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A microfluidic setup for consistent generation of droplets containing microspores was developed. Androgenesis and growth with final embryo formation can be induced. The system further enables dose–response studies, as shown with trichostatin A.

Visual Abstract, Highlights • AM is an important cause of cardiac dysfunction following some viral infections and has been previously linked with genetic host susceptibilities. • Sequencing data for genes related to cardiomyocyte structure and function was compared between patients with AM and sex- and ancestry-matched heart-healthy control subjects. • Putatively DVs among these genes were found in ∼16% of AM cases, contributing to viral susceptibility. • Implicated genes are ones classically associated with cardiomyopathy or neuromuscular disorders with cardiac involvement, suggesting shared mechanistic pathways. • Phenotypes, including outcomes, were similar in subjects who have AM with and without DV, therefore genetic testing will be necessary to uncover this subtype and inform risk in relatives., Summary Impairments in certain cardiac genes confer risk for myocarditis in children. To determine the extent of this association, we performed genomic sequencing in predominantly adult patients with acute myocarditis and matched control subjects. Putatively deleterious variants in a broad set of cardiac genes were found in 19 of 117 acute myocarditis cases vs 34 of 468 control subjects (P = 0.003). Thirteen genes classically associated with cardiomyopathy or neuromuscular disorders with cardiac involvement were implicated, including >1 associated damaging variant in DYSF, DSP, and TTN. Phenotypes of subjects who have acute myocarditis with or without deleterious variants were similar, indicating that genetic testing is necessary to differentiate them.

Background:Congenital heart disease (CHD) is the most common anomaly at birth, with a prevalence of ≈1%. While infants born to mothers with diabetes or obesity have a 2- to 3-fold increased incidence of CHD, the cause of the increase is unknown. Damaging de novo variants (DNV) in coding regions are more common among patients with CHD, but genome-wide rates of coding and noncoding DNVs associated with these prenatal exposures have not been studied in patients with CHD.Methods:DNV frequencies were determined for 1812 patients with CHD who had whole-genome sequencing and prenatal history data available from the Pediatric Cardiac Genomics Consortium’s CHD GENES study (Genetic Network). The frequency of DNVs was compared between subgroups usingttest or linear model.Results:Among 1812 patients with CHD, the number of DNVs per patient was higher with maternal diabetes (76.5 versus 72.1,ttestP=3.03×10−11), but the difference was no longer significant after including parental ages in a linear model (paternal and maternal correctionP=0.42). No interaction was observed between diabetes risk and parental age (paternal and maternal interactionP=0.80 and 0.68, respectively). No difference was seen in DNV count per patient based on maternal obesity (72.0 versus 72.2 for maternal body mass index 30,ttestP=0.86).Conclusions:After accounting for parental age, the offspring of diabetic or obese mothers have no increase in DNVs compared with other children with CHD. These results emphasize the role for other mechanisms in the cause of CHD associated with these prenatal exposures.Registration:URL:https://clinicaltrials.gov; NCT01196182.

Background Early reports indicate that AKI is common among patients with coronavirus disease 2019 (COVID-19) and associated with worse outcomes. However, AKI among hospitalized patients with COVID-19 in the United States is not well described. Methods This retrospective, observational study involved a review of data from electronic health records of patients aged ≥18 years with laboratory-confirmed COVID-19 admitted to the Mount Sinai Health System from February 27 to May 30, 2020. We describe the frequency of AKI and dialysis requirement, AKI recovery, and adjusted odds ratios (aORs) with mortality. Results Of 3993 hospitalized patients with COVID-19, AKI occurred in 1835 (46%) patients; 347 (19%) of the patients with AKI required dialysis. The proportions with stages 1, 2, or 3 AKI were 39%, 19%, and 42%, respectively. A total of 976 (24%) patients were admitted to intensive care, and 745 (76%) experienced AKI. Of the 435 patients with AKI and urine studies, 84% had proteinuria, 81% had hematuria, and 60% had leukocyturia. Independent predictors of severe AKI were CKD, men, and higher serum potassium at admission. In-hospital mortality was 50% among patients with AKI versus 8% among those without AKI (aOR, 9.2; 95% confidence interval, 7.5 to 11.3). Of survivors with AKI who were discharged, 35% had not recovered to baseline kidney function by the time of discharge. An additional 28 of 77 (36%) patients who had not recovered kidney function at discharge did so on posthospital follow-up. Conclusions AKI is common among patients hospitalized with COVID-19 and is associated with high mortality. Of all patients with AKI, only 30% survived with recovery of kidney function by the time of discharge.

