bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intervertebral disc degeneration in mice with type II diabetes induced by leptin receptor deficiency
Authors: Li Xinhua , Liu Xiaoming , Wang Yiru , Cao Fuming , Chen Zhaoxiong , Hu Zhouyang , Yu Bin , Feng Hang , Ba Zhaoyu , Liu Tao , Li Haoxi , Jiang Bei , Huang Yufeng , Li Lijun , Wu Desheng 
Published: February 2020

Abstract
Background
The leptin receptor-deficient knockout (db/db) mouse is a well-established model for studying type II diabetes mellitus (T2DM). T2DM is an important risk factor of intervertebral disc degeneration (IVDD). Although the relationship between type I diabetes and IVDD has been reported by many studies, few studies have reported the effects of T2DM on IVDD in db/db mice model.

Methods
Mice were separated into 3 groups: wild-type (WT), db/db, and IGF-1 groups (leptin receptor-deficient mice were treated with insulin-like growth factor-1 (IGF-1). To observe the effects of T2DM and glucose-lowering treatment on IVDD, IGF-1 injection was used. The IVD phenotype was detected by H&E and safranin O fast green staining among db/db, WT and IGF-1 mice. The levels of blood glucose and weight in mice were also recorded. The changes in the mass of the trabecular bone in the fifth lumbar vertebra were documented by micro-computed tomography (micro-CT). Tunnel assays were used to detect cell apoptosis in each group.

Results
The weight of the mice were 27.68 ± 1.6 g in WT group, which was less than 57.56 ± 4.8 g in db/db group, and 52.17 ± 3.7 g in IGF-1 injected group (P < 0.05). The blood glucose levels were also significantly higher in the db/db mice group. T2DM caused by leptin receptor knockout showed an association with significantly decreased vertebral bone mass and increased IVDD when compared to WT mice. The db/db mice induced by leptin deletion showed a higher percentage of MMP3 expression as well as cell apoptosis in IVDD mice than WT mice (P < 0.05), while IGF-1 treatment reversed this situation (P < 0.05).

Conclusions
T2DM induced by leptin receptor knockout led to IVDD by increasing the levels of MMP3 and promoting cell apoptosis. IGF-1 treatment partially rescue the phenotype of IVDD induced by leptin receptor knockout.
Pedicle frozen autograft–prosthesis composite reconstructions for malignant bone tumors of the proximal femur
Authors: Xu Gang , Miwa Shinji , Yamamoto Norio , Hayashi Katsuhiro , Takeuchi Akihiko , Igarashi Kentaro , Higuchi Takashi , Taniguchi Yuta , Araki Yoshihiro , Yonezawa Hirotaka , Morinaga Sei , Tsuchiya Hiroyuki 
Published: February 2020

Abstract
Background
Limb salvage surgery is becoming increasingly popular after tumor resection in the lower extremity. Biological reconstruction and use of megaprosthesis are main methods for malignant bone tumors of the proximal femur, which remain controversial due to short- and long-term complication in the proximal femur. Tumor-bearing bone treated by liquid nitrogen is one of biological reconstruction. This study aimed to evaluate the mid- and long-term functional outcomes and complications in patients treated with frozen autograft–prosthesis composite (FAPC) reconstructions in the proximal femur.

Methods
This retrospective study included 19 patients (10 women, 9 men) with malignant tumors of the proximal femur who underwent tumor-wide resection and FAPC reconstruction (mean age, 46 years; range, 9–77 years). The mean follow-up period of 69 months (range, 9–179 months). Functional outcomes, oncological outcome and complications were evaluated by Musculoskeletal Tumor Society score, clinical and radiological examinations.

Results
The overall survival rate was 68.4%, and the mean Musculoskeletal Tumor Society functional score was 26.4 points (88%). FAPC survival rates were 100 and 50% at 5 and 10 years, respectively. Five of the 19 patients (26%) had complications: 2 required prosthesis removal and 2 developed a deep infection around acetabular. Wear of the acetabulum occurred in 2 cases, while disease recurrence was occurred in 1 case. There were no cases of greater trochanter avulsion, obvious absorption around frozen bone, prosthesis loosening or leg length discrepancy.

