Should one go for individual- or group-level brain parcellations? A deep-phenotyping benchmark.

The analysis and understanding of brain characteristics often require considering region-level information rather than voxel-sampled data. Subject-specific parcellations have been put forward in recent years, as they can adapt to individual brain organization and thus offer more accurate individual summaries than standard atlases. However, the price to pay for adaptability is the lack of group-level consistency of the data representation. Here, we investigate whether the good representations brought by individualized models are merely an effect of circular analysis, in which individual brain features are better represented by subject-specific summaries, or whether this carries over to new individuals, i.e., whether one can actually adapt an existing parcellation to new individuals and still obtain good summaries in these individuals. For this, we adapt a dictionary-learning method to produce brain parcellations. We use it on a deep-phenotyping dataset to assess quantitatively the patterns of activity obtained under naturalistic and controlled-task-based settings. We show that the benefits of individual parcellations are substantial, but that they vary a lot across brain systems.

Open design of a reproducible videogame controller for MRI and MEG.

Videogames are emerging as a promising experimental paradigm in neuroimaging. Acquiring gameplay in a scanner remains challenging due to the lack of a scanner-compatible videogame controller that provides a similar experience to standard, commercial devices. In this paper, we introduce a videogame controller designed for use in the functional magnetic resonance imaging as well as magnetoencephalography. The controller is made exclusively of 3D-printed and commercially available parts. We evaluated the quality of our controller by comparing it to a non-MRI compatible controller that was kept outside the scanner. The comparison of response latencies showed reliable button press accuracies of adequate precision. Comparison of the subjects' motion during fMRI recordings of various tasks showed that the use of our controller did not increase the amount of motion produced compared to a regular MR compatible button press box. Motion levels during an ecological videogame task were of moderate amplitude. In addition, we found that the controller only had marginal effect on temporal SNR in fMRI, as well as on covariance between sensors in MEG, as expected due to the use of non-magnetic building materials. Finally, the reproducibility of the controller was demonstrated by having team members who were not involved in the design build a reproduction using only the documentation. This new videogame controller opens new avenues for ecological tasks in fMRI, including challenging videogames and more generally tasks with complex responses. The detailed controller documentation and build instructions are released under an Open Source Hardware license to increase accessibility, and reproducibility and enable the neuroimaging research community to improve or modify the controller for future experiments.

A cross-sectional study of the impact of the COVID-19 pandemic on an ophthalmology consult service in four Michigan community hospitals.

Purpose: During the coronavirus disease 2019 (COVID-19) pandemic, private practice, inpatient consult services, and academic residency programs in ophthalmology saw a decrease in patient encounters. This study elucidates how community hospital ophthalmology consult (OC) services were affected during the pandemic. We aim to determine whether there was a change in resident OC volume in a community-based ophthalmology program consult service during the COVID-19 pandemic. Secondary objectives included analyzing the change in the types of diagnoses and the number of patients seen for diabetic retinopathy over the same time. Methods: A retrospective cross-sectional study was conducted reviewing the electronic health record (EHR) charts from OCs for the period 2017-2021. Records were categorized by referral source and the nature of OCs (trauma, acute, or chronic); OCs were further grouped by year and weak of referral. An intermonth analysis of weekly OC counts in each category was performed for the average number of consults in February-April 2017-2019 and for February-April 2020. A one-tailed t-test was performed. All t-tests assumed equal variances. Results: Weekly OCs in 2020 revealed no statistically significant differences in overall cases or in acute or chronic cases when the volume before the COVID-19 pandemic was compared to the volume after the onset of the pandemic. However, a statistically significant increase in the average weekly trauma cases was noted when 2020 (an average of 2.7 cases per week) was compared to the weekly average for the same weeks of years 2017- 2019 (0.4; P = 0.016). This statistically significant increase in trauma in 2020 disappeared when comparing weeks 11-17 in 2020 (2.2 cases per week) and the average of 2017-2019 (1.1). Conclusion: This report outlines no significant change in OCs before and after the onset of the pandemic compared to three previous years. There was, however, an increase in trauma consults during the pandemic and an increase in the number (though not the proportion) of diabetic retinopathy (DR+) patients seen by residents. This report uniquely describes no significant changes in the resident volume of patients seen during the COVID-19 global pandemic.

