bluuebunny/crossref_metadata_2025 huggingface dataset:
Determinants of overall survival in patients with metastatic uveal melanoma
Authors: Demkowicz Patrick , Pointdujour‐Lim Renelle , Miguez Sofia , Lee Yesung , Jones Bailey S. C. L. , Barker Christopher A. , Bosenberg Marcus , Abramson David H. , Shoushtari Alexander N. , Kluger Harriet , Francis Jasmine H. , Sznol Mario , Bakhoum Mathieu F.
Published: June 2023

Background

Despite improvements in the treatment of primary uveal melanoma (UM), patients with metastatic disease continue to exhibit poor survival.

Methods

A retrospective review of metastatic UM patients at Yale (initial cohort) and Memorial Sloan Kettering (validation cohort) was conducted. Cox proportional hazards regression was used to determine baseline factors that are associated with overall survival, including sex, Eastern Cooperative Oncology Group (ECOG) Performance Status Scale, laboratory measurements, metastasis location, and use of anti‐CTLA‐4 and anti‐PD‐1 therapies. Differences in overall survival were analyzed using Kaplan–Meier analysis.

Results

A total of 89 patients with metastatic UM were identified; 71 and 18, in the initial and validation cohorts, respectively. In the initial cohort, median follow‐up was 19.8 months (range, 2–127 months) and median overall survival was 21.8 months (95% CI, 16.6–31.3). Female sex, anti–CTLA‐4, and anti–PD‐1 therapy were associated with better survival outcomes with adjusted death hazard ratios (HRs) of 0.40 (95% CI, 0.20–0.78), 0.44 (0.20–0.97), and 0.42 (0.22–0.84), respectively, whereas development of hepatic metastases and ECOG score ≥1 (per 1 U/L) were associated with worse survival outcomes with HRs of 2.86 (1.28–7.13) and 2.84 (1.29–6.09), respectively. In both the initial and validation cohorts, use of immune checkpoint inhibitors was associated with improved overall survival after adjusting for sex and ECOG score, with death HRs of 0.22 (0.08–0.56) and 0.04 (0.002–0.26), respectively.

Conclusions

Development of extrahepatic‐only metastases, ECOG of 0, immune checkpoint therapy, and female sex were each associated with more than 2‐fold reductions in risk of death.

Plain Language Summary

Metastatic uveal melanoma patients face limited treatment options and poor survival rates.

Results from this retrospective analysis indicate that immune checkpoint inhibitors, such as anti–CTLA‐4 and anti–PD‐1 therapies, were associated with improved survival outcomes. Factors such as extrahepatic‐only metastases, better baseline performance status, and female sex contributed to a more than 2‐fold reduction in death risk.

These findings highlight the potential of immunotherapy in treating metastatic uveal melanoma.
Prevalence, trends, and characteristics of trials investigating local therapy in contemporary phase 3 clinical cancer research
Authors: Sherry Alexander D. , Corrigan Kelsey L. , Kouzy Ramez , Jaoude Joseph Abi , Yang Yumeng , Patel Roshal R. , Totten Douglas J. , Newman Neil B. , Das Prajnan , Taniguchi Cullen , Minsky Bruce , Snyder Rebecca A. , Fuller C. David , Ludmir Ethan
Published: June 2023

Background

Although most patients with cancer are treated with local therapy (LT), the proportion of late‐phase clinical trials investigating local therapeutic interventions is unknown. The purpose of this study was to determine the proportion, characteristics, and trends of phase 3 cancer clinical trials assessing the therapeutic value of LT over time.

Methods

This was a cross‐sectional analysis of interventional randomized controlled trials in oncology published from 2002 through 2020 and registered on ClinicalTrials.gov. Trends and characteristics of LT trials were compared to all other trials.

Results

Of 1877 trials screened, 794 trials enrolling 584,347 patients met inclusion criteria. A total of 27 trials (3%) included a primary randomization assessing LT compared with 767 trials (97%) investigating systemic therapy or supportive care. Annual increase in the number of LT trials (slope [m] = 0.28; 95% confidence interval [CI], 0.15–0.39; p < .001) was outpaced by the increase of trials testing systemic therapy or supportive care (m = 7.57; 95% CI, 6.03–9.11; p < .001). LT trials were more often sponsored by cooperative groups (22 of 27 [81%] vs. 211 of 767 [28%]; p < .001) and less often sponsored by industry (5 of 27 [19%] vs. 609 of 767 [79%]; p < .001). LT trials were more likely to use overall survival as primary end point compared to other trials (13 of 27 [48%] vs. 199 of 767 [26%]; p = .01).

Conclusions

In contemporary late‐phase oncology research, LT trials are increasingly under‐represented, under‐funded, and evaluate more challenging end points compared to other modalities. These findings strongly argue for greater resource allocation and funding mechanisms for LT clinical trials.

Plain language summary

Most people who have cancer receive treatments directed at the site of their cancer, such as surgery or radiation.

We do not know, however, how many trials test surgery or radiation compared to drug treatments (that go all over the body).

We reviewed trials testing the most researched strategies (phase 3) completed between 2002 and 2020.

Only 27 trials tested local treatments like surgery or radiation compared to 767 trials testing other treatments.

