bluuebunny/crossref_metadata_2025 huggingface dataset:
Bioengineer mesenchymal stem cell for treatment of glioma by IL‐12 mediated microenvironment reprogramming and nCD47‐SLAMF7 mediated phagocytosis regulation of macrophages
Authors: Li Man , Lu Lisen , Xiao Qungen , Maalim Ali Abdi , Nie Bin , Liu Yanchao , Kahlert Ulf D. , Shu Kai , Lei Ting , Zhu Mingxin
Published: June 2024

High expression of cellular self‐activated immunosuppressive molecules and extensive infiltration of suppressive immune cells in the tumor microenvironment are the main factors contributing to glioma's resistance to immunotherapy. Nonetheless, technology to modify the expression of glioma cellular self‐molecules through gene editing requires further development. This project advances cell therapy strategies to reverse the immunosuppressive microenvironment of glioma (TIME). Bone marrow‐derived mesenchymal stem cells (MSCs) are engineered to express bioactive proteins and demonstrate tumor‐homing characteristics upon activation by TGF‐β. These MSCs are designed to secrete the anti‐tumor immune cytokine IL‐12 and the nCD47‐SLAMF7 fusion protein, which regulates T‐cell activity and macrophage phagocytosis. The engineered MSCs are then injected in situ into the glioma site, circumventing the blood‐brain barrier to deliver high local concentrations of bioactive proteins. This approach aims to enhance the M1 polarization of infiltrating macrophages, stimulate macrophage‐mediated tumor cell phagocytosis, activate antigen‐presenting cells, and promote effector CD8+ T cell infiltration, effectively controlling glioma. Additionally, the engineered MSCs may serve as a universal treatment for other tumors that express TGF‐β at high levels. This study proposes a novel treatment strategy for the clinical management of glioma patients.
Phosphoric Acid Electrolyte Uptake and Retention Analysis on UiO‐66‐NH2 Polybenzimidazole Nanocomposite Membranes
Authors: Wu Bo , Choo Hui Leng , Ng Wei Keat , Pang Ming Meng , Yoon Li Wan , Wong Wai Yin
Published: June 2024

High‐temperature proton exchange membrane fuel cells (HT‐PEMFCs) have a major advantage over low‐temperature fuel cells due to their better tolerance to higher carbon monoxide content in the hydrogen feed, simpler fuel processing, and better heat management. However, a key challenge in the development of HT‐PEMFCs is the potential for acid leaching from phosphoric acid‐doped polybenzimidazole membranes, which can reduce overall fuel cell performance. This study investigates the effect of post‐synthetic modification of the UiO‐66‐NH2 metal–organic framework (MOF) on the acid electrolyte uptake and retention of MOF/poly(4,4ʹ‐diphenylether‐5,5ʹ‐bibenzimidazole) (OPBI) nanocomposite membranes. Thermogravimetric analysis (TGA) was used to correlate the membrane properties with acid uptake. This work revealed that the presence of MOF with functional groups that can form hydrogen bonds with phosphoric acid molecules was able to alleviate the acid retention in the OPBI membrane with lower acid uptake. TGA demonstrated that the lower bound moisture content in the nanocomposite membranes was correlated to the lower acid uptake. In addition, the thermal stability of the nanocomposite membranes was found to improve.
Middle to Late Ordovician flare‐up of granitoids, South Altyn Tagh: Reworking of exhumed continental crust
Authors: Zhou Ningchao , Zhao Guochun , Yao Jinlong , Liu Qian , Han Yigui , Zhang Huishan , Ren Guangli
Published: June 2024

A flare‐up of granitoids occurred at 465–445 Ma in the South Altyn Tagh, synchronously with the exhumation of subducted continental crust. Nevertheless, it remains enigmatic whether a petrogenetic connection exists between them. Here, we report a 454–451 Ma monzogranite pluton, which is characterized by abundant inherited zircons, located in the northern margin of the South Altyn Tagh high‐pressure (HP)—ultrahigh‐pressure (UHP) metamorphic terrane. U–Pb ages and Hf–O isotopic compositions of inherited and synmagmatic zircons are investigated to trace the source rocks and petrogenesis of this pluton. The inherited zircons (zircons that predate the magmatism) exhibit a wide range of ages from 2618 to 484 Ma, displaying three major peaks at 1800–1100 Ma, 1000–800 Ma and 500 Ma. By comparing these inheritance age patterns with zircon spectra of main (meta‐)sedimentary sequences and the widespread Early Neoproterozoic granites (presently as granitic gneisses) in South Altyn Tagh, along with zircon εHf(t) and whole‐rock Nd isotopic composition, we argue that the main source rocks of the studied monzogranite are Early Neoproterozoic granitic gneisses and Late Mesoproterozoic paragneisses from the South Altyn Tagh HP–UHP metamorphic terrane. The ca. 500 Ma inherited zircons have a metamorphic origin, which is simultaneous with the peak metamorphic ages of HP–UHP metamorphic rocks in the Altyn Tagh Complex. These observations indicate that the source rocks of the monzogranite pluton are the subducted continental crust, which underwent metamorphism at ca. 500 Ma and followed by partial melting at 454–451 Ma. In addition, synmagmatic zircons exhibit variable δ18O and εHf(t) values ranging from 5.4 to 11.7‰ and from −19 to +10.3, respectively, indicating a minor contribution of mantle‐derived melts in the formation of the monzogranite. Given the studied pluton and contemporaneous extensive granitoids (465–445 Ma), characterized by similar geochemistry and source rocks, are synchronous with the final exhumation of subducted South Altyn Tagh continental crust, we propose that the reworking of exhumed continental crust at middle to lower crustal depths is their main petrogenesis.
Impulse oscillometry in patients with persistent post‐COVID‐19 symptoms: A retrospective study
Authors: Lu Chun‐Yu , Lin Sheng‐Hao , Chen Chun‐Min
Published: June 2024

