bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrasound classification-guided minimally invasive rotary cutting in granulomatous lobular mastitis
Authors: Liao Hongye , Guo Jujiang , Chen Xuming , Hua Zhipeng , Lin Juli , Weng Yiyin 
Published: November 2020

Abstract
Background
To summarize the clinical experience of ultrasound-guided minimally invasive surgery for granulomatous lobular mastitis (GLM), and explore the feasibility of this technique for treating GLM.

Methods
This retrospective study reviewed the clinical features and treatment outcome of 30 patients who were diagnosed pathologically as GLM from 2016.3 to 2019.5 in the Department of Breast Surgery, Women's and Children's Hospital, Xiamen University. These patients weretreated with ultrasound-guided Mammotome minimally invasive surgery, and we tried to classified the lesion into four distinct patterns (diffuse abscess mixed type, sheet hypoechoic type, localized abscess type, localized hypoechoic mass type) according to the sonographic findings and clinical symptoms to find out if these patterns correlated with treatment and recurrence rate.

Results
After a median follow-up of 12 months on average (4–42 months), 26 cases (86.7%) were cured without acute or chronic complications such as disseminated inflammation and bleeding. Post-operative bleeding occurred in 1 case, and 3 cases (10.00%) relapsed. The ultrasound classification had 0 cases of diffuse abscess mixed type, 17 cases (56.7%) of sheet hypoechoic type, 9 cases (30%) of localized abscess type, and 4 cases (13.3%) of localized hypoechoic mass type. All 3 recurrent cases were sheet hypoechoic type, which were cured after another open surgical resection and showed no recurrence during an average follow-up of 20 months (11–40 months).

Conclusions
In treating GLM patients with minimally invasive rotary cutting, ultrasound classification helps to select suitable patients, especially those with localized abscess and localized hypoechoic mass types with low recurrence rate, which is one of the safe and effective treatment methods.
Screening test accuracy of portable devices that can be used to perform colposcopy for detecting CIN2+ in low- and middle-income countries: a systematic review and meta-analysis
Authors: Taghavi Katayoun , Rohner Eliane , Basu Partha , Low Nicola , Rutjes Anne , Bohlius Julia 
Published: November 2020

Abstract
Background
Portable devices that can be used to perform colposcopy may improve cervical cancer screening in low- and middle-income countries (LMIC) where access to colposcopy is limited. The objective of this study was to systematically review the diagnostic test accuracy (DTA) of these devices for the detection of cervical intraepithelial neoplasia grade 2 or higher (CIN2+).

Methods
In accordance with our protocol (Prospero CRD42018104286), we searched Embase, Medline and the Cochrane Controlled Register of Trials up to 9/2019. We included DTA studies, which investigated portable devices with moderate-to-high optical magnification (≥ 6×) for colposcopy, as described in the manual for Colposcopy and Treatment by the International Agency for Research on Cancer, with a histopathological reference standard. We used the QUADAS-2 tool to assess study quality. We examined results for sensitivity and specificity in paired forest plots, stratified by stages in the clinical pathway. We pooled estimates of test accuracy for the index test, used as an add-on to other tests, using a bivariate random-effect model.

Results
We screened 1737 references and assessed 239 full-text articles for eligibility. Five single-gate DTA studies, including 2693 women, met the inclusion criteria. Studies evaluated two devices (Gynocular™ and Pocket) at different stages of the screening pathway. In three studies, which used the index test in an add-on capacity in 1273 women, we found a pooled sensitivity of 0.79 (95% CI 0.55–0.92) and specificity of 0.83 (95% CI 0.59–0.94). The main sources of bias were partial verification, incorporation and classification bias.

