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1.
Commun Chem ; 3(1): 10, 2020 Jan 22.
Article in English | MEDLINE | ID: mdl-36703408

ABSTRACT

Computation is playing an increasing role in the discovery of materials, including supramolecular materials such as encapsulants. In this work, a function-led computational discovery using an evolutionary algorithm is used to find potential fullerene (C60) encapsulants within the chemical space of porous organic cages. We find that the promising host cages for C60 evolve over the simulations towards systems that share features such as the correct cavity size to host C60, planar tri-topic aldehyde building blocks with a small number of rotational bonds, di-topic amine linkers with functionality on adjacent carbon atoms, high structural symmetry, and strong complex binding affinity towards C60. The proposed cages are chemically feasible and similar to cages already present in the literature, helping to increase the likelihood of the future synthetic realisation of these predictions. The presented approach is generalisable and can be tailored to target a wide range of properties in molecular material systems.

2.
Clin Cancer Res ; 2023 Jan 24.
Article in English | MEDLINE | ID: mdl-36693186

ABSTRACT

PURPOSE: Clinical genomic sequencing of pediatric tumors is increasingly uncovering pathogenic variants in adult-onset cancer predisposition genes (aoCPGs). Nevertheless, it remains poorly understood how often aoCPG variants are of germline origin and whether they influence tumor molecular profiles and/or clinical care. In this study, we examined the prevalence, spectrum, and impacts of aoCPG variants on tumor genomic features and patient management at our institution. EXPERIMENTAL DESIGN: This is a retrospective study of 1,018 children with cancer who underwent clinical genomic sequencing of their tumors. Tumor genomic data were queried for pathogenic variants affecting 24 pre-selected aoCPGs. Available tumor whole genome sequencing (WGS) data were evaluated for second hit mutations, loss of heterozygosity (LOH), DNA mutational signatures, and homologous recombination deficiency (HRD). Patients whose tumors harbored one or more pathogenic aoCPG variants underwent subsequent germline testing based on hereditary cancer evaluation and family or provider preference. RESULTS: Thirty-three patients (3%) had tumors harboring pathogenic variants affecting one or more aoCPGs. Among 21 tumors with sufficient WGS sequencing data, six (29%) harbored a second hit or LOH affecting the remaining aoCPG allele with four of these six tumors (67%) also exhibited a DNA mutational signature consistent with the altered aoCPG. Two additional tumors demonstrated HRD, of uncertain relation to the identified aoCPG variant. Twenty-one of 26 patients (81%) completing germline testing were positive for the aoCPG variant in the germline. All germline positive patients were counseled regarding future cancer risks, surveillance, and risk reducing measures. No patients had immediate cancer therapy changed due to aoCPG data. CONCLUSIONS: AoCPG variants are rare in pediatric tumors; however, many originate in the germline. Almost one third of aoCPG variants exhibit a second hit and/or confer an abnormal DNA mutational profile suggesting a role in tumor formation. AoCPG information aids in cancer risk prediction but is not commonly used to alter the treatment of pediatric cancers.

3.
BJOG ; 2023 Jan 22.
Article in English | MEDLINE | ID: mdl-36681887

ABSTRACT

BACKGROUND: Several human RCTs are investigating the effects of statins on preeclampsia (PE) and fetal growth restriction (FGR). This cross-species meta-analysis summarizes the preclinical evidence of statin use for PE and FGR. OBJECTIVES: Evaluate the effects of statins on maternal blood pressure (MBP) and birth weight (BW) in pregnancies complicated by PE or FGR. SEARCH STRATEGY: PubMed and Embase.com were searched on May 10th , 2022 using "statins" and "pregnancy". SELECTION CRITERIA: We included randomized controlled trials (RCTs) and cohorts with matched control groups as well as animal studies. DATA ANALYSIS: The main outcomes were MBP in mmHg and BW in grams. The standardized mean difference (SMD) with a 95% confidence interval was calculated. Subgroup analyses on species, statin, dose, timing and route of administration were performed if subgroups included at least 3 studies. RESULTS: Our data included 1 human and 12 animal studies. Prenatal administration of statins significantly reduced MBP during pregnancy (SMD = -2.28 mmHg [-4.43, -0.13] p=0.04). There was no significant effect of statins on BW (SMD 0.69, [-0.65, 2.03], p=0.28). Our subgroup analyses showed no effect for different doses, species and route of administration on MBP. CONCLUSIONS: Our cross-species meta-analyses demonstrate that statins only reduce maternal blood pressure in rodent pregnancies complicated by preeclampsia or fetal growth restriction and have no effect on birthweight across species. The broad confidence intervals, inconsistent direction of the observed effects across the studies and large risk of bias lead us to conclude that a solid base for further human RCTs is lacking.

