bluuebunny/crossref_metadata_2025 huggingface dataset:
Addition of immune checkpoint inhibitors to chemotherapy versus chemotherapy alone in patients with triple‐negative breast cancer: A systematic review and meta‐analysis
Authors: Gao Xin , Zhu Ying , Wang Peipei , Yu Lulin , Ruan Shanming , Shen Minhe , Zhang Kai
Published: December 2023

Background

Triple‐negative breast cancer (TNBC) is a relatively common malignant tumor with high mortality rates. There are limited treatment options and current therapy regimens often fall short of providing positive outcomes. The development of immune checkpoint inhibitors (ICIs) have provided a vital treatment option although efficacy has varied. Here, we review patient response to current TNBC treatment with and without the addition of ICIs.

Methods

A systematic search of PubMed, Cochrane, and EMBASE library databases was done to search eligible studies published from their inception through April 3, 2022. The primary outcome indicators used were progression‐free survival (PFS), overall survival (OS), pathological complete response rate (pCR) and objective remission rate (ORR), while adverse events (AEs) were also analyzed. Publication bias and sensitivity analyses and were performed to evaluate the quality of assessment.

Results

Overall, the meta‐analysis looked at seven randomized controlled trials (RCTs) that included 4631 patients with TNBC. Results showed an improvement in PFS for patients receiving ICI in addition to chemotherapy (CT) in both the intent‐to‐treat (ITT) population and PD‐L1 positive patients. Increased pCR rates were observed in all patients irrespective of PD‐L1 status as well as increased ORR in the ITT which was more notable in PD‐L1 positive subjects. While significant improvement in OS was observed only in PD‐L1 positive individuals, the use of ICIs plus CT resulted in severe adverse reactions, specifically immune‐related.

Conclusions

This study supports the increased efficacy of ICIs in combination with CT compared to CT alone in patients with TNBC, with the most notable benefit observed in PD‐L1 positive patients. However, combination therapy increases the risk of adverse reactions which warrants further investigation.
The heterogeneous impact of targeted therapy on the prognosis of stage III/IV colorectal cancer patients with different subtypes of TP53 mutations
Authors: Chen Jie , Chang Xiaona , Li Xinyi , Liu Jiaying , Wang Na , Wu Ying , Zheng Liduan , Nie Xiu
Published: December 2023

Background

The relationship between molecular characteristics and the prognosis of colorectal cancer (CRC) patients has not been fully understood. This study explored the impact of targeted therapy on the prognosis of CRC patients with different TP53 mutations, in the context of comprehensive treatment.

Methods

This study included patients with stage III/IV primary CRC from the electronic medical record system. TP53 mutations were detected via next‐generation sequencing (NGS) using formalin‐fixed paraffin‐embedded (FFPE) tissues. Applying two methods, we classified TP53 mutations as gain of function (GOF)/non‐GOF mutations or known/likely loss of function (LOF) mutations. Kaplan–Meier plot and parametric survival analysis were performed to evaluate the prognosis of CRC patients and identify potential predictors.

Results

There were 286 patients included, of which 166 (58.04%) patients received targeted therapy and 120 (41.96%) did not. There were 286 patients in the TP53 GOF classification set and 247 in the TP53 LOF classification set. Parametric survival analysis, adjusted for sex, onset, KRAS mutation, sidedness, stage, and surgery, showed that receiving targeted therapy predicted better overall survival (OS) among patients who harbored TP53 GOF mutations (HR 0.40, 95% confidence interval (CI) [0.21, 0.76], p = 0.005) or known LOF mutations (HR 0.21, 95% CI [0.07, 0.60], p = 0.002). However, there was no significant impact of receiving targeted therapy on OS among patients harboring TP53 non‐GOF mutations (HR 1.68, 95% CI [0.50, 5.63], p = 0.403) or likely LOF mutations (HR 0.90, 95% CI [0.34, 2.39], p = 0.837).

Conclusions

Receiving targeted therapy had a heterogeneous impact on the prognosis of CRC patients harboring different TP53 mutations. These results provide promising value for future personalized treatment and precision medicine.
The effectiveness of blinatumomab in clearing measurable residual disease in pediatric B‐cell acute lymphoblastic leukemia patients detected by next‐generation sequencing
Authors: Gu Min'er , Xia Yahong , Zhang Jingying , Tang Yongmin , Xu Weiqun , Song Hua , Xu Xiaojun
Published: December 2023

Background

Blinatumomab improved survival outcomes in B‐cell acute lymphoblastic leukemia (B‐ALL) patients with measurable residual disease (MRD) <10−4. However, data on blinatumomab clearing MRD with high sensitivity of 10−6 remain scarce. This study evaluates the effectiveness of blinatumomab in eradicating extremely low level (up to <10−6) of MRD, as detected by next‐generation sequencing (NGS), in children with B‐ALL.

Methods

Patients (n = 19) whose MRD was undetectable by multiparameter flow cytometry (MFC) (sensitivity of 10−4) but detectable by NGS after chemotherapy and followed by blinatumomab consolidation were included retrospectively.

Results

After one course of blinatumomab, 13/19 patients (68%) successfully achieved NGS‐MRD clearance (undetectable). With a median follow‐up of 13.3 months, three of patients who were NGS‐MRD positive relapsed within 1.8 months, while another three remained complete remission.

