Chemical Code Research Articles

Gas phase Elemental abundances in Molecular cloudS (GEMS)

Context. In the context of the IRAM 30 m Large Program Gas phase Elemental abundances in Molecular CloudS (GEMS), we present a study of thioformaldehyde (H2CS) and its deuterated versions (HDCS and D2CS) in several starless cores located in a selected set of star-forming filaments of Taurus, Perseus, and Orion. These regions have different star formation activities and, therefore, distinct physical and chemical conditions. Aims. Our goal is to investigate the influence of the environmental conditions on the abundances of these molecules in the cores, as well as the effect of time evolution. Methods. We have modelled the observed lines of H2CS, HDCS, and D2CS using the radiative transfer code RADEX. We have also used the chemical code Nautilus to model the evolution of these species depending on the characteristics of the starless cores. Results. We derive column densities and abundances for all the cores. We also derive deuterium fractionation ratios, Dfrac, which allow us to determine and compare the evolutionary stage between different parts of each star-forming region. Our results indicate that the north region of the B 213 filament in Taurus is more evolved than the south, while the north-eastern part of Perseus presents an earlier evolutionary stage than the south-western zone. Model results also show that Dfrac decreases with the cosmic-ray ionisation rate, while it increases with density and with the degree of sulphur depletion. In particular, we can only reproduce the observations when the initial sulphur depletion in the starless cores is at least one order of magnitude lower than the solar elemental sulphur abundance. Conclusions. The progressive increase in HDCS/H2CS and D2CS/H2CS with time makes these ratios powerful tools for deriving the chemical evolutionary stage of starless cores. However, they cannot be used to derive the temperature of these regions, since both ratios present a similar evolution at two different temperature ranges (~7–11 K and ~ 15–19 K). Regarding chemistry, (deuterated) thioformaldehyde is mainly formed through gas-phase reactions (double-replacement and neutral-neutral displacement reactions), while surface chemistry plays an important role as a destruction mechanism.

Drug Utilization 90% Profile of Antibiotics Use during the Period of 2013 – 2017 at a Private Teaching Hospital in Yogyakarta

Evaluation of antibiotics use plays an important role in antimicrobial stewardship programs to support the rational use of antibiotics at all healthcare facilities. This study aimed to describe the profile of drug utilization 90% (DU90%) of antibiotics use for hospitalized patients at a private teaching hospital in Yogyakarta over period of 2013 – 2017. Aggregate data of all systemic antibiotics having an anatomic therapeutic chemical (ATC) code and used for hospitalized patients during 2013 – 2017 were included in this study. Quantity of antibiotics use was expressed in defined daily dose (DDD) and final quantity was expressed in DDD/100 bed days. DU90% profile was obtained by calculating the cumulative use of antibiotics from the highest to the lowest percentage. There were 44 antibiotic agents used each year over the period of 2013 – 2017. However, there were only 10 – 12 agents within the DU90% segment. Cephalosporins group was identified as the most used antibiotics consistently over the period and the top three antibiotics that were consistently prescribed were: ceftriaxone, levofloxacin, and cefixime. It can be concluded that only about a quarter of the total antibiotic agents used in hospitals are within the DU90% segment and those antibiotic agents are relatively consistent, especially for the top three of the highest used antibiotics.

Molecular-level nucleation mechanism of iodic acid and methanesulfonic acid

Abstract. Both iodic acid (HIO3, IA) and methanesulfonic acid (CH3S(O)2OH, MSA) have been identified by field studies as important precursors of new particle formation (NPF) in marine areas. However, the mechanism of NPF in which IA and MSA are jointly involved is still unclear. Hence, we investigated the IA-MSA nucleation system under different atmospheric conditions and uncovered the corresponding nucleating mechanism at the molecular level for the first time, using a quantum chemical approach and Atmospheric Cluster Dynamics Code (ACDC). The findings show that the pure-IA nucleation rate was much lower than the results of CLOUD (Cosmics Leaving Outdoor Droplets) experiments. MSA can promote IA cluster formation through stabilizing IA via both hydrogen and halogen bonds, especially under conditions with lower temperatures, sparse IA, and rich MSA. However, the nucleation rate of the IA-MSA mechanism is much lower than that of field observations, indicating that the effect of additional nucleation precursors needs to be considered (e.g., H2SO4, HIO2, NH3, and amines). The IA-MSA nucleation mechanism revealed in this study may help to gain insight into the joint effect of marine sulfur- and iodine-containing components on marine NPF.

