bluuebunny/crossref_metadata_2025 huggingface dataset:
Nivolumab-induced diabetes mellitus—a case report with literature review of the treatment options
Authors: Daetwyler Eveline , Zippelius Alfred , Danioth Simona , Donath Marc Y. , Gut Lara
Published: October 2023

Background

Immune checkpoint inhibitor (ICI) treatment has become important for treating various cancer types, including metastatic renal cell carcinoma. However, ICI treatment can lead to endocrine immune-related adverse events (irAEs) by overstimulating the patient’s immune system. Here, we report a rare case of a new onset of diabetes mellitus (DM), caused by nivolumab, and we discuss the feasible treatment options with a focus on TNF antagonism.

Case presentation

A 50-year-old man was diagnosed with metastatic renal cell carcinoma. Due to systemic progression, a combined immunotherapy with ipilimumab and nivolumab was initiated, according to the current study protocol (SAKK 07/17). The administration of ipilimumab was stopped after 10 months, due to partial response as seen in the computer tomography (CT), and nivolumab was continued as monotherapy. Fourteen months after the start of the treatment, the patient was admitted to the emergency department with lethargy, vomiting, blurred vision, polydipsia, and polyuria. The diagnosis of DM with diabetic ketoacidosis was established, although autoantibodies to β-cells were not detectable. Intravenous fluids and insulin infusion treatment were immediately initiated with switching to a subcutaneous administration after 1 day. In addition, the patient received an infusion of the TNF inhibitor infliximab 4 days and 2 weeks after the initial diagnosis of DM. However, the C-peptide values remained low, indicating a sustained insulin deficiency, and the patient remained on basal bolus insulin treatment. Two months later, nivolumab treatment was restarted without destabilization of the diabetic situation.

Conclusions

In contrast to the treatment of other irAEs, the administration of corticosteroids is not recommended in ICI-induced DM. The options for further treatment are mainly based on the low numbers of case series and case reports. In our case, the administration of infliximab—in an attempt to salvage the function of β-cells—was not successful, and this is in contrast to some previous reports. This apparent discrepancy may be explained by the absence of insulin resistance in our case. There is so far no evidence for immunosuppressive treatment in this situation. Prompt recognition and immediate start of insulin treatment are most important in its management.
Clonal redemption of B cells in cancer
Authors: McCaw Tyler R. , Lofftus Serena Y. , Crompton Joseph G.
Published: October 2023

Potentially self-reactive B cells constitute a large portion of the peripheral B cell repertoire in both mice and humans. Maintenance of autoreactive B cell populations could conceivably be detrimental to the host but their conservation throughout evolution suggests performance of a critical and beneficial immune function. We discuss herein how the process of clonal redemption may provide insight to preservation of an autoreactive B cell pool in the context of infection and autoimmunity. Clonal redemption refers to additional recombination or hypermutation events decreasing affinity for self-antigen, while increasing affinity for foreign antigens. We then review findings in murine models and human patients to consider whether clonal redemption may be able to provide tumor antigen-specific B cells and how this may or may not predispose patients to autoimmunity.
Comparison of peripheral leukocyte parameters in patients receiving conventionally and hypofractionated radiotherapy schemes for the treatment of newly diagnosed glioblastoma
Authors: Greenlund Lindsey , Shanley Ryan , Mulford Kellen , Neil Elizabeth C. , Lawrence Jessica , Arnold Susan , Olin Michael , Pluhar G. Elizabeth , Venteicher Andrew S. , Chen Clark C. , Ferreira Clara , Reynolds Margaret , Cho L. Chinsoo , Wilke Christopher , Shoo B. Aika , Yuan Jianling , Dusenbery Kathryn , Kleinberg Lawrence R. , Terezakis Stephanie A. , Sloan Lindsey
Published: October 2023

Introduction

Treatment for glioblastomas, aggressive and nearly uniformly fatal brain tumors, provide limited long-term success. Immunosuppression by myeloid cells in both the tumor microenvironment and systemic circulation are believed to contribute to this treatment resistance. Standard multi-modality therapy includes conventionally fractionated radiotherapy over 6 weeks; however, hypofractionated radiotherapy over 3 weeks or less may be appropriate for older patients or populations with poor performance status. Lymphocyte concentration changes have been reported in patients with glioblastoma; however, monocytes are likely a key cell type contributing to immunosuppression in glioblastoma. Peripheral monocyte concentration changes in patients receiving commonly employed radiation fractionation schemes are unknown.

Methods

To determine the effect of conventionally fractionated and hypofractionated radiotherapy on complete blood cell leukocyte parameters, retrospective longitudinal concentrations were compared prior to, during, and following standard chemoradiation treatment.

Results

This study is the first to report increased monocyte concentrations and decreased lymphocyte concentrations in patients treated with conventionally fractionated radiotherapy compared to hypofractionated radiotherapy.

