bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact investing in biodiversity conservation with bonds: An analysis of financial and environmental risk
Authors: Thompson Benjamin S.
Published: May 2022

Impact 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

Background

Currently, 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 Methods

A 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.

Results

A 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.

Conclusion

First‐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

Two 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

Here, 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

1,4‐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.
Psoriasis‐like eruptions developed in an atopic dermatitis patient treated with dupilumab
Authors: Fujimoto Rai , Kataoka Yoko
Published: May 2022

This study investigates the development of psoriasis‐like eruptions from dupilumab treatment. Our case suggests that psoriasis‐like eruptions might occur during dupilumab treatment, particularly in Asians, and requires careful follow‐up. We believe that our study makes a significant contribution to the literature as it highlights a potential adverse effect of this treatment for atopic dermatitis.
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

Intravenous (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

Clinical 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

Background

High‐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.

Methods

We 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.

Results

The 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.

Conclusions

Our 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

Multinuclear 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

Purpose

The 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.

Methods

National 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.

Results

The 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%).

Conclusions

These 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

The 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

Research Summary

Global 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 Summary

This 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

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

The 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.
The relationship between oral language and storytelling prosody in preschool children
Authors: Chung Wei‐Lun , Yang Hui‐Chun
Published: May 2022

The study examined storytelling prosody (i.e., prosodic variations in retelling a story) and the relation with oral language in Taiwanese preschool children. One hundred and twenty‐eight preschool children aged 4 and 5 were recruited and given the following tasks: nonverbal intelligence, vocabulary, syntax, and storytelling prosody. Children's storytelling prosody was evaluated by a four‐point scale (i.e., expression‐and‐volume, phrasing, smoothness and pace). Results revealed that (i) storytelling prosody differed as a function of oral language, (ii) different dimensions of storytelling prosody (e.g., expression‐and‐volume and phrasing) were correlated with syntactic and vocabulary knowledge and (iii) language production predicted storytelling prosody in male children, but not female children. Together, oral language is correlated with storytelling prosody among preschool children, especially male children.

Highlights

This study examined the relationship between oral language and storytelling prosody.

128 preschool children's storytelling prosody was evaluated via a rating scale. Storytelling prosody differed as a function of oral language and was correlated with vocabulary and syntactic knowledge. Oral language only predicted storytelling prosody in male children, but not female children.

Results highlighted the relationship between oral language and storytelling prosody, which is an early predictor of reading comprehension.
Primary Ewing's sarcoma/primitive neuroectodermal tumor of the kidney and its clinical features
Authors: Saikawa Shiori , Taga Minekatsu , Matsuda Yasushi , Suzuki Koji , Yamaguchi Aina , Fukushima Mana , Imamura Yoshiaki , Ito Hideaki , Yokoyama Osamu
Published: May 2022

Introduction

Ewing sarcoma family tumor is a malignant tumor that is primarily of bone origin; it rarely occurs in the kidney.

Case presentation

A 22‐year‐old woman presented with hematuria. Computed tomography revealed a 6 × 6‐cm mass in the lower pole of the right kidney with invasion into the right renal vein. A right laparoscopic radical nephrectomy was performed. The tumor was completely encapsulated. Based on the small‐round‐cell histology, diffusely CD99‐positive tumor cells, and EWS (ex7)–FLi1 (ex6) fusion gene break point transcript, we diagnosed Ewing sarcoma/primitive neuroectodermal tumor of the kidney. After surgery, eight cycles of adjuvant chemotherapy including vincristine, doxorubicin (Adriamycin®), cyclophosphamide, ifosfamide, and etoposide were given. No evidence of recurrence has been observed 13 months from diagnosis.

Conclusion

This was a rare Ewing sarcoma family tumor in the kidney of a young female with no remarkable family medical history.
How do undergraduate engineering students conceptualize product design? An analysis of two third‐year design courses
Authors: Miska Jacob W. , Mathews Laura , Driscoll Jessica , Hoffenson Steven , Crimmins Sarah , Espera Alejandro , Pitterson Nicole
Published: May 2022

Background

Engineering education traditionally emphasizes technical skills, sometimes at the cost of under‐preparing graduates for the real‐world engineering context. In recent decades, attempts to address this issue include increasing project‐based assignments and engineering design courses in curricula; however, a skills gap between education and industry remains.