Contribution of an extensive medication-based comorbidity index (Rx-Risk) in explaining the excess mortality after hip fracture in older Norwegians: a NOREPOS cohort study

ObjectivesPatients with hip fracture are typically characterised by extensive comorbidities and excess mortality. Methods that account for a wide range of comorbidities are needed when attempting to identify causal associations...

Triptans and vascular comorbidity in persons over fifty: Findings from a nationwide insurance database - A cohort study.

ObjectiveTo gather information about prescription of triptans and to evaluate whether vascular comorbidity differs in users and nonusers of triptans over the age of 50 years.BackgroundBeyond the age of 50 years, migraine is still common—yet the incidence of vascular disorders increases. Triptans, medications for treating migraine attacks, are vasoconstrictive drugs and contraindicated in persons with vascular disorders.MethodsBased on a nationwide insurance database from 2011, we compared the prescription of vascular drugs (identified by Anatomical Therapeutic Chemical codes), vascular diagnoses and hospitalizations, between triptan users greater than 50 years and a matched control group.ResultsOf the 3,116,000 persons over 50 years, 13,833 (0.44%) had at least one triptan prescription; 11,202 (81%) were women. Thirty percent of the triptan users (13,833/47,336 persons) were over 50 years. Of those over 50 years, 6832 (49.4%) had at least one vascular drug and 870 (6.3%) had at least one inpatient vascular diagnosis; 15.7% (2166 of 13,833 users) overused triptans. We compared triptan‐users to 41,400 nonusers, using a 1:3 match. In triptan‐users, prescriptions of cardiac therapies and beta blockers were significantly more common (odds ratio [OR] = 1.35, 95% confidence interval [CI] = 1.24–1.47 and OR = 1.19, 95% CI = 1.14–1.25, respectively); whereas prescriptions of calcium channel blockers and renin/angiotensin inhibitors were significantly less common (OR = 0.82, 95% CI = 0.76–0.88 and OR = 0.75, 95% CI = 0.72–0.79, respectively). The prescriptions of antihypertensive, diuretic, and antilipidemic drugs as well as platelet inhibitors and direct thrombin inhibitors did not differ in users and nonusers. Triptan users had significantly more hospital stays (OR = 1.39, 95% CI = 1.33–1.45); however, the number of days spent in the hospital and more importantly the frequency of inpatient vascular diagnoses did not differ statistically significantly between the two groups.ConclusionIn persons over 50 years of age, a prescription of triptans is common. Vascular comorbidity is comparable in users and nonusers of triptans showing that triptans are prescribed despite vascular comorbidity and suggesting that triptan use does not increase vascular risk in patients with migraine over the age of 50 years. Nevertheless, regular evaluation for contraindications against triptans and for vascular risk factors is recommended in this age group.

Association between NSAID and Statin Therapy and the Incidence of Intravitreal Anti-vascular Endothelial Growth Factor Injections and Nd:YAG Laser Treatment after Cataract Surgery in Finland.

PurposeTo examine the association between the use of topical non-steroidal anti-inflammatory (NSAID) medication, systemic statin therapy, and the incidence rate of two of the most common postsurgical procedures in adult patients undergoing cataract surgery in Finland between January 1, 2010 and December 31, 2016.MethodsThis retrospective, nationwide cohort study considered 176,052 cataract operations coded with the International Classification of Disease coding: early adult (H25.0), normal (H25.1), other senile (H25.8), pre-senile (H26.02), or other (related to trauma, other eye disease, or medication). Operations were linked to purchased and reimbursed medications using Anatomical Therapeutic Chemical codes. The incidence rate of intravitreal anti-vascular endothelial growth factor (VEGF) injections, and neodymium-doped yttrium aluminum (Nd:YAG) laser treatments of posterior capsular opacification were evaluated using the Poisson regression model.Results In our registry cohort, patients with a prescription of topical NSAID (ketorolac) at the time of cataract surgery were less likely treated with intravitreal anti-VEGF injections after surgery (adjusted Poisson regression model IRR 0.3; 95% CI: 0.15–0.60, P = 0.0007), and also had reduced incidence of Nd:YAG laser (0.59, CI: 0.43–0.81, P = 0.0011) treatments. Unlike topical NSAID, the use of systemic statin therapy was not associated with these two most common surgical procedures (RR 1.04, 95% CI: 0.96–1.12, P = 0.33).ConclusionThe use of topical NSAIDs is associated with reduced rates of intravitreal anti-VEGF injections and Nd:YAG laser treatments after cataract surgery. More observational and experimental studies are warranted to confirm possible benefits of topical NSAID administration after cataract surgery.