Introduction

Impaired lung function has been observed in patients following COVID‐19 infection, with studies reporting persistent lung volume and diffusing capacity impairments. Some studies have demonstrated significantly higher small airway resistance in COVID‐19 positive cases. This retrospective study aims to examine impulse oscillometry (IOS) data of patients with persistent symptoms after COVID‐19 infection, focusing on the relationship between time and symptoms.

Material and Method

The study analyzed data from adult patients with persistent symptoms who underwent IOS testing within and after 84 days from the diagnosis date.

Result

The results showed that patients within 84 days and those between 31 and 84 days had higher small airway resistance values, indicating peripheral airway disease. Patients with dyspnea exhibited higher IOS values compared to those with cough symptoms, suggesting more significant impairment in the peripheral airways.

Conclusion

The study highlights the importance of using comprehensive diagnostic tools like IOS to assess respiratory impairments in post‐COVID‐19 patients, particularly in the small airways. Understanding the relationship between time and symptoms can provide valuable insights for the treatment of peripheral airway dysfunction in post‐COVID‐19 patients.
Predictors of 30‐day mortality following the first episode of stroke among patients admitted at referral hospitals in Dodoma, central Tanzania: A prospective longitudinal observational study
Authors: Chongolo Anna M. , Alphonce Baraka , Mbelele Peter M. , Meda John , Nyundo Azan
Published: June 2024

Background and Aims

Stroke is the leading cause of disability and the second most common cause of death after ischemic heart disease worldwide. Understanding predictors of early poststroke mortality provides opportunities for interventions and favorable outcomes. This study aimed to determine the incidence and predictors of 30‐day mortality among patients admitted with the first stroke at referral hospitals in Dodoma.

Methods

A prospective longitudinal observational design enrolled patients with acute stroke confirmed by CT scan or MRI admitted at referral hospitals in Dodoma. The National Institute of Health Stroke Scale was used to assess stroke severity at baseline. A comparison of risk factors, clinical profiles, and mortality was done using the Chi‐square test. A logistic regression model was used to determine the predictors of 30‐day mortality in patients with the stroke while the 30‐day probability of survival was estimated using Kaplan−Meier analysis.

Results

Out of 226 patients with first‐ever stroke, 121(54%) were males, and the population mean age was 63(15) years. The 140(62%) had Ischemic stroke, and 154(68%) survived at the 30th day. Patients with a history of smoking 2.4 [95% confidence interval (CI) (1.0−5.6), p = 0.048], loss of consciousness 2.7 [95% CI (1.2−6.4; p = 0.019] and unequal pupil size 13.7 [95% CI (4.1−58.1, p < 0.001 were significantly more associated with mortality within 30 days. The median survival was 7 (3−9) days, whereas alcohol drinkers and those aged above 60 years had a shorter time to mortality compared to non‐alcohol drinkers and those aged <60 years.

Conclusion

The study showed a high incidence of mortality within 30 days after the first stroke episode, with the highest proportion dying within 7 days of being hospitalized. Advanced age of ≥60 years, smoking, alcohol use, and severe stroke at admission warrant special attention.
Preferences of Iranian medical students for selecting the compulsory service plan packages: A discrete choice experiment
Authors: Homaie Rad Enayatollah , Hajizadeh Mohamad , Rajabpour Mohammad , Mohtasham‐Amiri Zahra , Rahbar‐Taramsari Morteza , Bahador Faezeh , Esmaeili Shoja Ehsan
Published: June 2024

Background and Aims

Health policymakers face challenges in designing compulsory plan packages for medical students to encourage them to work in disadvantaged regions. Using a discrete choice experiment, this study assessed the preferences of medical students for selecting the compulsory service plan packages in Guilan Province, Iran.

Methods

In total, 374 medical students responded to a survey inquiring about salary, distance from their residency city, availability of welfare amenities, work difficulty, the developmental status of their workplace, contract duration, and preference for urban or rural work settings.

Results

The study revealed that students favor a compulsory service package that provides higher salaries and shorter contract duration. They also show a preference for working within their home province over other factors. For the opportunity to serve in their city of residence, they would forgo an average of US$77.93 per month.

