Miracle-dz/UniFAR-FTUs huggingface dataset:
Obstetric analgesia and anaesthesia in SARS‐CoV‐2‐positive parturients across 10 maternity units in the north‐west of England: a retrospective cohort study

Since the start of the COVID‐19 pandemic, few studies have reported anaesthetic outcomes in parturients with SARS‐CoV‐2 infection. We reviewed the labour analgesic and anaesthetic interventions utilised in symptomatic and asymptomatic parturients who had a confirmed positive test for SARS‐CoV‐2 across 10 hospitals in the north‐west of England between 1 April 2020 and 31 May 2021. Primary outcomes analysed included the analgesic/anaesthetic technique utilised for labour and caesarean birth. Secondary outcomes included a comparison of maternal characteristics, caesarean birth rate, maternal critical care admission rate along with adverse composite neonatal outcomes. A positive SARS‐CoV‐2 test was recorded in 836 parturients with 263 (31.4%) reported to have symptoms of COVID‐19. Neuraxial labour analgesia was utilised in 104 (20.4%) of the 509 parturients who went on to have a vaginal birth. No differences in epidural analgesia rates were observed between symptomatic and asymptomatic parturients (OR 1.03, 95%CI 0.64–1.67; p = 0.90). The neuraxial anaesthesia rate in 310 parturients who underwent caesarean delivery was 94.2% (95%CI 90.6–96.0%). The rates of general anaesthesia were similar in symptomatic and asymptomatic parturients (6% vs. 5.7%; p = 0.52). Symptomatic parturients were more likely to be multiparous (OR 1.64, 95%CI 1.19–2.22; p = 0.002); of Asian ethnicity (OR 1.54, 1.04–2.28; p = 0.03); to deliver prematurely (OR 2.16, 95%CI 1.47–3.19; p = 0.001); have a higher caesarean birth rate (44.5% vs. 33.7%; OR 1.57, 95%CI 1.16–2.12; p = 0.008); and a higher critical care utilisation rate both pre‐ (8% vs. 0%, p = 0.001) and post‐delivery (11% vs. 3.5%; OR 3.43, 95%CI 1.83–6.52; p = 0.001). Eight neonates tested positive for SARS‐CoV‐2 while no differences in adverse composite neonatal outcomes were observed between those born to symptomatic and asymptomatic mothers (25.8% vs. 23.8%; OR 1.11, 95%CI 0.78–1.57; p = 0.55). In women with COVID‐19, non‐neuraxial analgesic regimens were commonly utilised for labour while neuraxial anaesthesia was employed for the majority of caesarean births. Symptomatic women with COVID‐19 are at increased risk of significant maternal morbidity including preterm birth, caesarean birth and peripartum critical care admission.
Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay. A lead optimization program focused on improving antiplasmodium potency, selectivity against human kinases, and absorption, distribution, metabolism, excretion, and toxicity properties and extended pharmacological profiles culminated in the identification of INE963 (1), which demonstrates potent cellular activity against Pf 3D7 (EC50 = 0.006 μM) and achieves “artemisinin-like” kill kinetics in vitro with a parasite clearance time of <24 h. A single dose of 30 mg/kg is fully curative in the Pf-humanized severe combined immunodeficient mouse model. INE963 (1) also exhibits a high barrier to resistance in drug selection studies and a long half-life (T1/2) across species. These properties suggest the significant potential for INE963 (1) to provide a curative therapy for uncomplicated malaria with short dosing regimens. For these reasons, INE963 (1) was progressed through GLP toxicology studies and is now undergoing Ph1 clinical trials.
Mulberry‐Leaves‐Derived Red‐Emissive Carbon Dots for Feeding Silkworms to Produce Brightly Fluorescent Silk