Morphology and Chemical Coding of Rat Duodenal Enteric Neurons following Prenatal Exposure to Fumonisins.

Simple SummaryFood contamination with toxins produced by various species of fungi (hereafter: mycotoxins) occurs frequently, and, for this reason, their activity in the bodies of animals is the subject of wide-ranging research. Although many aspects of the activity of fumonisins (mycotoxins produced by Fusarium) have been described, an open question is whether prenatal exposure to fumonisins may result in morphological changes, including in the enteric nervous system (ENS). The present study revealed that fumonisin administered via the gastrointestinal tract to pregnant rats did not substantially change the structure of the intestine/ENS of the offspring, but altered the neurochemical profile of its enteric neurons.Fumonisins (FBs), including fumonisin B1 and B2 produced by the fungus Fusarium verticillioides, are widespread mycotoxins contaminating crop plants as well as processed food. The aim of the experiment was to determine whether the exposure of 5-week-old pregnant rats to FBs at 60 mg/kg b.w. (group FB60) or 90 mg/kg b.w. (group FB90) results in morphological changes in the duodenum of weaned offspring, particularly the enteric nervous system (ENS). In addition, the levels of expression of galanin and vasoactive intestinal polypeptide (VIP) in the ENS were analysed by immunofluorescence in the control and experimental groups of animals. No significant morphological changes in the thickness of the muscle layer or submucosa of the duodenum were noted in group FB60 or FB90. In group FB90 (but not FB60), there was a significant increase in the width of the villi and in the density of the intestinal crypts. Immunofluorescence analysis using neuronal marker Hu C/D showed no significant changes in group FB60 or FB90 in the morphology of the duodenal ENS, i.e., the myenteric plexus (MP) and submucosal plexus (SP), in terms of the density of enteric ganglia in the MP and SP, surface area of MP and SP ganglia, length and width of MP and SP ganglia, surface area of myenteric and submucosal neurons, diameter of myenteric and submucosal neurons, density of myenteric and submucosal neurons, and number of myenteric and submucosal neurons per ganglion. In both groups, there was an increase (relative to the control) in the percentage of Hu C/D-IR/VIP-IR (IR-immunoreactive) and Hu C/D-IR/galanin-IR myenteric and submucosal neurons in the ganglia of both the MP and SP of the duodenum. In addition, in groups FB60 and FB90, there was an increase in the number of nerve fibres showing expression of VIP and galanin in the mucosa, submucosa and circular muscle layer of the duodenum. The results indicate that prenatal exposure to FBs does not significantly alter the histological structure of the duodenum (including the ENS) in the weaned offspring. The changes observed in the chemical code of the myenteric and submucosal neurons in both experimental groups suggest harmful activity of FBs, which may translate into activation of repair mechanisms via overexpression of neuroprotective neuropeptides (VIP and galanin).

Novelty detection in early olfactory processing of the honey bee, Apis mellifera.

Animals are constantly bombarded with stimuli, which presents a fundamental problem of sorting among pervasive uninformative stimuli and novel, possibly meaningful stimuli. We evaluated novelty detection behaviorally in honey bees as they position their antennae differentially in an air stream carrying familiar or novel odors. We then characterized neuronal responses to familiar and novel odors in the first synaptic integration center in the brain–the antennal lobes. We found that the neurons that exhibited stronger initial responses to the odor that was to be familiarized are the same units that later distinguish familiar and novel odors, independently of chemical identities. These units, including both tentative projection neurons and local neurons, showed a decreased response to the familiar odor but an increased response to the novel odor. Our results suggest that the antennal lobe may represent familiarity or novelty to an odor stimulus in addition to its chemical identity code. Therefore, the mechanisms for novelty detection may be present in early sensory processing, either as a result of local synaptic interaction or via feedback from higher brain centers.

