Miracle-dz/UniFAR-FTUs huggingface dataset:
Toxicity screening of two prevalent metal organic frameworks for therapeutic use in human lung epithelial cells

Introduction The flexibility and tunability of metal organic frameworks (MOFs), crystalline porous materials composed of a network of metal ions coordinated by organic ligands, confer their variety of applications as drug delivery systems or as sensing and imaging agents. However, such properties also add to the difficulty in ensuring their safe implementation when interaction with biological systems is considered. Methods In the current study, we used real-time sensorial strategies and cellular-based approaches to allow for fast and effective screening of two MOFs of prevalent use, namely, MIL-160 representative of a hydrophilic and ZIF-8 representative of a hydrophobic framework. The two MOFs were synthesized “in house” and exposed to human bronchial epithelial (BEAS-2B) cells, a pertinent toxicological screening model. Results Analysis allowed evaluation and differentiation of particle-induced cellular effects as well identification of different degrees and routes of toxicity, all in a high-throughput manner. Our results show the importance of performing screening toxicity assessments before introducing MOFs to biomedical applications. Discussion Our proposed screening assays could be extended to a wider variety of cell lines to allow for identification of any deleterious effects of MOFs, with the range of toxic mechanisms to be differentiated based on cell viability, morphology and cell–substrate interactions, respectively. Conclusion Our analysis highlights the importance of considering the physicochemical properties of MOFs when recommending a MOF-based therapeutic option or MOFs implementation in biomedical applications.
Deep sequencing analysis to identify novel and rare variants in pain-related genes in patients with acute postoperative pain and high morphine use

Purpose Most of the genetic variants that are reported to be associated with common pain phenotypes and analgesic use are common polymorphisms. The objective of our study was to identify new variants and investigate less common genetic variants that are usually not included in either small single-gene studies or high-throughput genotyping arrays. Patients and methods From a cohort of 1075 patients who underwent a scheduled total abdominal hysterectomy, 92 who had higher self-rated pain scores and used more morphine were selected for the re-sequencing of 105 genes. Results We identified over 2400 variants in 104 genes. Most were intronic with frequencies >5%. There were 181 novel variants, of which 30 were located in exons: 17 nonsynonymous, 10 synonymous, 2 non-coding RNA, and 1 stop-gain. For known variants that are rare (population frequency <1%), the frequencies of 54 exonic variants and eight intronic variants for the sequenced samples were higher than the weighted frequencies in the Genome Aggregation Database for East and South Asians (P-values ranging from 0.000 to 0.046). Overall, patients who had novel and/or rare variants used more morphine than those who only had common variants. Conclusion Our study uncovered novel variants in patients who reported higher pain and used more morphine. Compared with the general population, rare variants were more common in this group.
Thalassemia and hepatocellular carcinoma: links and risks

Abstract The increased survival and lifespan of thalassemia patients, in the setting of better iron overload monitoring and chelation, have also however increased the incidence of diseases and complications, which were less likely to develop. Among these, one of the most worrying in recent years is hepatocellular carcinoma (HCC). Due to blood transfusions, many patients with thalassemia are or have been infected with hepatitis C virus (HCV) or hepatitis B virus (HBV), especially those born before the 1990s or in countries in which universal HBV vaccination and safe blood programs are still not completely implemented. However, HCC has also been described in nontransfused patients and in those who are HCV- and HBV-negative. Therefore, other risk factors are involved in hepatocarcinogenesis in thalassemia. The following review analyzes recent literature on the role of different risk factors in the progression of liver disease in thalassemia as well as the importance of surveillance. Treatment of HCC in thalassemia is still highly debated and requires further studies.
Advantage of the F2:A1:B- IncF Pandemic Plasmid over IncC Plasmids in In Vitro Acquisition and Evolution of blaCTX-M Gene-Bearing Plasmids in Escherichia coli

