Miracle-dz/UniFAR-FTUs huggingface dataset:
Estimation of fetal weight: a comparison of clinical and sonographic methods

Abstract Fetal weight estimation is important in the management of labour and delivery. This study aimed to compare the accuracy of the clinical and ultrasound methods of fetal weight estimation. This was a prospective study involving 110 term cephalic singleton pregnancies delivered within 24 hours of clinical fetal weight estimation using Johnson’s and Dare’s formulae and ultrasound estimation at a Tertiary hospital in Abakaliki, Nigeria. The data were analysed with Stata 11 software. The sonographic estimation within 10% of the actual birth weight (ABW) of 68.2% was significantly greater than the accuracy of Johnson’s (23.6%), Dare’s (26.4%), and the combined clinical formulae (27.1%). The clinical methods overestimated the fetal weight. Both methods showed a positive correlation with the ABW. In conclusion, the sonographic method had a better accuracy than the clinical methods. However, fetal weight overestimation by clinical methods warrants their usefulness in resource-poor settings such that the clinical determination of a normal weight foetus will exclude fear of complications from macrosomia. Impact statement What is already known on this subject? An accurate estimation of fetal weight is important in the management of labour and delivery. However, there is limited evidence that any of the available methods of fetal weight estimation is more accurate than the others. What do the results of this study add? This study showed that the clinical methods using Johnson’s and Dare’s formulae had a significantly higher mean percentage and absolute mean percentage error compared to the sonographic estimation of fetal weight. The sonographic estimation within 10% of actual birth weight (ABW) of 68.2% was significantly greater than that of Johnson’s and Dare’s formulae with 23.6% and 26.4%, respectively. All of the methods showed a positive correlation with the ABW. What are the implications of these findings for clinical practice and/or further research? This implies that the sonographic method has a better accuracy than the clinical methods in estimating the fetal weight. However, the overestimation of fetal weight by the clinical methods warrants their usefulness in resource-poor settings such that the clinical determination of a normal weight foetus will exclude the fear of complications from macrosomia.
Histaminergic transmission slows progression of amyotrophic lateral sclerosis

Histamine is an immune modulator, neuroprotective, and remyelinating agent, beneficially acting on skeletal muscles and promoting anti‐inflammatory features in amyotrophic lateral sclerosis (ALS) microglia. Drugs potentiating the endogenous release of histamine are in trial for neurological diseases, with a role not systematically investigated in ALS. Here, we examine histamine pathway associations in ALS patients and the efficacy of a histamine‐mediated therapeutic strategy in ALS mice.
Prognostic value of circulating tumour cells in limited-stage small-cell lung cancer: analysis of the concurrent once-daily versus twice-daily radiotherapy (CONVERT) randomised controlled trial

Abstract Background The clinical significance of circulating tumour cells (CTCs) in limited-stage small-cell lung cancer (LS-SCLC) is not well defined. We report a planned exploratory analysis of the prevalence and prognostic value of CTCs in LS-SCLC patients enrolled within the phase III randomised CONVERT (concurrent once-daily versus twice-daily chemoradiotherapy) trial. Patients and methods Baseline blood samples were enumerated for CTCs using CellSearch in 75 patients with LS-SCLC who were enrolled in the CONVERT trial and randomised between twice- and once-daily concurrent chemoradiation. Standard statistical methods were used for correlations of CTCs with clinical factors. Log-rank test and Cox regression analyses were applied to establish the associations of 2, 15 and 50 CTC thresholds with progression-free survival (PFS) and overall survival (OS). An optimal CTC count threshold for LS-SCLC was established. Results CTCs were detected in 60% (45/75) of patients (range 0–3750). CTC count thresholds of 2, 15 and 50 CTCs all significantly correlate with PFS and OS. An optimal CTC count threshold in LS-SCLC was established at 15 CTCs, defining ‘favourable’ and ‘unfavourable’ prognostic risk groups. The median OS in <15 versus ≥15 CTCs was 26.7 versus 5.9 m (P = 0.001). The presence of ≥15 CTCs at baseline independently predicted ≤1 year survival in 70% and ≤2 years survival in 100% of patients. Conclusion We report the prognostic value of baseline CTC count in an exclusive LS-SCLC population at thresholds of 2, 15 and 50 CTCs. Specific to LS-SCLC, ≥15 CTCs was associated with worse PFS and OS independent of all other factors and predicted ≤2 years survival. These results may improve disease stratification in future clinical trial designs and aid clinical decision making. Trial registration ClinicalTrials.gov identifier: NCT00433563.
EditR: A Method to Quantify Base Editing from Sanger Sequencing

