Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of anti-androgenic activity of chemicals in fish studies: a data review

Abstract A systematic review was conducted on the sensitivity of fish testing guidelines to detect the anti-androgenic activity of substances. Sequence Alignment to Predict Across Species Susceptibility (SeqAPASS) was used to investigate the conservation of the androgen receptor (AR) between humans and fish, and among fish species recommended in test guidelines. The AR is conserved between fish species and humans (i.e. ligand binding domain [LBD] homology ≥70%) and among the recommended fish species (LBD homology >85%). For model anti-androgens, we evaluated literature data on in vitro anti-androgenic activity in fish-specific receptor-based assays and changes in endpoints indicative of endocrine modulation from in vivo studies. Anti-androgenic activity was most consistently and reliably detected in in vitro and in vivo mechanistic studies with co-exposure to an androgen (spiggin in vitro assay, Rapid Androgen Disruption Activity Reporter [RADAR] Assay, and Androgenised Female Stickleback Screen). Regardless of study design (Fish Short-Term Reproduction Assay [FSTRA], Fish Sexual Development Test [FSDT], partial or full life-cycle tests), or endpoint (vitellogenin, secondary sexual characteristics, gonadal histopathology, sex ratio), there was no consistent evidence for detecting anti-androgenic activity in studies without androgen co-exposure, even for the most potent substances (while less potent substances may induce no (clear) response). Therefore, based on studies without androgen co-exposure (35 FSTRAs and 22 other studies), the other studies (including the FSDT) do not outperform the FSTRA for detecting potent anti-androgenic activity, which if suspected, would be best addressed with a RADAR assay. Overall, fish do not appear particularly sensitive to mammalian anti-androgens.
Analysis of the Bile Acid Composition in a Fibroblast Growth Factor 19-Expressing Liver-Humanized Mouse Model and Its Use for CYP3A4-Mediated Drug–Drug Interaction Studies

Numerous biomedical applications have been described for liver-humanized mouse models, such as in drug metabolism or drug–drug interaction (DDI) studies. However, the strong enlargement of the bile acid (BA) pool due to lack of recognition of murine intestine-derived fibroblast growth factor-15 by human hepatocytes and a resulting upregulation in the rate-controlling enzyme for BA synthesis, cytochrome P450 (CYP) 7A1, may pose a challenge in interpreting the results obtained from such mice. To address this challenge, the human fibroblast growth factor-19 (FGF19) gene was inserted into the Fah−/−, Rag2−/−, Il2rg−/− NOD (FRGN) mouse model, allowing repopulation with human hepatocytes capable of responding to FGF19. While a decrease in CYP7A1 expression in human hepatocytes from humanized FRGN19 mice (huFRGN19) and a concomitant reduction in BA production was previously shown, a detailed analysis of the BA pool in these animals has not been elucidated. Furthermore, there are sparse data on the use of this model to assess potential clinical DDI. In the present work, the change in BA composition in huFRGN19 compared with huFRGN control animals was systematically evaluated, and the ability of the model to recapitulate a clinically described CYP3A4-mediated DDI was assessed. In addition to a massive reduction in the total amount of BA, FGF19 expression in huFRGN19 mice resulted in significant changes in the profile of various primary, secondary, and sulfated BAs in serum and feces. Moreover, as observed clinically, administration of the pregnane X receptor agonist rifampicin reduced the oral exposure of the CYP3A4 substrate triazolam. SIGNIFICANCE STATEMENT Transgenic expression of FGF19 normalizes the unphysiologically high level of bile acids in a chimeric liver-humanized mouse model and leads to massive changes in bile acid composition. These adaptations could overcome one of the potential impediments in the use of these mouse models for drug–drug interaction studies.
Broadband ESPAR antenna using sleeve wires

