bluuebunny/crossref_metadata_2025_split huggingface dataset:
Re-expression of miR-200s in claudin‐low mammary tumor cells alters cell shape and reduces proliferation and invasion potentially through modulating other miRNAs and SUZ12 regulated genes
Authors: Simpson K. , Conquer-van Heumen G. , Watson K. L. , Roth M. , Martin C. J. , Moorehead R. A. 
Published: February 2021

Abstract
Background
MicroRNAs are a class of non-coding RNAs that regulate gene expression through binding to mRNAs and preventing their translation. One family of microRNAs known as the miR-200 family is an important regulator of epithelial identity. The miR-200 family consists of five members expressed in two distinct clusters; the miR-200c/141 cluster and the miR-200b/200a/429 cluster. We have found that murine and human mammary tumor cells with claudin-low characteristics are associated with very low levels of all five miR-200s.

Methods
To determine the impact of miR-200s on claudin-low mammary tumor cells, the miR-200c/141 cluster and the miR-200b/200a/429 cluster were stably re-expressed in murine (RJ423) and human (MDA-MB-231) claudin-low mammary tumor cells. Cell proliferation and migration were assessed using BrdU incorporation and transwell migration across Matrigel coated inserts, respectively. miRNA sequencing and RNA sequencing were performed to explore miRNAs and mRNAs regulated by miR-200 re-expression while Enrichr-based pathway analysis was utilized to identify cellular functions modified by miR-200s.

Results
Re-expression of the miR-200s in murine and human claudin-low mammary tumor cells partially restored an epithelial cell morphology and significantly inhibited proliferation and cell invasion in vitro. miRNA sequencing and mRNA sequencing revealed that re-expression of miR-200s altered the expression of other microRNAs and genes regulated by SUZ12 providing insight into the complexity of miR-200 function. SUZ12 is a member of the polycomb repressor complex 2 that suppresses gene expression through methylating histone H3 at lysine 27. Flow cytometry confirmed that re-expression of miR-200s increased histone H3 methylation at lysine 27.

Conclusions
Re-expression of miR-200s in claudin-low mammary tumor cells alters cell morphology and reduces proliferation and invasion, an effect potentially mediated by SUZ12-regulated genes and other microRNAs.
Highly stable organic photothermal agent based on near-infrared-II fluorophores for tumor treatment
Authors: Xu Yunjian , Wang Shiqi , Chen Zhenjiang , Hu Rui , Li Shaoqiang , Zhao Yihua , Liu Liwei , Qu Junle 
Published: February 2021

Abstract
Background
The aim to develop a highly stable near-infrared (NIR) photoinduced tumor therapy agent stems from its considerable potential for biological application. Due to its long wavelength, biological imaging exhibits a high signal-to-background ratio, deep tissue penetration and maximum permissible light power, which can minimize damage to an organism during photoinduced tumor therapy.

Results
A class of stable NIR-II fluorophores (NIR998, NIR1028, NIR980, NIR1030, and NIR1028-S) based on aza–boron–dipyrromethene (aza-BODIPY) dyes with donor–acceptor-donor structures have been rationally designed and synthesized by harnessing the steric relaxation effect and intramolecular photoinduced electron transfer (IPET). These fluorophores exhibit an intense range of NIR-II emission, large Stokes shift (≥ 100 nm), excellent photothermal conversion performance, and superior stability against photobleaching. Among the NIR-II fluorophores, NIR998 possesses better NIR-II emission and photothermal conversion performance. NIR998 nanoparticles (NIR998 NPs) can be encapsulated by liposomes. NIR998 NPs show superior stability in the presence of light, heat, and reactive oxygen nitrogen species than that of indocyanine green NPs, as well as a higher photothermal conversion ability (η = 50.5%) compared to other photothermal agents. Finally, under the guidance of photothermal imaging, NIR998 NPs have been proven to effectively eliminate tumors via their excellent photothermal conversion performance while presenting negligible cytotoxicity.

Conclusions
Utilizing IPET and the steric relaxation effect can effectively induce NIR-II emission of aza-BODIPY dyes. Stable NIR998 NPs have excellent photothermal conversion performance and negligible dark cytotoxicity, so they have the potential to act as photothermal agents in biological applications.
Cost per DALY averted in low, middle- and high-income countries: evidence from the global burden of disease study to estimate the cost-effectiveness thresholds
Authors: Daroudi Rajabali , Akbari Sari Ali , Nahvijou Azin , Faramarzi Ahmad 
Published: February 2021

Abstract
Background
Determining the cost-effectiveness thresholds for healthcare interventions has been a severe challenge for policymakers, especially in low- and middle-income countries. This study aimed to estimate the cost per disability-adjusted life-year (DALY) averted for countries with different levels of Human Development Index (HDI) and Gross Domestic Product (GDP).

