bluuebunny/crossref_metadata_2025_split huggingface dataset:
EST-CE PARCE QU’ILS SONT MARIÉS QUE LES HOMMES MARIÉS GAGNENT PLUS QUE LES HOMMES NON-MARIÉS ?
Authors: Jeandidier Bruno 
Published: April 2021

La théorie économique du mariage pose l’hypothèse selon laquelle, du fait de la spécialisation au sein du couple, l’homme devrait bénéficier d’une prime au mariage. La littérature empirique internationale semble réfuter cette hypothèse. Nous proposons une revue de littérature empirique qui montre que la réfutation tiendrait au fait qu’une part de cette prime s’expliquerait plutôt par un effet de sélection et au fait que la prime nette de sélection serait faiblement corrélée à la spécialisation. D’autres logiques pourraient alors expliquer l’éventuelle prime au mariage des hommes : la discrimination des employeurs et l’effet de responsabilisation. Mais la littérature empirique relative à ces deux logiques alternatives est moins fournie et n’aboutit pas sur des conclusions tranchées : peu de travaux identifient clairement un effet de discrimination des employeurs et les travaux avançant l’idée d’un effet de responsabilisation, notamment en termes d’effet de la paternité, ne sont pas convergents.
Evaluation of the Efficacy of Chemical Insecticides and Biopesticides against Flea Beetle in Cabbage (Brassica oleracea var. Capitata)
Authors: Farhana Fatima , Latif Md. Abdul , Ali Mohammed 
Published: April 2021

Aims: This study aimed to evaluate chemical insecticides and bio-pesticides against flea beetle in cabbage.
Study Design: The experiment was laid out at a randomized complete block design with three replications.
Place and Duration of Study: Experimental farm of Sher-e-Bangla Agricultural University, Bangladesh during the period from October 2017 to March 2018.
Methodology: The experiment consisted of nine treatments viz. T1(Sevin 85 WP @ 2g/L of water), T2 (Decis 2.5 EC @ 1.0 ml/L of water), T3 (Voliam flexi @ 0.5 ml/L of water), T4 (Ripcord 10 EC @ 1.0 ml/L of water), T5 (Dursban 20EC @ 1 ml L-1 of water), T6 (Tobacco leaf extract @ 3 g L-1 of water), T7 (Neem seed kernel extract @ 3 g L-1 of water), T8 (Bioneem plus 1 EC @ 1 ml L-1 of water) and T9 (Untreated Control) were used at 7 days interval.
Results: Stripped flea beetle(Phyllotreta striolata) and white-spotted flea beetle (Monolepta signata), these two species of flea beetle were found in the experimental field. Among all the treatments T4 (Ripcord 10EC)performed the best in managing flea beetles based on the lowest percentage of leaf infestation (5.84%), lowest no. of holes per plant (6.13), lowest percentage of head infestation by number (18.04) and highest percentage of infestation reduction over control on all parameters at vegetative stage of plant. Again, the lowest leaf infestation intensity (5.73%), lowest number of holes per infested head (14.00), lowest percentage of infestation of head by number (6.69) were achieved at harvesting stage from the same treatment (T4) whereas the highest values of all these parameters were achieved from untreated control treatment (T9). T4 treatment provided the best performance in yield where yield was increased (112.51 %) over control, giving maximum yield 75.76 tons ha-1. Bioneem plus 1 EC (T8) performed the best among the biopesticides while the neem seed kernel extract showed less effectivity against flea beetle.
Conclusion: It is concluded that in case of chemical insecticides Ripcord 10EC while in case of biopesticides Bioneem plus 1 EC would be effective for flea beetle management.
Impact of Panchakarma Therapy and Diet Modification on Lipid Level on known Dyslipidemia Patients
Authors: Sane Rohit , Mandole Rahul , Amin Gurudatta , Ghadigaonkar Pravin 
Published: April 2021