Conclusion
Few studies have evaluated portable devices able to perform colposcopy, so their accuracy for the detection of CIN2+ remains uncertain. Future studies should include patient-relevant and long-term outcomes, including missed cases, overtreatment, residual and recurrent disease. To meet the challenge of eliminating cervical cancer in LMIC, methods for visual assessment of the cervix need urgent redress.
Characteristics of prescriptions and costs for acute upper respiratory tract infections in Chinese outpatient pediatric patients: a nationwide cross-sectional study
Authors: Wang Shan , Liu Lihua , Liu Jianchao , Miao Likun , Zhuang Qian , Guo Ning , Zhao Jing , Li Quanzheng , Ren Guoquan 
Published: November 2020

Abstract
Background
To understand the characteristics of prescriptions and costs in pediatric patients with acute upper respiratory infections (AURI) is important for the regulation of outpatient care and reimbursement policy. This study aims to provide evidence on these issues that was in short supply.

Methods
We conducted a retrospective cross-sectional study based on data from National Engineering Laboratory of Application Technology in Medical Big Data. All outpatient pediatric patients aged 0–14 years with an uncomplicated AURI from 1 January 2015 to 31 December 2017 in 138 hospitals across the country were included. We reported characteristics of patients, the average number of medications prescribed per encounter, the categories of medication used and their percentages, the cost per visit and prescription costs of drugs. For these measurements, discrepancies among diverse groups of age, regions, insurance types, and AURI categories were compared. Kruskal-Wallis nonparametric test and Student-Newman-Keuls test were performed to identify differences among subgroups. A multinomial logistic regression was conducted to examine the independent effects of those factors on the prescribing behavior.

Results
A total of 1,002,687 clinical records with 2,682,118 prescriptions were collected and analyzed. The average number of drugs prescribed per encounter was 2.8. The most frequently prescribed medication was Chinese traditional patent medicines (CTPM) (36.5% of overall prescriptions) followed by antibiotics (18.1%). It showed a preference of CPTM over conventional medicines. The median cost per visit was 17.91 USD. The median drug cost per visit was 13.84 USD. The expenditures of antibiotics and CTPM per visit (6.05 USD and 5.87 USD) were among the three highest categories of drugs. The percentage of out-of-pocket patients reached 65.9%. Disparities were showed among subgroups of different ages, regions, and insurance types.

Conclusions
The high volume of CPTM usage is the typical feature in outpatient care of AURI pediatric patients in China. The rational and cost-effective use of CPTM and antibiotics still faces challenges. The reimbursement for child AURI cases needs to be enhanced.
Costs and its drivers for diabetes mellitus type 2 patients in France and Germany: a systematic review of economic studies
Authors: Stegbauer Constance , Falivena Camilla , Moreno Ariadna , Hentschel Anna , Rosenmöller Magda , Heise Tim , Szecsenyi Joachim , Schliess Freimut 
Published: November 2020

Abstract
Background
Type 2 diabetes represents an increasingly critical challenge for health policy worldwide. It absorbs massive resources from both patients and national economies to sustain direct costs of the treatment of type 2 diabetes and its complications and indirect costs related to work loss and wages. More recently, there are innovations based on remote control and personalised programs that promise a more cost-effective diabetes management while reducing diabetes-related complications. In such a context, this work attempts to update cost analysis reviews on type 2 diabetes, focusing on France and Germany, in order to explore most significant cost drivers and cost-saving opportunities through innovations in diabetes care. Although both countries approach care delivery differently, France and Germany represent the primary European markets for diabetes technologies.

Methods
A systematic review of the literature listed in MEDLINE, Embase and EconLit has been carried out. It covered interventional, observational and modelling studies on expenditures for type 2 diabetes management in France or Germany published since 2012. Included articles were analysed for annual direct, associated and indirect costs of type 2 diabetes patients. An appraisal of study quality was performed. Results were summarised narratively.

Results
From 1260 records, the final sample was composed of 24 papers selected according to predefined inclusion/exclusion criteria. Both France and Germany revealed a predominant focus on direct costs. Comparability was limited due to different study populations and cost categories used. Indirect costs were only available in Germany. According to prior literature, reported cost drivers are hospitalisation, prescriptions, higher HbA1c and BMI, treatment with insulin and complications, all indicators of disease severity. The diversity of available data and included costs limits the results and may explain the differences found.

