marie , Müller Ulrike , von Schenck Ursula , Prieur Sigurd , Miller Robert 
Published: March 2021

Abstract
Background
Osteoarthritis (OA) is a common condition that is often associated with chronic pain. Pain often leads patients to seek healthcare advice and treatment. In this retrospective cohort analysis of German longitudinal healthcare claims data, we aimed to explore the healthcare resource utilisation (HRU) and related healthcare costs for patients with OA who develop chronic pain.

Methods
Patient-level data was extracted from the German Institut für Angewandte Gesundheitsforschung (InGef) database. Insured persons (≥18 years) were indexed between January 2015 and December 2017 with a recent (none in the last 2 years) diagnosis of OA. HRU and costs were compared between patients categorised as with (identified via diagnosis or opioid prescription) and without chronic pain. Unweighted HRU (outpatient physician contacts, hospitalisations, prescriptions for physical therapy or psychotherapy, and incapacity to work) and healthcare costs (medication, medical aid/remedy, psychotherapy, inpatient and outpatient and sick pay in Euros [quartile 1, quartile 3]) were calculated per patient for the year following index. Due to potential demographic and comorbidity differences between the groups, inverse probability of treatment weighting (IPTW) was used to estimate weighted costs and rate ratio (RR; 95% confidence interval) of HRU by negative binomial regression modelling.

Results
Of 4,932,543 individuals sampled, 238,306 patients with OA were included in the analysis: 80,055 (34%) categorised as having chronic pain (24,463 via opioid prescription) and 158,251 (66%) categorised as not having chronic pain. The chronic pain cohort was slightly older, more likely to be female, and had more comorbidities. During the year following index, unweighted and IPTW-weighted HRU risk and healthcare costs were higher in patients with chronic pain vs those without for all categories. This led to a substantially higher total annual healthcare cost ─ observed mean; €6801 (1439, 8153) vs €3682 (791, 3787); estimated RR = 1.51 (1.36, 1.66).

Conclusions
German patients with chronic pain and OA have higher healthcare costs and HRU than those with OA alone. Our findings suggest the need for better prevention and treatment of OA in order to reduce the incidence of chronic pain, and the resultant increase in disease burden experienced by patients.
Negligible therapeutic impact, false-positives, overdiagnosis and lead-time are the reasons why radiographs bring more harm than benefits in the caries diagnosis of preschool children
Authors:   CARDEC collaborative group, Pontes Laura Regina A. , Lara Juan Sebastian , Novaes Tatiane Fernandes , Freitas Julia Gomes , Gimenez Thais , Moro Bruna Lorena P. , Maia Haline C. M. , Imparato José Carlos P. , Braga Mariana M. , Raggio Daniela P. , Mendes Fausto M. 
Published: March 2021

Abstract
Background
To evaluate the clinical course and interventions required during two years of follow-up of dental surfaces of deciduous molars diagnosed, and consequently treated, by two different strategies: diagnosis made by clinical examination alone or associated with radiographs.

Methods
This is a secondary analysis of a two-arm randomized clinical trial with parallel groups related to the diagnostic strategy for caries detection in preschool children. 216 children (3–6 years old) were followed-up for two years. All dental surfaces were diagnosed by visual inspection and later, through radiographic assessment. Baseline treatment was made in accordance with the results obtained by visual inspection performed alone or combined with radiographic method, considering the allocated group. Dental surfaces with no restoration needs, or those restored at the beginning of the study were followed-up for two years. The treatment decision was made according to the allocated group. The outcome was the occurrence of failure (a new caries lesion or a restoration replacement) during the follow-up.

Results
4383 proximal and occlusal surfaces of deciduous molars in 216 preschool children were diagnosed and treated according to the abovementioned diagnostic strategies and followed-up for 24 months. The assessment of radiographs made change the initial decision reached by visual inspection in about 30% of the surfaces when all types of interventions were considered. However, most disagreements occurred for initial lesions, where radiographs tended to underestimate them. Discordances between methods occurred in less than 5% of all surfaces when considered lesions requiring operative treatment. For discrepancy cases, the placed interventions guided by following the radiographic results did not present less failures against those made following only visual inspection. As a matter of fact, the use of radiographs in the diagnostic strategy for caries detection in children brought more harms than benefits due to the occurrence of false-positives, overdiagnosis and lead-time bias.

Conclusions
Simultaneous association of visual inspection and radiographic assessment for caries detection in preschool children causes more harms than benefits, and therefore, visual inspection should be conducted alone in the regular clinical practice.
Trial registration Clinicaltrials.gov platform: NCT02078453, registered on 5th March 2014.