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One strategy to improve the photovoltaic properties of nonfullerene acceptors (NFAs), employed in state-of-art organic solar cells, is the rational fluorination or chlorination of these molecules. Although this modification improves important acceptor properties, little is known about the effects on the triplet states. Here, we combine the polarizable continuum model with an optimally tuned range-separated hybrid functional to investigate this issue. We find that fluorination or chlorination of NFAs decreases the degree of the highest occupied molecular orbital-lowest unoccupied molecular orbital (HOMO-LUMO) overlap along these molecules. Consequently, the energy gap between T

To better understand the impact of prenatal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection on infants, this study sought to compare the risk of hospital visits and of postnatal SARS-CoV-2 infection between infants born to mothers with and without prenatal SARS-CoV-2 infection. In this retrospective observational cohort study of 6871 mothers and their infants, overall rates of emergency department (ED) visits and hospital admissions in the first 90 days of life were similar for infants born to mothers with and without prenatal SARS-CoV-2 infection. Infants born to negative mothers were more likely than infants of positive mothers to be hospitalized after ED visit (relative risk: 3.76; 95% confidence interval: 1.27-11.13, P = .003). Five infants tested positive; all were born to negative mothers, suggesting that maternal prenatal SARS-CoV-2 infection may protect infants from postnatal infection. The lower acuity ED visits for infants born to mothers with prenatal SARS-CoV-2 infection may reflect a heightened level of concern among these mothers.

Background Cognitive dysfunction after surgery is a major issue in older adults. Here, we determined the effect of APOE4 on perioperative neurocognitive function in older patients. Methods We enrolled 140 English-speaking patients ≥60 yr old scheduled for noncardiac surgery under general anaesthesia in an observational cohort study, of whom 52 underwent neuroimaging. We measured cognition; Aβ, tau, p-tau levels in CSF; and resting-state intrinsic functional connectivity in six Alzheimer's disease-risk regions before and 6 weeks after surgery. Results There were no significant APOE4-related differences in cognition or CSF biomarkers, except APOE4 carriers had lower CSF Aβ levels than non-carriers (preoperative median CSF Aβ [median absolute deviation], APOE4 305 pg ml−1 [65] vs 378 pg ml−1 [38], respectively; P=0.001). Controlling for age, APOE4 carriers had significantly greater preoperative functional connectivity than non-carriers between several brain regions implicated in Alzheimer's disease, including between the left posterior cingulate cortex and left angular gyrus (β [95% confidence interval, CI], 0.218 [0.137–0.230]; PFWE=0.016). APOE4 carriers, but not non-carriers, experienced significant connectivity decreases from before to 6 weeks after surgery between several brain regions including between the left posterior cingulate cortex and left angular gyrus (β [95% CI], –0.196 [–0.256 to –0.136]; PFWE=0.001). Most preoperative and postoperative functional connectivity differences did not change after controlling for preoperative CSF Aβ levels. Conclusions Postoperative change trajectories for cognition and CSF Aβ, tau or p-tau levels did not differ between community dwelling older APOE4 carriers and non-carriers. APOE4 carriers showed greater preoperative functional connectivity and greater postoperative decreases in functional connectivity in key Alzheimer's disease-risk regions, which occur via Aβ-independent mechanisms.

Background/Objective SARS-CoV-2 continues to spread widely in the US and worldwide. Pregnant women are more likely to develop severe or critical illness than their non-pregnant counterparts. Known risk factors for severe and critical disease outside of pregnancy, such as asthma, diabetes, and obesity have not been well-studied in pregnancy. We aimed to determine which clinical and pregnancy-related factors were associated with severe and critical COVID illness in pregnancy. Study design This was a retrospective cohort study of women with confirmed intrauterine pregnancy and positive nasopharyngeal swab for SARS-CoV-2 who presented to an academic medical center in New York City from 1 March 2020 to 1 July 2020. Severe and critical COVID-19 disease was defined by World Health Organization criteria. Women with severe/critical disease were compared to women with asymptomatic/mild disease. Continuous variables were compared with Mann–Whitney or t-test and categorical variables were compared using chi-square and Fisher’s exact. Statistical significance was set at p

