pinecone/core-2020-05-10-deduplication huggingface dataset:
Concerted vs. Non-Concerted 1,3-Dipolar Cycloadditions of Azomethine Ylides to Electron-Deficient Dialkyl 2,3-Dicyanobut-2-enedioates

The quantum-chemical calculations of the thermal ring opening of 1-methyl-2,3-diphenyl- and 1,2,3-triphenylaziridine with formation of the corresponding azomethine ylides of S-, U-, and W-type as well as their cycloaddition to dimethyl acetylenedicarboxylate (DMAD) and dimethyl 2,3-dicyanobut-2- enedioate, were performed at the DFT B3LYP/6-31G(d) level of theory with the PCM solvation model. The calculations are in complete accordance with experimental results and explain the switch from the concerted to the non-concerted pathway depending on substituents in the dipolarophile and the ylide. It was found that strong electron-withdrawing substituents in dipolarophiles, such as in dialkyl dicyanobutenedioates, significantly reduce the barrier for the formation of zwitterionic intermediates in the reaction of azomethine ylides with such dipoles. This can render the stepwise cycloaddition competitive with the concerted one. However, the concertedness of the cycloaddition even to dipolarophiles with several electron-withdrawing substituents is governed by a fine balance of electronic and steric effects in both ylide and dipolarophile counterparts. The hypothesis that introduction of substituents in the azo- methine ylide that destabilize the positive charge in a corresponding zwitterion will favor the concerted cycloaddition even with dialkyl dicyanobutenedioates was tested theoretically and experimentally
Density functional study of interactions between fluorinated cyclohexanes and arenes

The authors thank a Grant # 2012/03933-5, Sao Paulo Research Foundation (FAPESP), for providing financial support for this research, for a scholarship (to R.A.C. #2011/01170-1, FAPESP). CNPq is also acknowledged for a fellowship (to R.R) and a studentship (to R.A.C.). We thank the Royal Society (Wolfson Merit Award for D.O' H.) and EaStCHEM (support for M.B. and access to a computing facility maintained by H. Fruchtl).1H-NMR Chemical shifts of all-syn-1,2,4,5-tetrafluorocyclohexane (1), all-syn-1,2,3,4-tetrafluorocyclohexane (2), and their complexes with benzene are calculated at the BHandH/6-311+G(2d,p) level. The observed shielding of certain resonances on going from CD2Cl2 to (D8)toluene solution is qualitatively reproduced in these model calculations, in particular when standard B3LYP/def2-TZVP optimised geometries are employed. The results are interpreted with the quantum theory of atoms in molecules (QTAIM) and non-covalent interactions (NCI) methods, and they indicate that aromatic molecules bind strongly (1.6 kcal mol−1) to the ‘positive face’ of these molecules. The level of theory is validated for the new compound all-syn-1,2,4,5-tetrafluoro-3-phenylcyclohexane (3), where a recently developed QM/MM protocol for optimisation of molecular crystals afforded excellent agreement between the B3LYP/def2-TZVP structure and that observed in the solid.PostprintPeer reviewe
Reduction of Thiocarbonyl Compounds with Lithium Diisopropylamide

Treatment of 4,4-disubstituted 2-phenyl-1,3-thiazole-5(4H)-thiones with lithium diisopropylamide (LDA; LiNiPr2) in THF at -78° yielded the corresponding 1,3-thiazole-5(4H)-thioles in moderate yields. Sequential treatment with LDA and MeI under the same conditions led to the 5-methylsulfanyl derivatives. Similarly, reaction of some cycloalkanethiones as well as diaryl thioketones with LDA and MeI gave cycloalkyl methyl sulfides and diarylmethyl methyl sulfides, respectively. A reaction mechanism via H transfer from LDA to the thiocarbonyl C-atom via a six-membered transition state is proposed for this unprecedented reduction of the C1⁄4S bond
Synthesis of Aib- and Phe(2Me)-Containing Cyclopentapeptides

