bluuebunny/crossref_metadata_2025 huggingface dataset:
Risk of all-cause and cause-specific mortality associated with immune-mediated inflammatory diseases in Korea
Authors: Kwon Oh Chan , Lee See Young , Chun Jaeyoung , Han Kyungdo , Kim Yuna , Kim Ryul , Park Min-Chan , Kim Jie-Hyun , Youn Young Hoon , Park Hyojin
Published: June 2023

Objective

Immune-mediated inflammatory disease (IMID) is associated with an increased risk of mortality. It is unclear whether the higher mortality is attributable to the IMIDs themselves or to the higher prevalence of comorbidities in IMIDs. We aimed to investigate whether IMIDs per se confer a higher risk of mortality.

Methods

From the Korean National Health Insurance Service-National Sample Cohort database, this population-based cohort study included 25,736 patients newly diagnosed with IMIDs between January 2007 and December 2017, and 128,680 individuals without IMIDs who were matched for age, sex, income, hypertension, type 2 diabetes, dyslipidemia, and the Charlson comorbidity index. All individuals were retrospectively observed through December 31, 2019. The outcomes included all-cause and cause-specific mortalities. Adjustments for age, sex, and comorbidities were performed using multivariable Cox proportional hazard regression analyses, and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for the outcomes were estimated.

Results

The adjusted risk of all-cause mortality was significantly lower in patients with IMIDs than that in those without (aHR, 0.890; 95% CI, 0.841–0.942). Regarding cause-specific mortality, cancer-specific (aHR, 0.788; 95% CI, 0.712–0.872) and cardiovascular disease-specific (aHR, 0.798; 95% CI, 0.701–0.908) mortalities were the two causes of death that showed significantly lower risks in patients with IMIDs. A similar trend was observed when organ based IMIDs were analyzed separately (i.e., gut, joint, and skin IMIDs).

Conclusion

After adjusting for comorbidities, IMIDs were associated with a lower risk of all-cause mortality compared to those without IMIDs. This was attributable to the lower risks of cancer-and cardiovascular disease-specific mortalities.
Preliminary study of anti-CD40 and ubiquitin proteasome antibodies in primary podocytopaties
Authors: Chebotareva Natalia , Cao Venzsin , Vinogradov Anatoliy , Alentov Igor , Sergeeva Natalia , Kononikhin Alexey , Moiseev Sergey
Published: June 2023

Background

Minimal change disease and focal segmental glomerulosclerosis are primary podocytopathies that are clinically presented in adults presenting with severe nephrotic syndrome. The pathogenesis of these diseases is not clear and many questions remain to be answered. A new concept about the role of changes in the antigenic determinant of podocytes and the production of anti-podocyte antibodies that cause podocyte damage is being developed. The aim of the study is to evaluate the levels of anti-CD40 and anti-ubiquitin carboxyl-terminal hydrolase L1 (anti-UCH-L1) antibodies in patients with podocytopathies in comparison with other glomerulopathies.

Methods

One hundred and six patients with glomerulopathy and 11 healthy subjects took part in the study. A histological study revealed primary FSGS in 35 patients (genetic cases of FSGS and secondary FSGS in the absence of NS were excluded), 15 had MCD, 21 - MN, 13 - MPGN, 22 patients - IgA nephropathy. The effect of steroid therapy was evaluated in patients with podocytopathies (FSGS and MCD). The serum levels of anti-UCH-L1 and anti-CD40 antibodies were measured by ELISA before steroid treatment.

Results

The levels of anti-UCH-L1 antibodies were significantly higher in MCD patients and anti-CD40 antibodies were higher in MCD and FSGS than in the control group and other groups of glomerulopathies. In addition, the level of anti-UCH-L1 antibodies was higher in patients with steroid-sensitive FSGS and MCD, and anti-CD40 antibodies were lower than in patients with steroid-resistant FSGS. An increase in anti-UCH-L1 antibody levels above 6.44 ng/mL may be a prognostic factor of steroid-sensitivity. The ROC curve (AUC = 0.875 [95% CI 0.718–0.999]) for response to therapy showed a sensitivity of 75% and specificity of 87.5%.

Conclusion

An increase in the level of anti-UCH-L1 antibodies is specific for steroid-sensitive FSGS and MCD, while an increase in anti-CD40 antibodies – for steroid-resistant FSGS, compared with other glomerulopathies. It suggests that these antibodies could be a potential factor for differential diagnosis and treatment prognosis.
Screening for potential novel probiotic Levilactobacillus brevis RAMULAB52 with antihyperglycemic property from fermented Carica papaya L.
Authors: Sreepathi Navya , Kumari V. B. Chandana , Huligere Sujay S. , Al-Odayni Abdel-Basit , Lasehinde Victor , Jayanthi M. K. , Ramu Ramith
Published: June 2023

