Miracle-dz/UniFAR-FTUs huggingface dataset:
Wireless, battery-free push-pull microsystem for membrane-free neurochemical sampling in freely moving animals

Extensive studies in both animals and humans have demonstrated that high molecular weight neurochemicals, such as neuropeptides and other polypeptide neurochemicals, play critical roles in various neurological disorders. Despite many attempts, existing methods are constrained by detecting neuropeptide release in small animal models during behavior tasks, which leaves the molecular mechanisms underlying many neurological and psychological disorders unresolved. Here, we report a wireless, programmable push-pull microsystem for membrane-free neurochemical sampling with cellular spatial resolution in freely moving animals. In vitro studies demonstrate the sampling of various neurochemicals with high recovery (>80%). Open-field tests reveal that the device implantation does not affect the natural behavior of mice. The probe successfully captures the pharmacologically evoked release of neuropeptide Y in freely moving mice. This wireless push-pull microsystem creates opportunities for neuroscientists to understand where, when, and how the release of neuropeptides modulates diverse behavioral outputs of the brain.
Digital surveillance: Monitoring the activity of Internet users searching for information related to early childhood caries

This study evaluated the behavior of Internet users from seven countries through the analysis of the monthly variation of the Relative Search Volume (RSV) for queries related to early childhood caries (ECC), retrieved by Google Trends application programming interface between January 2004 to December 2020. The association of RSV with years lived with disability (YLDs) for untreated dental caries in deciduous teeth and Internet penetration were tested by regression models. Forecasting models were developed to predict the interests until December 2021. Relevant topics linked to searches were assessed qualitatively. Increasing levels of interests were observed in most countries, regarding the comparison of periods 2004–2012 and 2013–2021, without influence of seasonality. These results were associated with YLDs only in France and with the Internet penetration in Mexico and France. Searches were mostly related to the definition, risk factors, and preventive care of ECC. The interests of Internet users in ECC-related information increased in the last years in all seven countries, although it was maintained low over time. It might indicate a lack of awareness about the negative consequences of the disease in the early stages of life. Specific policies should be developed toward the dissemination of oral health information and the prevention of the disease.
Highly multiplex PCR assays by coupling the 5′-flap endonuclease activity of Taq DNA polymerase and molecular beacon reporters

Significance We describe a highly multiplex PCR approach that can identify 10-fold more targets in current real-time PCR assays without additional enzymes or separate reactions. This single-step, single-tube, homogeneous detection approach, termed MeltArray, is achieved by coupling the 5′-flap endonuclease activity of the Taq DNA polymerase and multiple annealing sites of the molecular beacon reporters. The 5′-flap endonuclease cleaves a probe specifically into a “mediator” primer, and one molecular beacon reporter allows for the extension of multiple “mediator” primers to produce a series of fluorescent hybrids with different melting temperatures unique to each target. The overall number of targets detectable per reaction is equal to the number of the reporters multiplied by the number of mediator primers per reporter.
Clinically relevant orthotopic xenograft models of patient-derived glioblastoma in zebrafish

ABSTRACT An accurate prediction of the intracranial infiltration tendency and drug response of individual glioblastoma (GBM) cells is essential for personalized prognosis and treatment for this disease. However, the clinical utility of mouse patient-derived orthotopic xenograft (PDOX) models remains limited given current technical constraints, including difficulty in generating sufficient sample numbers from small tissue samples and a long latency period for results. To overcome these issues, we established zebrafish GBM xenografts of diverse origin, which can tolerate intracranial engraftment and maintain their unique histological features. Subsequent single-cell RNA-sequencing (scRNA-seq) analysis confirmed significant transcriptional identity to that of invading GBM microtumors observed in the proportionally larger brains of model animals and humans. Endothelial scRNA-seq confirmed that the zebrafish blood–brain barrier is homologous to the mammalian blood–brain barrier. Finally, we established a rapid and efficient zebrafish PDOX (zPDOX) model, which can predict long-term outcomes of GBM patients within 20 days. The zPDOX model provides a novel avenue for precision medicine of GBM, especially for the evaluation of intracranial infiltration tendency and prediction of individual drug sensitivity.
Mechanism and performance relevance of nanomorphogenesis in polyamide films revealed by quantitative 3D imaging and machine learning

