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The human gut microbiome represents an extended “second genome” harbouring about 1015 microbes containing >100 times the number of genes as the host. States of health and disease are largely mediated by host–microbial metabolic interplay, and the microbiome composition also underlies the differential responses to chemotherapeutic agents between people. Chemical information will be the key to tackle this complexity and discover specific gut microbiome metabolism for creating more personalised interventions. Additionally, rising antibiotic resistance and growing awareness of gut microbiome effects are creating a need for non-microbicidal therapeutic interventions. We classify chemical interventions for the gut microbiome into categories like molecular decoys, bacterial conjugation inhibitors, colonisation resistance-stimulating molecules, “prebiotics” to promote the growth of beneficial microbes, and inhibitors of specific gut microbial enzymes. Moreover, small molecule probes, including click chemistry probes, artificial substrates for assaying gut bacterial enzymes and receptor agonists/antagonists, which engage host receptors interacting with the microbiome, are some other promising developments in the expanding chemical toolkit for probing and modulating the gut microbiome. This review explicitly excludes “biologics” such as probiotics, bacteriophages, and CRISPR to concentrate on chemistry and chemical tools like chemoproteomics in the gut-microbiome context.
Clinical trials often struggle to recruit enough participants, with only 10% of eligible patients enrolling. This is concerning for conditions like stroke, where timely decision-making is crucial. Frontline clinicians typically screen patients manually, but this approach can be overwhelming and lead to many eligible patients being overlooked.
Methods:
To address the problem of efficient and inclusive screening for trials, we developed a matching algorithm using imaging and clinical variables gathered as part of the AcT trial (NCT03889249) to automatically screen patients by matching these variables with the trials’ inclusion and exclusion criteria using rule-based logic. We then used the algorithm to identify patients who could have been enrolled in six trials: EASI-TOC (NCT04261478), CATIS-ICAD (NCT04142125), CONVINCE (NCT02898610), TEMPO-2 (NCT02398656), ESCAPE-MEVO (NCT05151172), and ENDOLOW (NCT04167527). To evaluate our algorithm, we compared our findings to the number of enrollments achieved without using a matching algorithm. The algorithm’s performance was validated by comparing results with ground truth from a manual review of two clinicians. The algorithm’s ability to reduce screening time was assessed by comparing it with the average time used by study clinicians.
Results:
The algorithm identified more potentially eligible study candidates than the number of participants enrolled. It also showed over 90% sensitivity and specificity for all trials, and reducing screening time by over 100-fold.
Conclusions:
Automated matching algorithms can help clinicians quickly identify eligible patients and reduce resources needed for enrolment. Additionally, the algorithm can be modified for use in other trials and diseases.
Background: After a transient ischemic attack (TIA) or minor stroke, the long-term risk of subsequent stroke is uncertain. Methods: Electronic databases were searched for observational studies reporting subsequent stroke during a minimum follow-up of 1 year in patients with TIA or minor stroke. Unpublished data on number of stroke events and exact person-time at risk contributed by all patients during discrete time intervals of follow-up were requested from the authors of included studies. This information was used to calculate the incidence of stroke in individual studies, and results across studies were pooled using random-effects meta-analysis. Results: Fifteen independent cohorts involving 129794 patients were included in the analysis. The pooled incidence rate of subsequent stroke per 100 person-years was 6.4 events in the first year and 2.0 events in the second through tenth years, with cumulative incidences of 14% at 5 years and 21% at 10 years. Based on 10 studies with information available on fatal stroke, the pooled case fatality rate of subsequent stroke was 9.5% (95% CI, 5.9 – 13.8). Conclusions: One in five patients is expected to experience a subsequent stroke within 10 years after a TIA or minor stroke, with every tenth patient expected to die from their subsequent stroke.