Discussion

Understanding the impact of fractionation on peripheral blood leukocytes is important to inform selection of dose fractionation schemes for patients receiving radiotherapy.
Charge-controlled swelling gradients at 200-µm resolution in an open-porous polymeric structure for compliance modulation
Authors: Sarokin Yauheni , Aabloo Alvo , Must Indrek
Published: October 2023

Plants combine active and passive liquid-mediated mechanisms across broad spatial and temporal scales, inspiring technological developments, in particular involving variable stiffness. Swelling is of particular interest due to the abundance of plant models and applicable (bio)materials, yet existing control by environmental humidity sorption limits its applications. This work combined swellable polymeric structures with electroactive control: we considered an open-porous polymeric laminate that hosted an electrokinetic medium also co-acting as a swelling agent for the same polymer. A constant volume of liquid (an electrolytic solution) was electrokinetically pumped between the symmetrical laminate’s interior and surface layers: as the second moment of inertia increases from the centre to the surface, the pumping of liquid towards the surface decreases the laminate’s bending stiffness, and vice versa. Ion electrosorption on high-specific-surface-area carbon electrodes, deposited in three layers in the laminate by simple additive spraying, facilitated the ion current necessary for the electrokinetic pumping. Flexural rigidity of the 400 µm thick laminate varied by 7% in response to 2-V input, evidencing swelling gradients forming at half-laminate (i.e., 200-µm) resolution. Charge-driven local rearrangement of liquid allows for broader adoption of bioinspired (and biological) porous architectures, where the channels are defined collectively, not individually as in, e.g., soft lithography. Sub-mm resolution and low-voltage control of liquid offer a high level of integration at minimal assembly, positioning active swelling as a promising solution for wearable and bioinspired soft robotic applications.
Small but mighty: unlocking the catalytic power of individual iridium atoms on titanium oxide
Authors: Molina-Torres Mariana , Hernández-Cristóbal Orlando , Mendoza-Cruz Ruben
Published: October 2023

Graphical Abstract

Ir catalyst supported by TiO2.
E2VIDX: improved bridge between conventional vision and bionic vision
Authors: Hou Xujia , Zhang Feihu , Gulati Dhiraj , Tan Tingfeng , Zhang Wei
Published: October 2023

Common RGBD, CMOS, and CCD-based cameras produce motion blur and incorrect exposure under high-speed and improper lighting conditions. According to the bionic principle, the event camera developed has the advantages of low delay, high dynamic range, and no motion blur. However, due to its unique data representation, it encounters significant obstacles in practical applications. The image reconstruction algorithm based on an event camera solves the problem by converting a series of “events” into common frames to apply existing vision algorithms. Due to the rapid development of neural networks, this field has made significant breakthroughs in past few years. Based on the most popular Events-to-Video (E2VID) method, this study designs a new network called E2VIDX. The proposed network includes group convolution and sub-pixel convolution, which not only achieves better feature fusion but also the network model size is reduced by 25%. Futhermore, we propose a new loss function. The loss function is divided into two parts, first part calculates the high level features and the second part calculates the low level features of the reconstructed image. The experimental results clearly outperform against the state-of-the-art method. Compared with the original method, Structural Similarity (SSIM) increases by 1.3%, Learned Perceptual Image Patch Similarity (LPIPS) decreases by 1.7%, Mean Squared Error (MSE) decreases by 2.5%, and it runs faster on GPU and CPU. Additionally, we evaluate the results of E2VIDX with application to image classification, object detection, and instance segmentation. The experiments show that conversions using our method can help event cameras directly apply existing vision algorithms in most scenarios.
Phenotypic maps for precision medicine: a promising systems biology tool for assessing therapy response and resistance at a personalized level
Authors: Bhattacharyya Sayantan , Ehsan Shafqat F. , Karacosta Loukia G.
Published: October 2023

In this perspective we discuss how tumor heterogeneity and therapy resistance necessitate a focus on more personalized approaches, prompting a shift toward precision medicine. At the heart of the shift towards personalized medicine, omics-driven systems biology becomes a driving force as it leverages high-throughput technologies and novel bioinformatics tools. These enable the creation of systems-based maps, providing a comprehensive view of individual tumor’s functional plasticity. We highlight the innovative PHENOSTAMP program, which leverages high-dimensional data to construct a visually intuitive and user-friendly map. This map was created to encapsulate complex transitional states in cancer cells, such as Epithelial-Mesenchymal Transition (EMT) and Mesenchymal-Epithelial Transition (MET), offering a visually intuitive way to understand disease progression and therapeutic responses at single-cell resolution in relation to EMT-related single-cell phenotypes. Most importantly, PHENOSTAMP functions as a reference map, which allows researchers and clinicians to assess one clinical specimen at a time in relation to their phenotypic heterogeneity, setting the foundation on constructing phenotypic maps for personalized medicine. This perspective argues that such dynamic predictive maps could also catalyze the development of personalized cancer treatment. They hold the potential to transform our understanding of cancer biology, providing a foundation for a future where therapy is tailored to each patient’s unique molecular and cellular tumor profile. As our knowledge of cancer expands, these maps can be continually refined, ensuring they remain a valuable tool in precision oncology.
Case series: Intraoperative neuromonitoring and angiography in the surgical treatment of vascular malformations
Authors: Šmigoc Tomaž , Kozorog Ninna , Ravnik Janez
Published: October 2023

