NRL^{-/-} gene edited human embryonic stem cells generate rod-deficient retinal organoids enriched in S-cone-like photoreceptors

Organoid cultures represent a unique tool to investigate the developmental complexity of tissues like the human retina. NRL is a transcription factor required for the specification and homeostasis of mammalian rod photoreceptors. In Nrl‐deficient mice, photoreceptor precursor cells do not differentiate into rods, and instead follow a default photoreceptor specification pathway to generate S‐cone‐like cells. To investigate whether this genetic switch mechanism is conserved in humans, we used CRISPR/Cas9 gene editing to engineer an NRL‐deficient embryonic stem cell (ESC) line (NRL^{−/−}), and differentiated it into retinal organoids. Retinal organoids self‐organize and resemble embryonic optic vesicles (OVs) that recapitulate the natural histogenesis of rods and cone photoreceptors. NRL−/− OVs develop comparably to controls, and exhibit a laminated, organized retinal structure with markers of photoreceptor synaptogenesis. Using immunohistochemistry and quantitative polymerase chain reaction (qPCR), we observed that NRL^{−/−} OVs do not express NRL, or other rod photoreceptor markers directly or indirectly regulated by NRL. On the contrary, they show an abnormal number of photoreceptors positive for S‐OPSIN, which define a primordial subtype of cone, and overexpress other cone genes indicating a conserved molecular switch in mammals. This study represents the first evidence in a human in vitro ESC‐derived organoid system that NRL is required to define rod identity, and that in its absence S‐cone‐like cells develop as the default photoreceptor cell type. It shows how gene edited retinal organoids provide a useful system to investigate human photoreceptor specification, relevant for efforts to generate cells for transplantation in retinal degenerative diseases

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Dark matter interpretations of ATLAS searches for the electroweak production of supersymmetric particles in s√=8 s=8 TeV proton-proton collisions

A selection of searches by the ATLAS experiment at the LHC for the electroweak production of SUSY particles are used to study their impact on the constraints on dark matter candidates. The searches use 20 fb−1 of proton-proton collision data at s √ =8 s=8 TeV. A likelihood-driven scan of a five-dimensional effective model focusing on the gaugino-higgsino and Higgs sector of the phenomenological minimal supersymmetric Standard Model is performed. This scan uses data from direct dark matter detection experiments, the relic dark matter density and precision flavour physics results. Further constraints from the ATLAS Higgs mass measurement and SUSY searches at LEP are also applied. A subset of models selected from this scan are used to assess the impact of the selected ATLAS searches in this five-dimensional parameter space. These ATLAS searches substantially impact those models for which the mass m(χ ~ 0 1 ) m(χ~10) of the lightest neutralino is less than 65 GeV, excluding 86% of such models. The searches have limited impact on models with larger m(χ ~ 0 1 ) m(χ~10) due to either heavy electroweakinos or compressed mass spectra where the mass splittings between the produced particles and the lightest supersymmetric particle is small

Machine Learning Based Psychotic Behaviors Prediction from Facebook Status Updates

\ua9 2022 Tech Science Press. All rights reserved.With the advent of technological advancements and the widespread Internet connectivity during the last couple of decades, social media platforms (such as Facebook, Twitter, and Instagram) have consumed a large proportion of time in our daily lives. People tend to stay alive on their social media with recent updates, as it has become the primary source of interactionwithin social circles. Although social media platforms offer several remarkable features but are simultaneously prone to various critical vulnerabilities. Recent studies have revealed a strong correlation between the usage of social media and associated mental health issues consequently leading to depression, anxiety, suicide commitment, and mental disorder, particularly in the young adults who have excessively spent time on socialmedia which necessitates a thorough psychological analysis of all these platforms. This study aims to exploit machine learning techniques for the classification of psychotic issues based on Facebook status updates. In this paper, we start with depression detection in the first instance and then expand on analyzing six other psychotic issues (e.g., depression, anxiety, psychopathic deviate, hypochondria, unrealistic, and hypomania) commonly found in adults due to extreme use of social media networks. To classify the psychotic issues with the user\u27s mental state, we have employed different Machine Learning (ML) classifiers i.e., Random Forest (RF), Support Vector Machine (SVM), Na\uefve Bayes (NB), and K-Nearest Neighbor (KNN). The usedMLmodels are trained and tested by using different combinations of features selection techniques. To observe themost suitable classifiers for psychotic issue classification, a cost-benefit function (sometimes termed as \u27Suitability\u27) has been used which combines the accuracy of the model with its execution time. The experimental evidence argues that RF outperforms its competitor classifiers with the unigram feature set

Enhanced Electrical Conductivity of Silver Nanoparticles for High Frequency Electronic Applications