Bioinspired Design of an Uncharged Ambipolar Helical Scaffold To Achieve Efficient Solid-State Proton Conduction.

This work demonstrates highly efficient solid-state proton conduction in helical organic scaffolds inspired by the biomolecule gramicidin A. The scaffold, 1, derived from a pyridine-2,6-dicarboxamide (PDC) residue adopts a helical conformation that is stabilized by a network of strong bifurcated intramolecular H-bonds between the polar residues that align the inner (concave) face of the molecule, while the aromatic units in 1 are oriented outwards. As a result, the helix attains an ambipolar nature just like gramicidin A. Two different solid forms of 1 could be isolated: a yellow solid from high-polarity solvents and an orange solid from low-polarity solvents. Single-crystal X-ray diffraction (SCXRD) studies showed that in the former, molecules of 1 are stacked in a homochiral fashion, while in the latter heterochiral stacks of 1 were present. The yellow form exhibited an almost ∼300-fold higher conductivity (of up to 0.12 mS cm-1 at 95 °C and 95 % relative humidity) than the orange form as a result of closer intermolecular proximity and lower activation energy of 0.098 eV, thus indicating a Grotthus mechanism of proton transport. This study establishes the key role of bioinspired design and controlled stereo-organization of such discrete uncharged organic molecules in achieving efficient solid-state proton conduction.

Design, synthesis and evaluation of novel phenanthridine triazole analogs as potential antileishmanial agents.

Aim: To synthesize and screen phenanthridine and 1,2,3-triazole derivatives for antileishmanial activity. Methodology: Synthesized analogs were tested for antileishmanial activity against transgenic strain of Leishmania infantum promastigotes and ex vivo infections. Results: Compounds T01, T08 and T11 revealed significant activity with EC50 <30 µm and lacked toxicity in mouse spleen and HepG2 cells. T01 with EC50 3.07 µm is fourfold more potent than the drug miltefosine (EC50 12.6 µM) against L. infantum promastigotes. In silico studies indicate that the analogs are nontoxic. A molecular docking analysis was also carried out on the T01 and T08 to investigate the binding pattern at the active site of the chosen target trypanothione reductase. Conclusion: The results of this study reveal that phenanthridine triazoles exhibit antileishmanial activity.

Neurobehavioral and neurobiochemical effect of atomoxetine and N-acetylcysteine in streptozotocin diabetes induced endothelial dysfunction and related dementia.

Metabolic conditions like diabetes, is a major risk factor for the development of dementia of vascular origin. This study investigates the efficacy of atomoxetine (ATX) and N-acetylcysteine (NAC) in streptozotocin (STZ) diabetes induced vascular endothelium dysfunction and related dementia. Single dose STZ (50 mg/kg i.p) was administered to Albino Wistar rats (male, 200-250 g) by dissolving in citrate buffer. Morris water maze (MWM) and attentional set shifting tests (ASST) were used to assess the spatial learning, memory, reversal learning, and executive functioning in animals. Body weight, serum glucose, serum nitrite/nitrate, vascular endothelial function, aortic superoxide anion, brains' oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (IL-6, IL-10, TNF-α, and myeloperoxidase-MPO), acetylcholinesterase activity-AChE and histopathological changes were also assessed. Atomoxetine - ATX (2 mg kg-1/ 4 mg kg-1) and N-acetylcysteine- NAC (250 mg kg-1/ 500 mg kg-1) were used alone as well as in combination, as the treatment drugs. Donepezil (0.5 mg kg-1) was used as a positive control. STZ administered rats showed increase in serum glucose levels and decrease in body weight. Rats administered with STZ also showed reduction in learning, memory, reversal learning, executive functioning, impairment in endothelial function, increase in brains' oxidative stress, inflammation, AChE activity and histopathological changes. Administration of ATX and NAC in two different doses as well as in combination, significantly attenuated the STZ induced diabetes induced impairments in the behavioral, endothelial, biochemical parameters and histopathological changes. Co-treatment of ATX and NAC was better in comparison to the doses when given alone. Hence, STZ administration caused diabetes induced dementia of vascular origin which was attenuated by the administration of ATX and NAC. Therefore, these agents may be studied further for the assessment of their full potential in diabetes induced dementia of vascular origin conditions.

