bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact investing in biodiversity conservation with bonds: An analysis of financial and environmental risk
Authors: Thompson Benjamin S. 
Published: May 2022

AbstractImpact investments have the dual goals of generating profit and environmental and/or social impact from the same project or enterprise. This article examines recent impact investments in biodiversity conservation—specifically, debt finance in the form of conventional bonds and impact bonds. The proceeds of these bonds finance projects aiming to enhance forest management, sustainable agriculture, endangered species protection, ecosystem service provision, and nature‐based solutions to climate change such as REDD+. The article scrutinises whether these dual goals are achievable by evaluating the financial risks and impact risks within each bond's theory of change. Risks stem from projects with vague cashflow forecasts, project sites with low or ambiguous threat statuses, and simplified impact metrics that may measure activities or outputs—rather than impact. Risk mitigation strategies involve using baselines and counterfactuals to establish additionality, and guarantors to protect investors if revenues are insufficient. Implications for biodiversity management and for‐profit conservation are discussed.
First‐line immunotherapy or angiogenesis inhibitor combined with chemotherapy for advanced non‐small cell lung cancer with EGFR exon 20 insertions: Real‐world evidence from China
Authors: Yang Guangjian , Yang Yaning , Liu Runze , Li Weihua , Xu Haiyan , Hao Xuezhi , Li Junling , Zhang Shuyang , Xu Fei , Lei Siyu , Wang Yan 
Published: May 2022

AbstractBackgroundCurrently, survival benefit of immunotherapy in advanced non‐small cell lung cancer (NSCLC) with EGFR exon 20 insertions (ex20ins) is controversial, though it generally indicates poor response and activity. Compared with standard chemotherapy in combination with bevacizumab, first‐line chemotherapy plus immune checkpoint inhibitor (ICI) in advanced NSCLC with EGFR ex20ins remains elusive and lacks real‐world evidence.Patients and MethodsA retrospective real‐world study was conducted to evaluate clinical outcomes of chemotherapy alone (C), chemotherapy plus ICI (C + I), or chemotherapy plus angiogenesis inhibitors (C + A) as first‐line strategies for advanced NSCLC patients with EGFR ex20ins. Investigator‐assessed response and survival outcomes were compared between subgroups. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis was conducted to reveal concomitant alterations and explore the molecular landscape of ex20ins.ResultsA total of 164 patients were screened, identifying 35 kinds of ex20ins, and 122 cases treated with C, C + I, and C + A were finally included in the first‐line analysis. C + A achieved much better objective response rate (ORR, 38.1% vs. 18.2%) and significant progression‐free survival (PFS) benefit compared with C (median, 7.73 vs.5.93 months, HR = 0.60, 95% CI: 0.40–0.90, p = 0.014), and it showed similar ORR (38.1% vs. 40.0%), but higher disease control rate (DCR, 96.8% vs. 80.0%) and numerically longer median PFS (7.73 vs. 6.53 months, HR = 0.83, 95% CI: 0.44–1.56, p = 0.30) than C + I. There was no PFS difference between C + I and C, despite of PD‐L1 expression or tumor mutational burden. KEGG analysis revealed concomitant upregulation of PI3K/AKT signaling might mediate intrinsic resistance to ICI in ex20ins.ConclusionFirst‐line chemotherapy plus angiogenesis inhibitors might yield more survival benefits than chemotherapy alone for NSCLC with EGFR ex20ins, whereas, it suggests that chemotherapy in combination with ICI might not obtain a better survival benefit for this subset of patients. Activation of PI3K/AKT signaling might mediate intrinsic immunosuppression in NSCLC with EGFR ex20ins.
Two New Nor‐seco‐Isodhilarane‐Type Meroterpenoids from the Endophytic Fungus Penicillium purpurogenum
Authors: Zhang Ying , Xia Gui‐Yang , Wu Yu‐Zhuo , Wei Xiao‐Hong , Xia Huan , Wang Ling‐Yan , Lin Peng‐Cheng , Wang Ya‐Nan , Chen Li‐Xia , Lin Sheng 
Published: May 2022