Conclusions
Complication prevention and glycaemic control are widely recognized as the most effective ways to control diabetes treatment costs. The value propositions of self-based supports, such as hybrid closed-loop metabolic systems, already implemented in type 1 diabetes management, are the key points for further debates and policymaking, which should involve the perspectives of caregivers, patients and payers.
EZH2 promotes the expression of LPA1 by mediating microRNA-139 promoter methylation to accelerate the development of ovarian cancer
Authors: Wu Dongbo , Wu Fanglan , Li Birong , Huang Wei , Wang Donglian 
Published: November 2020

Abstract
Background
It has been known that ovarian cancer (OC) is a leading cause for women mortality globally. We aimed to analyze the underlying mechanism supporting that enhancer of zeste homolog 2 (EZH2) affected the development of OC via the involvement of microRNA-139 (miR-139)/transforming growth factor beta (TGF-β)/lysophosphatidic acid-1 (LPA1) axis.

Methods
High expression patterns of EZH2 and miR-139 and low LPA1 expression pattern in OC were evaluated using RT-qPCR and immunoblotting, while their correlation was assessed by the Spearman’s rank and Pearson’s correlation coefficient. Subsequently, dual-luciferase reporter gene assay was applied to validate the binding relationship between miR-139 and LPA1, while H3K27me enrichment was assessed by ChIP assay. After that, the effects of altered expression of EZH2, miR-194, or LPA1 on the cell biological functions and the expression pattern of TGF-related factors were evaluated.

Results
We found that EZH2 repressed the miR-139 expression pattern by recruiting H3K27me3 to promote miR-139 promoter methylation, while silencing of EZH2 suppressed in vitro cancer progression by increasing miR-139. LPA1 was a target of miR-139, and could activate the TGF-β signaling pathway, which hastened the OC progression. miR-139-targeted inhibition of LPA1 and LPA1-activated TGF-β signaling pathway were evidenced to be critical mechanisms underlying the effects of EZH2 on OC cells. Lastly, silencing of EZH2 inhibited the xenograft growth in vivo.

Conclusions
EZH2 could down-regulate miR-139 expression pattern by recruiting H3K27me3 to promote the miR-139 promoter methylation and activate the TGF-β pathway by up-regulating LPA1, which contributed to the progression of OC. The current study may possess potentials for OC treatment.
The double-edged sword effect of macrophage targeting delivery system in different macrophage subsets related diseases
Authors: Yuan Yuchuan , Long Ling , Liu Jiaxing , Lin Yongyao , Peng Cuiping , Tang Yue , Zhou Xuemei , Li Shuhui , Zhang Chengyuan , Li Xiaohui , Zhou Xing 
Published: November 2020

AbstractBackgroundMonocyte/macrophage-targeting delivery systems (MTDSs) have been focused upon as an emerging routine for delivering drugs to treat various macrophage-related diseases. However, the ability of MTDSs to distinguish different macrophage-related diseases and their impact on macrophage function and disease progression have not been systematically revealed, which is important for actively targeted therapeutic or diagnostic strategies.ResultsHerein, we used dextran-modified polystyrene nanoparticles (DEX-PS) to demonstrate that modification of nanoparticles by dextran can specifically enhance their recognition by M2 macrophages in vitro, but it is obstructed by monocytes in peripheral blood according to in vivo assays. DEX-PS not only targeted and became distributed in tumors, an M2 macrophage-related disease, but was also highly distributed in an M1 macrophage-related disease, namely acute peritonitis. Thus, DEX-PS acts as a double-edged sword in these two different diseases by reeducating macrophages to a pro-inflammatory phenotype.ConclusionsOur results suggest that MTDSs, even those designed based on differential expression of receptors on specific macrophage subtypes, lack the ability to distinguish different macrophage subtype-related diseases in vivo. In addition to the potential impact of these carrier materials on macrophage function, studies of MTDSs should pay greater attention to the distribution of nanoparticles in non-target macrophage-infiltrated disease sites and their impact on disease processes.
The tail of cryptochromes: an intrinsically disordered cog within the mammalian circadian clock
Authors: Parico Gian Carlo G. , Partch Carrie L. 
Published: November 2020

