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Abstract Objective In patients with Dravet syndrome (DS), fenfluramine reduced convulsive seizure frequency and provided clinical benefit in nonseizure endpoints (e.g., executive function, survival). In zebrafish mutant scn1 DS models, chronic fenfluramine treatment preserved neuronal cytoarchitecture prior to seizure onset and prevented gliosis; here, we extend these findings to a mammalian model of DS (Scn1a+/− mice) by evaluating the effects of fenfluramine on neuroinflammation (degenerated myelin, activated microglia) and survival. Methods Scn1a+/− DS mice were treated subcutaneously once daily with fenfluramine (15 mg/kg) or vehicle from postnatal day (PND) 7 until 35‐37. Sagittal brain sections were processed for immunohistochemistry using antibodies to degraded myelin basic protein (D‐MBP) for degenerated myelin, or CD11b for activated (inflammatory) microglia; sections were scored semi‐quantitatively. Apoptotic nuclei were quantified by TUNEL assay. Statistical significance was evaluated by 1‐way ANOVA with post‐hoc Dunnett's test (D‐MBP, CD11b, and TUNEL) or Logrank Mantel‐Cox (survival). Results Quantitation of D‐MBP immunostaining per 0.1 mm2 unit area of the parietal cortex and hippocampus CA3 yielded significantly higher spheroidal and punctate myelin debris counts in vehicle‐treated DS mice than in wild‐type mice. Fenfluramine treatment in DS mice significantly reduced these counts. Activated CD11b + microglia were more abundant in DS mouse corpus callosum and hippocampus than in wild‐type controls. Fenfluramine treatment of DS mice resulted in significantly fewer activated CD11b + microglia than vehicle‐treated DS mice in these brain regions. TUNEL staining in corpus callosum was increased in DS mice relative to wild‐type controls. Fenfluramine treatment in DS mice lowered TUNEL staining relative to vehicle‐treated DS mice. By PND 35‐37, 55% of control DS mice had died, compared with 24% of DS mice receiving fenfluramine treatment (P = 0.0291). Significance This is the first report of anti‐neuroinflammation and pro‐survival after fenfluramine treatment in a mammalian DS model. These results corroborate prior data in humans and animal models and suggest important pharmacological activities for fenfluramine beyond seizure reduction. Plain Language Summary Dravet syndrome is a severe epilepsy disorder that impairs learning and causes premature death. Clinical studies in patients with Dravet syndrome show that fenfluramine reduces convulsive seizures. Additional studies suggest that fenfluramine may have benefits beyond seizures, including promoting survival and improving control over emotions and behavior. Our study is the first to use a Dravet mouse model to investigate nonseizure outcomes of fenfluramine. Results showed that fenfluramine treatment of Dravet mice reduced neuroinflammation significantly more than saline treatment. Fenfluramine‐treated Dravet mice also lived longer than saline‐treated mice. These results support clinical observations that fenfluramine may have benefits beyond seizures.

Scleroglucan (SG) is resistant to harsh reservoir conditions such as high temperature, high shear stresses, and the presence of chemical substances. However, it is susceptible to biological degradation because bacteria use SG as a source of energy and carbon. All degradation effects lead to viscosity loss of the SG solutions, affecting their performance as an enhanced oil recovery (EOR) polymer. Recent studies have shown that nanoparticles (NPs) can mitigate these degradative effects. For this reason, the EOR performance of two new nanohybrids (NH-A and NH-B) based on carboxymethyl-scleroglucan and amino-functionalized silica nanoparticles was studied. The susceptibility of these products to chemical, mechanical, and thermal degradation was evaluated following standard procedures (API RP 63), and the microbial degradation was assessed under reservoir-relevant conditions (1311 ppm and 100 °C) using a bottle test system. The results showed that the chemical reactions for the nanohybrids obtained modified the SG triple helix configuration, impacting its viscosifying power. However, the nanohybrid solutions retained their viscosity during thermal, mechanical, and chemical degradation experiments due to the formation of a tridimensional network between the nanoparticles (NPs) and the SG. Also, NH-A and NH-B solutions exhibited bacterial control because of steric hindrances caused by nanoparticle modifications to SG. This prevents extracellular glucanases from recognizing the site of catalysis, limiting free glucose availability and generating cell death due to substrate depletion. This study provides insights into the performance of these nanohybrids and promotes their application in reservoirs with harsh conditions.

In this study, two new nanohybrids (NH-A and NH-B) were synthesized through carbodiimide-assisted coupling. The reaction was performed between carboxymethyl-scleroglucans (CMS-A and CMS-B) with different degrees of substitution and commercial amino-functionalized silica nanoparticles using 4-(dimethylamino)-pyridine (DMAP) and N,N′-dicyclohexylcarbodiimide (DCC) as catalysts. The morphology and properties of the nanohybrids were investigated by using transmission (TEM) and scanning electron microscopy (SEM), electron-dispersive scanning (EDS), attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (XRD), inductively coupled plasma atomic emission spectroscopy (ICP-OES), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and dynamic light scattering (DLS). The nanohybrids exhibited differences in structure due to the incorporation of polyhedral oligomeric silsesquioxane (POSS) materials. The results reveal that hybrid nanomaterials exhibit similar thermal properties but differ in morphology, chemical structure, and crystallinity properties. Finally, a viscosity study was performed on the newly obtained nanohybrid materials; viscosities of nanohybrids increased significantly in comparison to the carboxymethyl-scleroglucans, with a viscosity difference of 7.2% for NH-A and up to 32.6% for NH-B.

Summary: Chronic neurodegeneration and acute injuries lead to neuron losses via diverse processes. We compared retinal ganglion cell (RGC) responses between chronic glaucomatous conditions and the acute injury model. Among major RGC subclasses, αRGCs and intrinsically photosensitive RGCs (ipRGCs) preferentially survive glaucomatous conditions, similar to findings in the retina subject to axotomy. Focusing on an αRGC intrinsic factor, Osteopontin (secreted phosphoprotein 1 [Spp1]), we found an ectopic neuronal expression of Osteopontin (Spp1) in other RGCs subject to glaucomatous conditions. This contrasted with the Spp1 downregulation subject to axotomy. αRGC-specific Spp1 elimination led to significant αRGC loss, diminishing their resiliency. Spp1 overexpression led to robust neuroprotection of susceptible RGC subclasses under glaucomatous conditions. In contrast, Spp1 overexpression did not significantly protect RGCs subject to axotomy. Additionally, SPP1 marked adult human RGC subsets with large somata and SPP1 expression in the aqueous humor correlated with glaucoma severity. Our study reveals Spp1’s role in mediating neuronal resiliency in glaucoma.

Renal cell carcinoma with level IV tumor thrombus is a condition necessitating aggressive surgical management. Many solid organ malignancies often benefit from neoadjuvant treatments for tumor debulking and improvement of surgical outcomes. However, neoadjuvant treatments for renal cell carcinoma have been limited by its resistance to traditional chemotherapy and radiation. Emerging treatment modalities, such as immunotherapies, are exciting new options that may be therapeutically effective. The combination of nivolumab and ipilimumab has exhibited success in managing metastatic renal cell carcinoma. Limited data exist for its use in nonmetastatic renal cell carcinoma with tumor thrombus. This case illustrates the use of nivolumab and ipilimumab combination therapy in delaying tumor growth, producing observable tumor thrombus histologic and radiologic treatment changes, and, most importantly, facilitating a less invasive surgical approach of a level IV renal cell carcinoma tumor thrombus.