Conclusions

Our study was the first to demonstrate that blinatumomab could further eradicate MRD after patients achieve MFC‐MRD undetectable in B‐ALL patients.
Efficacy and outcome of molecular targeted therapies in elderly patients with hepatocellular carcinoma: Relative dose intensity associated with overall survival
Authors: Oura Kyoko , Morishita Asahiro , Takuma Kei , Nakahara Mai , Tadokoro Tomoko , Fujita Koji , Mimura Shima , Tani Joji , Ono Masafumi , Himoto Takashi , Masaki Tsutomu
Published: December 2023

Aim

Indications of drug therapies to elderly patients with hepatocellular carcinoma (HCC) should be carefully determined. The current study assessed the safety and efficacy of molecular targeted agents (MTAs) in the elderly patients with HCC, and identified factors associated with prognosis in a real‐world clinical setting.

Methods

In a retrospective observational study, clinical data of patients with unresectable HCC treated with sorafenib or lenvatinib as first‐line treatment at our hospital between 2011 and 2022, were investigated. Clinical parameters, therapeutic effects, adverse events (AEs), and prognosis were evaluated separately for the non‐elderly (<75 years old) and elderly patients (≥75 years old).

Results

Overall, 111 patients were enrolled, including 59 non‐elderly and 52 elderly patients. Compared to the non‐elderly patients, the elderly patients had significantly lower skeletal muscle mass and a significantly lower percentage of patients in poor general condition with performance status 2 or higher, but there were no differences in parameters related to liver function or nutritional status. There were no significant differences in the incidence of severe AEs and therapeutic effects between the groups. No significant difference in progression‐free survival was observed in the elderly and non‐elderly patients; however, overall survival (OS) for sorafenib treatment was shorter in the elderly patients than in the non‐elderly patients. Elderly patients consumed lower doses of both the drugs, and relative dose intensity (RDI) 4 weeks after treatment (4W‐RDI) was associated with OS. Further, OS in the elderly patients was significantly longer in the subgroup with high 4W‐RDI as compared to that in the subgroup with low 4W‐RDI.

Conclusions

MTAs can be safely administered to elderly patients with HCC. Furthermore, 4W‐RDI is associated with longer OS. Maintaining RDI in the early phase is crucial in predicting the success of treatment with MTAs, especially in the elderly patients.
The efficacy of Linum usitatissimum seeds to inhibit estrogen receptor as a natural therapy for PCOS: An in silico and in vitro analysis
Authors: Ahmad Fatima , Ahmed Abrar , Shakeel Alishba , Hussain Hafiza A. , Raza Syed A.
Published: December 2023

Polycystic ovarian syndrome (PCOS) is an endocrinological disorder aroused due to hormonal disturbances. It is characterized by anovulation due to an excess of androgen and estrogen hormones, thus leading to the formation of multiple cysts, imposing life‐threatening conditions. This manuscript aimed to introduce a natural estrogen receptor (ESR) inhibitors that can provide protection against PCOS. The computational analysis of Linum usitatissimum seeds  compounds against ESR alpha receptor was performed, and the binding affinities of the ligand compounds and receptor proteins were scrutinized. Nine lignin compounds were docked, and the results were compared with that of reference estrogen receptor inhibitors, clomiphene, and tamoxifen. The binding affinity scores for pinoresinol, lariciresinol, secoisolariciresinol, and matairesinol were −10.67, −10.66, −10.91, and −10.60 kcal mol−1, respectively. These were comparable to the binding affinity score of reference compounds −11.406 kcal mol−1 for clomiphene and −10.666 kcal mol−1 for tamoxifen. Prime MM‐GBSA studies showcased that Linum usitatissimum seeds compounds exhibit significant efficacy and efficiency towards receptor protein. Moreover, MD‐simulation studies were performed and the results depict that the lignin compounds form stable complexes at 300 K throughout the simulation time. For further clarity, in‐vitro experiments were carried out. The results exhibit the decline in cell proliferation in a concentration‐dependent manner by extract 1 (ethyl acetate) EX1 and extract 2 (petroleum ether) EX2. Hence, providing evidence regarding the anti‐estrogenic activity of the sample extracts. Collectively, these results showed that flax seed can reduce the levels of estrogen, which can induce ovulation and prevent cyst formation, and ultimately can provide protection against PCOS.
Engineering of Candida antarctica Lipase B for Enhanced Perhydrolysis Activity by Modulating the Potential Water Channel
Authors: Jeon Minjeong , Park Seongsoon
Published: December 2023

Although Candida antarctica lipase B (CAL‐B) naturally hydrolyzes an ester compounds, it can catalyze a variety of promiscuous reactions, such as perhydrolysis, aldol reaction, and Michael‐type reactions. Perhydrolysis is similar to hydrolysis but uses hydrogen peroxide instead of water molecules. It was recently proposed that water molecules access the active site of CAL‐B through a water channel. We hypothesized that hydrogen peroxide may also use the channel to enter the active site, and that the access of hydrogen peroxide is one of the key factors for perhydrolysis activity. We investigated the effects of mutations at two residues in the water channel of CAL‐B on the perhydrolysis activity. The residues, Pro280 and Ala281, are located at the constricted area of the water channel. We found that the substitution of Ala281 to a small and polar amino acid, such as serine or threonine, resulted in a noticeable increase in hydrolysis and perhydrolysis activity. The activity of the variant enzymes was up to three times and twice higher for the activities of hydrolysis and perhydrolysis, respectively, than those of CAL‐B. In contrast, the substitution of the Pro280 residue with a small and polar amino acid decreased both hydrolysis and perhydrolysis activities.
Survey of herbicide and fungicide use in peanut in North Carolina and Virginia in the United States
Authors: Jordan David L. , Anco Dan , Balota Maria , Langston David , Lux LeAnn , Shew Barbara , Brandenburg Rick L.
Published: December 2023