Our study has important implications for funding research and understanding cancer research priorities.
Fast Depolymerization of PET Bottle Mediated by Microwave Pre‐Treatment and An Engineered PETase**
Authors: Guo Boyang , Lopez‐Lorenzo Ximena , Fang Yuan , Bäckström Eva , Capezza Antonio Jose , Vanga Sudarsan Reddy , Furó István , Hakkarainen Minna , Syrén Per‐Olof
Published: June 2023

Recycling plastics is the key to reaching a sustainable materials economy. Biocatalytic degradation of plastics shows great promise by allowing selective depolymerization of man‐made materials into constituent building blocks under mild aqueous conditions. However, insoluble plastics have polymer chains that can reside in different conformations and show compact secondary structures that offer low accessibility for initiating the depolymerization reaction by enzymes. In this work, we overcome these shortcomings by microwave irradiation as a pre‐treatment process to deliver powders of polyethylene terephthalate (PET) particles suitable for subsequent biotechnology‐assisted plastic degradation by previously generated engineered enzymes. An optimized microwave step resulted in 1400 times higher integral of released terephthalic acid (TPA) from high‐performance liquid chromatography (HPLC), compared to original untreated PET bottle. Biocatalytic plastic hydrolysis of substrates originating from PET bottles responded to 78 % yield conversion from 2 h microwave pretreatment and 1 h enzymatic reaction at 30 °C. The increase in activity stems from enhanced substrate accessibility from the microwave step, followed by the administration of designer enzymes capable of accommodating oligomers and shorter chains released in a productive conformation.
Implementation of AI/DEEP learning disruption predictor into a plasma control system
Authors: Tang William , Dong Ge , Barr Jayson , Erickson Keith , Conlin Rory , Boyer Dan , Kates‐Harbeck Julian , Felker Kyle , Rea Cristina , Logan Nikolas , Svyatkovskiy Alexey , Feibush Eliot , Abbatte Joseph , Clement Mitchell , Grierson Brian , Nazikian Raffi , Lin Zhihong , Eldon David , Moser Auna , Maslov Mikhail
Published: June 2023

This paper reports on advances in the state‐of‐the‐art deep learning disruption prediction models based on the Fusion Recurrent Neural Network (FRNN) originally introduced in a 2019 NATURE publication [https://doi.org/10.1038/s41586‐019‐1116‐4]. In particular, the predictor now features not only the “disruption score,” as an indicator of the probability of an imminent disruption, but also a “sensitivity score” in real time to indicate the underlying reasons for the imminent disruption. This adds valuable physics interpretability for the deep learning model and can provide helpful guidance for control actuators now implemented into a modern plasma control system (PCS). The advance is a significant step forward in moving from modern deep learning disruption prediction to real‐time control and brings novel AI‐enabled capabilities relevant for application to the future burning plasma ITER system. Our analyses use large amounts of data from JET and DIII‐D vetted in the earlier NATURE publication. In addition to “when” a shot is predicted to disrupt, this paper addresses reasons “why” by carrying out sensitivity studies. FRNN is accordingly extended to use more channels of information, including measured DIII‐D signals such as (i) the “n1rms” signal that is correlated with the n = 1 modes with finite frequency, including neoclassical tearing mode and sawtooth dynamics; (ii) the bolometer data indicative of plasma impurity control; and (iii) “q‐min”—the minimum value of the safety factor relevant to the key physics of kink modes. The additional channels and interpretability features expand the ability of the deep learning FRNN software to provide information about disruption subcategories as well as more precise and direct guidance for the actuators in a PCS.
UHPLC–MS/MS method for the quantification of ultra‐traces of irinotecan and its metabolites in red blood cells and plasma to detect caregivers' contamination
Authors: Rodier Simon , Saint‐Lorant Guillaume , Since Marc , Lagadu Stéphanie , Benoist Hubert , Palix Agnès , Guilloit Jean‐Marc , Faveyrial Audrey , Divanon Fabienne , Delépée Raphaël
Published: June 2023

The occupational exposure of caregivers to antineoplastic agents has been demonstrated since 1979. Since the early 1990s, numerous studies from several countries have demonstrated the contamination of care facilities by antineoplastic drugs. As it is easier to sample, most contamination measurements in workers are carried out in urine sample. The distribution and elimination half‐lives of irinotecan suggest that blood can be considered as better than urine for the biomonitoring of a potential contamination of healthcare workers. We describe here the development and the validation of a UHPLC–MS/MS method to simultaneously quantify irinotecan, and two of its main metabolites, APC and SN‐38, at ultra‐trace levels in plasma and red blood cells (RBC). This method has been applied to blood samples collected from several healthcare services in a French comprehensive cancer center. The results demonstrate that the method is sensitive enough to identify a contamination of healthcare workers by irinotecan and SN‐38 at very low concentrations. Moreover, the results show that analysis of RBC is of great interest and complementary to that of serum.
Population structure and distribution of geladas (Theropithicus gelada, Ruppell 1835) in Kotu forest, Northern Ethiopia
Authors: Abate Degu , Girma Zerihun
Published: June 2023

