bluuebunny/crossref_metadata_2025_split huggingface dataset:
The reference genome and transcriptome of the limestone langur, Trachypithecus leucocephalus, reveal expansion of genes related to alkali tolerance
Authors: Que Tengcheng , Wang Huifeng , Yang Weifei , Wu Jianbao , Hou Chenyang , Pei Surui , Wu Qunying , Li Liu Ming , Wei Shilu , Xie Xing , Huang Hongli , Chen Panyu , Huang Yiming , Wu Aiqiong , He Meihong , Nong Dengpan , Wei Xiao , Wu Junyi , Nong Ru , Huang Ning , Zhou Qingniao , Lin Yaowang , Lu Tingxi , Wei Yongjie , Li Shousheng , Yao Jianglong , Zhong Yanli , Qin Huayong , Tan Luohao , Li Yingjiao , Li Weidong , Liu Tao , Liu Sanyang , Yu Yongyi , Qiu Hong , Jiang Yonghua , Li Youcheng , Liu Zhijin , Huang Cheng Ming , Hu Yanling 
Published: April 2021

Abstract
Background
Trachypithecus leucocephalus, the white-headed langur, is a critically endangered primate that is endemic to the karst mountains in the southern Guangxi province of China. Studying the genomic and transcriptomic mechanisms underlying its local adaptation could help explain its persistence within a highly specialized ecological niche.

Results
In this study, we used PacBio sequencing and optical assembly and Hi-C analysis to create a high-quality de novo assembly of the T. leucocephalus genome. Annotation and functional enrichment revealed many genes involved in metabolism, transport, and homeostasis, and almost all of the positively selected genes were related to mineral ion binding. The transcriptomes of 12 tissues from three T. leucocephalus individuals showed that the great majority of genes involved in mineral absorption and calcium signaling were expressed, and their gene families were significantly expanded. For example, FTH1 primarily functions in iron storage and had 20 expanded copies.

Conclusions
These results increase our understanding of the evolution of alkali tolerance and other traits necessary for the persistence of T. leucocephalus within an ecologically unique limestone karst environment.
Combating drug resistance in acute myeloid leukaemia by drug rotations: the effects of quizartinib and pexidartinib
Authors: Yang Jingmei , Lindström H. Jonathan G. , Friedman Ran 
Published: April 2021

Abstract
Background
Acute myeloid leukaemia (AML) is an aggressive blood cancer. In approximately 30% of the cases, driver mutations in the FLT3 gene are identified. FLT3 inhibitors are used in treatment of such patients together with cytotoxic drugs or (in refractory AML) as single agents. Unfortunately, resistance to FLT3 inhibitors limits their efficacy. Resistance is often due to secondary mutations in the gene encoding the molecular target. The gatekeeper mutation F691L confers resistance to specific FLT3 inhibitors such as quizartinib, but pexidartinib is much less resistance to this mutation. Pexidartinib alone is however sensitive to many other resistance mutations. In chronic myeloid leukaemia (CML), it has been suggested that rotation between drugs with a different landscape of resistance mutations might postpone the emergence of resistance.

Methods
We studied the effect of quizartinib and pexidartinib in AML cell lines that express FLT3 (MOLM-14 and MV4-11). Using a rotation protocol, we further examined whether the emergence of resistance could be postponed. Computational modelling was used to analyse the onset of resistance and suggest which mutations are most likely to occur in a quantitative fashion.

Results
The cells were sensitive to both inhibitors but quickly developed resistance that could be inherited, suggesting a genetic origin. Rotation protocols were not useful to postpone the emergence of resistance, which implies that such protocols, or changing from pexidartinib to quizartinib (or vice-versa) should not be used in patients. The computational modelling led to similar conclusions and suggested that F691L is the most common mutation to occur with quizartinib, and also when both drugs are used in rotation.

Conclusions
AML patients are not likely to benefit from a quizartinib/pexidartinib rotation protocol. A combination of tyrosine kinase inhibitors (with different molecular targets) might be more useful in the future. Development of specific FLT3 inhibitors that are less sensitive to resistance mutations might also lead to a better outcome.
FZD2 promotes TGF-β-induced epithelial-to-mesenchymal transition in breast cancer via activating notch signaling pathway
Authors: Tuluhong Dilihumaer , Chen Tao , Wang Jingjie , Zeng Huijuan , Li Hanjun , Dunzhu Wangmu , Li Qiurong , Wang Shaohua 
Published: April 2021

Abstract
Background
Breast cancer (BC) is one of the commonest female cancers, which is characterized with high incidence. Although treatments have been improved, the prognosis of BC patients in advanced stages remains unsatisfactory. Thus, exploration of the molecular mechanisms underneath BC progression is necessary to find novel therapeutic methods. Frizzled class receptor 2 (FZD2) belongs to Frizzled family, which has been proven to promote cell growth and invasion in various human cancers. The purpose of our current study was to detect the functions of FZD2 in BC and explore its underlying molecular mechanism.