In the surgical treatment of cerebral vascular malformations, e.g., aneurysms and arteriovenous malformations, the risk of ischemic complications is 6.7%, and a residual aneurysm is possible in 5.2% of these cases. Ischemic lesions can result in permanent neurological deficits, and a residual aneurysm can lead to the recurrence of the aneurysm in 2% of cases. In this article, we present five cases (two cases of ruptured aneurysms, two cases of non-ruptured aneurysms, and a case of arteriovenous malformation) in which we reduced the aforementioned risks with the use of intraoperative neuromonitoring and angiography. Intraoperative neuromonitoring (IONM) is used to measure motor and sensory-evoked potentials to detect brain hypoperfusion. Intraoperative angiography with the dye indocyanine green (ICG-A), which fluoresces in a vessel under a microscope after intravenous administration, helps to identify residual aneurysm sacs and distal blood flow. With the use of IONM and ICG-A, we identified abnormalities and adjusted our interventions and treatments. IONM and ICG-A can lead to a better outcome after surgical treatment of cerebral vascular abnormalities.
Visualizing interferential stimulation of human brains
Authors: Huang Yu
Published: October 2023

Introduction

Transcranial electrical stimulation (TES) is limited in focally stimulating deep-brain regions, even with optimized stimulation montages. Recently, interferential stimulation (IFS), also known as transcranial temporal interference stimulation (TI, TIS, or tTIS), has drawn much attention in the TES community as both computational and experimental studies show that IFS can reach deep-brain areas. However, the underlying electrodynamics of IFS is complicated and difficult to visualize. Existing literature only shows static visualization of the interfered electric field induced by IFS. These could result in a simplified understanding that there is always one static focal spot between the two pairs of stimulation electrodes. This static visualization can be frequently found in the IFS literature. Here, we aimed to systematically visualize the entire dynamics of IFS.

Methods and results

Following the previous study, the lead field was solved for the MNI-152 head, and optimal montages using either two pairs of electrodes or two arrays of electrodes were found to stimulate a deep-brain region close to the left striatum with the highest possible focality. We then visualized the two stimulating electrical currents injected with similar frequencies. We animated the instant electric field vector at the target and one exemplary off-target location both in 3D space and as a 2D Lissajous curve. We finally visualized the distribution of the interfered electric field and the amplitude modulation envelope at an axial slice going through the target location. These two quantities were visualized in two directions: radial-in and posterior–anterior.

Discussion

We hope that with intuitive visualization, this study can contribute as an educational resource to the community’s understanding of IFS as a powerful modality for non-invasive focal deep-brain stimulation.
Prefrontal cortical hemodynamics and functional network organization during Tai Chi standing meditation: an fNIRS study
Authors: Qi Liping , Wang Guo-Liang , Tian Zhi-Hao , Guan Shuo , Yang Shu-Ye , Yang Yu-Long , Liu Li-Qing , Lin Yong-Zhong
Published: October 2023

Introduction

Tai Chi standing meditation (Zhan Zhuang, also called pile standing) is characterized by meditation, deep breathing, and mental focus based on theories of traditional Chinese medicine. The purpose of the present study was to explore prefrontal cortical hemodynamics and the functional network organization associated with Tai Chi standing meditation by using functional near-infrared spectroscopy (fNIRS).

Methods

Twenty-four channel fNIRS signals were recorded from 24 male Tai Chi Quan practitioners (54.71 ± 8.04 years) while standing at rest and standing during Tai Chi meditation. The general linear model and the SPM method were used to analyze the fNIRS signals. Pearson correlation was calculated to determine the functional connectivity between the prefrontal cortical sub-regions. The small world properties of the FC networks were then further analyzed based on graph theory.

Results

During Tai Chi standing meditation, significantly higher concentrations of oxygenated hemoglobin were observed in bilateral dorsolateral prefrontal cortex (DLPFC), ventrolateral prefrontal cortex (VLPFC), frontal eye field (FEF), and pre-motor cortex (PMC) compared with the values measured during standing rest (p < 0.05). Simultaneously, significant decreases in deoxygenated hemoglobin concentration were observed in left VLPFC, right PMC and DLPFC during Tai Chi standing meditation than during standing rest (p < 0.05). Functional connectivity between the left and right PFC was also significantly stronger during the Tai Chi standing meditation (p < 0.05). The functional brain networks exhibited small-world architecture, and more network hubs located in DLPFC and VLPFC were identified during Tai Chi standing meditation than during standing rest.

Discussion

These findings suggest that Tai Chi standing meditation introduces significant changes in the cortical blood flow and the brain functional network organization.
SARS-CoV-2 seroprevalence in French 9-year-old children and their parents after the first lockdown in 2020
Authors: Charles Marie Aline , Ancel Pierre-Yves , Simeon Thierry , Marchand-Martin Laetitia , Zaros Cécile , Dufourg Marie-Noelle , Benhamou Valérie , Blanché Hélène , Deleuze Jean-François , Rahib Delphine , Lydie Nathalie , de Lamballerie Xavier , Carrat Fabrice
Published: October 2023

Introduction

Children have been significantly less affected by COVID-19 than adults and presented with milder and less symptomatic forms of the disease. However, there has been suggestion that children older than 10 years and adolescents exhibits features closer to that of young adults. Most studies combine children in different age-groups and lack sufficient numbers to explore in detail age specificities. We report data on a population-based sample of 2,555 children at the pivotal age of 9 years.

