bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of the Anion in Concentrated Electrolytes for Lithium-Sulfur Batteries
Authors: Kottarathil Aginmariya , Slim Zaher , Ahmad Ishfaq Hafiz , Jeschke Steffen , Żukowska Grażyna Zofia , Marczewski Maciej , Lech Katarzyna , Johansson Patrik , Wieczorek Wladyslaw
Published: June 2024

Highly concentrated electrolytes show promise in enhancing lithium-sulfur (Li-S) battery performance by mitigating polysulfide (PS) solubility. The role of the salt anion for the performance improvement(s) is however not well understood. Here a systematic characterization using (concentrated) electrolytes based on three different salts: LiTFSI, LiTf, and LiTDI, in a common DOL:DME solvent mixture is reported for a wide range of physicochemical and electrochemical properties: ionic conductivity, density, viscosity, speciation, and PS solubility. While increased salt concentration in general improves Li-S battery performance, the role of the salt anion introduces complexity. The 2 m LiTDI-based electrolyte, with a slightly higher viscosity and lower PS solubility, outperforms the LiTFSI-based counterpart in terms of accessible reversible capacity. Conversely, the 2 m LiTf-based electrolyte exhibits subpar performance due to the formation of ionic aggregates that renders more free solvent and, therefore higher PS solubility, which, however can be improved by using a 5 m concentrated electrolyte. Hence, using electrolyte salt concentration as a rational design route demands an understanding of the local molecular structure, largely determined/affected by the choice of anion, as well as how it connects to the global properties and in the end improved Li-S battery performance.
Surface mapping of gastric motor functions using MRI: a comparative study between humans and rats
Authors: Wang Xiaokai , Alkaabi Fatimah , Choi Minkyu , Di Natale Madeleine R. , Scheven Ulrich M. , Noll Douglas C. , Furness John B. , Liu Zhongming
Published: June 2024

A novel MRI technique can visualize how the stomach accommodates, mixes, and propels food for digestion in humans and animals alike. Digital models of gastric MRI reveal the functional maps, organization, and distinction of the stomach across individuals and species. This technique holds the unique potential to advance basic and clinical studies of functional gastric disorders.
Fungal chitin is not an independent mediator of allergic fungal asthma severity
Authors: Ellis Diandra A. , Jones MaryJane , Willems Hubertine M. E. , Cheung Suki , Makullah Mgayya , Aimanianda Vishukumar , Steele Chad
Published: June 2024

Humans with asthma sensitized to fungi often have more severe asthma than those who are not fungal-sensitized. Chitin makes up a significant portion of the cell wall of fungi and has been implicated as a pathogenic factor in allergic asthma. Ellis et al. demonstrate that chronic exposure to fungal chitin alone is unable to modulate lung function, even in the presence of differential lung chitinase activity.
Multiphase Solar Photovoltaic Prediction Model Based on Season, Hierarchical k‐Means Clustering, GRA‐PCC, SVM, and Neural Network
Authors: Arias Mariz B. , Bae Sungwoo
Published: June 2024

Solar photovoltaic (PV) has accounted for the highest percentage of power generation capacity among other renewables. However, solar PV power generation is highly variable because of different factors; therefore, accurate forecasting is critical for reliable integration into the power system. This paper proposes a multiphase solar PV prediction model that includes grouping, clustering, linking, classifying, and predicting using historical solar PV power and weather data. Seasonal variation is considered in the grouping phase, followed by hybrid hierarchical k‐means clustering to enhance data division in the clustering phase. A hybrid gray relational analysis‐Pearson correlation coefficient identifies significant weather factors impacting solar PV power in the linking phase. The classification phase employs a support vector machine to establish the relationship between the clusters and the relevant weather factors. Lastly, a neural network (NN) is trained to predict solar PV power. The solar PV power profiles are presented to show the variability in season and time. The simulation results of the proposed model showed relatively accurate forecasting results, including MAE of 0.408 MW, MSE of 460.51 MW, RMSE of 0.679 MW, nRMSE of 4.345%, and MRE of 2.266%. These results represent that the uncertainties of the proposed model are 6 and 12 times lower than those of the conventional methods (i.e., conventional NN and ARMAX). These results assure that the proposed model can provide more accurate solar PV power profiles for reliable power system integration.
Length‐Weight and Length‐Length Relations of 14 Freshwater Fish Species from the Qiantang River, China
Authors: Dai Yangxin , Xie Nan , Dai Yulai , Guo Wei , Tang Jinyu , Wang Yuxi
Published: June 2024

The Qiantang River, located in Zhejiang Province, China, is a crucial water resource with significant ecological and economic importance. This study aimed to evaluate fishery resources in the Qiantang River Basin by analyzing the length‐weight relationships (LWRs) and length‐length relationships (LLRs) of 14 fish species. Fish samples were collected between July 2021 and November 2023 using multipanel nylon gillnets and cage nets. Each specimen was measured for total length (TL) and standard length (SL), as well as weighed. Linear regression models were employed to estimate LWRs and LLRs, with statistical tests revealing significant relationships (P < 0.05) and high R2 values above 0.91. The study contributed new LWRs for two species and LLRs for three, deepening our understanding of their biology. These findings enriched FishBase and offered valuable data for fish stock assessments and management strategies in the Qiantang River Basin. Future research can utilize this foundation to explore population dynamics and promote sustainable management practices.
The Synergetic Roles of Stromal Vascular Fraction (SVF) and Extracellular Matrix (ECM) on Fat Graft Retention in Nude Mice
Authors: Sheng Lingling , Yu Ziyou , Fang Yuan , Zheng Danning , Cao Weigang
Published: June 2024

