Miracle-dz/UniFAR-FTUs huggingface dataset:
Imaging flow cytometry reveals a subset of TdT negative T‐ALL blasts with very low forward scatter on conventional flow cytometry

Studies in T‐cell acute lymphoblastic leukemia (T‐ALL) have shown that leukemic blast populations may display immunophenotypic heterogeneity. In the clinical setting, evaluation of measurable residual disease during treatment and follow‐up is highly dependent on knowledge of the diversity of blast subsets. Here, we set out to evaluate whether variation in expression of the blast marker, TdT, in T‐ALL blasts could correspond to differences in morphometric features.
Riboregulation in bacteria: From general principles to novel mechanisms of the trp attenuator and its sRNA and peptide products

Gene expression strategies ensuring bacterial survival and competitiveness rely on cis‐ and trans‐acting RNA‐regulators (riboregulators). Among the cis‐acting riboregulators are transcriptional and translational attenuators, and antisense RNAs (asRNAs). The trans‐acting riboregulators are small RNAs (sRNAs) that bind proteins or base pairs with other RNAs. This classification is artificial since some regulatory RNAs act both in cis and in trans, or function in addition as small mRNAs. A prominent example is the archetypical, ribosome‐dependent attenuator of tryptophan (Trp) biosynthesis genes. It responds by transcription attenuation to two signals, Trp availability and inhibition of translation, and gives rise to two trans‐acting products, the attenuator sRNA rnTrpL and the leader peptide peTrpL. In Escherichia coli, rnTrpL links Trp availability to initiation of chromosome replication and in Sinorhizobium meliloti, it coordinates regulation of split tryptophan biosynthesis operons. Furthermore, in S. meliloti, peTrpL is involved in mRNA destabilization in response to antibiotic exposure. It forms two types of asRNA‐containing, antibiotic‐dependent ribonucleoprotein complexes (ARNPs), one of them changing the target specificity of rnTrpL. The posttranscriptional role of peTrpL indicates two emerging paradigms: (1) sRNA reprograming by small molecules and (2) direct involvement of antibiotics in regulatory RNPs. They broaden our view on RNA‐based mechanisms and may inspire new approaches for studying, detecting, and using antibacterial compounds.
A Patent Review on SARS Coronavirus Main Protease (3CLpro) Inhibitors

The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) pandemic is an unprecedented global health emergency causing more than 4.2 million fatalities as of 30 July 2021. Only three antiviral therapies have been approved or granted emergency use authorization by the FDA. The SARS‐CoV‐2 3CL protease (3CLpro) is deemed an attractive drug target as it plays an essential role in viral polyprotein processing and pathogenesis, although no inhibitors have been approved. This patent review discusses SARS coronavirus 3CLpro inhibitors that have been filed up to 30 July 2021, giving an overview on the types of inhibitors that have generated commercial interest, especially amongst drug companies. Insights into the common structural motifs required for active site binding is also discussed.
The effects of hemodynamic monitoring using the PiCCO system on critically ill patients.

OBJECTIVE We aimed to evaluate the effects of hemodynamic monitoring using the pulse index continuous cardiac output (PiCCO) system with critically ill patients. METHODS In total, 292 patients with primary physiological abnormalities of hypotension (n = 180) or hypoxemia (n = 112) were evaluated. The attending physicians completed a questionnaire before each catheterization. After each catheterization, the attending physicians reviewed each chart to determine the possibility of altering the therapy. RESULTS In the hypotension subgroup, the attending physicians showed less accuracy in predicting the global end-diastolic index values (23.9%, 43/180), with a significant difference, and more accuracy in predicting the extravascular lung water index values (58.9%, 66/112), without a significant difference from the patients in the hypoxemia subgroup. In the hypotension patients, the lactate clearance rate within 6 h was significantly higher (36.4 ± 9.6 vs 21.3 ± 9.5; P<0.0001) when the hemodynamic monitoring led to therapeutic changes. CONCLUSIONS The hemodynamic variables obtained using the PiCCO system improved the accuracy of the bedside evaluations and led to alterations in the therapeutic plans, particularly among the hypotension patients. The therapy changes showed no improvement in the overall mortality but were associated with improved tissue perfusion among the hypotension patients.
Retina Vascular Structures near the Optic Disc and in the Macula in Primary Angle-Closure Suspects

