bluuebunny/crossref_metadata_2025_split huggingface dataset:
European Medicinal Chemistry Leaders in Industry (EMCL) – On the Status and Future of Medicinal Chemistry Research in Europe**
Authors: Ali Amjad , Bauser Marcus , Bertrand Sophie , Blackaby Wesley , Boss Christoph , Bossart Martin , Hall Adrian , Binch Hayley , Czechtizky Werngard , Gijsen Harrie , Haning Helmut , Hartung Ingo V. , Kilburn Paul , Lassalle Gilbert , Lücking Ulrich , Mack Jürgen , Missbach Martin , Otsomaa Leena , Torrens Antoni , Wagner Michael , Walter Magnus , Weinstabl Harald , van Hijfte Luc , von Nussbaum Franz 
Published: June 2023

AbstractThe status of industrial Medicinal Chemistry was discussed with European Medicinal Chemistry Leaders from large to mid‐sized pharma and CRO companies as well as biotechs. The chemical modality space has expanded recently from small molecules to address new challenging targets. Besides the classical SAR/SPR optimization of drug molecules also their ‘greenness’ has increasing importance. The entire pharma discovery ecosystem has developed significantly. Beyond pharma and academia new key players such as Biotech and integrated CROs as well as Digital companies have appeared and are now to a large extend fueled by VC money. Digitalization is happening everywhere but surprisingly did not change speed and success rates of projects so far. Future Medicinal Chemists will still have to be excellent synthetic chemists but in addition they must be knowledgeable in new computational areas such as data sciences. Their ability to collaborate and to work in teams is key.
Interactions between distal epiclastic and bio‐chemogenic sedimentation at the foothills of a mafic alkaline volcano: The case of the Oligocene Doupovské Hory Volcanic Complex (Czech Republic)
Authors: Rapprich Vladislav , Čáp Pavel , Erban Kochergina Yulia V. , Kadlecová Eva , Benkó Zsolt , Sakala Jakub , Rodovská Zuzana , Matějů Jan , Petrash Daniel A. 
Published: June 2023

AbstractLate Oligocene (ca 25 Ma) volcano‐sedimentary successions exposed on the western periphery of the Doupovské Hory Volcanic Complex reveal a complex sedimentation history influenced in various ways by decay of the alkali basalt volcanic edifice. Weathering of the volcanic rocks supplied abundant reactants that promoted carbonate precipitation in the peripheral palaeolakes—as evidenced by strongly non‐radiogenic 87Sr/86Sr values (0.7038–0.7041). On the other hand, the sediments of the initial shallow lake became deformed by the bulldozing effect of a debris avalanche. The debris flow and avalanche deposits filled up the original depression, modified the basin morphology and shifted the peripheral lacustrine setting further away from the volcano. At this stage, surface water influx from the surrounding granites conferred a more radiogenic character (87Sr/86Sr values 0.7046–0.7049) to the calcrete deposits. Fossil assemblages as well as limestone textures suggest significant seasonal water‐level fluctuations, possibly reflecting the alternating rainy and dry‐seasons of a prevalently humid Central‐European Late Oligocene climate. The seasonal drying out of the ponds resulted in significant 18O enrichments. Although the ca 0‰ δ13C values might suggest mixing of atmospheric and volcanic CO2 during carbonate precipitation, no active volcanic conduits of relevant age are known in the close vicinity. The lower δ13C values are likely a result of mantle degassing through rift faults, a phenomenon observed in the magmatically extinct Ohře Rift until present. This paper demonstrates that limestones derived from weathered alkaline basalts are characterised by highly non‐radiogenic Sr isotopic ratios (87Sr/86Sr ca 0.704), suggesting a magmatic origin for the Ca within these carbonates. Contrary to the notion of carbonatites being present when highly non‐radiogenic Sr isotopes are found, these results show that Sr isotopes in carbonates formed in alkali basalt‐sourced environments only reveal the source of the Sr (and Ca) ions, not necessarily the presence of carbonatite.
Global climate regulates dimensions of terrestrial ecosystem stability
Authors: Liu Pai , Chi Yonggang , Chen Jijing , Zhou Lei 
Published: June 2023