4.
Angew Chem Int Ed Engl ; : e202217987, 2023 Jan 13.
Article in English | MEDLINE | ID: mdl-36637345

ABSTRACT

We derive design principles for the assembly of rectangular tetramines into Zn8 L6 pseudo-cubic coordination cages. Because of the rectangular, as opposed to square, geometry of the ligand panels, and the possibility of either Δ or Λ handedness of each metal center at the eight corners of the pseudo-cube, many different cage diastereomers are possible. Each of the six tetra-aniline subcomponents investigated in this work assembled with zinc(II) and 2-formylpyridine in acetonitrile into a single Zn8 L6 pseudo-cube diastereomer, however. Each product corresponded to one of four diastereomeric configurations, with T, Th , S6 or D3 symmetry. The preferred diastereomer for a given tetra-aniline subcomponent was shown to be dependent on its aspect ratio and conformational flexibility. Analysis of computationally modeled individual faces or whole pseudo-cubes provided insight as to why the observed diastereomers were favored.

5.
Adv Mater ; : e2210098, 2023 Jan 12.
Article in English | MEDLINE | ID: mdl-36634684

ABSTRACT

Redox flow batteries (RFBs) have great potential for long-duration grid-scale energy storage. Ion conducting membranes are a crucial component in RFBs, allowing charge-carrying ions to transport while preventing the cross-mixing of redox couples. Commercial Nafion membranes are widely used in RFBs, but their unsatisfactory ionic and molecular selectivity as well as high costs limit the performance and the widespread deployment of this technology. To extend the longevity and reduce the cost of RFB systems, inexpensive ion-selective membranes are highly desired that concurrently deliver low ionic resistance and high selectivity towards redox-active species. In this work, high-performance RFB membranes are fabricated from blends of carboxylate- and amidoxime-functionalized polymers of intrinsic microporosity (PIMs) that exploit the beneficial properties of both polymers. The enthalpy-driven formation of cohesive interchain interactions, including hydrogen bonds and salt bridges, facilitates the microscopic miscibility of the blends, while ionizable functional groups within the sub-nanometer pores allow optimization of membrane ion transport functions. The resulting microporous membranes demonstrate fast cation conduction with low crossover of redox-active molecular species, enabling improved power ratings and reduced capacity fade in aqueous RFBs using anthraquinone and ferrocyanide as redox couples. This article is protected by copyright. All rights reserved.

6.
Cryo Letters ; 44(1): 37-46, 2023.
Article in English | MEDLINE | ID: mdl-36629840

ABSTRACT

BACKGROUND: Successful cryopreservation of bovine oocytes is very important for research and commercial applications. However, the survival and development rate of vitrified-thawed (VT) oocytes are lower than those of non-vitrified-thawed (non-VT) oocytes. OBJECTIVE: To investigate the effect of adding hydroxypropyl cellulose (HPC) to the vitrification solution for bovine oocytes. MATERIALS AND METHODS: For vitrification, bovine metaphase II oocytes were pretreated with a solution containing 10% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 5 min, exposed to a solution containing 30% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 30 s, and then directly plunged into liquid nitrogen. RESULTS: The survival rate of oocytes was significantly higher in the 50 HPC group than in the 0, 10, and 100 HPC groups. The reactive oxygen species level was lower in the non-VT and 50 HPC groups than in the other groups. The mRNA levels of proapoptotic genes (Bax) were lower in the non-VT, 0, and 50 HPC groups than in the other groups. The mRNA levels of antiapoptotic genes (BCl2) were higher in the non-VT than in the other groups. The development rates of embryos (day 8) obtained via parthenogenetic activation (PA) were determined in the non-VT, 0 HPC, and 50 HPC groups. The cleavage rate was significantly higher in the non-VT group. CONCLUSION: Supplementation of vitrification solution with HPC improves the survival of VT bovine oocytes and the development capacity of embryos derived from these oocytes via PA. doi.org/10.54680/fr23110110212.