Introduction: The main aim of this article was to study the retinal peripapillary and macular vascular structures in eyes with primary angle-closure suspects (PACS) using optical coherence tomography angiography (OCTA). Methods: In this cross-sectional study, control and PACS subjects were recruited from a community screening. Only one eye per subject was used for analysis. All participants underwent a questionnaire survey, physical and ophthalmic examinations, ocular biometry measurements, and OCTA. We compared basic demographics and vessel structure parameters between control and PACS eyes. Univariate and multivariate linear regression analyses were performed to investigate factors associated with vascular parameters in both groups. Results: Data from 254 subjects including 155 PACS and 99 controls were analyzed. In the peripapillary region, PACS eyes showed similar retina nerve fiber layer (RNFL) and vessel densities (VDs) including and excluding large vessels compared to control eyes. Compared to control eyes, all macular OCTA parameters showed significant differences in PACS eyes, including decreased superficial VD (p = 0.006) and deep VD (p = 0.004), larger fovea avascular zone (FAZ) area (p = 0.006), and longer FAZ perimeter (p = 0.004). Gender (p = 0.039), age (p < 0.001), and Garway-Heath superior hemisphere RNFL (p < 0.001) were risk factors influencing optic disc VD excluding large vessels. Axial length was the major factor affecting macula superficial and deep VDs (p = 0.004 and 0.001 respectively), while PACS was an independent factor associated with larger FAZ perimeter (p = 0.046). Conclusion: While PACS and control eyes have comparable RNFL and vascular structure around the optic nerve head, macular vascular structures are significantly different.
Embodiment-related risk factors for Posttraumatic Stress, Anxiety and Depression in female victims of intimate partner violence

ABSTRACT A central notion in the field of embodiment is that body sensorimotor processes and body mental representations influence emotion, cognition and behavior. By affecting the body, intimate partner violence (IPV) can leave victims with a fragile self, and significant physical and mental health problems. In this study, we aim to examine embodiment-related variables and mental health of female victims of IPV, as well as the impact of embodiment on mental health. A total of 38 female victims of IPV (mean age 40.3 ± 10.9 years) were recruited from shelters and the community. The study assessed the levels of Posttraumatic Stress Disorder (PTSD), Anxiety and Depression, and abilities of Movement Imagery, Interoceptive Accuracy, Interoceptive Sensibility, Body Ownership and Bodily Dissociation. Univariate, bivariate and binary regression analysis were used. PTSD, Anxiety and Depression were highly prevalent among our sample, alongside with altered values of body ownership and interoception. All three mental health disorders were significantly correlated with interoceptive self-regulation, interoceptive trusting, and bodily dissociation. For this group of women, each unit rise in the bodily dissociation scale increased two and six times the risk for developing Depression and Anxiety, respectively. The embodiment of female victims of IPV is altered, and higher bodily dissociation can be a risk factor for the development of mental health problems. Restoration of embodiment-related functions could be important for the victims to overcome the negative effects of violent relationships.
Factors associated with racing performance and career duration for Victorian-born Thoroughbreds.

The number of horses leaving the Australian Thoroughbred (TB) racing industry each year is of concern to animal welfare advocates, public and regulators. A horse's previous athletic performance is a significant driver of retirement from racing. Racehorse performance can be measured in terms of the total number of starts, duration of racing and prize money earned. This study investigated Australian racing records for the 2005 and 2010 Victorian TB foal crops to identify factors associated with total number of starts, racing career duration, prize money earned and age of last race start-up to the 10-year-old racing season. Racing Australia registered 4,577 TB horses born in Victoria in 2005 (n = 2,506) and 2010 (n = 2,071) that raced in Australia. Horses that started racing at 2-years of age had fewer race starts in their first racing season but an increased total number of starts, prize money and duration of racing. The median age of last start (LS) was five (Q1 4; Q3 7) years. Horses that had won a race, had a maximum handicap rating of 61 or above and those racing over distances of more than 2,400 m had an increased racing career duration and an age of last race start greater than 6-years of age. Horses participating in jumps races (n = 63) had the longest careers and older age of LS. These horses were more likely to have had a handicap rating over 80 and were just as likely to start their racing careers as 2-years-olds.
Redox Regulation in Cancer Cells during Metastasis

