Miracle-dz/UniFAR-FTUs huggingface dataset:
Nanohydroxyapatite-coated hydroxyethyl cellulose/poly (vinyl) alcohol electrospun scaffolds and their cellular response

ABSTRACT The present study focused on the preparation of nanohydroxyapatite (nHA)-coated hydroxyethyl cellulose/polyvinyl alcohol (HEC/PVA) nanofibrous scaffolds for bone tissue engineering application. The electrospun HEC/PVA scaffolds were mineralized via alternate soaking process. FESEM revealed that the nHA was formed uniformly over the nanofibers. The nHA mineralization enhanced the tensile strength and reduced the elongation at breakage of scaffolds. The wettability of the nanofibrous scaffolds was significantly improved. The in vitro biocompatibility of scaffolds was evaluated with human osteosarcoma cells. nHA-coated scaffolds had a favorable effect on the proliferation and differentiation of osteosarcoma cell and could be a potential candidate for bone regeneration. GRAPHICAL ABSTRACT
Fgf15 Neurons of the Dorsomedial Hypothalamus Control Glucagon Secretion and Hepatic Gluconeogenesis

The counterregulatory response to hypoglycemia is an essential survival function. It is controlled by an integrated network of glucose-responsive neurons, which trigger endogenous glucose production to restore normoglycemia. The complexity of this glucoregulatory network is, however, only partly characterized. In a genetic screen of a panel of recombinant inbred mice we previously identified Fgf15, expressed in neurons of the dorsomedial hypothalamus (DMH), as a negative regulator of glucagon secretion. Here, we report on the generation of Fgf15CretdTomato mice and their use to further characterize these neurons. We show that they were glutamatergic and comprised glucose-inhibited and glucose-excited neurons. When activated by chemogenetics, Fgf15 neurons prevented the increase in vagal nerve firing and the secretion of glucagon normally triggered by insulin-induced hypoglycemia. On the other hand, they increased the activity of the sympathetic nerve in the basal state and prevented its silencing by glucose overload. Higher sympathetic tone increased hepatic Creb1 phosphorylation, Pck1 mRNA expression, and hepatic glucose production leading to glucose intolerance. Thus, Fgf15 neurons of the DMH participate in the counterregulatory response to hypoglycemia by a direct adrenergic stimulation of hepatic glucose production while suppressing vagally induced glucagon secretion. This study provides new insights into the complex neuronal network that prevents the development of hypoglycemia.
The Feasibility of a School Nurse–Led Mindfulness Program

The purpose of this study was to evaluate the feasibility of a school nurse–led mindfulness program in a public school. Elementary students in an urban public school system are exposed to many stressors including poverty, family disturbances, and mental health conflicts. Previous research suggests that mindfulness interventions given by teachers promote prosocial behavior and stress reduction; however, there are no studies that have determined whether the school nurse could lead the program. A pre- to posttest design was employed using school-aged children enrolled in the fourth grade who were administered a mindfulness program. The participants were assessed for emotional states before and after the intervention. A total of 12 students completed the intervention. Students found the mindfulness program to be helpful, and the school nurse may be able to successfully complete the intervention. With appropriate planning, school nurses may be able to successfully implement the mindfulness curriculum in an urban public school.
Performance Evaluation of a Deep Learning System for Differential Diagnosis of Lung Cancer With Conventional CT and FDG PET/CT Using Transfer Learning and Metadata