Abstract CRISPR-Cas9-Cytidine deaminase fusion enzymes—termed “base editors”—allow targeted editing of genomic deoxycytidine to deoxythymidine (C:G→T:A) without the need for double-stranded break induction. Base editors represent a paradigm shift in gene editing technology due to their unprecedented efficiency to mediate targeted, single-base conversion. However, current analysis of base editing outcomes rely on methods that are either imprecise or expensive and time-consuming. To overcome these limitations, we developed a simple, cost-effective, and accurate program to measure base editing efficiency from fluorescence-based Sanger sequencing, termed “EditR. ” We provide EditR as a free online tool or downloadable desktop application requiring a single Sanger sequencing file and guide RNA sequence. EditR is more accurate than enzymatic assays, and provides added insight to the position, type, and efficiency of base editing. Furthermore, EditR is likely amenable to quantify base editing from the recently developed adenosine deaminase base editors that act on either DNA (adenosine deaminase base editors [ABEs]) or RNA (REPAIRs) (catalyzes A:T→G:C). Collectively, we demonstrate that EditR is a robust, inexpensive tool that will facilitate the broad application of base editing technology, thereby fostering further innovation in this burgeoning field.
Cord Blood Vitamin D Levels and Early Childhood Blood Pressure: The Healthy Start Study

Background Vitamin D deficiency is associated with cardiovascular events among adults, but it is unclear whether early‐life vitamin D deficiency influences cardiovascular risk factors in children. Methods and Results We measured total and bioavailable 25‐dihydroxyvitamin D (25OHD) in cord blood and in blood from 4‐ to 6‐year‐old children, and we assessed cardiovascular risk factors (blood pressure, arterial stiffness, body size, and adiposity) at 4 to 6 years. We tested for racial/ethnic differences in total and bioavailable 25OHD (n=715) and modeled the adjusted association between cord blood 25OHD and childhood cardiovascular risk factors (n=171). We observed racial/ethnic differences in total and bioavailable 25OHD levels in both cord and child blood samples (all P<0.05). Each 25‐nmol/L increase in cord blood total 25OHD was associated with a 2.5–mm Hg (SE 0.8) decrease in systolic blood pressure (P=0.002) and a 1.7–mm Hg (SE 0.6) decrease in diastolic blood pressure (P=0.01), independent of childhood 25OHD levels, race/ethnicity, and other covariates. There was no association between cord blood total 25OHD and any other cardiovascular risk factors. Cord blood levels of bioavailable and free 25OHD were not associated with any cardiovascular risk factor in childhood. Conclusions In this diverse prebirth cohort, we observed lower systolic and diastolic blood pressure among children with higher total 25OHD levels at birth. Our findings suggest that intrauterine exposure to vitamin D may contribute to early‐life programming of offspring blood pressure. Intervention studies are needed to determine whether increasing fetal vitamin D exposure can reduce the risk of elevated blood pressure in childhood.
PD‐(L)1 inhibitors vs. chemotherapy vs. their combination in front‐line treatment for NSCLC: An indirect comparison

