Up-Regulation of Kin17 Is Essential for Proliferation of Breast Cancer

Background: Kin17 is ubiquitously expressed at low levels in human tissue and participates in DNA replication, DNA repair and cell cycle control. Breast cancer cells are characterized by enabling replicative immortality and accumulated DNA damage. However, whether kin17 contributes to breast carcinogenesis remains unknown. Methodology/Principal Findings: In this study, we show for the first time that kin17 is an important molecule related to breast cancer. Our results show that kin17 expression was markedly increased in clinical breast tumors and was associated with tumor grade, Ki-67 expression, p53 mutation status and progesterone receptor expression, which were assessed in a clinicopathologic characteristics review. Knockdown of kin17 inhibited DNA replication and repair, blocked cell cycle progression and inhibited anchorage-independent growth, while increasing sensitivity to chemotherapy in breast cancer cells. Moreover, kin17 silencing decreased EGF-stimulated cell growth. Furthermore, overexpression of kin17 promoted DNA replication and cell proliferation in MCF-10A. Conclusions/Significance: Our findings indicate that up-regulation of kin17 is strongly associated with cellular proliferation, DNA replication, DNA damage response and breast cancer development. The increased level of kin17 was not only a consequence of immortalization but also associated with tumorigenesis. Therefore, kin17 could be a novel therapeuti

Better PROMs and higher return-to-sport rate after modular bicompartmental knee arthroplasty than after total knee arthroplasty for medial and patellofemoral compartment osteoarthritis

BackgroundTheoretical advantages of bicompartmental knee arthroplasty (BKA) over total knee arthroplasty (TKA) for bicompartmental (medial combined with patellofemoral) osteoarthritis (OA) are still unclear. This study aimed to compare patient-reported outcome measures (PROMs) and return-to-sport (RTS) rate between modular BKA and TKA in early follow-up.MethodsTwenty-five consecutive modular BKA cases with a minimum 2-year follow-up were matched with 50 TKA cases at 1:2 ratio. Demographic data and preoperative functional scores, including the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Knee Society Scores (KSSs), were analyzed to ensure comparability. Postoperative WOMAC score, KSS, range of motion (ROM), Forgotten Joint Score-12 (FJS-12), and RTS rates were compared. Operative time and blood loss were also analyzed.ResultsSignificant differences in the WOMAC-function (median 97.1 vs. 89.7, p < 0.001) and KSS-function (median 90.0 vs. 80.0, p = 0.003) scores were identified between the BKA and TKA groups. ROM was significantly greater in the BKA group than in the TKA group (median 125.0° vs. 120.0°, p = 0.004), in addition to the FJS-12 (median 89.6 vs. 53.1, p < 0.001). The overall RTS rate was significantly higher in the BKA group than in the TKA group (71.6% vs. 56.5%, p = 0.039). Operative time was significantly longer in the BKA group than in the TKA group (median 105.0 vs. 67.5 min, p < 0.001), but blood loss was similar (median 557.6 vs. 450.7 ml, p = 0.334).ConclusionModular BKA demonstrated better functional recovery, better joint perception, and higher RTS rate than TKA; thus, modular BKA can be a good alternative for bicompartmental OA

Whole Genome Distribution and Ethnic Differentiation of Copy Number Variation in Caucasian and Asian Populations

Although copy number variation (CNV) has recently received much attention as a form of structure variation within the human genome, knowledge is still inadequate on fundamental CNV characteristics such as occurrence rate, genomic distribution and ethnic differentiation. In the present study, we used the Affymetrix GeneChip® Mapping 500K Array to discover and characterize CNVs in the human genome and to study ethnic differences of CNVs between Caucasians and Asians. Three thousand and nineteen CNVs, including 2381 CNVs in autosomes and 638 CNVs in X chromosome, from 985 Caucasian and 692 Asian individuals were identified, with a mean length of 296 kb. Among these CNVs, 190 had frequencies greater than 1% in at least one ethnic group, and 109 showed significant ethnic differences in frequencies (p<0.01). After merging overlapping CNVs, 1135 copy number variation regions (CNVRs), covering approximately 439 Mb (14.3%) of the human genome, were obtained. Our findings of ethnic differentiation of CNVs, along with the newly constructed CNV genomic map, extend our knowledge on the structural variation in the human genome and may furnish a basis for understanding the genomic differentiation of complex traits across ethnic groups

A Neuroimaging Marker Based on Diffusion Tensor Imaging and Cognitive Impairment Due to Cerebral White Matter Lesions

Background: The peak width of skeletonized mean diffusivity (PSMD) is a new, fully automated, robust imaging marker for cerebral small vessel disease (SVD), strongly associated with processing speed. However, it has never been applied to cerebral white matter lesions (WMLs). Our study aimed to investigate the correlation between PSMD and cognition, particularly in the executive function of patients with WMLs.Methods: A total of 111 WML patients and 50 healthy controls (HCs) were enrolled, and their demographic information and cardiovascular disease risk factors were recorded. Subjects were divided into three groups: WMLs with normal cognition (WMLs-NC), WMLs with vascular cognitive impairment (WMLs-VCI), and HCs. They underwent conventional head magnetic resonance imaging and diffusion tensor imaging (DTI), followed by neuropsychological and psychological examinations, including the Montreal Cognitive Assessment (MoCA), and the executive function tests. We compared executive function and PSMD among the three groups and analyzed the correlation between PSMD and cognitive function in all subjects.Results: There were no significant differences in demographic characteristics (age, sex, education level, and cardiovascular disease risk factors) among the three groups (P &gt; 0.05), but there were significant differences in global cognition (P &lt; 0.0001), executive function (P &lt; 0.0001), and PSMD (P &lt; 0.0001). The average PSMD value (×10−4 mm2/s) was 2.40 ± 0.23, 2.68 ± 0.30, and 4.51 ± 0.39 in the HC, WMLs-NC, and WMLs-VCI groups, respectively. There was no correlation between PSMD and cognition in the HC group, but PSMD was significantly correlated with MoCA scores (r = −0.3785, P &lt; 0.0001) and executive function (r = −0.4744, P &lt; 0.0001) in the WMLs-NC group and in the WMLs-VCI group (r = −0.4448, P &lt; 0.0001 and r = −0.6279, P &lt; 0.0001, respectively).Conclusions: WML patients have higher PSMD and worse cognitive performance than HCs, and PSMD is strongly associated with global cognition and executive functions in WML patients. This result provides new insights into the pathophysiology of cognitive impairment in WML patients. PSMD could be a surrogate marker for disease progression and could thus be used in therapeutic trials involving WML patients

Qwen Technical Report

Large language models (LLMs) have revolutionized the field of artificial intelligence, enabling natural language processing tasks that were previously thought to be exclusive to humans. In this work, we introduce Qwen, the first installment of our large language model series. Qwen is a comprehensive language model series that encompasses distinct models with varying parameter counts. It includes Qwen, the base pretrained language models, and Qwen-Chat, the chat models finetuned with human alignment techniques. The base language models consistently demonstrate superior performance across a multitude of downstream tasks, and the chat models, particularly those trained using Reinforcement Learning from Human Feedback (RLHF), are highly competitive. The chat models possess advanced tool-use and planning capabilities for creating agent applications, showcasing impressive performance even when compared to bigger models on complex tasks like utilizing a code interpreter. Furthermore, we have developed coding-specialized models, Code-Qwen and Code-Qwen-Chat, as well as mathematics-focused models, Math-Qwen-Chat, which are built upon base language models. These models demonstrate significantly improved performance in comparison with open-source models, and slightly fall behind the proprietary models.Comment: 59 pages, 5 figure