Probiotics are live microorganisms with various health benefits when consumed in appropriate amounts. Fermented foods are a rich source of these beneficial organisms. This study aimed to investigate the probiotic potential of lactic acid bacteria (LAB) isolated from fermented papaya (Carica papaya L.) through in vitro methods. The LAB strains were thoroughly characterized, considering their morphological, physiological, fermentative, biochemical, and molecular properties. The LAB strain's adherence and resistance to gastrointestinal conditions, as well as its antibacterial and antioxidant capabilities, were examined. Moreover, the strains were tested for susceptibility against specific antibiotics, and safety evaluations encompassed the hemolytic assay and DNase activity. The supernatant of the LAB isolate underwent organic acid profiling (LCMS). The primary objective of this study was to assess the inhibitory activity of α-amylase and α-glucosidase enzymes, both in vitro and in silico. Gram-positive strains that were catalase-negative and carbohydrate fermenting were selected for further analysis. The LAB isolate exhibited resistance to acid bile (0.3% and 1%), phenol (0.1% and 0.4%), and simulated gastrointestinal juice (pH 3–8). It demonstrated potent antibacterial and antioxidant abilities and resistance to kanamycin, vancomycin, and methicillin. The LAB strain showed autoaggregation (83%) and adhesion to chicken crop epithelial cells, buccal epithelial cells, and HT-29 cells. Safety assessments indicated no evidence of hemolysis or DNA degradation, confirming the safety of the LAB isolates. The isolate's identity was confirmed using the 16S rRNA sequence. The LAB strain Levilactobacillus brevis RAMULAB52, derived from fermented papaya, exhibited promising probiotic properties. Moreover, the isolate demonstrated significant inhibition of α-amylase (86.97%) and α-glucosidase (75.87%) enzymes. In silico studies uncovered that hydroxycitric acid, one of the organic acids derived from the isolate, interacted with crucial amino acid residues of the target enzymes. Specifically, hydroxycitric acid formed hydrogen bonds with key amino acid residues, such as GLU233 and ASP197 in α-amylase, and ASN241, ARG312, GLU304, SER308, HIS279, PRO309, and PHE311 in α-glucosidase. In conclusion, Levilactobacillus brevis RAMULAB52, isolated from fermented papaya, possesses promising probiotic properties and exhibits potential as an effective remedy for diabetes. Its resistance to gastrointestinal conditions, antibacterial and antioxidant abilities, adhesion to different cell types, and significant inhibition of target enzymes make it a valuable candidate for further research and potential application in the field of probiotics and diabetes management.
Enabling oxygen-controlled microfluidic cultures for spatiotemporal microbial single-cell analysis
Authors: Kasahara Keitaro , Leygeber Markus , Seiffarth Johannes , Ruzaeva Karina , Drepper Thomas , Nöh Katharina , Kohlheyer Dietrich
Published: June 2023

Microfluidic cultivation devices that facilitate O2 control enable unique studies of the complex interplay between environmental O2 availability and microbial physiology at the single-cell level. Therefore, microbial single-cell analysis based on time-lapse microscopy is typically used to resolve microbial behavior at the single-cell level with spatiotemporal resolution. Time-lapse imaging then provides large image-data stacks that can be efficiently analyzed by deep learning analysis techniques, providing new insights into microbiology. This knowledge gain justifies the additional and often laborious microfluidic experiments. Obviously, the integration of on-chip O2 measurement and control during the already complex microfluidic cultivation, and the development of image analysis tools, can be a challenging endeavor. A comprehensive experimental approach to allow spatiotemporal single-cell analysis of living microorganisms under controlled O2 availability is presented here. To this end, a gas-permeable polydimethylsiloxane microfluidic cultivation chip and a low-cost 3D-printed mini-incubator were successfully used to control O2 availability inside microfluidic growth chambers during time-lapse microscopy. Dissolved O2 was monitored by imaging the fluorescence lifetime of the O2-sensitive dye RTDP using FLIM microscopy. The acquired image-data stacks from biological experiments containing phase contrast and fluorescence intensity data were analyzed using in-house developed and open-source image-analysis tools. The resulting oxygen concentration could be dynamically controlled between 0% and 100%. The system was experimentally tested by culturing and analyzing an E. coli strain expressing green fluorescent protein as an indirect intracellular oxygen indicator. The presented system allows for innovative microbiological research on microorganisms and microbial ecology with single-cell resolution.
Age-related decline of online visuomotor adaptation: a combined effect of deteriorations of motor anticipation and execution
Authors: Li Na , Liu Junsheng , Xie Yong , Ji Weidong , Chen Zhongting
Published: June 2023

The literature has established that the capability of visuomotor adaptation decreases with aging. However, the underlying mechanisms of this decline are yet to be fully understood. The current study addressed this issue by examining how aging affected visuomotor adaptation in a continuous manual tracking task with delayed visual feedback. To distinguish separate contributions of the declined capability of motor anticipation and deterioration of motor execution to this age-related decline, we recorded and analyzed participants' manual tracking performances and their eye movements during tracking. Twenty-nine older people and twenty-three young adults (control group) participated in this experiment. The results showed that the age-related decline of visuomotor adaptation was strongly linked to degraded performance in predictive pursuit eye movement, indicating that declined capability motor anticipation with aging had critical influences on the age-related decline of visuomotor adaptation. Additionally, deterioration of motor execution, measured by random error after controlling for the lag between target and cursor, was found to have an independent contribution to the decline of visuomotor adaptation. Taking these findings together, we see a picture that the age-related decline of visuomotor adaptation is a joint effect of the declined capability of motor anticipation and the deterioration of motor execution with aging.
Serial deep gray nuclear DTI changes in Parkinson’s disease over twelve years
Authors: Shih Yao-Chia , Ooi Leon Qi Rong , Li Hui-Hua , Allen John Carson , Hartono Septian , Welton Thomas , Tan Eng-King , Chan Ling Ling
Published: June 2023

Background

Deep gray nuclear pathology relates to motor deterioration in idiopathic Parkinson’s disease (PD). Inconsistent deep nuclear diffusion tensor imaging (DTI) findings in cross-sectional or short-term longitudinal studies have been reported. Long-term studies in PD are clinically challenging; decade-long deep nuclear DTI data are nonexistent. We investigated serial DTI changes and clinical utility in a case-control PD cohort of 149 subjects (72 patients/77 controls) over 12 years.

