bluuebunny/crossref_metadata_2025 huggingface dataset:
Histone‐Specific CD4+ T Cell Plasticity in Active and Quiescent Systemic Lupus Erythematosus
Authors: Ramirez Giuseppe A. , Tassi Elena , Noviello Maddalena , Mazzi Benedetta A. , Moroni Luca , Citterio Lorena , Zagato Laura , Tombetti Enrico , Doglio Matteo , Baldissera Elena M. , Bozzolo Enrica P. , Bonini Chiara , Dagna Lorenzo , Manfredi Angelo A.
Published: December 2023

Objective

The aim of this study was to assess whether circulating histone‐specific T cells represent tools for precision medicine in systemic lupus erythematosus (SLE).

Methods

Seroprevalence of autoantibodies and HLA‐DR beta (DRB) 1 profile were assessed among 185 patients with SLE and combined with bioinformatics and literature evidence to identify HLA–peptide autoepitope couples for ex vivo detection of antigen‐specific T cells through flow cytometry. T cell differentiation and polarization was investigated in patients with SLE, patients with Takayasu arteritis, and healthy controls carrying HLA‐DRB1*03:01 and/or HLA‐DRB1*11:01. SLE Disease Activity Index 2000 and Lupus Low Disease Activity State were used to estimate disease activity and remission.

Results

Histone‐specific CD4+ T cells were selectively detected in patients with SLE. Among patients with a history of anti‐DNA antibodies, 77% had detectable histone‐specific T cells, whereas 50% had lymphocytes releasing cytokines or upregulating activation markers after in vitro challenge with histone peptide antigens. Histone‐specific regulatory and effector T helper (Th) 1‐, Th2‐, and atypical Th1/Th17 (Th1*)‐polarized cells were significantly more abundant in patients with SLE with quiescent disease. In contrast, total Th1‐, Th2‐, and Th1*‐polarized and regulatory T cells were similarly represented between patients and controls or patients with SLE with active versus quiescent disease. Histone‐specific effector memory T cells accumulated in the blood of patients with quiescent SLE, whereas total effector memory T cell counts did not change. Immunosuppressants were associated with expanded CD4+ histone‐specific naive T (TN) and terminally differentiated T cells.

Conclusion

Histone‐specific T cells are selectively detected in patients with SLE, and their concentration in the blood varies with disease activity, suggesting that they represent innovative tools for patient stratification and therapy.

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Anti‐Inflammatory Effect of High‐Density Lipoprotein Blunted by Delivery of Altered MicroRNA Cargo in Patients With Rheumatoid Arthritis
Authors: Wu Qiong , Sheng Quanhu , Michell Danielle , Ramirez‐Solano Marisol , Posey Olivia , Phothisane Anastasiia , Shaik Shahensha , Vickers Kasey C. , Ormseth Michelle J.
Published: December 2023

Objective

High‐density lipoprotein (HDL) has well‐characterized anti‐atherogenic cholesterol efflux and antioxidant functions. Another function of HDL uncharacterized in rheumatoid arthritis (RA) is its ability to transport microRNAs (miRNAs) between cells and thus alter cellular function. The study's purpose was to determine if HDL‐miRNA cargo is altered and affects inflammation in RA.

Methods

HDL‐microRNAs were characterized in 30 RA and 30 control participants by next generation sequencing and quantitative polymerase chain reaction. The most abundant differentially expressed miRNA was evaluated further. The function of miR‐1246 was assessed by miRNA mimics, antagomiRs, small interfering RNA knockdown, and luciferase assays. Monocyte‐derived macrophages were treated with miR‐1246‐loaded HDL and unmodified HDL from RA and control participants to measure delivery of miR‐1246 and its effect on interleukin‐6 (IL‐6).

Results

The most abundant miRNA on HDL was miR‐1246; it was significantly enriched two‐fold on HDL from RA versus control participants. HDL‐mediated miR‐1246 delivery to macrophages significantly increased IL6 expression 43‐fold. miR‐1246 delivery significantly decreased DUSP3 1.5‐fold and DUSP3 small interfering RNA knockdown increased macrophage IL6 expression. Luciferase assay indicated DUSP3 is a direct target of miR‐1246. Unmodified HDL from RA delivered 1.6‐fold more miR‐1246 versus control participant HDL. Unmodified HDL from both RA and control participants attenuated activated macrophage IL6 expression, but this effect was significantly blunted in RA so that IL6 expression was 3.4‐fold higher after RA versus control HDL treatment.

Conclusion

HDL‐miR‐1246 was increased in RA versus control participants and delivery of miR‐1246 to macrophages increased IL‐6 expression by targeting DUSP3. The altered HDL‐miRNA cargo in RA blunted HDL's anti‐inflammatory effect.