This study focuses on modelling galaxy cluster gas profiles via a semi-parametric nodal approach. While traditional methods like the generalised Navarro–Frenk–White (gNFW) often encounter parameter degeneracy, our flexible node-based method precisely defines a cluster gas pressure profile. Using Planck space telescope data from the Coma region, our model, focused on the pressure-radius relationship, showcases enhanced flexibility over the gNFW. Bayesian analyses indicated an optimal five-node structure for the Coma cluster pressure profile.

Biopolymers emerge as promising candidates for enhanced oil recovery (EOR) applications due to their molecular structures, which exhibit better stability than polyacrylamides under harsh conditions. Nonetheless, biopolymers are susceptible to oxidation and biological degradation. Biopolymers reinforced with nanoparticles could be a potential solution to the issue. The nanofluids’ stability and performance depend on the nanoparticles’ properties and the preparation method. The primary objective of this study was to evaluate the effect of the preparation method and the nanoparticle type (SiO2, Al2O3, and TiO2) on the viscosity and stability of the scleroglucan (SG). The thickening effect of the SG solution was improved by adding all NPs due to the formation of three-dimensional structures between the NPs and the SG chains. The stability test showed that the SG + Al2O3 and SG + TiO2 nanofluids are highly unstable, but the SG + SiO2 nanofluids are highly stable (regardless of the preparation method). According to the ANOVA results, the preparation method and standing time influence the nanofluid viscosity with a statistical significance of 95%. On the contrary, the heating temperature and NP type are insignificant. Finally, the nanofluid with the best performance was 1000 ppm of SG + 100 ppm of SiO2_120 NPs prepared by method II.

This paper presents the methodology for synthesizing and characterizing two carboxymethyl EOR-grade Scleroglucans (CMS-A and CMS-B). An O-Alkylation reaction was used to insert a hydrophilic group (monochloroacetic acid—MCAA) into the biopolymer’s anhydroglucose subunits (AGUs). The effect of the degree of the carboxymethyl substitution on the rheology and thermal stability of the Scleroglucan (SG) was also evaluated. Simultaneous thermal analysis (STA/TGA-DSC), differential scanning calorimetry (DSC), X-ray Diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, Scanning Electron Microscopy, and Energy Dispersive Spectroscopy (SEM/EDS) were employed to characterize both CMS products. FTIR analysis revealed characteristic peaks corresponding to the carboxymethyl functional groups, confirming the modification. Also, SEM analysis provided insights into the structural changes in the polysaccharide after the O-Alkylation reaction. TGA results showed that the carboxymethylation of SG lowered its dehydroxylation temperature but increased its thermal stability above 300 °C. The CMS products and SG exhibited a pseudoplastic behavior; however, lower shear viscosities and relaxation times were observed for the CMS products due to the breakage of the SG triple helix for the chemical modification. Despite the viscosity results, the modified Scleroglucans are promising candidates for developing new engineering materials for EOR processes.

Mutations in the human progranulin (GRN) gene are a leading cause of frontotemporal lobar degeneration (FTLD). While previous studies implicate aberrant microglial activation as a disease-driving factor in neurodegeneration in the thalamocortical circuit in Grn–/– mice, the exact mechanism for neurodegeneration in FTLD-GRN remains unclear. By performing comparative single-cell transcriptomics in the thalamus and frontal cortex of Grn–/– mice and patients with FTLD-GRN, we have uncovered a highly conserved astroglial pathology characterized by upregulation of gap junction protein GJA1, water channel AQP4, and lipid-binding protein APOE, and downregulation of glutamate transporter SLC1A2 that promoted profound synaptic degeneration across the two species. This astroglial toxicity could be recapitulated in mouse astrocyte-neuron cocultures and by transplanting induced pluripotent stem cell–derived astrocytes to cortical organoids, where progranulin-deficient astrocytes promoted synaptic degeneration, neuronal stress, and TDP-43 proteinopathy. Together, these results reveal a previously unappreciated astroglial pathology as a potential key mechanism in neurodegeneration in FTLD-GRN.

Robert Arnold,1 Mario Angi2 1Alaska Blind Child Discovery, Alaska Children’s Eye and Strabismus, Anchorage, Alaska, 99508, USA; 2Senior Scientist, Department of Ophthalmology, University of Padua, Padua, Padua Province, ItalyCorrespondence: Robert Arnold, Alaska Blind Child Discovery, Alaska Children’s Eye and Strabismus, Office 280, 3500 Latouche Street, Anchorage, Alaska 99508, Tel +1-907 561-1917, Fax +1907 563-5373, Email eyedoc@alaska.netBackground: Novel devices target different facets of amblyopia risk factors (ARFs). Through birefringence, the Rebion blinq assesses binocular foveation. The Adaptica 2WIN is a multiradial infrared photorefractor that also estimates ocular alignment. PDI Check is a forced-choice, dynamic near-vision game for the autostereoscopic Nintendo 3DS.Methods: New and returning patients to a pediatric ophthalmology clinic had concomitant confirmatory exams after all three vision screens had been validated with ROC curves, Bland–Altman plots, and Alaska Blind Child Discovery ellipsoid grades. Exam outcomes were classified by ARF visual acuity, strabismus, binocularity, and refractive errors following the 2021 AAPOS guidelines and Bosque–Hunter rubric for the blinq.Results: A total of 202 ethnically diverse students aged 10± 4 (4– 19) years, 33% treatment-naïve, had a high (58%) prevalence of ARFs. Linear logMAR visual acuity, intereye differences, stereo and three-cone color correlated well between PDI Check and exams. Mean score on the 2WIN matched sphero-cylinder exam with ellipsoid scoring was 2.1± 1.5. For AAPOS 2021 refractive plus strabismus, sensitivity/specificity for PDI Check was 68%/59%, 2WIN 72%/95%, and blinq 87%/32%. For the amblyopia or strabismus rubric, PDI Check was 79%/68%, 2WIN 56%/65%, and blinq 94%/37%.Conclusion: Each device had advantages and disadvantages in screening this cohort of older, high-prevalence students, many of whom had already been treated. Validation methods should cover more than just refraction, as the new 2021 AAPOS guidelines do.Keywords: amblyopia, vision screening, strabismus, validation