Background Data on patients with coronavirus disease 2019 (COVID-19) who return to hospital after discharge are scarce. Characterization of these patients may inform post-hospitalization care. Objective To describe clinical characteristics of patients with COVID-19 who returned to the emergency department (ED) or required readmission within 14 days of discharge. Design Retrospective cohort study of SARS-COV-2-positive patients with index hospitalization between February 27 and April 12, 2020, with ≥ 14-day follow-up. Significance was defined as P < 0.05 after multiplying P by 125 study-wide comparisons. Participants Hospitalized patients with confirmed SARS-CoV-2 discharged alive from five New York City hospitals. Main Measures Readmission or return to ED following discharge. Results Of 2864 discharged patients, 103 (3.6%) returned for emergency care after a median of 4.5 days, with 56 requiring inpatient readmission. The most common reason for return was respiratory distress (50%). Compared with patients who did not return, there were higher proportions of COPD (6.8% vs 2.9%) and hypertension (36% vs 22.1%) among those who returned. Patients who returned also had a shorter median length of stay (LOS) during index hospitalization (4.5 [2.9,9.1] vs 6.7 [3.5, 11.5] days; Padjusted = 0.006), and were less likely to have required intensive care on index hospitalization (5.8% vs 19%; Padjusted = 0.001). A trend towards association between absence of in-hospital treatment-dose anticoagulation on index admission and return to hospital was also observed (20.9% vs 30.9%, Padjusted = 0.06). On readmission, rates of intensive care and death were 5.8% and 3.6%, respectively. Conclusions Return to hospital after admission for COVID-19 was infrequent within 14 days of discharge. The most common cause for return was respiratory distress. Patients who returned more likely had COPD and hypertension, shorter LOS on index-hospitalization, and lower rates of in-hospital treatment-dose anticoagulation. Future studies should focus on whether these comorbid conditions, longer LOS, and anticoagulation are associated with reduced readmissions. Electronic supplementary material The online version of this article (10.1007/s11606-020-06120-6) contains supplementary material, which is available to authorized users.

ZusammenfassungDas Konzept der Mentalisierungsfähigkeit, etabliert ausgehend von der Theory of Mind (ToM), beinhaltet jene menschliche Fähigkeit, die eigenen mentalen Zustände (z. B. Gedanken, Gefühle, Motive) sowie entsprechend jene des Gegenübers, in einen Sinn- und Bedeutungszusammenhang zu bringen und aus diesem mehr oder weniger tiefen Verständnis hilfreiche Erklärungsmodelle für Verhalten zu generieren. Entwickeln und entfalten sich menschliche mentale Funktionen und Fähigkeiten im „Gegenseitigen-aufeinander-bezogen-Sein“, so impliziert diese Weltsicht das Individuum als im Wesentlichen sozial determiniert. Leidensdruck infolge depressiver als auch schizophreniformer Störungen resultiert ganz wesentlich aus eingeschränkter Mentalisierungsfähigkeit, dies unabhängig von der unterschiedlichen Ätiologie der genannten Störungen.Die folgenden Ausführungen legen dar, inwieweit Defizite in der Mentalisierung bei schizophreniformen Störungsbildern in Erscheinung treten. Diese Defizite sind gekennzeichnet durch eine mangelhafte Ausbildung von Metarepräsentationen und zeigen je nach Symptomatik verschiedene prämentalistische Verarbeitungsmodi und deren spezifische Ausformungen (Hypo‑/Hypermentalisieren). An einer geschilderten Fallvignette wird dies verständlich.