Robust feature selection is vital for creating reliable and interpretable machine-learning (ML) models. When designing statistical prediction models in cases where domain knowledge is limited and underlying interactions are unknown, choosing the optimal set of features is often difficult. To mitigate this issue, we introduce a multidata (M) causal feature selection approach that simultaneously processes an ensemble of time series datasets and produces a single set of causal drivers. This approach uses the causal discovery algorithms PC$ {}_1 $ or PCMCI that are implemented in the Tigramite Python package. These algorithms utilize conditional independence tests to infer parts of the causal graph. Our causal feature selection approach filters out causally spurious links before passing the remaining causal features as inputs to ML models (multiple linear regression and random forest) that predict the targets. We apply our framework to the statistical intensity prediction of Western Pacific tropical cyclones (TCs), for which it is often difficult to accurately choose drivers and their dimensionality reduction (time lags, vertical levels, and area-averaging). Using more stringent significance thresholds in the conditional independence tests helps eliminate spurious causal relationships, thus helping the ML model generalize better to unseen TC cases. M-PC$ {}_1 $ with a reduced number of features outperforms M-PCMCI, noncausal ML, and other feature selection methods (lagged correlation and random), even slightly outperforming feature selection based on explainable artificial intelligence. The optimal causal drivers obtained from our causal feature selection help improve our understanding of underlying relationships and suggest new potential drivers of TC intensification.
Background: Some patients do poorly despite small infarcts after endovascular therapy(EVT) whilst others with large infarcts do well. We validated exploratory findings from the ESCAPE trial regarding factors associated with such discrepancies, in the ESCAPE-NA1 trial(NCT02930018). Methods: We identified “discrepant cases” with modified Rankin Scale(mRS)≥3 despite small follow-up infarct volume(FIV≤25th-percentile) on 24-hour CT/MRI or mRS≤2 despite large FIV(volume≥75th-percentile). We compared area-under-the-curve(AUC) of pre-specified logistic models containing (a)pre-treatment factors(age/cancer/vascular risk-factors) and (b)treatment-related/post-treatment factors(serious adverse events/SAEs) in identifying small-FIV/mRS≥3 and large-FIV/mRS≤2, with stepwise regression-derived models. Results: Among 1,091 patients, 42/287(14.6%) with FIV≤7mL(25th-percentile) had mRS≥3; 65/275(23.6%) with FIV≥92mL(75th-percentile) had mRS≤2. Pre-specified pre-treatment factors(age/cancer/vascular risk-factors) were associated with FIV≤7mL/mRS≥3; stepwise models selected similar variables(similar AUCs:0.92-0.93,p=0.42). SAEs(infarct-in-new-territory/recurrent stroke/pneumonia/heart failure) were strongly associated with FIV≤7mL/mRS≥3; stepwise models also identified onset-to-needle time and hemoglobin(24-hours) as treatment-related/post-treatment factors(similar AUCs:0.92-0.94,p=0.14). Younger age was associated with FIV≥92mL/mRS≤2; stepwise models also selected diabetes absence and baseline hemoglobin(similar AUCs:0.76-0.77,p=0.82). Absence of SAEs(stroke progression/pneumonia/intracerebral hemorrhage) was strongly associated with FIV≥92mL/mRS≤2; stepwise models also identified 24-hour hemoglobin, glucose, and BP(similar AUCs:0.79-0.80,p=0.030). Conclusions: FIV-mRS discrepancies are associated with pre-treatment factors like age/comorbidities; and post-treatment complications related to stroke evolution, secondary prevention, and post-acute care quality. Optimizing thrombolysis speed, BP, glucose, and hemoglobin are modifiable factors meriting further study.
Children with exposure to coronavirus disease 2019 in recent times (asymptomatic or symptomatic infection) approaching congenital heart surgery programme are in increasing numbers. Understanding outcomes of such children will help risk-stratify and guide optimisation prior to congenital heart surgery.
Objective:
The objective of the present study was to determine whether convalescent coronavirus disease 2019 children undergoing congenital heart surgery have any worse mortality or post-operative outcomes.