Methods

In April 2020, the participants in two French nationwide cohorts of children, Elfe and Epipage2, were invited to take part into an online survey about Covid related symptoms and family life during the lockdown. A second questionnaire was sent on May 5. This questionnaire also proposed to the child included in the cohort and to one of his/her parents to take part into a capillary blood collection for Covid serology. Families who agreed to the serological survey were sent kits for dried blood spots self-sampling (DBS) with instructions. Samples were processed with a commercial Elisa test (Euroimmun®, Lübeck, Germany) to detect anti-SARS-CoV-2 antibodies (IgG) directed against the S1 domain of the spike protein of the virus.

Results

Children's acceptance rate for the serological survey was around 60%. 2,555 serological results were analyzed. The weighted prevalence of a positive Elisa Spike serology was 2.8% in 9 yr-old children (95% CI: 1.7%–4.0%). Positive serology was found in 8.6% (7.4%–9.7%) of parents who provided blood. There was a significant association (p < 0.001) between serology of the child and parent from the same household with an odds ratio of 13.8 (7.9–24.2).

Discussion

We have shown that 9-yr old children had a lower susceptibility to SARS-Cov2 infection than adults with the initial Chinese strain, similar to younger children and estimated that around 3% of them have developed antibodies against SARS-Cov2 in France after the first wave of the Covid-19 epidemics.
Outbreak investigation of acute febrile illness from the Himalayan foothills: Solving the puzzle of fever
Authors: Satapathy Prakasini , Goel Kapil , Sharma Vikrant , Sarkar Subhabrata , Kang Mannat , Dhingra Shefali , Bora Ishani , Kaur Kanwalpreet , Arora Neeraj , Aggarwal Arun , Ratho Radha Kanta
Published: October 2023

In September 2022, Panchkula Civil Hospital reported an outbreak of acute febrile illness (AFI) in Pinjore, located in the Himalayan foothills, Haryana, North India. There was an upsurge of fever cases. Blood samples were taken from suspected patients (n = 58) with AFI and subjected to serology of dengue, chikungunya, Japanese encephalitis, leptospira and scrub typhus. The samples were also screened for West Nile & Zika virus RNA using real-time PCR. Viral strains were characterized by sequencing. Of the 58 cases of AFI, Dengue could be identified in 45 (77.58%) followed by JE and Chikungunya in 2 cases each (3.44%), respectively. Among Dengue positive cases, 44 had monoinfection (97.77%) and 1 patient had dengue and JE. None were positive for Zika, West Nile, Scrub typhus, and Leptospira with the testing protocol. Four patients developed dengue with warning signs, such as abdominal pain in one patient and recurrent vomiting in the remaining three. The dengue serotype could be determined in 17 samples and revealed serotype 2. Molecular evolution analysis based on the complete envelope gene revealed that all DENV-2 strains (n = 13) circulated in the outbreak area belonged to the DENV-2 cosmopoliton genotype. In the early stages of infection, relying only on clinical manifestations is ineffective, so both molecular and serological assays along with clinical diagnosis are noteworthy for determining the aetiology of AFI.
A pharmacovigilance study of etoposide in the FDA adverse event reporting system (FAERS) database, what does the real world say?
Authors: Cui Zhiwei , Cheng Feiyan , Wang Lihui , Zou Fan , Pan Rumeng , Tian Yuhan , Zhang Xiyuan , She Jing , Zhang Yidan , Yang Xinyuan
Published: October 2023

Introduction: Etoposide is a broad-spectrum antitumor drug that has been extensively studied in clinical trials. However, limited information is available regarding its real-world adverse reactions. Therefore, this study aimed to assess and evaluate etoposide-related adverse events in a real-world setting by using data mining method on the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database.

Methods: Through the analysis of 16,134,686 reports in the FAERS database, a total of 9,892 reports of etoposide-related adverse drug events (ADEs) were identified. To determine the significance of these ADEs, various disproportionality analysis algorithms were applied, including the reporting odds ratio (ROR), the proportional reporting ratio (PRR), the Bayesian confidence propagation neural network (BCPNN), and the multi-item gamma Poisson shrinker (MGPS) algorithms.

Results: As a result, 478 significant disproportionality preferred terms (PTs) that were identified by all four algorithms were retained. These PTs included commonly reported adverse events such as thrombocytopenia, leukopenia, anemia, stomatitis, and pneumonitis, which align with those documented in the drug’s instructions and previous clinical trials. However, our analysis also uncovered unexpected and significant ADEs, including thrombotic microangiopathy, ototoxicity, second primary malignancy, nephropathy toxic, and ovarian failure. Furthermore, we examined the time-to-onset (TTO) of these ADEs using the Weibull distribution test and found that the median TTO for etoposide-associated ADEs was 10 days (interquartile range [IQR] 2–32 days). The majority of cases occurred within the first month (73.8%) after etoposide administration. Additionally, our analysis revealed specific high-risk signals for males, such as pneumonia and cardiac infarction, while females showed signals for drug resistance and ototoxicity.