Endemic gelada populations outside protected areas are less investigated, and population census data are not available. As a result, a study was conducted to investigate the population size, structure, and distribution of geladas in Kotu forest and associated grasslands, in northern Ethiopia. The study area was stratified into five dominant habitat types namely, grassland, wooded grassland, plantation forest, natural forest, and bushland based on dominant vegetation type. Each habitat type was further divided into blocks, and a total counting technique was used to count the individuals of gelada. The total mean population size of gelada in Kotu forest was 229 ± 6.11. The mean ratio of male to female was 1:1.178. The gelada age composition comprised is as follows: 113 (49.34%) adults, 77 (33.62%) sub‐adults, and 39 (17.03%) juveniles. The mean number of group one‐male unit ranged from 1.5 ± 0.2 in the plantation forest to 4.5 ± 0.7 in the grassland habitat. On the other hand, all‐male unit social system group was recorded only from grassland (1.5) and plantation forest (1) habitats. The average band size (number of individuals per band) was 45.0 ± 2.53. The largest number of geladas was recorded from grassland habitat 68 (29.87%), and the lowest was recorded from plantation forest habitat 34 (14.74%). Even though, the sex ratio was female biased, the proportion of juveniles to other age classes was very low compared with geladas in relatively well‐protected areas, indicating negative consequences for the future viability of the gelada populations in the area. Geladas were widely distributed over open grassland habitat. Therefore, for sustainable conservation of the geladas in the area, there is a need for integrated management of the area with special attention on the conservation of the grassland habitat.
The clustering of spatially associated species unravels patterns in tropical tree species distributions
Authors: Pang Sean E. H. , Slik J. W. Ferry , Zurell Damaris , Webb Edward L.
Published: June 2023

Complex distribution data can be summarized by grouping species with similar or overlapping distributions to unravel spatial patterns and separate trends (e.g., of habitat loss) among spatially unique groups. However, such classifications are often heuristic, lacking the transparency, objectivity, and data‐driven rigor of quantitative methods, which limits their interpretability and utility. Here, we develop and illustrate the clustering of spatially associated species, a methodological framework aimed at statistically classifying species using explicit measures of interspecific spatial association. We investigate several association indices and clustering algorithms and show how these methodological choices drive substantial variations in clustering outcomes and performance. To facilitate robust decision‐making, we provide guidance on choosing methods appropriate to one's study objective(s). As a case study, we apply our framework to modeled tree distributions in Borneo and subsequently evaluate the impact of land‐cover change on separate species groupings. Based on the modeled distribution of 390 tree species prior to anthropogenic land‐cover changes, we identified 11 distinct clusters that unraveled ecologically meaningful patterns in Bornean tree distributions. These clusters then enabled us to quantify trends of habitat loss tied to each of those specific clusters, allowing us to discern particularly vulnerable species clusters and their distributions. This study demonstrates the advantages of adopting quantitatively derived clusters of spatially associated species and elucidates the potential of resultant clusters as a spatially explicit framework for investigating distribution‐related questions in ecology, biogeography, and conservation. By adopting our methodological framework and publicly available codes, practitioners can leverage the ever‐growing abundance of distribution data to better understand complex spatial patterns among species distributions and the disparate effects of global changes on biodiversity.
Sterically Demanding Novel Triazole Based Tertiary Phosphines: Synthesis, Transition Metal Chemistry and Catalytic Applications
Authors: Kote Basvaraj S. , Mohite Manali A. , Mondal Dipanjan , Pandey Madhusudan K. , Balakrishna Maravanji S.
Published: June 2023

Sterically demanding 2,6‐dibenzhydryl‐4‐methylphenyl and 1,2,3‐triazole based tertiary phosphines, [Ar*{1,2,3‐N3C(Ph)C(PR2)}] (R=Ph, 3; R=iPr, 4) were obtained by the temperature‐controlled lithiation of 1‐(2,6‐dibenzydryl‐4‐methyl)‐5‐iodo‐4‐phenyl‐1H‐1,2,3‐triazole (2) followed by the reaction with R2PCl (R=Ph, iPr). Treatment of 3 with H2O2, elemental sulfur and selenium yielded chalcogenides [Ar*{1,2,3‐N3C(Ph)C(P(E)Ph2)}] (E=O, 5; E=S, 6; E=Se, 7). The reaction of 3 with [Pd(COD)Cl2] in 1 : 1 molar ratio, afforded dimeric complex [Pd(μ2‐Cl)Cl{Ar*{1,2,3‐N3C(Ph)C(PPh2)}‐κ1‐P}]2 (8), whereas the reactions of 3 and 4 with [Pd(η3‐C3H5)Cl]2 in 2 : 1 molar ratios produced complexes [Pd(η3‐C3H5)Cl{Ar*{1,2,3‐N3C(Ph)C(PR2)}‐κ1‐P}] (R=Ph, 9; R=iPr, 10). Treatment of 3 with [Pd(OAc)2] in 1 : 1 molar ratio afforded a rare trinuclear complex [{Pd3(OAc)4}{Ar*{1,2,3‐N3C(C6H4)C(PPh2)}‐κ2‐C,P}2] (11). Treatment of 3 and 4 with [AuCl(SMe2)] resulted in [AuCl{Ar*{1,2,3‐N3C(Ph)C(PR2)}‐κ1‐P}] (R=Ph, 12; R=iPr, 13). Bulky phosphine 4 was very effective in Suzuki‐Miyaura coupling and amination reactions with very low catalyst loading. Molecular structures of 3–5, and 8–13 were confirmed by single‐crystal X‐ray diffraction studies.
Anionic Boraza‐Crown Ethers
Authors: Lenz Tabea , Hepp Alexander , Layh Marcus , Hebenbrock Marian
Published: June 2023

