bluuebunny/crossref_metadata_2025 huggingface dataset:
Electroacupuncture Ameliorates Mechanical Allodynia of a Rat Model of CRPS-I via Suppressing NLRP3 Inflammasome Activation in Spinal Cord Dorsal Horn Neurons
Authors: Zhang Yunwen , Chen Ruixiang , Hu Qimiao , Wang Jie , Nie Huimin , Yin Chengyu , Li Yuanyuan , Wei Huina , Liu Boyu , Tai Yan , Fang Junfan , Shao Xiaomei , Jin Xiaoqing , Fang Jianqiao , Liu Boyi
Published: May 2022

Complex regional pain syndrome type-I (CRPS-I) is a chronic neurological disorder that results in severe pain and affects patients' life quality. Conventional therapies usually lack effectiveness. Electroacupuncture (EA) is an effective physical therapy for relieving CRPS-I pain. However, the mechanism underlying EA-induced analgesia on CRPS-I still remain unknown. Spinal NLRP3 inflammasome was recently identified to contribute to pain and neuroinflammation in a rat model of CRPS-I by our group. Here, we aimed to study whether EA could inhibit spinal NLRP3 inflammasome activation, thus resulting in pain relief and attenuation of spinal neuroinflammation in the rat model of CRPS-I. We established the rat chronic post-ischemic pain (CPIP) model to mimic CRPS-I. CPIP rats developed remarkable mechanical allodynia that could be relieved by daily EA intervention. NLRP3 inflammasome was activated in spinal cord dorsal horn (SCDH) of CPIP rats, accompanied with over-production of pro-inflammatory cytokine IL-1β. Immunostaining revealed that the cellular distribution of NLRP3 was predominantly located in SCDH neurons. Pharmacological activation of NLRP3 inflammasome per se is sufficient to produce persistent mechanical allodynia in naïve animals, whereas blocking NLRP3 inflammasome attenuates mechanical allodynia of CPIP rats. EA exclusively reduced NLRP3 overexpression in SCDH neurons and attenuated spinal glial cell over-activation in CPIP rats. EA-induced anti-allodynia with attenuation of spinal glial cell over-activation were all mimicked by intrathecal blocking NLRP3 inflammasome and reversed by activating NLRP3 inflammasome, respectively, through pharmacological methods. Finally, spinal blocking IL-1β attenuated mechanical allodynia and spinal glial cell over-activation in CPIP rats, resembling the effects of EA. In all, these results demonstrate that spinal NLRP3 inflammasome activation contributes to mechanical allodynia of the rat model of CRPS-I and EA ameliorates mechanical allodynia through inhibiting NLRP3 inflammasome activation in SCDH neurons. Our study further supports EA can be used as an effective treatment for CRPS-I.
Clinical Practice Guidelines for the Management of Behavioral and Psychological Symptoms of Dementia: A Systematic Review With AGREE II
Authors: Ma Huixuan , Lu Xinliang , Zhou Aihong , Wang Fen , Zuo Xiumei , Zhan Minmin , Zou Qi , Gong Shuting , Chen Yufei , Lyu Jihui , Jia Longfei , Jia Jianping , Wei Cuibai
Published: May 2022

Background

High-quality clinical practice guidelines (CPGs) are important for the effective treatment of behavioral and psychological symptoms of dementia (BPSD). However, recommendations provided by different quality guidelines may lead to varied clinical practice outcomes.

Objective

To assess the quality of available CPGs for the management of BPSD and summarize the best recommendations for treating BPSD.

Methods

This was a systematic review of CPGs for the management of BPSD with data obtained from electronic databases and evaluated using the Appraisal of Guidelines for Research and Evaluation II instrument, consisting of six domains: “Scope and purpose”, “Stakeholder involvement”, “Rigor of development”, “Clarity of presentation”, “Applicability”, and “Editorial independence”. The criteria for high-quality guidelines were set as: the score of high-quality guidelines in the “Rigor of development” domain should be ≥60% and as well as a score of >60% in at least three other domains. High-quality guidelines were selected for recommendation extraction, and the final recommendations were formed in combination with the latest meta-analysis and randomized clinical-trial results.

Results

In term of median scores in each domain for the six included CPGs, “Scope and purpose” (87.5%) scored better than all others, whereas “Applicability” (46.5%) was the domain with the lowest score. Four CPGs (2015 APA, 2018 NICE, 2018 CANADA, 2020 EAN) met the criteria of high-quality guidelines and were used to extract recommendations. From these four CPGs, nine specific recommendations related to the management of BPSD were summarized, of which seven were related to pharmacological treatment and two to non-pharmacological treatment. These recommendations covered the applicability of antipsychotic drugs, medication recommendations, withdrawal times, and several suitable non-pharmacological therapies.