Plain Language Summary

Diseases and weeds can reduce yield of peanut (Arachis hypogaea L.) if effective control measures including fungicides and herbicides are not used. A survey of 76 farmers in North Carolina and Virginia at Cooperative Extension Service meetings was completed relative to fungicide and herbicide use in 2021. Eighty‐two percent of farmers made between three and five herbicide applications, while 68% of farmers made between four and five fungicide applications. 2,4‐DB was the herbicide applied most frequently. The fungicide chlorothalonil was applied the most often. Pydiflumetofen was applied by 61% of farmers. Results from this survey can be used to inform regulatory agencies on pesticide use patterns by defining the relative importance of individual or groups of pesticides currently used to suppress pests and prevent or mitigate associated economic losses.
[3+2] Cycloaddition of Alkynyl Boronates and in situ Generated Azomethine Ylide
Authors: Liashuk Oleksandr S. , Ryzhov Ihor A. , Hryshchuk Oleksandr V. , Volovenko Yulian M. , Grygorenko Oleksandr O.
Published: December 2023

Scalable [3+2] cycloaddition of alkynyl boronates and in situ generated unstabilized azomethine ylide is reported for the first time. The selective formation of either 1 : 1 or 1 : 2 cycloaddition products was achieved by carefully optimizing the reaction conditions, mainly by controlling the reactant stoichiometry, catalyst loading, and internal temperature. The developed protocol tolerated many valuable functional groups, including TMS, protected alcohol (as ether or THP derivatives), or aldehyde (as acetal). Further common C−C and C−heteroatom bond‐forming reactions, as well as scaled‐up procedures demonstrate the utility of the prepared compounds as building blocks for organic synthesis and drug discovery.
The impact of stoichiometry on the initial steps of crystal formation: Stability and lifetime of charged triple‐ion complexes
Authors: Koskamp Janou A. , Seepma Sergěj Y. M. H. , Peters Vincent F. D. , Toroz Dimitrios , Di Tommaso Devis , Wolthers Mariette
Published: December 2023

Minerals form in natural systems from solutions with varying ratios of their lattice ions, yet non‐stoichiometric conditions have generally been overlooked in investigations of new formation (nucleation) of ionic crystals. Here, we investigated the influence of cation:anion ratio in the solution on the initial steps of nucleation by studying positively and negatively charged triple ion complexes and subsequent particle size evolution. Our model systems are carbonates and sulfates of calcium and barium, as it was recently shown that solution stoichiometry affects the timing and rate of their nucleation. Molecular dynamics (MD) simulations and dynamic light scattering (DLS) flow experiments show that nucleation correlates with the stability and lifetime of the initial complexes, which were significantly impacted by the cation:anion stoichiometry and ion type. Specifically,
was found to have higher association constants and its lifetime was twofold longer than
. Similar trends were observed for
and
. Contrastingly, for
,
was found to have lower association constants and its lifetime was shorter than
. These trends in stability and lifetime follow the same asymmetrical behaviour as observed experimentally for particle formation using techniques like DLS. This suggests a causal relationship between the stability and lifetime of the initial charged complexes and the nucleation under non‐stoichiometric conditions.
Digitalisierung und Simulation sind Teil der Lösung
Authors: Bortz Michael
Published: December 2023

Welchen Beitrag kann die Wissenschaft leisten, den großen wirtschaftlichen Veränderungen zu begegnen, denen sich insbesondere die chemische Industrie aktuell stellen muss? Antworten zeigte der zweitägige Workshop “Mathematical Methods in Process Industry” Anfang Oktober am Fraunhofer‐Institut für Techno‐ und Wirtschaftsmathematik ITWM in Kaiserslautern auf. Im Diskurs zeigten Vertreter von Wirtschaft und Wissenschaft Lösungswege auf, die auf Digitalisierung und Simulation basieren und sich in der Praxis anwenden lassen.
Scale‐up begaster Fermenter
Authors: Gezork Klaus , Schorn Annika , Bußmann Niels
Published: December 2023

Besonders unter anspruchsvollen Betriebsbedingungen und bei hohen Produktionskapazitäten haben sich gerührte und begaste Fermenter aufgrund ihrer hervorragenden Leistung und Flexibilität weitgehend durchgesetzt. Die langjährige Erfahrung von Ekato und Forschung an diesen Fermentertypen haben das Verständnis erheblich vertieft.
Mit der richtigen Formel vor Cyberangriffen schützen
Authors: Rausse Dirk
Published: December 2023

Daten aus Industrieunternehmen sind ein lukratives Ziel für Angreifer, die inzwischen vermehrt auch KI‐Tools einsetzen. Während sich vernetzte Anlagen und Systeme zum Beispiel durch Firewalls, Antivirenprogramme und Co. gegen Hackerangriffe schützen lassen, gibt es noch einen weiteren bedeutenden Risikofaktor: die Mitarbeiter. Für einen effektiven Schutz vor Cybercrime, ist ein regelmäßiges Training nützlich, um für Phishing zu sensibilisieren und den Umgang mit KI‐Tools zu schulen.
Flüchtige Emissionen reduzieren
Authors: Dixon Matt
Published: December 2023