International audience; Background: The 5XFAD model of Alzheimer’s disease (AD) bearing five familial mutations of Alzheimer’s disease on human APP and PSEN1 transgenes shows deposits of amyloid-β peptide (Aβ) as early as 2 months, while deficits in long-term memory can be detected at 4 months using the highly sensitive olfactory-dependent tests that we previously reported. Objective: Given that detecting early dysfunctions in AD prior to overt pathology is of major interest in the field, we sought to detect memory deficits at earlier stages of the disease in 3-month-old male 5XFAD mice. Methods: To this end, we used the Helico Maze, a behavioral task that was recently developed and patented. This device allows deeper analysis of learning and subcategories of hippocampal-dependent long-term memory using olfactory cues. Results: Eight male 5XFAD and 6 male wild-type (WT: C57Bl6 background) mice of 3 months of age were tested in the Helico Maze. The results demonstrated, for the first time, a starting deficit of pure reference long-term memory. Interestingly, memory impairment was clearly correlated with Aβ deposits in the hippocampus. While we also found significant differences in astrogliosis between 5XFAD and WT mice, this was not correlated with memory abilities. Conclusion: Our results underline the efficiency of this new olfactory-dependent behavioral task, which is easy to use, with a small cohort of mice. Using the Helico Maze may open new avenues to validate the efficacy of treatments that target early events related to the amyloid-dependent pathway of the disease and AD progression.

Background There is increasing focus on the organisation of services for people with IBD. Patient experience of care is an important consideration in service delivery. The United Kingdom NHS Long Term Plan indicates the importance of support that is more differentiated for individuals, with more personalised care when needed, which starts with the question ‘What matters to you?”. This is particularly important for people with inflammatory bowel disease (IBD). Methods The aim was to identify ‘What matters to you?’ for people attending a single UK teaching centre IBD service and to relate it to patient experience and national standards of care. Invitations to take part in the AWARE-IBD quality improvement programme were sent to 4082 patients receiving IBD care at a single UK teaching centre in 2 rounds (October 2021 and May 2022). Invitation letters included an anonymous open-ended questionnaire asking patients “what matters to you?”. Responses were extracted as qualitative data and coded using two frameworks: Patient experience domains (Bull et al) (Communication, Patient-centred Care, Quality, Integration, Involvement, Accessibility, Environment and Facilities, Discomfort) and national IBD UK Standards. Frequencies for each coding strategy were calculated to determine the most important patient experience domains and IBD UK standards. Results Responses were received from 408 and 205 patients from each recruitment round (n=613). Figure 1 displays frequencies for each patient experience domain. Accessibility (47.5% and 53.2% respectively), Communication (19.6% and 12.7%) and Patient-Centred Care (15.7% and 11.2%) were expressed most frequently. Sub-themes included access to and contact with IBD nurse specialists, timely and accessible appointments and regular contact with a specialist IBD health care professional (HCP). Responses were coded to IBD UK standards, where possible (Table 1). Responses most frequently coded to statements relating to shared decision making, having a personalised care plan, access to an IBD nurse specialist including helpline and regular clinical review. 77 responses could not be coded to an IBD UK standard. Conclusion Access to the IBD service when needed matters most to patients with good communication of information and personalised, patient-centred care. Service organisation should therefore reflect these facets of patient experience and defined standards. Patient views that are not currently represented in published standards should be considered in future iterations. This study also highlights personalised written care plans and improved access to the IBD Nurse Advice line.

Background There is increasing international attention on delivery of services for people with Inflammatory bowel diseases (IBD). Experience of care is defined and measured as ‘what’ happened, ‘how’ and ‘how often’ and is an important facet of service provision. Socioeconomic deprivation may be associated with poor disease-related outcomes and sub-optimal utilisation of services but its effect on experience of care in people with inflammatory bowel disease has not been reported. Methods An invitation to participate in a research study nested within the AWARE-IBD quality improvement programme was sent to 4082 patients attending the IBD service at a single UK teaching centre in October 2021. A second invitation was sent in May 2022 followed by telephone recruitment targeted to those from the most deprived deciles based on the index of multiple deprivation (IMD), a measure of relative deprivation for small areas in England (‘lower-layer super areas’, approximately 1500 residents). Participants returned an IBD specific patient reported experience measure (PREM) via a web application comprising 38 items across 3 domains: ‘My Care Team’, “What matters to me’, ‘Living with Crohn’s or Colitis’. Each item was scored 1 (poorest experience) to 5 (best experience). Median scores for individual items and by domain was compared in the following demographic groups: IMD decile IMD (1 = most deprived; 10 = least deprived), age, gender, disease type (ulcerative colitis or Crohn’s disease). Results PREM responses were received from 249/4,082 (6%) patients. Patients from the most deprived decile were underrepresented in respondents compared to the invited cohort (Decile 1 22/249 (9%) vs 667/4,063(16%) p=0.002) and patients from the least deprived decile were over-represented; Decile 10: 38/249 (15%) vs 379/4063(9%) p=0.002). Respondents were otherwise broadly comparable to the invited cohort in terms of age, gender and disease type. Experience of care for respondents for individual PREM items or by domain did not differ according between IMD deciles (Figure 1), age, gender or disease type. Conclusion Measuring experience of care is an important part of IBD service quality improvement. No effect from socioeconomic deprivation was demonstrated. This finding conflicts with the literature on links between socioeconomic factors and quality of care and results across a service should be interpreted with caution. Experience of those at greatest risk is difficult to elicit with survey based experience measurement. Instead, tailored engagement exercises are required including qualitative and ethnographic approaches to better understand the impact of deprivation on experience.