Some recently described pentapeptides containing the alpha,alpha-disubstituted alpha-amino acids Aib and Phe(2Me) have been cyclized in DMF solution using diphenyl phosphorazidate (DPPA), O-(1H-benzotriazol-1-yl)-N,N,N’,N’-tetamethyluronium tetrafluoroborate/1-hydroxybenzotriazole (TBTU/HOBt), and diethyl phosphorocyanidate (DEPC), respectively, to give the corresponding cyclopentapeptides in fair-to-good yields. In the case of peptides with L-amino acids, and (R)- and (S)-Phe(2Me), the yields differed significantly in favor of the L/(R) combination. The conformations in the crystals of cyclo(Gly-Aib-(R,S)-Phe(2Me)-Aib-Gly) and cyclo(Gly-(R)-Phe(2Me)-Pro-Aib-Gly) have been determined by X-ray crystallography, leading to quite different results. In the latter case, the conformation in solution has been elucidated by NMR studies
1,3-Dipolar Cycloadditions of alpha-Diazo Ketones Derived from N-Protected (S)-Proline with Aromatic and Cycloaliphatic Thioketones

Enantiomerically pure alpha-oxo diazo compounds derived from (S)-proline were used for 1,3-dipolar cycloaddition with aryl and hetaryl thioketones, as well as with cycloalkanethiones. Whereas the reactions with hetaryl thioketones in boiling THF yield alpha,beta-unsaturated ketones via a cascade of cycloaddition, 1,3-dipolar electrocyclization, and desulfurization, the analogous reactions with thiobenzophenone and cycloalkanethiones result in the formation of 1,3-oxathiole derivatives. In the latter case, the 1,5-dipolar electrocyclization of the intermediate thiocarbonyl ylide is the key step of the reaction sequence. In all cases, the isolated products are optically active, i.e., the multistep processes occur with retention of the stereogenic center incorporated via the use of (S)-proline as the precursor of the diazo compounds
Synthesis of Cyclopentapeptides with Three to Five Aib Units

Four new Aib-containing cyclopentapeptides have been synthesized by cyclization of the corresponding linear pentapeptides using the diethyl phosphorocyanidate (DEPC)/EtN(iPr)2 method. The linear precursors were prepared via the 'azirine/oxazolone method', i.e., the Aib units were introduced by the reaction of amino acids or peptide acids with a 2,2-dimethyl-2H-azirin-3-amine, followed by selective hydrolysis of the terminal amide function. Most remarkably, cyclo[(Aib)5] exists in CDCl3 solution in a symmetrical conformation, i.e., no intramolecular H-bonds are detectable
Selenophen-2-yl-substituted thiocarbonyl ylides – at the borderline of dipolar and biradical reactivity

The reactions of aryl (selenophen-2-yl) thioketones with CH2N2 occur with spontaneous elimination of N2, even at low temperature (-65°), to give regioselectively sterically crowded 4,4,5,5-tetrasubstituted 1,3-dithiolanes and/or a novel type of twelve-membered dithia-diselena heterocycles as dimers of the transient thiocarbonyl S-methanides. The ratio of these products depends on the type of substituent located at C(4) of the phenyl ring. Whereas the formation of the 1,3-dithiolanes corresponds to a [3 + 2] cycloaddition of an intermediate thiocarbonyl ylide with the starting thioketone, the twelve-memberd ring has to be formed via dimerization of the 'thiocarbonyl ylide' with an extended biradical structure
Studies on the reactions of thiocarbonyl s-methanides with hetaryl thioketones

Dihetaryl thioketones react with thiocarbonyl ylides to give 1,3-dithiolanes in high yields. No competitive side reactions of the thiocarbonyl ylides were observed, evidencing the 'superdipolarophilic' character of this less-known group of thioketones. Depending on the type of substituents present in both the thiocarbonyl ylide and the thioketone, formal [3+2] cycloadditions occur with complete regioselectivity or with formation of a mixture of both regioisomers. Regioselective formation of the sterically more crowded 1,3-dithiolanes is explained via a mechanism involving stabilized 1,5-biradicals. In systems with less-efficient radical stabilization, e.g., in the case of adamantanethione S-methanide, substantial violation of the regioselectivity was observed as a result of steric hindrance
Excursion to the World of Heptacyclic Compounds Made of Azulenes and Acetylenedicarboxylates

