Miracle-dz/UniFAR-FTUs huggingface dataset:
miR-329 inhibits papillary thyroid cancer progression via direct targeting WNT1

Dysregulated microRNA-329 (miR-329) serves an important role in the progression of certain types of tumor. However, the exact function and mechanisms of miR-329 in papillary thyroid cancer (PTC) remain unknown. The present study investigated the function and mechanisms of miR-329 in regulating PTC cell progression. The results revealed that the expression of miR-329 was significantly downregulated in PTC tissues and cell lines compared with adjacent normal tissues and a human immortalized follicular cell line. miR-329 mimics notably decreased PTC cell proliferation, colony formation and WNT1 expression in vitro, as well as suppressing PTC tumor growth in vivo. In addition, luciferase assays determined that miR-329 was able to directly bind with the 3′untranslated region of WNT1. Furthermore, short interfering RNA-WNT1-induced downregulation of WNT1, which demonstrated similar effects to miR-329 overexpression. WNT1 overexpression rescued the tumor suppressive effects of miR-329 in PTC cells. The present study provided new insights into the role of miR-329 in PTC progression and suggests the potential application of miR-329 as a therapy for PTC.
Liver receptor homologue 1, a novel prognostic marker in colon cancer patients

Liver receptor homologue 1 (LRH-1) is an orphan nuclear receptor that is highly expressed in a variety of cancer tissues, promotes tumor cell proliferation and metastasis, and is involved in the tumor cell cycle and apoptosis. The aim of the present study was to assess the association between the expression of LRH-1 and the prognosis of patients with colon cancer. Immunohistochemistry was used to detect the expression of LRH1 in 128 cases of colon cancer and adjacent tissues. The 5-year survival rate was obtained from telephone follow-up data, outpatient review and through access to medical records. Positive expression of LRH-1 was found in 108/128 colon cancer samples, compared with 17/128 normal tissues. Statistical analysis showed that positive LRH-1 expression was significantly associated with clinical pathological stage, depth of invasion and lymph node metastasis. The overall survival (OS) rate of patients with positive LRH-1 expression was significantly lower than that of patients with low expression. Multivariate analysis showed that LRH-1 expression could be used as an independent predictor of OS. In conclusion, the present findings suggest that LRH-1 may serve an important role in the development and progression of colon cancer, with potential value as a prognostic molecular marker that could be used to assist in the diagnosis and evaluation of colon cancer. LRH-1 may become a target for novel therapies for patients with colon cancer.
Minor pulmonary malformations in a child

This case report describes an Italian female who was born at full term via Caesarean delivery, performed for breech presentation. She was the first child of healthy, unrelated parents. At birth, she weighed 2600 g (<3rd centile; −2 sd) and measured 45 cm in length (<3rd centile; −2 sd). Psychomotor development was normal for her age. The recommended immunisation schedule was administered. Newborn screening tests (hip ultrasound and acoustic reflexes) as well as echocardiography were normal. There was no known maternal exposure to teratogens or infections. The family history was unremarkable, except for retinitis pigmentosa and hypothyroidism (in the mother). Can you diagnose this child with minor pulmonary malformations and recurrent pulmonary symptoms? http://ow.ly/6zQB30jHZAP
A 125-klx Background Light Subtraction Architecture for 2-D and Time-of-Flight 3-D Cameras

In this paper, an in-pixel background light (BGL) subtraction architecture is presented for indoor/outdoor 2-D and 3-D imaging. The subtraction is performed using a pulsed modulation technique used in time-of-flight cameras. Mostly BGL subtraction is done using two capacitors. However, two capacitors cause mismatch effects; therefore, a single capacitor approach is proposed. Using a single capacitor, the BGL subtraction and distance estimation are performed in three operational phases. Hence, the proposed architecture can be used in applications where high-speed depth imaging is required. An image sensor with <inline-formula> <tex-math notation="LaTeX">$24\times24$ </tex-math></inline-formula> pixel array is designed with 48-<inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> pixel pitch and 17.36% fill factor. The measurement results of the chip fabricated in AMS 0.35-<inline-formula> <tex-math notation="LaTeX">$\mu \text{m}$ </tex-math></inline-formula> CMOS OPTO process show up to 125-klx BGL subtraction without using an optical filter with a background-to-signal ratio of 40 dB.
Hierarchical Neural Networks for Sequential Sentence Classification in Medical Scientific Abstracts