An enhancement in the electrical performance of low temperature screen-printed silver nanoparticles (nAg) has been measured at frequencies up to 220 GHz. We show that for frequencies above 80 GHz the electrical losses in coplanar waveguide structures fabricated using nAg at 350 °C are lower than those found in conventional thick film Ag conductors consisting of micrometer-sized grains and fabricated at 850 °C. The improved electrical performance is attributed to the better packing of the silver nanoparticles resulting in lower surface roughness by a factor of 3. We discuss how the use of silver nanoparticles offers new routes to high frequency applications on temperature sensitive conformal substrates and in sub-THz metamaterials

Electrical performance of carbon nanotube-polymer composites at frequencies up to 220 GHz

We have measured the sub-THz electrical response of screen printed carbon nanotube-poly(methyl methacrylate) polymer composites up to 220 GHz. The measured electrical losses using mm long coplanar waveguide geometries averaged as low as 0.15 dB/mm in the frequency range 40 GHz–110 GHz and showed a reduction in signal loss with increasing frequency; a behaviour opposite to that found in conventional metallic conductors. Between 140 and 220 GHz, the electrical losses averaged 0.28 dB/mm. We show that the low electrical losses are associated with the capacitive coupling between the nanotubes and discuss potential high frequency applications

Electrical performance of carbon nanotube-polymer composites at frequencies up to 220 GHz

We have measured the sub-THz electrical response of screen printed carbon nanotube-poly(methyl methacrylate) polymer composites up to 220 GHz. The measured electrical losses using mm long coplanar waveguide geometries averaged as low as 0.15 dB/mm in the frequency range 40 GHz–110 GHz and showed a reduction in signal loss with increasing frequency; a behaviour opposite to that found in conventional metallic conductors. Between 140 and 220 GHz, the electrical losses averaged 0.28 dB/mm. We show that the low electrical losses are associated with the capacitive coupling between the nanotubes and discuss potential high frequency applications

Enhanced Electrical Conductivity of Silver Nanoparticles for High Frequency Electronic Applications

An enhancement in the electrical performance of low temperature screen-printed silver nanoparticles (nAg) has been measured at frequencies up to 220 GHz. We show that for frequencies above 80 GHz the electrical losses in coplanar waveguide structures fabricated using nAg at 350 °C are lower than those found in conventional thick film Ag conductors consisting of micrometer-sized grains and fabricated at 850 °C. The improved electrical performance is attributed to the better packing of the silver nanoparticles resulting in lower surface roughness by a factor of 3. We discuss how the use of silver nanoparticles offers new routes to high frequency applications on temperature sensitive conformal substrates and in sub-THz metamaterials

Fetal fibronectin testing and pregnancy outcomes among Texas Medicaid patients at risk for preterm birth

OBJECTIVES: Fetal fibronectin (fFN) testing between the 24th and 34th weeks of pregnancy in patients with symptomatic preterm labor (PTL) helps assess the risk of spontaneous preterm birth (sPTB), yet the extent of its use is unknown. We assessed use of fFN testing among Texas Medicaid enrollees with symptomatic PTL and evaluated time to infant delivery and healthcare utilization/costs. STUDY DESIGN: Retrospective cohort study using medical and pharmacy claims for Texas Medicaid enrollees. METHODS: We identified pregnant women triaged through the emergency department (ED) and hospital labor-and-delivery units with symptomatic PTL between January 1, 2012, and May 31, 2015. Patients with fFN testing prior to delivery were propensity score matched 1:1 to patients without fFN testing. Primary outcomes included time to delivery from initial PTL encounter and all-cause maternal healthcare utilization and costs. RESULTS: A total of 29,553 women met the criteria for analysis, of whom 14% had a record of receiving fFN testing. Each matched cohort included 4098 patients. Compared with those who did not, patients who underwent fFN testing had significantly more clinical risk factors (mean [SD]: 1.7 [1.1] vs 1.1 [1.0]; P \u3c.0001) and were less likely to deliver during the initial hospital stay (odds ratio [OR], 0.539; 95% CI, 0.489-0.594), deliver ≤3 days following the hospital/ED encounter (OR, 0.499; 95% CI, 0.452-0.551); and receive their first PTL diagnosis during the initial hospital/ED encounter (OR, 0.598; 95% CI, 0.539-0.665). Patients who had an fFN test, compared with those who did not, had 17.5% higher total costs (P \u3c.0001) during the 5 months prior to delivery, but had gestation lengths 9.4 days longer (24.6 vs 15.2 days) than those without testing. CONCLUSIONS: Frequency of fFN testing was low in Texas Medicaid enrollees with symptomatic PTL. Patients with fFN testing had longer gestation periods and were less likely to deliver within ≤3 days of a hospital/ED encounter for PTL. These results support the role of fFN in screening for risk for sPTB among women with symptomatic PTL