Despite a fitness cost imposed on bacterial hosts, large conjugative plasmids play a key role in the diffusion of resistance determinants, such as CTX-M extended-spectrum β-lactamases. Among the large conjugative plasmids, IncF plasmids are the most predominant group, and an F2:A1:B- IncF-type plasmid encoding a CTX-M-15 variant was recently described as being strongly associated with the emerging worldwide Escherichia coli sequence type 131 (ST131)-O25b:H4 H30Rx/C2 sublineage. ABSTRACT Despite a fitness cost imposed on bacterial hosts, large conjugative plasmids play a key role in the diffusion of resistance determinants, such as CTX-M extended-spectrum β-lactamases. Among the large conjugative plasmids, IncF plasmids are the most predominant group, and an F2:A1:B- IncF-type plasmid encoding a CTX-M-15 variant was recently described as being strongly associated with the emerging worldwide Escherichia coli sequence type 131 (ST131)-O25b:H4 H30Rx/C2 sublineage. In this context, we investigated the fitness cost of narrow-range F-type plasmids, including the F2:A1:B- IncF-type CTX-M-15 plasmid, and of broad-range C-type plasmids in the K-12-like J53-2 E. coli strain. Although all plasmids imposed a significant fitness cost to the bacterial host immediately after conjugation, we show, using an experimental-evolution approach, that a negative impact on the fitness of the host strain was maintained throughout 1,120 generations with the IncC-IncR plasmid, regardless of the presence or absence of cefotaxime, in contrast to the F2:A1:B- IncF plasmid, whose cost was alleviated. Many chromosomal and plasmid rearrangements were detected after conjugation in transconjugants carrying the IncC plasmids but not in transconjugants carrying the F2:A1:B- IncF plasmid, except for insertion sequence (IS) mobilization from the fliM gene leading to the restoration of motility of the recipient strains. Only a few mutations occurred on the chromosome of each transconjugant throughout the experimental-evolution assay. Our findings indicate that the F2:A1:B- IncF CTX-M-15 plasmid is well adapted to the E. coli strain studied, contrary to the IncC-IncR CTX-M-15 plasmid, and that such plasmid-host adaptation could participate in the evolutionary success of the CTX-M-15-producing pandemic E. coli ST131-O25b:H4 lineage.
Size at birth, infant growth, and age at pubertal development in boys and girls

Purpose This study investigated whether size at birth and infant growth were associated with age of indicators of pubertal development in boys and girls. We hypothesized that restricted fetal growth and accelerated infant growth lead to earlier pubertal age. Patients and methods In total, 15,822 boys and girls answered questionnaires half-yearly with information on pubertal development: age at menarche, first ejaculation, voice break, Tanner stages, axillary hair, and acne. Birth weight and gestational age were used to calculate birth weight Z-scores. Changes in infant weight Z-score from 0 to 5, 5 to 12, and 0 to 12 months were estimated. We estimated the mean monthly difference in timing of puberty between children born small-for-gestational age (SGA) and large-for-gestational age (LGA) with children born appropriate-for-gestational age (AGA) as reference. We further investigated whether increasing infant weight Z-scores were associated with age at attaining indicators of pubertal development. Results Girls born SGA reached all pubertal markers at an earlier mean age than girls born AGA, as indicated by mean age differences below zero (eg, age at menarche: −2.3 months, 95% CI: −3.4, −1.2), except for breast development. Girls born LGA reached pubertal markers later than girls born AGA (eg, age at menarche: 1.7 months, 95% CI 0.5, 2.9). Boys born SGA and LGA achieved puberty earlier than boys born AGA, though with CIs crossing zero (eg, age at voice break for SGA: −0.7 months, 95% CI −2.1, 0.7 and for LGA: −0.7 months, 95% CI −2.1, 0.8). A 1-unit increase in weight Z-score from 0 to 12 months was associated with a mean age difference of −1.7 to −0.3 months for pubertal development in both sexes. Conclusion Small size at birth and rapid infant growth were associated with early pubertal age, most consistent and pronounced in girls.
LINC00565 promotes proliferation and inhibits apoptosis of gastric cancer by targeting miR-665/AKT3 axis