Background. Both stromal vascular fraction (SVF) and extracellular matrix (ECM) are of great concern to adipogenesis and angiogenesis. SVF and ECM are rich in adipose tissue and may provide structural and biochemical support and form a microenvironment for free granular fat. The present study was to investigate whether SVF‐gel, a mixture of SVF and ECM harvested by mechanical emulsification, could improve the long‐term volume retention of fat grafts. Methods. Human SVF‐gel of different percentages was mixed with microfat. According to the percentages of SVF‐gel into microfat, 4 groups were included in the study; they are the microfat group, 10% gel group, 30% gel group, and gel group. The fat grafts were transplanted in the subcutaneous layer on each flank in nude mice. The sample volume was measured to evaluate the fat retention rate 90 days post‐transplantation. Tissue integrity, collagen content, numbers of viable adipocytes, and density of blood vessels were examined by further detection. Results. The retention volume rates in the 30% gel group and gel group were significantly higher than the microfat group and the 10% gel group (p < 0.05). Equivalent fat integrity was observed in the four groups. Higher collagen volume, enhanced mRNA expression of VEGF, TNF‐α and adiponectin, more CD31‐positive blood vessels, and more regenerative adipocytes were observed in the 30% gel group and the gel group. The fat tissue in the 30% gel group showed similar structures as the normal fat tissue, while almost of the tissue in the gel group exhibited as fibrous tissue. Conclusion. SVF‐gel could improve fat graft retention while it came to a certain ratio into microfat via proangiogenic effect and fat regeneration which may be provided by SVF and ECM synergistically. SVF‐gel‐assisted fat grafting is a promising strategy to be used in clinical operations.
Exploring Fibrin Protein Hydrogels for the Production of Heteroatom‐Doped Porous Carbon Nanoarchitectures as Efficient Metal‐Free Oxygen Reduction Reaction Catalysts
Authors: Kim Woong-Ju , Choi Sun Hee , Kim Se In , Choi Ji Woong , Kang Jin Gu , Kim Dong-Wan
Published: June 2024

Although protein hydrogels are excellent carbonization precursors for synthesizing carbon nanoarchitectures as efficient metal‐free oxygen reduction reaction (ORR) catalysts, research on this topic has rarely been conducted. In this study, fibrin protein hydrogels templated with sodium chloride (NaCl) crystals are proposed as novel precursors for the manufacture of heteroatom‐doped planar carbon nanostructures containing internal pores. By systematically adjusting the carbonization conditions, it is revealed that their effects on material properties and ORR characteristics. The catalyst carbonized at 900°C for 12 hr demonstrated excellent performances in an alkaline solution, including onset potential (Eon; 0.86 V vs. reversible hydrogen electrode), diffusion‐limited current (–4.0 mA cm−2 at 0.05 V), electron transfer number (2.84), and durability (–18 mV shift in Eon after 30,000 cycles). This is attributed to the synergistic action of fast out‐of‐plane electron transport, sufficient adsorption sites, enhanced activity by heteroatom doping, and effective mass transfer through interconnected pores.
Conceptualizing Treatment Burden among People with Type 2 Diabetes
Authors: Bitterfeld Leandra , Reed Sean M.
Published: June 2024

Background. Treatment burden is an illness‐management workload level that exceeds an individual’s capacity to do that work. It is a complex concept that has not been comprehensively defined for people with type 2 diabetes (T2DM). Purpose. Provide a contemporary, holistic understanding of treatment burden among people with T2DM and understand its clinical implications. Methods. Walker and Avant’s 8‐step method for concept analysis was used. PubMed, CINAHL, Web of Science, Embase, and PsychInfo databases were searched from 2012 to 2023 to identify uses of the concept, defining attributes, antecedents, and consequences of treatment burden. Empirical referents were identified and modeled; contrary and related cases are presented. Findings. Thirty‐three articles were identified to extract the concept of treatment burden. Defining attributes were responsibility for self‐care, complexity of interactions with the healthcare system, perpetual emotional management, medical expenses, and social network interactions. Antecedents of treatment burden among people with T2DM were workload designated to the patient, resource scarcity, and understanding of the disease state. Consequences include impaired ability to conduct treatment regimen, impacted quality of life, realization of the necessity to work, and fatigue or exhaustion. Empirical referents cover various clinical tools, but none comprehensively capture all defining attributes. Discussion. Treatment burden is not dependent solely on the objective complexity of self‐care tasks. Instead, it is inextricably linked with one’s ecosystem, especially social interactions, interactions with the healthcare system, and available resources. Nurses and other healthcare professionals can use these findings to explore their patients’ burden experiences and select appropriate treatment.
TABLE 2 from Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1
Authors: He Ling , Ioannidis Angeliki , Hoffman Carter J. , Arambula Evelyn , Joshi Purva , Whitelegge Julian , Liau Linda M. , Kornblum Harley I. , Pajonk Frank
Published: June 2024