A broadband electrically steerable parasitic array radiator (ESPAR) antenna is presented. The proposed broadband ESPAR antenna consists of an active monopole, 12 parasitic sleeve wires, 6 parasitic elements and a ground structure. By introducing the sleeve wires into the ESPAR antenna, the operation bandwidth of the ESPAR antenna is broadened effectively. Six copper wires placed around the circular ground plane constitute the ground skirt of the ESPAR antenna. The ground skirt, with low wind resistance, reduces the elevation angle of the radiation beam. A broadband ESPAR antenna operating at 2.2 GHz is designed and fabricated. From the results, the impedance bandwidth, with a 2 VSWR, can operate from 1.70 to 2.70 GHz, which is wider than a conventional ESPAR antenna. The working band of the proposed ESPAR antenna covers the GSM1800/1900/UMTS, LTE2300/2500, and 2.4G‐WLAN bands. The electronic beam steering across a range from 0° to 360° with a step size of 60° is realized and the gain from 6.15 to 7.37 dBi is obtained over the operation band.
Corroboration of coupled musculoskeletal model and finite element predictions with in vivo RSA migration of an uncemented acetabular component

While finite element (FE) models have been used extensively in orthopedic studies, validation of their outcome metrics has been limited to comparison against ex vivo testing. The aim of this study was to validate FE model predictions of the initial cup mechanical environment against patient‐matched in vivo measurements of acetabular cup migration using radiostereometric analysis (RSA). Tailored musculoskeletal and FE models were developed using a combination of three‐dimensional (3D) motion capture data and clinical computerized tomography (CT) scans for a cohort of eight individuals who underwent primary total hip replacement and were prospectively enrolled in an RSA study. FE models were developed to calculate the mean modulus of cancellous bone, composite peak micromotion (CPM), composite peak strain (CPS) and percentage area of bone ingrowth. The RSA cup migration at 3 months was used to corroborate the FE output metrics. Qualitatively, all FE‐predicted metrics followed a similar rank order as the in vivo RSA 3D migration data. The two cases with the lowest predicted CPM (<20 µm), lowest CPS (<0.0041), and high bone modulus (>917 MPa) were confirmed to have the lowest in vivo RSA 3D migration (<0.14 mm). The two cases with the largest predicted CPM (>80 µm), larger CPS (>0.0119) and lowest bone modulus (<472 MPa) were confirmed to have the largest in vivo RSA 3D migration (>0.78 mm). This study enabled the first corroboration between tailored musculoskeletal and FE model predictions with in vivo RSA cup migration. Investigation of additional patient‐matched CT, gait, and RSA examinations may allow further development and validation of FE models.
Ionospheric Peak Electron Density and Performance Evaluation of IRI‐CCIR Near Magnetic Equator in Africa During Two Extreme Solar Activities

The F2 layer peak electron density (NmF2) was investigated over Korhogo (Geomagnetic: 1.26°S, 67.38°E), a station near the magnetic equator in the African sector. Data for 1996 and 2000 were, respectively, categorized into low solar quiet and disturbed and high solar quiet and disturbed. NmF2 prenoon peak was higher than the postnoon peak during high solar activity irrespective of magnetic activity condition, while the postnoon peak was higher for low solar activity. Higher NmF2 peak amplitude characterizes disturbed magnetic activity than quiet magnetic condition for any solar activity. The maximum peaks appeared in equinox. June solstice noontime bite out lagged other seasons by 1–2 h. For any condition of solar and magnetic activities, the daytime NmF2 percentage variability (%VR) measured by the relative standard deviation maximizes/minimizes in June solstice/equinox. Daytime variability increases with increasing magnetic activity. The highest peak in the morning time NmF2 variability occurs in equinox, while the highest evening/nighttime variability appeared in June solstice for all solar/magnetic conditions. The nighttime annual variability amplitude is higher during disturbed than quiet condition regardless of solar activity period. At daytime, variability is similar for all conditions of solar activities. NmF2 at Korhogo is well represented on the International Reference Ionosphere‐International Radio Consultative Committee (IRI‐CCIR) option. The model/observation relationship performed best between local midnight and postmidnight period (00–08 LT). The noontime trough characteristics is not prominent in the IRI pattern during high solar activity but evident during low solar conditions when compared with Korhogo observations. The Nash‐Sutcliffe coefficients revealed better model performance during disturbed activities.
Examining Bias in Published Surgical Glaucoma Clinical Trials