AbstractEcosystem stability represents the ability of the ecosystem to maintain and restore its functions. The indicators of ecosystem stability include temporal stability, resistance, and resilience, which are crucial parameters to predict the basic functions of the earth under global change. However, the correlation between the indicators of ecosystem stability and the dimensions of ecosystem stability at global scale remains unclear. Here, we quantified the global dimensions of ecosystem stability using moderate resolution imaging spectrometer (MODIS) enhanced vegetation index (EVI) data from 2001 to 2018 as well as climate variables and land standard species richness data. We revealed a strong positive correlation between temporal stability and resistance and no correlation between resistance and resilience at global scale. The dimension of ecosystem stability changed along the gradients of latitude or altitude. The dimensions of ecosystem stability were different among biomes, showing the lowest in the evergreen broad‐leaved forest (EBF) and the highest in the grassland (GRA). Climate factors were strongly associated with the changes in dimensions of ecosystem stability at global scale. These findings highlight the crucial role of dimensions in exploring ecosystem stability, potentially eliminating contradictions in the ecosystem service mechanism of the earth.
Design of Stereogenic‐at‐Iron Catalysts with a (3+2+1)‐Ligand Sphere
Authors: Baran Dominik , Hinterlang Lukas , Ivlev Sergei I. , Meggers Eric 
Published: June 2023

AbstractA stereogenic‐at‐iron(II) catalyst scaffold is introduced which contains one coordinated meridional tridentate imidazolidin‐2‐ylidene‐functionalized 2,2′‐bipyridine, one bidentate pyrazolylpyridine, and one monodentate acetonitrile ligand. This (3+2+1)‐coordination sphere implements a stereogenic iron center. A carbon stereocenter in the N‐heterocyclic carbene moiety controls the absolute metal‐centered configuration. The bench‐stable diamagnetic iron(II) complexes can be synthesized in a highly diastereoselective fashion from iron dibromide in an efficient one‐pot coordination reaction. The obtained enantiopure complexes were applied as chiral catalysts in the ring contraction of an isoxazole to a chiral 2H‐azirine (quantitative yields, up to 90 : 10 er).
Variable Temperature Crystal Structure of Cu4TiTe4
Authors: Lakshan Achintya , Petříček Václav , Jana Partha Pratim 
Published: June 2023

AbstractA variable temperature single crystal X‐ray diffraction study of the ternary compound, Cu4TiTe4 is reported between 200–400 K. The temperature dependent study indicates the compound undergoes an order‐disorder phase transition at ∼320 K. Below the transition temperature, the phase that crystallizes in the primitive cubic space group P
3 m with lattice parameter of a≈5.9 Å, transforms into the two‐fold superstructure. It is modeled as a fourfold twinned rhombohedral structure. The transition is reversible. To relate the phases, a group‐subgroup symmetry relations are established. Upon decreasing temperature, the atomic ordering is noticed in the occupationally disordered Cu‐sites of Cu4TiTe4. This characteristic structural rearrangement may have a significant impact on the electronic structure of Cu4TiTe4. Hence, the detailed structural characterization is supposed to be useful for further understanding of thermoelectric transport properties in the Cu4TiTe4.
New Type of Neutral Binuclear Spin‐Crossover Complex of Iron(III) with Twist of Two Disulfide Bridges as a Product of Electrochemical Oxidation of [FeIII(5Cl‐thsa)2]− Anions
Authors: Blagov Maxim A. , Spitsyna Nataliya G. , Lazarenko Vladimir A. , Ovanesyan Nikolai S. , Lobach Anatolii S. , Zorina Leokadiya V. , Simonov Sergey V. , Krapivin Vladimir B. , Dmitriev Alexei I. , Zhidkov Mikhail V. , Yagubskii Eduard B. 
Published: June 2023