Electrochromic and photochromic behaviour in a single metal-organic framework containing a redox-active linker.

A Zr-based metal organic framework with naphthalene diimide teracarboxylate linkers is reported for its dual electrochromic and photochromic behavior. MOF crystals display reversible yellow to green photochromism upon exposure to visible light and colourless to dark-brown reversible electrochromism on applying a potential of 0 to -2.5 V. The MOF thin film shows good colouration efficiency at 550 nm, which is the highest sensitivity of the human eye.

Novel phenanthridine amide analogs as potential anti-leishmanial agents: In vitro and in silico insights.

In the current work, sixteen novel amide derivatives of phenanthridine were designed and synthesized using 9-fluorenone, 4-Methoxy benzyl amine, and alkyl/aryl acids. The characterization of the title compounds was performed using LCMS, elemental analysis, 1HNMR, 13CNMR and single crystal XRD pattern was also developed for compounds A8. All the final analogs were screened in vitro for anti-leishmanial activity against promastigote form of L. infantum strain. Among the tested analogs, four compounds (A-06, A-11, A-12, and A-15) exhibited significant anti-leishmanial activity with EC50 value ranges from 8.9 to 21.96 µM against amastigote forms of tested L. infantum strain with SI ranges of 1.0 to 4.3. From the activity results it was found that A-11 was the most active compound in both promastigote and amastigotes forms with EC50 values 8.53 and 8.90 µM respectively. In-silico ADME prediction studies depicted that the titled compounds obeyed Lipinski's rule of five as that of the approved marketed drugs. The predicted in-silico toxicity profile also confirmed that the tested compounds were non-toxic. Finally, molecular docking and molecular dynamics study was also performed for significantly active compound (A-11) in order to study it's putative binding pattern at the active site of the selected leishmanial trypanothione reductase target as well as to understand the stability pattern of target-ligand complex for 100 ns. Single crystal XRD of compound A-08 revealed that the compound crystallizes in monoclinic C2/c space group and showed interesting packing arrangements.

High Pressure In Situ Single-Crystal X-Ray Diffraction Reveals Turnstile Linker Rotation Upon Room-Temperature Stepped Uptake of Alkanes.

The rare availability of suitable single-crystal X-ray diffraction (SCXRD) structural data allows for the direct interpretation of the response of a framework to gas sorption and may lead to the development of improved functional porous materials. We report an in situ SCXRD structural investigation of a flexible MOF subjected to methane, ethane, propane, and butane gas pressures. Supporting theoretical investigations indicate weak host-guest interactions for the crystallographically modelled gaseous guests and, in addition, reveal that a turnstile mechanism facilitates the transport of alkanes through the seemingly nonporous system. Inflections present in the adsorption isotherms are furthermore rationalized as due to gate-opening, but without the expected creation of new accessible space.

MOF based flexible, low-cost chemiresistive device as a respiration sensor for sleep apnea diagnosis.