Die meisten Anlagenbetreiber streben angesichts heutiger Umweltschutzvorhaben nach einem Netto‐Null‐Ziel. Dieses zu erreichen ist mitunter ein schwieriges Unterfangen. In Raffinerien und Chemieanlagen kann es an vielen Stellen zu einer unbeabsichtigten Freisetzung von Emissionen kommen. Hier spricht man auch von flüchtigen Emissionen. Diese stehen zunehmend im Fokus der Aufsichtsbehörden, was Anlagenbetreiber zusätzlich antreibt, sie zu reduzieren oder gar vollständig zu beseitigen.
Unterbrechungsfreie Gasversorgung
Authors: Karolius Frank‐Detlef
Published: December 2023

Scheinbar simpel, stellt die Versorgung mit technischen Gasen Nutzer schnell vor technische und logistische Herausforderungen, die innovative und verlässliche Lösungen erfordern. Eine solche Lösung sind Druckregelventile, die die Versorgung mit technischen Gasen in der geforderten Menge selbst bei einem Ausfall von Strom und Instrumentenluft durch eine mechanische Regelung sicherstellen.
In der Praxis erprobt
Authors: Fröhlich Dominik
Published: December 2023

Wasserstoff gilt als umweltfreundlicher Energieträger der Zukunft, weil er sehr flexibel einsetzbar ist, mit regenerativen Technologien hergestellt werden kann und sich gut transportieren sowie speichern lässt. Fluidische Komponenten, wie Ventile oder Durchflussregler, sind in der gesamten Wertschöpfungskette unerlässlich, bei der Wasserstofferzeugung ebenso wie bei der ‐verteilung und ‐nutzung.
Recent Advances in Pd‐Catalyzed Reactions Involving the “On‐Water” Mechanism†
Authors: Wei Dong , Lin Guo‐Qiang
Published: December 2023

Comprehensive Summary

As the chemical industry grapples with the need for more eco‐friendly practices, the use of water as a reaction medium is gaining attraction in organic transformations. This mini‐review delves into Pd‐catalyzed reactions that utilize the "on‐water" mechanism, spanning from 2019 to late 2023. These reactions are neatly categorized into several types: (A) Catalytic C—H activations, (B) Mizoroki‐ Heck‐type reactions, (C) Suzuki‐Miyaura reactions, and (D) Cyclization reactions. By showcasing the potential of water as a sustainable reaction medium for organic transformations, these reactions leave no doubt about the importance of embracing eco‐friendly practices in the chemical industry.

Key Scientists

In 1980, a seminal work by Breslow et al. showed an acceleration of reaction rate in the Diels‐Alder reaction. Sharpless and co‐workers noted a significant increase in the rate of the [2σ+2σ+2π] cycloaddition of quadricyclane and dimethyl azodicarboxylate (DMAD) when the reaction was conducted in water, as opposed to when it was carried out in organic solvents. The term "on‐water" was then coined to describe this phenomenon. This strategy was further expanded to transition‐metal catalyzed transformations by Ackermann in 2011. Later, Varma and Leazer disclosed a Pd‐catalyzed Mizoroki‐Heck type arylation of alkenes with diaryliodonium salts “on‐water”. The enantioselective version of "on‐water" process was not realized until 2014 by the Zhou group. Later on, the Schaub group described a Pd‐catalyzed Suzuki–Miyaura coupling reaction of electron‐poor aryl chlorides with water, using only 50 ppm of catalyst loading. Very recently, Liu and Lin extended the "on‐water" strategy to Pd‐catalyzed double Mizoroki‐Heck reactions. This mini‐review has focused on Pd‐catalyzed reactions involving the “on‐water” mechanism.
Recent Advances in C—F Bond Formation from Carbon‐Centered Radicals
Authors: Zhang Jihua , Wang Juanjuan , Cheng Qiang
Published: December 2023

Comprehensive Summary

Construction of C—F bonds is a direct and efficient method for introducing fluorine into pharmaceuticals, agrochemicals, and materials. Strategies such as nucleophilic, electrophilic, radical, and transition‐metal catalyzed fluorination have been developed to meet the demand of diverse C—F bond formation. Among them, radical fluorination has been witnessed with substantial advancement in a recent decade. Herein, we reviewed methods for formation of C—F bonds with carbon‐centered radicals as key intermediates, especially in recent five years. We introduce in the paper with different fluorinating reagents, strategies for radical generation, and application in late‐stage functionalization and synthesis of PET tracers. We also indicate the current limitations and propose the direction of the field for the future development.

Key Scientists

Radical fluorination was recognized as an old and uncontrolled reaction that may date back to the time when element fluorine was first mixed with organic compounds by Henri Moissan in 1891. The development of the field was slow in combination with discovery of new fluorinating reagents. Substantial changes took place in 2012, when the first example of carbon radical fluorination with robust and mild fluorinating reagents, such as NFSI and Selectfluor, was reported by the Sammis group. In the same year, Groves, Lectka, Li, and Boger led the pioneering works on aliphatic C—H fluorination, decarboxylative fluorination, and fluorofunctionalization of alkenes in a radical manner. Photoredox catalysis was introduced to radical fluorination in 2013 by the Chen group, which opens up a new avenue for diverse fluorinative transformations. Most of the previous works focus on radical fluorination to form C(sp3)–F bonds. In 2018, the challenging non‐directed aromatic C—H fluorination was solved by Ritter and coworkers. Direct arene fluorination with fluoride ion was later disclosed by the Nicewicz group in 2019. There are many other scientists that have also made tremendous contribution to the development of radical fluorination, with too limited space to list them all. We only list those with first discoveries that may point to the new direction of radical fluorination.
Nanomedicine Disrupts Stromal Barriers to Augment Drug Penetration for Improved Cancer Therapy†
Authors: Luo Guo‐Feng , Chen Wei‐Hai , Zhang Xian‐Zheng
Published: December 2023