AbstractAs a result of the electrochemical oxidation process, the [FeIII(5Cl‐thsa)2]− spin‐crossover (SCO) anion with N2S2O2 coordination sphere transforms into N4O2‐coordinated FeIII SCO neutral binuclear complex 2 with twist of two disulfide bridges. Each dimeric complex is a binuclear double‐stranded helicate with similar chirality of both Fe centers. The crystal structure of the complex 2 ⋅ 3H2O at 100 K has a monoclinic C2/c space group and contains large cavities (about 21.5 % of the unit cell volume) half‐filled by 3 water molecules per one dimer. The N4O2 coordination of iron(III) with two oxygen atoms (−O−) of phenoxy groups, two imine‐type (−Nim=) nitrogen atoms of azomethine groups, one amidrazone‐type (=NamidH) nitrogen atom and one ionized terminal group (−NionizH) of nitrogen has not been observed in CCDC so far. The oxidation state of the iron atoms in the dimeric complex was confirmed by 57Fe Mössbauer spectroscopy on 90 % enriched 57Fe sample. Mössbauer spectra and dc magnetic measurements demonstrated the partial HS‐HS→LS‐LS SCO in the 185–225 K temperature range. The details of the structure of complex 2 and the features of its magnetic properties were refined by theoretical analysis based on DFT calculations. The B3LYP* functional correctly predicting the energy of the spin‐crossover process was revealed.
Iodine‐Mediated One‐Pot Synthesis of 1,4,5‐Substituted Pyrazoles from MBH Acetates via Allyl Hydrazone Intermediate
Authors: Dahatonde Dipak J. , Ghosh Aritra , Vutla Adilakshmi , Batra Sanjay 
Published: June 2023

AbstractHerein, we report the regioselective one‐pot synthesis of 1,4,5‐trisubstituted pyrazoles by reacting Morita‐Baylis‐Hillman (MBH) acetates derived from aryl aldehydes with alkyl or aryl hydrazines in the presence of iodine under aerobic conditions. The reaction proceeds through sequential SN2′ nucleophilic substitution of substituted hydrazine onto the MBH acetate, I2‐catalyzed oxidation of the allylic hydrazine to allylic hydrazone, heating‐induced intramolecular aza‐Michael reaction and cyclization, and oxidative aromatization. The key intermediate, thes‐transallyl hydrazones were isolated in good yields by performing the reactions at room temperature. However, the allyl hydrazones prepared from the MBH acetates of aliphatic aldehydes did not furnish the pyrazole owing to the absence of an activated methylene group in the substrate. The synthetic applications of the pyrazoles in Ugi reactions, decarboxylative halogenation, Pd‐catalyzed benzoylation of the N‐aryl ring, and metal‐free tetrazole synthesis has been demonstrated.
Cold‐evoked potentials in clinical practice: A head‐to‐head contrast with laser‐evoked responses
Authors: Perchet Caroline , Hagiwara Koichi , Salameh Charbel , Garcia‐Larrea Luis 
Published: June 2023

AbstractBackgroundInnocuous cooling of the skin activates cold‐specific Aδ fibres, and hence, the recording of cold‐evoked potentials (CEPs) may improve the objective assessment of human thermo‐nociceptive function. While the feasibility of CEP recordings in healthy humans has been reported, their reliability and diagnostic use in clinical conditions have not been documented.MethodsHere, we report the results of CEP recordings in 60 consecutive patients with suspected neuropathic pain, compared with laser‐evoked potentials (LEPs) which are the gold standard for thermo‐algesic instrumental assessment.ResultsCEP recording was a well‐tolerated procedure, with only ~15 min of surplus in exam duration. The reproducibility and signal‐to‐noise ratio of CEPs were lower than those of LEPs, in particular for distal lower limbs (LLs). While laser responses were interpretable in all patients, CEPs interpretation was inconclusive in 5/60 because of artefacts or lack of response on the unaffected side. Both techniques yielded concordant results in 73% of the patients. In 12 patients, CEPs yielded abnormal values while LEPs remained within normal limits; 3 of these patients had clinical symptoms limited to cold sensations, including cold‐heat transformation.ConclusionsCEPs appear as a useful technique for exploring pain/temperature systems. Advantages are low cost of equipment and innocuity. Disadvantages are low signal‐to‐noise ratio for LL stimulation, and sensitivity to fatigue/habituation. Joint recording of CEPs and LEPs can increase the sensitivity of neurophysiological techniques to thin fibre‐ spinothalamic lesions, in particular, when abnormalities of cold perception predominate.SignificanceRecording of cold‐evoked potentials is a well‐tolerated, inexpensive and easy‐to‐use procedure that can be helpful in the diagnosis of abnormalities in the thin fibre‐ spinothalamic pathways. Supplementing LEPs with CEPs allows consolidating the diagnosis and, for some patients suffering from symptoms limited only to cold, CEPs but not LEPs may allow the diagnosis of thin fibre pathology. Optimal CEP recording conditions are important to overcome the low signal‐to‐noise ratio and habituation phenomena, which are less favourable than with LEPs.
Development and comparative evaluation of integrated solar‐driven off‐grid energy systems with hydrogen production and storage options for sustainable buildings
Authors: Erdemir Dogan , Dincer Ibrahim 
Published: June 2023

