Tag: nevin manimala

Sci Data. 2022 Apr 1;9(1):148. doi: 10.1038/s41597-022-01261-1.

ABSTRACT

Antibiotic resistance is a major threat to public health. The development of chemo-informatic tools to guide medicinal chemistry campaigns in the efficint design of antibacterial libraries is urgently needed. We present AB-DB, an open database of all-atom force-field parameters, molecular dynamics trajectories, quantum-mechanical properties, and curated physico-chemical descriptors of antimicrobial compounds. We considered more than 300 molecules belonging to 25 families that include the most relevant antibiotic classes in clinical use, such as β-lactams and (fluoro)quinolones, as well as inhibitors of key bacterial proteins. We provide traditional descriptors together with properties obtained with Density Functional Theory calculations. Noteworthy, AB-DB contains less conventional descriptors extracted from μs-long molecular dynamics simulations in explicit solvent. In addition, for each compound we make available force-field parameters for the major micro-species at physiological pH. With the rise of multi-drug-resistant pathogens and the consequent need for novel antibiotics, inhibitors, and drug re-purposing strategies, curated databases containing reliable and not straightforward properties facilitate the integration of data mining and statistics into the discovery of new antimicrobials.

PMID:35365662 | DOI:10.1038/s41597-022-01261-1

Sci Data. 2022 Apr 1;9(1):145. doi: 10.1038/s41597-022-01175-y.

ABSTRACT

During the second half of 2020, many European governments responded to the resurging transmission of SARS-CoV-2 with wide-ranging non-pharmaceutical interventions (NPIs). These efforts were often highly targeted at the regional level and included fine-grained NPIs. This paper describes a new dataset designed for the accurate recording of NPIs in Europe’s second wave to allow precise modelling of NPI effectiveness. The dataset includes interventions from 114 regions in 7 European countries during the period from the 1st August 2020 to the 9th January 2021. The paper includes NPI definitions tailored to the second wave following an exploratory data collection. Each entry has been extensively validated by semi-independent double entry, comparison with existing datasets, and, when necessary, discussion with local epidemiologists. The dataset has considerable potential for use in disentangling the effectiveness of NPIs and comparing the impact of interventions across different phases of the pandemic.

PMID:35365668 | DOI:10.1038/s41597-022-01175-y

Nat Commun. 2022 Apr 1;13(1):1733. doi: 10.1038/s41467-022-29391-5.

ABSTRACT

The terrestrial carbon cycle is a major source of uncertainty in climate projections. Its dominant fluxes, gross primary productivity (GPP), and respiration (in particular soil respiration, R_S), are typically estimated from independent satellite-driven models and upscaled in situ measurements, respectively. We combine carbon-cycle flux estimates and partitioning coefficients to show that historical estimates of global GPP and R_S are irreconcilable. When we estimate GPP based on R_S measurements and some assumptions about R_S:GPP ratios, we found the resulted global GPP values (bootstrap mean [Formula: see text] Pg C yr^-1) are significantly higher than most GPP estimates reported in the literature ([Formula: see text] Pg C yr^-1). Similarly, historical GPP estimates imply a soil respiration flux (Rs_GPP, bootstrap mean of [Formula: see text] Pg C yr^-1) statistically inconsistent with most published R_S values ([Formula: see text] Pg C yr^-1), although recent, higher, GPP estimates are narrowing this gap. Furthermore, global R_S:GPP ratios are inconsistent with spatial averages of this ratio calculated from individual sites as well as CMIP6 model results. This discrepancy has implications for our understanding of carbon turnover times and the terrestrial sensitivity to climate change. Future efforts should reconcile the discrepancies associated with calculations for GPP and Rs to improve estimates of the global carbon budget.

PMID:35365658 | DOI:10.1038/s41467-022-29391-5

Nat Commun. 2022 Apr 1;13(1):1738. doi: 10.1038/s41467-022-29463-6.

ABSTRACT

A hallmark of topological superconductivity is the non-Abelian statistics of Majorana bound states (MBS), its chargeless zero-energy emergent quasiparticles. The resulting fractionalization of a single electron, stored nonlocally as a two spatially-separated MBS, provides a powerful platform for implementing fault-tolerant topological quantum computing. However, despite intensive efforts, experimental support for MBS remains indirect and does not probe their non-Abelian statistics. Here we propose how to overcome this obstacle in mini-gate controlled planar Josephson junctions (JJs) and demonstrate non-Abelian statistics through MBS fusion, detected by charge sensing using a quantum point contact, based on dynamical simulations. The feasibility of preparing, manipulating, and fusing MBS in two-dimensional (2D) systems is supported in our experiments which demonstrate the gate control of topological transition and superconducting properties with five mini gates in InAs/Al-based JJs. While we focus on this well-established platform, where the topological superconductivity was already experimentally detected, our proposal to identify elusive non-Abelian statistics motivates also further MBS studies in other gate-controlled 2D systems.