Prediction of BBB permeability of statins and their involvements in brain tumor clinical trials
FIGURE 3 from Activation of the Mevalonate Pathway in Response to Anti-cancer Treatments Drives Glioblastoma Recurrences Through Activation of Rac-1
Authors: He Ling , Ioannidis Angeliki , Hoffman Carter J. , Arambula Evelyn , Joshi Purva , Whitelegge Julian , Liau Linda M. , Kornblum Harley I. , Pajonk Frank
Published: June 2024

Statins reduce treatment-induced upregulation of cholesterol biosynthesis in PDOXs. A, Brain and plasma levels of atorvastatin in C57BL/6 mice after a single injection (atorvastatin – 30 mg/kg, i.p.). B, Schematic of the experimental design underlying Fig. 3. C, The levels of total, free cholesterol and cholesterol-esters in the tumors harvested from the PDOX GBM mouse model at day 5 after the treatment of radiation in combination with QTP (30 mg/kg), atorvastatin (30 mg/kg) or simvastatin (7 mg/kg). D, The concentration of free fatty acid in the tumors harvested from the PDOX GBM mouse model at day 5 after the treatments. E, Heat map showing the results of qRT-PCR for the cholesterol biosynthesis–related genes in the tumor specimen harvested from the PDOX GBM mouse model at day 5 after the treatments using the human- and mouse-specific primers. F, Survival curves for NSG mice implanted intracranially with 3 × 105 HK374-GFP-Luciferase glioma cells and grafted for 3 days. Mice were irradiated and treated with saline or QTP (30 mg/kg, s.c., 5-day on/2-day off schedule) or triple combination of radiation plus QTP and simvastatin (7 mg/kg, i.p., 5-day on/2-day off schedule) continuously until they reached the study endpoint. log-rank (Mantel–Cox) test for comparison of Kaplan–Meier survival curves. G, Weight curves for the NSG mice in different treatment groups. All experiments have been performed with at least three biological independent repeats. P-values were calculated using one-way ANOVA. ns: not significant.
Frequency tagging of spatial attention using periliminal flickers
Authors: Ladouce Simon , Dehais Frédéric
Published: June 2024

Steady-State Visually Evoked Potentials (SSVEPs) manifest as a sustained rhythmic activity that can be observed in surface electroencephalography (EEG) in response to periodic visual stimuli, commonly referred to as flickers. SSVEPs are widely used in fundamental cognitive neuroscience paradigms and Brain-Computer Interfaces (BCI) due to their robust and rapid onset. However, they have drawbacks related to the intrusive saliency of flickering visual stimuli, which may induce eye strain, cognitive fatigue, and biases in visual exploration. Previous findings highlighted the potential of altering features of flicker stimuli to improve user experience. In this study, we propose to reduce the amplitude modulation depth of flickering stimuli down to the individuals’ perceptual visibility threshold (periliminal) and below (subliminal). The stimulus amplitude modulation depth represents the contrast difference between the two alternating states of a flicker. A simple visual attention task where participants responded to the presentation of spatially cued target stimuli (left and right) was used to assess the validity of such periliminal and subliminal frequency-tagging probes to capture spatial attention. The left and right sides of the screen, where target stimuli were presented, were covered by large flickers (13 and 15 Hz, respectively). The amplitude modulation depth of these flickers was manipulated across three conditions: control, periliminal, and subliminal. The latter two levels of flickers amplitude modulation depth were defined through a perceptual visibility threshold protocol on a single-subject basis. Subjective feedback indicated that the use of periliminal and subliminal flickers substantially improved user experience. The present study demonstrates that periliminal and subliminal flickers evoked SSVEP responses that can be used to derive spatial attention in frequency-tagging paradigms. The single-trial classification of attended space (left versus right) based on SSVEP response reached an average accuracy of 81.1% for the periliminal and 58% for the subliminal conditions. These findings reveal the promises held by the application of inconspicuous flickers to both cognitive neuroscience research and BCI development.
A survey of the Sumatran Ctenidae (Araneae). 3. Amauropelma mariae sp. n., one of the tiniest species of the genus
Authors: OMELKO MIKHAIL M. , FOMICHEV ALEXANDER A.
Published: June 2024

A new species, Amauropelma mariae sp. n., is described from Sumatra Island (Indonesia) on the basis of both sexes. The new species is illustrated and described in detail. The distribution map of all known Amauropelma species based on new and literature-derived records is given.
The Online and Offline Blended Teaching Reform and Exploration of Internet of Things Technology and Application
Authors: Han Jieqiong
Published: June 2024

In today's informatization, massive digital information has become a major advantage of modern education. Educators need to keep pace with the times and change traditional educational concepts. The professional teachers need to change traditional educational concepts, constantly innovate teaching methods and means, and give full play to the advantages of teaching resources. In the past three years, due to the impact of the epidemic around the world, online and offline hybrid teaching has broken the inherent form of "teacher-centered" traditional teaching. The teacher team makes full use of offline and offline advantageous resources to actively create a "student-centered" flipped classroom. The Internet of Things technology and application course is a core basic course for the Internet of Things engineering major. The faculty team actively carries out teaching research and reform, and carries out online and offline mixed teaching. As a teacher, we must really play the role of a guide and provide personalized, diversified and diversified teaching to students. The lecturer changes teaching methods and means, pays attention to individualized training, stimulates students' interest in independent learning, improves the spirit of innovation and cooperation, cultivates the ability to solve engineering problems, and establishes future study and work goals. Therefore, students' self-learning ability is continuously improved and their professional comprehensive quality is improved.
A Case of Cardiac Surgery-Associated Acute Kidney Injury
Authors: Wang Xia , Yang Jiaqi , Li Xuejie
Published: June 2024