Prevalent models based on artificial neural network (ANN) for sentence classification often classify sentences in isolation without considering the context in which sentences appear. This hampers the traditional sentence classification approaches to the problem of sequential sentence classification, where structured prediction is needed for better overall classification performance. In this work, we present a hierarchical sequential labeling network to make use of the contextual information within surrounding sentences to help classify the current sentence. Our model outperforms the state-of-the-art results by 2%-3% on two benchmarking datasets for sequential sentence classification in medical scientific abstracts.
Food Consumption as a Modifier of the Association between LEPR Gene Variants and Excess Body Weight in Children and Adolescents: A Study of the SCAALA Cohort

No studies showing that food consumption is a modifier of the association of variants of the leptin receptor gene (LEPR) with body weight have involved a Brazilian population. The aim of this study was to evaluate the modifying effect of dietary intake on the association between the LEPR gene and excess weight. In this study, 1211 children and adolescents aged 4–11 years were assessed. Participants were genotyped for 112 single-nucleotide variants of the LEPR gene. Anthropometric measurements were performed, and dietary data were obtained. Logistic regressions were used to study the associations of interest. Of the participants, 13.4% were overweight/obese. The risk allele (G) of the rs1137100 variant was associated with excess weight in individuals with fat consumption below the median (odds ratio OR = 1.92; 95% confidence interval CI = 1.18–3.14), with daily frequency of consumption of drink/artificial juice (OR = 2.15; 95% CI = 1.26–3.68) and refined cereals (OR = 2.17; 95% CI = 1.31–3.62) above the median. The risk allele (G) of variant rs1177681 was also associated with excess weight (OR = 2.74; 95% CI = 1.65–4.57) in subjects with a daily frequency of refined cereal consumption above the median. The association between LEPR and excess weight can be modulated by the type and distribution of dietary fatty acids, sugary drinks, and refined cereals.
Dose-Rate Sensitivity of 65-nm MOSFETs Exposed to Ultrahigh Doses

The radiation response of complementary metal–oxide–semiconductor (CMOS) gate oxides is typically insensitive to true dose-rate effects, but damage in deep-sub-micrometer technologies is dominated by ionization mechanisms in thick isolation oxides surrounding the transistors. Recent results in 65-nm FETs demonstrated that performance degradation in ultrahigh total ionizing dose (TID) experiments is due to defects in the isolation shallow trench isolation oxide or in the materials composing the lightly doped drain spacers. These insulators are thick, deposited, and crossed by a low electric field, characteristics similar to those typical of passivation oxides in linear bipolar technologies for which an enhanced low-dose-rate sensitivity (ELDRS) has been observed and systematically studied. We report in this paper the clear evidence of a dose-rate sensitivity of the TID-induced damage in both 130- and 65-nm CMOS technologies exposed to different radiation sources (X-rays and $\gamma $ -rays from a 60Co source). This sensitivity is attributed to mechanisms similar to those explaining ELDRS in bipolar devices and represents a significant challenge to the definition of a qualification procedure for circuits to be used in extreme radiation environments.
Lysosomal membrane permeabilization and cell death

Lysosomes are membrane‐enclosed organelles that mediate the intracellular degradation of macromolecules. They play an essential role in calcium regulation and have emerged as key signaling hubs in controlling the nutrient response. Maintaining lysosomal integrity and function is therefore crucial for cellular homeostasis. Different forms of stress can induce lysosomal membrane permeabilization (LMP), resulting in the translocation to the cytoplasm of intralysosomal components, such as cathepsins, inducing lysosomal‐dependent cell death (LDCD). Here, we review recent advances that have furthered our understanding of the molecular mechanisms of LMP and the methods used to detect it. We discuss several endolysosomal damage‐response mechanisms that mediate the repair or elimination of compromised lysosomes and summarize the role of LMP and cathepsins in LDCD and other cell death pathways. Finally, with the emergence of lysosomes as promising therapeutic targets for several human diseases, we review a variety of therapeutic strategies that seek to either destabilize lysosomes or to maintain, enhance or restore lysosomal function.
Baicalin provides neuroprotection in traumatic brain injury mice model through Akt/Nrf2 pathway