Purpose We aimed to evaluate the performance of a deep learning system for differential diagnosis of lung cancer with conventional CT and FDG PET/CT using transfer learning (TL) and metadata. Methods A total of 359 patients with a lung mass or nodule who underwent noncontrast chest CT and FDG PET/CT prior to treatment were enrolled retrospectively. All pulmonary lesions were classified by pathology (257 malignant, 102 benign). Deep learning classification models based on ResNet-18 were developed using the pretrained weights obtained from ImageNet data set. We propose a deep TL model for differential diagnosis of lung cancer using CT imaging data and metadata with SUVmax and lesion size derived from PET/CT. The area under the receiver operating characteristic curve (AUC) of the deep learning model was measured as a performance metric and verified by 5-fold cross-validation. Results The performance metrics of the conventional CT model were generally better than those of the CT of PET/CT model. Introducing metadata with SUVmax and lesion size derived from PET/CT into baseline CT models improved the diagnostic performance of the CT of PET/CT model (AUC = 0.837 vs 0.762) and the conventional CT model (AUC = 0.877 vs 0.817). Conclusions Deep TL models with CT imaging data provide good diagnostic performance for lung cancer, and the conventional CT model showed overall better performance than the CT of PET/CT model. Metadata information derived from PET/CT can improve the performance of deep learning systems.
Short-course IL-15 given as a continuous infusion led to a massive expansion of effective NK cells: implications for combination therapy with antitumor antibodies

Background Full application of cytokines as oncoimmunotherapeutics requires identification of optimal regimens. Our initial effort with intravenous bolus recombinant human interleukin-15 (rhIL-15) was limited by postinfusional reactions. Subcutaneous injection and continuous intravenous infusion for 10 days (CIV-10) provided rhIL-15 with less toxicity with CIV-10 giving the best increases in CD8+ lymphocytes and natural killer (NK) cells. To ease rhIL-15 administration, we shortened time of infusion. Treatment with rhIL-15 at a dose of 3–5 µg/kg as a 5-day continuous intravenous infusion (CIV-5) had no dose-limiting toxicities while effector cell stimulation was comparable to the CIV-10 regimen. Methods Eleven patients with metastatic cancers were treated with rhIL-15 CIV-5, 3 µg (n=4), 4 µg (n=3), and 5 µg/kg/day (n=4) in a phase I dose-escalation study (April 6, 2012). Results Impressive expansions of NK cells were seen at all dose levels (mean 34-fold), including CD56bright NK cells (mean 144-fold for 4 µg/kg), as well as an increase in CD8+ T cells (mean 3.38-fold). At 5 µg/kg/day, there were no dose-limiting toxicities but pulmonary capillary leak and slower patient recovery. This led to our choice of the 4 µg/kg as CIV-5 dose for further testing. Cytolytic capacity of CD56bright and CD56dim NK cells was increased by interleukin-15 assayed by antibody-dependent cellular cytotoxicity (ADCC), natural cytotoxicity and natural killer group 2D-mediated cytotoxicity. The best response was stable disease. Conclusions IL-15 administered as CIV-5 substantially expanded NK cells with increased cytotoxic functions. Tumor-targeting monoclonal antibodies dependent on ADCC as their mechanism of action including alemtuzumab, obinutuzumab, avelumab, and mogamulizumab could benefit from those NK cell expansions and provide a promising therapeutic strategy. Trial registration numbers NCT01572493, NCT03759184, NCT03905135, NCT04185220 and NCT02689453.
Gene Networks Underlying Cannabinoid and Terpenoid Accumulation in Cannabis1[OPEN]

Metabolite and transcriptome profiling of cannabis glandular trichomes differentiates strains and provides evidence for the coregulation of cannabinoid and terpenoid volatile biosynthesis Glandular trichomes are specialized anatomical structures that accumulate secretions with important biological roles in plant-environment interactions. These secretions also have commercial uses in the flavor, fragrance, and pharmaceutical industries. The capitate-stalked glandular trichomes of Cannabis sativa (cannabis), situated on the surfaces of the bracts of the female flowers, are the primary site for the biosynthesis and storage of resins rich in cannabinoids and terpenoids. In this study, we profiled nine commercial cannabis strains with purportedly different attributes, such as taste, color, smell, and genetic origin. Glandular trichomes were isolated from each of these strains, and cell type-specific transcriptome data sets were acquired. Cannabinoids and terpenoids were quantified in flower buds. Statistical analyses indicated that these data sets enable the high-resolution differentiation of strains by providing complementary information. Integrative analyses revealed a coexpression network of genes involved in the biosynthesis of both cannabinoids and terpenoids from imported precursors. Terpene synthase genes involved in the biosynthesis of the major monoterpenes and sesquiterpenes routinely assayed by cannabis testing laboratories were identified and functionally evaluated. In addition to cloning variants of previously characterized genes, specifically CsTPS14CT [(−)-limonene synthase] and CsTPS15CT (β-myrcene synthase), we functionally evaluated genes that encode enzymes with activities not previously described in cannabis, namely CsTPS18VF and CsTPS19BL (nerolidol/linalool synthases), CsTPS16CC (germacrene B synthase), and CsTPS20CT (hedycaryol synthase). This study lays the groundwork for developing a better understanding of the complex chemistry and biochemistry underlying resin accumulation across commercial cannabis strains.
BC-TFdb: a database of transcription factor drivers in breast cancer