Digitizing Chemical Synthesis in 3D Printed Reactionware.

Chemistry digitization requires an unambiguous link between experiments and the code used to generate the experimental conditions and outcomes, yet this process is not standardized, limiting the portability of any chemical code. What is needed is a universal approach to aid this process using a well-defined standard that is composed of syntheses that are employed in modular hardware. Herein we present a new approach to the digitization of organic synthesis that combines process chemistry principles with 3D printed reactionware. This approach outlines the process for transforming unit operations into digitized hardware and well-defined instructions that ensure effective synthesis. To demonstrate this, we outline the process for digitizing 3 MIDA boronate building blocks, an ester hydrolysis, a Wittig olefination, a Suzuki-Miyaura coupling reaction, and synthesis of the drug sulfanilamide.

Digitizing Chemical Synthesis in 3D Printed Reactionware

AbstractChemistry digitization requires an unambiguous link between experiments and the code used to generate the experimental conditions and outcomes, yet this process is not standardized, limiting the portability of any chemical code. What is needed is a universal approach to aid this process using a well‐defined standard that is composed of syntheses that are employed in modular hardware. Herein we present a new approach to the digitization of organic synthesis that combines process chemistry principles with 3D printed reactionware. This approach outlines the process for transforming unit operations into digitized hardware and well‐defined instructions that ensure effective synthesis. To demonstrate this, we outline the process for digitizing 3 MIDA boronate building blocks, an ester hydrolysis, a Wittig olefination, a Suzuki–Miyaura coupling reaction, and synthesis of the drug sulfanilamide.

Matching Drug Metabolites from Non-Targeted Metabolomics to Self-Reported Medication in the Qatar Biobank Study.

Modern metabolomics platforms are able to identify many drug-related metabolites in blood samples. Applied to population-based biobank studies, the detection of drug metabolites can then be used as a proxy for medication use or serve as a validation tool for questionnaire-based health assessments. However, it is not clear how well detection of drug metabolites in blood samples matches information on self-reported medication provided by study participants. Here, we curate free-text responses to a drug-usage questionnaire from 6000 participants of the Qatar Biobank (QBB) using standardized WHO Anatomical Therapeutic Chemical (ATC) Classification System codes and compare the occurrence of these ATC terms to the detection of drug-related metabolites in matching blood plasma samples from 2807 QBB participants for which we collected non-targeted metabolomics data. We found that the detection of 22 drug-related metabolites significantly associated with the self-reported use of the corresponding medication. Good agreement of self-reported medication with non-targeted metabolomics was observed, with self-reported drugs and their metabolites being detected in a same blood sample in 79.4% of the cases. On the other hand, only 29.5% of detected drug metabolites matched to self-reported medication. Possible explanations for differences include under-reporting of over-the-counter medications from the study participants, such as paracetamol, misannotation of low abundance metabolites, such as metformin, and inability of the current methods to detect them. Taken together, our study provides a broad real-world view of what to expect from large non-targeted metabolomics measurements in population-based biobank studies and indicates areas where further improvements can be made.

Blood pressure, antihypertensive drugs, and incident frailty: The Multidomain Alzheimer Preventive Trial (MAPT)

ObjectivesTo examine the association of (1) high and low blood pressure (BP) and (2) antihypertensive (AH) drug use with incident frailty. Study designWe conducted a secondary analysis of data from the Multidomain Alzheimer Preventive Trial (MAPT), in which 1394 non-frail community-dwelling participants aged ≥70 years were followed up for 5 years. BP was measured once at baseline in a lying position using a validated electronic device. High BP was defined as systolic BP ≥ 140 mm Hg and/or diastolic BP ≥ 90 mm Hg, and low BP as systolic BP ≤ 110 mm Hg and/or diastolic BP ≤ 70 mm Hg. AH drugs were assessed at baseline and classified according to the Anatomical Therapeutic Chemical (ATC) code. Main outcome measuresIncident frailty over the 5 years was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. ResultsLow BP was associated with a greater risk of frailty (HR = 1.43, 95% CI [1.07–1.92], p = 0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and those on two or more AH drugs were at the greatest risk of frailty. Neither high BP (HR = 0.84, 95% CI [0.63–1.22], p = 0.24) nor AH drug use (HR = 1.21, 95% CI [0.89–1.64], p = 0.22) was independently associated with incident frailty. ConclusionsLow BP could be used as a new marker for identifying older adults at higher risk of frailty.Clinicaltrials.gov registration number: NCT00672685.