Abstract Metastasis is an inefficient process in which the vast majority of cancer cells are fated to die, partly because they experience oxidative stress. Metastasizing cancer cells migrate through diverse environments that differ dramatically from their tumor of origin, leading to redox imbalances. The rare metastasizing cells that survive undergo reversible metabolic changes that confer oxidative stress resistance. We review the changes in redox regulation that cancer cells undergo during metastasis. By better understanding these mechanisms, it may be possible to develop pro-oxidant therapies that block disease progression by exacerbating oxidative stress in cancer cells. Significance: Oxidative stress often limits cancer cell survival during metastasis, raising the possibility of inhibiting cancer progression with pro-oxidant therapies. This is the opposite strategy of treating patients with antioxidants, an approach that worsened outcomes in large clinical trials.
The feasibility of modified pancreatogastrostomy in vivo and its effect on intestinal microecology.

PURPOSE To evaluate the feasibility of modified binding pancreatogastrostomy (MBPA) by comparing it with traditional pancreatogastrostomy (TPA) and to determine the surgical effects on the intestinal microecology. METHODS The surgical effects on the intestinal microecology of female Bama minipigs (n = 20) were determined by measuring the expressions of the intestinal microbial proteins in the gastric juice, gastric mucosa, and feces before and after MBPA and TPA. We then constructed an integrated interaction network based on the metabolomics and 16S amplicon data, the microbiota, the metabolites, and the associated pathways. RESULTS The average time required for anastomosis was significantly lower after MBPA than after TPA, but the breaking force did not significantly differ between them. We identified 25 and 51 differentially expressed metabolites and microbiota, respectively. An interaction network was constructed using 16 metabolites (including pyruvic and lactic acids), 27 microbiota (including Ruminococcaceae_UCG-00) and six pathways (including pyruvate metabolism). CONCLUSION Anastomosis might be achieved sooner and with less pancreatic leakage using MBPA compared with TPA. Pancreatogastrostomy inhibits Ruminococcaceae activity, leading to increased expressions of pyruvic and lactic acids in the gut.
Long non‐coding RNA LINC00514 promotes the proliferation and invasion through the miR‐708‐5p/HOXB3 axis in cervical squamous cell carcinoma

Long non‐coding RNA (lncRNA) LINC00514 is a cancer‐related lncRNA that has been proven to be implicated in the progression of several cancers. However, the biological function of LINC00514 in cervical squamous cell carcinoma (CSCC) remains unclear. Thus, we aimed to identify the LINC00514 expression profile in CSCC and determine its exact mechanism. Our results showed that the expression of LINC00514 was up‐regulated in human CSCC tissues and cell lines. Knockdown of LINC00514 significantly inhibited the proliferation and invasion of CSCC cells, as well as suppressed tumorigenesis of CSCC in vivo. In addition, LINC00514 was found to work as a miRNA sponge for miR‐708‐5p and suppressed the expression of miR‐708‐5p in CSCC cells. Homeobox B3 (HOXB3) was found to be a target gene of miR‐708‐5p. Rescue assays demonstrated that miR‐708‐5p inhibitor attenuated the effects of LINC00514 knockdown on cell proliferation and invasion in CSCC cells. In addition, overexpression of HOXB3 reversed the inhibitory effects of miR‐708‐5p mimics on cell proliferation and invasion. Taken together, our findings for the first time elucidated that lncRNA LINC00514 promotes the proliferation and invasion through the miR‐708‐5p/HOXB3 axis in CSCC. Thus, LINC00514/miR‐708‐5p/HOXB3 axis might be a promising therapeutic target for the treatment of CSCC.
How effective is cyanoacrylate closure in small saphenous vein insufficiency? A single center experience