Subject(s)
Cryopreservation , Vitrification , Animals , Cattle , Cryopreservation/veterinary , Oocytes/physiology , Cryoprotective Agents/pharmacology , Dietary Supplements , Ethylene Glycols/pharmacology
7.
Cryo Letters ; 44(1): 37-46, 2022.
Article in English | MEDLINE | ID: mdl-36625874

ABSTRACT

BACKGROUND: Successful cryopreservation of bovine oocytes is very important for research and commercial applications. However, the survival and development rate of vitrified-thawed (VT) oocytes are lower than those of non-vitrified-thawed (non-VT) oocytes. OBJECTIVE: To investigate the effect of adding hydroxypropyl cellulose (HPC) to the vitrification solution for bovine oocytes. MATERIALS AND METHODS: For vitrification, bovine metaphase II oocytes were pretreated with a solution containing 10% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 5 min, exposed to a solution containing 30% ethylene glycol supplemented with 0, 10, 50, or 100 ug/mL HPC for 30 s, and then directly plunged into liquid nitrogen. RESULTS: The survival rate of oocytes was significantly higher in the 50 HPC group than in the 0, 10, and 100 HPC groups. The reactive oxygen species level was lower in the non-VT and 50 HPC groups than in the other groups. The mRNA levels of proapoptotic genes (Bax) were lower in the non-VT, 0, and 50 HPC groups than in the other groups. The mRNA levels of antiapoptotic genes (BCl2) were higher in the non-VT than in the other groups. The development rates of embryos (day 8) obtained via parthenogenetic activation (PA) were determined in the non-VT, 0 HPC, and 50 HPC groups. The cleavage rate was significantly higher in the non-VT group. CONCLUSION: Supplementation of vitrification solution with HPC improves the survival of VT bovine oocytes and the development capacity of embryos derived from these oocytes via PA. doi.org/10.54680/fr23110110212.


Subject(s)
Cryopreservation , Vitrification , Animals , Cattle , Cryopreservation/veterinary , Oocytes/physiology , Cryoprotective Agents/pharmacology , Dietary Supplements , Ethylene Glycols/pharmacology
8.
Psychiatry Res ; 320: 115032, 2022 Dec 25.
Article in English | MEDLINE | ID: mdl-36610318

ABSTRACT

Suicide research/clinical work remain in dire need of effective tools that can better predict suicidal behavior. A growing body of literature has started to focus on the role that neuroimaging may play in helping explain the path towards suicide. Specifically, structural alterations of rostral anterior cingulate cortex (rost-ACC) may represent a biological marker and/or indicator of suicide risk in Major Depressive Disorder (MDD). Furthermore, the construct of "grit," defined as perseverance for goal-attainment and shown to be associated with suicidality, is modulated by rost-ACC. The aim was to examine relationships among rost-ACC gray matter volume, grit, and suicidality in U.S. Military Veterans. Participants were age-and-sex-matched Veterans with MDD: with suicide attempt (MDD+SA:n = 23) and without (MDD-SA:n = 37). Groups did not differ in depression symptomatology. Participants underwent diagnostic interview, clinical symptom assessment, and 3T-MRI-scan. A Group (SA-vs.-No-SA) x Cingulate-region (rostral-caudal-posterior) x Hemisphere (left-right) mixed-model-multivariate-ANOVA was conducted. Left-rost-ACC was significantly smaller in MDD+SA, Group x Cingulate-region x Hemisphere-interaction. Lower grit and less left-rost-ACC gray matter each predicted suicide attempt history, but grit level was a more robust predictor of SA. Both structural alterations of rost-ACC and grit level represent potentially valuable tools for suicide risk assessment.

9.
Phys Eng Sci Med ; 2023 Jan 02.
Article in English | MEDLINE | ID: mdl-36592283

ABSTRACT

Cadmium zinc telluride (CZT) has been actively researched and developed by researchers in various fields. In medical applications, especially photon-counting, CZT enables improved image quality, multi-material decomposition, and improved dose efficiency. Moreover, band gap engineering and selenium addition on CZT improved electrical, spectroscopic and structural properties, thereby supporting performance of CZT as a photon-counting detector. In this study, it is shown that Cd0.875Zn0.125Te0.98Se0.02 (CZTS) shows sufficient performance without loss of detection efficiency. We carried out a study involving the application of this CZTS on calculating bone mineral density (BMD) values, because this application has a novelty of new material for BMD sensor which follows the CdTe- or CdZnTe- based BMD detector. Anatomical images from different energy bins contained different information of attenuation although the images were taken in the same region at the same time. Moreover, calculated BMD values had a proper tendency depending on the amount of bone in that region. The final BMD value was 1.1972 g/cm2, which is close to the real value of 1.2 g/cm2. The introduction with a bone filter and a smaller pixel size will improve the accuracy and precision of photon-counting CZTS detectors for measuring BMD values. However, in this study the CZTS showed the feasibility that a photon-counting CZTS detector can help the measurement of BMD values and the diagnosis of osteoporosis.