Purpose/Hypothesis

This study aims to understand how undergraduate engineering students perceive product design before and after an upper‐level project‐based design course, as measured through concept maps. The purpose is to measure whether and how students account for the technical and nontechnical elements of design, as well as how a third‐year design course influences these design perceptions.

Design/Method

Concept maps about product design were collected from 105 third‐year engineering students at the beginning and end of a design course. Each concept map's content and structure were quantitatively analyzed to evaluate the students' conceptual understandings and compare them across disciplines in the before and after conditions.

Results

The analyses report on how student conceptions differ by discipline at the outset and how they changed after taking the course. Mechanical Engineering students showed a decrease in business‐related content and an increased focus on societal content, while students in the Engineering Management and Industrial and Systems Engineering programs showed an increase in business topics, specifically market‐related content.

Conclusion

This study reveals how undergraduate students conceptualize product design, and specifically to what extent they consider engineering, business, and societal factors. The design courses were shown to significantly shape student conceptualizations of product design, and they did so in a way that mirrored the topics in the course syllabi. The findings offer insights into the education‐practice skills gap and may help future educators to better prepare engineering students to meet industry needs.
Sofosbuvir‐based therapy for late pregnant women and infants with severe chronic hepatitis C: A case series study
Authors: Zeng Qing‐Lei , Yu Zu‐Jiang , Lv Jun , Zhang Hong‐Xu , Wang Bin , Dong Xiao‐Ping , Chen Zhi‐Min , Cui Guang‐Lin , Ji Fanpu
Published: May 2022

Data on sofosbuvir‐based therapy for pregnant women and infants with severe chronic hepatitis C (CHC) are lacking. Two late pregnant women and one female infant with severe CHC were enrolled for treatment. Pregnant Women 1 and 2 and Infant 3 were 30, 33, and 1.2 years old, respectively; the gestational ages of pregnant Women 1 and 2 were 31 and 26 weeks, respectively. Notably, pregnant Women 1 and 2 and Infant 3 had hepatitis C virus (HCV) RNA levels of 139 000, 198 000, and 8 450 000 IU/ml; alanine aminotransferase levels of 420, 781, and 220 U/L; and received sofosbuvir/ledipasvir, sofosbuvir/velpatasvir, and sofosbuvir/ledipasvir for 12 weeks, respectively. All three patients were safely cured with favorable tolerance, and two newborns were both breastfeeding and were consistently negative for the anti‐HCV antibody during the 1‐year follow‐up after birth. Additionally, two newborns and Infant 3 had normal growth parameters during the follow‐up year one. In conclusion, this case series study found that sofosbuvir‐based therapy for pregnant women and infants with severe CHC is safe and effective. The data may fill the gap and provide evidence of the use of sofosbuvir‐based therapy as a reference when similar severe CHC situations are encountered during clinical practice.
Cuprizone‐mediated demyelination reversibly degrades voiding behavior in mice while sparing brainstem reflex
Authors: Ramasamy Ramalakshmi , Hardy Cara C. , Crocker Stephen J. , Smith Phillip P.
Published: May 2022