Methods
The data about DALYs, per capita health expenditure (HE), HDI, and GDP per capita were extracted for 176 countries during the years 2000 to 2016. Then we examined the trends on these variables. Panel regression analysis was performed to explore the correlation between DALY and HE per capita. The results of the regression models were used to calculate the cost per DALY averted for each country.

Results
Age-standardized rate (ASR) DALY (DALY per 100,000 population) had a nonlinear inverse correlation with HE per capita and a linear inverse correlation with HDI. One percent increase in HE per capita was associated with an average of 0.28, 0.24, 0.18, and 0.27% decrease on the ASR DALY in low HDI, medium HDI, high HDI, and very high HDI countries, respectively. The estimated cost per DALY averted was $998, $6522, $23,782, and $69,499 in low HDI, medium HDI, high HDI, and very high HDI countries. On average, the cost per DALY averted was 0.34 times the GDP per capita in low HDI countries. While in medium HDI, high HDI, and very high HDI countries, it was 0.67, 1.22, and 1.46 times the GDP per capita, respectively.

Conclusions
This study suggests that the cost-effectiveness thresholds might be less than a GDP per capita in low and medium HDI countries and between one and two GDP per capita in high and very high HDI countries.
Seasons, weather, and device-measured movement behaviors: a scoping review from 2006 to 2020
Authors: Turrisi Taylor B. , Bittel Kelsey M. , West Ashley B. , Hojjatinia Sarah , Hojjatinia Sahar , Mama Scherezade K. , Lagoa Constantino M. , Conroy David E. 
Published: February 2021

AbstractBackgroundThis scoping review summarized research on (a) seasonal differences in physical activity and sedentary behavior, and (b) specific weather indices associated with those behaviors.MethodsPubMed, CINAHL, and SPORTDiscus were searched to identify relevant studies. After identifying and screening 1459 articles, data were extracted from 110 articles with 118,189 participants from 30 countries (almost exclusively high-income countries) on five continents.ResultsBoth physical activity volume and moderate-to-vigorous physical activity (MVPA) were greater in summer than winter. Sedentary behavior was greater in winter than either spring or summer, and insufficient evidence existed to draw conclusions about seasonal differences in light physical activity. Physical activity volume and MVPA duration were positively associated with both the photoperiod and temperature, and negatively associated with precipitation. Sedentary behavior was negatively associated with photoperiod and positively associated with precipitation. Insufficient evidence existed to draw conclusions about light physical activity and specific weather indices. Many weather indices have been neglected in this literature (e.g., air quality, barometric pressure, cloud coverage, humidity, snow, visibility, windchill).ConclusionsThe natural environment can influence health by facilitating or inhibiting physical activity. Behavioral interventions should be sensitive to potential weather impacts. Extreme weather conditions brought about by climate change may compromise health-enhancing physical activity in the short term and, over longer periods of time, stimulate human migration in search of more suitable environmental niches.
Sirtuin 3 protects against anesthesia/surgery-induced cognitive decline in aged mice by suppressing hippocampal neuroinflammation
Authors: Liu Qiang , Sun Yi-Man , Huang Hui , Chen Chen , Wan Jie , Ma Lin-Hui , Sun Yin-Ying , Miao Hui-Hui , Wu Yu-Qing 
Published: February 2021

Abstract
Background
Postoperative cognitive dysfunction (POCD) is a very common complication that might increase the morbidity and mortality of elderly patients after surgery. However, the mechanism of POCD remains largely unknown. The NAD-dependent deacetylase protein Sirtuin 3 (SIRT3) is located in the mitochondria and regulates mitochondrial function. SIRT3 is the only sirtuin that specifically plays a role in extending lifespan in humans and is associated with neurodegenerative diseases. Therefore, the aim of this study was to evaluate the effect of SIRT3 on anesthesia/surgery-induced cognitive impairment in aged mice.

Methods
SIRT3 expression levels were decreased after surgery. For the interventional study, an adeno-associated virus (AAV)-SIRT3 vector or an empty vector was microinjected into hippocampal CA1 region before anesthesia/surgery. Western blotting, immunofluorescence staining, and enzyme-linked immune-sorbent assay (ELISA) were used to measure the oxidative stress response and downstream microglial activation and proinflammatory cytokines, and Golgi staining and long-term potentiation (LTP) recording were applied to evaluate synaptic plasticity.