Conclusions
Due to without femoral osteotomy, this technique features satisfactory functional outcome and provide biomechanical stability that is comparable to those of other methods of biological reconstruction or megaprosthesis.
Monitoring of the invasion of Spartina alterniflora from 1985 to 2015 in Zhejiang Province, China
Authors: Li Nan , Li Longwei , Zhang Yinlong , Wu Ming 
Published: February 2020

Abstract
Background
Spartina alterniflora is an invasive plant on the coast of China that replaces native vegetation and has a serious negative impact on local ecosystems. Monitoring the spatial distribution of S. alterniflora and its changes over time can reveal its expansion mechanism, which is crucial for the management of coastal ecosystems. The purpose of this study was to map the distribution of S. alterniflora in Zhejiang Province from 1985 to 2015 using a time series of Landsat TM/OLI images and analyze the temporal and spatial patterns of expansion of this species.

Results
After analyzing the distribution of coastal vegetation, the vegetation index was calculated based on Landsat images for 4 years (1985, 1995, 2005 and 2015). According to a threshold determined based on expert knowledge, the distribution of S. alterniflora in Zhejiang Province was extracted, and the temporal and spatial changes in the distribution of S. alterniflora were analyzed. The classification accuracy was 90.3%. S. alterniflora has expanded rapidly in recent decades after being introduced into southern Zhejiang. Between 1985 and 2015, S. alterniflora increased its area of distribution by 10,000 hm2, and it replaced native vegetation to become the most abundant halophyte in tidal flats. Overall, S. alterniflora expanded from south to north over the decades of the study, and the fastest expansion rate was 463.64 hm2/year, which occurred between 1995 and 2005. S. alterniflora was widely distributed in the tidal flats of bays and estuaries and expanded outward as sediment accumulated.

Conclusions
This study reveals the changes over time in S. alterniflora cover in Zhejiang and can contribute to the control and management of this invasive plant.
Decursinol from Angelica gigas Nakai enhances endometrial receptivity during implantation
Authors: Kim Seong-Eun , Lee Joo Eun , Han Young-Hyun , Lee Se-In , Kim Do Kyung , Park Seok-Rae , Yu Seong-Lan , Kang Jaeku 
Published: February 2020

AbstractBackgroundEmbryo implantation is essential for a successful pregnancy, and an elaborate synchronization between the receptive endometrium and trophoblast is required to achieve this implantation. To increase ‘endometrial receptivity’, the endometrium undergoes transformation processes including responses of adhesion molecules and cellular and molecular cell to cell communication. Many natural substances from traditional herbs have been studied to aid in the achievement of successful implantation. In this study, we investigated positive effects on embryonic implantation with decursinol that is a major compound extracted fromAngelica gigasNakai known to be associated with promotion of healthy pregnancy in the traditional Korean herbal medicine.MethodsExpression of cell adhesion molecules after treatment of endometrial epithelial cells by decursinol (40 or 80 μM) was determined using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and western blot analysis. The alteration of endometrial receptivity by decursinol (40 or 80 μM) was identified with the in vitro implantation model between Ishikawa cells and JAr cell spheroids (diameter, 143 ± 16 μm). Exosomes secreted from Ishikawa cells after treatment of 80 μM decursinol or dimethyl sulfoxide (DMSO) as the vehicle were investigated with invasion of JAr cells and attachment of JAr spheroids to Ishikawa cells.ResultsDecursinol significantly (P < 0.05) increased the expression of important endometrial adhesion molecules such as integrin β1, β3, β5 and L-selectin mRNAs and integrin β5 and L-selectin in protein. The adhesion rate of JAr spheroids to decursinol-treated Ishikawa cells also increased significantly which was 2.4-fold higher than that of the control (P < 0.05). Furthermore, decursinol induced an increase in the release of exosomes from Ishikawa cells and decursinol-induced exosomes showed autocrine (to Ishikawa cells) and paracrine (to JAr cells) positive effects on our implantation model.ConclusionThese results propose that decursinol could serve as a new and alternative solution for patients who are infertile.
Chaenomelis fructus inhibits osteoclast differentiation by suppressing NFATc1 expression and prevents ovariectomy-induced osteoporosis
Authors: Kim Minsun , Kim Ho-Seok , Kim Jae-Hyun , Kim Eun-Young , Lee Bina , Lee Sung Yub , Jun Jae-Yun , Kim Min Beom , Sohn Youngjoo , Jung Hyuk-Sang 
Published: February 2020