Methods

Participating subjects underwent brain MRI at 1.5T; DTI metrics from segmented masks of caudate, putamen, globus pallidus and thalamus were extracted from three timepoints with 6-year gaps. Patients underwent clinical assessment, including Unified Parkinson Disease Rating Scale Part 3 (UPDRS-III) and Hoehn and Yahr (H&Y) staging. A multivariate linear mixed-effects regression model with adjustments for age and gender was used to assess between-group differences in DTI metrics at each timepoint. Partial Pearson correlation analysis was used to correlate clinical motor scores with DTI metrics over time.

Results

MD progressively increased over time and was higher in the putamen (p < 0.001) and globus pallidus (p = 0.002). FA increased (p < 0.05) in the thalamus at year six, and decreased in the putamen and globus pallidus at year 12. Putaminal (p = 0.0210), pallidal (p = 0.0066) and caudate MD (p < 0.0001) correlated with disease duration. Caudate MD (p < 0.05) also correlated with UPDRS-III and H&Y scores.

Conclusion

Pallido-putaminal MD showed differential neurodegeneration in PD over 12 years on longitudinal DTI; putaminal and thalamic FA changes were complex. Caudate MD could serve as a surrogate marker to track late PD progression.
Adaptive visual–tactile fusion recognition for robotic operation of multi-material system
Authors: Ding Zihao , Chen Guodong , Wang Zhenhua , Sun Lining
Published: June 2023

The use of robots in various industries is evolving from mechanization to intelligence and precision. These systems often comprise parts made of different materials and thus require accurate and comprehensive target identification. While humans perceive the world through a highly diverse perceptual system and can rapidly identify deformable objects through vision and touch to prevent slipping or excessive deformation during grasping, robot recognition technology mainly relies on visual sensors, which lack critical information such as object material, leading to incomplete cognition. Therefore, multimodal information fusion is believed to be key to the development of robot recognition. Firstly, a method of converting tactile sequences to images is proposed to deal with the obstacles of information exchange between different modalities for vision and touch, which overcomes the problems of the noise and instability of tactile data. Subsequently, a visual-tactile fusion network framework based on an adaptive dropout algorithm is constructed, together with an optimal joint mechanism between visual information and tactile information established, to solve the problem of mutual exclusion or unbalanced fusion in traditional fusion methods. Finally, experiments show that the proposed method effectively improves robot recognition ability, and the classification accuracy is as high as 99.3%.
When ‘good’ is not good enough: a retrospective Rasch analysis study of the Berg Balance Scale for persons with Multiple Sclerosis
Authors: Caselli Serena , Sabattini Loredana , Cattaneo Davide , Jonsdottir Johanna , Brichetto Giampaolo , Pozzi Stefania , Lugaresi Alessandra , La Porta Fabio
Published: June 2023

Background

The Berg Balance Scale (BBS) is one of the most used tools to quantify balance in Persons with Multiple Sclerosis, a population at high risk of falling.

Aim

To evaluate the measurement characteristics of the BBS in Multiple Sclerosis through Rasch analysis.

Design

Retrospective study.

Setting

Outpatients in three Italian Rehabilitation centers.

Population

Eight hundred and fourteen persons with Multiple Sclerosis able to stand independently for more than 3 s.

Methods

The sample (N = 1,220) was split into one validating (B1) and three confirmatory subsamples. Following the Rasch analysis performed on B1, the item estimates were exported and anchored to the three confirmatory subsamples. After obtaining the same final solution across all samples, we studied the convergent and discriminant validity of the final BBS-MS using the EDSS, the ABC scale, and the number of falls.

Results

The base analysis on the B1 subsample failed the monotonicity, local independence, and unidimensionality requirements and did not fit the Rasch model. After grouping locally dependent items, the BBS-MS fitted the model (χ28 = 23.8; p = 0.003) and satisfied all requirements for adequate internal construct validity (ICV). However, it was mistargeted to the sample, given the striking prevalence of higher scores (targeting index 1.922) with a distribution-independent Person Separation Index sufficient for individual measurements (0.962). The B1 item estimates were anchored to the confirmatory samples with confirmation of adequate fit (χ2 = [19.0, 22.8], value of ps = [0.015, 0.004]) and satisfaction of all ICV requirements for all subsamples. The final BBS-MS directly correlated with the ABC scale (rho = 0.523) and inversely with EDSS (rho = −0.573). The BBS-MS estimates significantly differed across groups according to the pre-specified hypotheses (between the three EDSS groups, between the ABC cut-offs, distinguishing ‘fallers’ vs. ‘non-fallers’, and between the ‘low’ vs. ‘moderate’ vs. ‘high’ levels of physical functioning; and, finally, between ‘no falls’ vs. ‘one or more falls’).