Approximately 2 million patients undergo cardiac surgery annually with 20% to 30% developing the cardiac surgery-associated acute kidney injury. Patient who has undergone cardiac surgery in the past week and meets the criteria for acute kidney injury can be classified as a cardiac surgery-associated acute kidney injury. The cardiac surgery-associated acute kidney injury may be caused by various factors during perioperative period. Preoperative risk factors include advanced age, female gender, pre-existing renal insufficiency, heart failure, left main coronary artery disease, diabetes, chronic obstructive pulmonary disease, peripheral vascular disease, liver disease, low cardiac output and hypotension. Intraoperative risk factors include the type of surgery (valve surgery, combined valve and coronary artery surgery, emergency and reoperations), low-flow cardiopulmonary bypass, hypothermic cardiopulmonary bypass, deep hypothermic circulatory arrest, cardiopulmonary bypass duration >100-120 minutes, hemodilution, hemolysis and hemoglobinuria due to prolonged cardiopulmonary bypass duration. We present the case of a 53-year-old female with severe valvular heart disease complicated by infecting human immunodeficiency virus. She experienced an acute kidney injury after cardiac surgery. The rationale for this case report is to learn about the risk factors of cardiac surgery-associated acute kidney injury and take measures to prevent it.
Suppression of Cold Air Outbreaks over the Interior of North America in a Warmer Climate
Authors: Hartig Kara , Tziperman Eli
Published: June 2024

In spite of the mean warming trend over the last few decades and its amplification in the Arctic, some studies have found no robust decline or even a slight increase in wintertime cold air outbreaks over North America. But fossil evidence from warmer paleoclimate periods indicates that the interior of North America never dropped below freezing even in the depths of winter, which implies that the maintenance of cold air outbreaks is unlikely to continue indefinitely with future warming. To identify key mechanisms affecting cold air outbreaks and understand how and why they will change in a warmer climate, we examine the development of North American cold air outbreaks in both a preindustrial and a roughly 8×CO2 scenario using the Community Earth System Model, version 2 (CESM2). We observe a sharp drop-off in the wintertime temperature distribution at the freezing temperature, suppressing below-freezing conditions in the warmer climate and above-freezing conditions in the preindustrial case. The disappearance of Arctic sea ice and loss of the near-surface temperature inversion dramatically decrease the availability of below-freezing air in source regions. Using an air parcel trajectory analysis, we demonstrate a remarkable similarity in both the dynamics and diabatic effects acting on cold air masses in the two climate scenarios. Diabatic temperature evolution along cold air outbreak trajectories is a competition between cooling from longwave radiation and warming from boundary layer mixing. Surprisingly, while both diabatic effects strengthen in the warmer climate, the balance remains the same, with a net cooling of about −6 K over 10 days.

Significance Statement

We compare a preindustrial climate scenario to a much warmer climate circa the year 2300 under high emissions to understand the physical processes that influence the coldest wintertime temperatures and how they will change with warming. We find that enhanced warming in the Arctic, and particularly over the Arctic Ocean due to the loss of wintertime sea ice, dramatically reduces the availability of cold air to be swept into North America. By tracing these cold air masses as they travel, we also find that they experience the same total amount of cooling in the much warmer climate as they did in the preindustrial climate even though many of the individual heating and cooling processes have gotten stronger.
Environmental or Personal Benefit? The Role of Message Appeal and Information Type in Destination Social Media Advertisements
Authors: Japutra Arnold , Can Ali Selcuk , Alphun Cihan
Published: June 2024

Destinations are increasingly focusing on sustainability awareness through tourism campaigns, but effective communication remains challenging. This research, rooted in consumption value theory, delves into the influence of message appeal (environmental vs. personal benefit) and information type (objective vs. subjective) on tourists’ behavioral intentions through two online experiments. Study 1 demonstrates the positive impact of environmental benefit message appeals on behavioral intentions toward destinations, both directly and indirectly, by enhancing destination brand quality and perceived green value. Study 2 validates these findings and extends the analysis to include click-through behavior as a proxy for real behavior. Our research emphasizes the importance of environmental benefits alongside objective information in destinations’ sustainability messages within social media advertisements. This approach serves to bolster destination brand quality, perceived green value, and ultimately, positive behavioral intentions.
Prime Minister, Minister, or Something Else? Determinants of Patronage Appointments and Politicization of the Bureaucracy at the Senior Level in Turkey (2002–2018)
Authors: Demirelli Levent , Aydin Recep
Published: June 2024

Patronage appointments have been a frequently used a common indicator used to gauge the level of politicization of bureaucracy in different countries. Studies tend to explain politicization based on governmental, prime ministerial, or ministerial alternation. By relying upon a unique dataset consisting of 12.832 decisions of appointment to higher echelons in the Turkish bureaucracy during the Justice and Development Party’s uninterrupted one-party governments between 2002 and 2018, this study, however, suggests that the patronage appointments, and thereby politicization of the bureaucracy, might very well have been triggered by the within “power bloc” crisis linked to Turkey’s socio-political conditions.
The Effects of Intervention Coursework on Science Achievement
Authors: Mansell Kristin E.
Published: June 2024

Background or Context:

With the implementation of three-dimensional science and high stakes testing, policymakers have bolstered science curriculum to include standards that engage students in scientific discourse while providing the needed guidelines for teaching science content. However, the field of science education has not been a policy focus to provide needed supports for struggling students to attain mastery of standards. This oversight leaves an evident gap in educational equity, because it fails to address challenges faced by students who may not meet science proficiency.