AbstractThis study presents the development of a new solar energy‐based integrated system where hydrogen production, storage, and power generation and heat storage subsystems are designed in a combined manner to meet the energy demands of multiple buildings in a community. It is also comprehensively analyzed and assessed under various criteria comparatively. A comprehensive study is established for a community with 80 156 residential buildings in Southern Ontario, Canada. Solar‐driven three different cases are investigated, which cover (i) solar energy and grid‐assisted, (ii) solar energy‐driven system integrated with hydrogen subsystems, and (iii) solar‐driven system integrated with hydrogen subsystems and heat storage for both heating and cooling purposes. The studied cases are assessed over the energy and exergy efficiencies. The results of this study indicate that it is possible to achieve solar‐driven and off‐grid operating conditions with hydrogen and heat storage systems. Only about 15% of the energy demand can be met by solar energy without any energy storage options (Case 1). Case 2 shows that it can be achieved off‐grid solar energy system with 1100 MWp of solar power plant capacity with the integration of hydrogen as an energy storage option. In the case of using hydrogen and heat storage together, off‐grid operating conditions can be reached with 750 MWp of power plant capacity. The heat storage integration helps reduce the capacity of the photovoltaic power plant by 32%. Furthermore, hydrogen and heat storage options are needed to cover both cooling and heating demands simultaneously to provide sustainable buildings.
Development of an Embryo Toxicity Test to Assess the Comparative Toxicity of Metal Exposure on Different Life Stages of Freshwater Gastropods
Authors: Osborne R. K. , Ijzerman M. M. , Venier C. , Prosser R. S. 
Published: June 2023

Abstract
Early life stages are commonly thought to be highly sensitive to environmental contaminants and may offer insight into the future health of a population. Despite the importance of studying early life stages, very few standard protocols for benthic invertebrates commonly used in ecotoxicological assessments measure developmental endpoints. The goal of the present study was to develop and optimize a robust standard protocol for studying embryonic endpoints in freshwater gastropods. The developed method was then used to characterize the sensitivity of four embryonic endpoints (viability, hatching, deformities, and biomass production), in conjunction with juvenile and adult mortality, for the snail Planorbella pilsbryi exposed to three metals (copper [Cu], cadmium [Cd], and nickel [Ni]). Biomass production was typically the most sensitive endpoint but was relatively variable, while embryo hatching was slightly less sensitive but highly consistent for all three metals. However, no single embryonic endpoint was consistently the most sensitive, which demonstrates the importance of assessing a broad range of endpoints and life stages in ecotoxicological risk assessment. Interestingly, the embryonic life stage of P. pilsbryi was considerably less sensitive to Cu exposure compared with juvenile and adult mortality. However, for Cd exposure, embryonic endpoints were the most sensitive, and for Ni exposure, embryonic endpoints were similar in sensitivity to juvenile and adult mortality. The present study has valuable applications in conducting developmental toxicity research with organisms lacking standardized testing protocol as well as future applications in multigenerational and in silico toxicity research. Environ Toxicol Chem 2023;42:1791–1805. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Incidence of Burkitt lymphoma in the United States during 2000 to 2019
Authors: Mburu Waruiru , Devesa Susan S. , Check David , Shiels Meredith S. , Mbulaiteye Sam M. 
Published: June 2023