Conclusion

The quality of CPGs for the management of BPSD requires improvement, especially for the “Applicability” domain. For psychotic-like symptoms in dementia, the use of antipsychotics should be based on the individual's risk-benefit ratio, and the use of atypical antipsychotics seems to be a better choice. Non-pharmacological treatments may be suitable for emotional symptoms and sleep disorders.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020209204.
Molecular Mechanisms of Neuroinflammation in ME/CFS and Long COVID to Sustain Disease and Promote Relapses
Authors: Tate Warren , Walker Max , Sweetman Eiren , Helliwell Amber , Peppercorn Katie , Edgar Christina , Blair Anna , Chatterjee Aniruddha
Published: May 2022

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a disease now well-documented as having arisen commonly from a viral infection, but also from other external stressors, like exposure to agricultural chemicals, other types of infection, surgery, or other severe stress events. Research has shown these events produce a systemic molecular inflammatory response and chronic immune activation and dysregulation. What has been more difficult to establish is the hierarchy of the physiological responses that give rise to the myriad of symptoms that ME/CFS patients experience, and why they do not resolve and are generally life-long. The severity of the symptoms frequently fluctuates through relapse recovery periods, with brain-centered symptoms of neuroinflammation, loss of homeostatic control, “brain fog” affecting cognitive ability, lack of refreshing sleep, and poor response to even small stresses. How these brain effects develop with ME/CFS from the initiating external effector, whether virus or other cause, is poorly understood and that is what our paper aims to address. We propose the hypothesis that following the initial stressor event, the subsequent systemic pathology moves to the brain via neurovascular pathways or through a dysfunctional blood-brain barrier (BBB), resulting in chronic neuroinflammation and leading to a sustained illness with chronic relapse recovery cycles. Signaling through recognized pathways from the brain back to body physiology is likely part of the process by which the illness cycle in the peripheral system is sustained and why healing does not occur. By contrast, Long COVID (Post-COVID-19 condition) is a very recent ME/CFS-like illness arising from the single pandemic virus, SARS-CoV-2. We believe the ME/CFS-like ongoing effects of Long COVID are arising by very similar mechanisms involving neuroinflammation, but likely with some unique signaling, resulting from the pathology of the initial SARS-CoV-2 infection. The fact that there are very similar symptoms in both ongoing diseases, despite the diversity in the nature of the initial stressors, supports the concept of a similar dysfunctional CNS component common to both.
Nodopathies in the Early Diagnosis of Axonal Forms of Guillain-Barré Syndrome
Authors: Urdiales-Sánchez Sara , González-Montaña José-Ramiro , Diaz-Pérez Ricardo , Calvo-Calleja Pablo , Gutiérrez-Trueba María-Antonia , Urdiales-Urdiales Javier
Published: May 2022

Introduction:

Guillain-Barré syndrome (GBS) has been classified into demyelinating and axonal subtypes or forms, such as acute motor axonal neuropathy (AMAN) and regional pharyngeal-cervical-brachial variant (PCBv).

Objective

To study the relationship between motor nerve conduction blocks (CBs) and prognosis in AMAN and PCBv.

Patients and Methods

We retrospectively analyzed six cases of AMAN and PCBv with serial nerve conduction studies (NCS) and electromyography (EMG).

Results

The serial NCS (1st−2nd and 3rd week) showed, as the most constant data, a decreased amplitude of the compound muscle action potential (CMAP) in 100% of cases. CBs were present in 66.6% of cases. EMG (3rd week) showed signs of severe denervation in 33.3%. All patients were treated from the 1st−2nd week of evolution with intravenous immunoglobulins (IVIGs). Patients with CBs (1st−2nd and 3rd week), showed reversible CBs or reversible conduction failure (RCF) and complete recovery at 1 month. Patients without CBs, with persistent reduced distal CMAP amplitude (dCMAP), showed severe acute denervation due to axonal degeneration (3rd week and 1st−3rd month) and a slow recovery of several months.

Conclusions

Not all axonal forms of GBS have a poor prognosis. This study of AMAN and PCBv shows that patients with CBs can have reversible CBs or RCF, and good prognosis. Patients without CBs, with persistent reduction of dCMAP amplitude decrement, have severe acute denervation, and a worse prognosis. AMAN and PCBv have a continuous spectrum ranging from CBs due to dysfunction/disruption of Nodes of Ranvier, called nodopathies, with reversible CBs or RCF and good prognosis, to axonal degeneration with worse prognosis.
Abnormal Fractional Amplitude of Low Frequency Fluctuation Changes in Patients With Dry Eye Disease: A Functional Magnetic Resonance Imaging Study
Authors: Liang Rong-Bin , Liu Li-Qi , Shi Wen-Qing , Sun Tie , Ge Qian-Min , Li Qiu-Yu , Shu Hui-Ye , Zhang Li-Juan , Shao Yi
Published: May 2022

Purpose

To investigate spontaneous brain activity in patients with dry eye (DE) and healthy control (HC) using the fractional amplitude of low frequency fluctuation (fALFF) technique with the aim of elucidating the relationship between the clinical symptoms of DE and changes in brain function.

Material and Methods

A total of 28 patients with DE and 28 matched healthy volunteers (10 males and 18 females in each group) were enrolled. Resting-state functional magnetic resonance imaging scans were performed in both groups. Then all subjects were required to complete a comprehensive Hospital Anxiety and Depression Scale (HADS). Receiver operating characteristic (ROC) curve analysis was used to evaluate the differences in fALFF values between the two groups and their diagnostic value. Linear correlations between HADS and fALFF values in different brain regions of DE patients were analyzed using the Pearson correlation coefficient.

Results

Patients with DE had significantly higher fALFF values in the left calcarine sulcus (CS) than the HC group, while fALFF values in the bilateral middle frontal gyrus (MFG) and right MFG/right inferior frontal gyrus (IFG) were significantly lower in DE patients than in HC group. fALFF values had a high diagnostic value for differentiating patients with DE from the HC group (P < 0.001). Right MFG and right MFG/IFG were significantly correlated with HADS values.