PMID:35365644 | DOI:10.1038/s41467-022-29463-6

Blood Cancer J. 2022 Apr 1;12(4):53. doi: 10.1038/s41408-022-00648-y.

ABSTRACT

The objective of this study is to examine the association between neighborhood socioeconomic status (nSES) and baseline allostatic load (AL) and clinical trial endpoints in patients enrolled in the E1A11 therapeutic trial in multiple myeloma (MM). Study endpoints were symptom burden (pain, fatigue, and bother) at baseline and 5.5 months, non-completion of induction therapy, overall survival (OS) and progression-free survival (PFS). Multivariable logistic and Cox regression examined associations between nSES, AL and patient outcomes. A 1-unit increase in baseline AL was associated with greater odds of high fatigue at baseline (adjusted OR [95% CI] = 1.21 [1.08-1.36]) and a worse OS (adjusted hazard ratio, [95% CI] = 1.21 [1.06-1.37]). High nSES was associated with worse baseline bother (middle OR = 4.22 [1.11-16.09] and high 4.49 [1.16-17.43]) compared to low nSES. There was no association between AL or nSES and symptom burden at 5.5 months, non-completion of induction therapy or PFS. Additionally, there was no association between nSES and OS. AL may have utility as a predictive marker for OS among patients with MM and may allow individualization of treatment. Future studies should standardize and validate AL patients with MM.

PMID:35365604 | DOI:10.1038/s41408-022-00648-y

BDJ Open. 2022 Apr 1;8(1):9. doi: 10.1038/s41405-022-00101-z.

ABSTRACT

OBJECTIVES: Understanding of lifelong control of disease processes associated with caries and its management is an essential part of dental education. This study evaluated the dental students’ knowledge of caries diagnosis and management using the International Caries Classification and Management System (ICCMS).

METHODS: A survey was conducted among undergraduate dental students at two dental schools, attending the sixth (centre 1) and seventh semester (centre 2), respectively. Medical histories, clinical images and radiographs of 12 patients were compiled as anonymous cases. For each case, a specific lesion was to be assessed. In addition, the students should determine the patient’s caries risk and select a treatment option. An expert report (consensus decision) was used as the reference standard. For statistical analysis, kappa statistics and binomial tests were used.

RESULTS: A total of 46 students participated in this study. The percentage of agreement of responses to the reference was: centre 1: 40.7-51.3%, centre 2: 57.9-67.9%. The corresponding Kappa values were: centre 1: 0.073-0.175, centre 2: 0.315-0.432. Overall, students tended to underestimate the codes compared to the reference standard (p < 0.001).

CONCLUSION: Introducing systematic content about caries diagnosis and management such as ICDAS and ICCMS in the learning objectives of undergraduate dental students can be proposed. However, in order to improve diagnosis and enable a more reliable choice of treatment options, attention should also be given to the way they are didactically taught.

PMID:35365612 | DOI:10.1038/s41405-022-00101-z

Wound Repair Regen. 2022 Apr 1. doi: 10.1111/wrr.13005. Online ahead of print.

ABSTRACT

The objective of this study was to develop a pilot physician driven patient pyoderma gangrenosum (PG) registry to summarise patient baseline demographics, PG-related medical history, treatments, and outcomes for patients with pyoderma gangrenosum. Standardised patient information was collected prospectively during clinical encounters between December 2019 and July 2021 at a single academic institution. Eligibility criteria for the study was a diagnosis of pyoderma gangrenosum determined by a PARACELSUS score of at least 10 for ulcerative patients. Main outcome measures included demographic data, PG related history and comorbidities, past and current treatments, healing outcomes, hospitalisations and recurrences of PG. The Pyoderma Gangrenosum Study (PYGAS) Registry currently includes 52 patients with 56 target lesions of four distinct PG subtypes (41 ulcerative, 12 peristomal, 2 vegetative and 1 bullous). For the 38 patients with 41 total ulcerative PG lesions, referrals to our institution most commonly came from dermatologists (42.1%). The median follow-up time in our initial registry was 5.5 months (95% CI = 4.1-11.5 months), with average time between follow-up visits at 1.1 months. These ulcers were most commonly treated with first-line systemic immunosuppressants (70.6%), such as corticosteroids or cyclosporine. Additional use of systemic immunomodulators at baseline visit was statistically significantly associated with healing (P = 0.048). This pilot study suggests that use of systemic immunomodulators has an impact on healing of PG patients. Wound care regimens are variable, and assessing their impact on treatment outcomes could be challenging. Standardisation of both wound care regimens and data collection in prospective clinical studies is necessary to assess their impact in PG treatment outcomes.