10.
Ann Neurol ; 2022 Dec 24.
Article in English | MEDLINE | ID: mdl-36565297

ABSTRACT

The occurrence of motor/vocal tics, that is, "extra movements" and/or "extra vocalizations," is the leading diagnostic criterion for tic disorders. We show that extra movements are common also in healthy controls, so that a surplus of movements per se is not indicative of the presence of a tic disorder. This questions the usefulness of Diagnostic and Statistical Manual of Mental Disorders, 5th edition criteria for tic disorders in clinical practice. Apparently, it is not solely a surplus of movements that defines tic disorders. Instead, movement characteristics and patterns seem to play a crucial role. ANN NEUROL 2023.

11.
J Pediatr Health Care ; 2022 Dec 15.
Article in English | MEDLINE | ID: mdl-36528486

ABSTRACT

INTRODUCTION: Families of children with special health care needs (CSHCN) routinely struggle to find suitable childcare. These families value childcare capable of supporting their child's needs, known as inclusive care, that requires trustworthy staff trained to safely care for CSHCN. METHOD: This study aimed to understand the training, experience, confidence, and perceived barriers to providing inclusive care for CSHCN from the perspective of childcare providers and directors. Childcare providers (n = 263) and directors (n = 418) responded to a statewide survey in Wisconsin in 2019. RESULTS: Results show that both childcare providers and directors perceive that the providers lack confidence in providing inclusive care. Lack of staffing, training, and expertise of childcare providers were the most frequently reported barriers to provide inclusive care. DISCUSSION: These findings confirm the need for additional education, training, resources, and research to create and maintain more inclusive childcare settings for CSHCN.

12.
Chem Sci ; 13(45): 13588-13599, 2022 Nov 23.
Article in English | MEDLINE | ID: mdl-36507173

ABSTRACT

How molecules pack has vital ramifications for their applications as functional molecular materials. Small changes in a molecule's functionality can lead to large, non-intuitive, changes in their global solid-state packing, resulting in difficulty in targeted design. Predicting the crystal structure of organic molecules from only their molecular structure is a well-known problem plaguing crystal engineering. Although relevant to the properties of many organic molecules, the packing behaviour of modular porous materials, such as porous organic cages (POCs), greatly impacts the properties of the material. We present a novel way of predicting the solid-state phase behaviour of POCs by using a simplistic model containing the dominant degrees of freedom driving crystalline phase formation. We employ coarse-grained simulations to systematically study how chemical functionality of pseudo-octahedral cages can be used to manipulate the solid-state phase formation of POCs. Our results support those of experimentally reported structures, showing that for cages which pack via their windows forming a porous network, only one phase is formed, whereas when cages pack via their windows and arenes, the phase behaviour is more complex. While presenting a lower computational cost route for predicting molecular crystal packing, coarse-grained models also allow for the development of design rules which we start to formulate through our results.

14.
Oper Dent ; 47(6): 597b-599, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36442230
15.
Chem Sci ; 13(38): 11368-11375, 2022 Oct 05.
Article in English | MEDLINE | ID: mdl-36320581

ABSTRACT

Maintaining close spatial proximity of functional moieties within molecular systems can result in fascinating emergent properties. Whilst much work has been done on covalent tethering of functional units for myriad applications, investigations into mechanically linked systems are relatively rare. Formation of the mechanical bond is usually the final step in the synthesis of interlocked molecules, placing limits on the throughput of functionalised architectures. Herein we present the synthesis of a bis-azide [2]catenane scaffold that can be post-synthetically modified using CuAAC 'click' chemistry. In this manner we have been able to access functionalised catenanes from a common precursor and study the properties of electrochemically active, emissive and photodimerisable units within the mechanically interlocked system in comparison to non-interlocked analogues. Our data demonstrates that the greater (co-)conformational flexibility that can be obtained with mechanically interlocked systems compared to traditional covalent tethers paves the way for developing new functional molecules with exciting properties.

16.
Chem Sci ; 13(40): 11912-11917, 2022 Oct 19.
Article in English | MEDLINE | ID: mdl-36320919

ABSTRACT

Cuboctahedral coordination cages of the general formula [Pd12L24]24+ (L = low-symmetry ligand) were analyzed theoretically and experimentally. With 350 696 potential isomers, the structural space of these assemblies is vast. Orientational self-sorting refers to the preferential formation of particular isomers within the pool of potential structures. Geometric and computational analyses predict the preferred formation of cages with a cis arrangement at the metal centers. This prediction was corroborated experimentally by synthesizing a [Pd12L24]24+ cage with a bridging 3-(4-(pyridin-4-yl)phenyl)pyridine ligand. A crystallographic analysis of this assembly showed exclusive cis coordination of the 3- and the 4-pyridyl donor groups at the Pd2+ ions.