Design:
Consecutive children undergoing congenital heart surgery from Oct 2020 to May 2021 were enrolled after testing for reverse transcription-polymerase chain reaction or rapid antigen test and immunoglobulin G antibody prior to surgery. Convalescent coronavirus disease 2019 was defined in any asymptomatic patient positive for immunoglobulin G antibodies and negative for reverse transcription-polymerase chain reaction or rapid antigen test anytime 6 weeks prior to surgery. Control patients were negative for any of the three tests. Mortality and post-operative outcomes were compared among the groups.
Results:
One thousand one hundred and twenty-nine consecutive congenital heart surgeries were stratified as convalescence and control. Coronavirus disease 2019 Convalescent (n = 349) and coronavirus disease 2019 control (n = 780) groups were comparable for all demographic and clinical factors except younger and smaller kids in control. Convalescent children had no higher mortality, ventilation duration, ICU and hospital stay, no higher support with extracorporeal membrane oxygenation, high flow nasal cannula, no higher need for re-intubations, re-admissions, and no higher infections as central line-associated bloodstream infection, sternal site infection, and ventilator-associated pneumonia on comparison with coronavirus disease 2019 control children.
Conclusions:
Convalescent coronavirus disease 2019 does not have any unfavourable outcomes as compared to coronavirus disease 2019 control children. Positive immunoglobulin G antibody screening prior to surgery is suggestive of convalescence and supports comparable outcomes on par with control peers.
We prove that the annihilating-ideal graph of a commutative semigroup with unity is, in general, not weakly perfect. This settles the conjecture of DeMeyer and Schneider [‘The annihilating-ideal graph of commutative semigroups’, J. Algebra469 (2017), 402–420]. Further, we prove that the zero-divisor graphs of semigroups with respect to semiprime ideals are weakly perfect. This enables us to produce a large class of examples of weakly perfect zero-divisor graphs from a fixed semigroup by choosing different semiprime ideals.
Cerebrospinal fluid rhinorrhoea takes place when there is a breakdown of the barriers separating the nasal cavity from the subarachnoid space. The aim of this study was to assess the surgical outcomes of endoscopic transnasal cerebrospinal fluid leak repair with and without fibrin glue.
Method
There were 43 patients with cerebrospinal fluid rhinorrhoea who underwent surgery for cerebrospinal fluid leak repair between 2014 and 2018. Patients were divided into group A, where fibrin glue was used, and group B, where fibrin glue was not used.
Results
It was found that 74.4 per cent of cases were due to spontaneous cerebrospinal fluid leak. The most common site of a leak was the cribriform plate (65 per cent). There was a success rate of 96.1 per cent (25 of 26) in group A and 83 per cent (15 of 17) in group B. There was no statistically significant difference between the results of the two groups (chi-square test: p = 0.31).
Conclusion
There was no statistically significant difference in the results of cerebrospinal fluid leak repair with and without fibrin glue.
Conventional planar manipulators have their links in a single plane. Increasing payload at the end effector/mobile platform can induce high stress in the links due to the cantilever nature of links. Thus, it limits the total vertical load that can be applied on the mobile platform. In contrast to the links in conventional planar parallel mechanisms, non-planar links are proposed in this paper, that is, links are made inclined to the horizontal plane and non-planar legs are constructed. Though the links are made non-planar, the end effectors’ planar motion is retained. For studying the application of such non-planar links in planar manipulators, new models of inertia, stiffness and leg dynamics have to be developed. In this article, these models are developed by the static analysis of the planar manipulators with non-planar links, and the performance is compared with the corresponding conventional planar manipulators.