The monitoring of respiratory disorders requires breath sensors that are fast, robust, and convenient to use and can function under real time conditions. A MOF based flexible sensor is reported for the first time for breath sensing applications. The properties of a highly porous HKUST-1 MOF and a conducting MoS2 material have been combined to fabricate an electronic sensor on a flexible paper support for studying sleep apnea problems. Extensive breath sensing experiments have been performed and interestingly the fabricated sensor is efficient in detecting various kinds of breaths such as deep, fast, slow and hydrated breath. The MOF breath sensor shows a fast response time of just ∼0.38 s and excellent stability with no decline in its performance even after a month. A plausible mechanism has been proposed and a smartphone based prototype has been prepared to demonstrate the real time applications of the hybrid device. This work demonstrates great potential for the application of MOFs in healthcare with a special focus on breath sensing and sleep apnea diagnosis.

Quest for an Optimal Methane Hydrate Formation in the Pores of Hydrolytically Stable Metal-Organic Frameworks.

Porous metal-organic frameworks (MOFs) capable of storing a relatively high amount of dry methane (CH4) in the adsorbed phase are largely explored; however, solid CH4 storage in confined pores of MOFs in the form of hydrates is yet to be discovered. Here we report a rational approach to form CH4 hydrates by taking advantage of the optimal pore confinement in relatively narrow cavities of hydrolytically stable MOFs. Unprecedentedly, we were able to isolate methane hydrate (MH) nanocrystals with an sI structure encapsulated inside MOF pores with an optimal cavity dimension. It was found that confined nanocrystals require cavities slightly larger than the unit cell crystal size of MHs (1.2 nm), as exemplified in the experimental case study performed on Cr-soc-MOF-1 vs smaller cavities of Y-shp-MOF-5. Under these conditions, the excess amount of methane stored in the pores of Cr-soc-MOF-1 in the form of MH was found to be ≈50% larger than the corresponding dry adsorbed amount at 10 MPa. More importantly, the pressure gradient driving the CH4 storage/delivery process could be drastically reduced compared to the conventional CH4-adsorbed phase storage on the dry Cr-soc-MOF-1 (≤3 MPa vs 10 MPa).

Discovery of 1,2,3-triazole based quinoxaline-1,4-di-N-oxide derivatives as potential anti-tubercular agents.

A series of thirty one novel 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-3-methylquinoxaline-1,4-dioxide (7a-l), 3-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6-chloro-2-methylquinoxaline-1,4-dioxide (8a-l) and 2-(((1-(substituted phenyl)-1H-1,2,3-triazol-4-yl)methoxy)carbonyl)-6,7-dichloro-3-methylquinoxaline-1,4-dioxide (9a-g) analogues were synthesized, characterized using various analytical techniques and single crystal was developed for the compounds 8 g and 9f. Synthesized compounds were evaluated for in vitro anti-tubercular activity against Mycobacterium tuberculosis H37Rv strain and two clinical isolates Spec. 210 and Spec. 192. The titled compounds exhibited minimum inhibitory concentration (MIC) ranging from 30.35 to 252.00 µM. Among the tested compounds, 8e, 8 l, 9c and 9d exhibited moderate activity (MIC = 47.6 - 52.0 µM) and 8a exhibited significant anti-tubercular activity (MIC = 30.35 µM). Furthermore, 8e, 8 l, and 9d were found to be less toxic against human embryonic kidney, HEK 293 cell lines. Finally, a docking study was also performed using MTB DNA Gyrase (PDB ID: 5BS8) for the significantly active compound 8a to know the exact binding pattern within the active site of the target enzyme.

Of Twists and Curves: Electronics, Photophysics, and Upcoming Applications of Non-Planar Conjugated Organic Molecules.

Non-planar conjugated organic molecules (NPCOMs) contain π-conjugation across their length and also exhibit asymmetry in their conformation. In other words, certain molecular fragments in NPCOMs are either twisted or curved out of planarity. This conformational asymmetry in NPCOMs leads to non-uniform charge-distribution across the molecule, with important photophysical and electronic consequences such as altered thermodynamic stability, chemical reactivity, as well as materials properties. Majorly, NPCOMs can be classified as having either Fused or Rotatable architectures. NPCOMs have been the focus of significant scientific attention in the recent past due to their exciting photophysical behavior that includes intramolecular charge-transfer (ICT), thermally activated delayed fluorescence (TADF) and long-lived charge-separated states. In addition, they also have many useful materials characteristics such as biradical character, semi-conductivity, dynamic conformations, and mechanochromism. As a result, rational design of NPCOMs and mapping their structure-property correlations has become imperative. Researchers have executed conformational changes in NPCOMs through a variety of external stimuli such as pH, temperature, anions-cations, solvent, electric potential, and mechanical force in order to tailor their photophysical, optoelectronic and magnetic properties. Converging to these points, this review highlights the lucrative electronic features, photophysical traits and upcoming applications of NPCOMs by a selective survey of the recent scientific literature.