Purpose, Objective, Research Question, or Focus of Study:

This study examines the association between a student’s enrollment in an intervention course and science outcomes. This is measured by achievement testing, describing student enrollment in an intervention course for both general intervention coursework and science-specific intervention coursework. The analysis further describes the teacher certification area for intervention courses to determine if certification impacts student achievement.

Research Design:

First, descriptive statistics were employed to better understand student characteristics of those enrolled in science intervention courses. Then, propensity score matching was used to match students through nearest neighbor matching based on covariates association with struggling learners. Additionally, teachers who teach intervention courses (general and science-specific) were examined by demographics and teacher certification pathway to determine if an association exists between certification pathway and student outcomes.

Conclusions or Recommendations:

Findings suggest that most students enrolled in a science-specific intervention course were not identified as a special education student. Those students enrolled in a science-specific intervention course had greater science outcomes than those students enrolled in a general intervention course. Additionally, teacher preparation pathway is important to consider during staffing initiatives because traditional certified teachers associate with higher student outcomes in science intervention courses, though more science intervention courses are taught by alternatively certified teachers.
Torments of Being Other
Authors: Yakira
Published: June 2024

I am bipolar. Writing has helped me during very troubled times. These are just some of the extracts written between 2013 and 2016, expressing despair, agony, loneliness, and desperation. My brother died when I was 7 years old and my father 2 years later. Fifty years later, it is the loss of my wonderful Jungian therapist that opened deep scars and mangled wounds. In the poem—the Dead came upon Me—I have tried to turn each expression of despair into one of hope. As the struggle of being bipolar continues, I am deeply aware of an affinity to so many others who suffer through being “other,” “troubled,” “isolated”—perhaps if this resonates with a few of the readers it has done some good. I am so grateful to those who have helped me along the way—and continue to do so. Particularly, thank you to Paul Ashton for showing me (in The Dead came upon Me) that words matter and that it is possible to accept “difference” or “otherness,” to use poetry or images to transform pain into something more meaningful and perhaps, with time, even into something of beauty
Development of mathematical correlations to predict performance of forced ventilated Photovoltaic-DSF system in hot composite climate
Authors: Preet Sajan , Mathur Sanjay , Mathur Jyotirmay , Sharma Manoj Kumar , Chowdhury Amartya
Published: June 2024

Performance of Photovoltaic-double skin façade (Photovoltaic-DSF) system in summer has been critical. Owing to high solar ingress, cooling requirement of a building significantly increases. Photovoltaic-DSF system provides a shield and controls the heat gain through fenestration in the interior spaces. In the present article, mathematical correlations are developed to analyse energy behaviour of forced-ventilated Photovoltaic-DSF system in India’s hot summer zone, that is, Jaipur. The Photovoltaic-DSF system has been installed and monitored for Jaipur’s summer months (May to July). L25 Orthogonal array of design parameters (air cavity thickness, air velocity and PV panel’s transparency) and their respective levels have been developed using Taguchi design to perform experiments. Based on experimental results, multiple linear regression has been used to forecast solar heat gain coefficient, PVs electrical power and daylighting illuminance indoors as function of design factors. The statistical significance of mathematical relationships is supported by variance analysis, which is found to be in good accord with field measurements ( R2 > 0.90). The proposed correlations are pragmatic in designing Photovoltaic-DSF systems for hot summer conditions. The Photovoltaic-DSF system with 30% transmittance and air velocity of 5 m/s in 200 mm air cavity thickness achieved maximum energy performance in hot summers.
Complete absence of GLUT1 does not impair human terminal erythroid differentiation
Authors: Martins Freire Catarina , King Nadine R. , Dzieciatkowska Monika , Stephenson Daniel , Moura Pedro L. , Dobbe Johannes G. G. , Streekstra Geert J. , D'Alessandro Angelo , Toye Ashley M. , Satchwell Timothy J.
Published: June 2024

The glucose transporter 1 (GLUT1) is 1 of the most abundant proteins within the erythrocyte membrane and is required for glucose and dehydroascorbic acid (vitamin C precursor) transport. It is widely recognized as a key protein for red cell structure, function, and metabolism. Previous reports highlighted the importance of GLUT1 activity within these uniquely glycolysis-dependent cells, in particular for increasing antioxidant capacity needed to avoid irreversible damage from oxidative stress in humans. However, studies of glucose transporter roles in erythroid cells are complicated by species-specific differences between humans and mice. Here, using CRISPR–mediated gene editing of immortalized erythroblasts and adult CD34+ hematopoietic progenitor cells, we generate committed human erythroid cells completely deficient in expression of GLUT1. We show that absence of GLUT1 does not impede human erythroblast proliferation, differentiation, or enucleation. This work demonstrates, to our knowledge, for the first time, generation of enucleated human reticulocytes lacking GLUT1. The GLUT1–deficient reticulocytes possess no tangible alterations to membrane composition or deformability in reticulocytes. Metabolomic analyses of GLUT1–deficient reticulocytes reveal hallmarks of reduced glucose import, downregulated metabolic processes and upregulated AMP-activated protein kinase signaling, alongside alterations in antioxidant metabolism, resulting in increased osmotic fragility and metabolic shifts indicative of higher oxidant stress. Despite detectable metabolic changes in GLUT1–deficient reticulocytes, the absence of developmental phenotype, detectable proteomic compensation, or impaired deformability comprehensively alters our understanding of the role of GLUT1 in red blood cell structure, function, and metabolism. It also provides cell biological evidence supporting clinical consensus that reduced GLUT1 expression does not cause anemia in GLUT1–deficiency syndrome.
Regulation of macrophage polarization by targeted metabolic reprogramming for the treatment of lupus nephritis
Authors: Zhao Limei , Tang Shuqin , Chen Fahui , Ren Xiya , Han Xiutao , Zhou Xiaoshuang
Published: June 2024