AbstractCryptochrome (CRY) proteins play an essential role in regulating mammalian circadian rhythms. CRY is composed of a structured N-terminal domain known as the photolyase homology region (PHR), which is tethered to an intrinsically disordered C-terminal tail. The PHR domain is a critical hub for binding other circadian clock components such as CLOCK, BMAL1, PERIOD, or the ubiquitin ligases FBXL3 and FBXL21. While the isolated PHR domain is necessary and sufficient to generate circadian rhythms, removing or modifying the cryptochrome tails modulates the amplitude and/or periodicity of circadian rhythms, suggesting that they play important regulatory roles in the molecular circadian clock. In this commentary, we will discuss how recent studies of these intrinsically disordered tails are helping to establish a general and evolutionarily conserved model for CRY function, where the function of PHR domains is modulated by reversible interactions with their intrinsically disordered tails.
Substantia nigra Smad3 signaling deficiency: relevance to aging and Parkinson’s disease and roles of microglia, proinflammatory factors, and MAPK
Authors: Liu Ying , Yu Lijia , Xu Yaling , Tang Xiaohui , Wang Xijin 
Published: November 2020

Abstract
Background
Smad3 signaling is indicated to regulate microglia activity. Parkinson’s disease (PD) neurodegeneration is shown to be associated with aging and neuroinflammation. However, it remains unclear about the relationship among Smad3 signaling, aging, neuroinflammation, and PD.

Methods
Rats were treated with SIS3 (a specific inhibitor of Smad3, intranigal injection) and/or lipopolysaccharide (intraperitoneal injection). We investigated the effect of SIS3 and lipopolysaccharide and their mechanism of action on motor behavior and nigrostriatal dopaminergic system in the rats. Furthermore, we explored the effect of SIS3 and LPS and their potential signaling mechanism of action on inflammatory response by using primary microglial cultures. Finally, we investigated the relationship among aging, Smad3 signaling, and neuroinflammation using animals of different ages.

Results
Both SIS3 and lipopolysaccharide induced significant behavior deficits and nigrostriatal dopaminergic neurodegeneration in the rats compared with the vehicle-treated (control) rats. Significantly increased behavior deficits and nigrostriatal dopaminergic neurodegeneration were observed in the rats co-treated with SIS3 and lipopolysaccharide compared with the rats treated with vehicle, SIS3, or lipopolysaccharide. Furthermore, both SIS3 and lipopolysaccharide induced significant microglia activation and proinflammatory factor (IL-1β, IL-6, iNOS, and ROS) level increase in the SN of rats compared with the control rats. Significantly enhanced microglial inflammatory response was observed in the rats co-treated with SIS3 and lipopolysaccharide compared with the other three groups. For our in vitro study, both SIS3 and lipopolysaccharide induced significant proinflammatory factor level increase in primary microglia cultures compared with the control cultures. Significantly increased inflammatory response was observed in the cultures co-treated with SIS3 and lipopolysaccharide compared with the other three groups. MAPK (ERK/p38) contributed to microglial inflammatory response induced by co-treatment with SIS3 and lipopolysaccharide. Interestingly, there was decrease in Smad3 and pSmad3 expression (protein) and enhancement of neuroinflammation in the mouse SN with aging. Proinflammatory factor levels were significantly inversely correlated with Smad3 and pSmad3 expression.

Conclusion
Our study strongly indicates the involvement of SN Smad3 signaling deficiency in aging and PD neurodegeneration and provides a novel molecular mechanism underlying the participation of aging in PD and helps to elucidate the mechanisms for the combined effect of multiple factors in PD.
Dosimetric analysis of local failures in skull-base chordoma and chondrosarcoma following pencil beam scanning proton therapy
Authors: Basler Lucas , Poel Robert , Schröder Christina , Bolsi Alessandra , Lomax Antony , Tanadini-Lang Stephanie , Guckenberger Matthias , Weber Damien C. 
Published: November 2020

Abstract
Background
Despite combined modality treatment involving surgery and radiotherapy, a relevant proportion of skull-base chordoma and chondrosarcoma patients develop a local recurrence (LR). This study aims to analyze patterns of recurrence and correlate LR with a detailed dosimetric analysis.