Précis: Our results demonstrate that, among randomized clinical trials examining the use of surgical treatments for glaucoma, the majority were not registered. Publication bias (PB) was less likely. More than a third of registered trials presented outcome reporting bias (ORB). Purpose: Despite the optimum of quality evidence provided by randomized controlled trials (RCTs), biases may be introduced and hinder their application. The primary objective of this study was to investigate ORB and PB in RCTs assessing surgical treatments of glaucoma, as well as their registration status. Materials and Methods: A literature review was conducted in MEDLINE, EMBASE, and CENTRAL databases. Inclusion criteria were RCTs published in English between 2007 and 2021 that focused on surgical treatments of patients of all ages with glaucoma or elevated intraocular pressure. Exclusion criteria included cadaveric and animal studies. Registration status was correlated with entries from clinical trial registries. PB was determined by the proportion of trials presenting statistically significant results. ORB was evaluated by comparing the study’s primary outcome with that listed in the trial registry. Trials quality was assessed using the Jadad score. Results: After deleting duplicates, 7561 citations were screened. One hundred sixty-one RCTs were eligible and included between 13 and 556 participants. Of the total, 91% studied an adult population and 71% included patients suffering from primary open angle glaucoma. Among included studies, 63% were not registered and 47% had statistically significant results. An upward trend in registration was observed with time. However, 37% of the studies showed discrepancies between objectives in cited clinical trial registries and the published results. Conclusion: PB in surgical glaucoma trials was not obvious. Among the minority of trials that were registered, more than a third presented ORB. Unregistered trials had lower quality. RCT registration is crucial for the transparent interpretation of studies, improved patient care in surgery, and informed decision-making.
Inclusion dispersion: effects on stress and effective properties

Summary A 3D stress analysis method based on Mura’s eigenstrains and Eshelby’s equivalency principle is proposed. Multiple inclusion interaction is considered, and thus the eigenstrains in each inclusion are no longer uniform. The multiple inclusion problem is solved from the governing elasticity equations to give a set of coupled singular integral equations in the unknown eigenstrains of each inclusion. The set of coupled singular integral equations are rewritten using numerical integration, to give a set of algebraic equations in the unknown eigenstrains. For illustrative purposes the inclusions are dispersed in a cubic arrangement of 3 by 3 by 3 inclusions, thus involving 27 inclusions. 4 different inclusion separation distances are considered and in each of the 4 situations 3 different inclusion stiffnesses are considered. The obtained stresses from the analysis are seen to be highly influenced by inclusion separation. It is found that the "center" inclusion is shielded by the other inclusions and this shielding effect displays a local minimum as the separation distance changes.
Study on a nano-porous gold/polyamidoamine (NPG/PAMAM)-based electrochemical aptamer biosensor for the detection of ochratoxin a in the red wine

Abstract In this study, a novel electrochemical aptamer sensor for detecting ochratoxin A (OTA) was constructed. First, a gold-copper alloy film was prepared via electrochemical deposition, and copper was selectively dissolved in constant potential mode for obtaining the nano-porous gold modified screen-printed carbon electrodes (NPG/SPCE). Then, 2-mercaptoethylamine was dropped on the NPG/SPCE surface and Au-S covalent bonds were formed for immobilizing the metal. Glutaraldehyde as cross-linking agent was added, which resulted in immobilization and attachment of PAMAM to the 2-mercaptoethylamine through the dehydration condensation reaction. During the preparation process, the nano-porous gold and PAMAM-modified layers were characterized by SEM, XRD, and IR spectroscopy, respectively. The characterization results showed that the nano-porous gold and PAMAM composite films were successfully modified. Finally, the OTA aptamer was cross-linked with PAMAM by glutaraldehyde to complete construction of the Apt/PAMAM/NPG/SPCE sensor. The electrochemical performance of this sensor was tested in ochratoxin A solutions with the DPV method. The results showed that the sensor’s reproducibility, stability, and specificity were good. The spiked recoveries in red wine ranged from 99.65%∼101.6%, with a linear range of 0.5 ng/mL∼20 ng/mL and a minimum detection limit of 0.141 ng/mL. Thus, the novel biosensor may provide a promising tool for the trace detection of OTA.
Linkage of whole genome sequencing and administrative health data in autism: A proof of concept study