Multiple sclerosis (MS) is a chronic, progressively debilitating demyelinating disease of the central nervous system (CNS). Nearly 80% of MS patients experience lower urinary tract dysfunction early in their diagnosis. This significantly affects the quality of life, and in latter stages of disease is a leading cause of hospitalization. Previously, animal models have shown that inflammatory demyelination in the CNS causes profound bladder dysfunction, but the confounding influence of systemic inflammation limits the potential interpretation of the contribution of CNS demyelination to bladder dysfunction. Since the micturition circuit has myelinated neuronal connections in the cortex, brainstem, and spinal cord, we examined alterations in bladder function in the cuprizone model characterized by demyelinating lesions in the cortex and corpus callosum that are independent of T‐cell–mediated autoimmunity. Herein, we report that a 4‐week dietary cuprizone treatment in C57Bl/6J mice induced alterations in voiding behavior with increased micturition frequency and reduced volume voided, similar to human MS bladder dysfunction. Subsequently, recovery from cuprizone treatment restored normal bladder function. Demyelination and remyelination were confirmed by Luxol Fast Blue staining of the corpus callosum. Additionally, we also determined that an 8‐week cuprizone treatment, resulting in chronic demyelination lacking spontaneous remyelination potential, is associated with an exacerbated voiding phenotype. Interestingly, while cuprizone‐induced CNS demyelination severely affected conscious (cortical) urinary behavior, the brainstem and spinal cord reflex remained unchanged, as confirmed by urethane‐anesthetized cystometry. This is the first study to show that cortical demyelination independent of inflammation can negatively impact urinary function.
Responses of vegetation phenology to the asymmetric changes of temperature in daytime and night‐time in the north of 20°N
Authors: Hou Xuehui , Gao Shuai , Li Xinhua , Wang Meng , Zhao Jia , Sui Xueyan , Liang Shouzhen
Published: May 2022

Focusing on the regional differences in the asymmetric effects of daytime and night‐time warming on plant phenology, (a) the start‐of‐season (SOS) and end‐of‐season (EOS) were extracted based on a normalized difference vegetation index (NDVI) dataset for areas north of latitude 20°N during 1982–2015; (b) the partial Pearson correlation coefficient between phenology and temperature was calculated, excluding the effects of precipitation, drought, and evapotranspiration; and (c) the asymmetric effects of daytime and night‐time temperatures on phenology were analysed from the perspectives of the entire study area, different climate regimes, and different altitudes. The results show that phenology showed opposing responses to changes in daytime temperature (Td) and night‐time temperature (Tn) in spring as well as autumn. However, such asymmetric effects were dependent on the climate. In arid/semi‐arid regions, increasing Td induced drought stress by facilitating evaporation from soil, resulting in a delayed SOS and an early EOS, while increasing Tn was beneficial for seed germination and leaf unfolding in the spring. In temperate climate regimes, the responses of phenology to warming in the day and night were more complicated due to different plant species and precipitation. In cold regions, increasing Td led to the advancement of the SOS, while increasing Tn delayed it. In contrast, night‐time warming in autumn significantly delayed the EOS and daytime warming advanced the EOS in cold regions. Warming affected the seasonal dynamics of plants in spring and autumn to a greater degree at higher altitudes than at lower altitudes, which is consistent with the results of previous studies. These results provide valuable insights into the patterns of the asymmetric relationship between the effects of changes in daytime and night‐time temperatures on plant phenology, over a range of regions and altitudes.
Curcumin alleviated lipopolysaccharide‐induced lung injury via regulating the Nrf2‐ARE and NF‐κB signaling pathways in ducks
Authors: Liu Xiao , Guan Pei Yue , Yu Chun Ting , Yang Hao , Shan An Shan , Feng Xing Jun
Published: May 2022

BACKGROUND

Under the intensive modern poultry farming system, the lung of duck is one of the main target organs for various bacterial and viral infections. Curcumin is a kind of natural polyphenol compound for which various beneficial biological functions exist, including being an anti‐inflammatory, antioxidant, and antiviral. The aim of this work was to investigate the mechanism of curcumin‐alleviated lipopolysaccharide (LPS)‐induced lung damage by the nuclear erythroid 2‐related factor 2 (Nrf2)‐antioxidant reaction element (ARE) and nuclear factor kappa B (NF‐κB) signaling pathway in ducks.

RESULTS

In total, 450 one‐day‐old male specific pathogen‐free ducks were randomly assigned into three dietary treatments: CON, basal diet; LPS, basal diet + LPS treatment; LPS + CUR, basal diet + LPS + 500 mg kg−1 of curcumin. At the end of the experiment (21 days), ducks in LPS treatment were challenged with 5 mg LPS per kilogram of body weight and the other two treatments were injected with the same dose of phosphate‐buffered saline solution. The results showed that LPS caused acute inflammation, oxidation stress, and lung injury. Dietary addition of curcumin significantly relieved the oxidation stress and inflammation parameters. Moreover, the results showed that remission may be through the signaling pathways of both Nrf2‐ARE and NF‐κB.