Methods
222 patients were treated with proton radiotherapy for chordoma (n = 151) and chondrosarcoma (n = 71) at the PSI between 1998 and 2012. All patients underwent surgery, followed by pencil-beam scanning proton therapy to a mean dose of 72.5 ± 2.2GyRBE. A retrospective patterns of recurrence analysis was performed: LR were contoured on follow-up MRI, registered with planning-imaging and the overlap with initial target structures (GTV, PTVhigh-dose, PTVlow-dose) was calculated. DVH parameters of planning structures and recurrences were calculated and correlated with LR using univariate and multivariate cox regression.

Results
After a median follow-up of 50 months, 35 (16%) LR were observed. Follow-up MRI imaging was available for 27 (77%) of these recurring patients. Only one (3.7%) recurrence was located completely outside the initial PTV (surgical pathway recurrence). The mean proportions of LR covered by the initial target structures were 48% (range 0–86%) for the GTV, 70% (range 0–100%) for PTVhigh and 83% (range 0–100%) for PTVlow. In the univariate analysis, the following DVH parameters were significantly associated with LR: GTV(V < 66GyRBE, p = 0.01), GTV(volume, p = 0.02), PTVhigh(max, p = 0.02), PTVhigh(V < 66GyRBE, p = 0.03), PTVhigh(V < 59GyRBE, p = 0.02), PTVhigh(volume, p = 0.01) and GTV(D95, p = 0.05). In the multivariate analysis, only histology (chordoma vs. chondrosarcoma, p = 0.01), PTVhigh(volume, p = 0.05) and GTV(V < 66GyRBE, p = 0.02) were independent prognostic factors for LR.

Conclusion
This study identified DVH parameters, which are associated with the risk of local recurrence after proton therapy using pencil-beam scanning for patients with skull-base chordoma and chondrosarcoma.
Metachronous cutaneous squamous cell carcinoma in a young patient as the only presenting symptom to uncover Lynch syndrome with MLH1 Germline mutation
Authors: Khaddour Karam , Fields Ryan C. , Ansstas Michael , Rosman Ilana S. , Ansstas George 
Published: November 2020

Abstract
Background
Cutaneous malignancies are rare complications of Lynch syndrome and can include Muir-Torre and Turcot syndromes that are associated with sebaceous gland tumors and keratoacanthomas. The incidence and clinical course of cutaneous squamous cell carcinoma have not been well documented in Lynch syndrome due to its rarity.

Case presentation
A 49-year male presented with an enlarging groin skin lesion that was biopsed and demonstrated cutaneous squamous cell carcinoma for which he underwent a surgical resection. The patient experienced later a recurrence of cutaneous squamous cell carcinoma around the resected margins. Next generation sequencing of tumor tissue revealed mutations in MSH6 and MLH1, in addition to high microsatellite instability. The patient underwent pembrolizumab treatment with complete resolution of the cutaneous lesion in the groin, but subsequently developed a new mass in the right antecubital fossa shortly after discontinuation of pembrolizumab. Repeat biopsy of the antecubital fossa lesion revealed a recurrence of cutaneous squamous cell carcinoma. Germline mutation testing revealed MLH1 mutation, compatible with Lynch syndrome, and the patient restarted pembrolizumab which was associated with a complete response. The patient was referred for genetic counseling and cancer screening.

Conclusions
Cutaneous squamous cell carcinoma, although rare, can be the initial presenting symptom in patients with Lynch syndrome. This association has been described in patients with germline mutations in MLH1. Lynch syndrome should be considered when evaluating young patients presenting with recurrent cutaneous squamous cell carcinoma with positive family history of malignancy and/ or without any identifiable risk factors for skin cancers, including those with a durable and rapid response to immunotherapy.