Methods
The level of FZD2 was measured in BC tissues by quantitative real-time polymerase chain reaction (qRT-PCR), western blot, immunohistochemistry (IHC), respectively. Cell Counting Kit-8 (CCK-8), colony formation assay, transwell assays, wound healing assay and flow cytometry analyses were separately conducted to detect cell viability, invasion, migration, apoptosis and cell cycle distribution. The levels of Epithelial-mesenchymal transition (EMT) biomarkers were examined by using Immunofluorescence assay. Xenograft tumorigenicity assay was performed to assess the effect of FZD2 on tumor growth in vivo.

Results
FZD2 mRNA and protein expression was abundant in BC tissues. Moreover, high level of FZD2 had significant correlation with poor prognosis in BC patients. In vitro functional assays revealed that silencing of FZD2 had suppressive effects on BC cell growth, migration and invasion. Animal study further demonstrated that FZD2 silencing inhibited BC cell growth in vivo. In addition, FZD2 induced EMT process in BC cells in a transforming growth factor (TGF)-β1-dependent manner. Mechanistically, knockdown of FZD2 led to the inactivation of Notch signaling pathway.

Conclusion
FZD2 facilitates BC progression and promotes TGF-β1-inudced EMT process through activating Notch signaling pathway.
Mild exacerbation of obesity- and age-dependent liver disease progression by senolytic cocktail dasatinib + quercetin
Authors: Raffaele Marco , Kovacovicova Kristina , Frohlich Jan , Lo Re Oriana , Giallongo Sebastiano , Oben Jude A. , Faldyna Martin , Leva Lenka , Giannone Antonino Giulio , Cabibi Daniela , Vinciguerra Manlio 
Published: April 2021

Abstract
Background
Nonalcoholic fatty liver disease (NAFLD) is increasingly prevalent and represents a growing challenge in terms of prevention and treatment. A minority of affected patients develops inflammation, subsequently fibrosis, cirrhosis and hepatocellular carcinoma (HCC). HCC is a leading cause of cancer-related death. An increased number of senescent cells correlate with age-related tissue degeneration during NAFLD-induced HCC. Senolytics are promising agents that target selectively senescent cells. Previous studies showed that whereas a combination of the senolytic drugs dasatinib and quercetin (D + Q) reduced NAFLD in mice, D + Q lacked efficacy in removing doxorubicin-induced β-gal-positive senescent cells in human HCC xenografted mice. Whether D + Q has an effect on the age-associated spectrum of NAFLD-inflammation-HCC remains unknown.

Methods
Here, we utilized an established model of age- and obesity-associated HCC, the low dose diethylnitrosamine (DEN)/high fat diet (HFD), a regimen promoting liver inflammation and tumorigenesis over a long period of 9 months. Four groups of mice each were created: group 1 included control untreated mice; group 2 included mice treated with D + Q; group 3 included mice undergoing the DEN/HFD protocol; group 4 included mice undergoing the DEN/HFD protocol with the administration of D + Q. At the end of the chemical/dietary regimen, we analyzed liver damage and cell senescence by histopathology, qPCR and immunoblotting approaches.

Results
Unexpectedly, D + Q worsened liver disease progression in the DEN/HFD mouse model, slightly increasing histological damage and tumorigenesis, while having no effect on senescent cells removal.

Conclusions
In summary, using an animal model that fully recapitulates NAFLD, we demonstrate that these compounds are ineffective against age-associated NAFLD-induced HCC.
Whole-exome sequencing reveals the etiology of the rare primary hepatic mucoepidermoid carcinoma
Authors: Hou Ping , Su Xiaoyan , Cao Wei , Xu Liping , Zhang Rongguiyi , Huang Zhihao , Wang Jiakun , Li Lixiang , Wu Linquan , Liao Wenjun 
Published: April 2021

Abstract
Background
Primary hepatic mucoepidermoid carcinoma (HMEC) is extremely rare and the molecular etiology is still unknown. The CRTC1-MAML2 fusion gene was previously detected in a primary HMEC, which is often associated with MEC of salivary gland in the literature.