Background The neuroprotective effects of Baicalin have been confirmed in several central nervous system (CNS) diseases. However, its possible effect on traumatic brain injury (TBI) model is still not clear. The present study is aimed to investigate the role and the underling mechanisms of 7-D-glucuronic acid-5,6-dihydroxyflavone (Baicalin) on TBI model. Methods The weight-drop model of TBI in Institute of Cancer Research mice was treated with Baicalin intraperitoneally at 30 minutes after TBI. LY294002 (LY) (a commonly used PI3K/Akt pathway inhibitor) was injected into the left ventricle at 30 minutes before TBI. All mice were euthanized at 24 hours after TBI to collect the brain tissue for a series of tests except for neurological function, which was measured at 2 hours and 1 and 3 days post-TBI. Results Baicalin administration significantly improved neurobehavioral function, alleviated brain edema, and reduced apoptosis-positive cells by terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay accompanied with the upregulation of B-cell lymphoma 2 (Bcl-2) and downregulation of Bcl-2-associated X protein (Bax) and cleaved-caspase 3 by Western blot. Besides, TBI-induced oxidant stress status was also restored in the Baicalin group by measuring malondialdehyde (MDA) content, glutathione peroxidase (GPx), and superoxide dismutase (SOD) levels in the injured brain cortex. Furthermore, translocation of Nrf2 to the nucleus was dramatically enhanced by Baicalin verified by immunofluorescence and Western blot analyses. Accordingly, its downstream antioxidative enzymes nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) were also activated by Baicalin confirmed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) and Western blot. However, cotreatment with Baicalin and LY could partly abolish Baicalin-induced activation of Nrf2 and its neuroprotective effects in TBI. Conclusion This study demonstrates that Baicalin provides a neuroprotective effect in TBI mice model via activating the Akt/Nrf2 pathway.
Adhesive-Free Bonding of Monolithic Sapphire for Pressure Sensing in Extreme Environments

This paper presents a monolithic sapphire pressure sensor that is constructed from two commercially available sapphire wafers through a combination of reactive-ion etching and wafer bonding. A Fabry–Perot (FP) cavity is sealed fully between the adhesive-free bonded sapphire wafers and thus acts as a pressure transducer. A combination of standard silica fiber, bonded sapphire wafers and free-space optics is proposed to couple the optical signal to the FP cavity of the sensor. The pressure in the FP cavity is measured by applying both white-light interferometry and diaphragm deflection theory over a range of 0.03 to 3.45 MPa at room temperature. With an all-sapphire configuration, the adhesive-free bonded sapphire sensor is expected to be suitable for in-situ pressure measurements in extreme harsh environments.
Compositional Analysis of the Associations between 24-h Movement Behaviours and Health Indicators among Adults and Older Adults from the Canadian Health Measure Survey

This study investigated the association between the allocation of time-use over the 24-h day between sleep, sedentary behaviour (SB), light-intensity physical activity (LPA) and moderate-to-vigorous-intensity physical activity (MVPA)) and health indicators. A cross-sectional analysis of Canadian Health Measures Survey data was undertaken using compositional data analysis. SB, LPA and MVPA were derived from Actical accelerometers, whilst sleep was self-reported by respondents. The analysis was stratified by age; adults (aged 18–64 years; n = 6322) and older adults (65–79 years; n = 1454). For adults, beneficial associations were observed between larger proportions of MVPA relative to time in other behaviours and body mass index (BMI), waist circumference, aerobic fitness, resting heart rate, high-density lipoprotein (HDL) cholesterol, triglycerides, blood glucose and insulin levels. More time spent in sleep relative to other movement behaviours was deleteriously associated with aerobic fitness, HDL cholesterol, insulin, C-reactive proteins and grip strength but beneficially with low-density lipoprotein cholesterol. Relative time spent in LPA was deleteriously associated with BMI and beneficially with triglycerides and grip strength. In older adults, these associations were blunted or disappeared but larger proportions of MVPA were associated with better mental health. The importance to health of MVPA when explicitly considered relative to other movement behaviours was confirmed.
Security in the Software Development Lifecycle