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Command filter‐based adaptive fixed‐time fault‐tolerant control for stochastic nonlinear systems with actuator hysteresis
Authors: Xu Ke , Wang Huanqing , Liu Peter Xiaoping
Published: December 2023

In this paper, an adaptive fault‐tolerant fixed‐time control problem is considered via command‐filter technique for stochastic nonlinear systems with sensor fault and actuator hysteresis. With the application of command‐filtering technique, a novel command‐filter compensate mechanism is designed, which implies that the improved control scheme not only eliminates “the explosion of complexity” but also realizes the compensate signal is bounded within fixed‐time interval. The unavailability of state variables caused by sensor fault is solved by applying parameter separation and regrouping approach. Meanwhile, an adaptive auxiliary signal is designed to cope with the backlash‐like hysteresis phenomenon, which can avoid singularity, reduce chattering, and facilitate controller design. Combining backstepping technique and Lyapunov stability theorem, an adaptive fault‐tolerant control approach is developed, which can guarantee all closed‐loop signals remain semi‐globally practical fixed‐time stable (SGPFS) in probability. The validity of the proposed strategy is illustrated by simulation examples.
Bayesian change point prediction for downhole drilling pressures with hidden Markov models
Authors: Erivwo Ochuko , Makis Viliam , Kwon Roy
Published: December 2023

In the drilling of oil wells, the need to accurately detect downhole formation pressure transitions has long been established as critical for safety and economics. In this article, we examine the application of Hidden Markov Models (HMMs) to oilwell drilling processes with a focus on the real time evolution of downhole formation pressures in its partially observed state. The downhole drilling pressure system can be viewed as a nonlinear, non‐degrading stochastic process whose optimum performance is in a region in its warning state prior to random failure in time. The differential pressure system is modeled as a hidden 3 state continuous time Markov process. States 0 and 1 are not observable and represent the normally pressured (initiating ) and abnormally pressured or warning (reducing ) states respectively. State 2 is the observable failure state (from negative and loss of well control). The signal process of the evolution of differential pressure is identified in the changes in the observable rate of penetration (ROP) encoded in drilling performance data. The state and observation parameters of the HMM are estimated using the Expectation Maximization (EM) algorithm and we show, for a univariate system with a depth dependent time relationship, that the model parameter updates of the EM algorithm equation have explicit solutions. A Bayesian inference model, to determine the safety threshold of the system and early failure prediction at each sampling epoch, is thereafter proposed. The application of our stochastic model of the dynamic evolution of downhole pressures in operational time is illustrated with a hindcast case example. The analysis showed strong early indication of probable failure in real time and was validated in the field post drilling system failure that resulted in significant recovery costs. The potential to predict the differential pressure state transitions ahead of the bit represents a capability not currently available in the industry. This opens up significant opportunity for value creation from optimizing drilling operations to deliver substantial savings in well construction costs.
A geopolitics of knowledge analysis of higher education internationalisation in Kazakhstan
Authors: Hwami Munyaradzi
Published: December 2023

This critical interpretive paper deploys Walter Mignolo's geopolitics of knowledge concept to examine higher education internationalisation in Kazakhstan. Amidst growing concerns about economic and environmental sustainability, elitism and cognitive justice, among other critical issues, internationalisation remains a vital government policy. By tracing Kazakhstan's development since independence from the Soviet Union and focusing on key higher education development policy frameworks, the paper argues and illustrates that: (1) the internationalisation of higher education in Kazakhstan promotes a specific representation of the world that is considered universal and modern; (2) the internationalisation of higher education in Kazakhstan illustrates the existing hierarchical global higher education system that is dominated by the West as centres of knowledge and learning while allocating other countries peripheral roles; and (3) the geopolitics of knowledge concept enables the reading of higher education internationalisation beyond what is knowledge to who, why and where knowledge is produced. The data for this paper came from a qualitative study that involved 15 semi‐structured interviews with graduates who studied abroad at Western universities through the government‐sponsored Bolashak Scholarship. Three focus group sessions with 21 graduate students at Nazarbayev University complemented the interviews. The qualitative data suggest that Mignolo's geopolitics of knowledge offers a close‐to‐perfect description of the internationalisation of higher education in Kazakhstan. The conclusion drawn from this post‐Soviet study is the universalisation of Western knowledge as nations utilise it for meaningful development, despite decolonial and cognitive justice concerns.
Molecular mechanism of Xiaohuoluo wan for rheumatoid arthritis by integrating in vitro and in vivo chemomics and network pharmacology
Authors: Qin Wanli , Zhang Kai , Yu Ziyang , Liu Heyuan , Li Hangyu , Dong Ling , Han Dongran , Li Tiangang
Published: December 2023

The cause of rheumatoid arthritis (RA) is unclear. Xiaohuoluo wan (XHLW) is a classical Chinese medicine that is particularly effective in the treatment of RA. Given the chemical composition of XHLW at the overall level has been little studied and the molecular mechanism for the treatment of RA is not clear, we searched for the potential active compounds of XHLW and explored their anti‐inflammatory mechanism in the treatment of RA by flexibly integrating the high‐resolution ultra‐performance liquid chromatography–mass spectrometry (UPLC–MS)‐based in vitro and in vivo chemomics, network pharmacology, and other means. The results of the study identified that the active compounds of XHLW, such as alkaloids, nucleosides, and fatty acids, may play an anti‐inflammatory role by regulating key targets such as IL‐2, STAT1, JAK3, and MAPK8, inducing immune response through IL‐17 signaling pathway, T‐cell receptor, FoxO, tumor necrosis factor (TNF), and so forth, inhibiting the release of inflammatory factors and resisting oxidative stress and other pathways to treat RA. The results of this study provide referable data for the screening of active compounds and the exploration of molecular mechanisms of XHLW in the treatment of RA.
Impulsivity, decision‐making, and risk behavior in bipolar disorder and major depression from bipolar multiplex families
Authors: Ramírez‐Martín Almudena , Sirignano Lea , Streit Fabian , Foo Jerome C. , Forstner Andreas J. , Frank Josef , Nöthen Markus M. , Strohmaier Jana , Witt Stephanie H. , Mayoral‐Cleries Fermin , Moreno‐Küstner Berta , Rietschel Marcella , Guzmán‐Parra Jose
Published: December 2023

Objectives

Bipolar disorder (BD) and major depressive disorder (MDD) are characterized by specific alterations of mood. In both disorders, alterations in cognitive domains such as impulsivity, decision‐making, and risk‐taking have been reported. Identification of similarities and differences of these domains in BD and MDD could give further insight into their etiology. The present study assessed impulsivity, decision‐making, and risk‐taking behavior in BD and MDD patients from bipolar multiplex families.