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Obesity is a global health problem that triggers fat liver accumulation. The prevalence of obesity and the risk of non-alcoholic steatohepatitis (NASH) among young obese Mexican is high. Furthermore, genetic predisposition is a key factor in weight gain and disrupts metabolism. Herein, we used Whole-Exome Sequencing to identify potential causal variants and the biological processes that lead to obesity with progression to NASH among Mexican patients.Whole-Exome Sequencing was performed in nine obese patients with NASH diagnosis with a BMI ≥30 kg/msup2/supand one control (BMI=24.2 kg/msup2/sup) by using the Ion S5supTM/supplatform. Genetic variants were determined by Ion Reporter software. Enriched GO biological set genes were identified by the WebGestalt tool. Genetic variants within ≥2 obese NASH patients and having scores of SIFT 0.0-0.05 and Polyphen 0.85-1.0 were categorized as pathogenic.A total of 1359 variants with a probable pathogenic effect were determined in obese patients with NASH diagnosis. After several filtering steps, the most frequent pathogenic variants found were rs25640-HSD17B4, rs8105737-OR1I1, rs998544-OR5R1, and rs4916685, rs10037067, and rs2366926 in ADGRV1. Notably, the primary biological processes affected by these pathogenic variants were the sensory perception and detection of chemical stimulus pathways in which the olfactory receptor gene family was the most enriched.Variants in the olfactory receptor genes were highly enriched in Mexican obese patients that progress to NASH and could be potential targets of association studies.

The minimum driving force strategy is applied to promote the exciton dissociation in organic solar cells (OSCs) without significant loss of open-circuit voltage. However, this strategy tends to promote Forster resonance energy transfer (FRET) from the donor to the acceptor (D–A), a consequence generally ignored until recently. In spite of the advances reported on this topic, the correlation between charge-transfer (CT) state binding energy and driving force remains unclear, especially in the presence of D–A FRET. To address this question, we employ a kinetic approach to model the charge separation in ten different D/A blends using non-fullerene acceptors. The model considers the influence of FRET on photoluminescence (PL) quenching efficiency. It successfully predicts the measured PL quenching efficiency for D or A photoexcitation in those blends, including the ones for which the D–A FRET process is relevant. Furthermore, the application of the model allows to quantifying the fractions of quenching loss associated with charge transfer and energy transfer. Fundamental relationships that controls the exciton dissociation was derived evidencing the key roles played by the Marcus inverted regime, exciton lifetime and mainly by the correlation between the driving force and binding energy of CT state. Based on those findings, we propose some strategies to maximize the quenching efficiency and minimize energy loss of OSCs in the presence of D–A FRET.

Organic photovoltaics (OPVs) hold promise for a cost-effective, eco-friendly, and sustainable technology to harvest solar energy. However, the widespread application of OPVs has been hindered mostl...