AbstractTwo new nor‐seco isodhilarane meroterpenoids (NSIMs), purpurogenolides F (1) and G (2), along with three known meroterpenoid analogs (3–5), were isolated from the cultures of an endophytic fungus, Penicillium purpurogenum. Structures and absolute configurations of the new NSIMs were determined based on extensive spectroscopic data analyses, including HR‐ESI‐MS, UV, IR, NMR chemical shift calculations together with DP4+ probability analysis, as well as ECD calculations. All the isolated meroterpenoids were assessed for their anti‐inflammatory activities, and compound 4 exhibited moderate inhibitory activity against the nitric oxide (NO) production in lipopolysaccharide (LPS) induced RAW 264.7 cells with an IC50 value of 20.85±2.31 μM.
Intra‐articular osteoid osteoma of the capitulum: A diagnostic challenge
Authors: Shariatzadeh Hooman , Bahrabadi Mehrdad , Amiri Shayan , Jahanshahi Fatemeh , Joudi Samad , Bahrabadi Marjan 
Published: May 2022

AbstractHere, we describe the first case of intra‐articular osteoid osteoma of the capitulum, which is presented as elbow pain, extension lack, and sensation of click in joint flexion. Surgical treatment either arthroscopic or open is more in use in this location of the tumor than cortical osteoid osteoma.
Resolution via diastereomeric amides of enantiopure 1,4‐benzoxathian‐2‐ and 3‐carboxylic acids and determination of their configuration
Authors: Straniero Valentina , Lodigiani Giulia , Suigo Lorenzo , Valoti Ermanno 
Published: May 2022

Abstract1,4‐Benzoxathiane, 2‐ or 3‐substituted, is an important scaffold, and despite its presence in several therapeutic agents, it is chemically unexploited. Furthermore, only a few examples in literature report this moiety in its enantiopure form. Here, taking advantage to the formation of diastereomeric amides by using (S)‐phenylethylamine, which show significant differences in terms of 1H‐nuclear magnetic resonance (NMR) spectra and other physical chemical properties, we defined for the first time the absolute configuration of each amide, both 2‐ or 3‐substituted. Moreover, the diastereomeric amides were further hydrolyzed in acid conditions, letting to the achievement of the corresponding 1,4‐benzoxathian carboxylic acids.
Intravenous Perampanel as an Interchangeable Alternative to Oral Perampanel: A Randomized, Crossover, Phase I Pharmacokinetic and Safety Study
Authors: Hussein Ziad , Majid Oneeb , Boyd Peter , Aluri Jagadeesh , Ngo Leock Y , Reyderman Larisa 
Published: May 2022

AbstractIntravenous (IV) drug administration enables treatment of epilepsy when oral administration is temporarily not feasible. Perampanel is a once‐daily antiseizure medication currently available as oral formulations. Study 050 (NCT03376997) was an open‐label, randomized, single‐dose, crossover study to evaluate the interchangeability of oral and IV perampanel in healthy subjects (N = 48). Bioequivalence of single 12‐mg doses of IV (30‐, 60‐, or 90‐minute infusion) and oral perampanel, ≥6 weeks apart, was assessed. Analyses indicated bioequivalence of area under the plasma concentration–time curve extrapolated to infinity for 30‐ and 60‐minute IV infusions and oral perampanel doses (geometric mean ratio [90% confidence interval], 0.93 [0.84–1.02] and 1.03 [0.97–1.09], respectively); however, IV maximum observed drug concentration (Cmax) values were 1.35‐ to 1.61‐fold higher than Cmax. Simulated plasma concentration–time profiles using pooled pharmacokinetic data further supported oral and IV perampanel interchangeability in two scenarios: 12‐mg per day IV dosing during a temporary 7‐day switch from oral steady‐state maintenance therapy, and treatment initiation with 2‐mg perampanel. Thirty‐four (70.8%) subjects experienced treatment‐related adverse events. The IV perampanel safety profile was similar to that of oral perampanel without new safety concerns. Perampanel IV infusions may be a suitable temporary alternative to oral perampanel for treatment maintenance and/or initiation.
Molecular Mechanism of Interaction of Curcumin with BSA, Surfactants and Live E. Coli Cell Membrane Revealed by Fluorescence Spectroscopy and Confocal Microscopy
Authors: Agarwala Pratibha , Bera Turban , Sasmal Dibyendu K. 
Published: May 2022