Biological morphogenesis has inspired many efficient strategies to diversify material structure and functionality using a fixed set of components. However, implementation of morphogenesis concepts to design soft nanomaterials is underexplored. Here, we study nanomorphogenesis in the form of the three-dimensional (3D) crumpling of polyamide membranes used for commercial molecular separation, through an unprecedented integration of electron tomography, reaction-diffusion theory, machine learning (ML), and liquid-phase atomic force microscopy. 3D tomograms show that the spatial arrangement of crumples scales with monomer concentrations in a form quantitatively consistent with a Turing instability. Membrane microenvironments quantified from the nanomorphologies of crumples are combined with the Spiegler-Kedem model to accurately predict methanol permeance. ML classifies vastly heterogeneous crumples into just four morphology groups, exhibiting distinct mechanical properties. Our work forges quantitative links between synthesis and performance in polymer thin films, which can be applicable to diverse soft nanomaterials.
Optimised point estimators for multi-stage single-arm phase II oncology trials

ABSTRACT The uniform minimum variance unbiased estimator (UMVUE) is, by definition, a solution to removing bias in estimation following a multi-stage single-arm trial with a primary dichotomous outcome. However, the UMVUE is known to have large residual mean squared error (RMSE). Therefore, we develop an optimisation approach to finding estimators with reduced RMSE for many response rates, which attain low bias. We demonstrate that careful choice of the optimisation parameters can lead to an estimator with often substantially reduced RMSE, without the introduction of appreciable bias.
The closest evolutionary relatives of pterosaurs: What the morphospace occupation of different skeletal regions tell us about lagerpetids

Exquisite discoveries and new interpretations regarding an enigmatic group of cursorial avemetatarsalians led to a new phylogenetic hypothesis regarding pterosaur affinities. Previously thought to be dinosaur precursors, lagerpetids are now considered to be the closest relatives to pterosaurs. This new hypothesis sheds light on a new explorable field, especially regarding the character acquisition and evolution within the pterosaur lineage. In the present study, the morphospace occupation of distinct skeletal regions of lagerpetids within the morphological spectrum of avemetatarsalians is investigated. This approach indicates which portions of the skeleton are more similar to the anatomy of pterosaurs and which portions present different homoplastic signals. The analyses demonstrate that the craniomandibular traits of lagerpetids are pterosaur‐like, the pectoral girdle and forelimb are dinosauromorph‐like and the axial skeleton and the pelvic girdle and hindlimb are unique and highly specialized among the analyzed sample. So, despite the close phylogenetic relationships, the postcranial skeleton of lagerpetids and pterosaurs are very different. The occurrence of two distinct and highly specialized groups of pterosauromorphs coexisting with a wide ecological range of dinosauromorphs during the Triassic suggests pressure for new niches occupation.
National Athletic Trainers' Association Position Statement: Reducing Intentional Head-First Contact Behavior in American Football Players.

OBJECTIVE To provide evidence-based recommendations for reducing the prevalence of head-first contact behavior in American football players with the aim of reducing the risk of head and neck injuries. BACKGROUND In American football, using the head as the point of contact is a persistent, well-documented, and direct cause of catastrophic head and cervical spine injury. Equally concerning is that repeated head-impact exposures are likely to result from head-first contact behavior and may be associated with long-term neurocognitive conditions such as dementia, depression, and chronic traumatic encephalopathy. CONCLUSIONS The National Athletic Trainers' Association proposes 14 recommendations to help the certified athletic trainer, allied health care provider, coach, player, parent, and broader community implement strategies for reducing the prevalence of head-first contact in American football.
Long‐Term Monitoring of an In Situ Activated Carbon Treatment to Reduce Polychlorinated Biphenyl Availability in an Active Harbor