We interviewed developers currently employed in industry to explore real-life software security practices during each stage of the development lifecycle. This paper explores steps taken by teams to ensure the security of their applications, how developers’ security knowledge inﬂuences the process, and how security ﬁts in (and sometimes conﬂicts with) the development workﬂow. We found a wide range of approaches to software security, if it was addressed at all. Furthermore, real-life security practices vary considerably from best practices identiﬁed in the literature. Best practices often ignore factors aﬀecting teams’ operational strategies. Division of labour is one example, whereby complying with best practices would require some teams to restructure and re-assign tasks—an eﬀort typically viewed as unreasonable. Other inﬂuential factors include company culture, security knowledge, external pressure, and experiencing a security incident.
Heterogeneously Integrated V-Band Amplifier

We report on heterogeneously integrated V-band amplifier realized in four layer interconnect InP heterojunction bipolar transistor (HBT). The amplifier chiplet is integrated onto a passive InP carrier wafer with two layers of interconnect using heterogeneous integrated interconnects, which enable electrically short connection between two technologies. The heterogeneously integrated interconnect or transition has measured loss of $\leq \pmb{0.1}\mathbf{dB}$ up to 30 GHz and ~0.4 dB at 90 GHz. Measured amplifier S-Parameters show almost no difference between before and after integration versions. Relatively flat output power between 11.5 and 12.5 dBm was demonstrated from 55 to 65 GHz. This is the first reported integration of V-band amplifier chiplets using heterogeneous integration, as well as lowest reported loss for heterogeneous interconnect transition.
Physio-Genetic Dissection of Dark-Induced Leaf Senescence and Timing Its Reversal in Barley1[OPEN]

The organelle-specific physiology in and gene medleys during stress-induced barley leaf senescence are reversible prior to terminal programmed cell death phase. Barley crop model was analyzed for early and late events during the dark-induced leaf senescence (DILS) as well as for deciphering critical time limit for reversal of the senescence process. Chlorophyll fluorescence vitality index Rfd was determined as the earliest parameter that correlated well with the cessation of photosynthesis prior to microautophagy symptoms, initiation of DNA degradation, and severalfold increase in the endonuclease BNUC1. DILS was found characterized by up-regulation of processes that enable recycling of degraded macromolecules and metabolites, including increased NH4+ remobilization, gluconeogenesis, glycolysis, and partial up-regulation of glyoxylate and tricarboxylate acid cycles. The most evident differences in gene medleys between DILS and developmental senescence included hormone-activated signaling pathways, lipid catabolic processes, carbohydrate metabolic processes, low-affinity ammonia remobilization, and RNA methylation. The mega-autophagy symptoms were apparent much later, specifically on day 10 of DILS, when disruption of organelles—nucleus and mitochondria —became evident. Also, during this latter-stage programmed cell death processes, namely, shrinking of the protoplast, tonoplast interruption, and vacuole breakdown, chromatin condensation, more DNA fragmentation, and disintegration of the cell membrane were prominent. Reversal of DILS by re-exposure of the plants from dark to light was possible until but not later than day 7 of dark exposure and was accompanied by regained photosynthesis, increase in chlorophyll, and reversal of Rfd, despite activation of macro-autophagy-related genes.
Clonal heterogeneity influences drug responsiveness in renal cancer assessed by ex vivo drug testing of multiple patient‐derived cancer cells

Renal cell cancer (RCC) has become a prototype example of the extensive intratumor heterogeneity and clonal evolution of human cancers. However, there is little direct evidence on how the genetic heterogeneity impacts on drug response profiles of the cancer cells. Our goal was to determine how genomic clonal evolution impacts drug responses. Finding from our study could help to define the challenge that clonal evolution poses on cancer therapy. We established multiple patient‐derived cells (PDCs) from different tumor regions of four RCC patients, verified their clonal relationship to each other and to the uncultured tumor tissue by genome sequencing. Furthermore, comprehensive drug‐sensitivity testing with 460 oncological drugs was performed on all PDC clones. The PDCs retained many cancer‐specific copy number alterations and mutations in driver genes such as VHL, PBRM1, PIK3C2A, KMD5C and TSC2 genes. The drug testing highlighted vulnerability in the PDCs toward approved RCC drugs, such as the mTOR‐inhibitor temsirolimus, but also novel sensitivities were uncovered. The individual PDC clones from different tumor regions in a patient showed distinct drug–response profiles, suggesting that genomic heterogeneity contributes to the variability in drug responses. Studies of multiple PDCs from a patient with cancer are informative for elucidating cancer heterogeneity and for the determination on how the genomic evolution is manifested in cancer drug responsiveness. This approach could facilitate tailoring of drugs and drug combinations to individual patients.
Intra- and Inter-Scanner Reliability of Voxel-Wise Whole-Brain Analytic Metrics for Resting State fMRI