Conclusion

Our study found that DE mainly involved functional disorders in the brain areas of the left CS, bilateral MFG and right MFG/right IFG, which helped us to find possible clinical features of DE disease and reflected the potential pathological mechanism of DE.
Transmembrane Batten Disease Proteins Interact With a Shared Network of Vesicle Sorting Proteins, Impacting Their Synaptic Enrichment
Authors: Rechtzigel Mitchell J. , Meyerink Brandon L. , Leppert Hannah , Johnson Tyler B. , Cain Jacob T. , Ferrandino Gavin , May Danielle G. , Roux Kyle J. , Brudvig Jon J. , Weimer Jill M.
Published: May 2022

Batten disease is unique among lysosomal storage disorders for the early and profound manifestation in the central nervous system, but little is known regarding potential neuron-specific roles for the disease-associated proteins. We demonstrate substantial overlap in the protein interactomes of three transmembrane Batten proteins (CLN3, CLN6, and CLN8), and that their absence leads to synaptic depletion of key partners (i.e., SNAREs and tethers) and altered synaptic SNARE complexing in vivo, demonstrating a novel shared etiology.
Bromodomains in Human-Immunodeficiency Virus-Associated Neurocognitive Disorders: A Model of Ferroptosis-Induced Neurodegeneration
Authors: Sfera Adonis , Thomas Karina G. , Andronescu Christina V. , Jafri Nyla , Sfera Dan O. , Sasannia Sarvin , Zapata-Martín del Campo Carlos M. , Maldonado Jose C.
Published: May 2022

Graphical Abstract

Both HIV-1 and cART alter the lysosomes, increasing intracellular iron and the risk of ferroptosis. Dysfunctional lysosomes release the ferroptosis drivers iron, Ca2+ and cathepsin B (catB), promoting neuronal and oligodendrocyte loss, reflected in the white and gray matter pathology. The host responds to lysosomal damage by activating an epigenetic axis comprised of bromodomain 4 (BRD4) and microRNA-29 family (miR-29) that promptly suppresses lysosomal function, lowering ferritinophagy. As there is an inverse relationship between miR-29 and BRD4, HIV-1 inhibition of miR-29, upregulates BRD4, blocking ferritinophagy. The BRD4/miR-29 system also inhibits iron regulatory protein-2 (IRP-2) and augments cystine/glutamate antiporter xCT (SLC7A11), lowering the odds of ferroptosis.
The “Loss” of Perineuronal Nets in Alzheimer's Disease: Missing or Hiding in Plain Sight?
Authors: Scarlett Jarrad M. , Hu Shannon J. , Alonge Kimberly M.
Published: May 2022

Perineuronal nets (PNNs) are chondroitin-sulfate glycosaminoglycan (CS-GAG) containing extracellular matrix structures that assemble around neurons involved in learning, memory, and cognition. Owing to the unique patterning of negative charges stemming from sulfate modifications to the attached CS-GAGs, these matrices play key roles in mediating glycan-protein binding, signaling interactions, and charged ion buffering of the underlying circuitry. Histochemical loss of PNN matrices has been reported for a range of neurocognitive and neurodegenerative diseases, implying that PNNs might be a key player in the pathogenesis of neurological disorders. In this hypothesis and theory article, we begin by highlighting PNN changes observed in human postmortem brain tissue associated with Alzheimer's disease (AD) and corresponding changes reported in rodent models of AD neuropathology. We then discuss the technical limitations surrounding traditional methods for PNN analyses and propose alternative explanations to these historical findings. Lastly, we embark on a global re-evaluation of the interpretations for PNN changes across brain regions, across species, and in relation to other neurocognitive disorders.
Bevacizumab, With Sorafenib and Cyclophosphamide Provides Clinical Benefit for Recurrent or Refractory Osseous Sarcomas in Children and Young Adults
Authors: Bodea Jessica , Caldwell Kenneth J. , Federico Sara M.
Published: May 2022

Objective

Children and adolescents with recurrent and metastatic solid tumors have a poor outcome. A previous phase 1 study (ANGIO1) targeting angiogenesis with bevacizumab, sorafenib, and cyclophosphamide, demonstrated a signal of activity in a subset of patients. Here we report the results of a cohort of pediatric and young adult patients treated at the recommended phase 2 doses.

Methods

Electronic medical records of patients with refractory or recurrent solid tumors who received ANGIO1 therapy were reviewed. Treatment cycles lasted 21 days and included bevacizumab, sorafenib, and cyclophosphamide. Toxicities were assessed using Common Terminology Criteria for Adverse Events, v5.0. Responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST1.1).

Results

Thirty-nine patients (22 male, 17 female; median age 15 years; range 1-22 years) received the treatment regimen. The most common diagnoses included bone sarcomas (n=21; 14 Ewing sarcoma, 7 osteosarcoma) and soft tissue sarcomas (n=9; 2 rhabdomyosarcoma, 3 synovial sarcoma, 2 desmoplastic small round cell tumors, and 2 high-grade sarcoma). The most common Grade 3 non-hematologic toxicities included hypertension (2, 5.4%) and hematuria (2, 5.4%). Five patients (13.5%) had a pneumothorax (3 at progressive disease, 1 post lung biopsy, and 1 spontaneous). Common Grade 3/4 hematologic toxicities were lymphopenia (19, 51%) and leukopenia (13, 35%). Sixteen patients (43.2%) developed palmar-plantar erythrodysesthesia Grade 2 or less. A total of 297 cycles were administered. Twenty-three patients required a dose reduction of cyclophosphamide, sorafenib or bevacizumab during therapy, all of whom continued to have clinical benefit following dose modification. One patient (Ewing sarcoma) achieved a complete response after 11 cycles; 2 patients (Ewing sarcoma, high grade sarcoma) achieved a partial response following cycles 2 and 4, respectively and 20 patients had stable disease as a best response.