Activated carbon–based amendments have been demonstrated as a means of sequestering sediment‐associated organic compounds such as polychlorinated biphenyls (PCBs). In a 2012 effort, an activated carbon amendment was placed at a 0.5‐acre amendment area adjacent to and underneath Pier 7 at the Puget Sound Naval Shipyard and Intermediate Maintenance Facility, Bremerton, Washington, USA to reduce PCB availability. Multiple postplacement monitoring events over a 3‐year period showed an 80%–90% reduction in PCBs, stability of activated carbon, and no significant negative impacts to the benthic community. To further evaluate the long‐term performance, a follow‐on to the approximately 7‐year (82‐month) postplacement monitoring event was conducted in 2019. The results of in situ porewater and bioaccumulation evaluations were consistent with previous observations, indicating overall PCB availability reductions of approximately 80%–90% from preamendment conditions. Multiple measurement approaches for quantifying activated carbon and amendment presence indicated that the amendment was present and stable in the amendment area and that the activated carbon content was similar to levels observed previously. As in the previous investigation, benthic invertebrate community metrics indicated that the amendment did not significantly impair benthic health. An application of carbon petrography to quantify activated carbon content in surface sediments was also explored. The results were found to correspond within a factor of 1.3 (on average) with those of data for the black carbon content via a black carbon chemical oxidation method, an approach that quantifies all forms of black carbon (including activated carbon). The results suggest that at sites with low soot‐derived black carbon content in sediment (relative to the targeted activated carbon dose), the black carbon chemical oxidation method would be a reasonable method for measurement of activated carbon dosage in sediment at sites amended with activated carbon. Environ Toxicol Chem 2022;41:1568–1574. © 2022 SETAC
THRSP identified as a potential hepatocellular carcinoma marker by integrated bioinformatics analysis and experimental validation

Hepatocellular carcinoma (HCC) is the most common malignant liver tumor with high mortality and poor prognosis worldwide. This study aimed to identify hub genes and investigate the underlying molecular mechanisms in HCC progression by integrated bioinformatics analysis and experimental validation. Based on the Gene Expression Omnibus (GEO) databases and The Cancer Genome Atlas (TCGA), 12 critical differential co-expression genes were identified between tumor and normal tissues. Via survival analysis, we found higher expression of LCAT, ACSM3, IGF1, SRD5A2, THRSP and ACADS was associated with better prognoses in HCC patients. Among which, THRSP was selected for the next investigations. We found that THRSP mRNA expression was negatively correlated with its methylation and closely associated with clinical characteristics in HCC patients. Moreover, THRSP expression had a negative correlation with the infiltration levels of several immune cells (e.g., B cells and CD4+ T cells). qRT-PCR verified that THRSP was lower expressed in HCC tissues and cell lines compared with control. Silencing of THRSP promoted the migration, invasion, proliferation, and inhibited cell apoptosis of HCCLM and Huh7 cell lines. Decreased expression of THRSP promoted HCC progression by NF-κB, ERK1/2, and p38 MAPK signaling pathways. In conclusion, THRSP might serve as a novel biomarker and therapeutic target of HCC.
Preparation and characterization of injectable gelatin/alginate/chondroitin sulfate/α-calcium sulfate hemihydrate composite paste for bone repair application

In this study, a group of injectable composite pastes with a novel formulation consisting of two inorganic components: α-calcium sulfate hemihydrate (α-CSH, P/L = 1.8–2.1 g/ml) and calcium-deficient hydroxyapatite (CDHA, P/L = 0.1 g/ml) nanoparticles; and three biopolymers: gelatin (2, 4 wt. %), alginate (1, 1.5 wt. %), and chondroitin sulfate (0.5 wt. %) were carefully prepared and thoroughly characterized with commensurate characterizations. The composite sample composed of gelatin (2 wt. %), alginate (1.5 wt. %), chondroitin sulfate (0.5 wt. %), and also CDHA nanoparticles and α-CSH with P/L ratios of 0.1 and 2.1 g/ml, respectively, exhibited optimal properties in terms of injectability, anti-washout performance, and rheological characteristics. After 14 days of immersion of the chosen sample in the simulated body fluid medium, a dense layer of apatite was formed on the surface of the composite paste. The cellular in vitro tests, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay (MTT), alkaline phosphatase assay, 4ʹ,6-diamidino-2-phenylindole staining, and cellular attachment, revealed the desirable response of MG-63 cells to the composite paste. The chondroitin sulfate significantly improved the injectability, anti-washout performance, and cellular response of the samples. Considering the promising features of the composite paste prepared in this research work, it could be considered as an alternative injectable bioactive material for bone repair applications.
Circular RNA hsa_circ_0119412 contributes to tumorigenesis of gastric cancer via the regulation of the miR-1298-5p/zinc finger BED-type containing 3 (ZBED3) axis

