bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of aromatase inhibitor treatment on global gene expression and its association with antiproliferative response in ER+ breast cancer in postmenopausal patients
Authors:   on behalf of the POETIC Trial Management Group and Trialists, Gao Qiong , López-Knowles Elena , Cheang Maggie Chon U. , Morden James , Ribas Ricardo , Sidhu Kally , Evans David , Martins Vera , Dodson Andrew , Skene Anthony , Holcombe Chris , Mallon Elizabeth , Evans Abigail , Bliss Judith M. , Robertson John , Smith Ian , Martin Lesley-Ann , Dowsett Mitch 
Published: December 2019

AbstractBackgroundEndocrine therapy reduces breast cancer mortality by 40%, but resistance remains a major clinical problem. In this study, we sought to investigate the impact of aromatase inhibitor (AI) therapy on gene expression and identify gene modules representing key biological pathways that relate to early AI therapy resistance.MethodsGlobal gene expression was measured on pairs of core-cut biopsies taken at baseline and at surgery from 254 patients with ER-positive primary breast cancer randomised to receive 2-week presurgical AI (n = 198) or no presurgical treatment (controln = 56) from the POETIC trial. Data from the AI group was adjusted to eliminate artefactual process-related changes identified in the control group. The response was assessed by changes in the proliferation marker, Ki67.ResultsHigh baselineESR1expression associated with better AI response in HER2+ tumours but not HER2− tumours. In HER2− tumours, baseline expression of 48 genes associated with poor antiproliferative response (p < 0.005) includingPERPandYWHAQ, the two most significant, and the transcription co-regulators (SAP130,HDAC4, andNCOA7) which were among the top 16 most significant. Baseline gene signature scores measuring cell proliferation, growth factor signalling (ERBB2-GS, RET/GDNF-GS, andIGF-1-GS), and immune activity (STAT1-GS) were significantly higher in poor AI responders. Two weeks of AI caused downregulation of genes involved in cell proliferation and ER signalling, as expected. Signature scores of E2F activation and TP53 dysfunction after 2-week AI were associated with poor AI response in both HER2− and HER2+ patients.ConclusionsThere is a high degree of heterogeneity in adaptive mechanisms after as little as 2-week AI therapy; however, all appear to converge on cell cycle regulation. Our data support the evaluation of whether an E2F signatures after short-term exposure to AI may identify those patients most likely to benefit from the early addition of CDK4/6 inhibitors.Trial registrationISRCTN,ISRCTN63882543, registered on 18 December 2007.
Endocrine-responsive lobular carcinoma of the breast: features associated with risk of late distant recurrence
Authors: Conforti Fabio , Pala Laura , Pagan Eleonora , Viale Giuseppe , Bagnardi Vincenzo , Peruzzotti Giulia , De Pas Tommaso , Bianco Nadia , Graffeo Rossella , Rocco Elena Guerini , Vingiani Andrea , Gelber Richard D. , Coates Alan S. , Colleoni Marco , Goldhirsch Aron 
Published: December 2019

AbstractBackgroundInvasive lobular carcinomas (ILCs) account for 10–15% of all breast cancers. They are characterized by an elevated endocrine responsiveness and by a long lasting risk of relapse over time. Here we report for the first time an analysis of clinical and pathological features associated with the risk of late distant recurrence in ILCs.Patients and methodsWe retrospectively analyzed all consecutive patients with hormone receptor–positive ILC operated at the European Institute of Oncology (EIO) between June 1994 and December 2010 and scheduled to receive at least 5 years of endocrine treatment.The aim was to identify clinical and pathological variables that provide prognostic information in the period beginning 5 years after definitive surgery. The cumulative incidence of distant metastases (CI-DM) from 5 years after surgery was the prospectively defined primary endpoint.ResultsOne thousand eight hundred seventy-two patients fulfilled the inclusion criteria. The median follow-up was 8.7 years.Increased tumor size and positive nodal status were significantly associated with higher risk of late distant recurrence, but nodal status had a significant lower prognostic value in late follow-up period (DM-HR, 3.21; 95% CI, 2.06–5.01) as compared with the first 5 years of follow-up (DM-HR, 9.55; 95% CI, 5.64–16.2; heterogeneitypvalue 0.002).Elevated Ki-67 labeling index (LI) retained a significant and independent prognostic value even after the first 5 years from surgery (DM-HR, 1.81; 95% CI 1.19–2.75), and it also stratified the prognosis of ILC patients subgrouped according to lymph node status.A combined score, obtained integrating the previously validated Clinical Treatment Score post 5 years (CTS5) and Ki-67 LI, had a strong association with the risk of late distant recurrence of ILCs.ConclusionWe identified factors associated with the risk of late distant recurrence in ER-positive ILCs and developed a simple prognostic score, based on data that are readily available, which warrants further validation.
Salivary gland proteome analysis of developing adult female Haemaphysalis longicornis ticks: molecular motor and TCA cycle-related proteins play an important role throughout development
Authors: Ren Shuguang , Zhang Baowen , Xue Xiaomin , Wang Xiaoshuang , Zhao Huaqu , Zhang Xiaoli , Wang Minjing , Xiao Qi , Wang Hui , Liu Jingze 
Published: December 2019