Robert Arnold,1 David Silbert,2 Heather Modjesky2 1Alaska Blind Child Discovery, Alaska Children’s Eye & Strabismus, Anchorage, Alaska, USA; 2CONESTOGA EYE, Lancaster, PA, USACorrespondence: Robert Arnold, Alaska Blind Child Discovery, Alaska Children’s Eye & Strabismus, 3500 Latouche #280, Anchorage, Alaska, 99508, USA, Tel +1 907 561-1917, Fax +1 907 563-5373, Email eyedoc@Alaska.netBackground: The American Association for Pediatric Ophthalmology and Strabismus (AAPOS) issued a 2021 update of Uniform Validation Guidelines for instrument-based pediatric vision screeners. With each update it is important for each manufacturer to update the Instrument Referral Criteria (IRC) programed into their devices in order to optimize sensitivity and specificity to detect AAPOS criteria.Methods: De-identified data comparing photoscreening with simultaneous confirmatory examinations constituted separate cohorts for the development of IRC via receiver operating characteristic (ROC) curves. The refractions of the devices were also compared.Results: This study defines three sets of refractive IRC (Sensitive, Medium, and Specific) for three leading infrared photoscreening devices, PlusoptiX A12, Welch-Allyn SPOT, and Adaptica 2WIN for children < 4 and ≥ 4 years in order to better target the 2021 AAPOS guidelines. The cohorts were similar but the SPOT group (n=755, mean age 9) was older with more astigmatism and the 2WIN (n=1362, mean age 7) was younger with more hyperopia and anisometropia compared to the cohort for PlusoptiX A12 (n=616, mean age 8). The age-based, medium magnitude IRC for anisometropia, hyperopia, astigmatism and myopia for SPOT were: < 4y: 1.5, 1.75, 3.25, 3.5 and ≥ 4y: 1.5, 1.75, 2.25, 2.0; for PlusoptiX: < 4y: 1.75, 3.0, 3.5, 3.5 and ≥ 4y: 1.75, 3.0, 2.5, 2.5; and for 2WIN: < 4y: 1.75, 2.5, 3.5, 3.5 and ≥ 4y: 1.5, 2.0, 2.5, 2.0. The mean ABCD ellipsoid spectacle matches differed; SPOT: 1.8± 1.3 (better) versus PlusoptiX: 1.9± 1.6 and 2WIN: 2.2± 1.4 (p< 0.001).Conclusion: The 2021 AAPOS exam guidelines foster early specificity before age 4 and sensitivity after age 4. These evidence-based IRC for current SPOT, PlusoptiX, and 2WIN photoscreeners should allow device manufacturers the data necessary to adjust their device IRC to maximize specificity, sensitivity or a medium between the two. This paper provides practical suggestions for better validation. Improved early screening combined with thorough treatment should reduce life-long vision impairment due to amblyopia.Keywords: amblyopia, vision screening, infrared autorefractor, refraction, amblyopia risk factors, visually significant refractive errors

Radial glial cells, the stem cells of the cerebral cortex, extend a long basal fiber that ends in basal endfeet. A new study in PLOS Biology found that non-muscle myosins control basal endfoot integrity to regulate interneuron organization.

Abstract Background English versions of the University of Washington Caregiver Stress (UW-CSS) and Benefit (UW-CBS) Scales were developed in the United States (US) to measure impact on caregivers of caring for a child/children. Caregiving stress and benefit are important constructs to study worldwide. The purpose of this study was to translate and validate the UW-CSS and UW-CBS into French, German, Italian, and Spanish languages. Method UW-CSS and UW-CBS were translated using forward and backward translation with reconciliation. Cognitive interviews (CIs) were completed with caregivers of children

PurposeSarcopenia is associated with decreased survival and increased complications in patients with renal cell carcinoma. Readily identifying patients with low muscle composition that may experience worse outcomes or would benefit from preoperative intervention is of clinical interest. Traditional body composition analysis methods are resource intensive; therefore, linear segmentation with routine imaging has been proposed as a clinically practical alternative. This study assesses linear segmentation’s prognostic utility in nonmetastatic renal cell carcinoma.Materials and MethodsA single institution retrospective analysis of patients that underwent nephrectomy for nonmetastatic renal cell carcinoma from 2005-2021 was conducted. Linear segmentation of the bilateral psoas/paraspinal muscles was completed on preoperative imaging. Total muscle area and total muscle index associations with overall survival were determined by multivariable analysis.Results532 (388 clear cell) patients were analyzed, with median (IQR) total muscle index of 28.6cm2/m2 (25.8-32.5) for women and 33.3cm2/m2 (29.1-36.9) for men. Low total muscle index was associated with decreased survival (HR=1.96, 95% CI 1.32-2.90, p

Robert Arnold Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, 99508, USACorrespondence: Robert Arnold, 3500 Latouche Street &num;280, Anchorage, AK, USA, Tel +19075611917, Fax +19075635373, Email eyedoc@alaska.net

Adult survivors of childhood Wilms tumor are at an increased risk of secondary malignant neoplasms. The presence of a solitary kidney further complicates clinical management in this population. Herein, we present the case of a 37 year old female with a history of childhood Wilms tumor presenting with a secondary renal neoplasm. We highlight important clinical considerations for renal function preservation and present a finding of predisposition to kidney stone formation due to urinary stasis from distorted ureter architecture secondary to tumor mass effect.

Andrew Arnold,1 Kyle Smith,2 Aaron Molina,2 Alex Damarjian,2 Tarah Desatoff,3 Robert Arnold4 1Pacific Northwest University College of Osteopathic Medicine, Yakima, WA, USA; 2PDI CHECK, Anchorage, AK, USA; 3Optometry Department, South Central Foundation, Wasilla, AK, USA; 4Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, USACorrespondence: Robert ArnoldAlaska Children’s EYE & Strabismus, 3500 Latouche #280, Anchorage, AK, 99508, USATel +1 907561-1917Fax +1 907563-5373Email eyedoc@alaska.netIntroduction: Classification of color deficiency has required substantial time and expense with the static Farnsworth-Munsell and Innova Rabin tests. Therefore, dynamic color tests were developed for the Nintendo 3DS.Methods: Fifteen color deficient patients and 17 age-matched normals performed Rabin color test in addition to PDI Check dynamic color games resembling Farnsworth-Munsell presentation (version 0.2.8) and 3-color iso-luminance gray (version 0.2.13).Results: Tests of red, green and blue cone-deficient with the v0.2.8 had sensitivity/specificity/PPV of 92%/86%/92% protanopes, 78%/90%/88% deutanopes and 87%/50%/93% tritanopes. Version 0.2.13 had sens/spec/PPV of 78%/83%/78% red-cone, 100%/85%/80% green cone and 67%/78%/33% blue cone. Corresponding IntraClass Correlation (ICC) utilizing v0.2.8 were red-cone 0.22 (− 0.02– 0.60), green-cone 0.34 (− 0.10– 0.67) and blue-cone 0.38 (0.12– 0.75). ICC for v0.2.13 was higher with protanope 0.62 (− 0.07– 0.87), deuteranope 0.64 (− 0.09– 0.88) and tritanope 0.31 (− 0.07– 0.70). The PDI Check color game took 65 seconds compared to 197 seconds for Innova Rabin.Conclusion: The PDI Check color game quickly identifies patients with inherited color deficiencies.Keywords: color blindness, deuteranomaly, protanomaly, Farnsworth-Munsell, Rabin color cone test, dynamic, vision screening