Making one out of two: Dimeric boraza‐crown ethers bridge the gap between metallacrowns and aza‐crown ethers with a strikingly simple synthesis. Dioxazaborocanes react with alkoxides to form the corresponding anionic boronates, which combine to form dimers upon ring‐opening reactions. The presence of the dimers was proven in the solid state and in solution by X‐ray crystallography and NMR spectroscopy, respectively. The influence of the sodium and potassium ions on the stability of boraza‐crown ethers was examined using DFT calculations. The dissociation of the dimers to the monomeric species was found to be endothermic, independently of the counterion. Finally, their ability to engage in cross‐coupling reactions was validated for two different compounds.
Acid Catalyzed Multicomponent Reaction to Access Functionalized N‐Benzhydryl Amides: A Tandem Ritter Reaction
Authors: Karu Sudheer Kumar , Malapaka Chandrasekharam
Published: June 2023

Acid catalyzed multicomponent reaction (MCR) for the synthesis of N‐benzhydryl amide derivatives from aldehydes, N,N‐disubstituted arylamines and nitriles is reported. The reaction is compatible with electronically differentiating aryl/heteroaryl aldehydes/acetals, different nucleophiles (cyclic and acyclic N,N‐disubstituted arylamines,β‐naphthols, 1,3 dicarbonyl, 1,3,5‐trimethoxy benzene), alkyl nitriles, aryl/heteroaryl nitriles in catalytic TFA/TfOH through tandem Ritter reaction. The one‐pot MCR with broad substrate scope generated a wide variety of sterically hindered N‐substituted amides and is successfully applied for the synthesis of isoindolinone.
Building the Campus as a Lab (CaaL) platform
Authors: Popoviciu Ciprian , Sawyer Colby
Published: June 2023

Internet of Things (IoT) related and IoT enabled education and research are becoming more prevalent in today's academic environment. One of the challenges faced by educators and researchers is the availability of resources to support lab based, hands on learning and research projects. Existing resources are often highly customized, balkanized, and difficult to manage. For new technology areas such as IoT, these environments rarely provide opportunities for resource sharing and interdisciplinary collaboration. In this paper, we describe the development of a multi‐tenant, IoT centric platform, the Environmental Sensing Data Network (ESDN) meant to support plug and play sensor deployment and the tools necessary for data management. The platform turns the University campus into an open platform that can be used to easily set up IoT based labs for education, research, campus infrastructure management and community applications innovation. The paper covers the development of a sensor augmentation module facilitating easy deployment and management. The operational tools and services integration are also described. We believe the platform is an important step in facilitating distance and in person education and research. ESDN is rapidly expanding beyond the multi‐site University campus supporting a growing number of research and community projects.
Study on mechanical properties and fracture modes of sandstone with cracks under triaxial compression
Authors: Liu Yongsheng , Liu Wang , Wang Cui
Published: June 2023

This study examines the mechanical properties and fracture modes of sandstone with single and double cracks under varying confining pressures through triaxial compression tests. The stress–strain curves, mechanical parameters, and fracture modes of both intact and cracked sandstone are analyzed based on experimental results. The study finds that the presence of cracks has a significant impact on the mechanical properties of sandstone, with greater damage observed with an increase in the number of cracks. The peak strength and strain of a cracked rock sample increase with the increase in crack angle. The fracture mode of sandstone is influenced by both crack angle and confining pressure. When the crack angle is small, the fracture mode is a combination of shear and tensile failure, while a large crack angle results in shear failure. Moreover, as the confining pressure increases, the degree of damage to the sandstone also increases.
Predictive control of permanent magnet synchronous motor based on Super‐Twisting sliding mode
Authors: Hu Jun , Lu Huacai , Zheng Bowen , Zhang Yan
Published: June 2023

To improve the anti‐interference ability and response speed of the permanent magnet synchronous motor control system and the problem of excessive chattering when the speed loop of the system is controlled by fast second‐order Super‐Twisting sliding mode control, an improved second‐order Super‐Twisting sliding mode controller is designed to replace the previous speed loop controller. The current loop uses model prediction to control current, which can effectively suppress chattering and improve the robustness of the whole system. The simulation results show that the response time of the system using this algorithm is not only 0.141 s faster than that of the traditional proportional integral control but also the overshoot is reduced by 10%. Then, under different working conditions, the strategy in this paper is compared with the traditional control method, and good characteristics are obtained. Finally, the whole system is used for experimental analysis. The experimental results show that this strategy has good rapidity and robustness.
Image transmission performance analysis through free space optical communication link using coherent QPSK modulation under various environmental conditions
Authors: Djir Amina , Meskine Fatiha , Tayebi Mohamed Larbi
Published: June 2023

Free space optics (FSO) technology has been used recently in many applications due to its various advantages such as high bandwidth, easy deployment, high security, free installation license and immunity to electromagnetic interference. However, this type of communication is vulnerable to meteorological conditions such as rain, haze and fog which significantly degrade the system's efficiency. To enhance the effectiveness of the FSO systems, Quadrature Phase Shift Keying (QPSK) modulation based on coherent detection constitutes a promising technique for achieving high spectral efficiency and long‐distance FSO links with the characteristics of low‐cost implementation and simple design. This work aims to investigate the performance of FSO communication links on image transmission under the presence of atmospheric attenuations. A comparative study has been made using QPSK modulation scheme and on–off‐keying (OOK) modulation scheme to estimate the maximum range that was used to recover an RGB transmitted image over an FSO link under different meteorological weathers. The obtained results clearly show that the quality of the received image has degraded significantly during transmission through free space yielding to limit the propagation range. Moreover, the proposed FSO communication system performs well when using QPSK modulation rather than OOK modulation in different environmental conditions. Thus, to improve the quality of the received image under adverse fog weather condition, high power and small beam divergence angle have been suggested to increase system's performance. The proposed solution increases the communication range of the FSO link by 230 m and 100 m for moderate and heavy fog, respectively.
Integrative physiological, transcriptome, and metabolome analyses reveal the associated genes and metabolites involved in cold stress response in common vetch (Vicia sativa L.)
Authors: Zhou Qiang , Cui Yue , Dong Shuwei , Luo Dong , Fang Longfa , Shi Zunji , Liu Wenxian , Wang Zengyu , Nan Zhibiao , Liu Zhipeng
Published: June 2023