Lupus nephritis (LN) is a severe and common manifestation of systemic lupus erythematosus (SLE) that is frequently identified with a poor prognosis. Macrophages play an important role in its pathogenesis. Different macrophage subtypes have different effects on lupus-affected kidneys. Based on their origin, macrophages can be divided into monocyte-derived macrophages (MoMacs) and tissue-resident macrophages (TrMacs). During nephritis, TrMacs develop a hybrid pro-inflammatory and anti-inflammatory functional phenotype, as they do not secrete arginase or nitric oxide (NO) when stimulated by cytokines. The infiltration of these mixed-phenotype macrophages is related to the continuous damage caused by immune complexes and exposure to circulating inflammatory mediators, which is an indication of the failure to resolve inflammation. On the other hand, MoMacs differentiate into M1 or M2 cells under cytokine stimulation. M1 macrophages are pro-inflammatory and secrete pro-inflammatory cytokines, while the M2 main phenotype is essentially anti-inflammatory and promotes tissue repair. Conversely, MoMacs undergo differentiation into M1 or M2 cells in response to cytokine stimulation. M1 macrophages are considered pro-inflammatory cells and secrete pro-inflammatory mediators, whereas the M2 main phenotype is primarily anti-inflammatory and promotes tissue repair. Moreover, based on cytokine expression, M2 macrophages can be further divided into M2a, M2b, and M2c phenotypes. M2a and M2c have anti-inflammatory effects and participate in tissue repair, while M2b cells have immunoregulatory and pro-inflammatory properties. Further, memory macrophages also have a role in the advancement of LN. Studies have demonstrated that the polarization of macrophages is controlled by multiple metabolic pathways, such as glycolysis, the pentose phosphate pathway, fatty acid oxidation, sphingolipid metabolism, the tricarboxylic acid cycle, and arginine metabolism. The changes in these metabolic pathways can be regulated by substances such as fish oil, polyenylphosphatidylcholine, taurine, fumaric acid, metformin, and salbutamol, which inhibit M1 polarization of macrophages and promote M2 polarization, thereby alleviating LN.
Enhancing cowpea wilt resistance: insights from gene coexpression network analysis with exogenous melatonin treatment
Authors: Gan Yudi , Tu Zhiwei , Yang Youxin , Cheng Liuyang , Wang Nan , Fan Shuying , Wu Caijun
Published: June 2024

Background

Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to pathogens; however the specific regulatory mechanism underlying the protective effect of melatonin pretreated of cowpea against Fusarium oxysporum remains known. Accordingly, the study sought to evaluate changes in the physiological and biochemical indices of cowpea following melatonin treated to facilitate Fusarium oxysporum resistance and elucidate the associated molecular mechanism using a weighted gene coexpression network.

Results

Treatment with 100 µM melatonin was effective in increasing cowpea resistance to Fusarium oxysporum. Glutathione peroxidase (GSH-PX), catalase (CAT), and salicylic acid (SA) levels were significantly upregulated, and hydrogen peroxide (H2O2) levels were significantly downregulated in melatonin treated samples in roots. Weighted gene coexpression network analysis of melatonin- and Fusarium oxysporum-treated samples identified six expression modules comprising 2266 genes; the number of genes per module ranged from 9 to 895. In particular, 17 redox genes and 32 transcription factors within the blue module formed a complex interconnected expression network. KEGG analysis revealed that the associated pathways were enriched in secondary metabolism, peroxisomes, phenylalanine metabolism, flavonoids, and flavonol biosynthesis. More specifically, genes involved in lignin synthesis, catalase, superoxide dismutase, and peroxidase were upregulated. Additionally, exogenous melatonin induced activation of transcription factors, such as WRKY and MYB.

Conclusions

The study elucidated changes in the expression of genes associated with the response of cowpea to Fusarium oxysporum under melatonin treated. Specifically, multiple defence mechanisms were initiated to improve cowpea resistance to Fusarium oxysporum.
Changes in tubular biomarkers with dietary intervention and metformin in patients with autosomal dominant polycystic kidney disease: a post-hoc analysis of two clinical trials
Authors: Wang Wei , You Zhiying , Steele Cortney N. , Gitomer Berenice , Chonchol Michel , Nowak Kristen L.
Published: June 2024

Background

Tubular biomarkers, which reflect tubular dysfunction or injury, are associated with incident chronic kidney disease and kidney function decline. Several tubular biomarkers have also been implicated in the progression of autosomal dominant polycystic kidney disease (ADPKD). We evaluated changes in multiple tubular biomarkers in four groups of patients with ADPKD who participated in one of two clinical trials (metformin therapy and diet-induced weight loss), based on evidence suggesting that such interventions could reduce tubule injury.