Transcription factors (TFs) are DNA-binding proteins, which regulate many essential biological functions. In several cancer types, TF function is altered by various direct mechanisms, including gene amplification or deletion, point mutations, chromosomal translocations, expression alterations, as well as indirectly by non-coding DNA mutations influencing the binding of the TF. TFs are also actively involved in breast cancer (BC) initiation and progression. Herein, we have developed an open-access database, BC-TFdb (Breast Cancer Transcription Factors database), of curated, non-redundant TF involved in BC. The database provides BC driver TFs related information including genomic sequences, proteomic sequences, structural data, pathway information, mutations information, DNA binding residues, survival and therapeutic resources. The database will be a useful platform for researchers to obtain BC-related TF-specific information. High-quality datasets are downloadable for users to evaluate and develop computational methods for drug designing against BC. Database URL: https://www.dqweilab-sjtu.com/index.php.
On the surface tension of molten salts and its temperature dependence

ABSTRACT A new equation, based on Eyring statistical thermodynamic theory, has been developed to calculate the surface tension and its temperature dependence of high-temperature molten salts. The derived equation has been applied to the calculation of the temperature dependence of the surface tension of molten alkali halides. The model used here is analytical and free of interatomic potentials usually used in computer simulation. The only data needed for the calculation are the sublimation energy and the temperature dependence of the liquid density, which are readily available. The need for such a model stems from the fact that the data in the literature are scarce and the temperature range studied is limited by the experimental demand of high temperatures and clean surface environment, which is difficult to attain. The ratio of surface to bulk Madelung constant was calculated to be 0.95, which is found to be constant for all molten salts studied. This finding is interesting and is presented for the first time. The error in this estimate did not exceed 1.3%. The values calculated do commensurate with the available experimental values for many of the molten salts. The results of temperature-dependent surface tension calculations of molten LiCl (910–1150 K), NaCl (1080–1230 K) and KCl (1050–1300 K) are fitted as = 223.5 − 0.0814 (T-Tm), = 114.4 − 0.091 (T-Tm) and = 91 − 0.066 (T-Tm) (mJ m−2), respectively, where the surface tension decreases linearly with temperature and agrees well with the existing data.
Plastic waste to fuels by hydrocracking at mild conditions

Bifunctional catalyst blend is active in hydrocracking of plastic waste to valuable fuels and lubricants with high yields. Single-use plastics impose an enormous environmental threat, but their recycling, especially of polyolefins, has been proven challenging. We report a direct method to selectively convert polyolefins to branched, liquid fuels including diesel, jet, and gasoline-range hydrocarbons, with high yield up to 85% over Pt/WO3/ZrO2 and HY zeolite in hydrogen at temperatures as low as 225°C. The process proceeds via tandem catalysis with initial activation of the polymer primarily over Pt, with subsequent cracking over the acid sites of WO3/ZrO2 and HY zeolite, isomerization over WO3/ZrO2 sites, and hydrogenation of olefin intermediates over Pt. The process can be tuned to convert different common plastic wastes, including low- and high-density polyethylene, polypropylene, polystyrene, everyday polyethylene bottles and bags, and composite plastics to desirable fuels and light lubricants.
Estimation of peptide elongation times from ribosome profiling spectra