Methods
A 64-year-old male was diagnosed with HMEC based on malignant squamous cells and mucus-secreting cells in immunohistochemical examination. Fluorescence in situ hybridization (FISH) was used to detect the CRTC1-MAML2 fusion gene in HMEC. Whole-exome sequencing and Sanger sequencing were used to reveal the molecular characteristics of HMEC and analysis was performed with public data. Pedigree investigation was performed to identify susceptibility genes.

Results
Hematoxylin–eosin staining and immunohistochemistry revealed that the tumor cells were composed of malignant epidermoid malignant cells and mucous cells, indicating a diagnosis of HMEC. The CRTC1-MAML2 fusion gene was not detected in the primary HMEC, and somatic mutations in GNAS, KMT2C and ELF3 genes were identified by sequencing. Analyses of public data revealed somatic GNAS alterations in 2.1% hepatobiliary tumors and relation with parasite infection. Heterozygous germline mutations of FANCA, FANCI, FANCJ/BRIP1 and FAN1 genes were also identified. Pedigree investigation verified that mutation of Fanconi’s anemia susceptibility genes were present in the pedigree.

Conclusions
Here we provide the first evidence of the molecular etiology of a rare HMEC associated with germline Fanconi’s anemia gene mutations and somatic GNAS R201H mutation.
Significance of mesothelin and CA125 expression in endometrial carcinoma: a retrospective analysis
Authors: Kakimoto Soichiro , Miyamoto Morikazu , Einama Takahiro , Takihata Yasuhiro , Matsuura Hiroko , Iwahashi Hideki , Ishibashi Hiroki , Sakamoto Takahiro , Hada Taira , Suminokura Jin , Ito Tsubasa , Suzuki Rie , Suzuki Ayako , Takano Masashi 
Published: April 2021

Abstract
Background
This study aimed to investigate the association between clinicopathologic factors, mesothelin, and cancer antigen (CA) 125 in endometrial carcinoma.

Methods
Between 1989 and 2017, patients with endometrial carcinoma who underwent total hysterectomy and bilateral salpingo-oophorectomy at our hospital were identified. The association between either or both immunochemical expression of mesothelin and CA125 and clinicopathological features were retrospectively examined.

Results
Among 485 patients, 171 were positive for mesothelin, 368 were positive for CA125, and 167 were positive for mesothelin and CA125. The expression of mesothelin and CA125 was positively correlated (p < 0.01). More patients with mesothelin expression showed myometrial invasion of more than 50% (p = 0.028) and positive lymphovascular invasion (p = 0.027). Similarly, more patients with co-expression of mesothelin and CA125 had myometrial invasion of more than 50% (p = 0.016) and positive lymphovascular invasion (p = 0.02). Patients with mesothelin expression and co-expression of mesothelin and CA125 demonstrated worse progression-free survival (PFS) and overall survival (OS). In the multivariate analysis, mesothelin expression and co-expression were poor prognostic factors for PFS (mesothelin expression: hazard ratio [HR] = 2.14, p < 0.01; co-expression: HR = 2.19, p < 0.01) and OS (mesothelin expression: HR = 2.18, p < 0.01; co-expression: HR = 2.22, p < 0.01).

Conclusions
Mesothelin expression and co-expression might be associated with tumor aggressiveness and poor prognosis in patients with endometrial carcinoma. Persons with mesothelin-expressing endometrial cancers present a particularly high medical unmet need.
Barriers for early initiation and exclusive breastfeeding up to six months in predominantly rural Sri Lanka: a need to strengthen policy implementation
Authors: Agampodi Thilini Chanchala , Dharmasoma Neerodha Kithmini , Koralagedara Iresha Sandamali , Dissanayaka Thushari , Warnasekara Janith , Agampodi Suneth Buddhika , Perez-Escamilla Rafael 
Published: April 2021

Abstract
Background
Sri Lanka was named as the first-ever ‘Green’ breastfeeding nation status by the World Breastfeeding Trends Initiative (WBTi) in January 2020. However, improvements are still needed. This study aims to identify barriers and facilitators for early initiation of breastfeeding and exclusive breastfeeding for 6 months in rural Sri Lanka.

Methods
We conducted in-depth interviews with 16 mothers with infants, who had been unable to practice early initiation of breastfeeding and/or exclusive breastfeeding (EBF), in six child-welfare clinics in Anuradhapura, Sri Lanka. Three focus group discussions were held with public health midwives (PHMs). Initial thematic analysis that built upon force field and social learning theories was performed.