Methods

Eighty‐two participants (BD type I, n = 25; MDD, n = 26; healthy relatives (HR), n = 17; and healthy controls (HC), n = 14) underwent diagnostic interviews and selected tests of a cognitive battery assessing neurocognitive performance across multiple subdomains including impulsivity (response inhibition and delay aversion), decision‐making, and risk behavior. Generalized estimating equations (GEEs) were used to analyze whether the groups differed in the respective cognitive domains.

Results

Participants with BD and MDD showed higher impulsivity levels compared to HC; this difference was more pronounced in BD participants. BD participants also showed lower inhibitory control than MDD participants. Overall, suboptimal decision‐making was associated with both mood disorders (BD and MDD). In risk‐taking behavior, no significant impairment was found in any group.

Limitations

As sample size was limited, it is possible that differences between BD and MDD may have escaped detection due to lack of statistical power.

Conclusions

Our findings show that alterations of cognitive domains—while present in both disorders—are differently associated with BD and MDD. This underscores the importance of assessing such domains in addition to mere diagnosis of mood disorders.
A recurrence‐predictive model based on eight genes and tumor mutational burden/microsatellite instability status in Stage II/III colorectal cancer
Authors: Gao Zhaoya , Wan Zhiyi , Yu Pengfei , Shang Yan , Zhu Guangsheng , Jiang Huiyuan , Chen Yawei , Wang Shengzhou , Lei Fuming , Huang Wensheng , Zeng Qingmin , Wang Yanzhao , Rong Wanshui , Hong Yuming , Gao Qingkun , Niu Pengfei , Zhai Zhichao , An Ke , Ding Changmin , Wang Yunfan , Gu Guoli , Wang Xin , Meng Qingkai , Ye Shengwei , Liu Haiyi , Gu Jin
Published: December 2023

Background

Although adjuvant chemotherapy (ACT) is widely used to treat patients with Stage II/III colorectal cancer (CRC), administering ACT to specific patients remains a challenge. The decision to ACT requires an accurate assessment of recurrence risk and absolute treatment benefit. However, the traditional TNM staging system does not accurately assess a patient's individual risk of recurrence.

Methods

To identify recurrence risk‐related genetic factors for Stage II/III CRC patients after radical surgery, we conducted an analysis of whole‐exome sequencing of 47 patients with Stage II/III CRC who underwent radical surgery at five institutions. Patients were grouped into non‐recurrence group (NR, n = 24, recurrence‐free survival [RFS] > 5 years) and recurrence group (R, n = 23, RFS <2 years). The TCGA‐COAD/READ cohort was employed as the validation dataset.

Results

A recurrence‐predictive model (G8plus score) based on eight gene (CUL9, PCDHA12, HECTD3, DCX, SMARCA2, FAM193A, AATK, and SORCS2) mutations and tumor mutation burden/microsatellite instability (TMB/MSI) status was constructed, with 97.87% accuracy in our data and 100% negative predictive value in the TCGA‐COAD/READ cohort. For the TCGA‐COAD/READ cohort, the G8plus‐high group had better RFS (HR = 0.22, p = 0.024); the G8plus‐high tumors had significantly more infiltrated immune cell types, higher tertiary lymphoid structure signature scores, and higher immunological signature scores. The G8plus score was also a predict biomarker for immunotherapeutic in advanced CRC in the PUCH cohort.

Conclusions

In conclusion, the G8plus score is a powerful biomarker for predicting the risk of recurrence in patients with stage II/III CRC. It can be used to stratify patients who benefit from ACT and immunotherapy.
Estimating the economic burden of colorectal cancer in China, 2019–2030: A population‐level prevalence‐based analysis
Authors: Wang Hong , Li Yan‐Jie , Lei Lin , Liu Cheng‐Cheng , Chen Wan‐Qing , Dai Min , Wang Xin , Lew Jie‐Bin , Shi Ju‐Fang , Li Ni , He Jie
Published: December 2023

Background

Colorectal cancer (CRC) is one of the most common cancers worldwide. Comprehensive data on the economic burden of CRC at a population‐level is critical in informing policymaking, but such data are currently limited in China.

Methods

From a societal perspective, the economic burden of CRC in 2019 was estimated, including direct medical and nonmedical expenditure, disability, and premature‐death‐related indirect expenditure. Data on disease burden was taken from the GBD 2019 and analyzed using a prevalence‐based approach. The per‐person direct expenditure and work loss days were from a multicenter study; the premature‐death‐related expenditure was estimated using a human capital approach. Projections were conducted in different simulated scenarios. All expenditure data were in Chinese Yuan (CNY) and discounted to 2019.

Results

In 2019, the estimated overall economic burden of CRC in China was CNY170.5 billion (0.189% of the local GDP). The direct expenditure was CNY106.4 billion (62.4% of the total economic burden), 91.4% of which was a direct medical expenditure. The indirect expenditure was CNY64.1 billion, of which 63.7% was related to premature death. The predicted burden would reach CNY560.0 billion in 2030 given constant trends for disease burden; however, it would be alternatively reduced to <CNY515.2 billion if the cancer prevention and control goals set by the United Nations and China for 2030 are achieved.