Conclusion

While financial incentives were the primary consideration for medical students when choosing compulsory service packages, a range of nonfinancial factors significantly influenced their decisions as well.
Evidence of the validity of the child self‐regulation & behaviour questionnaire for the Brazilian context
Authors: Lemos Natália Batista Albuquerque Goulart , Carson Valerie , Howard Steven , Cristi‐Montero Carlos , da Cunha Glacithane Lins , Mota Jéssica Gomes , Okely Antony , Bandeira Paulo Felipe Ribeiro , de Lucena Martins Clarice Maria
Published: June 2024

Poor early childhood self‐regulation is related to many mental health problems and antisocial behaviours, so it is important to use psychometrically sound instruments to assess children's self‐regulation and behavioural development. The aim of this study is to report the translation, adaptation, as well as explore the construct validity of the child self‐regulation & behaviour questionnaire (CSBQ) for the Brazilian context. The process consisted of different steps, such as transcultural translation, item intelligibility analysis, and psychometric analysis based on classical and contemporary theories. The validation process was carried out on a sample of 277 parents/caregivers (35.00 ± 6.72 years old) of 281 children (4.92 ± 1.45 years old; 156 females). The final Brazilian version showed adequate values of semantic, idiomatic, and conceptual equivalence. The validation process resulted in a seven‐dimensional model with 33 items. The validation of Brazilian CSBQ is promising for investigating early self‐regulation and behaviour problems in low‐middle income contexts.
Investigating the Involvement of C−X−C Motif Chemokine 5 and P2X7 Purinoceptor in Ectopic Calcification in Mouse Models of Duchenne Muscular Dystrophy
Authors: Rumney Robin M. H. , Pomeroy Joanna , Górecki Dariusz C.
Published: June 2024

Ectopic calcification of myofibers is an early pathogenic feature in patients and animal models of Duchenne muscular dystrophy (DMD). In previous studies using the Dmdmdx‐βgeo mouse model, we found that the dystrophin‐null phenotype exacerbates this abnormality and that mineralised myofibers are surrounded by macrophages. Furthermore, the P2X7 purinoceptor, functioning in immune cells offers protection against dystrophic calcification. In the present study, by exploring transcriptomic data from Dmdmdx mice, we hypothesised these effects to be mediated by C−X−C motif chemokine 5 (CXCL5) downstream of P2X7 activation. We found that CXCL5 is upregulated in the quadriceps muscles of Dmdmdx‐βgeo mice compared to wild‐type controls. In contrast, at the cell level, dystrophic (SC5) skeletal muscle cells secreted less CXCL5 chemokine than wild‐type (IMO) controls. Although release from IMO cells was increased by P2X7 activation, this could not explain the elevated CXCL5 levels observed in dystrophic muscle tissue. Instead, we found that CXCL5 is released by dystrophin‐null macrophages in response to P2X7 activation, suggesting that macrophages are the source of CXCL5 in dystrophic muscles. The effects of CXCL5 upon mineralisation were investigated using the Alizarin Red assay to quantify calcium deposition in vitro. In basal (low phosphate) media, CXCL5 increased calcification in IMO but not SC5 myoblasts. However, in cultures treated in high phosphate media, to mimic dysregulated phosphate metabolism occurring in DMD, CXCL5 decreased calcification in both IMO and SC5 cells. These data indicate that CXCL5 is part of a homoeostatic mechanism regulating intracellular calcium, that CXCL5 can be released by macrophages in response to the extracellular ATP damage‐associated signal, and that CXCL5 can be part of a damage response to protect against ectopic calcification. This mechanism is affected by DMD gene mutations.
The Prognostic Biomarker RAB7A Promotes Growth and Metastasis of Liver Cancer Cells by Regulating Glycolysis and YAP1 Activation
Authors: Zhang Jun‐Yuan , Zhu Xilin , Liu Ying , Wu Xiaopan
Published: June 2024

Activating transcription factor 6 (ATF6) and its downstream genes are involved in progression of hepatocellular carcinoma (HCC). Herein, we demonstrated that sulfhydration of Ras‐related protein Rab‐7a (RAB7A) was regulated by ATF6. High expression of RAB7A indicated poor prognosis of HCC patients. RAB7A overexpression contributed to proliferation, colony formation, migration, and invasion of HepG2 and Hep3B cells. Furthermore, we found that RAB7A enhanced aerobic glycolysis in HepG2 cells, indicating a higher degree of tumor malignancy. Mechanistically, RAB7A suppressed Yes‐associated protein 1 (YAP1) binding to 14‐3‐3 and conduced to YAP1 nuclear translocation and activation, promoting its downstream gene expression, thereby promoting growth and metastasis of liver cancer cells. In addition, knocking down RAB7A attenuated the progression of orthotopic liver tumors in mice. These findings illustrate the important role of RAB7A in regulating HCC progression. Thus, RAB7A may be a potential innovative target for HCC treatment.
Monovalent cation binding to model systems and the macrocyclic depsipeptide, emodepside
Authors: Subramanian Govindan , Manchanda Kanika , Mo Yirong , Sathe Rohit Y. , Bharatam Prasad V.
Published: June 2024

This study focuses on the systematic exploration of the emodepside conformations bound to monovalent K+ ion using quantum mechanical density functional theory (DFT) calculations at the M06‐2X/6‐31+G(d,p) level of theory. Nine conformers of emodepside and their complexes with K+ ion were characterized as stationary points on the potential energy surface. The conformational isomers were examined for their 3D structures, bonding, energetics, and interactions with the cation. A cavitand‐like structure (CC) is identified to be the energetically most stable arrangement. To arrive at a better understanding of the K+ ion binding, calculations were initially performed on complexes formed by the K+ and Na+ ions with model ligands (methyl ester and N,N‐dimethyl acetamide). Both the natural bond orbital (NBO) method and the block‐localized wavefunction (BLW) energy decomposition approach was employed to assess the bonding and energetic contributions stabilizing the ion‐bound model complexes. Finally, the solvent effect was evaluated through complete geometry optimizations and energy minimizations for the model ion‐ligand complexes and the emodepside‐K+ bound complexes using an implicit solvent model mimicking water and DMSO.
When consumer decisions are moral decisions: Moral Foundations Theory and its implications for consumer psychology
Authors: Ramos Guilherme A. , Johnson Wayne , VanEpps Eric M. , Graham Jesse
Published: June 2024