Conclusions

Intravenous bevacizumab combined with oral sorafenib and metronomic cyclophosphamide was tolerated and required minimal supportive care or additional clinic visits. Disease stabilization for prolonged time periods was observed in greater than half of the treated patients. Patients with bone sarcoma demonstrated a signal of activity suggesting possible benefit from incorporation of the therapy as a maintenance regimen in upfront setting, or as a palliative regimen.
A Nomogram Combined Radiomics and Clinical Features as Imaging Biomarkers for Prediction of Visceral Pleural Invasion in Lung Adenocarcinoma
Authors: Zha Xinyi , Liu Yuanqing , Ping Xiaoxia , Bao Jiayi , Wu Qian , Hu Su , Hu Chunhong
Published: May 2022

Objectives

To develop and validate a nomogram model based on radiomics features for preoperative prediction of visceral pleural invasion (VPI) in patients with lung adenocarcinoma.

Methods

A total of 659 patients with surgically pathologically confirmed lung adenocarcinoma underwent CT examination. All cases were divided into a training cohort (n = 466) and a validation cohort (n = 193). CT features were analyzed by two chest radiologists. CT radiomics features were extracted from CT images. LASSO regression analysis was applied to determine the most useful radiomics features and construct radiomics score (radscore). A nomogram model was developed by combining the optimal clinical and CT features and the radscore. The model performance was evaluated using ROC analysis, calibration curve and decision curve analysis (DCA).

Results

A total of 1316 radiomics features were extracted. A radiomics signature model with a selection of the six optimal features was developed to identify patients with or without VPI. There was a significant difference in the radscore between the two groups of patients. Five clinical features were retained and contributed as clinical feature models. The nomogram combining clinical features and radiomics features showed improved accuracy, specificity, positive predictive value, and AUC for predicting VPI, compared to the radiomics model alone (specificity: training cohort: 0.89, validation cohort: 0.88, accuracy: training cohort: 0.84, validation cohort: 0.83, AUC: training cohort: 0.89, validation cohort: 0.89). The calibration curve and decision curve analyses suggested that the nomogram with clinical features is beyond the traditional clinical and radiomics features.

Conclusion

A nomogram model combining radiomics and clinical features is effective in non-invasively prediction of VPI in patients with lung adenocarcinoma.
Peripheral Organ Equivalent Dose Estimation Procedure in Proton Therapy
Authors: Domingo Carles , Lagares Juan Ignacio , Romero-Expósito Maite , Sánchez-Nieto Beatriz , Nieto-Camero Jaime J. , Terrón Jose Antonio , Irazola Leticia , Dasu Alexandru , Sánchez-Doblado Francisco
Published: May 2022

The aim of this work is to present a reproducible methodology for the evaluation of total equivalent doses in organs during proton therapy facilities. The methodology is based on measuring the dose equivalent in representative locations inside an anthropomorphic phantom where photon and neutron dosimeters were inserted. The Monte Carlo simulation was needed for obtaining neutron energy distribution inside the phantom. The methodology was implemented for a head irradiation case in the passive proton beam of iThemba Labs (South Africa). Thermoluminescent dosimeter (TLD)-600 and TLD-700 pairs were used as dosimeters inside the phantom and GEANT code for simulations. In addition, Bonner sphere spectrometry was performed inside the treatment room to obtain the neutron spectra, some relevant neutron dosimetric quantities per treatment Gy, and a percentual distribution of neutron fluence and ambient dose equivalent in four energy groups, at two locations. The neutron spectrum at one of those locations was also simulated so that a reasonable agreement between simulation and measurement allowed a validation of the simulation. Results showed that the total out-of-field dose equivalent inside the phantom ranged from 1.4 to 0.28 mSv/Gy, mainly due to the neutron contribution and with a small contribution from photons, 10% on average. The order of magnitude of the equivalent dose in organs was similar, displaying a slow reduction in values as the organ is farther from the target volume. These values were in agreement with those found by other authors in other passive beam facilities under similar irradiation and measurement conditions.
Case Report: Safety and Efficacy of Enfortumab Vedotin in a Patient With Metastatic Urothelial Carcinoma Undergoing Peritoneal Dialysis
Authors: Collette Kaylyn R. , Myint Zin W. , Parasramka Saurabh V. , Ellis Carleton S.
Published: May 2022

The clinical management of metastatic urothelial carcinoma has significantly evolved with the emergence of monoclonal antibodies and antibody-drug conjugates (ADCs). Enfortumab vedotin (EV) was granted approval by the FDA in 2021 for patients with locally advanced or metastatic urothelial carcinoma who have received prior immunotherapy and platinum-containing chemotherapy. Little to no data exist for the use of EV in patients with concurrent end-stage renal disease (ESRD) using either hemodialysis or peritoneal dialysis (PD). Here, we present the case of a patient with metastatic urothelial carcinoma on PD who failed multiple lines of treatment but demonstrated an impressive response to EV without significant toxicity. We discuss the possible impact of peritoneal dialysis on the pharmacokinetics of ADCs and the potential for safe administration based on known pharmacokinetic data.
Regulatory T Cells: Therapeutic Opportunities in Uveitis
Authors: Lee Andrew YongJae , Foulsham William
Published: May 2022