Conclusions

The population‐level economic burden of CRC in China in 2019 seemed noteworthy, with the direct expenditure accounting for more than half. Without effectively reducing exposure to modifiable factors and expanding screening coverage, the burden would continue increasing.
Nutritional status associated with clinical outcomes in children with solid tumors: A retrospective cohort study from China
Authors: Li Yongzhen , Lu Zhongying , Ma Ao , Yao Wei , Dong Rui , Li Kai , Wu Min , Dong Kuiran , Qian Tian
Published: December 2023

Objective

To investigate the long‐term changes in nutritional status in children with solid tumors during treatment and the relationship between nutritional status and clinical outcomes.

Methods

This study was a retrospective medical records review of data from children who were diagnosed with solid tumors and followed up for more than 3 months from January 2016 to December 2021 in China. Patient demographics and clinical information, including nutritional status, parenteral nutrition use, intensive care unit (ICU) transfers, infection during hospitalization, hospitalization frequency, length of stay, hospitalization costs and antibiotic costs, were collected to analyze the nutritional status of children with different types of solid tumors, the dynamic changes in nutritional status during treatment, and the relationship between nutritional status and clinical outcomes.

Results

Among the 764 patients (383 males (50.1%); 381 females (49.9%); mean age: 2.58 years), 41.6% of the solid tumors were neuroblastomas, 17.1% were hepatoblastomas, and Wilms tumors as the third most common solid tumors (8.9%). The median follow‐up duration was 6 months (range: 3–40 months). At diagnosis, the proportion of children who were undernourished (underweight and wasting) versus overweight or obese were 26.71% versus 5.21% (25.86% vs. 2.89% in the third month; 29.77% vs. 2.28% in the sixth month; 24.77% vs. 3.27% in the 12th month). The body mass index Z scores decreased from the initial values after the first month (−0.56 (−1.47, 0.23) vs. −0.44 (−1.29, 0.41)) but improved later and decreased again at 6 months. The children in the undernutrition group had longer hospital stays (p < 0.001), higher hospitalization costs (p < 0.001), higher antibiotic costs (p < 0.001), a higher risk of neutropenia (OR = 4.781 (95% CI: 1.571–14.553), p = 0.006), and a higher risk of ICU transfers (OR = 1.498 (95% CI: 1.010–2.224), p = 0.044). No significant differences in those associations by malnutrition and infection, ICU duration, or length of parenteral nutrition were observed.

Conclusion

There is a considerable prevalence of malnutrition in children with solid tumors. Malnutrition is related to adverse clinical outcomes and increases in total hospital expenses and antibiotic costs.
Efficacy and safety of radiotherapy combined with anti‐angiogenic therapy and immune checkpoint inhibitors in MSS/pMMR metastatic colorectal cancer
Authors: Zhai Menglan , Zhang Zixuan , Wang Haihong , Ren Jinghua , Zhang Sheng , Li Mingjie , Liu Lichao , Li Lisha , Zhang Lan , Li Xin , Zhang Tao , Lin Zhenyu
Published: December 2023

Purpose

Several studies have demonstrated the effectiveness of anti‐angiogenic drugs in combination with immune checkpoint inhibitors (ICIs) in patients with microsatellite stable (MSS) or mismatch repair proficient (pMMR) metastatic colorectal cancer (mCRC). However, whether combination radiotherapy (RT) can further improve the prognosis of mCRC patients after second‐line treatment remains to be explored.

Methods

Retrospective analysis of data from mCRC patients who received anti‐angiogenic targeted therapy (TT) and immunotherapy (IT) with or without RT after the failure of standard therapy. Progression‐free survival (PFS), overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety were evaluated.

Results

A total of 82 patients who received TT + IT were analyzed. For RT group (n = 42) versus NRT group (n = 40), ORR was 21.4% (9/42) versus 5.0% (2/40); DCR was 83.8% (35/42) versus 65.0% (26/40). Compared with NRT group, RT improved PFS (median: 5.0 vs. 3.6 months; p = 0.04) and OS (median: 15.2 vs. 7.2 months; p = 0.01). In addition, in the population receiving RT, the PFS of RT sequential/simultaneous TT + IT was superior to TT + IT sequential RT (median: 7.1 vs. 6.2 vs. 3.5 months, p = 0.004). Multivariate analysis suggested RT was an independent prognostic factor for PFS and OS. No treatment‐related deaths were reported.

Conclusions

Compared with TT + IT, RT combined with TT + IT improved survival outcomes in MSS/pMMR mCRC patients, with manageable toxicity. RT sequential/simultaneous TT + IT treatment is expected to be the optimal strategy for MSS/PMMR mCRC.
Child Fatality Individual Case Reports: A 24‐Year National State‐by‐State Review
Authors: Mantell David M. , Chong Natalie , Takeno Todd , Pazdur Michelle , Walker Taylor
Published: December 2023

This study focused on the content of 1186 Child Fatality Review Board individual case reports collected nationally over a 24‐year period (1995–2019). This information, in contrast to group data, may yield important insights into the causative factors, especially for child fatality resulting from neglect and inflicted injury. The reports were collected from six of the 50 states and evaluated for the quality and amount of information. They were also surveyed for data identifying causative factors for neglect and inflicted injury. Only 25 (2 per cent) of 1186 reports that are publicly available contained sufficient information about the four major causative factors—cause of death, prior child protection agency involvement by the family, evidence of professional negligence or error and family history of at‐risk circumstances. The 25 cases were then reviewed and coded for presence of information about these factors. The findings demonstrate the need for federal intervention to provide specific guidelines for the states to track their cases, to use a common nomenclature, to investigate common causative factors and to practice common reporting procedures. In this way, a robust national database can be developed.
Consider FERPA when accessing student‐athletes’ academic records
Authors: Rainsberger Richard
Published: December 2023