Although researchers have considered the role of morality in consumer psychology over the years, such investigations often fail to (a) recognize the different values that consumers might hold, and (b) provide proper context for why different moral considerations emerge. Moral Foundations Theory (MFT; Graham et al., Advances in experimental social psychology, 2013, Academic Press; Haidt & Joseph, Daedalus, 2004, 133, 55) provides just such a conceptual framework for understanding the diversity of moral thought that exists across cultures and demographic groups. MFT describes morality not as a monolithic entity, but as a pluralistic set of intuitive values that were shaped by evolutionary pressures and edited by distinct cultures. We review the central claims of MFT and describe how the theory can offer new insights when applied to consumer psychology, providing examples from existing research on persuasion, emotion, and prosocial behavior.
What moral identity and competing selves can add to moral foundations theory: Comment on Ramos, Johnson, VanEpps & Graham (2024)
Authors: Reed Americus
Published: June 2024

In a provocative and insightful analysis, Ramos et al. (Journal of Consumer Psychology, 2024) propose the introduction of Moral Foundations Theory (hereafter MFT)—as a useful framework to (1) explain moral consumer decision‐making more granularly and (2) set forth unique, testable future hypotheses in the field of marketing and consumer psychology. I discuss and build on their analysis to expand (1) but also narrow (2). I couch their conceptualization in the context of a multiple‐identity framework (Consumer Psychology Review, 2021, 4, 100) and move slightly away from their useful but perhaps more taxonomic approach. I try to buttress their work by situating MFT in the context of how the process of moral identity (Journal of Personality and Social Psychology, 2002, 83, 1423) competes with other identities (cf. Journal of Marketing Research, 2020, 57, 375; Current Opinion in Psychology 2016, 10, 94) to help determine when and how the building blocks of moral foundations may become critical drivers of consumption in the areas of persuasion, emotions, and prosocial charitable consumer behavior.
Revisiting calculation of tilt angles for double‐tilt sample holders in transmission electron microscopes
Authors: Li Xing‐Zhong
Published: June 2024

We revisited the formula related to the overall tilt angle of a specimen using a side‐entry double‐tilt sample holder in a transmission electron microscope. Initially, we examined existing formulas in the literature for calculating the overall tilt angle. Subsequently, a new formula was derived, proven to better account for the actions of the double‐tilt holder, thereby providing improved accuracy in the calculation. This newly derived formula has been implemented in the Landyne software suite. Furthermore, we demonstrated the accuracy of the new formula through examples.

Research Highlights

A new formula has been derived to calculate overall tilt angles for side‐entry double‐tilt holders in TEM.
The relationship between the South China Sea summer monsoon onset and North Pacific meridional sea surface temperature anomalies
Authors: Zhao Yuxuan , Liu Ruoyu , Yao Chenwei , Li Shuai , Wu Zhiwei , Gong Zhiqiang , Feng Guolin
Published: June 2024

This study investigates the connection between significant sea surface temperature (SST) anomalies in the North Pacific during boreal spring (February–April, FMA) and the subsequent South China Sea (SCS) summer monsoon (SCSSM) onset. The SST anomalies, similar to the Pacific meridional mode (PMM), referred to as the PMM+ mode, are defined to examine the new influencing factor on the SCSSM onset. Our findings reveal that the (February–March–April, FMA) PMM+ has a noteworthy positive correlation with the subsequent May SCSSM onset date, with this correlation being minimally affected by the El Niño–Southern Oscillation (ENSO) during preceding winter. A robust positive PMM+ in boreal spring can be persist until May via atmosphere–ocean interaction. The cooling area over Western North Pacific would reduce precipitation heating, thereby generating Rossby waves that reinforce the formation of the anomalous anticyclone over the SCS. As a result, easterly winds and suppressed convection prevail over the SCS, making the SCSSM break out later than normal. Furthermore, the amplification of anticyclonic vorticity anomalies also strengthens the western North Pacific subtropical high (WNPSH) stronger and shifts its position further westward compared to normal years, thereby blocking active convection to the west of the SCS. Given the weakened relationship between El Niño–Southern Oscillation (ENSO) and the SCSSM onset in recent years, the PMM+ could be considered as a promising preceding signal for the SCSSM onset, thus holding significant implications for the SCSSM prediction efforts.
Extreme climate events and future population exposure under climate change in the Huaihe River basin of China based on CMIP6 multimodel ensembles projections
Authors: Yao Tian , Wu Chuanhao , Yeh Pat J.‐F. , Li Jiayun , Wang Xuan , Cheng Jiahao , Zhou Jun , Hu Bill X.
Published: June 2024