Comprehensive Summary

Tumor stroma composing diverse extracellular matrixes (ECM) and
stromal cells shapes a condensed physical barrier, which severely hampers the efficient accessibility of nanomedicine to tumor cells, especially these deep‐seated in the core of tumor. Such barrier significantly compromises the antitumor effects of drug‐loaded nanomedicine, revealing the remarkable importance of disrupting stromal barrier for improved tumor therapy with deep penetration ability. To achieve this goal, various nanoparticle‐based strategies have been developed, including direct depleting ECM components via delivering anti‐fibrotic agents or targeting stromal cells to suppress ECM expression, dynamic regulation of nanoparticles’ physicochemical properties (i.e., size, surface charge, and morphology), mechanical force‐driven deep penetration, natural/biomimetic self‐driven nanomedicine, and transcytosis‐inducing nanomedicine. All these nanostrategies were systemically summarized in this review, and the design principles for obtaining admirable nanomedicine were included. With the rapid development of nanotechnology, elaborate design of multifunctional nanomedicine provides new opportunities for overcoming the critical stromal barriers to maximize the therapeutic index of various therapies, such as chemotherapy, photodynamic therapy, and immunotherapy.

Key Scientists

In 2006, Chan et al. demonstrated that the size and shape of nanoparticles were important for biomedical applications, such as intracellular delivery rate and tissue penetration. In addition, the degradation of the structural collagen was confirmed to increase the diffusion of nanoparticles and macromolecules by Davies et al. in 2010. These findings reveal the importance of chemophysical properties of nanoparticles in determining their diffusion and the critical roles of stromal barrier in hindering nanoparticles penetration. On the basis of this, photoswitchable nanoparticles were developed by Kohane et al. for triggered tissue penetration and efficient drug delivery. In 2015, Nie et al. reported the targeted depletion of cancer‐associated fibroblasts by peptide assembly for enhanced antitumor drug delivery. In 2019, Shen et al. proposed the transcytosis strategy to promote the tumor penetration of nanoparticles. Very recently, Luo et al. reported the specific reversing of the biological function of cancer‐associated fibroblasts to suppress the generation of stromal matrix, greatly increasing the drug perfusion in tumor tissue. All these strategies fueled the design and construction of function‐specific nanoparticles for tumor therapy.
MMP‐2 regulates Src activation via repression of the CHK/MATK tumor suppressor in osteosarcoma
Authors: Maybee Deanna V. , Cromwell Christopher R. , Hubbard Basil P. , Ali Mohammad A. M.
Published: December 2023

Background

Doxorubicin, a first‐line anticancer drug for osteosarcoma treatment, has been the subject of recent research exploring the mechanisms behind its chemoresistance and its ability to enhance cell migration at sublethal concentrations. Matrix metalloproteinase‐2 (MMP‐2), a type IV collagenase and zinc‐dependent endopeptidase, is well‐known for degrading the extracellular matrix and promoting cancer metastasis. Our previous work demonstrated that nuclear MMP‐2 regulates ribosomal RNA transcription via histone clipping, thereby controlling gene expression. Additionally, MMP‐2 activity is regulated by the non‐receptor tyrosine kinase and oncogene, Src, which plays a crucial role in cell adhesion, invasion, and metastasis. Src kinase is primarily regulated by two endogenous inhibitors: C‐terminal Src kinase (Csk) and Csk homologous kinase (CHK/MATK).

Aim

In this study, we reveal that the MMP‐2 gene acts as an upstream regulator of Src kinase activity by suppressing its endogenous inhibitor, CHK/MATK, in osteosarcoma cells.

Methods and Results

We show that enhanced osteosarcoma cell migration which is induced by sublethal concentrations of doxorubicin can be overcome by inactivating the MMP‐2 gene or overexpressing CHK/MATK. Our findings highlight the MMP‐2 gene as a promising additional target for combating cancer cell migration and metastasis. This is due to its role in suppressing on the gene and protein expression of the tumor suppressor CHK/MATK in osteosarcoma.

Conclusion

By targeting the MMP‐2 gene, we can potentially enhance the effectiveness of doxorubicin treatment and reduce chemoresistance in osteosarcoma.
The European List of Key Medicines for Medical Education: A Modified Delphi Study
Authors: Donker Erik M. , Spitaleri Timpone Pietro , Brinkman David J. , Richir Milan C. , Papaioannidou Paraskevi , Likic Robert , Sanz Emilio J. , Christiaens Thierry , Costa João N. , De Ponti Fabrizio , Gatti Milo , Böttiger Ylva , Kramers Cornelis , Pandit Rahul , van Agtmael Michiel A. , Tichelaar Jelle ,   the Network of Teachers in Pharmacotherapy
Published: December 2023