Objective To describe the characteristics and birth outcomes of women with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection as community spread in New York City was detected in March 2020. Methods We performed a prospective cohort study of pregnant women with laboratory-confirmed SARS-CoV-2 infection who gave birth from March 13 to April 12, 2020, identified at five New York City medical centers. Demographic and clinical data from delivery hospitalization records were collected, and follow-up was completed on April 20, 2020. Results Among this cohort (241 women), using evolving criteria for testing, 61.4% of women were asymptomatic for coronavirus disease 2019 (COVID-19) at the time of admission. Throughout the delivery hospitalization, 26.5% of women met World Health Organization criteria for mild COVID-19, 26.1% for severe, and 5% for critical. Cesarean birth was the mode of delivery for 52.4% of women with severe and 91.7% with critical COVID-19. The singleton preterm birth rate was 14.6%. Admission to the intensive care unit was reported for 17 women (7.1%), and nine (3.7%) were intubated during their delivery hospitalization. There were no maternal deaths. Body mass index (BMI) 30 or higher was associated with COVID-19 severity (P=.001). Nearly all newborns tested negative for SARS-CoV-2 infection immediately after birth (97.5%). Conclusion During the first month of the SARS-CoV-2 outbreak in New York City and with evolving testing criteria, most women with laboratory-confirmed infection admitted for delivery did not have symptoms of COVID-19. Almost one third of women who were asymptomatic on admission became symptomatic during their delivery hospitalization. Obesity was associated with COVID-19 severity. Disease severity was associated with higher rates of cesarean and preterm birth.

The ideal time for birth in pregnancies diagnosed with vasa previa remains unclear. We conducted a systematic review aiming to identify the gestational age at delivery that best balances the risks for prematurity with that of pregnancy prolongation in cases with prenatally diagnosed vasa previa.Ovid MEDLINE, PubMed, CINAHL, Embase, Scopus, and Web of Science were searched from inception to January 2022.The intervention analyzed was delivery at various gestational ages in pregnancies prenatally diagnosed with vasa previa. Cohort studies, case series, and case reports were included in the qualitative synthesis. When summary figures could not be obtained directly from the studies for the quantitative synthesis, authors were contacted and asked to provide a breakdown of perinatal outcomes by gestational age at birth.Study appraisal was completed using the National Institutes of Health quality assessment tool for the respective study types. Statistical analysis was performed using a random-effects meta-analysis of proportions.The search identified 3435 studies of which 1264 were duplicates. After screening 2171 titles and abstracts, 140 studies proceeded to the full-text screen. A total of 37 studies were included for analysis, 14 of which were included in a quantitative synthesis. Among 490 neonates, there were 2 perinatal deaths (0.4%), both of which were neonatal deaths before 32 weeks' gestation. In general, the rate of neonatal complications decreased steadily from32 weeks' gestation (4.6% rate of perinatal death, 91.2% respiratory distress, 11.4% 5-minute Apgar score7, 23.3% neonatal blood transfusion, 100% neonatal intensive care unit admission, and 100% low birthweight) to 36 weeks' gestation (0% perinatal death, 5.3% respiratory distress, 0% 5-minute Apgar score7, 2.9% neonatal blood transfusion, 29.2% neonatal intensive care unit admission, and 30.9% low birthweight). Complications then increased slightly at 37 weeks' gestation before decreasing again at 38 weeks' gestation.Prolonging pregnancies until 36 weeks' gestation seems to be safe and beneficial in otherwise uncomplicated pregnancies with antenatally diagnosed vasa previa.

Alternate splicing events can create isoforms that alter gene function, and genetic variants associated with alternate gene isoforms may reveal molecular mechanisms of disease. We used subcutaneous adipose tissue of 426 Finnish men from the METSIM study and identified splice junction quantitative trait loci (sQTLs) for 6,077 splice junctions (FDR < 1%). In the same individuals, we detected expression QTLs (eQTLs) for 59,443 exons and 15,397 genes (FDR < 1%). We identified 595 genes with an sQTL and exon eQTL but no gene eQTL, which could indicate potential isoform differences. Of the significant sQTL signals, 2,114 (39.8%) included at least one proxy variant (linkage disequilibrium r(2) > 0.8) located within an intron spanned by the splice junction. We identified 203 sQTLs that colocalized with 141 genome-wide association study (GWAS) signals for cardiometabolic traits, including 25 signals for lipid traits, 24 signals for body mass index (BMI), and 12 signals for waist-hip ratio adjusted for BMI. Among all 141 GWAS signals colocalized with an sQTL, we detected 26 that also colocalized with an exon eQTL for an exon skipped by the sQTL splice junction. At a GWAS signal for high-density lipoprotein cholesterol colocalized with an NR1H3 sQTL splice junction, we show that the alternative splice product encodes an NR1H3 transcription factor that lacks a DNA binding domain and fails to activate transcription. Together, these results detect splicing events and candidate mechanisms that may contribute to gene function at GWAS loci.