As an economically important legume, Vicia sativa is commonly used as fodder for livestock and in health‐promoting foods for human consumption; however, cold stress is one of the most important limitations to its utilization at high altitudes. The shoot tissues of three cold‐resistant (Lan1, Lan2, and Lan3) and three cold‐sensitive (368, 521, and 538) accessions were collected after cold (4°C) treatment for 0, 6, and 48 h to assess their molecular regulatory mechanisms during cold stress via integrative analyses of their transcriptomes and metabolomes. Our Kyoto Encyclopedia of Genes and Genomes enrichment analysis showed that the biosynthesis of phenylpropanoids was the most enriched pathway in the cold stress response of V. sativa. A total of 18 differential metabolites were obtained in the biosynthesis of the phenylpropanoid pathway, and 722 differentially expressed genes (DEGs) showed a significant positive correlation with naringenin and p‐coumaric acid following a weighted gene co‐expression network analysis, while 84 DEGs showed significant negative associations. Moreover, four DEGs were overexpressed in yeast, and it was indicated that their biological function is to confer cold tolerance. These results provide a valuable resource for understanding the underlying molecular mechanism of V. sativa's response to cold stress and furthering the development of breeding research.
Preclinical study of pachyman inducing ferroptosis against ovarian cancer: Biological targets and underlying mechanisms
Authors: Li Bihui , Deng Yanyan , Lin Xuqiang , Wan Xiaowei , Liu Jiaqi
Published: June 2023

Ferroptosis has gained extreme purpose in targeting cancer treatment. Poria cocos Wolf, a traditional Chinese herb, has potential anticancer properties, but the action and mechanism against ovarian cancer remain undetailed. Pachyman (Poria cocos polysaccharides) refers to the pharmacologically bioactive ingredients rich in Poria cocos. This study aimed to identify the potent actions and the network mechanisms of pachyman against ovarian cancer through preclinical analysis. Online‐accessible database or platform was employed to predict candidate genes and core targets associated with ferroptosis in pachyman against ovarian cancer. Enrichment analyses were used to characterize the functional action and signaling mechanism in pachyman to treat ovarian cancer. Molecular docking imitation was conducted for verification of core target proteins. Network analysis uncovered that there were 30 mutual and 13 core genes targeting ferroptosis in pachyman and/against ovarian cancer, and additional enrichment analysis characterized that these core genes may act synergistically through multiple biological processes and molecular pathways associated with ferroptosis, including anti‐inflammatory action, immunoregulation, and microenvironment modulation. The strongest affinities in core target proteins between pachyman and sarcoma (SRC), signal transducer, and activator of transcription 3 (STAT3) were further validated using molecular docking method. In conclusion, pachyman may induce antiovarian cancer potentials via regulating ferroptosis‐associated biological functions and pharmacological mechanisms based on current bioinformatics findings. We reason that pachyman, the beneficial nutraceuticals, may be used clinically for future application in ovarian cancer treatment.
Modelling the ecological footprints, climate change and economic growth nexus
Authors: Pan Changjian , Cristia Juan Felipe Espinosa , Irfan Muhammad , Pan Zejiang , Ghardallou Wafa , Tahir Muhammad , Ali Basit
Published: June 2023

Ecological footprint (EF) is created by human demands for water, infrastructure, energy and food, among other things, resulting in pollution, depletion of resources and ecological disturbance. The sustainability goal in relation to EF is to reduce the impact of climate change on natural resources for long‐term growth. Pakistan is a country facing an ecological deficit and has difficulty striking a balance between economic development and environmental protection worldwide. As a result of its significant role in achieving sustainability, which is essential for human life, EF has become a global phenomenon. The study considered the nexus of economic growth, EF and its subcomponents for the economy of Pakistan. The Johansen co‐integration technique was used to analyse the short‐run (ECM) and long‐run relationship. The results showed that urbanisation, financial development, economic growth and temperature have positive effects on EFs, whereas rainfall and carbon dioxide emissions have a negative effect on EFs. The ECM test demonstrates that studied variables are responsible for 46% of disequilibrium in EF, which is less than the moderate threshold. On the contrary, in the model of EF, the coefficient of temperature in the long‐run speed is negative, indicating that the system is diverging from equilibrium and correcting its prior period disequilibrium at a rate of 663% a year, while that of CO2 emissions is positive, indicating that the system is converging towards equilibrium and correcting its prior period disequilibrium at a rate of 77.2% a year.
Central nervous system lymphomas—Assessment and treatment and prevention of central nervous system relapse
Authors: Ghione Paola , Lewis Katharine L. , Bobillo Sabela , Nayak Laksmi , Schorb Elisabeth , Nichelli Lucia , Ng Andrea , Savage Kerry J. , McKay Pam , Nastoupil Loretta , Soussain Carole , Cwynarski Kate
Published: June 2023