Conclusion

This study supports the internal construct validity and reliability of the BBS-MS in an Italian multicentre sample of persons with Multiple Sclerosis. However, as the scale is slightly mistargeted to the sample, it represents a candidate tool to assess balance, mainly in more disabled people with an advanced walking disability.
Empowering human-AI teams via Intentional Behavioral Synchrony
Authors: Naser Mohammad Y. M. , Bhattacharya Sylvia
Published: June 2023

As Artificial Intelligence (AI) proliferates across various sectors such as healthcare, transportation, energy, and military applications, the collaboration between human-AI teams is becoming increasingly critical. Understanding the interrelationships between system elements - humans and AI - is vital to achieving the best outcomes within individual team members' capabilities. This is also crucial in designing better AI algorithms and finding favored scenarios for joint AI-human missions that capitalize on the unique capabilities of both elements. In this conceptual study, we introduce Intentional Behavioral Synchrony (IBS) as a synchronization mechanism between humans and AI to set up a trusting relationship without compromising mission goals. IBS aims to create a sense of similarity between AI decisions and human expectations, drawing on psychological concepts that can be integrated into AI algorithms. We also discuss the potential of using multimodal fusion to set up a feedback loop between the two partners. Our aim with this work is to start a research trend centered on exploring innovative ways of deploying synchrony between teams of non-human members. Our goal is to foster a better sense of collaboration and trust between humans and AI, resulting in more effective joint missions.
Depletion-driven thermochemistry of molten salt reactors: review, method, and analysis
Authors: Walker Samuel A. , Tano Mauricio E. , Abou-Jaoude Abdalla , Calvin Olin
Published: June 2023

Molten salt reactors (MSRs) are innovative advanced nuclear reactors that utilize nuclear fuel by dissolving it in a high-temperature liquid salt. This unique feature differentiates MSRs from other types of reactors and allows for enhanced safety and economic performance. The liquid fuel also entails several multiphysics effects that can complicate reactor design and operation. One primary effect termed here as depletion-driven thermochemistry is a driving force in altering the multiphysics behavior of the reactor. Essentially, depletion-driven thermochemistry is the effect that fuel depletion has on changing the chemical redox potential of the fuel salt over time. As the fuel is consumed, the redox potential shifts toward a more oxidizing state. Without active control, the changing chemistry due to depletion increases corrosion thereby limiting reactor component lifetimes. Additionally, the changing redox potential of the fuel salt alters the vapor pressures of chemical species dissolved in the fuel salt. Changing vapor pressures of species in the fuel salt is an important parameter to understand when off-gassing volatile species during normal reactor operation, and for source term characterization during accident scenario transients. The present work represents a fundamental step toward modeling and coupling the driving physics (i.e., neutronics and chemistry) involved in altering the redox potential in an MSR. Here, the neutronic code Griffin models the depletion of the fuel-salt system, while the chemical equilibrium code Thermochimica calculates the thermochemical state of the isotopic inventory, using the Molten Salt Thermodynamic Database - Thermochemical (MSTDB-TC). These two codes are tightly coupled to predict the impact of fuel depletion in altering the chemistry in MSR systems. Redox potential control methods are discussed and can be modeled using this multiphysics approach. The vapor pressures of chemical species that could be extracted to an off-gas system, as determined by the reactor’s thermochemical state, are examined. The neutronics-chemistry coupling developed in this work is expected to have potential application for analyzing corrosion, source term evolution, and material safeguards in MSR systems. Lastly, suggestions for areas of further improvements of the models to expand these capabilities by incorporating other coupled physics effects is provided.
Effect of imbalance in dietary macronutrients on blood hemoglobin levels: a cross-sectional study in young underweight Japanese women
Authors: Tateishi Yuko , Ichikawa Reiko , Suzuki Katsuya , Kitahara Yoshiro , Someya Yuki , Tamura Yoshifumi
Published: June 2023

Background

Iron deficiency and underweight are common nutritional problems among young Japanese women, many of whom show unhealthy dietary patterns owing to a desire for thinness. We conducted a cross-sectional analysis of the relationship between iron status, nutritional status, and dietary intake among young Japanese women with underweight to identify dietary risk factors for iron deficiency.

Methods

Of the 159 young women (18–29 years of age) enrolled, 77 underweight and 37 normal-weight women were included in the study. They were further categorized into four groups based on quartiles of hemoglobin levels among all participants. Dietary nutrient intake was ascertained using a brief self-administered diet history questionnaire. Blood level of hemoglobin and nutritional biomarkers such as total protein, albumin, insulin-like growth factor-1 (IGF-1), and essential amino acids were measured.

Results

In underweight, the multiple comparison test showed that dietary intakes of fat, saturated fatty acid, and monosaturated fatty acid were significantly higher and carbohydrate intake was significantly lower in the group with the lowest hemoglobin level, whereas intakes of iron were the same across groups. Multivariate regression coefficients suggested that replacing fat with protein or carbohydrates increased hemoglobin levels under isocaloric conditions. Additionally, significant positive correlations were observed between hemoglobin levels and nutritional biomarkers.