CONCLUSION

In conclusion, dietary supplementation of 500 mg kg−1 of curcumin exhibited a lung‐protective effect in ducks. This experiment broadens the mode of metabolism actions of curcumin in the target organs and provides an insight for the application of curcumin in waterfowl feed. © 2022 Society of Chemical Industry.
Ultrasonic stimulation of milk fermentation: effects on degradation of pesticides and physiochemical, antioxidant, and flavor properties of yogurt
Authors: Yuan Shaofeng , Yang Fangwei , Yu Hang , Xie Yunfei , Guo Yahui , Yao Weirong
Published: May 2022

BACKGROUND

Ultrasound has the potential to increase microbial metabolic activity, so this study explored the stimulatory effect of ultrasound pre‐treatment on the degradation of four common pesticides (fenitrothion, chlorpyrifos, profenofos, and dimethoate) during milk fermentation by Lactobacillus plantarum and its effect on yogurt quality.

RESULTS

Appropriate ultrasound pretreatment significantly enhanced the growth of L. plantarum. The degradation percentages of pesticides increased by 19–38% under ultrasound treatment. Ultrasonic intensity, pulse duty cycle, and duration time were key factors affecting microbial growth and pesticide degradation. Under optimal ultrasonic pre‐treatment conditions, the degradation rate constants of four pesticides were at least 3.4 times higher than those without sonication. In addition, such ultrasound pretreatment significantly shortened yogurt fermentation time, increased the water holding capacity, hardness and antioxidant activity of the yogurt, and improved the flavor quality of the yogurt.

CONCLUSION

Ultrasonic pretreatment significantly accelerated the degradation of the four pesticides during yogurt fermentation. In addition, such ultrasound pretreatment increased the efficiency of yogurt making and improved the quality of yogurt in terms of water holding capacity, firmness, antioxidant activity, and flavor. These findings provide a basis for the application of ultrasound to the removal of pesticide residues and quality improvement of yogurt. © 2022 Society of Chemical Industry.
First investigation on polyphenols and glycosidic aroma precursors in a spontaneous colour mutant of ‘Glera’, the principal grape variety of Prosecco sparkling wine
Authors: Morreale Giacomo , Possamai Tyrone , Panighel Annarita , De Rosso Mirko , Lovat Lorenzo , Flamini Riccardo , Migliaro Daniele
Published: May 2022

BACKGROUND

Somatic mutations in Vitis spp. are relatively frequent and can generate new agronomically interesting phenotypes. We report the discovery, genetic and chemical characterization of ‘Glera rosa’, a mutant for the berry skin colour of ‘Glera’, the main white cultivar used to produce Prosecco wine.

RESULTS

We ascertained the relationship between the skin colour of ‘Glera rosa’ and the polymorphisms in the Myb‐gene transcription factors involved in polyphenol biosynthesis. We established that VvMybA1 was homozygous (VvMybA1a/VvMybA1a) in ‘Glera’ but heterozygous (VvmybA1a/VvmybA1b) in the ‘Glera rosa’ mutant. We verified that the VvMybA1a non‐functional allele contained Grapevine Retrotransposon 1 (Gret1), while in the VvmybA1b allele Gret1 was missing, and the gene function was partially restored. The effects of mutation on ‘Glera rosa’ grape metabolites were studied by high‐resolution mass spectrometry and gas chromatography/mass spectrometry analysis. Fifteen anthocyanins and five unique flavonols were found in the ‘Glera rosa’ mutant. The mutation also increased the contents of trans‐resveratrol and its derivatives (i.e., piceatannol, E‐ε‐viniferin, cis‐ and trans‐piceid) and of some flavonols in grape. Finally, the mutation did not significantly affect the typical aroma precursors of Glera grape such as glycosidic monoterpenes, norisoprenoids and benzenoids.