AbstractBackgroundTicks are notorious blood-feeding arthropods that can spread a variety of deadly diseases. The salivary gland is an important organ for ticks to feed on blood, and this organ begins to develop rapidly when ixodid ticks suck blood. When these ticks reach a critical weight, the salivary glands stop developing and begin to degenerate. The expression levels of a large number of proteins during the development and degeneration of salivary glands change, which regulate the biological functions of the salivary glands. Furthermore, to the best of our knowledge, there are only a few reports on the role of molecular motor and TCA cycle-related proteins in the salivary glands of ticks.ResultsWe used iTRAQ quantitative proteomics to study the dynamic changes in salivary gland proteins in femaleHaemaphysalis longicornisat four feeding stages: unfed, partially fed, semi-engorged and engorged. Using bioinformatics methods to analyze the dynamic changes of a large number of proteins, we found that molecular motor and TCA cycle-related proteins play an important role in the physiological changes of the salivary glands. The results of RNAi experiments showed that when dynein, kinesin, isocitrate dehydrogenase and citrate synthase were knocked down independently, the weight of the engorged female ticks decreased by 63.5%, 54.9%, 42.6% and 48.6%, respectively, and oviposition amounts decreased by 83.1%, 76.0%, 50.8%, and 55.9%, respectively, and the size of type III acini of females salivary glands decreased by 35.6%, 33.3%, 28.9%, and 20.0%, respectively.ConclusionsThe results showed that the expression of different types of proteins change in different characteristics in salivary glands during the unfed to engorged process of female ticks. Corresponding expression changes of these proteins at different developmental stages of female ticks are very important to ensure the orderly development of the organ. By analyzing these changes, some proteins, such as molecular motor and TCA cycle-related proteins, were screened and RNAi carried out. When these mRNAs were knocked down, the female ticks cannot develop normally. The research results provide a new protein target for the control of ticks and tick-borne diseases.
LINE-1 ORF2p expression is nearly imperceptible in human cancers
Authors: Ardeljan Daniel , Wang Xuya , Oghbaie Mehrnoosh , Taylor Martin S. , Husband David , Deshpande Vikram , Steranka Jared P. , Gorbounov Mikhail , Yang Wan Rou , Sie Brandon , Larman H. Benjamin , Jiang Hua , Molloy Kelly R. , Altukhov Ilya , Li Zhi , McKerrow Wilson , Fenyö David , Burns Kathleen H. , LaCava John 
Published: December 2019

Abstract
Background
Long interspersed element-1 (LINE-1, L1) is the major driver of mobile DNA activity in modern humans. When expressed, LINE-1 loci produce bicistronic transcripts encoding two proteins essential for retrotransposition, ORF1p and ORF2p. Many types of human cancers are characterized by L1 promoter hypomethylation, L1 transcription, L1 ORF1p protein expression, and somatic L1 retrotransposition. ORF2p encodes the endonuclease and reverse transcriptase activities required for L1 retrotransposition. Its expression is poorly characterized in human tissues and cell lines.

Results
We report mass spectrometry-based tumor proteome profiling studies wherein ORF2p eludes detection. To test whether ORF2p could be detected with specific reagents, we developed and validated five rabbit monoclonal antibodies with immunoreactivity for specific epitopes on the protein. These reagents readily detect ectopic ORF2p expressed from bicistronic L1 constructs. However, endogenous ORF2p is not detected in human tumor samples or cell lines by western blot, immunoprecipitation, or immunohistochemistry despite high levels of ORF1p expression. Moreover, we report endogenous ORF1p-associated interactomes, affinity isolated from colorectal cancers, wherein we similarly fail to detect ORF2p. These samples include primary tumors harboring hundreds of somatically acquired L1 insertions. The new data are available via ProteomeXchange with identifier PXD013743.