Sanjhai Ramdeen,1 Brandon Ferrell,1 Christopher Bonk,2 Laura Schubel,2 Robin Littlejohn,2 Muge Capan,3 Ryan Arnold,4 Kristen Miller1,2 1Georgetown University School of Medicine, Washington, DC, USA; 2National Center for Human Factors in Healthcare, MedStar Health Research Institute, Washington, DC, USA; 3Decision Sciences & MIS Department, LeBow College of Business, Drexel University, Philadelphia, PA, USA; 4Department of Emergency Medicine, Drexel University School of Medicine, Philadelphia, PA, USACorrespondence: Kristen MillerNational Center for Human Factors in Healthcare, MedStar Health Research Institute, 3007 Tilden Street NW, Suite 6N, Washington, DC, 20008, USATel +1 2022433873Fax +1 8553449800Email Kristen.E.Miller@medstar.netObjective: The goal of the study was to assess the criteria availability of eight sepsis scoring methods within 6 hours of triage in the emergency department (ED).Design: Retrospective data analysis study.Setting: ED of MedStar Washington Hospital Center (MWHC), a 912-bed urban, tertiary hospital.Patients: Adult (age ≥ 18 years) patients presenting to the MWHC ED between June 1, 2017 and May 31, 2018 and admitted with a diagnosis of severe sepsis with or without shock.Main Outcomes Measured: Availability of sepsis scoring criteria of eight different sepsis scoring methods at three time points— 0 Hours (T0), 3 Hours (T1) and 6 Hours (T2) after arrival to the ED.Results: A total of 50 charts were reviewed, which included 23 (46%) males and 27 (54%) females. Forty-eight patients (96%) were Black or African American. Glasgow Coma Scale was available for all 50 patients at T0. Vital signs, except for temperature, were readily available (> 90%) at T0. The majority of laboratory values relevant for sepsis scoring criteria were available (> 90%) at T1, with exception to bilirubin (66%) and creatinine (80%). NEWS, PRESEP and qSOFA had greater than 90% criteria availability at triage. SOFA and SIRS consistently had the least percent of available criteria at all time points in the ED.Conclusion: The availability of patient data at different time points in a patient’s ED visit suggests that different scoring methods could be utilized to assess for sepsis as more patient information becomes available.Keywords: sepsis, scoring systems, available criteria, emergency department, patient safety, quality improvement

The title heterocyclic compound, C20H27N, has been prepared in good yield (72%) via a BiCl3-catalyzed cationic Povarov reaction between N-propargyl-4-methylaniline and (±)-citronellal. The X-ray single-crystal study indicates that the structure consists of molecules connected by C—H...π contacts to produce chains, which pack in a sandwich–herringbone fashion along the b-axis direction. Hirshfeld surface analysis indicates that H...H interactions dominate by contributing 79.1% to the total surface. Energy frameworks and DFT calculations indicate a major contribution of dispersive forces to the total interaction energy.

Mason Keffalos,1 Samuel Martin,2 Robert Arnold2 1Boise State University, Boise, ID, USA; 2Alaska Blind Child Discovery, Anchorage, AK, USACorrespondence: Robert ArnoldAlaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, 3500 Latouche #280, Anchorage, AK, 99508, USATel +1 907561-1917Fax +1 907563-5373Email eyedoc@alaska.netBackground: Community photoscreening for amblyopia had successfully been adopted by many communities, however many clinics curtailed screening as a result of the COVID-19 pandemic. We modified three conventional devices and tested them for outdoor, drive-by socially distanced photoscreening and refraction.Methods: External frames that provide luminance control and focus distance were fashioned for plusoptiX S12 (Nuremberg, Germany), Adaptica 2WIN in Kaleidos case (Padova, Italy) and the Rebion blinq (Boston, USA). Children were screened by each device and then Retinomax (Righton, Japan) before AAPOS guideline validation.Results: Eighty-eight children average age 8± 7 years had precise refraction and alignment from which 69% AAPOS 2003 risk factors were determined. The sensitivity/specificity/inconclusive rate for plusoptiX was 85%/96%/16%, for 2WIN 79%/89%/5% and for blinq 43%/74%/8%. Blinq improved to 54%/70% when screening for amblyopia ± strabismus. Bland Altman analysis of spherical equivalent showed plusoptiX and 2WIN with less over-minus than Retinomax and J0 and J45 vectors highly reliable for astigmatism determination.Conclusion: The infrared photorefractors in modified cases reliably screened amblyopia risk factors and refraction. The birefringent scanner provided drive-by results but less reliably with wire-frame opaque case than without the case in a dimly lit room. Modified drive-by photoscreeners could help reduce amblyopia and provide socially distanced refraction during an extended pandemic.Keywords: amblyopia, photorefraction, ROC curve, Bland Altman, birefringent screen

Steven Brown,1 Clayton Rue,2 Kyle Smith,3 Robert Arnold4 1Martin Methodist University, Pulaski, TN, USA; 2NSCA Level III Instructor, Anchorage, AK, USA; 3Accurate Vision, Anchorage, AK, USA; 4Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, Anchorage, AK, USACorrespondence: Robert ArnoldThe Alaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, 3500 Latouche #280, Anchorage, AK, 99508, USATel +1 (907)561-1917Fax +1 (907)563-5373Email eyedoc@alaska.netBackground: Conventional near and stereo tests have a “floor effect;” inability to discriminate normal from super-normal. Shotgun champions require unique performance in binocularity and rapid color discrimination.Patients and Methods: Twenty-nine champion clay-target shooters, 14 normal Army and 12 color-normal subjects were tested with conventional near vision tests and on PDI-Check, a series of dynamic, near vision tests on the autostereoscopic Nintendo console.Results: Conventional tested shotgunners had all perfect Ishihara and 75% best 40 sec Stereo fly while Army had 92%perfect Ishihara and 69% best stereo fly. On PDI-Check, experienced shotgunners with median stereo of 17 (IQR 12– 41) arc sec were better than Army volunteers 59 (IQR 30 to 487) arc seconds (Mann–Whitney U=62, p=0.04). Median PDI-Check for shotgun compared to Army was 88% compared to 84% for blue cone, 90% compared to 84% for green and 77% compared to 72% (red, Mann–Whitney p=0.05). Adding dark cherry filter shooting glasses improved the red and green color detection (p< 0.01). This study lacked power to detect eye dominance using PDI Check color or stereo.Conclusion: Many champion shotgun shooters had outstanding dynamic near stereo and better-than-average color vision which could be optimized with dark filter spectacles for red and green hues. PDI Check not only helps identify abnormal binocularity and color vision, but it can clarify supranormal vision as well.Keywords: stereopsis, eye dominance, color vision

Abstract Background Studies of individuals with autism spectrum disorder (ASD) have revealed a strong multigenic basis with the identification of hundreds of ASD susceptibility genes. ASD is characterized by social deficits and a range of other phenotypes, implicating complex genetics and involvement of a variety of brain regions. However, how mutations and mis-expression of select gene sets are associated with the behavioral components of ASD remains unknown. We reasoned that for genes to be associated with ASD core behaviors they must be: (1) expressed in brain regions relevant to ASD social behaviors and (2) expressed during the ASD susceptible window of brain development. Methods Focusing on the amygdala, a brain region whose dysfunction has been highly implicated in the social component of ASD, we mined publicly available gene expression databases to identify ASD-susceptibility genes expressed during human and mouse amygdala development. We found that a large cohort of known ASD susceptibility genes is expressed in the developing human and mouse amygdala. We further performed analysis of single-nucleus RNA-seq (snRNA-seq) data from microdissected amygdala tissue from five ASD and five control human postmortem brains ranging in age from 4 to 20 years to elucidate cell type specificity of amygdala-expressed genes and their dysregulation in ASD. Results Our analyses revealed that of the high-ranking ASD susceptibility genes, 80 are expressed in both human and mouse amygdala during fetal to early postnatal stages of development. Our human snRNA-seq analyses revealed cohorts of genes with altered expression in the ASD amygdala postnatally, especially within excitatory neurons, with dysregulated expression of seven genes predicted from our datamining pipeline. Limitations We were limited by the ages for which we were able to obtain human tissue; therefore, the results from our datamining pipeline approach will require validation, to the extent possible, in human tissue from earlier developmental stages. Conclusions Our pipeline narrows down the number of amygdala-expressed genes possibly involved in the social pathophysiology of ASD. Our human single-nucleus gene expression analyses revealed that ASD is characterized by changes in gene expression in specific cell types in the early postnatal amygdala.