The Huaihe River basin (HRB) of China located in the climate transition zone between warm temperate and subtropical areas is highly sensitive to climatic change. However, the changes in future climate extreme events under anthropogenic warming and the population exposure to these climate extremes in HRB remain unexplored. Here, using the eight commonly used extreme climate indices and based on the bias‐corrections of 16 global climate models (GCMs) in CMIP6, we present a projection and uncertainty analysis of extreme events and investigate the corresponding population exposure risk in HRB under three shared socioeconomic pathways (SSP1‐2.6, SSP2‐4.5, SSP5‐8.5). The 16‐GCM ensemble mean projects an evident warming trend under all three scenarios with a total increase of 25.6–68.0 days in summer days (>25°C) by the end of the century in HRB. Larger increases (decreases) in maximum and minimum temperatures (frost days) are projected in the western HRB. Very heavy rain days (R20mm), maximum 5‐day precipitation (RX5day) and simple daily intensity index (SDII) will experience intensification across most of HRB (especially in southern and western HRB). The consecutive dry days is projected to decrease in northwestern HRB and increase in southern HRB. However, there is a large spatial variability in GCM uncertainty with a higher SSP scenario generally having higher uncertainty. Increases in summer days and R20mm exacerbate population exposure in HRB in near future (2030–2059), but in far future (2070–2099) although summer days (R20mm) continues to rise, population exposure is expected to decrease due to the rapid decline in population density.
Research on the visual location method for strawberry picking points under complex conditions based on composite models
Authors: Xie Hehe , Zhang Zhijie , Zhang Kailiang , Yang Li , Zhang Dongxing , Yu Yang
Published: June 2024

Background

Strawberry, being an important economic crop, requires a large amount of human labor for harvesting operations. Efficient and non‐destructive harvesting by strawberry harvesting robots requires the precise location of the picking points. Current algorithms for locating picking points encounter significant issues with location errors and minimal effective information in complex situations.

Results

To improve the accuracy of the location of picking points, this study proposes a visual location method based on composite models. This method employs object detection and instance segmentation models to detect fruits and segment peduncles sequentially, thereby enabling the identification of picking points and inclination on the peduncle. Different object detection algorithms and instance segmentation models were validated to explore the optimal model combination, and the Convolutional Block Attention Module (CBAM) was integrated into YOLOv8s‐seg to construct YOLOv8s‐seg‐CBAM. Test results show that the composite model built with YOLOv8s and YOLOv8s‐seg‐CBAM achieved a peduncle detection accuracy of 86.2%, with an inference time of 30.6 ms per image.

Conclusion

The picking point visual location method based on YOLOv8s and YOLOv8s‐seg‐CBAM composite models can better balance accuracy and efficiency and can provide more accurate guidance for automated harvesting. © 2024 Society of Chemical Industry.
Diagnostic accuracy of GPT‐4 on common clinical scenarios and challenging cases
Authors: Rutledge Geoffrey W.
Published: June 2024

Introduction

Large language models (LLMs) have a high diagnostic accuracy when they evaluate previously published clinical cases.

Methods

We compared the accuracy of GPT‐4's differential diagnoses for previously unpublished challenging case scenarios with the diagnostic accuracy for previously published cases.

Results

For a set of previously unpublished challenging clinical cases, GPT‐4 achieved 61.1% correct in its top 6 diagnoses versus the previously reported 49.1% for physicians. For a set of 45 clinical vignettes of more common clinical scenarios, GPT‐4 included the correct diagnosis in its top 3 diagnoses 100% of the time versus the previously reported 84.3% for physicians.

Conclusions

GPT‐4 performs at a level at least as good as, if not better than, that of experienced physicians on highly challenging cases in internal medicine. The extraordinary performance of GPT‐4 on diagnosing common clinical scenarios could be explained in part by the fact that these cases were previously published and may have been included in the training dataset for this LLM.
Of happy larks and unhappy owls: Why morning versus evening types feel different levels of happiness from experiential versus material purchases
Authors: Banerjee Pramit , Minchael Shashi
Published: June 2024

People can identify as morning types or evening types. Research has shown that evening types are generally less happy and have a lower sense of well‐being. While there is limited research in consumer psychology on chronotypes, one question may be asked: Would they gain from the experiential advantage (where people elicit greater happiness from experiential vs. material purchases) and become happier? We find that evening types, in fact, elicit lower levels of happiness from their experiential purchases compared to morning types and, in effect, feel happier from their material purchases. Furthermore, this is because of the greater subjective distance they feel from their experiential purchases. This research contributes to our understanding of long‐term happiness in a significant section of society—evening types and also calls on researchers to explore the topic of evening chronotype happiness and well‐being in greater depth from a marketing perspective.
Advantages and Challenges of Platform Trials for Disease Modifying Therapies in Parkinson's Disease
Authors: Fabbri Margherita , Rascol Olivier , Foltynie Tom , Carroll Camille , Postuma Ronald B. , Porcher Raphael , Corvol Jean Christophe
Published: June 2024