Discussion: These findings provide valuable insight into the occurrence of ADEs following etoposide initiation, which can potentially support clinical monitoring and risk identification efforts.
Current drugs for HIV-1: from challenges to potential in HIV/AIDS
Authors: Peng Yuan , Zong Yanjun , Wang Dongfeng , Chen Junbing , Chen Zhe-Sheng , Peng Fujun , Liu Zhijun
Published: October 2023

The human immunodeficiency virus (HIV) persists in latently infected CD4+T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (ACC008) are described. It is interestingly to note that the lack of the multipass transmembrane proteins serine incorporator 3 (SERINC3) and the multipass transmembrane proteins serine incorporator 5 (SERINC5) may be one of the reasons for the enhanced infectivity of HIV-1. This discovery of SERINC3 and SERINC5 provides new ideas for HIV-1 medication development. Therefore, we believe that in treating AIDS, antiviral medications should be rationally selected for pre-exposure and post-exposure prophylaxis to avoid the emergence of drug resistance. Attention should be paid to the research and development of new drugs to predict HIV mutations as accurately as possible and to develop immune antibodies to provide multiple guarantees for the cure of AIDS.
The impact of a maternal and offspring obesogenic diet on daughter’s oocyte mitochondrial ultrastructure and bioenergetic responses. Insights from an outbred mouse model
Authors: Xhonneux Inne , Marei Waleed F. A. , Meulders Ben , Andries Silke , Leroy Jo L. M. R.
Published: October 2023

Obesity affects oocyte mitochondrial functions and reduces oocyte quality and fertility. Obesity may also increase the risk of metabolic disorders in the offspring. Children are likely to follow their parents lifestyle and diet, which also contributes to the increased prevelance of obesity across generations. We hypothesise that the impact of obesogenic (OB) diet and obesity on oocyte mitochondrial functions is different in offspring born to obese mothers compared to those born to healthy mothers. To test this hypothesis, we fed a control (C, 10% fat, 7% sugar) or an OB diet (60% fat, 20% sugar) to female mice (for 7 weeks (w)) and then to their female offspring (for 7w after weaning) in a 2 × 2 factorial design (C » C, n = 35, C » OB, n = 35, OB » C n = 49 and OB » OB, n = 50). Unlike many other studies, we used an outbred Swiss mouse model to increase the human pathophysiological relevance. Offspring were sacrificed at 10w and their oocytes were collected. Offspring OB diet increased oocyte lipid droplet content, mitochondrial activity and reactive oxygen species (ROS) levels, altered mitochondrial ultrastructure and reduced oocyte pyruvate consumption. Mitochondrial DNA copy numbers and lactate production remained unaffected. Mitochondrial ultrastructure was the only factor where a significant interaction between maternal and offspring diet effect was detected. The maternal OB background resulted in a small but significant increase in offspring’s oocyte mitochondrial ultrastructural abnormalities without altering mitochondrial inner membrane potential, active mitochondrial distribution, mitochondrial DNA copy numbers, or ROS production. This was associated with reduced mitochondrial complex III and V expression and reduced pyruvate consumption which may be compensatory mechanisms to control mitochondrial inner membrane potential and ROS levels. Therefore, in this Swiss outbred model, while offspring OB diet had the largest functional impact on oocyte mitochondrial features, the mitochondrial changes due to the maternal background appear to be adaptive and compensatory rather than dysfunctional.
Genome-wide association studies using multi-models and multi-SNP datasets provide new insights into pasmo resistance in flax
Authors: He Liqiang , Sui Yao , Che Yanru , Wang Huixian , Rashid Khalid Y. , Cloutier Sylvie , You Frank M.
Published: October 2023

Introduction

Flax (Linum usitatissimum L.) is an economically important crop due to its oil and fiber. However, it is prone to various diseases, including pasmo caused by the fungus Septoria linicola.

Methods

In this study, we conducted field evaluations of 445 flax accessions over a five-year period (2012–2016) to assess their resistance to pasmo A total of 246,035 single nucleotide polymorphisms (SNPs) were used for genetic analysis. Four statistical models, including the single-locus model GEMMA and the multi-locus models FarmCPU, mrMLM, and 3VmrMLM, were assessed to identify quantitative trait nucleotides (QTNs) associated with pasmo resistance.

Results

We identified 372 significant QTNs or 132 tag QTNs associated with pasmo resistance from five pasmo resistance datasets (PAS2012–PAS2016 and the 5-year average, namely PASmean) and three genotypic datasets (the all SNPs/ALL, the gene-based SNPs/GB and the RGA-based SNPs/RGAB). The tag QTNs had R2 values of 0.66–16.98% from the ALL SNP dataset, 0.68–20.54%from the GB SNP dataset, and 0.52–22.42% from the RGAB SNP dataset. Of these tag QTNs, 93 were novel. Additionally, 37 resistance gene analogs (RGAs)co-localizing with 39 tag QTNs were considered as potential candidates for controlling pasmo resistance in flax and 50 QTN-by-environment interactions(QEIs) were identified to account for genes by environmental interactions. Nine RGAs were predicted as candidate genes for ten QEIs.

Discussion

Our results suggest that pasmo resistance in flax is polygenic and potentially influenced by environmental factors. The identified QTNs provide potential targets for improving pasmo resistance in flax breeding programs. This study sheds light on the genetic basis of pasmo resistance and highlights the importance of considering both genetic and environmental factors in breeding programs for flax.
Two related families of metal transferases, ZNG1 and ZNG2, are involved in acclimation to poor Zn nutrition in Arabidopsis
Authors: Zhang Lifang , Braynen Janeen , Fahey Audrey , Chopra Kriti , Cifani Paolo , Tadesse Dimiru , Regulski Michael , Hu Fangle , van Dam Hubertus J. J. , Xie Meng , Ware Doreen , Blaby-Haas Crysten E.
Published: October 2023