This study assessed the effect of climate on banana yield in the Philippines using provincial level yield data and different climatic variables (i.e. annual rainfall, frequency of wet days, precipitation seasonality, annual mean temperature, temperature seasonality, and annual mean diurnal temperature range) derived from Climate Research Unit – Time Series (CRU-TS) dataset from year 1991–2016. First, trend analysis was applied to the time series of banana yield data for each province to determine presence of linear trend. Then, based on the result of linear trend analysis, multiple regression analysis was used to assess the effect on climate on provincial-level banana yield. Trend analysis showed that 71% of banana producing area in the country experience significant yield trend while multiple regression analysis showed that only 10% of the banana producing areas in the country is significantly affected by climate. Compared to rainfall, temperature variables, specifically temperature seasonality has the greater influence on provincial-level banana yield in the Philippines. Keywords: Banana, Climate, Yield trend, Philippines

Background: Fragile X syndrome (FXS) is a leading genetic cause of autism and intellectual disability with cortical hyperexcitability and sensory hypersensitivity attributed to loss and hypofunction of inhibitory parvalbumin-expressing (PV) cells. Our studies provide novel insights into the role of excitatory neurons in abnormal development of PV cells during a postnatal period of inhibitory circuit refinement. Methods: To achieve Fragile X mental retardation gene (Fmr1) deletion and re-expression in excitatory neurons during the postnatal day (P)14-P21 period, we generated CreCaMKIIa/Fmr1Flox/y (cOFF) and CreCaMKIIa/Fmr1FloxNeo/y (cON) mice, respectively. Cortical phenotypes were evaluated in adult mice using biochemical, cellular, clinically relevant electroencephalogram (EEG) and behavioral tests. Results: We found that similar to global Fmr1 KO mice, the density of PV-expressing cells, their activation, and sound-evoked gamma synchronization were impaired in cOFF mice, but the phenotypes were improved in cON mice. cOFF mice also showed enhanced cortical gelatinase activity and baseline EEG gamma power, which were reduced in cON mice. In addition, TrkB phosphorylation and PV levels were lower in cOFF mice, which also showed increased locomotor activity and anxiety-like behaviors. Remarkably, when FMRP levels were restored in only excitatory neurons during the P14-P21 period, TrkB phosphorylation and mouse behaviors were also improved. Conclusions: These results indicate that postnatal deletion or re-expression of FMRP in excitatory neurons is sufficient to elicit or ameliorate structural and functional cortical deficits, and abnormal behaviors in mice, informing future studies about appropriate treatment windows and providing fundamental insights into the cellular mechanisms of cortical circuit dysfunction in FXS.

Recent research has highlighted wettability alteration as the main consequence of the different mechanisms involved in technologies such as adjusted brine composition water flooding (ABCW) and low-salinity water flooding (LSW). However, studies are still needed to give a phenomenological explanation, and the most influential components of the system (rock–oil–brine) must be clarified. This work focuses on determining the most relevant variables for the smart water effects to occur. Static (contact angles) and dynamic tests (coreflooding) were conducted. For the static tests, aged Berea slices, a specific crude oil (27° API, 10.5 cp at 60 °C), and mono and divalent inorganic salts (Na+, K+, Ca2+, and Mg2+/Cl−) were used in 3 different concentrations of 1000, 3000, and 5000 ppm (ionic strength variation between 0.015 and 0.06) to establish the wettability state by measuring the contact angles of the system. When salts containing chloride were evaluated, a decrease in oil wettability was observed at 5000 ppm. At 3000 and 1000 ppm, tendencies depended on the particular cation. Three brines were selected from the contact angle experiments to be used in coreflooding assays, considering a particular design to identify ion exchange from the rock–oil–brine system. The first assay was carried out in the absence of crude oil as a baseline to determine the ion exchange between the brine and the rock, and a second test considered crude oil to provide insight into ion exchange and its effect on displacement efficiency. Capillary electrophoresis was used in this research as a novel contribution to the systematic study of oil displacement tests, and it has proven to be a powerful tool for understanding the mechanisms involved. The results show that the variations in the concentrations detected in the displacement effluents were the product of the interactions between rock, oil, and brine since the concentrations measured in the absence of oil phase were comparable to those in the injection brine. Significant variations in the effluent ion concentrations were determined for the different brines used, and increases in the pressure differentials were observed for the KCl and CaCl2 brines. These results suggest that the oil–brine ion exchange (salting in/out) represents a relevant mechanism to explain the observed displacement efficiencies and differential pressures. The ionic enrichment of the water phase due to the salting in/out effect needs to be better understood.

Background: Photodynamic therapy activity against different biological systems has been reported for porphyrins. Porphyrin modifications through peripheral groups and/or by metal insertion inside the ring are main alternatives for the improvement of its photo-physical properties. In this study, we synthesized and characterized 5,10,15,20-tetrakis(4-bromophenyl)porphyrin and the dicloro-5,10,15,20-tetrakis(4-bromophenyl)porphyrinato Sn(IV). Methods: Metal-free porphyrin was synthesized using the Alder method, while the Sn(IV)-porphyrin complex was prepared by combining metal-free porphyrin with stannous chloride in DMF; the reaction yields were 47% and 64% respectively. Metal-free porphyrin was characterized by UV-Vis, FT-IR, ESI-mass spectrometry and 13C-NMR. Additionally, the Sn(IV) -porphyrin complex was characterized using UV-Vis and FT-IR. Cyclic voltammetry tests in four different solvents. The fluorescence quantum yield (Φf) was measured using fluorescein as a standard, the singlet oxygen quantum yield (ΦD) was estimated using the standard 5,10,15,20-(tetraphenyl)porphyrin (H2TPP) and the quencher of singlet oxygen 1,3-diphenylisobenzofuran (DPBF). Results: UV-Vis assay showed typical Q and Soret bands for porphyrin and its metallo-porphyrin complex. Compounds showed photoluminescence at the visible range of electromagnetic spectrum. The inclusion of the metal in the porphyrin core changed the Φf from 0.15 to 0.05 and the ΦD increased from 0.55 to 0.59. Finally, the effect of the compounds on the viability of L. panamensis was evaluated by means of the MTT test. The results showed that both compounds decreased the viability of the parasite; this inhibitory activity was greater under light irradiation; the porphyrin compound had IC50 of 16.5 μM and the Sn(IV)-porphyrin complex had IC50 of 19.2 μM. Conclusion: The compounds were synthesized efficiently, their characterization was carried out by different spectroscopy techniques and their own signals were evidenced for both structures, both compounds decreased the cell viability of L. panamensis.