Abstract
Background
Osteoporosis is related to the number and activity of osteoclasts. The goal of the present study was to demonstrate the effect of Chaenomelis Fructus (CF) on osteoclastogenesis and its mechanism of bone loss prevention in an OVX-induced osteoporosis model.

Methods
Osteoclasts were induced by RANKL in RAW 264.7 cells. TRAP assay was performed to measure the inhibitory effect of CF on osteoclast differentiation. Then, Expression of nuclear factor of activated T-cells (NFATc1), c-Fos which are essential transcription factors in osteoclastogenesis were detected using western blot and RT-PCR. The osteoclast-related markers were measured by RT-PCR. Moreover, the ability of CF to inhibit bone loss was researched by ovariectomized (OVX)-induced osteoporosis.

Results
Cell experiments showed that CF inhibited osteoclast differentiation and its function. Immunoblot analyses demonstrated that CF suppressed osteoclastogenesis through the NFATc1 and c-Fos signaling pathways. RT-PCR determined that CF inhibited osteoclast-related markers, such as tartrate-resistant acid phosphatase (TRAP), cathepsin K (CTK), osteoclast-associated immunoglobulin-like receptor (OSCAR), ATPase H+ Transporting V0 Subunit D2 (ATP6v0d2) and carbonic anhydrase II (CA2). In animal experiments, CF showed an inhibitory effect on bone density reduction through OVX. Hematoxylin and eosin (H&E) staining analysis data showed that CF inhibited OVX-induced trabecular area loss. TRAP staining and immunohistochemical staining analysis data showed that CF displayed an inhibitory effect on osteoclast differentiation through NFATc1 inhibition in femoral tissue.

Conclusion
Based on the results of in vivo and in vitro experiments, CF inhibited the RANKL-induced osteoclasts differentiation and its function and effectively ameliorated OVX-induced osteoporosis rats.
Beliefs and intention of heterosexual couples about undertaking Couple’s HIV Testing and Counselling (CHTC) services in Ethiopia
Authors: Hailemariam Tewodros Getachew , Rawstorne Patrick , Sisay Mitike Molla , Nathan Sally 
Published: February 2020

Abstract
Background
Couples HIV Testing & Counselling (CHTC) service is an approach that may enable more people to be reached and tested for HIV. However, little is known about how couples may use this service and what they think about CHTC as an approach to finding out their HIV status. This study aimed to understand how individuals who had ever been in an ongoing heterosexual relationship for 6 months or more intended to use CHTC in Ethiopia and their beliefs about its benefits and potential harms.

Methods
Qualitative in-depth interviews were conducted in Addis Ababa, the capital city of Ethiopia, in 2017. Semi-structured interviews were undertaken with individuals who had ever been in an ongoing heterosexual relationship (n = 21) and key-informants (n = 11) including religious leaders, health care providers, and case managers. The interviews were transcribed verbatim, and an inductive thematic analysis was conducted. The data were coded to look for concepts and patterns across the interviews and relevant themes identified which captured key aspects related to the individual’s views on undertaking HIV testing with a sexual partner.

Results
Most participants regarded CHTC as an important HIV testing approach for people who are in an ongoing heterosexual relationship and expressed the view that there was “nothing like testing together”. However, many of the individual participants revealed they would prefer first to get tested alone to find out their own HIV status. They feared the consequences if they were HIV-positive, including accusations of infidelity, relationship break-up, and being exposed in the community. Many also reported being pressured to undertake CHTC before marriage by a third party, including religious institutions. Key informant interviews also discussed the requirements for CHTC before marriage.