CONCLUSION

‘Glera rosa’ could be an interesting genetic source for the wine industry to produce Prosecco DOC rosé typology (made by adding up to 15% of ‘Pinot Noir’), which was introduced to the market in 2020 with a worldwide massive success. © 2022 Society of Chemical Industry.
A novel sensitive analytical method for the simultaneous analysis of vancomycin and teicoplanin in human urine via single high‐performance liquid chromatography coupled with photodiode array and mass spectrometry in series
Authors: Giakoumaki Maria , Sarigiannis Yiannis , Hapeshi Evroula
Published: May 2022

Analysis of vancomycin and teicoplanin in biological fluids is vital since they are used in the treatment of hospital infections. For the determination of both glycopeptides in urine, a sensitive and accurate analytical method using high‐performance liquid chromatography coupled with photodiode array and mass spectrometry was developed and validated. This research work is the first attempt to develop a chromatographic method for the determination of two glycopeptides with structural similarities. Moreover, the used non‐invasive sampling method is an advantage of this research effort, especially when the blood sampling is difficult. Urine was treated with acetonitrile and 5% trichloroacetic acid, followed by solid‐phase extraction. The chromatographic separation was established at a C18 column (4.6 × 150 mm, 5 μm), using a gradient method and an electrospray ionization source in a positive mode. The linearity of the method was R2≥ 0.9900. The precision was estimated with a maximum coefficient of variation below 15%, while the accuracy ranged from 64 to 121%. The limit of detection and quantification of both glycopeptides ranged from 0.076 up to 0.33 mg/L and 0.33 up to 2.1 mg/L, respectively, showing the same sensitivity as the triple quadrupole mass spectrometry, which is the most frequently used method.
Functional characterization and clinical significance of super‐enhancers in lung adenocarcinoma
Authors: Jiang Xiangxiang , Qin Na , Hua Tingting , Wei Xiaoxia , Li Yuancheng , Chen Congcong , Gong Linnan , Liu Su , Wang Cheng , Yin Rong , Jiang Yue , Dai Juncheng , Xu Lin , Shen Hongbing , Ma Hongxia
Published: May 2022

Super‐enhancers (SEs) are important transcriptional regulators in tumorigenesis; however, the functional characterization and clinical significance of SEs in lung adenocarcinoma (LUAD) remain unclear. By using H3K27ac ChIP‐seq data of two LUAD cell lines and eight lung tissues, we detected 1045 cancer‐specific and 5032 normal‐specific SEs. Compared to normal‐specific SEs, cancer‐specific SEs have different regulatory mechanisms where associated target genes were enriched in critical tumor‐related pathways and tended to be regulated by transcription factors of Fos Proto‐Oncogene, AP‐1 Transcription Factor Subunit and Jun Proto‐Oncogene, AP‐1 Transcription Factor Subunit families. By using expression data of 513 LUAD and 57 adjacent samples from The Cancer Genome Atlas and 80 tumor‐normal paired LUAD samples from the Nanjing Lung Cancer Cohort study, we performed differential expression analysis of target genes for SEs and defined 243 crucial SEs. Unsupervised clustering of crucial SEs revealed two subtypes with different levels of genomic aberrations (i.e., mutation and copy number alteration) and clinical outcomes (progression‐free interval: p = 0.030; disease‐free interval: p = 0.047). In addition, patients with adverse clinical outcomes were more sensitive to three small molecule inhibitors (bortezomib, doxorubicin, and etoposide), and their targets (PSMB5 and TOP2A) also have elevated expression levels among these patients. Taken together, our findings provided a comprehensive characterization of SEs in LUAD and emphasized their clinical significance in LUAD therapy.
Managerial incentives and the medium of exchange in takeovers
Authors: Oh Frederick Dongchuhl , Park Junghum
Published: May 2022