A college registrar recently posted on a professional discussion listserv that he had just found out that a staff member had added a coach and the athletics director as academic advisors to student‐athletes in the college's student information system.
Shed light on potential risks of signing NIL agreements with hedge fund companies
Authors: Romano Robert J.
Published: December 2023

The industry surrounding name, image, and likeness has grown to approximately $1 billion annually and is expected to increase over the coming years. What is interesting, however, is that none of the state legislation, or any NCAA rule or bylaw, addresses one of the newest trends in intercollegiate athletes: NIL hedge funding.
Learn how to practice self‐care and self‐awareness — 2 keys to leading well
Authors: Freebairn‐Smith Laura
Published: December 2023

Self‐care and self‐awareness are two of the most important habits of good leaders.
Demonstrate patience, transparency, understanding to successfully manage challenges and change
Authors: McCarthy Claudine
Published: December 2023

Kelley Hartley Hutton faced a significant challenge as Athletics Director when the athletics program underwent a major rebranding due to Indiana University Purdue University Fort Wayne becoming Purdue University Fort Wayne a few years ago.
Pemphigus vulgaris in a neonate born to a mother with pemphigus vulgaris: A case report
Authors: Anand Ayush , Awake Praneet , Bhosale Anand , Bindu Rajan , Kher Anjali , Bhanap Prasad
Published: December 2023

Key Clinical Message

Active pemphigus vulgaris in the mother can lead to neonatal pemphigus vulgaris, which is usually self‐limiting. Systemic corticosteroids are the mainstay of managing PV during pregnancy and until the child is breastfed.

Pemphigus vulgaris (PV) is a potentially life‐threatening autoimmune disease characterized by bullae and erosions over the skin and mucous membrane. PV is rarely reported in pregnant women and neonates. We reported the case of a 28‐year‐old Gravida 2 Parity 2 Living 1 who developed painful blisters and erosions in the oral cavity during third trimester of pregnancy. However, the diagnosis was delayed due to late presentation. The patient presented to our hospital at 37 weeks gestation with bullae and erosions distributed all over the body. Based on clinical evaluation and histopathology reports, she was diagnosed with PV. She delivered a child via cesarean section. The child also had similar lesions and was diagnosed with neonatal PV. Maternal PV was managed with prednisolone followed by azathioprine, leading to complete remission. No active intervention was required for neonatal PV as the condition was self‐limiting.
Numerical Investigation of Different Combustion Models for Dual‐Fuel Engine Combustion Processes
Authors: Liu Xicai , Wu Wenfeng , Wang Fubo , Wang Zhengquan , Guo Jia , Yu Hongliang
Published: December 2023

The combustion process of a dual‐fuel engine was calculated by characteristic timescale model (CTM), eddy breakup model (EBM), and coherent flamelet model (CFM) to verify the accuracy of the combustion models. The results show that the peak pressure calculated by EBM is 2.78 % higher than the experimental value, and the peak pressure calculated by CFM is closest to the experimental value. The EBM is the most accurate for CO2 emissions. The deviation of CO emissions from the experimental values calculated by CTM is the smallest (< 1 %). The NOx emission calculated by CTM is good agreement with the experimental value at low speed, and EBM is in best agreement with the experimental value at high speed. The hydrocarbon emission calculated by CFM is the most accurate, with a deviation of less than 0.6 %.
Adrenaline auto injectors pharmacokinetic/pharmacodynamic studies and potential consequences for clinical practice
Authors: Worm Margitta , Fox Adam T. , Wickman Magnus , Ring Johannes , Ebisawa Motohiro , Pouessel Guillaume , Smith Pete
Published: December 2023

Background

Anaphylaxis is a sudden multisystem allergic reaction which may result in a fatal outcome if not treated promptly. Guidelines worldwide suggest intramuscular adrenaline as the first‐line treatment for anaphylaxis outside a perioperative reaction. Adrenaline autoinjectors (AAIs) are widely used self‐administrable devices, especially in community settings. Different commercial AAIs have been authorized to be marketed in Europe. For an AAI to be efficacious, a rapid adrenaline delivery in patients, including those who are overweight or obese, resulting in an optimal cardiovascular (CV) response, is a key feature. AAIs are designed to achieve this requirement, which is reflected in their differing functional properties such as primary container selection, drug delivery mechanism (cartridge‐or syringe‐based), needle length, needle gauge, and adrenaline dose (150 μg, 300 μg, or 500 μg). However, the differences in functional properties across these devices may play a critical role in achieving these requirements as well as the differences in ergonomics in the handling of these devices.