In this review focused on lymphoma and the central nervous system (CNS), we summarize recent developments in the management of primary (PCNSL) and secondary CNS lymphoma (SCNSL), treatment of CNS lymphoma in the older population, the neuroradiological assessment of CNS lymphoma and finally highlight the ongoing debate on optimal CNS prophylaxis. The section on PCNSL focuses on the different approaches available for frontline treatment in Europe and the United States and discusses consolidation strategies. We then highlight available strategies to treat PCNSL in the elderly population, an area of unmet need. New therapies aiming at minimizing toxicity and prioritizing quality of life are emerging for these patients. Secondary CNS lymphoma, especially in the relapsed/refractory setting is another area of unmet need, and the efficacy of CAR‐T cell therapy is being explored. We provide an overview of the imaging challenges in the neuroradiological assessment of CNS lymphoma. Finally, the section on CNS prophylaxis summarizes recent findings from large retrospective studies challenging the efficacy of present approaches to prophylaxis in higher‐risk patients with lymphoma.
Cellular therapy in lymphoma
Authors: Sureda Anna , Lugtenburg Pieternella J. , Kersten Marie José , Subklewe Marion , Spanjaart Anne , Shah Nirali N , Kerbauy Lucila N , Roddie Clarie , Pennings Elise R. A. , Mahuad Carolina , Poon Michelle , Hendricks Candice L , Kamdar Manali , Jacobson Caron
Published: June 2023

CD19‐directed chimeric antigen receptor (CAR) T‐cell therapy has had a dramatic impact on the natural history and survival of patients with high‐risk B‐cell non‐Hodgkin lymphoma. Accompanying this success has been the development of new fields of medicine and investigation into toxicity risks and mitigation therapies, mechanisms of resistance and the development of novel and next generation products and strategies in order to address relapse, and issues related to global access and health care economics. This article is a survey of each of these areas as it pertains to the rapidly evolving field of CAR T‐cell therapy, written by an International community of lymphoma experts, who also happen to be women.
Experimental Investigation of an Oxidative C−C Coupling Reaction Catalyzed by HAuCl4
Authors: Krause Melanie T. S. , Schuppener Kim , Wegner Hermann A. , Engeser Marianne
Published: June 2023

Reaction monitoring by electrospray (ESI) mass spectrometry (MS) is a valuable technique to investigate reaction mechanisms. It allows a glimpse into the reacting solution and the characterization of transient intermediates by tandem mass spectrometry. Herein we studied an intriguing gold(III)‐catalyzed synthesis of dicoumarins which includes a combination of hydroarylation and homocoupling steps. Reactants and products could be detected in positive mode. In negative mode, some species corroborating proposed transient intermediates could be detected by direct infusion ESI of reacting solutions. The ions were characterized by accurate mass determinations and gas‐phase fragmentation. Thus, indications for the nature and ligand sphere of reaction intermediates in the catalytic cycle could be collected.
Lesion‐aware network for diabetic retinopathy diagnosis
Authors: Xia Xue , Zhan Kun , Fang Yuming , Jiang Wenhui , Shen Fei
Published: June 2023

Deep learning brought boosts to auto diabetic retinopathy (DR) diagnosis, thus, greatly helping ophthalmologists for early disease detection, which contributes to preventing disease deterioration that may eventually lead to blindness. It has been proved that convolutional neural network (CNN)‐aided lesion identifying or segmentation benefits auto DR screening. The key to fine‐grained lesion tasks mainly lies in: (1) extracting features being both sensitive to tiny lesions and robust against DR‐irrelevant interference, and (2) exploiting and re‐using encoded information to restore lesion locations under extremely imbalanced data distribution. To this end, we propose a CNN‐based DR diagnosis network with attention mechanism involved, termed lesion‐aware network, to better capture lesion information from imbalanced data. Specifically, we design the lesion‐aware module (LAM) to capture noise‐like lesion areas across deeper layers, and the feature‐preserve module (FPM) to assist shallow‐to‐deep feature fusion. Afterward, the proposed lesion‐aware network (LANet) is constructed by embedding the LAM and FPM into the CNN decoders for DR‐related information utilization. The proposed LANet is then further extended to a DR screening network by adding a classification layer. Through experiments on three public fundus datasets with pixel‐level annotations, our method outperforms the mainstream methods with an area under curve of 0.967 in DR screening, and increases the overall average precision by 7.6%, 2.1%, and 1.2% in lesion segmentation on three datasets. Besides, the ablation study validates the effectiveness of the proposed sub‐modules.
Accurate and fast extraction of adhesive cells based on concave points detection and matching
Authors: Liang Dan , Pi Yang‐Jun , Hu Kai , Cui Yu‐Guo , Huang Ye , Liang Dong‐Tai , Feng Shi‐Liang
Published: June 2023

Precise image segmentation of adhesive cells is a challenge during the cell detection process for biomedical image analyses. In this article, a new segmentation and extraction method for adhesive cells based on concave points detection and matching is proposed. First, image preprocessing is used to reduce interference information, which mainly includes sequential gray scale transformation, binarization, hole filling, adhesive cells recognition, and median filtering process. Second, an improved concave detection algorithm is presented which can reduce the interfering feature points and detect the concave points on the adhesive cells accurately. Third, precise extraction of adhesive cell contour is realized by concave matching based on ellipse fitting. Experiments of blood cell sample detection show that the average accuracy is 97.18% with a costing time of 3.36 s. The proposed method can effectively reduce the interference of multiple concave points and extract the cell contour from adhesive regions with higher accuracy and less time, which shows great application potential in the field of biological image detection and analyses.
Sports health information prediction system based on deep learning network
Authors: Liu Juan , Wang Shan
Published: June 2023