Traditional drug development in Parkinson's disease (PD) faces significant challenges because of its protracted timeline and high costs. In response, innovative master protocols are emerging and designed to address multiple research questions within a single overarching protocol. These trials may offer advantages such as increased efficiency, agility in adding new treatment arms, and potential cost savings. However, they also present organizational, methodological, funding, regulatory, and sponsorship challenges. We review the potential of master protocols, focusing on platform trials, for disease modifying therapies in PD. These trials share a common control group and allow for the termination or addition of treatment arms during a trial with non‐predetermined end. Specific issues exist for a platform trial in the PD field considering the heterogeneity of patients in terms of phenotype, genotype and staging, the confounding effects of symptomatic treatments, and the choice of outcome measures with no consensus on a non‐clinical biomarker to serve as a surrogate and the slowness of PD progression. We illustrate these aspects using the examples of the main PD platform trials currently in development with each one targeting distinct goals, populations, and outcomes. Overall, platform trials hold promise in expediting the evaluation of potential therapies for PD. However, it remains to be proven whether these theoretical benefits will translate into increased production of high‐quality trial data. Success also depends on the willingness of pharmaceutical companies to engage in such trials and whether this approach will ultimately hasten the identification and licensing of effective disease‐modifying drugs. © 2024 International Parkinson and Movement Disorder Society.
Unraveling the influence of metabolic signatures on immune dynamics for predicting immunotherapy response and survival in cancer
Authors: Ou Qiyun , Lu Zhiqiang , Cai Gengyi , Lai Zijia , Lin Ruicong , Huang Hong , Zeng Dongqiang , Wang Zehua , Luo Baoming , Ouyang Wenhao , Liao Wangjun
Published: June 2024

Metabolic reprogramming in cancer significantly impacts immune responses within the tumor microenvironment, but its influence on cancer immunotherapy effectiveness remains uncertain. This study aims to elucidate the prognostic significance of metabolic genes in cancer immunotherapy through a comprehensive analytical approach. Utilizing data from the IMvigor210 trial (n = 348) and validated by retrospective datasets, we performed patient clustering using non‐negative matrix factorization based on metabolism‐related genes. A metabiotic score was developed using a “DeepSurv” neural network to assess correlations with overall survival (OS), progression‐free survival, and immunotherapy response. Validation of the metabolic score and key genes was achieved via comparative gene expression analysis using qPCR. Our analysis identified four distinct metabolic classes with significant variations in OS. Notably, the metabolism‐inactive and hypoxia‐low class demonstrated the most pronounced benefit in terms of OS. The metabolic score predicted immunotherapeutic benefits with high accuracy (AUC: 0.93 at 12 months). SETD3 emerged as a crucial gene, showing strong correlations with improved OS outcomes. This study underscores the importance of metabolic profiling in predicting cancer immunotherapy success. Specifically, patients classified as metabolism‐inactive and hypoxia‐low appear to derive substantial benefits. SETD3 is established as a promising prognostic marker, linking metabolic activity with patient outcomes, advocating for the integration of metabolic profiling into immunotherapy strategies to enhance treatment precision and efficacy.
Clinical characteristics of a case of multiple mitochondrial dysfunction syndrome 3
Authors: Xu Hai , Ma Kai , Gao Yuye , Song Qijun , Chen Chaojin , Xu Xiao , Peng Jiaxi , Sun Yan
Published: June 2024

Objective

To further comprehend the phenotype of multiple mitochondrial dysfunction syndrome type 3 (MMDS3:OMIM#615330) caused by IBA57 mutation. We present a case involving a patient who experienced acute neurological regression, and the literature was reviewed.

Methods

Clinical data and laboratory test results were collected; early language and development progress were tested; and genetic testing was performed. Bioinformatics analysis was performed using Mutation Taster and PolyPhen‐2, and the literature in databases such as PubMed and CNKI was searched using MMDS3 and IBA57 as keywords.

Results

The child, aged 1 year and 2 months, had motor decline, unable to sit alone, limited right arm movement, hypotonia, hyperreflexia of both knees, and Babinski sign positivity on the right side, accompanied by nystagmus. Blood lactate levels were elevated at 2.50 mmol/L. Brain MR indicated slight swelling in the bilateral frontoparietal and occipital white matter areas and the corpus callosum, with extensive abnormal signals on T1 and T2 images, along with the semioval center and occipital lobes bilaterally. The multiple abnormal signals in the brain suggested metabolic leukoencephalopathy. Whole‐exome sequencing analysis revealed that the child had two heterozygous mutations in the IBA57 gene, c.286T>C (p.Y96H) (likely pathogenic, LP) and c.992T>A (p.L331Q) (variant of uncertain significance, VUS). As of March 2023, a literature search showed that 56 cases of MMDS3 caused by IBA57 mutation had been reported worldwide, with 35 cases reported in China. Among the 35 IBA57 mutations listed in the HGMD database, there were 28 missense or nonsense mutations, 2 splicing mutations, 2 small deletions, and 3 small insertions.