Abstract P003: Blood Pressure, Antihypertensive Drugs, And Incident Frailty: The Multidomain Alzheimer Preventive Trial

Objectives: To examine the association of (1) high and low BP levels and (2) AH drug use with incident frailty. Study design: We conducted a secondary analysis of the Multidomain Alzheimer Preventive Trial (MAPT). We included and followed-up for 5 years 1,394 non-frail community-dwelling participants aged ≥ 70 years. Main outcome measures: High BP was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg and low BP as systolic BP ≤ 110 mmHg and/or diastolic BP ≤ 70 mmHg. AH drugs were classified according to the Anatomical Therapeutic Chemical (ATC) code. Incident frailty was assessed using the Fried phenotype. Cox proportional hazards models were used for the analyses. Results: Low BP was associated with greater risk of frailty (HR = 1.43, 95% CI [1.07-1.92], p=0.02) after adjustment for age, sex, education, AH drug use, BMI, diabetes, ischemic heart disease, congestive heart failure, AF, stroke, MAPT randomization group, sit-to-stand chair test and pre-frailty. Participants with low BP and 2 AH drugs or more were those having the greatest risk. Neither high BP (HR = 0.84, 95% CI [0.63-1.22], p=0.24) nor AH drug use (HR = 1.21, 95% CI [0.89-1.64], p=0.22) were independently associated with incident frailty. Conclusions: Low BP could be used as a new marker for identifying older adults at higher risk of frailty. AH medications in older adults with low BP should be continuously reviewed to assure that their potential benefits outweigh potential risks.

The risk of pulmonary adverse drug reactions of rebamipide and other drugs for acid-related diseases: An analysis of the national pharmacovigilance database in South Korea.

ObjectiveThe objective of this case/non‐case study was to detect rebamipide‐related pulmonary adverse events (AE) compared with other drugs for acid‐related disorders based on population‐level data.MethodsFrom 2009 to 2018, AE reports on drugs for acid‐related disorders, which are anatomical therapeutic chemical code A02B drugs, in the Korea Adverse Events Reporting System (KAERS) database were examined. The reporting odds ratio (ROR) was calculated, and the odds of reporting pulmonary AE for rebamipide and all other A02B drugs were compared. Furthermore, a stratified analysis according to patients’ age and sex was conducted.ResultsAltogether 13 (0.05%) and 157 (0.11%) cases of pulmonary AE were reported for rebamipide and all other A02B drugs, respectively. The risk of reporting pulmonary AE was significantly lower for rebamipide than for all other A02B drugs (ROR 0.49, 95% confidence interval [CI] 0.28–0.87). The number of reports of pulmonary AE for rebamipide was significantly higher among patients aged ≥65 years than those aged <65 years (ROR 19.36, 95% CI 2.50–149.97).ConclusionsRebamipide was less often reported for pulmonary AE. However, healthcare professionals need to be aware of the risk of pulmonary AE in elderly patients.

Antidepressant discontinuation before or during pregnancy and risk of psychiatric emergency in Denmark: A population-based propensity score-matched cohort study.