The purpose of this review

Considering the dynamic pharmacokinetic/pharmacodynamic (PK/PD) profiles of different AAIs marketed in Europe and their effect on adrenaline delivery, the expert panel, also serving as author for this paper have carried out a detailed analysis of the PK/PD profiles of four AAIs, namely, Anapen, Emerade, EpiPen, and Jext, to delineate the adrenaline delivery and their subsequent physiological effects on the backdrop of device characteristics, dose strength, and the skin‐to‐muscle distances of the participants.
Discriminating Between Apoptosis, Necrosis, Necroptosis, and Ferroptosis by Microscopy and Flow Cytometry
Authors: Costigan Aoife , Hollville Emilie , Martin Seamus J.
Published: December 2023

Apoptosis is a mode of programmed cell death that plays important roles in tissue sculpting during development, in the maintenance of tissue homeostasis in the adult, and in the eradication of injured or infected cells during pathological processes. Numerous physiological as well as pathological stimuli trigger apoptosis, such as engagement of plasma‐membrane‐associated Fas, TRAIL, or TNF receptors, growth factor deprivation, hypoxia, radiation, and exposure to diverse cytotoxic drugs. Apoptosis is coordinated by members of the caspase family of cysteine proteases, which, upon activation, trigger a series of dramatic morphological and biochemical changes including retraction from the substratum, cell shrinkage, extensive and protracted plasma membrane blebbing, chromatin condensation, DNA hydrolysis, nuclear fragmentation, and proteolytic cleavage of numerous caspase substrates. These dramatic structural and biochemical alterations result not only in the controlled dismantling of the cell, but also in the rapid recognition and removal of apoptotic cells by phagocytes through the cell surface display of phagocytotic triggers such as phosphatidylserine. Necrosis, which is typically nonprogrammed or imposed upon the cell by overwhelming membrane or organelle damage, is characterized by high‐amplitude cell swelling, followed by rapid plasma membrane rupture and release of cellular contents into the extracellular space. Necrosis is often provoked by infectious agents or severe departure from physiological conditions due to toxins, temperature extremes, or physical injury. However, forms of programmed necrosis (necroptosis, pyroptosis, ferroptosis) can also occur in specific circumstances. Nonprogrammed and programmed necrosis can be distinguished from apoptosis by morphological features, based on the rapid uptake of vital dyes, and through the application of specific inhibitors of key molecules associated with the latter modes of cell death. This unit describes protocols for the measurement of apoptosis and necrosis and for distinguishing apoptosis from programmed as well as conventional necrosis. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC.

Basic Protocol 1: Analysis of cell morphology by phase‐contrast microscopy

Alternative Protocol 1: Assessment of morphological changes using eosin‐methylene blue staining

Alternative Protocol 2: Analysis of nuclear morphology by fluorescence microscopy

Support Protocol: Preparation of cytospins

Basic Protocol 2: Measurement of plasma membrane composition with annexin V and propidium iodide

Basic Protocol 3: Measurement of DNA fragmentation by flow cytometry

Alternative Protocol 3: Analysis of DNA fragmentation by the TUNEL assay

Basic Protocol 4: Measurement of caspase activation by flow cytometry

Basic Protocol 5: Discriminating between apoptosis, necrosis, necroptosis, and ferroptosis
Characterization of yellow‐green leaf1 mutant for improved phosphorus use efficiency and rapid offspring screening in Tartary buckwheat
Authors: Wang Yan , Chen Xuling , Guan Zhixiu , Yang Li , Xiang Dabing , Wan Yan , Jiang Kai , Liang Chenggang
Published: December 2023

Leaf color mutations provide valuable genetic resources for elucidating the molecular regulatory mechanisms of plant growth and serve as efficient tools for screening offspring in crossbreeding. In this study, a Tartary buckwheat (Fagopyrum tataricum) mutant with yellow‐green leaves (yl1) was isolated from 60Co‐γ‐radiation mutation bank. Compared to wild type (WT), yl1 showed similar biomass and yield, despite a lower chlorophyll content and net photosynthetic rate. However, yl1 displayed significantly higher total phosphorus content after 14 days of medium and low phosphorus treatment. By using yl1 as the maternal parent, hybrid offspring could be visually distinguished at the cotyledon stage. Genetic analysis revealed that the yl1 phenotype was attributed to a single recessive mutation. Combined metabolome and transcriptome analysis identified 205 differential expressed metabolites (DEMs) and 123 differential expressed genes enriched in 30 pathways or metabolisms between yl1 and WT. Remarkably, the upregulation of SPX3, 5PTase2, PHO1, PAP3, PAP2, PAP7, and IPAP16, which are involved in enhancing phosphorus absorption, assimilation, transport, and remobilization, along with PLDζ1, GDPD1, MGD2, and NPC4L, which contribute to improving lipid metabolism, collectively resulted in high accumulation of 41 phosphorus‐containing DEMs (including 37 lipids) in yl1. This study emphasizes the potential of yl1 for effective screening of offspring and uncovers the interplay between photosynthesis and lipid metabolism, providing valuable insights to improve phosphorus use efficiency in Tartary buckwheat.
Allometric relationships between sapwood area and shrub dimensions for six common Southern African savanna bush encroacher species: Universal or species‐specific?
Authors: Hendler Roi , Herkenrath Tim , Shikangalah Rosemary , Blaum Niels , Geissler Katja
Published: December 2023