Aim: To study the impact of panchakarma treatment and diet modification on the reduction of lipid levels in known dyslipidemia patients.
Study Design: Single–arm pilot study
Place and Duration of the Study: 50 centres of Madhavbaug clinic, Maharashtra, India, between March 2020 to September 2020.
Methodology: We included 35 known coronary artery disease patients (mean age 56.55+10.20 years) of which 74.29% were males and 25.71% were females that had a total cholesterol count of more than 200mg/dL. The study therapy viz. Ischemia Reversal Therapy included: herbal detoxification (minimum 14 sittings of 90 minute each) and the diet prescribed was low calorie : <800. The study time points were baseline and 90 days post treatment. The patients were screened for reduction in total cholesterol, low density lipids and weight and an increase in high density lipids.
Results: Primary finding (Mean±SD, Baseline Vs. 90-days): reduced Low Density Lipoproteins (LDL) (142.37±42.33 Vs. 106.42±37.60, p=0.0001) and Total Cholesterol (240.88±52.30 Vs. 174.91±39.61, p=0.001) levels while secondary findings (Mean±SD, Baseline Vs. 90-days): marginal increase HDL-C (41.66±11.77 Vs. 42.8±9.49, p=0.67) and reduction in weight (66.35±13.15 Vs. 62.3±11.78, p=0.19). Reduced dependency on statins by 83.33% post treatment whilst maintaining TC levels within normal range.
Conclusion: This Study results highlight the benefits of herbal detoxification therapy and diet modification to treat Dyslipidemia thereby reducing the dependency on statin therapy.
Small Pilot System for the Manufacture of in Situ Precipitated Calcium Carbonate in the Presence of Pulp Fibers
Authors: Dölle Klaus , Bajrami Bardhyl 
Published: April 2021

Paper fillers materials are less expensive than fiber, allowing reduced production costs and improvement of paper properties.
A small pilot scale in-situ laboratory calcium carbonate filler precipitation unit was developed and designed with the objective to provide enough pulp fiber containing in-situ precipitated calcium carbonate for a small 12-inch (304 mm) wide laboratory paper machine. The in-situ precipitation system requires the reactants calcium hydroxide and carbon dioxide and was tested with a eucalyptus pulp fiber pulp suspension.
The final precipitated in-situ filler content achieved was 38.2%, 55.5% and 66.6% based on initial eucalyptus pulp fiber content. The precipitation time from an initial pH of 12.77, 12.76 and 11.98 to an final pH of 7.29, 7.55, and 7.28 for the 3 kg, 6kg, and 9 kg of calcium hydroxide reactant addition was 45 minutes for the 3 kg and 9 kg calcium hydroxide addition and 40 min. for the 6 kg calcium hydroxide addition.
Angiotensin‐Converting Enzyme Inhibitors
Authors: Petrillo Edward W. 
Published: April 2021

Abstract
The discovery of captopril, the first orally active angiotensin‐converting enzyme inhibitor, showed that blockade of the renin‐angiotensin system effectively lowers blood pressure in a wide spectrum of patients with hypertension. Captopril was designed using a hypothetical model of the enzyme active site that subsequently guided the design of new classes of inhibitors. Because ACE inhibitors retard the progression of cardiovascular disease and the complications of diabetes, leading to an overall reduction in mortality, they have become one of the most widely used drug classes in cardiovascular medicine. New genetic and structural evidence has revealed that ACE has two functional catalytic domains with differences that may be exploited in the future to design inhibitors with superior properties.
Antiplatelet Agents
Authors: Chackalamannil Samuel 
Published: April 2021

AbstractIn addition to their life‐sustaining role in hemostasis and wound healing, platelets play a central role in the pathogenesis of coronary artery, cerebrovascular, and peripheral vascular diseases. Under pathologic conditions such as rupture of an atherosclerotic plaque, the platelet activation mechanism and coagulation mechanism synergize in the formation of an occlusive thrombus leading to ischemic disorders such as acute coronary syndrome and stroke. Antiplatelet agents are the mainstay of pharmacological approach for the treatment of ischemic vascular disorders. Platelets have multiple cell‐surface receptors that, upon activation by specific ligands, trigger a cascade of cellular events resulting in the activation of the integrin glycoprotein (GP) IIb/IIIa receptors. Activated GP IIb/IIIa receptors cross‐link with fibrinogen causing platelet to aggregate. Aggregated platelets get trapped by fibrin meshwork, produced by the proteolysis of fibrinogen by thrombin. Cell‐surface platelet receptors have been the target of antiplatelet therapy. For example, aspirin, the most widely used antiplatelet agent, inhibit the biosynthesis of thromboxane A2, the endogenous agonist that activates thromboxane receptors. The ADP antagonists such as clopidogrel and ticlopidine inhibit ADP‐mediated activation of purinergic P2Y12receptors. Glycoprotein IIb/IIIa antagonists such as abciximab, eptifibatide, and tirofiban inhibit GP IIb/IIIa receptors, which involve the final common pathway of platelet aggregation. Phosphodiesterase inhibitors are less widely used antiplatelet agents that potentiate intracellular cyclic AMP levels. Promising newer antiplatelet agents such as thrombin receptor antagonists with reduced bleeding liability, third‐generation thienopyridine ADP antagonists with improved potency and reversible ADP antagonists are at advanced stage of development.
Anticoagulants
Authors: Quan Mimi L. , Glunz Peter W. , Luettgen Joseph M. 
Published: April 2021