Seeking potent anti-tubercular agents: design and synthesis of substituted-N-(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents.

Pyrazinamide is an important first-line drug used in shortening TB therapy. In our current work, a series of novel substituted-N-(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives were designed, synthesized, and evaluated for their anti-tubercular activity against Mycobacterium tuberculosis H37Ra. Among the tested compounds, five compounds (6a, 6e, 6h, 6j and 6k) from Series-I and one compound (7e) from Series-II exhibited significant activity against Mycobacterium tuberculosis H37Ra with 50% inhibitory concentrations (IC50) ranging from 1.35 to 2.18 µM. To evaluate the efficacy of these compounds, we examined their IC90 values. Five of the most active compounds were found to be more active with IC90s ranging from 3.73 to 4.00 µM and one compound (6e) showed an IC90 of 40.32 µM. Moreover, single crystals were developed for 6d, 6f and 6n. In addition, most active compounds were evaluated for their cytotoxicity on HEK-293 (human embryonic kidney) cells. Our results indicate that the compounds are nontoxic to human cells. The molecular interactions of the derivatised conjugates in docking studies reveal their suitability for further development.

Synthesis, study of antileishmanial and antitrypanosomal activity of imidazo pyridine fused triazole analogues.

Four groups, thirty-five compounds in total, of novel 1,2,3-triazole analogues of imidazo-[1,2-a]-pyridine-3-carboxamides were designed and synthesized using substituted pyridine, propargyl bromide, 2-azidoethyl 4-methyl benzenesulfonate and substituted acetylenes. These compounds were characterized using 1H NMR, 13C NMR, LCMS and elemental analyses and a crystal structure was obtained for one of the significantly active compounds, 8f. All the synthesized and characterized compounds were screened in vitro for antileishmanial and antitrypanosomal activity against Leishmania major and Trypanosoma brucei parasites, respectively. Among the tested analogues, five compounds (8d, 8f, 8j, 10b and 10d) exhibited significant antileishmanial activity while three compounds (10b, 11a and 11b) showed substantial activity against T. brucei parasite. In silico ADME prediction studies depicted that the essential compounds obeyed Lipinski's rule of five. The predicted in silico toxicity profile suggested that the tested compounds would be non-toxic, which was confirmed experimentally by the lack of cytotoxicity against HeLa cells. Finally, a molecular docking study was also performed, for 10d the most active antileishmanial compound, to study its putative binding pattern at the active site of the selected leishmanial trypanothione reductase target.

Correction: Seeking potent anti-tubercular agents: design and synthesis of substituted-N-(6-(4-(pyrazine-2-carbonyl)piperazine/homopiperazine-1-yl)pyridin-3-yl)benzamide derivatives as anti-tubercular agents.

[This corrects the article DOI: 10.1039/D0RA01348J.].

Revisiting the water sorption isotherm of MOF using electrical measurements.

Water adsorption/desorption isotherms of Cr-soc-MOF-1 were monitored electrically, with the translation of proton conductivity measurements to physisorption isotherms in terms of S-shape and hysteresis features revealed by volumetry. Molecular modelling further established the relationship between the evolutive water-hydrogen bonded network and the "electrical" isotherm for this water-mediated proton conducting MOF.

An Electron-Rich Helical Host for the Exclusive Removal of a Planar Electron-Deficient Organic Compound.