This paper follows a recent article of Nambiar et al. (J. Fluid Mech., vol. 812, 2017, pp. 41–64) on the linear rheological response of a dilute bacterial suspension (e.g. E. coli) to impulsive starting and stopping of simple shear flow. Here, we analyse the time dependent nonlinear rheology for a pair of linear flows – simple shear (a canonical weak flow) and uniaxial extension (a canonical strong flow), again in response to impulsive initiation and cessation. The rheology is governed by the bacterium orientation distribution which satisfies a kinetic equation that includes rotation by the imposed flow, and relaxation to isotropy via rotary diffusion and tumbling. The relevant dimensionless parameters are the Péclet number $Pe\equiv \dot{\unicode[STIX]{x1D6FE}}\unicode[STIX]{x1D70F}$, which dictates the importance of flow-induced orientation anisotropy, and $\unicode[STIX]{x1D70F}D_{r}$, which quantifies the relative importance of the two intrinsic orientation decorrelation mechanisms (tumbling and rotary diffusion). Here, $\unicode[STIX]{x1D70F}$ is the mean run duration of a bacterium that exhibits a run-and-tumble dynamics, $D_{r}$ is the intrinsic rotary diffusivity of the bacterium and $\dot{\unicode[STIX]{x1D6FE}}$ is the characteristic magnitude of the imposed velocity gradient. The solution of the kinetic equation is obtained numerically using a spectral Galerkin method, that yields the rheological properties (the shear viscosity, the first and second normal stress differences for simple shear, and the extensional viscosity for uniaxial extension) over the entire range of $Pe$. For simple shear, we find that the stress relaxation predicted by our analysis at small $Pe$ is in good agreement with the experimental observations of Lopez et al. (Phys. Rev. Lett., vol. 115, 2015, 028301). However, the analysis at large $Pe$ yields relaxations that are qualitatively different. Upon step initiation of shear, the rheological response in the experiments corresponds to a transition from a nearly isotropic suspension of active swimmers at small $Pe$, to an apparently (nearly) isotropic suspension of passive rods at large $Pe$. In contrast, the computations yield the expected transition to a nearly flow-aligned suspension of passive rigid rods at high $Pe$. We probe this active–passive transition systematically, complementing the numerical solution with analytical solutions obtained from perturbation expansions about appropriate base states. Our study suggests courses for future experimental and analytical studies that will help understand relaxation phenomena in active suspensions.
In the present study, hot deformation behavior of a FCC high-entropy alloy CoCuFeMnNi has been investigated to explore the stress–strain response for a wide range of temperatures and strain rates. The deformation response has been examined by plotting a processing map and examining the evolution of microstructure and texture in each of the temperature–strain rate domain. Hot compression tests were carried out in the temperature range 850–1050 °C at strain rates varying from 0.001 s−1 to 10 s−1. Stress–strain curves indicate characteristic softening behavior due to dynamic recrystallization (DRX). DRX has been observed along grain boundaries, shear bands, as well as in the interior of deformed grains. The size of dynamically recrystallized grains shows a strong dependence on deformation temperature and increases with temperature. A high degree of twin formation takes place in the DRX grains evolved inside the shear bands, and the extent of twinning decreases at high temperatures. The optimal processing window has been estimated based on strain rate sensitivity and has been validated with detailed analyses of microstructure and texture. The best region for thermo-mechanical processing has been identified as in the temperature range 850–950 °C at strain rate 10−1 s−1.
Eight ruminally-fistulated wethers were used to examine the temporal effects of afternoon (PM; 1600h) v. morning (AM; 0800 h) allocation of fresh spring herbage from a perennial ryegrass (Lolium perenne L.)-based pasture on fermentation and microbial community dynamics. Herbage chemical composition was minimally affected by time of allocation, but daily mean ammonia concentrations were greater for the PM group. The 24-h pattern of ruminal fermentation (i.e. time of sampling relative to time of allocation), however, varied considerably for all fermentation variables (P⩽0.001). Most notably amongst ruminal fermentation characteristics, ammonia concentrations showed a substantial temporal variation; concentrations of ammonia were 1.7-, 2.0- and 2.2-fold greater in rumens of PM wethers at 4, 6 and 8h after allocation, respectively, compared with AM wethers. The relative abundances of archaeal and ciliate protozoal taxa were similar across allocation groups. In contrast, the relative abundances of members of the rumen bacterial community, like Prevotella 1 (P=0.04), Bacteroidales RF16 group (P=0.005) and Fibrobacter spp. (P=0.008) were greater for the AM group, whereas the relative abundance of Kandleria spp. was greater (P=0.04) for the PM group. Of these taxa, only Prevotella 1 (P=0.04) and Kandleria (P<0.001) showed a significant interaction between time of allocation and time of sampling relative to feed allocation. Relative abundances of Prevotella 1 were greater at 2h (P=0.05), 4h (P=0.003) and 6h (P=0.01) after AM allocation of new herbage, whereas relative abundances of Kandleria were greater at 2h (P=0.003) and 4h (P<0.001) after PM allocation. The early post-allocation rise in ammonia concentrations in PM rumens occurred simultaneously with sharp increases in the relative abundance of Kandleria spp. and with a decline in the relative abundance of Prevotella. All measures of fermentation and most microbial community composition data showed highly dynamic changes in concentrations and genus abundances, respectively, with substantial temporal changes occurring within the first 8h of allocating a new strip of herbage. The dynamic changes in the relative abundances of certain bacterial groups, in synchrony with a substantial diurnal variation in ammonia concentrations, has potential effects on the efficiency by which N is utilised by the grazing ruminant.