This paper adopts the deep network model constructed the results of the training are used to explore the detection of sports, and to verify the deep learning network model from the perspective of reliability and feasibility. The experimental results in this paper show that the comprehensive performance evaluation index FM increased by 2.6%, Pr increased by 0.7%, and Re increased by 4.4%. Therefore, the deep residual network structure used in the DRNTL method proposed in this paper can effectively improve the generalization ability of the network. Through the learning of a large amount of labeled data, the model can be applied to the detection of other untrained complex scenes. The engineering of the moving target detection method is of great significance.
Recurrent and convolutional neural networks for sequential multispectral optoacoustic tomography (MSOT) imaging
Authors: Juhong Aniwat , Li Bo , Liu Yifan , Yao Cheng‐You , Yang Chia‐Wei , Agnew Dalen W. , Lei Yu Leo , Luker Gary D. , Bumpers Harvey , Huang Xuefei , Piyawattanametha Wibool , Qiu Zhen
Published: June 2023

Multispectral optoacoustic tomography (MSOT) is a beneficial technique for diagnosing and analyzing biological samples since it provides meticulous details in anatomy and physiology. However, acquiring high through‐plane resolution volumetric MSOT is time‐consuming. Here, we propose a deep learning model based on hybrid recurrent and convolutional neural networks to generate sequential cross‐sectional images for an MSOT system. This system provides three modalities (MSOT, ultrasound, and optoacoustic imaging of a specific exogenous contrast agent) in a single scan. This study used ICG‐conjugated nanoworms particles (NWs‐ICG) as the contrast agent. Instead of acquiring seven images with a step size of 0.1 mm, we can receive two images with a step size of 0.6 mm as input for the proposed deep learning model. The deep learning model can generate five other images with a step size of 0.1 mm between these two input images meaning we can reduce acquisition time by approximately 71%.
Substituent effect on photophysical properties and proton transfer process of HBQ derivatives
Authors: Song Yao‐Dong , Wang Qian‐Ting , Pan Jia
Published: June 2023

Background

In view of the potential applications of 10‐hydroxybenzo [h] quinoline (HBQ) in biological probes and organic light‐emission devices, the excited state intramolecular proton transfer (ESIPT) mechanism of HBQ was investigated theoretically in the work.

Aims

In order to give a detailed reaction mechanism, the ESIPT of molecular system with hydrogen bond is systematically studied using density functional theory and density functional theory

Methods

Using density functional theory (DFT) and time‐dependent density functional theory (TDDFT), we investigate the photophysical properties and excited state proton transfer of 10‐hydroxybenzo [h] quinoline (HBQ)derivatives.

Results

The optimized structure shows that HBQ1 and HBQ2 have no stable structure in S1 state. The analysis of bond length parameters and infrared vibration spectroscopy proved that the substituent groups regulated the hydrogen bond strength in the S0 state.

Conclusion

Therefore, substitution position will affect the excited state intramolecular proton transfer and the photophysical properties of the molecule.
Physical training promotes remodeling of the skeletal muscle extracellular matrix: An ultrastructural study in a murine model of Down syndrome
Authors: Cisterna Barbara , Boschi Federico , Lacavalla Maria Assunta , Vattemi Gaetano Nicola Alfio , Zancanaro Carlo , Malatesta Manuela
Published: June 2023

Down syndrome (DS) is a genetically based disease caused by triplication of chromosome 21. DS is characterized by multi‐systemic premature aging associated with deficit in motor coordination, balance, and postural control. Using a morphological, morphometrical, and immunocytochemical ultrastructural approach, this study investigated in vastus lateralis muscle of Ts65Dn mouse, a murine model of DS, the effect of an adapted physical training on the extracellular matrix (ECM) characteristics and whether the forecasted exercise‐induced ECM remodeling impacts on sarcomere organization. Morphometry demonstrated thicker basement membrane and larger collagen bundles with larger interfibrillar spacing as well as irregularly arrayed myofibrils and lower telethonin density on Z‐lines in trisomic versus euploid sedentary mice. In agreement with the multi‐systemic premature aging described in DS, these ECM alterations were similar to those previously observed in skeletal muscle of aged mice. Adapted physical training induced remodeling of ECM in both trisomic and euploid mice, that is, enlargement of the collagen bundles associated with hypertrophy of collagen fibrils and reduction of the interfibrillar spacing. A re‐alignment of the myofibrils and a higher telethonin density on Z‐line was found in trisomic mice. Altogether, our findings suggest that physical training is an effective tool in limiting/counteracting the trisomy‐associated musculoskeletal structural anomalies. The current findings constitute a solid experimental background for further study investigating the possible positive effect of physical training on skeletal muscle performance.

Research Highlights

Vastus lateralis muscle of trisomic mice shows aging‐like alterations of extracellular matrix.

Training promotes extracellular matrix remodeling.