Fluorescent silk has promising applications in dazzling textiles, biological engineering, and medical products, but the natural Bombyx mori silk has almost no fluorescence. Here carbon dots (CDs) made from mulberry leaves are reported, which have a strong near‐infrared fluorescence with absolute quantum yield of 73% and a full width at half maximum of 20 nm. After feeding with such CDs, silkworms exhibit bright red fluorescence, grow healthily, cocoon normally, and turn to moths finally. The cocoons are pink in daylight and show bright red fluorescence under ultraviolet light. After breaking out of such cocoons, the red‐emissive moths can mate and lay fluorescent eggs which would hatch normally. The growth cycle of the second generation of the test silkworm is the same as that of the control group, which means such CDs have excellent biocompatiblility. Dissection and analyses on both the test silkworms and cocoons disclose the metabolic route of the CDs, that is, the fluorescent CDs are absorbed by silkworms from alimentary canals, then transferred to silk glands, and finally to cocoons, while those unabsorbed CDs are excreted with the feces. All experimental results confirm the excellent biocompatibility and fluorescence stability of such CDs.
Containing Attachment Concerns: Does Trait Mindfulness Buffer the Links between Attachment Insecurity and Maladaptive Sexual Motivations?

ABSTRACT Individuals reporting greater insecure attachment are more likely to report maladaptive sexual motivations, such as sex to avoid negative relational and personal outcomes (e.g., conflict). Despite the costs of such sexual motivations, research is less clear regarding what might buffer the extent to which attachment insecurities manifest in such motives. The current study examined whether trait mindfulness moderates the links between attachment insecurity and maladaptive sexual motives. Participants (N = 194) completed measures of trait mindfulness, general sexual motivations, and attachment. As predicted, the links between attachment anxiety and having sex to cope and affirm the self were eliminated among individuals reporting higher levels of the acting with awareness facet of trait mindfulness. No such buffering effects were seen for attachment avoidance. Instead, acting with awareness mindfulness appeared to increase the extent to which more avoidantly attached individuals reported coping and self-affirmation-based sexual motives. These findings contribute to knowledge regarding the potential utility and limits of mindfulness in relational and sexual contexts, perhaps suggesting that mindfulness may help anxiously attached individuals manage the extent to which attachment concerns manifest in maladaptive sexual motivations. Findings of the study may inform both theory regarding mindfulness in interpersonal functioning and how mindfulness interventions might be deployed in sex therapy contexts.
An International Survey on Utilization of Five Thyroid Nodule Risk Stratification Systems: A Needs Assessment with Future Implications.

BACKGROUND Multiple ultrasound-based risk stratification systems (RSSs) for thyroid nodules are used worldwide. Variations in structure, performance, and recommendations are confusing for physicians and patients and complicate management decisions. The goal of this study was to determine the factors that are associated with choice of RSS and barriers to RSS use. These results are intended to inform development of a universal international thyroid ultrasound RSS. METHODS An online survey with questions about usage of RSSs, ultrasound practice and volumes, training, specialty, practice type, and geographic region was made available to members of five professional societies via email. Subgroup analysis was performed to identify the factors that governed use of one or more of five leading RSSs: American Association of Clinical Endocrinology (AACE), American College of Endocrinology (ACE), and Associazione Medici Endocrinologi (AME) Medical Guidelines, American College of Radiology (ACR) Thyroid Imaging Reporting and Data System (ACR TI-RADS), American Thyroid Association (ATA) Guidelines, European Thyroid Association TIRADS (EU-TIRADS), and Korean Society of Thyroid Radiology/Korean Thyroid Association TIRADS (K-TIRADS). RESULTS There were 875 respondents from 52 countries (response rate not estimated due to overlapping society membership). More than seven specialties were represented, with most (538; 61.5%) in endocrinology. The choice of RSS was strongly associated with medical specialty and geographic region. Out of 692 respondents who indicated that their practice used an RSS, 213 (30.8%) used more than one. The specialties that were more likely to use multiple RSSs were surgery and others (40%), followed by endocrinology (33.0%), and radiology or nuclear medicine (17%) (p <0.001). Out of 271 (31.0%) respondents who indicated that they do not personally use an RSS, the majority (168; 62%) preferred to describe the specific sonographic characteristics/features that they believe are most relevant in a nodule. CONCLUSIONS Almost one-third of respondents indicated use of more than one RSS in practice, potentially leading to confusion, and a similar proportion reported not using a RSS for various reasons. A unified international system that addresses their concerns and simplifies risk classification of thyroid nodules may benefit practitioners and patients. This is particularly important as newer thyroid management options gain acceptance.
Differential Electrographic Signatures Generated by Mechanistically-Diverse Seizurogenic Compounds in the Larval Zebrafish Brain