AbstractClinical trials on the therapeutic effect of curcumin have proven to be highly effective against many diseases including cancer and Alzheimer's. However, the molecular mechanism of interaction of curcumin with protein and live cell membrane is poorly understood. Here, we report the mechanism of interaction of curcumin with bovine serum albumin (BSA) and live E. coli cell membrane in the presence of organized assemblies of sodium dodecyl sulfate (SDS) and cetrimonium bromide (CTAB) by fluorescence spectroscopy, laser‐scanning confocal microscopy, and computation. Enhanced binding constant, blue‐shifted emission spectra, and imaging of heterogeneous FRET on live bacteria cell membrane strongly indicate the complex formation of curcumin with strong hydrophobic interaction, which is further validated by computation. Finally, our results may shed light on the efficient strategy of applications of curcumin as a natural therapeutic lead in clinical trials against many life‐threatening diseases.
Single‐cell transcriptomics provides insights into the origin and microenvironment of human oesophageal high‐grade intraepithelial neoplasia
Authors: Liao Guobin , Dai Nan , Xiong Tiantian , Wang Liang , Diao Xinwei , Xu Zhizhen , Ni Yuanli , Chen Dingrong , Jiang Airui , Lin Hui , Dai Shuangshuang , Bai Jianying 
Published: May 2022

AbstractBackgroundHigh‐grade intraepithelial neoplasia (HIN) is the precursor of oesophageal squamous cell carcinoma. The molecular and functional properties of HIN are determined by intrinsic origin cells and the extrinsic microenvironment. Yet, these factors are poorly understood.MethodsWe performed single‐cell RNA sequencing of cells from HINs and adjacent tissues from the human oesophagus. We analysed the heterogeneity of basal layer cells and confirmed it using immunostaining. Aneuploid cells in HIN were studied using primary cell culture combined with karyotype analysis. We reconstructed the lineage relationship between tumour and normal populations based on transcriptome similarity. Integration analysis was applied to our epithelial data and published invasive cancer data, and results were confirmed by immunostaining and 3D organoid functional experiments. We also analysed the tumour microenvironment of HIN.ResultsThe basal layer contained two cell populations: KRT15highSTMN1low and KRT15highSTMN1high cells, which were located mainly in the interpapillary and papillary zones, respectively. The KRT15highSTMN1low population more closely resembled stem cells and transcriptome similarity revealed that HIN probably originated from these slow‐cycling KRT15highSTMN1low cells. 3D Organoid experiments and RNA‐sequencing showed that basal‐cell features and the differentiation ability of the normal epithelium were largely retained in HIN, but may change dramatically in tumour invasion stage. Moreover, the tumour microenvironment of HIN was characterised by both inflammation and immunosuppression.ConclusionsOur study provides a comprehensive single‐cell transcriptome landscape of human oesophageal HIN. Our findings on the origin cells and unique microenvironment of HIN will allow for the development of strategies to block tumour progression and even prevent cancer initiation.
Synthesis and Structure of Thiolate‐Bridged Diiron and Dicobalt Complexes Supported by Modified β‐Diketiminate Ligands
Authors: Feng Huajin , Yang Dawei , Mei Tao , Zhang Yahui , Wang Baomin , Qu Jingping 
Published: May 2022

AbstractMultinuclear metal thiolate complexes represent an important class of organometallic compound owing to their capacity that they can not only serve as bio‐mimicking functional platform but can also play as excellent cooperative catalysts. In this context, it is of long‐standing interest to construct new‐type transition metal complexes featuring sulfur donors. Herein we describe a synthetic method toward a novel unsymmetric β‐diketiminate ligand containing a thioether tether in a gram‐scale. This sulfur functionalized β‐diketiminate ligand was proved to be an ideal structural skeleton for coordination and stabilization of relatively unstable FeII and CoII ions to generate new thiolate‐bridged bimetallic complexes. These new complexes have been well‐defined by various spectroscopic characterizations and single‐crystal X‐ray diffraction analysis.
Opioid prescribing patterns for acute pain
Authors: Hadlandsmyth Katherine , Mosher Hilary J. , Bayman Emine O. , Mares Jasmine G. , Odom Annie S. , Lund Brian C. 
Published: May 2022