The intense anthropization of the Sanaga basin requires an acceleration of research on biodiversity and the conservation of its aquatic resources. In this framework, the ichthyofauna of the Mpem and Djim National Park (MpDNP) has been inventoried for the first time. The fish were sampled from 2017 to 2021 using diverse experimental fishing gears. A total of 79 species classified into 39 genera, 14 families, and 8 orders have been identified in the MpDNP. This ichthyofauna represents 46.7% of the 169 freshwater fish species known in the Sanaga basin. It contains 15 (62.5%) of the 24 endemic species reported in this basin, among them two Endangered and three Vulnerable species known on the IUCN Red List. Furthermore, two non-indigenous species have been inventoried. Siluriformes (36%) and Characiformes (22%) are the most represented in the MpDNP. It is suggested that the issues for conservation in this park must be focused as a priority on 15 endemic species, which may be ranged into two national protection classes A (5) and B (10), then on those in class C, which will be identified posteriorly as supplementary priorities for the offset of the residual impacts of the Nachtigal upstream hydropower plant development.

Sustainable development goal (SDG) 3 promotes well-being and healthy lives for people of all ages. However, based on the literature, one of the main challenges to achieving SDG 3 is inequality in access to health care. In order to support the efforts of the local government of the province to contribute to the achievement of SDG thru equitable access to health care, this study measured the spatial accessibility of healthcare facilities in Marinduque, Philippines. It used distance-based (i.e., travel-time) and area-based (i.e., enhanced two-step floating catchment analysis or E2SFCA) metrics. The distance from each healthcare facility to different villages in the province was established using QGIS and Google Maps. The distance traveled was measured using three (3) modes of transportation: tricycle, jeepney, and private vehicle. The E2SFCA scores were calculated for different population groups: the general population, women, children, and the elderly. Based on the results, island villages and those areas in the inner portion of the province lack physical access to healthcare facilities. Such a limitation was apparent in the distance- and area-based accessibility metrics. Among the population group considered in this study, the women population showed the lowest accessibility scores.

The fish diversity of the Adamawa lakes is among the most undocumented in Northern Cameroon. Faced with this lack of knowledge, an inventory of ichthyofauna and habitats characterization was conducted in nine lakes. Seven lakes (Assom, Gegouba, Massote, Mbalang, Ngaoundaba, Piou and Tizong) are located in the Sanaga Basin and two (Bini and Dang) are located in the Lake Chad Basin. In order to assess the composition and variation in fish assemblage, eight sampling campaigns were carried out seasonally between 2017 and 2018; they revealed 26 species of fish distributed in 6 orders, 9 families and 16 genera. Communities in Lakes Assom (13 species) and Bini (9 species) were the most diverse. Omnivorous (42.3%) and spawners in open water or on substrates of sand, gravel, rock or plants (69.2%) were the most represented. Nonmetric multidimensional scaling, analysis of similarities (ANOSIM), and similarity percentage analysis (SIMPER) revealed that fish species composition differed significantly among lakes. Canonical correspondence analysis (CCA) identified temperature, pH, TDS, and conductivity as variables explaining the most variation in fish species. The presence of four endemic species in the Sanaga Basin in lakes Assom, Gegouba, Massote and Piou, shows that these lakes stand out as hotspots for conservation due to the uniqueness of their ichthyofauna.

Immature excitatory neurons in the human amygdala persist throughout life and could be a substrate for plasticity. Here the authors find evidence that the maturation of these cells may be accelerated during puberty.

Outer radial glial (oRG) cells are a population of neural stem cells prevalent in the developing human cortex that contribute to its cellular diversity and evolutionary expansion. The mammalian Target of Rapamycin (mTOR) signaling pathway is active in human oRG cells. Mutations in mTOR pathway genes are linked to a variety of neurodevelopmental disorders and malformations of cortical development. We find that dysregulation of mTOR signaling specifically affects oRG cells, but not other progenitor types, by changing the actin cytoskeleton through the activity of the Rho-GTPase, CDC42. These effects change oRG cellular morphology, migration, and mitotic behavior, but do not affect proliferation or cell fate. Thus, mTOR signaling can regulate the architecture of the developing human cortex by maintaining the cytoskeletal organization of oRG cells and the radial glia scaffold. Our study provides insight into how mTOR dysregulation may contribute to neurodevelopmental disease.

Accurate RNA quantification at the single-cell level is critical for understanding the dynamics of gene expression and regulation across space and time. Single molecule FISH (smFISH), such as RNAscope, provides spatial and quantitative measurements of individual transcripts, therefore, can be used to explore differential gene expression among a heterogeneous cell population if combined with cell identify information. However, such analysis is not straightforward, and existing image analysis pipelines cannot integrate both RNA transcripts and cellular staining information to automatically output cell type-specific gene expression. We developed an efficient and customizable analysis method, Single-Molecule Automatic RNA Transcription Quantification (SMART-Q), to enable the analysis of gene transcripts in a cell type-specific manner. SMART-Q efficiently infers cell identity information from multiplexed immuno-staining and quantifies cell type-specific transcripts using a 3D Gaussian fitting algorithm. Furthermore, we have optimized SMART-Q for user experiences, such as flexible parameters specification, batch data outputs, and visualization of analysis results. SMART-Q meets the demands for efficient quantification of single-molecule RNA and can be widely used for cell type-specific RNA transcript analysis.

The pineapple is an essential fruit in Taiwan. Farmers separate pineapples into two types, according to the percentages of water in the pineapples. One is the “drum sound pineapple” and the other is the “meat sound pineapple”. As there is more water in the meat sound pineapple, the meat sound pineapple more easily rots and is more challenging to store than the drum sound pineapple. Thus, farmers need to filter out the meat sound pineapple, so that they can sell pineapples overseas. The classification, based on striking the pineapple fruit with rigid objects (e.g., plastic rulers) is most commonly used by farmers due to the negligibly low costs and availability. However, it is a time-consuming job, so we propose a method to automatically classify pineapples in this work. Using embedded onboard computing processors, servo, and an ultrasonic sensor, we built a hitting machine and combined it with a conveyor to automatically separate pineapples. To classify pineapples, we proposed a method related to acoustic spectrogram spectroscopy, which uses acoustic data to generate spectrograms. In the acoustic data collection step, we used the hitting machine mentioned before and collected many groups of data with different factors; some groups also included the noise in the farm. With these differences, we tested our deep learning-based convolutional neural network (CNN) performances. The best accuracy of the developed CNN model is 0.97 for data Group V. The proposed hitting machine and the CNN model can assist in the classification of pineapple fruits with high accuracy and time efficiency.