Conclusion

Dietary iron intake did not change across different hemoglobin groups among Japanese underweight women. However, our results suggested that an imbalanced dietary macronutrient induces anabolic status and hemoglobin synthesis deterioration among them. Especially, a higher fat intake may be a risk factor for lower hemoglobin.
The contradictory role of branched-chain amino acids in lifespan and insulin resistance
Authors: Yao He , Li Kai , Wei Jie , Lin Yajun , Liu Yinghua
Published: June 2023

Branched-chain amino acids (BCAAs; a mixture of leucine, valine and isoleucine) have important regulatory effects on glucose and lipid metabolism, protein synthesis and longevity. Many studies have reported that circulating BCAA levels or dietary intake of BCAAs is associated with longevity, sarcopenia, obesity, and diabetes. Among them, the influence of BCAAs on aging and insulin resistance often present different benefits or harmful effects in the elderly and in animals. Considering the nonobvious correlation between circulating BCAA levels and BCAA uptake, as well as the influence of diseases, diet and aging on the body, some of the contradictory conclusions have been drawn. The regulatory mechanism of the remaining contradictory role may be related to endogenous branched-chain amino acid levels, branched-chain amino acid metabolism and mTOR-related autophagy. Furthermore, the recent discovery that insulin resistance may be independent of longevity has expanded the research thinking related to the regulatory mechanism among the three. However, the negative effects of BCAAs on longevity and insulin resistance were mostly observed in high-fat diet-fed subjects or obese individuals, while the effects in other diseases still need to be studied further. In conclusion, there is still no definite conclusion on the specific conditions under which BCAAs and insulin resistance extend life, shorten life, or do not change lifespan, and there is still no credible and comprehensive explanation for the different effects of BCAAs and insulin resistance on lifespan.
Very low energy diets prior to bariatric surgery may reduce postoperative morbidity: a systematic review and meta-analysis of randomized controlled trials
Authors: McKechnie Tyler , Lee Yung , Dionne Joanna , Doumouras Aristithes , Parpia Sameer , Bhandari Mohit , Eskicioglu Cagla
Published: June 2023

Purpose

To optimize patients prior to bariatric surgery, very low energy diets (VLEDs) are often employed for 2–4 weeks preoperatively. They are known to result in preoperative weight loss, decrease liver volume, and decrease surgeon-perceived operative difficulty. Their impact on postoperative morbidity has been less extensively studied. We performed a focused systematic review and meta-analysis with the aim of comparing preoperative VLEDs prior to bariatric surgery with controls in terms of overall postoperative morbidity.

Methods

MEDLINE, Embase, and CENTRAL were searched from database inception to February 2023. Articles were eligible for inclusion if they were randomized controlled trials (RCTs) comparing postoperative morbidity in adult patients (i.e., over the age of 18) receiving a VLED with liquid formulation to those receiving a non-VLED control prior to elective bariatric surgery. Outcomes included overall 30-day postoperative morbidity and preoperative weight loss. An inverse variance meta-analysis was performed with GRADE assessment of the quality of evidence.

Results

After reviewing 2,525 citations, four RCTs with 294 patients receiving preoperative VLEDs with liquid formulation and 294 patients receiving a non-VLED control met inclusion. Patients receiving VLED experienced significantly more preoperative weight loss than patients receiving control (mean difference (MD) 3.38 kg, 95% confidence interval (CI) 1.06–5.70, p = 0.004, I2 = 95%). According to low certainty evidence, there was a non-significant reduction in 30-day postoperative morbidity in patients receiving VLED prior to bariatric surgery (risk ratio (RR) 0.67, 95%CI 0.39–1.17, p = 0.16, I2 = 0%).

Conclusion

The impact of preoperative VLEDs on postoperative outcomes following bariatric surgery remains unclear. It is possible that VLEDs may contribute to decreased postoperative morbidity, but further larger prospective trials are required to investigate the signal identified in this study.
Case report: 5-Fluorouracil treatment in patient with an important partial DPD deficiency
Authors: Schmitt Antonin , Royer Bernard , Boidot Romain , Berthier Joseph , Ghiringhelli François
Published: June 2023

Esophageal cancer is a cancer with poor prognosis and the standard 1st line treatment for metastatic or recurrent EC is systemic chemotherapy with doublet chemotherapy based on platinum and 5-fluorouracil (5-FU). However, 5-FU could be a source of severe treatment-related toxicities due to deficiency of dihydropyrimidine dehydrogenase (DPD). In this case report, a 74-year-old man with metastatic esophageal cancer was found to have partial DPD deficiency based on uracilemia measurements (about 90 ng/mL). Despite this, 5-FU was safely administered thanks to therapeutic drug monitoring (TDM). The case report highlights the importance of TDM in administering 5-FU to patients with partial DPD deficiency, as it allows individualized dosing and prevents severe toxicity.
Variability of extracellular vesicle release during storage of red blood cell concentrates is associated with differential membrane alterations, including loss of cholesterol-enriched domains
Authors: Ghodsi Marine , Cloos Anne-Sophie , Mozaheb Negar , Van Der Smissen Patrick , Henriet Patrick , Pierreux Christophe E. , Cellier Nicolas , Mingeot-Leclercq Marie-Paule , Najdovski Tomé , Tyteca Donatienne
Published: June 2023