AbstractBurkitt lymphoma (BL) is an aggressive B‐cell lymphoma that occurs worldwide. A study of BL in the US National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) program during 1973 to 2005 (n = 3043) revealed three age‐specific incidence peaks of BL and rates that were rising. We studied BL cases diagnosed in SEER 22 during 2000 to 2019 (n = 11 626) to investigate age‐specific BL incidence rates and temporal trends. The age‐standardized BL incidence rate was 3.96/million person‐years, with a 2.85:1 male‐to‐female ratio. The BL rate among both Hispanic and White individuals was higher than in Black individuals (4.52, 4.12 vs 3.14). Age‐specific BL rates showed peaks during pediatric, adult and elderly years in males and pediatric and elderly peaks in females. Based on 4524 BL cases with HIV status (SEER 13), only one peak in adult males (45 years) was observed. Overall age‐standardized BL incidence rates rose 1.2%/year (not significant) up to 2009 then fell significantly by 2.4%/year thereafter. Temporal trends in BL rates during 2000 to 2019 varied with age group as pediatric BL rates rose 1.1%/year, while elderly BL rates fell 1.7%/year and adult BL rates rose 3.4%/year until 2007 before falling 3.1%/year thereafter. Overall survival from BL was 64% at 2 years, being highest in pediatric patients and lowest in Black and elderly individuals vs other subgroups. Survival improved by 20% between 2000 and 2019. Our data suggest that BL age‐specific incidence rates are multimodal and that overall BL rates rose up to 2009 and then fell, suggesting changes in etiological factors or diagnosis.
Time to reconsider antibiotic prophylaxis in women with prolonged rupture of membranes: The trend of Enterobacteriaceae in peripartum infections
Authors: Abu Shqara Raneen , Glikman Daniel , Jad Saher , Rechnitzer Hagai , Lowenstein Lior , Frank Wolf Maya 
Published: June 2023

AbstractObjectiveThe proportion of neonatal early‐onset sepsis (EOS) by gram‐negative bacteria has increased. The authors examined bacterial distribution in the amniotic membrane cultures of women with peripartum fever (PPF) and related perinatal outcomes.MethodsThis retrospective study covered the period 2011 to 2019. The primary outcomes were Enterobacteriaceae‐positive birth culture rates in women with PPF and the trend of ampicillin resistance. Maternal and neonatal outcomes were compared between women with group B Streptococcus (GBS) and Enterobacteriaceae‐positive isolates. Bacterial distribution was also compared according to rupture of membrane (ROM) duration.ResultsAmong 621 women with PPF, the positive birth culture rate was 52%. Increasing prevalences of ampicillin‐resistant Enterobacteriaceae (81%) were noted. Positive birth cultures were associated with maternal bacteremia (P = 0.017) and neonatal EOS (P = 0.003). Prolonged ROM ≥18 h was associated with increased risk for Enterobacteriaceae‐positive cultures, while intrapartum ampicillin and gentamicin were associated with lower risk. Enterobacteriaceae‐positive compared with GBS‐positive birth cultures were associated with adverse maternal and neonatal outcomes.ConclusionPositive birth cultures were related to maternal bacteremia and neonatal sepsis. Adverse outcomes were more prevalent among women with Enterobacteriaceae‐positive versus GBS‐positive birth cultures. Prolonged ROM is a risk factor for Enterobacteriaceae‐positive birth cultures among women with PPF. Antibiotic prophylaxis treatment for prolonged ROM should be reconsidered.
Effectiveness of asynchronous feedback in teaching motivational interviewing skills
Authors: Dugan B. DeeAnn , Beall Jennifer , Thomas Michael C. 
Published: June 2023

AbstractIntroductionCommunication is an essential skill for pharmacists. Motivational interviewing is an advanced communication technique used for health behavior change. Studies have evaluated standardized patient (SP) simulation to develop communication skills; however, little is known about the use of SP simulations with asynchronous feedback in a telepharmacy scenario.ObjectiveThe objective of this study was to determine if the use of asynchronous embedded faculty feedback will improve students' motivational interviewing skills.MethodsDuring didactic training, students were introduced to motivational interviewing, practiced evaluation using a standardized rubric (max score 25), and participated in role‐play. Following training, students completed 2 weeks of lab simulation, one formative and one summative, in which students completed a 5‐min motivational interview with a SP via Zoom© which was recorded to allow for student self‐evaluation and asynchronous faculty video‐embedded feedback. Each encounter was assessed by faculty using the standardized rubric. The primary outcome measure was the difference in faculty evaluation scores of student interviews between the formative and summative labs. Secondary outcome measures included the difference in student self‐evaluation scores between the formative to summative labs and a number of students achieving competency (≥ 80%) or mastery (≥ 90%). Statistical analysis was completed using Wilcoxon signed rank tests (SAS® version 9.4).ResultsOne hundred fourteen students completed the study. Scores improved by a mean of 3.8 points between the formative and summative labs. Student self‐evaluation improved an average of 1.5 points between the labs. Competency and mastery were achieved by 89.5% and 52.6% of students, respectively. Score differences were not influenced by SP assigned. Use of SP and embedded asynchronous feedback in a motivational interviewing telepharmacy simulation resulted in improved student performance.