Methods

66 participants (26 M/40 F) with ADPKD and an estimated glomerular filtration rate (eGFR) ≥ 30 ml/min/1.73m2 who participated in either a metformin clinical trial (n = 22 metformin; n = 23 placebo) or dietary weight loss study (n = 10 daily caloric restriction [DCR]; n = 11 intermittent fasting [IMF]) were included in assessments of urinary tubular biomarkers (kidney injury molecule-1 [KIM-1], fatty-acid binding protein [FABP], interleukin-18 [IL-18], monocyte chemoattractant protein-1 [MCP-1], neutrophil gelatinase-associated lipocalin [NGAL], clusterin, and human cartilage glycoprotein-40 [YKL-40]; normalized to urine creatinine), at baseline and 12 months. The association of baseline tubular biomarkers with both baseline and change in height-adjusted total kidney volume (HtTKV; percent change from baseline to 12 months) and estimated glomerular filtration rate (eGFR; absolute change at 12 months vs. baseline), with covariate adjustment, was also assessed using multiple linear regression.

Results

Mean ± s.d. age was 48 ± 8 years, eGFR was 71 ± 16 ml/min/1.73m2, and baseline BMI was 30.5 ± 5.9 kg/m2. None of the tubular biomarkers changed with any intervention as compared to placebo. Additionally, baseline tubular biomarkers were not associated with either baseline or change in eGFR or HtTKV over 12 months, after adjustments for demographics, group assignment, and clinical characteristics.

Conclusions

Tubular biomarkers did not change with dietary-induced weight loss or metformin, nor did they associate with kidney disease progression, in this cohort of patients with ADPKD.
The advanced lung cancer inflammation index is associated with mortality in peritoneal dialysis patients
Authors: Ren Zhouhao , Wu Jiaying , Wu Shaorui , Zhang Mengwei , Shen Shuijuan
Published: June 2024

Background

There is still a very high morbidity and mortality rate for patients undergoing peritoneal dialysis (PD). The advanced lung cancer inflammation index (ALI) has been demonstrated to be associated with the prognosis in multiple types of cancers. Like in cancer, systemic chronic low-grade inflammation is one of the distinguishing features of PD patients. Therefore, we aimed to investigate the relationships between the ALI and all-cause and cardiovascular disease (CVD) mortality in PD patients.

Methods

Patients who started PD at Shaoxing People’s Hospital between 1 January 2013 and 31 December 2020 (n = 277) were recruited and followed up until 1 July 2023. They were divided into high-ALI group and low-ALI group according to the median of ALI. Kaplan–Meier curves and multivariate Cox regression analyses were used to assess the associations between the ALI and all-cause and CVD mortality. Receiver operating characteristic (ROC) curves were constructed, and the area under the curve (AUC) was calculated to determine the predictive power of the ALI for all- cause and CVD mortality.

Results

During the median follow-up of 40.50 months (interquartile range, 26.42–59.77 months), a total of 55 patients died, 31 of whom died due to CVD. Kaplan–Meier curves revealed that patients in the low-ALI group had significantly lower cumulative and cardiovascular cumulative survival rates than did those in the high-ALI group (all P < 0.001). After we corrected for confounders, the risk of all-cause and CVD mortality was significantly greater in the low-ALI group than in the high-ALI group [hazard ratio (HR) 1.944, 95% confidence interval (CI) 1.068–3.540, P = 0.030, and HR 2.672, 95% CI 1.188–6.009, P = 0.017, respectively]. The predictive value of ALI (AUC = 0.708, 95% CI 0.630–0.786, P < 0.001) for all-cause mortality was superior to albumin (AUC = 0.644, 95% CI 0.556–0.726, P < 0.001), body mass index (AUC = 0.581, 95% CI 0.496–0.659, P = 0.069) and neutrophil-to-lymphocyte ratio (AUC = 0.675, 95% CI 0.596–0.754, P < 0.001).

Conclusion

A lower ALI is an independent risk factor for all-cause and cardiovascular mortality in PD patients. The ALI may be an effective indicator for predicting outcomes in PD patients.
Study protocol for the MIND-PD study: a randomized controlled trial to investigate clinical and biological effects of mindfulness-based cognitive therapy in people with Parkinson’s disease
Authors: van der Heide Anouk , Goltz Franziska , de Vries Nienke M. , Bloem Bastiaan R. , Speckens Anne E. , Helmich Rick C.
Published: June 2024

Background

People with Parkinson’s disease (PD) are very sensitive to the effects of stress. The prevalence of stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic stress may accelerate disease progression, but evidence for this in humans is lacking. Mindfulness-based interventions (MBIs) train participants to focus on the present moment, on purpose and without judgement. Previous studies suggest that MBIs may alleviate stress and reduce depression and anxiety in PD. We aim to demonstrate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy for neuropsychiatric (and motor) symptoms in PD, and to identify the mechanisms underlying stress and stress reduction in PD.