Abstract We assessed similarities and differences in the electrographic signatures of local field potentials (LFPs) evoked by different pharmacological agents in zebrafish larvae. We then compared and contrasted these characteristics with what is known from electrophysiological studies of seizures and epilepsy in mammals, including humans. Ultimately, our aim was to phenotype neurophysiological features of drug-induced seizures in larval zebrafish for expanding knowledge on the translational potential of this valuable alternative to mammalian models. LFPs were recorded from the midbrain of 4-d-old zebrafish larvae exposed to a pharmacologically diverse panel of seizurogenic compounds, and the outputs of these recordings were assessed using frequency domain analysis. This included analysis of changes occurring within various spectral frequency bands of relevance to mammalian CNS circuit pathophysiology. From these analyses, there were clear differences in the frequency spectra of drug-exposed LFPs, relative to controls, many of which shared notable similarities with the signatures exhibited by mammalian CNS circuits. These similarities included the presence of specific frequency components comparable to those observed in mammalian studies of seizures and epilepsy. Collectively, the data presented provide important information to support the value of larval zebrafish as an alternative model for the study of seizures and epilepsy. These data also provide further insight into the electrophysiological characteristics of seizures generated in nonmammalian species by the action of neuroactive drugs.
Computational analysis of the optical response of ZnSe with d-orbital defects

The doping of wide band-gap semiconducting ZnSe by transition metal (TM) atoms finds applications from mid-infrared lasing, sensing, photoelectrochemical cells, to nonlinear optics. Yet understanding the response of these materials at the atomic and electronic level is lacking, particularly in comparing a range of TM dopants, which were studied primarily by phenomenological crystal-field theory. In this work, to investigate bulk ZnSe singly doped with first-row TM atoms, specifically Ti through Cu, we applied a first-principles approach and crystal-field theory to explain the origin of the infrared absorption. We show that the use of an appropriate exchange–correlation functional and a Hubbard U correction to account for electron correlation improved the determination of the electronic transitions in these systems. We outline an approach for the calculation of the crystal-field splitting from first-principles and find it useful in providing a measure of dopant effects, also in qualitative comparison to our experimental characterization for ZnSe doped with Fe, Cr, and Ni. Our calculated absorption spectra indicate absorption signatures in the mid-infrared range, while the absorption in the visible portion of the spectrum is attributed to the ZnSe host. Our calculations will potentially motivate further experimental exploration of TM-doped ZnSe. Finally, the methods used here provide a route towards computational high-throughput screening of TM dopants in III–V materials through a combination of the electronic band structure and crystal-field theory.
Comparison of FDA Table of Pharmacogenetic Associations and Clinical Pharmacogenetics Implementation Consortium guidelines