Whether genetic testing in autism can help understand longitudinal health outcomes and health service needs is unclear. The objective of this study was to determine whether carrying an autism‐associated rare genetic variant is associated with differences in health system utilization by autistic children and youth. This retrospective cohort study examined 415 autistic children/youth who underwent genome sequencing and data collection through a translational neuroscience program (Province of Ontario Neurodevelopmental Disorders Network). Participant data were linked to provincial health administrative databases to identify historical health service utilization, health care costs, and complex chronic medical conditions during a 3‐year period. Health administrative data were compared between participants with and without a rare genetic variant in at least 1 of 74 genes associated with autism. Participants with a rare variant impacting an autism‐associated gene (n = 83, 20%) were less likely to have received psychiatric care (at least one psychiatrist visit: 19.3% vs. 34.3%, p = 0.01; outpatient mental health visit: 66% vs. 77%, p = 0.04). Health care costs were similar between groups (median: $5589 vs. $4938, p = 0.4) and genetic status was not associated with odds of being a high‐cost participant (top 20%) in this cohort. There were no differences in the proportion with complex chronic medical conditions between those with and without an autism‐associated genetic variant. Our study highlights the feasibility and potential value of genomic and health system data linkage to understand health service needs, disparities, and health trajectories in individuals with neurodevelopmental conditions.
Microbial Primer: An introduction to biofilms – what they are, why they form and their impact on built and natural environments

Biofilms are complex communities of microbes that are bound by an extracellular macromolecular matrix produced by the residents. Biofilms are the predominant form of microbial life in the natural environment and although they are the leading cause of chronic infections, they are equally deeply connected to our ability to bioremediate waste and toxic materials. Here we highlight the emergent properties of biofilm communities and explore notable biofilms before concluding by providing examples of their major impact on our health and both natural and built environments.
Acute Cardiorespiratory Coupling Impairment in Worsening Sleep Apnea-Related Intermittent Hypoxemia

Objective: Hypoxic load is one of the main characteristics of obstructive sleep apnea (OSA) contributing to sympathetic overdrive and weakened cardiorespiratory coupling (CRC). Whether this association changes with increasing hypoxic load has remained obscure. Therefore, we aimed to study our hypothesis that increasing hypoxic load acutely decreases the CRC. Methods: We retrospectively analyzed the electrocardiography and nasal pressure signals in 5-min segment pairs (n = 36 926) recorded during clinical polysomnographies of 603 patients with suspected OSA. The segment pairs were pooled into five groups based on the hypoxic load severity described with the the total integrated area under the blood oxygen saturation curve during desaturations. In these severity groups, we determined the frequency-domain heart rate variability (HRV) parameters, the HRV and respiratory high-frequency (HF, 0.15–0.4 Hz) peaks, and the difference between those peaks. We also computed the spectral HF coherence between HRV and respiration in the HF band. Results: The ratio of low-frequency (LF, 0.04–0.15 Hz) to HF power increased from 1.047 to 1.805 (p < 0.001); the difference between the HRV and respiratory HF peaks increased from 0.001 Hz to 0.039 Hz (p < 0.001); and the spectral coherence between HRV and respiration in the HF band decreased from 0.813 to 0.689 (p < 0.001) as the hypoxic load increased. Conclusion and Significance: The vagal modulation decreases and CRC weakens significantly with increasing hypoxic load. Thus, the hypoxic load could be utilized more thoroughly in contemporary OSA diagnostics to better assess the severity of OSA-related cardiac stress.
Design of compact and miniaturize asymmetric SIR-DRA filter-antenna subsystem

Abstract The proposed work presents a compact filter–antenna subsystem design using asymmetric stepped impedance resonator filter and cylindrical dielectric resonator antenna. A cylindrical dielectric resonator antenna is excited from stepped impedance resonator through slot. The DRA is excited for HEM11 mode. Rather than utilizing customary 50 Ω interfaces, some intermediate impedance between filter and antenna is optimized to get the desired results. The assembly of both filter and antenna into one module leads to compactness in the RF front-end. The designed filter antenna subsystem has efficiency of 93%.
Optogenetic spinal stimulation promotes new axonal growth and skilled forelimb recovery in rats with sub-chronic cervical spinal cord injury