Rational prescribing is essential for the quality of health care. However, many final‐year medical students and junior doctors lack prescribing competence to perform this task. The availability of a list of medicines that a junior doctor working in Europe should be able to independently prescribe safely and effectively without supervision could support and harmonize teaching and training in clinical pharmacology and therapeutics (CPT) in Europe. Therefore, our aim was to achieve consensus on such a list of medicines that are widely accessible in Europe. For this, we used a modified Delphi study method consisting of three parts. In part one, we created an initial list based on a literature search. In part two, a group of 64 coordinators in CPT education, selected via the Network of Teachers in Pharmacotherapy of the European Association for Clinical Pharmacology and Therapeutics, evaluated the accessibility of each medicine in his or her country, and provided a diverse group of experts willing to participate in the Delphi part. In part three, 463 experts from 24 European countries were invited to participate in a 2‐round Delphi study. In total, 187 experts (40%) from 24 countries completed both rounds and evaluated 416 medicines, 98 of which were included in the final list. The top three Anatomical Therapeutic Chemical code groups were (1) cardiovascular system (n = 23), (2) anti‐infective (n = 21), and (3) musculoskeletal system (n = 11). This European List of Key Medicines for Medical Education could be a starting point for country‐specific lists and could be used for the training and assessment of CPT.
Local adaptation and broad performance are synergistic to productivity in modern barley
Authors: Ewing Patrick M. , Kantar Michael B. , Killian Erik , Neyhart Jeffrey L. , Sherman Jamie D. , Williams Jessica L. , Lachowiec Jennifer A. , Eberly Jed O.
Published: December 2023

Crop populations have enormous impacts on agricultural productivity, yet decelerating gains from breeding suggest that selection strategies need to be reconsidered to better align priorities of breeders and growers. Breeders benefit from releasing broadly adapted varieties that perform acceptably well across their target region; growers benefit from selecting a variety that specializes in their specific location. We tested whether these interests are compatible using 182 entries in a mega‐population of malting barley (spring, two‐row, multi‐environment trial [S2MET] population; Hordeum vulgare L.), which was grown across the northern United States. We assessed the strength of genetic–environment interactions (G×E), quantified local adaptation benefits, and tested whether local adaptation and genetic yield potential were correlated. Breeding programs favored broad adaptation (p < 0.001). Still, 63% of entries (114) were among the top 10%, best performing at some locations, and among the worst 10% at others. Some of the best overall entries were specialists, performing especially well in their home locations, and in general, genetic potential and local specialization were positively correlated (p < 0.001). These results suggest that breeding for local performance and broad performance are mutually supporting goals. Releasing broadly excellent, locally exceptional varieties may accelerate genetic gain to meet projected global agricultural demand.
Exploring ‘Future three’ curriculum scenarios in practice: Learning from the GeoCapabilities project
Authors: Béneker T. , Bladh G. , Lambert D.
Published: December 2023

This paper has its origins in the EU Comenius funded GeoCapabilities project. From its outset, the project developed and researched the notion of powerful disciplinary knowledge (PDK) as an underlying principle of curriculum making in the context of secondary school geography teaching. The work, led from the UCL Institute of Education and involving school teachers, teacher educators and other stakeholders across eight mainly European jurisdictions, was framed by Young and Muller's ‘three educational scenarios’ (Young & Muller, European Journal of Education, 45, 2010 and 11). The three futures heuristic is discussed as a means to distinguish qualities of curriculum thought. Future 3 scenarios, which posit teachers as curriculum makers with responsibility to engage in essential ‘knowledge work’, provide a principled platform on which to develop ambitious educational classroom encounters. Knowledge working with PDK and (as we go on to argue) other powerful ways of knowing the world, is seen as a bridge between social realist epistemological principles and practical classroom content selections. This opens the possibility of responding to Deng's (Journal of Curriculum Studies, 54, 2022) call for developing practical theories of content with teachers. Although the authors are geographers in education drawing on different international perspectives and traditions, the paper addresses matters of interest applicable to a variety of specialist subject domains across the secondary school curriculum.
A long‐term study of size variation in Northern Goshawk Accipiter gentilis across Scandinavia, with a focus on Norway
Authors: Walker Samuel J. , Lislevand Terje , Meijer Hanneke J. M.
Published: December 2023

Changing climate and growing human impacts are resulting in globally rising temperatures and the widespread loss of habitats. How species will adapt to these changes is not well understood. The Northern Goshawk (Accipiter gentilis) can be found across the Holarctic but is coming under more intense pressure in many places. Studies of recent populations in Finland and Denmark have shown a marked decline in body size of Northern Goshawks over the past century. Here we investigate long‐term changes to Norwegian populations of Northern Goshawk by including material from the Middle Ages. We measured 240 skeletons of modern Northern Goshawks from Norway, Sweden, Denmark and Finland, and 89 Medieval Goshawk bones. Our results show that Norwegian and Swedish female Goshawks have decreased in size over the past century, whilst males showed little decline. Medieval female Goshawks were larger than contemporary females. A decline in forest habitats and a concomitant shift towards smaller prey likely drove a shift to smaller body size in Northern Goshawks. Our study shows that significant body size changes in birds can occur over relatively short time spans in response to environmental factors, and that these effects can sometimes differ between sexes.
A neural network model for rapid prediction of analyte focusing in isotachophoresis
Authors: Jangra Amit , Shriyam Shaurya , Santiago Juan G. , Bahga Supreet Singh
Published: December 2023

We present the development and demonstration of a neural network (NN) model for fast and accurate prediction of whether or not a chosen analyte is focused by an isotachophoresis (ITP) buffer system. The NN model is useful in the rapid evaluation of possible ITP chemistries applicable to analytes of interest. We trained and tested the NN model for univalent species based on extensive data sets of over 10,000 anionic and 10,000 cationic ITP simulations. The NN model uses as inputs the mobilities and the acid dissociation constants of leading electrolyte ion, trailing electrolyte ion, counterion, and a single analyte as well as the leading‐to‐counterion concentration ratio of the leading zone. The output then indicates whether the chosen electrolyte system yields stable ITP focusing of the analyte. The prediction accuracy of the NN model is over 97.7%. We demonstrate the applicability of the NN by validating its predictions with reported experimental data for anionic and cationic ITP. We have packaged the NN model in a free, web‐based application named IONN (isotachophoresis on neural network), which can be used to rapidly screen ITP electrolyte systems.
Presentation and Performance of a Planar Solid Oxide Fuel Cell with Chaotic Gas Channels
Authors: Wang Ke , An Bo , Li Xingchen , Fang Dongyang , Wang Yongqing , Huijuan Su
Published: December 2023