ABSTRACT Circular RNAs (circRNAs) are associated with the progression of gastric cancer (GC). This study investigates the regulation of the circular RNA, hsa_circ_0119412 in GC and its effects on GC cells. The expression of hsa_circ_0119412, microRNA (miR)-1298-5p, and zinc finger BED-type containing 3 (ZBED3) were measured by quantitative reverse transcription-PCR (qRT-PCR) and Western blotting. The cell counting kit-8 (CCK-8) assay, flow cytometry, transwell, and animal assays were performed to identify the roles of hsa_circ_0119412, miR-1298-5p, and ZBED3 in the viability, apoptosis, invasion, and growth of GC cells. The relationship between hsa_circ_0119412, miR-1298-5p, and ZBED3 was confirmed by luciferase, RNA immunoprecipitation (RIP), and RNA pull-down assays. Our data revealed that hsa_circ_0119412 and ZBED3 expression was upregulated in GC, while miR-1298-5p expression was downregulated. Both the knockdown of hsa_circ_0119412/ZBED3 and miR-1298-5p overexpression inhibited GC cell growth and invasion, and enhanced cell apoptosis, while miR-1298-5p interference or ZBED3 overexpression showed the opposite trend. Mechanistically, hsa_circ_0119412 sponges miR-1298-5p, which regulates ZBED3 expression. Silencing hsa_circ_0119412 inhibits the progression of GC, at least in part, by targeting the miR-1298-5p/ZBED3 axis. graphic abstract
Risk of asthma exacerbation associated with opioid and nonopioid analgesic use in children with current asthma

BACKGROUND: In the United States, asthma occurs in a vast proportion of children and adolescents. Asthma exacerbation is an acute episodic event typically characterized by difficulty in breathing, chest tightness, coughing, or wheezing. Severe asthma exacerbation can be life-threatening and lead to service utilizations such as hospitalizations and emergency department (ED) visits. Opioid analgesic use can trigger an asthma exacerbation through 2 pharmacological mechanisms. Despite the potential mechanisms, there is lack of empirical evidence to determine the risk of asthma exacerbation and its association with opioid use. OBJECTIVE: To evaluate the risk of asthma exacerbation in children with current asthma receiving an opioid vs a nonopioid analgesic. METHODS: Eligible individuals aged under 18 years with current asthma and receiving an incident analgesic prescription were identified from a large Medicaid managed care database during 2013-2018. Current asthma was defined as receipt of an asthma diagnosis and an antiasthmatic medication in the 12 months before analgesic medication initiation. Asthma exacerbation was defined as a hospitalization or ED visit with asthma as either the primary or secondary diagnosis within 3 days of receipt of an analgesic prescription. A weighted multivariable logistic regression using inverse probability treatment weighting was performed to test the association between use of analgesic medication and risk of asthma exacerbation. RESULTS: This study included 13,359 children with current asthma who filled either an incident opioid (n = 5,363, 40.1%) or nonopioid analgesic (n = 7,996, 59.9%) prescription. Asthma exacerbation was observed in 24 (0.5%) opioid analgesic recipients and 22 (0.3%) nonopioid analgesic recipients within 3 days of analgesic initiation. Weighted logistic regression results showed that children receiving opioid analgesics (adjusted odds ratio = 1.6, 95% CI = 0.9-2.9) did not have a statistically significantly higher risk of asthma exacerbation than their nonopioid analgesic recipient counterparts in the propensity score-weighted multivariable analysis. CONCLUSIONS: Asthma exacerbation associated with analgesic use in children with current asthma was an uncommon event, and the risk was comparable among children receiving opioid vs nonopioid analgesics.
Altered muscle strength and flexibility among a subgroup of women with chronic nonspecific low back pain: Cross-sectional case-control study