Transfusion of red blood cell concentrates is the most common medical procedure to treat anaemia. However, their storage is associated with development of storage lesions, including the release of extracellular vesicles. These vesicles affect in vivo viability and functionality of transfused red blood cells and appear responsible for adverse post-transfusional complications. However, the biogenesis and release mechanisms are not fully understood. We here addressed this issue by comparing the kinetics and extents of extracellular vesicle release as well as red blood cell metabolic, oxidative and membrane alterations upon storage in 38 concentrates. We showed that extracellular vesicle abundance increased exponentially during storage. The 38 concentrates contained on average 7 × 1012 extracellular vesicles at 6 weeks (w) but displayed a ∼40-fold variability. These concentrates were subsequently classified into 3 cohorts based on their vesiculation rate. The variability in extracellular vesicle release was not associated with a differential red blood cell ATP content or with increased oxidative stress (in the form of reactive oxygen species, methaemoglobin and band3 integrity) but rather with red blood cell membrane modifications, i.e., cytoskeleton membrane occupancy, lateral heterogeneity in lipid domains and transversal asymmetry. Indeed, no changes were noticed in the low vesiculation group until 6w while the medium and the high vesiculation groups exhibited a decrease in spectrin membrane occupancy between 3 and 6w and an increase of sphingomyelin-enriched domain abundance from 5w and of phosphatidylserine surface exposure from 8w. Moreover, each vesiculation group showed a decrease of cholesterol-enriched domains associated with a cholesterol content increase in extracellular vesicles but at different storage time points. This observation suggested that cholesterol-enriched domains could represent a starting point for vesiculation. Altogether, our data reveal for the first time that the differential extent of extracellular vesicle release in red blood cell concentrates did not simply result from preparation method, storage conditions or technical issues but was linked to membrane alterations.
Field traffic-induced soil compaction under moderate machine-field conditions affects soil properties and maize yield on sandy loam soil
Authors: Nawaz Muhammad Mohsin , Noor Mehmood Ali , Latifmanesh Hojatollah , Wang Xinbing , Ma Wei , Zhang Weijian
Published: June 2023

Soil compaction due to field trafficking involves a complex interplay of machine-soil properties. In contrast to previous studies simulating worst field scenarios, this two-year field experiment investigated the effects of traffic-induced compaction involving moderate machine operational specifications (axle load, 3.16 Mg; mean ground contact pressure, 77.5 kPa) and lower field moisture contents (< field capacity) at the time of trafficking on soil physical properties, spatial root distribution, and corresponding maize growth and grain yield in sandy loam soil. Two compaction levels, i.e. two (C2) and six (C6) vehicle passes, were compared with a control (C0). Two maize (Zea mays L.) cultivars, i.e. ZD-958 and XY-335, were used. Results showed topsoil (< 30 cm) compaction with increases in bulk density (BD) and penetration resistance (PR) up to 16.42% and 127.76%, respectively, in the 10-20 cm soil layer in 2017. Field trafficking resulted in a shallower and stronger hardpan. An increased number of traffic passes (C6) aggravated the effects, and the carryover effect was found. Higher BD and PR impaired root proliferation in deeper layers of topsoil (10-30 cm) and promoted shallow horizontal root distribution. However, XY-335, compared with ZD-958, showed deeper root distribution under compaction. Compaction-induced reductions in root biomass and length densities were respectively up to 41% and 36% in 10-20 cm and 58% and 42% in the 20-30 cm soil layer. Consequent yield penalties (7.6%-15.5%) underscore the detriments of compaction, even only in topsoil. In crux, despite their low magnitude, the negative impacts of field trafficking under moderate machine-field conditions after just two years of annual trafficking foreground the challenge of soil compaction.
A transformer-based approach for early prediction of soybean yield using time-series images
Authors: Bi Luning , Wally Owen , Hu Guiping , Tenuta Albert U. , Kandel Yuba R. , Mueller Daren S.
Published: June 2023

Crop yield prediction which provides critical information for management decision-making is of significant importance in precision agriculture. Traditional manual inspection and calculation are often laborious and time-consuming. For yield prediction using high-resolution images, existing methods, e.g., convolutional neural network, are challenging to model long range multi-level dependencies across image regions. This paper proposes a transformer-based approach for yield prediction using early-stage images and seed information. First, each original image is segmented into plant and soil categories. Two vision transformer (ViT) modules are designed to extract features from each category. Then a transformer module is established to deal with the time-series features. Finally, the image features and seed features are combined to estimate the yield. A case study has been conducted using a dataset that was collected during the 2020 soybean-growing seasons in Canadian fields. Compared with other baseline models, the proposed method can reduce the prediction error by more than 40%. The impact of seed information on predictions is studied both between models and within a single model. The results show that the influence of seed information varies among different plots but it is particularly important for the prediction of low yields.
Diversity of retromer-mediated vesicular trafficking pathways in plants
Authors: Jha Suryatapa Ghosh , Larson Emily R.
Published: June 2023

The plant endomembrane system is organized and regulated by large gene families that encode proteins responsible for the spatiotemporal delivery and retrieval of cargo throughout the cell and to and from the plasma membrane. Many of these regulatory molecules form functional complexes like the SNAREs, exocyst, and retromer, which are required for the delivery, recycling, and degradation pathways of cellular components. The functions of these complexes are well conserved in eukaryotes, but the extreme expansion of the protein subunit families in plants suggests that plant cells require more regulatory specialization when compared with other eukaryotes. The retromer is associated with retrograde sorting and trafficking of protein cargo back towards the TGN and vacuole in plants, while in animals, there is new evidence that the VPS26C ortholog is associated with recycling or ‘retrieving’ proteins back to the PM from the endosomes. The human VPS26C was shown to rescue vps26c mutant phenotypes in Arabidopsis thaliana, suggesting that the retriever function could be conserved in plants. This switch from retromer to retriever function may be associated with core complexes that include the VPS26C subunit in plants, similar to what has been suggested in other eukaryotic systems. We review what is known about retromer function in light of recent findings on functional diversity and specialization of the retromer complex in plants.
Pollination, pollen tube growth, and fertilization independently contribute to fruit set and development in tomato
Authors: Tran Long T. , Sugimoto Koichi , Kasozi Michael , Mitalo Oscar W. , Ezura Hiroshi
Published: June 2023