Metal homeostasis has evolved to tightly modulate the availability of metals within the cell, avoiding cytotoxic interactions due to excess and protein inactivity due to deficiency. Even in the presence of homeostatic processes, however, low bioavailability of these essential metal nutrients in soils can negatively impact crop health and yield. While research has largely focused on how plants assimilate metals, acclimation to metal-limited environments requires a suite of strategies that are not necessarily involved in metal transport across membranes. The identification of these mechanisms provides a new opportunity to improve metal-use efficiency and develop plant foodstuffs with increased concentrations of bioavailable metal nutrients. Here, we investigate the function of two distinct subfamilies of the nucleotide-dependent metallochaperones (NMCs), named ZNG1 and ZNG2, that are found in plants, using Arabidopsis thaliana as a reference organism. AtZNG1 (AT1G26520) is an ortholog of human and fungal ZNG1, and like its previously characterized eukaryotic relatives, localizes to the cytosol and physically interacts with methionine aminopeptidase type I (AtMAP1A). Analysis of AtZNG1, AtMAP1A, AtMAP2A, and AtMAP2B transgenic mutants are consistent with the role of Arabidopsis ZNG1 as a Zn transferase for AtMAP1A, as previously described in yeast and zebrafish. Structural modeling reveals a flexible cysteine-rich loop that we hypothesize enables direct transfer of Zn from AtZNG1 to AtMAP1A during GTP hydrolysis. Based on proteomics and transcriptomics, loss of this ancient and conserved mechanism has pleiotropic consequences impacting the expression of hundreds of genes, including those involved in photosynthesis and vesicle transport. Members of the plant-specific family of NMCs, ZNG2A1 (AT1G80480) and ZNG2A2 (AT1G15730), are also required during Zn deficiency, but their target protein(s) remain to be discovered. RNA-seq analyses reveal wide-ranging impacts across the cell when the genes encoding these plastid-localized NMCs are disrupted.
Non-destructive prediction of isoflavone and starch by hyperspectral imaging and deep learning in Puerariae Thomsonii Radix
Authors: Hu Huiqiang , Wang Tingting , Wei Yunpeng , Xu Zhenyu , Cao Shiyu , Fu Ling , Xu Huaxing , Mao Xiaobo , Huang Luqi
Published: October 2023

Accurate assessment of isoflavone and starch content in Puerariae Thomsonii Radix (PTR) is crucial for ensuring its quality. However, conventional measurement methods often suffer from time-consuming and labor-intensive procedures. In this study, we propose an innovative and efficient approach that harnesses hyperspectral imaging (HSI) technology and deep learning (DL) to predict the content of isoflavones (puerarin, puerarin apioside, daidzin, daidzein) and starch in PTR. Specifically, we develop a one-dimensional convolutional neural network (1DCNN) model and compare its predictive performance with traditional methods, including partial least squares regression (PLSR), support vector regression (SVR), and CatBoost. To optimize the prediction process, we employ various spectral preprocessing techniques and wavelength selection algorithms. Experimental results unequivocally demonstrate the superior performance of the DL model, achieving exceptional performance with mean coefficient of determination (R2) values surpassing 0.9 for all components. This research underscores the potential of integrating HSI technology with DL methods, thereby establishing the feasibility of HSI as an efficient and non-destructive tool for predicting the content of isoflavones and starch in PTR. Moreover, this methodology holds great promise for enhancing efficiency in quality control within the food industry.
Past the Pandemic: a virtual intervention supporting the well-being of healthcare workers through the COVID-19 pandemic
Authors: Millar Amanda M. , Doria Amanda M. , Choi Leslie M. , McGladrey Laura , Duffy Korrina A. , Berkowitz Steven J.
Published: October 2023

To decrease burnout and improve mental health and resiliency among doctors, nurses, and hospital staff during the COVID-19 pandemic, the University of Colorado partnered with ECHO Colorado to offer the state’s healthcare workforce an interactive, psychoeducational, and online intervention that encouraged connection and support. The series utilized the Stress Continuum Model as its underlying conceptual framework. Between July 2020 and February 2022, 495 healthcare workers in Colorado participated in the series across eight cohorts. One-way repeated measures ANOVAs were performed to test for differences in pretest and posttest scores on series’ objectives. Healthcare workers showed significant improvement from pretest to posttest in (1) knowing when and how to obtain mental health resources, F(1, 111) = 46.497, p < 0.001, (2) recognizing of the importance of being socially connected in managing COVID-related stress, F(1, 123) = 111.159, p < 0.001, (3) managing worries, F(1, 123) = 94.941, p < 0.001, (4) feeling prepared to manage stressors related to the pandemic, F(1, 111) = 100.275, p < 0.001, (5) feeling capable in dealing with challenges that occur daily, F(1, 111) = 87.928, p < 0.001, and (6) understanding the Stress Continuum Model F(1, 123) = 271.049, p < 0.001. This virtual series showed efficacy in improving the well-being of healthcare workers during a pandemic and could serve as a model for mental health support for healthcare workers in other emergency response scenarios.
Teaching STEAM in the shaolin staff program: ways to stimulate student engagement in learning
Authors: Chen Haidong , Rao Feixue , Chen Ran , Lin Zhaowei
Published: October 2023