Background Numerous studies have shown that long noncoding RNA (lncRNA) is involved in gastric cancer (GC). A relevant microarray containing gastric cancer-related lncRNAs was downloaded from The Cancer Genome Atlas database. Methods qRT-PCR was used to analyze LINC00565 and AKT3 expression in tumor tissues and cell lines. Proliferative, colony formation and apoptotic abilities of GC cells after transfection of sh-LINC00565 were determined by CCK-8, colony formation assay and flow cytometry, respectively. RIP was enrolled to detect the interaction between LINC00565, AKT3 and miR-665. Dual luciferase assay was used to confirm the relation between miR-665 and LINC00565 and AKT3. Results Expression level of LINC00565 in GC tissue was highly expressed in GC, which was negatively correlated to prognosis of GC patients. The results showed that knockdown of LINC00565 decreased proliferative and colony formation abilities, and induced apoptosis of GC cells. Pearson analysis showed that LINC00565 was positively correlated with AKT3. Besides, AKT3 was significantly up-regulated in GC. In addition, knockdown of LINC00565 down-regulated AKT3. In order to explore the mechanism, we found that miR-665 could bind to LINC00565 by bioinformatics. Dual-luciferase reporter gene assay and RIP assay both verified the binding relationship between miR-665 and AKT3. Finally, rescue experiments were carried out to explore whether AKT3 could reverse the anti-cancer effect of low-level LINC00565 on GC development. Conclusion In summary, the expression of LINC00565 is upregulated in GC. LINC00565 can be used as the sponge of miR-665 to up-regulate the expression of AKT3, thus promoting the progression of GC.
Epidermal growth factor receptor (EGFR) gene alteration and protein overexpression in Malaysian triple-negative breast cancer (TNBC) cohort

Background Epidermal growth factor receptor (EGFR) is a member of the ErbB family of tyrosine kinase receptor proteins that plays important roles in tumour cell survival and proliferation. EGFR has been reported to be overexpressed in up to 78% of triple-negative breast cancer (TNBC) cases suggesting it as a potential therapeutic target. The clinical trials of anti-EGFR agents in breast cancer showed low response rates. However, a subgroup of patients demonstrated response to EGFR inhibitors highlighting the necessity to stratify patients, who might benefit from effective combination therapy that could include anti EGFR-agents. Population variability in EGFR expression warrants systematic evaluation in specific populations. Purpose To study EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort to determine the possibility of using anti-EGFR combinatorial therapy for this population. Patients and methods In this study, we evaluated 58 cases of Malaysian TNBC patient samples for EGFR gene copy number alteration and EGFR protein overexpression using fluorescence in-situ hybridization (FISH) and immunohistochemistry (IHC) methods, respectively. Results EGFR protein overexpression was observed in about 30% while 15.5% displayed high EGFR copy number including 5.17% gene amplification and over 10% high polysomy. There is a positive correlation between EGFR protein overexpression and gene copy number and over expression of EGFR is observed in ten out of the 48 low copy number cases (20.9%) without gene amplification. Conclusion This study provides the first glimpse of EGFR alterations and expressions in a multi ethnic Malaysian TNBC patient cohort emphasising the need for the nationwide large scale EGFR expression evaluation in Malaysia.
Synergistic effect of a retinoid X receptor-selective ligand bexarotene and docetaxel in prostate cancer

Purpose To explore if bexarotene (BEX) synergistically enhances docetaxel (DTX) cytotoxicity in castration-resistant prostate cancer cell lines. Materials and methods MTT assay was used to measure the cytotoxic effect of DTX and BEX on castration-resistant prostate cancer (CRPC) cell proliferation and the combination index (CI) values calculated to analyze the interaction between DTX and BEX. Flow cytometry and Western blot analysis identified the underlying mechanism for the synergistic effect of BEX and DTX. Results When mitotic slippage happens, BEX can synergistically strengthen the anti-proliferation of DTX in a way of significantly down-regulating cyclinB1 and CDK1 expression, and then arresting cells in G2 phase. Conclusion Results from this study showed that BEX-induced G2 arrest and DTX-induced mitotic arrest probably contributed to the synergistic effect of BEX and DTX.
Consumers’ Implicit Motivation Of Purchasing Luxury Brands: An EEG Study