Abstract
Although blood circulation is highly regulated, dysfunctional activities resulting from either deficient or excessive coagulation have serious health consequences. Insufficient clotting can lead to prolonged bleeding and hemophilia‐related conditions. Over activation of coagulation can lead to thrombosis‐related disorders, such as deep venous thrombosis, pulmonary embolism, and stroke, which together are a major cause of morbidity and mortality. Studies of the biological pathways leading to coagulation, and the resultant development and refinement of the coagulation cascade, have identified many potential biological targets for therapeutic intervention. The major challenge regarding the treatment and prevention of thromboembolic diseases is the requirement for effective anticoagulant therapy without exposing patients to an increased risk of bleeding. Preclinical and clinical evaluations of anticoagulant agents highlight this efficacy/bleeding dichotomy. This article presents the medicinal chemistry efforts leading to the discovery of inhibitors of the coagulation cascade, resulting in marketed thrombin and Factor Xa inhibitors. Also reported is the progress toward identifying emerging anticoagulants.
Ion Channels as Therapeutic Drug Targets
Authors: Garcia Maria L. , Kaczorowski Gregory J. 
Published: April 2021

AbstractIon channels comprise a large and diverse family of proteins that control many physiological functions. For this reason, a number of inherited diseases result from mutations in specific genes that alter the functions of given ion channels. Drugs used to treat a variety of pathophysiological conditions derive their benefits from interacting with specific ion channel(s), and efforts to develop novel ion channel drugs that would address unmet clinical needs are ongoing in pharmaceutical, biotech, and academic institutions. During the past period of time, major developments in functional screening technologies have afforded the study of these proteins in high‐density formats. In addition, a large body of information concerning the structure of different ion channels has become available. In some cases, intimate details of the interactions between drugs and ion channels have been obtained, which may help with designing more potent and selective ion channel modulators. Although a number of ion channel modulators have entered clinical development, lack of therapeutic efficacy or toxicity issues have caused termination of the development of many of these agents. Nonetheless, with all accumulated experience and new technological advancements, expectations are high for the successful development of novel ion channel modulators in the future.
Drug Discovery Beyond the Rule of Five
Authors: DeGoey David A. , Cox Philip B. 
Published: April 2021

Abstract
Approximately 6% of orally administered drugs have physicochemical properties that are beyond Lipinski's rule of five (bRo5). However, in the past five years, there have been 22 new oral bRo5 drugs approved by the FDA, which account for 21% of new oral drug approvals. The significant increase in the percentage of bRo5 drug approvals represents a shift in the types of drug targets undertaken by medicinal chemists including a larger number of protein–protein interaction (PPI) inhibitors, such as BCL‐2 inhibitors, and nontraditional drug targets such as NS5A inhibitors for the treatment of hepatitis C (HCV). The shift away from more druggable enzyme and GPCR targets has resulted in the development of larger molecules that have physicochemical properties that far exceed those previously expected to yield adequate solubility and permeability for oral absorption. Due to frequently lower solubility and permeability, conducting drug discovery research in bRo5 chemical space is difficult and represents a challenge for medicinal chemists to move away from the more well‐understood Ro5 chemical space. In this article, we review the current state of the art for drug discovery bRo5 including a review of the literature, an analysis of physicochemical properties and case studies of the approved classes of bRo5 drugs.
Fragment‐Based Lead Discovery
Authors: Hubbard Roderick E. 
Published: April 2021