Results
Main barriers for EBF were clustered at three time periods; during the first 2–3 days, 2–3 weeks, and 4–5 months postpartum. Early barriers included cesarean section pain, poor breast latch, maternal exhaustion, suboptimal maternity ward environment, and lack of support for breastfeeding. Around 2–3 weeks postpartum mothers introduced water or infant formula due to social norms and poor support. On-demand feeding was misunderstood. Around 4 and 5 months postpartum, EBF ended due to return to work. PHMs reported a heavy workload limiting their time to support breastfeeding.

Conclusion
EBF interruption was due to diverse individual- and environnmental- level barriers that varied across the first 6 months. To improve EBF, Sri Lanka should focus on strengthening policies for reducing the excessive rates of cesarean section, improving support in maternity ward facilities, fostering on-demand breastfeeding, enhancing support for working mothers and reducing the work load of PHMs.
An improved method for the segmentation of roots from X-ray computed tomography 3D images: Rootine v.2
Authors: Phalempin Maxime , Lippold Eva , Vetterlein Doris , Schlüter Steffen 
Published: April 2021

AbstractBackgroundX-ray computed tomography is acknowledged as a powerful tool for the study of root system architecture of plants growing in soil. In this paper, we improved the original root segmentation algorithm “Rootine” and present its succeeding version “Rootine v.2”. In addition to gray value information, Rootine algorithms are based on shape detection of cylindrical roots. Both algorithms are macros for the ImageJ software and are made freely available to the public. New features in Rootine v.2 are (i) a pot wall detection and removal step to avoid segmentation artefacts for roots growing along the pot wall, (ii) a calculation of the root average gray value based on a histogram analysis, (iii) an automatic calculation of thresholds for hysteresis thresholding of the tubeness image to reduce the number of parameters and (iv) a false negatives recovery based on shape criteria to increase root recovery. We compare the segmentation results of Rootine v.1 and Rootine v.2 with the results of root washing and subsequent analysis with WinRhizo. We use a benchmark dataset of maize roots (Zea maysL. cv. B73) grown in repacked soil for two scenarios with differing soil heterogeneity and image quality.ResultsWe demonstrate that Rootine v.2 outperforms its preceding version in terms of root recovery and enables to match better the root diameter distribution data obtained with root washing. Despite a longer processing time, Rootine v.2 comprises less user-defined parameters and shows an overall greater usability.ConclusionThe proposed method facilitates higher root detection accuracy than its predecessor and has the potential for improving high-throughput root phenotyping procedures based on X-ray computed tomography data analysis.
Harmonizing healthcare and other resource measures for evaluating economic costs in substance use disorder research
Authors: Papp Michelle A. , Leff Jared A. , Murphy Sean M. , Yang April , Crane Heidi M. , Metsch Lisa R. , Del Rio Carlos , Feaster Daniel J. , Rich Josiah D. , Schackman Bruce R. , McCollister Kathryn E. 
Published: April 2021

Abstract
Background
Standardization and harmonization of healthcare resource utilization data can improve evaluations of the economic impact of treating people with substance use disorder (SUD), including reductions in use of expensive hospital and emergency department (ED) services, and can ensure consistency with current cost-effectiveness and cost-benefit analysis guidelines.

Methods
We examined self-reported healthcare and other resource utilization data collected at baseline from three National Institute on Drug Abuse (NIDA)-funded Seek, Test, Treat, and Retain intervention studies of individuals living with/at risk for HIV with SUD. Costs were calculated by multiplying mean healthcare resource utilization measures by monetary conversion factors reflecting cost per unit of care. We normalized baseline recall timeframes to past 30 days and evaluated for missing data.

Results
We identified measures that are feasible and appropriate for estimating healthcare sector costs including ED visits, inpatient hospital and residential facility stays, and outpatient encounters. We also identified two self-reported measures to inform societal costs (days experiencing SUD problems, participant spending on substances). Missingness was 8% or less for all study measures and was lower for single questions measuring utilization in a recall period.