A genetic etiology is identified for one-third of patients with congenital heart disease (CHD), with 8% of cases attributable to coding de novo variants (DNVs). To assess the contribution of noncoding DNVs to CHD, we compared genome sequences from 749 CHD probands and their parents with those from 1,611 unaffected trios. Neural network prediction of noncoding DNV transcriptional impact identified a burden of DNVs in individuals with CHD (n = 2,238 DNVs) compared to controls (n = 4,177; P = 8.7 × 10-4). Independent analyses of enhancers showed an excess of DNVs in associated genes (27 genes versus 3.7 expected, P = 1 × 10-5). We observed significant overlap between these transcription-based approaches (odds ratio (OR) = 2.5, 95% confidence interval (CI) 1.1-5.0, P = 5.4 × 10-3). CHD DNVs altered transcription levels in 5 of 31 enhancers assayed. Finally, we observed a DNV burden in RNA-binding-protein regulatory sites (OR = 1.13, 95% CI 1.1-1.2, P = 8.8 × 10-5). Our findings demonstrate an enrichment of potentially disruptive regulatory noncoding DNVs in a fraction of CHD at least as high as that observed for damaging coding DNVs.

Despite substantial advances in the study, treatment, and prevention of cardiovascular disease, numerous challenges relating to optimally screening, diagnosing, and managing patients remain. Simultaneous improvements in computing power, data storage, and data analytics have led to the development of new techniques to address these challenges. One powerful tool to this end is machine learning (ML), which aims to algorithmically identify and represent structure within data. Machine learning’s ability to efficiently analyze large and highly complex data sets make it a desirable investigative approach in modern biomedical research. Despite this potential and enormous public and private sector investment, few prospective studies have demonstrated improved clinical outcomes from this technology. This is particularly true in cardiology, despite its emphasis on objective, data-driven results. This threatens to stifle ML’s growth and use in mainstream medicine. We outline the current state of ML in cardiology and outline methods through which impactful and sustainable ML research can occur. Following these steps can ensure ML reaches its potential as a transformative technology in medicine.

This review highlights new advances in the emerging field of ‘Fungi-on-a-Chip’ microfluidics for single-cell studies on fungi and discusses several future frontiers, where we envisage microfluidic technology development to be instrumental in aiding our understanding of fungal biology. Fungi, with their enormous diversity, bear essential roles both in nature and our everyday lives. They inhabit a range of ecosystems, such as soil, where they are involved in organic matter degradation and bioremediation processes. More recently, fungi have been recognized as key components of the microbiome in other eukaryotes, such as humans, where they play a fundamental role not only in human pathogenesis, but also likely as commensals. In the food sector, fungi are used either directly or as fermenting agents and are often key players in the biotechnological industry, where they are responsible for the production of both bulk chemicals and antibiotics. Although the macroscopic fruiting bodies are immediately recognizable by most observers, the structure, function, and interactions of fungi with other microbes at the microscopic scale still remain largely hidden. Herein, we shed light on new advances in the emerging field of Fungi-on-a-Chip microfluidic technologies for single-cell studies on fungi. We discuss the development and application of microfluidic tools in the fields of medicine and biotechnology, as well as in-depth biological studies having significance for ecology and general natural processes. Finally, a future perspective is provided, highlighting new frontiers in which microfluidic technology can benefit this field.

Infrared spectroscopy provides unique information on the composition and dynamics of biochemical systems by resolving the characteristic absorption fingerprints of their constituent molecules. Based on this inherent chemical specificity and the capability for label-free, noninvasive, and real-time detection, infrared spectroscopy approaches have unlocked a plethora of breakthrough applications for fields ranging from environmental monitoring and defense to chemical analysis and medical diagnostics. Nanophotonics has played a crucial role for pushing the sensitivity limits of traditional far-field spectroscopy by using resonant nanostructures to focus the incident light into nanoscale hot-spots of the electromagnetic field, greatly enhancing light-matter interaction. Metasurfaces composed of regular arrangements of such resonators further increase the design space for tailoring this nanoscale light control both spectrally and spatially, which has established them as an invaluable toolkit for surface-enhanced spectroscopy. Starting from the fundamental concepts of metasurface-enhanced infrared spectroscopy, a broad palette of resonator geometries, materials, and arrangements for realizing highly sensitive metadevices is showcased, with a special focus on emerging systems such as phononic and 2D van der Waals materials, and integration with waveguides for lab-on-a-chip devices. Furthermore, advanced sensor functionalities of metasurface-based infrared spectroscopy, including multiresonance, tunability, dielectrophoresis, live cell sensing, and machine-learning-aided analysis are highlighted.