Conclusion
The findings of this study suggest that people may be concerned about undertaking couples HIV testing without prior individual HIV testing. The intention of many to first test alone has policy and cost implications and underscores the possible harms of the implementation of CHTC in Ethiopia. Future research should examine whether the views identified in this qualitative study are reflected more broadly among couples in the community.
Betulinic acid shows anticancer activity against equine melanoma cells and permeates isolated equine skin in vitro
Authors: Weber Lisa A. , Meißner Jessica , Delarocque Julien , Kalbitz Jutta , Feige Karsten , Kietzmann Manfred , Michaelis Anne , Paschke Reinhard , Michael Julia , Pratscher Barbara , Cavalleri Jessika-M. V. 
Published: February 2020

Abstract
Background
Equine malignant melanoma (EMM) is a frequently occurring dermoepidermal tumor in grey horses. Currently available therapies are either challenging or inefficient. Betulinic acid (BA), a naturally occurring triterpenoid, is a promising compound for cancer treatment. To evaluate the potential of BA as a topical therapy for EMM, its anticancer effects on primary equine melanoma cells and dermal fibroblasts and its percutaneous permeation through isolated equine skin were assessed in vitro.

Results
BA showed antiproliferative and cytotoxic effects on both primary equine melanoma cells and fibroblasts in a time- and dose-dependent manner. The lowest half-maximal inhibitory concentrations were obtained 96 h after the beginning of drug exposure (12.7 μmol/L and 23.6 μmol/L for melanoma cells eRGO1 and MelDuWi, respectively, in cytotoxicity assay). High concentrations of the compound were reached in the required skin layers in vitro.

Conclusion
BA is a promising substance for topical EMM treatment. Further clinical studies in horses are necessary to assess safety and antitumoral effects in vivo.
Intra-arterial versus standard intravenous administration of lutetium-177-DOTA-octreotate in patients with NET liver metastases: study protocol for a multicenter, randomized controlled trial (LUTIA trial)
Authors: Ebbers Sander C. , Braat Arthur J. A. T. , Moelker Adriaan , Stokkel Marcel P. M. , Lam Marnix G. E. H. , Barentsz Maarten W. 
Published: February 2020

Abstract
Background
Lutetium-177-DOTA-octreotate (177Lu-DOTATATE) significantly increases survival and response rates in patients with grade I and grade II neuroendocrine tumors (NETs). However, survival and response rates are significantly lower in patients with bulky liver metastases. Increasing the tumor-absorbed dose in liver metastases may improve response to 177Lu-DOTATATE. The LUTIA (Lutetium Intra-Arterial) study aims to increase the tumor-absorbed dose in liver metastases by intra-arterial (IA) administration of 177Lu-DOTATATE, compared to conventional intravenous (IV) administration.

Methods
A multicenter, within-patient randomized controlled trial (RCT) in 26 patients with progressive, liver-dominant, unresectable grade I or grade II NET will be conducted. Patients with bilobar bulky disease will be randomly allocated to receive IA treatment into either the left or the right hepatic artery. Using this approach, one liver lobe will be treated intra-arterially (first-pass effect), while the contralateral lobe will receive an intravenous treatment as a second-pass effect. The primary endpoint of this study is the difference in tumor-to-non-tumor ratio of 177Lu-DOTATATE uptake between the two liver lobes on post-treatment SPECT/CT (IA versus IV). Secondary endpoints include absorbed dose in both liver lobes, tumor response, dose-response relationship, toxicity, uptake in extrahepatic lesions, and renal uptake.

Discussion
This multicenter, within-patient RCT will investigate whether IA administration of 177Lu-DOTATATE results in a higher activity concentration in liver metastases compared to IV administration.

Trial registration
ClinicalTrials.gov, NCT03590119. Registered on 17 July 2018.
Thrombotic microangiopathy and liver toxicity due to a combination therapy of leflunomide and methotrexate: a case report
Authors: Pliquett Rainer Ullrich , Lübbert Christoph , Schäfer Christoph , Girndt Matthias 
Published: February 2020

Abstract
Background
Treatment of active rheumatoid arthritis may necessitate a methotrexate mono- or combination therapy. As in the present case, novel side effects may occur, when escalating therapy.