Objectives The present study was aimed to evaluate the efficacy and early outcomes of n-butyl cyanoacrylate (NBCA) ablation in small saphenous vein (SSV) insufficiency. Methods In this single-center, retrospective, single-arm study, NBCA ablation was performed in 80 patients with SSV insufficiency between September 2018 and May 2020. Primary outcomes (anatomic success rate and occlusion rate) and secondary outcomes (VCSS and AVVQ scores) of the patients were analyzed. Results No technical failure and device-related complications were encountered. Anatomic success rate was 100% after procedures. Each treated SSV was occluded on colored Doppler ultrasonography immediately after the procedure, and all veins remained occluded at 2 weeks after the procedure. Partial recanalization was observed in five patients at 12-month follow-up. Kaplan–Meier analysis revealed an occlusion rates at 6 months and 12 months follow-up were 97.5% and 93.75%, respectively. The mean pretreatment VCSS (4.72 ± 2.04) decreased to 1.61 ± 0.93, 0.87 ± 0.58, and 0.73 ± 0.52 at 2 weeks, 6 months, and 12 months after treatment, respectively (p < .001). The mean pretreatment AVVQ score (11.92 ± 2.23) decreased to 8.2 ± 1.89, 4.2 ± 1.16, and 3.32 ± 1.19 at 2 weeks, 6 months, and 12 months after treatment, respectively (p < .001). The Clinical, Etiologic, Anatomic, and Pathophysiology clinical classification at 12 months demonstrated a significant reduction in disease severity compared with preoperative values (p < .001). There was no mortality and major adverse events including anaphylaxis and pulmonary thromboembolism (PTE) related to procedure after follow-ups. Moreover, there were no symptoms or signs of any sural nerve injury and no cases of skin necrosis, infection, or hyperpigmentation. In addition, no hematoma, deep venous thrombosis, and hypersensitivity reactions were observed. Phlebitis-like abnormal reaction was observed in three patients (3.8%). Conclusions In conclusion, in patients with SSV insufficiency, NBCA ablation with VenaBlock® system appears to be an effective and reliable treatment method. At the 12-month follow-up, the NBCA of SSVs showed a low recanalization rate and had a satisfactory improvement on the VCSS and AVVQ scores.
Clinical significance of SIRT3 and inflammatory factors in multiple myeloma patients with bortezomib-induced peripheral neuropathy: a cohort study

Abstract The present study aimed to investigate the role of SIRT3 and inflammatory factors in bortezomib-induced peripheral neuropathy (PN). This prospective observational cohort study included a total of 159 patients of multiple myeloma patients during June 2016 to June 2019. All patients received the strategy of bortezomib and dexamethasone and were further divided into the PN group and the non-PN group. Serum SIRT3, CRP, IL-6 and TNF-α levels were measured by enzyme-linked immunosorbent assay (ELISA). During the study period, 76 (47.8%) patients developed PN. The inflammatory factors all gradually decreased and SIRT3 levels were gradually increased after treatment by bortezomib combined with dexamethasone compared with the baseline. The levels of all inflammatory factors were markedly higher, while SIRT3 levels were lower in PN patients compared with the non-PN patients at the same time point after treatment. In PN grade III patients, the serum levels of CRP, IL-6 and TNF-α were significantly higher, while serum levels of SIRT3 were markedly lower than the grade I–II patients. SIRT3 was negatively correlated with CRP, IL-6 and TNF-α. After nursing treatment and reduction of bortezomib dose, the levels of SIRT3 significantly increased, while levels of inflammatory decreased in PN patients with grade III. SIRT3 and inflammatory factors showed the potential for diagnosis of bortezomib-induced PN. Besides, SIRT3, IL-6 and TNF-α were the independent risk factors for MM patients developing PN after treatment of bortezomib. Higher inflammatory factors and lower SIRT3 might be associated with the development of bortezomib-induced PN in multiple myeloma patients, which might be reversed by decreased bortezomib dose and proper nursing treatment.
Effects of Assisted Dorsiflexion Timing on Voluntary Efforts and Compensatory Movements: A Feasibility Study in Healthy Participants

