Miracle-dz/UniFAR-FTUs huggingface dataset:
BST-236, a novel cytarabine prodrug for patients with acute leukemia unfit for standard induction: a phase 1/2a study.

High-dose cytarabine is the backbone of acute myeloid leukemia (AML) treatment. Nevertheless, its use in older patients is considerably limited due to increased toxicity. BST-236 (INN aspacytarabine) is a novel cytarabine prodrug designed to deliver high-dose cytarabine to target cells with reduced systemic exposure to free cytarabine. This phase 1/2a dose-escalation study was designed to evaluate BST-236 safety, pharmacokinetics, and efficacy in older or unfit-for-intensive-therapy patients with acute leukemia. Twenty-six patients, unfit for standard therapy, who were either relapsed/refractory or newly diagnosed, received BST-236 in 6 dose-escalating cohorts (range 0.3 to 6 g/m2 per day). BST-236 was administered intravenously once daily over 60 minutes for 6 consecutive days. The median age was 76.5 (26 to 90), with 84.6% of patients ≥70 years. BST-236 was safe and well tolerated. The maximal tolerated dose was 6 g/m2 per day. Overall response rate was 29.6%. A subgroup analysis of newly diagnosed patients with AML, de novo or secondary to myelodysplastic syndrome, unfit for standard induction (median age 78), demonstrated overall response of 45.5%. The median overall survival was 6.5 months and was not reached in patients achieving complete remission. The findings of this phase 1/2 study suggest that BST-236 safely delivers high and efficacious cytarabine doses to older patients who are unfit for standard induction and lays the foundation for further studies of BST-236 in AML. This trial was registered at www.clinicaltrials. gov as #NCT02544438.
DCLK1 promotes malignant progression of breast cancer by regulating Wnt/β-Catenin signaling pathway.

OBJECTIVE The study was aimed to investigate the expression of doublecortin-like kinase-1 (DCLK1) in breast cancer (BCa) tissues and cells and further study its association with clinicopathology and prognosis of BCa patients. PATIENTS AND METHODS Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was used to examine the expression of DCLK1 in 44 BCa tumor tissues, as well as adjacent normal tissues. Also, the interplay between DCLK1 level and clinical data or the prognosis of BCa patients was analyzed. QRT-PCR was further used to verify the level of DCLK1 in BCa cell lines. In addition, the DCLK1 knockdown model was constructed using lentivirus in BCa cell lines. Next, cell counting kit-8 (CCK-8) and cell clone formation and tranwell assays were used to analyze the effect of DCLK1 on the biological function of BCa cells. Finally, it was explored whether DCLK1 can act through the Wnt/β-Catenin signaling pathway. RESULTS In this research, qRT-PCR results revealed that the level of DCLK1 in BCa tumor tissues was remarkably higher than in adjacent tissues. Compared to patients with a low-level of DCLK1, the pathology grading in patients with high-level was higher and the overall survival rate was lower. Similarly, proliferation, as well as the invasion and migration ability of cells in DCLK1 knockdown group was remarkably down-regulated when compared to negative control group. Moreover, the Western Blot results revealed that silencing DCLK1 remarkably decreased the expression of key proteins in Wnt/β-Catenin pathways such as β-Catenin, c-myc, and cyclinD1, thereby promoting the malignant progression of BCa. In addition, the Wnt/β-Catenin pathway inhibitor was found to be able to reverse the impact of DCLK1 overexpression on BCa cell proliferative and metastatic capacity. CONCLUSIONS DCLK1 expression was found remarkably increased in BCa tissues and closely associated with the pathological stage, as well as poor prognosis of BCa patients. Furthermore, DCLK1 may promote the malignant progression of BCa by inhibiting the Wnt/β-Catenin pathway.
Time-Lag Between Symptom Onset and Diagnosis of Subacute Thyroiditis – How to Avoid the Delay of Diagnosis and Unnecessary Overuse of Antibiotics