Objectives The objectives of this study were to establish days between birth and death for neonates over a 14-year period, determine if days between birth and death have changed over time across gestational age cohorts, and identify diagnoses which may put infants at high risk of prolonged hospitalization leading to death. Study Design This was a single-site, retrospective chart review of inborn infants who died prior to hospital discharge. Results Two hundred and thirty-nine patients born between 1/1/2006 and 12/31/2020 met inclusion criteria. Days until death ranged from 0 to 300 with a median of 6 days (interquartile range = 23). Median days until death increased over time, with a statistically significant increase between epoch 1 and epoch 2 (p = 0.016) but not between epoch 2 and epoch 3 (p = 0.618). Extremely premature infants died earlier than more mature infants (p Conclusions Our findings demonstrate an increase in time to death for newborns who did not survive to hospital discharge over a 14-year period. This trend suggests that the dynamics informing Meadows' assertion that “doomed infants die early” may be shifting, with some seriously ill infants who die before hospital discharge surviving longer than previously described. More research is needed to understand how best to care for babies who will not survive to discharge and to explore when supports such as palliative care consultation may be beneficial. Key Points As per W. Meadow, “Doomed infants die early”

We explored rates of premature births and neonatal intensive care unit (NICU) admissions at the Mount Sinai Hospital after the implementation of COVID-19 lockdown measures (March 16, 2020) and phase one reopening (June 8, 2020), comparing them to those of the same time periods from 2012-2019. Mount Sinai Hospital is in New York City (NYC), an early epicenter of COVID-19 in the United States, which was heavily impacted by the pandemic during the study period. Among 43,963 singleton births, we observed no difference in either outcome after the implementation of lockdown measures when compared to the same trends in prior years (p=0.09-0.35). Of interest, we observed a statistically significant decrease in premature births after NYC phase one reopening compared to those of the same time period in 2012-2019 across all time windows (p=0.0028-0.049), and a statistically significant decrease in NICU admissions over the largest time window (2.75 months) compared to prior years (p=0.0011).

In display technologies or data processing, planar and subwavelength free-space components suited for flat photonic devices are needed. Metasurfaces, which shape the optical wavefront within hundreds of nanometers, can provide a solution for thin and portable photonic devices, for example, as CMOS-compatible modules. While conventional electro-optic modulators are inconvenient to operate in free space configurations, its principle can largely be applied to the development of active metasurfaces with the prospect of modulation speeds up to the GHz region. We extend this principle of the linear electro-optic effect to a metasurface in lithium niobate with an optical resonance in the visible. We exploit the electric and optical field overlap inside the metasurface to enhance the light matter interaction. Hence, the modulation of the transmitted light is increased by 2 orders of magnitude, namely, by a factor of 80, compared to the unstructured substrate. Furthermore, we investigate the influence of the dispersive optical resonance on the wavelength-dependence of the modulation and achieve fast and continuous modulation of light at low voltage and MHz speed. This proof-of-concept work is a first important step toward the use of lithium niobate resonant nanostructures for free space modulation., ACS Photonics, 8 (10), ISSN:2330-4022

Subcellular RNAseq promises to dissect transcriptional dynamics but is not well characterized. Furthermore, FACS may introduce bias but has not been benchmarked genome-wide. Finally, D1 and D2 dopamine receptor-expressing medium spiny neurons (MSNs) of the nucleus accumbens (NAc) are fundamental to neuropsychiatric traits but have only a short list of canonical surface markers. We address these gaps by systematically comparing nuclear-FACS, whole cell-FACS, and RiboTag affinity purification from D1- and D2-MSNs. Using differential expression, variance partitioning, and co-expression, we identify the following trade-offs for each method. RiboTag-seq best distinguishes D1- and D2-MSNs but has the lowest transcriptome coverage. Nuclear-FACS-seq generates the most differentially expressed genes and overlaps significantly with neuropsychiatric genetic risk loci, but un-annotated genes hamper interpretation. Whole cell-FACS is more similar to nuclear-FACS than RiboTag, but captures aspects of both. Using pan-method approaches, we discover that transcriptional regulation is predominant in D1-MSNs, while D2-MSNs tend towards cytosolic regulation. We are also the first to find evidence for moderate sexual dimorphism in these cell types at baseline. As these results are from 49 mice (nmale = 39, nfemale = 10), they represent generalizable ground-truths. Together, these results guide RNAseq methods selection, define MSN transcriptomes, highlight neuronal sex differences, and provide a baseline for D1- and D2-MSNs.