In this study, a series of electron-rich helical hosts, viz. Pyr-HAC, Anth-HAC and Ben-HAC, containing pyrene, anthracene and benzene residues, respectively, at their periphery, were screened for their interaction with different planar electron-deficient organic guests (PEDOGs). A strong and highly selective charge-transfer interactions (CTI) was observed between the host Pyr-HAC and the guest 1,2,4,5-tetracyano-benzene (TCNB), leading to a yellow-to-bright-red color change in both the solubilized and the solid state. The interaction between Pyr-HAC and TCNB also induced profound structural and morphological changes. Pyr-HAC self-assembled into belt-like morphology created by homochiral stacking of the host molecules, but in the Pyr-HAC⊃TCNB complex, square bipyramids containing intertwined heterochiral C2 -double helices of Pyr-HAC were observed. Other PEDOGs did not induce any of the above changes in Pyr-HAC. Detailed UV/Vis absorption and fluorescence spectroscopy, NMR, and X-ray diffraction studies confirmed this selectivity, which arises due to CTI assisted by complementary, directional intermolecular hydrogen bonding (DIHB) between Pyr-HAC and TCNB. This allowed for the exclusive extraction of TCNB from a solution enriched in other PEDOGs. Thus, this study provides a ground work for designing responsive helical hosts towards CTI-driven selective "catch-and-release" of guests.

Unprecedented Ultralow Detection Limit of Amines using a Thiadiazole-Functionalized Zr(IV)-Based Metal-Organic Framework.

A luminescent Zr(IV)-based metal-organic framework (MOF), with the underlying fcu topology, encompassing a π-conjugated organic ligand with a thiadiazole functionality, exhibits an unprecedented low detection limit of 66 nM for amines in aqueous solution. Markedly, this ultralow detection is driven by hydrogen-bonding interactions between the linker and the hosted amines. This observation is supported by density functional theory (DFT) calculations, which clearly corroborate the suppression of the twisting motion of thiadiazole core in the presence of amine, reducing significantly the nonradiative recombination pathways and subsequently enhancing the emission intensity. Credibly, nicotine regarded as a harmful chemical and bearing an amine pending group is also detected with high sensitivity, positioning this MOF as a potential sensor for practical environmental applications. This finding serves also as a benchmark to understand the sensing mechanism in MOFs.

The effect of renal transplantation on left ventricular function, electrocardiography, and mechanical synchrony by gated myocardial perfusion imaging.

BACKGROUND: Depressed left ventricular ejection fraction (LVEF), LV mechanical dyssynchrony (LVMD), and prolonged QTc interval predict poor outcomes in end-stage renal disease (ESRD). Renal transplantation improves mortality in ESRD patients but the effects of transplantation on these indices remain undefined. METHODS: We identified patients with myocardial perfusion imaging (MPI) before and after renal transplantation. A control group consisted of ESRD patients who underwent 2 MPIs but did not receive a transplant. Changes in LVEF, LVMD indices [phase standard deviation (SD) and bandwidth (BW)] by MPI, and electrocardiogram (ECG) indices were determined. RESULTS: The study population consisted of 32 ESRD patients (53% male, 50 ± 11 years, 59% African American, 65% diabetic). The second MPI was performed 31 months (13-59 months) after renal transplantation. LVEF (72 ± 10% vs. 67 ± 10%, P < 0.001) but not SD (22 ± 15° vs. 22 ± 11°, P = 0.9) or BW (58 ± 35° vs. 57 ± 29°, P = 0.9) improved after transplantation. There were no changes in these indices in the control group. QTc (425 ± 30 ms vs. 447 ± 32 ms, P = <0.001) but not QRS (90 ± 21 ms vs. 90 ± 21 ms, P = 0.9) improved significantly after renal transplantation. CONCLUSIONS: LVEF and QTc improved after renal transplantation but LVMD indices and QRS did not change, which suggests that LVMD and electrical dyssynchrony may be irreversible in ESRD.