Conclusion

MMDS3 predominantly manifests in infancy, with primary symptoms including feeding difficulties, neurological functional regression, muscle weakness, with severe cases potentially leading to mortality. Diagnosis is supported by elevated lactate levels, multisystem impairment (including auditory and visual systems), and distinctive MRI findings. Whole‐exome sequencing is crucial for diagnosis. Currently, cocktail therapy offers symptomatic relief.
Hybrid integration of BAW resonators with an on‐chip inductor to improve the stopband rejection of the N78 band filter
Authors: Jiang Hong , Xuan Weipeng , Ding Rui , Zhang Biao , He Xingli , Jin Hao , Gao Feng , Dong Shurong , Luo Jikui
Published: June 2024

This paper demonstrates a 3.4 GHz micro‐acoustic filter with excellent in‐band insertion loss, rectangle coefficient, and out‐of‐band rejection. The proposed filter was based on a novel topology by integrating the bulk acoustic wave (BAW) resonators with an on‐chip clamping inductor, the introduction of the lumped components is beneficial for improving the filters' stopband rejection while having minimal influence on the rectangle coefficient and in‐band insertion loss. Al0.8Sc0.2N material was selected as the piezoelectric film of the BAW device and the inductor was fabricated on the same wafer with BAW devices. The manufactured filter has a minimum in‐band insertion loss of ~ 1.5 dB, a 3 dB bandwidth of about 170 MHz, and a stopband rejection of nearly ‐30 dB. The experimental results verify the design and show great applications for 5G communication and beyond.
Fine-solids removal by foam fractionation in a low-salinity marine recirculating aquaculture system (RAS)
Authors: Pfeiffer Timothy , Baptiste Richard , Wills Paul S.
Published: June 2024

Objective

We sought to evaluate several methods of operation of a foam fractionator for fine-solids removal (organic matter < 55 μm) in a commercial-scale, low-salinity (11–13‰) recirculating aquaculture system (RAS) for marine finfish production.

Methods

The total suspended solids (TSS) concentrations of the RAS microscreen drum filter inflow and outflow and the foam fractionator outflow were obtained under various foam fractionator operating conditions. The outflow TSS concentration of the drum filter also served as the inflow TSS concentration for the foam fractionator. Sample collection for TSS determination was divided into two categories: particles greater than 55 μm and particles less than 55 μm. The difference between inflow and outflow TSS concentrations was used to determine the removal percentage for each particle class of each unit. Additionally, the volume of foammate produced under operating conditions by the fractionator and the amount of solids contained within the foammate were quantified. Flow through the foam fractionator was also obtained to determine the amount of solids removed per volume of influent water treated.

Result

The influent TSS concentration for the seven different operating conditions evaluated ranged from 4.8 to 6.3 mg/L, with the percentage of particles less than 55 μm ranging from 69.75% to as high as 86.1%. The drum filter removed over 90% of the particles larger than 55 μm and removed 8–26% of the particles smaller than 55 μm. No difference was observed in the overall removal efficiency of the drum filter, which ranged from 19% to 44%. There was no significant difference in the foam fractionator overall removal efficiency, which ranged from 6.5% to 38.5%. Operating the foam fractionator at a high water head height (HHH) with the submersible aspirating impeller provided the greatest removal percentage of particles less than 55 μm (26.9%). However, at the HHH, only half the amount of solids was removed compared to using a Venturi injector with ozone, but energy use was roughly 26% greater.

Conclusion

The foam fractionator was operated at the HHH, about 0.31 m higher than the low water head height, for production operation. Additionally, Venturi injection of ozone provided the greatest removal of solids for the volume of influent water treated over a 12-h operational period. The submersible aspirating impeller showed potential for low-cost use with reasonable solids removal and warrants further evaluation.
An improved MPSP‐based path‐following control method for USV with input disturbances
Authors: Li Ao , Hu Xiaoxiang , Dong Kejun , Xiao Bing
Published: June 2024

This study proposes an improved model predictive static programming (MPSP) based path‐following control method for unmanned surface vessel (USV) subject to input disturbances. The method addresses the challenges of accurate USV dynamics modeling, unpredictable maritime environments, and limited power and energy systems. A trajectory generator is designed to construct smooth reference trajectories, and the MPSP algorithm is adapted to handle path‐following problems while considering state and input constraints. An event‐triggered mechanism is introduced to reduce computational burden and conserve energy. Comparative simulations demonstrate the superiority of the proposed method over open‐loop tracking and the original MPSP approach in terms of tracking accuracy, disturbance rejection, and overall control performance. The improved MPSP‐based control method offers a robust and efficient solution for USV path‐following tasks, ensuring accurate tracking even in the presence of environmental disturbances and system uncertainties.
Interaction of the tumor suppressor SMAD4 and WNT signaling in progression to oral squamous cell carcinoma
Authors: Yang Jing , Lewis James S , Zi Jinghuan , Andl Thomas , Lee Ethan , Andl Claudia D , Liu Qi , Beauchamp Robert D , Means Anna L
Published: June 2024

SMAD4 is a tumor suppressor mutated or silenced in multiple cancers, including oral cavity squamous cell carcinoma (OSCC). Human clinical samples and cell lines, mouse models and organoid culture were used to investigate the role that SMAD4 plays in progression from benign disease to invasive OSCC. Human OSCC lost detectable SMAD4 protein within tumor epithelium in 24% of cases, and this loss correlated with worse progression‐free survival independent of other major clinical and pathological features. A mouse model engineered for KrasG12D expression in the adult oral epithelium induced benign papillomas, however the combination of KrasG12D with loss of epithelial Smad4 expression resulted in rapid development of invasive carcinoma with features of human OSCC. Examination of regulatory pathways in 3D organoid cultures of SMAD4+ and SMAD4− mouse tumors with Kras mutation found that either loss of SMAD4 or inhibition of TGFβ signaling upregulated the WNT pathway and altered the extracellular matrix. The gene signature of the mouse tumor organoids lacking SMAD4 was highly similar to the gene signature of human head and neck squamous cell carcinoma. In summary, this work has uncovered novel mechanisms by which SMAD4 acts as a tumor suppressor in OSCC. © 2024 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Influence of Z‐pin material on the mechanical properties of fine Z‐pin reinforced composites
Authors: Ji Guobiao , Cheng Liang , Wang Qing , Li Jiangxiong , Ke Yinglin
Published: June 2024