Azulenes and acetylenedicarboxylates react under acid catalysis (Brønsted or Lewis) and form (2aRS,8aSR)-2a,8a-dihydrocyclopenta[cd]azulene-1,2-dicarboxylates as intermediate products, which then dimerize by central bond-formation between C(2a1) and C(2’a1) and various peripheral C,C’-atoms of the dihydroazulene fragments, depending on the substituents present. The reactions are often accompanied by the formation of side-products, such as 2-(azulen-1-yl)fumarates and -maleates and others caused by H-shifts of the primary intermediates. H-Shifts between the two tetrahydrocyclopenta[ cd]azulene parts of the heptacyclic structures were also found
3D-Printing inside the glovebox: a versatile tool for inert-gas chemistry combined with spectroscopy

3D-Printing with the well-established ‘Fused Deposition Modeling’ technology was used to print totally gas-tight reaction vessels, combined with printed cuvettes, inside the inert-gas atmosphere of a glovebox. During pauses of the print, the reaction flasks out of acrylonitrile butadiene styrene were filled with various reactants. After the basic test reactions to proof the oxygen tightness and investigations of the influence of printing within an inert-gas atmosphere, scope and limitations of the method are presented by syntheses of new compounds with highly reactive reagents, such as trimethylaluminium, and reaction monitoring via UV/VIS, IR, and NMR spectroscopy. The applicable temperature range, the choice of solvents, the reaction times, and the analytical methods have been investigated in detail. A set of reaction flasks is presented, which allow routine inert-gas syntheses and combined spectroscopy without modifications of the glovebox, the 3D-printer, or the spectrometers. Overall, this demonstrates the potential of 3D-printed reaction cuvettes to become a complementary standard method in inert-gas chemistry
Synthesis of Macrocyclic Lactones via Ring Transformation of 4-(w-Hydroxyalkyl)-1,3-oxazol-5(4H)-ones

The synthesis of alpha-benzamido-alpha-benzyl lactones 23 of various ring size was achieved either via ‘direct amide cyclization’ by treatment of 2-benzamido-2-benzyl-omega-hydroxy-N,N-dimethylalkanamides 21 in toluene at 90 – 110° with HCl gas or by ‘ring transformation’ of 4-benzyl-4-(omega-hydroxyalkyl)-2-phenyl-1,3-oxazol-5(4H)-ones under the same conditions. The precursors were obtained by C-alkylations of 4-benzyl-2-phenyl-1,3-oxazol-5(4H)-one (15) with THP- or TBDMS-protected omega-hydroxyalkyl iodides. Ring opening of the THP-protected oxazolones by treatment with Me2NH followed by deprotection of the OH group gave the diamides 21, whereas deprotection of the TBDMS series of oxazolones 25 with TBAF followed by treatment with HCl gas led to the corresponding lactones 23 in a one-pot reaction
Allelopathic Activity of the Iron Chelator Anachelin - A Molecular Hybrid with a Dual Mode of Action

One of the compounds suggested to be responsible for the cyanobacterial dominance over competing green algae is identified. Evidence is provided on the molecular, chemical level that the iron chelator anachelin from the cyanobacterium Anabaena cylindrica promotes both the growth of cyanobacteria and reduces the growth of competing chlorophytes. These results illustrate a molecular strategy of addressing two challenges (nutrient availability and algal competition) by one molecule. Such strategies could be implied in harmful algal blooms in marine and freshwater environments
Durable remission in a patient with leptomeningeal relapse of a MYC/BCL6-positive double-hit DLBCL treated with lenalidomide monotherapy

Secondary central nervous system involvement is an uncommon event that typically occurs early in the natural history of diffuse large B-cell lymphoma and presents as leptomeningeal dissemination in two-thirds of cases. The prognosis of this event is dismal, and treatment options are meagre. Although major validated risk factors for central nervous system dissemination are clinical, concomitant MYC/BCL2 rearrangements as well as MYC/BCL2 protein expression have been recently associated with an increased risk of this complication. Here we present the first case, to our knowledge, of a MYC/BCL6-positive double-hit diffuse large B-cell lymphoma relapsing in the leptomeninges that achieved an outstanding durable remission with single-agent lenalidomide following salvage chemotherapy
CD8 (+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2‐deoxycoformycin.

Hematol Oncol. 2002 Jun;20(2):87-93.