BACKGROUND: Historically, prenatal screening has focused primarily on the detection of fetal aneuploidies. Cell-free DNA now enables noninvasive screening for subchromosomal copy number variants, including 22q11.2 deletion syndrome (or DiGeorge syndrome), which is the most common microdeletion and a leading cause of congenital heart defects and neurodevelopmental delay. Although smaller studies have demonstrated the feasibility of screening for 22q11.2 deletion syndrome, large cohort studies with confirmatory postnatal testing to assess test performance have not been reported. OBJECTIVE: This study aimed to assess the performance of single-nucleotide polymorphism-based, prenatal cell-free DNA screening for detection of 22q11.2 deletion syndrome. STUDY DESIGN: Patients who underwent single-nucleotide polymorphism-based prenatal cell-free DNA screening for 22q11.2 deletion syndrome were prospectively enrolled at 21 centers in 6 countries. Prenatal or newborn DNA samples were requested in all cases for genetic confirmation using chromosomal microarrays. The primary outcome was sensitivity, specificity, positive predictive value, and negative predictive value of cell-free DNA screening for the detection of all deletions, including the classical deletion and nested deletions that are ≥500 kb, in the 22q11.2 low-copy repeat A-D region. Secondary outcomes included the prevalence of 22q11.2 deletion syndrome and performance of an updated cell-free DNA algorithm that was evaluated with blinding to the pregnancy outcome. RESULTS: Of the 20,887 women enrolled, a genetic outcome was available for 18,289 (87.6%). A total of 12 22q11.2 deletion syndrome cases were confirmed in the cohort, including 5 (41.7%) nested deletions, yielding a prevalence of 1 in 1524. In the total cohort, cell-free DNA screening identified 17,976 (98.3%) cases as low risk for 22q11.2 deletion syndrome and 38 (0.2%) cases as high risk; 275 (1.5%) cases were nonreportable. Overall, 9 of 12 cases of 22q11.2 were detected, yielding a sensitivity of 75.0% (95% confidence interval, 42.8-94.5); specificity of 99.84% (95% confidence interval, 99.77-99.89); positive predictive value of 23.7% (95% confidence interval, 11.44-40.24), and negative predictive value of 99.98% (95% confidence interval, 99.95-100). None of the cases with a nonreportable result was diagnosed with 22q11.2 deletion syndrome. The updated algorithm detected 10 of 12 cases (83.3%; 95% confidence interval, 51.6-97.9) with a lower false positive rate (0.05% vs 0.16%; P

SARS-CoV-2 is known to impact multiple organ systems, with growing data to suggest the potential for placental infection and resultant pathology. Understanding how maternal COVID-19 disease can affect placental histopathology has been limited by small study cohorts with mild disease, review by multiple pathologists, and potential confounding by maternal-fetal comorbidities that can also influence placental findings. This study aims to identify pathologic placental findings associated with COVID-19 disease and severity, as well as to distinguish them from changes related to coexisting maternal-fetal comorbidities.This is an observational study of 61 pregnant women with confirmed SARS-CoV-2 infection who delivered and had a placental histological evaluation at NYU Langone Health between March 19, 2020 and June 30, 2020. Primary outcomes were the prevalence of placental histopathologic features and their association with maternal-fetal comorbidities and severity of COVID-19 related hypoxia. Analysis was performed using Fisher's exact test andSixty-one placentas were included in the study cohort, 71% from pregnancies complicated by at least one maternal-fetal comorbidity. Twenty-five percent of placentas were small for gestational age and 77% exhibited at least one feature of maternal vascular malperfusion. None of the histopathologic features in the examined placentas were associated with the presence of any specific maternal-fetal comorbidity. Thirteen percent of the cohort required maternal respiratory support for COVID-19 related hypoxia. Villous trophoblast necrosis was associated with maternal supplemental oxygen requirement (67In pregnancies complicated by COVID-19 disease, there was a high prevalence of placental histopathologic changes identified, particularly features of maternal vascular malperfusion, which could not be attributed solely to the presence of maternal-fetal comorbidities. The significantly increased prevalence of villous trophoblast necrosis in women needing respiratory support suggests a connection to the severity of COVID-19 illness.