Abstract Purpose Healthcare professionals need a clear understanding of information about gene-drug interactions in order to make optimal use of pharmacogenetic (PGx) testing. In this report, we compare PGx information in the US Food and Drug Administration (FDA) Table of Pharmacogenetic Associations with information presented in Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines. Summary Information from CPIC guidelines and the FDA Table of Pharmacogenetic Associations do not have a high level of concordance. Many drugs mentioned in CPIC guidelines are not listed in the FDA table and vice versa, and the same gene-drug association and dosing recommendation was reported for only 5 of the 126 drugs included in either source. Furthermore, classification of drugs in specific sections of the FDA table does not correlate well with CPIC-assigned or provisionally assigned clinical actionability levels. The Pharmacogenomics Knowledge Base (PharmGKB) clinical annotation levels are generally high for drugs mentioned in CPIC guidelines. PharmGKB clinical annotation levels are often unassigned or are lower level for drugs listed on the FDA table but not in CPIC guidelines. These differences may be due in part to FDA having access to PGx information that is unavailable in published literature and/or because PGx classifications are based on criteria other than clinical actionability. Conclusion There are important differences between the PGx information presented in the FDA Table of Pharmacogenetic Associations and in CPIC guidelines. FDA and CPIC have different perspectives when evaluating PGx associations and use different approaches and information resources when considering clinical validity related to specific medicines. Understanding how information sources developed by each group differ and can be used together to form a holistic view of PGx may be helpful in increasing adoption of these information sources in practice.
Extracellular vesicle formation in Lactococcus lactis is stimulated by prophage‐encoded holin–lysin system

Gram‐positive bacterial extracellular membrane vesicles (EVs) have been drawing more attention in recent years. However, mechanistic insights are still lacking on how EVs are released through the cell walls in Gram‐positive bacteria. In this study, we characterized underlying mechanisms of EV production and provide evidence for a role of prophage activation in EV release using the Gram‐positive bacterium Lactococcus lactis as a model. By applying a standard EV isolation procedure, we observed the presence of EVs in the culture supernatant of a lysogenic L. lactis strain FM‐YL11, for which the prophage‐inducing condition led to an over 10‐fold increase in EV production in comparison with the non‐inducing condition. In contrast, the prophage‐encoded holin–lysin knockout mutant YL11ΔHLH and the prophage‐cured mutant FM‐YL12 produced constantly low levels of EVs. Under the prophage‐inducing condition, FM‐YL11 did not show massive cell lysis. Defective phage particles were found to be released in and associated with holin–lysin‐induced EVs from FM‐YL11, as demonstrated by transmission electron microscopic images, flow cytometry and proteomics analysis. Findings from this study further generalized the EV‐producing phenotype to Gram‐positive L. lactis, and provide additional insights into the EV production mechanism involving prophage‐encoded holin–lysin system. The knowledge on bacterial EV production can be applied to all Gram‐positive bacteria and other lactic acid bacteria with important roles in fermentations and probiotic formulations, to enable desired release and delivery of cellular components with nutritional values or probiotic effects.
R&D, Patents, and Productivity

Zvi Griliches, a world-renowned pioneer in the field of productivity growth, has compiled in a single volume his pathbreaking research on R&D and productivity. Griliches addresses the relationship between research and development (R&D) and productivity, one of the most complex yet vital issues in today's business world. Using econometric techniques, he establishes this connection and measures its magnitude for firm-, industry-, and economy-level data. Griliches began his studies of productivity growth during the 1950s, adding a variable of "knowledge stock" to traditional production function models, and his work has served as the point of departure for much of the research into R&D and productivity. This collection of essays documents both Griliches's distinguished career as well as the history of this line of thought. As inputs into production increasingly taking the form of "intellectual capital" and new technologies that are not as easily measured as traditional labor and capital, the methods Griliches has refined and applied to R&D become crucial to understanding today's economy.
Estimation of Breast Cancer Overdiagnosis in a U.S. Breast Screening Cohort