Motivation Non-coding rare variants (RVs) may contribute to Mendelian disorders but have been challenging to study due to small sample sizes, genetic heterogeneity and uncertainty about relevant non-coding features. Previous studies identified RVs associated with expression outliers, but varying outlier definitions were employed and no comprehensive open-source software was developed. Results We developed Outlier-RV Enrichment (ORE) to identify biologically-meaningful non-coding RVs. We implemented ORE combining whole-genome sequencing and cardiac RNAseq from congenital heart defect patients from the Pediatric Cardiac Genomics Consortium and deceased adults from Genotype-Tissue Expression. Use of rank-based outliers maximized sensitivity while a most extreme outlier approach maximized specificity. Rarer variants had stronger associations, suggesting they are under negative selective pressure and providing a basis for investigating their contribution to Mendelian disorders. Availability and implementation ORE, source code, and documentation are available at https://pypi.python.org/pypi/ore under the MIT license. Supplementary information Supplementary data are available at Bioinformatics online.

The rapid design and implementation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines is testament to a successfully coordinated global research effort. While employing a variety of different technologies, some of which have been used for the first time, all approved vaccines demonstrate high levels of efficacy with excellent safety profiles. Despite this, there remains an urgent global demand for coronavirus disease 2019 vaccines that require further candidates to pass phase 3 clinical trials. In the expectation of SARS-CoV-2 becoming endemic, researchers are looking to adjust the vaccine constructs to tackle emerging variants. In this review, we outline different platforms used for approved vaccines and summarize latest research data with regards to immunogenicity, dosing regimens and efficiency against emerging variants.

The psychological strain of many psychiatric disorders arises from difficulties encountered in social interactions. Social withdrawal is often the first symptom of neuropsychiatric disorders. The authors explore the various options for training social cognition skills. Social cognition was assessed using the Movie for the Assessment of Social Cognition (MASC). After completion of mentalization-based therapy (MBT) training, MASC scores improved significantly in health care providers (p = .006, r = .57). Mentalizing (operationalized with reflective functioning [RF]) was assessed in the MBT group (Group A) and compared with RF in a control group (Group B). RF was significantly higher in Group A (RF = 4.35, SD = 1.19) than in Group B (RF = 3.43, SD = 1.70) (p = .0385; Cohen's d = 0.65). MBT might be a promising intervention in social cognition training. Mentalizing skills might be associated with attitude.

Irritable bowel syndrome (IBS), as part of the functional somatic syndromes, is frequent in the general population. Medical care and morbidity costs are high, and so is the psychological and somatic strain. The etiopathogenesis of IBS is still poorly understood, it is assumed to be multifactorial and to include biopsychosocial factors. Links between the intestine, psyche, nervous system (e.g., via the hypothalamic–pituitary–adrenal axis (HPA-Axis/neurotransmitters) and with the microbiome, the immune system have lately been investigated. Factors such as personality traits, mentalization, and early attachment strategies (deactivating and hyperactivating) have been suggested to influence IBS with relevance for treatment regimens. At this time, data on reflective functioning (RF) is lacking. Within a cross-sectional, we examined the mentalizing capacity of a clinical sample (n = 90) consisting of patients with IBS (n = 30), affective disorders (AD, n = 28), and non-affective psychosis (NAP, n = 32). The reflective functioning scale was used based on the brief reflective function interview (BRFI). The results revealed severe impairment in patients with IBS concerning their mentalizing ability, which was comparable to patients with affective disorders. Patients with non-affective-psychosis showed the lowest mentalizing ability. Thus, psychotherapeutic treatment with a focus on mentalization could be a promising approach.