Miracle-dz/UniFAR-FTUs huggingface dataset:
AMPK-dependent phosphorylation is required for transcriptional activation of TFEB and TFE3

ABSTRACT Increased macroautophagy/autophagy and lysosomal activity promote tumor growth, survival and chemo-resistance. During acute starvation, autophagy is rapidly engaged by AMPK (AMP-activated protein kinase) activation and MTOR (mechanistic target of rapamycin kinase) complex 1 (MTORC1) inhibition to maintain energy homeostasis and cell survival. TFEB (transcription factor E3) and TFE3 (transcription factor binding to IGHM enhancer 3) are master transcriptional regulators of autophagy and lysosomal activity and their cytoplasm/nuclear shuttling is controlled by MTORC1-dependent multisite phosphorylation. However, it is not known whether and how the transcriptional activity of TFEB or TFE3 is regulated. We show that AMPK mediates phosphorylation of TFEB and TFE3 on three serine residues, leading to TFEB and TFE3 transcriptional activity upon nutrient starvation, FLCN (folliculin) depletion and pharmacological manipulation of MTORC1 or AMPK. Collectively, we show that MTORC1 specifically controls TFEB and TFE3 cytosolic retention, whereas AMPK is essential for TFEB and TFE3 transcriptional activity. This dual and opposing regulation of TFEB and TFE3 by MTORC1 and AMPK is reminiscent of the regulation of another critical regulator of autophagy, ULK1 (unc-51 like autophagy activating kinase 1). Surprisingly, we show that chemoresistance is mediated by AMPK-dependent activation of TFEB, which is abolished by pharmacological inhibition of AMPK or mutation of serine 466, 467 and 469 to alanine residues within TFEB. Altogether, we show that AMPK is a key regulator of TFEB and TFE3 transcriptional activity, and we validate AMPK as a promising target in cancer therapy to evade chemotherapeutic resistance. Abbreviations: ACACA: acetyl-CoA carboxylase alpha; ACTB: actin beta; AICAR: 5-aminoimidazole-4-carboxamide ribonucleotide; AMPK: AMP-activated protein kinase; AMPKi: AMPK inhibitor, SBI-0206965; CA: constitutively active; CARM1: coactivator-associated arginine methyltransferase 1; CFP: cyan fluorescent protein; CLEAR: coordinated lysosomal expression and regulation; DKO: double knock-out; DMEM: Dulbecco’s modified Eagle’s medium; DMSO: dimethyl sulfoxide; DQ-BSA: self-quenched BODIPY® dye conjugates of bovine serum albumin; EBSS: Earle’s balanced salt solution; FLCN: folliculin; GFP: green fluorescent protein; GST: glutathione S-transferases; HD: Huntington disease; HTT: huntingtin; KO: knock-out; LAMP1: lysosomal associated membrane protein 1; MEF: mouse embryonic fibroblasts; MITF: melanocyte inducing transcription factor; MTORC1: MTOR complex 1; PolyQ: polyglutamine; RPS6: ribosomal protein S6; RT-qPCR: reverse transcription quantitative polymerase chain reaction; TCL: total cell lysates; TFE3: transcription factor binding to IGHM enhancer 3; TFEB: transcription factor EB; TKO: triple knock-out; ULK1: unc-51 like autophagy activating kinase 1.
Potential therapeutic applications of phytoconstituents as immunomodulators: Pre‐clinical and clinical evidences

Autoimmune and infectious diseases are the major public health issues and have gained great attention in the last few years for the search of new agents with therapeutic benefits on the host immune functions. In recent years, natural products (NPs) have been studied broadly for their multi‐targeted activities under pathological conditions. Interestingly, several attempts have been made to outline the immunomodulatory properties of NPs. Research on in‐vitro and in‐vivo models have shown the immunomodulatory activity of NPs, is due to their antiinflammatory property, induction of phagocytosis and immune cells stimulation activity. Moreover, studies on humans have suggested that phytomedicines reduce inflammation and could provide appropriate benefits either in single form or complex combinations with other agents preventing disease progression, subsequently enhancing the efficacy of treatment to combat multiple malignancies. However, the exact mechanism of immunomodulation is far from clear, warranting more detailed investigations on their effectiveness. Nevertheless, the reduction of inflammatory cascades is considered as a prime protective mechanism in a number of inflammation regulated autoimmune diseases. Altogether, this review will discuss the biological activities of plant‐derived secondary metabolites, such as polyphenols, alkaloids, saponins, polysaccharides and so forth, against various diseases and their potential use as an immunomodulatory agent under pathological conditions.
Offline bioregeneration of spent activated carbon loaded with real Produced Water and its adsorption capacity for benzene and toluene