With the advancement of technology and change in education concepts, applying STEAM pedagogy to physical education has become an innovative trend. This study investigates whether physics analysis based on STEAM concepts can increase junior high students’ participation in learning Shaolin Staff. Forty students were randomly assigned to experimental and control groups. The mean and standard deviation of age in the experimental group was 13.95 ± 0.83, and in the control group was 13.85 ± 0.81. The experimental group received STEAM teaching involving physics analysis, while the control group received conventional movement instruction. Student learning engagement was evaluated through questionnaires. Results are expected to show the experimental group being more engaged in learning. Introducing physics analysis may deepen understanding of related principles to movements. The study’s results found that the scores of motivation, attention, and intention to learn independently were significantly higher in the experimental group than in the control group (p < 0.01). The scores of interfering emotions were significantly lower in the experimental group than in the control group (p < 0.01), which verified that the STEAM teaching method could effectively improve learning engagement. This study promotes STEAM education in martial arts and provides insights on utilizing STEAM to boost student engagement.
Factor structure of the brief psychiatric rating scale-expanded among outpatients with psychotic disorders in five Southeast European countries: evidence for five factors
Authors: Bajraktarov Stojan , Blazhevska Stoilkovska Biljana , Russo Manuela , Repišti Selman , Maric Nadja P. , Dzubur Kulenovic Alma , Arënliu Aliriza , Stevovic Lidija Injac , Novotni Ljubisha , Ribic Emina , Konjufca Jon , Ristic Ivan , Novotni Antoni , Jovanovic Nikolina
Published: October 2023

The Brief Psychiatric Rating Scale (BPRS) is a useful tool for measuring the severity of psychopathological symptoms among patients with psychosis. Many studies, predominantly in Western countries, have investigated its factor structure. This study has the following aims: (a) to further explore the factor structure of the BPRS-Expanded version (BPRS-E, 24 items) among outpatients with psychotic disorders in Southeast European countries; (b) to confirm the identified model; and (c) to investigate the goodness-of-fit of the three competing BPRS-E factor models derived from previous studies. The exploratory factor analysis (EFA) produced a solution with 21 items grouped into five factors, thus supporting the existence of a fifth factor, i.e., Disorganization. A follow-up confirmatory factor analysis (CFA) revealed a 19-item model (with two items removed) that fit the data well. In addition, the stability of two out of three competing factor models was confirmed. Finally, the BPRS-E model with 5 factors developed in this cross-national study was found to include a greater number of items compared to competing models.
Relationship of widowhood with pulse pressure, fasting blood glucose, and mental health in older adults: a propensity matching score analysis
Authors: Zhang Yi , Chen Xiangfan , Sun Yimei , Feng Sujuan , Wang Fang , Gu Haiyan , Jia Hanyu , Zhang Quanxing , Ding Wenbin , Lu Hongjian , Zhang Jidong
Published: October 2023

Background

Transitioning from marriage to widowhood presents inevitable and significant challenges for many older adults. This study explored the impact of widowhood on a range of mental health outcomes, including pulse pressure and fasting blood glucose levels, among older adults in nursing homes.

Methods

This cross-sectional study utilized cluster random sampling to recruit participants, with data analyzed from 388 older Chinese adults. Psychosocial traits were assessed using the Perceived Social Support from Family scale (PSS-Fa) for family support, the Generalized Anxiety Disorder 7-item scale (GAD-7) for anxiety symptoms, and the 9-item Patient Health Questionnaire (PHQ-9) for depressive symptoms and suicidal ideation. Propensity score matching (PSM) was employed to control for confounding factors. A multivariate linear regression analysis was performed to explore the relationship between widowhood, mental health outcomes, pulse pressure, and fasting blood glucose levels.

Results

After applying PSM, the sample size was refined to 268 (N = 134 for both married and widowed groups) from the initial 388, excluding 120 unmatched cases. Widowed older adults were found to have notably lower family support (β = −0.81, p = 0.002), increased depressive symptoms (β = 1.04, p = 0.043), elevated pulse pressure (β = 8.90, p < 0.001), and higher fasting blood glucose levels (β = 3.22, p = 0.027). These associations exhibited greater beta values compared to pre-matching analysis.

Conclusion

Our findings revealed that widowed participants had reduced family support, an increased risk of depressive symptoms, heightened pulse pressure, and elevated fasting blood glucose in comparison to their married counterparts. Interventions focusing on social support, mental health, and cardiovascular well-being could be advantageous for this at-risk group.
The occupational burnout among medical staff with high workloads after the COVID-19 and its association with anxiety and depression
Authors: Sun Hao , Zhang Tengfei , Wang Xinyu , Wang Caixia , Zhang Mengqiao , Song Hongjiang
Published: October 2023

Objective

After the end of COVID-19, medical staff were immediately faced with a high workload, leading to widespread occupational burnout. This study aims to explore the level and influencing factors of burnout among medical staff during this period, as well as its relationship with anxiety and depression.

Methods

The participants’ levels of burnout were assessed using Maslach Burnout Inventory-Human Services Survey (MBI-HSS), and the reliability and validity of the questionnaire were evaluated through Cronbach’s α and Confirmatory Factor Analysis (CFA). Independent sample t-test, chi-square test, and Pearson analysis were employed to determine the correlation between two sets of variables. Univariate and multivariate logistic regression analyses were conducted to identify significant factors influencing burnout. Finally, nomograms were used to predict the probability of burnout occurrence.