Abstract Ribosome profiling spectra bear rich information on translation control and dynamics. Yet, due to technical biases in library generation, extracting quantitative measures of discrete translation events has remained elusive. Using maximum likelihood statistics and data set from Escherichia coli we develop a robust method for neutralizing technical biases (e.g. base specific RNase preferences in ribosome-protected mRNA fragments (RPF) generation), which allows for correct estimation of translation times at single codon resolution. Furthermore, we validated the method with available datasets from E. coli treated with antibiotic to inhibit isoleucyl-tRNA synthetase, and two datasets from Saccharomyces cerevisiae treated with two RNases with distinct cleavage signatures. We demonstrate that our approach accounts for RNase cleavage preferences and provides bias-corrected translation times estimates. Our approach provides a solution to the long-standing problem of extracting reliable information about peptide elongation times from highly noisy and technically biased ribosome profiling spectra.
Selective modulation of a pan-essential protein as a therapeutic strategy in cancer.

Cancer dependency maps, which use CRISPR/Cas9 depletion screens to profile the landscape of genetic dependencies in hundreds of cancer cell lines, have identified context-specific dependencies that could be therapeutically exploited. An ideal therapy is both lethal and precise, but these depletion screens cannot readily distinguish between gene effects that are cytostatic or cytotoxic. Here, we employ a diverse panel of functional genomic screening assays to identify NXT1 as a selective and rapidly lethal in vivo-relevant genetic dependency in MYCN-amplified neuroblastoma. NXT1 heterodimerizes with NXF1 and together they form the principle mRNA nuclear export machinery. We describe a previously unrecognized mechanism of synthetic lethality between NXT1 and its paralog NXT2: their common essential binding partner NXF1 is lost only in the absence of both. We propose a potential therapeutic strategy for tumor-selective elimination of a protein that, if targeted directly, is expected to cause widespread toxicity.
Effect of Two Interventions on Sleep Quality for Adolescent and Young Adult Cancer Survivors

Background Sleep disturbance is common among adolescent and young adult (AYA) cancer survivors. Physical activity (PA) and behavioral activation (BA) therapy have been reported as enhancing sleep quality, but few studies exist on the effects of such interventions combined with technology to promote sleep quality in AYA cancer patients. Objective The aim of this study was to investigate the feasibility and effects of intelligent wearable device–based PA therapy and internet-based modified BA therapy to improve sleep quality among AYA cancer patients. Methods A randomized controlled trial with 143 AYA cancer patients was conducted. Participants were randomly assigned to a control group (n = 48), which performed routine care, a PA group (n = 47), which received 8-week PA therapy based on intelligent wearable devices, and a BA group (n = 48), which participated in internet-based modified BA therapy for 8 weeks. Results At 1 week and 3 months after the intervention for sleep quality, there were statistically significant differences between the PA group and the control group (P = .020), but no statistically significant difference between the BA group and the control group. Conclusions The intelligent wearable device–based PA therapy has more advantages than internet-based modified BA therapy in improving the overall state of AYA cancer patients, and the intervention effect was sustained for at least 3 months. Implications for Practice Developing and implementing PA plans for AYA cancer survivors can improve their sleep quality. Social media, intelligent wearable devices, and mobile health applications have unique advantages in promoting sleep quality for AYA cancer survivors.
Genome-wide analyses of tandem repeats and transposable elements in patchouli.

Patchouli, Pogostemon cablin (Blanco) Benth. , is a traditional Chinese medicinal plant from the order Lamiales. It is considered a valuable herb due to its essential oil content and range of therapeutic effects. This study aimed to explore the evolutionary history of repetitive sequences in the patchouli genome by analyzing tandem repeats and transposable elements (TEs). We first retrieved genomic data for patchouli and four other Lamiales species from the GenBank database. Next, the content of tandem repeats with different period sizes was identified. Long terminal repeats (LTRs) were then identified with LTR_STRUC. Finally, the evolutionary landscape of TEs was explored using an in-house PERL program. The analysis of repetitive sequences revealed that tandem repeats constitute a higher proportion of the patchouli genome compared to the four other species. Analyses of TE families showed that most of the repetitive sequences in the patchouli genome are TEs, and that recently inserted TEs make up a comparatively larger proportion than older ones. Our analyses of LTR retrotransposons in their host genome indicated the existence of ancient LTR retrotransposon expansion, and the escape of these elements from natural selection revealed their ages. Our identification and analyses of repetitive sequences should provide new insights for further investigation of patchouli evolution.
PD-L1 tumor-intrinsic signaling and its therapeutic implication in triple-negative breast cancer