Purpose This study aims to explore consumers’ implicit motivations for purchasing luxury brands based on the functional theories of attitudes by using event-related potentials (ERPs). Methods Brand authenticity and logo prominence were used to modulate the social-adjustive function and value-expressive function, respectively. Twenty right-handed healthy female undergraduates and graduates participated in an experiment that has a 2 brand authenticity (genuine/counterfeit) × 2 brand prominence (prominent logo/no logo) design. In the experiment, participators browsed different luxury handbags with different brand authenticity and logo prominence, and then reported their purchase intentions on a five-point scale. Meanwhile, EEGs were recorded from the subjects throughout the experiment. In the analysis process, three ERP components, which can, respectively, reflect the cognitive conflict (N200), emotional conflict (N400) and motivational emotional arousal (LPP) during the evaluation of marketing-related stimuli, were mainly focused. Results For counterfeit brands, the no logo condition elicited significant larger N200 amplitude, marginally significant larger N400 amplitude and significant smaller LPP amplitude than the prominent logo condition. However, for genuine brands, this modulation effect of logo prominence cannot be found. These results imply that consumers’ implicit social motivations for purchasing luxury brands come from the satisfaction of at least one social goal. When one goal cannot be satisfied, consumers will more expect the satisfaction of another one. If this expectation is violated, it seems to be unexpected and unacceptable. Thus, greater anticipation conflict (N200) and emotion conflict (N400) will be induced, and the purchase motivation (LPP) cannot be aroused. Conclusion Consumers’ preferences for luxury brands are based on the satisfaction of their social goals. These social goals always coexist and perform as compensation with each other. The dissatisfaction of one social goal would promote their expectation of the satisfaction of another social goal.
Association between a teacher’s work passion and a student’s work passion: a moderated mediation model

Purpose Research in the education domain has noted the importance of work-based passion and has repeatedly highlighted how passion influences positive work outcomes. However, far too little attention has been given to investigating whether one’s passion can be transferred to others. Using two theoretical lenses – crossover theory (CT) and emotional contagion theory (ECT) – the present study intends to deepen our understanding by examining whether a teacher’s work passion can be transferred to a student. Methods To address this knowledge gap, we recruited students and their subject teachers (n=226 teacher-student dyads) from the major business schools of Pakistan, based on the convenience sampling method, during the period from November to December 2018. An exploratory factor analysis was run to extract the dimension underlying each construct. A confirmatory factor analysis was conducted using AMOS 24.0 to assess the discriminant and convergent validity of the measurement model. The SPSS PROCESS macro was used to test the hypotheses using SPSS 24.0. Results Consistent with the hypotheses, our results show that a teacher’s work passion can be transferred to a student’s work passion indirectly via emotional contagion. Our data further establish that the transference of a teacher’s work passion to a student’s work passion via emotional contagion is more significant when the teacher is educated at PhD level than when she/he is non-PhD educated. Conclusion To the best of the authors’ knowledge, this study has been one of the first attempts to thoroughly examine work passion transference from teachers to students in the area of higher education and offers several managerial and theoretical implications alongside future opportunities for practitioners and research scholars.
A spotlight on alirocumab in high cardiovascular risk patients with type 2 diabetes and mixed dyslipidemia: a review on the emerging data

Abstract Diabetes is a significant and independent risk factor for atherosclerotic cardiovascular disease (ASCVD), leading to morbidity and mortality among this population. The prevention of macrovascular complications, such as CVD, peripheral arterial disease, and cerebrovascular accident, in patients with diabetes is obtained through multifactorial risk reduction, including mixed dyslipidemia management and adequate glycemic control. For patients with diabetes, it is crucial to initiate adequate dyslipidemia therapy to achieve recommended low-density lipoprotein cholesterol (LDL-C) goal of <70 mg/dL or target non-high-density lipoprotein goal of <100 mg/dL. Lipid-lowering therapies (LLTs), such as statins and ezetimibe, are the cornerstone for plasma LDL-C lowering; however, individuals with diabetes are often unable to achieve target lipid goals with these therapies alone and frequently require additional treatments. A new class of LLTs, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, provides a novel approach to lowering lipids in persons with high CV risk, such as those with diabetes. The clinical data presented in this review indicate the potential benefits of alirocumab in patients with diabetes and its value as a treatment option in patients with diabetic dyslipidemia with no significant safety concerns.
Rotational stability of a new multicomponent intraocular lens