Southern African savanna rangelands are facing a widespread degradation pattern called bush encroachment. This is associated with implications for various aspects of the water cycle and in particular canopy transpiration. At the individual‐tree scale, it is estimated by scaling sap‐flux density by sapwood area. However, the direct measurement of sapwood area is impracticable at landscape scale and general allometric equations of the West‐Brown‐Enquist (WBE) model relating sapwood area to primary size measures seem to fail for some species and climates. Therefore, we conducted intensive field measurements to establish species‐specific allometric relationships between sapwood area and sizes (stem diameter, crown area) in six dominant shrub species involved in bush encroachment in Namibia (Colophospermum mopane, Senegalia mellifera, Vachellia reficiens, Dichrostachys cinerea, Vachellia nebrownii, Catophractes alexandri). We found strong allometric relationships between sapwood area and stem diameter as well as between sapwood area and crown area for all six species. These relations are largely in line with the WBE theory but still provide estimates that are more accurate. Only in D. cinerea, the sapwood area was significantly smaller than predicted by the WBE theory, which might be caused by a larger need for stabilizing heartwood. Our results are useful to estimate water loss via transpiration at a large scale using remote sensing techniques and can promote our understanding of the ecohydrological conditions that drive species‐specific bush encroachment in savannas. This is particularly important in the light of climate change, which is considered to have major implications on ecohydrological processes in savannas.
Positive association between emerald ash borer residence time and accumulation of invasive plants
Authors: Gougherty Andrew V. , Elliott Jessica M. , LaRue Elizabeth A. , Gallion Joey , Fei Songlin
Published: December 2023

Invasive forest pests can affect the composition and physical structure of forest canopies that may facilitate invasion by non‐native plants. However, it remains unclear whether this process is generalizable across invasive plant species at broad spatial scales, and how other landscape characteristics may simultaneously facilitate non‐native plant invasion. Here, we assembled a dataset of over 3000 repeatedly measured forest plots and quantified the impact of emerald ash borer (EAB, Agrilus planipennis) residence time, land cover, and forest structure on the accumulation and coverage of invasive plants. We show plots in counties with longer EAB residences tended to accumulate more invasive plants than plots with shorter EAB residences. On average, nearly half of the plots with ash (Fraxinus spp.) in counties with EAB accumulated an additional 0.48 invasive plant species over the 5‐ to 6‐year resample interval compared to plots with ash in counties without EAB at the time of sampling. Increases in invasive species coverage were also evident in counties with EAB—although residence time did not have a strong effect, while forest gap fraction and vertical complexity were each negatively associated with increased coverage. This work has implications for understanding how invasive forest pests can facilitate the spread of non‐native plants.
Numerical and experimental investigation of the deviation of microparticles inside the microchannel using the vortices caused by the ICEK phenomenon
Authors: Ghadamgahi Seyed Mohammad Ehsan , Shahmardan Mohammad Mohsen , Nazari Mohsen , Mansouri Hamed , Hashemi Nicole N
Published: December 2023

One field of study in microfluidics is the control, trapping, and separation of microparticles suspended in fluid. Some of its applications are related to cell handling, virus detection, and so on. One of the new methods in this field is using ICEK phenomena and dielectrophoresis forces. In the present study, considering the ICEK phenomena, the microparticles inside the fluid are deviated in the desired ratio using a novel ICEK microchip. The deviation is such that after the microparticles reach the floating electrode, they are trapped in the ICEK flow vortex and deviated through a secondary channel that was placed crosswise and noncoplanar above the main channel. For simulation verification, an experimental test is done. The method used for making two noncoplanar channels and separating the particles in the desired ratio with a simple ICEK microchip is an innovation of the present study. Moreover, the adjustment of the percentage of separation of microparticles by adjusting the parameters of the applied voltage and fluid inlet velocity is one of the other innovations of the present experimental study. We observed that for input velocities of 150–1200 µm/s with applied voltages of 10–33 V, 100% of the particles can be directed toward the secondary‐channel.
Dry sliding wear characteristics of Al7075 alloy‐reinforced with SiC and cenosphere particles
Authors: Balaji Y. S. , Keerthiprasad K. S. , Babu E. R. , Om Prakash B. , Anjinappa Chandrashekar , Sharma Prabhakar , Razak Abdul , Wodajo Anteneh Wogasso
Published: December 2023

Aluminum metal matrix composite (AMMC) is employed in all engineering applications, most notably as a substitute for conventional metals in the fields of defense, automotive, and aerospace. AMMC should have a wide variety of structural, mechanical, thermal, wear, and corrosion qualities that may require mutually exclusive features at an optimal level to achieve this. The current research focuses on the stir casting process for producing SiC and cenosphere reinforced Al7075 alloys. The response surface method's (RSM) face‐centered central composite design (CCD) was used to design the number of experimental trials, and a response surface technique was enforced to forecast the optimum combination of processing variables in the wear process. The SiC reinforcement improved the wear resistance of Al7075‐SiC‐cenosphere composites substantially. Overall, the experiments show that Al7075‐6 wt% SiC‐5 wt% cenosphere has excellent tribological properties. The hybrid Al7075/SiC/Cenosphere composites were shown to be effective, fit, and suitable in the ideal wear process parameters (load of 10 N, sliding distance of 1000 m, and sliding velocity of 1.5 m/s) for lowering wear rate (0.38035 × 10−3 mm3/m) at 6wt% SiC reinforced composite. This suggests that the combination of SiC and cenosphere improves the wear resistance of AMMC.
Innovative energy storage system harnessing gravity and electromagnetic for sustainable power solutions
Authors: El Hammoumi Aboubakr , El Majid Badre , Motahhir Saad
Published: December 2023