The insertion of finer Z‐pins is an effective method to reduce the microstructure damage and maintain the in‐plane performance of composite laminates. In this paper, an ultrasound guided insertion process is proposed to achieve the insertion of fine Z‐pins and the influence of Z‐pin material on the mechanical properties of Ø0.11 mm Z‐pin reinforced composite laminates is revealed based on experiments and simulations. For in‐plane mechanical properties, stainless steel Z‐pins help to reduce the loss of compression modulus and compression strength. For the interlaminar mechanical properties, stainless steel Z‐pins and carbon fiber Z‐pins exhibit bilinear and trilinear bridging laws respectively, resulting in the mode‐I maximum load and fracture toughness of carbon fiber Z‐pin reinforced composites being greater than that of stainless steel Z‐pin reinforced composites. By adjusting the insertion spacing, it is found that for unidirectional composite laminates reinforced by Ø0.11 mm carbon fiber Z‐pins with an insertion spacing of 2 mm, the compression strength reduction is only 3.39% while the mode‐I fracture toughness can be improved by 14.4 times in comparison with the unpinned specimens, achieving a better balance between in‐plane performance loss and interlaminar reinforcement effect.

Highlights

The effect of Z‐pin material on fine Z‐pin reinforced composites is studied.

The compression properties are simulated by the RVE model.

The mode‐I fracture properties are simulated by the DCB unit strip model.
Screening potential antileukemia agents from duckweed: Integration of chemical profiling, network pharmacology, and experimental validation
Authors: Liu Jing , Huang Mengjun , Yang Yan , Zeng Yan , Yang You , Guo Qulian , Liu Wenjun , Guo Ling
Published: June 2024

Introduction

The identification of active dietary flavonoids in food is promising for novel drug discovery. The active ingredients of duckweed (a widely recognized food and herb with abundant flavonoids) that are associated with acute myeloid leukemia (AML) have yet to be identified, and their underlying mechanisms have not been elucidated.

Objectives

The objective of this study was to identify novel constituents exhibiting antileukemia activity in duckweed through the integration of chemical profiling, network pharmacology, and experimental validation.

Methods

First, high performance liquid chromatography‐tandem mass spectrometry (HPLC‐MS/MS) was used to characterize the primary constituents of duckweed. Subsequently, AML cell‐xenograft tumor models were used to validate the anticancer effect of duckweed extract. Furthermore, network pharmacology analysis was conducted to predict the potential active compounds and drug targets against AML. Lastly, based on these findings, two monomers (apiin and luteoloside) were selected for experimental validation.

Results

A total of 17 compounds, all of which are apigenin and luteolin derivatives, were identified in duckweed. The duckweed extract significantly inhibited AML cell growth in vivo. Furthermore, a total of 88 targets for duckweed against AML were predicted, with key targets including PTGS2, MYC, MDM2, VEGFA, CTNNB1, CASP3, EGFR, TP53, HSP90AA1, CCND1, MMP9, TNF, and MAPK1. GO and KEGG pathway enrichment analyses indicated that these targets were primarily involved in the apoptotic signaling pathway. Lastly, both apiin and luteoloside effectively induced apoptosis through CASP3 activation, and this effect could be partially reversed by a caspase inhibitor (Z‐VAD).

Conclusion

Duckweed extract has an antileukemic effect, and apiin derived from duckweed shows potential as a treatment for AML.
First‐year students' psychological resilience and college adjustment: A person‐oriented approach
Authors: Gao Lili , Zhang Na , Yang Weimin , Deng Xiaopeng
Published: June 2024

Previous research has concentrated on psychological resilience as a holistic structure and has found that resilience positively affects college adjustment. However, it is suggested by existing literature that college students' resilience is a multidimensional construct. Furthermore, there is limited understanding regarding the categorizations of resilience among first‐year college students and its influence on their college adjustment. This study aimed to identify the profiles of first‐year college students' resilience, including individual powers and supportive powers, and explore the effects of varying resilience profiles on first‐year students' college adjustment. A valid sample of 771 first‐year college students from 28 Chinese colleges participated in this survey. The online surveys were conducted through Wenjuanxing platform. Data were analyzed using latent profile analysis to identify first‐year college students' different resilience profile and examine the relationships with college adjustment. Four groups featuring unique resilient characteristics were discovered: well‐resilient students, students with low individual power but high supportive power, students with high individual power but low supportive power, and mal‐resilient students with low individual power and low supportive power. Well‐resilient first‐year students reported the best condition of college adjustment compared to the other groups, which supports the conservation of resources (COR) theory. These results provide insight into first‐year college students' particular and heterogeneous circumstances at the beginning of the college experience. They also refined the COR theory by identifying individual‐specific relationships between psychological resilience and college adjustment.