Case presentation
A 63-year-old Caucasian female patient with rheumatoid arthritis on methotrexate for 8 years and on leflunomide for 6 years was admitted for weakness, edema, ascites, and petechiae of the lower legs. Comorbidities included a urinary tract infection, metabolic syndrome with obesity, type-2 diabetes without necessity for insulin or oral antidiabetics, and non-alcoholic fatty liver disease. Laboratory results showed acute liver failure, oliguric acute kidney injury, thrombocytopenia, and schistocyte-positive, Coombs-negative hemolytic anemia. On admission, her ADAMTS13 activity was decreased, and her leflunomide plasma level was elevated (120 μg/l). Due to severe hypoalbuminemia, an intravascular hypovolemia, and severe metabolic alcalosis with hypokalemia were found.
For the newly diagnosed thrombotic microangiopathy, leflunomide and methotrexate were discontinued, and 4 units of fresh-frozen plasma were given. Steroid therapy was administered for 5 days, until thrombotic thrombocytopenic purpura was excluded. Intravenous human albumin, oral vitamin K, and cholestyramine were administered for liver failure and leflunomide overdosage, respectively. Liver biopsy revealed a non-alcoholic fatty liver disease transforming into liver cirrhosis. After 2 weeks, our patient was discharged. However, within 3 weeks after discharge, our patient was rehospitalized for a relapse of acute liver failure, urinary tract infection, and influenza. Leflunomide and methotrexate were not reintroduced before or thereafter. Over a period of 11 months after discharge, her thrombotic microangiopathy subsided, and her renal and liver function fully recovered.

Conclusions
Under a combination of leflunomide and methotrexate, liver toxicity and, for the first time, thrombotic microangiopathy occurred as side effects. Non-alcoholic fatty liver disease may have predisposed for the drug-induced liver toxicity.
Coupling library Jcup3: its philosophy and application
Authors: Arakawa Takashi , Inoue Takahiro , Yashiro Hisashi , Satoh Masaki 
Published: February 2020

AbstractIn this paper, we describe the design of the coupling library, Jcup, and report its various applications, including the coupling between global atmospheric and oceanic models of different grid systems. Jcup is a software library mainly focused on weather/climate models and was developed for coupling the components of various models. Jcup has the flexibility to be applied to an unspecified number of components of earth system models. To achieve a high level of safety and versatility, we classified the processes of the general coupling software into processes that change the value of the data and those that do not and placed the former outside of the program and under the control of the user. Consequently, Jcup exhibits two features: (1) the correspondence relationship between grid indexes is used as input information, and (2) the user can implement an arbitrary interpolation code. Jcup was applied to atmosphere-ocean coupling, IO component coupling, and the coupling between the seismic model and structure model, and the validity and usefulness of the design were demonstrated.
Amphiphilic hyperbranched polymers: synthesis, characterization and self-assembly performance
Authors: Ren Longfang , Niu Qiaoxuan , Zhao Jing , Qiang Taotao 
Published: February 2020

Abstract
A series of amphiphilic hyperbranched polymers (AHP-s, the “s” refers to the algebra of AHP) were synthesized by the reaction between hydroxyl-terminated hyperbranched polymers (HBP-s, the “s” refers to the algebra of HBP) and palmitoyl chloride. FTIR, NMR and GPC were used to determine the structure of AHP-s, the results showed that AHP-s exhibits core-shell structure. The thermal properties of polymers were investigated by DSC and TGA. It was found that AHP-2, AHP-3 and AHP-4 display higher thermal stability than AHP-1 (AHP-1, AHP-2, AHP-3 and AHP-4 represent the first, second, third and fourth generation AHP, respectively). Furthermore, the self-assembly performance of AHP-s in THF solvent was investigated by TEM and SEM. Finally, the encapsulation capacity of the AHP-s for methyl orange (MO) was explored at different concentrations of AHP-s and pH conditions. It was found that AHP-s is capable of accommodating hydrophilic guest MO. Moreover, the higher generation of AHP-s, the stronger encapsulation capacity obtained. And the encapsulation capacity closely associated with the pH of encapsulation system.

Graphical abstract