Abstract
Fragment‐based discovery is an effective approach to finding hit compounds that bind to a target. Fragments can be found that bind to most sites on most proteins, providing a rich source of chemical ideas for the medicinal chemist to develop into hits and leads. There are two distinctive activities in fragment‐based discovery: (i) finding fragments that bind and (ii) evolving the fragments to hit compounds which can then be progressed using conventional (structure‐guided) optimization. A wide variety of methods have been developed for screening, many based on biophysical approaches to identify and then characterize the binding of the relatively low affinity (but efficient) compounds – a separate section summarizes the key features of the methods. Perhaps the most difficult aspect of fragment‐based discovery is deciding which fragments to evolve – another section describes some recent projects to highlight the key strategies that are used. The article concludes with some summary statements on the main features and advantages of the approach and a discussion about future directions.
Clinical Development – A Primer
Authors: Chachad Siddharth 
Published: April 2021

Abstract

Objective
: Clinical development of a drug product is a long and complex process, so it is rather impossible to capture all the aspects of this process in details in this article. Accordingly, the key objective of this article is to present an overview of how a new medicinal product undergoes clinical evaluation to ensure that ultimately quality medicine with proven safety and efficacy is delivered to the end user, i.e. patient who consumes it for health benefit. An attempt is also made to briefly cover clinical development of biological drugs, which can require a different approach to supporting the dose justification and assessing immunogenicity risks as compared to chemically synthesized drug products.

Method
: The information covered in this article is based on personal experience in the area of clinical development for regulatory submissions worldwide, regulatory guidance documents and legislations, as well as extensive literature surveillance using key terms such as clinical research, phases of development, efficacy, safety, new drug product, new chemical entity, new therapeutic entity, generics, biologics and biosimilars, oncology trials, modeling, and simulation. Clinical development is a process driven not only by science and regulations but also significantly by cost and time. The interested reader is encouraged to review clinical trial guidelines on the Food and Drug Administration (FDA) website and websites of other regulatory authorities such as European Medicines Agency (EMA), Therapeutic Goods Administration (TGA), and Health Canada. Those with further interest may also visit Clinical Trial Registry websites including
www.clinicaltrials.gov
to get familiar to different types of clinical study designs across phases of development carried out by sponsors as research studies or in pursuance of their marketing authorization applications.
Recent Advances in Chemistry Technologies and Applications to Medicinal Chemistry
Authors: Bogdan Andrew R. , Gesmundo Nathan J. , Webster Matthew P. , Wang Ying , Vasudevan Anil 
Published: April 2021

Abstract
Successful drug discovery is a team sport, wherein several disciplines contribute customized scholarship toward the common goal of delivering medications that can have a remarkable impact on patients' lives. In the realm of medicinal chemistry, there have been significant advances in molecular‐/structure‐based design, organic synthesis, and chemistry technologies, the interplay of all of which can have a significant impact on reducing cycle times, cost of goods, and improving the probability of technical success of drug discovery. This article covers the evolution and application of some of the newer chemistry technologies in medicinal chemistry.
Function of Proteins Identified as Part of the Nuclear Matrix
Authors: Zhang Yuwen , Huo Xiangru , Wen Bo 
Published: April 2021

Abstract

Nuclear matrix (NM) is an intranuclear protein network originally found after high‐salt or lithium diiodosalicylate extraction and nuclease treatment. Proteins identified as part of the NM comprise a multifunctional platform for various nuclear functions. NM contains proteins involved in chromatin packaging, deoxyribonucleic acid (DNA) replication, transcription, ribonucleic acid (RNA) splicing, DNA repair and cell signalling. Dysfunction of NM proteins may result in defective cell functions, abnormal organogenesis and disorders such as progeria and some cancers.

Key Concepts

Some NM proteins bind to chromatin via its scaffold/matrix‐attached regions (S/MARs), help chromatin loop formation or organise higher order chromatin architecture.

The deoxyribonucleic acid (DNA) replication machinery can be attached to certain nuclear matrix (NM) proteins.

Some NM proteins are associated with transcription factories and regulate gene expression.