PMID:35363927 | DOI:10.1111/wrr.13005

Cogn Sci. 2022 Apr;46(4):e13121. doi: 10.1111/cogs.13121.

ABSTRACT

The extraction of cooccurrences between two events, A and B, is a central learning mechanism shared by all species capable of associative learning. Formally, the cooccurrence of events A and B appearing in a sequence is measured by the transitional probability (TP) between these events, and it corresponds to the probability of the second stimulus given the first (i.e., p(B|A)). In the present study, nonhuman primates (Guinea baboons, Papio papio) were exposed to a serial version of the XOR (i.e., exclusive-OR), in which they had to process sequences of three stimuli: A, B, and C. In this manipulation, first-order TPs (i.e., AB and BC) were uninformative due to their transitional probabilities being equal to .5 (i.e., p(B|A) = p(C|B) = .5), while second-order TPs were fully predictive of the upcoming stimulus (i.e., p(C|AB) = 1). In Experiment 1, we found that baboons were able to learn second-order TPs, while no learning occurred on first-order TPs. In Experiment 2, this pattern of results was replicated, and a final test ruled out an alternative interpretation in terms of proximity to the reward. These results indicate that a nonhuman primate species can learn a nonlinearly separable problem such as the XOR. They also provide fine-grained empirical data to test models of statistical learning on the interaction between the learning of different orders of TPs. Recent bioinspired models of associative learning are also introduced as promising alternatives to the modeling of statistical learning mechanisms.

PMID:35363923 | DOI:10.1111/cogs.13121

Biometrics. 2022 Apr 1. doi: 10.1111/biom.13639. Online ahead of print.

NO ABSTRACT

PMID:35363907 | DOI:10.1111/biom.13639

Cochrane Database Syst Rev. 2022 Apr 1;4:CD013846. doi: 10.1002/14651858.CD013846.pub2.

ABSTRACT

BACKGROUND: Patent ductus arteriosus (PDA) is associated with significant morbidity and mortality in preterm infants. Cyclooxygenase inhibitors (COX-I) may prevent PDA-related complications. Controversy exists on which COX-I drug is the most effective and has the best safety profile in preterm infants.

OBJECTIVES: To compare the effectiveness and safety of prophylactic COX-I drugs and ‘no COXI prophylaxis’ in preterm infants using a Bayesian network meta-analysis (NMA).

SEARCH METHODS: Searches of Cochrane CENTRAL via Wiley, OVID MEDLINE and Embase via Elsevier were conducted on 9 December 2021. We conducted independent searches of clinical trial registries and conference abstracts; and scanned the reference lists of included trials and related systematic reviews.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) that enrolled preterm or low birth weight infants within the first 72 hours of birth without a prior clinical or echocardiographic diagnosis of PDA and compared prophylactic administration of indomethacin or ibuprofen or acetaminophen versus each other, placebo or no treatment.

DATA COLLECTION AND ANALYSIS: We used the standard methods of Cochrane Neonatal. We used the GRADE NMA approach to assess the certainty of evidence derived from the NMA for the following outcomes: severe intraventricular haemorrhage (IVH), mortality, surgical or interventional PDA closure, necrotizing enterocolitis (NEC), gastrointestinal perforation, chronic lung disease (CLD) and cerebral palsy (CP).