Conclusions
We recommend including measures representing units of service with specific recall periods (e.g., 6 months vs. lifetime), and collecting healthcare resource utilization data using single-question measures to reduce missingness.
Gap balancing improve squat function and knee function: a randomized controlled trial comparing gap balancing and measured resection
Authors: Xiao Qingfang , Liu Bo , Zhao Binghao 
Published: April 2021

AbstractObjectiveWe compared the measured resection (MR) technique and the gap balancing (GB) technique in patients with knee osteoarthritis after primary total knee arthroplasty (TKA) in China to understand the effects of the two techniques on knee function and squat function.MethodsFrom March 2017 to September 2019, a prospective randomized controlled trial was conducted with 96 patients with knee osteoarthritis undergoing primary TKA from March 2017 to September 2019 randomized to GB group (n= 48) and MR group (n= 48). Intraoperative indicators (operation time, osteotomy volume of medial and lateral of posterior femoral condyles, external rotation angle) were recorded during operation. At 1, 3, 6, and 12 months after surgery, all the patients came to the hospital for review and underwent the pain severity, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), knee joint range of motion, Oxford Knee Score (OKS), and American Knee Society Score (AKSS) tests. All patients were followed up for more than 1 year.ResultsThe osteotomy volume of the medial femoral condyle in the GB group was higher than that in the MR group (P<0.05), and the operation time in the GB group was shorter than that in the MR group (P<0.05). At 1, 3, 6, and 12 months after surgery, the pain severity in the GB group was lower than that in the MR group (P<0.05), the knee range of motion in the GB group was larger than that in the MR group (P<0.05), the WOMAC of the GB group was lower than that of the MR group (P<0.05), the OKS of the GB group was higher than that of the MR group (P<0.05), the AKSS of the GB group was higher than that of the MR group. The incidence of postoperative complications in the GB group (4.17%) was significantly lower than that in the MR group (18.75%) (P<0.05).ConclusionThe GB technique can effectively shorten the operation time, relieve pain, improve knee range of motion, improve squat function and knee function, reduce osteoarthritis index, and reduce the occurrence of complications, which is worthy of clinical popularization and application.
Matrix-associated autologous chondrocyte implantation with autologous bone grafting of osteochondral lesions of the talus in adolescents: patient-reported outcomes with a median follow-up of 6 years
Authors: Körner Daniel , Gonser Christoph E. , Döbele Stefan , Konrads Christian , Springer Fabian , Keller Gabriel 
Published: April 2021

Abstract
Background
This study presents patient-reported outcome measures after combined matrix-associated autologous chondrocyte implantation and autologous bone grafting in high-stage osteochondral lesions of the talus in adolescents.

Methods
A total of 12 adolescent patients (13 ankles) received matrix-associated autologous chondrocyte implantation and autologous bone grafting for a solitary osteochondral lesion of the talus at a single centre. The Foot and Ankle Outcome Score and Foot and Ankle Ability Measure were defined as outcome measures (median follow-up 80 months [range 22–107 months]). Pre- and postoperative ankle radiographs were evaluated according to the van Dijk ankle osteoarthritis scale.

Results
The study population consisted of four male and nine female cases (mean age at the time of surgery, 17.7 ± 2.1 years). Eight lesions were classified as traumatic and five as idiopathic. Twelve lesions were located medial vs one lateral in the coronal plane and all central in the sagittal plane. The median lesion size and depth were 1.3 cm2 (range 0.9–3.2 cm2) and 5 mm (range 5–9 mm), respectively.
There were no perioperative complications in any of the cases.
In 9 cases patient-reported outcome measures were available. The results of the Foot and Ankle Outcome Score subscales were symptoms, 70 ± 14; pain, 83 ± 10; activities of daily living, 89 ± 12; sports/recreational activities, 66 ± 26; and quality of life, 51 ± 17. The mean overall Foot and Ankle Outcome Score was 78 ± 13.
The results of the Foot and Ankle Ability Measure subscales were activities of daily living, 81 ± 20; function/activities of daily living, 84 ± 13; sports, 65 ± 29; and function/sports, 73 ± 27. According to the function overall subscale of the Foot and Ankle Ability Measure, in two cases, the patients assessed the ankle function as normal, in three as nearly normal, and in three as abnormal (missing data, n = 1).
Preoperative van Dijk scale: stage 0 in five cases and stage I in eight cases; postoperative van Dijk scale: stage 0 in four cases, stage I in 9 cases

Conclusions
Patient-reported outcome measures following matrix-associated autologous chondrocyte implantation and autologous bone grafting for high-stage osteochondral lesions of the talus in adolescents show heterogeneous results. Long-term limitations mainly affect sports and recreational activities. Osteochondral lesions of the talus are associated with osteoarthritis, even preoperatively. However, we did not find significant osteoarthritis progression after matrix-associated autologous chondrocyte implantation and autologous bone grafting in the long term.