In flowering plants, pollination, pollen tube growth, and fertilization are regarded as the first hierarchical processes of producing offspring. However, their independent contributions to fruit set and development remain unclear. In this study, we examined the effect of three different types of pollen, intact pollen (IP), soft X-ray-treated pollen (XP) and dead pollen (DP), on pollen tube growth, fruit development and gene expression in “Micro-Tom” tomato. Normal germination and pollen tube growth were observed in flowers pollinated with IP; pollen tubes started to penetrate the ovary at 9 h after pollination, and full penetration was achieved after 24 h (IP24h), resulting in ~94% fruit set. At earlier time points (3 and 6 h after pollination; IP3h and IP6h, respectively), pollen tubes were still in the style, and no fruit set was observed. Flowers pollinated with XP followed by style removal after 24 h (XP24h) also demonstrated regular pollen tubes and produced parthenocarpic fruits with ~78% fruit set. As expected, DP could not germinate and failed to activate fruit formation. Histological analysis of the ovary at 2 days after anthesis (DAA) revealed that IP and XP comparably increased cell layers and cell size; however, mature fruits derived from XP were significantly smaller than those derived from IP. Furthermore, there was a high correlation between seed number and fruit size in fruit derived from IP, illustrating the crucial role of fertilization in the latter stages of fruit development. RNA-Seq analysis was carried out in ovaries derived from IP6h, IP24h, XP24h and DP24h in comparison with emasculated and unpollinated ovaries (E) at 2 DAA. The results revealed that 65 genes were differentially expressed (DE) in IP6h ovaries; these genes were closely associated with cell cycle dormancy release pathways. Conversely, 5062 and 4383 DE genes were obtained in IP24h and XP24h ovaries, respectively; top enriched terms were mostly associated with cell division and expansion in addition to the ‘plant hormone signal transduction’ pathway. These findings indicate that full penetration of pollen tubes can initiate fruit set and development independently of fertilization, most likely by activating the expression of genes regulating cell division and expansion.
Integrated transcriptomics and metabolomics analysis provide insight into the resistance response of rice against brown planthopper
Authors: Shi Shaojie , Zha Wenjun , Yu Xinying , Wu Yan , Li Sanhe , Xu Huashan , Li Peide , Li Changyan , Liu Kai , Chen Junxiao , Yang Guocai , Chen Zhijun , Wu Bian , Wan Bingliang , Liu Kai , Zhou Lei , You Aiqing
Published: June 2023

Introduction

The brown planthopper (Nilaparvata lugens Stål, BPH) is one of the most economically significant pests of rice. The Bph30 gene has been successfully cloned and conferred rice with broad-spectrum resistance to BPH. However, the molecular mechanisms by which Bph30 enhances resistance to BPH remain poorly understood.

Methods

Here, we conducted a transcriptomic and metabolomic analysis of Bph30-transgenic (BPH30T) and BPH-susceptible Nipponbare plants to elucidate the response of Bph30 to BPH infestation.

Results

Transcriptomic analyses revealed that the pathway of plant hormone signal transduction enriched exclusively in Nipponbare, and the greatest number of differentially expressed genes (DEGs) were involved in indole 3-acetic acid (IAA) signal transduction. Analysis of differentially accumulated metabolites (DAMs) revealed that DAMs involved in the amino acids and derivatives category were down-regulated in BPH30T plants following BPH feeding, and the great majority of DAMs in flavonoids category displayed the trend of increasing in BPH30T plants; the opposite pattern was observed in Nipponbare plants. Combined transcriptomics and metabolomics analysis revealed that the pathways of amino acids biosynthesis, plant hormone signal transduction, phenylpropanoid biosynthesis and flavonoid biosynthesis were enriched. The content of IAA significantly decreased in BPH30T plants following BPH feeding, and the content of IAA remained unchanged in Nipponbare. The exogenous application of IAA weakened the BPH resistance conferred by Bph30.

Discussion

Our results indicated that Bph30 might coordinate the movement of primary and secondary metabolites and hormones in plants via the shikimate pathway to enhance the resistance of rice to BPH. Our results have important reference significance for the resistance mechanisms analysis and the efficient utilization of major BPH-resistance genes.
StMAPK1 functions as a thermos-tolerant gene in regulating heat stress tolerance in potato (Solanum tuberosum)
Authors: Zhu Xi , Duan Huimin , Zhang Guodong , Jin Hui , Xu Chao , Chen Shu , Zhou Chuanmeng , Chen Zhuo , Tang Jinghua , Zhang Yu
Published: June 2023

Background and aims

Mitogen-activated protein kinases (MAPKs) have been reported to respond to various stimuli including heat stress. This research aimed to investigate whether StMAPK1 is implicated in the transduction of the heat stress signal to adapt heat stress as a thermos-tolerant gene.