Conclusions
Although somatic retrotransposition provides unequivocal genetic evidence for the expression of ORF2p in human cancers, we are unable to directly measure its presence using several standard methods. Experimental systems have previously indicated an unequal stoichiometry between ORF1p and ORF2p, but in vivo, the expression of these two proteins may be more strikingly uncoupled. These findings are consistent with observations that ORF2p is not tolerable for cell growth.
Obesity-induced nucleosome release predicts poor cardio-metabolic health
Authors: Lo Re Oriana , Maugeri Andrea , Hruskova Jana , Jakubik Juraj , Kucera Jan , Bienertova-Vasku Julie , Oben Jude A. , Kubala Lukas , Dvorakova Adela , Ciz Milan , Vinciguerra Manlio 
Published: December 2019

Abstract
Objective
While circulating nucleosome levels are high in obese mouse models, it is unknown where these nucleosomes originate from and whether they are a marker of cardio-metabolic health in humans. Here, we aimed to determine whether an association exists between circulating nucleosomes and the risk of developing obesity, metabolic syndrome (MetS) and/or a dysfunctional cardiovascular performance.

Methods
We randomly selected 120 participants of the Kardiovize Brno 2030 study across three BMI strata: BMI 18–25, 25–30, and > 30. We assessed the association between circulating nucleosome levels and the risk of obesity, MetS, and poor cardiovascular health. We then cultured human neutrophils, adipocytes, and hepatoma cells to study nucleosome origins in a fat-rich environment.

Results
Circulating nucleosome levels positively correlated with BMI (R = 0.602, p < 0.05), fatty liver index (R = 0.622, p < 0.05), left ventricular mass (R = 0.457, p < 0.05), and associated with MetS (p < 0.001) and poor cardiovascular health (p < 0.001). Incubating neutrophils with 1–10 μM free fatty acids triggered nucleosome production without concomitant cell death. Nucleosomes were not produced during pre-adipocyte differentiation or upon incubation of hepatic cells with palmitic acid.

Conclusions
Neutrophils are a bona fide source of circulating nucleosomes in an obesogenic environment and in overweight/obese patients. High nucleosome levels are associated with MetS and cardiovascular performance, and might represent novel candidate biomarkers for cardio-metabolic health.
α-Synuclein conformational strains spread, seed and target neuronal cells differentially after injection into the olfactory bulb
Authors: Rey Nolwen L. , Bousset Luc , George Sonia , Madaj Zachary , Meyerdirk Lindsay , Schulz Emily , Steiner Jennifer A. , Melki Ronald , Brundin Patrik 
Published: December 2019

AbstractAlpha-synuclein inclusions, the hallmarks of synucleinopathies, are suggested to spread along neuronal connections in a stereotypical pattern in the brains of patients. Ample evidence now supports that pathological forms of alpha-synuclein propagate in cell culture models and in vivo in a prion-like manner. However, it is still not known why the same pathological protein targets different cell populations, propagates with different kinetics and leads to a variety of diseases (synucleinopathies) with distinct clinical features. The aggregation of the protein alpha-synuclein yields different conformational polymorphs called strains. These strains exhibit distinct biochemical, physical and structural features they are able to imprint to newly recruited alpha-synuclein. This had led to the view that the clinical heterogeneity observed in synucleinopathies might be due to distinct pathological alpha-synuclein strains.To investigate the pathological effects of alpha-synuclein strains in vivo, we injected five different pure strains we generated de novo (fibrils, ribbons, fibrils-65, fibrils-91, fibrils-110) into the olfactory bulb of wild-type female mice. We demonstrate that they seed and propagate pathology throughout the olfactory network within the brain to different extents. We show strain-dependent inclusions formation in neurites or cell bodies. We detect thioflavin S-positive inclusions indicating the presence of mature amyloid aggregates.In conclusion, alpha-synuclein strains seed the aggregation of their cellular counterparts to different extents and spread differentially within the central nervous system yielding distinct propagation patterns. We provide here the proof-of-concept that the conformation adopted by alpha-synuclein assemblies determines their ability to amplify and propagate in the brain in vivo. Our observations support the view that alpha-synuclein polymorphs may underlie different propagation patterns within human brains.
Extra upper limb practice after stroke: a feasibility study
Authors: Schneider Emma J. , Ada Louise , Lannin Natasha A. 
Published: December 2019

Abstract
Background
There is a need to provide a large amount of extra practice on top of usual rehabilitation to adults after stroke. The purpose of this study was to determine if it is feasible to add extra upper limb practice to usual inpatient rehabilitation and whether it is likely to improve upper limb activity and grip strength.