We comprehensively compared the therapeutic effects and safety of PD‐1/L1 antibodies (I), chemotherapy (C) or their combination (I + C) as first‐line treatments for advanced NSCLC. Online databases were searched to identify RCTs. Survival outcomes and safety events were pooled by indirect treatment comparison. Main subgroup analyses were conducted according to PD‐L1 expression. A total of 11 RCTs involving 6,731 patients were included. Overall, PD‐1/L1 inhibitors showed no difference to chemotherapy in PFS (HR 0.90, 0.65–1.24) and OS (HR 0.84, 0.64–1.09), while I + C was superior to chemotherapy both in PFS (HR 0.64, 0.58–0.71) and OS (HR 0.74, 0.62–0.89). I + C also showed advantages over PD‐1/L1 in PFS (HR 0.71, 0.51–0.99) but not OS (HR 0.88, 0.64–1.22). In the PD‐L1 < 1% subgroup, I + C was beneficial both in OS (HR 0.78, 0.67–0.90) and PFS (HR 0.72, 0.65–0.80) than chemotherapy. In PD‐L1 ≥ 50% population, PD‐1/L1 had longer OS than chemotherapy (HR 0.71, 0.60–0.84); I + C also had longer OS (HR 0.61, 0.49–0.77) and PFS (HR 0.41,0.34–0.49) than chemotherapy. In indirect analysis (PD‐L1 ≥ 50%), I + C was superior to PD‐1/L1 in terms of PFS (HR 0.54, 0.35–0.82), but not OS (HR 0.86, 0.65–1.14). Both treatment‐related and immune‐mediated adverse events occurred most frequently in the combination therapy group. We suggest that a combination regimen is preferable as first‐line treatment for NSCLC patients with different PD‐L1 expression, in the meanwhile, in cautious of side effects.
Pharmacokinetics and bioequivalence of two different 20 mg olmesartan tablets: A randomized, single-dose, two-period crossover study in healthy Korean male volunteers

Olmesartan is an angiotensin receptor blocker (ARB) and is widely used in clinical practice to treat hypertension. To compare the pharmacokinetic (PK) parameters and tolerability of two oral formulations of olmesartan (test drug: OMETAN® 20 mg tablet, reference drug: OLMETEC® 20 mg tablet) and assess their bioequivalence, a randomized, single dose, two-treatment crossover clinical study was conducted. At each period, 40 subjects received the test drug or the reference drug. Blood samples were collected at pre-dose and up to 48 h after study drug administration of each period. Plasma concentrations of olmesartan were measured using liquid chromatography-tandem mass spectrometry. To evaluate PK profiles, maximum plasma concentration (C max) and area under the concentration-time curve from zero to last measurable time (AUClast) were estimated using a noncompartmental method. Tolerability was evaluated based on the incidence of adverse events, vital signs, electrocardiograms, and laboratory tests. A total of 39 subjects completed the study. The geometric mean ratio and 90% confidence intervals (CI) of test drug to reference drug were 1.027 (0.969–1.088) for Cmax and 1.014 (0.957–1.074) for AUClast, respectively. There were no serious ad verse events and both formulations of olmesartan were well tolerated. The OMETAN 20 mg tablet was judged to be bioequivalent to the OLMETEC 20 mg tablet.
Effects of the ABCB1 and ABCG2 polymorphisms on the pharmacokinetics of afatinib in healthy Chinese volunteers

Abstract 1. Afatinib is an oral, selective tyrosine kinase inhibitor (TKI) primarily transported by P-glycoprotein (MDR1, gene code ABCB1) and breast cancer resistance protein (BCRP, gene code ABCG2). In the present study, the effects of ABCB1 and ABCG2 genetic polymorphisms on the pharmacokinetics of afatinib in healthy Chinese were investigated. 2. Blood samples from 24 healthy participants who received afatinib were used for genotyping ABCB1 (1236C>T, 2677G > T/A, 3435C>T) and ABCG2 (34G>A, 421C>A) polymorphisms. Subsequently, the association between afatinib plasma concentrations and target single-nucleotide polymorphisms (SNPs) was analyzed. 3. Among the five polymorphisms, plasma concentrations of afatinib in healthy subjects with ABCB1 1236CC–3435CC were remarkably higher than in other genotype subjects. No significant differences of afatinib exposure were found between the ABCG2 wild-type and heterozygous groups. 4. The ABCB1 genetic polymorphism influenced the plasma exposure of afatinib, and gene testing before drug administration may be useful for clinically individualized use of afatinib. Our data suggest the usefulness of afatinib pharmacogenetics in treatment optimization.
Clinicians’ Concerns About Mobile Ecological Momentary Assessment Tools Designed for Emerging Psychiatric Problems: Prospective Acceptability Assessment of the MEmind App