Herein, we report the detailed optoelectronic characteristics of low cost fabricated pristine and 1, 5, 10, and 15 wt% Mg-doped ZnO films on the FTO substrate (MZO/FTO) through the spin coating technique. High crystallinity and single phase of the film were confirmed by X-ray diffraction investigation. The average crystallite size was in the range of 46–78 nm. Homogeneous distribution of Mg doping in ZnO was approved by elemental mapping analysis. The fiber-like surface morphology was confirmed by the scanning electron microscopy analysis. Optical transparency was observed in the range of 40–80% for the fabricated films. The optical band gaps for direct and indirect transitions obtained from Tauc’s relation are in the range of 3.103–3.283 eV and 2.423–2.968 eV, respectively. It is also observed that the energy gap of MZO films decreases with an increase in Mg doping from 1 to 15%. The respective stable values of absorption and refractive indices are obtained in the range of ∼0.036–0.088 and ∼1.71–2.1. The linear and nonlinear optical susceptibilities as well as the nonlinear refractive index values were calculated. Additionally, Z-scan measurement was carried out at 532 nm wavelength. The nonlinear absorption coefficient and the imaginary part of third-order nonlinear susceptibility were estimated and corresponding values are obtained in the range of 0.35–123 (×10−5) cm/W and 0.084–29.7 (×10−8) e.s.u., respectively. Moreover, the optical limiting threshold values were obtained in the range of 2.57–6.34 kJ/cm2. The MZO/FTO films are showing strong optical limiting behavior compared to pristine. The output results suggest that MZO films are better contenders for optoelectronic applications.
Perovskite materials are sensitive to environmental conditions. Here we report the synthesis and characterization of a hydrophobic alkylammonium lead(II) iodide perovskite with enhanced stability in water. Water stability was achieved by growing a shell of 4-[(N-3-butyne)carboxyamido]anilinium lead(II) iodide over methylammonium lead(II) iodide. As a proof of concept, the water-splitting reaction was performed using our new material coated on TiO2, and a 7-fold increase in applied bias photon-to-current efficiency was observed as compared with standard p25-TiO2. Such simple and versatile chemical modification to induce high water stability is useful toward exploring new applications for the perovskite materials.
We consider inviscid, incompressible shear flows with variable density and variable cross section. For this problem, we derived a new estimate for the growth rate of an unstable mode and a parabolic instability region which intersects semiellipse instability region under some condition.