Cd8(+)/V beta 5.1(+) large granular lymphocyte leukemia associated with autoimmune cytopenias, rheumatoid arthritis and vascular mammary skin lesions: successful response to 2-deoxycoformycin.
Granjo E, Lima M, Correia T, Lisboa C, Magalhães C, Cunha N, Teixeira MA, Queirós ML, Candeias J, Matutes E.

Department of Clinical Haematology, Hospital Geral de São João, Porto, Portugal. npp46740@mail.telepac.pt

Abstract
We report a case of CD8(+)/V beta 5.1(+) T-cell large granular lymphocyte leukemia (T-LGL leukemia) presenting with mild lymphocytosis, severe autoimmune neutropenia, thrombocytopenia, polyarthritis and recurrent infections with a chronic disease course. Immunophenotyping showed an expansion of CD3(+)/TCR alpha beta(+)/CD8(+bright)/CD11c(+)/CD57(-)/CD56(-) large granular lymphocytes with expression of the TCR-V beta 5.1 family. Southern blot analysis revealed a clonal rearrangement of the TCR beta-chain gene. Hematopoietic growth factors, high dose intravenous immunoglobulin and corticosteroids were of limited therapeutic benefit to correct the cytopenias. During the disease course, the patient developed a severe cutaneous leg ulcer and bilateral vascular mammary skin lesions. Treatment with 2-deoxycoformycin resulted in both clinical and hematological complete responses, including the resolution of vascular skin lesions. Combined immuno-staining with relevant T-cell associated and anti-TCR-V beta monoclonal antibodies proved to be a sensitive method to assess the therapeutic effect of 2-deoxycoformicin and to evaluate the residual disease.

Copyright 2002 John Wiley & Sons, Ltd.
PMID: 12111871 [PubMed - indexed for MEDLIN
Contextual and psychosocial influences on antiretroviral therapy adherence in rural Zimbabwe: towards a systematic framework for programme planners

Great progress has been made in achieving universal access to antiretroviral therapy (ART). However, for successful viral suppression, patients must adhere to rigid and complex treatment regimens. With three quarters of antiretroviral (ARV) users in Africa adhering successfully, African countries have achieved extraordinary levels of adherence given the levels of poverty in which many ARV users live. Nevertheless, one quarter of ARV users still struggle to adhere and run the risk of experiencing viral replication, clinical progression or even drug resistance. Much has been written about ART adherence, but little has been done to systematically categorise the spectrum of factors that influence ART. In this paper, we use a Zimbabwean case study to develop a framework for ART programme planners and implementers seeking to identify and tackle social obstacles to adherence. We draw on interviews and group discussions with 25 nurses and 53 adult ARV users, which we analysed through a three-tiered thematic approach, allowing us to categorise our findings into broader dimensions that can transcend our case study and be applied elsewhere. Our findings suggest that ART adherence is influenced by the material, symbolic, relational and institutional contexts in which ARV users live as well as the patient's motivation, participation and psychosocial responses to ART. This framework allows us to examine both the social context in which ART programmes are located and the psychosocial factors that influence patient behaviours. We offer this framework as a resource for ART programme planners and implementers seeking to improve ART compliance in resource-poor settings
Service providers' views of community participation at six Australian primary healthcare services: scope for empowerment and challenges to implementation

This is the peer reviewed version of the following article: [Freeman, T., Baum, F.E., Jolley, G.M., Lawless, A., Edwards, T., Javanparast, S., & Ziersch, A. (2014). Service providers’ views of community participation at six Australian primary health care services: Scope for empowerment and challenges to implementation. International Journal of Health Planning and Management, Early View, DOI: 10.1002/hpm.225], which has been published in final form at DOI:10.1002/hpm.2253. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Community participation is a key principle of comprehensive primary health care \ud
(PHC). There is little literature on how community participation is implemented at Australian PHC services. As part of a wider study conducted in partnership with five South Australian PHC services, and one Aboriginal community controlled health service in the Northern Territory, 68 staff, manager, regional health executives and departmental funders were interviewed about community participation, perceived benefits, and factors that influenced implementation. Additional data was collected through analysis of policy documents, service reports on activity, and a web-based survey completed by 130 staff. A variety of community participation strategies was reported, ranging from consultation and participation as a means to improve service quality and acceptability, through to substantive and structural participation strategies with an emphasis on empowerment. The Aboriginal community controlled health service in our study reported the most comprehensive community participation. Respondents from all were positive about the benefits of participation, but reported that efforts to involve service users had to compete with a centrally directed model of care emphasising individual treatment services, particularly at state-managed services. More empowering substantive and structural participation strategies were less common than consultation or participation used to achieve prescribed goals. The most commonly reported barriers to community participation were budget and lack of flexibility in service delivery. The current central control of the state-managed services needs to be replaced with more local management decision making if empowering community participation is to be strengthened and embedded more effectively in the culture of services
Understanding implementation of comprehensive geriatric care programs: a multiple perspective approach is preferred