Regulatory T cells (Tregs) are critical for the maintenance of immune tolerance and the suppression of excessive inflammation. Many inflammatory autoimmune disorders, including autoimmune uveitis, involve the loss of the suppressive capacities of Tregs. Over the past decade, Tregs’ therapeutic potential in uveitis has garnered increasing attention. Specific subsets of Tregs, including TIGIT+ and PD-1+ Tregs, have emerged as potent immunosuppressors that may be particularly well-suited to cell-based therapeutics. Studies have elucidated the interaction between Treg development and the gut microbiome as well as various intracellular signaling pathways. Numerous cell-based therapies and therapeutic molecules have been proposed and investigated using the murine experimental autoimmune uveitis (EAU) model. However, certain challenges remain to be addressed. Studies involving the use of Tregs in human patients with uveitis are lacking, and there are concerns regarding Tregs’ production and purification for practical use, their plasticity towards inflammatory phenotypes, immunogenicity, and tumorigenicity. Nevertheless, recent research has brought Tregs closer to yielding viable treatment options for uveitis.
Blocking CD47 Shows Superior Anti-tumor Therapeutic Effects of Bevacizumab in Gastric Cancer
Authors: Shi Chenyang , Li Jiaxin , Fan Guorong , Liu Yu
Published: May 2022

Background: Bevacizumab (Avastin®), a humanized antiangiogenic monoclonal antibody, is widely used in the clinical treatment of tumour diseases. However, recent research has shown that the beneficial antiangiogenic effects of these agents have been limited in a number of patients due to complex immunosuppressive mechanisms. Here, we report a synergistic antitumour strategy through simultaneous blockade of VEGF and CD47 signalling to enhance the curative effect of advanced gastric cancer.

Method: A BGC-823 gastric tumour model was chosen to evaluate antitumour efficacy. Macrophage migration and phagocytosis were evaluated to determine immune-related resistance to bevacizumab therapy. Synergistic antitumour activity was observed on the basis of tumour volume, tumour weight, tumour inhibition rate, tumour angiogenesis and tumour metastasis when bevacizumab was combined with an anti-CD47 monoclonal antibody.

Results: Our study demonstrated that synergistic therapy targeting CD47 and VEGF reversed macrophage migration and phagocytosis, which were inhibited by antiangiogenic therapy and enhanced antitumour effects. Moreover, blockade of CD47 induced by antiangiogenic therapy inhibited tumour metastasis.

Conclusion: Our data provide an effective strategy to attenuate resistance to bevacizumab therapy, promoting clinical cancer treatment with antiangiogenic drugs in combination with CD47-targeting inhibitors.
Fish Allergenicity Modulation Using Tailored Enriched Diets—Where Are We?
Authors: Schrama Denise , Czolk Rebecca , Raposo de Magalhães Cláudia , Kuehn Annette , Rodrigues Pedro M.
Published: May 2022

Food allergy is an abnormal immune response to specific proteins in a certain food. The chronicity, prevalence, and the potential fatality of food allergy, make it a serious socio-economic problem. Fish is considered the third most allergenic food in the world, affecting part of the world population with a higher incidence in children and adolescents. The main allergen in fish, responsible for the large majority of fish-allergic reactions in sensitized patients, is a small and stable calcium-binding muscle protein named beta-parvalbumin. Targeting the expression or/and the 3D conformation of this protein by adding specific molecules to fish diets has been the innovative strategy of some researchers in the fields of fish allergies and nutrition. This has shown promising results, namely when the apo-form of β-parvalbumin is induced, leading in the case of gilthead seabream to a 50% reduction of IgE-reactivity in fish allergic patients.
Induced Genetic Variations in Stomatal Density and Size of Rice Strongly Affects Water Use Efficiency and Responses to Drought Stresses
Authors: Pitaloka Mutiara K. , Caine Robert S. , Hepworth Christopher , Harrison Emily L. , Sloan Jennifer , Chutteang Cattleya , Phunthong Chutima , Nongngok Rangsan , Toojinda Theerayut , Ruengphayak Siriphat , Arikit Siwaret , Gray Julie E. , Vanavichit Apichart
Published: May 2022

Rice (Oryza sativa L.) is an important food crop relied upon by billions of people worldwide. However, with increasing pressure from climate change and rapid population growth, cultivation is very water-intensive. Therefore, it is critical to produce rice that is high-yielding and genetically more water-use efficient. Here, using the stabilized fast-neutron mutagenized population of Jao Hom Nin (JHN) - a popular purple rice cultivar - we microscopically examined hundreds of flag leaves to identify four stomatal model mutants with either high density (HD) or low density (LD) stomata, and small-sized (SS) or large-sized (LS) stomata. With similar genetic background and uniformity, the stomatal model mutants were used to understand the role of stomatal variants on physiological responses to abiotic stress. Our results show that SS and HD respond better to increasing CO2 concentration and HD has higher stomatal conductance (gs) compared to the other stomatal model mutants, although the effects on gas exchange or overall plant performance were small under greenhouse conditions. In addition, the results of our drought experiments suggest that LD and SS can better adapt to restricted water conditions, and LD showed higher water use efficiency (WUE) and biomass/plant than other stomatal model mutants under long-term restricted water treatment. Finally, our study suggests that reducing stomata density and size may play a promising role for further work on developing a climate-ready rice variety to adapt to drought and heat stress. We propose that low stomata density and small size have high potential as genetic donors for improving WUE in climate-ready rice.
The Effect of Transformational Change on Performance: An Employee’s Stress Appraisals Perspective
Authors: Yan Lei , Wang Li , Shen Xiangdong , Li Pengfei , Guo Jia
Published: May 2022