Abstract Clinical symptoms of subacute thyroiditis (SAT) may be misleading and the proper diagnosis is significantly delayed, and many unnecessary therapeutic methods are used, including application of antibiotics. The purpose of the study is to analyze the reasons and frequency of delayed SAT diagnosis and unnecessary antibiotic treatment and to propose a simple algorithm to facilitate the diagnosis and prevent antibiotic abuse. Sixty-four SAT patients were divided into groups depending on the period of time from the first symptoms of SAT to diagnosis and on the unnecessary use of antibiotics. Data from medical history and laboratory test results were analyzed for individual groups to determine the reasons for delayed diagnosis and incorrect treatment. In 73% of patients, the diagnosis was delayed from over two weeks up to six months. Among 62 patients who provided data on antibiotic use, 29 (46.77%) were treated with one or more antibiotics due to SAT symptoms. Fever, preceding infection, increased C-reactive protein (CRP), and WBC were characteristic for the antibiotic treated group. Fever, preceding infection, increased CRP and WBC are typical for both SAT and infection and are the main symptoms leading to misdiagnosis and unnecessary antibiotic treatment in SAT. Thus, in all patients with neck pain or other SAT-like symptoms, thorough clinical examination of the neck is mandatory. When firm and/or tender thyroid nodule/goitre is present and erythrocyte sedimentation rate /CRP is increased, patient should be promptly referred to an endocrinologist, and antibiotics are not recommended.
Fourteen (14) cases of acute focal bacterial nephritis in children

To investigate clinical features, laboratory, and imaging characters in Chinese children, we conducted a retrospective study on 14 children with acute focal bacterial nephritis (AFBN) admitted in Beijing Children’s Hospital during January 2005 to December 2009. Six girls and eight boys with a mean age of 4.7 years (range: 0.3-11.4 years) were followed up on average 1.7 years (range: 0.5-3.5 years). Leukocyturia was found in 10/14 children. Urine cultures were positive in 10/14 cases; E. coli was the most common cause of AFBN. A combination of nephromegaly and focal mass was found in 11/14 patients. Urinary tract anomalies were found in 8 children. Two boys had underlying disease of acute lymphatic leukemia under chemotherapy. AFBN resolved on average 3-12 weeks after therapy. Ultrasound and enhanced CT were not necessary in cases of fever of unknown origin, even if pyuria nor urine culture is positive. Vesicoureteral reflux (VUR), malignancy and renal vascular malformation are potential risk factors of AFBN; careful radiological investigations should be performed.
Dark microbial CO2 fixation in temperate forest soils increases with CO2 concentration

Dark, that is, nonphototrophic, microbial CO2 fixation occurs in a large range of soils. However, it is still not known whether dark microbial CO2 fixation substantially contributes to the C balance of soils and what factors control this process. Therefore, the objective of this study was to quantitate dark microbial CO2 fixation in temperate forest soils, to determine the relationship between the soil CO2 concentration and dark microbial CO2 fixation, and to estimate the relative contribution of different microbial groups to dark CO2 fixation. For this purpose, we conducted a 13C‐CO2 labeling experiment. We found that the rates of dark microbial CO2 fixation were positively correlated with the CO2 concentration in all soils. Dark microbial CO2 fixation amounted to up to 320 µg C kg−1 soil day−1 in the Ah horizon. The fixation rates were 2.8–8.9 times higher in the Ah horizon than in the Bw1 horizon. Although the rates of dark microbial fixation were small compared to the respiration rate (1.2%–3.9% of the respiration rate), our findings suggest that organic matter formed by microorganisms from CO2 contributes to the soil organic matter pool, especially given that microbial detritus is more stable in soil than plant detritus. Phospholipid fatty acid analyses indicated that CO2 was mostly fixed by gram‐positive bacteria, and not by fungi. In conclusion, our study shows that the dark microbial CO2 fixation rate in temperate forest soils increases in periods of high CO2 concentrations, that dark microbial CO2 fixation is mostly accomplished by gram‐positive bacteria, and that dark microbial CO2 fixation contributes to the formation of soil organic matter.
Use of Falls Risk Increasing Drugs in Residents at High and Low Falls Risk in Aged Care Services