Materials and methods

Potato plants were cultivated under mild (30°C) and acute (35°C) heat stress conditions to analyze mRNA expression of StMAPKs and physiological indicators. StMAPK1 was up-regulated and down-regulated by transfection. Subcellular localization of StMAPK1 protein was observed by fluorescence microscope. The transgenic potato plants were assayed for physiological indexes, photosynthesis, cellular membrane integrity, and heat stress response gene expression.

Results

Heat stress altered the expression prolife of StMAPKs. StMAPK1 overexpression changed the physiological characteristics and phenotypes of potato plants under heat stresses. StMAPK1 mediates photosynthesis and maintains membrane integrity of potato plants in response to heat stress. Stress response genes (StP5CS, StCAT, StSOD, and StPOD) in potato plants were altered by StMAPK1 dysregulation. mRNA expression of heat stress genes (StHSP90, StHSP70, StHSP20, and StHSFA3) was affected by StMAPK1.

Conclusions

StMAPK1 overexpression increases the heat-tolerant capacity of potato plants at the morphological, physiological, molecular, and genetic levels.
Mental health problems in unaccompanied young refugees and the impact of post-flight factors on PTSS, depression and anxiety–A secondary analysis of the Better Care study
Authors: Hornfeck Fabienne , Eglinsky Jenny , Garbade Maike , Rosner Rita , Kindler Heinz , Pfeiffer Elisa , Sachser Cedric
Published: June 2023

Background

Unaccompanied young refugees (UYRs) show elevated levels of mental distress such as post-traumatic stress symptoms (PTSS), depression, and anxiety. The individual post-arrival situation in the host country plays an important role in increasing or reducing mental health risks for these vulnerable children and youth. The study aims at examining the impact of pre- and post-migration factors on the mental health of UYRs.

Methods

A cross-sectional survey of N = 131 young refugees (81.7% male, M = 16.9 years old) was conducted in 22 children and youth welfare service (CYWS) facilities in Germany. The participants provided information about pre- and post-flight experiences. Standardized measures were used to assess post-traumatic stress symptoms (CATS-2), symptoms of depression (PHQ-9), and anxiety (GAD-7). Daily stressors were assessed with the Daily Stressors Scale for Young Refugees (DSSYR), sociocultural adaptation with the Brief Sociocultural Adaptation Scale (BSAS), satisfaction with social support with the Social Support Questionnaire (SSQ6-G).

Results

Our results demonstrated clinical levels of PTSS in 42.0% of the participants, depression in 29.0%, and anxiety in 21.4%. Hierarchical regression analyses revealed that a higher number of traumatic events and social daily stressors predicted higher levels in all three domains of mental health problems. PTSS and anxiety were also predicted by the distress related to the residence status, depressive symptoms were additionally predicted by sociocultural adaptation, less family contact and length of stay. The satisfaction with social support was not a significant predictor in the regression models.

Conclusion

Unaccompanied young refugees in CYWS facilities are a highly vulnerable population. As traumatic events, daily stressors and level of contact to family directly impacted UYRs mental health, interventions should be trauma-focused, but also contain modules on how to cope with daily stressors. On the policy and practical level, stakeholders in host countries are called for establishing measures to reduce post-migration stressors and enhance support for UYRs on all levels.
A phase 1/2 trial to assess safety and efficacy of a vaporized 5-methoxy-N,N-dimethyltryptamine formulation (GH001) in patients with treatment-resistant depression
Authors: Reckweg Johannes T. , van Leeuwen Cees J. , Henquet Cécile , van Amelsvoort Therese , Theunissen Eef L. , Mason Natasha L. , Paci Riccardo , Terwey Theis H. , Ramaekers Johannes G.
Published: June 2023

Background

Treatment-resistant depression (TRD) is a substantial public health burden, but current treatments have limited effectiveness. The aim was to investigate the safety and potential antidepressant effects of the serotonergic psychedelic drug 5-MeO-DMT in a vaporized formulation (GH001) in adult patients with TRD.

Methods

The Phase 1 part (n = 8) of the trial investigated two single dose levels of GH001 (12 mg, 18 mg) with a primary endpoint of safety, and the Phase 2 part (n = 8) investigated an individualized dosing regimen (IDR) with up to three increasing doses of GH001 (6 mg, 12 mg, and 18 mg) within a single day, with a primary endpoint of efficacy, as assessed by the proportion of patients in remission (MADRS ≤ 10) on day 7.

Results

Administration of GH001 via inhalation was well tolerated. The proportion of patients in remission (MADRS ≤ 10) at day 7 was 2/4 (50%) and 1/4 (25%) in the 12 mg and 18 mg groups of Phase 1, respectively, and 7/8 (87.5%) in the IDR group of Phase 2, meeting its primary endpoint (p < 0.0001). All remissions were observed from day 1, with 6/10 remissions observed from 2 h. The mean MADRS change from baseline to day 7 was −21.0 (−65%) and − 12.5 (−40%) for the 12 and 18 mg groups, respectively, and − 24.4 (−76%) for the IDR.

Conclusion

Administration of GH001 to a cohort of 16 patients with TRD was well tolerated and provided potent and ultra-rapid antidepressant effects. Individualized dosing with up to three doses of GH001 on a single day was superior to single dose administration.

Clinical Trial registration: Clinicaltrials.gov Identifier NCT04698603.