This study aims to determine the specific impact of employees’ perceptions of transformational change on in-role performance and how stress assessment can mediate the relationship between transformational change and in-role performance. According to the cognitive appraisal theory, the same individual has different appraisals of the same stressors, including challenge, and hindrance appraisal. As an important stressor, transformational change also affects individuals differently depending on their assessments. This study integrates employees’ challenge or hindrance appraisal of transformational change into a conceptual model to distinguish between the roles of the two appraisals. It examines it as a mediating mechanism between transformational change and in-role performance. Additionally, 313 employees who recently experienced transformational change were used as samples to test the hypothesis. The results show that transformational change negatively affects employees’ in-role performance; hindrance appraisal negatively mediates the relationship between transformational change and in-role performance, and challenge appraisal positively mediates the relationship between transformational change and in-role performance. The originality and value of this research extend the application of stress appraisals in organizational change management. Research shows that, in the context of major change, employees’ in-role performance is reduced by the impact of transformational change. However, when employees positively appraise organizational change, the negative effects of change are weakened.
Changes in Climate Vulnerability and Projected Water Stress of The Gambia's Food Supply Between 1988 and 2018: Trading With Trade-Offs
Authors: Hadida Genevieve , Ali Zakari , Kastner Thomas , Carr Tony W. , Prentice Andrew M. , Green Rosemary , Scheelbeek Pauline
Published: May 2022

Background

The coexistence of under- and overnutrition is of increasing public health concern in The Gambia. Fruits, vegetables and pulses are essential to healthy and sustainable diets, preventing micronutrient deficiencies and non-communicable diseases, while cereals significantly contribute to energy intake. However, environmental changes are predicted to intensify, reducing future yields of these crops if agricultural productivity and resilience are not improved. The Gambia is highly climate-vulnerable and import-dependent, but the extent of its reliance on other climate-vulnerable countries for its supply of nutritionally important crops is currently unknown.

Methods

We used United Nations Food and Agriculture Organization data, with novel origin-tracing algorithms applied, to analyse The Gambia's supply of cereals, fruits, vegetables and pulses between 1988 and 2018. The climate vulnerability of countries was assessed using Notre Dame Global Adaptation Initiative (ND-GAIN) index scores, and projected water stress (2040) assessed using World Resources Institute (WRI) scores. Multilevel generalized linear mixed-effects models were used to identify changes in the overall climate vulnerability and projected water stress of supply.

Results

Between 1988 and 2018, The Gambia's supply of cereals, fruits, vegetables and pulses diversified, with the proportion domestically produced falling (Cereals: 61.4%–27.7%; Fruits: 93.0%–55.7%; Vegetables: 24.6%–16.3%; Pulses: 100.0%–76.0%). The weighted-average ND-GAIN scores improved (indicating less climate vulnerability) for supply of all crops except cereals, but the weighted-average WRI score for supply deteriorated (indicating increased projected water stress) for all crops except vegetables. When just considering imports, weighted-average ND-GAIN scores deteriorated for fruits and cereals while showing no significant change for other food groups, and the WRI score deteriorated for cereals only.

Conclusions

Despite some notable improvements in the environmental vulnerability of The Gambia's supply of nutritionally important crops (particularly vegetables), considerable, and in some cases increasing, proportions of their supply are produced in countries that are vulnerable to climate change and future water stress. This may have implications for the availability, affordability, and hence consumption of these crops in The Gambia, ultimately exacerbating existing nutritional challenges. Exploring the options to strengthen supply resilience—such as altering trade patterns, agricultural techniques and diets—should be prioritized.
Impact of Particulate Matter on Hospitalizations for Respiratory Diseases and Related Economic Losses in Wuhan, China
Authors: Qin Guiyu , Wang Xuyan , Wang Tong , Nie Dewei , Li Yanbing , Liu Yan , Wen Haoyu , Huang Lihong , Yu Chuanhua
Published: May 2022

Background

Prior studies have reported the effects of particulate matter (PM) on respiratory disease (RD) hospitalizations, but few have quantified PM-related economic loss in the central region of China. This investigation aimed to assess the impacts of PM pollution on the risk burden and economic loss of patients admitted with RD.

Methods

Daily cases of RD admitted to the hospital from 1 January 2015 to 31 December 2020 were collected from two class-A tertiary hospitals in Wuhan, China. Time series analysis incorporated with a generalized additive model (GAM) was adopted to assess the impacts of fine particulate matter (PM2.5) and inhalable particulate matter (PM10) exposures on patients hospitalized with RD. Stratified analyses were performed to investigate underlying effect modification of RD risk by sex, age, and season. The cost of illness (COI) approach was applied to evaluate the related economic losses caused by PM.