Background Many mental disorders are preceded by a prodromal phase consisting of various attenuated and unspecific symptoms and functional impairment. Electronic health records are generally used to capture these symptoms during medical consultation. Internet and mobile technologies provide the opportunity to monitor symptoms emerging in patients’ environments using ecological momentary assessment techniques to support preventive therapeutic decision making. Objective The objective of this study was to assess the acceptability of a Web-based app designed to collect medical data during appointments and provide ecological momentary assessment features. Methods We recruited clinicians at 4 community psychiatry departments in France to participate. They used the app to assess patients and to collect data after viewing a video of a young patient’s emerging psychiatric consultation. We then asked them to answer a short anonymous self-administered questionnaire that evaluated their experience, the acceptability of the app, and their habit of using new technologies. Results Of 24 practitioners invited, 21 (88%) agreed to participate. Most of them were between 25 and 45 years old, and greater age was not associated with poorer acceptability. Most of the practitioners regularly used new technologies, and 95% (20/21) connected daily to the internet, with 70% (15/21) connecting 3 times a day or more. However, only 57% (12/21) reported feeling comfortable with computers. Of the clinicians, 86% (18/21) would recommend the tool to their colleagues and 67% (14/21) stated that they would be interested in daily use of the app. Most of the clinicians (16/21, 76%) found the interface easy to use and useful. However, several clinicians noted the lack of readability (8/21, 38%) and the need to improve ergonometric features (4/21, 19%), in particular to facilitate browsing through various subsections. Some participants (5/21, 24%) were concerned about the storage of medical data and most of them (11/21, 52%) seemed to be uncomfortable with this. Conclusions We describe the first step of the development of a Web app combining an electronic health record and ecological momentary assessment features. This online tool offers the possibility to assess patients and to integrate medical data easily into face-to-face conditions. The acceptability of this app supports the feasibility of its broader implementation. This app could help to standardize assessment and to build up a strong database. Used in conjunction with robust data mining analytic techniques, such a database would allow exploration of risk factors, patterns of symptom evolution, and identification of distinct risk subgroups.
Evaluation of the Antimicrobial Activity of a Formulation Containing Ascorbic Acid and Eudragit FS 30D Microparticles for the Controlled Release of a Curcumin–Boric Acid Solid Dispersion in Turkey Poults Infected with Salmonella enteritidis: A Therapeutic Model

The selection of components within a formulation or for treatment must stop being arbitrary and must be focused on scientific evidence that supports the inclusion of each one. Therefore, the objective of the present study was to obtain a formulation based on ascorbic acid (AA) and Eudragit FS 30D microparticles containing curcumin–boric acid (CUR–BA) considering interaction studies between the active components carried out via Fourier transform infrared spectrometry (FTIR) and differential scanning calorimetry (DSC) to minimize antagonistic effects, and comprehensively and effectively treat turkey poults infected with Salmonella enteritidis (S. enteritidis). The DSC and FTIR studies clearly demonstrated the interactions between AA, BA, and CUR. Consequently, the combination of AA with CUR and/or BA should be avoided, but not CUR and BA. Furthermore, the Eudragit FS 30D microparticles containing CUR–BA (SD CUR–BA MP) showed a limited release of CUR–BA in an acidic medium, but they were released at a pH 6.8–7.0, which reduced the interactions between CUR–BA and AA. Finally, in the S. enteritidis infection model, turkey poults treated with the combination of AA and SD CUR–BA MP presented lower counts of S. enteritidis in cecal tonsils after 10 days of treatment. These results pointed out that the use of an adequate combination of AA and CUR–BA as an integral treatment of S. enteritidis infections could be a viable option to replace the indiscriminate use of antibiotics.
Polarized Two-Photon Absorption and Heterogeneous Fluorescence Dynamics in NAD(P)H

Two-photon absorption (2PA) finds widespread application in biological systems, which frequently exhibit heterogeneous fluorescence decay dynamics corresponding to multiple species or environments. By combining polarized 2PA with time-resolved fluorescence intensity and anisotropy decay measurements, we show how the two-photon transition tensors for the components of a heterogeneous population can be separately determined, allowing structural differences between the two fluorescent states of the redox cofactor NAD(P)H to be identified. The results support the view that the two states correspond to alternate configurations of the nicotinamide ring, rather than folded and extended conformations of the entire molecule.
Blood Biomarkers for Traumatic Brain Injury: A Quantitative Assessment of Diagnostic and Prognostic Accuracy