This paper presents a model of the medium of exchange in takeovers in which managerial incentives influence the choice of an offer by a bidder manager. We consider a framework where the offer is proposed to the target depending on the bidder manager's private information on synergy and private benefits. We identify the case where the choice of the medium of exchange in the offer reveals whether the proposed merger is intended to create a synergy or to pursue empire building. We demonstrate that the perception of the bidder manager with a high appetite for increasing firm size raises the proportion of cash in the offer. Moreover, an increase in the cash flow rights held by the bidder manager leads to a reduction in the proportion of cash in the offer.
Linoleic Acid‐Rich Oil Alters Circulating Cardiolipin Species and Fatty Acid Composition in Adults: A Randomized Controlled Trial
Authors: Cole Rachel M. , Angelotti Austin , Sparagna Genevieve C. , Ni Ai , Belury Martha A.
Published: May 2022

Scope

Higher circulating linoleic acid (LA) and muscle‐derived tetralinoleoyl‐cardiolipin (LA4CL) are each associated with decreased cardiometabolic disease risk. Mitochondrial dysfunction occurs with low LA4CL. Whether LA‐rich oil fortification can increase LA4CL in humans is unknown. The aims of this study are to determine whether dietary fortification with LA‐rich oil for 2 weeks increases: 1) LA in plasma, erythrocytes, and peripheral blood mononuclear cells (PBMC); and 2) LA4CL in PBMC in adults.

Methods and results

In this randomized controlled trial, adults are instructed to consume one cookie per day delivering 10 g grapeseed (LA‐cookie, N = 42) or high oleate (OA) safflower (OA‐cookie, N = 42) oil. In the LA‐cookie group, LA increases in plasma, erythrocyte, and PBMC by 6%, 7%, and 10% respectively. PBMC and erythrocyte OA increase by 7% and 4% in the OA‐cookie group but is unchanged in the plasma. PBMC LA4CL increases (5%) while LA3OA1 CL decreases (7%) in the LA‐cookie group but are unaltered in the OA‐cookie group.

Conclusions

LA‐rich oil fortification increases while OA‐oil has no effect on LA4CL in adults. Because LA‐rich oil fortification reduces cardiometabolic disease risk and increases LA4CL, determining whether mitochondrial dysfunction is repaired through dietary fortification is warranted.
DNA damage and microdosimetry for carbon ions: Track structure simulations as the key to quantitative modeling of radiation‐induced damage
Authors: Moeini Hossein , Mokari Mojtaba
Published: May 2022

Purpose

Dose distribution in carbon‐ion irradiations is generally envisaged to have therapeutic advantages over protons, primarily due to the carbon ion's comparatively higher relative biological effectiveness in the tumor than in the encompassing healthy tissues. The objective of this work was to simulate the overall physical and chemical reactions of primary carbon ions impinging on liquid water and, as such, to investigate the DNA‐damage yields in the form of strand breaks (SBs) and in connection with the expected microdosimetric quantities.

Materials and methods

Using a B‐DNA model and Geant4‐DNA, we simulated the primary and secondary interactions in a spherical medium of water. Subsequently, we categorized DNA damages based on their complexity utilizing the concept of μ‐randomness. We assumed a threshold of 17.5 eV for a direct SB and a probability of 0.13 for an indirect SB triggered by chemical reactions of hydroxyl radicals. Microdosimetric quantities were extracted for three cylindrical volumes representing typical subcellular organisms.

Results

For fully ionized carbons of 8–256 MeV/u, the yield results appeared to be considerably influenced by the chemical reactions—indicating the important role of secondary electrons in inflicting damage. However, it was mostly the direct‐damage spectrum that determined the overall shape of the damage spectrum. At all primary energies, it was more probable to break each DNA strand at one point—the two points being less than 10 bp apart—than to break only one strand at two random points. Unlike proton's mean‐specific‐energy results, which showed more sensitivity to the volume increase of the smallest cylinder than of the larger ones, carbon‐ion results showed no such sensitivity.

Conclusion

The growth of the yield ratio of the single‐ and double‐strand breaks (DSB) with the particle energy was estimated for protons to be about 2 times that of alphas and 92 times that of carbon ions. Unlike the proton results, which suggested significant correlations between the DSB yields and mean‐specific (and lineal) energies, carbon ions exhibited no such correlations.