ABSTRACT Objective To compare muscle strength and flexibility among a subgroup of women with extension-related chronic nonspecific low back pain (CNLBP) with healthy controls. Methods In this case-control study, 32 subjects with and without extension-related CNLBP were tested (n = 16 in each group). Gluteal, abdominal, paravertebral, and hamstring strength, along with hip flexor flexibility and hamstring flexibility were compared between groups. Data were analyzed using the Mann–Whitney test (p < .007). Results The CNLBP subgroup displayed significantly lower strength of all muscles analyzed (p < .007), with the exception of gluteus medius. The flexibility of the hip flexors and hamstrings were not significantly reduced among the women with CNLBP (p > .007). Discussion The present study showed that alterations in muscle strength, but not flexibility, partly consistent with those previously hypothesized but not objectively reported, were present among a subgroup of women with extension-related CNLBP. These results may have implications for the selection of therapeutic exercises among this subgroup of people with CNLBP.
Defective autophagy contributes to endometrial epithelial-mesenchymal transition in intrauterine adhesions

ABSTRACT Intrauterine adhesions (IUA), characterized by endometrial fibrosis, is a common cause of uterine infertility. We previously demonstrated that partial epithelial-mesenchymal transition (EMT) and the loss of epithelial homeostasis play a vital role in the development of endometrial fibrosis. As a pro-survival strategy in maintaining cell and tissue homeostasis, macroautophagy/autophagy, conversely, may participate in this process. However, the role of autophagy in endometrial fibrosis remains unknown. Here, we demonstrated that autophagy is defective in endometria of IUA patients, which aggravates EMT and endometrial fibrosis, and defective autophagy is related to DIO2 (iodothyronine deiodinase 2) downregulation. In endometrial epithelial cells (EECs), pharmacological inhibition of autophagy by chloroquine (CQ) promoted EEC-EMT, whereas enhanced autophagy by rapamycin extenuated this process. Mechanistically, silencing DIO2 in EECs blocked autophagic flux and promoted EMT via the MAPK/ERK-MTOR pathway. Inversely, overexpression of DIO2 or triiodothyronine (T3) treatment could restore autophagy and partly reverse EEC-EMT. Furthermore, in an IUA-like mouse model, the autophagy in endometrium was defective accompanied by EEC-EMT, and CQ could inhibit autophagy and aggravate endometrial fibrosis, whereas rapamycin or T3 treatment could improve the autophagic levels and blunt endometrial fibrosis. Together, we demonstrated that defective autophagy played an important role in EEC-EMT in IUA via the DIO2-MAPK/ERK-MTOR pathway, which provided a potential target for therapeutic implications. Abbreviations: ACTA2/α-SMA: actin alpha 2, smooth muscle; AMPK: adenosine 5’-monophosphate-activated protein kinase; AKT/protein kinase B: AKT serine/threonine kinase; ATG: autophagy related; CDH1/E-cadherin: cadherin 1; CDH2/N-cadherin: cadherin 2; CQ: chloroquine; CTSD: cathepsin D; DIO2: iodothyronine deiodinase 2; DEGs: differentially expressed genes; EECs: endometrial epithelial cells; EMT: epithelial-mesenchymal transition; FN1: fibronectin 1; IUA: intrauterine adhesions; LAMP1: lysosomal associated membrane protein 1; LPS: lipopolysaccharide; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MTOR: mechanistic target of rapamycin kinase; Rapa: rapamycin; SQSTM1/p62: sequestosome 1; T3: triiodothyronine; T4: tetraiodothyronine; TFEB: transcription factor EB; PBS: phosphate-buffered saline; TEM: transmission electron microscopy; TGFB/TGFβ: transforming growth factor beta.