AbstractThe disposal of water produced during the petroleum extraction (Produced Water) is a relevant issue due to the occurrence of contaminants. Adsorption on activated carbon is one of the best available technologies for the removal of synthetic organic chemicals from water. However, the replacement and disposal of exhausted carbon is quite expensive and the spent carbon may have to be handled as hazardous waste. The bioregeneration of spent carbon could be a feasible solution; however, hypersaline wastewaters, like Produced Water, are often recalcitrant to biological process due to the strong inhibition by salts (mainly NaCl), elevated temperature, and presence in solution of biocides. In this study, adsorption kinetics, isotherms, and rapid small-scale column tests have been performed to select the type of granular activated carbon (GAC) with the best adsorption capacity of target monoaromatic compounds (benzene and toluene). Continuous-flow pre-loaded GAC biological regeneration experiments were con.
Diagnostic yield of whole-exome sequencing in non-syndromic intellectual disability.

BACKGROUND Aetiological diagnosis in non-syndromic intellectual disability (NSID) still poses a diagnostic challenge to clinicians. METHODS Screening is currently achieved by chromosomal microarrays followed by whole-exome sequencing (WES). In search for the aetiological yield of WES in patients with NSID, 59 unrelated patients were studied. RESULTS Among the 59 patients, 44 (74.6%) were from consanguineous unions. Epilepsy was present in 11 (37.9%), behavioural problems in 12 (41.4%) and autistic features in 14 (48.3%). WES analysis resulted in molecular diagnosis in 29 patients (49.2%). Some of the genes were specific for nervous system functioning, like HERC1, TBC1D7, LINS, HECW2, DEAF1, HNMT, DLG3, NRXN1 and HUWE1. Others were ubiquitously expressed genes involved in fundamental cellular processes, like IARS, UBE3A, COQ4, TAF1, SETBP1, ARV1, ZC4H2, KAT6A, ASXL3, THOC6, HNRNPH2, TUBA8 and KIF1A. Twenty-two (75.8%) were consanguineously married; however, only 12 (41.4%) of the detected genes caused autosomal recessive phenotypes. CONCLUSIONS This cohort suggests that recessive genes probably represent an actually smaller subgroup of NSID, even among families with consanguinity. Although in societies with high consanguinity rates, considering the recessive inheritance first seems to be an advantageous strategy, de novo mutations in autosomal dominantly expressed genes represent the major aetiological group in patients with NSID, even among those patients from consanguineous families.
Analysis of survey on menstrual disorder among teenagers using Gaussian copula model with graphical lasso prior

A high prevalence of menstrual disturbance has been reported among teenage girls, and research shows that there are delays in diagnosis of endometriosis among young girls. Using data from the Menstrual Disorder of Teenagers Survey (administered in 2005 and 2016), we propose a Gaussian copula model with graphical lasso prior to identify cohort differences in menstrual characteristics and to predict endometriosis. The model includes random effects to account for clustering by school, and we use the extended rank likelihood copula model to handle variables of mixed-type. The graphical lasso prior shrinks the elements in the precision matrix of a Gaussian distribution to encourage a sparse graphical structure, where the level of shrinkage is adaptable based on the strength of the conditional associations among questions in the survey. Applying our proposed model to the menstrual disorder data set, we found that menstrual disturbance was more pronouncedly reported over a decade, and we found some empirical differences between those girls with higher risk of developing endometriosis and the general population.
Characteristics and influencing factors of Airbnb spatial distribution in China’s rapid urbanization process: A case study of Nanjing