Methods

In a prospective randomized controlled trial (RCT), we investigate whether 8 weeks of MBCT, as compared to care as usual, can reduce symptoms of anxiety and depression in people with PD. We aim to include 124 PD patients, who experience mild-moderate symptoms of anxiety and depression, are eligible for magnetic resonance imaging (MRI) and naïve to mindfulness, and who have a disease duration ≤ 10 years. Every participant is followed for 12 months. Clinical and biochemical assessments take place at baseline (T0), after 2 months (T1), and after 12 months (T2); MRI assessments take place at T0 and T2. Our primary outcome is the total score on the Hospital Anxiety and Depression Scale (HADS) at T1, while correcting for the HADS score at T0, age, and gender. Beyond testing the effects of MBCT on symptoms of anxiety and depression in PD, we explore whether MBCT: (1) has an effect on motor symptom severity, (2) influences cerebral and biochemical markers of stress, and (3) leads to a change in biomarkers of PD progression.

Discussion

MIND-PD is one of the first RCTs with a 1-year follow-up to investigate the effects of MBCT on symptoms of anxiety and depression in PD, and to explore possible mechanisms underlying stress and stress reduction in PD. Insight into these mechanisms can pave the way to new treatment methods in the future.

Trial registration

ClinicalTrials.gov, NCT05779137. Registered on 12 January 2023.
The effect of mandala coloring and free coloring on the happiness in veterans with post-traumatic stress disorder in the Covid-19 pandemic: a randomized clinical trial
Authors: Nasiri Mohammad-Amin , Sajadi Seyedeh Azam , Farsi Zahra , Heidarieh Marzie
Published: June 2024

Background

Post-traumatic stress disorder (PTSD) can lead to complications such as depression and grief, which are more prevalent in veterans than in the general population. Recently, art-making, including mandala coloring, has gained attention as a potential treatment for PTSD patients.

Methods

This randomized clinical trial was conducted on 84 male veterans diagnosed with PTSD and hospitalized at the Milad Psychiatric Center in Tehran, Iran. The patients were recruited using a convenience sampling method and were assigned to either the mandala coloring group or the free coloring group. The Post-Traumatic Stress Disorder Checklist DSM-5 and the Oxford Happiness Scale were used to collect data. The intervention group colored mandala designs, while the control group colored squares freely. Coloring was done twice a week for three weeks.

Results

The mean baseline happiness scores did not differ significantly between mandala coloring group and free coloring group (p = 0.376). However, at the end of study, happiness scores were significantly higher in mandala coloring group than in free coloring group (p < 0.001). After the intervention, happiness score of both groups increased significantly (p < 0.001).

Conclusion

Both coloring methods increased veterans’ happiness scores; however, mandala coloring was more effective than free coloring. It is recommended that art-making be added to conventional treatments for veterans with PTSD.

Trial registration

This study was registered in Iranian Registry of clinical trials (No. IRCT20210604051491N1, 29/08/2021).
Thoracic lymphangitis as an immune-related adverse event: a case report
Authors: Kobayashi Haruki
Published: June 2024

The efficacy of immune checkpoint inhibitors (ICIs) has been widely recognized in several cancers and is now being used in the perioperative setting for lung cancer.

We recently encountered an immune-related adverse event that has not been previously reported: thoracic lymphangitis, which occurred after postoperative ICI treatment for lung cancer. The patient complained of breathlessness and her condition rapidly progressed to hypoxia grade 3. Chest computed tomography revealed significant lymphostasis. With high-dose steroid treatment, the patient showed improvement.

Therefore, as the frequency of neoadjuvant, adjuvant, and perioperative ICI use is expected to increase, it is crucial to understand and monitor this adverse event.
Immunoreactivity of LMO7 and other molecular markers as potential prognostic factors in oropharyngeal squamous cell carcinoma
Authors: Israelsson Pernilla , Oda Husam , Öfverman Charlotte , Stefansson Kristina , Lindquist David
Published: June 2024

Background

Despite the better prognosis associated with human papillomavirus (HPV)-positive oropharyngeal squamous cell carcinoma (OPSCC), some patients experience relapse and succumb to the disease; thus, there is a need for biomarkers identifying these patients for intensified treatment. Leucine-rich repeats and immunoglobulin-like domain (LRIG) protein 1 is a negative regulator of receptor tyrosine kinase signaling and a positive prognostic factor in OPSCC. Studies indicate that LRIG1 interacts with the LIM domain 7 protein (LMO7), a stabilizer of adherence junctions. Its role in OPSCC has not been studied before.

Methods

A total of 145 patients diagnosed with OPSCC were enrolled. Immunohistochemical LMO7 expression and staining intensity were evaluated in the tumors and correlated with known clinical and pathological prognostic factors, such as HPV status and LRIG1, CD44, Ki67, and p53 expression.

Results

Our results show that high LMO7 expression is associated with significantly longer overall survival (OS) (p = 0.044). LMO7 was a positive prognostic factor for OS in univariate analysis (HR 0.515, 95% CI: 0.267–0.994, p = 0.048) but not in multivariate analysis. The LMO7 expression correlated with LRIG1 expression (p = 0.048), consistent with previous findings. Interestingly, strong LRIG1 staining intensity was an independent negative prognostic factor in the HPV-driven group of tumors (HR 2.847, 95% Cl: 1.036–7.825, p = 0.043).

Conclusions

We show for the first time that high LMO7 expression is a positive prognostic factor in OPSCC, and we propose that LMO7 should be further explored as a biomarker. In contrast to previous reports, LRIG1 expression was shown to be an independent negative prognostic factor in HPV-driven OPSCC.