Training may be an effective tool to counteract trisomy‐associated alterations of skeletal muscle.
Evaluation of type 1 diabetes mellitus as a risk factor of Parkinson's disease in a Drosophila model
Authors: Sanz Francisco José , Martínez‐Carrión Guillermo , Solana‐Manrique Cristina , Paricio Nuria
Published: June 2023

Diabetes mellitus (DM) is a chronic metabolic disease characterized by high blood glucose levels, resulting from insulin dysregulation. Parkinson's disease (PD) is the most common neurodegenerative motor disorder caused by the selective loss of dopaminergic (DA) neurons in the substantia nigra pars compacta. DM and PD are both age‐associated diseases that are turning into epidemics worldwide. Previous studies have indicated that type 2 DM might be a risk factor of developing PD. However, scarce information about the link between type 1 DM (T1DM) and PD does exist. In this work, we have generated a Drosophila model of T1DM based on insulin deficiency to evaluate if T1DM could be a risk factor to trigger PD onset. As expected, model flies exhibited T1DM‐related phenotypes such as insulin deficiency, increased content of carbohydrates and glycogen, and reduced activity of insulin signaling. Interestingly, our results also demonstrated that T1DM model flies presented locomotor defects as well as reduced levels of tyrosine hydroxylase (a marker of DA neurons) in brains, which are typical PD‐related phenotypes. In addition, T1DM model flies showed elevated oxidative stress levels, which could be causative of DA neurodegeneration. Therefore, our results indicate that T1DM might be a risk factor of developing PD, and encourage further studies to shed light into the exact link between both diseases.
Transmitting affective job insecurity (AJI) within teams: Layoff effects of AJI convergence on intrateam power struggles and team outcomes
Authors: Lam Wing , Chen Ziguang , Wu Wen , Lee Cynthia
Published: June 2023

Extant research on job insecurity (JI) largely focuses on the individual level, rather than considering the process of JI at collective, team levels. But employees' worries and anxiety about potential job losses create affective job insecurity (AJI), which can converge over time in teams, especially following dramatic changes such as layoffs. Drawing on a multilevel theory of emergence in teams and uncertainty reduction theory, this study offers theoretical predictions of AJI convergence, as well as its potential influences on team functioning and outcomes. A four‐wave, post‐layoff survey of 468 employees and 91 supervisors confirms two major predictions. First, AJI convergence exists within teams over time, as established by a consensus emergence model. Second, teams with members who converge at a high level of AJI experience intrateam power struggles that impair both team performance and team proactivity. By theorizing about the phenomenon of AJI convergence, this study not only expands the notion of JI from the individual to the team level, noting its harmful effects on teams, but also highlights the need for both team members and team leaders to pay close attention to such convergence and its potentially detrimental effects following layoffs.
Stochastic disaggregation of seasonal precipitation forecasts of the West African Regional Climate Outlook Forum
Authors: Houngnibo Mandela Coovi Mahuwètin , Ali Abdou , Agali Alhassane , Waongo Moussa , Lawin Agnidé Emmanuel , Cohard Jean‐Martial
Published: June 2023

Seasonal rainfall forecasts from the West African Regional Climate Outlook Forum (RCOF) are essential for adapting to climate variability. However, their temporal aggregated nature is a strong limitation, especially when used with impact models requiring daily resolution, such as hydrological or crop models. To address this issue, this study proposes a temporal disaggregation method for these forecasts using in situ data from two districts (Kandi and Parakou) in northern Benin, spanning from 1971 to 2020. A resampling technique was used to construct a daily historical record that aligns with seasonal rainfall forecasts. Three stochastic disaggregation models for rainfall (SRGs) were developed, including two parametric models (SRG1 and SRG2) and one semiparametric (SRG3). Their parameters were estimated from the resampled record to generate daily synthetic data replicating the forecasts. Evaluation of the SRGs revealed that SRG2, which combined a first‐order Markov chain with a mixed exponential distribution, performs well in simulating various characteristics of the rainy season, including dry spells, wet spells and daily precipitations. Furthermore, SRG2 maintained the trends of the initial forecasts and outperformed SRG1 and SRG3, as confirmed by the chi‐square test. Indeed, a good agreement was observed between the probabilities of the initial prediction and those calculated from the temporal disaggregation with the SRG2 method. Also, for the forecasts expressed by probabilities 15–35–50 and 20–50–30, the cumulative distribution function curves (CDF) of the SRGs exhibited appropriate shifts compared to climatology. These forecasts were specific to the Kandi area in 2008 and 2003, respectively, during the West African RCOFs. Although this study focused specifically on the Kandi and Parakou districts, the temporal disaggregation methodology used can be applied to other locations within West Africa or other RCOFs worldwide. This study offers valuable guidance for generating sector‐specific seasonal forecasts for the West African region.
A 4‐week advance in the growing season in Napa Valley, California,USA
Authors: Cayan Daniel R. , DeHaan Laurel , Tyree Mary , Nicholas Kimberly A.
Published: June 2023

The growing season start and duration, along with other temperature‐related measures of importance to premium wine grapes in Napa Valley, California have changed as climate over the western United States has warmed. The growing season start has varied from year to year with a standard deviation of about 3 weeks, but over the 1958–2016 record a linear fit to the time sequence shows it advanced by more than 4 weeks. Over the study period, advances in the growing season were strongly influenced by temperature increases beginning in the late 1960s with warm anomalies generally persisting through recent years. The date upon which the growing season accumulated 1400 growing degree‐days also shifted earlier by about 4 weeks. Other measures swung to a warmer status, including the mean temperature of the last 45 days of the growing season, which warmed by over 1.5°C. Warming days and especially warming nights contributed to the growing season advance as well as trends towards warmer expressions of other viticultural measures. Years with earlier and warmer growing seasons experienced a substantial reduction in the number of daily cool extremes, and an increase in daily warm extremes, including the number of days whose temperature reaches or exceeds 35°C.