Results

A total of 51,676 inpatients with a primary diagnosis of RD were included for the analysis. PM2.5 and PM10 exposures were associated with increased risks of hospitalizations for RD. Subgroup analysis demonstrated that men and children in the 0–14 years age group were more vulnerable to PM, and the adverse effects were promoted by low temperature in the cold season. A 152.4 million China Yuan (CNY) economic loss could be avoided if concentrations of PM2.5 and PM10 declined to 10 and 20 μg/m3, respectively.

Conclusions

PM2.5 and PM10 concentrations were positively associated with RD hospitalization. Men and children were more vulnerable to PM. Effective air pollution control measures can reduce hospitalizations significantly and save economic loss substantially.
Prevalence of Human Papillomavirus Among Chinese Han and Mongols Minority Women in Inner Mongolia, China: Reflected by Self-Collected Samples in CHIMUST
Authors: Guo Chunlei , Du Hui , Qu Xinfeng , Duan Xianzhi , Li Jingran , Li Ruizhen , Jin Hua , Wang Chun , Zhao Chao , Bao Juncui , Luo Hongxue , Wei Lihui , Belinson J. L. , Wu Ruifang
Published: May 2022

Background

The disparities of hr-HPV infection among races/ethnicities have not been fully discussed. This study aimed to investigate the difference of hr-HPV infection between Chinese Han and Mongols minority women in Inner Mongolia.

Methods

Genotyping and histopathology data of Chinese Han and Mongols minority women in Inner Mongolia from Chinese Multi-Center Screening Trial were used to analyze the hr-HPV prevalence, and type-specific distribution in abnormal pathology results.

Results

The hr-HPV infection rates of Han women was 15.9% while of Mongols was 21.6% (P < 0.001). The most prevalent genotypes in Han women were ranked as HPV-16,−52,−18/-58,−31/-39, and−59 while in Mongols were−16,−31,−58,−18 and−52. When analyzing the age-specific of hr-HPV infection, two peaks were found at age of 40–44 (20.5%) and 55–59 (23.5%) years in Han women while three peaks were observed at age of 30–34 (22.1%), 45–49 (22.9%), and 55–59 (31.8%) years, respectively, in Mongols. HPV-16 accounting for 62.5 and 53.8% of the CINII+ in Han and Mongols, respectively.

Conclusion

The prevalence of hr-HPV was significantly different between the Han and Mongols minority women in Inner Mongolia, races/ethnicities background should be taken into consideration for the refinement of cervical cancer screening strategies and vaccine implementation in China.
A Lightweight Network for Accurate Coronary Artery Segmentation Using X-Ray Angiograms
Authors: Tao Xingxiang , Dang Hao , Zhou Xiaoguang , Xu Xiangdong , Xiong Danqun
Published: May 2022

An accurate and automated segmentation of coronary arteries in X-ray angiograms is essential for cardiologists to diagnose coronary artery disease in clinics. The existing deep learning-based coronary arteries segmentation models focus on using complex networks to improve the accuracy of segmentation while ignoring the computational cost. However, performing such segmentation networks requires a high-performance device with a powerful GPU and a high bandwidth memory. To address this issue, in this study, a lightweight deep learning network is developed for a better balance between computational cost and segmentation accuracy. We have made two efforts in designing the network. On the one hand, we adopt bottleneck residual blocks to replace the internal components in the encoder and decoder of the traditional U-Net to make the network more lightweight. On the other hand, we embed the two attention modules to model long-range dependencies in spatial and channel dimensions for the accuracy of segmentation. In addition, we employ Top-hat transforms and contrast-limited adaptive histogram equalization (CLAHE) as the pre-processing strategy to enhance the coronary arteries to further improve the accuracy. Experimental evaluations conducted on the coronary angiograms dataset show that the proposed lightweight network performs well for accurate coronary artery segmentation, achieving the sensitivity, specificity, accuracy, and area under the curve (AUC) of 0.8770, 0.9789, 0.9729, and 0.9910, respectively. It is noteworthy that the proposed network contains only 0.75 M of parameters, which achieves the best performance by the comparative experiments with popular segmentation networks (such as U-Net with 31.04 M of parameters). Experimental results demonstrate that our network can achieve better performance with an extremely low number of parameters. Furthermore, the generalization experiments indicate that our network can accurately segment coronary angiograms from other coronary angiograms' databases, which demonstrates the strong generalization and robustness of our network.
The Pop and Color of Our Electrified Muscles
Authors: Hamstreet Tiffany , Muceli Silvia
Published: May 2022

We humans have more than 600 muscles in our bodies! You constantly use your muscles to eat, breathe, make faces, and run around! How many muscles do you think a person uses to play the piano, dance the macarena, or play basketball? How do you think the muscles get the message to move? We cannot see our muscles under the skin, so it is easy to forget about them. If you make the “strong arm” pose by flexing your elbow and clenching your fist, you might see a muscle bulge. Or if you get a lot of exercise, your muscles might get tired or sore. Would you like to be able to see what your muscles are doing under your skin? If you could listen really closely, do you think muscles make any sound? In fact, with some special recording equipment, it is possible to see and hear what muscles are doing!
Bovine Coronavirus Co-infection and Molecular Characterization in Dairy Calves With or Without Clinical Respiratory Disease
Authors: Frucchi Ana Paula S. , Dall Agnol Alais M. , Bronkhorst Dalton E. , Beuttemmuller Edsel A. , Alfieri Amauri A. , Alfieri Alice F.
Published: May 2022