The abnormal expression or genetic variants of NM genes may cause development abnormalities and diseases.
Strongly Luminescent Dion–Jacobson Tin Bromide Perovskite Microcrystals Induced by Molecular Proton Donors Chloroform and Dichloromethane
Authors: Wang Shixun , Popović Jasminka , Burazer Sanja , Portniagin Arsenii , Liu Fangzhou , Low Kam‐Hung , Duan Zonghui , Li Yanxiu , Xiong Yuan , Zhu Yuanming , Kershaw Stephen V. , Djurišić Aleksandra B. , Rogach Andrey L. 
Published: April 2021

AbstractLead‐free 2D perovskites based on tin halide octahedron slabs with Dion–Jacobson (DJ) phases have drawn attention due to their improved stability; still, reports on light‐emitting DJ lead‐free perovskites are scarce. Herein, a room‐temperature ligand assisted re‐precipitation method is used to produce ODASnBr4 perovskite microcrystals (ODA denotes protonated 1,8‐octanediamine). After incorporating molecular dopants chloroform and dichloromethane, not only the crystallinity of the DJ perovskite phase improves, but their emission becomes much stronger due to the formation of hydrogen bonds between [SnBr6]4− octahedra and acidic CH proton donors. ODASnBr4 microcrystals doped with these molecules show a high photoluminescence quantum yield (PLQY) approaching 90%, and their emission remains stable under a continuous UV irradiation, with less than 10% loss in intensity over 6 h. Moreover, by tuning the pristine ODASnBr4 with various degrees of exposure to the molecular dopants, the maximum of their self‐trapped exciton emission can be fine‐tuned over a spectral range of 570–608 nm while maintaining high PLQYs of 83–88%. This provides a convenient way to adjust the spectral position of DJ perovskite emission without changing halides or A‐site spacers. Thus, stable and strongly emitting lead‐free DJ perovskite materials have been developed.
A Versatile Cationic Organic Network Adsorbent for the Highly Efficient Removal of Diverse Water Contaminants
Authors: Li Zhi‐Jun , Zhang Qi , Xue Hua‐Dong , Zheng Xu‐Dong , Qi Hui‐Li , Li Hui‐Cheng 
Published: April 2021

AbstractWater decontamination is of great importance to address the increasing shortage of water resources, ion‐exchange‐driven adsorption being one of the most efficient approaches to this aim. Despite the advances achieved in this field, particularly with the emergence of ionic organic networks as a new class of adsorbents for water treatment, the development of adsorbents with high performance is still highly desired. This paper describes the facile preparation of a new cationic organic network, denoted as CON‐LDU3, via a quaternization reaction between 1,2,4,5‐tetra(pyridin‐4‐yl)benzene and 1,4‐bis(bromomethyl)benzene. The cationic framework and abundant exchangeable Br− anions render CON‐LDU3 as a suitable adsorbent to capture anionic contaminants from water. CON‐LDU3 displays fast kinetics and high capacity for the removal of CrO42−, reaching the kinetic constant and maximum capacity values of 0.0539 g mg−1 min−1 and 232 mg g−1, respectively. Moreover, this adsorbent can be regenerated by simple washing with KBr solution, and it can be recycled for at least eight times. CON‐LDU3 also exhibits excellent performance in the adsorption of some emerging organic water contaminants such as orange G and diclofenac sodium. Therefore, this study demonstrates the high potential of CON‐LDU3 as a versatile adsorbent for water remediation.
Multiplexing Liquid Biopsy with Surface‐Enhanced Raman Scattering Spectroscopy
Authors: Abalde‐Cela Sara , Wu Lei , Teixeira Alexandra , Oliveira Kevin , Diéguez Lorena 
Published: April 2021

AbstractAmong the main challenges faced in cancer research, early detection, metastatic pathways and biomarker discovery are being tackled both by researchers and technology‐based companies. The development of novel technologies that can advance the state‐of‐the‐art for those defined challenges is critical in order to enhance the survival rates as well as to significantly lower cancer associated costs, not to mention social and human impact. In the recent years, the field of liquid biopsy has grown tremendously due to its capacity to obtain and study tumor material in a non‐invasive way. Liquid biopsy arises as an alternative diagnostic tool based on the analysis of biomarkers present in body fluids. The characterization of those biomarkers is commonly made by already well‐established standard technologies, usually limited in terms of sensitivity, selectivity, multiplexing, high‐throughput, and/or speed of analysis. Unfortunately, highly sensitive molecular diagnostic technologies still have high associated costs preventing their universal application. In this review, the authors aim to provide the reader with a general comprehension on how surface‐enhanced Raman scattering (SERS) spectroscopy can overcome those bottlenecks. The combination of SERS and liquid biopsy may fulfill the holy grail of the so‐called precision medicine, ultimately contributing to the dream of cancer chronification.