Abstract Background High throughput methods for profiling the transcriptomes of single cells have recently emerged as transformative approaches for large-scale population surveys of cellular diversity in heterogeneous primary tissues. However, the efficient generation of such atlases will depend on sufficient sampling of diverse cell types while remaining cost-effective to enable a comprehensive examination of organs, developmental stages, and individuals. Results To examine the relationship between sampled cell numbers and transcriptional heterogeneity in the context of unbiased cell type classification, we explored the population structure of a publicly available 1.3 million cell dataset from E18.5 mouse brain and validated our findings in published data from adult mice. We propose a computational framework for inferring the saturation point of cluster discovery in a single-cell mRNA-seq experiment, centered around cluster preservation in downsampled datasets. In addition, we introduce a “complexity index,” which characterizes the heterogeneity of cells in a given dataset. Using Cajal-Retzius cells as an example of a limited complexity dataset, we explored whether the detected biological distinctions relate to technical clustering. Surprisingly, we found that clustering distinctions carrying biologically interpretable meaning are achieved with far fewer cells than the originally sampled, though technical saturation of rare populations such as Cajal-Retzius cells is not achieved. We additionally validated these findings with a recently published atlas of cell types across mouse organs and again find using subsampling that a much smaller number of cells recapitulates the cluster distinctions of the complete dataset. Conclusions Together, these findings suggest that most of the biologically interpretable cell types from the 1.3 million cell database can be recapitulated by analyzing 50,000 randomly selected cells, indicating that instead of profiling few individuals at high “cellular coverage,” cell atlas studies may instead benefit from profiling more individuals, or many time points at lower cellular coverage and then further enriching for populations of interest. This strategy is ideal for scenarios where cost and time are limited, though extremely rare populations of interest (

Abstract Background Tumor-associated macrophages (TAMs) are abundant in gliomas and immunosuppressive TAMs are a barrier to emerging immunotherapies. It is unknown to what extent macrophages derived from peripheral blood adopt the phenotype of brain-resident microglia in pre-treatment gliomas. The relative proportions of blood-derived macrophages and microglia have been poorly quantified in clinical samples due to a paucity of markers that distinguish these cell types in malignant tissue. Results We perform single-cell RNA-sequencing of human gliomas and identify phenotypic differences in TAMs of distinct lineages. We isolate TAMs from patient biopsies and compare them with macrophages from non-malignant human tissue, glioma atlases, and murine glioma models. We present a novel signature that distinguishes TAMs by ontogeny in human gliomas. Blood-derived TAMs upregulate immunosuppressive cytokines and show an altered metabolism compared to microglial TAMs. They are also enriched in perivascular and necrotic regions. The gene signature of blood-derived TAMs, but not microglial TAMs, correlates with significantly inferior survival in low-grade glioma. Surprisingly, TAMs frequently co-express canonical pro-inflammatory (M1) and alternatively activated (M2) genes in individual cells. Conclusions We conclude that blood-derived TAMs significantly infiltrate pre-treatment gliomas, to a degree that varies by glioma subtype and tumor compartment. Blood-derived TAMs do not universally conform to the phenotype of microglia, but preferentially express immunosuppressive cytokines and show an altered metabolism. Our results argue against status quo therapeutic strategies that target TAMs indiscriminately and in favor of strategies that specifically target immunosuppressive blood-derived TAMs.

Robert Arnold, 1 Mason Keffalos, 2 Samuel Martin 1 1Alaska Blind Child Discovery, Anchorage, AK, USA; 2Boise State University, Boise, ID, USACorrespondence: Robert ArnoldAlaska Blind Child Discovery, Alaska Children’s EYE & Strabismus, 3500, Latouche #280, Anchorage, AK, 99508, USATel +1 907561-1917Fax +1 907563-5373Email eyedoc@alaska.net Thank you for the opportunity to respond to the excellent and informative letter by Dr. David Hunter. For our attempt at Drive by Photoscreening,1 the wire-and-opaque-plastic shielded sufficient ambient light so that blinq could get a reading outdoors, but the performance of blinq suffered compared to conventional indoor use. We surmised this may have been due to the lack of facial view for the aiming beams, but we agree with Dr. Hunter that disruption of infrared light could also have been the culprit. View the original paper by Keffalos and colleagues This is in response to the Letter to the Editor

The accumulation of cyanobacteria produced due to eutrophication processes and the increment of different pollutants in water as a result of industrial processes affects aquatic environments such as the ocean, rivers, and swamps. In this work, cyanobacterial biomass was used as a biosorbent for the removal of a commercial dye, methylene blue (MB). Thus, MB was removed from biomass obtained from cyanobacterial samples collected from the swamp located in the Colombian Caribbean. Spectroscopical techniques such as FTIR, SEM, EDX measurements were used for the physico-chemical characterization of the bio-adsorbent material. Furthermore, we present the effect of various adsorption parameters such as pH, MB dose, time, and adsorbent concentration on the adsorbent equilibrium process. Three different isotherm models were used to model the MB adsorption on biomass. The functional groups identified on biomass suggest that these models are suitable for the characterization of the sorption of cationic dyes on the surfaces of the biomass; in addition, an SEM assay showed the heterogeneous surface of the biomass’ morphology. The equilibrium tests suggested a multilayer type adsorption of MB on the biomass surface. The kinetics results show that a pseudo-second order kinetic model was suitable to describe the MB adsorption on the biomass surface. Finally, the herein obtained results give an alternative to resolve the eutrophication problems generated by cyanobacterial growth in the swamp “Ciénaga de Malambo”.

Developmental and epileptic encephalopathies (DEEs) are complex conditions characterized primarily by seizures associated with neurodevelopmental and motor deficits. Recent evidence supports sigma-1 receptor modulation in both neuroprotection and antiseizure activity, suggesting that sigma-1 receptors may play a role in the pathogenesis of DEEs, and that targeting this receptor has the potential to positively impact both seizures and non-seizure outcomes in these disorders. Recent studies have demonstrated that the antiseizure medication fenfluramine, a serotonin-releasing drug that also acts as a positive modulator of sigma-1 receptors, reduces seizures and improves everyday executive functions (behavior, emotions, cognition) in patients with Dravet syndrome and Lennox-Gastaut syndrome. Here, we review the evidence for sigma-1 activity in reducing seizure frequency and promoting neuroprotection in the context of DEE pathophysiology and clinical presentation, using fenfluramine as a case example. Challenges and opportunities for future research include developing appropriate models for evaluating sigma-1 receptors in these syndromic epileptic conditions with multisystem involvement and complex clinical presentation.

The dynamics of progenitor cells in human neocortex development has not been studied directly. Here, the authors timelapse image human neuroepithelial (NE) and radial glial (RG) cells in embryonic brain slices and find properties of NE cells and RG that are mimicked in cerebral organoids.

It is becoming increasingly popular and straightforward to collect data in cognitive psychology through web-based studies. In this paper, I review issues around web-based data collection for the purpose of numerical cognition research. Provided that the desired type of data can be collected through a web-browser, such online studies offer numerous advantages over traditional forms of physical lab-based data collection, such as gathering data from larger sample sizes in shorter time-windows and easier access to non-local populations. I then present results of two replication studies that employ classical paradigms in numerical cognition research: the number-size congruity paradigm and comparison to a given standard, which also included a masked priming manipulation. In both replications, reaction times and error rates were comparable to original, physical lab-based studies. Consistent with the results of original studies, a distance effect, a congruity effect, and a priming effect were observed. Data collected online thus offers a level of reliability comparable to data collected in a physical lab when it comes to questions in numerical cognition.