Flow condition in gas channels determines the distribution and diffusion of reactants, governing electrochemical reactions in the solid oxide fuel cell (SOFC). It is found that the magnitude and direction of fluid velocity change with the geometric position in the channel, which leads to larger secondary flow velocity components and enhances mass transfer between fluids. Laser Doppler velocimetry experiment is conducted to verify the accuracy of numerical results of fluid flow in chaotic flow channels. Herein, a 3D numerical model with coupled multiphysics fields is built to evaluate fluid flow in channels and SOFC performance. The distribution characteristics of reactants in chaotic flow channel and the characteristics of temperature distribution, current density and power density in SOFCs caused by structures of straight and chaotic flow channels are analyzed and discussed. Compared with conventional straight flow channel SOFCs, the average current density of SOFC with chaotic flow channel is improved and the power density is increased by 9.7%. The reactant homogeneity in the electrode is also improved, which reduces the concentration polarization loss of SOFC.
The 1870s Saskatchewan River avulsion: Ice jam or open water flood? A probabilistic approach for cold climate river avulsions
Authors: Kupferschmidt Cody , Arnaud Emmanuelle
Published: December 2023

Cold climate rivers can experience avulsions due to both open water and ice jam flooding; however, most existing models for evaluating avulsions only consider open water flows. We present a novel approach for determining site‐specific probabilities of avulsion cause (open water vs. ice jam flooding) by combining historical flow data, channel cross‐sections and known avulsion history for the study area. The approach is applied to the Cumberland Marshes region of the Saskatchewan River in Central Canada, which experienced an avulsion in the mid‐1870s that some researchers have suggested may have been triggered by an ice jam. For the study area, overbank flooding was found to occur much more frequently due to ice jams than open‐water floods. Based on an average avulsion return period of 660 years in the study area, the probability of historical avulsions being caused by ice jam flooding was estimated to range from 61% and 80%, using a range of annual ice jam probabilities between 0.1 and 0.5. Results from the study suggest ice jam flooding as the most likely cause of the 1870s avulsion, which is also supported by historical evidence. The developed methodology is relatively simple to apply and could be easily implemented at other cold‐climate sites to evaluate avulsion risks.
Improving estimates of land protection costs in a tropical biodiversity hotspot
Authors: Nolte Christoph , Reboredo Segovia Ana , Ochoa‐Quintero Jose Manuel , Burbano‐Girón Jaime
Published: December 2023

Accurate estimates of the costs of land protection are useful for understanding where biodiversity conservation goals can be achieved at the lowest cost to society. However, because of the scarcity of high‐quality cost maps for tropical countries, conservation planning studies often ignore cost or rely on untested proxies, such as agricultural rent or land‐use intensity. Here, we show how analysts can estimate land protection costs using original data of public land acquisitions, global predictor datasets, and simple machine‐learning models. For the Colombian Andes, a global biodiversity hotspot, we found that the principal driver of the cost of land protection is urban proximity, not agricultural rent. We derived cost estimates that predict public land protection costs more accurately than available cost proxies and identified new protection priorities for 143 threatened bird species. A more systematic collection of cost records of land protection will help inform public decisions on national and global biodiversity protection priorities.
Emerging opportunities for wildlife conservation with sustainable autonomous transportation
Authors: Silva Inês , Calabrese Justin M
Published: December 2023

Autonomous vehicles (AVs) are expected to play a key role in the future of transportation, and to introduce a disruptive yet potentially beneficial change for wildlife–vehicle interactions. However, this assumption has not been critically examined, and reducing the number of wildlife–vehicle collisions (WVCs) may be beyond current technological capabilities. Here, we introduce a conceptual framework encompassing the intersection between AV technology and wildlife conservation to reduce WVCs. Our proposed framework integrates the development of robust warning systems and animal detection methods for AV systems, and the incorporation of wildlife–vehicle interactions into decision‐making algorithms. With large‐scale AV deployment a looming reality, it is vital to incorporate conservation and sustainability into the societal, ethical, and legal implications of AV technology. We intend our framework to help ecologists and conservationists foster the necessary interdisciplinary collaborations with AV developers and policy makers to reduce WVCs and concomitant biodiversity loss.
A novel film based on a cellulose/sodium alginate/gelatin composite activated with an ethanolic fraction of Boswellia sacra oleo gum resin
Authors: Bhatia Saurabh , Shah Yasir Abbas , Al‐Harrasi Ahmed , Ullah Sana , Anwer Md Khalid , Koca Esra , Aydemir Levent Yurdaer , Khan Mahbubar Rahman
Published: December 2023