Results
Overexpression of SIRT3 in the CA1 region attenuated anesthesia/surgery-induced learning and memory dysfunction as well as synaptic plasticity dysfunction and the oxidative stress response (superoxide dismutase [SOD] and malondialdehyde [MDA]) in aged mice with POCD. In addition, microglia activation (ionized calcium binding adapter molecule 1 [Iba1]) and neuroinflammatory cytokine levels (tumor necrosis factor-alpha [TNF-α], interleukin [IL]-1β and IL-6) were regulated after anesthesia/surgery in a SIRT3-dependent manner.

Conclusion
The results of the current study demonstrate that SIRT3 has a critical effect in the mechanism of POCD in aged mice by suppressing hippocampal neuroinflammation and reveal that SIRT3 may be a promising therapeutic and diagnostic target for POCD.
The relationship between cerebral blood flow and venous sinus pressure: can hyperemia induce idiopathic intracranial hypertension?
Authors: Bateman Alexander Robert , Bateman Grant Alexander , Barber Tracie 
Published: February 2021

Abstract
Background
It has been shown that idiopathic intracranial hypertension (IIH) in children is associated with cerebral hyperemia, which induces an increase in cerebral venous pressure. The current literature suggests venous pressure scales with blood flow in a linear fashion, however, a linear relationship would not raise the pressure high enough to induce IIH. There is, however, some evidence to suggest that this relationship could be quadratic in nature. The purpose of this paper is to characterize the relationship between cerebral blood flow and the pressure drop across the cerebral venous system.

Methods
10 CT venogram data sets were collected for this study, with 5 useable geometries created. Computational fluid dynamics (CFD) models were generated using these geometries, with 10 simulations conducted per patient. The flow rates tested ranged from 200 mL/min to 2000 mL/min. 3D pressure and velocity streamline distributions were created and analyzed for each CFD model, with pressure drops across the cerebral venous system determined. The effective and hydraulic diameters were determined at the superior sagittal sinus, transverse sinus and both proximal and distal sigmoid sinuses.

Results
A quadratic relationship between blood flow and sinus pressure was found, with correlations of 0.99 or above in all five patients. The presence of vortical blood flow was found to explain this trend, with fluid curl and pressure drop correlations being above 0.97. This suggests that the presence of high blood flow should be considered in the diagnostic workup of IIH.

Conclusions
The cerebral venous sinus blood flow and pressure response relationship are quadratic in nature, with the major cause of this being the degree of rotation induced in the flow. The elevated blood flow found in children with IIH can explain the increased ICP that is found, secondary to the increase in venous pressure that develops.
Mismatch repair deficiency is associated with specific morphologic features and frequent loss of ARID1A expression in ovarian clear cell carcinoma
Authors: Ge Huijuan , Xiao Yaoxin , Qin Guangqi , Gu Yanzi , Cai Xu , Jiang Wenhua , Tu Xiaoyu , Yang Wentao , Bi Rui 
Published: February 2021

Abstract
Background
Ovarian clear cell carcinoma (OCCC) is the second subtype of ovarian epithelial carcinoma reported to be closely related to Lynch syndrome (LS). ARID1A mutation is an important pathogenetic mechanism in OCCC that leads to loss of ARID1A expression in approximately half of OCCCs. However, the correlation of MMR status and ARID1A deficiency is unclear. The current study aimed to identify the clinical and histopathological characteristics of OCCC associated with dMMR and to further explore the association between dMMR and ARID1A deficiency.

Methods
A cohort of 176 primary OCCC patients was enrolled and review included histological characteristics (nuclear atypia, necrosis, mitosis, stromal hyalinization, and background precursors) and host inflammatory response (tumor-infiltrating lymphocytes, peritumoral lymphocytes, intratumoral stromal inflammation and plasma cell infiltration). Immunohistochemical staining of MLH1, PMS2, MSH2, MSH6 and ARID1A was performed using tissue microarrays.

Results
dMMR was detected in 10/176 tumors (6 %), followed by MSH2/MSH6 (6/176), MLH1/PMS2 (3/176), and MSH6 (1/176). The average age of patients with dMMR was younger than that of patients with intact MMR (46 y vs. 53 y). Tumors with diffuse intratumoral stromal inflammation remained significantly associated after multivariate analysis. ARID1A expression was absent in 8 patients with dMMR (8/10), which is a significantly higher frequency than that observed in patients with intact MMR (80 % vs. 43.2 %).