MAIN RESULTS: We included 28 RCTs (3999 preterm infants). Nineteen RCTs (n = 2877) compared prophylactic indomethacin versus placebo/no treatment, 7 RCTs (n = 914) compared prophylactic ibuprofen versus placebo/no treatment and 2 RCTs (n = 208) compared prophylactic acetaminophen versus placebo/no treatment. Nine RCTs were judged to have high risk of bias in one or more domains.We identified two ongoing trials on prophylactic acetaminophen. Bayesian random-effects NMA demonstrated that prophylactic indomethacin probably led to a small reduction in severe IVH (network RR 0.66, 95% Credible Intervals [CrI] 0.49 to 0.87; absolute risk difference [ARD] 43 fewer [95% CrI, 65 fewer to 16 fewer] per 1000; median rank 2, 95% CrI 1-3; moderate-certainty), a moderate reduction in mortality (network RR 0.85, 95% CrI 0.64 to 1.1; ARD 24 fewer [95% CrI, 58 fewer to 16 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and surgical PDA closure (network RR 0.40, 95% CrI 0.14 to 0.66; ARD 52 fewer [95% CrI, 75 fewer to 30 fewer] per 1000; median rank 2, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic indomethacin resulted in trivial difference in NEC (network RR 0.76, 95% CrI 0.35 to 1.2; ARD 16 fewer [95% CrI, 42 fewer to 13 more] per 1000; median rank 2, 95% CrI 1-3; high-certainty), gastrointestinal perforation (network RR 0.92, 95% CrI 0.11 to 3.9; ARD 4 fewer [95% CrI, 42 fewer to 137 more] per 1000; median rank 1, 95% CrI 1-3; moderate-certainty) or CP (network RR 0.97, 95% CrI 0.44 to 2.1; ARD 3 fewer [95% CrI, 62 fewer to 121 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty) and may result in a small increase in CLD (network RR 1.10, 95% CrI 0.93 to 1.3; ARD 36 more [95% CrI, 25 fewer to 108 more] per 1000; median rank 3, 95% CrI 1-3; low-certainty). Prophylactic ibuprofen probably led to a small reduction in severe IVH (network RR 0.69, 95% CrI 0.41 to 1.14; ARD 39 fewer [95% CrI, 75 fewer to 18 more] per 1000; median rank 2, 95% CrI 1-4; moderate-certainty) and moderate reduction in surgical PDA closure (network RR 0.24, 95% CrI 0.06 to 0.64; ARD 66 fewer [95% CrI, from 82 fewer to 31 fewer] per 1000; median rank 1, 95% CrI 1-2; moderate-certainty) compared to placebo. Prophylactic ibuprofen may result in moderate reduction in mortality (network RR 0.83, 95% CrI 0.57 to 1.2; ARD 27 fewer [95% CrI, from 69 fewer to 32 more] per 1000; median rank 2, 95% CrI 1-4; low-certainty) and leads to trivial difference in NEC (network RR 0.73, 95% CrI 0.31 to 1.4; ARD 18 fewer [95% CrI, from 45 fewer to 26 more] per 1000; median rank 1, 95% CrI 1-3; high-certainty), or CLD (network RR 1.00, 95% CrI 0.83 to 1.3; ARD 0 fewer [95% CrI, from 61 fewer to 108 more] per 1000; median rank 2, 95% CrI 1-3; low-certainty). The evidence is very uncertain on effect of ibuprofen on gastrointestinal perforation (network RR 2.6, 95% CrI 0.42 to 20.0; ARD 76 more [95% CrI, from 27 fewer to 897 more] per 1000; median rank 3, 95% CrI 1-3; very low-certainty). The evidence is very uncertain on the effect of prophylactic acetaminophen on severe IVH (network RR 1.17, 95% CrI 0.04 to 55.2; ARD 22 more [95% CrI, from 122 fewer to 1000 more] per 1000; median rank 4, 95% CrI 1-4; very low-certainty), mortality (network RR 0.49, 95% CrI 0.16 to 1.4; ARD 82 fewer [95% CrI, from 135 fewer to 64 more] per 1000; median rank 1, 95% CrI 1-4; very low-certainty), or CP (network RR 0.36, 95% CrI 0.01 to 6.3; ARD 70 fewer [95% CrI, from 109 fewer to 583 more] per 1000; median rank 1, 95% CrI 1-3; very low-certainty). In summary, based on ranking statistics, both indomethacin and ibuprofen were equally effective (median ranks 2 respectively) in reducing severe IVH and mortality. Ibuprofen (median rank 1) was more effective than indomethacin in reducing surgical PDA ligation (median rank 2). However, no statistically-significant differences were observed between the COX-I drugs for any of the relevant outcomes.

AUTHORS’ CONCLUSIONS: Prophylactic indomethacin probably results in a small reduction in severe IVH and moderate reduction in mortality and surgical PDA closure (moderate-certainty), may result in a small increase in CLD (low-certainty) and results in trivial differences in NEC (high-certainty), gastrointestinal perforation (moderate-certainty) and cerebral palsy (low-certainty). Prophylactic ibuprofen probably results in a small reduction in severe IVH and moderate reduction in surgical PDA closure (moderate-certainty), may result in a moderate reduction in mortality (low-certainty) and trivial differences in CLD (low-certainty) and NEC (high-certainty). The evidence is very uncertain about the effect of acetaminophen on any of the clinically-relevant outcomes.

PMID:35363893 | DOI:10.1002/14651858.CD013846.pub2