Objective. Spinal cord injury (SCI) leads to debilitating sensorimotor deficits that greatly limit quality of life. This work aims to develop a mechanistic understanding of how to best promote functional recovery following SCI. Electrical spinal stimulation is one promising approach that is effective in both animal models and humans with SCI. Optogenetic stimulation is an alternative method of stimulating the spinal cord that allows for cell-type-specific stimulation. The present work investigates the effects of preferentially stimulating neurons within the spinal cord and not glial cells, termed ‘neuron-specific’ optogenetic spinal stimulation. We examined forelimb recovery, axonal growth, and vasculature after optogenetic or sham stimulation in rats with cervical SCI. Approach. Adult female rats received a moderate cervical hemicontusion followed by the injection of a neuron-specific optogenetic viral vector ipsilateral and caudal to the lesion site. Animals then began rehabilitation on the skilled forelimb reaching task. At four weeks post-injury, rats received a micro-light emitting diode (µLED) implant to optogenetically stimulate the caudal spinal cord. Stimulation began at six weeks post-injury and occurred in conjunction with activities to promote use of the forelimbs. Following six weeks of stimulation, rats were perfused, and tissue stained for GAP-43, laminin, Nissl bodies and myelin. Location of viral transduction and transduced cell types were also assessed. Main Results. Our results demonstrate that neuron-specific optogenetic spinal stimulation significantly enhances recovery of skilled forelimb reaching. We also found significantly more GAP-43 and laminin labeling in the optogenetically stimulated groups indicating stimulation promotes axonal growth and angiogenesis. Significance. These findings indicate that optogenetic stimulation is a robust neuromodulator that could enable future therapies and investigations into the role of specific cell types, pathways, and neuronal populations in supporting recovery after SCI.
The effects of intervention with intravenous edaravone in Study 19 on hospitalization, tracheostomy, ventilation, and death in patients with amyotrophic lateral sclerosis

Intravenous (IV) edaravone is a US Food and Drug Administration–approved treatment for amyotrophic lateral sclerosis (ALS), shown in clinical trials to slow physical functional decline. In this study we compared the effect of IV edaravone (edaravone‐first group) versus placebo followed by IV edaravone (placebo‐first group) on survival and additional milestone events.
A thermally tunable THz metamaterial frequency-selective surface based on barium strontium titanate thin film

In this paper we propose a design method for a thermally tunable frequency-selective surface (FSS) in the THz frequency range employing barium strontium titanate (BST) thin film. Due to the excellent thermoelectric properties of BST, different relative permittivities can be obtained at different temperatures. With this ability, the passband frequency of the FSS can be tuned by changing the temperature of the BST thin film. The metallic element array of the FSS is designed using the metamaterial method. A convenient method for thermal control is proposed that uses micro-fabricated electric heating wires; these can provide different temperatures by altering the input electric current. Full wave simulations show good performance of thermally tunable frequency selective transmission at THz frequencies. The proposed FSS is then fabricated and measured. The experimental results agree well with the simulation. By changing the temperature of the BST thin film, the passband can be tuned from 0.826 THz to 0.905 THz. This work proposes a THz tunable FSS based on BST thin film, which promotes connections between ferroelectric films and tunable THz functional devices.
Blinding Models for Scientific Peer-Review of Biomedical Research Proposals: A Systematic Review

Objective: The aim of this systematic review is to estimate: (i) the overall effect of blinding models on bias; (ii) the effect of each blinding model; and (iii) the effect of un-blinding on reviewer's accountability in biomedical research proposals. Methods: Systematic review of prospective or retrospective comparative studies that evaluated two or more peer review blinding models for biomedical research proposals/funding applications and reported outcomes related to peer review efficiency. Results: Three studies that met the inclusion criteria were included in this review and assessed using the QualSyst tool by two authors. Conclusion: Our systematic review is the first to assess peer review blinding models in the context of funding. While only three studies were included, this highlighted the dire need for further RCTs that generate validated evidence. We also discussed multiple aspects of peer review, such as peer review in manuscripts vs proposals and peer review in other fields.