As the multi-center studies with resting-state functional magnetic resonance imaging (RS-fMRI) have been more and more applied to neuropsychiatric studies, both intra- and inter-scanner reliability of RS-fMRI are becoming increasingly important. The amplitude of low frequency fluctuation (ALFF), regional homogeneity (ReHo), and degree centrality (DC) are 3 main RS-fMRI metrics in a way of voxel-wise whole-brain (VWWB) analysis. Although the intra-scanner reliability (i.e., test-retest reliability) of these metrics has been widely investigated, few studies has investigated their inter-scanner reliability. In the current study, 21 healthy young subjects were enrolled and scanned with blood oxygenation level dependent (BOLD) RS-fMRI in 3 visits (V1 – V3), with V1 and V2 scanned on a GE MR750 scanner and V3 on a Siemens Prisma. RS-fMRI data were collected under two conditions, eyes open (EO) and eyes closed (EC), each lasting 8 minutes. We firstly evaluated the intra- and inter-scanner reliability of ALFF, ReHo, and DC. Secondly, we measured systematic difference between two scanning visits of the same scanner as well as between two scanners. Thirdly, to account for the potential difference of intra- and inter-scanner local magnetic field inhomogeneity, we measured the difference of relative BOLD signal intensity to the mean BOLD signal intensity of the whole brain between each pair of visits. Last, we used percent amplitude of fluctuation (PerAF) to correct the difference induced by relative BOLD signal intensity. The inter-scanner reliability was much worse than intra-scanner reliability; Among the VWWB metrics, DC showed the worst (both for intra-scanner and inter-scanner comparisons). PerAF showed similar intra-scanner reliability with ALFF and the best reliability among all the 4 metrics. PerAF reduced the influence of BOLD signal intensity and hence increase the inter-scanner reliability of ALFF. For multi-center studies, inter-scanner reliability should be taken into account.
Non-small cell lung cancer leptomeningeal metastases treated with intrathecal therapy plus osimertinib and temozolomide and whole-brain radiation therapy: a case report

Rationale Leptomeningeal metastasis (LM) is an important cause of mortality in patients with non-small cell lung cancer (NSCLC). As the symptoms of LM and its early clinical manifestations are nonspecific, early diagnosis of LM is difficult. However, there are few treatment options for LM, which leads to a poor prognosis; thus, increased clinical attention is necessary. The effects of most systemic chemotherapies on metastatic brain tumors (brain metastases and LMs) are limited as they cannot pass the blood–brain barrier; therefore, whole-brain radiation therapy is a therapeutic option. Osimertinib is a potent and irreversible third-generation oral epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI). It binds to EGFR with high affinity when the EGFR T790M mutation is present together with sensitizing mutations. The clinical efficacy of osimertinib in NSCLC patients carrying the T790M mutation has been demonstrated in clinical trial NCT02468661. Intrathecal injection of chemotherapeutic drugs can be directed to a specific lesion. Temozolomide is one such drug, and its effect has been confirmed. Patient and interventions We treated a 38-year-old patient with NSCLC who carried the EGFR L858R mutation. We administered a combination of oral osimertinib and oral temozolomide plus an intrathecal injection of cytarabine and whole-brain radiation therapy for symptomatic multiple brain metastases. Outcomes The patient showed a marked response to this combination therapy. To date (after ~18 months), no recurrence or new lesions have been observed and he is asymptomatic. His disease-free survival surpasses that achieved with any monotherapy for LM. Lessons This is the first report to demonstrate the response to combination therapy in an NSCLC patient with LM. These findings indicate the potential utility of chemotherapy combined with radiotherapy combined with targeted therapy combined with local treatment, as each treatment acts via a different mechanism, enhancing their therapeutic effects.