Falls are associated with considerable morbidity and mortality in aged care services and falls risk increasing drugs (FRIDs) are often overlooked as a contributor to falls. This study aims to investigate the association between the risk of falling and use of FRIDs from aged care services. Inverse-probability-weighted multinomial logistic regression was used to estimate the association between falls risk and regular FRIDs in 383 residents from six Australian aged care services. Overall, residents at high and low falls risk had similar prevalence of FRIDs. Prevalence of antipsychotics and sedative-hypnotics was low. Residents at high falls risk had higher adjusted odds of using ≥2 psychotropic medications (odds ratio [OR] = 1.75, 95% confidence interval [CI] = 1.17-2.61) and ≥2 medications that cause/worsen orthostatic hypotension (OR = 3.59, 95% CI = 2.27-5.69). High prevalence of FRIDs was mainly attributable to medications for which residents had clinical indications. Clinicians appeared to have largely avoided FRIDs that explicit criteria deem potentially inappropriate for high falls risk.
Lipase-Catalyzed Chemoselective Ester Hydrolysis of Biomimetically Coupled Aryls for the Synthesis of Unsymmetric Biphenyl Esters

Lipases are among the most frequently used biocatalysts in organic synthesis, allowing numerous environmentally friendly and inexpensive chemical transformations. Here, we present a biomimetic strategy based on iron(III)-catalyzed oxidative coupling and selective ester monohydrolysis using lipases for the synthesis of unsymmetric biphenyl-based esters under mild conditions. The diverse class of biphenyl esters is of pharmaceutical and technical relevance. We explored the potency of a series of nine different lipases of bacterial, fungal, and mammalian origin on their catalytic activities to cleave biphenyl esters, and optimized the reaction conditions, in terms of reaction time, temperature, pH, organic solvent, and water–organic solvent ratios, to improve the chemoselectivity, and hence control the ratio of unsymmetric versus symmetric products. Elevated temperature and increased DMSO content led to an almost exclusive monohydrolysis by the four lipases Candida rugosa lipase (CRL), Mucor miehei lipase (MML), Rhizopus niveus lipase (RNL), and Pseudomonas fluorescens lipase (PFL). The study was complemented by in silico binding predictions to rationalize the observed differences in efficacies of the lipases to convert biphenyl esters. The optimized reaction conditions were transferred to the preparative scale with high yields, underlining the potential of the presented biomimetic approach as an alternative strategy to the commonly used transition metal-based strategies for the synthesis of diverse biphenyl esters.
Lysobacter enzymogenes employs diverse genes for inhibiting hyphae growth and spore germination of soybean fungal pathogens.

Lysobacter enzymogenes strain C3 (LeC3) is a potential biocontrol agent for plant diseases caused by fungi and oomycetes. Understanding the interaction between LeC3 and soybean pathogens at the molecular level could help improve its biocontrol efficacy. In this study, we obtained mutants with decreased abilities in inhibiting hyphae growth of the white mold pathogen Sclerotinia sclerotiorum. Insertion sites for 50 mutants, which no longer inhibited S. sclerotiorum hyphae growth in dual cultural assay, were determined and seven mutants were selected for further characterization. These seven mutants also completely lost their abilities in suppressing spore germination of Fusarium virguliforme, the causal agent of soybean sudden death syndrome. Furthermore, mutation of the seven genes, which encode diguanylate cyclase (Dgc), transcriptional regulators from the TetR family (TetR1 and TetR2), hemolysin III family channel protein (YqfA), type IV secretion system VirB10 protein (T4SS, VirB10), phenol hydroxylase (Ph), and phosphoadenosine phosphosulfate reductase (CysH), respectively, led to reduced production and/or secretion of four extracellular enzymes and heat stable antifungal factor (HSAF). These results suggested that these seven genes play important roles in L. enzymogenes in suppressing hyphae growth and spore germination of fungal pathogens, probably by influencing production and/or secretion of extracellular enzymes and HSAF.
Prognostic and clinicopathological significance of long non-coding RNA UCA1 in colorectal cancer