Blood biomarkers have been explored for their potential to provide objective measures in the assessment of traumatic brain injury (TBI). However, it is not clear which biomarkers are best for diagnosis and prognosis in different severities of TBI. Here, we compare existing studies on the discriminative abilities of serum biomarkers for four commonly studied clinical situations: detecting concussion, predicting intracranial damage after mild TBI (mTBI), predicting delayed recovery after mTBI, and predicting adverse outcome after severe TBI (sTBI). We conducted a literature search of publications on biomarkers in TBI published up until July 2018. Operating characteristics were pooled for each biomarker for comparison. For detecting concussion, 4 biomarker panels and creatine kinase B type had excellent discriminative ability. For detecting intracranial injury and the need for a head CT scan after mTBI, 2 biomarker panels, and hyperphosphorylated tau had excellent operating characteristics. For predicting delayed recovery after mTBI, top candidates included calpain-derived αII-spectrin N-terminal fragment, tau A, neurofilament light, and ghrelin. For predicting adverse outcome following sTBI, no biomarker had excellent performance, but several had good performance, including markers of coagulation and inflammation, structural proteins in the brain, and proteins involved in homeostasis. The highest-performing biomarkers in each of these categories may provide insight into the pathophysiologies underlying mild and severe TBI. With further study, these biomarkers have the potential to be used alongside clinical and radiological data to improve TBI diagnostics, prognostics, and evidence-based medical management.
Measuring the Delay Time Distribution of Binary Neutron Stars. II. Using the Redshift Distribution from Third-generation Gravitational-wave Detectors Network

We investigate the ability of current and third-generation gravitational wave (GW) detectors to determine the delay time distribution (DTD) of binary neutron stars (BNSs) through a direct measurement of the BNS merger rate as a function of redshift. We assume that the DTD follows a power-law distribution with a slope Γ and a minimum merger time tmin, and also allow the overall BNS formation efficiency per unit stellar mass to vary. By convolving the DTD and mass efficiency with the cosmic star formation history, and then with the GW detector capabilities, we explore two relevant regimes. First, for the current generation of GW detectors, which are only sensitive to the local universe but can lead to precise redshift determinations via the identification of electromagnetic counterparts and host galaxies, we show that the DTD parameters are strongly degenerate with the unknown mass efficiency and therefore cannot be determined uniquely. Second, for third-generation detectors such as Einstein Telescope and Cosmic Explorer, which will detect BNS mergers at cosmological distances but with a redshift uncertainty inherent to GW-only detections (δ(z)/z ≈ 0.1z), we show that the DTD and mass efficiency can be well constrained to better than 10% with a year of observations. This long-term approach to determining the DTD through a direct mapping of the BNS merger redshift distribution will be supplemented by more near-term studies of the DTD through the properties of BNS merger host galaxies at z ≈ 0.
Energy-Efficient Resource Allocation in OFDMA Networks

The widespread application of multimedia wireless services and requirement of ubiquitous access have triggered rapidly booming energy consumption at both the base station side. Hence, energy-efficient design in wireless networks is very important and is becoming an inevitable trend. In this paper, we study energy-efficient resource allocation in downlink cellular OFDMA networks. For the downlink transmission, the weighted energy efficiency (EE) is maximized under certain prescribed per-user quality- of-service (QoS) requirements. We first obtain the optimal solution then propose a suboptimal approach by exploring the inherent structure and property of the energy-efficient design to reduce complexity. Simulation results show that the energy-efficient design greatly improves EE compared with that of the conventional spectral-efficient design and our low- complexity suboptimal approaches can achieve promising tradeoff between performance and complexity.
A mathematical model for Alzheimer’s disease: An approach via stochastic homogenization of the Smoluchowski equation

In this note, we apply the theory of stochastic homogenization to find the asymptotic behavior of the solution of a set of Smoluchowski's coagulation-diffusion equations with non-homogeneous Neumann boundary conditions. This system is meant to model the aggregation and diffusion of $\beta$-amyloid peptide (A$\beta$) in the cerebral tissue, a process associated with the development of Alzheimer's disease. In contrast to the approach used in our previous works, in the present paper we account for the non-periodicity of the cellular structure of the brain by assuming a stochastic model for the spatial distribution of neurons. Further, we consider non-periodic random diffusion coefficients for the amyloid aggregates and a random production of A$\beta$ in the monomeric form at the level of neuronal membranes.