Boswellia sacra and its derivatives exhibit notable bioactive properties, which have been the subject of extensive scientific research; however, their potential applications in food packaging remain largely untapped. In the current study, cellulose, sodium alginate, and gelatin composite edible films were fabricated with the addition of different concentrations (0.2% and 0.3%) of the ethanolic fraction of Boswellia sacra oleo gum resin (BSOR). The resultant films were examined for their physical, chemical, mechanical, barrier, optical, and antioxidant properties. Moreover, the films were characterized using Scanning Electron Microscopy (SEM), X‐ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) to study the impact of incorporating BSOR on the morphological, crystalline, and chemical properties of the films. The addition of BSOR increased the film thickness (0.026–0.08 mm), water vapor permeability (0.210–0.619 (g.mm)/(m2.h.kPa), and the intensity of the yellow color (3.01–7.20) while reducing the values of both tensile strength (6.67–1.03 MPa) and elongation at break (83.50%–48.81%). SEM and FTIR analysis confirmed the interaction between the BSOR and film‐forming components. The antioxidant properties of the edible films were significantly increased with the addition of BSOR. The comprehensive findings of the study demonstrated that BSOR possesses the potential to serve as an efficient natural antioxidant agent in the fabrication of edible films.
Synthesis of N‐Doped Graphene Photo‐Catalyst for Photo‐Assisted Charging of Li‐Ion Oxygen Battery
Authors: Kaçar Nilay , Lökçü Ersu , Çayirli Meltem , Özden Reşat Can , Coskun Sahin , Toparli Cigdem , Çelikyürek İbrahim , Anik Mustafa
Published: December 2023

In this work, nitrogen (N)‐doped graphene film is synthesized, as a photo‐catalyst, on one side of the copper foam by chemical vapor deposition and the copper foam is directly used as an electrode after porous Pd@rGO cathode loading to the other side of the foam for the photo‐assisted charging of the Li‐ion oxygen battery. The amount of urea (CO(NH2)2), which is used as N atom source, is optimized to get maximum photo‐anodic currents from the n‐type graphene films. The optical band gap and the valance band edge potential of the optimized N‐doped graphene film are determined as 2.00 eV and 3.71 VLi+/Li, respectively. X‐ray photoelectron spectra provided that the atomic percent of N atoms in the graphene film is 1.34% and the graphitic, pyrrolic and pyridinic N atom percentages are 54.01%, 42.20% and 3.79%, respectively. The photo‐assisted charging tests indicated that the N‐doped graphene film photo‐catalyst reduced the charging potential significantly even at 1000 mA g−1 (0.1 mA cm−2) current density and improved the cyclic discharge‐charge performance of the Li‐ion oxygen battery considerably.
Ba3(PO4)2 Photocatalyst for Efficient Photocatalytic Application
Authors: Naciri Yassine , Ahdour Ayoub , Benhsina Elhassan , Hamza Mahmoud Adel , Bouziani Asmae , Hsini Abdelghani , Bakiz Bahcine , Navío Jose Antonio , Ghazzal Mohamed Nawfal
Published: December 2023

Barium phosphate (Ba3(PO4)2) is a class of material that has attracted significant attention thanks to its chemical stability and versatility. However, the use of Ba3(PO4)2 as a photocatalyst is scarcely reported, and its use as a photocatalyst has yet to be reported. Herein, Ba3(PO4)2 nanoflakes synthesis is optimized using sol‐gel and hydrothermal methods. The as‐prepared Ba3(PO4)2 powders are investigated using physicochemical characterizations, including XRD, SEM, EDX, FTIR, DRS, J–t, LSV, Mott‐Schottky, and EIS. In addition, DFT calculations are performed to investigate the band structure. The oxidation capability of the photocatalysts is investigated depending on the synthesis method using rhodamine B (RhB) as a pollutant model. Both Ba3(PO4)2 samples prepared by the sol‐gel and hydrothermal methods display high RhB photodegradation of 79% and 68%, respectively. The Ba3(PO4)2 obtained using the sol‐gel process exhibits much higher stability under light excitation after four regeneration cycles. The photocatalytic oxidation mechanism is proposed based on the active species trapping experiments where O2•‒ is the most reactive species. The finding shows the promising potential of Ba3(PO4)2 photocatalysts and opens the door for further investigation and application in various photocatalytic applications.
Predictive modeling of energy‐related greenhouse gas emissions in Ghana towards a net‐zero future
Authors: Sokama‐Neuyam Yen Adams , Amezah Samuel Mawulikem , Adjei Stephen , Adenutsi Caspar Daniel , Erzuah Samuel , Quaye Jonathan Atuquaye , Ampomah William , Sarkodie Kwame
Published: December 2023

Ghana is determined to reduce greenhouse gas (GHG) emissions by at least 15% by 2030 and attain net‐zero emissions by 2070. However, like many developing countries, Ghana must utilize its limited resources effectively to actualize its climate goals. Currently, climate policies in the country are not driven by emission data, which has important implications on effective utilization of resources and selection of efficient mitigation techniques. We analyzed energy consumption and GHG emission data between 1990 and 2016 from Ghana's energy sector which is responsible for about 36% of the country's total emissions. Predictive models were then developed using machine learning to forecast energy related emissions up to 2030. Based on the analysis and projections, attainable data‐driven recommendations were proposed to direct climate policies in the country. We found that between 1990 and 2016, petroleum fuel consumption increased by about 64.5% and the corresponding GHG emissions increased by 303%. The projections suggests that by 2030, energy sector emissions could increase by 131% compared to 2016 levels. Transport sector emission is also projected to increase by a whopping 219% and fuel consumption could hit 6742 ktoe by 2030, which is about 106% increase from the 2016 benchmark. The findings from this work will direct policy for effective mitigation of GHG emissions in the country while ensuring effective utilization of climate resources to pursue its net‐zero targets. © 2023 Society of Chemical Industry and John Wiley & Sons, Ltd.