Abstract Objective: Urothelial cancer-associated 1 (UCA1), an oncogenic long non-coding RNA, was aberrantly upregulated in colorectal cancer (CRC). This study aimed to further explore the clinical value of UCA1 in CRC. Methods: Eligible studies were retrieved by searching Pubmed, Embase, Cochrane Library, Web of Science, Chinese National Knowledge Infrastructure, and Wanfang databases. Pooled hazard ratio (HR) and odds ratio (OR) with 95% confidence interval (CI) were applied to assess the prognostic role and clinical significance of UCA1. Results: A total of 7 eligible studies with 775 cancer patients were recruited in the meta-analysis. The results showed that UCA1 overexpression was significantly correlated with poor overall survival in patients with CRC (HR = 2.25, 95% CI: 1.77–2.87, P < .001). There was also a significantly negative association between high UCA1 levels and tumor differentiation (OR = 2.84, 95% CI: 1.87–4.31, P < .001), lymph node metastasis (OR = 3.48, 95% CI: 2.24–5.41, P < .001), distant metastasis (OR = 2.67, 95% CI: 1.32–5.38, P = .006), tumor node metastasis stage (OR = 3.01, 95% CI: 2.16–4.18, P < .001), tumor invasion depth (OR = 2.18, 95% CI: 1.03–4.61, P = .04), and tumor size (OR = 2.27, 95% CI: 1.56–3.32, P < .001). Conclusions: Our study revealed that UCA1 overexpression was associated with poor prognosis and more advanced clinicopathological features, suggesting that UCA1 may serve as an indicator for unfavorable outcome of patients with CRC.
Maximal Treadmill Performance of Children with Cerebral Palsy

Nine children with spastic cerebral palsy (CP) and 9 controls (mean age 13.5 and 14.0, respectively) completed a maximal walking test on the treadmill. Initial gradient was set at 0% with a speed increase every 2 minutes until the “fastest walking speed” was achieved in the third stage. The gradient was then increased by 2.5–5% every 2 minutes. VO2max of the CP children was significantly lower (p = .001) than that of the controls (32.7 vs. 45.2 ml · kg1 · min−1). There was no significant difference in maximal heart rate between the two groups (189 vs. 197). However, the CP subjects had significantly higher (p = .007) ventilatory equivalent for O2 compared to the controls (41.4 vs. 33.6). The lower VO2max values of the CP children might reflect inefficient ventilation, compromised circulation, and local fatigue in the spastic limb muscles.
The Endocannabinoid System in Pediatric Inflammatory and Immune Diseases

Endocannabinoid system consists of cannabinoid type 1 (CB1) and cannabinoid type 2 (CB2) receptors, their endogenous ligands, and the enzymes responsible for their synthesis and degradation. CB2, to a great extent, and CB1, to a lesser extent, are involved in regulating the immune response. They also regulate the inflammatory processes by inhibiting pro-inflammatory mediator release and immune cell proliferation. This review provides an overview on the role of the endocannabinoid system with a major focus on cannabinoid receptors in the pathogenesis and onset of inflammatory and autoimmune pediatric diseases, such as immune thrombocytopenia, juvenile idiopathic arthritis, inflammatory bowel disease, celiac disease, obesity, neuroinflammatory diseases, and type 1 diabetes mellitus. These disorders have a high social impact and represent a burden for the healthcare system, hence the importance of individuating more innovative and effective treatments. The endocannabinoid system could address this need, representing a possible new diagnostic marker and therapeutic target.
Pancreas lipiodol embolism induced acute necrotizing pancreatitis following transcatheter arterial chemoembolization for hepatocellular carcinoma