In the face of increasing global energy demand and growing dependence on renewable sources, there exists a compelling need for innovative energy storage solutions. Traditional methods, while effective, face limitations in terms of scalability, adaptability, cost, and environmental impact. This urgency is particularly evident in the intermittent nature of renewable sources like solar and wind. To bridge the gap between energy production and demand, there is a compelling call for innovative storage technologies that not only overcome current limitations but also align with the evolving landscape of sustainable energy solutions. This short communication introduces a preliminary design concept for an innovative energy storage system (ESS) designed to store excess electrical energy generated during off‐peak periods, particularly from renewable sources, for subsequent retrieval during peak demand. The proposed storage solution capitalizes on the principles of electromagnetic induction and gravitational potential energy, providing an inventive and sustainable approach to energy storage. The proposed ESS can promise a swift and effective storage solution, particularly for remote, off‐grid areas, boasting high energy autonomy, minimal maintenance requirements, and negligible environmental impact. The preliminary design specifics and distinctive features of the proposed ESS are outlined, along with a discussion on the challenges associated with its development and implementation.
Metastatic small cell bladder cancer treated with sequential systemic therapy including pembrolizumab and amrubicin: A case report
Authors: Mitani Kazutaka , Tsuboi Ichiro , Tanaka Gen , Yosioka Saori , Yokoyama Shuhei , Kobayashi Yusuke , Nakajima Hirochika , Nagami Taichi , Ogawa Kohei , Wada Koichiro
Published: December 2023

Introduction

Small cell bladder cancer is a relatively rare tumor, representing <1% of all bladder tumors. Amrubicin monotherapy is used as second‐line treatment for small cell lung cancer in Japan.

Case presentation

A 79‐year‐old woman presented with gross hematuria and was diagnosed with small cell bladder cancer (T2 or higher). Neoadjuvant chemotherapy with etoposide and cisplatin resulted in a partial response. Robot‐assisted radical cystectomy was performed, and radical resection was achieved. As we identified metastasis in the pleura 1 year later, we administered carboplatin and etoposide, which resulted in a partial response. Although pembrolizumab was initiated as maintenance therapy, it was not effective. Amrubicin was given as third‐line therapy, and stable disease was achieved without serious adverse effect for 6 months.

Conclusion

Although there is no established treatment for metastatic small cell bladder cancer, the current case report suggests the effectiveness of amrubicin in this setting.
A qualitative study exploring patient experiences and opinions of warfarin patient self‐management in the US healthcare system
Authors: Wilson Aaron S. , Slager Stacey , Jones Aubrey E. , Vazquez Sara R. , Barnes Geoffrey D. , Sylvester Katelyn , Chan Linh , Ragheb Bishoy , Witt Daniel M.
Published: December 2023

Background

Despite consensus guideline recommendations, the use of warfarin patient self‐management (PSM) in the United States (US) healthcare system remains underutilized.

Objectives

To gain an understanding of the barriers and facilitators to warfarin PSM in US healthcare systems through qualitative exploration of the opinions of select US patients receiving warfarin therapy.

Methods

Individual patient interviews were conducted at five geographically diverse sites. Grounded theory analysis was performed on interview transcriptions using the consolidated framework for implementation research (CFIR) to identify facilitators and barriers to PSM implementation within the US healthcare system.

Results

A total of 40 patients were interviewed. Four major themes emerged from the interviews: (1) “Patients are resourceful problem solvers who know themselves better than clinicians” (CFIR domain “Characteristics of Individuals”); (2) The provider‐patient relationship is key to successful PSM (CFIR domains “Inner Setting” and “Intervention Characteristics”); (3) Patients are willing and interested in trying PSM if not already doing so (CFIR domains “Process,” “Intervention Characteristics,” “Inner Setting, and “Characteristics of Individuals”); and (4) Point‐of‐care international normalized ratio (INR) monitoring is an important PSM facilitator (CFIR “Intervention Characteristics,” “Outer Setting,” “Inner Setting,” and “Process” domains).

Conclusions

Interview participants were willing and interested in trying PSM. Core elements of warfarin PSM include timely access to INR results, and a framework to support PSM decision making. Home INR monitoring is likely ideal for facilitating PSM implementation as is maintaining strong provider‐patient relationships where providers, including clinical pharmacists, trust their patients and act as a safety net for PSM decision making.
Adolescents' mental health in the social‐media era: The role of offline and online need‐based experiences
Authors: Van de Casteele Marlies , Flamant Nele , Ponnet Koen , Soenens Bart , Van Hees Valerie , Vansteenkiste Maarten
Published: December 2023

Introduction

Debate about the precise role of social media use (SMU) in the mental health of today's adolescents is still ongoing. The present study adds to the literature by focusing on adolescents' experiences during SMU and in their offline activities through the lens of basic psychological needs, which are central to self‐determination theory.

Methods

To examine the joint and supplementary effects of need‐experiences in the offline and SMU domain (i.e., SMU satisfaction, offline satisfaction, SMU frustration, offline frustration) on several indicators of adolescents' mental health (i.e., vitality, life satisfaction, sleep quality, anxiety, and depression), polynomial regression analyses were used. Three cross‐sectional samples were collected in Belgium, including early to mid‐adolescents during the COVID‐pandemic (Sample 1;N = 447;Mage = 14.26; 54.4% female) as well as postpandemic (Sample 2;N = 179,Mage = 15.25; 54.2% female), and among college students in postpandemic times (Sample 3;N = 4977;Mage = 20.72; 69.1% female).

Results

The results showed that need‐experiences common to both domains were a robust factor associated with mental health. This finding was obtained across all samples and outcomes, with need satisfaction playing a beneficial and need frustration a harmful role. We further found that offline need‐experiences serve as a more crucial predictor of adolescents' mental health than need experiences on social media.

Conclusions

Adolescents' experiences of need satisfaction and need frustration on social media and in offline activities are central to their mental health. However, only relying on SMU as a single source of need satisfaction may not be recommended, given that offline experiences seem to be more decisive.