AbstractPurposeThe current study aimed to identify patients presenting with acute pain who may be at risk for a complicated trajectory, via identifying clusters of early opioid prescribing patterns.MethodsNational Veterans Affairs administrative data were utilized to build a cohort of outpatients with acute pain presentations and no more than minimal opioid use in the prior year. Latent Class Analyses (LCAs) identified clusters of early opioid prescribing patterns. The risk of progression to long‐term opioid use was contrasted between LCA clusters using log‐binomial regression, adjusting for confounding variables.ResultsThe 2018 cohort included N = 191,283. Among the 27,890 who received an initial opioid prescription, LCA classes were identified using: first supply day, total days dispensed across 30 days, opioid type, dose and number of prescriptions across the first 30 days. In the three‐class model: class 1 indicated an immediate, low‐dose and brief supply; class 2 included delayed, low‐dose and longer duration prescriptions and class 3 included delayed, high‐dose and moderate duration prescriptions. Adjusted relative risk ratios for progression to long‐term opioid use in the following year were 3.33 (95% CI: 2.71–4.10) for class 1 (absolute risk 1.1%); 7.76 (95% CI: 6.69–8.99) for class 2 (3.1%) and 6.81 (95% CI: 5.72–8.12) for class 3 (2.4%) compared to patients who did not receive an acute opioid prescription (0.3%).ConclusionsThese clusters of acute opioid prescribing could facilitate the identification of patients who may benefit from enhanced pain care earlier in the pain trajectory and decrease future reliance on long‐term opioid therapy.
A novel game theory based reliable proof‐of‐stake consensus mechanism for blockchain
Authors: Bala Kirti , Kaur Pankaj Deep 
Published: May 2022

AbstractThe prominent achievement of blockchain technology stimulates exceptional innovation. The major component of blockchain is the consensus mechanism. The standard consensus mechanisms specifically Proof‐of‐Work (PoW) rely on mining procedures and stake‐based mechanisms such as Proof‐of‐Stake (PoS) rely on massive stake investment as the sole criteria for selection of leader nodes. However, PoW impose huge computational power requirements and latter may incorporate malicious nodes as leader nodes in anonymous blockchain. These issues might fuel the way for distrust among the participants in blockchain. Henceforth, a novel game theory based reliable PoS mechanism for blockchain has been proposed. Federated learning has been used to compute trust_score for each node. The nodes are trained on locally generated dataset. Further, a game theoretic approach has been proposed that uses a reward and punishment scheme to ensure threshold level of trust_score maintenance by each node. Finally, a crop insurance use case has been developed with the consensus mechanism and blockchain coded in python. The insurance claims are made to operate through smart contract based mobile app system to impart more authenticity. The system is tested and results show an intrusion accomplishment rate reduced by approximate 40% when compared to the standard PoS mechanism and by approximately 33% for algorand, 29% for ouroboros and 20% for tendermint. The mean absolute error also decreases by 30% within specific time. Furthermore, the proposed federated learning‐based system is compared with basic neural network‐based machine learning model and the results reveal that a significant reduction in average training time amounting to 8.35 second is achieved. Test accuracy has also been analyzed for various learning mechanisms.
Navigating three vectors of power: Global strategy in a world of intense competition, aggressive nation states, and antagonistic civil society
Authors: Buckley Peter J. 
Published: May 2022

AbstractResearch SummaryGlobal strategy must negotiate three vectors of external power: State policies (that often conflict across national boundaries), the demands of civil society, and market pressures. The global strategies of corporations must reflect their two enduring and non‐replicable advantages—innovation and flexibility. These qualities are essential in the face of increased government regulation together with intensification of non‐market strategies as well as improving responses to the increased exigencies of international competition. A radical reappraisal of global strategies is therefore necessary. The global strategies of corporations here are analyzed using the “governance triangle” that examines governance through coordination (the role of the state), governance through competition (the market), and governance through argumentation (civil society). Future global strategies must contend with this web of constraint.Managerial SummaryThis paper suggests that managers need to recognize the web of constraints surrounding their strategic decisions. The three key vectors of external power are the state and government regulation, the power of civil society exercised through argumentation, and competitive action. Recognition of increasing pressure from the three vectors of power is the first step in reformulating global strategy. A wider acknowledgement and inclusion of stakeholders and increasing non‐market strategic activity are no longer optional but are mandatory. Navigating these constraints suggests a new web of opportunity where the true long‐run advantages of successful firms—flexibility and innovation—can be implemented.
Setting up criteria for drug‐induced autoimmune‐like hepatitis through a systematic analysis of published reports
Authors: Björnsson Einar S. , Medina‐Caliz Inmaculada , Andrade Raul J. , Lucena M. Isabel 
Published: May 2022