Method
A prospective, single-group, pre- and post-test study was carried out. Twenty adults with upper limb activity limitations who had some movement in the upper limb completed an extra hour of upper limb practice, 6 days per week for 4 weeks. Feasibility was measured by examining recruitment, intervention (adherence, efficiency, acceptability, safety) and measurement. Clinical outcomes were upper limb activity (Box and Block Test, Nine-Hole Peg Test) and grip strength (dynamometry) measured at baseline (week 0) and end of intervention (week 4).

Results
Of the 212 people who were screened, 42 (20%) were eligible and 20 (9%) were enrolled. Of the 20 participants, 12 (60%) completed the 4-week program; 7 (35%) were discharged early, and 1 (5%) withdrew. Participants attended 342 (85%) of the possible 403 sessions and practiced for 324 (95%) of the total 342 h. In terms of safety, there were no study-related adverse events. Participants increased 0.29 blocks/s (95% CI 0.19 to 0.39) on the Box and Block Test, 0.20 pegs/s (95% CI 0.10 to 0.30) on the Nine-Hole Peg Test, and 4.4 kg (95% CI 2.9 to 5.9) in grip strength, from baseline to end of intervention.

Conclusions
It appears feasible for adults who are undergoing inpatient rehabilitation and have some upper limb movement after stroke to undertake an hour of extra upper limb practice. The magnitude of the clinical outcomes suggests that further investigation is warranted and this study provides useful information for the design of a phase II randomized trial.

Trial registration
Australian and New Zealand Clinical Trial Registry (ACTRN12615000665538).
Modern Chinese nationalism and the awakening of self-consciousness of the Chinese Nation
Authors: Zheng Dahua 
Published: December 2019

AbstractThe concept of “Chinese nation” has a close relationship with the rise, development and upsurge of modern Chinese nationalism from its proposition to establishment, and to universal identification among people of all ethnic groups. The period of the late Qing Dynasty and the early Republic of China was the formation stage of modern Chinese nationalism and also the stage of the proposition and initial usage of the concept of “Chinese nation”: Modern Chinese nationalism developed around the period of the May 4th Movement. Under the impetus of the establishment of national self-determination theory, especially the rise of a national self-determination movement, the concept of “Chinese nation” was accepted and adopted by more and more people and finally established and formed. After the September 18th Incident, especially after the North China Incident and the July 7th Marco Polo Bridge Incident, the worsening national crisis promoted the upsurge of modern Chinese nationalism, and this upsurge made the concept of “Chinese nation” more widely and deeply disseminated and accepted.
Soil replacement combined with subsoiling improves cotton yields
Authors: LI Pengcheng , WANG Shulin , QI Hong , WANG Yan , ZHANG Qian , FENG Guoyi , ZHENG Cangsong , YU Xueke , LIN Yongzeng , DONG Helin 
Published: December 2019

Abstract
Background
Long-term rotary tillage has led to the deterioration of cotton production in northern China. This deterioration is due to the disturbance of topsoil, a dense plough pan at the 20–50 cm depth, and the decreased water storage capacity. A 2-yr field experiment was performed from 2014 to 2015 to explore a feasible soil tillage approach to halting the deterioration. The experiment consisted of four treatments: replacing the topsoil from the 0–15 cm layer with the subsoil from the 15–30 cm layer (T1); replacing the topsoil from the 0–20 cm layer with the subsoil from the 20–40 cm layer and subsoiling at the 40–55 cm layer (T2); replacing the topsoil from the 0–20 cm layer with the subsoil from the 20–40 cm layer and subsoiling at the 40–70 cm layer (T3); and conventional surface rotary tillage within 15 cm as the control (CK).