As in other countries, short-term rentals for tourism services are growing rapidly in China’s tourist cities, which are mainly operated through Airbnb. This paper explores whether the spatial distribution of Airbnb in China’s rapid urbanization process exhibits characteristics, paths, and drivers that are different from those of cities in other countries. Airbnb is a model for the global sharing economy, but it is increasingly influenced by other functions and facilities in cities as it grows. In this paper, the zero-expansion negative binomial regression was used to study the factors affecting the spatial distribution of Airbnb in Nanjing, China. The results showed that the spatial distribution of Airbnb listings was correlated with the distribution of cultural attractions, universities, public transport accessibility, shopping centers, and business apartments. By analyzing the driving forces of Airbnb’s development in Nanjing, this paper found that a large number of business apartments developed in cities were essential providers of Airbnb listings, and affected its spatial distribution. The gap between short-term and long-term rentals was also correlated with the distribution of Airbnb. In addition, similar to the previous literature findings, the increase in the proportion of professional hosts changes the original intention of Airbnb for sharing and communication. Our empirical results applies to the current situation of Airbnb in Chinese cities, which is conducive to the government’s more intelligent management and effective promotion of the Airbnb market. Our findings also provide positive references for urban renewal policies and public participation methods in China.
Privacy-Preserving Synthetic Trajectory Data Generation

A major open research challenge is developing privacy-preserving machine learning methods that both achieve high performance and privacy guarantees even though the original training data contains sensitive personal information. The applications are abundant, from making cities safer, via on-demand public transportation systems to improved medical diagnosis. The goal of our PhD projects is to develop new machine learning methods for creating synthetic spatio-temporal trajectory data sets preserving the privacy of the individuals in the original data. We will 1) extend generative adversarial network (GAN) methods to learn generative spatio-temporal trajectory models and 2) develop new Bayesian Optimization methods for creating tailored privacy-preserving synthetic data sets using these generative models.
A Social Media–Promoted Educational Community of Joint Replacement Patients Using the WeChat App: Survey Study

Background Much effort has been made to optimize the results of total hip arthroplasty and total knee arthroplasty. With the rapid growth of social media use, mobile apps, such as WeChat, have been considered for improving outcomes and patient satisfaction after total hip arthroplasty and total knee arthroplasty. Objective We aimed to evaluate the effectiveness of a WeChat-based community as an intervention for overall patient satisfaction. Methods The study was conducted among discharged in-hospital patients who received hip or knee procedures in the First Affiliated Hospital of the University of Science and Technology of China from April 2019 to January 2020. An educational online social community was constructed with the WeChat app. Participants willing to join the community were enrolled in a WeChat group and received 3 months of intervention and follow-up. Those who were not willing to use the account were included in a control group and received routine publicity via telephone, mail, and brochures. The Danish Health and Medicine Authority patient satisfaction questionnaire was used to score perioperative patient education and overall satisfaction. The contents in the group chat were analyzed using natural language processing tools. Results A total of 3428 patients were enrolled in the study, including 2292 in the WeChat group and 1236 in the control group. Participants in the WeChat group had higher overall satisfaction scores than those in the control group (mean 8.48, SD 1.12 vs mean 6.66, SD 1.80, P<.001). The difference between the two groups was significant for primary surgery based on subgroup stratification. To control confounding factors and explore the effects of WeChat participation as a mediating variable between perioperative patient education and overall satisfaction, hierarchical regression was utilized. An interpatient interaction model was found in the community group chat, and it contributed to overall satisfaction. Patients in the group with more interpatient interactions were more likely to have better overall satisfaction. Conclusions The social media–promoted educational community using WeChat was effective among joint replacement patients. Provision of more perioperative education is associated with more active patient participation in the community and therefore more patient satisfaction in terms of the overall joint procedure. Community group chat could facilitate interactions among patients and contribute to overall satisfaction.
Chemical composition, impact from biomass burning, and mass closure for PM2.5 and PM10 aerosols at Hyytiälä, Finland, in summer 2007