Women prescribed antidepressants face the dilemma of whether or not to continue their treatment during pregnancy. Currently, limited evidence is available on the efficacy of continuing versus discontinuing antidepressant treatment during pregnancy to aid their decision. We aimed to estimate whether antidepressant discontinuation before or during pregnancy was associated with an increased risk of psychiatric emergency (ascertained by psychiatric admission or emergency room visit), a proxy measure of severe exacerbation of symptoms/mental health crisis. We carried out a propensity score-matched cohort study of women who gave birth to live-born singletons between January 1, 1997 and June 30, 2016 in Denmark and who redeemed an antidepressant prescription in the 90 days before the pregnancy, identified by Anatomical Therapeutic Chemical (ATC) code N06A. We constructed 2 matched cohorts, matching each woman who discontinued antidepressants before pregnancy (N = 2,669) or during pregnancy (N = 5,467) to one who continued antidepressants based on propensity scores. Maternal characteristics and variables related to disease severity were used to generate the propensity scores in logistic regression models. We estimated hazard ratios (HRs) of psychiatric emergency in the perinatal period (pregnancy and 6 months postpartum) using stratified Cox regression. Psychiatric emergencies were observed in 76 women who discontinued antidepressants before pregnancy and 91 women who continued. There was no evidence of higher risk of psychiatric emergency among women who discontinued antidepressants before pregnancy (cumulative incidence: 2.9%, 95% confidence interval [CI]: 2.3% to 3.6% for discontinuation versus 3.4%, 95% CI: 2.8% to 4.2% for continuation; HR = 0.84, 95% CI: 0.61 to 1.16, p = 0.298). Overall, 202 women who discontinued antidepressants during pregnancy and 156 who continued had psychiatric emergencies (cumulative incidence: 5.0%, 95% CI: 4.2% to 5.9% versus 3.7%, 95% CI: 3.1% to 4.5%). Antidepressant discontinuation during pregnancy was associated with increased risk of psychiatric emergency (HR = 1.25, 95% CI: 1.00 to 1.55, p = 0.048). Study limitations include lack of information on indications for antidepressant treatment and reasons for discontinuing antidepressants. In this study, we found that discontinuing antidepressant medication during pregnancy (but not before) is associated with an apparent increased risk of psychiatric emergency compared to continuing treatment throughout pregnancy.

The Extent of Heavy Metal Pollution by Chemical Partitioning and Risk Assessment Code of Sediments of Sewage-Fed Fishery Ponds at East Kolkata Wetland, a Ramsar Site, India

Sewage contaminated with toxic metals is being naturally treated in ponds at East Kolkata Wetlands (EKW) for fish cultivation traditionally. From the aquatic phase, these metals get settled on sediment and undergo partitioning. Some fractions are available and may accumulate in the cultivated products. The present study highlights the degree of partition of heavy metals Lead (Pb), Cadmium (Cd) and Chromium (Cr) in these pond sediments. The study reveals that Pb and Cr are significant (39% and 30%, respectively) in Fe-Mn bound fractions. Residual fraction is in the order of Pb > Cr > Cd. The easily available fraction of metals recorded higher in Cd (43.0%) and Cr (42.0%).The risk assessment code (RAC) analysis records that these metals could be considered as potential risk group of metals for higher mobility and availability in these pond ecosystems and is a significant concern for aquaculture products.

Antihypertensive and lipid-lowering drugs usage after primary stroke in a large representative sample of the French population.

The aim of the study is to describe the use of antihypertensive and lipid-lowering drugs in post-stroke secondary prevention in France. This is a prospective cohort study based on a representative sample of the French health insurance system database. All patients aged 45 and over, hospitalized for a first stroke between 1 January 2009 and 31 December 2014 were included. For each drug class, identified using Anatomical Therapeutic Chemical (ATC) codes, patients were followed from the first drug supply after stroke until the end of study period (31 December 2017), or exit date of the database or death. Adherence was defined by the proportion of days covered and persistence by the absence of a treatment gap of more than 91 days. A total of 2674 patients were included, median age was 75.0 years (interquartile range 63.0-83.0) and 51.2% were women. For patients treated with a drug of interest after stroke, median follow-up was 4.8 years (interquartile range 3.4-6.5). Regarding antihypertensive drugs, adherence at 8 years was 84.1% and persistence was 71.0%. For lipid-lowering drugs adherence at 8 years was 68.6% and persistence was 49.4%. Adherence and persistence were lower for patients starting treatment at time of stroke (antihypertensive drugs: 70.9% for adherence and 52.6% for persistence; lipid-lowering drugs: 62.3% and 43.1%) compared to patients already treated (antihypertensive drugs: 87.2% and 75.2%; lipid-lowering drugs: 73.6% and 54.5%). In this large representative sample of patients hospitalized for a first stroke in France, post-stroke therapeutic management remains suboptimal compared to guidelines, notably regarding lipid-lowering drugs. This trend was more pronounced for newly treated patients.