New N-propargyl tetrahydroquinolines 6a-g have been synthesized efficiently through the cationic Povarov reaction (a domino Mannich/Friedel-Crafts reaction), catalyzed by Indium (III) chloride (InCl3), from the corresponding N-propargylanilines preformed, formaldehyde and N-vinylformamide, with good to moderate yields. All tetrahydroquinoline derivatives obtained were evaluated in vitro as free radical scavengers. Results showed that compound 6c presents a potent antioxidant effect compared with ascorbic acid, used as a reference compound. ADME predictions also revealed favorable pharmacokinetic parameters for the synthesized compounds, which warrant their suitability as potentials antioxidant. Additionally, a theoretical study using Molecular Quantum Similarity and reactivity indices were developed to discriminate different reactive sites in the new molecules in which the oxidative process occurs.

Germinal matrix hemorrhage (GMH) is a devastating neurodevelopmental condition affecting preterm infants, but why blood vessels in this brain region are vulnerable to rupture remains unknown. Here we show that microglia in prenatal mouse and human brain interact with nascent vasculature in an age-dependent manner and that ablation of these cells in mice reduces angiogenesis in the ganglionic eminences, which correspond to the human germinal matrix. Consistent with these findings, single-cell transcriptomics and flow cytometry show that distinct subsets of CD45+ cells from control preterm infants employ diverse signaling mechanisms to promote vascular network formation. In contrast, CD45+ cells from infants with GMH harbor activated neutrophils and monocytes that produce proinflammatory factors, including azurocidin 1, elastase and CXCL16, to disrupt vascular integrity and cause hemorrhage in ganglionic eminences. These results underscore the brain's innate immune cells in region-specific angiogenesis and how aberrant activation of these immune cells promotes GMH in preterm infants.

Abstract Glioblastoma multiforme (GBM) is the most common and aggressive type of primary brain tumor. Epidermal growth factor (EGF) and platelet‐derived growth factor (PDGF) receptors are frequently amplified and/or possess gain‐of‐function mutations in GBM. However, clinical trials of tyrosine‐kinase inhibitors have shown disappointing efficacy, in part due to intra‐tumor heterogeneity. To assess the effect of clonal heterogeneity on gene expression, we derived an approach to map single‐cell expression profiles to sequentially acquired mutations identified from exome sequencing. Using 288 single cells, we constructed high‐resolution phylogenies of EGF‐driven and PDGF‐driven GBMs, modeling transcriptional kinetics during tumor evolution. Descending the phylogenetic tree of a PDGF‐driven tumor corresponded to a progressive induction of an oligodendrocyte progenitor‐like cell type, expressing pro‐angiogenic factors. In contrast, phylogenetic analysis of an EGFR‐amplified tumor showed an up‐regulation of pro‐invasive genes. An in‐frame deletion in a specific dimerization domain of PDGF receptor correlates with an up‐regulation of growth pathways in a proneural GBM and enhances proliferation when ectopically expressed in glioma cell lines. In‐frame deletions in this domain are frequent in public GBM data.

In industry, silica nanoparticles (NPs) are obtained by the fuming and the precipitation method. Fumed silica NPs are commonly used in the preparation of nanocomposites because they have an extremely low bulk density (160–190 kg/m3), large surface area (50–600 m2/g), and nonporous surface, which promotes strong physical contact between the NPs and the organic phase. Fumed silica has fewer silanol groups (Si–OH) on its surface than the silica prepared by the Stöber method. However, the number of –OH groups on the fumed silica surface can be increased by pretreating them with sodium hydroxide (NaOH) before further surface modification. In this study, the effectiveness of the NaOH pretreatment was evaluated on commercial fumed silica NPs with a surface area of 200 m2/g. The number of surface –OH groups was estimated by potentiometric titration. The pretreated fumed NPs, and the precipitated NPs (prepared by the Stöber method) were modified with 3-aminopropyltriethoxysilane (APTES) to obtain A200S and nSiO2-APTES, respectively. The NPs were characterized using electron dispersive scanning (EDS), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared spectroscopy (FT-IR), thermogravimetric analysis (TGA), X-ray diffraction (XRD), BET (Brunauer–Emmett–Teller) analysis, and ζ-potential. XRD confirmed the presence of the organo-functional group on the surface of both NPs. After the amino-functionalization, the ζ-potential values of the nSiO2 and A200 changed from −35.5 mV and −14.4 mV to +26.2 mV and +11.76 mV, respectively. Consequently, we have successfully synthesized functionalized NPs with interesting, specific surface area and porosity (pore volume and size), which can be attractive materials for chemical and energy industries.

In this study, a set of advanced characterization techniques were used to evaluate the morphological, structural, and thermal properties of a novel molecular hybrid based on silica nanoparticles/hydrolyzed polyacrylamide (CSNH-PC1), which was efficiently obtained using a two-step synthetic pathway. The morphology of the nanohybrid CSNH-PC1 was determined using scanning electron microscopy (SEM), dynamic light scattering (DLS), and nanotracking analysis (NTA) techniques. The presence of C, N, O, and Si atoms in the nanohybrid structure was verified using electron dispersive scanning (EDS). Moreover, the corresponding structural analysis was complemented using powder X-ray diffraction (XRD) and attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FT-IR). The covalent bond between APTES-functionalized SiO2 nanoparticles (nSiO2-APTES), and the hydrolyzed polyacrylamide (HPAM) chain (MW ≈ 20.106 Da) was confirmed with high-resolution X-ray spectroscopy (XPS). Finally, the thermal properties of the nanohybrid were evaluated by using thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC). The results showed that the CSNH-PC1 has a spherical morphology, with sizes between 420–480 nm and higher thermal resistance compared to HPAM polymers without modification, with a glass transition temperature of 360 °C. The integration of these advanced characterization techniques implemented here shows promising results for the study and evaluation of new nanomaterials with multiple applications.

In this study, a family of porphyrins based on 5,10,15,20-Tetrakis(4-ethylphenyl)porphyrin (1, Ph) and six metallo-derivatives (Zn2+(2, Ph-Zn), Sn4+(3, Ph-Sn), Mn2+ (4, Ph-Mn), Ni2+ (5, Ph-Ni), Al3+ (6, Ph-Al), and V3+ (7, Ph-V)) were tested as photosensitizers for photodynamic therapy against Leishmania braziliensis and panamensis. The singlet oxygen quantum yield value (ΦΔ) for (1–7) was measured using 1,3-diphenylisobenzofuran (DPBF) as a singlet oxygen trapping agent and 5,10,15,20-(tetraphenyl)-porphyrin (H2TPP) as a reference standard; besides, parasite viability was estimated by the MTT assay. After metal insertion into the porphyrin core, the ΦΔ increased from 0.76–0.90 and cell viability changed considerably. The ΦΔ and metal type changed the cytotoxic activity. Finally, (2) showed both the highest ΦΔ (0.90) and the best photodynamic activity against the parasites studied (IC50 of 1.2 μM).