Bovine respiratory disease (BRD) is considered a major cause of morbidity and mortality in young calves and is caused by a range of infectious agents, including viruses and bacteria. This study aimed to determine the frequency of viral and bacterial pathogens detected in calves with BRD from high-production dairy cattle herds and to perform the molecular characterization of N and S1 genes in identified bovine coronavirus (BCoV) strains. Nasal swabs were collected from 166 heifer calves, namely, 85 symptomatic and 81 asymptomatic calves aged between 5 and 90 days, from 10 dairy cattle herds. Nasal swabs were evaluated using molecular techniques for the identification of viruses (BCoV, bovine alphaherpesvirus 1, bovine viral diarrhea virus, bovine parainfluenza virus 3, and bovine respiratory syncytial virus) and bacteria (Pasteurella multocida, Mannheimia haemolytica, Histophilus somni, andMycoplasma bovis). In addition, five and two BCoV-positive samples were submitted to N and S1 gene amplification and nucleotide sequencing, respectively. The frequency of diagnosis of BCoV was higher (56%, 93/166) than the frequency ofP. multocida(39.8%, 66/166) andM. haemolytica(33.1%, 55/166). The three microorganisms were identified in the calves of symptomatic and asymptomatic heifer calve groups. All other pathogens included in the analyses were negative. In the phylogenetic analysis of the S1 gene, the Brazilian strains formed a new branch, suggesting a new genotype, called # 15; from the N gene, the strains identified here belonged to cluster II. This study describes high rates of BCoV,P. multocida, andM. haemolyticain heifer calves from high-production dairy cattle herds with BRD. Additionally, the molecular characterization provides evidence that the circulating BCoV strains are ancestrally different from the prototype vaccine strains and even different BCoV strains previously described in Brazil.
Single-Cell Transcriptome Profiling Signatures and Alterations of Microglia Associated With Glioblastoma Associate Microglia Contribution to Tumor Formation
Authors: Xia Hailong , Deng Lei , Meng Shu , Liu Xipeng , Zheng Chao
Published: May 2022

Glioblastoma (GBM), which occasionally occurs in pediatric patients, is the most common tumor of the central nervous system in adults. Clinically, GBM is classified as low-grade to high-grade (from 1 to 4) and is characterized by late discovery, limited effective treatment methods, and poor efficacy. With the development of immunotherapy technology, effective GBM treatment strategies are of great significance. The main immune cells found in the GBM tumor microenvironment are macrophages and microglia (MG). Both these monocytes play important roles in the occurrence and development of GBM. Macrophages are recruited during tumorigenesis, whereas MG is present in the brain during embryonic development. Interestingly, the accumulation of these monocytes is inversely proportional to the survival of adult GBM patients but not the pediatric GBM patients. This study used single-cell RNA-seq data to reveal the heterogeneity of MG in tumor lesions and to explore the role of different MG subtypes in the occurrence and development of GBM. The results may help find new targets for immunotherapy of GBM.
Data Preprocessing Method and API for Mining Processes from Cloud-Based Application Event Logs
Authors: El-Gharib Najah Mary , Amyot Daniel
Published: May 2022

Process mining (PM) exploits event logs to obtain meaningful information about the processes that produced them. As the number of applications developed on cloud infrastructures is increasing, it becomes important to study and discover their underlying processes. However, many current PM technologies face challenges in dealing with complex and large event logs from cloud applications, especially when they have little structure (e.g., clickstreams). By using Design Science Research, this paper introduces a new method, called cloud pattern API-process mining (CPA-PM), which enables the discovery and analysis of cloud-based application processes using PM in a way that addresses many of these challenges. CPA-PM exploits a new application programming interface, with an R implementation, for creating repeatable scripts that preprocess event logs collected from such applications. Applying CPA-PM to a case with real and evolving event logs related to the trial process of a software-as-a-service cloud application led to useful analyses and insights, with reusable scripts. CPA-PM helps producing executable scripts for filtering event logs from clickstream and cloud-based applications, where the scripts can be used in pipelines while minimizing the need for error-prone and time-consuming manual filtering.
Development of Durability Test Device for Magnetorheological Fluids with Two Types of Rotors and Their Long-Term Torque Characteristics
Authors: Kikuchi Takehito , Abe Isao , Ueshima Yuya , Akaiwa Shuichi , Tsuji Hitoshi
Published: May 2022

Magnetorheological fluids (MRFs) are composites of micron-sized and/or nano-sized Fe particles and nonmagnetic oils, and their rheological properties change with changes in the magnetic field. To distinguish between material and mechanical deterioration, we developed a durability test system without the influence of mechanical sealing and bearing on the MRFs. We used a set of rotors and stators to create a V-shaped MRF layer. However, the test device produces a constant magnetic field with a permanent magnet instead of an electromagnetic coil to make a compact design and cannot be tested under various dynamic magnetic inputs. Therefore, we developed a durability test system with an electric magnet to create a variable magnetic input and two sets of rotors, and compared their magnetic properties and the results of the durability tests. From the findings, the measured torque for the parallel plate case was lower than the predicted value. In contrast, the V-shaped disk exhibits a higher torque than the estimated values. Durability tests for the two types of MRFs were conducted. The torque variation for the nano MRF is significantly smaller for both the parallel and V-shaped plates. In addition, the duration of both MRFs for the V-shaped plate was much shorter than that for the parallel plate.