Although the immune checkpoint role of programmed death ligand 1 (PD-L1) has been established and targeted in cancer immunotherapy, the tumor-intrinsic role of PD-L1 is less appreciated in tumor biology and therapeutics development, partly because of the incomplete mechanistic understanding. Here we demonstrate a potentially novel mechanism by which PD-L1 promotes the epithelial-mesenchymal transition (EMT) in triple-negative breast cancer (TNBC) cells by suppressing the destruction of the EMT transcription factor Snail. PD-L1 directly binds to and inhibits the tyrosine phosphatase PTP1B, thus preserving p38-MAPK activity that phosphorylates and inhibits glycogen synthase kinase 3β (GSK3β). Via this mechanism, PD-L1 prevents the GSK3β-mediated phosphorylation, ubiquitination, and degradation of Snail and consequently promotes the EMT and metastatic potential of TNBC. Significantly, PD-L1 antibodies that confine the tumor-intrinsic PD-L1/Snail pathway restricted TNBC progression in immunodeficient mice. More importantly, targeting both tumor-intrinsic and tumor-extrinsic functions of PD-L1 showed strong synergistic tumor suppression effect in an immunocompetent TNBC mouse model. Our findings support that PD-L1 intrinsically facilitates TNBC progression by promoting the EMT, and this potentially novel PD-L1 signaling pathway could be targeted for better clinical management of PD-L1–overexpressing TNBCs.
Emotional symptoms, mental fatigue and behavioral adherence after 72 continuous days of strict lockdown during the COVID-19 pandemic in Argentina

Background: An early, total, and prolonged lockdown was adopted in Argentina during the first wave of COVID-19 as the main sanitary strategy to reduce the spread of the virus in the population. Reports from early stages of the lockdown evidenced elevated emotional symptomatology. Aims: The aim of this study was to explore: 1) if the prolongation of the lockdown was associated with elevated emotional symptoms; 2) if the prolonged lockdown affected adherence, a phenomenon called 'behavioral fatigue'; and 3) how financial concerns in a developing country affected adherence to the lockdown and emotional status of the population. Method: A survey was designed to evaluate the psychological correlates of the pandemic after an average of 72 days of continuous lockdown in Argentina. The survey included standardized questionnaires to assess the severity of depressive (PHQ-9) and anxious (GAD-7) symptoms, a questionnaire to evaluate mental fatigue, and several additional instruments to assess other variables of interest: risk perception, lockdown adherence, financial concerns, daily stress, loneliness, intolerance to uncertainty, negative repetitive thinking, and cognitive problems. Three LASSO regression analyses were carried to evaluate the predictive role of the different variables over depression, anxiety, and lockdown adherence Results: The survey was responded by 3617 individuals over the age of 18 (85.2% female) from all the provinces of Argentina. Using the Oxford stringency index, Argentina had one of the most stringent and prolonged lockdowns when the sample was collected with 63 to 77 continuous days with a stringency index of more than 85/100. 45.6% of the sample met the cut-off for depression and 27% for anxiety. Previous mental health treatment, low income, being younger, and being female were associated with higher levels of emotional symptoms. Mental fatigue, cognitive failures, and financial concerns were also associated with emotional and subjective complaints, but not with adherence to the lockdown. In the regression models, mental fatigue, cognitive failures, and loneliness were the most important variables to predict depression, meanwhile intolerance to uncertainty and lockdown difficulty were the most important in the case of anxiety. Perceived threat was the most important variable predicting lockdown adherence. Conclusions: Emotional symptoms persisted and even increased during the extended lockdown, but we found no evidence of behavioral fatigue. Instead, mental fatigue, cognitive difficulties, and financial concerns were expressions of the emotional side of the pandemic and the restrictive measures.