A comprehensive chemical aerosol characterisation was carried out at the forested site of Hyytiala, Finland, from 2 to 30 August 2007. PM2.5 and PM10 Nuclepore polycarbonate and quartz fibre filter samples were taken in parallel, typically for separate day-time and night-time periods. All samples were analysed for the particulate mass by weighing. The Nuclepore filters were analysed for over 20 elements by particle-induced X-ray emission (PIXE) spectrometry and for major anions and cations by ion chromatography. The quartz fibre filters were analysed for organic and elemental carbon by a thermal-optical transmission technique. A number of samples exhibited high K, Zn, and oxalate levels, indicating an impact from biomass burning. A noteworthy episode occurred on 12-13 August, when air masses were advected from the southern part of European Russia where extensive biomass burning had occurred. In the aerosol chemical mass closure calculations, eight aerosol types were considered. Organic matter (OM) contributed by far the most to the PM2.5 and PM10 mass; it accounted for about 70% of the average PM2.5 and PM10 mass and 48% of the coarse (PM10–2.5) aerosol. Crustal matter, deduced from the PIXE data, provided a rather small contribution; only 3% in PM2.5, 13% in PM10, and 32% in the coarse aerosol. The mean PM2.5 and PM10 mass concentrations and their attribution to the eight aerosol types for the 2007 campaign at Hyytiala were similar to those for the cold period of a 2006 summer campaign at the forested site of K-puszta, Hungary. OM was more important and nitrate was clearly less important at Hyytiala, though. Copyright © 2011 John Wiley & Sons, Ltd.
Acquiring photoacoustic signature of hematocrit variation from plexus layer of in-silico human skin phantom

Optical penetration inside human skin is constrained by the wavelength dependent scattering and absorption losses by tissue microstructure and chromophores. This computational study investigates whether the signature of hematocrit variation from plexus i.e., the first skin layer having very small blood volume percentage distributed in capillary vessels, is retained by the detected photoacoustic response. The in-silico skin phantom is irradiated by a light source equivalent to a small footprint and low power (below 5 W) continuous wave LASER diode. As the low fluence can be compensated by exploiting strong absorption by targeted chromophores (hemoglobin molecules), an irradiation of wavelength 405 nm has been used to generate detectable pressure from capillary blood vessels of plexus. Optical energy deposition inside the tissue has been modelled using Monte Carlo technique and the pressure wave is computed using k-wave. It is found that with the increase in hematocrit from 10% to 50%, photoacoustic amplitude monotonically increases and gets almost doubled. The increment is about 30% in the range of hematocrit of physiological interest (from 30% to 50%). The variation follows a quadratic relationship for the entire hematocrit range. This photoacoustic signature of hematocrit variation has further been validated against minimum detectable pressure (800 Pa). This numerical model is expected to be an important basis to realize the idea of low cost small footprint in-vivo photoacoustic hematocrit measurement device.
R‐MACLO‐IVAM regimen followed by maintenance therapy induces durable remissions in untreated mantle cell lymphoma ‐ Long term follow up results

We present long‐term combined results of two clinical trials implementing R‐MACLO‐IVAM induction followed by thalidomide or rituximab maintenance in 44 patients with untreated mantle cell lymphoma (MCL). The first 22 patients (UM‐MCL1 ClinicalTrials.gov identifier NCT00450801) received maintenance with thalidomide (200 mg daily until relapse/intolerable toxicity) and a subsequent cohort of 22 patients (UM‐MCL2 ClinicalTrials.gov identifier NCT00878254) received rituximab (375 mg/m2 IV weekly × 4, repeated every 6 months for 3 years). Considering all 44 patients, 41 (93.2%) achieved complete response (CR), two (4.5%) partial response (PR), and one (2.3%) was not evaluated for response. With a median follow up of 7.2 years (range < 1 month to 16 years), the 5‐year progression‐free survival (PFS) was 55.6% (95% CI: 38.9%‐69.4%) and median PFS 7.9 years (95% CI: 3.7–11 years). The 5‐year OS was 83.3% (95% CI: 68.1%‐91.7%) and median OS was not reached. Patients with blastic variant (n = 6) had a 5‐year PFS and OS of 20.8% and 60%, respectively. Myelosuppression was the most common adverse event during immunochemotherapy. Long‐term treatment‐related mortality was 6.8%. Note, R‐MACLO‐IVAM followed by maintenance therapy is an effective regimen to induce long‐term remission in MCL without need for consolidation with ASCT.
Integrating human services and criminal justice data with claims data to predict risk of opioid overdose among Medicaid beneficiaries: A machine-learning approach