DDREL: From drug-drug relationships to drug repurposing

Analyzing the relationships among various drugs is an essential issue in the field of computational biology. Different kinds of informative knowledge, such as drug repurposing, can be extracted from drug-drug relationships. Scientific literature represents a rich source for the retrieval of knowledge about the relationships between biological concepts, mainly drug-drug, disease-disease, and drug-disease relationships. In this paper, we propose DDREL as a general-purpose method that applies deep learning on scientific literature to automatically extract the graph of syntactic and semantic relationships among drugs. DDREL remarkably outperforms the existing human drug network method and a random network respected to average similarities of drugs’ anatomical therapeutic chemical (ATC) codes. DDREL is able to shed light on the existing deficiency of the ATC codes in various drug groups. From the DDREL graph, the history of drug discovery became visible. In addition, drugs that had repurposing score 1 (diflunisal, pargyline, fenofibrate, guanfacine, chlorzoxazone, doxazosin, oxymetholone, azathioprine, drotaverine, demecarium, omifensine, yohimbine) were already used in additional indication. The proposed DDREL method justifies the predictive power of textual data in PubMed abstracts. DDREL shows that such data can be used to 1- Predict repurposing drugs with high accuracy, and 2- Reveal existing deficiencies of the ATC codes in various drug groups.

Ethanol Exposure During the Intravenous Administration of Chemotherapeutic Drugs: An Analysis of Clinical Practice and a Literature Review

Injectable cytotoxics may be formulated with ethanol. This study sought to quantify the amount of ethanol exposure during chemotherapy infusions. We first reviewed the antineoplastic drugs (Anatomical Therapeutic and Chemical code L01) and oncologic supportive care drugs (eg, antiemetics) currently available in France, to identify preparations containing ethanol. The amount of ethanol in the final chemotherapy preparation was calculated. Next, we performed a 2-year, single-center, retrospective analysis of injectable antineoplastic drug compounding in routine clinical practice in a French university medical center. Finally, we reviewed our results with regard to the literature data. Ten of the 60 cytotoxic products on the market contained ethanol at concentrations of up to 790 mg/mL, depending on the drug, formulation, and supplier. Several final preparations contained more than 3 g of ethanol per infusion (the maximum recommended by the European Medicines Agency); this was notably the case for gemcitabine, paclitaxel (up to 20 g ethanol per injection, for both), and etoposide (up to 50 g ethanol per infusion). The analysis of our compounding activity showed that 3,172 (4.99%) of the 63,613 chemotherapy preparations (notably paclitaxel) contained more than 3 g of ethanol. None of the oncologic supportive care drugs contained ethanol. Patients are exposed to ethanol during the infusion of antineoplastic drugs. With a view to better patient care, physicians and pharmacists should carefully evaluate the risk of ethanol exposure throughout the course of cytotoxic drug treatment.

Revealing which Combinations of Molecular Lines are Sensitive to the Gas Physical Parameters of Molecular Clouds

Atoms and molecules have long been thought to be versatile tracers of the cold neutral gas in the universe, from high-redshift galaxies to star forming regions and proto-planetary disks, because their internal degrees of freedom bear the signature of the physical conditions where these species reside. However, the promise that molecular emission has a strong diagnostic power of the underlying physical and chemical state is still hampered by the difficulty to combine sophisticated chemical codes with gas dynamics. It is therefore important 1) to acquire self-consistent data sets that can be used as templates for this theoretical work, and 2) to reveal the diagnostic capabilities of molecular lines accurately. The advent of sensitive wideband spectrometers in the (sub)- millimeter domain (e.g., IRAM-30m/EMIR, NOEMA, …) during the 2010s has allowed us to image a significant fraction of a Giant Molecular Cloud with enough sensitivity to detect tens of molecular lines in the 70 – 116 GHz frequency range. Machine learning techniques applied to these data start to deliver the next generation of molecular line diagnostics of mass, density, temperature, and radiation field.