Abstract Rationale: Transcatheter arterial chemoembolization (TACE) is recognized as one of the most commonly used modalities for non-surgical treatment for advanced hepatocellular carcinoma (HCC). Ectopic lipiodol embolism is an extremely rare complication of TACE. Patient concerns: A 61-year-old man who had a 10-year history of cirrhosis caused by hepatitis B infection was diagnosed with ascites and HCC. Subsequently, the patient underwent TACE. However, he experienced persistent left upper abdominal pain, poor appetite, nausea, moderate fever and accompanied by elevation of serum and urine amylase on the 2nd and 3nd day after treatment. Diagnoses: The patient was diagnosed as having acute hemorrhagic necrotizing pancreatitis based on biochemical and inflammatory markers and CT findings. We deduced that the acute necrotizing pancreatitis was caused by a small branch of the left hepatic artery feeding the pancreas tail and embolizing the drug and lipiodol shunting to the tail of the pancreas. Interventions: The patient was treated for 5 days according to the comprehensive treatment of acute necrotizing pancreatitis, by the inhibition of the secretion of pancreatic juice, relieving pain, and total parenteral nutrition and forbidding diet. The symptoms of the patient were observed to improve, and SAMS and urinary amylase (UAMS) level decreased to 143 IU/L and 254 IU/L, respectively and oral diet was permitted. Outcome: After a period of 2 weeks, the contrast abdominal CT showed slightly decreased fluid collection of the peri-pancreatic space. Moreover, it also showed flocculous and linear high-density shadow in the pancreatic tail, suggesting lipiodol deposition in the pancreatic tail. Subsequently, the symptoms were observed to abate, and the patient left the hospital. On the 21st day after TACE, the patient had a follow up in our outpatient department; the biochemical characteristics and inflammatory markers were observed to be normal Conclusion: AP is still a rare complication after TACE. Etiology is still attributed to the occurrence of shunting and embolization drug reflux. Strategies strengthening the catheter tip that is placed as close to the distal branches of the hepatic artery for the possible careful injection of embolic materials is still the key to avoid post-TACE AP.
Substantiating synesthesia: a novel aid in a case of grapheme-colour synesthesia and concomitant dyscalculia

ABSTRACT Here we present the case of SP, a 21-year-old female with life-long dyscalculia. SP was subsequently diagnosed with grapheme-color synesthesia, a diagnosis that serendipitously catalyzed our development of a novel aid:The digit-color calculator (DCC). The DCC substantiates SP’s color concurrents, dramatically ameliorating her difficulties with basic calculations. We envisage the DCC and its analogues may assist others in educational settings, particularly if they experience difficulties with the acquisition of literacy and numeracy. Further devices that leverage synesthesia may also have the potential to improve the quality of life for others with trait synesthesia regardless of concomitant disorder.
Window of opportunity treatment in breast cancer

Window of opportunity therapies, which involve short‐term administration of systemic therapy between cancer diagnosis and surgery, have raised significant interest in recent years as a mean of assessing the sensitivity of a patient's cancer to therapy prior to surgery. There is now compelling evidence that in patients with early stage hormone‐receptor positive breast cancer, a 2‐week preoperative treatment with standard hormone therapies in a preoperative window period provides important prognostic information, which in turn helps to aid decision‐making regarding treatment options. Changes in short‐term biomarker endpoints such as cell proliferation measured by Ki‐67 can act as surrogate markers of long‐term outcomes. Paired tissues obtained pre‐ and post‐investigational treatment, without having to subject the patient to additional biopsies, can then be used to conduct translational research to investigate predictive biomarkers and pharmacodynamics. In this review, we will examine the utility and challenges of window of opportunities therapies in breast cancer in the current literature, and the current Australian and international trial landscape in this clinical space.
Characteristics and Performance Evaluation of QZSS Onboard Satellite Clocks

In the Global Navigation Satellite System (GNSS) community, the Quasi-Zenith Satellite System (QZSS) is an augmentation system for users in the Asia-Pacific region. However, the characteristics and performance of four QZSS satellite clocks in a long-term scale are unknown at present. However, it is crucial to the positioning, navigation and timing (PNT) services of users, especially in Asia-Pacific region. In this study, the characteristics and performance variation of four QZSS satellite clocks, which including the phase, frequency, frequency drift, fitting residuals, frequency accuracy, periodic terms, frequency stability and short-term clock prediction, are revealed in detail for the first time based on the precise satellite clock offset products of nearly 1000 days. The important contributions are as follows: (1) It is detected that the times of phase and frequency jump are 2.25 and 1.5 for every QZSS satellite clock in one year. The magnitude of the frequency drift is about 10−18. The periodic oscillation of frequency drift of J01 and J02 satellite clocks is found. The clock offset model precision of QZSS is 0.33 ns. (2) The two main periods of QZSS satellite clock are 24 and 12 hours, which is the influence of the satellite orbit; (3) The frequency stability of 100, 1000 and 10,000 s are 1.98 × 10−13, 6.59 × 10−14 and 5.39 × 10−14 for QZSS satellite clock, respectively. The visible “bump” is found at about 400 s for J02 and J03 satellite clocks. The short-term clock prediction accuracy of is 0.12 ns. This study provides a reference for the state monitoring and performance variation of the QZSS satellite clock.