Health system data incompletely capture the social risk factors for drug overdose. This study aimed to improve the accuracy of a machine-learning algorithm to predict opioid overdose risk by integrating human services and criminal justice data with health claims data to capture the social determinants of overdose risk. This prognostic study included Medicaid beneficiaries (n = 237,259) in Allegheny County, Pennsylvania enrolled between 2015 and 2018, randomly divided into training, testing, and validation samples. We measured 290 potential predictors (239 derived from Medicaid claims data) in 30-day periods, beginning with the first observed Medicaid enrollment date during the study period. Using a gradient boosting machine, we predicted a composite outcome (i.e., fatal or nonfatal opioid overdose constructed using medical examiner and claims data) in the subsequent month. We compared prediction performance between a Medicaid claims only model to one integrating human services and criminal justice data with Medicaid claims (i.e., integrated model) using several metrics (e.g., C-statistic, number needed to evaluate [NNE] to identify one overdose). Beneficiaries were stratified into risk-score decile subgroups. The samples (training = 79,087, testing = 79,086, validation = 79,086) had similar characteristics (age = 38±18 years, female = 56%, white = 48%, having at least one overdose = 1.7% during study period). Using the validation sample, the integrated model slightly improved on the Medicaid claims only model (C-statistic = 0.885; 95%CI = 0.877–0.892 vs. C-statistic = 0.871; 95%CI = 0.863–0.878), with small corresponding improvements in the NNE and positive predictive value. Nine of the top 30 most important predictors in the integrated model were human services and criminal justice variables. Using the integrated model, approximately 70% of individuals with overdoses were members of the top risk decile (overdose rates in the subsequent month = 47/10,000 beneficiaries). Few individuals in the bottom 9 deciles had overdose episodes (0-12/10,000). Machine-learning algorithms integrating claims and social service and criminal justice data modestly improved opioid overdose prediction among Medicaid beneficiaries for a large U.S. county heavily affected by the opioid crisis.
Threshold for defining fever varies with age, especially in children: A multi‐site diagnostic accuracy study

The American Academy of Pediatrics and the European Centre for Pediatric and Adolescent Medicine guideline define fever as a temperature >38.0°C for all ages and recommend use of rectal thermometers in children <3 years. Based on new literature, this definition of fever using a fixed threshold of 38.0°C needs to be re‐examined.
Hearing, Vision, or Dual Sensory Impairment and Dementia Risk.

and are prevalent chronic conditions among older have associated with increased risk of a wide array of secondary physical and mental ailments. growing evidence suggests a robust link between these sensory deficits and dementia. Two predominant theories support this association: cascade theory and common cause theory. The cascade theory postulates a lengthy period of hearing or vision loss may not a person’s cognitive load to sequestration, functional
On a nearly proton‐ordered structure for ice IX

Single‐crystal neutron diffraction shows that ice IX, the low‐temperature modification of ice III, has an almost completely proton‐ordered structure in which the ordered component contains two types of water molecules, type 1 in a site of no point symmetry, and type 2 on a twofold axis, each forming four hydrogen bonds in a three‐dimensional framework. The configuration of the water molecules is slightly but significantly altered from that of water vapor. Independent O–D distances, which do not differ significantly from one another, average 0.982± 0.003 A (corrected for thermal motion), and are increased by 0.012 A over the vapor value. The shift in O–D stretching frequency ν1 from vapor to ice IX corresponds to a slope dν1/dr≅ −20 000 cm−1. A−1, which agrees with the slope predicted from spectroscopic anharmonicity constants. D–O–D bond angles (104.7± 0.4°, 106.0± 0.2°) are not decreased from the vapor value (104.5°) despite the smaller O··· O··· O angles into which the water molecules donate protons (98.