Purpose To evaluate the rotational stability of the Precisight multicomponent intraocular lens (MCIOL) following primary implantation and after enhancement procedures. Patients and methods Prospective, single-center study of eyes that underwent routine cataract surgery with implantation of a non-toric MCIOL, (Precisight, InfiniteVision, Optics, Strasbourg, France). The axis of the MCIOL was measured with a line bisecting the two dialing holes in the front lens. Intraoperative orientation was determined using a digital surgical guidance system while the postoperative orientation was determined using slit-lamp imaging. Two populations were analyzed: eyes that only underwent cataract surgery (PRIM) and eyes that also underwent enhancement (ENH), consisting of surgical front optic exchange. Both populations had 3 observation visits: first implantation (P-Op); 3 months (3mo) and 6 months (6mo) after primary surgery. The ENH group had an additional fourth visit that corresponded to the enhancement surgery (E-Op). The main outcome measure was mean absolute change in MCIOL orientation (degrees). The effects of axial length (AL) and anterior chamber depth (ACD) on IOL rotational stability were examined. Results Thirty-three eyes received MCIOL of which 29 had usable orientation images. Of these, 12 were in the PRIM group and 17 underwent ENH. Regarding the mean absolute rotation, among PRIM eyes, P-Op to 3mo was 3.03±2.45 degrees; P-Op to 6mo, 2.28±1.54 degrees; and 3–6mo, 2.37±1.56 degrees. Among the ENH eyes, P-Op to 3mo was 3.09±1.68; E-Op to 6mo, 2.71±3.30 and P-Op to 6mo, 3.62±3.42. There were no significant differences in the IOL rotation. There were no statistical differences in rotational stability between the ENH and PRIM groups. There was no correlation between IOL rotation and AL or ACD. Conclusion Precisight appears to be rotationally stable. The enhancement procedure does not affect rotational stability.
Enumeration And Characterization Of Circulating Tumor Cells And Its Application In Advanced Gastric Cancer

Background Advanced gastric cancer (aGC) has a high global incidence and a high mortality rate and because of its high malignancy and heterogeneity, the existing methods for prognosis are limited, and a new treatment model is necessary. Circulating tumor cells (CTCs) could be considered as a “liquid biopsy” for tumor diagnosis and for monitoring treatment responses and predicting clinical outcome. Clinical studies support the efficacy of programmed cell death 1 (PD-1) immunotherapy in a subset of aGC. Methods Cell capture efficiency, as described by the CanPatrol CTC enrichment technique, was validated using artificial blood samples as well as blood samples from 32 aGC patients. Clinicopathologic data of patients were collected from the hospital information system. We used CanPatrol for CTC isolation, classification, and clinical analysis. Results A cell capture efficiency of >80% was achieved. Significant correlation was observed between CTC enumeration and clinicopathology parameters, including the Lauren classification (r=0.470, P=0.008), perineural invasion (r=0.393, P=0.029), TNM stage (r=0.740, P<0.001), and Ki-67 level (r=0.510, P=0.005). When compared to the traditional methods, monitoring CTC subtypes exhibits higher sensitivity of evaluating the disease status. Enumeration of epithelial CTC subset and its relative abundance in the total CTC pool are highly correlated with clinical efficacy. CTC programmed cell death ligand-1 (PD-L1) could be successfully detected for immunotherapy in addition to PD-L1 immunohistochemistry and microsatellite instability. Conclusion We provide a new method that allows for the simple and effective detection of CTCs in aGC. It has potential clinical applications in monitoring prognosis and guiding future individualized immunotherapy.