BACKGROUND Mammography screening can lead to overdiagnosis-that is, screen-detected breast cancer that would not have caused symptoms or signs in the remaining lifetime. There is no consensus about the frequency of breast cancer overdiagnosis. OBJECTIVE To estimate the rate of breast cancer overdiagnosis in contemporary mammography practice accounting for the detection of nonprogressive cancer. DESIGN Bayesian inference of the natural history of breast cancer using individual screening and diagnosis records, allowing for nonprogressive preclinical cancer. Combination of fitted natural history model with life-table data to predict the rate of overdiagnosis among screen-detected cancer under biennial screening. SETTING Breast Cancer Surveillance Consortium (BCSC) facilities. PARTICIPANTS Women aged 50 to 74 years at first mammography screen between 2000 and 2018. MEASUREMENTS Screening mammograms and screen-detected or interval breast cancer. RESULTS The cohort included 35 986 women, 82 677 mammograms, and 718 breast cancer diagnoses. Among all preclinical cancer cases, 4.5% (95% uncertainty interval [UI], 0.1% to 14.8%) were estimated to be nonprogressive. In a program of biennial screening from age 50 to 74 years, 15.4% (UI, 9.4% to 26.5%) of screen-detected cancer cases were estimated to be overdiagnosed, with 6.1% (UI, 0.2% to 20.1%) due to detecting indolent preclinical cancer and 9.3% (UI, 5.5% to 13.5%) due to detecting progressive preclinical cancer in women who would have died of an unrelated cause before clinical diagnosis. LIMITATIONS Exclusion of women with first mammography screen outside BCSC. CONCLUSION On the basis of an authoritative U.S. population data set, the analysis projected that among biennially screened women aged 50 to 74 years, about 1 in 7 cases of screen-detected cancer is overdiagnosed. This information clarifies the risk for breast cancer overdiagnosis in contemporary screening practice and should facilitate shared and informed decision making about mammography screening. PRIMARY FUNDING SOURCE National Cancer Institute.
Trends of perinatal mental health referrals and psychiatric admissions in Queensland

Background: Perinatal depression is often underdiagnosed; consequently, many women suffer perinatal depression without follow-up care. Screening for depressive symptoms during the perinatal period has been recommended in Australia to increase detection and follow-up of women suffering from depressive symptoms. Screening rates have gradually increased over the last decades in Australia. Objective: To explore trends in referrals of women to community mental health services during the perinatal period, and prenatal and postnatal admissions to psychiatric units, among those who gave birth in Queensland between 2009 and 2015. Method: Retrospective analyses of data from three linked state-wide administrative data collections. Trend analyses using adjusted Poisson regression models examined 426,242 births. Outcome variables included referrals to specialised mental health services; women admitted with a mood disorder during the second half of their pregnancy and during the first 3 months of the postnatal period; and women admitted with non-affective psychosis disorders during the second half of their pregnancy and during the first 3 months of the postnatal period. Results: We found an increase in mental health referrals during the perinatal period over time (adjusted incidence rate ratio, 1.07; 95% confidence interval, [1.06, 1.08]) and a decrease in admissions with mood disorders during the first 3 months of the postnatal period (adjusted incidence rate ratio, 0.95; 95% confidence interval, [0.94, 0.98]). We did not find any changes in rates of admission for other outcomes. Conclusion: Since the introduction of universal screening in Queensland, referrals for mental health care during the perinatal period have increased, while admissions for mood disorders in the first 3 months after delivery decreased.
Growth-rate-dependent and nutrient-specific gene expression resource allocation in fission yeast

During growth on nitrogen sources, growth-rate-correlated gene expression is a trade-off between the stress and growth programmes, whereas medium-specific gene expression reflects metabolic states. Cellular resources are limited and their relative allocation to gene expression programmes determines physiological states and global properties such as the growth rate. Here, we determined the importance of the growth rate in explaining relative changes in protein and mRNA levels in the simple eukaryote Schizosaccharomyces pombe grown on non-limiting nitrogen sources. Although expression of half of fission yeast genes was significantly correlated with the growth rate, this came alongside wide-spread nutrient-specific regulation. Proteome and transcriptome often showed coordinated regulation but with notable exceptions, such as metabolic enzymes. Genes positively correlated with growth rate participated in every level of protein production apart from RNA polymerase II–dependent transcription. Negatively correlated genes belonged mainly to the environmental stress response programme. Critically, metabolic enzymes, which represent ∼55–70% of the proteome by mass, showed mostly condition-specific regulation. In summary, we provide a rich account of resource allocation to gene expression in a simple eukaryote, advancing our basic understanding of the interplay between growth-rate-dependent and nutrient-specific gene expression.