Results
The results indicated that the soil bulk densities at the 20–40 cm layer in T2 were 0.13 g·cm− 3 and 0.15 g·cm− 3 lower than those obtained from CK in 2014 and 2015, respectively. The total nitrogen (N) and the available phosphorus (P) and potassium (K) contents from the 20–40 cm layer in T2 and T3 were significantly higher than those in CK and T1. The amount of soil water stored in the 0–40 cm layer of T2 at the squaring stage of cotton was 15.3 mm and 13.4 mm greater than that in CK in 2014 and 2015, respectively, when the weather was dry. Compared with CK, T2 increased cotton lint yield by 6.1 and 10.2 percentage points in 2014 and 2015, respectively, which was due to the improved roots within the 20–60 cm layer, the greater number of bolls per plant and the higher boll weight in the T2 treatment.

Conclusions
The results suggested that soil replacement plus subsoiling would be a good alternative to current practices in order to break through the bottleneck constraining cotton production in northern China. Replacing the topsoil in the 0–20 cm layer with the soil from the 20–40 cm layer plus subsoiling at the 40–55 cm layer would be the most effective method.
Posterior condylar offset changes and its effect on clinical outcomes after posterior-substituting, fixed-bearing total knee arthroplasty: anterior versus posterior referencing
Authors: Chang Moon Jong , Kang Seung-Baik , Chang Chong Bum , Han Do Hwan , Park Hyung Jun , Hwang Keummin , Park Jisu , Hwang Il-Ung , Lee Seung Ah. , Oh Sohee 
Published: December 2019

AbstractBackgroundWe sought to determine whether there was a difference in the posterior condylar offset (PCO), posterior condylar offset ratio (PCOR) and clinical outcomes following total knee arthroplasty (TKA) with anterior referencing (AR) or posterior referencing (PR) systems. We also assessed whether the PCO and PCOR changes, as well as patient factors were related to range of motion (ROM) in each referencing system.MethodsThis retrospective study included 130 consecutive patients (184 knees) with osteoarthritis who underwent primary posterior cruciate ligament (PCL)-substituting fixed-bearing TKA. The difference between preoperative and postoperative PCO and PCOR values were calculated. Clinical outcomes including ROM and Western Ontario and McMaster University (WOMAC) scores were evaluated. Furthermore, multiple linear regression analysis was performed to determine the factors related to postoperative ROM in each referencing system.ResultsThe postoperative PCO was greater in the AR group (28.4 mm) than in the PR group (27.4 mm), whereas the PCO was more consistently preserved in the PR group. The mean postoperative ROM after TKA was greater in the AR group (129°) than in the PR group (122°), whereas improvement in WOMAC score did not differ between the two groups. Preoperative ROM was the only factor related to postoperative ROM in both groups.ConclusionsThere was no difference in postoperative PCO in AR and PR group and the PCO was not associated with postoperative ROM. PCO was more consistently preserved after surgery in the PR group. The postoperative PCO and PCOR changes did not affect the postoperative ROM. Furthermore, similar clinical outcomes were achieved in the AR and PR groups.Trial registrationRetrospectively registered (Trial registration number:06-2010-110).
Comparison of the postoperative analgesic effect for infiltration between the popliteal artery and the capsule of the posterior knee and that of periarticular multimodal drug injection in total knee arthroplasty: retrospective study in the immediate postoperative period
Authors: Jung Dae-Won , Shon Won-Yong , Seo Seung-Suk , Kim Ok-Gul , Lee In-Seung 
Published: December 2019

AbstractBackgroundThe aim of this study is to compare the postoperative analgesic effect of infiltration between the popliteal artery and the capsule of the knee (IPACK) and the effect of periarticular multimodal drug injection (PMDI) in addition to adductor canal block (ACB) after total knee arthroplasty.MethodsAmong patients who received total knee arthroplasty from June 2017 to December 2017, 50 who underwent ACB with additional IPACK and 50 who received ACB with additional PMDI were selected for this study. We compared the postoperative pain numerical rating scale (NRS), the number of times patient-controlled analgesia was administered and the amount administered, the total amount of opioids given, and complications associated with the procedure between the two groups.ResultsNRS measured at rest and 45° knee flexion at days 1 and 2 after surgery was significantly lower in the IPACK group than in the PMDI group. The resting NRS measured at day 3 after surgery was also significantly lower in the IPACK group than in the PMDI group, and the NRS at 45° knee flexion measured from day 3 to day 5 showed a significant reduction in the IPACK group. No complications relating to the procedure occurred.ConclusionsIPACK may be a better option than PMDI for controlling acute phase pain in patients undergoing total knee arthroplasty.