17.
Chem Mater ; 34(20): 9042-9054, 2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36313398

ABSTRACT

Amorphous metal-organic frameworks (aMOFs) are a class of disordered framework materials with a defined local order given by the connectivity between inorganic nodes and organic linkers, but absent long-range order. The rational development of function for aMOFs is hindered by our limited understanding of the underlying structure-property relationships in these systems, a consequence of the absence of long-range order, which makes experimental characterization particularly challenging. Here, we use a versatile modeling approach to generate in silico structural models for an aMOF based on Fe trimers and 1,3,5-benzenetricarboxylate (BTC) linkers, Fe-BTC. We build a phase space for this material that includes nine amorphous phases with different degrees of defects and local order. These models are analyzed through a combination of structural analysis, pore analysis, and pair distribution functions. Therefore, we are able to systematically explore the effects of the variation of each of these features, both in isolation and combined, for a disordered MOF system, something that would not be possible through experiment alone. We find that the degree of local order has a greater impact on structure and properties than the degree of defects. The approach presented here is versatile and allows for the study of different structural features and MOF chemistries, enabling the derivation of design rules for the rational development of aMOFs.

18.
Nat Chem ; 2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36302869

ABSTRACT

Chiral π-conjugated molecules bring new functionality to technological applications and represent an exciting, rapidly expanding area of research. Their functional properties, such as the absorption and emission of circularly polarized light or the transport of spin-polarized electrons, are highly anisotropic. As a result, the orientation of chiral molecules critically determines the functionality and efficiency of chiral devices. Here we present a strategy to control the orientation of a small chiral molecule (2,2'-dicyano[6]helicene) by the use of organic and inorganic templating layers. Such templating layers can either force 2,2'-dicyano[6]helicene to adopt a face-on orientation and self-assemble into upright supramolecular columns oriented with their helical axis perpendicular to the substrate, or an edge-on orientation with parallel-lying supramolecular columns. Through such control, we show that low- and high-energy chiroptical responses can be independently 'turned on' or 'turned off'. The templating methodologies described here provide a simple way to engineer orientational control and, by association, anisotropic functional properties of chiral molecular systems for a range of emerging technologies.

19.
Occup Med (Lond) ; 2022 Oct 25.
Article in English | MEDLINE | ID: mdl-36282619

ABSTRACT

We describe the case of a 52-year-old male who presented with two episodes of acute exacerbations (AE) of chronic obstructive pulmonary disease (COPD) during work, while suspending live chickens for slaughter. The patient was exposed to high levels of bioaerosols, including endotoxins and microorganisms. Endotoxins can induce bronchoconstriction and airway inflammation, and COPD patients are more vulnerable to airway infections caused by microorganisms inhaled with bioaerosols. This study suggests that a high level of bioaerosols may induce airway infections, resulting in acute exacerbations of COPD.

20.
JCO Precis Oncol ; 6: e2200323, 2022 10.
Article in English | MEDLINE | ID: mdl-36265116

ABSTRACT

PURPOSE: Clinical genomic testing is increasingly being used to direct pediatric cancer care. Many centers are interested in offering testing of tumors and paired germline tissues at or near the time of cancer diagnosis. We conducted this study to better understand parent preferences surrounding timing and content of consent conversations for clinical germline genetic testing of their children with cancer as a part of real-time cancer care. PATIENTS AND METHODS: A seven-question survey developed by the Division of Cancer Predisposition and collaborators at St Jude Children's Research Hospital (St Jude) was distributed to members of the St Jude Patient Family Advisory Council, which included parents of childhood cancer survivors and bereaved parents whose children with cancer had died. Parents were asked to provide free text comments after each question. Qualitative methods were used to derive codes from parent comments, and survey results were depicted using descriptive statistics. RESULTS: The survey was completed by 172 parents. Ninety-three (54%) endorsed an approach for consent conversations ≥ 1 month after cancer diagnosis, whereas 58 (34%) endorsed an approach at 1-2 weeks and 21 (12%) at 1-2 days. Needing time to adjust to a new or relapsed cancer diagnosis and feeling overwhelmed were frequent themes; however, parents acknowledged the urgency and importance of testing. Parents desired testing of as many cancer-related genes as possible, with clinical utility the most important factor for proceeding with testing. Most parents (75%) desired germline results to be disclosed in person, preferably by a genetic counselor. CONCLUSION: Parents described urgency and benefits associated with germline testing, but desired flexibility in timing to allow for initial adjustment after their child's cancer diagnosis.


Subject(s)
Neoplasms , Parents , Humans , Child , Genetic Testing/methods , Neoplasms/diagnosis , Germ Cells , Informed Consent
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