Background: The Prevention and Reactivation Care Program (PReCaP) provides a novel approach targeting hospital-related functional decline among elderly patients. Despite the high expectations, the PReCaP was not effective in preventing functional decline (ADL and iADL) among older patients. Although elderly PReCaP patients demonstrated slightly better cognitive functioning (Mini Mental State Examination; 0.4 [95% confidence interval (CI) 0.2–0.6]), lower depression (Geriatric Depression Scale 15; –0.9 [95% –1.1 to –0.6]), and higher perceived health (Short-form 20; 5.6 [95% CI 2.8–8.4]) 1 year after admission than control patients, the clinical relevance was limited. Therefore, this study aims to identify factors impacting on the effectiveness of the implementation of the PReCaPand geriatric care ‘as usual’. Methods: We conducted semi-structured interviews with 34 professionals working with elderly patients in three hospitals, selected for their comparable patient case mix and different levels of geriatric care. Five non-participatory observations were undertaken during multidisciplinary meetings. Patient files (n = 42), hospital protocols, and care plans were screened for elements of geriatric care. Clinical process data were analysed for PReCaP components. Results: The establishment of a geriatric unit and employment of geriatricians demonstrates commitment to geriatric care in hospital A. Although admission processes are comparable, early identification of frail elderly patients only takes place in hosptial A. Furthermore, nursing care in the hospital A geriatric unit excels with regard to maximizing patient independency, an important predictor for hospital-related functional decline. Transfer nurses play a key role in arranging post-discharge geriatric follow-up care. Geriatric consultations are performed by geriatricians, geriatric nurses, and PReCaP case managers in hospital A. Yet hospital B consultative psychiatric nurses provide similar consultation services. The combination of standardized procedures, formalized communication channels, and advanced computerization contributes significantly to geriatric care in hospital B. Nevertheless, a small size hospital (hospital C) provides informal opportunities for information sharing and decision making, which are essential in geriatric care, given its multidisciplinary nature. Conclusions: Geriatric care for patients with multimorbidity requires a multidisciplinary approach in a geriatric unit. Geriatric care, which integrates medical and reactivation treatment, by means of early screening of risk factors for functional decline, promotion of physical activity, and adequate discharge planning, potentially reduces the incidence of functional decline in elderly patients. Yet low treatment fidelity played a major role in the ineffective implementation of the PReCaP. Treatment fidelity issues are caused by various factors, including the complexity of projects, limited attention for implementation, and inadequate interdisciplinary communication
The use and design of the BSC in the health care sector: a systematic literature review for Italy, Spain, and Portugal

The aim of this paper is to gain a better understanding of how the balanced scorecard (BSC) has evolved in Spain, Italy, and Portugal. It reviews all the articles on the BSC in the health care sector written between 1992 and 2015 by Spanish, Italian, or Portuguese authors and published in Spanish, Italian, or Portuguese as well as in English. Our study first shows the state of knowledge on BSC in health care for a homogeneous group of Southern European countries. Second, it uncovers the perspectives, indicators, and generation used in the countries under observation to reveal the extent to which this management tool has evolved. Third, it analyses international variations in design and use within the health care context, especially in
the United States. Moreover, it also highlights a number of important issues. The BSC is in its early stage of development in these 3 countries, which do not use it as a tool to implement strategy and align all of the elements that help integrate the organization.info:eu-repo/semantics/publishedVersio