Conclusions
Our study indicates that diffuse intratumoral stromal inflammation of OCCCs is associated with dMMR, with loss of MSH2/MSH6 expression being most frequent. dMMR is strongly associated with the loss of ARID1A expression in OCCC.
Dosimetric predictors of nephrotoxicity in patients receiving extended-field radiation therapy for gynecologic cancer
Authors: Kunogi Hiroaki , Yamaguchi Nanae , Terao Yasuhisa , Sasai Keisuke 
Published: February 2021

Abstract
Purpose
We sought dosimetric predictors of a decreasing estimated glomerular filtration rate (eGFR) in gynecological oncology patients receiving extended-field radiation therapy (EFRT).

Materials and methods
Between July 2012 and April 2020, 98 consecutive cervical or endometrial cancer patients underwent EFRT or whole-pelvis radiation therapy (WPRT) with concurrent cisplatin chemotherapy in our institution. To explore the effect of concurrent cisplatin chemotherapy on renal function, the renal function of the WPRT patients was examined. Of the 98 patients, 34 cervical or endometrial cancer patients underwent EFRT including extended-field intensity-modulated radiation therapy (EF-IMRT) and 64 cervical cancer patients underwent WPRT with cisplatin. Of the 34 EFRT patients, 32 underwent concurrent cisplatin chemotherapy. Excluding patients exhibiting recurrences within 6 months, 31 EFRT patients were analyzed in terms of the dose-volume kidney histograms (the percentages of kidney volumes receiving 12, 16, 20, and 24 Gy) and the post- to pre-treatment eGFR ratios. We calculated Pearson correlation coefficients between the renal dose volume and the percentage eGFR reductions of the 31 EFRT patients, and those treated via EF-IMRT. Renal dose constraint significance was evaluated using the Mann–Whitney U test.

Results
The eGFR value after WPRT with cisplatin remained largely unchanged for 12 months, unlike that after EFRT. In EFRT patients, a strong correlation was evident between the KV20Gy dose and the post- to pre-treatment eGFR ratio (correlation coefficients − 0.80 for all patients and − 0.74 for EF-IMRT patients). In EF-IMRT patients, the kidney volume receiving 20 Gy tended to correlate negatively with the eGFR reduction. The Mann–Whitney U test showed that patients with KV20Gy values < 10% retained significantly better renal function than did patients with KV20Gy values > 10% (P = 0.002).

Conclusions
Imposition of a severe kidney dose constraint during EF-IMRT may reduce nephrotic toxicity. Future prospective investigations of kidney-sparing EF-IMRT are required.
Implementation, adherence, and results of systematic SARS-CoV-2 testing for asymptomatic patients treated at a tertiary care regional radiation oncology network
Authors: Prabhu Roshan S. , Dhakal Reshika , Hicks Amy S. , McBride James , Patrick Alicia L. , Corso Christopher D. , Murphy Tomain , Thonen Melissa , Lipford Edward H. , Raghavan Derek , Burri Stuart H. 
Published: February 2021

Abstract
Background
Coronavirus disease 2019 (COVID-19) caused by the SARS-CoV-2 virus is a current pandemic. We initiated a program of systematic SARS-CoV-2 polymerase chain reaction (PCR) testing in all asymptomatic patients receiving radiotherapy (RT) at a large radiation oncology network in the Charlotte, NC metropolitan region and report adherence and results of the testing program.

Methods
Patients undergoing simulation for RT between May 18, 2020 and July 10, 2020 within the Levine Cancer Institute radiation oncology network who were asymptomatic for COVID-19 associated symptoms, without previous positive SARS-CoV-2 testing, and without recent high-risk contacts were included. PCR testing was performed on nasal cavity or nasopharyngeal swab samples. Testing was performed within 2 weeks of RT start (pre-RT) and at least every 4 weeks during RT for patients with prolonged RT courses (intra-RT). An automated task based process using the oncology electronic medical record (EMR) was developed specifically for this purpose.

Results
A total of 604 unique patients were included in the cohort. Details on testing workflow and implementation are described herein. Pre-RT PCR testing was performed in 573 (94.9%) patients, of which 4 (0.7%) were positive. The adherence rate to intra-RT testing overall was 91.6%. Four additional patients (0.7%) tested positive during their RT course, of whom 3 were tested due to symptom development and 1 was asymptomatic and identified via systematic testing. A total of 8 (1.3%) patients tested positive overall. There were no known cases of SARS-CoV-2 transmission from infected patients to clinic staff and/or other patients.