Abstract
Nitrofurantoin, minocycline, methyldopa and infliximab, have been found to induce autoimmune‐like hepatitis (DI‐AILH). Evidence for other drugs and herbal and dietary supplements (HDS) is unclear. The aims of the study were to establish criteria to define and review the published evidence of suspected DI‐AILH. Search was undertaken in Pubmed using search terms “drug‐induced liver injury,” “autoimmune hepatitis,” and “drug‐induced autoimmune hepatitis.” DI‐AILH was defined as (1) drug as a potential trigger of liver injury with autoimmune features and histological findings compatible with AIH; (2) no or incomplete recovery or worsening of liver tests after discontinuation of the drug; (3) corticosteroids requirement or spontaneous recovery; (4) follow‐up without immunosuppression (IS) and no relapse of AIH at least 6 months after discontinuation of IS; and (5) drugs potentially inducing AILH with a chronic course. Cases fulfilling the first four criteria were considered probable DI‐AILH with three possible DI‐AILH. A total of 186 case reports were identified for conventional drugs (n = 148; females 79%; latency 2.6 months) and HDS (n = 38; females 50%). The most commonly reported agents of DI‐AILH were interferons (n = 37), statins (n = 24), methylprednisolone (MPS) (n = 16), adalimumab (n = 10), imatinib (n = 8), and diclofenac (n = 7). Tinospora cordifolia and Khat were the only HDS with probable DI‐AILH cases. No relapses of AIH were observed when IS was stopped after interferons, imatinib, diclofenac, and methylprednisolone. Conclusion: Beyond well‐recognized nitrofurantoin, methyldopa, hydralazine, minocycline, and infliximab as causes of DI‐AILH, interferons, imatinib, adalimumab, and MPS were the best‐documented agents leading to probable DI‐AILH. Khat and Tinospora cordifolia were the only HDS found to be able to induce DI‐AILH. Long‐term immunosuppression appears to be rarely required in patients with DI‐AILH due to these drugs.
Elotuzumab plus lenalidomide and dexamethasone in relapsed/refractory multiple myeloma: Extended 3‐year follow‐up of a multicenter, retrospective clinical experience with 319 cases outside of controlled clinical trials
Authors: Bruzzese Antonella , Derudas Daniele , Galli Monica , Martino Enrica Antonia , Rocco Stefano , Conticello Concetta , Califano Catello , Giuliani Nicola , Mangiacavalli Silvia , Farina Giuliana , Lombardo Alessandra , Brunori Marino , Rossi Elena , Antonioli Elisabetta , Ria Roberto , Zambello Renato , Di Renzo Nicola , Mele Giuseppe , Marcacci Gianpaolo , Pietrantuono Giuseppe , Palumbo Gaetano , Cascavilla Nicola , Cerchione Claudio , Belotti Angelo , Criscuolo Clelia , Uccello Giuseppina , Curci Paola , Vigna Ernesto , Mendicino Francesco , Iaccino Enrico , Mimmi Selena , Botta Cirino , Vincelli Donatella , Sgherza Nicola , Bonalumi Angela , Cupelli Luca , Stocchi Raffaella , Martino Massimo , Ballanti Stelvio , Gangemi Dominella , Gagliardi Alfredo , Gamberi Barbara , Pompa Alessandra , Tripepi Giovanni , Frigeri Ferdinando , Consoli Ugo , Bringhen Sara , Zamagni Elena , Patriarca Francesca , De Stefano Valerio , Di Raimondo Francesco , Palmieri Salvatore , Petrucci Maria Teresa , Offidani Massimo , Musto Pellegrino , Boccadoro Mario , Cavo Michele , Neri Antonino , Morabito Fortunato , Gentile Massimo 
Published: May 2022

AbstractThe combination of elotuzumab, lenalidomide, and dexamethasone (EloRd) enhanced the clinical benefit over Rd with a manageable toxicity profile in the ELOQUENT‐2 trial, leading to its approval in relapsed/refractory multiple myeloma (RRMM). The present study is a 3‐year follow‐up update of a previously published Italian real‐life RRMM cohort of patients treated with EloRd. This revised analysis entered 319 RRMM patients accrued in 41 Italian centers. After a median follow‐up of 36 months (range 6–55), 236 patients experienced disease progression or died. Median progression‐free survival (PFS) and overall survival (OS) were 18.4 and 34 months, respectively. The updated multivariate analyses showed a significant reduction of PFS and OS benefit magnitude only in cases with International Staging System stage III. Major adverse events included grade 3/4 neutropenia (18.5%), anemia (15.4%), lymphocytopenia (12.5%), and thrombocytopenia (10.7%), while infection rates and pneumonia were 33.9% and 18.9%, respectively. No new safety signals with longer follow‐up have been observed. Of 319 patients, 245 (76.7%) reached at least a partial remission. A significantly lower response rate was found in patients previously exposed to lenalidomide. In conclusion, our study confirms that EloRd is a safe and effective regimen for RRMM patients, maintaining benefits across multiple unfavorable subgroups.