Results

This study collected a total of 1,550 questionnaires, and after excluding 45 questionnaires that were duplicates or incomplete, a sample of 1,505 (97.1%) participants were included in the final statistical analysis. Both Cronbach’s α and the fit indices of CFA demonstrated excellent adaptability of the Chinese version of MBI-HSS in this study. The overall prevalence rates for emotional exhaustion (EE), depersonalization (DP), and diminished personal accomplishment (PA) were 52.4, 55.3, and 30.6%, respectively. Obtaining psychological support, health condition, relationship with family members, and insufficient sleep were identified as common contributing factors to burnout among medical staff. Additionally, age and promotion pressure were also associated with burnout among doctors, and exceeding legal working hours was an important factor for nurse burnout. The C-index for the nomograms predicting burnout among doctors and nurses was 0.832 and 0.843, respectively. Furthermore, burnout exhibited a significant linear correlation with anxiety and depression.

Conclusion

After the end of COVID-19, medical staff in high workload environments were facing severe burnout, which might lead to anxiety and depression. The occupational burnout of medical staff needed to be taken seriously and actively intervened.
The necessity for enhancing awareness of tuberculosis starting from the early college semesters: empirical evidence from a cross-sectional research
Authors: Chen Xinyi , Peng Ying , Zhou Lin , Wang Fei , Chen Bin , Qu Yan
Published: October 2023

Background

College students, especially those in the lower grades, constitute the main high-risk population for tuberculosis (TB). Insufficient knowledge about TB among college students contributes to an increased risk of TB infection. In Zhejiang Province, China, limited research has been conducted recently on the awareness of TB in schools among college students. Therefore, this study aims to gain insight into TB knowledge among low-grade college students in Zhejiang Province and develop effective strategies for TB education targeted at this specific population.

Methods

A cross-sectional survey was conducted between 1st and 20th May 2022 in 20 colleges in Zhejiang Province, southeastern China. The survey aimed to assess the level of TB awareness among 1st and 2nd-year college students. Chi-square tests were performed to compare the rates, while multivariate logistic regression was used to identify the factors influencing the overall awareness level of students' regarding key knowledge about TB.

Results

A total of 4,414 lower-grade students participated in the study. The total awareness rate and entire awareness rate of key TB knowledge were 81.6 and 25.3%, respectively. Participants who demonstrated a relatively poor understanding of the definition were (51.0%), curable outcomes (75.7%), and preventive measures of TB (76.1%). Female participants [adjusted odds ratio (aOR):1.44; 95% confidence interval (CI):1.25–1.65], medical students (aOR:2.00; 95%CI:1.63–2.64), had a high level of monthly expenditures (aOR:2.50; 95%CI:1.49–4.19), had prior TB health education (aOR:1.95; 95%CI:1.68–2.25) and previous exposure to TB patients (aOR:2.13; 95% CI:1.48–3.08) indicating a better level of awareness of key knowledge about TB. Among the students, 58.5% expressed their willingness to acquire TB knowledge through “broadcasting, television, films, and audiovisual materials.”

Conclusions

The total awareness rate of key knowledge among low-grade college students in Zhejiang did not meet the national requirements. To effectively prevent TB in schools, it is crucial to develop a comprehensive understanding of the disease among college students. Therefore, it is necessary to enhance TB awareness through theoretical and practical education, starting from the early semesters of college.
Adverse childhood experiences: impacts on adult mental health and social withdrawal
Authors: Wakuta Manabu , Nishimura Tomoko , Osuka Yuko , Tsukui Nobuaki , Takahashi Michio , Adachi Masaki , Suwa Toshiaki , Katayama Taiichi
Published: October 2023

Background

Adverse childhood experiences (ACEs) have been found to negatively impact adult mental health outcomes. Numerous studies have highlighted on ACEs in family and community settings. However, few have examined the impact of ACEs in school settings, despite the potential influence on social participation. Hikikomori, characterized by severe social withdrawal, was first studied in Japan and has gained recognition in recent years. The present study aims to present the concept of ACEs specific to schools and investigate the impact of both school ACEs and traditional ACEs on adult mental health and Hikikomori.

Methods

A total of 4,000 Japanese adults, aged 20–34, were recruited through an Internet survey form. All data were obtained in October 2021. Participants answered questions regarding their ACEs in the family (10 items), school ACEs (five teacher-related items and two bullying-related items), depressive/anxiety symptoms, and Hikikomori (remaining at home for more than 6 months).

Results

A significant association with depressive/anxiety symptoms was shown in both ACEs and school ACEs. An increase of one point in the ACE scores was associated with a 24% increase in the risk of depressive/anxiety symptoms. School ACE scores also demonstrated a significant association with depressive/anxiety symptoms, with an increase of one point associated with a 44% increase in the risk of these symptoms. As for Hikikomori, a significant association was shown in the school ACEs only: a 29% increased risk of Hikikomori for every one-point increase in school ACE scores. Both school ACE scores for teacher-related and bullying-related factors revealed a significant association with Hikikomori; the rates of increased risk were 23 and 37%, respectively.

Conclusion

These results suggest that school ACEs, rather than ACEs in the family, are associated with the risk of Hikikomori. School ACEs are important for social adaptation, and reducing traumatic experiences in school settings may have the potential to prevent problems in later life, specifically in terms of social participation.