Conclusions
We detailed the workflows used to implement systematic SARS-CoV-2 for asymptomatic patients at a large radiation oncology network. Adherence rates for pre-RT and intra-RT testing were high using this process. This information allowed for appropriate delay in initiating RT, minimizing the occurrence of RT treatment interruptions, and no known cases of transmission from infected patients to clinic staff and/or other patients.
Tips and tricks to achieve osteotomy healing and prevent refracture after ulnar shortening osteotomy
Authors: Kang Jong Woo , Cha Soo Min , Kim Sang-gyun , Choi In Cheul , Suh Dong Hun , Park Jong Woong 
Published: February 2021

AbstractBackgroundParallel osteotomy is essential for favorable osteotomy reduction and healing and technically challenging during diaphyseal ulnar shortening osteotomy (USO). This study aimed to evaluate the advantages of guided osteotomy for parallel osteotomy and reduction osteotomies, healing over freehand osteotomy. It also aimed to identify surgical factors affecting healing after diaphyseal USO.MethodsBetween June 2005 and March 2016, 136 wrists that had undergone diaphyseal USO for ulnar impaction syndrome (UIS) were evaluated. The wrists were divided into two groups according to the osteotomy technique (group 1: freehand osteotomy, 74 wrists; group 2: guided osteotomy, 62 wrists). The osteotomy reduction gap and time to osteotomy healing (union and consolidation) were compared between the groups. A multiple regression test was performed to identify the surgical factors affecting healing. The cut-off length of the reduction gap to achieve osteotomy union on time and the cut-off period to decide the failure of complete consolidation were statistically calculated.ResultsThe baseline characteristics did not differ between the two groups. The osteotomy reduction gap and time to osteotomy union, and complete consolidation were shorter in group 2 than in group 1 (p= 0.002, < 0.001, 0.002). The osteotomy reduction gap was a critical surgical factor affecting both time to osteotomy union and complete consolidation (p< 0.001, < 0.001). The use of a dynamic compression plate affected only the time to complete consolidation (p< 0.001). The cut-off length of the osteotomy reduction gap to achieve osteotomy union on time was 0.85 mm. The cut-off period to decide the failure of complete consolidation was 23.5 months after osteotomy.ConclusionsThe minimal osteotomy reduction gap was the most important for timely osteotomy healing in the healthy ulna, and guided osteotomy was beneficial for reducing the osteotomy reduction gap.
Effect of denosumab switched from bisphosphonates in preventing joint destruction in postmenopausal rheumatoid arthritis patients with anti-cyclic citrullinated peptide antibodies
Authors: Mori Yu , Izumiyama Takuya , Kurishima Hiroaki , Kamimura Masayuki , Baba Kazuyoshi , Mori Naoko , Itoi Eiji 
Published: February 2021

Abstract
Introduction
This study aimed to determine the effects of denosumab treatment on the joint destruction of Japanese females with rheumatoid arthritis (RA) and anti-cyclic citrullinated peptide (CCP) antibodies.

Materials and methods
This retrospective longitudinal study included 56 patients treated with denosumab and 50 patients treated with bisphosphonate. All participants were positive for anti-CCP antibodies. All patients also had a history of osteoporosis treatment with bisphosphonate, which was either continued or switched to 60 mg of subcutaneous denosumab injection every 6 months. To assess the progression of joint destruction, hand and foot radiographs were taken, and changes in modified total Sharp score (mTSS), erosion score (ERO), and joint space narrowing score (JSN) were evaluated at 12 months and 24 months. The changes in BMD of the lumbar spine and hip were also assessed at 12 months.

Results
At 12 months, there were significant differences in the change of ERO (p = 0.015) and mTSS (p = 0.01). Similarly, there were significant differences in the change of ERO (p = 0.013) and mTSS (p = 0.003) at 24 months. In contrast, no significant difference was observed in the changes of JSN and clinical parameters. There were significant differences in the changes in BMD in the femoral neck (p = 0.011) and total hip (p = 0.012).

Conclusion
Denosumab treatment might be effective for the inhibition of bone erosion progression in the patients with RA, and it potentially contributes to the treatment of osteoporosis and prevention of destructive arthritis in patients with switching treatment from bisphosphonate.