In previous research, we found that modulating the assistance timing of dorsiflexion may affect a user’s voluntary efforts. This could constitute a focus area based on assistive strategies that could be developed to foster patients’ voluntary efforts. In this present study, we conducted an experiment to verify the effects of ankle dorsiflexion assistance under different timings using a high-dorsiflexion assistive system. Nine healthy and young participants wore a dorsiflexion-restrictive device that enabled them to use circumduction or steppage gaits. On the basis of the transition from the stance to the swing phase of the gait, the assistance timings of the high-dorsiflexion assistive system were set to have delays, which ranged from 0 to 300 ms. The index results from eight out of nine participants evaluated compensatory movements and revealed positive strong/moderate correlations with assistance delay times (r = 0.627–0.965, p <.001), whereas the other participants also performed compensatory movement when dorsiflexion assistance timing was late. Meanwhile, the results from tibialis anterior surface electromyography from six out of nine participants showed positive strong/moderate correlations with dorsiflexion assistance delay times (r = 0.598–0.922, p <.001), indicating that tuning the assistance timing did foster these participants’ voluntary dorsiflexion movements. This result indicates that there should be a trade-off between ensuring voluntary dorsiflexion movements and preventing incorrect gait patterns at different assistance timings. The findings of this feasibility study indicate the potential of developing an adaptive control method to ensure voluntary efforts during robot-assisted gait rehabilitation based on assistance timing modification. A new assistance mechanism should also be required to stimulate and motivate a patient’s voluntary efforts and should reinforce the effects of active gait rehabilitation.
Diminished YAP1 affects mitochondrial dynamics in IDH1 mutant glioma.

Mutation in isocitrate dehydrogenase 1 (IDH1) gene, leading to the production of oncometabolite D-2-hydroxyglutarate (2-HG) from α-ketoglutarate, is associated with better prognosis in glioma. As Yes-associated protein 1 (YAP1) is an important regulator of tumor progression, its role in glioma expressing IDH1 R132H mutation was investigated. Diminished nuclear YAP1 in IDH1 mutant patient gliomas and cell lines was accompanied by decreased TFAM levels. Luciferase reporter assays and chromatin immunoprecipitation indicated the functionality of TEAD2 site on TFAM promoter in mediating its YAP1-dependent expression. YAP1-dependent mitochondrial fragmentation and ROS generation was accompanied by decreased TERT levels and increased mitochondrial TERT localization in IDH1 R132H cells. Treatment with Bosutinib that prevents extranuclear TERT shuttle, further elevated ROS in IDH1 R132H cells and triggered apoptosis. Importantly, Bosutinib elevated ROS levels and induced apoptosis in IDH1 WT cells upon concurrent depletion of YAP1. These findings highlight the involvement of YAP1 in coupling mitochondrial dysfunction with TERT mitochondrial shuttle to constitute an essential non-canonical function of YAP1 in regulating redox homeostasis.
Attentional Bias Toward Threat in Sexually Victimized Hispanic Women: A Dot Probe Study

ABSTRACT The current study examined attentional bias toward threat in Hispanic college women exposed to lifetime sexual victimization in childhood, adulthood, and both childhood and adulthood. Response latencies and attention bias scores were compared between victimized and non-victimized individuals. Participants were 20 women exposed to adulthood sexual victimization (AS group), 15 exposed to childhood sexual victimization (CS group), 8 exposed to both childhood and adulthood sexual assault (revictimization: RV group), and 20 not endorsing sexual victimization (NS group). They were asked to complete the dot-probe task. The CS group and RV group were combined to create the CS-RV group. Among the AS and CS-RV groups, response latencies were faster when attention was engaged to threat than when attention was engaged to non-threat. The NS group did not demonstrate such differences. When response latencies were compared among the three groups, the CS-RV group had slower response latencies than the NS group. The CS-RV and AS groups revealed similarly significantly elevated bias scores toward threat words than the NS group. Hispanic college women exposed to lifetime sexual victimization display elevated levels of attention bias compared to non-victimized women. Further, the current findings align with an integrative cognitive model for explaining maladaptive informational processing in trauma victims.