Dietary protein is considered more satiating than carbohydrate, and whey protein is more satiating than other protein sources. The purported satiating effect of whey protein may be due to direct effects of the unique mixture of proteins in whey, due to the effects of peptides released upon digestion and/or its amino acid composition. The objective of the present study was to compare the satiating effects of intact whey protein isolate (WPI) or a free amino acid mixture (AAM) simulating the amino acid composition of the WPI. A single-blind completely randomised block design included twenty, healthy, adult women (age 24·2 (sem 0·8) years) of normal weight (BMI 22·7 (sem 0·4) kg/m2). Following consumption of isoenergetic (approximately 1800 kJ) preload meals enriched (52 g amino acid equivalent) with WPI or AAM, consumption of an ad libitum test meal 120 min later and subjective feelings of appetite using visual analogue scales (VAS) were determined. There were no significant differences (P=0·24) in the ad libitum test meal intakes between the WPI (268·5 (sem 27·3) g) and the AAM (238·4 (sem 22·7) g) preload meals. Subjective VAS ratings of appetite did not differ significantly between the WPI and the AAM preload meals (P>0·05). Intact whey protein and a free AAM simulating the whey protein showed similar effects on satiety. This suggests that the satiating effect of whey protein may be related to its specific amino acid composition.
Morinda reticulata Gamble and Morinda umbellata Linn. (Rubiaceae) are medicinally important climbers distributed as a mixed population in southern Western Ghats of India. A close morphological resemblance of these two species misleads the harvester in the identification of plant parts for preparation of herbal medicines. Though both species contain anthraquinone derivatives and share common medicinal properties for treating stomach disorders, each of these species has unique curative properties for treating selective diseases. Conventional methods are not reliable for identification of these species due to similarities in morphology. Thus, misidentification often leads to the deterioration of the quality of medicines. Thus, authentication utilizing conserved gene sequences in the chloroplast genome of these two Morinda spp. has been attempted for precise identification. Here we report the use of two barcoding genes (maturase kinase and ribulose 1,5-bisphosphate carboxylase large subunit) to distinguish M. reticulata and M. umbellata based on single nucleotide polymorphism. The present findings can be used for authenticating leaf samples of M. reticulata and M. umbellata.
Faecal specimens of diarrhoea cases (n=2495, collected between November 2007 and October 2009) from Infectious Diseases and Beliaghata General (ID&BG) Hospital, Kolkata, India, were screened by RT–PCR using specific primers targeting region C of the capsid gene of noroviruses (NoVs) to determine the seasonal distribution and clinical characteristics of NoVs associated with diarrhoea. NoV infection was detected in 78 cases, mostly in children aged <2 years. In 22/78 positive cases, the virus was detected as the sole agent; others were as mixed infections with other enteric pathogens. Sequencing of NVGII strains showed clustering with GII.4 NoVs followed by GII.13 and GII.6 NoVs. Clinical characteristics of the diarrhoeic children and adults in Kolkata indicated that NoV infections were detected throughout the year and were associated with a mild degree of dehydration.
Indian gooseberry, popularly known as amla, is harvested from two species of Phyllanthus, namely Phyllanthus emblica and Phyllanthus indofischeri. Although these two species are characterized on vegetative and reproductive features, development of reliable and authentic identification based on molecular approaches is necessary for precise identification. Most of the commercial orchards of Indian gooseberry are established with mixture of the two species. Introduction of unauthentic clones and seedlings in the establishment of orchards and differences in the growth of these two species under different elevations are the major constrains in identification. The present work aims to study the changes in vegetative and reproductive features under different elevations and to develop a simple molecular tool for precise identification of these two species based on single nucleotide polymorphisms in trnL (UAA) intron sequences of chloroplast DNA. Genomic DNA of leaf tissues of P. emblica and P. indofischeri, collected from the authentic source, was subjected to polymerase chain reaction amplification using trnL (UAA) intron gene-specific primers. The amplified product with the molecular weight of 540 bp was sequenced and used as reference for identification of these two species. The trnL (UAA) introns sequenced from 60 individual trees in three different orchards were compared with trnL (UAA) intron of authentic samples, and confirmed that these orchards have 76% population of P. indofischeri and remaining 24% is occupied by P. emblica. Thus, trnL (UAA) intron is a potential DNA marker for precise identification of these two species. The importance of the present study and its practical application in genetic improvement of Indian gooseberry are discussed.
Polarimetry of the BL Lac object OJ 287 has been carried out over the last decade in optical bands with the 1.2-m telescope of Mt. Abu Observatory, operated by Physical Research Laboratory, India. OJ 287 underwent several polarization outbursts during this period.